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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 505 records · Page 28Linked to original sources
PubMed1996

Processing of a precursor of 72-kilodalton type IV collagenase/gelatinase A by a recombinant membrane-type 1 matrix metalloproteinase.

Membrane-type 1 matrix metalloproteinase that is associated with the proteolytic activation of progelatinase A was expressed as a recombinant fusion protein in Escherichia coli. The recombinant enzyme cleaved the propeptide sequence of gelatinase A in a sequence-specific manner. A mutant progelatinase A that has a substitution of Asn(66)-Leu to Ile-Val was not processed at all. The processing was blocked by tissue inhibitor of metalloproteinases-2 or BB-94 but not by tissue inhibitor of metalloproteinases-1. Thus, membrane-type 1 matrix metalloproteinase is a direct activator of progelatinase A without requiring additional proteases.

Animals↗
PubMed1996

Cortical glucose metabolism in psychiatric wandering patients with vascular dementia.

The cerebral metabolic rate for glucose (CMRglc) in 18 patients with vascular dementia (VD) and 15 age-matched normal subjects was measured with positron emission tomography (PET) and the 18F-fluorodeoxyglucose technique. Nine of the 18 VD patients manifested abnormal wandering behavior with some psychiatric symptoms: they showed relatively spared CMRglc, which was higher than that of nonwandering patients, especially in the bilateral frontal lobes, left parietal lobe, left temporo-parieto-occipital region, left occipital lobe, and cerebellum. The results suggest that psychiatric wandering behavior of patients with VD could be correlated with partial sparing of CMRglc in the regions listed above.

Aged↗
PubMed1996

Cholecystokinin receptor antagonist, loxiglumide, inhibits invasiveness of human pancreatic cancer cell lines.

Recently, cholecystokinin has been reported to be important in regulating the growth of pancreatic cancer. We investigated the effect of loxiglumide (LXG), a cholecystokinin receptor antagonist, on the invasiveness of two human pancreatic cancer cell lines. Cells were treated with LXG for 24 h, and examined in the invasion assay. The expression and activity of MMP-9 in supernatants from cancer cells were analyzed by Western blotting and zymogram. Interestingly, the invasiveness of cancer cells and expression of MMP-9 were decreased by LXG in a dose-dependent manner. LXG may be a useful therapeutic agent against pancreatic cancer.

Blotting, Western↗
PubMed1996

Pancreatic islet cells express BST-1, a CD38-like surface molecule having ADP-ribosyl cyclase activity.

Cyclic ADP-ribose (cADPR), a well-known stimulator of ca(2+) release from the intracellular Ca(2+) pool, has recently emerged as a potential regulator of insulin secretion in pancreatic beta cells. As recently described, BST-1 is a glycosyl-phosphatidylinositol (GPI)-anchored surface molecule that exhibits homology with CD38 and Aplysia ADP-ribosyl cyclase. Like CD38, BST-1 has both ADP-ribosyl cyclase and cADPR hydrolase activities. As a step toward elucidating the physiological role of cADPR in insulin secretion we examined whether BST-1 is expressed in pancreatic islet cells. Sensitive reverse transcription-polymerase chain reaction detected almost as abundant expression of BST-1 mRNA in pancreatic islets as CD38 mRNA. Immunohistochemical analyses utilizing mirror image sections revealed that BST-1 protein is expressed in a majority of the cells in pancreatic islets and that at least beta cells and, to an even greater extent, alpha cells express BST-1. These observations suggest the involvement of multiple enzymes in the regulation of cADPR concentrations in pancreatic islet cells.

ADP-ribosyl Cyclase↗
PubMed1996

K-ras and p53 mutations in stage I gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct.

BACKGROUND: An anomalous junction of the pancreaticobiliary duct (AJPBD) was thought to be an important risk factor for gallbladder carcinoma in Japan. In this report, we compared K-ras and p53 mutations in Stage I gallbladder carcinomas (GC) of patients with AJPBD with those in patients without AJPBD: METHODS: We examined 6 GC of patients with AJPBD and 20 GC of patients without AJPBD: Immunohistochemistry was performed for p53 protein. K-ras and p53 mutations were examined using genomic DNA extracted from the cancer regions. The methods of polymerase chain reaction (PCR) single strand conformation polymorphism analysis were performed for mutations in exons 5-8 of p53. The methods of PCR restriction fragment length polymorphism were performed for mutation in codon 12 of K-ras. RESULTS: p53 positivity was 67% in GC of patients with AJPBD and 65% in GC of patients without AJPBD: p53 mutations were found in exons 7 and 8 in GC of patients with AJPBD and in exons 5, 6, and 7 in GC of patients without AJPBD: The incidence of K-ras mutation in GC of patients with AJPBD (50%) was greater than that in patients without AJPBD (6%) (P < 0.05). CONCLUSIONS: These results suggest that K-ras mutation may be important in the early stage of carcinogenesis of the gallbladder mucosa with AJPBD, and that p53 mutations may also contribute to the early stage of carcinogenesis of the gallbladder mucosa, regardless of AJPBD:

Adenocarcinoma↗
PubMed1996

Proteins that interact with GTP in Streptomyces griseus and its possible implication in morphogenesis.

By cross-linking with [alpha-32P]GTP or [gamma-32P]GTP with or without UV treatment, several proteins of Streptomyces griseus were shown to interact with GTP in specific ways. After gel electrophoresis, 19 bands of radioactivity were found; 12 bands were assigned as GTP-binding proteins and 6 bands as phosphorylated proteins. One band was assumed to be a guanylylated protein. The profile of radioactive bands was similar between cells prepared from liquid or solid culture, but markedly different between growth phases. A mutant (strain M-1) defective in aerial mycelium formation, which was originally found as a decoyinine-resistant isolate, was found to have a different profile of phosphorylated proteins.

Bacterial Proteins↗
PubMed1996

Polyclonal B cell chronic lymphoproliferative disease with hairy cell morphology: a case report and clonal studies.

We describe a patient who has a chronic polyclonal B lymphocyte proliferation with a hairy-cell appearance. A 48-year-old Japanese woman with marked splenomegaly, systemic lymphadenopathy, and leukocytosis was referred to out hospital. Laboratory examination revealed marked polyclonal IgG hypergammaglobulinemia. Morphologic examination of the patient's peripheral blood, including May-Giemsa staining and scanning electron microscopy, showed a monotonous proliferation of hairy-appearing mature lymphocytes. An immunophenotypic study revealed an expansion of cells with mature B cell antigens positive for CD11c; however, light-chain restriction was not seen. The lack of both immuno-globulin heavy-chain and T cell receptor gene rearrangements by Southern blot analysis indicated the polyclonal nature of the proliferating B cells. This was confirmed further by a clonal analysis of the patient's lymphocytes using an X-chromosome-linked restriction fragment polymorphism within the X-linked phosphoglycerate kinase (PGK) gene. Since chronic B cell lymphoproliferation with a hairy cell appearance has not been described previously, this case might be extremely rare, and has important implication for the pathogenesis of mature B cell lymphoproliferative diseases, including hairy cell leukemia.

B-Lymphocytes↗
PubMed1996

Expression of cripto in human gall bladder lesions.

The expression of cripto, a member of the epidermal growth factor (EGF) family, was examined by immunohistochemistry in benign lesions and carcinomas of the gall bladder. Cripto expression was detected in 6 (67 percent) of 9 hyperplasias, 4 (58 percent) of 7 adenomas, and 89 (68 percent) of 132 adenocarcinomas of the gall bladder. The degree of cripto expression was not correlated with depth of tumour invasion, tumour stage or patient prognosis. The incidence of cases with cripto expression was significantly higher in papillary and well-differentiated adenocarcinomas (positive 73 percent; strongly positive 38 percent) than in moderately and poorly differentiated adenocarcinomas (positive 54 percent; strongly positive 17 percent) (P < 0.05). These results suggest that cripto expression may not relate to progression in gall bladder carcinomas, but may be associated with tumour differentiation.

Adenocarcinoma↗
PubMed1996

Elevated levels of the soluble form of bone marrow stromal cell antigen 1 in the sera of patients with severe rheumatoid arthritis.

OBJECTIVE: Bone marrow stromal cell antigen 1 (BST-1) is a novel glycosyl phosphatidylinositol-anchored ectoenzyme, which is overexpressed on bone marrow stromal and synovial cell lines derived from patients with rheumatoid arthritis (RA). To investigate the pathophysiologic roles of BST-1 in RA, we established an enzyme-linked immunosorbent assay (ELISA) system to detect the soluble form of BST-1 (sBST-1) and examined levels of sBST-1 in the sera of RA patients. METHODS: Concentrations of sBST-1 in sera from healthy donors and from patients with RA, osteoarthritis, Sjögren's syndrome, and systemic lupus erythematosus were measured with the ELISA. RESULTS: In 7% of the RA patient samples (10 of 143), concentrations of serum sBST-1 were higher (approximately 30-50-fold) than in non-RA samples. Serum sBST-1 concentrations showed no correlation with age, C-reactive protein level, or rheumatoid factor level. All RA patients with high concentrations of serum sBST-1 had severe disease with involvement of several large joints. CONCLUSION: We believe the measurement of serum sBST-1 may have prognostic value, but further analysis is necessary to clarify the clinical significance of elevated sBST-1 in RA.

ADP-ribosyl Cyclase↗
PubMed1996

T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases.

This paper shows that elimination of a small subpopulation of peripheral T cells can elicit activation/expansion of self-reactive T cells from the remaining T cells and produce a wide spectrum of organ-specific and systemic autoimmune diseases in normal mice; reconstitution of the eliminated T-cell population prevents autoimmune development. This regulatory T-cell population expresses the CD25 molecule, apparently includes 'activated' T cells, and suppresses immune responses to non-self as well as self antigens in an antigen-nonspecific manner. Although the degree of abnormality in the T-cell regulation significantly influences the spectrum, incidence, and severity of autoimmune disease, the T-cell abnormality itself cannot determine the specificities of the elicited autoimmune responses since a comparable degree of abnormality causes different autoimmune diseases depending on the mouse strains used. Host genetic elements thus significantly contribute to determining the specificities. These findings taken together indicate that one aspect of natural self-tolerance is maintained by a T cell-mediated or -dependent control of potentially pathogenic self-reactive T cells in the periphery, and that defective control, caused by environmental insults or genetic abnormalities, suffices to activate self-reactive T cells, eliciting various autoimmune diseases depending on the genetic makeup of the host.

Animals↗
PubMed1996

Increased production of B cell growth factor (BCGF) in Sjögren's syndrome.

The objective of this investigation to clarify possible roles of B cell growth factor (BCGF) in the abnormal activation of B cells in Sjögren's syndrome (SS). Lymphocyte subsets of peripheral blood from 20 patients with SS (14 with primary SS and six with secondary SS) and 11 healthy donors were analysed by flow cytometry. Supernatants of peripheral blood T cells obtained from patients with SS and from donors, cultured with or without PHA, were studied using bioassay with a B cell line, KS-3.F10. The number of CD20+ cells and CD4+DR+ cells was significantly increased in SS patients compared with healthy donors. T cells from SS patients showed increased production of BCGF, whether or not they were stimulated with PHA. The enhancement of BCGF production by PHA had a positive correlation with the percentage of CD4+CD45RA+ cells, and a negative correlation with the focus score of lip biopsy. Our experiments showed that BCGF production by T cells was spontaneously increased in SS patients. The accelerated BCGF production with PHA stimulation may be related to the increase of CD4+CD45RA+ cells and the decrease of the inflammation determined by the grade of cell infiltration into salivary glands, but not by the increase of CD20+ cells.

Adult↗
PubMed1996

Cloning and chromosomal mapping of the mouse DNA-dependent protein kinase gene.

Severe combined immune deficiency (scid) mice are assumed to have two types of abnormalities: one is high radiosensitivity and the other is abnormal recombination in immunoglobulin and T-cell receptor genes. The human chromosome 8 q1.1 region has an ability to complement the scid aberrations. Moreover, the localization of the subunit DNA-dependent protein kinase [DNA-PKcs] participating in DNA double-strand break repair in the same locus was clarified. In scid mouse cells, the number of DNA-PKcs products and extent of DNA-PK activity remarkably decrease. These observations gave rise to the assumption that DNA-PKcs is the scid factor itself. In order to determine whether the DNA-PKcs gene is the scid gene, we isolated the mouse DNA-PKcs gene and investigated its chromosomal locus by fluorescence in situ hybridization (FISH). Consequently, it became clear that the mouse DNA-PKcs gene existed in the centromeric region of mouse chromosome 16, determined by cross-genetic study, as a scid locus. This finding strongly suggests that mouse DNA-PKcs is the scid gene.

Amino Acid Sequence↗
PubMed1996

Injection-incision--assisted snare resection of large sessile colorectal polyps.

BACKGROUND: It can be difficult, even for experienced endoscopists, to completely remove large sessile colorectal polyps. We attempted to remove large sessile colorectal polyps without complication and residual tumors. METHOD: Our new technique is characterized by submucosal pre-injection with a large volume of saline solution and then circumferential incision outside the lesion before resection using a special needle-tipped snare. The mean size of 33 polyps (including 9 elevated sessile, 20 flat nodular [villous], and 4 flat sessile polyps), was 4.0 cm (range, 3.0-8.5 cm). RESULTS: Twenty-five (76%) were resected piecemeal and the remainder as a single specimen. Mild to moderate bleeding occurred in 3 (9.1%), but there was no clinically significant bleeding or perforation. No residual or recurrent tumors were recognized. Invasive carcinoma was revealed most frequently (44%) in elevated sessile polyps; none occurred in flat nodular polyps. CONCLUSION: Our removal technique appears to be safe and effective. Flat nodular polyps of any size are a particularly good indication for removal by this technique.

Adult↗