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Biomedical subjects

Y Okamoto

Publications and source records attributed to Y Okamoto.

At least 343 records · Page 19Linked to original sources
PubMed1996

Localization of HIV-1 in human thymic implant in SCID-hu mice after intravenous inoculation.

Human immunodeficiency virus type 1 (HIV-1) was immunohistochemically and ultrastructurally localized in human thymus implants in SCID-hu mice 3 weeks after intravenous (i.v.) inoculation of the virus. A viral antigen (gp120) was predominantly distributed in and around the epithelial cells in Hassall's corpuscles as demonstrated by fluorescence immunohistochemistry. Occasional solitary round cells positive for the viral antigen but negative for cytokeratin were detected in the perivascular areas. Ultrastructural examinations clearly revealed a number of mature viral particles in the intercellular spaces of the Hassall's corpuscles. Thus the present study indicates the possibility that thymic epithelial cells in Hassall's corpuscles act as a target and/or reservoir in an early stage of HIV infection.

Animals↗
PubMed1996

Preferential requirement of CD3 zeta-mediated signals for development of immature rather than mature thymocytes.

Antigen recognition signals by the TCR are transduced through activation motifs present in the cytoplasmic region of CD3 chains. In vitro analysis has suggested that the CD3zeta chain mediates different signals from other CD3 chains. To analyze the in vivo function of CD3zeta-mediated signals for T cell development, mice expressing a mutant CD3zeta chain lacking all the activation motifs were generated by introducing the transgene into zeta-knockout mice. Mature CD4(+) single-positive (SP) thymocytes in these mice were greater in number than in zeta-deficient mice, and the promoted differentiation was indicated by the changes of CD69 and HSA phenotypes. We found that even in the absence of activation motifs in CD3zeta, these mature cells became functional, being able to induce Ca2+ mobilization and proliferation upon stimulation. On the other hand, CD4(-)CD8(-) double-negative (DN) thymocytes, most of which were arrested at the CD44(-)CD25(+) stage similarly to those in zeta-deficient mice, could not be promoted for differentiation into CD4(+)CD8(+) double-positive thymocytes in these mice in spite of the fact that the expression of the transgene in DN thymocytes was higher than that of zeta in wild-type mice. These results demonstrate the preferential dependence of the promotion of development and/or expansion of DN thymocytes rather than mature thymocytes upon the activation signals through the zeta chain and suggest differential requirements of TCR signaling for mature SP and immature DN thymocyte developments in vivo.

Animals↗
PubMed1996

Isolation and identification of myosin I from porcine aorta media smooth muscle.

A complex of 110-kDa heavy chain and calmodulin was isolated from porcine aorta media smooth muscle and identified as myosin I. The isolated myosin I consisted of equimolar amounts of 110-kDa heavy chain and calmodulin. The addition of exogenous calmodulin to the complex revealed that a maximum of two molecules of calmodulin could be bound to the heavy chain. Isolated complex bound to F-actin in an ATP-dependent manner and its Mg(2+)-ATPase activity was activated by F-actin. In addition, it bound to phospholipid, which is a characteristic property of myosin I. Calcium ions induced a structural change, which was revealed by a difference in the cleavage pattern and for rate of cleavage by alpha-chymotrypsin. This behavior was similar to that reported for brush border myosin I [L.M. Collins and A. Bretscher (1988) J. Cell. Biol. 106, 367-373]. Calcium-dependent structural change of a complex of 110-kDa heavy chain and calmodulin was found from its solubility change at various NaCl concentrations in the presence of ATP. A complex of 116-kDa heavy chain and calmodulin, possibly another type of myosin I, was also isolated. A polyclonal antibody against the complex of 110-kDa heavy chain and calmodulin did not recognize the 116-kDa heavy chain. This result suggests that at least two types of myosin Is may exist at the protein level in porcine aorta media smooth muscle.

Adenosine Triphosphatases↗
PubMed1996

Specialty choice and understanding of primary care among Japanese medical students.

To assess specialty choice and understanding of primary care among Japanese medical students, all students from seven Japanese medical schools (three public and four private) were surveyed, using a written questionnaire. A total of 3377 students provided data for the study. Of the students surveyed, 89.8% wanted to become clinicians, and 79.3% wanted to have general clinical ability. About half of the respondents, 54.9%, replied that they had some, or great, interest in primary care, but it was found that their understanding of primary care was inadequate. Almost half (56.3%) of the students answered that they had some idea of what a general practitioner did. This proportion was nearly the same through all years of medical school. While 1245 (36.9%) students (most of them in the fifth or sixth year) replied that they had received some clinical training while working in hospitals, only 203 (6.0%) students had worked in private clinics (the sites where most primary care is still provided), and 129 (3.8%) students had experience in providing home visits and home care. An even greater number, 64.3%, replied that they had inadequate information about the career options available to them. The study found that although many Japanese medical students want to obtain broad clinical competence, their understanding of primary care is insufficient. In order to increase the number of primary care providers the system of medical education in Japan must provide primary care doctors to act as role models, and must make available information about postgraduate primary care programmes. These programmes need to be increased, as do rewarding positions for programme graduates.

Career Choice↗
PubMed1996

Oncofetal expression of blood group-related antigen on morules in thyroid carcinoma.

Morule formation in association with characteristic biotinrich 'optically clear nuclei' were found in 7 of 2514 cases of thyroid carcinoma. The seven patients were all young females aged from 20 to 36 years who were suffering from either papillary carcinoma (six cases) or follicular carcinoma (one case). The ABH (O) blood group (BG) types were A in three, AB in two and H(O) in two patients. Immunohistochemical study revealed that ABH(O) and Lewis BG antigens were expressed more specifically on morules than on ordinary neoplastic cells of papillary or follicular carcinoma. Lewis BG antigens tested in the present study were as follows: CA50, CA19-9, stage-specific embryonic antigen 1 (SSEA-1), and sialyl SSEA-1. Ulex europaeus agglutinin I (UEA-I) histochemistry showed a positive reaction on all the morules of blood groups A and H(O) patients, but yielded completely negative results on the morules of type AB patients. Sequential digestion by neuraminidase and alpha-galactosidase unmasked the reactivity for UEA-I even on the morules of type AB patients. The consistent reactivity for UEA-I on the morules seemed to be related to specific expression of BG antigens, which were characterized as oncofetal expression. It is suggested that the morules in thyroid carcinoma might be a kind of fetal component induced by the differentiation of the neoplastic cells to the stage of immature embryonic cells.

Adenocarcinoma, Follicular↗
PubMed1996

Role of albumin and high-density lipoprotein as endotoxin-binding proteins in rats with acute and chronic alcohol loading.

In the present study, the role of albumin and high-density lipoprotein (HDL) as endotoxin (Et)-binding proteins in chronically alcohol-fed rats was studied. In acute ethanol-loaded rats, the Et clearance in the blood was slightly prolonged, and the amount of albumin and HDL- bound Et in the blood was markedly increased. In chronic ethanol-loaded rats, the Et clearance was significantly faster than that in the control, and HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5 g/kg body weight of ethanol load, the Et clearance was much prolonged, and blood tumor necrosis factor and ALT was elevated, when HDL-bound Et was not further increased. Et-binding capacity of total proteins, albumin, and HDL in the hepatocyte culture medium were increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. In the culture experiment in the chronic ethanol-loaded rats, such increases were not observed. These results suggest that the increase in Et-binding capacity of HDL and albumin may serve as a protective mechanism against Et in chronic ethanol-loaded rats. An addition of high-dose ethanol to these rats may lead to impaired Et binding and inactivation, which may finally result in increased endotoxicity.

Alcoholic Intoxication↗
PubMed1996

Identification of amino acids involved in recognition by dengue virus NS3-specific, HLA-DR15-restricted cytotoxic CD4+ T-cell clones.

The majority of T-cell clones derived from a donor who experienced dengue illness following receipt of a live experimental dengue virus type 3 (DEN3) vaccine cross-reacted with all four serotypes of dengue virus, but some were serotype specific or only partially cross-reactive. The nonstructural protein, NS3, was immuno-dominant in the CD4+ T-cell response of this donor. The epitopes of four NS3-specific T-cell clones were analyzed. JK15 and JK13 recognized only DEN3 NS3, while JK44 recognized DEN1, DEN2, and DEN3 NS3 and JK5 recognized DEN1, DEN3, and West Nile virus NS3. The epitopes recognized by these clones on the DEN3 NS3 protein were localized with recombinant vaccinia viruses expressing truncated regions of the NS3 gene, and then the minimal recognition sequence was mapped with synthetic peptides. Amino acids critical for T-cell recognition were assessed by using peptides with amino acid substitutions. One of the serotype-specific clones (JK13) and the subcomplex- and flavivirus-cross-reactive clone (JK5) recognized the same core epitope, WITDFVGKTVW. The amino acid at the sixth position of this epitope is critical for recognition by both clones. Sequence analysis of the T-cell receptors of these two clones showed that they utilize different VP chains. The core epitopes for the four HLA-DR15-restricted CD4+ CTL clones studied do not contain motifs similar to those proposed by previous studies on endogenous peptides eluted from HLA-DR15 molecules. However, the majority of these dengue virus NS3 core epitopes have a positive amino acid (K or R) at position 8 or 9. Our results indicate that a single epitope can induce T cells with different virus specificities despite the restriction of these T cells by the same HLA-DR15 allele. This finding suggests a previously unappreciated level of complexity for interactions between human T-cell receptors and viral epitopes with very similar sequences on infected cells.

Amino Acid Sequence↗
PubMed1996

Inhibitory effects of 1-hydroxyethylidene-1,1-bisphosphonate and Chinese traditional (kampo) medicines on calcification of the heart and tongue in DBA/2NCrj mice.

The effects of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) and two Chinese traditional (Kampo) medicines, Dai-saiko-to and Saiko-ka-ryukotsu-borei-to on spontaneous soft tissue (heart and tongue) mineralization in DBA/2NCrj mice were studied. These agents were given orally for 4 weeks to DBA/2NCrj mice. After 2 weeks of administration in the heart, 0.006 and 0.03% (w/v) HEBP decreased calcium content by 90 and 30%, respectively, while 0.27 and 2.7 mg/ml Dai-saiko-to reduced calcium content by 30 and 45%, respectively. Saiko-ka-ryukotsu-borei-to (0.27 mg/ml) reduced both calcium and phosphorus content by 50 and 35%, respectively. However, their inhibitory effects on the heart were not observed after 4 weeks of administration. The compounds delayed the onset of increases of bulk calcium and phosphorus content. In the tongue, at 4 weeks, 0.006 and 0.03% (w/v) HEBP reduced calcium content by 30 and 45%, respectively, while two Kampo medicines (at both concentrations used) significantly reduced the content of calcium (by 27-79%) and phosphorus (by 24-32%). These results strongly suggest that two Kampo medicines as well as HEBP may be useful in preventing and curing soft tissue calcification.

Animals↗
PubMed1996

Addition of lithium to chronic antidepressant treatment potentiates presynaptic serotonergic function without changes in serotonergic receptors in the rat cerebral cortex.

The effects of the addition of short-term lithium to long-term administration of antidepressants (clomipramine or citalopram) on the levels of 5-HT and 5-HIAA and serotonergic receptors were studied in the rat cortex. The addition of short-term Li to long-term antidepressant treatment potentiated an increase in 5-HIAA, although Li alone had no effect. On the serotonergic receptors, the addition of short-term Li had no effect. It is speculated that the therapeutic action of Li when added to antidepressants in the treatment of refractory depression may partly have its basis in the further activation of the presynaptic serotonergic system.

Animals↗
PubMed1996

Effects of clomipramine and verapamil on 5-HT-induced intracellular calcium changes in individual C6 rat glioma cells.

The effects of antidepressants and calcium (Ca2+) antagonists on serotonin (5-HT)-induced Ca2+ increase were investigated in single C6BU-1 glioma cells with digital imaging microscopy. Application of 5-HT (100 nM-100 microM) caused a rapid and reversible rise of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner. In the absence of extracellular Ca2+, the sustained phase of the [Ca2+]i response was strongly reduced, which was greater than the suppression of the initial peak. This suggests that the peak value is mainly due to internal Ca2+ storage sites, and the sustained phase is mainly composed of Ca2+ influx. The sustained phase was significantly attenuated by 100 nM clomipramine and verapamil. The present findings demonstrate that clomipramine and verapamil, in their therapeutic concentrations, have a common action of inhibiting Ca2+ influx, and suggest that the calcium antagonistic effect may play an important role in clinical effects of antidepressants.

Animals↗
PubMed1996

Chemoembolization of head and neck cancer with carboplatine microcapsules.

Fourteen patients with malignant tumor in the head and neck region were treated with infusion of carboplatine microcapsules (CBDCA-mc) via percutaneous super-selective catheterization. A microcatheter was advanced into a feeding artery using a coaxial catheter system. Eleven patients had over 30% reduction of the tumor size on CT within 1 month after embolization. Twelve patients had an increased amount of low attenuation tissue in the tumor on CT after embolization, suggesting increased necrosis in the tumor. No definite hematologic toxicity was found. A majority of patients complained of moderate pain in the embolized region immediately after embolization, easily relieved by i.v. analgesics. Chemoembolization using CBDCA-mc may be an effective therapeutic modality in advanced cases of head and neck cancer.

Aged↗
PubMed1996

Biological activity of analogues of YM022. Novel (3-amino substituted phenyl)urea derivatives of 1,4-benzodiazepin-2-one as gastrin/cholecystokinin-B receptor antagonists.

A series of (3-substituted phenyl)urea analogues of the potent gastrin/cholecystokinin (CCK)-B receptor antagonist YM022 has been prepared. Structure-activity relationship studies of this series suggested that a number of analogues retained good in vitro potency for gastrin/CCK-B receptor. In particular, the (3-amino substituted phenyl)urea derivatives (10-12) were more potent inhibitors of pentagastrin-induced gastric acid secretion in rats than YM022 on intraduodenal (i.d.) administration.

Animals↗
PubMed1996

Amino acids and peptides. XLIV. Synthesis of stereoisomeric pentapeptides of thiol proteinase inhibitor.

Stereoisomers of thiol proteinase inhibitor (TPI) were synthesized by a conventional solution method. Among them, iNoc-D-Gln-Val-Val-Ala-Ala-pNA weakly inhibited the amidolytic activity of papain, although iNoc-Gln-Val-Val-Ala-Ala-pNA inhibited papain activity fairly potently. However, the other five D-amino acid-containing peptides did not show any inhibitory effects on papain. The circular dichroism (CD) spectra of the enzyme-peptides mixtures were measured in order to study the relationship between the peptide anilides-papain interaction and the inhibitory activity.

Amino Acid Sequence↗
PubMed1996

Pharmacologically active components of a Peruvian medicinal plant, huanarpo (Jatropha cilliata).

From Jatropha cilliata M. Arg., a Peruvian medicinal plant, isoorientin and orientin were isolated as anxiolytic components by using the isolation guide of anti-conflict effect in mice. Several related flavonoids were also tested for this effect. Another bioassay-guided isolation using the acetic acid-induced writhing method gave a coumarin compound, fraxetin, as an analgesic principle.

Analgesics↗