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Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 181 records · Page 10Linked to original sources
PubMed1996

A gamma Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I.

A new type of gamma Gly-268 (GGA) to Glu (GAA) substitution has been identified in a homozygous dysfibrinogen by analyses of the affected polypeptide and its encoding gene derived from a 58 year-old man manifesting no major bleeding or thrombosis. The functional abnormality was characterized by impaired fibrin assembly most likely due to failure to construct properly aligned double-stranded fibrin protofibrils. This presumption was deduced from the following findings: (1) Factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains progressed in a normal fashion, indicating that the contact between the central E domain of one fibrin monomer and the D domain of another took place normally; (2) Nevertheless, factor XIIIa-catalyzed cross-linking of the fibrinogen gamma-chains was obviously delayed, suggesting that longitudinal association of D domains of different fibrin monomers, ie, D:D association was perturbed; (3) Plasminogen activation catalyzed by tissue-type plasminogen activator was not as efficiently facilitated by polymerizing fibrin monomer derived from the patient as by the normal counterpart. Therefore, gamma Gly-268 would not be involved in the 'a' site residing in the D domain, which functions as a complementary binding site with the thrombin-activated 'A' site in the central E domain, but would be rather involved in the D:D self association sites recently proposed for human fibrinogen. Thus, the gamma Glu-268 substitution newly identified in this homozygous dysfibrinogen seems to impair proper alignment of adjacent D domains of neighboring fibrin molecules in the double-stranded fibrin protofibril, resulting in delayed fibrin gel formation.

Afibrinogenemia↗
PubMed1996

Elevation of the plasma histamine concentration in the coronary circulation in patients with variant angina.

In the present study plasma histamine was found to be elevated in the great cardiac vein in 8 of 11 patients with variant angina but in none of 8 control patients. Although further investigation is required to determine the exact cause-and-effect relation between histamine release and provocation of spontaneous variant anginal attacks, the present study presents clinical evidence that histamine may well be related to episodes of variant angina as suggested in animal studies.

Adult↗
PubMed1996

A gene encoding a major Kunitz proteinase inhibitor of storage organs of winged bean is also expressed in the phloem of stems.

Winged bean Kunitz chymotrypsin inhibitor (WCI) accumulates abundantly in seeds and tuberous roots, and small amounts of the WCI protein and mRNA can also be detected in stems. In this study, we analyzed the localization of the WCI protein in stems of winged bean. The results demonstrated that the WCI protein was localized in sieve tubes. Furthermore, we showed that the 5' region of the WCI-3b gene, which exhibited strong transcriptional activity in developing seeds, also promoted transcription of a reporter gene in the phloem of stems of transgenic tobacco.

Fabaceae↗
PubMed1996

Relapses or reinfections: analysis of a case of Clostridium difficile-associated colitis by two typing systems.

Immunoblotting and pulsed-field gel electrophoresis of Clostridium difficile isolates were employed to differentiate reinfection by a newly acquired strain from relapse by an original strain in a 10-year-old patient with four episodes of C. difficile-associated colitis. Immunoblot typing demonstrated subserogroup K-1 of serogroup K for the first and second organisms, subserogroup A-1 of serogroup A for the third organism, and subserogroup G-4 of serogroup G for the fourth organism. PFGE analysis revealed consistent results with immunoblot analysis except that the strains from the fourth episode, whose DNA constantly degraded, were nontypable by this method. Five separate isolates of C. difficile from a specimen of each episode showed identical PFGE patterns, indicating that infections of multiple strains probably did not occur in this patient. These typing results suggested that the second episode after a 17-day course of vancomycin therapy represented a relapse by the strain causing the first episode, and that the third and fourth episodes after tapering vancomycin therapy were reinfections by other strains. Both immunoblot and PFGE typing systems are promising tools for analyzing recurrence of C. difficile infection.

Anti-Bacterial Agents↗
PubMed1996

Bradykinin and nitric oxide in infectious disease and cancer.

Vascular pathophysiology at the sites of bacterial infection and cancerous tissues share numerous common events similar to inflammatory tissue. Among them enhanced vascular permeability is the universal and hallmark event mediated by bradykinin. All 16 or more bacterial or fungal proteases we have examined activated one or more steps of the kinin generating Hageman-factor-kallikrein cascade. In the meantime, most of the microbial proteases rapidly inactivated various plasma inhibitors such as alpha 1-protease inhibitor and alpha 2-macroglobulin. In addition to the extracellular proteases, bacterial cell wall components (negatively charged LPS) of gram-negative bacteria and teichoic acid moieties of gram-positive bacteria activate the Hageman-factor-kallikrein system and exert hypotensive effects via kinin generation. Endotoxin (LPS) also induces nitric oxide synthase (NOS) which appears to exhibit a rather slow, but significant, effect in relaxing the vascular tone of the infected animal (thus hypotension). Furthermore, bacterial proteases can activate the matrix metalloproteinase (collagenase) resulting in exacerbation of tissue injury in the diseased animal. Many tumor cells or tissues excrete plasminogen activator, and hence activate plasminogen. The plasmin thus generated activates procollagenases, as well as the Hageman-factor-kallikrein system, resulting in pronounced extravasation. Fluid accumulation in pleural and ascitic carcinomatoses is largely due to the activated bradykinin-generating system. We can also demonstrate and control enhanced vascular permeability using kallikrein inhibitors, especially the polymer-conjugated soybean trypsin inhibitor which exhibits a prolonged plasma t1/2, kinin antagonists, NOS inhibitors, NO scavengers, inhibitors of prostaglandins and others. Bacterial proteases induce shock in mice which can be prevented by the soybean trypsin inhibitor by blocking the kallikrein-kinin cascade. Therapeutic use of kinin antagonists and a kallikrein inhibitor has been made for infectious diseases such as septicemia and in tumor pathology.

Animals↗
PubMed1996

Further evidence of bradykinin involvement in septic shock: reduction of kinin production in vivo and improved survival in rats by use of polymer tailored SBTI with longer t1/2.

Involvement of bradykinin in septic shock and its therapeutic endeavor using soybean trypsin inhibitor (SBTI, Kunitz type) were investigated in an in vivo model of septic shock induced by pseudomonal elastase. Pseudomonal elastase injection at 0.5 mg/kg i.v. to guinea pigs resulted in elevation level of bradykinin in the blood from < 1 ng/ml to 25 ng/ml which was accompanied by a drop of mean arterial blood pressure (MABP) (about 45 mmHg). When native soybean trypsin inhibitor (SBTI, Kunitz type, 20 kDa) was injected, into this model, induction of bradykinin generation and hypotension by the bacterial protease treatment was completely obliterated as judged by the both levels of bradykinin and MABP. Specifically, by the treatment with SBTI, bradykinin levels did not increase and the drop of the blood pressure was minimal (< 10 mmHg) in this time frame (< 30 min). We designed and prepared succinylated gelatin-conjugated SBTI (suc-gel SBTI) with enlarged molecular mass (M(r) approximately 110,000) and higher area under the curve of the plasma concentration, which exhibits about 6 times longer plasma half-life (t1/2) and about 4 times larger area under the curve of plasma concentration. Suc-gel-SBTI suppressed the pseudomonal protease-induced shock much more effectively than native SBTI, the conjugate exhibited its effect for more than 3 h, while the native SBTI showed the effect only within 2 h after i.v. injection.

Animals↗
PubMed1996

Hodgkin disease occurring in a patient with extremely high serum antibody titers to Epstein-Barr virus--associated antigens without chronic illness.

PURPOSE: We described for the first time a patient with long-lasting, extremely high serum antibody titer against Epstein-Barr virus (EBV) viral capsid antigen and early antigen without clinical symptoms suggestive of active EBV infection; the patient finally developed Hodgkin disease (HD) after 7 years of follow-up. PATIENT AND METHODS: High serum EBV antibody titers were noted at 2 years of age. Immunological evaluation was performed at the age of 7 years. EBV-specific cytotoxic T-lymphocyte activity was normal. None of the other results showed any significant abnormalities except for the abnormal antibody titers against EBV-associated antigens. RESULTS: The patient developed HD at the age of 9 years. In addition, EBV genomes were found in the nuclei of Hodgkin and Reed-Sternberg cells in the lymph node. CONCLUSIONS: This case suggests that (a) a patient with extremely high serum antibody titers against EBV-associated antigens may develop HD after a prolonged period, even though no clinical symptom suggestive of active EBV infection is observed; (b) EBV may play an important role in the occurrence of HD.

Antigens, Viral↗
PubMed1996

Bradykinin generation triggered by Pseudomonas proteases facilitates invasion of the systemic circulation by Pseudomonas aeruginosa.

To elucidate the mechanism of bacterial exoprotease in promotion of the intravascular dissemination of Pseudomonas aeruginosa, we examined the possible involvement of bradykinin (whose generation is induced by pseudomonal proteases in septic foci) in the invasion by bacteria, and in access of bacterial toxins to systemic blood circulation. P. aeruginosa 621 (PA 621), which produces very little protease, was injected intraperitoneally into mice together with pseudomonal exoproteases (elastase/alkaline protease). Dissemination of bacteria from the peritoneal septic foci to the blood was assessed by counting viable bacteria in the blood and spleen by use of the colony-forming assay. The results showed that pseudomonal proteases markedly enhanced (10- to 100-fold) intravascular dissemination of bacteria in mice. This enhancement was induced not only by pseudomonal proteases but also by bradykinin. More importantly, the increased spread of PA 621 induced by pseudomonal protease and bradykinin was significantly augmented by the addition of kininase inhibitors, indicating the direct involvement of bradykinin in bacterial dissemination. Similarly, bradykinin caused effective dissemination of pseudomonal toxins such as endotoxin (lipopolysaccharide) and exotoxin A when the toxins were injected into the peritoneal cavity with bradykinin. Furthermore, the lethality of the infection with PA 621 was strongly enhanced by pseudomonal proteases given i.p. simultaneously with PA 621. On the basis of these results, it is strongly suggested that pseudomonal proteases as well as bradykinin generated in infectious foci are involved in facilitation of bacterial dissemination in vivo.

Animals↗
PubMed1996

Comparison of two fetal growth curves in screening for high-risk neonates.

The International Statistical Classification of Diseases and Related Health Problems (ICD-10) defines the 10th percentiles on the fetal growth curve as the cutoff point for light- and small-for-gestational-age infants, instead of the mean bodyweight -1.5 standard deviation (SD) on the fetal growth curve, which has been used in Japan since 1983. Data on a 5260 sample of term neonates who were born during the 30-month period between January 1993 and June 1995 were obtained. The clinical usefulness of the 10th percentiles and mean bodyweight -1.5 SD cutoff on the fetal growth curve as screening criteria for high-risk neonates of light- and small-for-gestational-age infants was evaluated. There was a statistically significant higher morbidity rate among the neonates whose birthweight was below mean bodyweight -1.5 SD than for those whose birthweight was below the 10th percentile cut off. But there was no significant difference between the morbidity rate of neonates whose birthweight was between mean bodyweight -1.5 SD and the 10th percentile cutoff and the morbidity rate of neonates whose birthweight was above the 10th percentile cutoff. Therefore, mean bodyweight -1.5 SD on the fetal growth curve is a more effective means of screening for high-risk light- and small-for-gestational-age infants than the 10th percentile cutoff on the fetal growth curve.

Birth Weight↗
PubMed1996

Dexamethasone and bacterial meningitis in Pakistan.

The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.

Ampicillin↗
PubMed1996

Postabsorptive factors are important for satiation in rats after a lipid meal.

We examined satiation after intraduodenal infusion of triglyceride with or without Pluronic L-81 (L-81) in rats. L-81 suppresses lipid transport into mesenteric lymph by preventing the formation of chylomicrons. Under unrestrained conditions, a lipid emulsion was infused into 24-h fasted rats intraduodenally for 8 h. After the infusion, food intake during the first 30 min and blood samples were measured. Food intake after the 8-h lipid infusion decreased significantly (-75%) compared with that of rats infused with vehicle only, and the effect of the lipid meal was time dependent. The satiation effect of the lipid was lost as a result of L-81 treatment, but food intake was still significantly decreased (-22%). The loss of inhibition of food intake by the feeding of lipid plus L-81 was totally reversed by the cessation of L-81 infusion. In rats infused with the lipid emulsion, plasma levels of triglyceride and apolipoprotein A-IV increased significantly. This increase was abolished by the presence of L-81 in the lipid infusate. The present study indicates that postabsorptive factors are important for anorexia observed after a lipid meal in addition to preabsorptive factors. This study further supports our previous conclusion that apolipoprotein A-IV is an important postabsorptive factor for satiation after a lipid meal.

Animals↗
PubMed1996

[A case of advanced esophageal cancer showing good partial response by combination therapy of low dose 5-FU and low dose CDDP].

A 66-year-old man with a complaint of dysphagia was diagnosed as advanced esophageal cancer. Barium swallow examination of the esophagus showed a narrowing 10 cm in length at Ei (type 3), and biopsy specimen from the lesion on endoscopic examination revealed adenosquamous carcinoma. Multiple lymph node metastasis were detected by CT scan. He was treated with a combination of low dose 5-fluorouracil (5-FU) and low dose cisplatin (CDDP). The regimen consisted of 5-FU (300 mg/body/day continuous infusion) and CDDP (10 mg/body/day continuous infusion) for 3 weeks. After 2 courses of this regimen, his symptoms disappeared, and only mild irregularity of the esophageal wall remained on Barium swallow examination. The effect of the therapy was evaluated as a partial response. No side effect was observed. From this case, the possibility that CDDP is able to function as a biochemical modulator for 5-FU was suggested.

Aged↗
PubMed1996

[A case of advanced gastric cancer with lung and liver metastasis treated by CDDP and 5-FU].

A 62-year-old man suffering from advanced gastric cancer with multiple lung and liver metastasis was treated with FP (CDDP . 5-FU) therapy. As a result, lung metastasis disappeared completely and liver metastasis was significantly reduced in size (93%). Then, total gastrectomy, splenectomy and micro-wave-coagulation of the liver tumors were performed. Therefore, it can be said that FP therapy is an effective neoadjuvant chemotherapy.

Adenocarcinoma↗
PubMed1996

[Pregnancy outcome in long-term survivors with adult acute leukemia, malignant lymphoma and breast cancer].

By means of a mail questionnaire, we evaluated the influence of treatment for acute leukemia on offspring of long-term survivors and determined whether pregnancy in patients (or spouses) induced relapse of acute leukemia. In 322 replies from the 445 institutions where a questionnaire was sent, there were 1,136 adult long-term survivors. We analyzed 43 adults who had become pregnant or a father after postremission therapy. The mean age at leukemia onset was 26.4 and 21.6 years for males and females, respectively. Forty-six normal children (26 boys and 20 girls) were born to long-term survivors including 7 pairs of siblings and a pair of twin sisters. There were no malformed babies. The average duration until delivery was 79 months after diagnosis and 49 months after the final postremission therapy. Four of 38 parents of live offspring died (3 relapse, 1 other disease), and the other 34 parents of live offspring were in complete remission at the point of this survey. The literature since 1986 (except case report) was reviewed for the current situation of pregnancy outcome in long-term survivors after chemotherapy for adult acute leukemia, malignant lymphoma and breast cancer.

Acute Disease↗
PubMed1996

[Treatment outcome of 288 cases of renal cell carcinoma].

The clinical outcome was analyzed on 288 patients with renal cell carcinoma who were admitted to the Niigata Cancer Center Hospital during the 33 years from 1961 to 1993; 254 patients had had nephrectomy and 244 of them had undergone curable operations. The survival rate was calculated by the Kaplan-Meier method. The 3-, 5- and 10-year survival rates by all causes of death in all 288 patients were 64.8, 55.9 and 36.4%, respectively. According to the stage based on the general rules for clinical and pathological studies on renal cell carcinoma (The 2nd Edition), the 5-year survival rate was 89.5, 78.7, 51.1 and 13.7% for stages I (n = 31), II (n = 128), III (n = 38) and IV (n = 83), respectively. The 5-year survival rate for the patients (n = 88) from 1961 to 1985 was 40.9%, while the rate for the patients (n = 200) from 1986 to 1993 was 64.3%. This improvement of survival rate for the patients after 1986 was brought by the increase of the stage I or II cases and by the improvement of the survival in the stage III cases after 1986. The 5-year disease-specific survival rate for the patients over 50 years old was 55.5%, while the rate for the patients under 50 years old was 83.6%. Female, low pT, low grade and small tumor size were proven to be favourable prognostic factors in renal cell carcinoma.

Adult↗
PubMed1996

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral↗