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Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 397 records · Page 22Linked to original sources
PubMed1991

Effect of diabetes on photochemically induced thrombosis in femoral artery and platelet aggregation in rats.

Effect of diabetes on thrombogenesis was examined by using a thrombus model with photochemical reaction in the rat femoral artery. In streptozotocin-induced diabetic rats for 8 weeks, the formation of thrombus following endothelial injury was significantly slower than that in non-diabetic rats. Insulin treatment normalized the abnormality of thrombogenesis. Aggregation in washed platelets from rats with diabetes was enhanced. However, platelet aggregation in whole blood was reduced in diabetic rats, and plasma from diabetic rats attenuated platelet aggregation. These results suggest that plasma factor(s) and/or other blood cells modify the hyperaggregability of platelets per se in vivo in diabetic rats. Treatment with insulin improved the aggregation in whole blood and washed platelets. In conclusion, diabetes induces the prolongation of thrombogenesis in the rat femoral artery. Hypoaggregability of whole blood is likely to be partly involved in the abnormal thrombogenesis.

Animals↗
PubMed1991

Pharmacokinetic and pharmacodynamic profiles of vapiprost, a selective, long-lasting thromboxane receptor antagonist, after single and multiple oral administration to healthy volunteers.

A selective thromboxane A2 (TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties. The time-profile of vapiprost concentration in plasma was determined and the effects of the drug on platelet aggregation in platelet-rich plasma (PRP) induced by a stable TXA2 receptor agonist U-46619, adenosine diphosphate (ADP) and collagen, and platelet aggregation in whole blood induced by U-46619 ex vivo were simultaneously examined and compared. In the single-dose study (5, 10, and 20 mg/man) the plasma concentrations of the drug were fitted well to a one-compartment open model with a first-order absorption. The area under plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) showed dose-related increases, whereas the mean elimination half-lives (t1/2) remained approximately constant within the range of 0.99-1.1 hour. The drug was hardly recovered unchanged in urine. The platelet aggregation in PRP induced by collagen or U-46619 and the secondary aggregation by ADP were inhibited; that induced by U-46619 was the most specifically and completely inhibited at 2 hours after administration of any dose. The duration for maintaining the significant inhibition tended to depend on the dose and ranged from 24 to 36 hours after administration, which was much longer than expected from the plasma concentration of drug. The time-profile of inhibiting whole blood platelet aggregation that was induced by U-46619 was almost parallel to that of platelet aggregation in PRP by the same aggregant. The bleeding time was slightly prolonged 2 and 8 hours after administrations of 10 and 20 mg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Effects of DPI 201-106, a novel cardiotonic agent, on hemodynamics, cardiac electrophysiology and arrhythmias induced by programmed ventricular stimulation in dogs with subacute myocardial infarction: a comparative study with dobutamine.

DPI 201-106 (DPI), a novel and potent cardiotonic agent, exhibits its effects by prolonging the open state of Na+ channels, resulting in an increase in action potential duration, and thus, is supposed to share the class III antiarrhythmic activity. The effects of DPI on the hemodynamics, intraventricular conduction and refractoriness of heart, and the incidence of arrhythmias induced by programmed electrical ventricular stimulation (PES) were compared with (+/-)-dobutamine. Dogs which survived for 5 to 7 days after the induction of myocardial infarction were used as the model. The presence of subacute myocardial infarction caused by occluding the left anterior descending coronary artery elicited a mild left ventricular dysfunction represented by a significant decrease in peak LV dp/dt by about 20%. Both i.v. bolus injection of DPI (1, 3 and 5 mg/kg) and i.v. continuous infusion of dobutamine (3, 5 and 10 micrograms/kg/min), which were administered in a cumulative manner, dose-dependently improved the hemodynamic parameters. At the higher doses of both DPI (3 and 5 mg/kg) and dobutamine (5 and 10 micrograms/kg/min) the control values were reached or even exceeded. DPI dose-dependently increased the effective refractory period (ERP) of both non-infarcted and infarcted ventricular myocardia to a similar degree, but the conduction time showed a frequency-dependent increase in the infarcted myocardium to a greater degree than in the non-infarcted myocardium after DPI. In contrast, dobutamine decreased the ERP in both non-infarcted and infarcted myocardia, and slightly increased the difference of refractoriness between the non-infarcted and infarcted zones with no effect on the intraventricular conduction. In the PES study, DPI (3 and 5 mg/kg) produced a significant decrease in the incidence of ventricular tachycardia, whereas dobutamine (5 and 10 micrograms/kg/min) tended to worsen the arrhythmias. These findings suggest that cardiotonic agents with a class III antiarrhythmic property such as DPI may be potentially useful for the management of heart failure accompanied by ischemic heart disease.

Animals↗
PubMed1991

A novel MHC class I-related molecule expressed on mouse thymic stroma cells and mature lymphocytes.

A monoclonal antibody (mAb) TP-3 has been established by immunizing rats with the BALB/c mouse thymic epithelial cell line TEL-2. The TP-3 antigen is expressed on stroma cells of thymus, spleen, and lymph node in syngeneic BALB/c mice (H-2d). This antigen is also expressed at a low level on the cell surface of immature thymocytes, and at a high level on mature T and B cells. In allogeneic mice such as C57BL/6 (H-2b) or C3H (H-2k), no cells expressed the TP-3 antigen. Using H-2 congenic mice, reactivity with mAb TP-3 was found to map to a region of H-2DdLd or between Dd and Qa, suggesting that TP-3 is a major histocompatibility complex (MHC) class I antigen. However, immunoprecipitation analysis indicated that this antigen is not identical to the classical mouse class I molecules in terms of molecular size, antigenicity, and tissue distribution.

Animals↗
PubMed1991

The measurement of ofloxacin in hair as an index of exposure.

Several strands of hair were collected from each of patients who had been taking ofloxacin against bacterial infections some time in the past. In 10 out of total 14 subjects studied the drug was detected only in the hair portions corresponding to the administration period with the assumption of the hair growth rate of about 1 cm/month. Even in a subject who had received 300 mg/day of ofloxacin only for two days the drug could be detected in the corresponding portion. In 3 subjects the drug was detected in some other portion(s) than the corresponding ones. This might be due to the uncertainty of having used the drug on the other occasion. Only in one subject the dosage history could not be deduced from the drug distribution along hair length. In 3 subjects, who had taken the drug within 1 month, hair samples were collected every month for 3 or 4 consecutive months. The front of drug appearance in hair was clearly shown to move outwards along hair shaft every month at a pace of 1-1.5 cm/month. These results suggest that ofloxacin is excreted into human scalp hair, captured there and moves outwards along the hair shaft at its own growth rate. This leads to the concept that the distribution of ofloxacin along hair length can be used for knowing the individual exposure or non-exposure to the drug, and even for knowing hair growth rate when the innoculation(s) of the drug is strictly supervised and recorded.

Adult↗
PubMed1991

Clinical evaluation of endoscopic injection sclerotherapy for bleeding esophageal varices in liver cirrhosis with hepatocellular carcinoma.

Endoscopic injection sclerotherapy (EIS) for rupture of esophageal varices was carried out in 13 patients of liver cirrhosis with hepatocellular carcinoma (HCC). Sclerotherapy was performed by intravariceal injections of 5% ethanolamine oleate. According to the manual for the staging of cancer, these HCCs were classified as Stage I in 1 case, II in 1 case, III in 2 cases, and IV in 9 cases. There was no difference between post EIS prognosis and stage. Child's classification of these patients were class A in 1 case, B in 5 cases, and C in the remaining 7 cases. Only in 1 case of Child's A and 1 case of Child's B who were less advanced clinically and were free from icterus and ascites did EIS produce favorable results, it arresting esophageal variceal hemorrhage and led to a relatively good outcome. We suggest that emergency EIS for rupture of esophageal varices should be performed in patients with relatively good general conditions, irrespective of the stage of HCC.

Adult↗
PubMed1991

Establishment of primary cultures of pulp cells from bovine permanent incisors.

A primary culture method was established by comparing the different effects of four methods of enzymatic separation--trypsin, collagenase with and without trypsin pretreatment, and a trypsin-collagenase mixture--and five media: DMEM, DMEM and Ham's F 12 mixture, F 12, RPMI 1640 and Medium 199. The trypsin pretreatment/collagenase method was most preferable considering the high number of isolated cells, satisfactory adhesion, good growth and a single population at subconfluence. DMEM and the DMEM/F-12 mixture resulted in the best adhesion, cell growth and cell number at confluence. Primary cells separated by the trypsin pretreatment/collagenase method and cultured in DMEM were responsive to parathyroid hormone at the proliferating stage and had higher alkaline phosphatase activity than cells cultured from gingiva and mucosa after reaching confluence. The long-term cultured cells formed nodules that were slightly mineralized. These results indicate that the cultured pulp cells had properties characteristic of pulp cells in vivo. This enzymatic separation method may be useful in studies of the regulation of pulp metabolism and odontoblast differentiation.

Animals↗
PubMed1991

Comparison of the effects of pirmenol and lidocaine on intraventricular conduction in canine myocardial infarction.

Effects of pirmenol hydrochloride and lidocaine hydrochloride on intraventricular conduction were examined in the infarcted heart of anesthetized dogs. The effects of the drugs on the excitation induced by ventricular stimulations were determined with coupling intervals between 150 and 1,000 ms. Effects of the drugs on the His bundle electrocardiograms were also examined. Pirmenol in doses of 1-5 mg/kg prolonged the conduction time in the infarcted zones over a wide range of coupling intervals. Pirmenol at 5 mg/kg blocked the delayed conduction at a short coupling interval in the infarcted zones. The effect of pirmenol on the conduction time in the normal zone was slight. Lidocaine in doses of 3 and 10 mg/kg prolonged the conduction time in the infarcted zone at a short coupling interval. Pirmenol did not significantly prolong PQ or AH interval. In conclusion, pirmenol selectively depressed the delayed conduction in the infarcted zone, which could result in a reentrant pathway. The effect of pirmenol on delayed conduction was dependent on the coupling interval and was quite different from that of lidocaine.

Animals↗
PubMed1991

Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model.

We report a new and reproducible model of thrombosis in the rat femoral artery. The thrombosis is initiated by endothelial injury subsequent to photochemical reaction between systemically injected rose bengal (10 mg/kg, i.v.) and transillumination of filtered xenon lamp (wave length: 540 nm) from the outside of the vessel. The blood flow of the femoral artery, which was monitored by a pulsed doppler flow meter, was fully stopped in 348.68 +/- 36.18 sec (n = 12) after i.v. injection of rose bengal under irradiation with green light. The formation of massive thrombosis was readily evident by visual inspection. The processes of primary endothelial injury and the subsequent formation of thrombosis during this manipulation were observed by light microscopy and analysed by the scanning and transmission electron microscopy. Pretreatment with heparin (30, 100 or 300 units/kg, i.v.) 10 min before rose bengal injection dose-dependently prolonged the time required to interrupt the blood flow. The thrombolytic activity of a tissue-type plasminogen activator (tPA) was also investigated. After the establishment of stable thrombotic occlusion of the femoral artery, infusion of tPA was started from the contralateral femoral vein for 30 min at the rate of 30 or 100 micrograms/kg/min. The occluded artery was reperfused in 2 out of 10 rats and in 9 out of 12 at the lower and higher rates of tPA infusion, respectively. That heparin could prevent the arterial occlusion and that tPA could reperfuse the occluded artery are observations consistent with the histopathological ones that the primary lesion of endothelium injured photochemically activates the platelet aggregation to form platelet-rich thrombus with extensions of erythrocyte-rich lesions. This model is expected to be a useful tool for evaluating the antithrombotic and thrombolytic agents.

Animals↗
PubMed1991

Ofloxacin in human hair determined by high performance liquid chromatography.

A procedure is presented for quantitating ofloxacin (OFLX) in human scalp hair by high performance liquid chromatography (HPLC) with a fluorescence detector. An octadecylsilane (ODS) column was used and the mobile phase was a mixture of potassium phosphate buffer (pH 2.6) and acetonitrile. The recovery of OFLX was 90.9-93.8% and within- and between-run precisions were 0.35-1.41% and 1.41-5.49% as the coefficient of variation (CV), respectively, when 5-50 ng OFLX was added to 1 mg blank hair. The calibration curve was linear in the range of 0.5-50 ng/tube (0.5 ml). Interference with other quinolone derivatives could be avoided according to the difference in their retention times or fluorescence spectra. Several pieces of hair were obtained from each of twelve healthy male volunteers, who had taken OFLX (100, 300 or 900 mg total dose) over a 1-3 day period 2 weeks before the hair sampling. In all hair samples except one obtained from a volunteer, who had taken the lowest dose, the 2-cm long segments nearest the scalp contained OFLX (5-45 ng/mg hair), while the upper segments did not. A highly significant positive correlation was observed between the total dose and the concentration of OFLX in the 2-cm long hair segments. Such a positive correlation was also revealed in rat hair sampled after repeated i.p. administration of OFLX over a 5-week period. These results suggest that the measurement of OFLX in hair by the present method would be useful for testing patient compliance in clinical pharmacology as well as for application to forensic science.

Adult↗
PubMed1991

Recombinant human-mouse chimeric monoclonal antibody specific for human adenocarcinoma associated antigen.

We have recently described a class-switched (IgM to IgG1) human-mouse chimeric antibody. In the present study, a human-mouse chimeric antibody specific for human adenocarcinoma-associated antigen YH206 antigen was constructed by fusing murine variable region genes (V kappa and VH) to human constant region genes (gamma 1, kappa). The murine variable domain genes were isolated from a functional murine hybridoma cell line, YH206, which secreted IgM monoclonal antibody specific for YH206 antigen. The fusion genes of heavy and light chains were introduced into the immunoglobulin non-producing mouse myeloma cell line X63-Ag8.653 by electroporation. We obtained transformants which secreted class-switched human-mouse chimeric antibodies specific for YH206 antigen. A dot immunobinding assay demonstrated that the class-switched chimeric antibody retained the ability to bind to the YH206 antigen.

Adenocarcinoma↗
PubMed1991

Pure apocrine nevus. A study of light-microscopic and immunohistochemical features of a rare tumor.

The pure apocrine nevus is a rare tumor. A new case of pure apocrine nevi of the bilateral axillary regions in a 48-year-old man is herein reported. The patient had two soft masses of both axillae. The time of onset of the masses was unknown. They were not accompanied by problems of sweating. Histologically, these lesions comprised numerous apocrine glands extending from the reticular layer of the dermis to the subcutaneous tissue. In addition, sections from both of the lesions were stained by immunoperoxidase techniques for the presence of epithelial membrane antigen, carcinoembryonic antigen, and the alpha and beta subunits of S100 protein. Immunohistochemical features of the tumor stained by these antibodies are consistent with a pure proliferation of mature, well-differentiated apocrine glands. The tumor of the present case seems to have developed spontaneously. It is believed, therefore, that the tumor seen in this patient is best categorized as a pure apocrine nevus.

Antigens, Neoplasm↗
PubMed1991

Effects of protamine on vascular smooth muscle of rabbit mesenteric artery.

Systemic hypotension is commonly observed in association with protamine administration after cardiopulmonary bypass. However, little information is available concerning the action of protamine on vascular smooth muscle. Thus, we investigated the action of protamine on vascular tissues using tension recording and microelectrode methods. Protamine (5-500 micrograms/ml) inhibited contractions induced by norepinephrine (NE)- or elevated K+ in a concentration-dependent manner in both endothelium-intact and -denuded strips. Protamine inhibition of NE contractions was less profound after endothelial denudation, whereas protamine inhibition of K(+)-induced contractions was less affected by prior denudation. In endothelium-intact strips, the protamine-induced inhibition was significantly reduced by inhibitors of the endothelium-derived relaxing factor pathway, including oxyhemoglobin, methylene blue, or NG-nitro-L-arginine, whereas the contractile inhibition was enhanced by superoxide dismutase. In endothelium-denuded strips, protamine inhibited Ca(2+)-induced contraction evoked in Ca(2+)-free solution containing 100 mM K+ and inhibited the NE-induced contraction under the following conditions: 1) in Ca(2+)-free solution; 2) after nifedipine treatment; and 3) after depletion of stored Ca2+ by A23187 or ryanodine. In membrane-permeabilized strips, protamine did not modify Ca(2+)-induced contraction. Protamine (50-500 micrograms/ml) did not modify the membrane potential of either endothelium-intact or -denuded strips. Furthermore, protamine irreversibly impaired acetylcholine-induced endothelium-dependent relaxant response, implying a toxic effect of protamine on the endothelium. We conclude that protamine exerts its inhibition on vascular smooth muscles in both an endothelium-dependent and -independent manner; i.e., the endothelium-dependent component is mediated probably by endothelium-derived relaxing factor, and direct smooth muscle effects are due to the inhibition of both Ca(2+)-influx and the NE-induced Ca2+ release from intracellular stores.

Animals↗
PubMed1991

The measurement of haloperidol and reduced haloperidol in neonatal hair as an index of placental transfer of maternal haloperidol.

Hair samples were collected at time of delivery from three neonates and their schizophrenic mothers, who had been taking haloperidol (HP) during the perinatal period to control worsening psychotic symptoms. Maternal hair was cut into 1-cm lengths, and concentrations of HP and its major metabolite, reduced haloperidol (RHP), were measured by high-performance liquid chromatography. Neonatal hair was cut into halves, and the concentrations of HP and RHP in each half were measured. The distribution of both HP and RHP along the maternal hair paralleled the dosage of HP when hair growth was assumed to be 1 cm per month. In the upper half of hair from each of two neonates neither HP nor RHP was detected. Only HP was detected in the lower half from one, and a small peak of HP in the chromatogram was observed in the other, though under the detection limit. In the third neonate both HP and RHP were detected from both halves of hair, but the concentration of HP was larger in the lower half than in the upper. These findings suggest the possibility of monitoring the transfer of maternal HP through placenta by measuring HP and RHP concentrations in neonatal hair.

Adult↗
PubMed1991

Evidence for a link between mechanical and electrical alternans in acutely ischaemic myocardium of anaesthetized dogs.

In order to examine the relation between mechanical alternans and associated electrical alternans during acute myocardial ischaemia, we determined the effect of a ventricular premature beat and calcium antagonists on mechanical and electrical alternans during acute coronary occlusion in anaesthetized dogs. Isometric contractions and unipolar electrocardiograms were recorded from ischaemic myocardium. During coronary occlusion, mechanical alternans was accompanied by electrical alternans, which was an alternate change in the ST segment elevation, i.e. the higher ST and the lower ST. Electrical alternans was frequently discordant and in some cases accompanied by discordant mechanical alternans. Both discordant electrical and mechanical alternans became concordant and were potentiated after the ventricular premature beat. In all cases, concordant mechanical alternans was accompanied by concordant electrical alternans and vice versa. In this situation, the higher and the lower ST corresponded to the larger and the smaller contractions respectively. Thus, a fixed correspondence was observed between mechanical and electrical alternans. A fixed correspondence was also observed between mechanical alternans and the variation in the time taken for repolarization of the monophasic action potential. Verapamil and diltiazem inhibited both electrical and mechanical alternans. The present results support the idea that a common mechanism, such as a beat-to-beat cycle of the transmembrane and intracellular movement of calcium ions, may play a role in the mechanisms of electrical and mechanical alternans.

Animals↗
PubMed1991

Enantioselective disposition of ofloxacin in humans.

The enantioselective disposition of ofloxacin (OFLX) was studied in healthy subjects after oral administration of (+/-)-OFLX at a dose of 200 mg. S-(-)-OFLX and R-(+)-OFLX concentrations in serum and urine were measured separately by high-performance liquid chromatography, and various pharmacokinetic parameters were calculated from the data. The ratio of S-(-) to R-(+) enantiomer concentrations in serum showed a increase with time, with S/R ratios of 1.01 at 2 h and 1.31 at 24 h. The terminal elimination half-life of S-(-)-OFLX was 6.9 h, which was significantly greater (P less than 0.05) than that of the R-(+) enantiomer (6.3 h). S-(-)-OFLX also revealed a significantly greater area under the concentration-time curve in serum, mean residence time, and total body clearance than the R-(+) enantiomer did. The renal clearance of S-(-)-OFLX (7.14 liters/h/1.73 m2) was significantly lower than that of the R-(+) enantiomer (7.53 liters/h/1.73 m2). Although the difference in the pharmacokinetic parameters of the enantiomers was small, their disposition in humans was found to be stereoselective. The difference between the enantiomers may be explained by the difference in their renal excretion.

Administration, Oral↗
PubMed1991

Recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract.

A retrospective analysis of 53 patients with an upper urinary tract (UUT) transitional cell carcinoma, which was treated surgically, was performed in relation to the development of a subsequent bladder tumor. In 19 of the 53 patients (35.8%) bladder tumors developed following surgery of a UUT tumor. The simultaneous occurrence of a bladder tumor and more than two tumors in the UUT had a significant influence on the rate of bladder tumor recurrence. On the other hand, location, mode of growth, grade, stage and vascular invasion of the UUT tumor, and history of bladder tumors did not seem to be related to the frequency of subsequent bladder tumors. These findings suggest that the diversity of UUT tumors at the time of diagnosis is an important factor in bladder tumor recurrence. Therefore, clinical and pathological examinations should be carefully performed in patients with UUT tumors.

Aged↗