intracerebroventricular-intravascular-injection-viral-particles

Intracerebroventricular and Intravascular Injection of Viral Particles and Fluorescent Microbeads into the Neonatal Brain

In the study on the pathogenesis of viral encephalitis, the infection method is critical. The first of the two main infectious routes to the brain is the ...

Hamamatsu University School of Medicine

A new screening method to detect antimitotic substances utilizing purified porcine brain microtubule proteins was developed. This method observes the inhibitory and stimulatory activities on microtubule polymerization and inhibitory activity on depolymerization in sequence. Two glycolipids, 1-O-beta-D-galactopyranosyl-2,3-di-O-acylglycerol and 1-O-tetrahydroxycyclopentyl-2-O-acyl-3-O-alkylglycerol were isolated from Okinawan marine sponge Pseudoceratina sp. by this screening method. These compounds stimulated the microtubule polymerization at 10 degrees C.

A new screening method for antimitotic substances and isolation of glycolipids as stimulators of tubulin polymerization from Okinawan sponge Pseudoceratina sp.

Two new polybrominated diphenyl ethers (1 and 2) were isolated by bioassay-guided separations together with nine known compounds (3-11) from the marine sponge Phyllospongia dendyi collected from Palau. The structures were assigned on the basis of their spectral data. Compounds 3, 7, and 10 showed inhibitory activities to the assembly of microtubule proteins (IC(50): 29.6, 33.5, and 20.9 microM, respectively) and to the meiotic maturation of starfish oocytes (IC(50): 3.6, 4.2, and 4.2 microM, respectively), while 1, 2, 4-6, 8, 9, and 11 were not active at 100 microM. Two phenolic hydroxyls are required for their bioactivities.

Isolation and characterization of polybrominated diphenyl ethers as inhibitors of microtubule assembly from the marine sponge Phyllospongia dendyi collected at Palau.

A 56-year-old man with chief complaints of dry cough and dyspnea was admitted. He had severe hypoxemia, and his chest radiographs showed enhancement of pulmonary artery opacities with multiple defects on pulmonary blood flow scintigraphy. Enhanced computed tomography (CT) revealed swelling of the mediastinum and hilar lymph nodes, but no apparent thrombi in the pulmonary arteries was seen. A biopsy specimen of a left neck lymph node showed poorly differentiated adenocarcinoma, including signet-ring cell carcinoma components, but the origin was unclear. Despite receiving chemotherapy, his respiratory condition worsened, and he died 3 days after admission. Routine autopsy failed to clarify the tumor origin, but a detailed dissection of specimens confirmed early gastric cancer. Additionally, pathology of the pulmonary arteries was compatible with pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Accompanied with early gastric cancer, this is an extremely rare but important case of PTTM.

[A case of pulmonary tumor thrombotic microangiopathy induced by early gastric cancer].

α-Fetoprotein (AFP)-producing ovarian tumors (APOTs) are rarely encountered in postmenopausal women, irrespective of whether they are of the germ cell or non-germ cell type. The APOTs that do occur in postmenopausal women are characterized by variable histologies such as hepatoid carcinoma, yolk sac tumor, and epithelial malignancies, most of which are combined. We herein present a case with APOT, which arose in a 58-year-old, gravida 2, para 2, postmenopausal woman. Preoperatively, the tumor, which was in the right ovary, was found to produce AFP (102768.0 ng/mL). The tumor was evenly composed of glands mimicking secretory endometrial gland or fetal gut accompanied by abundant stroma. Immunohistochemically, these glands were positive for SALL4, glypican-3, and hepatocyte nuclear factor 1β. We considered the present case as an AFP-producing adenocarcinoma with adenofibroma showing germ cell differentiation, but it seemed controversial that this tumor should be designated as a yolk sac tumor of the glandular type. The expression profiles of SALL4, OCT4, glypican-3, and hepatocyte nuclear factor 1β were thought to provide interesting implications to characterize the present case.

α-Fetoprotein-producing ovarian tumor in a postmenopausal woman with germ cell differentiation.

Pulmonary cytomegalovirus (CMV) infection causes fatal CMV pneumonia (CMVp) in immunocompromised patients; however, the mechanisms underlying CMV-infection-induced pulmonary lesion development remain largely unknown. We examined the relationship between CMVp patterns and intrapulmonary viral tropism, including expression of inflammatory cytokines and related molecules. Double immunohistochemistry of CMV antigen and cellular markers showed that epithelial tropism was associated with a diffuse alveolar damage (DAD) pattern (CMVp-DAD) while stromal tropism was associated with a predominantly interstitial inflammation/fibrosis (IIF) (CMVp-IIF) or a combination of DAD and IIF (CMVp-complex). Transforming growth factor (TGF)-β1 expression was relevant to CMV-induced tissue injury, and its expression was higher in CMVp-complex and CMVp-IIF than in CMVp-DAD. Expression of integrin β6 (ITGB6), an adhesion molecule and important activator of TGF-β1 in interstitial pneumonia, was lost in CMV-infected pneumocytes, especially CMVp-DAD, whereas CMV-negative pneumocytes in CMVp-complex and CMVp-IIF showed overexpression. Diffuse interleukin (IL)-8 up-regulation and strong expression were present in both CMV-infected pneumocytes and stromal cells only in CMVp-IIF cases with marked interstitial neutrophilic infiltration. On the basis of viral tropism and the expression of TGF-β1, ITGB6, and IL-8, we conclude that CMV-infected pulmonary cells play an important role in the development of diverse CMVp patterns.

Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia.

We report a rare case of ovarian leiomyoma with extensive edema in a 55-year-old woman. Magnetic resonance (MR) imaging revealed an ovarian mass with distinct portions of predominantly low intensity and predominantly high intensity on T2-weighted image. The portion with low signal showed weak enhancement on contrast study, and the portion with high intensity suggested extensive edema of fibrous stroma. Furthermore, the mass showed low signal intensity similar to that of the myometrium on diffusion-weighted image and yielded high values on apparent diffusion coefficient (ADC) map image. Extensive edema of ovarian leiomyoma shows unusual MR imaging findings that require careful interpretation.

Unusual MR findings in ovarian leiomyoma.

Carcinosarcoma of the uterine cervix is less common than its counterpart in the uterine corpus. On the other hand, mesonephric adenocarcinoma is also a rare neoplasm in the uterine cervix, and it has been reported that mesonephric adenocarcinomas are often accompanied by sarcomatous components. We present a case of mesonephric adenocarcinoma with a sarcomatous component which arose in a 63-year-old postmenopausal woman. The hysterectomy specimen grossly showed an exophytic mass measuring 1.8 cm in the uterine cervix. Histologically, diffuse mesonephric hyperplasia and adenocarcinoma with malignant spindle cell proliferation was recognized, and therefore the tumor was diagnosed as "mesonephric adenocarcinoma with a sarcomatous component." The review of the literature of cervical carcinosarcoma and cervical mesonephric adenocarcinoma revealed that 16% of cervical carcinosarcoma is of mesonephric duct origin, and that mesonephric adenocarcinoma seems to be more likely to have sarcomatous change. We think the presence of a sarcomatous component in the cervical biopsy specimen could be helpful in the diagnosis of mesonephric duct origin.

Mesonephric adenocarcinoma with a sarcomatous component, a notable subtype of cervical carcinosarcoma: a case report and review of the literature.

The characteristic morphology called broccoli sign combines a stalk and prolapsed tumor and is a useful diagnostic indicator of prolapsed tumor of the uterine body. Magnetic resonance (MR) imaging findings of broccoli sign are common for uterine submucosal leiomyomata but not well described for other tumors of the endometrial cavity, such as endometrial polyp, atypical polypoid adenomyoma, endometrial carcinoma, carcinosarcoma, and adenosarcoma. Both benign and malignant masses of the uterine body can show broccoli sign. The MR imaging features of prolapsed uterine tumor with broccoli sign resemble those of usual uterine body tumors, but the location is different. We describe the MR imaging features of prolapsed uterine tumors with broccoli sign.

Benign and malignant tumor of the uterine body with broccoli sign: MR imaging features for differential diagnosis.

Myofibroblasts play a crucial role in tissue repair. The functional similarities and differences between myofibroblasts and fibroblasts are not fully understood because they have not been separately isolated from a living body. The purpose of this study was to establish a method for the direct isolation of myofibroblasts and fibroblasts from injured lungs by using fluorescence-activated cell sorting and to compare their functions.

Direct isolation of myofibroblasts and fibroblasts from bleomycin-injured lungs reveals their functional similarities and differences.

We report the case of a 78-year-old man with multiple bone tumours and three round, smooth nodules in the right lung. He was referred to our hospital because of the left femoral neck pathological fracture. The histological characteristics of the femoral tumour corresponded to clear cell carcinoma, and bone and lung lesions were regarded as metastatic from an unknown primary site, since there was no clinical evidence of renal carcinoma. His general conditions gradually declined, and he died 2 months after the operation. At autopsy, no neoplasia lesion was found in the kidneys. Although clear cell components were histologically dominant in the affected organs such as the lungs, bones and liver, neoplastic tubular structures also existed. Immunohistochemically, atypical cells were positive for napsin-A. The final diagnosis was adenocarcinoma of the lung origin with prominent clear cell features.

A bone metastasis of non-small cell lung carcinoma with prominent clear cell features.

Congenital cytomegalovirus (CMV) infection is the leading viral cause of neurodevelopmental disorders in humans, with the most severe and permanent sequelae being those affecting the cerebrum. As the fetal immune reactions to congenital CMV infection in the brain and their effects on cerebral development remain elusive, our aim was to investigate primitive innate immunity to CMV infection and its effects on cerebral corticogenesis in a mouse model for congenital CMV infection using a precise intraplacental inoculation method.

Aberrant fetal macrophage/microglial reactions to cytomegalovirus infection.

Cytomegalovirus (CMV) is a prevalent pathogen in intrauterine infections that causes congenital anomalies such as CMV encephalitis, which is characterized by the focal areas of reactive gliosis, reactive mononuclear cells, microglial nodules, and ventriculoencephalitis. To elucidate the mechanisms of CMV susceptibility in the developing brain, cell tropism and the infectious dynamics of CMV infection were investigated. We evaluated intraventricular and intravascular infections from the perspective of the distribution of CMV and its receptor (β1 integrin) in the earliest phase of infection. Murine CMV (MCMV) immediate early 1-positive cells were colocalized mainly with meninges and choroid plexus (after intraventricular infection) or with endothelial cells and pericytes (after intravascular infection). Using green fluorescent protein-expressing recombinant MCMV particles and fluorescent microbeads (100 to 300 nm), we revealed that CMV particle size is the primary factor determining the initial CMV distribution. β1 Integrin inhibition using a shRNA and functional blocking antibody significantly reduced MCMV infection. IHC analysis, flow cytometric, and brain slice analyses strongly support that high-level β1 integrin-expressing cells (eg, endothelial cells, pericytes, meninges, choroid plexus, and neural stem progenitor cells) are the first targets of MCMV. Therefore, our data demonstrate that the initial distributions of MCMV particles and β1 integrin determine the distinct pattern of infection in the brain in the acute phase.

Article	Year
A new screening method for antimitotic substances and isolation of glycolipids as stimulators of tubulin polymerization from Okinawan sponge Pseudoceratina sp. The Journal of antibiotics\| PubMed ID: 12014440	2002
Isolation and characterization of polybrominated diphenyl ethers as inhibitors of microtubule assembly from the marine sponge Phyllospongia dendyi collected at Palau. Journal of natural products\| PubMed ID: 15043436	2004
[A case of pulmonary tumor thrombotic microangiopathy induced by early gastric cancer]. Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society\| PubMed ID: 21400909	2011
α-Fetoprotein-producing ovarian tumor in a postmenopausal woman with germ cell differentiation. Annals of diagnostic pathology\| PubMed ID: 22056036	2013
Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia. Pathology international\| PubMed ID: 22924849	2012
Unusual MR findings in ovarian leiomyoma. Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine\| PubMed ID: 23474962	2013
Mesonephric adenocarcinoma with a sarcomatous component, a notable subtype of cervical carcinosarcoma: a case report and review of the literature. Diagnostic pathology\| PubMed ID: 23651629	2013
Benign and malignant tumor of the uterine body with broccoli sign: MR imaging features for differential diagnosis. Japanese journal of radiology\| PubMed ID: 23719762	2013
Direct isolation of myofibroblasts and fibroblasts from bleomycin-injured lungs reveals their functional similarities and differences. Fibrogenesis & tissue repair\| PubMed ID: 23927729	2013
A bone metastasis of non-small cell lung carcinoma with prominent clear cell features. BMJ case reports\| PubMed ID: 24518396	2014
Aberrant fetal macrophage/microglial reactions to cytomegalovirus infection. Annals of clinical and translational neurology\| PubMed ID: 25356429	2014
Cytomegalovirus initiates infection selectively from high-level β1 integrin-expressing cells in the brain. The American journal of pathology\| PubMed ID: 25797647	2015

Shiori Meguro

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