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Biomedical subjects

H Okubo

Publications and source records attributed to H Okubo.

At least 19 recordsLinked to original sources
PubMed1992

Plasma plasminogen activator inhibitor activity and tissue plasminogen activator levels in patients with unstable angina and those with coronary spastic angina.

Plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (TPA) antigen were measured in venous samples in 14 patients with unstable angina consisting of eight patients with organic stenosed coronary arteries and six patients with coronary spastic angina (unstable angina group); in 14 patients with stable exertional angina (stable exertional angina group); and in 14 patients with chest pain syndrome (chest pain syndrome group). The plasma levels of PAI activity were higher (p less than 0.01) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (12.3 +/- 1.0 versus 5.1 +/- 0.7 and 4.8 +/- 0.6 IU/ml). The plasma levels of TPA antigen were also higher (p less than 0.05) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (10.2 +/- 1.3 versus 6.5 +/- 0.8 and 6.0 +/- 0.7 ng/ml). There were no significant differences in PAI activity and TPA antigen levels between the stable exertional angina group and the chest pain syndrome group. Furthermore, both PAI activity and TPA antigen levels in the unstable angina group decreased to the levels in the stable exertional angina group and the chest pain syndrome group after treatment (p less than 0.01). In conclusion, the increased plasma PAI activity in patients with unstable angina and in those with coronary spastic angina indicates that the fibrinolytic system is impaired in these patients.

Angina, Unstable↗
PubMed1991

Choroidal and ciliary body blood flow analysis: application of laser Doppler flowmetry in experimental animals.

Laser Doppler flowmetry (LDF) measures the flux of red blood cells in a vascular network embedded in tissue. In the present report, choroidal and ciliary body blood flow was measured continuously using an LDF technique in pentobarbital anesthetized cats. Blood flow measurements were made from the choroid beneath the lateral and superior rectus muscles and from the surface above the ciliary body 2-3 mm posterior to the limbus. In some experiments, the sympathetic nerve to the eye was stimulated; in others, intraocular pressure (IOP) was monitored manometrically with a controlled saline infusion delivered into the anterior chamber to gradually elevate IOP. Norepinephrine (NE) and methacholine (MC) also were tested for their effects on choroidal blood flow when given intravenously and intra-arterially. Transient bilateral carotid artery occlusions produced a significant drop in blood flow, but flow did not decrease to zero probably due to collateral contribution of the vertebral circulation. Sympathetic nerve stimulation produced a frequency-dependent decrease in both choroidal and ciliary body blood flow with the latter exhibiting a lower threshold and a greater magnitude of effect. Gradual elevation of IOP produced a proportional decrease in choroidal blood flow. The level of intraocular pressure required to decrease blood flow was dependent on the existing ocular perfusion pressure. Both intravenous and intra-arterially administered NE produced dose-dependent decreases of choroidal blood flow despite graded increases of systemic arterial blood pressure. In contrast, MC produced dose-dependent increases of choroidal blood flow in conjunction with graded decreases of systemic blood pressure. The results of the present report demonstrate the validity of the LDF technique for performing continuous reading of blood flow changes in the choroid and ciliary body of experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Long posterior ciliary arterial blood flow and systemic blood pressure.

The purpose of the current study was to investigate the relationship between systemic blood pressure (BP) and long posterior ciliary arterial (LPCA) blood flow (BF) in response to autonomic drugs, and to determine the types of receptors involved. LPCA BF was measured in anesthetized rabbits at the retrobulbar region using laser Doppler flowmetry. The observation that most of the short posterior ciliary arteries diverge from two LPCAs in rabbits was confirmed using a vascular casting technique. Therefore, the LPCA BF at the retrobulbar region should be representative of total uveal BF. Norepinephrine (IV) increased systemic BP and decreased LPCA BF. These responses were suppressed only slightly by yohimbine, but were inhibited markedly by prazosin and by the combination of yohimbine and prazosin. B-HT 920 (IV), a selective alpha-2 adrenoceptor agonist, increased systemic BP and decreased LPCA BF. B-HT 920 (IA) also decreased LPCA BF, with all effects of B-HT 920 antagonized by yohimbine. Methacholine (IV) decreased systemic BP and increased LPCA BF whether administered IV or IA. These effects were blocked uniformly by atropine. The current results suggest that LPCA BF is controlled both by systemic BP and local ocular vascular tone. There are vasoconstrictive alpha-1 and alpha-2 adrenoceptors and vasodilative muscarinic receptors in the rabbit ocular vascular tree.

Adrenergic alpha-Agonists↗
PubMed1990

Effects of amino acids on acute alcohol intoxication in mice--concentrations of ethanol, acetaldehyde, acetate and acetone in blood and tissues.

Condensation reactions between some SH-amino acids (L-and D-cysteine 1%) and acetaldehyde (50 microM) were studied in vitro experiment. In the aqueous solution, free acetaldehyde was reduced to 41.3% by L-cysteine and to 36.4% by D-cysteine. In the reaction with human blood medium, after the medium was deproteinized with perchloric acid reagent, acetaldehyde was reduced to 47.0% by L-cysteine and to 43.8% by D-cysteine. D-Cysteine appears to have great stability of reacting acetaldehyde. In vitro experiment reactability for D-cysteine exhibited 3-8% higher than that for L-cysteine. Next, effects of some amino acids on alcohol metabolism were studied in male ICR mice. The animals were given ethanol through a gastric catheter at a dose of 2 g/kg and they were intraperitoneally injected L-cysteine (300 mg/kg), D-cysteine (300 mg/kg), L-alanine (300 mg/kg) and control (saline), respectively in the period of one hour before the injection of ethanol. Blood and tissues samples were analyzed for ethanol, acetaldehyde, acetate and acetone during alcohol intoxication in mice by head space gas chromatography. In the groups administered D-cysteine and L-cysteine, the mice showed a definitely faster oxidation and disappearance of ethanol. Especially in the D-cysteine group, ethanol levels in blood, liver and brain remained lower than that in the other groups (p less than 0.01). Acetaldehyde levels in blood, liver and brain remained low by L-cysteine. Ethanol metabolites during alcohol oxidation by chemical reactabilities of L- and D-cysteine showed different distribution in the mice, respectively. In the mice received L-alanine, acetate and acetone levels in blood, liver and brain were distinctly reduced (p less than 0.01). L-Alanine is reported to supply an abundance of pyruvic acid that performs the NAD-generating system. NAD produced is introduced to alcohol metabolism and the TCA cycle. It was thus presumed that the L- or/and D-cysteine, and L-alanine was effective in acute alcohol intoxication by heavy drinking.

Acetaldehyde↗
PubMed1990

[Cytogenetical study on the etiology of partial mole].

The cytogenetical etiology of partial mole (PM) was studied by means of the Q-banding technique in 49 cases during the period between Sep. 1976 and Nov. 1986. Moreover, histological examinations were performed in 39 cases concentrating on the existence of fetal components and trophoblastic hyperplasia, etc. The results were as follows. 1. Karyotype analysis showed triploidy (24 cases), normal diploidy (10 cases), trisomy (9 cases) and other anomalies (mosaic, translocation etc.) (6 cases). These results are quite different from those of many western authors, who reported that most cases of PM are triploidy. 2. The criteria of PM in Japan differ from those of WHO Scientific Group in regard to trophoblastic hyperplasia. 3. Our cases were reclassified on the basis of the definition drawn up by the WHO Scientific Group. Nevertheless, the rate of triploidy was only 54.5%, which is lower than that reported by many western authors. These results show that the development of PM cannot be explained cytogenetically at present, in contrast with complete mole.

Diploidy↗
PubMed1989

Induction of polymorphonuclear leukocyte-derived hepatocyte stimulating factor and effects on alpha 2-macroglobulin synthesis.

We investigated the kinetics of production of the hepatocyte stimulating factor (HSF) by peritoneal exudate- and peripheral circulating blood-polymorphonuclear leukocytes (PMNLs). Effects of the HSFs on alpha-2-macroglobulin (a2M) synthesis and a2M specific gene expression in primary cultured adult rat hepatocytes were also examined. Peritoneal exudate-PMNLs were collected 3 hr after the injection of alkaline-denatured casein into the peritoneal cavity of rats. Secretion of HSF into the culture medium began within 15 min after the start of incubation and practically a full secretion was noted within 3 hr. Lipopolysaccharide or other agents were not required to induce HSF from the PMNLs. Inhibitors of protein or DNA synthesis, cycloheximide, actinomycin D or puromycin, did not inhibit the secretion of HSF by rat PMNLs thereby suggesting that preformed and pooled HSF in the PMNLs was secreted during incubation. Peripheral circulating blood-PMNLs collected from a healthy man did not secrete HSF, in the absence of stimulation but did secrete HSF after vigorous agitation during incubation at 37 degrees C. The PMNL-HSF induced the synthesis of a2M and the accumulation of a2M mRNA in primary cultured rat hepatocytes. However, the effect was evident only with dexamethasone present in the culture medium. Furthermore, the effects of the PMNL-HSFs on a2M and albumin protein synthesis were reciprocal: The PMNL-HSF induced a2M synthesis, whereas it suppressed albumin synthesis.

Albumins↗
PubMed1989

[A four-year follow-up study of hepatocellular carcinoma with bone metastasis].

A 68-year-old male was admitted to hospital for treatment of a hepatocellular carcinoma with a bone metastasis. By TAE and the administration of PSK, the tumor was necrotized and the AFP level returned to normal range. We presume that this combination therapy of TAE and PSK was able to maintain normal cellular immunity and bring about this good result.

Adjuvants, Immunologic↗
PubMed1988

[A case of non-functional adrenocortical adenoma showing enlargement in size during follow-up period].

A case of non-functional adrenocortical adenoma is reported. The patient was a 62-year-old woman with the chief complaint of right hypochondoralgia. The small right adrenal tumor was found incidentally by ultrasonography on examination for cholecystolithiasis. Since there was no evidence of malignancy from biochemical data, observation of the tumor was performed for 3 months. However, the lesion was gradually increased in size. Therefore, right adrenalectomy was performed. Histological findings revealed benign adrenocortical adenoma. In the Japanese literature this case seems to be the 36th case of non-functional adrenocortical adenoma.

Adenoma↗
PubMed1987

Kupffer cells modulate natural killer cell activity in vitro by producing prostaglandins.

The effect of Kupffer cells on natural killer (NK) cell-mediated cytotoxicity was examined. Kupffer cells prepared from rat liver suppressed NK activity against K562 cells and other tumor cell lines through a soluble factor secreted into the culture supernatant. When human peripheral blood mononuclear cells were incubated with the Kupffer cell-culture supernatant, a significant reduction of the cytotoxic activity was observed in the 6-hr chromium-release assay. This activity was dose dependent and was evident at various effector/target cell ratios. Lipopolysaccharide stimulated generation of the suppressive factor released from Kupffer cells in a dose-dependent manner. Suppression of the NK activity was observed when the Kupffer cell-culture supernatant was present in the assay system, whereas pretreatment of effector/target cells with the supernatant had minimal inhibitory effects. Autologous monocytes in human peripheral mononuclear cells were not related to this suppression. The suppressive factor in the fraction had a molecular weight below 10,000. Indomethacin, an inhibitor of prostaglandin synthesis, ameliorated the suppressive effects. These results suggest that Kupffer cells may modulate NK activity by producing PGs (E1, E2, and F2 alpha).

Animals↗
PubMed1987

Sequence analysis of the putative regulatory region of rat alpha 2-macroglobulin gene.

Rat alpha 2-macroglobulin (alpha 2M) is an acute-phase reactant, concentration of which in serum increases more than 100-fold in the course of inflammation. Glucocorticoid and some protein factors such as interleukin 1 (IL-1) have been known to be involved in the regulation of this plasma protein synthesis. To understand the regulatory mechanism of alpha 2M production at the molecular level, we isolated genomic DNA clones of rat alpha 2M gene and characterized the promoter region of the gene by comparing the nucleotide sequence with those of other acute-phase reactant genes. Several possible regulatory signals were identified. Particularly, a sequence (T/A)T(C/G)TGGGA(A/T) was found about at 170 bp upstream from a putative capping site, which was also found in the 5'flanking region of various acute-phase reactant genes.

Animals↗
PubMed1987

Kupffer cell stimulation of alpha 2-macroglobulin synthesis in rat hepatocytes and the role of glucocorticoid.

When stimulated with lipopolysaccharide (LPS), primary cultures of Kupffer cells from the rat secreted a hepatocyte-stimulating factor (Kupffer factor) which induced the synthesis of alpha 2-macroglobulin (a2M) by hepatocytes. The effect of this Kupffer factor was found only when dexamethasone was present in the hepatocyte culture medium. Dexamethasone alone stimulated the a2M synthesis, to some extent, in a dose-dependent manner. When both Dex and the Kupffer factor were added to the medium, cultured hepatocytes synthesized 100-fold a2M, quantitative evidence that explains the in vivo phenomenon in which the serum a2M concentration increases more than 100-fold in the acute phase. A co-culture study with hepatocytes and Kupffer cells indicated that the latter cells have a major function in the induction of a2M synthesis in vivo. A hybridization study with rat a2M cDNA showed that the concentration of mRNA increased in cultured hepatocytes in the presence of the Kupffer factor, but only when dexamethasone was present. From these results we concluded that Kupffer cells secrete a hepatocyte-stimulating factor when stimulated by LPS and that glucocorticoid is essential for the induction of a2M in rat hepatocytes. The effect of the Kupffer factor and glucocorticoid appears to be regulated in the pretranslational, probably the transcriptional, phase.

Animals↗
PubMed1987

[Clinical and histological studies on vaginal reconstruction after radical hysterectomy].

The extensive resection of vagina has a prime importance to obtain the remission in patients with invasive carcinoma of cervix. Maintenance of optimal length, configuration and physiologic function of vagina has been neglected because of malignant nature of lesions. Thus, sexual frigidity coupled with dyspareunia was usually a serious problem faced by postoperative patients. In order to resolve this problem we devised a new attempt to obtain sufficient regeneration of vagina in postoperative patients. The protection procedure for a shortened vagina consists of enlargement of the vaginal vault and promotion of epithelial regeneration. Vaginal length in 145 patients who had received the protection procedure as well as the radical hysterectomy was 7.0 +/- 0.1 cm, being not different from the one in 187 patients with simple hysterectomy. However, significantly shortened length was observed in 21 patients hysterectomized radically who had not the protection. The influence of preserved ovarian functions into the regeneration process of vagina was investigated. The mean length was 7.3 cm in 75 patients with ovarian conservation and 6.3 cm in 7 patients with bilateral oophorectomy. The latter was significantly shorter than the former. However, administration of synthetic estrogens alone was incomplete for the full reconstruction of remnant vagina. Adjuvant radiotherapy was not an obstacle in obtaining the optimal vaginal length. The mean length of irradiated group was 7.4 cm, being not different from the one of the nonirradiated group. Regeneration process of vagina was investigated histologically. New vaginal lumen consisted originally of the remnant vagina and granulation tissues obliterating dead spaces in the pelvic floor. Then, epithelia stained with iodine followed to cover the granulation. Enlargement of such areas directed into the deep part of vault was evident with the passage of time following the operation. As a result, epithelial covering of the whole reconstructed vagina was completed within 2 months after the operation. Those results indicated the clinical availability of the protection procedure in radically hysterectomized patients. Then, ovaries conserved either by orthotopic manner or transposition plays some role for the reconstruction of remnant vagina.

Adult↗
PubMed1986

Human lymphocytes synthesize C-reactive protein.

We obtained evidence for the synthesis and secretion of C-reactive protein (CRP) by peripheral mononuclear cells in culture. Human mononuclear cells isolated from peripheral blood, after depletion of platelets, were cultured in glutamine-depleted RPMI 1640 supplemented with [3H]glutamine in the presence of 10-O-tetradecanoyl-phorbol-13-acetate (TPA). Anti-CRP antiserum was added to the culture medium, and the resultant immunoprecipitate was analyzed in SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The immunoprecipitate consisted of CRP, heavy and light chains of IgG, and only the CRP protein band had radioactivity, indicating that CRP was synthesized by mononuclear cells. In the populations of mononuclear cells, T-cell preparations mainly synthesized CRP, under stimulation of a factor derived from activated monocytes. Studies using the inhibitors of phospholipid metabolism suggested that generation of the monocyte factor was relevant to metabolites of an arachidonate cascade.

B-Lymphocytes↗
PubMed1986

Selective partial IgM deficiency: functional assessment of T and B lymphocytes in vitro.

Seven patients with selective IgM deficiency (SIgMD) were studied for cell surface immunoglobulin (SmIg), T-cell subpopulations, and immunoglobulin (Ig) synthesis in vitro by peripheral blood lymphocytes (PBL). Serum IgM levels were less than 25 mg/dl, while IgA, IgG, and IgD were within normal levels. The patients had respiratory or urinary tract infections and two were diagnosed as having systemic lupus erythematosus (SLE). T/B-cell ratios in PBL were within normal ranges. Percentage ratios of B cells bearing SmIg were normal in five patients and decreased in two; however, normal values were seen after 7 days of culture in the presence of PWM. OKT4/OKT8 ratios decreased in five of seven patients, in whom two were due to a decrease in OKT4 and two to an increase in OKT8 cells. One showed a decrease in OKT4 and an increase in OKT8. Analysis of lymphocyte function for Ig synthesis in vitro, using a coculture of counterpart T and B cells from healthy individuals and patients with SIgMD, revealed that the increased function of IgM isospecific suppressor T cells (Ts) was responsible for the IgM deficiency in all seven patients.

Adult↗
PubMed1986

Expression of rat alpha 2-macroglobulin gene during pregnancy.

Rat alpha 2-macroglobulin (alpha 2M) is a typical acute phase protein, the concentration of which in serum increases more than 100-fold after inflammation. It is also known that the protein increases during pregnant (and neonatal) stages. Using a specific cDNA probe, expression of the alpha 2M gene during pregnancy was studied at the mRNA level. During inflammation, the liver is almost the only organ producing alpha 2M, but during pregnancy the placenta and uterus were found to be major organs producing a large amount (70-80% of that of inflamed liver) of alpha 2M mRNA at days 12-15. The yolk sac, maternal liver and fetal (or neonatal) liver also produced a small but significant amount (5-20% of that of inflamed liver) of the mRNA. Southern blotting analysis showed that only one copy of the alpha 2M gene was present in a haploid rat genome. These results indicated that a single alpha 2M gene has the ability to respond to two completely-different physiological states.

Animals↗
PubMed1986

Polymorphonuclear leukocytes and the induction of alpha 2-macroglobulin synthesis.

Peritoneal exudate-polymorphonuclear leukocytes (PMNLs) secreted a factor, PMN factor (PMN-F), which stimulated hepatocytes to synthesize alpha 2-macroglobulin (a2M), in vitro. The synthesis of a2M was enhanced by the factor in the presence of dexamethasone (Dex), and the effect was dose-dependent. After harvesting from the peritoneal exudate, PMNLs released the factor within 1 hr of the incubation. Physicochemical properties of the factor were as follows: nondialyzable, heat-labile, stable in wide pH change, inactivated by a protease inhibitor, aprotinin, and apparent molecular weight being 12,000-21,000, determined by gel filtration. Treatment of PMNLs with zymosan resulted in increases in the activity of lysosomal enzymes but not that of the factor. These results indicate that the factor is a protease other than lysosomal enzymes.

Animals↗