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Biomedical subjects

F Kobayashi

Publications and source records attributed to F Kobayashi.

At least 73 records · Page 4Linked to original sources
PubMed1995

Severe chronic active hepatitis induced by UFTR containing tegafur and uracil.

A 77-year-old female patients developed severe hepatic injury after the administration of UFTR, which contains tegafur and uracil, for postoperative chemotherapy of colon cancer. Liver damage was recognized 10 months after its administration. Serum markers for viral hepatitis and various autoantibodies were negative. The wedged biopsied liver specimen revealed advanced chronic active hepatitis with periportal confluent necrosis, marked intralobular spotty necrosis, and significant proliferation of pseudo-bile ductules. Although the cessation of the drug and conservative therapies improved hepatic function, an accidental readministration of UFTR caused her severe hepatic damage again. These findings suggest that liver injury in the present case was caused by UFTR. Histological findings were unique. Although tegafur is known to worsen hepatic function when given to patients with liver cirrhosis, UFTR may also cause severe hepatic injury in those without preexisting liver disease.

Aged↗
PubMed1995

Relationship between lupus anticoagulant (LAC) and pregnancy-induced hypertension.

Lupus anticoagulant (LAC), a serum antiphospholipid autoantibody, is believed to be one of the causes of infertility or fetal loss. The purpose of the present study was to evaluate the role of LAC in the pathogenesis of hypertension during pregnancy. In this study, 20 pregnant women with hypertension were classified into two groups: 14 patients who did not have hypertension before the pregnancy but developed it during the pregnancy (pregnancy-induced hypertension; Group A) and 6 patients who had hypertensive or renal disease before the pregnancy, and developed further hypertension during the pregnancy (pregnancy-aggravated hypertension; Group B). A LAC coagulation assay was performed, and the presence of LAC in each group was compared. All 14 patients in group A were LAC-negative. In contrast, 3 of the 6 patients in group B were LAC-positive, and had clinical autoimmune diseases. The incidence of pregnancy-induced hypertension was also examined in 15 pregnancies from 9 LAC-positive women who had a history of repeated fetal loss but no systemic autoimmune disease (Group C). None of these 15 pregnancies had hypertensive complications, even when they reached term. In the placentas of LAC-positive women, no characteristic changes other than fibrinoid degeneration and microscopic infarction were observed upon histological examination. These results suggest that LAC does not relate with the onset of hypertension during pregnancy.

Adult↗
PubMed1995

Biochemical and topological analysis of adult T-cell leukaemia-derived factor, homologous to thioredoxin, in the pregnant human uterus.

Adult T-cell leukaemia-derived factor (ADF), homologous to thioredoxin, displays various biological activities, such as radical scavenging action and the reduction of protein disulphide bonds. We examined the biochemical and immunohistochemical localization of ADF in the pregnant human uterus, using two heteroantibodies to ADF, antibody C and W. Immunohistochemically, decidua and trophoblast cells were intensely stained by antibody C. The concentration of ADF-like substance in the decidua was 95.9 ng/mg protein, determined by enzyme-linked immunosorbent assay. The molecular weight of ADF-like substance in these tissues was determined by gel electrophoresis to be 13 kDa, the same as that of recombinant ADF. These findings indicate that abundant ADF is present in decidua and trophoblast cells; the localization of such a potent dithiol reducing substance may be beneficial in protecting the fertilized egg and placental trophoblasts from the cytotoxic effects of oxygen radicals.

Adult↗
PubMed1995

A variant alkaline phosphatase found in a case of gastric carcinoma with super bone scan.

A rare case of gastric carcinoma associated with increased serum variant alkaline phosphatase activities is presented. A 54 year old man had extremely high serum alkaline phosphatase activity (18,607 U/l) with normal calcium and phosphate concentrations. His bone scintigram showed abnormal findings, 'super bone scan'. He was diagnosed as having Borrmann type 4 gastric carcinoma with diffuse bone metastases by examinations of the upper gastrointestinal tract and iliac bone biopsy. The alkaline phosphatase isozyme of this patient was of the bone type as measured by cellulose acetate membrane electrophoresis and the placenta/bone type by agarose gel electrophoresis, respectively. Immunoelectrophoresis and the immunoprecipitation method using monoclonal antibodies against various alkaline phosphatase isozymes, however, showed that his serum alkaline phosphatase had the liver type antigenicity. Furthermore, it had a larger molecular size and different sugar chains compared with the common liver type alkaline phosphatase. These findings suggest that a unique variant alkaline phosphatase was produced by gastric cancer cells, which is possibly an explanation for the high serum alkaline phosphatase activities in this patient.

Alkaline Phosphatase↗
PubMed1995

Assessment of job stress dimensions based on the job demands- control model of employees of telecommunication and electric power companies in Japan: reliability and validity of the Japanese version of the Job Content Questionnaire.

To investigate the reliability and validity of 4 selected scales from the Japanese version of the Job Content Questionnaire (JCQ. Karasek, 1985)-decision latitude, psychological demand, supervisor support, and coworker support-a survey was conducted on a total of 626 employees of telephone and electric companies in Japan. The survey questionnaire was composed of 22 items. Data from 472 male and 108 female respondents were analyzed. Cronbach's alpha coefficients for the four JCQ scales ranged from .61 to .89 for men and from .65 to .87 for women. Scree plots based on factor analyses of scale items indicated that one major factor explained 30% to 75% of each scale variance in men and women. Factor structures of the 22 items for men and women were consistent with those theoretically expected Distributions of the decision latitude scores among occupations for men and women were similar to those in the U.S. national samples; the scores significantly and positively correlated with occupational class. It is suggested that the JCQ scales are reliable and valid instruments for assessing job stressors in a Japanese working population.

Journal Article↗
PubMed1995

Possible involvement of different mechanisms in sudden death induced by endothelin-1 and big endothelin-1.

The effects of diltiazem and phosphoramidon on sudden death induced by endothelin (ET)-1 and by big ET-1 were compared in rodents. Diltiazem (2 mg/kg, i.v.) remarkably diminished the lethal toxicity of ET-1 with a reduction in the extent of the rise in plasma immunoreactive ET-1-like activity (IR-ET-1), tissue IR-ET-1 accumulation in the heart and the rise in plasma potassium concentration. In big ET-1-induced lethality, diltiazem only slightly prolonged the latency and did not reduce the mortality. Although diltiazem moderately inhibited the rise in plasma IR-ET-1 and potassium concentration in these mice, it did not affect the accumulation of IR-ET-1 in the heart, lung or kidney. Phosphoramidon (2 mg/kg, i.v.) decreased the lethality of big ET-1 with the decrement in elevation of IR-ET-1 in the heart, lung and plasma as well as with the decrease in plasma potassium concentration, but it failed to improve any parameters in ET-1-induced lethality. In anesthetized rats, ET-1 (5 nmol/kg, i.v.) elevated ST-segment of electromyocardiograms, and diltiazem (2 mg/kg, i.v.) significantly reversed this change. Big ET-1 (25 nmol/kg, i.v.) also induced the ST-segment elevation, which was significantly inhibited by phosphoramidon but not by diltiazem. These findings suggest that accumulation of ET-1 in the heart, which may lead to lethal cardiac ischemia, is an important factor in the lethality of ET-1, while additional factors (such as hemoconcentration and bronchoconstriction) may be involved in big ET-1-induced lethality.

Anesthesia↗
PubMed1994

Expression of biologically active receptors for natriuretic peptides in the human uterus during pregnancy.

Human amnion cells secrete a large amount of brain natriuretic peptide (BNP). In the present study, to elucidate the possible roles of amniotic BNP during the course of human pregnancy, the tissue distributions of biologically active receptors of natriuretic peptides, atrial natriuretic peptide (ANP)-A receptor and ANP-B receptor in the human uterus during pregnancy were investigated by Northern blot analysis and an in vitro guanosine 3',5'-cyclic phosphate (cGMP) generation assay, the second messenger of natriuretic peptides, using crude membrane preparations. Both ANP-A and ANP-B receptor mRNAs were detected in the tissues of decidua vera, chorion laeve, myometrium and placenta. The in vitro cGMP generation assay revealed that the expression of ANP-A receptor was more prominent than that of ANP-B receptor in these tissues. On the other hand, in amniotic tissue only ANP-B receptor mRNA was weakly expressed but ANP-A receptor mRNA was not detected.

Atrial Natriuretic Factor↗
PubMed1994

Detection of adult T-cell leukemia-derived factor/human thioredoxin in human serum.

Adult T-cell leukemia (ATL)-derived factor (ADF), originally defined as an inducer of interleukin-2 receptor/alpha-chain (IL-2R/p55) of human T-lymphotropic virus type I (HTLV-I) positive T cells, is a human homologue of redox-active coenzyme thioredoxin (Trx) of Escherichia coli. In this study, an enzymatic assay system based on the dithiol-dependent insulin-reducing activity of ADF/Trx was established (insulin-reducing assay) to determine the amount of ADF/Trx in human serum using NADPH and Trx reductase purified from human placenta. Insulin-reducing activity was detected in all of the serum samples from healthy volunteers (n = 30) screened by this assay, with a mean +/- SD of 10.9 +/- 2.4 U/l. This mean value corresponds with the concentration of 223 ng recombinant ADF/Trx (rADF/Trx)/ml. Human serum is known to contain several redox-active proteins with ADF/Trx motifs. To differentiate the contribution of these proteins and ADF/Trx to the insulin-reducing activity, the anti-rADF/Trx monoclonal antibody (mAb)-conjugated affinity column-depleted sera obtained from an identical source was used for analysis. The affinity column-depleted sera demonstrated a loss of over 99% of the original activity, while control column depleted sera lost less than 4%. Furthermore, the amount of affinity-purified ADF/Trx molecules eluted from the same column almost corresponded with the amount estimated by the insulin-reducing activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A case of sarcoidosis revealed in the course of IgA nephropathy.

A 36 year old man, who had been proteinuric for 14 years due to immunoglobulin A (IgA) nephropathy, was admitted because of an acute exacerbation in renal dysfunction with hypercalcemia. He had presented with aortic regurgitation and increased pulmonary marking by chest X-ray, but laboratory examinations had failed to make an exact diagnosis. On admission, noncaseating epithelioid granulomas were disclosed by muscle and skin biopsies. Ophthalmological evaluation revealed old uveitis and retinal changes consistent with sarcoidosis. In this case, IgA nephropathy was thought to be the initial manifestation of sarcoidosis that developed latently. Sarcoidosis should be considered in a differential diagnosis of IgA nephropathy.

Adult↗
PubMed1994

Diltiazem facilitates endothelin clearance from the blood stream to reduce toxic elevation of plasma endothelin level in rodents.

Pretreatment with diltiazem at a dose of 2 mg kg-1 intravenously protected against sudden death induced by intravenous administration of endothelin-1 (ET-1, 5 nmol kg-1), with an apparent decrease in the plasma immunoreactive-ET-1 (IR-ET-1) in mice. These effects, which were also observed in anaesthetized rats, disappeared in rats with bilateral ligation of the renal arteries. In the latter, the exogenous ET-1-induced elevation of plasma IR-ET-1 tended to be higher than that in the sham-operated controls. Furthermore, in anaesthetized rats, diltiazem inhibited ET-1-induced decreases in renal blood flow and increased renal accumulation of IR-ET-1. These results indicate that part of the clearance of ET-1 from the bloodstream occurs in the kidney, and that diltiazem enhances the elimination of the peptide, presumably by improvement in the renal circulation, this action leading to alleviation of the toxic effects of ET-1.

Anesthesia↗
PubMed1994

Characterization of CA125 glycoprotein using 3 monoclonal antibodies with different specificities.

CA125 and CA130 in various tissues were characterized using the monoclonal antibodies OC125, 130-22, and 145-9. CA125 and CA130 were eluted in the same fraction in 130-22 affinity chromatography. A sandwich immunoradiometric assay using these antibodies in combination was established. When the solid phase of the assay was changed from OC125 to 145-9, the amount of 125I-OC125 that reacted with CA125 in the amnion increased more than that in other samples. On SDS-PAGE, CA125 and CA130 epitopes in the amnion migrated to different positions. These results indicate that CA125 and CA130 are located on different subunits of the same glycoprotein, and that their synthesis is regulated differently in various tissues.

Amnion↗
PubMed1994

Transforming growth factor-beta stimulates, and glucocorticoids and epidermal growth factor inhibit brain natriuretic peptide secretion from cultured human amnion cells.

We previously reported the massive secretion of brain natriuretic peptide (BNP) from human amnion cells and suggested the possible role of BNP in the maintenance of human pregnancy. In this study, to elucidate the regulatory mechanism of BNP secretion from amnion cells, we measured the BNP level in the culture medium of amnion cells by RIA after incubation in the presence of various substances. Among the agents examined, cortisol (1 x 10(-7) to 1 x 10(-6) mol/L), dexamethasone (1 x 10(-8) to 1 x 10(-6) mol/L), and epidermal growth factor (EGF; 2 x 10(-11) to 2 x 10(-8) mol/L) inhibited BNP secretion from the cultured amnion cells in a dose-dependent manner. By contrast, transforming growth factor-beta (TGF beta; 4 x 10(-11) to 4 x 10(-9) mol/L) caused a 3- to 5-fold increase in BNP secretion. TGF beta-augmented BNP secretion was abolished by the addition of cortisol or EGF to the culture medium. Moreover, in this study, we revealed the presence of bioactive TGF beta in human amniotic fluid (approximately 4 x 10(-10) mol/L). The present finding of tight regulation of BNP secretion from amnion cells by cortisol, EGF and TGF beta, all at the concentrations physiologically present in human amniotic fluid, implies a physiological role of BNP secretion from amnion cells in the pregnant uterus.

Amnion↗
PubMed1994

Inhibitory activities of metal chelators on endothelin-converting enzyme. I. In vitro studies.

The effects of various metal chelators on endothelin (ET)-converting enzyme (ECE) activity were examined in vitro. Three chelators, 2,3-dimercapto-1-propanol (DMP), toluene-3,4-dithiol (TDT) and 8-mercaptoquinoline (8-MQ), were found to dose-dependently inhibit ECE activity, but this inhibition was much weaker compared with EDTA. In the presence of Zn2+, the inhibitory activity of all these compounds, including EDTA, was abolished. The addition of Ca2+ and Mg2+ markedly attenuated the inhibitory activity of EDTA, but the other three chelators were still able to inhibit ECE. ECE, once inactivated by EDTA or 8-MQ, was reactivated by the addition of divalent cations such as Zn2+ and Mn2+. These compounds also inhibited angiotensin-converting enzyme activity in a manner similar to the inhibition exhibited towards ECE. Chelate-titration indicated that DMP, TDT and 8-MQ chelate Zn2+ but not Ca2+ and Mg2+. These results suggest that the ECE inhibition exhibited by these compounds is mainly attributable to their chelating activities. The metal-selective chelating activity by DMP, TDT and 8-MQ may contribute to the retention of ECE inhibition in the presence of Ca2+ and Mg2+.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Inhibitory activities of metal chelators on endothelin-converting enzyme. II. In vivo studies.

The effects of metal chelators on endothelin (ET)-converting enzyme (ECE) activity in vivo were examined. Three compounds, (2,3-dimercapto-1-propanol (DMP), toluene-3,4-dithiol (TDT) and 8-mercaptoquinoline (8-MQ)), which inhibited ECE in in vitro studies, exhibited inhibitory activity towards big ET-1-induced sudden death in mice, while EDTA did not. Similar results were obtained in big ET-1-induced hypertension. Big ET-1-induced hemoconcentration was inhibited by pretreatment with 8-MQ or EDTA but not with DMP or TDT. The elevation of immunoreactive ET-1 (IR-ET-1) in plasma after administration of big ET-1 was inhibited by pretreatment with the three compounds but not by EDTA. On the other hand, no chelator inhibited the elevation of IR-ET-1 in lung tissue after injection of big ET-1. Taking into consideration the in vitro results, more selective chelating activity of the compounds towards Zn2+ rather than Ca2+ and Mg2+ may contribute to the inhibition of big ET-1-induced responses in vivo. The ET-1 formation involved in big ET-1-induced hemoconcentration may have different physiological characteristics from that involved in big ET-1-induced sudden death or hypertension.

Animals↗
PubMed1994

Substituted 1,8-naphthyridin-2(1H)-ones as selective phosphodiesterase IV inhibitors.

New substituted 1,8-naphthyridin-2(1H)-ones have been found to exhibit highly selective phosphodiesterase (PDE) IV inhibition. These compounds inhibited polymorphonuclear leukocyte activation induced by N-formylmethionyl-leucyl-phenylalanine and caused relaxation of isolated guinea pig trachea precontracted by histamine or leukotriene D4. In anesthetized guinea pigs, presensitized with the antigen, these compounds also alleviated airway constriction induced by the antigen. Since these compounds differ in their chemical structure compared with theophylline and other PDE IV inhibitors so far reported and some of them have been shown to be well tolerated in acute toxicity studies, they will provide a new tool for investigating the possible relationship between PDE IV inhibition and anti-asthmatic activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Possible mechanisms of sudden death and hemoconcentration induced by endothelin-1 and big endothelin-1 in mice.

We investigated the profiles of sudden death and hemoconcentration induced by endothelin-1 (ET-1) and big endothelin-1 (big ET-1) in mice using various compounds as pharmacological tools. In ET-1-induced sudden death (5 nmol/kg, i.v.), pretreatment with the Ca(2+)-channel blockers, diltiazem, nifedipine or verapamil at a dose of 2 mg/kg, i.v. significantly inhibited the mortality and prolonged the latency to death. These Ca(2+)-channel blockers, however, failed to inhibit the rise in hematocrit (Ht), namely hemoconcentration, induced by ET-1 (2.5 nmol/kg). A beta-adrenoceptor agonist, isoproterenol (1 mg/kg) tended to prolong the latency, whereas, a beta-adrenoceptor blocker, propranolol (2 mg/kg), and an alpha- and beta-adrenoceptor blocker, labetalol (5 mg/kg), aggravated the sudden death. Esculetin (10 mg/kg) and fenbufen (10 mg/kg), which are enzyme inhibitors in the arachidonate cascade, prevented only the hemoconcentration. Anti-arrhythmic drugs, lidocaine (1 mg/kg) and disopyramide (20 mg/kg) did not improve any parameters. Big ET-1 also caused sudden death (20 and 25 nmol/kg, i.v.) and hemoconcentration (10 nmol/kg, i.v.). Of several proteinase inhibitors, only a metalloproteinase inhibitor, phosphoramidon (2 mg/kg i.v.), prevented the sudden death and the hemoconcentration induced by big ET-1 but not by ET-1. Ca(2+)-channel blockers exerted their protective effects only when a lower dose of big ET-1 was employed. These results indicate that the sudden death caused by both peptide is mainly due to myocardial ischemia and respiratory disorder, and that hemoconcentration caused by them is due to their vasoconstrictor action but to their effects on the vascular permeability via secondary endogenous factors.

Adrenergic alpha-Antagonists↗
PubMed1994

Novel and potent aldose reductase inhibitors: 4-benzyl- and 4-(benzothiazol-2-ylmethyl)-3,4-dihydro-3-oxo-2H-1,4-benzothiazine-2-ac etic acid derivatives.

A number of 1,4-benzothiazine-2-acetic acid derivatives (1, 2 and 3) and their bioisosteres (15b, 16, 18 and 20b) were synthesized and evaluated in vitro for the ability to inhibit aldose reductase (AR) in porcine lens. The compounds which exhibited potent activity in vitro were also assayed in vivo for inhibitory activity against sorbitol accumulation in the erythrocytes, sciatic nerve and lens of streptozotocin-diabetic rats. The 4-(substituted benzothiazol-2-ylmethyl)-1,4-benzothiazine-2-acetic acid derivatives (2 and 3) showed more potent AR inhibitory activity than did the 4-(4-bromo-2-fluorobenzyl)-1,4-benzothiazine-2-acetic acid derivatives (1). 4-(4,5,7-Tri-fluorobenzothiazol-2-ylmethyl)-3,4-dihydro-3- oxo-2H-1,4-benzothiazine-2-acetic acid (2q, SPR-210) showed not only a potent AR-inhibitory activity in vitro (IC50 9.5 x 10(-9) M) but also a significant reduction in sorbitol accumulation in rat sciatic nerve (ID50 0.1 mg/kg) and lens (ID50 9.8 mg/kg). Optical resolution of the racemic SPR-210 was achieved by means of a diastereomer salt method using (-)-brucine. The biological activities of both enantiomers, (+)- and (-)-SPR-210, were comparable to that of the racemate.

Acetates↗