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Biomedical subjects

H Nishikawa

Publications and source records attributed to H Nishikawa.

At least 73 records · Page 4Linked to original sources

Deep venous thrombosis and pulmonary thromboembolism associated with a huge uterine myoma--a case report.

A 51-year-old woman with a large uterine myoma suffered from acute pulmonary thromboembolism. Venography revealed thrombosis in the right common iliac vein and almost complete obstruction of the left common iliac vein. The ascending lumbar vein showed collateral drainage. Treatment was initiated with continuous intravenous heparin sodium, and a Greenfield filter was inserted to prevent the extension of the pulmonary embolism during and after hysterectomy. After a total hysterectomy, venography revealed restoration of patency in the bilateral common iliac veins, and no flow was seen in the ascending lumbar vein. Thorough clinical examinations failed to identify any other prothrombotic conditions. These results suggest that a large uterine myoma compressed veins in the pelvis, and the resulting impaired blood flow caused deep venous thrombosis and pulmonary thromboembolism.

Female↗

[Stress-induced anxiety and endogenous anxiogenic substances].

Anxiety observed in animals subjected to stress was stated in relation to anxiety level and biological backgrounds of animals, changes in neurotransmitters and causal stressors. 1. Anxiety is thought to be a negative emotion caused by many kinds of stress such as restraint stress, SART (specific alternation of rhythm in temperature) stress (a repeated cold stress caused by environmental temperature), social stress, etc. 2. Emotional behavior in those stressed animals were attenuated by anxiolytics like diazepam, a benzodiazepine receptor agonist and buspirone, a serotonin (5-HT) 1A agonist. 3. Stressed rats had changed brain levels of a variety of neurotransmitters such as corticotropin-releasing factor (CRF), noradrenaline, 5-HT, dopamine, acetylcholine, histamine, cholecystokinin, etc. The percentage of time spent on the open arms of an elevated plus-maze apparatus decreased in those stressed animals. Abnormal elevated plus-maze behaviors were attenuated by diazepam, buspiron and a CRF antagonist. 4. Anxiety level differs according to the coping strategy of the recipients. Rats of different strain, sex, aging and/or family display different behaviors in elevated plus-maze. 5. Stress-induced anxiety-related behaviors were observed when levels of some neurotransmitters became unbalanced. Thus modulators of unbalanced brain substances are thought to have anxiolytic properties.

Adaptation, Psychological↗

Characterization of protease-activated receptors in rat peritoneal mast cells.

Activation of protease-activated receptor (PAR)-1 or PAR-2 elicits inflammation most probably via mast cell degranulation in vivo. The present study aimed at characterizing PARs in rat peritoneal mast cells (PMC). Messenger RNA for PAR-1, but not for PAR-2, was detected in PMC. Thrombin, the PAR-1 agonist SFLLR-NH2 or the PAR-2 agonist SLIGRL-NH2 failed to induce histamine release from PMC. Surprisingly, the PAR-2-inactive control peptide LSIGRL-NH2 triggered histamine release from PMC. Thus, PAR-1, but not PAR-2, are expressed in PMC, whereas neither PAR-1 nor PAR-2 are considered to be involved in degranulation of PMC. LSIGRL-NH2 does not appear to be appropriate as a control peptide for PAR-2 in inflammation studies.

Animals↗

Differential expression of small heat shock proteins in reactive astrocytes after focal ischemia: possible role of beta-adrenergic receptor.

Small heat shock proteins (sHSPs), a family of HSPs, are known to accumulate in the CNS, mainly in astrocytes, in several pathological conditions such as Alexander's disease, Alzheimer's disease, and Creutzfeldt-Jakob disease. sHSPs may act not only as molecular chaperones, protecting against various stress stimuli, but may also play a physiological role in regulating cell differentiation and proliferation. In the present study, we have demonstrated that transient focal ischemia in rats dramatically induced HSP27 but not alpha B-crystallin (alphaBC), both of which are members of sHSPs, in reactive astrocytes. In contrast, in vitro chemical ischemic stress induced both HSP27 and alphaBC in cultured glial cells to the same extent. Dibutyryl cAMP (dBcAMP) and isoproterenol, a beta-adrenergic receptor (betaAR) agonist, enhanced HSP27 expression but suppressed alphaBC, and changed the shape of the cells to a stellate form. dBcAMP and isoproterenol inhibited cell proliferation under normal conditions. An increase in betaAR-like immunoreactivity was also observed in reactive astrocytes in vivo. These results, together with recent findings that betaAR plays an important role in glial scar formation in vivo, raise the possibility that betaAR activation modulates sHSP expression after focal ischemia and is involved in the transformation of astrocytes to their reactive form.

Animals↗

Impact of tranilast on restenosis after coronary angioplasty: tranilast restenosis following angioplasty trial (TREAT).

BACKGROUND: Tranilast is an antiallergic drug that suppresses the release of cytokines such as platelet-derived growth factor, transforming growth factor-beta1, and interleukin-1beta and prevents keloid formation after skin injury. Treatment with this drug reduced the restenosis rate after percutaneous transluminal coronary angioplasty in a preliminary study. METHODS AND RESULTS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial. A total of 255 patients with 289 lesions were randomly assigned to treatment with the oral administration of 600 mg/d tranilast, 300 mg/d tranilast, or a placebo for 3 months after successful angioplasty. Angiographic follow-up was done at 3 months, and a clinical follow-up examination was performed at 12 months. Two hundred ten (72.7%) lesions of 188 (73.7%) of the patients met the criteria and were eligible for the assessment of restenosis. The restenosis rates defined as >/=50% loss of the initial gain were 14.7% in the 600 mg/d tranilast group, 35.2% in the 300 mg/d tranilast group, and 46.5% in the placebo group (P <. 0001 for 600 mg/d tranilast vs placebo). The restenosis rates defined as percent diameter stenosis of >/=50% at follow-up were 17. 6% in the 600 mg/d tranilast group, 38.6% in the 300 mg/d tranilast group, and 39.4% in the placebo group (P =.005 for 600 mg/d tranilast vs placebo). CONCLUSIONS: The oral administration of 600 mg/d of tranilast for 3 months markedly reduced the restenosis rate after percutaneous transluminal coronary angioplasty.

Administration, Oral↗

Effects of intensive lipid lowering by low-density lipoprotein apheresis on regression of coronary atherosclerosis in patients with familial hypercholesterolemia: Japan Low-density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS).

Twenty-five heterozygous familial hypercholesterolemic patients treated with LDL-apheresis and drugs and 11 patients treated with drugs underwent follow-up angiography 2.3 years later. One-hundred thirteen lesions were measured by quantitative angiography. Mean LDL-cholesterol levels during the trial were 140 +/- 34 mg/dl in the apheresis group and 170 +/- 58 mg/dl (P < 0.05) in the control group. The mean changes in minimal lumen diameter of lesions were +0.19 +/- 0.30 mm (improved) in the apheresis group (n = 76) and -0.44 +/- 0.40 mm (worsened) in the control group (n = 37) (P < 0.0001). When progression and regression were defined as a change in minimal lumen diameter of +/- 0.67 mm, in the apheresis group, two (8%) patients had progression, 19 (76%) stayed unchanged and four (16%) had regression, but in the control group seven (64%) patients had progression and four (36%) stayed unchanged. The frequency of regression or no change was significantly higher in the apheresis group than in the control group (P < 0.004). Intensive cholesterol lowering therapy with LDL-apheresis and lipid lowering drugs can achieve a substantial decrease in LDL-cholesterol levels to induce regression of coronary lesions in familial hypercholesterolemic patients with advanced coronary artery disease.

Adult↗

Unilateral examination of olfactory threshold using the Jet Stream Olfactometer.

OBJECTIVE: The Jet Stream Olfactometer, a modification by the T&T olfactometer, has been recently developed and is now commercially available. This Jet Stream Olfactometer can routinely measure the unilateral sense of smell. Clinical usefulness of the Jet Stream Olfactometer was evaluated. METHODS: Twenty-three patients with sinus-related symptoms were examined. Unilateral olfactory acuity was examined using the Jet Stream Olfactometer and compared it with the anatomy of the olfactory cleft by computed tomographic (CT) scans. RESULTS: In 13 of the 23 patients examined the right olfactory threshold was similar to that of the left. Of these 13, in seven patients there was transport damage of the odorants and in the other six there was sensorineural damage. Ten patients showed an apparent difference between the right and left smell thresholds. Anosmia in seven of these ten patients was due to a conductive olfactory disturbance resulting from rhinosinusitis, whereas sensorineural damage was recognized in the other three patients. The difference in the detection threshold between the right and left nasal cavities was well correlated to that of the opacity between the right and left olfactory clefts. CONCLUSION: Jet Stream Olfactometer provides a convenient and reliable means for assessing the ability of unilateral smell.

Adult↗

Relationship of coffee consumption with serum lipids and lipoproteins in Japanese men.

PURPOSE: To examine the relationship of instant coffee and brewed coffee with serum lipids and lipoproteins in Japanese men. METHODS: Study subjects were 4587 male self-defense officials aged 48-56 years who had a preretirement health examination at one of the three hospitals of the Self-Defense Forces from October 1986 to December 1992. A self-administered questionnaire ascertained lifestyle characteristics including consumption of a limited number of foods and beverages by all of the men. Serum concentrations of total cholesterol (TC), triglycerides (TG), and high density lipoprotein (HDL) cholesterol were measured, and low density lipoprotein (LDL) cholesterol levels were calculated from the values of TC, TG, and HDL cholesterol. RESULTS: While the consumption of brewed coffee was unrelated to any parameter of serum lipids and lipoproteins, instant coffee consumption showed a highly significant positive association with serum LDL cholesterol levels and an inverse association with serum TG levels. After adjustment for body mass index, smoking, alcohol use, green tea consumption, rank, and hospital, for each cup of instant coffee per day, LDL cholesterol levels were 0.82 mg/dl (95% confidence interval (CI) 0.29-1.35) higher, and TG levels in a natural log-scale were 0.014 mg/dl (95% CI 0.006-0.022) lower. There was also a tendency for a positive association between instant coffee intake and serum TC levels (trend p = 0.09). HDL cholesterol levels were unrelated to instant coffee consumption. These associations did not change after additional adjustment for selected foods and beverages associated with serum lipids and lipoproteins. CONCLUSIONS: The findings suggest that instant coffee, not brewed coffee, may be associated with raised levels of serum LDL cholesterol and decreased levels of serum TG.

Coffee↗

Coffee drinking and serum gamma-glutamyltransferase: an extended study of Self-Defense Officials of Japan.

PURPOSE: To examine the effect of coffee drinking on serum gamma-glutamyltransferase (GGT) level in relation to alcohol drinking, smoking, and degree of obesity in middle-aged Japanese men. METHODS: From 1986 to 1994, a total of 7,637 male officials of the Self-Defense Forces of Japan aged 48-59 years received a preretirement health examination. Coffee drinking was ascertained by a self-administered questionnaire, and serum GGT level was measured. After excluding 1,360 men with a possible pathologic condition influencing liver enzyme levels and 182 former alcohol drinkers, effect of coffee drinking on serum GGT was examined by a multiple linear regression model and analysis of variance adjusting for alcohol drinking, smoking, and body mass index (BMI). RESULTS: The adjusted percentage of difference in serum GGT was -4.3 (95% CI = -5.0; -3.5) per cup of coffee. The inverse coffee-GGT relation was most prominent among men drinking > or = 30 ml of ethanol and smoking > or = 15 cigarettes daily; and positive associations of alcohol and smoking with GGT were attenuated by coffee drinking, more clearly among men with BMI > or = 25.00 kg/m2. Adjusted percentages of difference in serum GGT were -2.6% (p = 0.0003) per cup of brewed coffee, and -5.1% (p = 0.0001) per cup of instant coffee, independently of each other. CONCLUSIONS: The present study suggests that coffee consumption may weaken GGT-induction by alcohol, and possibly by smoking. These effect modifications by coffee may differ according to the degree of obesity.

Alcohol Drinking↗

Impaired glucose tolerance, diabetes mellitus, and gallstone disease: an extended study of male self-defense officials in Japan.

Few studies have investigated the relation between glucose tolerance status and ultrasonographically determined gallstone disease. Using a 75-g oral glucose tolerance test, we examined the association of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) with gallstone disease in Japanese men. Subjects were men aged 48 to 59 of the Japan Self-Defense Forces who received a preretirement health examination between October 1986 to December 1994. After exclusion of 12 men under insulin treatment in the consecutive series of 7637 men, 174 were found to have gallstones; 103 were at the state of postcholecystectomy, and 6899 had normal gallbladder. IGT and NIDDM were associated with a modestly increased risk of gallstone disease; adjusted odds ratios were 1.3 (95% confidence interval [CI]: 0.9-1.8) for IGT and 1.3 (95% CI: 0.8-2.0) for NIDDM after adjustment for hospital, rank, smoking, alcohol use, and body mass index. Adjusted odds ratio for IGT and NIDDM combined was 1.3 (95% CI: 1.0-1.7, p=0.08). When prevalent gallstones and postcholecystectomy were considered separately, NIDDM showed a significant, positive association with postcholecystectomy, but not with prevalent gallstones. The findings add to evidence that glucose intolerance is associated with a modest increase in the risk of gallstone disease.

Cholecystectomy↗

Enhancement of vascular permeability by specific activation of protease-activated receptor-1 in rat hindpaw: a protective role of endogenous and exogenous nitric oxide.

1. To clarify the role of the first thrombin receptor/protease-activated receptor (PAR)-1 in an inflammatory process, we tested and characterized the effect of intraplantar (i.pl.) administration of the highly specific PAR-1 agonist TFLLR-NH2 in rat hindpaw. 2. TFLLR-NH2 administered i.pl. at 0.01-0.03 micromol per paw enhanced vascular permeability in the hindpaw and produced paw oedema in a dose-dependent manner. This effect was almost completely abolished by repeated pretreatment with compound 48/80 to deplete inflammatory mediators in mast cells. 3. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester or N-iminoethyl-L-ornithine, preadministered i.pl., stereospecifically potentiated the i.pl. TFLLR-NH2-induced permeability increase, while the NO donor sodium nitroprusside or NOC-18, given i.pl., suppressed the effect of TFLLR-NH2. 4. These findings demonstrate that specific activation of PAR-1 produces increased vascular permeability accompanied by oedema formation in the rat hindpaw, predominantly via mast cell degranulation, and that endogenous and exogenous NO plays a protective role in the PAR-1-mediated inflammatory event.

Animals↗

Modulation by protease-activated receptors of the rat duodenal motility in vitro: possible mechanisms underlying the evoked contraction and relaxation.

1 The present study examined effects of agonist enzymes and receptor-activating peptides for protease-activated receptors (PARs) on duodenal motility in the rat, and also investigated possible mechanisms underlying the evoked responses. 2 Thrombin at 0.03-0.1 microM and the PAR-1-activating peptide SFLLR-NH2 at 3-100 microM or TFLLR-NH2 at 10-50 microM produced a dual action, relaxation followed by contraction of the duodenal longitudinal muscle. The PAR-2-activating peptide SLIGRL-NH2 at 10-100 microM elicited only small contraction. Trypsin at 0.08 microM induced small contraction, or relaxation followed by contraction, depending on preparations. The PAR-4-activating peptide GYPGKF-NH2 at 1000 microM exhibited no effect. 3 The contractile responses of the duodenal strips to TFLLR-NH2 and to SLIGRL-NH2 were partially attenuated by the L-type calcium channel blocker nifedipine (1 microM), the protein kinase C inhibitor GF109203X (1 microM) and the tyrosine kinase inhibitor genistein (15 microM), but were resistant to indomethacin (3 microM) and tetrodotoxin (1-10 microM). 4 The relaxation of the preparations exerted by TFLLR-NH2 was unaffected by indomethacin (3 microM), propranolol (5 microM), NG-nitro-L-arginine methyl ester (100 microM) and tetrodotoxin (1-10 microM). This relaxation was resistant to either GF109203X (1 microM) or genistein (15 microM), but was, remarkably, attenuated by combined application of these two kinase inhibitors. 5 Apamin (0.1 microM), an inhibitor of calcium-activated, small-conductance potassium channels, but not charybdotoxin (0.1 microM), completely abolished the PAR-1-mediated duodenal relaxation, and significantly enhanced the PAR-1-mediated contraction. 6 These findings demonstrate that PAR-1 plays a dual role, suppression and facilitation of smooth muscle motility in the rat duodenum, while PAR-2 plays a minor excitatory role in the muscle, and that PAR-4 is not involved in the duodenal tension modulation. The results also suggest that the contractile responses to PAR-1 and PAR-2 activation are mediated, in part, by activation of L-type calcium channels, protein kinase C and tyrosine kinase, and that the relaxation response to PAR-1 activation occurs via activation of apamin-sensitive, but charybdotoxin-insensitive, potassium channels, in which both protein kinase C and tyrosine kinase might be involved synergistically.

Animals↗

Gallstone disease risk in relation to body mass index and waist-to-hip ratio in Japanese men.

OBJECTIVE: To examine the relation of body mass index (BMI) and waist-to-hip ratio (WHR) to gallstones and postcholecystectomy risk in middle-aged Japanese men. DESIGN: Cross-sectional study. SUBJECTS: We used 174 men with prevalent gallstones, 104 with postcholecystectomy and 6909 with normal gallbladder in the consecutive series of 7637 men aged 48-59y receiving a preretirement health examination at four hospitals of the Japan Self-Defense Forces between 1986 and 1994. MEASUREMENTS: Gallbladder status was assessed by abdominal ultrasonography after an overnight fast. BMI was calculated as weight in kilogram divided by height in square meters, and WHR was used as a measure of central obesity. Analysis of the WHR was limited to a subset of data for the period 1991-1994 (gallstones 113, postcholecystectomy 66 and normal gallbladder 4410). RESULTS: After adjustment for hospital, rank in the Self-Defense Forces, cigarette smoking, alcohol use and glucose tolerance, BMI was significantly associated with an increased risk of both prevalent gallstones and postcholecystectomy. WHR also showed a significant positive association with each of the two conditions. When BMI and WHR were mutually adjusted for, both of the obesity indices tended to be associated positively with prevalent gallstones and postcholecystectomy. CONCLUSION: These findings indicate that obesity is associated with increased gallstone risk in men.

Asian People↗

Recall phenomenon following epirubicin.

The case history is presented of a 46-year-old lady who was treated postoperatively for breast cancer with combination chemotherapy containing the antitumour agent epirubicin. The second cycle was complicated by a mild extravasation injury in the antecubital fossa, which settled with conservative management. Two weeks after a subsequent infusion into a different extremity she developed inflammation at the original site of injury, which rapidly led to tissue breakdown requiring surgical debridement and microvascular free flap reconstruction. To our knowledge, epirubicin has never been previously associated with 'recall reactions'. Histological evaluation of the debrided tissue has revealed a possible underlying mechanism for the cell damage.

Antibiotics, Antineoplastic↗

Twin-to-twin transfusion syndrome with hydrops: a retrospective analysis of ten cases.

We retrospectively studied 10 cases of twin-to-twin transfusion syndrome (TTTS) with fetal hydrops. TTTS was diagnosed sonographically between the 17-31 weeks of gestation. All twins were delivered by emergency cesarean section because of cardiac decompensation of one or both fetuses. The mean (+/-SD) age at diagnosis was 26.1 +/- 4.5 and the mean age at delivery was 28.8 +/- 2.0 weeks. Gestational age at birth was similar in survivors and nonsurvivors. However, surviving infants were diagnosed later in gestation (23.6 +/- 4.8 vs. 28.7 +/- 1.9 weeks; p < 0.01); and gestational age at appearance of hydrops were later in survivors (26.1 +/- 3.2 vs. 29.2 +/- 2.4 weeks; p < 0.05). Overall survival rate was 50% (10 of 20 infants). All survivors were delivered within 3 days after the appearance of fetal hydropic changes. Extrauterine treatment in earlier stages of TTTS might improve the outcome. Nevertheless, more aggressive intrauterine treatment should be considered in the most severe cases of TTTS developing before 24-25 weeks' gestation.

Cesarean Section↗

Identification of human cytochrome P450 isoforms involved in the metabolism of S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid.

1. To identify the cytochrome P450 (CYP) isoenzymes responsible for the major metabolic pathways of S-2-[4-(3-methyl-2-thienyl)phenyl] propionic acid (S-MTPPA) in man, the metabolism of S-MTPPA was examined using human liver microsomes and microsomes containing cDNA-expressed CYP isozymes (CYP1A2, 2A6, 2B6, 2C9-Arg, 2C9-Cys, 2C19, 2D6-Val, 2E1 and 3A4). 2. S-MTPPA was mainly oxidized to the 5-hydroxylated metabolite of the thiophene ring (MA6) with human liver microsomes in the presence of NADPH. The formation of MA6 was inhibited by SKF 525-A, suggesting that CYP plays role in the formation of MA6. 3. Eadie-Hofstee plots for the 5-hydroxylation of S-MTPPA in the range 5-100 microM were linear for all samples studied, suggesting that the formation of MA6 by human liver microsomes follows simple Michaelis-Menten kinetics. Apparent Vmax = 1.42+/-0.64 nmol/min/mg protein; Km = 12+/-5 microM. 4. Among the CYP inhibitors examined (alpha-naphthoflavone, sulphaphenazole, omeprazole, quinidine and troleandomycin), sulphaphenazole (a CYP2C9 inhibitor) showed the most potent inhibitory effect on the 5-hydroxylation of S-MTPPA by human liver microsomes. 5. When incubated with microsomes containing cDNA-expressed CYP isozymes, S-MTPPA was substantially oxidized to MA6 only by CYP2C9. 6. These results suggest that formation of the major metabolite of S-MTPPA, MA6, in human liver microsomes is catalysed predominantly by a single CYP isoenzyme, namely CYP2C9.

Anti-Inflammatory Agents, Non-Steroidal↗