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S Okamoto

Publications and source records attributed to S Okamoto.

At least 361 records · Page 20Linked to original sources
PubMed1995

Plasma endotoxin in typhoid fever.

Plasma endotoxin contents of the patients with sepsis or typhoid fever were measured by two sophisticated chromogenic limulus tests; Endospecy and Toxicolor tests. Endospecy test is the endotoxin-specific test and Toxicolor is responsible for both endotoxin and (1,3)-beta-D-glucan. Plasma was pretreated by our new PCA method which resolved the problem as to the detection of a lesser amount of plasma endotoxin when pretreated by the conventional PCA method. Although Toxicolor values have been reported to exceed more than the Endospecy value, under complicated pathophysiological situations, almost all specimens of these patients had a similar value, except in one expired septic shock case. In 18 typhoid fever cases, Salmonella typhi was isolated only from the bile in 5 cases, however endotoxemia occurred in 11 cases (61.1%). Within the first 4 days, the incidence of endotoxemia was higher (10/14, 71.4%). These results suggest that endotoxin assay seemed to be a useful tool for the diagnosis of typhoid fever.

Bacteremia↗
PubMed1994

Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma.

BACKGROUND: Several uncontrolled trials have suggested that dose intensity of chemotherapy is a crucial determinant of treatment outcome for patients with non-Hodgkin's lymphoma (NHL). To explore the possibility of increasing dose intensity, a dose-escalation study of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) using recombinant human granulocyte colony stimulating factor (rhG-CSF) was initiated. METHODS: First, the feasibility of standard dose CHOP (750 mg/m2 cyclophosphamide intravenously [i.v.] on Day 1;50 mg/m2 doxorubicin i.v. on Day 1; 1.4 mg/m2 vincristine i.v. on Day 1; and 100 mg/body prednisolone orally on Days 1-5) repeated biweekly at the original dose was assessed. rhG-CSF was given subcutaneously at doses of 2-5 micrograms/kg every day or every other day on Days 3-13. The safety of increasing the dose of cyclophosphamide during biweekly CHOP then was tested. Besides the standard dose (750 mg/m2), two dose levels of cyclophosphamide were set (1200 mg/m2 and 1500 mg/m2 in patients younger than 61 years of age, and 1200 mg/m2 in patients 61-75 years old). RESULTS: Twenty-seven patients with NHL who had received minimal or no previous treatment were enrolled in this study. In the 750 mg/m2 group, 9 patients received 3-6 cycles of treatment (mean, 3.9 cycles), in the 1200 mg/m2 group, 10 patients received 3-6 cycles (mean, 4.8), and in the 1500 mg/m2 group, all 8 patients received 6 cycles. No significant differences among the groups were observed in the extent and the duration of neutropenia in each cycle, and a leukocyte count of more than 3000/microliters on Day 15 was achieved in all 131 cycles. Hemoglobin values and platelet counts, however, decreased in the later cycles in the 1500 mg/m2 group. Two patients were hepatitis-B virus carriers, one of whom died of fulminant hepatitis after completion of six cycles. Another patient developed a transient increase of transaminases after the second cycle. One other patient developed Grade 4 mucositis (World Health Organization scale). The numbers of patients who achieved complete and partial responses, respectively, were 4 (50%) and 2 (25%) in the 750 mg/m2 group, 8 (80%) and 2 (20%) in the 1200 mg/m2 group, and 8 (100%) and 0 (0%) in the 1500 mg/m2 group. CONCLUSIONS: The dose of cyclophosphamide in biweekly CHOP can be increased up to 1500 mg/m2 with no increase in the incidence of treatment-related early mortalities without any organ damage in younger patients. The efficacy of this dose intensification of CHOP currently is being investigated in a multicenter prospective randomized trial using three different dose levels of cyclophosphamide.

Adult↗
PubMed1994

Imposing deviant immunity on the presensitized state.

Delayed hypersensitivity (DH) is an important immune effector modality that successfully wards off intracellular pathogens and many parasites, but also causes immunopathogenic injury to vital tissues. Particularly in the eye, DH has devastating effects that can lead to blindness. Ags injected into the anterior chamber of the eye of naive mice elicit a deviant form of systemic immunity in which DH is selectively down-regulated. Expression of DH in this model system is curtailed by regulatory CD8+ T cells. At present, we have determined whether injection of Ag into the anterior chamber of eyes of specifically sensitized mice also impairs DH expression. Our results indicate that DH is blunted or eliminated in previously primed mice when heterologous proteins, retinal autoantigens, or minor histocompatibility Ags are injected into the anterior chamber. Suppression is achieved in this system by Ag-specific CD8+ T cells, and failed DH can be imposed on immunized mice by i.v. injections of peritoneal exudate cells pulsed with Ag in vitro in the presence of TGF-beta. Thus, the immune regulatory mechanisms that operate to protect the eye from immunogenic inflammation can be invoked in previously sensitized mice. In addition, tolerance could not be generated in presensitized mice by either i.v. injection of soluble Ag or painting of hapten on UVB-exposed skin. It seems that the strategies used by the eye to create a deviant state of immunity in the face of pre-existing conventional immunity may be unique.

Animals↗
PubMed1994

Novel mechanism of glucocorticoid-mediated gene repression. Nuclear factor-kappa B is target for glucocorticoid-mediated interleukin 8 gene repression.

A glucocorticoid, dexamethasone, inhibited the production of a leukocyte chemotactic cytokine, interleukin 8 (IL-8), as well as mRNA expression by a glioblastoma cell line, T98G, stimulated with interleukin 1 (IL-1). Dexamethasone also inhibited IL-8 promoter-driven chloramphenicol acetyltransferase (CAT) activities induced by IL-1, suggesting that dexamethasone inhibited IL-8 production mainly at the transcriptional level. Moreover, CAT assay revealed that the nuclear factor-kappa B (NF-kappa B) binding site was the crucial cis-element required for conferring IL-1 responsiveness in conjunction with the CCAAT enhancer binding protein/nuclear factor-IL-6 (NF-IL6) and/or the AP-1 binding site(s). Mutation of either the AP-1 or NF-IL6 binding site did not abolish IL-8 gene repression by dexamethasone, suggesting that these sites were not targets for dexamethasone. Trimerized kappa B sequence in the IL-8 gene was enough for conferring the induction by IL-1 and inhibition by dexamethasone of CAT activity. Finally, dexamethasone diminished the IL-1-induced formation of NF-kappa B complexes, which were identified immunochemically to consist of p50 and p65, without reducing the amount of translocated factors. Collectively, dexamethasone interfered with the binding of the most essential transcription factor, NF-kappa B, to its cognate cis-element, thereby suppressing the transcription of IL-8 gene.

Amino Acid Sequence↗
PubMed1994

The interleukin-8 AP-1 and kappa B-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization.

FK506, an immunosuppressant, inhibits the production of several cytokines in T lymphocytes. We observed that FK506 suppressed the transcription of a chemotactic cytokine, interleukin-8 (IL-8) in a human T cell line, Jurkat cells, activated by phorbol 12-myristate 13-acetate (PMA) and calcium (Ca2+) ionophore (ionomycin). By deleted and mutated analysis of the IL-8 promoters, the AP-1 and kappa B-like sites were identified as the responsive elements for PMA and ionomycin. FK506 suppressed the transcriptions through the AP-1 or kappa B-like sites induced by PMA plus Ca(2+)-mobilizing agents, but not those induced by Ca(2+)-independent stimuli. In gel retardation analysis, FK506 had little effect on the binding to the AP-1 site of PMA/ionomycin-induced nuclear factors, which were recognized with anti-JunD or c-Fos antibody. In contrast, FK506 or EGTA (Ca2+ chelator) similarly affected the formation of kappa B-like site binding complexes, which were not recognized by any antibodies against the human Rel family proteins (c-Rel, p65, p50, and p49). Furthermore, we confirmed the previous report that FK506 suppressed the PMA/ionomycin-induced activation through authentic kappa B site of immunoglobulin (Ig) gene, to which NF-kappa B binding was also decreased by FK506, indicating that both IL-8 kappa B-like site and Ig kappa B site are FK506-sensitive in spite of the difference of binding factors. Our results indicate that not only the reported IL-2 NF-AT and NFIL-2A sites and Ig kappa B site, but also the IL-8 AP-1 and kappa B-like sites are terminals of FK506-sensitive pathway involving Ca2+ mobilization.

Base Sequence↗
PubMed1994

Triiodothyronine resuscitates the impaired liver function after Pringle's maneuver.

OBJECTIVE: To evaluate the changes in thyroid hormone levels and the effectiveness of exogenous triiodothyronine (T3) in shock caused by prolonged use of Pringle's maneuver (cross-clamping of hepatic triads). DESIGN: Pringle's maneuver was performed on dogs for 1 hour. In the T3 group (n = 7), 1 microgram/kg per hour of T3 was administered intravenously for 3 hours after declamping. In the control group (n = 7), the same volume of saline solution without T3 was administered. MAIN OUTCOME MEASURES: Serum T3, reverse T3, thyroxine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the ketone body ratio (AKBR), which reflect the hepatic energy charge, were measured. Tissue blood flow, tissue blood velocity, and tissue blood mass of the liver were measured by means of a laser Doppler flowmeter. Oxygen saturation of the hemoglobin in the liver tissue was measured by tissue near-infrared spectroscopy. Dogs were observed until the seventh postoperative day. RESULTS: In the control group, the low T3 syndrome was observed. None of the dogs recovered from the shock and none survived for more than 24 hours. In the T3 group, all dogs recovered from the shock and survived. In the control group, hepatic tissue blood flow and oxygen saturation of hemoglobin in liver tissue were decreased, and the AKBR was deteriorated. In the T3 group, however, these parameters were markedly improved. CONCLUSION: It is suggested that T3 administration is beneficial in managing the critical resuscitation period of liver function after Pringle's maneuver is performed in dogs.

Alanine Transaminase↗
PubMed1994

Effect of biliary drainage on serum 7 alpha-hydroxycholesterol level in patients with obstructive jaundice.

Percutaneous transhepatic biliary drainage was performed in 15 patients with obstructive jaundice and the serum 7 alpha-hydroxycholesterol level was monitored for 2 weeks by capillary gas-liquid chromatography-mass spectrometry. Before biliary drainage, the serum 7 alpha-hydroxycholesterol level was 130 +/- 52 pmole/ml, which was significantly lower than the normal value (238 +/- 100 pmole/ml). After biliary drainage, the serum 7 alpha-hydroxycholesterol level was decreased to 117 +/- 48 pmole/ml on the first day. There were two groups of patients as classified by the behavior of the serum 7 alpha-hydroxycholesterol level after the third day. In one group of patients (responders), the serum level increased significantly up to 525 +/- 83 pmole/ml at the end of the 2 weeks. In another group (nonresponders), the serum level did not increase and remained 145 +/- 86 pmole/ml. The serum bilirubin level tended to improve faster in the responders (decline index = -0.234 +/- 0.152) than in the nonresponders (decline index = -0.057 +/- 0.067; P < 0.05) and a statistically significant correlation was found between the decline index and the total 7 alpha-hydroxycholesterol level on Days 7 or 14. As the serum 7 alpha-hydroxycholesterol level is considered to reflect hepatic bile acid synthesis, which is one of the important functions of the liver, we conclude that the increased serum 7 alpha-hydroxycholesterol level after biliary drainage in the responders indicates recovered liver function and that the low serum level in the nonresponders suggests more severe hepatocellular damage in patients with obstructive jaundice.

Aged↗
PubMed1994

Effects of pravastatin and ursodeoxycholic acid on cholesterol and bile acid metabolism in patients with cholesterol gallstones.

To investigate the effects of pravastatin and ursodeoxycholic acid (UDCA) on cholesterol and bile acid metabolism in humans, 41 patients with cholesterol gallstone disease were allocated to four groups and treated with pravastatin (20 mg/day), UDCA (600 mg/day), both pravastatin and UDCA, or neither drug (control) for 1-2 weeks prior to elective cholecystectomy. Cholesterol 7 alpha-hydroxylase activity and serum levels of total 7 alpha-hydroxycholesterol were significantly increased by pravastatin and unaffected by UDCA. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was markedly increased by pravastatin and decreased by UDCA. UDCA significantly decreased biliary cholesterol concentration and the cholesterol saturation index and prolonged the nucleation time; however, pravastatin alone had little effect on biliary lithogenicity. Serum total and low-density lipoprotein (LDL)-cholesterol levels were reduced most by the combined administration of pravastatin and UDCA. In conclusion, at a dose of 20 mg/day, pravastatin increased bile acid synthesis but did not decrease biliary lithogenicity. UDCA had no significant effect on bile acid synthesis, but markedly decreased biliary lithogenicity.

Adult↗
PubMed1994

Evolutionary conservation of chymotrypsinogen gene: genomic analysis and protein modeling.

Chymotrypsinogen is widely present in various animal pancreases. To study evolutionary relationship of chymotrypsinogen gene in species, we used a cDNA probe of human prechymotrypsinogen to investigate the species distribution of chymotrypsinogen gene, and designed oligodeoxynucleotide primers to investigate the genomic organization in the three domains of active sites. The genomic analyses showed that chymotrypsinogen gene is evolutionary conserved in species. On the basis of the deduced amino acid residues, a three-dimensional model for human chymotrypsinogen was further built by computer graphics. The model showed high similarity to the X-ray crystal structure of bovine chymotrypsinogen A, thus, demonstrated that the three-dimensional structure is more conserved in evolution than protein sequences.

Animals↗
PubMed1994

Cerebral vasospasm caused by cisternal injection of polystyrene latex beads in rabbits is inhibited by a serine protease inhibitor.

During subarachnoid hemorrhage (SAH), coagulated blood in the subarachnoid space may be regarded as foreign by the immune system. To investigate how cerebral arteries are affected by activation of the host immune system, foreign body, polystyrene latex beads were injected into the cerebrospinal fluid (CSF) space of rabbits, and the caliber changes of the basilar arteries were studied for 7 days by angiography. Prolonged arterial narrowing peaking on day 2 was observed after cisternal injection of the beads. The increase in peak narrowing correlated with an increase in the number of beads injected. The course of the change in vessel caliber over 7 days was similar to that seen in cerebral vasospasm caused by SAH. Also investigated was the preventive effect of the synthetic serine protease inhibitor, FUT-175 on the arterial narrowing caused by the cisternal injection of the latex beads. The administration of FUT-175 significantly prevented latex beads-induced vasospasm (p < 0.01). The possible role of a non-specific immune response is discussed, and also the role of the serine protease cascades in the development of cerebral vasospasm.

Animals↗
PubMed1994

Effects of protease inhibitor and immunosuppressant on cerebral vasospasm after subarachnoid hemorrhage in rabbits.

The possible role of the immune-defense system in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. We used a synthetic serine protease inhibitor, gabexate mesilate (GM), a glucocorticoid, betamethasone sodium phosphate (B-P), and an immunosuppressant, ciclosporin (Cyclosporin A, CYA), to prevent cerebral vasospasm. These agents were administered intra-venously every 12 hours for three injections, starting 20 minutes after SAH. In the group treated with GM, B-P, or CYA, there were no statistically significant differences in arterial calibers between treated and untreated controls on day 2. The synthetic serine protease inhibitor, FUT-175 has been reported to prevent cerebral vasospasm when the treatment is started 20 minutes after SAH in rabbits [38]. In rabbits treated with FUT-175 at different starting times from 3 to 6 hours, reductions in arterial caliber on day 2 were significantly prevented in each group. The contrasting effects of the two serine protease inhibitors, GM and FUT-175, are discussed.

Animals↗
PubMed1994

Serum 7 alpha-hydroxycholesterol reflects hepatic bile acid synthesis in patients with obstructive jaundice after external biliary drainage.

To examine the hypothesis that serum levels of 7 alpha-hydroxycholesterol reflect bile acid synthesis in the liver, we analyzed serum 7 alpha-hydroxycholesterol and bile acid output in 13 patients with obstructive jaundice after relief of biliary obstruction. Before biliary drainage, the serum level of 7 alpha-hydroxycholesterol was 92 +/- 12 pmol/ml (mean +/- S.E.M.) and was significantly lower than the control value (226 +/- 26 pmol/ml, p < 0.01). After biliary drainage, serum 7 alpha-hydroxycholesterol level and biliary bile acid outputs began to rise in some patients, indicating reversible liver dysfunction. In other patients, serum 7 alpha-hydroxycholesterol levels and bile acid outputs did not increase, suggesting severe or irreversible liver dysfunction. On and after the third day of biliary decompression, serum 7 alpha-hydroxycholesterol levels correlated well with bile acid excretion (p < 0.01, r = 0.93). Other liver function parameters, such as serum bilirubin, serum bile acids, albumin, and bile flow, also revealed significant correlation with serum 7 alpha-hydroxycholesterol levels. We conclude that the serum 7 alpha-hydroxycholesterol level clearly reflects bile acid synthesis in the liver and that it may serve as a useful parameter for the assessment of hepatic functional recovery in patients with obstructive jaundice after biliary drainage.

Aged↗
PubMed1994

Comparison of energy metabolism during the growing period in quail lines selected for body weight.

1. The present study was conducted to compare body weight, daily weight gain, relative growth rate, food intake, food conversion efficiency, abdominal fat weight, thyroid weight, plasma T4 concentration, body temperature, oxygen consumption, carbon dioxide production and heat production among three Japanese-quail lines selected for body weight: a random bred line (RR) and lines for large (LL) or small (SS) body weight. 2. T4 concentration increased in the order SS, RR, LL in both sexes and did not vary significantly between sexes; the SS line had a significantly higher value than that of the LL line. 3. The body temperatures of SS, RR and LL lines were 42.45, 42.03 and 41.25 degrees C in males, and 42.7, 42.03 and 41.63 degrees C in females. 4. The oxygen consumptions of SS, RR and LL lines were 63.4, 46.0 and 43.8 ml/kgW0.75 min. in males, and 61.4, 44.8 and 37.2 in females. The value for SS was significantly higher than those of RR and LL lines in both sexes (P < 0.01). The carbon dioxide productions of SS, RR and LL lines were 31.8, 33.8 and 27.3 ml/kgW0.75 min. in males, and 31.2, 31.9 and 27.3 in females. In both sexes, that of the LL line was significantly lower than those of the SS and RR lines (P < 0.01). 6. The heat productions of SS, RR and LL lines were 1.178, 0.994 and 0.842 kJ/kgW0.75 min. in males, and 1.142, 0.879 and 0.736 in females. In both sexes, the heat production of the SS line was higher than those of the RR and LL lines (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Polyarthritis associated with hepatitis C virus infection.

Two cases of polyarthritis associated with hepatitis C infection are reported. In Patient 1, stiffness and polyarthritis occurred during the acute stage of hepatitis. The arthritic symptoms lasted for 4 months. A transient polyarthritis recurred 4 yr later. The persistent presence of anti-hepatitis C viral antibodies was noted. Hepatitis C viral RNA (HCV RNA) was identified in the serum using the polymerase chain reaction proving that the patient was a carrier. In Patient 2, polyarthritis occurred associated with chronic hepatitis C liver disease. Synovial biopsy showed infiltration of mononuclear cells. HCV RNA was demonstrated in both serum and SF. These cases suggest an aetiologic association between arthritis and hepatitis C antigenaemia.

Adult↗
PubMed1994

Relationship between Helicobacter pylori infection and gastric acid secretion in young healthy subjects.

We studied the relationship between Helicobacter pylori (H. pylori) infection and gastric acid secretion, along with fasting serum gastrin levels, in 55 asymptomatic healthy volunteers under 30 years old (29 H. pylori-positive, 26 H. pylori-negative). Mean scores of antral gastritis were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. There was no significant difference in both basal and maximal acid output between H. pylori-positive and H. pylori-negative subjects. Fasting serum gastrin levels were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Sex did not significantly affect gastritis scores, gastric acid secretion, or fasting serum gastrin levels, although maximal acid output was slightly higher in H. pylori-negative men than in H. pylori-positive men. Our results suggest that H. pylori infection has no direct effect on gastric acid secretion in young healthy subjects, although it induces hypergastrinemia.

Adult↗