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Biomedical subjects

M Katoh

Publications and source records attributed to M Katoh.

At least 127 records · Page 7Linked to original sources
PubMed1999

The fibronectin extra domain A activates matrix metalloproteinase gene expression by an interleukin-1-dependent mechanism.

The extra domain-A (EDA), present in fibronectin (FN) molecules arising from alternatively spliced transcripts, appears only during specific biological and pathogenic processes. However, its function is poorly understood. To define the physiologic role of this domain in joint connective tissue, the biological effects on rabbit cartilage explants, chondrocytes, and synovial cells were studied. A recombinant EDA protein (rEDA) increased proteoglycan release (3. 6-fold) in cartilage explant cultures and markedly induced production of matrix metalloproteinase (MMP)-1 in chondrocytes. In addition, rEDA induced MMP-1, MMP-3, and MMP-9 in synovial cells. These effects were elicited only by rEDA, while its neighboring type III repeats, III(11) or III(12), scarcely had any such effects. Interestingly, reorganization of F-actin stress fibers accompanied MMP-1 expression in synovial cells treated with rEDA, suggesting alteration of cellular phenotype. Subsequent Northern blotting revealed expression of pro-inflammatory cytokines, including interleukin (IL)-1alpha and IL-1beta, was induced by rEDA prior to MMP-1 expression. Delayed MMP-1 expression suggests that rEDA-induced IL-1s promote MMP-1 expression in an autocrine manner. This hypothesis is supported by the reduction of EDA-induced MMP-1 production by IL-1 receptor antagonist. The effect of EDA on MMP-1 production was reduced by connection with an adjacent type III repeat on either the NH(2) or COOH side of EDA and was abolished by connection on both sides of EDA, suggesting that exposure of either the NH(2) or COOH terminus of EDA domain by proteolytic cleavage releases the inducing activity. In agreement with these results, full-length cellular FN did not induce MMP-1 production. Furthermore, a 160-kDa EDA-positive FN fragment, which was purified from human placental tissue and corresponds to the region from NH(2) terminus through the EDA, induced MMP-1 production. Taken together, these results suggest that the EDA in FN fragments triggers alterations of cell physiology and plays a role in matrix degradation in joint connective tissue.

Alternative Splicing↗
PubMed1999

Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders.

The human melatonin 1a (hMella) receptor gene was screened for mutations using genomic DNA samples from patients with circadian rhythm sleep disorders and control subjects by single strand conformational polymorphism analysis (SSCP). We found seven mutations, two of which predict amino acid changes R54W and A157V, respectively. The prevalence of the R54W variant and that of the A157V variant were several times more common in non-24-h sleep-wake syndrome subjects than among control subjects, although the incidence was not significant in our study group. When expressed in COS-7 cells, the R54W mutant receptor exhibited significantly reduced B(max) and slightly enhanced affinity (reduced K(d)) compared to the wild type receptor, while the A157V variant receptor showed similar binding characteristics to the wild type. The identification of variants in the hMella receptor will provide a useful tool for analyzing genetic predisposition toward various diseases related to melatonin function and to clarify the physiological role of melatonin receptors in humans.

Alleles↗
PubMed1999

Molecular cloning of Frizzled-10, a novel member of the Frizzled gene family.

The Frizzled genes encode WNT receptors. Frizzled-10 (FZD10), a novel member of the Frizzled gene family, has been cloned and characterized. Nucleotide sequence analysis showed that human FZD10 gene encodes a seven-transmembrane-receptor of 581 amino acids, with the N-terminal cysteine-rich domain and the C-terminal Ser/Thr-Xxx-Val motif. Larger amounts of FZD10 mRNA, 4.0 kb in size, were detected in the placenta and fetal kidney, followed by fetal lung and brain. In adult brain, FZD10 mRNA was abundant in the cerebellum. Among cancer cell lines, FZD10 was highly expressed in a cervical cancer cell line, HeLa S3, and moderately in a colon cancer cell line, SW480. The FZD10 gene was mapped to human chromosome 12q24.33. FZD10 shares 65.7% amino-acid identity with Frizzled-9 (FZD9). FZD10 and FZD9 constitute a subfamily among the Frizzled genes.

Adult↗
PubMed1999

Spectra of gpt mutations in ethylnitrosourea-treated and untreated transgenic mice.

We have established a new transgenic mouse mutagenicity assay for the efficient detection of point mutations and deletions in vivo (Nohmi et al. [1996] Env. Mol. Mutagen. 28:465-470). In this assay, the gpt gene of Escherichia coli is used as a reporter for the detection of point mutations. Treatment of mice with ethylnitrosourea (ENU, 150 mg/kg) enhances by several-fold the mutant frequency of gpt in bone marrow. Here, we report the mutation spectra of the gpt gene recovered from bone marrow of ENU-treated and untreated transgenic mice. In the gpt mutants rescued from ENU-treated mice, more than 90% of the mutations were base change mutations; the predominant types were A:T to T:A transversions and G:C to A:T transitions. On the contrary, in the mutants rescued from untreated mice, 54% were base substitutions and the remainders were short deletions and insertions. Among untreated mice, the most frequently observed base substitution was G:C to A:T transitions (7/14 mutants). Three of these occurred at 5'-CpG-3' sites. Interestingly, the mutation spectra of the gpt gene were different from those of the gpt gene in ENU-treated and untreated E.coli, whereas they were similar to those of the lacZ and lacI genes in ENU-treated and untreated other transgenic mice or cultured mammalian cells. We also report the establishment of homozygous transgenic mice that have transgene lambdaEG10 DNA in both chromosome 17 of C57BL/6J mouse.

Animals↗
PubMed1999

Spi(-) selection: An efficient method to detect gamma-ray-induced deletions in transgenic mice.

Despite the importance of genome rearrangement in the etiology of cancer and human genetic disease, deletion mutations are poorly detectable by transgenic rodent mutagenicity tests. To facilitate the detection and molecular analysis of deletion mutations in vivo, we established a transgenic mouse model harboring a lambdaEG10 shuttle vector that includes the red and gam genes for Spi(-) (sensitive to P2 interference) selection [Nohmi et al. (1996] Environ. Mol. Mutagen. 28:465-470]. This selection has a great advantage over other genetic systems, because phage deletion mutants can be preferentially selected as Spi(-) plaques, which can then be subjected to molecular analysis. Here, we show nucleotide sequences of 41 junctions of deletion mutations induced by gamma-irradiation. Unlike spontaneous deletion mutants, more than half of the large deletions occurred between short homologous sequences from one to eight bp. The remaining junctions had no such homologous sequences. Intriguingly, two Spi(-) mutants had P (palindrome)-like nucleotide additions at the breakpoints, which are frequently observed in the coding junctions of V(D)J recombination, suggesting that broken DNA molecules with hairpin structures can be intermediates in the repair of radiation-induced double-strand breaks. We conclude that Spi(-) selection is useful for the efficient detection of deletion mutations in vivo and that most rearrangements induced by gamma-rays in mice are mediated by illegitimate recombination through DNA end-joining.

Animals↗
PubMed1999

An abdominal desmoid tumor involving the xyphoid and costal chondrium associated with pregnancy: report of a case.

We report herein the case of a 27-year-old woman found to have an abdominal desmoid tumor involving the xyphoid and costal chondrium associated with pregnancy. The patient was referred to our department on the third day after delivery for investigation of a fist-sized, firm tumor in the infrasternal angle, first noticed during the eighth month of gestation. Computed tomography and magnetic resonance imaging revealed a well-defined mass, 9 x 7.5 cm in size, invading the xyphoid. The tumor could be radically excised with the xyphoid, a lower part of sternum, and the chondrium of the bilateral sixth and seventh ribs, including 1.5 cm of free margin. The resected specimen measured 10 x 11.5 x 11.5 cm and weighed 395 g. Histological examination revealed the lesion to be a desmoid tumor consisting of spindle cells with small, elongated nuclei infiltrating dense collagenous fibers. The patient had an uneventful postoperative course and was discharged on the 11th postoperative day. There has been no evidence of recurrence in the 6 months since her operation. This case is of interest with regard to the possible contribution of sex hormones, especially estrogen, to desmoid tumor development.

Adult↗
PubMed1999

Severe stenosis of the internal carotid artery presenting as loss of consciousness due to the presence of a primitive hypoglossal artery: a case report.

BACKGROUND: Symptoms of ischemic attacks in the internal carotid system usually involve focal cerebral dysfunction, i.e., hemiparesis or aphasia. However, an ischemic attack in the vertebrobasilar artery system usually presents with combined symptoms. The variety of manifestations included in the vertebrobasilar profile makes the potential pattern of symptoms considerably more variable and complex than that in the carotid system. Manifestations can include syncope and also vertigo. METHOD AND RESULTS: A 42-year-old woman experienced frequent attacks of faintness with vertigo. Angiography demonstrated severe stenosis of the left internal carotid artery with a persistent primitive hypoglossal artery just distal to the stenosis. The right internal carotid artery was normal and cross circulation through the anterior communicating artery was not well developed. Both vertebral arteries were hypoplastic. The patient underwent carotid endarterectomy and, thereafter the episodes of syncope completely disappeared. CONCLUSION: It was supposed that global ischemia including the brain stem occurred because of stenosis of the left internal carotid artery attributable to the presence of a primitive hypoglossal artery.

Adult↗
PubMed1999

Leiomyosarcoma of the heart and its pulmonary metastasis, both with prominent osteoclast-like multinucleated giant cells expressing tartrate-resistant acid phosphatase activity.

An autopsy case of cardiac leiomyosarcoma and its pulmonary metastasis, both with osteoclast-like multinucleated giant cells (OMGC) mimicking the so-called giant cell variant of malignant fibrous histiocytoma (MFH), is reported. The patient, a 70-year-old male, was admitted for sudden dyspnea. Extensive work-up established only a left atrial tumor mass. Three months after admission, the patient developed multiple intracranial and pulmonary metastases, followed by a worsening clinical course characterized by semicoma and dyspnea, and subsequently died 6 months after the onset of his symptoms. At subsequent autopsy, the left atrial polypoid tumor was found to have invaded destructively to the left half of the cardiac wall. Histology of the cardiac tumor revealed a bimorphic sarcoma in which a poorly differentiated leiomyosarcoma comfirmed by histologic and immunohistochemical findings was juxtaposed to a small nodule with features closely mimicking giant cell MFH. The pulmonary metastatic nodules exhibited features that were entirely indistinguishable from giant cell MFH except for the fact that a minority of polymorphic cells manifested myogenic differentiation. We believe that such a MFH-like pattern represents a pleomorphic form of leiomyosarcoma rather than a dedifferentiated one. The OMGC within the MFH-like component coexpressed CD68 and tartrate-resistant acid phosphatase activity.

Acid Phosphatase↗
PubMed1999

Primary liver carcinoma complicating membranous obstruction of the inferior vena cava.

A rare autopsy case of primary liver carcinoma complicating a pre-existing, incomplete membranous obstruction of the inferior vena cava (MOVC) is reported. The patient, a 67-year-old Japanese male, was admitted to hospital following a 2 year illness of a left chest wall tumor and a 3 month illness with progressive abdominal pain. Computed tomography scans of the abdomen displayed space-occupying lesions in the third and seventh hepatic segments, respectively. One month later, the patient developed edema of the lower extremities and marked venous dilatation of the abdominal trunk. At that time, Doppler examination revealed the presence of intrahepatic large venovenous collaterals. The patient subsequently succumbed 82 days after hospitalization. At subsequent autopsy, the inferior vena cava was completely obstructed by tumor thrombus, which was formed caudally and cranially to a thin membrane and mimicked the valve, with calcification and elastic lamina, at the phrenic portion. Intrahepatic large collateral pathways were found between submembranous and supramembranous hepatic veins. Anomalous absence of the ostia of the middle hepatic vein was found. In addition, the portal venous trunk was occluded by tumor thrombus. Histology of hepatic tumors revealed a combined hepatocellular and cholangiocellular carcinoma in the non-cirrhotic liver with severe acute centrilobular congestion. In MOVC patients such as the case presented, malignancy-induced thrombosis was deemed to be an important factor in prognosis.

Aged↗
PubMed1999

Renal involvement of thrombotic thrombocytopenic purpura: special reference to the glomeruloid structures.

We report the case of a 9-year-old girl with biopsy-proven renal thrombotic microangiopathy in thrombotic thrombocytopenic purpura (TTP), with particular reference to the glomeruloid structures. The renal biopsy sample from this TTP patient revealed platelet thrombus deposition, a glomeruloid structure and aneurysm with relative sparing of the glomeruli. The glomeruloid structure displayed a proliferation of mainly capillary-sized channels lined by Factor VIII-related, antigen-positive plump endothelial cells embedded in the edematous connective tissue. These glomeruloid vessels communicated with the aneurysmal segment at the end portion of the arteriolar branch. We believe that the glomeruloid structures in TTP represent not merely organization or recanalization of thrombus but rather active angiogenesis through aneurysmal dilation in the arteriolized vessel, probably initiated by platelet agglutination.

Aneurysm↗
PubMed1999

LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids.

Mammalian imprinted genes are frequently arranged in clusters on particular chromosomes. The imprinting cluster on human chromosome 11p15 is associated with Beckwith-Wiedemann syndrome (BWS) and a variety of human cancers. To clarify the genomic organization of the imprinted cluster, an extensive screen for differentially expressed transcripts in the 11p15 region was performed using monochromosomal hybrids with a paternal or maternal human chromosome 11. Here we describe an imprinted antisense transcript identified within the KvLQT1 locus, which is associated with multiple balanced chromosomal rearrangements in BWS and an additional breakpoint in embryonal rhabdoid tumors. The transcript, called LIT1 (long QT intronic transcript 1), was expressed preferentially from the paternal allele and produced in most human tissues. Methylation analysis revealed that an intronic CpG island was specifically methylated on the silent maternal allele and that four of 13 BWS patients showed complete loss of maternal methylation at the CpG island, suggesting that antisense regulation is involved in the development of human disease. In addition, we found that eight of eight Wilms' tumors exhibited normal imprinting of LIT1 and five of five tumors displayed normal differential methylation at the intronic CpG island. This contrasts with five of six tumors showing loss of imprinting of IGF2. We conclude that the imprinted gene domain at the KvLQT1 locus is discordantly regulated in cancer from the imprinted domain at the IGF2 locus. Thus, this positional approach using human monochromosomal hybrids could contribute to the efficient identification of imprinted loci in humans.

Animals↗
PubMed1999

The characterization of Shiga toxin-non-producing Escherichia coli serotype O157:H7 isolated from carcasses of cattle at a slaughter house.

A bacteriological investigation of Shiga toxin (Stx)-producing Escherichia coli (STEC) O157:H7 was performed on 298 carcasses of cattle at slaughter houses between July 1996 and January 1997 in Gifu Prefecture, Japan. As a result, four Stx-non-producing Escherichia coli O157:H7 strains were isolated from two slaughtered carcasses of cattle. The purpose of this study was to examine the characterization of isolates. Isolates possessed the E. coli attaching and effacing gene (eaeA), and hemolysin gene (hlyA), and harbored 3.0-MDa and 60-MDa plasmids. The Xba I pulsed-field gel electrophoresis (PFGE) pattern showed three similar patterns. Consequently, a closely related genotype of Stx-non-producing E. coli O157:H7 may widely exist in cattle.

Abattoirs↗
PubMed1999

Pathogenic role of oxidative stress in vascular angiotensin-converting enzyme activation in long-term blockade of nitric oxide synthesis in rats.

Inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) activates vascular angiotensin-converting enzyme (ACE) and causes oxidative stress. We investigated the role of oxidative stress in the pathogenesis of ACE activation in rats. Studies involved aortas of rats receiving no treatment, L-NAME, L-NAME plus L-arginine, or L-NAME plus an antioxidant drug (N-acetylcysteine, allopurinol, or ebselen) for 7 days. L-NAME significantly increased oxidative stress (O(2)(-)) and ACE activity. The increased O(2)(-) production was normalized by removal of endothelium. Immunohistochemistry showed the increased ACE activity in the endothelial layer. Treatment with antioxidant drugs did not affect the L-NAME-induced increase in systolic arterial pressure but did prevent increases in vascular O(2)(-) production and ACE activity. These results implicate oxidative stress in the pathogenesis of vascular ACE activation in rats with long-term inhibition of NO synthesis. The observed effects of antioxidant drugs on ACE activation do not appear to involve the hypertension induced by L-NAME.

Animals↗
PubMed1999

Ca(2+)/calmodulin and p85 cooperatively regulate an initiation of cytokinesis in Tetrahymena.

Tetrahymena p85 differs in mobility in two-dimensional SDS-polyacrylamide gel electrophoresis between wild-type and temperature-sensitive cell-division-arrest mutant cdaA1 cell extracts, and is localized to the presumptive division plane before the formation of the division furrow. The p85 contained three identical sequences which show homology to the calmodulin binding site of Ca(2+)/calmodulin dependent protein kinase Type II in Saccharomyces cerevisiae. We found the p85 directly interacts with Tetrahymena calmodulin in a Ca(2+)-dependent manner, using a co-sedimentation assay. We next examined the localization of p85 and calmodulin during cytokinesis using indirect immunofluorescence. The results showed that both proteins colocalize in the division furrow. This is the first observation that calmodulin is localized in the division furrow. Moreover, the direct interaction between p85 and Ca(2+)/calmodulin was inhibited by Ca(2+)/calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide HCl. When the cells were treated with the drug just before the beginning of cytokinesis, the drug also inhibited the localization of p85 and calmodulin to the division plane, and the formation of the contractile ring and division furrow. Therefore, we propose that the Ca(2+)/calmodulin signal and its target protein p85 cooperatively regulate an initiation of cytokinesis and may be also concerned with the progression of cytokinesis in Tetrahymena.

Actins↗
PubMed1999

Dexamethasone inhibits collagen degradation induced by the combination of interleukin-1 and plasminogen in cartilage explant culture.

Glucocorticoids ameliorate erosion in animal osteoarthritis (OA) models and suppress synthesis of matrix metalloproteinases (MMP). However, in in vitro studies, their inhibitory effects on matrix degradation of cartilage have not been well documented by monitoring aggrecan. Collagen was monitored in this study to examine the effects of dexamethasone in cartilage explant culture. Dexamethasone clearly blocked collagen degradation induced by the combination of interleukin-1 (IL-1) and plasminogen at the concentration of 10(-9) M, which is much lower than the concentrations reportedly required to inhibit matrix synthesis. In addition, MMP-1 and MMP-3 were suppressed by dexamethasone treatment in a similar range of concentrations. The conversion of plasminogen to plasmin, however, was not blocked by treatment with dexamethasone. These results suggest that the inhibitory effect of dexamethasone on collagen degradation may be due to suppression of MMP production rather than suppression of fibrinolytic cascade. Thus, the ability of glucocorticoids to inhibit matrix degradation in vitro, which could be clearly shown by monitoring collagen degradation, may endorse their efficacy in animal OA models and suggest potential therapeutic effectiveness.

Animals↗