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Biomedical subjects

C Yamamoto

Publications and source records attributed to C Yamamoto.

At least 91 records · Page 5Linked to original sources
PubMed1996

Presence of the voltage-gated potassium channels sensitive to charybdotoxin in inhibitory presynaptic terminals of cultured rat hippocampal neurons.

To determine whether the charybdotoxin-sensitive subtypes of voltage-gated K+ channels (Kv1.2 and Kv1.3) exist in inhibitory pre-synaptic terminals, effects of K+ channel blockers including TEA, charybdotoxin (ChTX), iberiotoxin (IbTX), kaliotoxin (KTX) and margatoxin (MgTX) on the inhibitory transmission were examined with cultured rat hippocampal neurons. Monosynaptic inhibitory postsynaptic currents (IPSCs) evoked by electrical stimulation of single presynaptic neurons were recorded from the whole-cell clamped postsynaptic neurons. In the presence of TEA, application of ChTX greatly increased the amplitude of IPSCs. A specific maxi-K+ channel blocker IbTX failed to augment IPSCs. KTX and MgTX, both of which block Kv1.3 but not Kv1.2, mimicked the facilitating effect of ChTX. In the absence of TEA, application of ChTX increased the IPSC amplitude significantly, while IbTX was without effect. These results indicate that the ChTX-sensitive subtypes of voltage-gated K+ channels, most likely Kv1.3, contribute to the repolarization of action potentials at presynaptic terminals of hippocampal inhibitory neurons, and that the ChTX-induced facilitation of the transmission can be explained by its effects on the Kv channels rather than maxi-K+ channels.

Animals↗
PubMed1996

A metabotropic glutamate receptor agonist DCG-IV suppresses synaptic transmission at mossy fiber pathway of the guinea pig hippocampus.

The effects of specific metabotropic glutamate receptor (mGluR) agonists on field excitatory postsynaptic potentials (fEPSPs) at mossy fiber-CA3 synapses were examined in guinea pig hippocampal slice preparations. Application of a novel and potent group II-selective mGluR agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 0.1 microM) reversibly reduced the fEPSPs. Both the group III-selective agonist DL-2-amino-4-phosphonobutyric acid (AP4; 50 microM) and the broad-spectrum agonist 1S,3R-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD; 5 microM) also reversibly suppressed the fEPSPs. These results suggest that multiple mGluR subtypes (belonging to groups II and III) are expressed at mossy fiber synapses of the guinea pig hippocampus and activation of the receptors reduces the synaptic excitation, although we cannot exclude the possibility that guinea pig mossy fiber-CA3 synapses express a single class of mGluRs with unique pharmacological profiles.

Aminobutyrates↗
PubMed1996

Interaction between cadmium and zinc in the production and sulfation of glycosaminoglycans in cultured bovine vascular endothelial cells.

Previously, we showed that cadmium stimulates the production of glycosaminoglycans (GAGs) but inhibits their sulfation in cultured bovine aortic endothelial cells. The effect of zinc on such alterations of GAGs induced by cadmium was investigated in the present study. The incorporation of [3H]glucosamine and [35S]sulfate into GAGs was determined by the cetylpyridinium chloride precipitation method as a marker of GAG production and GAG sulfation, respectively. The incorporation of both [3H]glucosamine and [35S]sulfate was not changed in GAGs accumulated in the endothelial cell layer and the conditioned medium after exposure to zinc at 20 micrometers or less alone. A simultaneous exposure of the endothelial cell layer to zinc at 20 micrometers or less and cadmium at 2 micrometers resulted in prevention of the cadmium-induced decrease in [35S]sulfate incorporation; however, the cadmium-induced increase in [3H]glucosamine incorporation was not affected by zinc. Characterization of GAGs in the cell layer revealed that such an interaction between zinc and cadmium occurred in both heparan sulfate and the other GAGs. Zinc significantly prevented the inhibition of either [3H]thymidine or [3H]leucine incorporation caused by cadmium with less accumulation of intracellular cadmium suggesting that zinc decreased intracellular cadmium and protected endothelial cells from cadmium-induced inhibition of DNA and protein synthesis. The present data showed that a simultaneous exposure to cadmium and zinc resulted in an increase in heparan sulfate without a reduction of sulfation in the endothelial cell layer. The alteration may potentiate the antihrombogenic property of vascular endothelium.

Animals↗
PubMed1996

Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection.

BACKGROUND: A region associated with sensitivity to interferon has been identified in the nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) genotype 1b. The region spans amino acid residues 2209 to 2248 (NS5A2209-2248) of HCV-J, a strain of HCV-1b whose complete genomic sequence has been identified. We examined whether the NS5A2209-2248 sequence present before therapy could be used as a predictor of the response to interferon therapy in patients with chronic HCV-1b infection. METHODS: We retrospectively analyzed 84 patients with chronic HCV-1b infection who had received interferon alfa (total dose, 516 million to 880 million units) for six months. Pretreatment serum samples were analyzed. The amino acid sequence of NS5A2209-2248 was determined by direct sequencing of the HCV genome amplified by the polymerase chain reaction (PCR) and was compared with the established sequence for HCV-J. RESULTS: A complete response, as evidenced by the absence of HCV RNA in serum on nested reverse-transcription PCR for six months after therapy, did not occur in any of the 30 patients whose NS5A2209-2248 sequences were identical to that of HCV-J (wild type). Five of 38 patients (13 percent) with 1 to 3 changes in NS5A2209-2248 (intermediate type) had complete responses, as did all 16 patients with 4 to 11 amino acid substitutions (mutant type), indicating that the mutant type was significantly associated with a complete response (P < 0.001). Although baseline serum HCV RNA levels, as measured by a branched-chain DNA assay, were lower in patients with the mutant type of NS5A2209-2248 than in those with the other types (P < 0.001), multivariate analyses revealed that the number of amino acid substitutions in NS5A2209-2248 was the only variable associated with an independent effect on the outcome of interferon therapy (odds ratio, 5.3; 95 percent confidence interval, 1.6 to 18; P = 0.007). CONCLUSIONS: In patients with chronic HCV-1b infection, there is a substantial correlation between responses to interferon and mutations in the NS5A gene.

Amino Acid Sequence↗
PubMed1996

Effects of cadmium on the release of tissue plasminogen activator and plasminogen activator inhibitor type 1 from cultured human vascular smooth muscle cells and fibroblasts.

To evaluate the toxicity of cadmium on the blood fibrinolytic system during hemostasis, human vascular smooth muscle cells and human fibroblasts were cultured in the presence of cadmium chloride. It was found that cadmium markedly decreased the release of both tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor type-1 antigen (PAI-1:Ag) from vascular smooth muscle cells. Other heavy metals including lead, manganese, mercury and nickel also decreased the t-PA:Ag and PAI-1:Ag release, however, cadmium was the most potent inhibitor. On the other hand, the release of t-PA:Ag was significantly increased whereas that of PAI-1:Ag was unaffected in fibroblasts after exposure to cadmium. Of the tested heavy metals, only cadmium increased the t-PA:Ag release from the cells. Electrophoretic enzymography revealed that cadmium reduced the activity of plasminogen activators in the conditioned medium of both vascular smooth muscle cells and fibroblasts. Cadmium markedly decreased the incorporation of [3H]leucine accompanied with a significant increase in the leakage of lactate dehydrogenase in vascular smooth muscle cells; however, the metal did not change these markers in fibroblasts. These results suggest that the regulation of fibrinolysis mediated by vascular smooth muscle cells and fibroblasts during hemostasis may be disturbed by cadmium.

Cadmium↗
PubMed1996

Endotoxin rejection by ultrafiltration through high-flux, hollow fiber filters.

The efficacy of endotoxin (ET) rejection of four hollow fiber membranes with comparable sieving properties was evaluated in an ultrafiltration experiment. The solution conditioned with type I lipopolysaccharide (LPS) from Escherichia coli, 80,000 endotoxin units (EU)/L, was filtered through polyesterpolymer alloy (PEPA), polymethyl methacrylate (PMMA), polyacrylonitrile (PAN), and polysulfone (PS) membranes. The ET activity of the filtrate was not detectable in PEPA and PMMA, 6.4 +/- .04 (mean +/- SD) EU/L in PAN, and 10.3 +/- 1.1 EU/L in PS. The ET activity of the filtrate of type II LPS from Acinetobacter solution, 80,000 EU/L, was not detectable in PEPA, 3.7 +/- 0.4 EU/L in PMMA, 16.5 +/- 1.5 EU/L in PAN, and 20.7 +/- 1.4 EU/L in the PS filter. The order of the rejection capability coincided with the adsorptive capacity as shown by the decrement in ET levels of solutions filled within the filter modules in the adsorption equilibrium experiment. In conclusion complete rejection of ET molecules can be achieved by ultrafiltration through hydrophobic membranes having a high adsorptive capacity in addition to an appropriate sieving property for ET molecules.

Acinetobacter↗
PubMed1996

Immunolocalization of basic fibroblast growth factor during wound repair in rat retina after laser photocoagulation.

BACKGROUND: Basic fibroblast growth factor (bFGF) stimulates the mitogenesis of various cells and plays a key role in wound repair. We studied the immunohistochemical localization of bFGF during wound repair in the rat retina after laser photocoagulation. METHODS: Krypton laser photocoagulation was performed on the eyes of pigmented rats. The eyes were enucleated on days 1, 3, 7, 14 and 28 after the photocoagulation, and the immunohistochemical localization of bFGF was assessed. Two different monoclonal antibodies and one polyclonal antibody against bFGF as first antibodies were used. RESULTS: Marked immunoreactivity for bFGF was found in the ganglion cell layer, and weak immunoreactivity for bFGF was found in the retinal pigment epithelial (RPE) cells of the normal adult rat retina. On day 3 after laser photocoagulation, the nuclei and cytoplasm of proliferating RPE cells at the center of the photocoagulated lesion showed intense bFGF immunoreactivity. The nuclei of RPE cells around the lesion showed intense bFGF immunoreactivity. Macrophages that migrated into the lesion showed positive staining for bFGF. These immunoreactivity decreased with time. Controls (0.05 M Tris-HCl buffer, normal serum, or these same antibodies preabsorbed with bFGF) did not show positive staining. CONCLUSION: The finding of an elevated expression of bFGF immunoreactivity in the photocoagulated lesion suggests that bFGF may play a role in wound repair in the rat retina after laser photocoagulation.

Animals↗
PubMed1996

Eosinophilia in premature infants: correlation with chronic lung disease.

We attempted to clarify the possible pathophysiological significance of eosinophilia in bronchopulmonary dysplasia (BPD). The subjects studied were 17 premature infants, i.e. seven with respiratory distress syndrome (RDS) followed by bronchopulmonary dysplasia (the BPD group: four with stage IV and three with stage III BPD) and 10 infants without BPD (the non-BPD group), who comprised seven with RDS, two with meconium aspiration syndrome and one with transient tachypnea of the newborn. Peripheral eosinophil counts, the number of nuclei of eosinophils and serum eosinophilic cationic protein (ECP) levels, and ECP and polymorphonuclear leukocyte (PMN) elastase levels of intratracheal aspirates (TA) were determined once a week during the first 4 weeks of life. Peripheral eosinophil counts were higher in infants with BPD than those in the non-BPD group. Hypersegmented nuclei of peripheral eosinophils with more than four nuclei were more frequently present in the infants with BPD. A good correlation was observed between peripheral eosinophil counts and serum ECP levels. ECP levels of the TA in the infants with BPD were significantly elevated. There was a good correlation between ECP and PMN elastase levels of the TA. Lung tissue specimens of two infants of the BPD group, both of whom had patent ductus arteriosus (PDA), were obtained from the lower portion of the left lung when they underwent an operative procedure for PDA at 24 and 25 days of life, respectively. Immunohistochemical staining of eosinophil-derived granular major basic protein (MBP) was performed on the lung tissue specimens. Infiltration of a few MBP-staining eosinophils was observed on the specimens from both infants. Our results suggest that peripheral eosinophils in sick premature infants may be activated and appear to be correlated with the severity of BPD. Further studies will be needed to more clarify the physiological role of eosinophils in premature infants.

Blood Proteins↗
PubMed1996

Expression of basic fibroblast growth factor mRNA in developing choroidal neovascularization.

PURPOSE: Basic fibroblast growth factor (bFGF) is an angiogenic peptide that may be important in the pathogenesis of choroidal neovascularization. We attempted to determine the transcription of the bFGF gene during the development of experimentally induced choroidal neovascularization. METHODS: Rat bFGF cDNA was inserted in the pBluescript to prepare antisense and sense riboprobes. Multiple krypton laser burns were applied to the posterior poles of the eyes of pigmented rats according to a protocol described for producing subretinal neovascularization in these animals. At intervals of up to 4 weeks after photocoagulation, the eyes were removed and cut into thin sections. The sections were subjected to histopathological analysis, cell proliferation study, or in situ hybridization with digoxigenin (DIG)-labeled single-strand riboprobes synthesized from rat bFGF cDNA. RESULTS: In normal adult rat retinas, bFGF mRNA expression was mainly observed in the ganglion cell layer and the inner nuclear layer. After laser photocoagulation, proliferation of RPE cells, fibroblast-like cells and cells in the choroid in the lesions were observed. Expression of bFGF mRNA was observed in the lesions 3 days to 2 weeks after laser treatment. Signals of bFGF mRNA were detected in the proliferating RPE-like cells, choroidal vascular endothelial cells and fibroblast-like cells, all of which are essential for neovascularization. However, bFGF mRNA expression was no longer detectable in these cells 4 weeks after photocoagulation. CONCLUSIONS: Our findings indicate that bFGF is normally transcribed in ganglion cells and the inner nuclear cell layer. During the neovascularization that followed laser photocoagulation, bFGF mRNA expression was detected within the laser lesions. It is thus probable that bFGF acts as a mediator in the neovascularization process.

Animals↗
PubMed1996

[Interleukin-8 in sputum from patients with pulmonary emphysema].

We measured concentrations of interleukin-8 (IL-8) in sputum from 38 patients with pulmonary emphysema, from 30 patients with bronchial asthma, and in induced sputum from 10 healthy subjects. Concentrations of IL-8 were significantly higher in sputum from patients with emphysema than in sputum from patients with asthma (mean +/- SE: 22,961 +/- 1,412 pg/ml and 9,135 +/- 1,590 pg/ml, respectively, p<0.0001) and were also higher than in sputum from healthy subjects (3,253+/-687 pg/ml, p<0.0001). Concentrations of IL-8 in sputum from patients with emphysema were unrelated to whether the patient was a current smoker or an ex-smoker, and did not correlate with concentrations of IL-8 in serum. Concentrations of IL-8 in sputum from patients with emphysema correlated significantly with FEV1% (r=-0.78, p<0.0001) and with %RV/TLC (r=0.63, p<0.01). These data suggest that IL-8 is mainly involved in chronic airway inflammation and that concentrations of IL-8 in sputum are closely related to airflow obstruction in patients with pulmonary emphysema.

Female↗
PubMed1996

[Expression of basic fibroblast growth factor and its receptor in the process of wound healing of rat retina after laser photocoagulation].

We investigated the expression of mRNA of basic fibroblast growth factor (bFGF) and FGF receptor 1 in rat retina after laser photocoagulation using in situ hybridization method. Pigmented rats (Brown Norway strain) received weak photocoagulation by krypton laser (500 microns, 0.05 sec, 60 mW) in the posterior retina. On 1, 3, 5, 7, 14 days after laser photocoagulation, the rats were fixed by perfusion with phosphate-buffered 4% paraformaldehyde and the eyes were enucleated. The eyes were further fixed by immersion in the same fixative, then quickly frozen in liquid nitrogen and finally sectioned with a cryostat. In situ hybridization was performed on frozen sections with digoxigenin (DIG) labeled riboprobes synthesized from rat bFGF cDNA and FGF receptor 1 cDNA. In normal chorioretinal tissue, the signals of bFGF and FGF receptor 1 mRNA were seen in the ganglion cell layer and inner nuclear layer. On day 3 after photocoagulation, we observed expression of bFGF and FGF receptor 1 mRNA in the proliferating retinal pigment epithelial (RPE) cells and endothelial cells of choriocapillaris at the photocoagulated lesion. We also observed expression of bFGF mRNA in some macrophage-like cells. On day 14 after photocoagulation, these expressions had disappeared. Our results suggest that bFGF may be involved in the process of retinal wound healing after laser photocoagulation.

Animals↗
PubMed1996

[Investigation of soluble tumor necrosis factor receptor in patients with active tuberculosis].

It is assumed that soluble tumor necrosis factor receptor I and II (sTNF-RI, II) play important roles in the regulation of tumor necrosis factor alpha (TNF-alpha) activity. We measured the levels of circulating sTNF-R in patients with active pulmonary tuberculosis (n = 31) and the correlation between TNF-alpha and sTNF-R in serum level was investigated. We also compared sTNF-R levels before and after the treatment in 7 cases. Significant increase of circulating sTNF-R were found in patients with tuberculosis compared with the normal controls (n = 28) (p < 0.01). Moreover, significant positive correlations were found between TNF-alpha and sTNF-R I and II (r = 0.520, r = 0.553) in serum comparing sTNF-R levels before and after the treatment for patients with tuberculosis, significant fall was found in sTNF-R I, but not in sTNF-R II. As a result, it is suggested that sTNF-R regulates TNF-alpha activity in patients with tuberculosis, and that sTNF-R I levels could be used as one of the indices to evaluate the clinical activity of tuberculosis.

Adult↗
PubMed1996

[Interaction between nutrition and production of IL-1 beta, TNF alpha, and IL-6 by peripheral blood monocytes in patients with lung cancer].

Altered nutrient intake and metabolism are responsible for the progressive loss of body weight observed in most patients with advanced cancer, but the precise mechanism is still controversial. Under stressful conditions, some inflammatory cytokines such as IL-1 beta, TNF alpha, and IL-6 have a hypermetabolic effect and cause proteolysis and lipolysis in muscle and in fat tissues. To elucidate the mechanism of malnutrition in patients with lung cancer and normal food intake, we focused on the relationship between abnormal metabolism and these inflammatory cytokines. Patients with lung cancer were confirmed to be malnourished, and this malnutrition was found to be caused by hypermetabolism as estimated with visceral proteins, plasma levels of amino acids, and anthropometric indices. The production of IL-1 beta, TNF alpha, and IL-6 by blood monocytes was significantly higher in these patients than in healthy controls, and it correlated significantly and inversely with indices of nutrition. The present results suggest that nutritional status and these cytokines are closely related in patients with lung cancer. IL-1 beta, TNF-alpha, and IL-6 may serve as anti-cancer bioactive molecules, but "overfunctioning" of these cytokines may induce a hypermetabolic status that causes malnutrition, i.e. cancer cachexia.

Adult↗
PubMed1996

[Analysis of body composition by dual energy X-ray absorptiometry and its relation to pulmonary function in patients with pulmonary emphysema].

The purpose of this study was to investigate body composition in patients with chronic obstructive pulmonary disease, and its relation to pulmonary function. Seventeen men with pulmonary emphysema who were being treated as outpatients were divided into three groups, according to ideal body weight (IBW): group A, %IBW > or = 90%; group B, 90 > %IBM > or = 80; and group C, %IBW < 80. All underwent body composition analysis by dual energy X-ray absorptiometry. Fat mass and bone mineral content were significantly lower in groups B and C than in control subjects. Lean mass was significantly lower in group C than in control subjects. By contrast, group A did not differ significantly from control subjects. Lean mass correlated significantly with %VC, FEV1, RV/TLC, and MVV. These data suggest that lean mass is low in moderately and severely malnourished patients, that bone mineral content and fat mass are low in mildly malnourished patients, and that abnormal body composition is associated with ventilatory impairment in patients with chronic obstructive pulmonary disease.

Absorptiometry, Photon↗