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Find video protocols related to scientific articles indexed in Pubmed.
Mitotane for 21-Hydroxylase Deficiency in an Infertile Man.
N. Engl. J. Med.
PUBLISHED: 11-20-2014
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To the Editor: Men with classic 21-hydroxylase deficiency are at risk for infertility.(1) The mechanisms are complex and involve three factors: gonadotropin inhibition due to the excessive secretion of progestin by the adrenal glands, obstruction of the rete testis, and destruction of the testes by testicular adrenal rest tumors.(1) We took advantage of the antisecretory and antitumoral activities of mitotane, a drug that induces "chemical adrenalectomy,"(2),(3) in an attempt to restore the fertility of a man with both 21-hydroxylase deficiency and azoospermia. The 21-hydroxylase deficiency was suspected at birth because of salt wasting and was confirmed by elevated serum . . .
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Discovery and Characterization of the Tuberculosis Drug Lead Ecumicin.
Org. Lett.
PUBLISHED: 11-20-2014
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The new tuberculosis (TB) lead ecumicin (1), a cyclic tridecapeptide, was isolated from Nonomuraea sp. MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS(2). Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey's analysis.
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Clues to the Electrical Switching Mechanism of Carbazole-Containing Polyimide Thin Films.
ACS Appl Mater Interfaces
PUBLISHED: 11-20-2014
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The electrical memory mechanism of carbazole-containing polyimides (PIs) in nanoscale thin films was investigated. For this investigation, a series of poly(3,3'-dihydroxy-4,4'-biphenylene-co-3,3'-bis(N-ethylenyloxycarbazole)-4,4'-biphenylene hexafluoroisopropylidenedi-phthalimide)s (6F-HAB-HABCZn PIs) with various compositions was synthesized as a model carbazole-containing polymer system. The thermal, optical, and electrochemical properties of the PIs were determined. Furthermore, the chemical compositions, as well as the nanoscale thin film morphologies and electron densities, were analyzed, providing detailed information on the population and positional distribution of carbazole moieties in thin films of the PIs. Devices with the polymers and aluminum top and bottom electrodes were fabricated and tested electrically. The PI thin film layers in the devices exhibited electrically permanent memory behavior, which was governed by trap-limited space-charge limited conduction and ohmic conduction. The memory characteristics were found to originate from the incorporated carbazole moieties rather than from the other chemical components. Furthermore, the memory characteristics depended significantly on the population and positional distribution of carbazole moieties in the PI layer, as well as the film thickness. Considering that the PI backbone is not conjugated, the present results collectively indicate that the electrical memory behavior of the PI films is driven by the carbazole moieties acting as charge traps and a hopping process using the carbazole charge-trap sites as stepping-stones.
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Intramuscular diclofenac for the prevention of post-ERCP pancreatitis: a randomized trial.
Endoscopy
PUBLISHED: 11-19-2014
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Background and study aims: Rectal nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The aim of this study was to determine whether intramuscular diclofenac reduces the risk of PEP. Patients and methods: Patients who underwent ERCP were randomized to receive either 90?mg of diclofenac or placebo by intramuscular injection immediately after the procedure. PEP was defined as elevated serum amylase levels (at least three times the upper limit of normal 24 hours after the procedure) associated with new or worsened upper abdominal, epigastric, or back pain. Results: In total, 380 patients were randomized, and 343 were eligible for analysis. The two groups were similar regarding clinical and demographic factors, as well as patient- and procedure-related risk factors for PEP. PEP developed in 20/170 patients (11.8?%) in the placebo group and in 22/173 patients (12.7?%) in the diclofenac group (P?=?0.87). Multivariate regression analysis failed to illustrate that intramuscular diclofenac prevented PEP (odds ratio 0.79; 95?% confidence interval 0.39?-?1.25; P?=?0.51). Conclusion: Prophylactic intramuscular diclofenac had no beneficial preventive effect on PEP.Clinicaltrials.gov NCT01717599.
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Sex steroids, precursors and metabolites deficiencies in men with isolated hypogonadotropic hypogonadism and panhypopituitarism: a GCMS-based comparative study.
J. Clin. Endocrinol. Metab.
PUBLISHED: 11-14-2014
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Context: Both testicular and adrenal steroid secretions are impaired in men with panhypopituitarism (Hypo-Pit), whereas only testicular steroid secretion is impaired in men with isolated gonadotropin deficiency (IHH) caused by normosmic congenital hypogonadotropic hypogonadism (nCHH) or Kallmann syndrome (KS). Objective: To compare serum levels of sex steroids, precursors and metabolites between men with complete IHH and those with Hypo-Pit. Patients: We studied 42 healthy men, 16 untreated men with IHH (nCHH/KS) and 23 men with Hypo-Pit (14 with craniopharyngioma, 9 with congenital hypopituitarism) receiving hydrocortisone, thyroxin and GH replacement therapy but not testosterone. Methods: Gas chromatography/mass spectrometry (GCMS) was used to measure serum levels of sex steroids (testosterone (T), dihydrotestosterone (DHT), and estradiol (E2)), their precursors (pregnenolone, 17hydroxy-pregnenolone, dehydroepiandrosterone, androstenediol, progesterone, 17hydroxy-progesterone, androstenedione) and their metabolites (androsterone, estrone, estrone sulfate), as well as pregnenolone and DHEA sulfate esters (PREGS and DHEAS). Results: All the above-mentioned steroids, and notably T, DHT and E2, were significantly lower in IHH patients than in controls but remained well above the detection limit of the relevant assays. In Hypo-Pit men, all these steroids were dramatically and significantly lower than in IHH. Interestingly, T, DHT and E2, as well as PREGS and DHEAS, were undetectable or barely detectable in Hypo-Pit men. Conclusions: Steroid deficiencies are marked but partial in men with complete IHH. In contrast, men with Hypo-Pit have a very severe overall steroid deficiency. These deficiencies could affect health and quality of life.
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Secondary amenorrhea associated with high serum 17-hydroxyprogesterone levels revealing a heterozygous CYP21A2 mutation in a woman with Addison disease.
Clin. Endocrinol. (Oxf)
PUBLISHED: 10-30-2014
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A 24-year-old woman consulted our department for infertility and a 2-year history of secondary amenorrhea after discontinuing oral contraception. She had experienced puberty at a normal age, had had regular spontaneous menses and no history of hirsutism. Primary adrenal insufficiency (PAI) was suspected at age 18 years, following 10 kg weight loss, digestive symtoms, low blood pressure and skin pigmentation, associated with hyponatremia and hyperkalemia. The diagnosis was confirmed at that time by a very low cortisol level (24 nmol/L at 8 am; normal range 189-486) and a markedly elevated ACTH level (252 pmol/L at 8 am; normal range: 2.2-13.2). Autoimmune PAI was diagnosed following the detection of a very high titer of anti-21-hydroxylase autoantibodies (2150 U/L; normal <1; I(125) labeled, 21 hydroxylase, radioactive immunoprecipitation specific assay, RSR, Cardiff, UK). This article is protected by copyright. All rights reserved.
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Prognostic Significance of Volume-Based FDG PET/CT Parameters in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation Therapy.
Yonsei Med. J.
PUBLISHED: 10-18-2014
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We investigated the prognostic role of volume-based parameters measured on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scans in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiation therapy (CRT).
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Correlation Between Helicobacter pylori Infection, IgE Hypersensitivity, and Allergic Disease in Korean Adults.
Helicobacter
PUBLISHED: 09-27-2014
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The correlation between allergic disease and Helicobacter pylori infection is still controversial in endemic areas. The aim of this study was to determine whether H. pylori infection is related to allergic disease and/or immunoglobulin E (IgE) hypersensitivity in Korean adults.
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Heterolayered, one-dimensional nanobuilding block mat batteries.
Nano Lett.
PUBLISHED: 09-22-2014
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The rapidly approaching smart/wearable energy era necessitates advanced rechargeable power sources with reliable electrochemical properties and versatile form factors. Here, as a unique and promising energy storage system to address this issue, we demonstrate a new class of heterolayered, one-dimensional (1D) nanobuilding block mat (h-nanomat) battery based on unitized separator/electrode assembly (SEA) architecture. The unitized SEAs consist of wood cellulose nanofibril (CNF) separator membranes and metallic current collector-/polymeric binder-free electrodes comprising solely single-walled carbon nanotube (SWNT)-netted electrode active materials (LiFePO4 (cathode) and Li4Ti5O12 (anode) powders are chosen as model systems to explore the proof of concept for h-nanomat batteries). The nanoporous CNF separator plays a critical role in securing the tightly interlocked electrode-separator interface. The SWNTs in the SEAs exhibit multifunctional roles as electron conductive additives, binders, current collectors and also non-Faradaic active materials. This structural/physicochemical uniqueness of the SEAs allows significant improvements in the mass loading of electrode active materials, electron transport pathways, electrolyte accessibility and misalignment-proof of separator/electrode interface. As a result, the h-nanomat batteries, which are easily fabricated by stacking anode SEA and cathode SEA, provide unprecedented advances in the electrochemical performance, shape flexibility and safety tolerance far beyond those achievable with conventional battery technologies. We anticipate that the h-nanomat batteries will open 1D nanobuilding block-driven new architectural design/opportunity for development of next-generation energy storage systems.
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Draft genome sequences of six enterohepatic helicobacter species isolated from humans and one from rhesus macaques.
Genome Announc
PUBLISHED: 09-13-2014
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Draft genome sequences of seven enterohepatic Helicobacter species, H. bilis, H. canadensis, H. canis, H. cinaedi, H. winghamensis, H. pullorum, and H. macacae, are presented. These isolates were obtained from clinical patients and a nonhuman primate. Due to potential zoonotic risks, we characterized antibiotic resistance markers and Helicobacter virulence factors.
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Arabidopsis AtERF71/HRE2 functions as transcriptional activator via cis-acting GCC box or DRE/CRT element and is involved in root development through regulation of root cell expansion.
Plant Cell Rep.
PUBLISHED: 09-11-2014
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AtERF71/HRE2 binds to GCC box or DRE/CRT as transcription activator and plays an important role in root development via root cell expansion regulation. AtERF71/HRE2 transcription factor, a member of the AP2/ERF family, plays a key role in the stress response. GCC box and DRE/CRT, both essential cis-acting elements, have been shown to be recognized by AP2/ERF family transcription factors. However, it remains unclear whether or not AtERF71/HRE2 directly interacts with GCC box and/or DRE/CRT. Here, we showed that AtERF71/HRE2 binds to GCC box and DRE/CRT by electrophoretic mobility shift assay (EMSA). Binding of AtERF71/HRE2 to GCC box and DRE/CRT was also detected by fluorescence measurement and surface plasmon resonance spectroscopy (BIAcore) experiments. Folding properties of AtERF71/HRE2 proteins were characterized by CD spectroscopy, and AtERF71/HRE2 showed thermal stability as evidenced by two endothermic peaks (T d) at 53 and 65 °C. In addition, AtERF71/HRE2 showed transcriptional activation activity via GCC box and DRE/CRT in Arabidopsis protoplasts. Interestingly, AtERF71/HRE2 OXs showed increased primary root length due to elevated root cell expansion. Our data indicate that AtERF71/HRE2 binds to both GCC box and DRE/CRT, transactivates expression of genes downstream via GCC box or DRE/CRT, and plays an important role in root development through regulation of root cell expansion.
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Orange juice intake reduces patient discomfort and is effective for bowel cleansing with polyethylene glycol during bowel preparation.
Dis. Colon Rectum
PUBLISHED: 09-10-2014
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Many patients report discomfort because of the unpleasant taste of bowel preparation solutions.
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A pilot study of S-1-based concurrent chemoradiotherapy in patients with biliary tract cancer.
Cancer Chemother. Pharmacol.
PUBLISHED: 08-17-2014
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S-1 chemotherapy is effective against advanced biliary tract cancer. The purpose was to evaluate the efficacy and safety of S-1-based concurrent chemoradiotherapy in patients with advanced biliary tract cancer.
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Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study.
J. Clin. Endocrinol. Metab.
PUBLISHED: 08-05-2014
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Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients.
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Development of a selective agar plate for the detection of Campylobacter spp. in fresh produce.
Int. J. Food Microbiol.
PUBLISHED: 08-02-2014
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This study was conducted to develop a selective medium for the detection of Campylobacter spp. in fresh produce. Campylobacter spp. (n=4), non-Campylobacter (showing positive results on Campylobacter selective agar) strains (n=49) isolated from fresh produce, indicator bacteria (n=13), and spoilage bacteria isolated from fresh produce (n=15) were plated on four Campylobacter selective media. Bolton agar and modified charcoal cefoperazone deoxycholate agar (mCCDA) exhibited higher sensitivity for Campylobacter spp. than did Preston agar and Hunt agar, although certain non-Campylobacter strains isolated from fresh produce by using a selective agar isolation method, were still able to grow on Bolton agar and mCCDA. To inhibit the growth of non-Campylobacter strains, Bolton agar and mCCDA were supplemented with 5 antibiotics (rifampicin, polymyxin B, sodium metabisulfite, sodium pyruvate, ferrous sulfate) and the growth of Campylobacter spp. (n=7) and non-Campylobacter strains (n=44) was evaluated. Although Bolton agar supplemented with rifampicin (BR agar) exhibited a higher selectivity for Campylobacter spp. than did mCCDA supplemented with antibiotics, certain non-Campylobacter strains were still able to grow on BR agar (18.8%). When BR agar with various concentrations of sulfamethoxazole-trimethoprim were tested with Campylobacter spp. (n=8) and non-Campylobacter (n=7), sulfamethoxazole-trimethoprim was inhibitory against 3 of 7 non-Campylobacter strains. Finally, we validated the use of BR agar containing 50mg/L sulfamethoxazole (BRS agar) or 0.5mg/L ciprofloxacin (BRCS agar) and other selective agars for the detection of Campylobacter spp. in chicken and fresh produce. All chicken samples were positive for Campylobacter spp. when tested on mCCDA, BR agar, and BRS agar. In fresh produce samples, BRS agar exhibited the highest selectivity for Campylobacter spp., demonstrating its suitability for the detection of Campylobacter spp. in fresh produce.
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The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 07-31-2014
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Mutations in CHD7, a gene previously implicated in CHARGE (coloboma, heart defect, choanal atresia, retardation of growth and/or development, genital hypoplasia, ear anomalies) syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating vs nontruncating mutations in KS and CHH patients is still unknown.
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Endoscopic flushing with pronase improves the quantity and quality of gastric biopsy: a prospective study.
Endoscopy
PUBLISHED: 07-14-2014
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Pronase, a proteolytic enzyme, is known to improve mucosal visibility during esophagogastroduodenoscopy (EGD), but little is known about its effects on gastric biopsy. This study assessed whether endoscopic flushing with pronase improves the quality of gastric biopsy.
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The lack of antitumor effects of o,p'DDA excludes its role as an active metabolite of mitotane for adrenocortical carcinoma treatment.
Horm Cancer
PUBLISHED: 06-10-2014
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Mitotane (o,p'DDD) is the most effective treatment of advanced adrenocortical carcinoma (ACC) but its mechanism of action remains unknown. Previous studies suggested that o,p'DDA may represent the active metabolite of mitotane. We aimed at reevaluating the potential role and pharmacological effects of o,p'DDA. Functional consequences of o,p'DDA exposure were studied on proliferation, steroidogenesis, and mitochondrial respiratory chain in human H295R and SW13 adrenocortical cells. Mitotane and its metabolites were quantified using high-performance liquid chromatography combined to an ultraviolet detection in these cells treated with o,p'DDD or o,p'DDA and in human adrenal tissues. Dose-response curves up to 300 ?M showed that, as opposed to o,p'DDD, o,p'DDA did not inhibit cell proliferation nor alter respiratory chain complex IV activity, gene expression nor induce mitochondrial biogenesis, oxidative stress, or apoptosis. However, whereas mitotane drastically decreased expression of genes involved in steroidogenesis, o,p'DDA slightly reduced expression of some steroidogenic enzymes and exerts weak anti-secretory effects only at high doses. While o,p'DDD concentration was significantly reduced by 40 % in H295R cell supernatants after 48 h incubation, o,p'DDA levels remained unchanged suggesting that o,p'DDA was not efficiently transported into the cells. o,p'DDA was not detected in cell homogenates or supernatants after 48 h exposure to o,p'DDD, consistent with the absence of o,p'DDA production in these models. Finally, unlike o'p'DDD, we found that o,p'DDA content was undetectable in two ACC and one normal adrenal gland of mitotane-treated patients, suggesting a lack of cellular uptake and in situ production. Our results demonstrate that o,p'DDD, but not o,p'DDA, induces functional alterations in adrenal cells.
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ID1201, the ethanolic extract of the fruit of Melia toosendan ameliorates impairments in spatial learning and reduces levels of amyloid beta in 5XFAD mice.
Neurosci. Lett.
PUBLISHED: 06-03-2014
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A previous study has demonstrated the anti-amyloidogenic effects of the ethanolic extract of Meliae Fructus (ID1201) using cell lines with stably expressed human Swedish mutant APP695 and ?-secretase 1, and 5Xfamilial AD (FAD) mice carrying five mutations. Here, we investigated the effects of ID1201 on cognitive impairment in 5XFAD mice. Daily administration of ID1201 was commenced at 3 months of age and continued for 3 months. Mice were serially trained in cued/response and place/spatial training tasks in the Morris water maze. After this training, testing for strategy preference was conducted. Non-transgenic control mice with vehicle treatment, vehicle-treated 5XFAD, and ID1201-treated 5XFAD mice showed equivalent performance in cued/response training. However, as training progressed to the subsequent place/spatial learning, vehicle-treated control and ID1201-treated 5XFAD mice differed significantly from vehicle-treated 5XFAD mice in measures of spatial learning (search error and adaptive spatial learning strategy). In the strategy preference test that followed, control mice preferred a place/spatial strategy relative to vehicle-treated 5XFAD mice, but differences between ID1201-treated 5XFAD mice and vehicle-treated 5XFAD mice were not significant. Additionally, ID1201 treatment reduced hippocampal levels of insoluble A?42 and increased cortical levels of soluble amyloid precursor protein ?. These results indicate that ID1201 may possess potential as a therapeutic agent for Alzheimer's disease by decreasing A? deposits.
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Growth characteristics and biofilm formation of various spoilage bacteria isolated from fresh produce.
J. Food Sci.
PUBLISHED: 05-27-2014
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This study investigated the characteristics of spoilage bacteria isolated from fresh produce including growth at various temperatures, biofilm formation, cell hydrophobicity, and colony spreading. The number of spoilage bacteria present when stored at 35 °C was significantly greater than when stored at lower temperatures, and maximum population size was achieved after 10 h. However, Bacillus pumilus, Dickeya zeae, Pectobacterium carotovorum subsp. Carotovorum Pcc21, and Bacillus pumilus (RDA-R) did not grow at the storage temperature of 5 °C. The biofilm formation by Clavibacter michiganensis, Acinetobacter calcoaceticus, and A. calcoaceticus (RDA-R) are higher than other spoilage bacteria. Biofilm formation showed low correlation between hydrophobicity, and no significant correlation with colony spreading. These results might be used for developing safe storage guidelines for fresh produce at various storage temperatures, and could be basic information on the growth characteristics and biofilm formation properties of spoilage bacteria from fresh produce.
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Congenital hypogonadotropic hypogonadism and Kallmann syndrome as models for studying hormonal regulation of human testicular endocrine functions.
Ann. Endocrinol. (Paris)
PUBLISHED: 05-09-2014
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Men with Kallmann syndrome (KS) and those with congenital isolated hypogonadotropic hypogonadism with normal olfaction share a chronic, usually profound deficit, in FSH and LH, the two pituitary gonadotropins. Many studies indicate that this gonadotropin deficiency is already present during fetal life, thus explaining the micropenis, cryptorchidism and marked testicular hypotrophy already present at birth. In addition, neonatal activation of gonadotropin secretion is compromised in boys with severe CHH/Kallmann, preventing the first phase of postnatal testicular activation. Finally, CHH is characterized by the persistence, in the vast majority of cases, of gonadotropin deficiency at the time of puberty and during adulthood. This prevents the normal pubertal testicular reactivation required for physiological sex steroid and testicular peptide production, and for spermatogenesis. CHH/KS thus represents a pathological paradigm that can help to unravel, in vivo, the role of each gonadotropin in human testicular exocrine and endocrine functions at different stages of development. Recombinant gonadotropins with pure LH or FSH activity have been used to stimulate Leydig's cells and Sertoli's cells, respectively, and thereby to clarify their paracrine interaction in vivo. The effects of these pharmacological probes can be assessed by measuring the changes they provoke in circulating testicular hormone concentrations. This review discusses the impact of chronic gonadotropin deficiency on the endocrine functions of the interstitial compartment, which contains testosterone-, estradiol- and INSL3-secreting Leydig's cells. It also examines the regulation of inhibin B and anti-Mullerian hormone (AMH) secretion in the seminiferous tubules, and the insights provided by studies of human testicular stimulation with recombinant gonadotropins, used either individually or in combination.
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SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma.
Int. J. Cancer
PUBLISHED: 04-02-2014
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Cyclophosphamide-dacarbazine-vincristine regimen is recommended for the treatment of malignant pheochromocytoma and paraganglioma (MPP); however, dacarbazine is the only recognized active drug in neuroendocrine tumours. We investigated the therapeutic benefit of temozolomide (TMZ), an oral alternative to dacarbazine, in patients with MPP. This is a retrospective study of consecutive patients with documented progressive MPP. We examined the correlation between Succinate dehydrogenase B (SDHB) mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression in the French nation-wide independent cohort of 190 pheochromocytomas or paragangliomas (PP). Progression-free survival (PFS) according to RECIST 1.1 and PERCIST 1.0 criteria was the primary end point. Fifteen consecutive patients with MPP were enrolled; ten (67%) carried a mutation in SDHB. The mean dose intensity of TMZ was 172 mg/m(2) /d for 5 days every 28 days. Median PFS was 13.3 months after a median follow-up of 35 months. There were five partial responses (33%), seven stable (47%) and three progressive diseases (20%). Grade 3 toxicities were lymphopenia in two patients and hypertension in one. Partial responses were observed only in patients with mutation in SDHB. MGMT immunohistochemistry was negative in tumour samples from four patients who responded to treatment. SDHB germline mutation was associated with hypermethylation of the MGMT promoter and low expression of MGMT in 190 samples of the French nation-wide independent cohort. This study demonstrates that TMZ is an effective antitumour agent in patients with SDHB-related MPP. The silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB-mutated tumours may explain this finding.
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Targeted exon sequencing fails to identify rare coding variants with large effect in rheumatoid arthritis.
Arthritis Res. Ther.
PUBLISHED: 03-22-2014
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IntroductionAlthough it has been suggested that rare coding variants could explain the substantial missing heritability, very few sequencing studies have been performed in rheumatoid arthritis (RA). We aimed to identify novel functional variants with rare to low frequency using targeted exon sequencing of RA in Korea.MethodsWe analyzed targeted exon sequencing data of 398 genes selected from a multifaceted approach in Korean RA patients (n¿=¿1,217) and controls (n¿=¿717). We conducted a single-marker association test and a gene-based analysis of rare variants. For meta-analysis or enrichment test, we also used ethnically matched independent samples of Korean genome-wide association studies (GWAS) (n¿=¿4,799) or immunochip data (n¿=¿4,722).ResultsAfter stringent quality control, we analyzed 10,588 variants of 398 genes from 1,934 Korean RA case-controls. We identified 13 non-synonymous variants with nominal association in single variant association tests. In a meta-analysis, we did not find any novel variant with genome-wide significance for RA risk. Using a gene-based approach, we identified 17 genes with nominal burden signals. Among them, VSTM1 showed the greatest association with RA (P¿=¿7.80¿×¿10¿4). In the enrichment test using Korean GWAS, although the significant signal appeared to be driven by total genic variants, we found no evidence for enriched association of coding variants only with RA.ConclusionsWe were unable to identify rare coding variants with large effect to explain the missing heritability for RA in the current targeted resequencing study. Our study raises skepticism about exon sequencing of targeted genes for complex diseases like RA.
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Rebleeding after initial endoscopic hemostasis in peptic ulcer disease.
J. Korean Med. Sci.
PUBLISHED: 03-20-2014
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Endoscopic hemostasis is the first-line treatment for upper gastrointestinal bleeding (UGIB). Although several factors are known to be risk factors for rebleeding, little is known about the use of antithrombotics. We tried to verify whether the use of antithrombotics affects rebleeding rate after a successful endoscopic hemostasis for peptic ulcer disease (PUD). UGIB patients who underwent successful endoscopic hemostasis were included. Rebleeding was diagnosed when the previously treated lesion bled again within 30 days of the initial episode. Of 522 UGIB patients with PUD, rebleeding occurred in 93 patients (17.8%). The rate of rebleeding was higher with aspirin medication (P=0.006) and after a long endoscopic hemostasis (P<0.001). Of all significant variables, procedure time longer than 13.5 min was related to the rate of rebleeding (OR, 2.899; 95% CI, 1.768-4.754; P<0.001) on the logistic regression analysis. The rate of rebleeding after endoscopic hemostasis for PUD is higher in the patients after a long endoscopic hemostasis. Endoscopic hemostasis longer than 13.5 min is related to rebleeding after a successful endoscopic hemostasis for PUD.
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Combining the serum pepsinogen level and Helicobacter pylori antibody test for predicting the histology of gastric neoplasm.
J Dig Dis
PUBLISHED: 03-08-2014
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To determine whether the combination test of serum pepsinogen (PG) levels and Helicobacter pylori (H. pylori) antibody was effective for predicting the incidence and histology of gastric neoplasms.
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Nutlin-3 induces BCL2A1 expression by activating ELK1 through the mitochondrial p53-ROS-ERK1/2 pathway.
Int. J. Oncol.
PUBLISHED: 03-04-2014
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Nutlin-3 which occupies the p53 binding pocket in HDM2, has been reported to activate apoptosis through both the transcriptional activity-dependent and -independent programs of p53. Transcription-independent apoptosis by nutlin-3 is triggered by p53 which is translocated to mitochondria. However, we previously demonstrated that the nutlin-3-induced mitochondrial translocation of p53 stimulates ERK1/2 activation, an anti-apoptosis signal, via mitochondrial ROS generation. We report on how nutlin-3-stimulated ERK1/2 activity inhibits p53-induced apoptosis. Among the anti-apoptotic BCL2 family proteins, BCL2A1 expression was increased by nutlin-3 at both the mRNA and protein levels, and this increase was prevented by the inhibition of ERK1/2. TEMPO, a ROS scavenger, and PFT-? , a blocker of the mitochondrial translocation of p53, also inhibited BCL2A1 expression as well as ERK1/2 phosphorylation. In addition, nutlin-3 stimulated phosphorylation of ELK1, which was prevented by all compounds that inhibited nutlin-3-induced ERK1/2 such as U0126, PFT-? and TEMPO. Moreover, an increase in BCL2A1 expression was weakened by the knockdown of ELK1. Finally, nutlin-3-induced apoptosis was found to be potentiated by the knockdown of BCL2A1, as demonstrated by an increase of in hypo-diploidic cells and Annexin V-positive cells. Parallel to the increase in apoptotic cells, the knockdown of BCL2A1 augmented the cleavage of poly(ADP-ribose) polymerase-1. It is noteworthy that the augmented levels of apoptosis induced by the knockdown of BCL2A1 were comparable to those of apoptosis induced by U0126. Collectively, these results suggest that nutlin-3-activated ERK1/2 may stimulate the transcription of BCL2A1 via the activation of ELK1, and BCL2A1 expression may contribute to the inhibitory effect of ERK1/2 on nutlin-3-induced apoptosis, thereby constituting a negative feedback loop of p53-induced apoptosis.
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Validation of group B borderline resectable pancreatic cancer: retrospective analysis.
Gut Liver
PUBLISHED: 02-24-2014
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Among borderline resectable pancreatic cancer (BRPC), group B BRPC patients have findings that are suggestive but not diagnostic of metastasis. In this study, we attempted to validate whether group B could truly be categorized as a borderline resectable group.
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Notch pathway activation is associated with pancreatic cancer treatment failure.
Pancreatology
PUBLISHED: 02-22-2014
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Pancreatic cancer is resistant to conventional treatment. The aim of the study was to confirm the hypothesis that changes in cancer stem cells (CSCs) and developmental pathway after treatment was responsible for treatment failure in pancreatic cancer.
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Arabidopsis HRE1?, a splicing variant of AtERF73/HRE1, functions as a nuclear transcription activator in hypoxia response and root development.
Plant Cell Rep.
PUBLISHED: 02-17-2014
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HRE1? shows transcriptional activation activity in its C-terminal region via GCC box but not DRE/CRT and plays an important role in root development via root meristem cell division regulation. AtERF73/HRE1 protein, a member of the Arabidopsis AP2/ERF family, contains a conserved AP2/ERF DNA-binding domain. Here, we studied the molecular function of HRE1?, a splicing variant of AtERF73/HRE1, as well as its role in root development. HRE1?-overexpressing transgenic plants (OXs) showed tolerance to submergence. HRE1? showed transcriptional activation activity via GCC box but not DRE/CRT. The 121-211 aa region of HRE1? was responsible for the transcriptional activation activity, and the region was conserved among homologs of other species but was not found in other Arabidopsis proteins. HRE1? OXs showed increased primary root length due to elevated root cell division. Our results suggest that HRE1? functions as a transcription activator in the nucleus, and plays an important role in root development through regulation of root meristem cell division.
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The effect of preceding biopsy on complete endoscopic resection in rectal carcinoid tumor.
J. Korean Med. Sci.
PUBLISHED: 02-14-2014
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Biopsy of rectal carcinoid tumor is commonly taken before endoscopic resection. However the preceding biopsy can inhibit complete resection by causing blurred tumor border and fibrosis of the tissue. The objective of the study was to investigate the effect of preceding biopsy on complete endoscopic resection in rectal carcinoid tumor. It was also determined if rectal carcinoid tumors can be macroscopically distinguished by endoscopy. We reviewed retrospectively the records of patients with rectal carcinoid tumor who had undergone an endoscopic treatment at our hospital, during a 7-yr period. The resection margin was clear in 57 of 98 cases. The preceding biopsy was taken in 57 cases and the biopsy was significantly associated with the risk of incomplete tumor resection (OR, 3.696; 95% CI, 1.528-8.938, P = 0.004). In 95.9% of the cases, it was possible to suspect a carcinoid tumor by macroscopic appearance during initial endoscopy. The preceding biopsy may disturb complete resection of rectal carcinoid tumor. In most cases, the carcinoid tumor could be suspected by macroscopic appearance. Therefore the preceding biopsy is not essential, and it may be avoided for the complete resection.
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Effect of pronase premedication on narrow-band imaging endoscopy in patients with precancerous conditions of stomach.
Dig. Dis. Sci.
PUBLISHED: 01-28-2014
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Narrow-band imaging (NBI) endoscopy improves the detection of intestinal metaplasia. However, strategies to improve the visibility and diagnostic performance of NBI should be sought, as endoscopic views are often obscured by the presence of mucus.
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Ketoconazole in Cushing's disease: is it worth a try?
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-28-2014
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The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However, ketoconazole is frequently used as a drug to lower circulating cortisol levels. Several pharmacological agents have recently been approved for the treatment of Cushing's disease (CD) despite limited efficacy or significant side effects. Ketoconazole has been used worldwide for more than 30 years in CD, but in the absence of a large-scale study, its efficacy and tolerance are still under debate.
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[Congenital hypogonadotropic hypogonadism and Kallmann syndrome in males].
Presse Med
PUBLISHED: 01-20-2014
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Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are a group of rare disorders responsible for complete or partial pubertal failure due to lack or insufficient secretion of the pituitary gonadotropins LH and FSH. The underlying neuroendocrine abnormalities are classically divided into two main groups: molecular defects of the gonadotrope cascade leading to isolated normosmic CHH (nCHH), and developmental abnormalities affecting the hypothalamic location of GnRH neurons, but also olfactory bulbs and tracts morphogenesis and responsible for KS. Identification of genetic abnormalities related to CHH/KS has provided major insights into the pathways critical for the development, maturation and function of the gonadotrope axis. In patients affected by nCHH, particularly in familial cases, genetic alterations affecting GnRH secretion (mutations in GNRH1, GPR54/KISS1R and TAC3 and TACR3) or the GnRH sensitivity of gonadotropic cells (GNRHR) have been found. Mutations in KAL1, FGFR1/FGF8/FGF17, PROK2/PROKR2, NELF, CHD7, HS6ST1, WDR11, SEMA3A, SOX10, IL17RD2, DUSP6, SPRY4, and FLRT3 have been associated with KS but sometimes also with its milder hyposmic/normosmic CHH clinical variant. A number of observations, particularly in sporadic cases, suggest that CHH/KS is not always a monogenic mendelian disease as previously thought but rather a digenic or potentially oligogenic condition. Before the age of 18 years, the main differential diagnosis of isolated nCHH is the relatively frequent constitutional delay of growth and puberty (CDGP). However, in male patients with pubertal delay and low gonadotropin levels, the presence of micropenis and/or cryptorchidism argues strongly in favor of CHH and against CDGP. CHH/KS are not always congenital life-long disorders as initially thought, because in nearly 10 % of patients the disease seems not permanent, as evidenced by partial recovery of the pulsatile activity of the hypothalamic-pituitary-gonadal axis after discontinuation of treatment in adulthood (the so-called reversible CHH/KS). The clinical and hormonal diagnosis and the therapeutic management as well as the genetic counseling of these patients will be discussed here based on the experience acquired in our department during the past 30 years, from monitoring more than 400 patients with these rare conditions.
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The clinical features and treatment modality of esophageal neuroendocrine tumors: a multicenter study in Korea.
BMC Cancer
PUBLISHED: 01-13-2014
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Neuroendocrine tumors (NETs) of the esophagus are extremely rare, and few cases have been reported worldwide. Thus, a comprehensive nationwide study is needed to understand the characteristics of and treatment strategy for esophageal NETs.
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The Arabidopsis chloroplast protein S-RBP11 is involved in oxidative and salt stress responses.
Plant Cell Rep.
PUBLISHED: 01-11-2014
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S-RBP11, a chloroplast protein, which was isolated using activation tagging system, is shown to be the first Arabidopsis small RNA-binding group protein involved in oxidative and salt stress responses. Activation tagging is one of the most powerful tools in reverse genetics. In this study, we isolated S-RBP11, encoding a small RNA-binding protein in Arabidopsis, by salt-resistant activation tagging line screen and then characterized its function in the abiotic stress response. The isolated activation tagging line of S-RBP11 as well as transgenic plants overexpressing S-RBP11 showed increased tolerance to salt and MV stresses compared to WT plants, whereas s-rbp11 mutants were more sensitive to salt stresses. Transcription of S-RBP11 was elevated upon MV treatment but not NaCl or cold treatment. Interestingly, S-RBP11 protein was localized in the chloroplast and the N-terminal 34 amino acid region of S-RBP11 was necessary for its chloroplast targeting. Our results suggest that S-RBP11 is a chloroplast protein involved in the responses to salt and oxidative stresses.
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Testicular histological and immunohistochemical aspects in a post-pubertal patient with 5 alpha-reductase type 2 deficiency: case report and review of the literature in a perspective of evaluation of potential fertility of these patients.
BMC Endocr Disord
PUBLISHED: 01-08-2014
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Testicular morphology and immunohistochemical studies have never been reported in genetically documented adult patients with 5 alpha-reductase type 2 deficiency (5?-R2 deficiency).
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Current progress toward eradicating Helicobacter pylori in East Asian countries: differences in the 2013 revised guidelines between China, Japan, and South Korea.
World J. Gastroenterol.
PUBLISHED: 01-06-2014
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New 2013 guidelines on Helicobacter pylori (H. pylori) infection have been published in China, Japan, and South Korea. Like the previous ones, these new guidelines differ between the three countries with regard to the indications for H. pylori eradication, diagnostic methods, and treatment regimens. The most profound change among all of the guidelines is that the Japanese national health insurance system now covers the expenses for all infected subjects up to second-line treatment. This makes the Japanese indications for eradication much wider than those in China and South Korea. With regard to the diagnosis, a serum H. pylori antibody test is not recommended in China, whereas it is considered to be the most reliable method in Japan. A decrease relative to the initial antibody titer of more than 50% after 6-12 mo is considered to be the most accurate method for determining successful eradication in Japan. In contrast, only the urea breath test is recommended after eradication in China, while either noninvasive or invasive methods (except the bacterial culture) are recommended in South Korea. Due to the increased rate of antibiotics resistance, first-line treatment is omitted in China and South Korea in cases of clarithromycin resistance. Notably, the Japanese regimen consists of a lower dose of antibiotics for a shorter duration (7 d) than in the other countries. There is neither 14 d nor bismuth-based regimen in the first-line and second-line treatment in Japan. Such differences among countries might be due to differences in the approvals granted by the governments and national health insurance system in each country. Further studies are required to achieve the best results in the diagnosis and treatment of H. pylori infection based on cost-effectiveness in East Asian countries.
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Ligand-dependent stabilization of androgen receptor in a novel mouse ST38c Sertoli cell line.
Mol. Cell. Endocrinol.
PUBLISHED: 01-06-2014
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Mature Sertoli cells (SC) are critical mediators of androgen regulation of spermatogenesis, via the androgen receptor (AR) signaling. Available immortalized SC lines loose AR expression or androgen responsiveness, hampering the study of endogenous AR regulation in SC. We have established and characterized a novel clonal mouse immortalized SC line, ST38c. These cells express some SC specific genes (sox9, wt1, tjp1, clu, abp, inhbb), but not fshr, yet more importantly, maintain substantial expression of endogenous AR as determined by PCR, immunocytochemistry, testosterone binding assays and Western blots. Microarrays allowed identification of some (146) but not all (rhox5, spinlw1), androgen-dependent, SC expressed target genes. Quantitative Real-Time PCR validated regulation of five up-regulated and two down-regulated genes. We show that AR undergoes androgen-dependent transcriptional activation as well as agonist-dependent posttranslational stabilization in ST38c cells. This cell line constitutes a useful experimental tool for future investigations on the molecular and cellular mechanisms of androgen receptor signaling in SC function.
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Pilon: An Integrated Tool for Comprehensive Microbial Variant Detection and Genome Assembly Improvement.
PLoS ONE
PUBLISHED: 01-01-2014
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Advances in modern sequencing technologies allow us to generate sufficient data to analyze hundreds of bacterial genomes from a single machine in a single day. This potential for sequencing massive numbers of genomes calls for fully automated methods to produce high-quality assemblies and variant calls. We introduce Pilon, a fully automated, all-in-one tool for correcting draft assemblies and calling sequence variants of multiple sizes, including very large insertions and deletions. Pilon works with many types of sequence data, but is particularly strong when supplied with paired end data from two Illumina libraries with small e.g., 180 bp and large e.g., 3-5 Kb inserts. Pilon significantly improves draft genome assemblies by correcting bases, fixing mis-assemblies and filling gaps. For both haploid and diploid genomes, Pilon produces more contiguous genomes with fewer errors, enabling identification of more biologically relevant genes. Furthermore, Pilon identifies small variants with high accuracy as compared to state-of-the-art tools and is unique in its ability to accurately identify large sequence variants including duplications and resolve large insertions. Pilon is being used to improve the assemblies of thousands of new genomes and to identify variants from thousands of clinically relevant bacterial strains. Pilon is freely available as open source software.
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A Biodiversity Indicators Dashboard: Addressing Challenges to Monitoring Progress towards the Aichi Biodiversity Targets Using Disaggregated Global Data.
PLoS ONE
PUBLISHED: 01-01-2014
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Recognizing the imperiled status of biodiversity and its benefit to human well-being, the world's governments committed in 2010 to take effective and urgent action to halt biodiversity loss through the Convention on Biological Diversity's "Aichi Targets". These targets, and many conservation programs, require monitoring to assess progress toward specific goals. However, comprehensive and easily understood information on biodiversity trends at appropriate spatial scales is often not available to the policy makers, managers, and scientists who require it. We surveyed conservation stakeholders in three geographically diverse regions of critical biodiversity concern (the Tropical Andes, the African Great Lakes, and the Greater Mekong) and found high demand for biodiversity indicator information but uneven availability. To begin to address this need, we present a biodiversity "dashboard" - a visualization of biodiversity indicators designed to enable tracking of biodiversity and conservation performance data in a clear, user-friendly format. This builds on previous, more conceptual, indicator work to create an operationalized online interface communicating multiple indicators at multiple spatial scales. We structured this dashboard around the Pressure-State-Response-Benefit framework, selecting four indicators to measure pressure on biodiversity (deforestation rate), state of species (Red List Index), conservation response (protection of key biodiversity areas), and benefits to human populations (freshwater provision). Disaggregating global data, we present dashboard maps and graphics for the three regions surveyed and their component countries. These visualizations provide charts showing regional and national trends and lay the foundation for a web-enabled, interactive biodiversity indicators dashboard. This new tool can help track progress toward the Aichi Targets, support national monitoring and reporting, and inform outcome-based policy-making for the protection of natural resources.
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Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor.
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Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.
N. Engl. J. Med.
PUBLISHED: 11-29-2013
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Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushings syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands.
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Insulin-like Peptide 3 (INSL3) in Men With Congenital Hypogonadotropic Hypogonadism/Kallmann Syndrome and Effects of Different Modalities of Hormonal Treatment: A Single-Center Study of 281 Patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 11-15-2013
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Context:Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty.Objective:To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation.Patients:We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men.Methods:Serum INSL3 was immunoassayed with a validated RIA.Results:Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS.Conclusions:INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.
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[Cytomegalovirus jejunitis diagnosed with single-balloon enteroscopy].
Korean J Gastroenterol
PUBLISHED: 10-29-2013
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Cytomegalovirus (CMV) infections are usually diagnosed in immunocompromised patients. A 74-year-old male without any significant medical history visited our center because of abdominal pain and diarrhea which began about a month ago. Abdominal computed tomography revealed segmental enhanced bowel wall thickening on jejunum and single-balloon enteroscopy showed multiple geographic shaped ulcerations covered with exudates on proximal jejunum. Biopsy samples taken during endoscopic examination demonstrated necrotic fibrinopurulent tissue debris and benign ulcer. Nested-PCR analysis of CMV DNA from jejunal tissue was positive. The patient was finally diagnosed with CMV jejunitis and was treated by intravenous ganciclovir for 14 days after which, abdominal pain and diarrhea improved. Our case shows that CMV jejunitis can occur in an immunocompetent adult as multiple jejunal ulcers which can be diagnosed using a single-balloon enteroscope.
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Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53.
Int. J. Oncol.
PUBLISHED: 10-04-2013
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A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-?, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin?3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-?, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-? reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.
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Wilms tumor gene 1 enhances nutlin-3-induced apoptosis.
Oncol. Rep.
PUBLISHED: 09-27-2013
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Nutlin-3, a human double minute 2 (HDM2) antagonist, induces cell cycle arrest or apoptosis by upregulating p53 in cancer cells. WT1, the product of Wilms tumor gene 1, has been shown to interact with p53, but the effect of WT1 on nutlin-3-induced apoptosis has yet to be examined. To address this issue, we analyzed the inhibitory effect of nutlin-3 on cell growth as a function of Wt1 expression status using a Wt1-inducible U2OS cell line. In the absence of Wt1 expression, nutlin-3 induced cell cycle arrest with marginal cytotoxicity. Furthermore, upon Wt1 expression, nutlin-3 exerted a marked degree of cell death, as evidenced by the accumulation of hypo-diploid cells and LDH release. During cell death induction, cytochrome c was released into the cytosol, and caspase-9 and -3 were activated, suggesting that an intrinsic apoptotic pathway may be involved in this cell death. Consistent with this, z-VAD-Fmk, a pan-caspase inhibitor and the overexpression of BCL-XL attenuated the cell death. Nutlin-3 caused an increase in the mRNA levels of both BCL-XL and BAK, as well as their corresponding protein levels in mitochondria. In the presence of Wt1, nutlin-3-induced BCL-XL expression was attenuated while the expression of nutlin-3-induced BAK was potentiated. Collectively, these results suggest that WT1 potentiates nutlin-3-induced apoptosis by downregulating the expression of BCL-XL while upregulating that of BAK, which leads to the activation of an intrinsic apoptotic pathway.
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Molecular screening for a personalized treatment approach in advanced adrenocortical cancer.
J. Clin. Endocrinol. Metab.
PUBLISHED: 08-26-2013
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Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. In ACC, no personalized approach has emerged but no extensive molecular screening has been performed to date.
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Depletion of Aurora A leads to upregulation of FoxO1 to induce cell cycle arrest in hepatocellular carcinoma cells.
Cell Cycle
PUBLISHED: 08-09-2013
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Aurora A kinase has drawn considerable attention as a therapeutic target for cancer therapy. However, the underlying molecular and cellular mechanisms of the anticancer effects of Aurora A kinase inhibition are still not fully understood. Herein, we show that depletion of Aurora A kinase by RNA interference (RNAi) in hepatocellular carcinoma (HCC) cells upregulated FoxO1 in a p53-dependent manner, which induces cell cycle arrest. Introduction of an RNAi-resistant Aurora A kinase into Aurora A-knockdown cells resulted in downregulation of FoxO1 expression and rescued proliferation. In addition, silencing of FoxO1 in Aurora A-knockdown cells allowed the cells to exit cytostatic arrest, which, in turn, led to massive cell death. Our results suggest that FoxO1 is responsible for growth arrest at the G2/M phase that is induced by Aurora A kinase inhibition.
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Distinctive expansion of potential virulence genes in the genome of the oomycete fish pathogen Saprolegnia parasitica.
PLoS Genet.
PUBLISHED: 06-01-2013
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Oomycetes in the class Saprolegniomycetidae of the Eukaryotic kingdom Stramenopila have evolved as severe pathogens of amphibians, crustaceans, fish and insects, resulting in major losses in aquaculture and damage to aquatic ecosystems. We have sequenced the 63 Mb genome of the fresh water fish pathogen, Saprolegnia parasitica. Approximately 1/3 of the assembled genome exhibits loss of heterozygosity, indicating an efficient mechanism for revealing new variation. Comparison of S. parasitica with plant pathogenic oomycetes suggests that during evolution the host cellular environment has driven distinct patterns of gene expansion and loss in the genomes of plant and animal pathogens. S. parasitica possesses one of the largest repertoires of proteases (270) among eukaryotes that are deployed in waves at different points during infection as determined from RNA-Seq data. In contrast, despite being capable of living saprotrophically, parasitism has led to loss of inorganic nitrogen and sulfur assimilation pathways, strikingly similar to losses in obligate plant pathogenic oomycetes and fungi. The large gene families that are hallmarks of plant pathogenic oomycetes such as Phytophthora appear to be lacking in S. parasitica, including those encoding RXLR effectors, Crinklers, and Necrosis Inducing-Like Proteins (NLP). S. parasitica also has a very large kinome of 543 kinases, 10% of which is induced upon infection. Moreover, S. parasitica encodes several genes typical of animals or animal-pathogens and lacking from other oomycetes, including disintegrins and galactose-binding lectins, whose expression and evolutionary origins implicate horizontal gene transfer in the evolution of animal pathogenesis in S. parasitica.
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Low Prevalence of Microsatellite Instability in Interval Gastric Cancers.
Dig. Dis. Sci.
PUBLISHED: 05-18-2013
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Esophagogastroduodenoscopy (EGD) is recommended at 2-year intervals in countries with a high prevalence of gastric cancer. The aim of this study was to determine whether interval gastric cancers that develop within 2 years of a previous complete screening are associated with microsatellite instability (MSI).
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Early Gastric Cancer-Like Advanced Gastric Cancer versus Advanced Gastric Cancer-Like Early Gastric Cancer.
Clin Endosc
PUBLISHED: 03-31-2013
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Improvements in the endoscopic evaluation and management of gastric cancer have made it possible to determine the depth of invasion during endoscopic examination. The aim of this study was to elucidate the differences between early gastric cancer (EGC) that resembles advanced gastric cancer (AGC) and AGC that resembles EGC.
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Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.
Am. J. Hum. Genet.
PUBLISHED: 03-14-2013
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Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ~12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH.
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Is the proton pump inhibitor test helpful in patients with laryngeal symptoms?
Dig. Dis. Sci.
PUBLISHED: 02-27-2013
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The association of gastroesophageal reflux disease (GERD) and laryngeal symptoms is not clear. We aimed to examine the symptomatic and endoscopic relations between GERD and laryngeal symptoms and also to evaluate the response to a 2-week proton pump inhibitor (PPI) trial.
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Efficacy of concurrent chemoradiotherapy with 5-fluorouracil or gemcitabine in locally advanced biliary tract cancer.
Cancer Chemother. Pharmacol.
PUBLISHED: 02-25-2013
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There is no established standard treatment for patients with locally advanced biliary tract cancer (BTC).
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Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness.
Am. J. Hum. Genet.
PUBLISHED: 02-25-2013
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Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.
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Survival of foodborne pathogens at different relative humidities and temperatures and the effect of sanitizers on apples with different surface conditions.
Food Microbiol.
PUBLISHED: 02-04-2013
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We investigated the effects of factors such as relative humidity (RH) and temperature on pathogen survival on apples with different surface conditions. Apples with different surface conditions (unblemished, bruised, or cut) were inoculated with three pathogens (Escherichia coli O157:H7, Salmonella Typhimurium, and Staphylococcus aureus) and stored at different RH levels (RH 100, 85, or 68%) at 4 °C or 15 °C for 2 days. S. aureus survived most readily on apple surfaces; it had no significant reduction on any of the apple surfaces for any of the three RH levels after 2 days of storage. The reduction levels of E. coli O157:H7 and S. Typhimurium on unblemished and bruised apple surfaces were higher at RH of 85% and 68% than at RH of 100% at 15 °C; and reduction levels were approximately 3 log(10) CFU/apple at 4 °C in RH of 68%. No significant reduction in any of the three pathogens on cut apple surfaces was observed for any RH level. The effectiveness of chemical sanitizers (chlorine sanitizer and 2% lactic acid) in reducing pathogens (E. coli O157:H7, S. Typhimurium, and S. aureus) on apple surfaces (unblemished, bruised, or cut) was also evaluated. Treatment with chlorine sanitizer and 2% lactic acid for 5 min significantly reduced pathogen levels on unblemished and bruised apple surfaces but not on cut apple surfaces. In conclusion, the surface conditions of the apple significantly affected pathogen survival and the effectiveness of sanitizing methods.
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Computed tomography of the anterior skull base in Kallmann syndrome reveals specific ethmoid bone abnormalities associated with olfactory bulb defects.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-24-2013
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Kallmann syndrome (KS) is characterized by congenital hypogonadotropic hypogonadism (CHH) and an impaired sense of smell related to defective development of the olfactory system.
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Inhibitory effect of cinnamon powder on pathogen growth in laboratory media and oriental-style rice cakes (sulgidduk).
J. Food Prot.
PUBLISHED: 01-16-2013
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There has been an increasing interest in the use of natural plant materials as alternative food preservatives. We examined the antimicrobial effects of natural plant materials used as additives against foodborne pathogens in laboratory media and Sulgidduk, oriental-style rice cakes. Cinnamon, mugwort, and garlic powder solutions (3%) were tested for their antimicrobial activities against pathogens in laboratory media. Sulgidduk prepared with different amounts of cinnamon powder (1, 3, and 6%) was inoculated with a Staphylococcus aureus or Bacillus cereus cocktail. The samples were air or vacuum packaged and stored at 22 ± 1°C for 72 h, and microbial growth was determined. Cinnamon powder showed more inhibitory properties against pathogens such as Salmonella enterica serovar Typhimurium, Escherichia coli O157:H7, Listeria monocytogenes, S. aureus, and B. cereus than did mugwort or garlic powder. The populations of S. aureus and B. cereus in Sulgidduk containing cinnamon powder were significantly lower than in the control during storage time. Different packaging methods did not result in a significant difference in pathogen growth. In a sensory evaluation, Sulgidduk containing 1 and 3% cinnamon powder did not significantly differ from the control sample in any of the attributes tested other than flavor. These results indicate that natural plant materials such as cinnamon powder could be used as food additives to improve the microbiological stability of rice cakes.
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What is the next step for gastric atypical epithelium on histological findings of endoscopic forceps biopsy?
Dig Liver Dis
PUBLISHED: 01-14-2013
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Gastric atypical epithelium on endoscopic biopsy is borderline lesions between benign and malignant. Definitive management of this lesion remains debatable.
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ERK1/2 activation mediated by the nutlin?3?induced mitochondrial translocation of p53.
Int. J. Oncol.
PUBLISHED: 01-10-2013
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Nutlin-3 is a small-molecule antagonist of murine double minute 2 (MDM2) that blocks its binding to p53, leading to an increase in p53 protein levels. The tumor suppressor p53 induces growth arrest or apoptosis in response to genotoxic stress. Along with its growth-suppressive effect, it has been reported that p53 stimulates the mitogen-activated protein kinase (MAPK) pathway via the upregulation of heparin- binding epidermal growth factor-like growth factor (HB-EGF), an epidermal growth factor receptor (EGFR) ligand, and discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor, at the transcription level. In this study, we propose a novel mechanism involved in the p53-induced MAPK activation. Nutlin-3 induced the phosphorylation of EGFR, MAPK/ERK kinase (MEK)1/2 and extracellular signal-regulated kinase (ERK)1/2 in U2OS human osteosarcoma cells harboring wild-type p53. This phosphorylation was completely inhibited by p53 siRNA, but not by pifithrin (PFT)-?, an inhibitor of the trans-criptional activity of p53. While the nutlin-3-induced EGFR phosphorylation was prevented by the inactivation of ERK1/2, the nutlin-3-induced MEK1/2-ERK1/2 phosphorylation was still observed in the cells in which EGFR phosphorylation was inhibited using EGFR siRNA and AG1478, an inhibitor of EGFR tyrosine kinase. Of note, nutlin-3 caused the accumulation of mitochondrial reactive oxygen species (ROS) and this correlated with the mitochondrial translocation of p53. 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO), a ROS scavenger, prevented the phosphorylation of ERK1/2. PFT-?, which prevented the mitochondrial localization of p53, suppressed ERK1/2 phosphorylation, as well as ROS accumulation. Finally, we analyzed the effect of ERK1/2 activation on nutlin-3-induced apoptosis. The knockdown of MEK1/2 and ERK1/2 activity using U0126, a MEK inhibitor, or siRNAs, resulted in the enhancement of nutlin-3-induced apoptosis. In addition, TEMPO and PFT-? also promoted nutlin-3-induced apoptosis. Taking the above findings into account, it can be concluded that nutlin-3 activates ERK1/2 prior to EGFR phosphorylation via ROS generation following the mitochondrial translocation of p53 and that nutlin-3-induced ERK1/2 activation may play a role in protecting U2OS cells from p53-dependent apoptosis, constituting a negative feedback loop for p53-induced apoptosis.
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Expression and characterization of androgen receptor coregulators, SRC-2 and HBO1, during human testis ontogenesis and in androgen signaling deficient patients.
Mol. Cell. Endocrinol.
PUBLISHED: 01-04-2013
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Androgen receptor (AR) is essential for testicular physiology and spermatogenesis. SRC-2 and HBO1 are two AR coregulators yet their expression and roles in human testis are unknown. For the first time, we studied by immunohistochemistry and RT-PCR, the expression and distribution of these two coregulators during human testicular ontogenesis, in patients with altered AR signaling (Androgen insensitivity syndrome, AIS) and evaluated the functional impact of SRC-2 and HBO1 on AR signaling in a Sertoli cell context. SRC-2 was present in Sertoli cells at all developmental stages. HBO1 was barely or focally detected in the fetal testis yet its expression, in Sertoli and germ cells, drastically increased postnatally from early infancy to adulthood. In transient co-transfection studies we showed that SRC-2 induced, while HBO1 inhibited AR-mediated transactivation of reporter constructs in murine Sertoli SMAT1 cells. HBO1, but not SRC-2, expression was reduced in testes of patients with AIS compared to normal testes.
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R31C GNRH1 mutation and congenital hypogonadotropic hypogonadism.
PLoS ONE
PUBLISHED: 01-01-2013
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Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified in a CpG islet in nine nCHH subjects from four unrelated families, giving evidence for a putative "hot spot". Interestingly, all the nCHH patients carry this mutation in heterozygosis that strikingly contrasts with the recessive inheritance associated with frame shift and non-sense mutations. Therefore, after exclusion of a second genetic event, a comprehensive functional characterization of the mutant R31C GnRH was undertaken. Using different cellular models, we clearly demonstrate a dramatic reduction of the mutant decapeptide capacity to bind GnRH-receptor, to activate MAPK pathway and to trigger inositol phosphate accumulation and intracellular calcium mobilization. In addition it is less able than wild type to induce lh-beta transcription and LH secretion in gonadotrope cells. Finally, the absence of a negative dominance in vitro offers a unique opportunity to discuss the complex in vivo patho-physiology of this form of nCHH.
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Evolutionary dynamics of the accessory genome of Listeria monocytogenes.
PLoS ONE
PUBLISHED: 01-01-2013
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Listeria monocytogenes, a foodborne bacterial pathogen, is comprised of four phylogenetic lineages that vary with regard to their serotypes and distribution among sources. In order to characterize lineage-specific genomic diversity within L. monocytogenes, we sequenced the genomes of eight strains from several lineages and serotypes, and characterized the accessory genome, which was hypothesized to contribute to phenotypic differences across lineages. The eight L. monocytogenes genomes sequenced range in size from 2.85-3.14 Mb, encode 2,822-3,187 genes, and include the first publicly available sequenced representatives of serotypes 1/2c, 3a and 4c. Mapping of the distribution of accessory genes revealed two distinct regions of the L. monocytogenes chromosome: an accessory-rich region in the first 65° adjacent to the origin of replication and a more stable region in the remaining 295°. This pattern of genome organization is distinct from that of related bacteria Staphylococcus aureus and Bacillus cereus. The accessory genome of all lineages is enriched for cell surface-related genes and phosphotransferase systems, and transcriptional regulators, highlighting the selective pressures faced by contemporary strains from their hosts, other microbes, and their environment. Phylogenetic analysis of O-antigen genes and gene clusters predicts that serotype 4 was ancestral in L. monocytogenes and serotype 1/2 associated gene clusters were putatively introduced through horizontal gene transfer in the ancestral population of L. monocytogenes lineage I and II.
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Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells.
Endocr. Relat. Cancer
PUBLISHED: 01-01-2013
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Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane is the most effective medical therapy for adrenocortical carcinoma, but its molecular mechanism of action remains poorly understood. Although mitotane is known to have mitochondrial (mt) effects, a direct link to mt dysfunction has never been established. We examined the functional consequences of mitotane exposure on proliferation, steroidogenesis, and mt respiratory chain, biogenesis and morphology, in two human adrenocortical cell lines, the steroid-secreting H295R line and the non-secreting SW13 line. Mitotane inhibited cell proliferation in a dose- and a time-dependent manner. At the concentration of 50??M (14?mg/l), which corresponds to the threshold for therapeutic efficacy, mitotane drastically reduced cortisol and 17-hydroxyprogesterone secretions by 70%. This was accompanied by significant decreases in the expression of genes encoding mt proteins involved in steroidogenesis (STAR, CYP11B1, and CYP11B2). In both H295R and SW13 cells, 50??M mitotane significantly inhibited (50%) the maximum velocity of the activity of the respiratory chain complex IV (cytochrome c oxidase (COX)). This effect was associated with a drastic reduction in steady-state levels of the whole COX complex as revealed by blue native PAGE and reduced mRNA expression of both mtDNA-encoded COX2 (MT-CO2) and nuclear DNA-encoded COX4 (COX4I1) subunits. In contrast, the activity and expression of respiratory chain complexes II and III were unaffected by mitotane treatment. Lastly, mitotane exposure enhanced mt biogenesis (increase in mtDNA content and PGC1? (PPARGC1A) expression) and triggered fragmentation of the mt network. Altogether, our results provide first evidence that mitotane induced a mt respiratory chain defect in human adrenocortical cells.
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Revising a personal genome by comparing and combining data from two different sequencing platforms.
PLoS ONE
PUBLISHED: 01-01-2013
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For the robust practice of genomic medicine, sequencing results must be compatible, regardless of the sequencing technologies and algorithms used. Presently, genome sequencing is still an imprecise science and is complicated by differences in the chemistry, coverage, alignment, and variant-calling algorithms. We identified ~3.33 million single nucleotide variants (SNVs) and ~3.62 million SNVs in the SJK genome using SOLiD and Illumina data, respectively. Approximately 3 million SNVs were concordant between the two platforms while 68,532 SNVs were discordant; 219,616 SNVs were SOLiD-specific and 516,080 SNVs were Illumina-specific (i.e., platform-specific). Concordant, discordant, and platform-specific SNVs were further analyzed and characterized. Overall, a large portion of heterozygous SNVs that were discordant with genotyping calls of single nucleotide polymorphism chips were highly confident. Approximately 70% of the platform-specific SNVs were located in regions containing repetitive sequences. Such platform-specificity may arise from differences between platforms, with regard to read length (36 bp and 72 bp vs. 50 bp), insert size (~100-300 bp vs. ~1-2 kb), sequencing chemistry (sequencing-by-synthesis using single nucleotides vs. ligation-based sequencing using oligomers), and sequencing quality. When data from the two platforms were merged for variant calling, the proportion of callable regions of the reference genome increased to 99.66%, which was 1.43% higher than the average callability of the two platforms, representing ~40 million bases. In this study, we compared the differences in sequencing results between two sequencing platforms. Approximately 90% of the SNVs were concordant between the two platforms, yet ~10% of the SNVs were either discordant or platform-specific, indicating that each platform had its own strengths and weaknesses. When data from the two platforms were merged, both the overall callability of the reference genome and the overall accuracy of the SNVs improved, demonstrating the likelihood that a re-sequenced genome can be revised using complementary data.
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A man with a DAX1/NR0B1 mutation, normal puberty, and an intact hypothalamic-pituitary-gonadal axis but deteriorating oligospermia during long-term follow-up.
Eur. J. Endocrinol.
PUBLISHED: 01-01-2013
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DAX1/NR0B1 mutations cause primary adrenal insufficiency in early childhood and hypogonadotropic hypogonadism (HHG), leading to absent or incomplete sexual maturation. The aim of the study was to prospectively investigate gonadotrope and testicular functions in a patient carrying a DAX1 mutation, who had spontaneous puberty and normal virilization but oligospermia.
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Inhibitory effects of UV treatment and a combination of UV and dry heat against pathogens on stainless steel and polypropylene surfaces.
J. Food Sci.
PUBLISHED: 12-02-2011
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Pathogens that contaminate the surfaces of food utensils may contribute to the occurrence of foodborne disease outbreaks. We investigated the efficacy of UV treatment combined with dry heat (50 °C) for inhibiting 5 foodborne pathogens (Escherichia coli O157:H7, Salmonella Typhimurium, Pseudomonas aeruginosa, Listeria monocytogenes, and Staphylococcus aureus) on stainless steel and polypropylene surfaces in this study. We inoculated substrates with each of the 5 foodborne pathogens cultured on agar surface and then UV treatment alone or a combination of both UV and dry heat (50 °C) was applied for 30 min, 1 h, 2 h, and 3 h. The initial populations of the 5 pathogens before treatment were 8.02 to 9.18 and 8.73 to 9.16 log?? CFU/coupon on the surfaces of stainless steel and polypropylene coupons, respectively. UV treatments for 3 h significantly inhibited S. Typhimurium, L. monocytogenes, and S. aureus on the stainless steel by 3.06, 2.18, and 2.70 log?? CFU/coupon, and S. aureus on the polypropylene by 3.11 log?? CFU/coupon, respectively. The inhibitory effects of the combined UV and dry heat treatment (50 °C) increased as treatment time increased, yielding significant reductions in all samples treated for 3 h, with the exception of S. aureus on polypropylene. The reduction level of E. coli O157:H7 treated for 3 h on the surface of stainless steel and polypropylene treated was approximately 6.00 log?? CFU/coupon. These results indicate that combined UV and dry heat (50 °C) treatments may be effective for controlling microbial contamination on utensils and cooking equipment surfaces as well as in other related environments.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.