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Biomedical subjects

S Fukumoto

Publications and source records attributed to S Fukumoto.

At least 109 records · Page 6Linked to original sources
PubMed1997

Efficacy of doramectin against intestinal nematodes and sarcoptic manage mites in naturally infected swine.

Endectocidal efficacy of doramectin administered intramuscularly at a dosage of 300 micrograms/kg was evaluated in 464 pigs naturally infected with intestinal nematodes or mange mites on 14 commercial farms in Japan. By doramectin treatment, fecal egg counts were reduced > 99% for Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, and Trichuris suis; worm counts of T. suis and mite counts of Sarcoptes scabiei reduced 90.1% on Day 21 and 99.5% on Day 28 following treatment, respectively.

Animals↗
PubMed1997

A new synthetic steroid, osaterone acetate (TZP-4238), increases cortical bone mass and strength by enhancing bone formation in ovariectomized rats.

A new synthetic steroid, 17 alpha-acetoxy-chloro-2-oxa-4,6-pregnadiene-3,20-dione (osaterone acetate, TZP-4238), has a potent antiandrogenic and gestagenic action with virtually no estrogenic and androgenic activity in their classical target organs. In the present study, the effects of TZP-4238 on the structure, strength, and turnover of the rat long bones were examined. Female Wistar rats at 12 weeks of age were ovariectomized (OVX) and treated with TZP-4238 or 17 beta-estradiol (E2) every day for 12 weeks. TZP-4238 significantly increased the diameters and maintained bone mineral density (BMD) of the femur of OVX rats. Although the BMD of the total femur was higher in E2-treated rats than that in TZP-treated rats, E2 did not increase the diameters of the femurs. To examine the effects of TZP-4238 and E2 on the BMD of different regions of the femur, the BMD was further analyzed by dividing it into 20 regions of equal longitudinal length. E2 increased the BMD of the distal and proximal metaphysis, regions rich in trabecular bone, but had no effect on the BMD of the femoral diaphysis compared with OVX control rats. In contrast, 2.5 and 12.5 mg/kg TZP-4238 increased the BMD of the femoral diaphysis, regions rich in cortical bone, but did not affect the BMD at the distal metaphysis. In agreement with the changes in the BMD of different regions of the femur, TZP-4238 but not E2 increased the physical strength of the femoral diaphysis assessed by a three-point bending test. Histomorphometric analyses of the cross-sections of the tibia revealed that TZP-4238 increased but E2 reduced the periosteal bone formation rate compared with OVX rats. In addition, TZP-4238 caused an increase in serum bone alkaline phosphatase with only a mild and transient decrease in urinary deoxypyridinoline excretion, while E2 reduced both of these parameters. These results demonstrate that TZP-4238 increases the dimension, BMD, and physical strength of the rat long bones by enhancing cortical bone formation, while estrogen maintains trabecular BMD by inhibiting bone resorption. Because the physical strength of long bones is affected by cortical bone mass and geometry, the effect of TZP-4238 on cortical bone may have a potential for the treatment of osteoporosis with reduced cortical bone formation.

Androgen Antagonists↗
PubMed1997

Inhibition of bone resorption by pamidronate cannot restore normal gain in cortical bone mass and strength in tail-suspended rapidly growing rats.

To clarify how the changes in bone formation and resorption affect bone volume and strength after mechanical unloading, the effect of inhibition of bone resorption by a potent bisphosphonate, pamidronate, on bone mineral density (BMD), histology, and strength of hind limb bones was examined using tail-suspended growing rats. Tail suspension for 14 days reduced the gain in the BMD of the femur at both the metaphysis rich in trabecular bone and the diaphysis rich in cortical bone. Treatment with pamidronate increased the total BMD as well as that of the metaphysis of the femur but had almost no effect on the BMD of the diaphysis in both control and tail-suspended rats. Histological examinations revealed that 14-day tail suspension caused a loss of secondary cancellous bone with a reduction in the trabecular number and thickness in comparison with control rats. In the femoral diaphysis, the diameter and cortical bone thickness increased to a lesser degree in tail-suspended rats when compared with rats without tail suspension, and a marked reduction in bone formation and the layers of alkaline phosphatase-positive cells was observed at the periosteal side. Pamidronate treatment increased secondary cancellous bone but could not restore normal growth-induced periosteal bone apposition and bone strength. Because the material strength of the femoral diaphysis at the tissue level was not affected by pamidronate treatment, the inability of pamidronate to prevent the reduction in physical strength of the femoral diaphysis does not appear to be due to a change in the quality of newly formed bone. These results demonstrate that tail suspension reduces the growth-induced periosteal modelling drift and that the antiresorptive agent pamidronate is unable to restore normal periosteal bone apposition.

Amino Acids↗
PubMed1997

Peripheral primitive neuroectodermal tumor involving the paravertebral and retroperitoneal regions.

A rare case of peripheral primitive neuroectodermal tumor (PNET) is reported. A 68-year-old woman complaining of lumbago was admitted to our hospital. Diagnosis was made based on pathological findings characterized by Homer Wright-type rosettes. Ultrastructural examination showed the presence of neurosecretory granules and short cytoplasmic processes, which were highly suggestive of neural differentiation. Chromosomal analysis of the neoplastic cells revealed translocation (11;22)(q24;q12), which is often found in Ewing's sarcoma and Askin tumor. These results strengthen the hypothesis of a common histogenesis for these small round cell tumors, and suggest common oncogenesis for these neoplasms.

Aged↗
PubMed1997

Helicobacter pylori infection accelerates gene expression of glicentin in the gastric mucosa. Its association with intestinal metaplasia of the stomach.

BACKGROUND: Glicentin is an intestinal polypeptide hormone which seems to promote intestinal metaplasia (IM) in the gastric mucosa. The aim of this study was to clarify whether Helicobacter pylori infection accelerates glicentin gene expression. METHOD: Glicentin mRNA was investigated by reverse-transcription polymerase chain reaction using gastric biopsies from 47 patients examined endoscopically and denying IM. RESULTS: IM was observed in 18 (38.3%) cases histologically, but not in the other 29 (62.7%). Glicentin mRNA was significantly correlated with histological IM (P < 0.01) and was positively correlated with H. pylori infection (P < 0.05). CONCLUSION: Our results indicate that H. pylori infection is associated with the induction of glicentin in the gastric mucosa, thus supporting the hypothesis that H. pylori infection accelerates IM of the stomach.

Adult↗
PubMed1996

Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system.

Gangliosides, sialic acid-containing glycosphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to lay essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted beta 1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2.4.1.92) gene. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.

Animals↗
PubMed1996

Angiotensin-converting enzyme gene polymorphism is associated with carotid arterial wall thickness in non-insulin-dependent diabetic patients.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the ACE gene has been shown to be associated with cardiovascular disease in healthy subjects as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM). We investigated the relationship between the ACE gene polymorphism and the wall thickness of both carotid and femoral arteries in NIDDM patients. METHODS AND RESULTS: We measured the intimal plus medial thickness (IMT) of both carotid and femoral arteries using high-resolution B-mode ultrasonography in 288 Japanese NIDDM patients (160 men, 128 women). No significant differences among the three genotypes were found with respect to age, sex, duration of diabetes, body mass index, blood pressure, plasma glucose, hemoglobin AIC, total cholesterol, triglycerides, HDL cholesterol, or cigarette-years. Plasma ACE levels were strongly associated with I/D polymorphism, with an additive effect of the D alleles. The carotid IMT of the patients carrying the D allele (DD+ID genotype) was significantly higher than that of the patients not carrying the D allele (II genotype) (P = .037), whereas the femoral IMT was not affected by the I/D polymorphism. Multiple regression analysis demonstrated that the risk factors for carotid IMT of patients with NIDDM were age, non-HDL cholesterol, and D allele of the ACE gene (R2 = .155, P < .0001). CONCLUSIONS: The D allele of the ACE gene may be a risk factor for the development of wall thickening of the carotid but not the femoral artery in NIDDM patients.

Adolescent↗
PubMed1996

Site restricted and neuron dominant expression of alpha 2,8sialyltransferase gene in the adult mouse brain and retina.

Gene expression of the alpha 2,8sialyltransferase (alpha 2,8S-T) responsible for GD3 synthesis in the adult mouse brain and retina was analysed by reverse transcription-polymerase chain reaction/Southern blotting (RT-PCR/Southern) and in situ hybridization. Among various portions of the brain, high levels of 9.5 kb mRNA were observed in the retina and midbrain. Results of RT-PCR/Southern did not necessarily correlate with the enzyme activities in the individual sites. In situ hybridization analysis revealed that this gene was characteristically expressed in the inner segment of photoreceptor cells, some nuclei in the midbrain, cranial nerve nuclei in the pons-medulla, Purkinje cells in the cerebellum, pyramidal cells of the hippocampus and granular cells of the dentate gyrus. In the retina, the alpha 2,8S-T gene was broadly expressed over the layers during development, and retained high expression levels in the photoreceptor cells of adult mice consistent with high expression of GD3. Destruction of neurons in the hippocampus and dentate gyrus by injection of kainic acid and colchicine respectively resulted in the disappearance of the hybridization signal, suggesting that the alpha 2,8S-T gene was mainly expressed by neurons.

Aging↗
PubMed1996

Growth factor mRNA expression in normal colorectal mucosa and in uninvolved mucosa from ulcerative colitis patients.

This study was carried out to investigate the expression of various growth factors (GFs) involved in mucosal healing and thereby to clarify whether there are potential differences in the expression of GFs between normal colonic mucosa and the uninvolved mucosa of ulcerative colitis (UC). GF mRNA was investigated by reverse transcription polymerase chain reaction in colorectal biopsies from 20 normal controls and 15 UC patients. The positive rates (%) for mRNA expression for normal/UC were: epidermal growth factor (EGF) 65/53, transforming growth factor (TGF)-alpha 100/87, TGF-beta 1 60/33, insulin like growth factor-I 45/33, platelet-derived growth factor-A 55/67, basic fibroblast growth factor 0/0, hepatocyte growth factor (HGF) 50/53, EGF receptor 20/27, erb-B2 75/73, and HGF receptor (c-MET) 55/67. Semiquantitation of mRNA showed significantly lower expression of TGF-beta 1 (P < 0.05) in UC. Differences in expression and mRNA levels were not statistically significant for any other GFs. Our results indicate that mucosa in chronic persistent UC has a low basal expression of TGF-beta 1 mRNA, and, since TGF-beta 1 is a multifunctional GF that plays important roles in regulating repair and regeneration following tissue injury, this low expression may be partially responsible for the intractability of the disease.

Case-Control Studies↗
PubMed1996

Cytokine gene expression in the gastric mucosa: its role in chronic gastritis.

There have been few studies of cytokine expression in the gastric mucosa of patients with chronic gastritis. In the present study, to elucidate the expression of cytokines in the gastric mucosa and the immunopathological roles played by these cytokines in chronic gastritis, we investigated cytokine gene expression, by reverse transcription polymerase chain reaction, in gastric biopsy specimens obtained from 29 endoscopically normal patients with chronic gastritis. The cytokines examined and the mRNA positivity were: interleukin (IL)-1 beta (21%), IL-2 (0%), IL-3 (7%), IL-4 (41%), IL-5 (17%), IL-6 (53%), IL-8 (98%), interferon gamma (IFN-gamma) (69%), and tumor necrosis factor alpha (TNF-alpha) (24%). Although the histological severity of the gastritis was closely associated with Helicobacter pylori infection, the positivities of these cytokine mRNAs did not show a relationship with either H. pylori infection or with histological inflammation. Our findings suggest that the gastric mucosa responds to all exogenous antigens, including H. pylori, in the same fashion immunologically, and that these cytokines do not contribute to the induction of inflammation associated with H. pylori infection.

Female↗
PubMed1996

Expression of interferon-alpha receptor mRNA in the liver in chronic liver diseases associated with hepatitis C virus: relation to effectiveness of interferon therapy.

To investigate whether interferon-alpha receptor (IFN-alpha Rc) expression was related to the effectiveness of interferon therapy in hepatitis C virus (HCV)-associated chronic liver disease (CLD). IFN-alpha Rc mRNA was investigated by reverse transcription polymerase chain reaction (RT-PCR) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 40 patients with HCV-associated CLD who subsequently received IFN-alpha therapy. IFN-alpha Rc mRNA in the liver was detected in 18 of 20 (90%) responders to IFN and in 5 of 20 (25%) non-responders (P < 0.01). In PBMCs, IFN-alpha Rc mRNA was detected in all patients regardless of response to IFN. Increased histological hepatitis activity and liver fibrosis were significantly related to the absence of IFN-alpha Rc mRNA. The HCV-RNA genotype showed no significant relationship to IFN-alpha Rc mRNA expression. Our results suggest that IFN-alpha Rc mRNA expression in the liver, but not in PBMCs, is closely associated with the effectiveness of IFN-alpha therapy in HCV-associated CLD.

Antiviral Agents↗
PubMed1996

Angiotensin converting enzyme gene polymorphism and renal artery resistance in patients with insulin dependent diabetes mellitus.

The present study was carried out to elucidate whether renal hemodynamic changes are associated with angiotensin converting enzyme (ACE) gene polymorphism in patients with insulin dependent diabetes mellitus (IDDM). We studied 32 Japanese patients with IDDM (aged 15 +/- 3 years in mean +/- SD) without renal failure or retinopathy. Renal hemodynamics were examined by duplex Doppler sonography and arterial resistance index was calculated. ACE genotypes were determined by polymerase chain reaction amplification. Resistance index (RI) of arcuate arteries in IDDM patients with DD genotype was significantly elevated, being 0.64 +/- 0.04, 0.66 +/- 0.05, and 0.71 +/- 0.05 for II, ID and DD genotype groups, respectively (II vs. DD, p < 0.02). In patients with DD genotype with normoalbuminuria (n = 27), it was also significantly elevated in DD genotype patients (II vs. DD, p < 0.02). In addition, multiple regression analysis with a forward elimination procedure showed that only the ACE genotype was associated with RI of arcuate arteries (R2 = 0.24, p < 0.01) among the parameters of sex, age, IDDM duration, body mass index, HbA1c, plasma glucose levels, serum levels of total cholesterol and creatinine, urinary albumin excretion index, mean blood pressure and ACE genotype. The present study demonstrated that renal arterial resistance is elevated in IDDM patients with DD genotype. ACE gene polymorphism which could be linked to intrarenal circulatory disturbance may be associated with the initiation and progression of diabetic nephropathy.

Adolescent↗
PubMed1996

Heterogeneity in the expression pattern of two ganglioside synthase genes during mouse brain development.

Gangliosides are synthesized by sequential catalytic reaction of multiple glycosyltransferases. GM2/GD2 synthase and GD3 synthase are key enzymes for ganglioside synthesis, because their relative activities regulate the main profiles of ganglioside expression. Mouse GD3 synthase (EC 2.4.99.8) cDNA was cloned by eukaryotic expression cloning, and its mRNA expression as well as that of GM2/GD2 synthase gene during the development of the mouse CNS was analyzed by using northern blotting, reverse transcription-polymerase chain reaction, and in situ hybridization. When brain tissue was analyzed as a whole mass, a typical pattern corresponding to the reported findings obtained by biochemical analyses was observed, i.e., high expression of GD3 synthase gene in the early stage and gradual increase of GM2/GD2 synthase gene expression in the late stage of the development. However, the results of in situ hybridization of these two genes revealed that the expression kinetics of these two genes were heterogeneous among various sites in the brain under development. These findings suggest that various expression patterns of the two genes reflect differences in the course of the development of individual sites, and also different ganglioside components are required in individual portions of the brain for development and maintenance of the function.

Amino Acid Sequence↗
PubMed1996

Hepatitis B virus with X gene mutation is associated with the majority of serologically "silent" non-b, non-c chronic hepatitis.

Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically "silent" non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C-terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically "silent" NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.

Adult↗
PubMed1996

Relationship between the intrahepatic expression of interferon-alpha receptor mRNA and the histological progress of hepatitis C virus-associated chronic liver diseases.

Histological progress is one of the predictors of an unfavourable response to interferon (IFN) therapy in hepatitis C virus (HCV)-associated chronic liver diseases (CLD). The aim of the present study was to investigate whether histological progress has an association with the expression of IFN receptor (IFN-Rc) in the liver. Expression of mRNA of the IFN-Rc for IFN-alpha was investigated by reverse transcription polymerase chain reaction using liver biopsy specimens from 37 HCV-associated CLD comprising 11 liver cirrhosis (LC) and 26 chronic hepatitis (CH) cases. IFN-alpha and IFN-beta mRNA were detected in over 90% of subjects. In contrast, the detection rate of IFN-Rc mRNA in chronic persistent hepatitis, chronic hepatitis 2A, chronic hepatitis 2B and liver cirrhosis (LC) was 100, 71.4, 22.2 and 0%, respectively. The absence of IFN-Rc mRNA was significantly associated with the severity of fibrosis of the liver. These results indicated that IFN-Rc expression decreases with the histological progress of the disease, suggesting that lower expression of IFN-Rc mRNA may be partially responsible for the poor IFN response in LC.

Adult↗
PubMed1996

Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon efficacy in chronic hepatitis C.

To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1 beta, -2, -4, -6, -8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta mRNAs were investigated semiquantitatively by reverse transcription polymerase chain reaction using serial liver biopsies taken before and after IFN-alpha treatment from 24 patients with CH(C), including 12 responders and 12 non-responders. Before IFN treatment, IL-2, TNF-beta, IFN-gamma and IL-8 mRNA were associated with severe hepatitis activity whereas IL-4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL-2, TNF-beta and IFN-gamma mRNAs were significantly greater in IFN non-responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro-inflammatory cytokines, whereas non-responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN-alpha treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN-alpha that reduces hepatitis activity, aside from an anti-viral effect. A difference in cytokine network may be involved in IFN response in CH(C).

Adult↗
PubMed1996

The fumagillin analogue TNP-470 inhibits DNA synthesis of vascular smooth muscle cells stimulated by platelet-derived growth factor and insulin-like growth factor-I. Possible involvement of cyclin-dependent kinase 2.

The effect of an angiogenesis inhibitor, TNP-470, on DNA synthesis and its underlying signaling cascades stimulated by platelet-derived growth factor (PDGF)-BB and insulin-like growth factor (IGF)-I were examined in bovine vascular smooth muscle cells (SMCs). PDGF-BB (10 ng/mL)- and IGF-I (100 ng/mL)-stimulated increase in DNA synthesis was completely abolished by simultaneous treatment with TNP-470 (1.0 ng/mL). TNP-470 had no effects on PDGF receptor autophosphorylation or early signal transduction, such as activation of mitogen-activated protein kinase and immediate early gene expression. PDGF-BB induced an increase in mRNA levels of cyclin D1, cyclin-dependent kinase (cdk) 4, and cdk2, as well as the activity of cdk2, which preceded the G1/S boundary, as estimated by the kinetics of DNA synthesis. The PDGF-BB-induced activation of cdk2 was inhibited by TNP-470, which was correlated with decreased cdk2 mRNA levels. In contrast, TNP-470 had no or less marked effect on cyclin D1 and cdk4 mRNA levels induced by PDGF-BB. TNP-470 also inhibited a much smaller increase in cdk2 mRNA levels and activation stimulated by IGF-I. In conclusion, TNP-470 potently inhibits DNA synthesis of SMCs, and this inhibition is associated with decreased levels of cdk2 mRNA and activity.

Animals↗