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Biomedical subjects

M Tobe

Publications and source records attributed to M Tobe.

At least 55 records · Page 3Linked to original sources

Segmental mediolytic arteritis. Clinicopathologic study and three-dimensional analysis.

We describe the first recorded case of segmental mediolytic arteritis (SMA) in Japan. A 71-year-old Japanese woman developed sudden abdominal pain and went into shock during hospitalization for treatment of valvular heart disease. Laparotomy revealed a ruptured pseudoaneurysm of the left gastric artery. Histological examination of the resected artery revealed multiple extensive areas of the dilated wall where the media had partially or totally disappeared with or without the intima. These features were typical of those described previously for SMA (1,2). Three-dimensional analysis of the arterial lesions revealed that the residual media formed branches and cavities down the long axis of the artery, indicating that the major cause of the medial disappearance was arterial dissection. Three months later, the patient died of sepsis. Autopsy revealed pseudoaneurysm formation at three different locations in the splenic artery. Histologically, these pseudoaneurysms showed destructive changes in the arterial wall similar to those described above, with organization and thrombosis, and were considered to be the end-stage lesion of SMA. This case is considered to be the fifth adult case of SMA in the literature and the first one showing chronic changes.

Aged↗

[A surgically treated case of acute pulmonary embolism owing to deep vein thrombosis of the leg mainly caused by uterine myoma].

A 49-year-old woman with deep vein thrombosis of the left leg suddenly complained of slight dyspnea during her hospitalization. Enhanced chest CT and pulmonary arterial DSA revealed pulmonary emboli, while phlebography of the left leg and lower abdominal CT showed a uterine myoma compressing the left external iliac vein, which was regarded as a chief cause of deep vein thrombosis of the left leg. The patient became dyspneic severely with a rapid increase of pulmonary arterial pressure and a decrease of arterial oxygen pressure. Therefore, pulmonary embolectomy and deep vein thrombectomy of the left leg and pelvis was performed using a cardiopulmonary bypass. Hysterectomy was also performed after weaning the bypass. The postoperative course was uneventful without recurrence of pulmonary embolism. This was a very rare case of pulmonary embolism, because, as far as we investigated, no literature has reported deep vein thrombosis of the leg caused by uterine myoma. We emphasize the availability of the enhanced CT for diagnosis of pulmonary embolism.

Acute Disease↗

Carcinogenic effects of bis(2,3-dibromopropyl)-phosphate in Wistar rats.

Four groups of 40 Wistar rats of each sex per dose level were fed diets containing 0, 80, 400 or 2000 ppm of the magnesium salt of bis(2,3-dibromopropyl)phosphate (Bis-BP) for 24 months. A high incidence of tumours was induced, in both sexes, in the digestive system. Tumours included papillomas and adenocarcinomas of the tongue, oesophagus and forestomach, adenocarcinomas of the intestine and hepatocellular adenomas (neoplastic nodules) and carcinomas. Pre-terminal mortalities were associated with an increased incidence of forestomach papillomas in both sexes, adenocarcinomas of the small intestine in male rats and increased incidence of hepatocellular carcinomas in females. The data suggest that Bis-BP is a more potent proximate carcinogen than tris-(2,3-dibromopropyl)phosphate (Tris-BP).

Animals↗

[A study on the usefulness of the OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)].

We studied the usefulness of the OECD combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox) using cyclophosphamide (CP), which is well known for its toxicological properties. CP was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague-Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body weight and food consumption were observed in males given 6.7 mg/kg and in all treated females. One, 3 and 12 females died during pregnancy in the groups given 3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group. Leukopenia and anemia were evident in treated males. The thymus and spleen weights were significantly decreased in treated rats. Histopathologically, atrophy of the thymus, spleen and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss and postnatal death of pups were found in treated dams. The body weight of pups from treated dams was significantly lowered. Thus, most of the known toxicological properties of CP regarding systemic toxicity and reproductive/developmental toxicity were clearly demonstrated in this study. Therefore ReproTox can be considered a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume, although teratogenic potential and adverse effects on spermatogenesis and fertility were not detected under the present experimental conditions.

Administration, Oral↗

[Combined chronic toxicity/carcinogenicity test of tris(2-chloroethyl)phosphate (TCEP) applied to female mouse skin].

Tris(2-chloroethyl)phosphate (TCEP), a widely used flame retardant, was tested for its skin chronic toxicity/carcinogenicity using female Slc: ddY mice. TCEP (5 and 50%) dissolved in ethanol was applied to the shaved skin twice a week for 79 weeks. The control group received ethanol under similar condition. In addition, 5 animals in each group were killed at 6 and 12 months and used for the chronic toxicity study. In body weight, food consumption and survival rate, there was no significant difference between the control and treated groups. Spleen weight was decreased in the 50% group. No significant difference in the incidence of tumors and other non-neoplastic lesions of the skin and other organs was found between the control and treated groups. The results indicate that under the conditions of the present study, TCEP has no carcinogenicity and toxicity for the skin.

Administration, Topical↗

[Acute and subacute toxicity studies of Bis(2,3-dibromopropyl) phosphate magnesium in rat].

Acute and subacute oral toxicity tests of Bis(2,3-dibromopropyl) phosphate magnesium (Bis-BP.Mg) were carried out in Wistar rats. In the acute toxicity test, Bis-BP.Mg suspended in arabic gum was administered orally to a group consisting of 10 male and 10 female rats, and they were observed for 14 days. LD50 values of male and female rats were 283 (253 approximately 314) mg/kg and 261 (219 approximately 310) mg/kg, respectively. As toxic symptoms, eyelid closure, crouching, shivering and staggering gait were observed in the treated groups of both sexes. In gross findings, hypertrophy, discoloration and necrotic change of the liver, and hypertrophy and discoloration of the kidney were observed in the treated groups. In histopathological examination, necrosis, desquamation, large nuclei formation of the tubular epithelium, and tubular dilatation of the kidney and necrosis of the liver cells were observed in the treated groups. In the subacute toxicity test, groups of rats consisting of 5 males and 5 females were fed a commercial diet containing 0, 30, 100, 300 and 1000 ppm Bis-BP.Mg for 45 days. In body weight and food consumption, there were no significant difference between the control and treated groups. Significant increases were observed in the liver and kidney weights of male rats fed 1000 ppm Bis-BP.Mg. Histopathologically, desquamation, swelling, and large nuclei formation of the tubular epithelium and tubular dilatation of the kidney were observed, but they were much less frequent than those in the acute toxicity test. It was concluded that Bis-BP.Mg has apparent renal toxicity.

Administration, Oral↗

A simple method for screening assessment of acute toxicity of chemicals.

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD50 values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD50 values reported in the literature. Our toxicological data also showed that LD50 values were about 2-2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD50 of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD50 values of chemicals and for screening for necessity for classical full LD50 test using many animals.

Ammonium Sulfate↗

[Tricuspid annuloplasty and right ventricular function in mitral valve disease].

From 1985 to 1987, we examined relationship between the lesion of tricuspid valve and right ventricular function in 31 patients (male: 9, female: 22) with mitral valve disease. The median age at operation was 52 years (range 37-69 years). Group I consisted of 17 patients (MS: 10, MSR: 5, MR: 2) accompanied with tricuspid regurgitation (TR) and Group II 14 patients (MS: 12, MSR: 2) without TR. In all cases of Group I tricuspid annuloplasty (TAP) were performed correctly. De Vega methods were done in 12 cases and Carpentier rings were used in 5 cases. Cardiac catheterization was done before and after operation. And right ventricular volume was measured by right ventricular angiography. In both groups pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac index were improved postoperatively. Pulmonary artery resistance (PAR) and total pulmonary resistance (TPR) in Group I were significantly higher before operation but there were no difference between two groups postoperatively. Right ventricular end-diastolic volume index (RVEDVI) and right ventricular end-systolic volume index (RVESVI) in Group I were significantly improved postoperatively, but in Group II these were within normal range both pre- and postoperatively. Preoperative PAR was correlated inversely with postoperative right ventricular ejection fraction (RVEF). It means that patients with severe pulmonary vascular lesion had postoperative lower right ventricular function. In both groups, RVESVI was in inverse correlation with RVEF pre- and postoperatively. In both groups, there was an inverse correlation between the per cent change of RVESVI and that of RVEF. This means that RVESVI influenced right ventricular pump function.

Adult↗

[Evaluation of the thromboexclusion technique for thoracic aortic aneurysms].

From 1981 to 1987 most of DeBakey III type dissecting aneurysms and a part of descending aortic aneurysms were treated by thromboexclusion technique. The effects of the operation by thromboexclusion technique on the patients were compared with those of the operation by temporary bypass technique. Blood loss during an operation was smaller and blood pressure during an operation was more stable in the thromboexclusion technique group, although the difference was not statistically significant. Furthermore, no paraplegia was observed in the thromboexclusion technique group. The respiratory support period was longer and the number of patients with postoperative myocardial injury was greater in the thromboexclusion technique group, although the difference was not statistically significant. Ten patients treated by thromboexclusion techniques were examined by computed tomography. In 7 out of 10 patients (70%), thrombosis occurred in the false lumen of dissecting aneurysm or in the aneurysmal lumen of descending aortic aneurysm. When only the patients without the leakage of blood into the aneurysm through the permanent aortic clamp were examined, thrombosis was observed in 100% of them. Even though the blood flow was reversed, thromboexclusion technique did not have a bad effect on renal function in the long-term. Postoperatively, however, progressive hypertrophy of the left ventricle was recognized, and furthermore, an injury to the aortic wall caused by permanent aortic clamp was observed at an autopsy. This suggests that further long-term follow-up of patients treated by thromboexclusion technique is necessary.

Aged↗

Chronic toxicity study on formaldehyde administered orally to rats.

Groups of 20 male and 20 female Wistar rats were given formaldehyde solution in their drinking water at concentrations of 0.50, 0.10, 0.02 and 0% for 24 months. Significant decreases in body weight and food and water intake were observed in the 0.50% group of both sexes and all rats in this group died by 24 months. Various non-neoplastic lesions were observed in rats, mostly in the 0.50% group. In this group, erosions and/or ulcers were evident in both the forestomach and glandular stomach. In the forestomach, squamous cell hyperplasia with or without hyperkeratosis and downward growth of basal cells were observed. Glandular hyperplasia of the fundic mucosa was noted along the limiting ridge. A few of such changes of the upper GI tract were seen in the 0.10% group. No toxicological abnormalities were found in 0.02% group of both sexes. There were no significant differences in the incidences of any tumors among groups of both sexes. Based on these findings, the no observable effect level of formaldehyde was 0.02% in the drinking water (10 mg/kg body wt./day).

Administration, Oral↗

[Combined long-term toxicity/carcinogenicity test of alpha-bromocinnamic aldehyde (BCA) applied to female mouse skin].

Bromocinnamic aldehyde (BCA), an antibacterial/antifungal agent, was tested for its chronic toxicity/carcinogenicity in female Slc:ddY mice. The animals received 0.25%, 1.0% and 4.0% of BCA dissolved in olive oil applied to the shaved back skin area twice a week for 79 weeks. The control group received olive oil alone under similar conditions. In addition to these animals, 5 animals in each group were killed at 6 and 12 months for investigation of the time-related toxic effect of BCA. A slight inhibition of body weight increase and a slight decrease in the survival rate were seen in the 4.0% BCA-treated group. No significant changes were observed in hematological parameters at 6, 12 and 18 months. In chemical biochemistry determination in the blood at 6 and 12 months, a significant decrease in non-esterified fatty acid and phospholipid values was observed in the experimental groups. Histopathologically, necrosis, scabbing, cell infiltration and thickening of the epidermis were noted at the site of application in the 4.0% BCA group. Moreover, extramedullary hematopoiesis and amyloid degeneration were detected in the spleen, while the incidence of adenomas in the lung decreased with a dose-response. These changes seemed to be the result of a non-specific inflammatory reaction to the irritation effects of the agent on the skin. No significant differences in the incidence of tumors were found between the control and experimental groups, not only at the site of application but also in other organs, although lung adenomas decreased dose-dependently in all treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes↗

[Acute and subacute toxicity studies of tris (1,3-dichloro-2-propyl) phosphate on mice].

Slc/ddY mice (10 male, 10 female per group) were given a single p.o. intubation of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) in olive oil and were observed for 14 days. LD50 values of male and female mice were 2.67 (2.52 approximately 2.83) and 2.25 2.25 (2.12 approximately 2.39) g/kg, respectively. The animals revealed ataxic gait, hyperactivity, and convulsion. Slc/ddY mice (12 male, 12 female er group) were administered diet containing 1.33, 0.42, 0.13, 0.04, and 0.01% of TDCPP for 3 months. Male and female mice of the 1.33% group showed emaciation, rough hair, and tremor; and all animals died within one month. Hematological studies showed slight anemia in males of the 0.42% group and females of the 0.42% and 0.13% groups. They also exhibited a tendency to increase ALP and GPT levels. The animals of the 0.42%, 0.13% and 0.04% groups exhibited tendency to increase liver weights and kidney weights in both sexes. Histopathologically, very slight focal necrosis was recognized in the liver in only 2 females of the 0.42% group. The NOEL under this condition is 0.01% in the diet of tris (1,3-dichloro-2-propyl) phosphate (male: 13.2 mg/kg/day, female: 15.3 mg/kg/day).

Administration, Oral↗

[Toxicity of 2-mercaptobenzothiazole in mice].

2-mercaptobenzothiazole (MBT) has been used mainly as a vulcanization accelerator in rubber manufacture and an intermediate in the production of other accelerators. Acute and chronic toxicity studies were performed to evaluate its potential to induce toxicological effect using Slc:ddY mice. The oral LD50 values of MBT (mg/kg) were as follows: (1) suspension in 5% gum arabic solution: 1558 for males and 1490 for females. (2) suspension in olive oil: 3148 for males. Convulsion was the major change in general conditions observed. The acute toxicity of MBT in males was stronger when suspended in 5% gum arabic solution than that when suspended in olive oil. A 20-month chronic toxicity study of MBT on mice was carried out with dose levels of 30, 120, 480 and 1920 ppm in the diet. Inhibition of body weight gain was observed in the 1920 ppm group of the males from the initial stage of treatment. Histopathologically, cell infiltration in the interstitium of kidney in the 1920 and 480 ppm groups of the males were found at 20th month. It was concluded that no observable effect level of MBT was 120 ppm (14.6 mg/kg/day for males and 13.52 mg/kg/day for females).

Administration, Oral↗

Comparison of the toxicity of p-dichlorobenzene (p-DCB) administered to male F344 rats orally or by the inhalation route.

The organ distribution and toxicity of p-DCB were compared in rats after either inhalation or oral administration. Male F344 rats were exposed to 500 or 125 ppm for 24 hr in a whole body inhalation chamber (H and L groups) or received a single dose of 300 mg/kg by gavage (PO group). The concentrations of p-DCB in the serum, liver, kidney and fatty tissues were measured by gas chromatography at intervals during and up to 24 hr after the treatment. Peak serum values for the L and H groups were lower than in the PO animals, but the organ/serum distribution ratios of p-DCB tended to be higher, in some cases markedly, in rats receiving the inhalation treatment. Significant increases in the levels of blood urea nitrogen, hepatic glutamic oxaloacetic transaminase and glutamic pyruvate transaminase and significant decreases in the levels of serum total cholesterol were observed only in the inhalation groups. Microscopically, the appearance of numerous eosinophilic droplets, together with swelling and desquamation of the proximal tubular epithelium of the kidney was especially noteworthy in H and L p-DCB treated groups. Thus, both biochemical and histopathological abnormalities induced by p-DCB were more pronounced in rats administered the compound by the inhalation route.

Administration, Inhalation↗

Acute toxicity tests on 113 environmental chemicals.

Acute toxicity tests on 113 environmental chemicals were conducted by the order of the Japanese government agencies. the LD50s or LC50s for 23 household chemicals, 11 medical drugs, 10 drug additives, 20 food additives, 13 industrial chemicals, 14 environmental pollutants, 12 agricultural chemicals and 5 organic solvents are presented together with the major toxic signs and symptoms and macroscopic changes in tissues. These toxicity data will be useful as an information source for regulatory purposes and also for prediction of the potential for acute toxicity of a wide variety of new chemicals.

Animals↗

[A case of ruptured aneurysm of the sinus of Valsalva with bacterial endocarditis].

A 21-year-old male with ruptured aneurysm of sinus of Valsalva caused by bacterial endocarditis is presented. The patient complained of palpitation and a attack of fever. Continuous murmur was heard with a thrill at the third intercostal space of the left sternal border. On plain chest x-ray film pulmonary congestion and increase in pulmonary flow were observed. Cardiac catheterization showed step up of oxygen contents at the level of right ventricle and left to right shunt of 36.5%. Aortography demonstrated the aneurysm of the sinus of Valsalva ruptured to right ventricle. The operation was performed by right ventricular approach. Aneurysmal sac was resected and its orifice was closed with mattress sutures. Bacteriological examination at the time of operation revealed Staphylococcus aureus. Postoperative course was uneventful.

Adult↗

Tris (2,3-dibromopropyl) phosphate nephrotoxicity in the rat: histological and biochemical changes in renal components by 13C-NMR spectra.

Rats receiving a single oral dose of 286.8 mumol/kg tris(2,3-dibromopropyl)phosphate (Tris-BP) showed pyknosis of the renal tubular epithelial cells on Day 1, necrosis on Day 2, regeneration from Day 3 and large nuclei formation from Day 4. 13C-NMR spectra were applied to clarify changes of the renal low-molecular-weight components in the kidney injured by Tris-BP, and sialic acid and inositol were found as the desired marker components. The lesions produced by Tris-BP were characterized by changes in the renal components and enzyme activities. Increases in sialic acid content of the kidney were observed both on Day 1, suggesting destruction of the epithelial cell membrane, and on Day 5, suggesting regeneration accompanied by an increase of inositol content on Days 7 and 10. Renal activity of cytoplasmic enzyme, alanine aminopeptidase, was decreased on Days 1 and 5 and elevated on Days 7 and 10. Lactate dehydrogenase activity showed a tendency to decrease in the kidneys on Day 1 and to increase significantly on Days 2, 5, 6 and 7.

Animals↗