Search PubMed⌕ Search

Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 541 records · Page 30Linked to original sources
PubMed1990

Underlying mechanisms of atrophic state of brown adipose tissue in obese Zucker rats.

The mechanisms involved in brown adipose tissue (BAT) atrophy in obese rats were investigated. In urethan-anesthetized adult obese (fa/fa) and lean (Fa/?) rats, colonic temperature (Tc), interscapular BAT (IBAT) temperature (TIBAT), and the TIBAT-Tc gradient were measured after microknife cut in the prepontine region and during norepinephrine (NE) infusion. The knife cut tests the neural control of IBAT since it suppresses a tonic inhibition of thermogenesis revealing a sustained reflex stimulation of BAT. The NE infusion tests the metabolic capacity of BAT. In 22 degrees C-acclimated lean rats, the cut induced marked hyperthermia, TIBAT that rose faster than Tc, and a reversed temperature gradient. By contrast, in the obese rat, the cut had practically no effect, and NE infusion caused only slight increases in Tc and TIBAT. In cold-acclimated obese rats, an almost complete response to NE infusion and a partial response to knife cut were observed. After adrenalectomy, the responses were similar in lean and obese rats. An operational model to account for these results and for the deficit in diet-induced thermogenesis in fa/fa rats is proposed.

Adipose Tissue↗
PubMed1990

[Participation of the sensory nerves in the inflammatory response induced by irritants].

Participation of the sensory neurons, especially substance P (SP)-containing neurons, in the inflammatory response induced by formalin (FOR), croton oil (CRO), mustard oil (MUS), carrageenin (CAR), dextran (DEX) and egg white (EGG) was studied in mice and rats. FOR-induced foot edema was significantly inhibited by denervation of the sciatic nerve of rats, but it was slightly facilitated by that of the saphenous nerve. CAR-induced edema was not influenced by denervation of both nerves. In mice pretreated with capsaicin of the sciatic nerve, the early phase of foot edema induced by FOR, CRO or MUS was significantly inhibited. Edema induced by CAR, DEX or EGG was not inhibited by the capsaicin treatment. Spantide (an SP antagonist) at 0.1 mg/kg showed the same result as the capsaicin treatment. FOR, CRO or MUS caused a marked plasma extravasation, which was inhibited by spantide. The weak plasma extravasation elicited by CAR, DEX or EGG was not inhibited by spantide. FOR, CRO or MUS caused an intense biphasic nociceptive response; and the early phase of the response was inhibited by spantide. CAR, DEX or EGG caused little or no nociception. These findings suggest that SP antidromically released from the primary sensory neurons may induce potent vascular responses such as vasodilatation and plasma extravasation in the early phase of inflammation induced by FOR, CRO and MUS, whereas inflammatory responses induced by CAR, DEX and EGG may progress through different processes.

Animals↗
PubMed1990

Effects of FRG-8701 on gastric acid secretion, gastric mucosal lesions by necrotizing agents and experimental gastric or duodenal ulcer in rats.

Effects of FRG-8701, a new histamine H2-receptor antagonist, on gastric acid secretion, necrotizing agents-induced gastric lesions and acute gastric or duodenal ulcer in rats were studied. In lumen-perfused rats, intravenous injection of FRG-8701 reduced gastric acid secretion, and its antisecretory effect was almost equipotent to that of famotidine but the duration of action was substantially longer. In pylorus-ligated rats, the antisecretory effect of intraduodenal FRG-8701 administration was about 7 times more potent than that of cimetidine. FRG-8701 effectively inhibited macroscopic gastric hemorrhagic lesions induced by various kinds of necrotizing agents. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ED50 values for these lesions ranged from 1.1 to 9.4 mg/kg. On the other hand, famotidine failed to reduce these lesions, and the cytoprotective effect of cimetidine was observed only in high doses compared with the doses for antisecretory activity. In addition, the cytoprotective effect of FRG-8701 was not affected by the treatment of indomethacin or N-ethylmaleimide. FRG-8701 showed antiulcer activity against stress and indomethacin gastric ulcer and mepirizole duodenal ulcer. Its antiulcer effect was 5-15 times more potent than that of cimetidine. These results indicate that FRG-8701 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.

Acetamides↗
PubMed1990

HAF, hepatoma aggregation factor produced by Streptomyces sp. strain No. A-6143.

We searched for a new cell aggregation factor for hepatoma AH109A cells, and found one we called HAF in the culture filtrate of Streptomyces sp. strain No. A-6143 isolated from a soil sample. HAF was purified by salting-out with ammonium sulfate. DEAE-cellulose column chromatography, gel filtration on Sephadex G-100, and hydroxylapatite column chromatography, HAF was glycoprotein which had a molecular weight of about 73,000. HAF was stable from pH 6 to 8 at 37 degrees C and up to 40 degrees C at pH 8.0 and the aggregation activity of HAF was maximum around pH 8 at 30 degrees C. The activity was not influenced by some saccharides, but it was inhibited by EDTA and EGTA: moreover HAF activity was restored by the addition of calcium ions. HAF aggregated hepatoma AH136B and COS-7 cells as well as hepatoma AH109A cells, but it was inert to other cancer cells and human erythrocytes. These properties proved that HAF is completely different from other aggregation factors for cancer cells so far reported.

Animals↗
PubMed1990

Features of regenerated clones with or without fusion treatment between auxotrophic mutants of Streptomyces antibioticus and their antibiotic productivity.

During experiments on protoplast fusion of complementary auxotrophic mutants (194 and 11M-21) of Streptomyces antibioticus for strain improvement, the clones (typified by F-40) regenerated on minimal regeneration medium (MRM) were found to be prototrophs, and to produce an antibiotic different from those produced by the parent strain. The protoplast regeneration of each parent was examined as a negative control experiment. In the regenerated clones of 194, half of them produced actinomycins similar to those produced by the original mutant 194, but others (typified by R-20) seemed to produce antibiotics similar to those produced by F-40. In the taxonomic characterization of morphological, cultural, and physiological properties of each strain, F-40, R-20, and the parent mutant 194 had no significant differences with a few exceptions. The problem here is whether the antibiotic of R-20 is the same as that of F-40, which was first isolated and found to be a peptide antibiotic different from actinomycins, with activity against Gram-negative and Gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed1990

Roles of substance P and somatostatin on transmission of nociceptive information induced by formalin in spinal cord.

Nociceptive response induced by 0.5% Formalin in the hindpaw of mice had two peaks, 0-5 min (first phase) and 15-20 min (second phase). By using the distinct biphasic response, the nature of the transmitter systems activated by Formalin in the spinal cord was studied for the purpose of determining the difference of the role of substance P (SP) and somatostatin (SST). The injection of (D-Pro2, D-Trp7,9)SP, (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP and SP antiserum inhibited only the first phase response. The i.t. injection of -Aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr- (an SST antagonist), SST antiserum and cysteamine (an SST depletor) inhibited only the second phase. This result indicates that SP is involved in the transmission of the first phase, and SST is involved in the transmission of the second phase of the Formalin-induced nociceptive response. With regard to other nociceptive stimuli, two i.t. SP antagonists produced a significant analgesia in the hot plate and tail pinch tests but had no effect in the acetic acid writhing test. However, i.t. SST antagonist and cysteamine produced a significant analgesia in the writhing test but had no effect in the hot plate and tail pinch test. These results suggest that SP participates in the transient pain induced by such acute stimuli as hot plate, tail pinch and the first phase of Formalin response and that SST participates in the prolonged and inflammatory pain induced by stimuli such as acetic acid and the second phase response.

Animals↗
PubMed1990

[The use of Pugh score to evaluate the prognostic and therapeutic influence of drinking in patients with decompensated liver cirrhosis].

The aim of this study is to evaluate the clinical usefulness of Pugh score in the prognosis of the patients (pts.) with decompensated liver cirrhosis (DLC). To determine the influence of heavy drinking with respect to the prognosis of DLC patients, 128 cases of DLC were divided into two groups including the 31 heavy drinker group (Group A) and 97 non-alcoholic group (Group B). At the time of admission, the both groups showed similar Pugh score. However, after initial two hospitalized weeks, Group A started to show significantly lower points of Pugh score than that of in Group B. Fifteen pts. (48%) in Group A and 55 pts. (57%) in Group B had greater than 9 in Pugh score at the time of admission. In Group A, 10 of 15 pts. declined the scores after initial two weeks and 9 of them lived more than one year after admission. In contrast, none of those 55 pts. in Group B declined their Pugh score after admission and 45 of them died within one year. It was concluded that Pugh score was extremely useful to evaluate the prognosis of DLC pts., and DLC pts. who had greater than 9 Pugh score were seemed to be critical. It was suggested that DLC pts. due to heavy drinking tend to improve Pugh score comparing to no alcoholic DLC pts.

Adult↗
PubMed1990

[Clinical study of male patients with primary biliary cirrhosis (PBC)].

We studied 10 male and 23 female patients with PBC to determine whether the clinical and histological features of this disease differed in male and female patients. There were no significant difference between men and women in age distribution and biochemical examinations. In female patients, autoimmune associated conditions such as sicca syndrome, Raynaud syndrome and arthritis were observed 22%, 13% and 36%, respectively. By contrast, no male patients developed those conditions. 80% of the male patients and 70% of the female patients belonged to asymptomatic PBC, and early histological stage, such as Scheuer's I and II were observed 90% of the male patients and 78% of the female patients, respectively. No male patients showed clinical or histological progression during follow-up period (median was 64 months). Nevertheless, not a few female patients showed progression including 3 cases who died during the follow-up period (median was 47 months). We concluded that male patients with PBC tend to have favorable prognosis comparing to female patients.

Adult↗
PubMed1990

Osseous changes and abnormalities of mineral metabolism in daunomycin rats.

We examined whether daunomycin rats could be used as an experimental model of human chronic renal failure in terms of their osseous changes and mineral metabolism. The daunomycin rats revealed hyperphosphatemia and osteodystrophic bone changes. In this respect, they were similar to human chronic renal failure. A high calcium level was found in the daunomycin rats at first due to the effect of the daunomycin injection, but later there was a lower calcium level than in the control rats due to chronic renal failure. We conclude that daunomycin rats can be successfully used as an experimental model of chronic renal failure from the standpoint of their osseous changes and mineral metabolism.

Animals↗
PubMed1990

[Daunomycin rats. Second Report. Is it possible to use daunomycin rats as an experimental model of chronic renal failure?].

We have previously reported that daunomycin rats can be used as an experimental model of chronic renal failure. We have since studied whether the result were reproducible by repeating the experiment. In this experiment we used larger numbers of rats and many more parameters of investigation compared with the previous experiment. The period of observation was extended to 42 weeks. Twenty-one female Wistar rats were given an injection of 12 mg/Kg of daunomycin into the jugular vein by the one-shot method. Ten control rats were injected with physiological saline. Eighteen daunomycin rats developed chronic renal failure within the observation period. Renal failure was confirmed by the levels of BUN and creatinine, the uremic peak 2a and the pathological findings. One rat died from a tumor and another rat died from thrombosis of the descending aorta. In only one rat was not at the level defined as chronic renal failure, although it was impaired even in this case. There was a correlation between the lifespan of the daunomycin rats and the amount of urine protein at 4 weeks. Rats with heavy proteinuria at 4 weeks died of uremia at an early age. There was a variety of evidence of daunomycin damage when rats were autopsied, not only in the renal glomeruli but also in the pancreas, liver and spleen. Some parts of the pancreas and liver showed vacuolated cells. We supposed that these various changes of many internal organs of daunomycin rats were secondary changes for chronic renal failure. We reconfirmed that daunomycin rats can be used as an experimental model of chronic renal failure.

Animals↗
PubMed1990

[Three dimensional CT reconstruction image using a personal computer].

Three dimensional (3D) images were reconstructed from axial CT slices using the personal computer. Some devices of the program made it possible to decrease the image processing time and to produce the realistic images with cubic effect. The thresholding in the conventional 3 D imaging was not practical especially in the display of the soft tissues. The employment of the volume rendering technique and MRI data will give a clue to the solution of these problems.

Humans↗
PubMed1989

Localization of chemotactic activity and 64 kD protein phosphorylation for human polymorphonuclear leukocytes in N-terminus of the chemotactic protein LUCT/IL-8.

A synthetic peptide, AVLPRSAKEL (LU10), the N-terminal amino acid sequence of chemotactic protein (LUCT/IL-8), showed chemotactic activity to polymorphonuclear leukocytes (PMN) with an ED50 of 5 nM for comparable to that of LUCT. Native LUCT and LU10 specifically induced the phosphorylation of 64 kD protein of PMN, and serine residue in the 64 kD protein was major phosphorylated amino acid. Furthermore, native LUCT enhanced the release of myeloperoxidase and beta-glucuronidase from PMN in the presence of cytochalasin B and FMLP, but LU10 did not. These results strongly suggest that the active site for both chemotactic stimulation and 64 kD protein phosphorylation is localized on the sequence of N-terminal 10 amino acids of LUCT.

Amino Acid Sequence↗
PubMed1989

Protein kinase C phosphorylation of desmin at four serine residues within the non-alpha-helical head domain.

We reported that phosphorylation by either cAMP-dependent protein kinase or protein kinase C (Ca2+/phospholipid-dependent enzyme) in vitro induces disassembly of the desmin filaments (Inagaki, M., Gonda, Y., Matsuyama, M., Nishizawa, K., Nishi, Y., and Sato, C. (1988) J. Biol. Chem. 263, 5970-5978). For this subunit protein, Ser-29, Ser-35, and Ser-50 within the non-alpha-helical head domain were shown to be the sites of phosphorylation for cAMP-dependent protein kinase (Geisler, N., and Weber, K. (1988) EMBO J. 7, 15-20). In the present work, we identified the sites of desmin phosphorylated in vitro by other protein kinase which affects the filament structure. The protein kinase C-phosphorylated desmin was hydrolyzed with trypsin, and the phosphorylated peptides were isolated by reverse-phase chromatography. Sequential analysis of the purified phosphopeptides, together with the known primary sequence, revealed that Ser-12, Ser-29, Ser-38, and Ser-56 were phosphorylated by protein kinase C. All four sites are located within the non-alpha-helical head domain of desmin. Ser-12, Ser-38, and Ser-56, specifically phosphorylated by protein kinase C, have arginine residues at the carboxyl-terminal side (Arg-14, Arg-42, and Arg-59, respectively). Ser-29 phosphorylated by both protein kinase C and cAMP-dependent protein kinase has arginine residues at the amino and carboxyl termini (Arg-27 and Arg-33). These findings support the view that the head domain-specific phosphorylation strongly influences desmin filament structure; however, each protein kinase differed with regard to site recognition on this domain.

Amino Acid Sequence↗
PubMed1989

Induction of soft tissue tumours in F344 rats by subcutaneous, intramuscular, intra-articular, and retroperitoneal injection of nickel sulphide (Ni3S2).

The carcinogenicity of nickel sulphide (Ni3S2) injected into subcutaneous (s.c.), intramuscular (i.m.), or retroperitoneal intrafat (i.f.) tissue, or the intra-articular space (i.a.) of male F344 rats was studied. Rats were given a single injection of 0.5 mg of Ni3S2 and were observed for 48 weeks. Malignant soft tissue tumours were induced in 18/19 rats (95 per cent) by s.c. injection, 19/20 rats (95 per cent) by i.m. injection, in 16/19 rats (84 per cent) by i.a. injection, and in 9/20 rats (45 per cent) by i.f. injection of Ni3S2. The i.f. injection of Ni3S2 resulted in a lower tumour incidence and the appearance of tumours 10 weeks later than its injection by other routes. The tumours were examined histologically, ultrastructurally, and immunohistochemically with antibodies against desmin, vimentin, and cytokeratin. The 62 tumours induced by injection of Ni3S2 by different routes were identified as rhabdomyosarcomas (RMS, 35), malignant fibrous histiocytomas (MFH, 18), fibrosarcomas (FS, 5), and unclassified sarcomas (4). All 19 tumours induced by i.m. injection of Ni3S2 were rhabdomyosarcomas; those induced by s.c. or i.f. injection were mainly MFHs. However, a number of RMSs were also found in groups that received i.a., s.c., and i.f. injections; five FSs also developed in these groups. Four sarcomas induced by s.c. and i.a. injections were not classified. No synovial sarcoma developed.

Animals↗
PubMed1989

Expression of a viral gene in insulin-producing cell lines renders them susceptible to immunological destruction.

The gene coding for the glycoprotein D of herpes simplex virus type 1 was cloned into plasmids under the transcriptional control of the SV40 promoter-enhancer or the rat insulin 1 promoter-enhancer sequences. These plasmids were transfected into rat insulinoma cells (RINm5F) and mouse NIH/3T3 cells and the expression of glycoprotein D was examined using cell surface immunofluoresence. The rat insulin 1 promoter-enhancer sequences directed efficient expression in RINm5F cells, but not in NIH/3T3 cells. In contrast, the SV40 promoter-enhancer sequences worked well in NIH/3T3 cells, but not in RINm5F cells. Expression of glycoprotein D did not interfere with insulin production by RINm5F cells. When stable cel lines expressing glycoprotein D were exposed to anti-herpes simplex virus type 1 antibodies and complement, they were destroyed. These studies provide additional evidence that specific promoter-enhancer elements are required for efficient gene expression in certain cell types and demonstrate that the expression of foreign antigens on the surface of insulin-producing cells can lead to their immunological destruction.

Animals↗
PubMed1989

Pharmacokinetic study of iminodibenzyl antipsychotic drugs, clocapramine and Y-516 in dog and man.

The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4'-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16 +/- 0.01 (mean +/- SD, n = 3) for CCP and 0.29 +/- 0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43 +/- 0.07 and 0.79 +/- 0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63 +/- 0.05 and 0.63 +/- 0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗