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Biomedical subjects

M Koyama

Publications and source records attributed to M Koyama.

At least 55 records · Page 3Linked to original sources
PubMed2000

Inhibition of progressive reduction of islet beta-cell mass in spontaneously diabetic Goto-Kakizaki rats by alpha-glucosidase inhibitor.

The Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, exhibits mild hyperglycemia with a reduction of beta-cell mass. The mechanism for islet structural changes in this model and whether the changes are affected by metabolic control are not known. In the present study, we examined the process of islet changes in male GK rats aged 6, 8, 12, 24, and 36 weeks. Treatment effects with an alpha-glucosidase inhibitor (Voglibose; Takeda, Osaka, Japan) for 24 weeks (12 to 36 weeks of age) were also evaluated. The beta-cell mass increased until 8 weeks of age in both GK and control rats, but the increase was significantly (P < .01) smaller in GK rats versus at 8 weeks of age. Thereafter, the beta-cell mass decreased in GK rats, whereas it remained constant in controls. Voglibose treatment significantly (P < .01) inhibited the reduction of beta-cell mass in GK rats. Proliferative activity of beta cells as measured by bromodeoxyuridine (BrdU) uptake was significantly (P < .05) lower in GK rats versus control rats at 6 and 8 weeks, but the difference disappeared after 12 weeks of age, regardless of Voglibose treatment. The present study thus demonstrates a progressive loss of beta cells in GK rats that was mitigated by Voglibose treatment. We consider that the beta-cell loss in GK rats was due to an early impairment in proliferative activity and reduced survival. Voglibose did not appear to stimulate beta-cell proliferation, but exerted its effect via a reduction of hyperglycemia.

Aging↗
PubMed2000

New target region of allelic loss in hepatocellular carcinomas within a 1-cM interval on chromosome 6q23.

BACKGROUND/AIMS: Frequent allelic losses on the long arm of chromosome 16 in several types of human cancers have suggested that 16q harbors one or more genes that are important for suppressing tumorigenesis in the tissues in question. METHODS: To identify the locations of putative tumor suppressor genes involved in hepatocellular carcinoma, we examined 96 primary hepatocellular carcinomas for their patterns of allelic loss at 18 microsatellite marker loci distributed along this chromosome arm. RESULTS: Allelic loss at one or more loci was observed in 48 (50%) of these tumors. The highest frequency of loss of heterozygosity (42%) was observed with marker D6S311 on chromosome 6q23. Through detailed deletion mapping of tumors having partial or interstitial deletions, we identified two commonly deleted regions at 6q23 and at 6q26-27. CONCLUSIONS: The common region at 6q23 lay within a 1-cM interval, flanked by D6S977 and D6S311. The previously documented deletion region that includes the M6P/IGF2R locus was confined to a 20-cM region at band 6q26-27 in our panel of tumors. The location we defined at 6q23 for a putative suppressor of hepatocellular carcinoma has not been reported before.

Adult↗
PubMed2000

Elevations of group II phospholipase A2 concentrations in serum and amniotic fluid in association with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether the elevation of secretory group II phospholipase A(2) concentration in the serum and amniotic fluid in preterm labor is associated with intrauterine inflammation. STUDY DESIGN: Serum and amniotic fluid were collected from women with preterm delivery (<37 weeks' gestation; n = 38) and term delivery (n = 20). Phospholipase activity was measured with a highly sensitive system that was based on reverse-phase high-performance liquid chromatographic separation of 9-anthracenylmethyl derivatives of fatty acids released by phospholipase A(2). The concentrations of immunoreactive isozymes (group I or II) of secretory phospholipase A(2) were assayed with a radioimmunoassay kit with a monoclonal antibody against human pancreatic phospholipase A(2) and splenic IIA phospholipase A(2). Localization of immunoreactive group II phospholipase A(2) in the amniotic membrane was determined by immunostaining visualized with the Vectastain ABC (Vector Laboratories, Inc, Burlingame, Calif) method. RESULTS: Enzymatic activities of phospholipase A(2) in the serum and amniotic fluid specimens obtained from patients in preterm labor with chorioamnionitis were significantly higher than those in specimens from patients in term labor. Significant elevations of phospholipase A(2) activities were observed in patients with preterm labor without histologically evident chorioamnionitis. The activity of phospholipase A(2) was clearly correlated with the concentration of the immunoreactive group II phospholipase A(2). Group II phospholipase A(2) was localized in amniotic cells obtained from patients with a pathologically determined diagnosis of chorioamnionitis. The predictive value for chorioamnionitis of the group II phospholipase A(2) concentration was relatively higher than the predictive values of the concentrations of C-reactive protein and interleukins 6 and 8. CONCLUSION: Significant elevations of group II phospholipase A(2) concentrations were detected in the serum and amniotic fluid of women with preterm labor. Group II phospholipase A(2) concentration may be a useful indicator for preterm labor, and phospholipid metabolism is certainly activated both in preterm labor and in apparent inflammatory diseases.

Amniotic Fluid↗
PubMed2000

Oncostatin M is produced during pregnancy by decidual cells and stimulates the release of HCG.

Oncostatin M (OSM) is a member of the interleukin-6 superfamily and a multifunctional cytokine that effects the growth and differentiation of many different cell types. OSM concentrations in the sera of pregnant women were found to be significantly higher than those of non-pregnant women. Western blot analysis revealed that the OSM protein was present in the decidua and chorionic tissue in each trimester. Throughout pregnancy, the amount of the OSM protein in the decidua was larger than that in the chorionic tissue. Immunohistochemistry using an anti-OSM monoclonal antibody demonstrated that OSM was mainly localized in the decidual glands and stroma. OSM transcripts in the decidua and the chorionic tissue were detected during each trimester by reverse transcription-polymerase chain reaction (RT-PCR). The regulation of human chorionic gonadotrophin (HCG) release by the placenta in first trimester stimulated with recombinant OSM was also investigated. Stimulation of the placenta by OSM augmented HCG release in a time- and dose-dependent manner. HCG release induced by recombinant human OSM was completely blocked by antibodies against OSM and the signal transducer, gp130, but only partially inhibited by antibodies against the leukaemia inhibiting factor (LIF) receptor. These results suggest that OSM molecules produced by decidual glands and stromal cells during pregnancy have an important role in placental endocrine function.

Antibodies, Monoclonal↗
PubMed2000

Increased concentrations of secretory leukocyte protease inhibitor in peritoneal fluid of women with endometriosis.

Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. We investigated whether SLPI was present in the peritoneal fluid of women with endometriosis and to clarify the role of SLPI in the pathogenesis of endometriosis. Western blot analyses revealed that SLPI protein was detected as a 12 kDa band in peritoneal fluid. The peritoneal fluid concentrations of SLPI, elastase and interleukin-6 were assayed by enzyme-linked immunosorbent assays (ELISA). SLPI concentrations and the SLPI/elastase ratio in the peritoneal fluid of women with endometriosis were higher than in samples from women without endometriosis. There was no significant correlation between concentrations of SLPI and interleukin-6 in the peritoneal fluid. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining in peritoneal macrophages, but not lymphocytes. The present findings suggest that SLPI found in the peritoneal fluid of patients with endometriosis may contribute to the pathogenesis of endometriosis.

Adult↗
PubMed2000

Lymphocytic interstitial pneumonia: follow-up CT findings in 14 patients.

The aim of the present study was to assess the evolution of various computed tomographic (CT) findings of lymphocytic interstitial pneumonia (LIP) with determination of potentially reversible or irreversible features. The study included 14 patients with biopsy-proved LIP who had serial thin-section CT examination 4 to 82 months (median 13 months) apart. Initial and follow-up CT scans were evaluated independently and then directly compared with each other by two observers. The main parenchymal abnormalities on the initial CT scan consisted of ground-glass attenuation (n = 14), thickening of interlobular septa (n = 13), centrilobular nodules (n = 12), cystic airspaces (n = 10), and airspace consolidation (n = 4). On follow-up CT, nine patients improved, one showed no change, and four showed increased extent of disease. With the exception of cysts, the parenchymal opacities were reversible. On follow-up CT, new cysts were seen in three patients; these developed mainly in areas with centrilobular nodules on initial CT. Honeycombing was seen on follow-up CT in four patients; in three patients it developed in areas of airspace consolidation and in one patient it developed in an area with ground-glass attenuation on initial CT. The majority of patients with LIP improved on follow-up. However, airspace consolidation may progress to honeycombing and centrilobular nodules may precede cystic formation.

Adult↗
PubMed2000

Distribution of IkappaB proteins in gastric mucosa and other organs of mouse and gerbil.

The NF-kappaB/IkappaB complex is a major transcription regulator of inflammatory and immune responses. Helicobacter pylori infection causes chronic inflammation in gastric mucosa by inducing dissociation of the inhibitory IkappaB protein from the complex with a resulting increased expression of interleukin (IL)-8. To clarify which of several known IkappaB proteins could be involved in this inflammatory response, we undertook immunohistochemical examination of normal mouse stomach as well as other murine tissues for comparison, using polyclonal antibodies specific for alpha-, beta-, gamma-, and in-isoforms of IkappaB. The results showed strong immunoreactivity for the alpha-isoform in parietal cells and for the beta-isoform in pit cells of the stomach, along with the presence of these proteins in various other sites. Comparative staining revealed a similar but not identical distribution of IkappaB proteins in the Mongolian gerbil, a rodent model for H. pylori infection. The findings suggest that the alpha- and beta-isoforms are dominant IkappaB proteins in gastric parietal and foveolar cells, respectively, and point to a role for these transcription regulators in modulating pathological responses in stomach and other organs. (J Histochem Cytochem 48:191-199, 2000)

Animals↗
PubMed2000

[Clinical evaluation of hepatic blood flow and oxygen metabolism during thoracoabdominal aortic surgery using pulse dye-densitometry combined with hepatic venous oxygen saturation].

OBJECTIVE: There has been no report that pulse dye-densitometry (PDD), a novel non-invasive modality for monitoring hepatic blood flow (HBF), was applied during cardio-pulmonary bypass (CPB). We investigated weather PDD was useful to measure HBF during thoracoabdominal aortic surgery using partial CPB. Furthermore, HBF and hepatic metabolism were assessed during selective visceral perfusion or shunt using PDD, hepatic venous oxygen saturation (ShO2), and analysis of hepatic metabolic products. METHODS: A prospective study was carried out in eight patients who underwent thoracoabdominal aortic surgery from April 1998 to October 1999. Operative adjuncts were partial CPB with mild hypothermia in six (femoral veno-arterial bypass: FF group) and deep hypothermic circulatory arrest in two (DHCA group). Measurements were performed at following five time points; just before initiating CPB, just after establishing CPB, during selective visceral perfusion, during selective visceral shunt, and just after weaning CPB. RESULTS: Plasma clearance rate of indocyanine green measured by PDD well correlated with that obtained by in vitro spectrophotometry (p < 0.0001, R2 = 0.644). PDD demonstrated that decreased IIBF during selective visceral perfusion or shunt was well compensated by increased hepatic oxygen extraction rate in FF group and reduced oxygen consumption in DHCA group. Lactic acid extraction ratio and arterial ketone body ratio also decreased during this period. ShO2 during selective visceral shunt correlated with systemic systolic arterial pressure (SAP), and it showed a marked decrease under 20% when SAP was below 80 mmHg. Postoperative time course of serum total bilirubin and alanine aminotransferase of almost patients were within acceptable limits except the patient who required large amount of homologous blood transfusion. CONCLUSIONS: PDD proved to be a useful modality that enabled non-invasive monitoring of HBF even during partial CPB. Decreased HBF during selective visceral perfusion or shunt in thoracoabdominal aortic surgery was within physiological compensation, which led us conclude that it might be effective adjuncts, for visceral organ protection.

Adult↗
PubMed2000

[Sphincter-preserving surgery for lower rectal cancer aimed at improving postoperative bowel function].

Much attention has been focused on sphincter-preserving surgery for patients with lower rectal cancer, leading to renewed interest in the outcome of postoperative bowel function. Some patients who undergo sphincter-preserving surgery experience bowel dysfunction, such as frequent stools, severe constipation, soiling, and incontinence. These symptoms were thought to be correlate with lower resting pressure, lower rectal compliance, sensory disturbance of the anal canal, spasm, and delayed transit in the colon above the anastomosis. To improve postoperative bowel function, reconstruction with the colonic J-pouch has been performed, which results in a satisfactory functional outcome. About 80% of patients with a J-pouch were able to tolerate over 10 minutes after feeling the desire to defecate. An anorectal manometric study showed no abnormal spastic movement of the neorectum and a transit study showed that the J-pouch group was superior to the straight group with respect to the smoothness of movement of radiopaque markers from the cecum to anal ring, although a small number of markers were retained in the colonic J-pouch. Patients who received a colonic J-pouch had fewer defecation problems in daily life. Further study is need to improve postoperative bowel movement in patients who undergo sphincter-preserving surgery.

Anal Canal↗
PubMed2000

Unique postural control of upside-down swimming catfish, Synodontis nigriventris, not affected by the change of gravity.

In general, most fishes maintain a swimming posture with the dorsal side towards the water surface under normal gravity condition. In contrast to normal fishes, a catfish Synodontis nigriventris, shows a unique postural control. The catfish keeps its posture with the ventral side towards the water surface and the dorsal side towards water bottom under normal gravity. This evidence leads one to assume that the upside-down posture of the catfish is controlled by gravity sensation in a manner different from that of other fishes. However, it has remained unclear to date whether the gravity sensation contributes to the unique postural control of this catfish. We examined its postural control in intact and labyrinth-removed catfish using a clinostat which generates a specific gravity environment (pseudo-microgravity) on earth. In addition, we examined its postural control under microgravity during parabolic flights.

Animals↗
PubMed1999

Effects of macrophage colony-stimulating factor (M-CSF) on protease production from monocyte, macrophage and foam cell in vitro: a possible mechanism for anti-atherosclerotic effect of M-CSF.

M-CSF is a growth factor that stimulates proliferation and differentiation of monocyte/macrophage-lineage cells. In our previous studies, M-CSF regresses atherosclerotic lesions preformed in aorta of high cholesterol-fed rabbit. Immunohistochemical analysis indicated that extracellular matrix (ECM), such as collagen, was especially eliminated in the intima of atherosclerotic lesion. To define the collagen-lowering potential of M-CSF, we have studied the effects of M-CSF on production of collagen-degrading proteases, such as MMP-1, -9 and urokinase in vitro. Monocytes freshly isolated from human peripheral blood produced MMP-9, but not urokinase, and M-CSF enhanced MMP-9 production. Macrophages were prepared by culturing monocytes for 10 days in the presence or absence of M-CSF, and protease production was assayed. M-CSF augmented production of MMP-9 and urokinase in a dose-dependent manner. M-CSF also enhanced MMP-1 production of macrophages, but not significantly. Foam cells were prepared by culturing macrophages in the presence of acetyl LDL, and protease production from these cells were also elevated by M-CSF. These results suggest that M-CSF exogenously administered in atherosclerotic rabbits might regress the thickened intima by activating macrophages to degrade collagen accumulated in the lesion.

Animals↗
PubMed1999

Increase in hepatic content of oleic acid induced by dehydroepiandrosterone in the rat.

The effects of dehydroepiandrosterone (DHEA) on the acyl composition of lipids in rat liver were studied. The content of oleic acid (18:1) in hepatic lipids was increased markedly by feeding rats a diet containing 0.5% (w/w) DHEA for 14 days. Treatment of rats with DHEA caused an increase in the activity of the terminal desaturase of the stearoyl-CoA desaturation system, without changing either the activity of NADH-cytochrome b5 reductase or the microsomal content of cytochrome b5. Among the changes observed in hepatic lipids, the increase in 18:1 content in phosphatidylcholine (PtdCho) was the most prominent; an approximately 2.5-fold increase in the proportion of 18:1 was induced at position 2, but not at position 1, by DHEA. This selective elevation of 18:1 at position 2 of PtdCho seems to be produced by the concerted actions of the induced 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase and the induced stearoyl-CoA desaturase. The content of 18:1 in serum lipids was unchanged by DHEA treatment, suggesting that secretion of lipids containing 18:1 into the circulation was not affected by DHEA. These results suggest that the elevation of hepatic content of 18:1 caused by DHEA treatment is mainly due to the induction of stearoyl-CoA desaturase.

Animals↗
PubMed1999

PF1070A, a novel and potent inducer of the synthesis of metallothionein.

Using mouse Ltk(-) cells (L13-17 cells) that had been transfected with a plasmid in which the lacZ gene had been ligated downstream of 1.4 kbp of the sequence of the promoter of the mouse gene for metallothionein-I (MT-I) as a reporter gene, we examined 268 organic compounds for the ability to activate this promoter. We found that PF1070A, an antibiotic produced by Humicola sp., efficiently activated the MT promoter and caused marked enhancement of beta-galactosidase activity in L13-17 cells. The extent of activation by PF1070A was almost equivalent to that by of zinc ions, the most effective known inducer of the synthesis of MT. PF1070A also caused marked elevation of the levels of the mRNA for MT and of MT itself in L13-17 cells. A similar result was obtained in human HeLa-S3 cells. When PF1070A was added to the culture medium simultaneously with cadmium ion or dexamethasone, the level of expression of the reporter gene was markedly elevated, compared to the level of expression induced by each agent independently. The effect of PF1070A was reduced considerably by deletion of nucleotides at positions -150 and -149 from the site of initiation of transcription in the promoter region of the MT gene and also by deletion of the seven bases located at positions -49 to -43. Since no known cis element was found in these two regions, PF1070A might be a new type of inducer of MT synthesis that promotes expression of the gene for MT via a mechanism completely different from those exploited by other known agents. These results also suggest the presence of a system for control of transcription of the gene for MT that has not previously been recognized. Both cadmium ions and bismuth ions induce the synthesis of MT by acting on the metal response element (MRE). Bismuth ions had no significant effect on the promoter activity that had already reached a maximum level in response to treatment with the optimal concentration of cadmium ion. By contrast, PF1070A further and markedly increased the promoter activity. This result suggests that it is possible to increase the concentration of MT in tissue using PF1070A as an inducer even in cases where the MRE-mediated activation of the MT promoter has already been induced by the accumulation of cadmium, as is the case in a clinical setting. PF1070A may prove to be an excellent inducer of MT synthesis that is effective and clinically applicable. Moreover, use of PF1070A in combination with salts of heavy metals might be useful in controlling expression of a transfected gene that is regulated by the MT promoter since PF1070A can activate the MT promoter to an extent that cannot be achieved with heavy metal ions alone, when PF1070A is used in combination with zinc ions at a concentration of the latter considerably below the toxic level.

Animals↗
PubMed1999

The effect of labyrinthectomy on postural control of upside-down swimming catfish, Synodontis nigriventris, under pseudomicrogravity.

The catfish (Synodontis nigriventris) has a unique habitat of keeping an upside-down posture under normal gravity. We examined its postural control under pseudomicrogravity generated artificially, and the effect of unilateral labyrinthectomy on the postural control. The stable swimming posture under pseudomicrogravity was observed in the upside-down swimming catfish but not in the catfish (Corydoras paleatus), which has normal swimming habitat. Furthermore, although S. nigriventris but not C. paleatus could keep the stable swimming posture under normal gravity condition after unilateral labyrinthectomy, the labyrinthectomized fishes could not keep it under pseudomicrogravity. Seven days after the operation, S. nigriventris alone partially recovered the ability to keep an upside-down swimming posture, and did completely, to the control level, 25 days after the operation. Furthermore, when S. nigriventris was under pseudomicrogravity in dark conditions, it showed disturbed swimming postures. These results suggest that the upside-down swimming catfish has superior ability of postural control depending on the labyrinth.

Animals↗
PubMed1999

Inactivation of both alleles of the DPC4/SMAD4 gene in advanced colorectal cancers: identification of seven novel somatic mutations in tumors from Japanese patients.

Loss of heterozygosity (LOH) of loci on chromosome 18q occurs in a majority of colorectal cancers. The DPC4/SMAD4 gene, lying in close proximity to the DCC gene at 18q21.1, was recently identified as a candidate tumor suppressor for the genesis of pancreatic cancer as well as a predisposing gene for Juvenile Polyposis Syndrome (JPS). The gene product functions as a cytoplasmic mediator in the signaling pathway of transforming growth factor beta (TGF-beta). To investigate the potential role of DPC4/SMAD4 gene in colorectal cancers, we examined 73 tumors of clinical stages II or III from Japanese patients, for LOH at 18q21 and also for subtle mutations anywhere within the coding region of DPC4/SMAD4. LOH was identified in 50 (78%) of the 64 tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in seven of those tumors: two frameshift mutations, a 1-bp deletion (326 del T) in exon 8 and a 1-bp insertion (50-51 ins A) in exon 1; two nonsense mutations, Arg445Ter in exon 10 and Glu538Ter in exon 11; and three missense mutations, Asn129Lys in exon 2, Tyr95Asn in exon 2, and Asp355Glu in exon 8. Three of the seven mutations were observed in the mad homology 1 (MH1) domain encoded by exons 1 and 2. In all of the tumors carrying intragenic mutations of one allele, LOH analysis had shown that the other allele was missing. The results demonstrated that inactivation of both alleles of the DPC4/SMAD4 gene occurs in a substantial proportion of advanced colorectal cancers, and that the DPC4/SMAD4 gene probably exerts a tumor-suppressor effect for colorectal carcinogenesis that fulfills the criterion of the two-hit concept proposed by Knudson [A.G. Knudson, Hereditary cancer, oncogenes, and anti-oncogenes, Cancer Res. 45 (1985) 1437-1443.].

Alleles↗
PubMed1999

Rectal adenocarcinoid with lymph node metastasis.

We describe a case of a rare variant of a rectal carcinoid tumor that showed mucous gland differentiation accompanied by a lymph node metastasis with a histological appearance similar to that of the primary site. The tumor consisted of a typical argyrophilic carcinoid component and of goblet cell glands. The carcinoid component was positive for neuron-specific enolase, chromogranin A and synaptophysin. The goblet cells stained positively with periodic acid-Schiff (PAS) and alcian blue, and expressed carcinoembryonic antigen, but were negative for neuroendocrine markers. This case suggests that carcinoid tumor can differentiate towards mucus glands, which can also be found in the metastatic site.

Adenocarcinoma↗