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Articles by Lars Tönges in JoVE

 JoVE Clinical and Translational Medicine

नैदानिक ​​और Amyotrophic पार्श्व स्केलेरोसिस के लिए एक माउस मॉडल (ए एल एस) में स्पाइनल कॉर्ड को हटाने परीक्षण


JoVE 3936 3/17/2012

1Dept. of Neurology, University Medicine Göttingen, 2DFG Research Center for the Molecular Physiology of the Brain (CMPB), Göttingen, Germany

Amyotrophic पार्श्व काठिन्य (ए एल एस) के लिए एक माउस मॉडल चिकित्सकीय और behaviorally जांच की है. एक साथ immunohistological विश्लेषण के लिए एक शर्त के रूप में रीढ़ की हड्डी की तैयारी में विस्तार से दर्शाया जाता है.

Other articles by Lars Tönges on PubMed

Interplay of Host and Infectious Agents

In this group we would like to answer the question why people show a different response against certain pathogens. In many infections the course of the disease can range from asymptomatic carriage to the severest forms even death. In the past we have analysed candidate genes and their role in the course of malaria and could detect some polymorphisms influencing infectious diseases in the genes encoding NOS2, MBL2, IFNa, FCN2, and receptors for IFNg and IFNa. Having worked initially mainly on malaria we broadened our spectrum also to other infectious diseases like hepatitis B, Leprosy, schistosomiasis. Here we give a short overview about ongoing projects.

A Rare Origin of Abductor Pollicis Longus

Abductor pollicis longus is known for its variations in the form of multiple tendons at its insertion. The present case reports about a variation in the origin of abductor pollicis longus (APL) which has not been cited in the medical literature until date. It has been shown that the intersection area where the APL and extensor pollicis brevis cross over the tendons of the extensor carpi radialis (ECR) tendons in the forearm can contribute to Intersection syndrome. This can be applied to the present variation where the two bellies of APL entrap the ECR tendons. An awareness of this unusual finding may be clinically relevant for surgical approaches in the forearm region.

Retroperitoneal Ganglioneuroma in Children: CT and MRI Features with Histologic Correlation

To demonstrate the CT and MRI features with histologic correlation of retroperitoneal ganglioneuromas in children.

Awareness and Attitude of the General Public Toward HIV/AIDS in Coastal Karnataka

To assess the awareness and attitude of the general public toward people living with HIV/AIDS (PLWHA) in Mangalore, a city in Coastal Karnataka.

Anomalous Branching Pattern of the External Carotid Artery: a Case Report

Variations in the branching pattern of the external carotid artery (ECA) are well known and documented. The variation in the present case was compared with those reported before. An anomalous unilateral variation in the branching pattern of the left ECA was observed in a male embalmed cadaver. In this case, the ECA gives a direct branch directly to the submandibular salivary gland, a thyrolingual trunk, an auriculo-occipital trunk and a facial artery with an unusual course. The embryogenesis of such a combination of anomalies is not clear, but the anatomic consequences may have important clinical implications. Anatomical knowledge of the origin, course, and branching pattern of the external carotid artery will be useful to surgeons when ligating the vessels during head and neck surgeries.

New Evidence on Iron, Copper Accumulation and Zinc Depletion and Its Correlation with DNA Integrity in Aging Human Brain Regions

Deoxyribonucleic acid (DNA) conformation and stability play an important role in brain function. Earlier studies reported alterations in DNA integrity in the brain regions of neurological disorders like Parkinson's and Alzheimer's diseases. However, there are only limited studies on DNA stability in an aging brain and the factors responsible for genomic instability are still not clear. In this study, we assess the levels of Copper (Cu), Iron (Fe) and Zinc (Zn) in three age groups (Group I: below 40 years), Group II: between 41-60 years) and Group III: above 61 years) in hippocampus and frontal cortex regions of normal brains. The number of samples in each group was eight. Genomic DNA was isolated and DNA integrity was studied by nick translation studies and presented as single and double strand breaks. The number of single strand breaks correspondingly increased with aging compared to double strand breaks. The strand breaks were more in frontal cortex compared to hippocampus. We observed that the levels of Cu and Fe are significantly elevated while Zn is significantly depleted as one progresses from Group I to Group III, indicating changes with aging in frontal cortex and hippocampus. But the elevation of metals was more in frontal cortical region compared to hippocampal region. There was a clear correlation between Cu and Fe levels versus strand breaks in aging brain regions. This indicates that genomic instability is progressive with aging and this will alter the gene expressions. To our knowledge, this is a new comprehensive database to date, looking at the levels of redox metals and corresponding strand breaks in DNA in two brain regions of the aging brain. The biological significance of these findings with relevance to mental health will be discussed.

Time-dependent Changes of Immunologic Responses After Burn Injury and Immunomodulation by Cimetidine and Pyrimethamine in an Animal Model

Severe suppression of the immune system is the major cause of infections following burn injury. The aim of this study was to investigate the time-related alterations of immune responses following thermal injury in an animal model and also to modulate immune responses by use of the immunomdulators cimetidine and pyrimethamine. Male Balb/c mice were anesthetized and given a 10% total body surface area full-thickness burn. The time-dependent changes of delayed type hypersensitivity (DTH) and antibody responses to sheep red blood cell (SRBC) were assessed at post-burn days (PBD). The effects of different doses of cimetidine and pyrimethamine on DTH response were also quantitated at 10 PBD. Marked suppression of DTH response occurred during 30 days after burn trauma, with maximal suppression occurring between 10 to 14 days after burn injury. Simultaneously the antibody response to SRBC was significantly increased after thermal trauma. Cimetidine (at doses of 10 and 15 mg/kg) and pyrimethamine (at doses of 5 and 10 mg/kg) significantly augmented DTH response after thermal injury. These results showed that the severe time-dependent alterations occurred in DTH and antibody responses following burn injury. Cimetidine and pyrimethamine also restore burn-induced suppression of DTH response following thermal trauma.

Plasmodium Ovale Infection in Malaysia: First Imported Case

Plasmodium ovale infection is rarely reported in Malaysia. This is the first imported case of P. ovale infection in Malaysia which was initially misdiagnosed as Plasmodium vivax.

EVALUATION OF BIOCOMPATIBILITY OF INDIGENOUSLY PRODUCED PURE TITANIUM - AN EXPERIMENTAL STUDY IN RABBITS

Abstract The indigenously produced Pure Titanium Dental Implants are economical and useful for common human use in India. The aim of this study is to test the biocompatibility of the indigenously produced Pure Titanium Dental Implant material obtained from DMRL (Defense Metallurgical Research Laboratory) Hyderabad, and INMAS (Institute of Nuclear Medicine and Allied science) Delhi. An experimental study in Rabbits was done to study the amount of ordered bone formation around screw and cylinder type of indigenously produced pure titanium metal implant specimens. The experimental animals were sacrificed at time-points of 4 weeks, 6 weeks, 8 weeks, 12 weeks, and 16 weeks from the date of implantation. The histopathological examination of the animal sacrificed at 16 weeks demonstrates the presence of osteoblastic cell proliferation and early ordered bone formation towards implant site indicating the signs of osseointegration of both screw and cylinder type indigenously produced pure titanium specimens.

Humanised Substitutes for Animal Sera in Human Mesenchymal Stem Cell Culture and Differentiation

The use of animal sera in cell culture is a major deterrent for using such cells in cellular therapy owing to potential contamination with xenogenic agents. This necessitates the development of 'humanized' supplements to overcome such problems. This study investigates the use of two 'human-derived' supplements, namely human platelet lysate (hPL) and umbilical cord blood serum (UCBS), in human mesenchymal stem cell (hMSCs) culture. Properties of hMSCs cultured in either of these supplements including growth kinetics and the differentiation potential were better than those cultured in animal sera-supplemented media. This is also the first report concerning hepatogenic differentiation of hMSCs cultured in UCBS-supplemented media. Development of 'humanized' alternatives to FBS could be revolutionary in terms of extrapolating results from in-vitro cultured / expanded hMSCs to direct clinical cellular therapeutic strategies.

Prevalence of Orthostatic Hypotension in a Series of Elderly Mexican Institutionalized Patients

Orthostatic hypotension (OH) is a common problem among the elderly. It is associated with an increase in morbidity and mortality, but its prevalence in Mexico is unknown.

Assessment of ERBB2 and EGFR Gene Amplification and Protein Expression in Gastric Carcinoma by Immunohistochemistry and Fluorescence in Situ Hybridization

ABSTRACT:

De Novo 7p Partial Trisomy Characterized by Subtelomeric FISH and Whole-genome Array in a Girl with Mental Retardation

ABSTRACT: Chromosome rearrangements involving telomeres have been established as one of the major causes of idiopathic mental retardation/developmental delay. This case of 7p partial trisomy syndrome in a 3-year-old female child presenting with developmental delay emphasizes the clinical relevance of cytogenetic diagnosis in the better management of genetic disorders. Application of subtelomeric FISH technique revealed the presence of interstitial telomeres and led to the ascertainment of partial trisomy for the distal 7p segment localized on the telomeric end of the short arm of chromosome 19. Whole-genome cytogenetic microarray-based analysis showed a mosaic 3.5 Mb gain at Xq21.1 besides the approximately 24.5 Mb gain corresponding to 7p15.3- > pter. The possible mechanisms of origin of the chromosomal rearrangement and the clinical relevance of trisomy for the genes lying in the critical regions are discussed.

The Prevalence of Hyperuricemia in China: a Meta-analysis

The prevalence of hyperuricemia varied in different populations and it appeared to be increasing in the past decades. Recent studies suggest that hyperuricemia is an independent risk factor for cardiovascular disease. However, there has not yet been a systematic analysis of the prevalence of hyperuricemia in China.

Online-video Based Resistance Training Improves the Physical Capacity of Junior Basketball Athletes

Junior basketball athletes require a well-designed resistance training program to improve their physical development. Lack of expert supervision and resistance training in junior development pathways may be overcome by implementing an online video-based program. The aim of this study was to compare the magnitude of improvement (change) in physical performance, strength and functional movement patterns of junior basketball athletes employing either a fully supervised, or an online video-based resistance training program. Thirty-eight junior basketball athletes (males n=17; age 14 ± 1 y; height 1.79 ± 0.10 m; mass 67 ± 12 kg; females n=21; age 15 ± 1 y; height 1.70 ± 0.07 m; mass 62 ± 8 kg; mean ± SD) were randomly assigned into a supervised resistance training group (SG, n=13), video training group (VG, n=13) or control group (CG, n=12) and participated in a six week controlled experimental trial. Pre- and post-testing included measures of physical performance (20 m sprint, step-in vertical jump, agility, sit and reach, line drill, Yo-Yo intermittent recovery level 1), strength (15 s push up and pull up) and functional movement screening (FMS). Both SG and VG achieved 3-5% ± 2-4% (mean ± 90% confidence limits) greater improvements in several physical performance measures (vertical jump height, 20 m sprint time and Yo-Yo endurance performance) and a 28% ± 21% greater improvement in push up strength compared to the CG. The SG attained substantially larger gains in FMS scores over both the VG (12% ± 10%) and CG (13% ± 8%). Video-based training appears to be a viable option to improve physical performance and strength in junior basketball athletes. Qualified supervision is recommended to improve functional movement patterns in junior athletes.

Compromised Perfusion in Femoral Head in Normal Rats: Distinctive Perfusion MRI Evidence of Contrast Washout Delay

Objectives: The femoral head is prone to osteonecrosis. This study investigated dynamic contrast-enhanced (DCE) MRI contrast washout features of the femoral head and compared the data with data from other bony compartments in normal rats.Methods: Seven-month-old Wistar rats were used. DCE MRI of the right hip (n = 18), right knee (n = 12) and lumbar spine (n = 10) was performed after an intravenous bolus injection of Gd-DOTA (0.3 mmol kg(-1)). Temporal resolution was 0.6 sec for hip and spine, and 0.3 sec for knee. The total scan duration was 8 min for hip and spine, and 4.5 min for knee. The regions of interest for enhancement measurement included femoral head, proximal femoral diaphysis, distal femoral diaphysis and epiphysis, proximal tibial epiphysis and diaphysis, and lumbar vertebrae L1-5.Results: Femoral head showed no enhancement signal decay during the DCE MRI period, while all other bony compartments showed a contrast washin phase followed by a contrast washout phase. In the knee joint, the contrast washout of the proximal tibia diaphysis was slower that of other bony compartments of the knee.Conclusion: Based on the evidence of delayed contrast washout, this study showed blood perfusion in femoral head could be compromised in normal rats.

Cochlear Implantation in Children with Jervell and Lange-Nielsen Syndrome - a Cautionary Tale

OBJECTIVE AND IMPORTANCE: Jervell and Lange-Nielsen (JLN) syndrome is a rare cause of congenital profound hearing loss associated with a prolonged QT interval on the electrocardiogram. Children presenting for cochlear implantation with this condition may be asymptomatic but are at risk of sudden death. Screening and subsequent careful management is therefore required to ensure a successful outcome. We present our experience of cochlear implantation in children with JLN syndrome, including two who died unexpectedly, and suggest a protocol for management of such cases. CLINICAL PRESENTATION: Four cases of cochlear implantation in JLN syndrome are described. None had any previous cardiological family history. Two were diagnosed pre-operatively but, despite appropriate management under a cardiologist, died from cardiac arrest; the first in the perioperative period following reimplantation for infection, and the second unrelated to his cochlear implant surgery. The other two patients were diagnosed only subsequent to their implantation and continue to use their implants successfully. CONCLUSION: These cases highlight the variation in presentation of JLN syndrome, and the spectrum of disease severity that exists. Our protocol stresses the importance of careful assessment and counselling of parents by an experienced implant team.

Reduction in Breast Cancer Risk Associated with Meeting the WCRF/AICR Cancer Prevention Recommendations

In 2007 the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published eight recommendations related to body weight, physical activity and dietary behaviors aimed at reducing cancer incidence worldwide. These were based on a comprehensive review of the literature on these topics in relation to each of the common cancers. An expert panel operationalized seven of those recommendations (maintaining normal body weight, participating in moderate physical activity for at least 30 minutes per day, avoiding energy-dense foods, eating 5 or more servings of non-starchy fruits and vegetables per day, limiting consumption of red meat to no more than 18 oz per week, limiting alcohol consumption to one drink per day for women and two drinks per day for men, and limiting sodium consumption to 2400 mg per day), and we examined their association with breast cancer incidence over eight years of follow-up in the VITamins And Lifestyle (VITAL) Study cohort. Participants included 24,916 women aged 50-76 years at baseline in 2000-2002 who had no history of cancer and who had complete data for the recommendations evaluated. Incident cancers (n = 694) were tracked through the Western Washington Surveillance, Epidemiology and End Results (SEER) database. The median number of recommendations followed was 3 (0-7). After adjusting for age, education, race/ethnicity, mammogram in previous two years, history of breast cancer in a first-degree relative, years of combined estrogen plus progestin hormone therapy use, age at menarche, age at first birth, and age at menopause, the hazard ratios and 95% confidence intervals associated with meeting 1, 2, 3, 4, 5, and 6-7 recommendations compared with meeting none of the recommendations were: 0.57 (0.35, 0.95), 0.63 (0.39, 1.02), 0.55 (0.34, 0.88), 0.46 (0.28, 0.74), 0.44 (0.26, 0.75), and 0.31 (0.15, 0.65). These results suggest that meeting the WCRF/AICR recommendations could substantially decrease breast cancer risk.

Criminal Recidivism and Mortality Among Patients Discharged from a Forensic Medium Secure Hospital

Background: One of the goals in forensic psychiatric care is to reduce the risk of recidivism, but current knowledge about the general outcome of forensic psychiatric treatment is limited. Aims: To analyse the rate of criminal recidivism and mortality after discharge in a sample of patients sentenced to forensic psychiatric treatment in a Swedish county. Methods: All offenders in Örebro County, Sweden, sentenced to forensic psychiatric treatment and discharged during 1992-2007 were included: 80 males and eight females. Follow-up data was retrieved from the Swedish National Council for Crime Prevention, the National Cause-of-Death register and clinical files. Mean follow-up time was 9.4 years. Results: The mean age at discharge was 40 years. Schizophrenia, other psychoses and personality disorders were the most prevalent diagnoses. Thirty-eight percent of those still alive and still living in the country re-offended and were sentenced to a new period of forensic psychiatric treatment or incarceration during follow-up. Four male re-offenders committed serious violent crimes. Substance-related diagnosis was significantly associated with risk of recidivism and after adjustment for diagnoses, age and history of serious violent crime, the Hazard Ratio was 4.04 (95% CI 1.51-10.86, P = 0.006). Of all included patients, 23% had died at the end of follow-up (standardized mortality rate 10.4). Conclusions: Since repetition of serious violent crimes was unusual, results indicate a positive development subsequent to treatment for those alive at follow-up. Clinical implications: The high mortality rate suggests that more attention should be paid in evaluation of the patients' somatic and psychiatric health during and after care in order to prevent premature death.

Novel Therapeutic Approaches to CNS Metastases in Malignant Phaeochromocytomas - Case Report of the First Patient with a Large Cystic CNS Lesion

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