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Biomedical subjects

N Ishihara

Publications and source records attributed to N Ishihara.

At least 73 records · Page 4Linked to original sources

Net increase of platelet membrane tyrosine specific-protein kinase activity by phorbol myristate acetate.

Tyrosine protein kinase (TPK) activity in rabbit platelets after stimulation by phorbol myristate acetate (PMA) or thrombin was directly estimated by 32P incorporation from (gamma-32P)ATP (adenosine triphosphate) into synthetic peptide angiotensin II. By PMA-treatment a net increase of TPK activity was obtained, while thrombin acted on the TPK quickly but stimulation was limited within the range attained by the control after lengthy incubation. The responsive TPK to these stimulators was localized mainly in membrane but much less in cytosol. The specific activity of the particulate TPK was low in the sonicate of control ice cold platelets but increased about 6-fold when the platelets were incubated at 37 degrees C. On a brief contact of platelets with PMA at 37 degrees C the TPK was fully activated and reached a maximum value about 130% of the control. Determination of phosphotyrosine phosphatase in the stimulated platelet sonicate revealed that its participation in the above described increase of 32P-incorporation was meagre. The quick response suggested a possible role of TPK in the signal transduction through the platelet cell membrane.

Adenosine Triphosphate↗

Increased endothelin concentration in CSF from patients with subarachnoid hemorrhage.

A considerable quantity of endothelin-like immunoreactivity was demonstrated as present in the CSF of patients with subarachnoid hemorrhage. The endothelin levels in the CSF raised from 0.4 +/- 0.2 (Mean +/- SD) pmol/L at Day 0-1 to 2.2 +/- 0.6 pmol/L at Day 6 and the levels decreased gradually. The result suggest that endothelin may contribute the generation of vasospasm often observed in subarachnoid hemorrhage.

Endothelins↗

Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage.

A radioimmunoassay method for endothelin was developed. Antisera raised against endothelin 1 showed significant crossreaction with endothelin 2 and 3 (45 and 13%, respectively). Considerable endothelin immunoreactivity was shown to be present in the cerebrospinal fluid of patients with a subarachnoid hemorrhage, ranging from 0.3 pmol/l cerebrospinal fluid to 4.5 pmol/l cerebrospinal fluid, though no endothelin immunoreactivity was observed in the cerebrospinal fluid of controls and patients with cerebral infarction, subdural haematoma or brain tumours. Endothelin immunoreactivity was also observed in two out of five cerebrospinal fluid samples from patients with cerebral bleeding. Reverse phase high performance liquid chromatography showed that the main immunoreactive component in cerebrospinal fluid appeared to elute at the same position. There was, however, an immunoreactive component which eluted at the same position as endothelin 3. These results may support the idea that endothelin immunoreactivity in the cerebrospinal fluid originate mainly from endothelial and neural tissues and that endothelin may contribute to the generation of the vasospasm often observed in subarachnoid hemorrhage, a conclusion based on the exceptionally high endothelin immunoreactivity in cerebrospinal fluid observed in patients with subarachnoid haemorrhage.

Aged↗

[A case of neoplastic angioendotheliosis--serial study of magnetic resonance imaging].

The case of a 59-year-old man who was diagnosed as having neoplastic angioendotheliosis by biopsy of a small hemangioma on the skin is reported. The clinical features were characterized by hypersomnia, memory disturbance, disorientation to time and mild left hemiplegia including the face. Laboratory findings showed an elevated erythrocyte sedimentation rate, increased serum LDH, increased CSF protein and pleocytosis in the CSF. The CSF level of IgG was also elevated and was associated with the appearance of oligoclonal IgG bands. The biopsy specimen of the hemangioma on the skin revealed that some small vessels were packed with atypical mononuclear cells which were positive for anti-B cell antibody. Magnetic resonance imaging (MRI) of the brain detected multiple lesions located in the cerebellum, thalamus and caudate nucleus. The left paramedian thalamic lesion might be responsible for his characteristic mood and behavioral changes. The serial MRI study disclosed that some lesions progressively enlarged and duplicated in number. These findings might be typical for neoplastic angioendotheliosis, in which the rapidly proliferating cells occluded small vessels one after another in the central nervous system. The serial study of MRI may serve an important diagnostic purpose in this disease, although most patients with this disease, so far, have been diagnosed by autopsy.

Brain Neoplasms↗

Effect of N-benzyl-D-glucamine dithiocarbamate on lipid peroxidation in testes of rats treated with cadmium.

The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on lipid peroxidation in testes, liver, and kidney of rats after cadmium injection was studied. Rats were injected subcutaneously with 5 mg CdCl2/kg and 30 min later they were injected intraperitoneally with BGD (400 mumol/kg). Cadmium treatment resulted in a significant increase in the lipid peroxidation in these organs, with a particularly remarkable increase in the testes. The increased lipid peroxidation in these organs was decreased to the control level by BGD injection after cadmium treatment. The lipid peroxidation in microsomes in testes was significantly increased compared to that of the control. BGD treatment significantly decreased the cadmium concentration in the microsomes in testes of cadmium-treated rats. The lipid peroxidation in liver and kidney microsomes was little changed. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the testes, liver, and kidney were little changed by cadmium treatment. The catalase activity in the testes was increased after cadmium injection and BGD treatment significantly decreased the increased enzyme activity. These results suggest relatively small contribution of SOD, GSH-Px, and catalase in cadmium-induced lipid peroxidation in the testes. The depressive effect of BGD on the increased lipid peroxidation in the testes of rats treated with cadmium may be in part related to the decrease in the cadmium concentration in the microsomes in testes.

Animals↗

Effect of glycerol on ischemic edema evaluated by somatosensory evoked potentials.

Glycerol is administered to reduce intracranial pressure by clinically enhancing cerebral edema. In this study, the effect of glycerol on ischemic edema was evaluated in 34 cerebral infarct patients by serial SEP. Evoked potentials were obtained by stimulating the hemiparetic median nerve 60 times with duration of 0.1 msec. N20 wave of SEP was analyzed by signal processor. SEP was monitored every 30 min for 3 hr after glycerol administration. Improvements of CCT, which means interpeak latency between N13 and N20, were observed in 14 patients. In seven patients, N20 waves were observed after IV administration of glycerol even though N20 waves were not observed before glycerol administration. The patients in acute stage or with the small infarction of basal ganglia showed these electrophysiological improvements. No CCT changes were observed in nine patients, and no N20 waves were obtained in two patients even after glycerol administration. In conclusion, electrophysiologically, glycerol effect on ischemic edema was well recognized in acute staged infarct patients and the patients with small infarction of basal ganglia.

Aged↗

Identification and characterization of adipokinetic hormone (Locusta migratoria)-like immunoreactivity in the human cerebrospinal fluid.

Using an antiserum raised against locust adipokinetic hormone I, considerable quantity of adipokinetic hormone-like immunoreactivity was demonstrated in the human cerebrospinal fluid. The immunoreactivity was characterized by gel permeation and high performance liquid chromatography. The main immunoreactive component in the cerebrospinal fluid coeluted with adipokinetic hormone I. These results suggest that adipokinetic hormone may contribute to the neuronal function in the human central nervous system.

Chromatography, Gel↗

Stabilization of blood platelet microtubular system by staurosporine.

The stimulative effects of phorbol myristate acetate (PMA) on rabbit platelet shape change and platelet adhesion were completely inhibited by staurosporine (STS)-pretreatment. When the platelets were observed by whole mount immuno transmission electron microscopy (TEM), STS was found to stabilize platelet microtubular cytoskeleton. Electrophoretic analysis of the isolated marginal bundles of cytoskeleton after STS-PMA treatment revealed a newly formed 200 K high molecular weight protein band accompanied with heavy losses of tubulin monomers. These bundles of STS-treated platelets as observed in immuno TEM responded poorly to the anti alpha- or beta-tubulin antibody as compared with those of the control platelets. The results suggest that sts favour the specific assembly of tubulin bundles with a possible involvement of the microtubular associated proteins (MAPs). The resultant tight marginal bundles (MB) of cytoskeleton will stabilize the platelets and resist the effects of exogeneously added stimulants such as PMA.

Alkaloids↗

Histogenesis of gallbladder carcinoma from investigation of early carcinoma and microcarcinoma.

Carcinomas of the gallbladder can be grossly divided into two types: carcinoma in adenoma (CIA) and carcinoma without adenoma (CWA). The histogenesis of both types of gallbladder carcinoma (CIA and CWA) was investigated in association with metaplastic changes in 35 early carcinomas larger than 5 mm in diameter and 16 microcarcinomas up to 5 mm in largest diameter. In five early CIAs and two micro-CIAs, the carcinoma was surrounded by the adenoma, and the areas of both carcinoma and adenoma mainly showed gastric-type metaplasia (GM). On the other hand, 90% of the other 30 early CWAs showed GM and/or intestinal-type metaplasia (IM) in the tumor, and all of them were surrounded by GM and/or IM. Seven of the other 14 micro-CWAs showed GM and/or IM in the tumor as well as in the surrounding mucosa, and had non-neoplastic metaplastic glands underneath the carcinoma tissue. The remaining seven micro-CWAs showed no or only mild metaplasia in the tumor and were surrounded by proper mucosa without metaplasia. From these data, it is concluded that carcinoma of CIA possibly arises from adenoma mainly with GM, and that CWA originates either from the upper part of the metaplastic mucosa or from the proper mucosa of the gallbladder. In addition, some CWA may undergo secondary metaplastic changes during tumor growth.

Adenocarcinoma↗

Increased neuropeptide Y concentrations in cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage.

We investigated the possible relation between neuropeptides and cerebral vasoconstriction in samples of ventricular or cisternal cerebrospinal fluid from 14 patients with subarachnoid hemorrhage. Neuropeptide Y, calcitonin gene-related peptide, atrial natriuretic peptide, and pituitary polypeptide 7B2 were present in the cerebrospinal fluid of these patients. Concentrations of calcitonin gene-related peptide and 7B2 were not significantly different from those in control subjects, but that of atrial natriuretic peptide was significantly lower. Although the mean concentration of neuropeptide Y was not significantly higher than control, consecutive determinations showed an increase 6-11 days after the onset of subarachnoid hemorrhage. An initially high 7B2 concentration decreased gradually, although half the patients showed a second increase greater than 10 days after the onset. Considering the well-recognized vasoconstrictive effect of neuropeptide Y, it is possible that this increase in its concentration in the cerebrospinal fluid plays a role in the pathogenesis of the cerebral vasospasm that is often seen after subarachnoid hemorrhage.

Aged↗

[Clinical study on the relationship between middle cerebral artery lesions and Binswanger type infarction].

To investigate the relationship between middle cerebral artery (MCA) trunk lesions and the etiology of Binswanger type (B type) infarction, which was demonstrated as a diffuse subcortical low density area/high intensity area by CT/MRI, patients with both MCA lesions and B type infarction were studied clinically. Eighteen patients with B type infarction were diagnosed among 224 patients with MCA occlusion/stenosis on angiography accounting for 8%. The incidence was as high as 25% in M2 stenosis. The mean age of B type infarction patients was 64 years and 16 of them were men. Chronologically stepwize/slowly-progressive deterioration of clinical manifestations were observed in 14. All patients had hemiplegia, though half of them were mild or moderate in severity. Furthermore, aphasia, Gerstmann syndrome and dementia were present in 10, 1 and 2 patients, respectively. Twelve had a history of hypertension, while 11 showed transient decreases with marked changes (more than 31 mmHg in mean arterial blood pressure) in arterial blood pressure during their clinical course. Out of 9 patients in whom cerebral blood flow (CBF) was measured by 133Xe injection method/inhalation method, 7 demonstrated mild to moderate decreases in mean CBF (more than 30 ml/100 g/min) with no relation to the severity of MCA lesions. These findings suggested that hemodynamic mechanisms associated with hypoperfusion due to marked fluctuations in blood pressure are accelerating factors of B type infarction and MCA lesions, even though ischemia in the subcortical area due to leptomeningeal anastomosis may be mild or moderate.

Aged↗

Pituitary protein 7B2-like immunoreactivity in cerebrospinal fluid: comparison with other neuropeptides.

A pituitary protein, designated 7B2, was demonstrated to be present in the cerebrospinal fluid (CSF) obtained from control subjects and patients with various cerebrovascular accidents (CVAs). Although there was not any significant difference in mean immunoreactive 7B2 concentrations among various CVA groups, the CSF immunoreactive 7B2 levels in control subjects were 10 to 100 times higher than those in control plasma samples. Immunoreactive calcitonin gene-related peptide (CGRP) and immunoreactive atrial natriuretic peptide (ANP) levels in the CSF were comparable to those in corresponding normal plasma samples. The CSF ANP concentrations in patients with cerebral bleeding and subarachnoid hemorrhage were significantly lower than those in control subjects. Gel chromatography or high-performance liquid chromatography indicated that the main immunoreactivities of 7B2, CGRP, and ANP coeluted with corresponding standard material. The high CSF concentrations of immunoreactive 7B2 observed might indicate a functional role of 7B2 in the central nervous system.

Adult↗

Autoradiographic analysis of second-messenger systems in the gerbil brain.

Quantitative in-vitro autoradiographic study was performed to localize two prominent second-messenger systems (the adenylate cyclase and phosphoinositide systems) in the normal gerbil brain. [3H] Forskolin and [3H] phorbol 12, 13-dibutyrate (PDBu) were used to identify the regional distribution of adenylate cyclase and protein kinase C, respectively. The localization of the forskolin binding was not uniform, being particularly concentrated in the striatum, the accumbens nucleus, the olfactory tubercle, the substantia nigra, the CA3 region of the hippocampus and the molecular layer of the cerebellum. On the other hand, the PDBu binding was rather uniform, although the superficial layer of the cerebral neocortices, the strata oriens of the CA1 region of the hippocampus and the molecular layer of the cerebellum showed relatively dense binding. Quantitative autoradiography of the second-messenger systems in the brain is expected to provide important information concerning the role of neurotransmitters in the pathophysiology of various conditions.

Animals↗

Increase of plasma methionine-enkephalin levels in patients at the acute stage of cerebral infarction.

We investigated the participation of endogenous opioid peptide in cerebral ischaemia. In 13 patients with supratentorial infarction, the plasma immunoreactive methionine-enkephalin concentration at the acute stage (30.77 +/- 3.54 pg/ml) was significantly higher than that at the chronic stage (20.37 +/- 2.07 pg/ml) or that of the control subjects (19.64 +/- 1.71 pg/ml). However, it was unrelated to infarct size or patient severity. The increased methionine-enkephalin, which appears to originate from the sympatho-adrenal system or infarcted brain, may play a role in the evolution of cerebral ischaemia.

Aged↗

Evidence of the induction of de novo synthesis of delta-aminolaevulinate dehydratase by lead.

Inhibition of delta-aminolaevulinate (ALA) dehydratase (porphobilinogen synthase: EC 4.2.1.24) coupled with an increase in the enzyme concentration was observed in the liver of rats exposed to lead by mouth for 150 days. ALA dehydratase concentration increased by 25% in rats exposed to lead and cell free translation also showed an increase in de novo synthesis of ALA dehydratase by 20% in the liver of rats exposed to lead. The addition of lead in vitro to the cell free translation system had no effect on the de novo synthesis of ALA dehydratase. These results suggest that exposure to lead caused a transcription dependent induction of ALA dehydratase which might compensate for the enzyme inhibition by lead.

Animals↗