Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 19 recordsLinked to original sources

PubMed1992

Reversible interactions between plasminogen activators and plasminogen activator inhibitor-1.

We have shown that the urokinase (UK) kringle domain contains a high-affinity plasminogen activator inhibitor-1 (PAI-1) binding site, responsible for the 10-fold faster complex formation between UK and PAI-1 than between PAI-1 and low-molecular-weight urokinase (LMWUK). Complex formation between UK and PAI-1, but not between LMWUK and PAI-1, was suppressed 10-fold in the presence of peptide U-107 derived from the UK kringle domain. Peptide U-373 derived from the UK catalytic domain slowed complex formation between UK and PAI-1 and also LMWUK and PAI-1. Inactivation of tissue-type plasminogen activator (tPA) by PAI-1 was slowed 10-fold in the presence of peptides derived from the tPA finger and kringle-2 domains. DFP-inactivated (DIP) UK and both forms of DIP-tPA inhibited PAI-1 binding to U-107 and to U-373 whereas single-chain urokinase-type PA (scuPA) was unable to compete with either peptide for PAI-1 binding. These data suggest that the reversible PAI-1 binding site in the UK A-chain plays a role in the rapid association with PAI-1 as important as those that reside in the tPA A-chain and that reversible PAI-1 binding sites are expressed on the surface of UK upon conversion from scuPA, in contrast to tPA.

Amino Acid Sequence↗

PubMed1992

TFC-612, a prostaglandin E1 derivative, enhances fibrinolytic activity in rats.

TFC-612 inhibited thrombus formation on wire coils inserted into the lumen of the inferior vena cava of rats after 5 oral doses of 1.0 and 3.2 mg/kg and subcutaneous doses of 1.0 and 3.2 micrograms/rat/hr. This compound showed slight inhibition of platelet aggregation induced by collagen at 1.0 and 3.2 mg/kg (po) and significant inhibition at 10 mg/kg. TFC-612 had no effect on the plasma coagulation system at 3.2 mg/kg. Conversely, oral doses of 0.32-3.2 mg/kg dose- dependently enhanced fibrinolytic activity as measured by euglobulin clot lysis time and lysis area on fibrin plates by euglobulin fraction. TFC-612 did not enhance fibrinolytic activity in vitro. These results suggest that the enhancement of fibrinolytic activity by TFC-612, which may be due to an increase in tissue plasminogen activator release or reduction of plasminogen activator inhibitors release, contributes to its inhibition of thrombus formation.

Alprostadil↗

PubMed1992

Does an increase in prostaglandin E2 in the blood circulation contribute to a febrile response in rabbits?

We investigated the effect of intravenous injection of human recombinant interleukin-1 beta (IL-1) on rectal temperature and prostaglandin E2 concentration in venous and arterial blood and in the push-pull perfusate in the third ventricle of rabbits. Changes in plasma prostaglandin E2 concentration in blood obtained from the marginal ear vein paralleled changes in body temperature during both monophasic and biphasic fevers. The plasma concentration of prostaglandin E2 in blood obtained from the jugular vein increased during the first phase of the biphasic fever. However, no increase in the prostaglandin E2 level in the carotid arterial blood was observed during the biphasic fever. The levels of prostaglandin E2 in the push-pull perfusate in the third ventricle were markedly elevated during both monophasic and biphasic fevers. Intracarotid infusion of prostaglandin E2 did not produce a fever nor result in a change in the prostaglandin E2 concentration of the push-pull perfusate in the third ventricle. The present results suggest that prostaglandin E2 from the blood circulation does not contribute to fever production in rabbits.

Animals↗

PubMed1992

Hodgkin's disease of the maxillary gingiva. A case report.

A case of extranodal Hodgkin's disease limited to the maxillary gingiva is presented. After appropriate staging procedures, treatment consisted of chemotherapy. The patient is alive and free of disease 2.10 years after initial presentation.

Gingival Neoplasms↗

PubMed1992

Interactions between the finger and kringle-2 domains of tissue-type plasminogen activator and plasminogen activator inhibitor-1.

We have shown that plasminogen activator inhibitor-1 (PAI-1) inhibits the fibrin binding of both the single chain and two chain forms of tissue-type plasminogen activator (tPA) through two different mechanisms. PAI-1 inhibits the finger domain-dependent fibrin binding of diisopropylfluorophosphate-inactivated single chain tPA and the kringle-2 domain-dependent fibrin binding of diisopropylfluorophosphate-inactivated two chain tPA. In accordance with the data, preformed complexes of single chain tPA/PAI-1 and of two chain tPA/PAI-1 lost the fibrin binding abilities mediated by the finger and kringle-2 domains, respectively. These effects of PAI-1 appear to be mediated by steric hindrance of the fibrin binding sites after PAI-1 binding to adjacent regions in the functional domains of tPA. We thus propose a model in which a PAI-1 binding site resides in the finger domain of a single chain, and plays a role in the reversible association of single chain tPA and PAI-1. Conformational changes may take place during the conversion of single chain tPA to two chain tPA, resulting in burying of the original PAI-1 binding site and exposure of an alternate PAI-1 binding site on the surface of the kringle-2 domain.

DNA-Binding Proteins↗

PubMed1992

Structure and regulated expression of Kunitz chymotrypsin inhibitor genes in winged bean [Psophocarpus tetragonolobus (L.) DC].

We analyzed the structure and the expression of Kunitz chymotrypsin inhibitor (WCI) genes in winged bean. WCI was encoded by a multigene family which comprised at least seven members. From their primary structures, four genes (WCI-2, WCI-3a, WCI-3b, and WCI-x) were expected to be functional ones and the other three (WCI-P1, WCI-P2, and WCI-P3) to be pseudogenes. The nucleotide sequences of the WCI-3a and WCI-3b genes were nearly identical, and they encoded the WCI-3 protein, the major chymotrypsin inhibitor in seeds. The WCI-2 gene also encoded the chymotrypsin inhibitor found in seeds and the WCI-x gene was expected to encode an unidentified chymotrypsin inhibitor. WCI messenger RNA and protein accumulated mainly in developing seeds and tuberous roots, small amounts of WCI mRNA being present in stems and pericarps. In seeds, transient accumulation of WCI mRNA was observed during the seed maturation period. These results suggest that the expression of WCI genes is regulated organ-specifically and developmentally in winged bean.

Amino Acid Sequence↗

PubMed1992

Running training attenuates the ACTH responses in rats to swimming and cage-switch stress.

The present study was carried out to investigate the effect of running training on adrenocorticotrophic hormone (ACTH) response in rats to swimming or cage-switch stress to determine whether, after physical training, a cross-adaptation develops in the ACTH responses induced by different types of stresses. Rats were trained by two different kinds of exercises and for two different periods of training: 1) swimming for 4 wk (4W-swimming), 2) running for 4 wk (4W-running), and 3) running for 10 wk (10W-running). Remaining rats were used for control for 4 wk (4W-control) and 10 wk (10W-control). The ACTH response induced by swimming stress was reduced after training by swimming (62.4%) or by running (13.8-16.4%). These training periods also attenuated the ACTH response induced by cage-switch stress (62.4% in the swimming group, 23.8-34.6% in the running groups). After swimming stress, the 4W-swimming and 10W-running groups showed smaller increases in blood glucose than the control groups. In addition, the increased levels of blood lactate in all the trained rats were significantly smaller than those in the control groups, suggesting that an adaptation was achieved after physical training. These results suggest that after running training, cross-adaptation is developed in the ACTH response induced by different types of physical (swimming) or psychological (cage-switch) stresses.

Adrenocorticotropic Hormone↗

PubMed1992

An increased ability to generate hydrogen peroxide in certain polymorphonuclear leukocytes in neonates.

We performed a quantitative assay of the hydrogen peroxide generation in polymorphonuclear leukocytes using single cell analysis by flow cytometry. The study population included premature neonates (n = 10), term neonates (n = 28) and healthy adults (n = 29). The ability to generate hydrogen peroxide in neonatal polymorphonuclear leukocytes was totally reduced compared with adults, however, some polymorphonuclear leukocytes in neonates demonstrated highly accentuated hydrogen peroxide generation.

Adult↗

PubMed1992

The studies of cell damaging and cell growth factors which induce cardiomyopathy.

We demonstrated that phosphatidylinositide-specific phospholipase C (PLC) activity was greater in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) then in hamster controls (F1b). Inositol trisphosphate (IP3) production was markedly greater in both of the cardiomyopathic hamsters, BIO 14.6 and BIO 53.58. We have also determined the sarcoplasmic reticulum (SR) function of heart. Calcium uptake into SR markedly increased in BIO 14.6. On the other hand, it significantly decreased in BIO 53.58 compared with F1b. It is well known that IP3 stimulates calcium release from SR. In BIO 14.6, calcium release from SR stimulated by IP3 increased, but its effect decreased in BIO 53.58 compared with F1b. These results suggest that PI response may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in the BIO 53.58 hamster the sarcoplasmic reticulum deteriorate in function. It was concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes. The expression of angiotensinogen mRNA was observed in the hamster heart. There was no differences in its expression level between F1b, BIO 14.6 and BIO 53.58. There was no effect of ages on its expression in these hamster hearts. We have also determined the distribution of angiotensinogen in these hamsters. At 4 weeks of age, the immunohistochemical study revealed that angiotensinogen was widely distributed in subendocardium in these hamsters. There was no difference in its distribution between F1b, BIO 14.6 and BIO 53.58. But at 20 weeks old of age its immunoreactivity decreased in BIO 53.58.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1992

Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart.

The accumulation of both Inositol-(1,4,5)-trisphosphate (IP3) and Inositol-(1,3,4,5)-tetrakisphosphate (IP4) after hormonal stimulation has a physiological role, possibly in altering Ca2+ levels in cardiac tissue. However, the accumulation of inositol polyphosphate under pathophysiological conditions has not been studied. In our experiments the metabolism of phatidylinositol and IP3 in cardiac myocytes as investigated. It was shown that basal levels of cytosolic phosphatidylinositol specific phospholipase C (PI-PLC), phosphatidylinositol-(4,5)-bisphosphate specific phospholipase C (PIP2-PLC) activities markedly increased in stroke-prone spontaneously hypertensive rats (SHRSP) with age compared with age matched Wistar Kyoto rats (WKY). IP3 kinase and IP3 phosphatase activities also increased in SHRSP hearts with age. Their activities increased in WKY, but to a lesser extent than in SHRSPs. These data suggest that a PI turnover pathway such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride-protein kinase C pathway may have an important role in the development of hypertrophy in SHRSP heart.

Animals↗

PubMed1992

Antitumor activity of Toxoplasma lysate antigen against methylcholanthrene-induced tumor-bearing rats.

Growth of the tumor autoinduced by 20-methylcholanthrene (MC) in rats was inhibited after administration of Toxoplasma lysate antigen (TLA). The antitumor activity of TLA was most obvious in the early stage of tumoral growth. When TLA was administered to rats before the appearance of tumour, tumor formation was delayed slightly. Histopathological studies revealed dense growths of spindle tumor cells in untreated control rat, while enlarged central necrosis with the infiltration of lymphocytes and neutrophils was apparent in TLA-treated rats. According to the immunohistological examination of tumor tissue with anti-Thy-1 antibody, the rats treated with TLA showed large Thy-1 positive granular cells, whereas the untreated rats indicated only a few small Thy-1 positive cells. These observations indicate that TLA is a useful modifier of biological responses to MC-induced tumors.

Animals↗

PubMed1992

Postremission therapy without prednisolone improves survival in adults with acute leukemia.

This prospective randomized clinical trial was to clarify whether postremission therapy without prednisolone (PSL) was more effective than therapy with PSL in improving the 5-year survival of adults with acute leukemia. Thirty consecutive adult patients with newly achieved complete remission were randomized to receive postremission therapy either with or without PSL between September 1985 and September 1988. The patients ranged from 16 to 57 years in age. Patients treated without PSL had a significantly better 5-year survival rate than those receiving PSL according to Kaplan-Meier analysis (53.5% vs 15.3%, p < 0.05). In the group treated without PSL, eight out of 15 patients were alive at 72 months, and seven patients maintained their first complete remission at 72 months. Among patients with acute lymphoblastic leukemia (ALL) who were treated without PSL the median duration of remission was 24 months, and the survival rate at 72 months was 50.0%. On the other hand, the median survival was only 13 months for the 5 patients with ALL treated with PSL. Thus, it is desirable that adults with acute leukemia are treated by postremission therapy without PSL.

Acute Disease↗

PubMed1992

[Clinical studies on cefprozil granules in pediatric skin soft tissues infections].

Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients. An inoculum size of 10(6) CFU/ml was used in the MIC-determinations. CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1). To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d. and 14 cases of q.i.d.) was administered for an average of 6 days. The results obtained are summarized as follows. 1. With regard to the 53 isolates of S. aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml. 45 strains (84.9%) were inhibited at 0.78 micrograms/ml. MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S. aureus (MRSA) was 100 micrograms/ml. The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively. The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively. CFPZ showed the second highest activity after MCIPC against S. aureus. 2. CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses. 3. For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively. The efficacy rates on these days were 90.4, 100 and 100%, respectively. The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater. Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days. 4. Bacteriological effects of CFPZ were determined against 60 strains of S. aureus.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1992

[Pharmacokinetic and clinical studies on cefprozil granules in the pediatric field].

Cefprozil (CFPZ), a newly developed oral cephalosporin in a fine granular form for pediatric use, was administered to children with bacterial infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) against the following 84 strains isolated from cases to which CFPZ was administered; 55 strains of Gram-positive cocci (GPC) including 2 strains of Staphylococcus aureus, 49 strains of Streptococcus pyogenes, 4 strains of Streptococcus pneumoniae, and 29 strains of Gram-negative bacilli (GNB) including 10 strains of Haemophilus influenzae, 18 strains of Escherichia coli, and 1 strain of Proteus mirabilis. MIC determination of these strains was done with an inoculum size of 10(6) CFU/ml. In pharmacokinetic studies, serum concentrations, urinary concentrations and urinary recovery rates were investigated using bioassay and high-performance liquid chromatography (HPLC). CFPZ was orally administered 30 minutes before meals to 9 children with ages ranging from 7 years and 1 month to 12 years and 3 months. Three groups of 3 children were tested with doses of 4.0, 7.5 and 15.0 mg/kg, respectively. In addition to the above, clinical and bacteriological studies were performed in a total of 160 cases consisting of children with ages ranging 5 months to 12 years and 5 months. A mean dose of 8.6 mg/kg in 3-4 divided doses (130 cases of t.i.d. and 30 cases of q.i.d.) was administered for an average of 7 days. The 160 cases included 34 cases of pharyngitis, 5 cases of tonsillitis, 8 cases of acute bronchitis, 8 cases of pneumonia, 52 cases of scarlet fever, 4 cases of acute purulent otitis media, 47 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of posthitis. Adverse reactions and abnormal clinical laboratory test results were also examined in 166 cases, including 6 cases excluded from the evaluation of clinical efficacy. The results obtained are summarized as follows: 1. With regard to GPC, MICs of CFPZ against 2 strains of S. aureus were 0.78 or 1.56 micrograms/ml and CFPZ showed the second highest activity to MCIPC. MICs of CFPZ against 49 strains of S. pyogenes were all less than 0.025 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1992

[A case of diffuse large cell lymphoma treated with combination chemotherapy of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and BEMP (bleomycin, etoposide, mitoxantrone, procarbazine) with complete remission].

A 73-year-old man with diffuse large cell lymphoma was treated with noncross resistant alternating combination chemotherapy of CHOP and BEMP, consisting of cyclophosphamide (1,000 mg/body, i.v., day 1), doxorubicin (60 mg/body, i.v., day 1), vincristine (2 mg/body, i.v., day 1), prednisolone (100 mg/body, p.o., day 1-5), bleomycin (30 mg/body, i.v., day 22), etoposide (80 mg/body, i.v., day 22-24), mitoxantrone (6 mg/body, i.v., day 22), and procarbazine (100 mg/body, p.o., day 22-26). Following the three courses' administration of CHOP and BEMP, complete remission was obtained with a remission duration of over ten months. Leukocytopenia was a dose-limiting factor. It is concluded that noncross resistant alternating combination chemotherapy of CHOP and BEMP is effective for diffuse large cell lymphoma.

Administration, Oral↗

PubMed1992

Gene analyses of abnormal fibrinogens with a mutation in the gamma chain.

In four abnormal fibrinogens with a point mutation in the gamma chain, all characterized by impaired fibrin polymerization, we identified single base exchanges in the respective mutant gamma chain genes by polymerase chain reaction followed by DNA sequence analysis. These base exchanges accounted for the amino acid substitutions previously reported from our laboratory. They were exchanges of C to T (CGC for gamma Arg-275 to TGC for Cys) in fibrinogen Osaka II, T to G (AAT for gamma Asn-308 to AAG for Lys) in fibrinogen Kyoto I, T to C (ATG for gamma Met-310 to ACG for Thr) in fibrinogen Asahi, and G to T (GAT for gamma Asp-330 to TAT for Tyr) in fibrinogen Kyoto III. These base exchanges were found to reside in exon VIII of the gamma chain gene. Since many abnormal molecules are associated with polymerization defects, unless associated with the impaired release of fibrinopeptides A and/or B, exon VIII of the gamma chain gene may deserve careful study to define the structural alterations.

DNA Mutational Analysis↗

PubMed1992

[A randomized controlled study on imipenem/cilastatin sodium in comparison to aztreonam + lincomycin in treating severe infections in patients with malignant tumors or hematological diseases].

A randomized controlled study was conducted to compare effects of imipenem (IPM) (1.0-1.5 g/day) with those of aztreonam (AZT) (4 g/day) +lincomycin (LCM) (1,200-2,400 mg/day) in patients with malignant tumors or hematological diseases and severe infections. A total of 95 patients entered the study between October 1989 and March 1991. Forty-seven patients were treated with IPM and the remaining 48 patients were given AZT+LCM. No statistically significant differences existed in age, sex or underlying diseases between the 2 groups. Overall, the clinical cure rate of the IPM group was 53%; This was significantly higher than the 31% cure rate obtained in the AZT+LCM group (P less than 0.05). The difference was significant in patients whose granulocyte counts were less than 1,000/microliters, but not in those whose granulocyte counts were 1,000/microliters or higher. Side effects were observed in 5 patients given IPM and one given AZT+LCM. In conclusion, no significant differences appeared to exist regarding clinical efficacy and safety between the 2 treatment regimens.

Adolescent↗

PubMed1992

[Mitral valve replacement in a patient with hereditary hemorrhagic telangiectasia].

A 46-year-old female with mitral insufficiency complicated by hereditary hemorrhagic telangiectasia (Osler's disease) underwent successfully mitral valve replacement. The patient had a history of repeated large-volume nasal bleeding. Mitral valve replacement using a xenograft was safely performed with various attempts for preventing abnormal postoperative hemorrhage.

Bioprosthesis↗