Biomedical subjects
Publications and source records attributed to T Suga.
1H NMR spectroscopy has been used to demonstrate specific binding of rat 80S ribosomes to the major conformer of an antitumor bicyclic hexapeptidic glucoside, RA-XII, isolated from Rubia cordifolia, in a fast exchange process.
A 32-year-old adult case of glomerulocystic kidney disease (GCK) is reported. He had brain and muscle atrophy, probably due to congenital malformation. Progressive renal failure developed and he died. Autopsy disclosed multiple tiny cysts exclusively in the renal cortices. Microscopic study revealed that the cysts were dilated Bowman's spaces. This case is the 12th adult case reported in the world.
A new embolization agent combining ethanol-estrogen and polyvinyl acetate was evaluated angiographically and histologically in 18 canine renal arterial systems. Peripheral vessels of less than 100 microns diameter were obliterated by thrombus induced by ethanol-estrogen, and larger vessels were obliterated by polyvinyl acetate casts and/or thrombus. This embolization method is easily controlled and has fewer adverse effects, so is suitable for intravascular applications, especially in the head and neck regions.
We tried continuous local arterial-infusion chemotherapy using 5-FU + CDDP with an implanted reservoir, for patients with severely advanced hepatocellular carcinoma (HCC), who had no indications for operation, PEIT or TAE. Arterial-infusion was continued for one week, followed by a one-week no-infusion period, and this treatment was repeated 1-32 times, and patients were observed for 36-549 days. Until the end of April 1993, the one-year survival rate was 61.1%. There were 3 partial remission (PR) cases, 3 progressive disease (PD) cases and the other cases showed no change (NC). Only one patient had any side effects, and all could continue as outpatients for 94.0% of the entire therapy. The patients' evaluation of QOL revealed no differences of QOL according to the length of the whole therapy, the history of rehospitalization during therapy, response to therapy, etc. But PR cases tended to show improved QOL. Therefore we considered this as effective therapy for the elongation of the life-span and the improvement of QOL.
We attempted continuous local arterial-infusion chemotherapy using reservoir for patients with severely advanced hepatocellular carcinoma (HCC), with no indications for operation, PEIT or TAE because of the advanced clinical stage, Vp-factor, and so on. Twenty-two HCC patients were given continuous arterial-infusion of 5-FU + CDDP and were observed for 36-443 days from June, 1991 to December, 1992. Until the end of 1992, we had 3 partial response (PR) cases and 3 progressive disease (PD) cases, and the other cases showed no change (NC). Except for a case in which therapy was stopped because of renal failure, no patients were disturbed by side effects, and 68.2% of the patients completed all of their therapy as outpatients. Because CDDP can amplify the effect of 5-FU in addition to its own effect as a biochemical modulator, and because continuous infusion can strengthen the effect of 5-FU and reduce the side effects of CDDP, we consider continuous local arterial-infusion of 5-FU and CDDP to be an effective therapy for severely advanced HCC. This treatment does not cure the carcinoma but helps to slow its progress and assure good QOL.
Treatment of cultured rat-hepatocytes with 50 microM dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) for up to 5 days resulted in a progressive increase in peroxisomal beta-oxidation and carnitine acetyltransferase activity. After 5 days, the increases in activity were 2.6- and 4.8-fold for peroxisomal beta-oxidation and 11.7- and 17.1-fold for carnitine acetyltransferase over the initial activity, in DHEA- and DHEAS-treated cells, respectively. The stimulation of the activity of these enzymes by the respective agents was dose-related; it was maximum with 50 to 100 microM DHEA and 50 to 250 microM DHEAS, although DHEAS was more effective for stimulation than DHEA. Western blot analyses revealed the induction of acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme and carnitine acetyltransferase in the treated cells. Moreover, induction of fatty acid omega-hydroxylase proteins (P-450IVAS) was also revealed. These results indicate that DHEA and DHEAS act directly on hepatocytes. The induction of hepatic peroxisomal beta-oxidation enzymes and several other enzymes in rats administered with DHEA could be accounted for, at least in part, by the direct action of DHEA and its sulfate-conjugate (DHEAS) on liver cells.
The complement-dependent bactericidal factor, Ra-reactive factor, binds specifically to Ra polysaccharide, which is common to some strains of Gram-negative enterobacteria, and its is a complex of proteins composed of a polysaccharide-binding component and a component that is presumably responsible for the complement activation. The former component consists of two different 28-kDa polypeptides, P28a and P28b. We determined the partial amino acid sequences of P28a and P28b, and the results indicated that these polypeptides were similar to two species of mannose-binding protein, MBP-C and MBP-A (alternative names, liver and serum mannan-binding proteins, respectively), which have been isolated from rat liver and/or serum [Drickamer, K., Dordal, M. S., & Reynolds, L. (1986) J. Biol. Chem. 261, 6878-6887; Oka, S., Itoh, N., Kawasaki, T., & Yamashina, I. (1987) J. Biochem. 101, 135-144]. Thus, we cloned the respective cDNAs, using as probes synthetic oligonucleotides for which the sequences had been deduced from the amino acid sequences of P28a and P28b and of rat MBP cDNAs. The primary structures of P28a and P28b deduced from the cloned cDNAs are homologous to one another. They have three domains, a short NH2-terminal domain, a collagen-like domain, and a domain homologous to regions of some carbohydrate-binding proteins, as has been reported for rat MBPs. Southern and Northern blotting analyses using these cDNAs indicated that the P28a and P28b polypeptides are the products of two unique mouse genes which are expressed in hepatic cells.
We developed a specific method for direct determination of peroxisomal beta-oxidation activity in cultured human skin fibroblasts. When control fibroblasts were incubated with N-(alpha-methylbenzyl)azelaamic acid (C9), a specific peroxisomal substrate, C5 and C7, the chain-shortened products, were detected with cell concentration and incubation time dependencies and no other products including C3 were detected. In glutaric aciduria type I and type II fibroblasts, the formation rates of C2 units liberated from C9 were almost similar to that in control cells. In contrast to these cell types, the fibroblasts from patient of Zellweger syndrome, in which peroxisomal beta-oxidation was impaired, showed no conversion of C9 to C5 and C7. The lack of the C2 units liberation in Zellweger fibroblasts was not due to an impairment of mitochondrial beta-oxidation and/or activation of C9 to C9-CoA derivative for subsequent beta-oxidation reaction, but rather, appeared to be due to the specific defect of peroxisomal beta-oxidation system. These results indicate that C9 is a useful substrate for the estimation of peroxisomal beta-oxidation activity in cultured human skin fibroblasts.
Trifluoperazine, a calmodulin antagonist, suppressed the clofibric acid-evoked induction of the peroxisomal cyanide-insensitive fatty acyl-CoA oxidizing system and carnitine acetyltransferase in rat liver and also in cultured rat hepatocytes. H-7, a potent inhibitor of protein kinase C, also suppressed the induction of these enzymes by clofibric acid, bezafibrate, Wyl4,643 or mono(2-ethylhexyl)phthalate in cultured rat hepatocytes. This suppressive effect was also confirmed by the protein composition of hepatocytes treated with clofibric acid and these antagonists, where the increase in the amount of peroxisomal bifunctional enzyme by peroxisome proliferator was markedly suppressed by above two antagonists. Profile of the time-dependent changes in the activities of the two enzymes after clofibric acid treatment showed that there might be two phases in the induction process. The initial phase (0-3 days after the treatment) showed a relative low inducing rate and subsequent phase (3-5 days after the treatment) showed an abrupt induction. The suppressive effect of the above two antagonists was significant in the later phase. In a time course study of the induction process of peroxisomal catalase, bifunctional enzyme or 69 kDa integral membrane protein using immunochemical detection, the induction of the membrane protein by clofibric acid was delayed compared with that of the bifunctional enzyme, where the induction was inhibited almost completely by nicardipine. These experimental results suggest that calmodulin- and protein kinase C-dependent processes play an important role in the process of marked induction of peroxisomal enzymes and membrane protein by drugs in rat liver.
The in-vivo effect of dehydroepiandrosterone (DHEA) on hepatic enzyme activities of rats, mice, hamsters and guinea pigs was investigated. After DHEA treatment (300 mg/kg body weight, per os, 14 days), the activities of peroxisomal beta-oxidation, catalase, carnitine acetyltransferase, carnitine palmitoyltransferase, lauric acid omega-hydroxylation, 1-acylglycerophosphocholine acyltransferase, malic enzyme and cytosolic palmitoyl-CoA hydrolase were increased in rats and in mice although to a smaller extent in the latter. These enzyme activities, however, were unchanged in hamsters with the exception of omega-hydroxylation (2.5-fold increase) and 1-acylglycerophosphocholine acyltransferase (2.0-fold increase). No significant changes were observed in any of these enzyme activities in guinea pigs. Immunoblot analysis confirmed the induction of peroxisomal acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme in rats and mice. These results indicate that there are species differences in the inducing effect of DHEA on hepatic peroxisome proliferation-associated enzymes, which correlates well with the enzyme induction observed with other peroxisome proliferators.
CT studies of 50 patients with spontaneous subarachnoid haemorrhage (SAH) and 100 randomly selected patients were reviewed with regard to the size of the frontal and temporal horns of the lateral ventricles. The temporal horn was classified into four grades, based on the size of its posterior portion at the level of the midbrain. The horn was clearly visible in 66% of patients with SAH, but in only 2% of controls. In the SAH group, the temporal horn tended to dilate sooner than the frontal horn after haemorrhage and could be seen clearly in a larger proportion of patients. Thus, assessment of the size of the temporal horn appears to be a simple and sensitive method for assessing ventricular dilatation. In addition, dilatation of the temporal horn may prove to be an important indirect sign suggesting SAH in patients in whom no high density clot is seen on CT.
A glycoside showing a strong growth inhibition of lettuce was isolated from the root-stalks of Gleichenia japonica and its structure was established to be the 3-O-alpha-rhamnopyranosyl-(1----2)-beta-glucopyranoside of 13-O-alpha-rhamnopyranosyl-(+)-3 beta-hydroxymanool. In addition, two related glycosides were also isolated and they were characterized as the 3-O-beta-fucopyranosyl-(1----3)-alpha-rhamnopyranosyl-(1----2)-beta- glucopyranoside of 13-O-alpha-rhamnopyranosyl-(+)-3 beta-hydroxymanool and the 13-O-rhamnopyranoside of the same diterpene alcohol. The diterpene alcohol accelerated the growth of lettuce.
The aim of the present study was to further investigate the role of the adrenergic system on insulin action using the euglycemic clamp technique. Whole-body glucose metabolism (GM) was calculated as the glucose infusion rate for maintaining euglycemia under insulin infusion and used as an indicator of insulin sensitivity. Euglycemic clamps were performed in adrenodemedullated, epinephrine-treated, phentolamine-treated (alpha-blockade), propranolol-treated (beta-blockade), and epinephrine plus phentolamine and/or propranolol-treated rats. The following results were obtained at an insulin level of approximately 80 mU/l. GM in adrenodemedullated rats (13.97 +/- 0.98 mg/kg/min) was significantly higher than that of the control rats (10.26 +/- 0.50 mg/kg/min, P less than 0.01). GM in epinephrine-treated rats (1.7 mg/kg body weight/h) was 2.12 +/- 0.49 mg/kg/min (P less than 0.001 vs. control). Dose-response curves for phentolamine and propranolol established maximally effective doses (3.0 mg and 12 mg/kg body weight/h, respectively). Using these doses, GM in epinephrine plus phentolamine-treated rats (4.90 +/- 0.39 mg/kg/min) was significantly higher than that of epinephrine alone and GM in epinephrine and propranolol-treated rats (4.49 +/- 0.47 mg/kg/min) was also significantly higher than that of the epinephrine alone. GM in the epinephrine plus both propranolol and phentolamine (5.94 +/- 0.45 mg/kg/min) was significantly higher than that of the epinephrine alone, but not different from either treatment alone and was not additive. Neither phentolamine alone (9.48 +/- 1.45 mg/kg/min), propranolol alone (10.36 +/- 0.55 mg/kg/min) or the combination of blockades (11.14 +/- 0.65 mg/kg/min) had any effect on GM.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunohistochemical staining of enoyl CoA hydratase (ECH), a key peroxisomal enzyme, revealed that the putative preneoplastic lesions induced in livers by administration of the peroxisome proliferator (PP) clofibrate (0.3% in diet) to rats for 60 weeks or more, lacked this enzyme so that they could be detected as ECH-negative foci. ECH and other peroxisomal enzymes such as acyl CoA oxidase, catalase and carnitine-dependent acetyltransferase were also either not or only weakly expressed in most hepatic hyperplastic nodules and hepatomas induced by ciprofibrate (0.025% in diet), Wy-14,643 (0.1%) or BR-931 (0.2%), while being strongly induced in surrounding hepatocytes. These results indicate that the expression of ECH and other peroxisomal enzymes is repressed in putative preneoplastic and neoplastic lesions induced by PPs in rat livers and that these peroxisomal enzymes might therefore be used as negative markers.
In order to clarify the minimum requirements for renal biopsy size for a more accurate interpretation of renal biopsy information by light microscopy, we reanalyzed 92 open renal biopsy specimens in 92 patients with IgA nephropathy retrospectively. The mean number of functioning glomeruli per square millimeter in open renal biopsy specimens from 38 patients with a poor outcome was 1.2 +/- 0.4. In contrast, the mean number in 54 biopsy specimens from 54 patients with stable conditions for 10 years was 3.0 +/- 0.6. Therefore, there was a significant reduction (p less than 0.0001) in the numbers of functioning glomeruli in patients with a poor outcome. We found that the most important point in predicting the severity of tissue damage was detection not of the total numbers of glomeruli but of the density of glomeruli in given specimens in patients with IgA nephropathy. A biopsy sample of 1 mm x 7 mm in size of cortical origin is the minimum necessary to confidently interpret biopsy specimens from patients with IgA nephropathy.
We examined stereoselectivities of enzymes related to bile acid formation in hepatic peroxisomes using two stereoisomers of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) and its coenzyme A (CoA) derivatives. The activity of acyl-CoA synthetase for 25 S-THCA was 1.4-times higher than that for 25 R-THCA. The difference was also observed after clofibrate-treatment. This activity was located in microsomes, differing from palmitoyl-CoA synthetase located in mitochondria, peroxisomes and microsomes. There was no stereoselectivity in the reaction of peroxisomal fatty acyl-CoA oxidase for THCA isomers, and the activity was one tenth of that for acyl-CoA synthetase. Considering the overall reaction of peroxisomal bile acid formation, the stereoselective difference observed in THCA-CoA synthesis should be denied. Thus, the previous finding that the overall formation of bile acid from THCA was not stereoselective was further confirmed. Furthermore, the activity for THCA oxidation was not induced by clofibric acid, suggesting that there would be different isozymes of peroxisomal acyl-CoA oxidase against THCA-CoA and palmitoyl-CoA.
A new liquid embolization material applicable to intracranial lesions was evaluated by selective renal artery embolization in mongrel dogs. Absolute and diluted ethanol, estrogen, and estrogen in 25% ethanol (ethanol-estrogen) were injected. The embolization and side effects were investigated angiographically and histologically. Ethanol-estrogen caused similar embolization to absolute ethanol, but no direct damage to perivascular tissue, and is considered a promising embolization agent in intravascular surgery.
The authors report an experimental trial of intra-aneurysmal occlusion using fibrin glue. Nowadays, with the development of microsurgical techniques and aneurysmal clips, results of direct radical operations have been improving. But quite a few aneurysms cannot be clipped because of their size, location, broad neck etc. Some authors have treated these aneurysms with innovative techniques (detachable balloon techniques etc). In these methods, the occlusive state of the aneurysms is not always obtainable because of the size of their neck. Besides, it is not always possible to preserve the parent arteries of the aneurysms. Experimental aneurysms in cervical carotid arteries of dogs are treated by direct injection with fibrin glue. During its injection, influx of fibrin glue was prevented by occlusion of the aneurysmal orifices with inflated polyethylene angioplastic balloons. The aneurysms which were completely (100%) filled by the injection of fibrin glue (100% infused group) were totally obliterated in 10 (71%) of the 14 cases. The parent arteries were completely preserved in all instances. Follow-up study demonstrated satisfactory maintenance of this occluded state in the aneurysms in the 100% infused group. In completely occluded cases, all aneurysms maintained this state. On the other hand, 1 of the 4 incompletely obliterated aneurysms recanalized partially. These occluded aneurysms were studied by a light microscope (LM) and a scanning electron microscope (SEM). At day 7 after the occluding procedure, the margin of the aneurysmal orifice was covered by a layer of fibroblasts. At day 21, almost half of the aneurysmal cavity had been substituted with connective tissue. The orifice of the aneurysms was covered with an endothelial layer.(ABSTRACT TRUNCATED AT 250 WORDS)