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Biomedical subjects

T Shibata

Publications and source records attributed to T Shibata.

At least 559 records · Page 31Linked to original sources

Longitudinal changes of plasma pancreatic enzymes and hormones in experimental pancreatolithiasis in dogs.

Plasma pancreatic enzymes and hormones were longitudinally observed after producing partial obstruction of the major pancreatic duct in dogs to study an initial state of chronic pancreatitis or pancreatolithiasis. Fasting plasma immunoreactive cationic trypsin was elevated during the first six months and then decreased in a subgroup with pancreatic calculi, marked fibrosis, or duct dilatation when compared with the corresponding opposite at the end of the 12-month period. Similar but less prominent changes were found in fasting plasma immunoreactive pancreatic polypeptide (IRPP). Plasma amylase, glucose, or immunoreactive insulin or glucagon (IRG) show no significant variation. Plasma IRG and IRPP responses to intravenous insulin were reduced in the subgroups with marked pancreatic changes towards the end of the 12-month period. These results suggest that plasma pancreatic enzymes and hormones remain elevated as long as pancreatic damage is mild and then start to decline as the damage progresses in chronic pancreatitis or pancreatolithiasis.

Amylases↗

Serum pancreatic stone protein in pancreatic diseases.

Serum pancreatic stone protein (PSP) was determined in sera of pancreatic and nonpancreatic diseases using enzyme immunoassay specific to human PSP to study the diagnostic and pathophysiological significance of PSP. Serum PSP in acute pancreatitis (mean +/- SD = 1075.4 +/- 2849.1 ng/mL, n = 33) was significantly higher than that in controls (78.6 +/- 31.8 ng/mL, n = 37, p < 0.01), chronic pancreatitis (156.8 +/- 82.8 ng/mL, n = 32, p < 0.05), and pancreatic cancer (148.468.8 ng/mL, n = 26, p < 0.05). No significant difference was found between noncalcified and calcified chronic pancreatitis. Serum PSP levels were significantly higher in chronic renal failure under hemodialysis (1796.0 +/- 1492.9 ng/mL) than in other diseases such as peptic ulcer, liver cirrhosis, gallstone, and diabetes mellitus. Low but significant correlation was obtained between serum PSP and serum immunoreactive trypsin (r = 0.22, p < 0.05). Increased serum PSP levels in acute pancreatitis and chronic renal failure suggest that serum PSP levels reflect reflex from pancreatic secretion, release from damaged pancreatic acinar cells, or retention in circulation, and can be useful for diagnosis of acute pancreatitis, but not chronic calcified pancreatitis.

Acute Disease↗

The effect of sevoflurane on rat liver mitochondrial respiration.

The effect of sevoflurane on rat liver mitochondrial respiration has been investigated with a Clark type oxygen electrode at 25 degrees C, pH 7.4. The higher susceptibility of NADH-linked substrate (glutamate) oxidation (with respect to succinate oxidation) to the damages by sevoflurane has been confirmed.

Journal Article↗

Increased lung injury in pulmonary hypertensive patients during open heart operations.

To investigate lung injury in adult open heart operations during extracorporeal circulation, we measured plasma chemiluminescence levels. Nineteen patients were divided into two groups depending on preoperative pulmonary artery pressure: a pulmonary hypertension group (n = 11) and a control group (n = 8). Plasma samples were taken simultaneously from arterial and central venous lines at six different points during and early after operation. Arteriovenous difference of chemiluminescence (counts/10 seconds) increased significantly only in the pulmonary hypertension group (from -19.1 +/- 8.3 at the end of cross-clamping to 23.7 +/- 12.4 at the end of bypass; p < 0.01). There was a positive correlation between peak values of arterial plasma chemiluminescence and postoperative respiratory index in the pulmonary hypertension group (p < 0.05). In addition, during the first 12 hours postoperatively, arteriovenous difference of chemiluminescence in the pulmonary hypertension group changed significantly from negative to positive values (p < 0.05). These data suggest that free radical activity (detected by chemiluminescence) was deeply involved in lung injury during and also early after open heart operations, especially in pulmonary hypertensive patients.

Adult↗

Articular fractures of the digits: a prospective study.

We report a prospective study of 92 articular fractures of the digits. The treatment protocol was based on functional stability and acceptable alignment rather than on joint congruity. 54% of patients had good results, with 22% fair and 24% poor results being recorded. These results are similar to reports of treatment of finger fractures in general and suggest that for articular fractures of the digits, stability and alignment are more important factors than joint congruity in determining short-term outcome. Compound fractures and those associated with comminution, significant soft tissue damage and marked displacement at presentation have a worse prognosis.

Adolescent↗

Steroid hormones protect spinal cord neurons from glutamate toxicity.

The effects of steroid hormones on glutamate neurotoxicity were examined in cultured spinal cord neurons. The extent of neuronal damage, produced by glutamate exposure for 15 min, was estimated based on the activity of lactate dehydrogenase released from degenerated neurons to the media during 24 h of post-exposure incubation. This damage was dependent on the glutamate concentrations used. The addition of dexamethasone, a synthetic steroid, in post-exposure media remarkably reduced the extent of damage in a dose-dependent manner. The half effective concentration for the steroid was approximately 0.7 microM, which was in the range of pharmacological concentration. Dexamethasone was effective even when it was added 2 h after glutamate exposure. Some endogenous steroid hormones--aldosterone, progesterone and testosterone--also showed similar neuroprotective effects. However, cholesterol, a precursor of these steroid hormones, had no effect on glutamate neurotoxicity. This direct protective effect on neurons against glutamate neurotoxicity may explain, at least partly, the mechanisms of beneficial effects of steroid hormones on in vivo spinal cord injury.

Aldosterone↗

MION-ASF: biokinetics of an MR receptor agent.

Receptor-directed MR contrast agents are currently being designed to improve sensitivity and specificity of MR imaging and to provide for functional MR imaging. In the current study we have synthesized a conjugate of asialofetuin (ASF), a bovine plasma protein with a known, high affinity for the hepatic asialoglycoprotein receptor, and a well defined, single crystal superparamagnetic label (monocrystalline iron oxide nanoparticle, MION). MION-ASF is cleared from the circulation more than 300 times faster than MION, has a 3.7 times higher hepatic accumulation, increases liver R2 relaxivity 2.8-fold compared to MION, and accumulates in hepatocytes unlike MION, which accumulates only in macrophages. Competition assays indicate that receptor-mediated hepatocyte uptake can be competitively blocked and that this effect can be demonstrated by imaging. These studies indicate that sensitive iron oxide based probes can be developed for functional MR imaging.

Animals↗

UDP glucuronosyltransferase gene expression is involved in the stimulation of ascorbic acid biosynthesis by xenobiotics in rats.

Wistar-Shi (genotype +/+), heterozygous Gunn (j/+) and homozygous Gunn (j/j) rats was injected intraperitoneally with 3-methylcholanthrene (3MC) dissolved in corn oil. In rats of all genotypes the hepatic concentration of UDP glucuronosyltransferase (UDPGT) mRNA was increased at 48 and 96 h after the treatment with 3MC. Hepatic activity of 4-nitrophenol UDPGT was increased by 3MC in Wistar-Shi rats and heterozygous Gunn rats but not in homozygous Gunn rats. Urinary ascorbic acid excretion increased 72 and 96 h after the injection with 3MC in Wistar-Shi and heterozygous Gunn rats but not in homozygous Gunn rats. Ninety-six hours after the injection with 3MC, the hepatic concentration of ascorbic acid in Wistar-Shi rats was 90% higher than that in the corresponding control group, whereas in heterozygous and homozygous Gunn rats the increases were 70 and 30%, respectively. Wistar-Shi rats and homozygous Gunn rats were also injected daily for 3 d with sodium phenobarbital. In rats of both genotypes, the activity and hepatic concentration of chloramphenicol-UDPGT mRNA and liver and urine ascorbic acid concentration were increased by sodium phenobarbital. The data indicate that the stimulation of the expression of both the 4-nitrophenol and chloramphenicol UDPGT genes plays a key role in the ascorbic acid biosynthesis induced by 3MC and sodium phenobarbital.

Analysis of Variance↗

Modulation of the shedding of a rat tumor-associated antigen by growth regulation and anti-cancer drugs.

CE7 antigen is shed from A3 cell surfaces by cells grown in medium containing a sufficient (10%) amount of fetal calf serum (FCS), but shedding of the antigen decreases with a decrease in FCS content in the culture medium. However, the cells contain similar amounts of antigen as evidenced by Western blotting, indicating that low FCS levels interfere with antigen shedding but not antigen synthesis. Antigen expression by A3 cells treated with mitomycin C gradually shifted from negative to a strong positive with time, and on day 2, two peaks corresponding to negative and positive cells within the population can be observed. In contrast, A3 cells treated with bleomycin and cyclophosphamide shifted as a whole from negative to weakly positive. When A3 cells in media containing 10% FCS were incubated at 4 degrees C, although the cells did not proliferate, antigen expression could not be detected by flow cytometry.

Animals↗

Effect of a new synthetic trypsin inhibitor on taurocholate-induced acute pancreatitis in rats.

The effect of a novel synthetic trypsin inhibitor, 4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate (ONO-3307), on severe acute pancreatitis was studied by changing its timing, frequency, and dose in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of ONO-3307 administration: group A, 2 mg/0.5 ml of ONO-3307 s.c. 1 h before and after induction of pancreatitis; group B, 2 mg/0.5 ml s.c. 1 and 3 h after; group C, 4 mg/1 ml s.c. 1 h before; group D, 4 mg/1 ml s.c. 1 h after. The survival rate at 24 h was significantly improved in group A (75% in A vs. 17% in control; p < 0.01) and in group B (57 vs. 29%; p < 0.05), but not in group C or D. Amylase and immunoreactive trypsin in serum and ascites of the treated were significantly lower than those of controls in both groups A and B. The survival rates were improved dose dependently when ONO-3307 was administered 1 h before and after induction of pancreatitis. ONO-3307 showed favorable effects on the initial stage of severe acute pancreatitis when given in divided doses to maintain the effective serum levels.

Acute Disease↗

Genetic polymorphism of the sixth component of complement (C6) in the pig.

Using agarose gel isoelectric focusing and immunoblotting with rabbit anti-rabbit C6, a genetic polymorphism has been found in the sixth component of complement (C6) in six breeds of pigs. The C6 locus was highly polymorphic. Family data indicated that pig C6 phenotypes were inherited by means of five codomonant alleles named C6A, C6B, C6C, C6D and C6E at a single autosomal locus. C6 deficiency in two of 241 individuals tested was found, which suggested the presence of a null allele in pig populations. Marked breed differences among the gene frequencies and heterozygosities at C6 locus were observed.

Animals↗

IgG3 cryoglobulins in autoimmune MRL-lpr/lpr mice: immunopathogenesis, therapeutic approaches and relevance to similar human diseases.

MRL-lpr/lpr mice spontaneously develop an autoimmune disease resembling systemic lupus erythematosus and rheumatoid arthritis. One of the unique serological abnormalities in this strain is remarkably high concentrations of cryoglobulins. Analysis of immunoglobulin components in their cryoglobulins has shown selective enrichment of a particular IgG subclass, IgG3. As IgG3 enrichment is also found in two other cryoglobulins, which are induced after injection with bacterial lipopolysaccharides or infection with malaria, IgG3 apparently represents a major source of murine cryoglobulins. Studies on murine IgG3 monoclonal antibodies (mAbs) have clearly shown that murine IgG3 have the unique physiochemical property to self associate through non-specific IgG3 Fc-Fc interaction, and that most of them can generate monoclonal cryoglobulins. Most strikingly, IgG3 monoclonal cryoglobulins with rheumatoid factor (RF) activity induce extensive pathological manifestations: skin vascular purpura and glomerulonephritis with 'wire loop' lesions. Although the cryoglobulin activity of IgG3 RF mAb is solely responsible for the generation of glomerular lesions (both RF and cryoglobulin activities are necessary for skin vascular lesions), the absence of nephritogenic activity by some IgG3 cryoglobulins supports the idea that qualitative features of cryoglobulins are critical to determine their pathogenic activity. The demonstration of a positive correlation between the production of IgG3 cryoglobulins and the development of lupus nephritis in MRL-lpr/lpr mice further substantiates the pathological importance of cryogenic autoantibodies. On the other hand, it should be emphasised that non-cryogenerating IgG3 autoantibodies may not be harmful, but even protective, as a result of their interaction with pathogenic IgG3 cryoglobulins. Finally, the development of an experimental model of cryoglobulinaemia associated with vascular and glomerular disease certainly represents an invaluable opportunity to study the molecular mechanisms responsible for the generation of cryoglobulins and their associated tissue lesions, and also to assess various therapeutic approaches. Our demonstration that anti-idiotypic mAb can prevent the pathogenic effects of the cryoprecipitable IgG3 RF mAb suggests strongly that such a therapeutic approach might be successful in similar diseases in man.

Animals↗

Inhibitors of the arachidonic acid cascade dissociate 48/80-induced Ca2+ influx and Ca2+ release in mast cells.

Effects of inhibitors of the arachidonic acid cascade on Ca2+ release from intracellular stores and Ca2+ influx through the plasma membrane during stimulus-secretion coupling were examined using rat peritoneal mast cells loaded with fura-2. Compound 48/80 (48/80) was used as a secretagogue. A phospholipase inhibitor, p-bromophenacyl bromide (PBPB), or a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), inhibited the 48/80 (1 microgram/ml)-induced release of histamine, Ca2+, and Mn2+ influxes, but the cyclooxygenase inhibitor, indomethacin (approximately 50 microM), inhibited neither Ca2+ nor Mn2+ influxes. The Ca2+ release induced by 1 microgram/ml of 48/80 was little inhibited by PBPB, NDGA, or indomethacin. The Ca2+ release was activated and saturated with lower concentrations of 48/80 than was the Ca2+ influx. The percent inhibition of the Ca2+ release by 25 microM PBPB was increased by lowering the concentration of 48/80, but NDGA (10 microM) did not inhibit the Ca2+ release induced by low concentrations of 48/80 (0.03-0.1 microgram/ml). These results suggest that activation of the Ca2+ release and the Ca2+ influx were differently regulated and that full activation of Ca2+ influx needs the arachidonic acid cascade produced by higher concentrations of 48/80 than does the Ca2+ release. Lipoxygenase metabolites of arachidonic acid are potential modulators of the Ca2+ influx.

Acetophenones↗

Demonstration of antidiarrheal and antimotility effects of wood creosote.

Wood creosote administered to rats prevented castor-oil-induced diarrhea with an ED50 of 53 mg/kg p.o. This antidiarrheal effect was apparently produced by acceleration of net fluid absorption from the intestine, as shown by a 52% decrease (p < 0.001) of residual fluid volume in an intestinal loop, and partly by suppression of intestinal motility. Wood creosote also inhibited spontaneous longitudinal contractions of isolated ileal segments in rats (IC50 = 28 mg/l) and guinea pigs (IC50 = 17 mg/l). Contractions of the guinea pig ileum induced by electrical stimulation, bradykinin and acetylcholine were also inhibited dose-dependently. We conclude that wood creosote has an antidiarrheal activity and that this effect is exerted by inhibition of intestinal motility and by augmentation of net fluid absorption from the intestine.

Acetylcholine↗

Suppression of intestinal smooth muscle contraction by 4-ethylguaiacol, a constituent of wood creosote.

Wood creosote, a mixture of phenolic compounds, suppresses in vitro contractions of rat intestine. To identify a compound in wood creosote able to inhibit intestinal motility, we screened its constituent phenolic compounds and found 4-ethylguaiacol (4-EG) as an active compound. It suppressed the spontaneous phasic (IC50 = 513 +/- 48 mumol/l) as well as spasmogenic-agent-induced tonic longitudinal contractions of isolated rat ileum in a reversible and concentration-dependent manner. KCl-depolarization-induced tonic contraction, which was susceptible to a calcium channel blocking agent, was also suppressed by 4-EG with an IC50 of 433 +/- 41 mumol/l. Furthermore, calcium-ionophore-induced contraction, which was affected by an influx of extracellular calcium ion that bypassed calcium channels, was suppressed by 4-EG with an IC50 of 97 +/- 18 mumol/l. These results support the concept that the effect of wood creosote to suppress intestinal motility is attributable, partially or entirely, to its component 4-EG and that this effect of 4-EG on the intestinal muscle is produced at some stage(s) of the muscle contraction process after influx of extracellular calcium into the cytosol of smooth muscle.

Animals↗

The effect of somatostatin analogue octreotide on amylase secretion from mouse pancreatic acini.

To clarify whether somatostatin has an inhibitory effect on pancreatic acinar cells, we studied the effect of a long-acting analogue of somatostatin, octreotide, on amylase secretion from isolated mouse pancreatic acini. Octreotide (100 nM) had no inhibitory effects on amylase secretion stimulated by secretin or vasoactive intestinal polypeptide (VIP), while reducing the increase of cyclic adenosine 3',5'-monophosphate (cAMP). On the other hand, octreotide inhibited synergistic amylase secretion induced by secretin or VIP in combination with cholecystokinin (CCK). Octreotide also reduced synergistic amylase secretion by secretin or VIP in combination with calcium ionophore A23187. CCK and A23187 did not alter the increase of cAMP induced by secretin and the inhibitory effect of octreotide on cAMP production. Octreotide did not significantly inhibit amylase secretion stimulated by dibutyryl cAMP (dbcAMP) alone, but reduced synergistic amylase secretion by dbcAMP+A23187. Results obtained above reveal that octreotide has a direct inhibitory effect on amylase secretion from mouse pancreatic acini and probably affects stimulus secretion coupling at a point distal to the production of cAMP, besides inhibiting adenylate cyclase.

Amylases↗