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Biomedical subjects

H Okamura

Publications and source records attributed to H Okamura.

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

Inhibitory mechanism of CO2 inhalation on slowly adapting pulmonary stretch receptors in the anesthetized rabbit.

The inhibitory effects of CO2 on slowly adapting pulmonary stretch receptors (SARs) were studied before and after administration of acetazolamide, a carbonic anhydrase inhibitor, or nifedipine, a calcium channel blocker, in anesthetized, artificially ventilated rabbits after vagus nerve section. CO2 inhalation (maximal tracheal CO2 concentration ranging from 7.2% to 9.5%) for approximately 60 sec decreased the receptor activity during both inflation and deflation. The magnitude of decreased receptor activity during deflation became more pronounced than that seen during inflation. Acetazolamide treatment (20 mg/kg) diminished the inhibitory responses of slowly adapting pulmonary stretch receptors to CO2 inhalation, which were not significantly influenced by pretreatment with nifedipine (1 mg/kg). Furthermore, CO2 inhalation before and after vagal denervation had no effect on total lung resistance and dynamic lung compliance. In another series of experiments, the staining to determine the presence of carbonic anhydrase enzymatic reaction was not found in the smooth muscle of either extrapulmonary or intrapulmonary bronchi. These results suggest that CO2-induced inhibition of slowly adapting pulmonary stretch receptors is not related to the change in bronchomotor tone.

Administration, Inhalation↗
PubMed1996

Effects of estrogen and progesterone on plasma platelet-activating factor-acetylhydrolase activity and low-density lipoprotein cholesterol concentration in men.

OBJECTIVE: We examined the effects of estrogen and progesterone on the plasma platelet-activating factor (PAF)-acetylhydrolase activity and lipoprotein concentrations in men. METHOD: Ten healthy men received 6 days of oral mestranol (0.24 mg/day) followed by 6 days of oral norethisterone (20 mg/day). The PAF-acetylhydrolase activity and lipoprotein profiles were determined in each subject prior to and following mestranol loading and following norethisterone administration. RESULT: The mestranol caused a significant decrease in both the plasma PAF-acetylhydrolase activity and the low-density lipoprotein (LDL) cholesterol concentrations of 26.4% and 26.9%, respectively; norethisterone appeared to revert the PAF-acetylhydrolase activity and LDL cholesterol concentrations to the levels observed prior to mestranol loading. In addition, the plasma PAF-acetylhydrolase activity was positive correlated with the LDL cholesterol concentration (r = 0.58, P < 0.001). CONCLUSION: The results of this study indicate that mestranol and norethisterone exert an effect on the plasma PAF-acetylhydrolase activity in men, possibly by influencing plasma LDL cholesterol concentrations.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

Effects of parathyroidectomy and calcium supplementation on the pressor response to angiotensin II in conscious rats.

OBJECTIVE: We evaluated the effect of parathyroidectomy (PTx) and of calcium supplementation on the pressor response to angiotensin II (Ang II) in conscious rats. STUDY DESIGN: PTx and sham surgery were performed on 10-week-old male Wistar rats. The mean arterial pressure (MAP), heart rate, and the effective pressor dose of Ang II (EPD) which defined as the dose of Ang II required to elicit a rise of 20 mmHg in MAP, were evaluated in PTx and sham operated rats. Intracellular free calcium in platelets was assessed with the fluorescent dye, fura-2 acetoxymethyl ester. In addition, after administering a dose of supplemental calcium chloride, a 10, 20, or 40 mg/rat, we determined the changes in the MAP, EPD, and serum calcium level. RESULTS: The EPD in the PTx rats was significantly lower than the sham operated rats. The serum concentration of calcium in PTx was also significantly lower than the sham operated rats. A statistically significant negative relationship was observed between the EPD and intracellular free calcium in PTx rats. Following administration of 20 mg of calcium chloride (7.4 mg of elemental calcium) to the PTx rats, the EPD returned to the level seen in sham operated rats. CONCLUSION: Results suggest that a depletion of parathyroid hormone is associated with the pressor response to Ang II, and is involved in the regulation of intracellular free calcium.

Angiotensin II↗
PubMed1995

Time course of the induction of VGF mRNA in the dorsal vagal complex in rats with cysteamine-induced peptic ulcers.

The time course of induction of VGF mRNA in the dorsal vagal complex of the medulla oblongata was investigated in rats with duodenal ulcer induced with cysteamine by in situ hybridization histochemistry. In control rats, weak VGF mRNA signals were detected in a few neurons in the nucleus tractus solitarii and dorsal motor nucleus of vagus. After the cysteamine administration (450 mg/kg, s.c.), VGF mRNA signals began to increase after 3 h, reached at peak level at 12 h, and decreased slightly at 24 h, but remained high after 48 h. The time course of duodenal ulcer score was absent at 3 h, very low at 6 h, about grade 1 at 12 h, and grade 2 or more at 24 and 48 h. The present results support the hypothesis that the increase of the central neuronal activity of the vagus nerve precedes ulcer generation in the duodenum.

Analysis of Variance↗
PubMed1995

Changes in vasoactive intestinal peptide mRNA levels in the rat suprachiasmatic nucleus following p-chlorophenylalanine (PCPA) treatment under light/dark conditions.

Photic stimulus and serotonin (5-hydroxytryptamine; 5-HT) are two factors known to regulate vasoactive intestinal peptide (VIP) synthesis in the suprachiasmatic nucleus (SCN). To explore the role of 5-HT in the photic stimulus-induced change in VIP synthesis, we investigated the changes in level of VIP mRNA under a 12 h light/12 h dark cycle following depletion of 5-HT by intraperitoneal administration of p-chlorophenylalanine (PCPA) methyl ester (200 mg/kg concentration) for 3 successive days. To estimate VIP mRNA expression, we performed in situ hybridization using imaging plates combined with microcomputer-based imaging analysis. In light-phase, total signals of VIP mRNA from the PCPA-treated rats showed a significant decrease compared with those from the saline-treated control rats. However, in dark-phase, there were no significant decreases between the PCPA-treated rats and the saline-control rats. The present results strongly suggest that 5-HT neuronal inputs to the SCN interfere with the effect of photic stimulus on VIP synthesis at the mRNA level.

Animals↗
PubMed1995

p80/85 cortactin associates with the Src SH2 domain and colocalizes with v-Src in transformed cells.

Expression of oncogenic variants of pp60src leads to dramatic changes in cytoskeletal organization characteristic of transformation. Activated Src associates with the cytoskeletal matrix, resulting in tyrosine phosphorylation of specific cytoskeletal substrates. We have previously shown that stable association of Src with the cytoskeletal matrix is mediated by the Src SH2 domain in a phosphotyrosine-dependent interaction. In this report, we demonstrate that one of the cytoskeletal binding partners of Src is p80/85 cortactin. The association was observed in lysates of transformed cells but was not seen in normal fibroblasts. The interaction could be reconstituted in vitro using transformed cell extracts and a glutathione S-transferase (GST) fusion protein containing the Src SH2 domain but not with GST-Src SH3 or with GST-Src SH2 containing a point mutation in the FLVRES sequence. Confocal microscopy revealed that cortactin redistributed and colocalized with v-Src and a Src SH3 deletion mutant in transformed cells. However, in cells expressing a Src SH2 deletion mutant, the redistribution of cortactin and colocalization with Src did not occur. Furthermore, biochemical fractionation of transformed cells indicated that a significant increase in cortactin distribution to the cytoskeletal fraction occurred, which correlated with a shift in the tyrosine-phosphorylated form of the protein. Cortactin fractionated from cells expressing kinase-defective or myristylation-defective Src mutants did not exhibit this shift. These data suggest a molecular mechanism by which tyrosine phosphorylation of cortactin and association with the Src SH2 domain influence the cytoskeletal reorganization induced in Src-transformed cells.

Animals↗
PubMed1995

Cloning of a new cytokine that induces IFN-gamma production by T cells.

The mechanism underlying the differentiation of CD4+ T cells into functionally distinct subsets (Th1 and Th2) is incompletely understood, and hitherto unidentified cytokines may be required for the functional maturation of these cells. Here we report the cloning of a recently identified IFN-gamma-inducing factor (IGIF) that augments natural killer (NK) activity in spleen cells. The gene encodes a precursor protein of 192 amino acids and a mature protein of 157 amino acids, which have no obvious similarities to any peptide in the databases. Messenger RNAs for IGIF and interleukin-12 (IL-12) are readily detected in Kupffer cells and activated macrophages. Recombinant IGIF induces IFN-gamma more potently than does IL-12, apparently through a separate pathway. Administration of anti-IGIF antibodies prevents liver damage in mice inoculated with Propionibacterium acnes and challenged with lipopolysaccharide, which induces toxic shock. IGIF may be involved in the development of Th1 cells and also in mechanisms of tissue injury in inflammatory reactions.

Amino Acid Sequence↗
PubMed1995

Differences of somatostatin mRNA in the rat suprachiasmatic nucleus under light-dark and constant dark conditions: an analysis by in situ hybridization.

Daily profiles of somatostatin mRNA expression were investigated in the rat suprachiasmatic nucleus (SCN) by semiquantitative in situ hybridization histochemistry. Under 12 h light/12 h dark conditions, somatostatin mRNA signals were higher during the day time (Zeitgeber time (ZT) 1) than during the night time (ZT 16). This day-night difference was still maintained in constant darkness where the somatostatin mRNA was higher in the subjective day (circadian time (CT) 1) than in the subjective night (CT 16). Together with previous Northern blot hybridization studies, the present observation suggests that the level of somatostatin mRNA in SCN neurons is controlled by the circadian clock, independent of photic environment.

Animals↗
PubMed1995

Dopamine D2-like receptors labeled by [3H]YM-09151-2 in the rat hippocampus: characterization and autoradiographic distribution.

Dopamine D2-like receptor labeled by [3H]YM-09151-2 in the rat hippocampus proper was examined by in vitro receptor autoradiography. In the dorsal hippocampus, [3H]YM-09151-2 bindings were high in the whole layers of CA1, the stratum pyramidale of CA4 and the stratum molecular of gyrus dentatus, moderate in the stratum oriens of CA3 and hilus of the gyrus dentatus, and low in remaining CA3 and the subiculum. In the ventral hippocampus, the binding densities were high in the stratum oriens and the stratum radiatum of CA1, the stratum pyramidale of CA4, and the stratum moleculare of gyrus dentatus, moderate in the stratum lacnosum moleculare of CA1 and the hilus of the gyrus dentatus. Saturation analysis using hippocampal sections demonstrated that the Kd value was about five times higher than that using striatal sections. The rank order potency of competition on [3H]YM-09151-2 binding by dopaminergic ligands in the hippocampus was YM-09151-2 > (+)-butaclamol > dopamine > sulpiride > SCH-23390; which shows the appropriate dopamine D2-like receptor profile. The hippocampal [3H]YM-09151-2 binding did not represent serotonergic receptors (5-HT1A and 5-HT2) and sigma receptor, since Ki values of ketanserine, serotonin, 8-OH-DPAT and DTG were much lower than D2-like receptor antagonists. These findings suggest tha [3H]YM-09151-2 binds hippocampal D2-like receptor site with different association kinetics of striatal D2-like receptor site, and demonstrates widespread distribution of D2-like receptor in the hippocampus with distinct region-specific profile.

Animals↗
PubMed1995

In situ hybridization histochemistry of vgf mRNA in the rat suprachiasmatic nucleus: co-localization with vasopressin/neurophysin and VIP/PHI.

The expression of vgf gene, first isolated as a gene induced by nerve growth factor in PC12 cells, was investigated in neurons of the suprachiasmatic nucleus (SCN) by in situ hybridization. In the rat forebrain, the vgf mRNA was found most densely in the SCN. Neurons which express vgf mRNA were found both in the dorsomedial and ventrolateral subdivisions. Soluble-labeling of vgf in situ hybridization and peptide immunocytochemistry demonstrated that vgf mRNA was expressed in most vasopressin- and neurophysin-immunoreactive neurons in the dorsomedial part and in vasoactive intestinal peptide (VIP)- and peptide histidine isoleucine amide (PHI)-immunoreactive neurons in the ventrolateral part. These findings suggest that vgf is a highly expressed gene in both vasopressin/neurophysin neurons and VIP/PHI neurons which were speculated to be involved in the generation and entrainment of circadian rhythm.

Animals↗
PubMed1995

Transient expression of estrogen receptor-immunoreactivity (ER-IR) in the layer V of the developing rat cerebral cortex.

Occurrence of estrogen receptor-immunoreactivity (ER-IR) in the cerebral cortex was examined in neonatal and adult rats. In newborn rats of postnatal day 1 (= day of birth) and postnatal day 5 (PD1 and PD5, respectively), ER-IR was not evident in the neocortex. On postnatal days 7, 10 and 13 (PD7, PD10 and PD13 respectively), a group of cells with distinct ER-IR appeared in the layer V of the auditory cortex. At the PD10, weak but specific ER-IR were also appeared in the somatosensory and the visual cortices. Among these areas, the ER-IR positive neurons occurred most frequently in the auditory cortex at PD10 rats. By examination of adjacent sections, one stained with Cresyl violet and the another stained with acethylcholinesterase (AChE) histochemistry, it was revealed that the region with ER-IR at PD7 to PD13 was limited to layer V of the neocortex. These signals, however, disappeared at PD15. In layer II of the neocortex, on the other hand, weak ER-IR signals were detected throughout the area sporadically at PD21 and in adults. The ER-IR detected transiently in the auditory cortex by the antiserum might contribute to maturation and establishment of the neurons of the rat auditory circuit.

Animals↗
PubMed1995

Lateromedial gradient of the susceptibility of midbrain dopaminergic neurons to neonatal 6-hydroxydopamine toxicity.

The topography-dependent vulnerability of midbrain dopaminergic neurons to neonatal intracranial exposure to 6-hydroxydopamine (6-OHDA) was investigated at adult age by the quantitative analysis of cell counts of tyrosine hydroxylase-immunopositive neurons. In all cases of intracisternal 6-OHDA treatment, A9 dopaminergic neurons in the substantia nigra (SN) were much more vulnerable to death than more medially located A10 dopaminergic neurons. Moreover, within each cell group, there were also lateromedial topographic gradients. In the A9 neuronal group, cells located in the pars lateralis of the SN and the lateral part of the pars compacta of the SN were more susceptible to 6-OHDA toxicity than those located more medially. In the A10 neuronal group, cells located in the medial part of the ventral tegmental area were more resistant to toxicity than those located more laterally, and dopaminergic cells in the midline midbrain areas (interfascicular nucleus and rostral linear nucleus of raphe) were completely spared from 6-OHDA toxicity. These findings revealed that 6-OHDA is not equally toxic to all midbrain dopaminergic neurons in neonates and that the lateromedial vulnerability pattern shows similarities to those reported in Parkinson's disease.

Animals↗
PubMed1995

Activated (HLA-DR+) T-lymphocyte subsets in cervical carcinoma and effects of radiotherapy and immunotherapy with sizofiran on cell-mediated immunity and survival.

A prospective randomized trial on 312 patients with locally advanced cervical carcinoma (FIGO stages IB-IV) was carried out. The 5-year survival in 90 patients treated with radiotherapy and antitumor polysaccharide sizofiran, an extract from the culture broth of Schizophyllum commune Fries, in combination was significantly (P = 0.045) better than that in 82 patients treated with radiotherapy alone. Treatment with sizofiran and 5-fluorouracil in combination improved (P = 0.003) the 5-year survival in 60 patients treated with radiotherapy. In 244 cervical carcinoma patients, the percentage of activated CD8+ (CD8+HLA-DR+) T cells in the CD8+ T-cell subsets in peripheral lymphocytes increased significantly as the disease progressed. A similar tendency was observed in the percentage of activated CD4+ (CD4+HLA-DR+) T cells in the CD4+ T-cell subsets. These immunologic parameters were significantly increased by radiotherapy, but not by surgery. Sizofiran accelerated a recovery in the activated CD8+ T cells in the CD8+ T-cell subsets compared with that of sizofiran nontreated patients after radiotherapy. Our data show that possible immune impairment in cervical carcinoma may be caused by disturbances in cell-mediated immunity, and that sizofiran is an effective immunotherapeutic agent for cervical carcinoma because it stimulates a rapid recovery of the immunologic parameters impaired by radiotherapy.

CD4-CD8 Ratio↗
PubMed1995

Immunological disorder against the Epstein-Barr virus infection and prognosis in patients with cervical carcinoma.

Epstein-Barr virus antigen-specific killer T cell (EBV-KT) activity and Epstein-Barr virus (EBV) shedding at uterine cervix and oropharynx were examined in patients with cervical carcinoma. EBV-KT activity was determined by a modified EBV-induced B cell focus regression assay. EBV shedding was examined by infectivity assay. EBV-KT activity in the patients was decreased significantly compared with that of controls (P < 0.001) and became increasingly lower as the clinical stage of the disease advanced. EBV-KT activity was changed by treatment, and decreased EBV-KT activity after treatment was clearly related to patient survival. EBV shedding at oropharynx and uterine cervix were also higher in the patients than in the controls (P < 0.01 and < 0.05). These results suggest that EBV-KT activity is closely associated with the prognosis in patients with cervical carcinoma and that it may be a useful parameter in monitoring the cell-mediated immunity of patients with cervical carcinoma.

Adult↗
PubMed1995

Activated (HLA-DR+) T-lymphocyte subsets in early epithelial ovarian cancer and malignant ovarian germ cell tumors.

We examined peripheral blood T-lymphocyte subsets before initiation of therapy in 79 healthy controls, 3 patients with endometriosis, 95 patients with common epithelial tumors of the ovary, 15 patients with ovarian germ cell tumors, and 3 patients with ovarian sex cord-stromal tumors. In stage Ia/Ib patients with epithelial ovarian cancer, the percentages of activated CD4+ (CD4+HLA-DR+) T cells and activated CD4+ T cells in the CD4+ T-cell subsets were significantly higher than those of healthy controls and patients with benign or borderline epithelial tumors of the ovary. These immunologic parameters were subsequently decreased in patients in stage Ic and more advanced stages. In malignant ovarian germ cell tumors, a similar increase in the CD4+ T-cell subsets was observed. Moreover, the percentage of activated CD8+ T cells in the CD8+ T-cell subsets in stage Ia/Ib patients increased significantly compared with those in healthy controls and patients with benign tumors. Our findings indicate that activated T lymphocytes may play some roles in oncogenesis and progression of both epithelial ovarian cancer and malignant ovarian germ cell tumors.

CD4-Positive T-Lymphocytes↗