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Biomedical subjects

K Misugi

Publications and source records attributed to K Misugi.

At least 19 recordsLinked to original sources
PubMed1997

Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors.

Matrilysin is believed to play important roles in tumor progression and metastasis. In the present study, we analyzed matrilysin-producing cells in various human cancer tissues by immunohistochemistry and in situ hybridization. Tumor cells in colorectal carcinomas, pancreatic carcinomas, transitional-cell carcinomas of the kidney and small-cell lung carcinomas were frequently positive for matrilysin. In addition, we found that endothelial cells of arterioles and venules adjacent to matrilysin-positive tumors expressed matrilysin mRNA and protein. The endothelial cells adjacent to matrilysin-negative tumors and those in normal tissues were negative for matrilysin. Furthermore, analyses by casein zymography, Western blotting and RT-PCR showed that matrilysin was weakly expressed by cultured human umbilical vein endothelial cells. Our results suggest that the expression of matrilysin in vascular endothelial cells and in tumor cells may be regulated by common soluble factors, and that endothelial cell-derived matrilysin may contribute to tumor angiogenesis and tumor metastasis.

Animals↗
PubMed1996

A nude mouse Wilms' tumor line (KCMC-WT-1) derived from an aniridia patient with monoalleleic partial deletion of chromosome 11p.

BACKGROUND: A candidate tumor suppressor gene, WT-1, is believed to have an important role in the pathogenesis of Wilms' tumor, especially that occurring in patients with congenital aniridia. METHODS: To obtain a stable tumor line to work with, Wilms' tumor tissue was serially transplanted in athymic nude mice. Biopsied Wilms' tumor tissue, derived from an aniridia patient, was transplanted subcutaneously to an athymic nude mouse, and then transplanted serially. Histopathologic and molecular biologic studies were performed on the xenotransplants. RESULTS: The aniridia patient showed partial deletion in one short arm of chromosome 11, which bears the WT-1 gene. The tumor was successfully transplanted in the nude mouse. Although the tumor contained blastemic, organoid, and stromal histologic elements, the organoid element began to decrease after more than 20 passages. Cytogenetic analysis revealed an additional abbreviation of one long arm of chromosome 6. Dot blot analysis showed that the copy number of WT-1 gene was decreased to half the amount in the tumor, in spite of the WT-1 transcript with normal size detected by Northern blotting. CONCLUSIONS: The tumor is expected to bear one WT-1 gene with minute abnormalities as well as one congenitally deleted gene. This tumor line is useful when examining the effect caused by introduction of WT-1 gene to Wilms' tumor in vivo.

Alleles↗
PubMed1996

Von Hippel-Lindau tumour suppressor gene. Localization of expression by in situ hybridization.

Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is responsible not only for VHL disease, but also for sporadic renal cell carcinoma and cerebellar haemangioblastoma. The distribution of VHL gene expression in the mouse embryo was recently studied by in situ hybridization, along with human VHL in 14-week-old fetal kidney: there was widely distributed expression in the former and expression in the tubules and blastema in the latter. Adult human tissue and other fetal organs were not examined. The present paper describes an in situ hybridization study to assess the function of the VHL gene in adult human tissues and in tissues of human fetus at 28 weeks of gestation. The expression of the VHL gene was limited to the adult and fetal brain and kidney, and the adult prostate. Nerve cells in adult and fetal brain were positive, including the cerebellar Purkinje cells. In adult and fetal kidney, the proximal tubular epithelium, the putative origin of the common type of renal cell carcinoma, showed intense signal, whereas the distal nephron, glomeruli, and nephrogenic blastema showed no significant signal. The prostate showed significant signal in the basal epithelium. The adrenal, pancreas, and epidydimis showed no significant signal, in spite of the frequent occurrence at these sites of neoplastic or hamartomatous lesions in VHL disease.

Animals↗
PubMed1996

Ventromedial hypothalamic lesion-induced vagal hyperactivity stimulates rat pancreatic cell proliferation.

BACKGROUND & AIMS: Ventromedial hypothalamic (VMH) lesions cause an increase in DNA content in the rat pancreas. This study examined the role of cell proliferation in the mitotic response of the rat pancreas after VMH lesion formation. METHODS: Alterations in rat pancreatic DNA content, DNA synthesis, and labeling indices using antiproliferation cell nuclear antigen molecular antibody were measured 0,1,3, and 7 days after VMH lesion formation. Additionally, the effects of vagotomy, atropine, or anti-insulin antibody on VMH lesion-induced alterations in DNA synthesis were examined. Pancreatic samples were also treated with double immunostaining: first for PCNA and then for insulin, glucagon, and somatostatin. RESULTS: Pancreatic weight, DNA content, and DNA synthesis increased in animals receiving VMH lesions. Proliferation was primarily observed in islet B and acinar cells beginning 1 day after VMH lesion formation, reaching a maximum rate after 3 days. VMH lesion-induced stimulation of DNA synthesis was completely inhibited by vagotomy or atropine administration but not by anti-insulin antibody. CONCLUSIONS: Vagal hyperactivity produced by VMH lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism.

Analysis of Variance↗
PubMed1996

Cloning of the cDNA encoding mouse PP5/TFPI-2 and mapping of the gene to chromosome 6.

Placental protein 5 (PP5)/tissue factor pathway inhibitor-2 (TFPI-2) is a new homologue of TFPI, which contains three tandemly repeated Kunitz-type proteinase inhibitory (KPI) domains and potently inhibits the extrinsic blood coagulation cascade. In this study, mouse PP5/TFPI-2 cDNA was cloned using a human PP5/TFPI2 cDNA fragment as a probe. The characteristic three KPI domains with short spacer sequences and a basic amino acid stretch in the carboxyl-terminal region present in human PP5/TFPI-2 were well conserved in mouse PP5/TFPI-2. In general, the P1 reactive site residues of active KPI domains are basic amino acids. However, the putative P1 residues of the first, second, and third KPI domains were glutamine, aspartic acid, and serine, respectively. Mouse PP5/TFPI-2 mRNA was highly expressed in developing placenta as in humans. Adult liver and kidney also contained a significant amount of its transcripts. The mouse PP5/TFPI-2 gene was found to be located in the R-positive A2 band by the direct R-banding FISH and identified at 2.7 cM proximal to D6Mit 1 by interspecific backcross analysis.

Amino Acid Sequence↗
PubMed1996

Differential expression of laminin-5/ladsin subunits in human tissues and cancer cell lines and their induction by tumor promoter and growth factors.

We previously reported a new laminin variant containing laminin gamma 2 (or B2t) chain, ladsin, which exerted prominent cell-scattering, cell-adhesion, and cell-migration activities. In the present study, this laminin was further characterized, and gene expression of its three subunits in various human tissues and cancer cell lines was examined by Northern blotting. cDNA cloning of the largest subunit of ladsin and partial amino acid sequencing of its beta (or B1) subunit revealed that ladsin was identical to laminin-5 (kalinin/epiligrin/ nicein). Among various human tissues, placenta, lung, and fetal kidney expressed high levels of mRNAs for the three subunits of laminin-5 (laminin alpha 3EPA, beta 3, and gamma 2 chains). Most gastric and squamous carcinoma cell lines constitutively expressed all of the three subunit mRNAs, while other types of carcinoma cell lines expressed one or two of them. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) strongly enhanced the gene expression of the three subunits, increasing 2 to 8-fold the secretion of laminin-5 from carcinoma cells into culture medium. However, TPA treatment did not increase the secretion of laminin beta 1 chain, a subunit of laminins-1, -3, and -6. The unique properties and inducibility by TPA and EGF of laminin-5 suggest that it is associated with growth and migration of cancer cells.

Blotting, Northern↗
PubMed1995

A case of tracheal agenesis delivered of a patient with mosaic Turner's syndrome.

We describe a female infant with tracheal agenesis associated with severe complicated malformations including the cardiovascular system. The patient was born of a mother with mosaic Turner's syndrome at 35 weeks of gestation after premature rupture of the membranes during treatment for polyhydramnios. The patient died 2 days after birth and the autopsy disclosed tracheal agenesis and associated multiple anomalies.

Abnormalities, Multiple↗
PubMed1995

Establishment of two rat osteosarcoma cell lines (YROS-1 and YROS-2) induced by radioactive phosphorus.

Two rat osteosarcoma cell lines, YROS-1 and YROS-2, were established from two experimental osteosarcomas and induced by internal irradiation with radioactive phosphorus. Both cell lines formed a monolayer cell sheet in vitro with focal piling. The YROS-1 cells were refractile and spindle or polygonal in shape, whereas the YROS-2 cells were flat, spread and polygonal in shape. Ultrastructurally, the YROS-1 cells had well-developed rough-surfaced endoplasmic reticulum with focal pericellular deposition of calcified matrix, whereas YROS-2 had abundant polysomes and intracytoplasmic filaments. Both cell lines grew stably with population doubling times of 23 and 39 h, respectively. Flow cytometry revealed that YROS-1 was rich in proliferating cells compared to YROS-2, with a higher colony-forming efficiency. YROS-1 showed high alkaline phosphatase activity, while YROS-2 possessed low activity. When subcutaneously transplanted into lumbodorsal area of athymic nude mice, only YROS-1 formed tumors with frequent lung metastasis.

Animals↗
PubMed1995

[Clinico-pathological aspect of HIV-sero positive inpatients].

To describe the clinico-pathological aspect of HIV/AIDS inpatients, we reviewed HIV/AIDS inpatients in our hospital since 1988. We evaluated risk factors, CD4 counts, CD4/8 ratio, cause of death and the survival time after diagnosis of AIDS. A total of 13 HIV sero-positive subjects were admitted to our hospital, including 11 cases (85%) with AIDS. One patient was a foreigner. All cases were male; age range 18-70 years. Hemophiliacs and sexually transmitted patients account for 62% and 38% of cases, respectively. There were no cases of intravenous drug users. In all cases with AIDS, CD4+ cells and CD4/8 ratio significantly decreased with median value of 73/microns and 0.18, respectively. Six cases (54%) were decreased and autopsy were done in four cases. Findings of autopsy revealed HIV encephalopathy and systemic various infection, including Pneumocystis carinii, cytomegalovirus, papilloma virus and pox virus. Cytomegalovirus infection was found in all cases; one had innumerable inclusion bodies in lung, adrenal gland and intestines. The median survival time after diagnosis of AIDS were 26 months.

AIDS-Related Opportunistic Infections↗
PubMed1994

Establishment and characterization of a malignant melanoma cell line (YP-MEL) derived from a patient with neurocutaneous melanosis.

A cell line, YP-MEL, was established from an intracranial malignant melanoma occurring in a neurocutaneous melanosis (NCMsis) patient. The established cell line was successfully cultured in serum-free medium with a doubling time of 41 h. The cells were refractile and small in size, with occasional pigmented giant cells. Histochemical and immunohistochemical features were compatible with common malignant melanoma and its cell line. Chromosome analysis revealed many supernumerary chromosomes and marker chromosomes including double minutes (DMs). When transplanted into nude mice, YP-MEL formed tumors histologically consistent with the original tumor. Addition of sera to the medium caused cellular spreading and elongation of cytoplasmic processes with an increase of melanin contents and tyrosinase activity. Because there was no melanoma cell line derived from a NCMsis patient, YP-MEL might be a beneficial tool for study on NCMsis.

Biopsy↗
PubMed1994

Establishment of three rat soft tissue tumor cell lines with different degrees of myogenic differentiation.

Soft tissue malignancies often show divergent differentiation, including myogenic lineage. Five rat tumors induced with 20-hydroxymethylcholanthrene (20-OH-MCA), were cultured in vitro, and three cell lines (YMC-1, YMC-2, YMC-3) were established from them. YMC-2 and -3 cells were spindle-shaped, and YMS-1 cells round and epithelioid. In confluency, YMC-3 cells formed myotubes. The nude mouse xenotransplants showed morphological features consistent with their myogenic phenotypes. Muscle-specific enzyme activities were highest in YMC-3 cells. These lines may be useful in the investigation of the myogenic differentiation of undifferentiated mesenchymal cells.

Animals↗
PubMed1994

cDNA cloning and mRNA expression of a serine proteinase inhibitor secreted by cancer cells: identification as placental protein 5 and tissue factor pathway inhibitor-2.

A serine proteinase inhibitor was purified from conditioned medium of the human glioblastoma cell line T98G. Analysis of its partial amino acid sequences indicated that this protein was identical to placental protein 5 (PP5), a placenta-derived glycoprotein with serine proteinase inhibitor activity, the amino acid sequence of which had been partially determined. cDNA cloning of PP5 demonstrated that it belonged to the Kunitz-type serine proteinase inhibitor family, having three putative Kunitz-type inhibitor domains, and that it was identical to a recently reported inhibitor, tissue factor pathway inhibitor-2 (TFPI-2) [Sprecher et al. (1994) Proc. Natl. Acad. Sci. USA 91, 3353-3357]. PP5/TFPI-2 transcripts were highly abundant in the full-term placenta and widely expressed in various adult human tissues, such as the liver, skeletal muscle, heart, kidney, and pancreas. Several ovarian carcinoma cells as well as T98G also contained significant amounts of the transcripts.

Amino Acid Sequence↗
PubMed1994

Chromophobe renal cell carcinoma: a report of two cases.

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cells possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.

Adult↗
PubMed1993

Polyclonal B cell activation and antigen-specific stimulation in mice with chronic graft-versus-host reaction.

Primary chronic graft-versus-host reaction (GVHR) was induced in (C57BL/10 x DBA/2)F1 (BDF1) mice via the transfer of parental DBA/2 derived lymphocytes. A significant increase in the absolute number of IgM- and IgG-secreting cells was found in recipient BDF1 mice at 3 weeks post-transfer. The increase included B cells reactive with both self- and non-self-antigens, without being skewed toward the production of autoantibodies. Later in the disease process (approximately 6-8 weeks post-transfer), we detected an increased number of B cells that secreted antibodies reactive with a select subset of autoantigens in about 30% of BDF1 recipients (3 of 9 mice). These findings suggest that not only antigen-specific stimulation, which was detected in a late stage, but also initial polyclonal activation may account for chronic GVHR.

Animals↗
PubMed1993

Three-dimensional study of glomerular lesions in murine chronic graft-versus-host reaction by the quick-freezing and deep-etching method.

In murine chronic graft-versus-host reaction (GVHR), the immune complex composed of antoantibodies has been considered to induce human lupus-like nephritis. We prepared the replica membranes and immunoelectron-microscopic specimens of glomeruli of GVHR mice. The immunoelectron-microscopic examination revealed that immune deposits were noted mainly in the mesangial matrices and subepithelial area. The replica membranes showed various sizes of the deposits in the same portions. Moreover, fine fibrils around the deposits were strongly disrupted. Microfilaments were increased in the cytoplasm of podocytes and endothelial cells were slightly detached from glomerular basement membrane. In this model system, the immune deposits might play an important role in keeping the glomerular integrity.

Animals↗
PubMed1992

Peculiar axonal debris with subsequent astrocytic response (foamy spheroid body). A topographic, light microscopic, immunohistochemical and electron microscopic study.

Foamy spheroid bodies (FSBs) are described, as newly identified pathological structures occurring in human brain. FSBs favoured the substantia nigra pars reticulata (SNPR) and/or globus pallidus (GP) in degenerative conditions especially postencephalitic parkinsonism, progressive supranuclear palsy, pallido-nigro-luysial atrophy and multiple system atrophy. No FSBs were observed anywhere in the presence of substantia nigra pars compacta (SNPC) degeneration, such as occurs in idiopathic Parkinson's disease, or luysio-pallidal system degeneration, such as found in dentato-rubro-pallido-luysial atrophy or Joseph's disease. FSBs were also occasionally identified in the substantia nigra (SN) and/or GP of aged persons. In addition to SN and GP lesions, FSBs were seen in diffuse axonal lesions of long fibre tracts (the corpus callosum, the superior cerebellar peduncle) after non-missile head injuries, and in peri-infarct lesions. Under the light microscope, FSBs appear as slightly eosinophilic, foamy and nearly round objects with vague outlines, measuring approximately 10-50 microns in diameter. Some FSBs contain coarse, eosinophilic clusters at their periphery. FSB stained black when stained by the Gallyas silver method. Some FSBs were immunohistochemically positive for synaptophysin and 68 kDa neurofilament. Glial fibrillary acidic protein-positive fibres were observed alongside and/or inside some FSBs. Electron microscopically, FSBs were found to consist of collections of neuritic debris containing a variety of dense bodies and a small number of both mitochondria and neurofilaments. Some such collections were surrounded by astrocytic processes. These findings strongly suggest that FSBs are collections of small axonal debris destined for removal by astrocytes in due course. A variety of factors (degeneration of the SNPR and/or the GP, injury, infarction, ageing) seemed to be responsible for the histogenesis of FSBs.

Adult↗