Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 415 records · Page 23Linked to original sources

PubMed1991

Altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes.

The present study was undertaken to clarify the altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes by use of the laser-Doppler flowmeter. Drugs were administered intraarterially via the subclavian artery in a dose range that did not affect the systemic blood pressure. Both arachidonic acid and papaverine hydrochloride increased inner ear blood flow dose-dependently. Diabetic rats at 12 weeks, but not at 8 weeks, after the induction of diabetes showed a significant decrease in arachidonic acid response. However, there were no differences in papaverine response between diabetic and control rats. Pretreatment with ONO-3708, a selective thromboxane A2 antagonist, reversed the attenuated response to arachidonic acid found in diabetic rats. An increased response to thromboxane A2, which decreased inner ear blood flow, was also found in 12-week diabetic rats. In electrocochleograms, the latency in 12-week diabetic rats was significantly delayed compared with that in control rats, and this prolonged latency improved with insulin treatment. These results suggest that the responsiveness of inner ear blood flow to prostaglandins may be altered in individuals with diabetes mellitus.

Animals↗

PubMed1991

Dentinal fluid movement associated with loading of restorations.

Post-operative biting sensitivity is a significant clinical problem after placement of posterior resin composites and may be due to dentinal fluid movement. The occlusal surfaces of extracted teeth were filled with amalgam (control) or various posterior resin composites, and the movement of the dentinal fluid induced by the loading of the restorations was studied. In addition, the firing of pulpal nerves induced by the loading of class 5 resin composite restorations in canine teeth of dogs was also investigated. When the entire cavity was etched with an acid gel and then filled with resin composite, dentinal fluid movement in response to loading was significantly (p less than 0.01) greater than in the amalgam-filled or unoperated controls. The dog canine tooth filled with resin composite showed firing of pulpal nerves when loaded. These results suggest that the movement of dentinal fluid induced by masticatory pressure on resin composite restorations may elicit biting sensitivity.

Acid Etching, Dental↗

PubMed1991

A differential alteration in the responsiveness of isolated cardiac muscles to alpha- and beta-adrenergic agonists in DOCA-salt hypertensive rats.

We examined the alteration of the responsiveness to adrenergic agonists and changes in the density of adrenoreceptors in the hearts of rats with deoxycorticosterone acetate (DOCA)-salt hypertension in order to determine the relationship between changes in adrenoreceptor responsiveness and adrenoreceptor density in this hypertension model. The maximal increase in the tension development with phenylephrine in the presence of propranolol and with isoproterenol decreased to a larger extent in the latter, but the PD2 values for these agonists did not change. Decreases in maximal tension development with phenylephrine and Ca2+ were similar. The density of alpha- and beta-adrenoceptors decreased similarly. In conclusion, whereas a decreased adrenoreceptor density may not significantly contribute to a decreased agonist responsiveness in DOCA-salt hypertensive rats, altered Ca2+ sensitivity contributes to the observed reduction in agonist responsiveness.

Adrenergic alpha-Agonists↗

PubMed1991

Coupling interval-related effects of class I antiarrhythmic drugs, mexiletine, cibenzoline and disopyramide, on ventricular activation in canine myocardial infarction.

Time-dependent inhibition of sodium channels by class I antiarrhythmic drugs has been observed in isolated cardiac muscles or cells. We examined coupling interval-related effects of class I antiarrhythmic drugs, mexiletine, cibenzoline and disopyramide, on ventricular activation in canine infarcted myocardium. A ventricular stimulation with various coupling intervals was applied to the right ventricle, and activation delays (time intervals between the initiation of a deflection and the final rapid deflection of a bipolar electrocardiogram) of infarcted and normal zones were measured. The premature stimulation produced a delayed activation and in some animals, caused reentrant beats. Mexiletine (3 and 10 mg/kg), cibenzoline (1 and 4 mg/kg) and disopyramide (1 and 4 mg/kg) further enhanced or blocked the delayed activation. The effects of these drugs were more marked at shorter coupling intervals, although cibenzoline and disopyramide showed significant effects also at long coupling intervals. The effect of these drugs on the activation in the normal zone was less than that in the infarcted zone. In conclusion, mexiletine, cibenzoline and disopyramide showed a coupling interval-related depression of delayed activation in infarcted myocardium, which may be a reflection of their time-dependent inhibition of sodium channels.

Animals↗

PubMed1991

Actions of FRC-8653 on smooth muscle cells of the rabbit mesenteric artery.

In ring preparations of the rabbit mesenteric artery, the Ca-contraction, but not the noradrenaline (NA)-contraction, was inhibited by FRC-8653 (10(-9)-10(-5) M) in a concentration-dependent manner, although with a potency 50-100 times weaker than that of nicardipine. The actions of FRC-8653 on Ca-contraction appeared more slowly (over 1 hr) than those of nicardipine. FRC-8653 (up to 10(-5) M) and nicardipine (up to 10(-7) M) did not change the resting membrane potential of smooth muscles. The amplitude of the evoked excitatory junction potential (e.j.p.) was inhibited by FRC-8653, but not by nicardipine, with no alteration in the facilitation process of the e.j.p.s. The inhibition by FRC-8653 of the e.j.p. appeared rapidly and was reversible. FRC-8653 inhibited the membrane depolarization of smooth muscles elicited by ATP, but not by NA or high [K+]o solution. ATP-induced contractions were also inhibited by FRC-8653. The amplitudes of action potentials evoked by current stimuli were decreased by FRC-8653, with no significant change in the electrotonic potentials. Thus, FRC-8653 has properties similar to those of the dihydropyridine Ca-antagonists, but differs from them in that 1) its inhibitory actions on Ca influx appear slowly and 2) sympathetic transmission is inhibited, possibly by inhibition of the postjunctional events for e.j.p. generation.

Animals↗

PubMed1991

The effects of beta-blockers and diazepam on heart rate of conscious conditioned rats.

1. Fischer male rats were trained to avoid shock in a shuttle box. After this procedure, a small ECG transmitter was incorporated under the skin of thorax. 2. In saline group, when in the shuttle box heart rate significantly increased, and decreased while exposed to the buzzer. 3. When beta-blocker (carteolol, pindolol, propranolol) was injected, heart rate did not increase after the rat was put in the shuttle box, but decreased after exposed to the buzzer. Change in heart rate was not shown when diazepam was injected. 4. These results indicated that diazepam is more effective than beta-blocker in terms of instability of heart rate in conditioned rats.

Adrenergic beta-Antagonists↗

PubMed1991

Phenotypic characteristics of T cells interacted with synovial cells.

We demonstrated the phenotypic characteristics of T cells interacted with synovial fibroblast-like cells. A small percentage of peripheral blood T cells adhered to synovial fibroblast-like cells. When synovial cells were treated with interferon-gamma or interleukin-1 beta, the percentage of T cells that adhered to the treated cells markedly increased in comparison with the value for untreated synovial cells. The kinesis of T cell adherence to treated synovial cells differed from that of HLA-DR antigen expression on synovial cells. T cell adherence was not blocked by mouse monoclonal anti-HLA-DR and anti-HLA-ABC antibodies. The phenotypes of the adherent and nonadherent T cells were investigated with a flow cytometer. The CD29 + subset was more adhesive than the CD45RA + subset to IL-1 beta-stimulated synovial cells. The proportions of high density lymphocyte function associated antigen (LFA)-1 alpha and LFA-1 beta were greater in the adherent than in the nonadherent T cells, and the mean fluorescence intensities of LFA-1 alpha, LFA-1 beta and CD2 molecules on adherent T cells were significantly higher than those on nonadherent T cells. Our results support the concept that an interaction between infiltrating lymphocytes and synovial cells occurs in the synovium, resulting in the initiation and perpetuation of immune responses in synovial tissue in rheumatoid arthritis.

Adult↗

PubMed1991

A case of adult T cell leukemia complicated by proliferative synovitis.

A 60-year-old woman was admitted to our hospital with symmetrical arthritis of the knees. During the 2 years preceding admission, she had experienced recurrent arthritis. A histological examination of her synovial tissue showed prominent villous proliferation of the synovial cells, prominent vascularity throughout and an inflammatory infiltrate composed of abnormal mononuclear cells. Three months later, she developed fever, skin eruptions, lymphadenopathy and hepatosplenomegaly. She also had hypercalcemia and there was abnormal lymphocytosis in her blood smears. She was diagnosed as having adult T cell leukemia. Parenteral chemotherapy treatment with adriamycin and cyclophosphamide gave remission of all the manifestations of disease, including arthritis. Her leukemia recurred, however, and she died 6 months after the diagnosis was made.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

[Effects of opioids on Ca2+ flux of polymorphonuclear leukocytes].

The effects of opioids on Ca2+ influx were evaluated using rat polymorphonuclear leukocytes, comparing with those of nicardipine and TMB-8, 8-(N, N diethyl amino) 3, 4, 5 trimethoxybenzoate. Selective opioid kappa-agonist, U-50488H, inhibited Ca2+ influx caused by f-Met-Leu-Phe (fMLP). U-50488H also strongly inhibited the elevation of intracellular free Ca2+ concentration in Ca2+ free medium. In contrast, mu-agonist, morphine showed no effects. The purified enantiomers of U-50488H exerted no difference in their effects on Ca2+ mobilization of PMNs, and naloxone did not antagonize the effects of U-50488H. Both nicardipine and TMB-8 inhibited the Ca2+ flux. The inhibitory effects of TMB-8 were potentiated by lowering extracellular free Ca2+. These results suggest that U-50488H may interfere with the Ca2+ regulatory system of PMNs via opioid receptor non-mediated pathway. The effect was suspected to be caused by selective inhibition of Ca2+ release from intracellular Ca2+ store sites by affecting post-receptor mechanisms of f-MLP.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

Selective elimination of double-positive immature thymocytes by a thymic epithelial cell line.

A cloned epithelial cell line, TEL-2, has been established from the stroma tissues of normal mouse thymus. Incubation of mouse thymocytes on TEL-2 cells resulted in the selective elimination of double-positive (CD4+CD8+) cells from the culture, whereas single-positive (CD4+CD8- or CD4-CD8+) thymocytes remaining in the culture were concentrated in non-integrated cell population. The CD3- or CD3 low-positive thymocytes were also eliminated by the TEL-2 cells from the culture, followed by the concentration of CD3 high-positive cells in the culture. Only intact viable thymocytes were integrated into TEL-2 cells. Electron microscopic examination showed that the integrated cells into TEL-2 cytoplasm were gradually degenerated. Mature single-positive T cells, mature B cells or double-negative thymocytes were not integrated into TEL-2 cells. The TEL-2 cell may provide information on the mechanism of selective disappearance of double-positive immature cells from the thymus.

Animals↗

PubMed1990

Effects of antidepressants on the intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation in the dog heart after myocardial infarction.

The effects of mianserin, a tetracyclic antidepressant, and adinazolam, a new triazolobenzodiazepine which has antidepressant activity, on intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation were studied in the dog heart after myocardial infarction and compared to the effects of amitriptyline, a standard tricyclic antidepressant. Amitriptyline at a dose of 1 mg/kg significantly slowed ventricular conduction in a frequency-dependent manner and at doses of 2 and 3 mg/kg significantly slowed ventricular conduction in infarcted ventricular myocardium. Amitriptyline also significantly slowed ventricular conduction in normal myocardium. Amitriptyline increased the incidence of ventricular arrhythmias induced by the programmed ventricular stimulation and prolonged the intraventricular delayed conduction resulting in re-entrant ventricular arrhythmia. On the other hand, mianserin and adinazolam at doses of 1-3 mg/kg had no significant effects on intraventricular conduction in infarcted and normal myocardium and on the incidence of arrhythmias induced by programmed ventricular stimulation. From these results, we can expect that mianserin and adinazolam may have a much lower cardiac toxicity than amitriptyline.

Amitriptyline↗

PubMed1990

Antiarrhythmic effects of a benzothiazine derivative (SD-3211) and its stereoisomer (SA3212) in anaesthetized rats and isolated perfused rat hearts compared with bepridil.

The antiarrhythmic effects of a new calcium channel blocking agent (SD-3211) and its stereoisomer with additional sodium channel blocking activity (SA3212), were compared with those of a known antiarrhythmic drug (bepridil), using the left coronary artery ligation- and reperfusion-associated arrhythmia models both in isolated rat hearts and in anaesthetized rats. Isolated and perfused rat hearts were subjected to regional ischaemia for 15 min and subsequent reperfusion for 5 min. SD-3211 and SA3212 showed dose-dependently prolongations of the time interval between coronary ligation and first appearance of ventricular premature beats, reductions in the number of total ventricular premature beats during the ligation period and reductions in the incidence of reperfusion-induced ventricular fibrillation. The values of the negative logarithm of IC50 (mol/l) of SD-3211, SA3212 and bepridil were 7.97, 7.41 and 6.64 for the reduction of ventricular premature beats during ligation and 6.43, 7.49 and 6.17 for the reduction of ventricular fibrillation during reperfusion, respectively. In a separate study on force of concentration and coronary flow in perfused heart paced at 340-360 beats/min SD-3211 caused a significant negative inotropic effect between 10(-7) and 10(-6) mol/l. SA3212 at the concentration of less than 10(-6) mol/l did not result in any significant change in force of contraction. The coronary flow was increased dose-dependently by SA3212, while it was first increased and then reduced in the presence of higher concentration of SD-3211 (greater than 10(-7) mol/l). Hearts of anesthetized rats were also subjected to regional ischaemia for 7 min and subsequent reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1990

Effects of bepridil and lidocaine on the intraventricular conduction in acutely ischaemic and infarcted canine myocardium.

Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans.

Animals↗

PubMed1990

A new model for photochemically induced thrombosis in the inner ear microcirculation and the use of hearing loss as a measure for microcirculatory disorders.

A new photochemical method was employed to cause disorders in the inner ear's microcirculation, using the rat as an animal model. Hearing loss was used as a measure for establishing the altered microcirculation. Under pentobarbital anesthesia, the middle ear was opened by a ventral approach. The lateral wall of the cochlea was then illuminated with a filtered xenon lamp (wavelength 540 nm) while rose bengal was infused intravenously. Photoactivated rose bengal produces oxygen radicals and oxygen singlets, which subsequently damage the vascular epithelium to cause the adhesion and aggregation of platelets in the small vessels. Disintegration of the inner ear hair cells at the irradiated site became evident 24 h after the illumination. These findings further suggest that the photochemical occlusion in the inner ear's microcirculation led to ischemic damage of the stria vascularis and the hair cells in the inner ear. When the action potential (AP) of the cochlea was measured with an electrocochleogram a gradual decrease occurred after the illumination. When acetylsalicylic acid was injected intravenously before treatment, the time required to completely suppress the AP was prolonged in a dose-dependent manner. Findings indicate that our method causes a photochemically induced occlusion in the inner ear's microcirculation and is therefore potentially useful for evaluating the various effects of drugs on the ear.

Action Potentials↗

PubMed1990

Human scalp hair as evidence of individual dosage history of haloperidol: a possible linkage of haloperidol excretion into hair with hair pigment.

We report a method for determining haloperidol concentration in human scalp hair and discuss a possible linkage of haloperidol excretion into hair with the hair pigment melanin. First, an animal study was conducted to support the idea that hair contains amounts of haloperidol corresponding to the doses given and pigmented hair contains much more drug than does unpigmented hair. The haloperidol concentration was measured using a radioimmunoassay technique after hairs were dissolved in 2.5 N NaOH solution and the drug extracted. Pigmented and albino rats, whose hair from an area on the back had been removed beforehand by plucking, were administered either 1, 3, or 10 mg of haloperidol (i.p.) per kg body weight every day for 3 weeks. At the end of the administration period hair which had newly grown on the denuded area was plucked and collected. In each of the two groups classified by hair color the drug levels in the hair correlated with the doses given; however, the concentrations in the hair from the albino rats were much lower than those in the hair from the pigmented rats (which was less than 8.5%). Second, black and white hair was collected from each of seven human subjects with grizzled hair, who were receiving or had been administered haloperidol at fixed daily doses for more than 1 month, and the concentration of haloperidol in each type of hair was measured. In the same subject the concentration in the white hair was found to be much lower than that in the black (less than 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

An ultrastructural study of the differentiation of mesenchymal cells in implants of allogeneic dentine matrix on the amputated dental pulp of the dog.

The sequential transition of the cells adjacent to autolysed antigen-extracted allogeneic dentine matrix was observed in a cavity on the amputated pulp in vivo. One week post-operatively, cells having poorly developed organelles and many free ribosomes, reminiscent of dedifferentiated or embryonic cells, were seen in migration and forming attachments to the allogeneic dentine matrix. Two weeks post-operatively, the cells close to that matrix had polarized nuclei and a clear distal area with minute processes, suggestive of preodontoblasts. Matrix vesicles were observed in the newly formed predentine-like matrix close to the allogeneic matrix. Some of the matrix vesicles contained needle-like crystals. Four weeks post-operatively, long, polarized cells with a well-developed endoplasmic reticulum and Golgi apparatus were seen. They contacted via a terminal web with desmosomes and tight junctions, and each had a long process extending into the predentine-like matrix, suggesting that they were identical to odontoblasts. These findings suggest that in the repair of the amputated pulp implanted with allogeneic dentine matrix the differentiation of odontogenic cells and initial mineralization may be analogous to those in normal dentinogenesis.

Animals↗

PubMed1990

The induction of reparative dentine in the amputated dental pulp of the dog by bone morphogenetic protein.

Reparative dentine was formed in the cavity of the amputated pulp when capped with crude allogeneic BMP. This began with a slight cell-mediated immune response and was followed by resorption of BMP and proliferation of migratory spindle-shaped mesenchymal cells, together with vascular invasion. Four weeks postoperatively, there were osteodentinoblasts embedded in forming matrix and/or osteodentinocytes trapped within osteodentine in some parts of the cavity. Other parts were filled with pulpal tissue. Eight weeks postoperatively, odontoblasts were forming tubular dentine next to the osteodentine. In albumin-implanted controls, a little osteodentine and no tubular dentine were seen. These findings suggest that dissolved BMP stimulates mitosis of mesenchymal cells and may induce differentiation of osteodentinocytes. The resultant osteodentine may play some role in the differentiation of odontoblasts.

Animals↗

PubMed1990

A new method for extracting DNA or RNA for polymerase chain reaction.

The use of glass powder suspension for the extraction of RNA or DNA was studied to simplify the procedures of polymerase chain reaction (PCR). Using this procedure, proviral DNA of human T-lymphotropic virus type-1 (HTLV-1) in the blood of an asymptomatic virus carrier and viral RNA of human immunodeficiency virus (HIV) in the blood of an AIDS patient were easily detected by PCR employing glass powder. The use of glass powder is a simple and highly efficient procedure for the extraction of DNA or RNA, and can be applied for routine PCR.

Acquired Immunodeficiency Syndrome↗