[Removal of upper brain stem arterio-venous malformations].
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Biomedical subjects
Publications and source records attributed to N Hashimoto.
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gamma gamma-Enolase is considered a specific protein of neuron, which is called neuron specific enolase (NSE). Recent reports clarified that NSE exists not only in neurons but also in neuroendocrine cells, thrombocytes and lymphocytes. Besides normal neuronal tissues, high serum levels of NSE were noticed in the patients with neuroblastomas, small cell carcinomas of the lung, and malignant gliomas, etc. In order to clarify the usefulness of NSE as a marker for intracranial neoplasms or an indicator for prognosis of the patients with intra-cranial tumors, we studied serum, CSF and intratumoral fluid levels of NSE in 62 patients with intra-cranial tumors by radioimmunoassay. Serum level of NSE in healthy adults ranged from 4.1 to 8.9 ng/ml (5.6 +/- 1.38 ng/ml, n = 15) and that of CSF ranged from 4.9 to 7.3 ng/ml (means 6.1 ng/ml, n = 3). Serum samples from patients with malignant gliomas and primitive neuroectodermal tumors contained abnormally high level of NSE, of which mean value were 22.3 ng/ml and 16.1 ng/ml, respectively. However, serum samples from patients with low grade gliomas and other intracranial tumors arising from non-neuroectodermal tissues were within normal range. In 9 patients, not only serum levels but CSF levels and/or intratumoral cyst levels of NSE were examined at the same time. Except one meningioma case, CSF levels of NSE were higher (4.9-55.3 ng/ml, mean: 19.3 ng/ml) than that of serum levels (2.3-17.3 ng/ml, mean: 12.7 ng/ml). Mean NSE concentrations of intratumoral fluids in both malignant and benign tumors were 181.7 ng/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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In this study we show that a rapid colorimetric determination of alkaline phosphatase (APase) activity can be used in conjunction with a multiwell scanning photometer to quantitatively measure lymphokine-dependent B cell proliferation. Despite the fact that only activated but not resting B cells exhibit APase activity, i.e., that APase expression in B cells is variable, the results obtained by monitoring the enzyme activity were very similar to those obtained by measuring thymidine incorporation in two murine B cell systems. With regard to a potential application to the screening of the effects of hybridoma supernatants on B cells, it is relevant that HAT medium has practically no influence on the colorimetric B cell proliferation assay. Another advantage of the method is that since T cells and macrophages lack APase activity, one can detect the proliferation of B cells even in the presence of a high number of such cells, for example, in studying a T cell-dependent response.
In a recent report from our laboratory (J. Exp. Med. 1984. 160: 1070), it has been shown that B cells which have been activated with lipopolysaccharide (LPS) plus anti-Ig antibodies express interleukin 2 (IL2) receptors and proliferate in response to pure IL2. In the present study, we have investigated the role of IL2 during proliferative B cell responses supported by various T cell supernatants (SN) as well as by LPS itself. The following results were obtained: (a) B cells activated with LPS plus anti-Ig were found to proliferate in response to either recombinant IL2, T cell SN or fresh LPS; (b) a monoclonal anti-IL2 receptor antibody (PC61) could completely inhibit the effects of recombinant IL2 or various T cell SN (cloned T helper cell SN, EL4 SN, concanavalin A-spleen cell SN or mixed leukocyte culture SN), but did not interfere with the effect of LPS; (c) B cells activated with LPS or LPS plus anti-Ig were not found to secrete detectable amounts of IL2 by themselves. Thus, the data demonstrate that LPS-stimulated B cell proliferation requires neither B cell autocrine nor T cell-derived IL2. On the other hand, with regard to LPS plus anti-Ig-activated B cells, IL2 appeared to be the only growth-promoting activity that could be detected in the supernatants obtained from total normal spleen cell populations.
We have previously shown (J. Exp. Med. 1984. 160: 1170) that murine B cells activated with lipopolysaccharide (LPS) and rabbit anti-mouse Ig antibodies together (LPS-RaMIg blasts) express high-affinity interleukin 2 receptors (IL 2R) and respond to IL 2. This is not the case for B cells activated with either LPS alone (LPS blasts) or anti-Ig alone. In the present study IL 2R function and expression were further investigated by using this model. First, it was found that LPS-RaMIg blasts internalize IL 2 in a time- and temperature-dependent manner very similar to that occurring in CTLL (T lineage) cells. LPS blasts, however, did not internalize IL 2. LPS blasts were found to express 12 times less binding sites for anti-IL 2R monoclonal antibody (PC 61 monovalent Fab) as compared to LPS-RaMIg blasts and at least 30 times less IL 2 binding sites of high as well as of lower affinity. Second, with regard to the requirements for receptor expression, it was observed that either anti-Ig or phorbol diester (phorbol-12-myristate 13-acetate) can induce IL 2R and IL 2 responsiveness (proliferation assay) in LPS blasts but not in fresh B cells. Taken together these results provide further evidence for the similarity of IL 2R function in activated B and T cells, confirm that surface-Ig cross-linkage and phorbol-12-myristate 13-acetate have similar effects on B cells and suggest that LPS on the one hand, and phorbol-12-myristate 13-acetate or anti-Ig on the other provide complementary signals necessary for IL 2R expression.
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Seroepidemiological studies of hemorrhagic fever with renal syndrome (HFRS) virus infection were carried out among urban rats (Rattus norvegicus and Rattus rattus) and small field rodents in Hokkaido, Japan. An urban rat colony that was seropositive to SR-11 strain of HFRS virus (laboratory rat origin) was demonstrated in February 1983 at a dumping ground area of Kami-iso Town near Hakodate port. An HFRS-related virus, named KI-262 strain, was isolated from the lung tissue of a seropositive rat using Vero-E6 cell culture. Antigenicity of the isolate was closely related to Hantaan 76-118 and SR-11 strains by the indirect immunofluorescent antibody (IFA) test. No seropositive rat was found among the 861 rats captured in 38 other regions. It is unclear whether or not the infected rats in the positive area were introduced from abroad, though the area is located near Hakodate International Port. Furthermore, higher positive rates of urban rats in the Kami-iso area were observed in the spring and winter than in the summer and fall. Significantly high proportion of positive cases was observed among adult rats (six months or older) than among younger animals. The seasonal and age distribution of positive cases suggested that the virus was not readily transmitted from one infected rat to another. One seropositive case of a small field mouse (Clethrionomys rufocanus bedfordiae) was detected around the Kami-iso area.
A series of periodic increases in intracellular free calcium concentration ([Ca2+]i) occurred upon fertilization in golden hamster eggs. The spatial distribution of the Ca2+ transients was investigated in single zona-free, aequorin-injected eggs, inseminated by single sperm. A supersensitive TV camera system for recording Ca2+-aequorin luminescence enabled us to observe the spatial distribution of the Ca2+ rise. In the first response, which usually occurred 10-30 sec after the sperm attachment, the increase in [Ca2+]i began near the sperm attachment site, and the Ca2+ rise spread over the entire egg within 4-7 sec. The Ca2+ rise attained its peak in 5-8 sec, declined with almost even distribution, and ceased in 12-17 sec. The spreading Ca2+ rise was repeated in the second and sometimes the third response, starting from the same focus, but spreading more rapidly (approximately 2 sec). In succeeding responses [Ca2+]i increased synchronously in the whole cytoplasm within 1 sec. When additional sperm attached to the egg after the occurrence of the first response by the first sperm, the spread of the Ca2+ rise could take place from near the site of additional sperm attachment but only in the second or third response.
A long-term follow-up study of pituitary adenomas showed that 60 out of 83 patients with mild or moderate suprasellar extension, but only three out of 19 patients with huge or invasive adenomas, were alive at a mean post-operative period of 12.8 and 12 years, respectively. Cerebral ischemic attacks and complications of radiotherapy affected their fate and quality of survival. Patients in the post-computed tomography scan era had a good prognosis, and this may be due partly to the brevity of the postoperative period.
Two cases of ruptured aneurysms in the cerebral arteries in patients with established systemic lupus erythematosus are presented. A 32-year-old woman with a 3-year history of systemic lupus erythematosus was found to have a ruptured cerebral aneurysm at the top of the basilar artery. Another 38-year-old woman with a 4-year history of lupus erythematosus had a ruptured aneurysm in the anterior communicating artery. Both were treated surgically. Cerebral aneurysms associated with systemic lupus erythematosus are reviewed in the literature and the pathogenesis of these aneurysms is discussed.
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Five monoclonal antibodies were prepared against Chlamydia (C.) psittaci strain Pigeon-1041 isolated from a feral pigeon in Sapporo. Reactions of these antibodies to chlamydiae were examined using five strains of C. psittaci and two strains of C. trachomatis in an enzyme-linked immunosorbent assay, microimmunofluorescent test and complement fixation test. The antibodies were divided into two groups: three genus-specific (A2, D2, and I21) and two strain-specific (F2 and H9) antibodies. The antigenic determinant site of A2 was KIO4 sensitive, but those of D2, F2, and H9 were not affected greatly by KIO4 treatment. Nine C. psittaci strains from feral pigeons and 16 strains from budgerigars were classified into three groups and four groups, respectively, by reaction patterns against the monoclonal antibodies.
Percutaneous transluminal angioplasty was performed on 10 patients with unilateral renovascular hypertension (7 with atheromatous and 3 with fibromuscular stenoses) who were then followed for an average of 42 months (range, 24 to 67 months). Dilation of the stenosis was initially successful in all patients except one who had severe atheromatous stenosis. Among patients with atheromatous disease, normotension was attained for 40, 25 and 24 months in 3 patients given no antihypertensive medication and for 67 and 55 months in 2 patients given only nicardipine. The remaining one patient had a recurrent stenosis 3 months after angioplasty. All patients with fibromuscular dysplasia have been normotensive without any hypotensive medication for more than 4 years. Plasma renin activity declined within one week after angioplasty and remained unchanged thereafter in all patients except the one case suffering from a recurrent stenosis. Renal blood flow and glomerular filtration rate remained increased after angioplasty. These results suggest that hypertension can be controlled and renal dysfunction in patients with renal artery stenosis caused by atheroma or fibromuscular dysplasia improved for long periods by percutaneous transluminal angioplasty. The antihypertensive effect obtained by this procedure was more valuable for the patients with fibromuscular dysplasia than in those with atheromatous disease.
ACTH responses to corticotropin-releasing hormone (CRH) were studied in three patients with the ectopic ACTH syndrome caused by lung cancer. Plasma ACTH responded to synthetic CRH in two of three patients. Tumor tissues obtained from these two patients contained CRH and ACTH. In one patient, tumor ACTH secretion was stimulated by CRH in vitro. Tumor CRH was immunologically, chromatographically, and biologically similar to hypothalamic CRH. In addition, multiple forms of immunoreactive beta-endorphin were present in plasma and the tumor extracts. From these results, we conclude that some patients with the ectopic ACTH syndrome have tumors that produce both ACTH and CRH and that CRH can stimulate ACTH secretion by such tumors. Other patients with the ectopic ACTH syndrome do not have ACTH responses to CRH. Therefore, procedures other than CRH testing are needed to differentiate patients with Cushing's syndrome due to ectopic ACTH/CRH production from those with Cushing's disease, since the latter also usually have ACTH responses to CRH.
General pharmacological action of 4-(o-Benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride, MCI-2016) was examined with regard to the effects mainly on the central nervous system. MCI-2016, at 30-100 mg/kg, p.o., only showed a weak sleep prolongation effect (mice), anti-convulsant action (mice) and a moderate facilitation of exploratory behavior, but produced no remarkable behavioral changes. Above the doses of 200 to 300 mg/kg, p.o., MCI-2016 produced a decrease in muscle or body tone, mydriasis and a slight decrease of locomotor activity. The drug, however, showed little influence on exploratory behavior, conditioned avoidance response and normal body temperature (rats). Normal body temperature in rabbits was also little affected by MCI-2016. Effects on EEG was characterized by moderate activation of spontaneous EEG and potentiation of arousal response by stimulation of the midbrain reticular formation (1.5-5 mg/kg, i.v.). The drug, however, did not significantly change the sleep-wakefulness cycle and REM-sleep in rats. MCI-2016 also showed little influence on spinal reflex potentials and neuromuscular junction at high doses (10 mg/kg, i.v.). These results may indicate that MCI-2016 has slight influence on overall behavioral and motor changes. Effects of MCI-2016 on acetic acid-induced writhing, carrageenin edema and corneal reflex were also examined. MCI-2016 showed moderate analgesic and anti-inflammatory actions at 50-100 mg/kg, p.o., and also showed local anesthetic action. The duration of local anesthetic action was relatively long but the drug produced no local damage.
MCI-2016 at 3 mg/kg, i.v., caused slight changes in systemic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and ECG but at 10 mg/kg, i.v., it caused a significant increase in RR, decrease in SBP, increase or decrease in HR and a moderate change in ECG. Biphasic changes in SBP, HR and blood flow were sometimes observed after high doses. MCI-2016 also decreased SBP at 30 mg/kg, i.p., in SHR. MCI-2016 (50 mg/kg, p.o./day) showed little influence on SBP, HR and ECG in conscious beagle dogs. In isolated hearts, MCI-2016 decreased HR and contractility at the concentrations above 10(-5) g/ml, and 30 micrograms, i.a. MCI-2016 prolonged the AVCT at 10 mg/kg, i.v. MCI-2016 (i.v. or i.a.) moderately increased cerebral and femoral artery blood flows. MCI-2016 did not change CMRO2, but decreased MVO2. Coronary and renal artery flows were moderately increased by 10 mg/kg, i.v., of MCI-2016. Renal function was suppressed after 10 mg/kg, i.v., or 300 mg/kg, p.o., of MCI-2016. MCI-2016 potentiated the action of NE (increase in SBP, contractions of nictitating membrane and vas deferens), but showed little anti-cholinergic action. In contrast, MCI-2016 moderately increased gastrointestinal motility and salivatory response. As for the influence on isolated smooth muscles, MCI-2016 antagonized the contraction of blood vessels by high K+ at 10(-6) g/ml, or more, and it depressed the contractions by ACh, 5-HT, histamine and BaCl2 and also depressed spontaneous movements of uterus and ileum at 10(-5) M or more, in a nonspecific manner. MCI-2016 had no influence on liver damage and bile secretion, but inhibited stress ulcer and gastric acid secretion on the one hand, and caused gastric damage (125 mg/kg p.o., or more) on the other hand.
The general pharmacological action of TRQ was investigated, and the following results were obtained: With regard to its influence on the central nervous system, TRQ moderately potentiated the actions of hexobarbital (sleeping time) and methamphetamine (stereotyped behavior) at doses above 100 mg/kg, p.o. TRQ, however, had little influence on behavioral changes, EEG and motor function. TRQ only had slight influence on the respiratory and cardiovascular system at doses ranging from 0.1 to 3 mg/kg, i.v. Significant decrease in SBP and increases of HR, FAF and respiratory rate were observed after high doses (10-30 mg/kg, i.v.) of TRQ. TRQ also had little influence on contractility and pacemaker in isolated hearts, but moderately increased the coronary flow. The inhibitory effect of TRQ on the isolated smooth muscle was observed at high concentration and was non-specific. Furthermore, TRQ exhibited little influence on the autonomic nervous system. Among the effects of TRQ on the gastrointestinal system, it was shown that TRQ moderately increased the outflow of bile after doses above 1 mg/kg, i.v. TRQ also showed no remarkable actions on other aspects of the gastrointestinal system and blood coagulation system. Considering the present results, it may be suggested that there should be no serious problems in the application of TRQ as a hepatoprotective agent.