Biomedical subjects
Publications and source records attributed to N Takeda.
As part of our search for active agents against systemic fungal infections, a new series of triazole compounds with a thiolane ring was synthesized. Their antifungal activities were investigated in vitro and in vivo. Some of these thiolanetriazoles showed promising activity, comparable to that of ketoconazole, against a mouse systemic Candida albicans infection, after oral or parenteral dosing.
Triazole compounds with an oxazolidine ring were designed and synthesized as a potential inhibitor of the fungal cytochrome P450 14 alpha-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (4R,5R)-3-acyl-4-methyloxazolidine derivatives 4 exhibited remarkably high efficacy after oral or parenteral dosing. The potent activity of 4 is hypothesized to be a consequence of a structural similarity between 4 and lanosterol, a target molecule of the cytochrome P450 14 alpha-demethylase. Highly stereoselective synthesis of these oxazolidines is also described.
Alterations of myocardial contractility and energetics were examined in cardiac hypertrophy induced by different types of cardiac overload. Myocardial contractility was estimated by isometric contraction of isolated left ventricular papillary muscles. Myocardial energetics were assessed from ventricular myosin isoenzyme patterns obtained by pyrophosphate gel electrophoresis. Cardiac hypertrophy was induced by endurance swim-training and sustained pressure-overload by abdominal aortic constriction or volume-overload created by an arteriovenous shunt. In swim-trained hypertrophied myocardium, isometric developed tension (T) and dT/dtmax showed a tendency to increase and response of dT/dtmax to isoproterenol increased significantly as compared with sedentary rats. Training shifted the left ventricular myosin isoenzyme pattern toward VM-1, which has the highest ATPase activity. In pressure- or volume-overloaded myocardium, dT/dtmax decreased significantly and mechanical response to isoproterenol also decreased (or tended to decrease in volume-overloaded hearts) as compared with the respective sham-operated controls. In pressure- or volume-overloaded hearts, left ventricular myosin isoenzyme pattern shifted toward VM-3, which has the lowest ATPase activity. These results indicate that alterations in myocardial contractility, mechanical catecholamine responsiveness and myocardial energetics in hypertrophied myocardium do not always display the same trend, but are greatly influenced by the causes or duration of cardiac overload.
Variations in the patterns of origin of the inferior alveolar, the posterior deep temporal and the masseteric arteries when the maxillary artery passed medial to the pterygoideus lateralis muscle on 30 sides of 24 heads (10.8%) among a total of 278 sides of 139 heads of the Japanese, were investigated. The results obtained may be summarized as follows: 1. The maxillary artery gave off a common trunk between the inferior alveolar and the posterior deep temporal (76.7%), the latter distal to the former (16.7%) and in contact with their origins (6.7%). The masseteric artery always arose from the posterior deep temporal in 24 heads. 2. The above-mentioned common trunk was observed in 52.1% of males and 47.9% of females, as well as on 56.5% of left sides and 43.5% of right sides. 3. It can be said that the maxillary artery always passed medial to the pterygoideus lateralis, when the inferior alveolar arose in common with the posterior deep temporal.
A case of metastatic carcinoid tumor in the right occipital lobe originating from a primary tumor in the right colon is reported in a 68-year-old man. The tumor had a high bromodeoxyuridine labeling index. Although immunohistochemical studies of the tumor specimen showed positive reactivity for serotonin and somatostatin, blood levels of serotonin and urinary 5-hydroxyindoleacetic acid content were normal. This suggests that coexistence of somatostatin with serotonin in the tumor tissue might lead to inhibition of serotonin release by "autocrine regulation." The neurological complications of carcinoid tumors, including intracranial metastasis, are discussed briefly.
To the best of our knowledge little if any information is available concerning human laryngeal mucosal blood volume presumably because the larynx is an anatomical position which renders the measurement of blood flow there difficult. With the advent of a reflectance spectrophotometer, however, studies of tissue blood flow have been facilitated to a great extent. As a result, attempts have been made to determine mucosal blood volume in various organs and tissues including the gastric mucosa. Recently, an ultra-thin fiber probe (1.8 m min diameter) for measurement of tissue blood volume has been developed. Using a laryngeal flexible fiberscope attached with this newly developed probe in the opening for the forceps, an attempt was made to measure laryngeal mucosal blood volume by the method of reflectance spectrophotometry, determining IHb and ISO2 the former of which is a parameter of hemoglobin in the tissue blood vessels and the latter, a parameter of hemoglobin oxygen saturation in the tissue blood vessels. IHb of the vocal folds is significantly low, about half those of the false folds and arytenoid region, whereas ISO2 is significantly higher in the false folds and arytenoid region than in the vocal folds. The hemodynamics in the vocal folds as a high-speed vibrator are specific, unlike in other laryngeal regions. We have plans to determine laryngeal tissue blood volume at more sites so as to investigate the laryngeal tissue distribution of blood volume in greater detail. Furthermore, tissue blood volume in morbid conditions will also be determined for information which will be of value in clinical applications.
The neutralizing antibody of 160 serum specimens collected in 1978 from healthy residents in five prefectures in Japan was titrated against both the virulent standard strains and the Sabin vaccine strains of three types of poliovirus. Antibody-positive rates with both strains of respective types at a level of 1:4 were comparable in all three types of poliovirus. However, the geometric mean titers (GMTs) obtained against both strains showed statistically significant difference depending on the age-cohort's previous history of exposure to the wild or the vaccine strains of polioviruses: the younger age cohorts showed higher GMTs to the Sabin strains, while adults responded higher to the virulent standard strains. The difference was most pronounced in type 1.
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A 32-year-old female was admitted to our hospital because of abdominal fullness, jaundice and pretibial edema in November, 1987. Leukocyte count of peripheral blood showed 13300/microliters with 84% leukemic cells and bone marrow was normocellular with 63.6% leukemic cells. Leukemic cells had azurophilic large granules with basophilic cytoplasm and positive for CD 2, OKIa 1, NKH-1 and negative for CD 3, CD 4, CD 8, CD 16. T cell receptor (TCR) genes for beta, gamma and delta chain and immunoglobulin heavy chain gene were in germ line configuration. These cells also had natural killer (NK) activity and antibody dependent cell mediated cytotoxicity (ADCC) activity. These observations suggested that they were derived from NK cell lineage. It is often difficult to demonstrate their clonalities in lymphoproliferative disorder of granular lymphocytes (LDGL). In the present case, the analysis of EBV genome using termini probe demonstrated polyclonal bands, while we found constant chromosome abnormalities; 47 XX, +3. From these observations, this case was considered to have several clones, and one of which could be detected by chromosome analysis. The analysis of EBV genome using termini probe may be useful to demonstrate their clonalities in LDGL in addition to conventional chromosome analysis.
Reported are five patients who developed a carcinoma of the reconstructed gastric tube. In 3 of the 5 patients, the esophageal cancer was preceded by a gastric cancer, and the intervals before the gastric cancer was detected were 34, 24, and 60 months. The gastric tube the had been reconstructed by the retrosternal rout was resected with a median sternotomy in cases 1 and 2. In case 3, since a liver and lung metastasis had been detected by routine examination, surgery was not performed. Cases 4 and 5 had an esophageal cancer associated with a simultaneous early gastric cancer located in the lesser curvature of the upper body. Thus, a esophagectomy and a partial gastrectomy were performed. Twenty-eight and 21 months later, respectively, an early gastric cancer was found at the stump of the gastric tube that had been reconstructed by the retrosternal route. Endoscopic laser therapy was subsequently employed for both patients. Because of these findings, the author have concluded that postoperative serial examination of the gastric tube are very important, since cases of a gastric tube cancer are increasing.
The fact that amphetamine, a noradrenaline releaser, prevents motion sickness leads the hypothesis of Wood and Graybiel that the noradrenergic neuron system in the brain stem acts against the development of motion sickness. To evaluate the hypothesis, the effects of rotational stress on the turnovers of noradrenaline and dopamine in the rat brain stem were examined. Rats were rotated about two axes simultaneously (double rotational) or about one axis (single rotation) for 60 min. Measurement of kaolin intake (pica) induced by rotation, as an index of motion sickness, showed that double rotation produced motion sickness, whereas single rotation did not. Both single and double rotation significantly increased the turnovers of noradrenaline and dopamine in the brain stem. However, there were no significant differences between the increases in catecholamine turnover induced by double and single rotations. Moreover, pretreatment of rats with methamphetamine (5 mg/kg) just before double rotation, which prevented the induction of motion sickness by double rotation, did not affect increases of the catecholamine turnover in the brain stem by double rotation. These findings do not support the hypothesis of Wood and Graybiel, suggesting that the catecholaminergic neuron systems in the brain stem are not involved in motion sickness and that the therapeutic effect of methamphetamine is not due to its direct effect on the brain stem.
Osteosarcoma is the one of the tumors that's prognosis have been improved dramatically by the introduction of chemotherapy consisting mainly of adriamycin, high-dose methotrexate with Leucovorin rescue and cisplatinum. Now, the purpose of the treatment for osteosarcoma are assurance of their life and functional and beautiful limb-sparing. Recently, preoperative chemotherapy for limb saving is given to patients with osteosarcoma of the extremities. The five year survival rate increased to 65% and limb sparing rate became above 50%. It is generally accepted that pre- and post-operative chemotherapy can inhibit pulmonary micro metastasis and prove to be of great significance in improving the survival rate of patients with osteosarcoma of extremities and achieve limb salvage operation.
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A 62-year-old man was admitted to our hospital in Oct. 1986, because of easy fatigability, generalized pigmentation and lymph node swelling. Radiological examination showed massive adrenal tumor and two lung tumors. Endocrinological findings showed cortisol 8.3 micrograms/dl, aldosterone 35.3 ng/dl, ACTH 348 pg/ml, and non reacting pattern was observed in ACTH-overloading test, suggesting a presence of Addison's disease. A diagnosis of malignant lymphoma (Non-Hodgkin's lymphoma, diffuse large cell type) was made by lymph node biopsy, and radiotherapy to bulky bilateral adrenal tumors and cervical lymph nodes was performed with some response. Then, treatment with VEPA and PEP-VP regimens were carried out, and adrenal tumor became remarkably small in size. However, adrenal function did not recover. He relapsed in Jan. 1987 and died of multiple organ failure.
The localization, origin and fine structure of nerve terminals immunoreactive for calcitonin gene-related peptide (CGRP) were examined in the vestibular end-organs of rats using immunocytochemistry. Many CGRP-like immunoreactive (CGRP-IR) fibers were observed in the vestibular sensory epithelial layer. By electronmicroscopy, CGRP-IR terminals were found to make synaptic contacts with the chalyces of the vestibular nerves terminating on type I cells. The origin of these vestibular CGRP-IR fibers was examined by a combination of a retrograde fiber tracing technique (using Fast blue) and immunocytochemistry. Injections of the tracer into the vestibular cistern, resulted in fast blue-labeled neurons bilaterally in the area dorsolateral to the genu of the facial nerve; these labeled neurons also contained CGRP. These findings indicate that CGRP-IR fibers originate bilaterally from the area dorsolateral to the genu of the facial nerve and that CGRP plays a modulatory role in the transmission of vestibular information from type I cells.
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In 107 patients with non-insulin dependent diabetes(NIDDM), plasma growth hormone(GH) responses during standard arginine test (0.5 g/kg of body weight) were studied and analyzed in comparison with those in 17 normal subjects. The indices of the responsiveness of GH, peak value of GH, sum of GH values(sigma GH), area of GH curve(integral of GH), sum of GH values above fasting level(sigma delta GH) and area of GH curve above fasting level(integral of delta GH) during the test (2 hr) were calculated. Data were also analyzed with multiple regression analysis using stepwise method for variable selection. Basal level of GH was significantly higher in diabetic patients than in normal subjects (2.1 +/- 1.7 vs. 1.6 +/- 0.5 ng/ml, mean +/- SD, p less than 0.05), and sigma GH and integral of GH were also higher in diabetic patients. There was a significantly positive correlation between fasting plasma glucose(FPG) and basal level of GH (r = 0.24, n = 107, p less than 0.05), and the indices of GH responses except delta GH and GH peak value (r = 0.24 to 0.31, p less than 0.05 to 0.01). Some indices of GH responses (sigma delta GH, sigma GH, integral of delta GH and integral of GH) were significantly higher in the poor control group (patients with FPG above 180 mg/dl, n = 29) of diabetic patients than in the good control group (patients with FPG below 140 mg/dl, n = 59), or in the group with no abnormal findings of retinopathy (n = 46). During the follow-up of retinopathy for 2.5 years on the average, progression of retinopathy was found in 21 out of 107 patients. Significantly higher GH, and GH in the patients with increasing severity of retinopathy were revealed retrospectively compared to the patients without it. However, there were no significant differences in these parameters between both groups matched by FPG or severity of retinopathy. Multiple regression analysis to the basal GH level and GH responses during arginine infusion as criterion variables of various predictor variables (total 44 factors: biochemical laboratory data, indices of glucose and insulin response to oral glucose load, indices of glucose response to arginine, age, age of the onset, obese index, duration of retinopathy, neuropathy, and therapy) were performed in 86 patients using forward and backward method for variable selection. Basal plasma level of GH showed close positive association with therapy and proteinuria and negative association with age and obesity. Five of 6 indices of GH responsiveness showed significant relationship with retinopathy.(ABSTRACT TRUNCATED AT 400 WORDS)