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Biomedical subjects

H Koike

Publications and source records attributed to H Koike.

At least 127 records · Page 7Linked to original sources
PubMed1996

Macular coloboma-like lesions and pigment abnormalities as complications of cryotherapy for retinopathy of prematurity in very low birth-weight infants.

PURPOSE: Cryotherapy for retinopathy of prematurity (ROP) is effective in reducing the incidence of blindness in premature infants. However, macular complications associated with successful treatment have not yet been well studied. METHODS: Eighteen very low birth-weight (< 1,251 g) infants (32 eyes) who received cryotherapy for ROP were examined serially for regression of disease and for development of macular abnormalities. Patient characteristics and treatment factors were evaluated to identify risk factors associated with the development of macular abnormalities after successful cryotherapy. RESULTS: Eleven of 32 eyes (34.4%) that had undergone cryotherapy developed significant macular abnormalities, including macular coloboma-like change (six eyes), macular hyperpigmentation (two eyes), irregularly mottled macular hyperpigmentation and hypopigmentation (two eyes), and macular hyperpigmentation and hypopigmentation with subretinal proliferation (one eye). Corrected visual acuity in affected eyes ranged from 0.15 to 0.03 (20/133 to 20/666) compared with 1.0 to 0.2 (20/20 to 20/100) in treated eyes without macular abnormality (P = .0002). No difference in gestational age was noted between infants who did or did not develop macular coloboma-like lesions or pigment abnormalities. Eyes with macular abnormality had more posterior disease (P = .037) and received significantly more cryotherapy than did eyes without macular abnormality (P = .0005). CONCLUSIONS: In very low birth-weight infants receiving cryotherapy for ROP, development of macular coloboma-like lesions and macular pigment abnormalities were related to greater severity of ROP and a greater amount of cryotherapy. Macular abnormalities were associated with markedly worse visual outcomes than were treated eyes without macular abnormality.

Birth Weight↗
PubMed1996

Differential-display polymerase chain reaction identifies nucleophosmin as an estrogen-regulated gene in human vascular smooth muscle cells.

PURPOSE: Atheroprotective effects of estrogen (E2) are well documented and are due in part to direct effects of E2 on vascular cells. We recently demonstrated that human vascular smooth muscle cells (VSMCs) express a functional E2 receptor capable of activatine gene expression. This study was designed to identify E2-regulated genes in human VSMCs. METHODS: VSMC mRNA was screened by differential-display polymerase chain reaction (ddPCR) to identify E2-regulated genes. Quiescent human VSMCs were stimulated with 10% fetal bovine serum in the absence or presence of 10(-8) mol/L E2, and total cellular RNA was harvested. ddPCR was performed in triplicate on each RNA sample and differentially expressed candidate genes were isolated. Differential expression of candidate genes were confirmed by dot blotting and positive bands were identified by sequence analysis. E2-mediated regulation at the protein level was investigated by immunoblotting. RESULTS: ddPCR of RNA harvested from aortic VSMCs identified a 462 bp gene product, EAo8, as a candidate E2- regulated gene. Dot blotting with probes derived from four independent VSMC cultures demonstrated a 5.8 +/- 3.9-fold increase in EAo8 expression in response to E2 treatment (p < 0.05 vs control). Sequence analysis identified EAo8 as nucleophosmin, a nucleolar phosphprotein implicated in the regulation of cell growth and protein synthesis. E2-induced expression of nucleophosmin protein was demonstrated by immunoblotting in both saphenous vein and mammary artery VSMCs. CONCLUSIONS: E2 induces nucleophosmin expression in human VSMCs, and ddPCR is a useful approach for studying estrogen-regulated gene expression in VSMCs.

Cells, Cultured↗
PubMed1996

A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C.

Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A "rebound" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone.

Adult↗
PubMed1996

Reduction of rat myocardial ischemia and reperfusion injury by sialyl Lewis x oligosaccharide and anti-rat P-selectin antibodies.

Polymorphonuclear leukocytes (PMN) are directly involved in development of ischemic myocardial injury. Adhesion of PMN to endothelial cells is an initial step that triggers a sequential process leading to acute inflammatory responses. Interaction between P-selectin and its oligosaccharide ligand, sialyl Lewis x (sLex), plays an important role in the early stage of the adhesion. To examine the role of P-selectin in various animal disease models especially in rats, we have cloned rat E- and P-selectin cDNAs and established monoclonal antibodies against these rat selectins. In this report, we describe the generation and characterization of anti-rat P-selectin antibodies (ARPs). These antibodies detect cell surface P-selectin on thrombin-stimulated rat platelets. More importantly, intravenous administration of ARP2-4 reduced infarction developed after 30 min of ischemia followed by 24 h of reperfusion in a rat myocardial injury model. In addition, similar protective effect was also observed by administration of a sLex-oligosaccharide. These results indicate that cell adhesion mediated via P-selectin is involved in the development of ischemia and reperfusion injury in rat heart.

Animals↗
PubMed1996

Gene cloning, purification, and characterization of NfsB, a minor oxygen-insensitive nitroreductase from Escherichia coli, similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri.

nfsB, encoding a minor oxygen-insensitive nitroreductase, was isolated by PCR using primers corresponding to two amino acid sequences conserved among the major flavin reductase from Vibrio fischeri and classical nitroreductases from Salmonella typhimurium and Enterobacter cloacae. The gene product, NfsB, was purified to homogeneity from extracts of Escherichia coli cells overexpressing it. NfsB was found to be situated at 13 min on the E. coli map. Biochemical analysis indicated NfsB to be a polypeptide having a calculated molecular weight of 23,904, capable of forming a homodimer and associated tightly with FMN as a prosthetic group. Although it exhibited a lower affinity to the NfsB apoenzyme than FMN, FAD could serve as an effective substitute for FMN. It was also shown that NfsB has a broad electron acceptor specificity and is associated with a low level of the NAD(P)H-flavin oxidoreductase. The NfsB catalysis obeys the ping pong Bi-Bi mechanism. The Km value for NADH varied depending on the second substrate used.

Amino Acid Sequence↗
PubMed1996

Protective effect of beraprost sodium, a stable prostacyclin analogue, in development of monocrotaline-induced pulmonary hypertension.

Experimental pulmonary hypertension (PH) was induced by a single injection of monocrotaline (MCT), a pyrrolizidine alkaloid extracted from Crotalaria spectabilis. The effect of beraprost sodium, a stable prostacyclin analogue, on the development of MCT-induced PH in rats was studied. Chronic administration of beraprost sodium at a dose of 30 micrograms/kg/day initiated on the same day as MCT injection decreased the degree of PH determined by weight ratio of right ventricular free wall to that of left ventricle plus septum depending on the duration of administration. Although the injection of prostaglandin E1 (PGE1) at a dose of 200 micrograms/kg/day initiated 1 week after MCT injection did not decrease the degree of PH significantly, beraprost sodium administration at doses of 30 and 100 micrograms/kg/day decreased the degree of PH significantly. The cytoprotective effect of beraprost sodium against endothelial cell (EC) damage is believed to be involved in inhibiting development of PH in MCT-injected rats. The amounts of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) produced by alveolar macrophages decreased in accordance with the inhibiting effect of beraprost sodium on development of PH, indicating that beraprost sodium inhibited the development of PH in MCT-injected rats not only through its effect of vasodilation and anti-platelet aggregation in pulmonary circulation but also through its antiinflammatory effects.

Alprostadil↗
PubMed1996

Possible involvement of altered Na+ -Ca2+ exchange in negative inotropic effects of class I antiarrhythmic drugs on rabbit and rat ventricles.

We investigated the way in which Na+ channel blocking class I antiarrhythmic drugs, lidocaine (30 mu M), flecainide (30 mu M), and RS-2135 (100 mu M) affected contractions elicited by several protocols in rat and rabbit ventricular strips. Rabbit ventricles showed a positive force-frequency relation, and antiarrhythmic drugs inhibited the contraction, flattening the force-frequency curve. In contrast, rat ventricles showed a negative force-frequency relation, and the drugs shifted the force-frequency curve downward. Rapid-cooling contracture (RCC) also showed a positive or negative dependence on the frequency of preceding stimulation in rabbit or rat ventricles, respectively. All drugs inhibited the RCC, suggesting that they reduced the Ca2+ content in the sarcoplasmic reticulum. Ryanodine (1 mu M) abolished the RCC in both muscles and the contraction in rat muscles, but partially decreased contractions at high frequencies in rabbit ventricles. Antiarrhythmic drugs caused a further inhibition of contractions in the presence of ryanodine in rabbit ventricles. These results indicate that inhibition of Na+ channels by antiarrhythmic drugs alters Na+ -Ca2+ exchange, resulting in a decrease in the Ca2+ content in the sarcoplasmic reticulum (SR) and the Ca2+ entry through the exchanger.

Animals↗
PubMed1996

Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase.

We identified the nfsA gene, encoding the major oxygen-insensitive nitroreductase in Escherichia coli, and determined its position on the E. coli map to be 19 min. We also purified its gene product, NfsA, to homogeneity. It was suggested that NfsA is a nonglobular protein with a molecular weight of 26,799 and is associated tightly with a flavin mononucleotide. Its amino acid sequence is highly similar to that of Frp, a flavin oxidoreductase from Vibrio harveyi (B. Lei, M. Liu, S. Huang, and S.-C. Tu, J. Bacteriol. 176:3552-3558, 1994), an observation supporting the notion that E. coli nitroreductase and luminescent-bacterium flavin reductase families are intimately related in evolution. Although no appreciable sequence similarity was detected between two E. coli nitroreductases, NfsA and NfsB, NfsA exhibited a low level of the flavin reductase activity and a broad electron acceptor specificity similar to those of NfsB. NfsA reduced nitrofurazone by a ping-pong Bi-Bi mechanism possibly to generate a two-electron transfer product.

Amino Acid Sequence↗
PubMed1996

Conversion of NfsB, a minor Escherichia coli nitroreductase, to a flavin reductase similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri, by a single amino acid substitution.

NfsB is an oxygen-insensitive nitroreductase of Escherichia coli with significant amino acid sequence homology to the major flavin reductase (FRase I) of Vibrio fischeri. Here, we show that NfsB is convertible to an FRase I-like flavin reductase three times as active as the authentic FRase I by a single amino acid substitution in the least-conserved region.

Amino Acid Sequence↗
PubMed1996

Effects of beraprost sodium, a prostacyclin analogue, on diabetic neuropathy in streptozotocin-induced diabetic rats.

The effects of beraprost sodium (BPS), a stable prostacyclin analogue, on motor nerve conduction velocity and nerve blood flow of the sciatic nerve were investigated in streptozotocin-induced diabetic rats, and they were compared with the effects of epalrestat (aldose reductase inhibitor). Treatment with BPS for 4 weeks significantly inhibited the decrease in motor nerve conduction velocity and nerve blood flow dose-dependently, but epalrestat had no effect on nerve blood flow. Morphological changes of the myelinated fibers of the sciatic nerve were observed macroscopically. The mean axonal area and the mean circularity index of diabetic control rats were significantly less than that of normal rats, while after 6 weeks of BPS treatment, these decreases of the axonal area and the circularity index were inhibited. The enlargement of the mean lumen area of microvessels in the diabetic rats was significantly inhibited after 6 weeks of BPS treatment. Additionally, augmentation of the washed platelet aggregation in diabetic rats was significantly normalized by BPS. It was suggested that BPS is effective on diabetic neuropathy via amelioration of the decrease of blood supply to the structure. The effects of BPS on platelets might also contribute to the improvement of neuronal circulatory deficiency.

Animals↗
PubMed1996

Antianginal effect of RS-5773, a diltiazem congener, in the methacholine-induced anginal model in rats.

The antianginal effect of RS-5773 ((2S,3S)-3-acetoxy-8-benzyl-2,3-dihydro-5-[2-(dimethylamino)- ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one hydrochloride), a newly developed benzothiazepine derivative, was evaluated in an angina model rat. Close-coronary artery injections of methacholine in anesthetized rats evoked ischemic electrocardiographic (ECG) changes (S wave elevation of about 0.6 mV). The ECG changes produced by methacholine were reproducible for as long as 6 hr. Intravenous and intraduodenal administration of RS-5773, diltiazem or clentiazem produced dose-dependent suppressions of the ischemic ECG changes. RS-5773 exceeded the other two agents both in the maximum suppressive effect on S wave elevation and in the duration of action after intravenous administration. The antianginal potency expressed as AUC (area under the curve), i.e., the percent suppression of S wave elevation integrated over time, revealed that RS-5773 was 16 times and 7 times more potent than diltiazem and clentiazem, respectively. A similar order of potency difference was observed after intraduodenal administration, and RS-5773 sustained its effect for about 6 hr at 3 mg/kg. In addition, RS-5773 did not cause excessive hypotension or depression of atrioventricular conduction. These results suggest that RS-5773 has a preferable profile as an antianginal agent.

Angina Pectoris, Variant↗
PubMed1996

Asymptomatic pulmonary hypertension complicated with antiphospholipid syndrome case.

A 48-year-old woman with antiphospholipid syndrome (APS) developed pulmonary hypertension without any thromboembolic episode. Multiple pulmonary perfusion defects suggestive of pulmonary thrombosis or in situ thrombosis were observed. Deep venous thrombosis (DVT) of the right femoral vein without symptoms was also detected by contrast venography. Asymptomatic pulmonary hypertension complicated with a hypercoagulable state such as in this case suggests that not only recurrent asymptomatic pulmonary thrombosis, but also in situ thrombosis in pulmonary vessels are possible and important factors in the pathogenesis of pulmonary hypertension.

Antiphospholipid Syndrome↗
PubMed1996

[Urodynamic evaluation of alpha-1 blocker tamsulosin on benign prostatic hyperplasia using pressure-flow study].

BACKGROUND: In order to evaluate the precise effect of alpha-1 blocker on benign prostatic hyperplasia, symptomatic and urodynamic parameters were compared between before and after 4 week administration of tamsulosin hydrochloride (0.2 mg/day) on 18 patients with untreated benign prostatic hyperplasia. METHODS: Symptoms were scored with international prostate symptom score (I-PSS) and urodynamic parameters were measured with pressure-flow study. RESULTS: The total score of I-PSS decreased significantly although the peak urinary flow rates, average flow rates or post-void residuals did not show a significant improvement after the treatment. On the other hand, the statistical analysis of pressure-flow studies revealed a significant decrease of vesical pressure at opening, at peak flow and at end of voiding after the treatment. In one patient, in whom the voided volume and urinary flow rate kept the same level throughout the treatment course, the total energy expelled from the bladder was calculated with the formula given as W = integral (pQ)dt. Both the detrusor work and vesical work (sum of detrusor contraction and abdominal straining) showed a marked decrease after the treatment. CONCLUSIONS: It is suggested that alpha-1 blocker relieves overload of the detrusor and improves symptoms by reducing the energy demands for bladder emptying, even in case the flow rate does not improve. The urodynamic procedure including pressure flow study is a useful means for not only diagnosing bladder outflow obstruction but also assessing overload or impaired contractility of the detrusor.

Adrenergic alpha-Antagonists↗
PubMed1996

[Clinical study of primary carcinoma in situ of the bladder].

In our department 14 patients with primary carcinoma in situ of the bladder were treated. Thirteen patients were male and 1 patient was female. Most of the patients complained of irritative vesical symptoms such as painful urination and/or pollakisuria. Cystoscopic examination revealed no overt tumor but some abnormal findings like localized or diffuse hyperemia or fine granular changes were noted. In 4 patients, total cystectomy was performed primarily and 10 other patients were treated at first with intravesical chemotherapy or intravesical BCG. Five of those 10 patients (50%) developed invasive cancer and total cystectomy was performed secondarily in them. Invasive cancer occurred in the bladder wall in 2 patients, in the prostate in 2 patients and in both bladder and prostate in 1 patient. Five-year and 10-year survival rates of 14 patients in this study were 66.7% and 44.4%, respectively.

Administration, Intravesical↗
PubMed1996

Occlusive thrombosis in the femoral artery of the rabbit: a pharmacological model for evaluating antiplatelet and anticoagulant agents.

Arterial thrombosis in the rabbit was established as a novel model to evaluate the effects of antithrombotic agents. Endothelial injury was produced by applying electrical stimulation to the femoral artery. The process of primary endothelial injury, and subsequent platelet activation and fibrin formation were confirmed by electron microscopy. In this model, vessel occlusion occurred within 30 min after stimulation without changes in heart rate and blood pressure. Using this model, several agents were evaluated for their antithrombotic activities: aspirin (30 mg/kg, p.o.), ticlopidine (10-100 mg/kg, p.o.), heparin (300 unit/kg, i.v.), PPACK (10-33 micrograms/kg/min, i.v.), WEB-2347 (1 mg/kg, p.o.) and nicardipine (10 micrograms/kg, i.v.). Fifty per cent decrease in vessel temperature (T1/2), assessed by a thermic probe, averaged 15.1 +/- 1.2 (n = 11, p.o.) and 15.6 +/- 1.9 min (n = 8, i.v.) in the vehicle groups, and this was significantly prolonged by aspirin (23.0 +/- 2.6 min), ticlopidine at a dose of 100 mg/kg (24.6 +/- 2.5 min), heparin (27.2 +/- 2.8 min) and PPACK at a dose of 33 micrograms/kg (30.0 min). However, WEB-2347 and nicardipine were without effect. The effect of aprosulate, a new class of polyanion with anticoagulant activity, was further examined. Aprosulate (1-30 mg/kg, i.v.) inhibited thrombus formation in a dose-dependent manner. These results show that acute occlusive thrombus can be readily and reproducibly formed in the rabbit femoral artery and suggest that this thrombus formation depends on the activation of both platelets and blood coagulation. The merit of this model lies in its simplicity for evaluating the antithrombotic effects of antiplatelet and anticoagulant agents and is therefore expected to be extensively used in the future.

Animals↗
PubMed1996

In vitro effects of aprosulate sodium, a novel anticoagulant, on platelet activation: possible mechanism for antiplatelet action.

Aprosulate sodium, a bis-lactobionic acid amide derivative, is a novel synthetic polyanion with potent anticoagulant activities. In the present study, the effects of aprosulate on platelet aggregation were investigated in a plasma-free system. Aprosulate inhibited thrombin (0.03-0.3 U/ml)-induced aggregation in rat washed platelets in a concentration-dependent manner, with an IC50 value of 0.38 microgram/ml. In contrast, aprosulate, at up to 10 micrograms/ml, did not affect collagen (1 microgram/ml)- or ADP (3 microM)-induced aggregation. In fura 2-loaded platelets, aprosulate (1-10 micrograms/ml) inhibited intracellular Ca2+ mobilization induced by thrombin, but not that by ADP. Protamine, a highly basic protein, abolished aprosulate-mediated inhibition of thrombin-induced platelet aggregation, suggesting that the observed inhibition is primarily due to the negative charge contained on the aprosulate molecule. In human platelets, aprosulate inhibited thrombin-induced aggregation, but failed to inhibit platelet aggregation induced by SFLLRN, a synthetic tethered ligand of a thrombin receptor. Antiplatelet profiles of aprosulate were largely similar to those of heparin, although heparin inhibited both thrombin- and collagen-induced aggregation. These in vitro studies indicate that aprosulate is capable of inhibiting thrombin-induced platelet activation and that this effect is independent of its anticoagulant activity. These results suggest that the polyanionic feature of aprosulate plays an essential role in promoting its antiplatelet activities, and that a plausible mechanism to explain the observed inhibition conferred by this agent, would be one which involves blocking the platelet-thrombin interaction.

Adenosine Diphosphate↗
PubMed1995

Lipoteichoic acid-induced neutrophil adhesion via E-selectin to human umbilical vein endothelial cells (HUVECs).

We investigated whether lipoteichoic acid (LTA) induces the expression of E-selectin and neutrophil adhesion to human umbilical vein endothelial cells (HUVECs). LTA (0.01-30 micrograms/ml) induced the expression of E-selectin in a concentration-dependent manner with maximal response at 10 micrograms/ml. The expression level of E-selectin increased from 2 h after stimulation by LTA with the maximal level at 4-8 h. Neutrophil adhesion to LTA-treated HUVECs correlated with the levels of E-selectin expression. In addition, the adhesion was clearly inhibited by anti-human E-selectin monoclonal antibody CY-1787 as well as a sialyl Lewis X (SLeX) oligosaccharide. LTA-induced expression of E-selectin was inhibited by protein kinase C inhibitors, H-7 and staurosporine. These results indicate that LTA induced the expression of E-selectin and neutrophils adhered to HUVECs via E-selectin.

Cell Adhesion↗