Biomedical subjects
Publications and source records attributed to T Takagi.
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An improved mouse metabolism cage, remodeled after the conventional makeshift type to permit accurate measurement of urine volume, avoiding or minimizing fecal contamination of urinary constituents and undue stress on the animal under test, is described. The structure of the cage is illustrated in detail in Figures 1 and 2. The principal points of modification include: 1) a semi-level top surface of the glass globe separator to accommodate the mouse in a less stressful posture of reduced instability; 2) a steeper gradient of the lateral spherical surface of the glass globe separator avoid contamination of urine by feces, drinking water leaks and debris of diet, along with a shortened urine collecting tail (27 mm) and a receptacle for water leaks; and 3) an insulator installed at the bottom to prevent escape of the animal. Performance tests of the cage demonstrated accurate measurements of urine output and water intake and assays of urinary constituents, with complete prevention against escape of mice.
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The inhibitory effect of a new H2-receptor antagonist YM-11170 on gastric acid response to histamine and food was compared with that of cimetidine in the conscious dog with a Heidenhain pouch. When given intravenously at a steady state of gastric secretion by continuous infusion of histamine. YM-11170 was 42 times more potent and 1.3 times longer-lasting (p less than 0.05) than cimetidine in reducing the total acid output. The higher potency of YM-11170 than that of cimetidine was also demonstrated in oral antisecretory tests with histamine. The oral ED50 relative to i.v. ED50 as an indirect indication of absorption rate of the drugs was 2.9 for YM-11170 and 2.7 for cimetidine. The secretory response to food stimulation was also antagonized by oral administration of YM-11170 with 40 times greater potency than that of cimetidine. The antisecretory effects of the drugs on the histamine-induced gastric secretion were characterized by a marked decrease in the secretory volume. No behavioral change was observed in association with the H2-blockers. These results indicate that YM-11170 is a very potent inhibitor of gastric acid secretion and also suggest that the absorption rate of YM-11170 from the gastro-intestinal tract is similar to that of cimetidine.
A new H2-blocker, 3-[[[2-[(diaminoethylene)amino]-4-thiazolyl]ethyl]thio]-N2-sulfamoyl propionamidine (YM 11170) inhibited gastric secretion of both acid and pepsin, when given intraduodenally to pylorus-ligated rats. The effectiveness of YM-11170 in the inhibition of acid output was 50 times as potent as that of cimetidine. The higher antisecretory activity of YM-11170 than that of 1-cyano-2-methyl-3-[2-[[(5-methylimidazol-4-yl)-methyl]thio]ethyl]guanidine (cimetidine) was also demonstrated by oral or i.v. administration. The development of gastric ulcer induced by either indometacin or acetylsalicylic acid in rats was markedly suppressed by YM-11170 with higher potency than by cimetidine. In castrated and androgenized rats, the decrease in the seminal vesicle and ventral prostate weights was not observed after treatment with YM-11170. These results suggest that YM-11170 is a potent antisecretory agent without antiandrogenic activity.
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Twenty-two patients with malignant lymphoma and its allied diseases, consisting of 6 with Hodgkin's disease, 10 with non-Hodgkin's's diffuse lymphoma, 4 with leukemic lymphosarcoma and 2 with immunoblastic lymphadenopathy, were entered into this study. The treatment schedule was intravenous drip infusion of the drug, at a dose of 2.3 to 5.4 mg/kg (150 mg to 300 mg/day), for consecutive 4 to 14 days. The total dose given ranged from 1050 to 2500 mg. Four of the 6 patients with Hodgkin's disease and 5 of the 10 patients with non-Hodgkin's diffuse lymphoma showed a good response. The response started from 3 to 7 days after beginning of BH-AC administration and remission induced by BH-AC persisted for 4 weeks. Clinical toxicities such as anorexia, nausea and vomiting were very mild, but hematological toxicities such as thrombocytopenia, leukopenia, and anemia were frequent especially in the patients who were totally given more than 2100 mg. This study suggested that malignant lymphoma responded definitely to single administration of BH-AC and that BH-AC might be a new useful drug for multi-combined chemotherapy of malignant lymphoma.
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For the purpose of studying immunogenetic factors related to disease susceptibility to cervical carcinoma (squamous cell carcinoma), HLA-A,B and DR typings were performed by the standard microlymphocytotoxicity test using about 240 typing antisera in 66 Japanese patients with cervical carcinoma and 206 healthy individuals. The results obtained were as follows: 1) The patients had a significant association with HLA-Bw46 (gene frequency = 6.3%, relative risk = 3.9, p less than 0.025), compared with the controls (g.f. = 1.7%). 2) The patients had a significant association with HLA-DRw8 (g.f. = 17.3%, r.r. = 2.3, p less than 0.05), compared with the controls (g.f. = 8.9%). 3) When the patients with cervical carcinoma were divided into two groups, i.e. 53 patients with invasive carcinoma of the cervix and 13 patients with carcinoma in situ of the cervix, the former had a more significant association with both HLA-Bw46 (g.f. = 6.8%, r.r. = 4.3) and HLA-DRW8 (g.f. = 19.2%, r.r. = 2.6) than the total patients, compared with the controls. However, the latter showed only a negligible association when compared with the controls. 4) The significant linkage disequilibrium between HLA-Bw46 and HLA-DRw8 was found in the patients with cervical carcinoma (haplotype frequency = 0.059, delta = 0.047, p less than 0.002), but not in the controls (h.f. = 0.0097, delta = 0.0075). 5) On the other hand, the significant linkage disequilibrium between HLA-A2 and HLA-Bw46 was found in both the patients and the controls.
Pseudomonas cepacia (Ps. cepacia), usually a non-pathogenic organism, has been described recently as a cause of human disease. The authors have recently observed 3 children with meningitis caused by Ps. cepacia. These cases were treated successfully with an oral administration of Sulfamethoxazole-Trimethoprim, after treatment with antibiotics had failed. Case 1 was a 7 month old male with a V-P shunt, who had suffered from hydrocephalus following intraventricular hemorrhage in the neonatal period.
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The present study is a retrospective clinicoradiological correlative investigation of subarachnoid hemorrhage associated with ruptured aneurysms. There were 360 patients in whom the source of subarachnoid hemorrhage was shown by angiography to be a ruptured aneurysm, and 302 of them underwent surgery. Arterial vasospasm was demonstrated in 113 of 360 patients (31%). When the time relationship between the subarachnoid hemorrhage and vasospasm was considered, vasospasms were revealed in 35 patients (31%) to ten days after a hemorrhage. In these cases with preoperative vasospasm, 17 patients were operated within 14 days and 43 patients later than two weeks. On the examination, their clinical state was graded according to Hunt and Hess. The surgical results were also grade in five groups (excellent, good, fair, poor and died) according to the functional results at discharge from the hospital. Of 35 patients of grade I and II at operation, 23 patients (66%) were of excellent or good results. However, of 14 patients of grade IV and V at operation, only on patient took good result. Of 12 patient in whom severe vasospasm was demonstrated and surgery was delayed more than two weeks, 8 patients (66%) had good result. Postoperative vasospasm was recognized in 2 patients, who took poor result. Surgery was carried out in 32 patients on the first or second day after subarachnoid hemorrhage, and 7 patients (22%) of them took good result. The overall mortality was 59% (19 patients). In ten patients, surgery was carried out on the third or fourth day after subarachnoid hemorrhage. Five patients had good result (50%) and four (40%) died. Considering the relationship between the timing and result of surgery, the mortality was 35% in patients operated on in the first week, whereas there were only 38 deaths among the 252 patients operated on after that interval. Among the death patients who were in grade IV or V at admission, intracranial hematoma was seen in 73%. It was concluded that in patients classified as grade I or II, the operation should be performed as soon as possible to prevent another rupture. In grade IV and V patients with severe damage by large hematoma, the mortality and morbidity were high even after evacuation of the hematoma. Patients with marked and diffuse vasospasm should be given conservative treatment at first and then operated on when the patients condition becomes good.
A totally thrombosed large arteriovenous malformation (AVM) which operated as an intracranial space occupying lesion was presented. The patient was a 24-year-old woman who had had frequent attacks of loss of consciousness since the age of 13 years and had been on anticonvulsant medication at the psychiatric department of our hospital. She was referred to our clinic with bitemporal girdle pain, nausea and vomiting. Neurological examination revealed right homonymous hemianopsia, sensory aphasia and choked discs in both ocular fundi. Computed tomogram demonstrated a well defined large high density area with mottled calcification in rostromedial part of the left occipital lobe. The midline structures were displaced to the right side with deformity of the lateral ventricles. Left carotid angiogram showed upward displacement of M2 portion of the left middle cerebral artery. Fine vessels were observed as a capillary blush at the distal part of the pericallosal artery. Teratoma or calcified glioma was suspected preoperatively. But surgery revealed that the large mass was a totally thrombosed AVM. Possible mechanisms for the spontaneous enlargement of the thrombosed AVM were discussed. Cases of totally thrombosed AVM causing displacement of the midline structures or deformity of the ventricles without massive hematoma or disturbance of cerebrospinal fluid circulation have not yet been reported.
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