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Biomedical subjects

R Watanabe

Publications and source records attributed to R Watanabe.

At least 307 records · Page 17Linked to original sources

Neurovirulence of murine coronavirus JHM temperature-sensitive mutants in rats.

The murine coronavirus strain JHM is highly neurotropic in rats and has a marked tendency to cause demyelinating central nervous system diseases after intracerebral inoculation. The clinical diseases observed range from an acute encephalomyelitis occurring within 2 weeks postinfection to a subacute demyelinating encephalomyelitis developing several weeks or months postinfection. Uncloned wild-type virus induced both acute and subacute diseases, whereas cloned JHM virus grown in tissue culture caused only acute disease without the pronounced lesions of primary demyelination. In contrast, temperature-sensitive mutants selected from that clone were capable of inducing subacute demyelinating encephalomyelitis after prolonged incubation times. Viruses recovered from diseased animals were still temperature sensitive. Inoculation of temperature-sensitive mutants into suckling rats (age, 10 to 15 days) produced high rates of subacute demyelinating diseases running a more chronic course; these diseases often were not fatal. Those rats which did not show clinical signs frequently revealed inflammatory demyelinating lesions. These findings indicate that the rate and type of clinical disease are dependent on the neurovirulence of the virus mutant used for inoculation and the age of the animals at the time of infection.

Aging↗

Promotion of hepatocarcinogenesis in vivo and in vitro.

Various chemicals including phenobarbital (PB) have been shown to act as promoters in hepatocarcinogenesis in rodents. The effect of initiation and/or promotion of chemicals can be quantitatively measured by scoring the number and size of enzyme-altered islands (EAI). The effect of promotion is proportional to the period of treatment and is much greater when the promoter is given earlier after initiation. A unique aspect of hepatic promoters is their inhibitory action against carcinogenesis when given simultaneously with a carcinogen, reducing both the initiating and promoting activities of the carcinogen. With the aid of the promoting action of PB, carcinogenic activity of pure initiators is demonstrated. Promoting effect of PB was found at as low a dose as 5 ppm, which corresponds to 20 mg per 50 kg person per day, a dose several times less than the common therapeutic dose. In an attempt to analyze the mechanism of promotion and also to develop a model system for detecting environmental promoters in vitro, hepatic cells obtained from animals during carcinogenic treatment were transferred to a culture system. Cells comprising EAI after a certain critical stage gave rise to proliferative epithelial cell foci. Some hepatic promoters showed a growth enhancing effect on these foci while others did not, suggesting both the existence of direct action by some promoters on initiated cells and the presence of different promoter mechanisms. Chronic treatment with PB selectively induced gamma-glutamyl transpeptidase activity in "spontaneous" hepatomas of C3H mice, suggesting that PB may enhance the expression of altered gene functions of initiated cells.

Animals↗

The effect of pyrrolnitrin on mitochondrial reactions: the induction of swelling.

An antifungal antibiotic, pyrrolnitrin, was found to show very similar biological activities to those of imidazole antimycotics on isolated mitochondria. Pyrrolnitrin caused drastic swelling of mitochondria in isotonic solutions of alkali metal salts and of sucrose without any addition of substrate for the respiratory chain in mitochondria. The swelling induced by pyrrolnitrin was characterized by a biphasic swelling process; a very fast initial swelling and thereafter a very slow speed secondary swelling. The increase of pyrrolnitrin concentration exponentially increased the magnitude of over-all rapid swelling. Pyrrolnitrin enhance the latent ATPase activity of mitochondria at the similar range of concentrations to those needed for the induction of the swelling. The concentrations of pyrrolnitrin where mitochondrial swelling was induced were found to be far lower than those needed for the exhibition of inhibitory effect on the electron transport system of mitochondria.

Adenosine Triphosphatases↗

Chlorination-induced enhancement of biological activities in imidazole antimycotics. A possible explanation to the molecular mechanism for their antimycotic activities.

The effect of imidazole antimycotics (clotrimazole, econazole, and miconazole) on mitochondrial functions were compared by the experiment with isolated rat liver mitochondria and it was found that their potencies in the uncoupling effect on oxidative phosphorylation, in the stimulation of latent ATPase activity, and in the induction of swelling in mitochondria were enhanced by the increased chlorination of the molecule, i.e. miconazole greater than econazole greater than clotrimazole.

Animals↗

Regional distribution of cholinergic neurons in human spinal cord transections in the patients with and without motor neuron disease.

Regional distribution of enzymic activities in acetylcholine (ACh) metabolism was examined on thinly-sectioned transverse slices of human spinal cords obtained during autopsy of 5 motor neuron disease (MND) and 5 control patients without MND. Choline acetyltransferase (ChAT) activity was highly concentrated in the ventral horn regions (gray and white matters) of cervical, thoracic and lumbar spinal cord of non-MND patients. This enzyme activity was found to be remarkably low in the ventral gray and white matter of MND patients compared with that of the controls. Although the distribution of acetylcholinesterase (AChE) activity was found to be high in both ventral and dorsal gray matter of the spinal cord, little difference was observed between each corresponding region of MND and control patients, except relatively low enzyme activity in the cervical ventral horn region of MND patients. Muscarinic cholinergic receptors, examined as specific [3H]quinuclidinylbenzilate ([3H]QNB) binding, was also highly concentrated in the ventral and dorsal gray matter of the control spinal cord, and was strongly reduced in the ventral horn region of MND patients, indicating a quite similar distribution pattern of ChAT activity. These biochemical changes of cholinergic transmission system may be paralleled to the morphological degeneration of the spinal lower motor neurons in MND patients. Activity of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase), a marker enzyme of central myelin structure, was evenly distributed throughout the whole spinal cord section, without regard to the gray and white matter, of both MND and control patients.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Simultaneous bilateral renal artery reconstruction and intraoperative renal protection. A case report.

A 22-year-old Japanese man with bilateral renal artery stenosis associated with hypertension underwent successful surgery of simultaneous bilateral renal artery reconstruction under conditions of intraoperative renal perfusion with St. Thomas Hospital solution which is used for cardioplegia in open heart surgery. Circulation in the left kidney was interrupted for 58 minutes and that of the right kidney for 35 minutes. The patient fully recovered with no serious impairment of renal function. In addition to these stenotic lesions of the renal artery, there were medial necrosis of the aorta and fibromuscular dysplasia of the superior mesenteric artery. Administration of SQ14,225, an angiotensin I converting enzyme inhibitor, was effective in controlling hypertension during the preoperative period.

Adult↗

Effect of bone-derived growth factor on DNA, RNA, and proteoglycan synthesis in cultures of rabbit costal chondrocytes.

Calvariae and chondrocytes in culture have been reported to release growth factors which stimulate bone and cartilage growth respectively. In the present studies, we examined the effects of bone-derived growth factor (BDGF) on DNA, RNA and proteoglycan synthesis in cultured rabbit chondrocytes. Two partially purified fractions of BDGF were tested, one with an approximate molecular weight (MW) of 20-30,000 and with greater activity on calvarial DNA labeling (BDGF I) and another with an approximate MW 6-13,000 and greater activity on bone collagen labeling (BDGF II). Both fractions had a similar effect and increased the incorporation of -3H-uridine into acid insoluble residues in chondrocytes and the incorporation of 35SO4(2-), 3H-glucosamine and 3H-serine into proteoglycans. However, BDGF II had a greater stimulatory effect on the incorporation of 3H-thymidine than BDGF I. These findings suggest that factor(s) released by bone cells are capable of stimulating cartilage metabolism and growth.

Animals↗

Dissecting aneurysm during pregnancy and the puerperium.

According to Schnitker, Mandel, Hirst and their associates, approximately half of the dissecting aneurysms in women under 40 years of age are associated with pregnancy. This significant relationship between dissecting aneurysm and pregnancy has been discussed by considering hemodynamic stress and also the hormonal changes of pregnancy. In this report, we describe five patients with dissecting aneurysm during pregnancy or the puerperium, review the literature and discuss the influence of pregnancy on the pathogenesis of this disease.

Adult↗

Induction of gamma-glutamyl transpeptidase activity by dietary phenobarbital in "spontaneous" hepatic tumors of C3H mice.

Biochemical features of spontaneous hepatic tumors in C3H mice were studied histochemically in comparison with those of neoplastic lesions developed in animals fed dietary phenobarbital (PB) continuously or treated with diethylnitrosamine (DEN) during 11 approximately 14 weeks of age. All 42 spontaneous hepatic tumors that developed in control mice by 74 weeks of age were completely negative for gamma-glutamyl transpeptidase (gamma-GTPase) activity. Dietary phenobarbital enhanced hepatic tumorigenesis remarkably, and 32 out of 43 tumors found at 70 weeks showed multifocal gamma-GTPase activity. DEN induced gamma-GTPase-positive islands of hepatocytes, but 12 out of 13 tumors larger than 5 mm in diameter that developed by 60 weeks were gamma-GTPase-negative. The phenomenon of induction of gamma-GTPase activity by PB in "spontaneous" hepatic tumors appears to be important both for elucidating the mechanism of promotion by PB and also for analyzing multisteps of carcinogenesis.

Animals↗

Mechanisms of inhibition by simultaneously administered phenobarbital of 3'-methyl-4-(dimethylamino)azobenzene-induced hepatocarcinogenesis in the rat.

The mechanisms of inhibition by simultaneously administered phenobarbital of 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB)-induced hepatocarcinogenesis in the rat were studied. Weanling rats were fed a diet containing 0.06% 3'-Me-DAB or 0.06% 3'-Me-DAB and 0.05% phenobarbital for 3 weeks, followed by either basal diet or a diet containing 0.05% phenobarbital as a promoter. The number and the size of enzyme-altered islands and the number of tumors larger than 5 mm in diameter were scored at week 12 and week 40, respectively. The simultaneous feeding of phenobarbital and 3'-Me-DAB resulted in a significant decrease in the number and size of enzyme-altered islands and in the number of tumors, in comparison with those scored in animals fed 3'-Me-DAB alone. It was concluded that the simultaneous feeding of phenobarbital inhibits both the initiation of carcinogenesis and also the promotive action of the carcinogen resulting from its selective toxicity on the liver tissue.

Animals↗