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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 1,153 records · Page 64Linked to original sources
PubMed1986

Electrophysiological and behavioral assessments of dopamine autoreceptor activation to apomorphine in rats.

Single neuronal activity was recorded extracellularly in the substantia nigra pars compacta (SNC) in rats anesthetized with chloral hydrate. Haloperidol in a dose of 10 micrograms/kg had no significant effects on the SNC neurons. R(-)apomorphine (cumulative i.v. dose of 40 micrograms/kg, given as: 5, 5, 10 and 20 micrograms/kg) inhibited the firing rate of dopaminergic neurons, in a dose-dependent manner. Haloperidol (cumulative i.v. dose of 10 micrograms/kg, as: 2.5, 2.5 and 5 micrograms/kg) reversed the effect of apomorphine. Complete reversal of the firing rate to haloperidol was observed with a dose of 10 micrograms/kg. In rats pretreated with 10 micrograms/kg of haloperidol, there was a dramatic shift to the right of the apomorphine dose-response curve (cumulative i.v. dose of 800 micrograms/kg, as: 50, 50, 100, 200 and 400 micrograms/kg), and this inhibition was reversed by haloperidol (cumulative i.v. dose of 400 micrograms/kg, as: 50, 50, 100 and 200 micrograms/kg). Apomorphine in doses of 40 micrograms/kg and 800 micrograms/kg elicited yawning behavior and stereotypy, respectively. Apomorphine in a dose of 800 micrograms/kg elicited stereotypy in rats treated 3 min before with 10 micrograms/kg of haloperidol. Therefore, electrophysiological determinations of events in the SNC dopaminergic neurons are given support by the behavior observed in these rats.

Animals↗
PubMed1986

[A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration].

A phase I study of VP was undertaken using the methods of a single (40 cases; range of dose levels 30-540 mg/m2) and 5-day (41 cases; range of dose levels 40-140 mg/m2/day) intravenous administration. The dose-limiting toxicity of VP was moderate to severe leukopenia. MTD was estimated to be 540 mg/m2 for a single and 140 mg/m2/day for 5-day administration. The median days to WBC nadir from the start of therapy and to recovery from reaching the nadir were 10 and 10.5 for single, and 15 and 7 for 5-day administration, respectively. Thrombocytopenia was less frequent and less pronounced than leukopenia. Mild gastrointestinal disturbances and alopecia were frequently observed. Transient hepatic dysfunction, fever, headache, fatigue, dyspnea, hypotension, and pain along the vein were also encountered in a small number of patients. There were no cases with renal, neurologic or cardiac toxicity. Objective tumor regression was seen in one case each of IBL(CR), bladder cancer, non-Hodgkin's lymphoma and ATL (PR). The post-infusion plasma decay of VP in 4 cases given 80-120 mg/m2 by a single administration was biphasic with t1/2 alpha ranging from 0.13 to 0.39 h and t1/2 beta ranging from 3.33 to 4.85 h. No accumulation of VP was found in plasma after five repeated daily doses. Doses of 360-480 mg/m2 by single and 80-100 mg/m2/day by 5-day administration repeated every 3 to 4 weeks can therefore be recommended for phase II studies in good-risk patients.

Adult↗
PubMed1985

[Evidence for the existence of inactive renin in the rat brain. Part II. Distribution of inactive renin in the brain of spontaneously hypertensive rats].

Inactive renin in the brain of spontaneously hypertensive rat was investigated. The results are as follows. Treatment with either trypsin or glandular kallikrein of the brain tissue extract caused a rapid and apparent increase in the renin activity at either 0 or 27 degrees C. The molecular weight of the active renin was estimated to be 41,000 or 50,000 daltons, while that of the trypsin-activatable inactive renin was found to be 44,000 or 57,000 daltons on a column chromatography with Sephadex G-100. The contents of the active renin was the highest in the hypothalamus, followed by the striatum, thalamus, midbrain, medulla oblongata, cerebral cortex and cerebellum, while the contents of the trypsin-activatable inactive renin was the highest in the hypothalamus, followed by the striatum, thalamus, cerebellum, midbrain, cerebral cortex and medulla oblongata. These results suggest that inactive renin(s) exist in the brain of spontaneously hypertensive rat. It seems likely that the brain renin-angiotensin system is modulated by the conversion of inactive to active renin(s), which, in turn, plays at least in part a role in the blood pressure regulation through generation of angiotensin II in spontaneously hypertensive rats.

Animals↗
PubMed1985

Multiple forms of immunoreactive renin in human pituitary tissue.

Immunoreactive renin was demonstrated in pituitary tissues of postmortem human subjects with different diseases. The specific immunoreactive renin activity comprised the majority of the tissue renin-like activity (mean, 83%), indicating the absence of nonspecific actions of proteases such as cathepsin D. We used three pituitary specimens with high levels of the specific renin activity for further biochemical characterization of the enzyme. Small differences were found in the molecular mass (45 K, 42 K and 37 K), binding to concanavalin A-Sepharose, and isoelectric points (pI) (4.72, 4.78, 4.86, 5.06, 5.28 and 5.44). These results seem to be interpreted as evidence for the presence of specific renin in the human pituitary with microheterogeneity.

Chromatography, Affinity↗
PubMed1985

Contralateral circling behavior induced by intranigral microinjections of taurine and GABA in rats.

Circling behavior induced by unilateral microinjections of taurine and gamma-aminobutyric acid (GABA) into the substantia nigra zona reticulata (SNR) was studied in rats. Both taurine (10-100 micrograms/rat) and GABA (30-300 micrograms/rat) induced the contralateral circling behavior in a dose-dependent manner when they were microinjected into the SNR. Neither compound induced ipsilateral circling. An ipsilateral injection of 6-hydroxydopamine (6-OHDA) into the nucleus caudatus putamen (CPU) caused a reduction of the dopamine (DA) content in the injected side and decreased the circling behavior induced by taurine but not GABA. Electrolesion of the ipsilateral nucleus ventromedialis thalami (VM) decreased both taurine- and GABA-induced circling. In contrast, only GABA-induced circling was reduced by the electrolesion of the ipsilateral nucleus parafascicularis thalami (PF). Electrolesion of the ipsilateral nucleus accumbens (ACB) did not modify the circling behavior induced by GABA, but did decrease the circling induced by taurine. Electrolesion of the ipsilateral globus pallidus (GP) or nucleus entopeduncularis (EP) did not attenuate the circling behavior induced by either taurine or GABA. These results suggest that taurine-induced circling behavior may be mediated by the nigrostriatal-nigrothalamic system, and the ACB. In contrast, the nigrothalamic system may play an important role in GABA-induced circling behavior.

Animals↗
PubMed1985

Effects on the caudate spindle in rats of taurine and gamma-aminobutyric acid (GABA) microinjected into the substantia nigra: involvement of the dopaminergic system.

Spindle bursts (caudate spindle) were recorded from the frontal cortex in rats. The bilateral intranigral microinjection of taurine suppressed the caudate spindle, whereas the same dose of gamma-aminobutyric acid (GABA) did not suppress the caudate spindle. These results indicate that suppression of the caudate spindle induced by taurine may relate to activation of the nigrostriatal dopaminergic neurons.

Animals↗
PubMed1985

Effects on the caudate spindle in rats of dopamine microinjected into the caudate nucleus.

We examined the caudate spindle in control and pargyline-pretreated rats following bilateral application of 3 doses (15, 50 and 150 micrograms/site) of dopamine (DA) into the caudate nucleus. The highest dose of DA (150 micrograms) suppressed the spindle, whereas lower doses (15, 50 micrograms) enhanced the spindle in control rats. Haloperidol given into the bilateral caudate nucleus increased the spindle in control rats. In pargyline-pretreated rats, 50 and 150 micrograms DA caused marked suppression, but 15 micrograms DA caused enhancement. These findings indicate that the DA system may mediate the development of the caudate spindle. Suppression of the caudate spindle induced by intracaudate DA injection may be due to stimulation of postsynaptic DA receptors and enhancement mediated by DA autoreceptors on the DA nerve terminals in the caudate nucleus with a subsequent inhibition of DA neurotransmission.

Animals↗
PubMed1985

Inhibitory effect of sodium salicylate on ADP-induced platelet aggregation and on 45Ca2+ uptake into platelets.

The effects of sodium salicylate (SS) on ADP-induced platelet aggregation and on a metabolism of calcium in platelets were studied, using gel-filtrated platelets (GFP). SS inhibited dose-responsively ADP-induced aggregation in the presence of fibrinogen and Ca2+. It was found that extracellular 45Ca2+ was rapidly taken up into platelets after stimulation by ADP, while SS significantly inhibited this activity. On the other hand, SS had no effect on platelet aggregation induced by 0.11-1.0 microM ionophore A23187. Therefore, it was found that the inhibitory effect of SS on ADP-induced platelet aggregation may be due to the inhibition of the active influx of extracellular Ca2+ into platelets during aggregation.

Adenosine Diphosphate↗
PubMed1985

Enzyme immunoassay of human protein C by using monoclonal antibodies.

An enzyme-linked immunosorbent assay (ELISA) for measuring human protein C by using two monoclonal antibodies directed toward the heavy chain of protein C is reported. This assay enabled the determination of protein C in concentrations of 10 to 400 ng/ml in less than 3 hours with a single antigen-antibody reaction. Within-run and between-run coefficients of variation were less than 8%. The mean concentrations of protein C in plasma of 42 normal subjects, 24 patients with liver disease, 27 with DIC, 48 with warfarin therapy and 15 with congenital protein C deficiency, were 4.2, 3.0, 2.3, 2.1 and 1.9 micrograms/ml, respectively. The results obtained with the present ELISA correlated well with those of radioimmunoassay (r = 0.935, n = 81) as well as those of Laurell's Rocket method (r = 0.910, n = 81) by using rabbit anti-human protein C serum. The present method was sensitive and specific for measurement of protein C and also PIVKA-protein C in plasma.

Antibodies, Monoclonal↗
PubMed1985

[Biochemical properties of renin in human pituitary tissue].

The biochemical properties of renin, extracted from human pituitary specimens obtained at autopsy, were studied using a specific antirenin antibody raised against human kidney renin. The following results were obtained. The molecular weight of pituitary renin was estimated to be about 37,000 daltons by gel filtration through Sephadex G-100. The optimum pH of pituitary renin was between 6.0 approximately 7.0, while that of a renin-like substance which did not react with the antirenin antibody had an acidic pH of 4.0, with a pH comparable to that of the cathepsin D-like enzyme in the pituitary tissue. The presence of two different isoelectric-point species of pituitary renin was revealed by isoelectric focusing, one with a point of pH 4.47 and the other with that of pH 5.77. The Km value of pituitary renin was 37.9 microM for synthetic human renin substrate. Affinity chromatography of the pituitary renin on a Concanavalin-Sepharose column showed that most (87.4%) of the pituitary renin did not contain glycoprotein residues. Treatment with either trypsin or glandular kallikrein increased the renin activity, indicating the presence of an inactive form of renin in the pituitary tissue. From these findings, it is concluded that specific renin exists in human pituitary tissue. It seems likely that the pituitary renin is of local origin rather than contamination of the circulating enzyme.

Chromatography, Affinity↗
PubMed1985

[The acute effects of the new angiotensin I-converting enzyme inhibitor, enalapril maleate, on blood pressure, plasma renin, aldosterone and kinins in hypertensive patients].

The acute antihypertensive effect of a new long-acting oral angiotensin I-converting enzyme (ACE) inhibitor, enalapril maleate, was assessed in 20 hypertensive patients, of whom 14 had essential hypertension, 4 had renovascular hypertension, one had hypertension associated with chronic renal failure, and one had primary aldosteronism. Enalapril maleate significantly lowered the blood pressure in either low-renin or normal- and high-renin hypertensives. There was a significant correlation for all patients as a group between the pretreatment levels of serum ACE activity and the reduction in mean blood pressure (r = -0.454, p less than 0.05, n = 20) 2 h after drug administration. The serum ACE activity decreased maximally 3 to 4 hours after drug administration and did not return to baseline levels within 24 h. There was a significant correlation between the reduction in mean blood pressure and changes in ACE activity 90 min and 2 h after drug administration, respectively, for all patients as a group (r = 0.495, p less than 0.05, n = 20, at 90 min; r = 0.508, p less than 0.05, n = 20, at 2 h). The plasma renin activity (PRA) significantly increased in normal- and high-renin hypertensives but not in low-renin hypertensives. There was a close correlation between the reduction in mean blood pressure and the PRA 8 h after drug administration in normal- and high-renin patients (r = -0.623, p less than 0.05, n = 13), while no such relationship was observed in low-renin patients. The plasma aldosterone concentration (PAC) significantly decreased within 3 h, the lowest values occurring at 8 h after drug administration, and it returned to baseline levels within 24 h in all patients. No relationship was found between the reduction in mean blood pressure and changes in PAC after drug administration in either low-renin or normal- and high-renin hypertensives. The plasma bradykinin concentration (PBC) increased within 1 h, the highest values occurring at 3 h after drug administration, and returned to baseline levels within 24 h in low-renin hypertensives, while the PBC was significantly increased at 4 h and had not returned to baseline levels within 24 h in normal- and high-renin hypertensives. There was a significant correlation between percentage changes in mean blood pressure and those in PBC 90 min after drug administration in normal- and high-renin hypertensives (r = -0.556, p less than 0.05, n = 13), while no relationship was observed between them in low-renin hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

The synaptic relationship between vasoactive intestinal polypeptide (VIP)-like immunoreactive neurons and their axon terminals in the rat small intestine: light and electron microscopic study.

The present study demonstrates synaptic contacts between vasoactive intestinal polypeptide (VIP)-like immunoreactive neurons and immunoreactive axon terminals in the submucous and myenteric plexuses of the rat small intestine. Our observations suggest that VIP afferents directly affect the VIP neurons in the small intestine via synapses.

Animals↗
PubMed1985

Synthesis and secretion of protein C inhibitor by the human hepatoma-derived cell line, Hep G2.

The site of synthesis of protein C inhibitor, a recently identified human plasma inhibitor against activated protein C, is not known. We have studied the production and secretion of protein C inhibitor by an established human liver cell line derived from hepatocellular carcinoma (Hep G2). The concentration of protein C inhibitor, as measured by a specific radioimmunoassay, increased in the medium of Hep G2 cells with time. There was no evidence for a significant intracellular pool of this protein. Protein C inhibitor secreted from Hep G2 cells (G2 protein C inhibitor) inhibited the activity of purified activated protein C in a functional assay. De novo synthesis of protein C inhibitor was demonstrated by the presence of specific immunoprecipitable radioactivity in the medium after 5 h of labeling of the cells with [35S]methionine. Analysis of the immunoprecipitates by SDS-polyacrylamide gel electrophoresis showed a peak of radioactivity corresponding to Mr 57 000. These results indicate that the liver is a site of protein C inhibitor production.

Blood Proteins↗
PubMed1985

Prognostic factors influencing relapse of squamous cell carcinoma of the maxillary sinus.

In 95 surgically staged patients with squamous cell carcinoma of the maxillary sinus, multivariate regression analyses were employed to identify prognostic factors. Possible prognostic factors for local control were TNM stage and type of surgical procedures: T2 or T3 tumors and use of total maxillectomy showed better local control rates (P less than 0.01). High radiation doses of 40 Gy or more also seemed to be of prognostic significance: P less than 0.2 for 40 to 60 Gy, and P less than 0.1 for 60 Gy or more. The risk of cervical relapse increased when the cheek or alveolus was grossly involved (P less than 0.2). However, since cervical relapse frequently accompanied uncontrollable primary recurrence or distant spread, and since cervical relapse alone was frequently salvaged by radical neck dissection, prophylactic irradiation to the neck is not recommended. Sex, age, nodal state, addition of chemotherapy, total doses of bleomycin or 5-fluorouracil (5-FU), or intra-arterial administration of chemotherapeutic agents did not appear to be of prognostic significance.

Adult↗
PubMed1985

Cytotoxic factor production by Kupffer cells elicited with Lactobacillus casei and Corynebacterium parvum.

The ability of Kupffer cells, spleen macrophages, pulmonary macrophages, and peritoneal macrophages (PM) to produce cytotoxic factor (CTF) was investigated in vitro. The production of CTF by Kupffer cells elicited with Corynebacterium parvum (CP) or Lactobacillus casei YIT9018 (LC9018) was higher than that of spleen, pulmonary macrophages, or PM. In addition, oxygen radical (OR) production by Kupffer cells or PM was measured. The production of OR by Kupffer cells or PM was significantly augmented by i.v. or i.p. injection of LC9018 or CP. No significant correlation was observed between the increase in OR production by Kupffer cells or PM and CTF production by Kupffer cells or PM elicited with either organism. It was suggested that activated Kupffer cells may be one important source of CTF production in serum and that the CTF-producing macrophages may be different from the OR-producing macrophages.

Adjuvants, Immunologic↗