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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 973 records · Page 54Linked to original sources
PubMed1996

Neural and skin cell-specific expression pattern conferred by steel factor regulatory sequence in transgenic mice.

We have produced transgenic mice expressing a lacZ reporter gene under the control of a fragment of a Steel factor (SLF). The function of this gene is essential for the development of hematopoietic cells, germ cells, melanocytes and pacemaker cells of the intestine. The expression of the transgene, containing 2 kb DNA 5' regulatory sequence, was restricted to neural and skin tissues in appropriate spatial and temporal pattern compared with endogenous SLF mRNA expression. This indicates that the regulatory elements necessary for the neural and skin specific expression are present in this 2 kb DNA sequence, although strong position-dependence of transgene expression was observed. As we could not detect transgene expression in hematopoietic tissues and germ cells after extending 10 kb upstream, elements important for these organs must reside in other regions. Our results indicate that neural crest derived enteric ganglion cells provide SLF to the neighboring pace maker cells expressing c-kit, the receptor for SLF. Cells expressing the transgene in the intestine are ganglion cells derived from neural crest since homozygosity for the lethal spotting (Is) mutation results in loss of such ganglion cells in transgenic mice. We have also shown that the dermal papillae of the hair follicle expresses the transgene, suggesting its roles to support the c-kit dependent growth and development of melanocytes in the hair follicle.

Animals↗
PubMed1996

Successful repair of intimal dissection following coronary angioplasty with a 48-hour inflation of spiral inflation coil and local delivery of heparin.

We report on an unusual patient with a threatened occlusive dissection, in whom prolonged (48-hr) inflation of a balloon catheter with localized heparin infusion proved successful. This intracoronary infusion catheter maintained distal coronary flow on a unique spiral coil design, and may provide an alternative or a bridge to emergency operation or stent implantation.

Aged↗
PubMed1996

Stereoselective pharmacokinetics of [14C]-labeled KE-298, a new anti-rheumatic drug, in rats.

The stereoselective pharmacokinetics of two enantiomers of [14C]-labeled KE-298 [2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanonic acid] were investigated in rats. The blood levels of radioactivity after the oral administration of (+)-(S)-[14C]KE-298 were higher than that for (-)-(R)-[14C]KE-298; the AUC of the former was approximately twice that of the latter. No significant stereoselectivity was observed in absorption rate. The tissue/ plasma level ratios at 30 min after oral administration of (-)-(R)-[14C]KE-298 in the liver and kidney, the major metabolic and/or excretory organs, were 2 to 3 times higher than those for (+)-(S)-[14C]KE-298. Neither was evidence of stereoselectivity found in the excretion of radioactivity. During incubation with isolated rat hepatocytes in vitro, the metabolic rates of KE-298 enantiomers were not significantly different. Plasma protein binding 20 min after the oral administration of (+)-(S)-[14C]KE-298 and (-)-(R)-[14C]KE-298 was 99.3% and 97.0% respectively. Comparing the unbound fraction, (-)-(R)-[14C]KE-298 was approximately 4 times higher than (+)-(S)-[14C]KE-298. In order to make clear the relationship between stereoselective pharmacokinetics and protein binding for [14C]KE-298, the comparative pharmacokinetics of (+)-(S)-[14C]KE-298 and (-)-(R)-[14C]KE-298 were investigated in analbuminemic rats. In these animals, no evidence of stereoselectivity was found for either blood level-time profiles or plasma protein binding. These results revealed that the stereoselective pharmacokinetics of KE-298 in rats might be due to enantiomeric differences in binding to plasma albumin.

Animals↗
PubMed1996

Effects of beta-blockers on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts.

Previous reports, based on clinical trials and animal experiments, suggest that beta-blockers may be useful in the prevention of atherosclerosis. Betaxolol, a new beta1-selective blocker, was shown to decrease plasma total and LDL cholesterol levels or to have no adverse effect on those [1-4]. While many reports deal with metabolism of triglyceride and high density lipoprotein, fewer publications about cholesterol metabolism are currently available. To clarify the mechanism by which beta-blockers affect lipid metabolism, we examined the effects of beta-blockers on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts. L-propranolol, a nonselective beta-blocker, increased HMG CoA reductase activity and decreased LDL receptor activity. However, d-propranolol had no major effects on HMG CoA reductase activity. These results suggest that beta-blockers act on HMG CoA reductase through the beta receptors. Beta1-blocking action should decrease HMG CoA reductase activity and increase LDL receptor activity. In fact, betaxolol, a beta1-selective blocker, decreased HMG CoA reductase activity and increased LDL receptor activity, but metoprolol had no major effect. We speculate that the discrepancy between betaxolol and metoprolol in the effect on HMG CoA reductase and the LDL receptor might be due to the difference of the extent of beta1-selectivity. We conclude that beta1-selective blockers are antihypertensive agents potentially valuable in the prevention of atherosclerosis.

Adrenergic beta-Antagonists↗
PubMed1996

Early results of a reinforced biosynthetic ovine collagen vascular prosthesis for small arterial reconstruction.

The efficacy of a reinforced biosynthetic ovine collagen (RBOC) vascular prosthesis developed for small arterial reconstruction was assessed by examining 30 grafts in 29 patients with arteriosclerosis obliterans. The operative procedures performed were femorofemoral bypass in 2 patients, above-knee femoropopliteal bypass in 28 patients, and below-knee femoropopliteal bypass in 1 patient. Femoropopliteal bypass was simultaneously performed in two patients undergoing femorofemoral bypass using one or two grafts. The indications for surgery were intermittent claudication in 27 patients and to salvage the limb in 2 patients. The longest follow-up period was 49 months, and there were six graft failures, occurring 1, 1, 9, 17, 17, and 23 months after implantation, respectively; caused by compression of the graft from outside in two, infection in one, anastomotic intimal hyperplasia in one, and unknown factors in two. Thus, the primary cumulative patency rate for above-knee femoropopliteal bypass at 3 years was 83.7%, and the secondary patency rate was 91.2%. No aneurysmal change was observed. Moreover, the RBOC was able to be used without preclotting, and its handling and suturing characteristics were satisfactory. Our findings suggest that this vascular prosthesis may be an acceptable alternative for above-knee femoropopliteal bypass.

Aged↗
PubMed1996

High serum alpha-fetoprotein concentration associated with pseudoinfarction of a cirrhotic liver: report of a case.

We report herein the case of a 65-year-old man with cirrhosis of the liver in whom a portal vein thrombus was found to be the cause of a marked elevation in serum alpha-fetoprotein (AFP). The patient presented with fever and abdominal pain, and a diagnostic work-up revealed a liver mass and an increased serum AFP concentration of 91,000 ng/ml. The mass gradually regressed, and the AFP concentration simultaneously decreased to 163 ng/ml. However, because hepatocellular carcinoma (HCC) could not be ruled out, a partial hepatectomy was performed. Histological examination of the resected specimen revealed a thrombus of the portal vein surrounded by the fibrosis associated with liver cirrhosis, but no neoplastic lesion was found. Thus, portal thrombus associated with liver cirrhosis might induce an extremely high level of AFP production.

Aged↗
PubMed1996

Influence of glutamine-supplemented parenteral nutrition on intestinal amino acid metabolism in rats after small bowel resection.

Glutamine (Gln)-supplemented total parenteral nutrition (TPN) has been shown to improve mucosal adaptation after massive small bowel resection (SBR); however, its influences on intestinal amino acid metabolism remain unknown. In this study, intestinal amino acid flux, circulating plasma aminogram, mucosal glutaminase activity and protein, and DNA content were measured 7 days after massive SBR in rats receiving either standard (Std) or Gln-supplemented TPN. Sham-operated rats and rats fed chow after enterectomy served as controls. The uptake of Gln and the release of citrulline (Cit) by the remaining intestine was significantly decreased, with reduced mucosal glutaminase activity after SBR in the Chow and Std-TPN groups. Glutamine supplementation resulted in significantly increased gut Gln uptake compared with Std-TPN (P < 0.01). Mucosal glutaminase activity, mucosal protein, and DNA content was also increased by Gln; however, the gut release of Cit remained unchanged (P > 0.05). The subsequent decrease in circulating arginine (Arg) in the Gln-TPN group compared with the Std-TPN group (P < 0.05) was attributed to an insufficient exogenous supply. These findings show that Gln-supplemented TPN improves mucosal growth and gut Gln uptake after SBR. However, the intestinal production of Cit, which remained low in both TPN groups, may lead to an insufficiency of endogenous Arg synthesis. Thus, both Gln and Arg may be essential amino acids after SBR.

Amino Acids↗
PubMed1996

Source models of sleep spindles using MEG and EEG measurements.

MEG measurements can detect brain sources that are difficult to detect with EEG measurements. The purpose of this study was to investigate models of sleep spindles using both MEG and EEG activities that had been recorded simultaneously. The components of magnetic fields perpendicular to the surface of the head were measured using a DC-SQUID with a first-derivative gradiometer. We propose three models for sleep spindles. In the first model, the source slides into the superficial region of the head so as to be perpendicular to it's surface, and with this model, the power spectrum of the MEG is decreased. In the second model, the source slides into the deeper structures, so that it is perpendicular to the surface. Here, the power spectra of both the MEG and EEG are decreased. The third model has source perpendicular to the surface, leaning and sliding into the deeper structures. Here, the power spectrum of the EEG is decreased but that of the MEG is not.

Brain↗
PubMed1996

Genetic basis of the neurovirulence of type 1 polioviruses isolated from vaccine-associated paralytic patients.

We examined four type 1 polioviruses isolated from the stools of patients with vaccine-associated paralytic poliomyelitis in China. All of these isolates were shown to be Sabin derived viruses by restriction fragment length polymorphism assay after polymerase chain reaction and by sequencing of the viral genome encoding the viral coat protein, VP1. However, the same analysis of the 3D coding region suggested that two of the four isolates had the sequence of wild type poliovirus in the tested region. Furthermore there were also point mutations in the 5' non-coding region. One was a single base change from U to C at nucleotide position 525, and the other three were from G to A at position 480. All the four strains were more neurovirulent that Sabin type 1 virus in transgenic mice with human poliovirus receptor gene. The data showed that the nucleotide positions of type 1 poliovirus which were identified to be in favor of the high neurovirulence were indeed changed during natural transmission, and suggested that the point mutation alone or a recombination of the vaccine type with wild type genome results in an acquisition of neurovirulence.

Animals↗
PubMed1996

Autocrine growth inhibition of IL-1 beta-treated cultured human aortic smooth muscle cells: possible role of nitric oxide.

This study was designed to investigate whether interleukin (IL)-1 beta would stimulate nitric oxide (NO) production in cultured aortic vascular smooth muscle cells (VSMCs), and to determine the basic effect of the liberated NO on VSMC proliferation. NO production was estimated from nitrite concentration of culture medium in multi-well plates, determined by the Griess method. VSMCs were IL-1 beta-pretreated in insert cups, and co-cultured with untreated VSMC in the wells. 3H-thymidine (3H-Tdr) incorporation into the VSMC in wells was evaluated for VSMC proliferative activity. IL-1 beta stimulated NO production in VSMCs in a concentration-dependent manner. This effect was further enhanced by the addition of a membrane-permeable cyclic adenosine monophosphate derivative, dibutyryl cyclic AMP (db-cAMP), and was significantly reduced by concomitant use of an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). IL-1 beta-pretreated VSMCs significantly inhibited 3H-Tdr incorporation of the co-cultured VSMC. This inhibitory effect was significantly enhanced by the addition of db-cAMP, while this inhibition was significantly decreased by preincubation with L-NAME, and was abolished in the L-arginine-free medium. These results suggest that, in human VSMC, IL-1 beta stimulates NO production that is enhanced by intracellular cAMP accumulation, and that the liberated NO inhibits further VSMC proliferation in an autocrine fashion.

Aorta↗
PubMed1996

Paracrine effect of human vascular endothelial cells on human vascular smooth muscle cell proliferation: transmembrane co-culture method.

To investigate the role endothelial cells have on underlying smooth muscle cell proliferation, human aortic vascular smooth muscle cells were co-cultured with human aortic endothelial cells at different cell densities, using a transmembrane co-culture method. Subconfluent endothelial cells subseeded at low (0.5 x 10(4) cells/well) and medium densities (2.0 x 10(4) cells/well) stimulated smooth muscle cell proliferation by 43 +/- 14% (P < 0.01) and 39 +/- 8% (P < 0.02), respectively. However, this stimulatory effect on smooth muscle cell proliferation was not evident in confluent endothelial cells subseeded at high cell density (8.0 x 10(4) cells/well). Treatment of smooth muscle cells with trapidil, at 10(-6) M, for anti-platelet derived growth factor (PDGF) effect or with endothelin-1 receptor blocker FR 139317, at 10(-6) M failed to inhibit this stimulatory effect. These results imply that subconfluent human endothelial cells are able to exert a stimulatory effect on human smooth muscle cell proliferation, and that this endothelial paracrine growth effect may not be mediated by endothelin or PDGF.

Aorta↗
PubMed1996

Role of platelet-activating factor in pathogenesis of galactosamine-lipopolysaccharide-induced liver injury.

In an attempt to clarify the role of platelet-activating factor (PAF) in the pathogenesis of hepatic injury induced by galactosamine (GalN) plus lipopolysaccharide (LPS), effects of WEB 2086 (PAF receptor antagonist) on hepatic injury in vivo as well as on neutrophil adherence to hepatic endothelial cells in vitro have been investigated, as we have recently clarified the role of neutrophils in this experimental model of hepatic injury. Although an enhanced serum TNF-alpha level after GalN-LPS administration was not reduced by WEB 2086, hepatic injury and hepatic neutrophil accumulation in the liver after GalN-LPS administration were attenuated by WEB 2086. An in vitro study revealed that an enhanced neutrophil adhesion to hepatic endothelial cells by stimulation with the sera that were collected from the GalN-LPS-treated rats, was reduced in the presence of WEB 2086 in a dose-dependent manner. In addition, LPS, TNF-alpha, and PAF were found to enhance the neutrophil adherence to hepatic endothelial cells, which was reduced in the presence of WEB 2086. These results suggest that PAF play an important role in the GalN-LPS induced hepatic injury and that PAF receptor antagonist reduces the neutrophil adherence to hepatic endothelial cells in the liver.

Animals↗
PubMed1996

Gastric duplication cyst: evaluation by endoscopic ultrasonography and magnetic resonance imaging.

Endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) are becoming popular methods for examining tumorous lesions along the upper gastrointestinal tract. Though duplication cysts are uncommon, EUS findings from gastric duplication cysts have accumulated and proven very useful for preoperative diagnosis. There have been few reports, however, concerning MRI findings from these cysts. We report herein the case of a 25-year-old man with a gastric duplication cyst. EUS demonstrated a cystic mass adjacent to the fourth layer of the stomach wall. MRI revealed a cyst containing low signal-intensity fluid and high signal-intensity fluid separated by levels. In addition to the characteristic findings from preoperative examinations, the unique histological findings from the cyst are also described.

Adult↗
PubMed1996

Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa.

A microorganism with close immunohistological and genetic resemblance to Helicobacter pylori was found in the resected gallbladder mucosa of a 41-year-old woman. The woman was admitted to hospital complaining of fever and right hypochondrial pain. Cholecystectomy was carried out under the diagnosis of gallstones and cholecystitis. A microorganism resembling H. pylori (stained with H&E, Giemsa, and Wartin-Starry) was detected incidentally on pathological examination. The microorganism was also positive for immunohistochemical staining. An amplification reaction was seen on genetic examination by the polymerase chain reaction (PCR) method (urease beta-genes). Our findings suggest that H. pylori may be present in tissues other than gastric mucosa.

Adult↗
PubMed1996

The requirement for and mobilization of calcium during induction by sodium ascorbate and by hydrogen peroxide of cell death.

The requirement for and mobilization of Ca2+ ions during induction of cell death by sodium ascorbate were compared with those during induction of cell death by hydrogen peroxide. When HL-60 cells were incubated with sodium ascorbate, a rapid increase in the intracellular concentration of Ca2+ ions and subsequent apoptotic cell death, characterized by cell shrinkage, nuclear fragmentation and cleavage of internucleosomal DNA to yield fragments that were multiples of 180-200 base pairs, were induced. However, these effects of sodium ascorbate were significantly reduced in Ca2+-depleted medium. By contrast, hydrogen peroxide induced similar apoptosis associated phenomena in the presence and in the absence of extracellular Ca2+ ions. The intracellular concentration of the reduced form of glutathione was not significantly affected and glutathione disulfide was undetectable during the early stages of apoptosis. These data suggest that sodium ascorbate and hydrogen peroxide initiate cell death by different mechanisms.

Apoptosis↗
PubMed1996

Sympathetic nerve activity in the spasm-induced coronary artery region is associated with disease activity of vasospastic angina.

OBJECTIVES: We assessed the relation between sympathetic nerve activity and disease activity of vasospastic angina. BACKGROUND: The autonomic nervous system has been proposed to play a key role in attacks of vasospastic angina. A unique feature of vasospastic angina attacks is periodic fluctuation, which complicates the assessment of disease activity. METHODS: Twenty-five patients with left anterior descending coronary artery (LAD) spasm were studied: 12 with recent onset of chest pain (group 1) and 13 free of angina for more than 3 months after discontinuing medication (group 2). Group 1 underwent iodine-123 metaiodobenzylguanidine (MIBG) imaging (in the active phase) and atropine-stress MIBG imaging early after diagnostic angiography, and repeat MIBG imaging when they were free of angina for more than 3 months with medication (in the stable phase). Group 2 also underwent MIBG imaging (in remission). On a bull's-eye map, quantitative analysis of percent uptake and washout rate of MIBG was performed regionally. RESULTS: In group 1 in the active phase, the washout rate of the LAD territory was significantly lower than the rates in the stable phase, in remission and during atropine-stress MIBG imaging. The regional washout rate of the territories of the right coronary artery and the circumflex artery in the active phase was also significantly lower than that during atropine-stress MIBG imaging. The washout rate of the LAD territory in the active phase was significantly lower than the rates of the other two regions. In contrast, there were no significant differences in the distribution of regional percent uptake in every image. A similar distribution of washout rate was observed among group 1 patients in the stable phase, in group 1 patients during atropine-stress MIBG imaging and in group 2 patients. CONCLUSIONS: The MIBG washout rate of the spasm-induced coronary artery territory changed according to the degree of disease activity. Thus, sympathetic nerve activity could reflect disease activity of vasospastic angina.

3-Iodobenzylguanidine↗
PubMed1996

Evidence for amelioration of endothelial cell dysfunction by erythropoietin therapy in predialysis patients.

Evidence for the involvement of endothelial cells in the pathogenesis or erythropoietin-induced hypertension, and for endothelial cell damage in patients with chronic renal failure, has emerged and appears to be of major concern. We, therefore, investigated the effect of recombinant human erythropoietin (rHuEPO) therapy on endothelium-derived hormones in predialysis patients with progressive renal anemia. At the entry to the trial, the serum thrombomodulin concentration (Tm) and plasma endothelin-1 concentration (ET-1) in the predialysis patients were significantly higher than those in age- and sex-matched normal subjects. Following a 16 week period of treatment with 6000IU rHuEPO given intravenously once a week, patients' hematocrit increased from 27.1 +/- 2.6% to 34.6 +/- 3.2% (n = 16, P < .001). A positive correlation was found between Tm and serum creatinine concentration (Cr) (r = 0.61, P < .05 (n = 16), but no correlation was found between ET-1 and Cr. Tm and Tm/Cr significantly decreased from 7.9 +/- 2.8 ng/mL to 6.6 +/- 2.4 ng/mL (P < .01, n = 16), and from 2.1 +/- 0.7 (x10(-10) to 1.6 +/- 0.7 (x10(-10), P < .01, n = 16), respectively. However, there was no change in ET-1 as a result of the rHuEPO therapy. Creatinine clearance (Ccr), Cr, total amount of daily Tm excretion, Tm clearance/Ccr, daily urinary protein and albumin excretion, and blood pressure also remained unchanged throughout the trail. The present study indicates that correcting anemia by rHuEPO therapy reduces an abnormally elevated Tm in predialysis patients while blood pressure and renal function remain unchanged, suggesting that rHuEPO has a beneficial effect on endothelial cell dysfunction in chronic renal failure patients. This effect may be mediated via an improved oxygen supply to the endothelial cells due to the amelioration of anemia by rHuEPO.

Adult↗