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Biomedical subjects

K Kato

Publications and source records attributed to K Kato.

At least 307 records · Page 17Linked to original sources

Structural basis of the interaction between IgG and Fcgamma receptors.

The binding of multivalent antigen-antibody complexes to receptors for the Fc portion of IgG (FcgammaR) induces the clustering of the FcgammaR and triggers cell activation leading to defence reactions against pathogens. The Fc portion of IgG consists of two identical polypeptide chains which are related to each other by a 2-fold axis and are folded in two structural domains, the C(H)2 domain, near the flexible hinge region of the IgG molecule, and the C(H)3 domain. We studied the interaction in solution between the Fc fragment of mouse IgG2b and the extracellular region of mouse FcgammaRII. We find that one Fc molecule binds one FcgammaRII molecule only. Using NMR spectroscopy, we show that FcgammaRII binds to a negatively charged area of the C(H)2 domain, corresponding to the lower hinge region, and that the binding of FcgammaRII onto one of the two symmetrically related sites on the Fc induces a conformational change in the other site. We therefore propose a model that explains why IgG molecules are unable to trigger FcgammaR-mediated cellular responses spontaneously in the absence of crosslinking by multivalent antigens.

Animals↗

Gene expression in mouse cerebellum during its development.

Genes expressed during the cerebellar development of the mouse were identified in 3'-directed cDNA libraries prepared from the postnatal day 4, day 12, and week 6 cerebellar tissues. Among about 5500 clones selected randomly from each library, there were approximately 3500 distinct species. A total of 7728 species were identified in the three libraries, 1346 of which were known genes in the GenBank, 3041 EST-matching genes, and 3341 new genes. Relative expression levels at the three postnatal stages were quantitated by adapter-tagged competitive PCR for 130 known genes that appeared six times or more in one of the libraries. Genes for ribosomal proteins and some cytoskeletal and nuclear proteins were abundantly expressed at the early stage, coincidently with extensive proliferation of granule cells as the major cerebellar component. Genes related to brain functions, including those for mitochondrial activities and some ion channel systems, were more active at a later stage when the majority of granule cells were engaged in axon extension and synapse formation or the cerebellum had reached maturity. Compared to these stage-specifically expressed genes, genes for transcriptional regulation, signal transduction, protein modification, and basic cellular functions, in general, were not abundantly expressed at any stage of development.

Animals↗

Application of the cell block method, utilizing mount quick mounting medium.

Our objective was to determine the applicability of cell transfer and cell block methods using Mount Quick (Daido Sangyo, Saitama, Japan) mounting medium (MQ) for hematoxylin-eosin (H&E) and immunohistochemical staining of several limited amounts of biological materials in slide preparations. The materials investigated were histopathologically confirmed malignant mesotheliomas (pleural effusions) and malignant lymphomas, a malignant melanoma, and an amelanotic melanoma in sealed slides. Monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cancer antigen 125 (CA-125), vimentin, thrombomodulin (TM), cytokeratin, UCHL-1, L-26, melanoma-specific antigen (HMB45), and S-100 protein (S-100) were applied in the investigation. The malignant mesotheliomas were found to be positive for EMA, cytokeratin, vimentin, TM, and CA-125, and negative for CEA, with no differences being observed in findings from direct contact preparations. Using T-cell-type malignant lymphomas for immunohistochemistry, UCHL-1 positivity and L-26 negativity were clearly demonstrated. The malignant melanoma and amelanotic melanoma materials stained strongly for HMB45 and S-100. Cell transfer employing MQ is a suitable approach for immunohistochemical investigations of limited materials. In addition, cell blocks derived from MQ-embedded smears can be used for both H&E and immunohistochemical staining. Diagn. Cytopathol. 2000;22:117-119.

Biomarkers, Tumor↗

The relationship between persistent secretion of RANTES and residual infiltration of eosinophils and memory T lymphocytes after Helicobacter pylori eradication.

Helicobacter pylori (HP)-infected gastric mucosa displays a conspicuous infiltration of mononuclear cells as well as neutrophils. RANTES is a potent chemoattractant peptide for memory T lymphocytes and eosinophils. RANTES protein concentration and the numbers of RANTES-, CD45RO-, and major basic protein (MBP)-positive cells were therefore evaluated in the gastric mucosa from 51 patients with HP-positive chronic gastritis before and after HP eradication and from 22 HP-negative healthy volunteers. RANTES protein concentration was significantly elevated in HP-positive cases and remained high after HP eradication. The numbers of RANTES-, CD45RO-, and MBP-positive cells were significantly increased in HP-positive cases and were well correlated with RANTES protein levels. All tended to decrease after HP eradication, but did not reach the level of HP-negative cases, even at 24 months after HP eradication. It was concluded that persistent expression and secretion of RANTES were closely related to residual infiltration of memory T lymphocytes and eosinophils, for a prolonged period after HP eradication. This seems to be an important mechanism of prolonged gastric mucosal immune response against HP infection, even after HP eradication, and of persistent mucosal damage and atrophy.

Adult↗

Cytokines production of U5A2-13-positive T cells by stimulation with glycolipid alpha-galactosylceramide.

We have previously established and reported a novel monoclonal antibody (mAb), U5A2-13, which recognizes a phenotypically similar population of natural killer (NK)-like T cells. Using U5A2-13 mAb, we now describe the functional properties of U5A2-13(+) T cells in both NK1.1-positive or -negative mouse strains. Similar to NK1.1(+) T cells, hepatic U5A2-13(+) T cells of C57BL/6 (NK1.1(+) strain) mice, but not U5A2-13(-) T cells, could be induced to produce large amounts of IL-4 and IFN-gamma by stimulation with glycolipid alpha-galactosylceramide (alpha-GalCer) present on dendritic cells (DC) in a dose-dependent manner. The abundant production of these cytokines from U5A2-13(+) T cells of BALB/c (NK1.1(-) strain) mice is similar to that noted in C57BL/6 mice. Cytokine production by cultures stimulated with DC of beta2-microglobulin-deficient mice was significantly less than that of cultures stimulated with DC of intact mice. Overall, U5A2-13(+) T cells recognize alpha-GalCer presented by CD1d, indicating that U5A2-13(+) T cells can be used to analyze NK-like T cell function in various strains of mice.

Animals↗

Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes.

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has been implicated in the pathogenesis of diabetic retinopathy, and recent studies have suggested that apoptosis may be involved in pericyte loss. The present study was conducted to investigate whether high glucose induces apoptosis in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor, SNK-860, was also examined. After a 5 day incubation with various concentrations of glucose (5.5-40 m M) in the presence or absence of SNK-860, the cell viability and the percentages of dead cells were measured, and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percentages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 m M glucose. In the staining of nuclei with Hoechst 33342, the percentage of apoptotic cells in total cells counted under high glucose was higher than that under 5.5 m M glucose. DNA electrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less than that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that the polyol pathway hyperactivity plays an important role in inducing apoptosis in pericytes by high glucose.

Aldehyde Reductase↗

Endometrial carcinoma remaining after term pregnancy following conservative treatment with medroxyprogesterone acetate.

BACKGROUND: Successful pregnancies after conservative progestin treatment to young women with endometrial carcinoma have recently been reported. However, it is not known for certain whether the lesion is completely eradicated in such patients. We present a case of residual endometrial carcinoma after term pregnancy which had been treated conservatively before the pregnancy began. CASE: A 28-year-old woman with endometrial carcinoma received conservative treatment with high-dose medroxyprogesterone acetate (MPA) and then conceived. After delivery at term, atypical cells were found in the endometrial curettage specimen. A hysterectomy was performed 6 months after delivery and revealed the presence of a small focus of intramucosal, grade 1, endometrioid-type adenocarcinoma. Immunohistochemically, the tumor cells were positive for estrogen and progesterone receptors. CONCLUSION: We concluded that while MPA treatment had been effective, it had not completely eradicated the carcinomatous lesion, which remained during and after the term pregnancy.

Adenocarcinoma↗

FDG PET in the clinical evaluation of sarcoidosis with bone lesions.

We report a case of sarcoidosis with osseous involvement. Whole-body fluorine-18-fluorodeoxyglucose (FDG) PET scanning demonstrated multiple sites of FDG uptake in the hilar lymph nodes, right ulna, bilateral feet, and subcutaneous tissue of the extremities. FDG PET scanning provides useful information for the detection of sarcoidosis with systemic distribution, even when osseous lesions are included.

Adult↗

Spinal cartilaginous meningioma in a child: a case report.

Cartilage-containing meningiomas are extremely uncommon, and such tumors located in the spinal cord of a child have not previously been reported. We describe a case of cartilaginous spinal meningioma in a 13-year-old girl. The tumor lacked typical histopathological features of meningioma on light microscopic examination, and the final diagnosis was possible only after an extensive study by electron microscopic examination. The case is evaluated with a focus on differential diagnosis and review of the literature.

Adolescent↗

Glial pathology in development of cerebellar dysplasia in the hereditary cerebellar vermis defect (CVD) rat.

The cerebellar vermis defect (CVD) rat is a new neurological mutant characterized by a cerebellar vermis defect and dysplasia in the cerebellum, especially at the cerebellopontine junctions. In this study, the cytokinetics of glia in terms of the development of cerebellar dysplasia in the CVD rat was investigated using glial fibrillary acidic protein (GFAP) and vimentin immunohistochemistry. In the cerebellar hemispheres, dislocation of the Bergmann glia was observed from postnatal day 5 (P5) in lesions with abnormally aggregated external granule cells (EGCs). Rearranging Bergmann glia were often seen around the EGCs penetrating into the white matter. In the cerebellopontine junctional areas, Bergmann glia were induced after penetration of the Purkinje cells, identified with calbindin immunohistochemistry, and EGCs into the pons from P10. Bergmann fibers were frequently arranged perivascularly. In the clusters of Purkinje cells without EGC settlement in the pons, a small number of Bergmann fibers were observed and their alignment was completely disturbed. These findings suggest that morphological changes in the Bergmann glia depend on their contact with Purkinje cells, but that the orientation of their processes may be influenced by EGC settlement. These glial fibers in the CVD rat may play an important role in the aberrant migration of EGCs, resulting in the development of cerebellar dysplasia.

Animals↗

Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats.

RATIONALE: The use of neonatal hippocampal lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. OBJECTIVE: To examine the role of NMDA neurotransmission in the neonatal ventral hippocampal damaged rat. METHODS: In initial experiments, we compared the effects of mild environmental stress (HAB) and the injection of saline and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. We also examined the effects of a single injection of phencyclidine (PCP, 10 mg/kg, IP) on locomotor activity and extracellular levels of dopamine (DA) and its metabolites in the nucleus accumbens (NAc) of lesioned and sham-operated rats using an in vivo brain microdialysis method. RESULTS: Compared with sham-operated controls, the lesioned rats showed increased locomotor activity at postnatal day 56 (PD56) but not at PD35 after HAB and MAP administration. Similarly, the lesioned rats showed increased locomotor activity at PD56 but not at PD35 after PCP administration. Unexpectedly, the increase in DA levels was significantly greater in the sham-operated rats than in the lesioned rats. CONCLUSIONS: The results suggest that neonatal hippocampal lesioned rats are accompanied by the dysfunction of NMDA neurotransmission. They also suggest that hyperresponsiveness to PCP following neonatal hippocampal lesions does not depend on the extracellular DA concentration in the NAc.

Animals↗

KL-6 as a novel marker for activities of interstitial pneumonia in connective tissue diseases.

The objective of this study was to determine the role of serum KL-6 levels as a marker for the activity of interstitial pneumonia in patients with connective tissue diseases. The serum concentrations of KL-6, a glycoprotein produced mainly by pulmonary type II epithelial cells, were measured in 21 patients with connective tissue disease. The activity of interstitial pneumonia was compared with the associated serum KL-6 concentrations. Serum KL-6 concentrations in patients with interstitial pneumonia were significantly higher than those in the controls. Among patients with active interstitial pneumonia, serum KL-6 concentrations following the treatment (after improvement) were significantly lower than the pretreatment values. The extent of the pulmonary fibrosis correlated positively with the serum KL-6 concentrations during the inactive phase of the interstitial pneumonia. These results suggest that sequential measurement of serum KL-6 levels is a new and useful means for the evaluation of interstitial pneumonia in patients with connective tissue diseases.

Antigens↗

Nonfunctioning endocrine tumor of the pancreas with extrapancreatic growth and cyst formation: report of a case.

We report a case of nonfunctioning endocrine tumor of the pancreas with extrapancreatic growth and cyst formation. A 48-year-old woman was admitted to our hospital with an upper abdominal mass, which was detected during a routine medical checkup. The preoperative diagnosis was a solid cystic tumor of the pancreas. The tumor, which measured about 7cm in diameter, arose from the head of the pancreas and had a thin stalk, measuring about 1 cm in diameter. The histopathological diagnosis was a malignant nonfunctioning endocrine tumor of the pancreas. Cyst formation occurred in 67% of the reported cases with extrapancreatic growth in Japan. It is speculated that the cyst formation in this disease is related to the large size of the tumor and to the extrapancreatic growth.

Abdominal Pain↗

Synthesis, subcellular localization and VP16 interaction of the herpes simplex virus type 2 UL46 gene product.

We developed a rabbit polyclonal antiserum reactive against a recombinant 6x His-UL46 fusion protein expressed in Escherichia coli, and using this antiserum identified the UL46 gene product of herpes simplex virus type 2 (HSV-2) to be phosphoproteins with apparent molecular masses of 82-, 84-, and 86-kDa in infected Vero cells. The UL46 protein was produced in the late phase of infection in a manner highly dependent on viral DNA synthesis, and was mainly distributed at the edge of the nucleus in the cytoplasm. Although its kinetics of production and its progress of distribution were different from those of the major tegument protein VP16 (the UL48 gene product or alpha-trans-inducing factor (alphaTIF)), most of the UL46 protein colocalized with VP16 in the late phase of infection, and copurified with it in column chromatography. Moreover, our data showed that the HSV-2 UL46 protein, when coexpressed with VP16, enhanced alpha4 promotor-regulated gene expression in a transient luciferase reporter assay, while the expression of the UL46 protein alone suppressed it.

Animals↗

Hepatoid adenocarcinoma: a new clinicopathological entity and the hypotheses on carcinogenesis.

Hepatoid adenocarcinoma is reviewed in its clinicopathological and oncogenetic aspects. This variant of adenocarcinoma has been found to be an alpha-fetoprotein (AFP) -producing carcinoma arising in extrahepatic organs, and it mimics hepatocellular carcinoma in terms of morphology and function. Vascular invasion, usually prominent, is often complicated by extensive liver metastases. A prompt and accurate diagnosis of hepatoid adenocarcinoma is important because the prognosis is very poor compared with that of common types of adenocarcinoma. The characteristic features of hepatoid adenocarcinoma are summarized on the basis of our own experiences and the literature. In addition, a possible molecular mechanism that under-lies the ectopic appearance of the hepatic phenotype is discussed.

Adenocarcinoma↗