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Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 145 records · Page 8Linked to original sources
PubMed1998

[Risk factors for clinical prognosis in bacterial meningitis beyond the neonatal period].

A retrospective clinical study of 64 cases with bacterial meningitis beyond the neonatal period in the department of pediatrics of St. Mary's Hospital (1985-1995) was conducted. Haemophilus influenzae (H. influenzae) (28 cases, 43.8%) and Streptococcus pneumoniae (S. pneumoniae) (23 cases, 35.9%) were common pathogens. The prognosis was classified into three groups; normal (42 cases, 65.6%), neurological sequelae (17 cases, 26.6%) and death (5 cases, 7.8%). We analyzed the risk factors associated with their outcome. The body temperature at admission, platelet count, CSF examination (WBC, glucose, GOT, GPT) were prognostic factors. The prognosis of bacterial meningitis caused by S. pneumoniae was worse than those due to H. influenzae (p = 0.0347).

Adolescent↗
PubMed1998

[Regional lymph node metastasis in renal pelvic or ureteral cancer].

BACKGROUND: The objective of this study is to evaluate the frequency of regional lymph node metastasis, clinical outcomes and histopathological findings of renal pelvic or ureteral cancer with regional lymph node metastasis. PATIENTS AND METHODS: One hundred and sixty three patients with renal pelvic or ureteral cancer were treated in our hospital between 1961 and 1995. Eighty nine in 155 patients underwent lymph node dissection. Frequency of regional lymph node metastasis, clinical outcomes and histopathological findings of these 89 patients were investigated. Patient survival rates were determined by actuarial calculation using Kaplan-Meier method with log-rank test. RESULTS: The status of lymph node involvement was pN0 in 61 (68.5%), pN1 in 5 (5.6%), pN2 in 15(16.9%) and pN3 in 8 patients (9.0%). The 5-year survival rate was 78.8%, 12.5%, 20.0% and 0% for pN0 pN(+), pN1, pN2 and pN3 respectively. In 28 patients with regional lymph node metastasis, patients with distant metastasis were all dead within 1.2 years and the 3- or 5-yer survival rates of patients without distant metastasis were 31.4% and 15.7%. The difference between two groups were obvious (p < 0.01). The 3-year survival rate was 100%, 66.7%, 33.3% and 0% for pT1, pT2, pT3 and pT4 patients with M0 and pN(+) respectively. CONCLUSION: Our data suggested that conventional treatments were not effective for almost patients with regional lymph node metastasis. However in the patients with low grade, under pT3 and M0, pN1-2, the possibility of long time survival was shown.

Adult↗
PubMed1998

[Treatment of recurrent gastric cancer].

The recurrence rate of resected gastric cancer with curative intent was around 20%. When early gastric cancer was excluded, the rate was around 30%. Peritoneal dissemination accounted for half the recurrences, and was followed by hematogeneous metastasis, including hepatic metastasis. Chemotherapy was the main treatment modality because the possibility of curative resection was very low. Systemic chemotherapies based on biochemical modulation, particularly CDDP/5-FU therapy, have been routinely performed. For localized diseases, loco-regional therapies like drug administration via hepatic artery and intraperitoneal administration have been also applied.

Antineoplastic Agents, Phytogenic↗
PubMed1998

[Basic and clinical studies on tazobactam/piperacillin in pediatric field].

A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows: 1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce beta-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against beta-lactamase nonproducing strains were < or = 0.025 microgram/ml in 5 strains and 0.39 microgram/ml in 1 strain, and the values were similar to those of PIPC and SBT/CPZ. While the MIC of TAZ/PIPC against the high beta-lactamase producing strain was 0.78 microgram/ml; similar to that of SBT/CPZ and smaller than that of PIPC. 2. The results of clinical effects on 7 diseases in 33 cases were as follows: TAZ/PIPC was clinically judged "excellent" in 17 (51.5%); good in 14 (42.4%); fair in 2 (6.1%). No case with no response was seen in this study, and the total efficacy rate of "excellent" and "good" was 93.9%. 3. Bacteriological effects were evaluated in 17 strains of 4 species, and all of them were eradicated. 4. Adverse reactions were judged in 35, which consisted of 33 in which the clinical effects were evaluated and 2 dropped from this study. Of these cases, diarrhea was observed in 4 (11.4%). 5. Laboratory tests revealed an increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases (6.9%). Biochemical profile showed an increase in GPT alone and abnormal increases in both GOT and GPT in 1 each out of 21 cases.

Acute Disease↗
PubMed1998

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)].

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.

Adult↗
PubMed1998

[Late phase II study of YNK-01 (an oral prodrug of cytarabine) for hepatocellular carcinoma].

Twenty-three patients with hepatocellular carcinoma (HCC) were enrolled in this cooperative study conducted in Hirosaki University Hospital. They were treated with YNK-01, a prodrug of cytarabine for oral administration. YNK-01 was given for 2 weeks and repeated every 4 weeks for as long as possible. There were 13 patients with NC, 10 with PD, and no PR. Among NC cases, 5 patients were maintained with NC for longer than 6 months. The main side effects of YNK-01 were anemia, leukopenia, thrombocytopenia, and symptoms of the alimentary tract (nausea, anorexia, diarrhea, etc), but no severe side effects over Grade 3 were observed.

Administration, Oral↗
PubMed1998

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗
PubMed1997

Transgenic Galphaq overexpression induces cardiac contractile failure in mice.

The critical cell signals that trigger cardiac hypertrophy and regulate the transition to heart failure are not known. To determine the role of Galphaq-mediated signaling pathways in these events, transgenic mice were constructed that overexpressed wild-type Galphaq in the heart using the alpha-myosin heavy chain promoter. Two-fold overexpression of Galphaq showed no detectable effects, whereas 4-fold overexpression resulted in increased heart weight and myocyte size along with marked increases in atrial naturietic factor ( approximately 55-fold), beta-myosin heavy chain ( approximately 8-fold), and alpha-skeletal actin ( approximately 8-fold) expression, and decreased ( approximately 3-fold) beta-adrenergic receptor-stimulated adenylyl cyclase activity. All of these signals have been considered markers of hypertrophy or failure in other experimental systems or human heart failure. Echocardiography and in vivo cardiac hemodynamic studies indeed revealed impaired intrinsic contractility manifested as decreased fractional shortening (19 +/- 2% vs. 41 +/- 3%), dP/dt max, a negative force-frequency response, an altered Starling relationship, and blunted contractile responses to the beta-adrenergic agonist dobutamine. At higher levels of Galphaq overexpression, frank cardiac decompensation occurred in 3 of 6 animals with development of biventricular failure, pulmonary congestion, and death. The element within the pathway that appeared to be critical for these events was activation of protein kinase Cepsilon. Interestingly, mitogen-activated protein kinase, which is postulated by some to be important in the hypertrophy program, was not activated. The Galphaq overexpressor exhibits a biochemical and physiologic phenotype resembling both the compensated and decompensated phases of human cardiac hypertrophy and suggests a common mechanism for their pathogenesis.

Animals↗
PubMed1997

Comparison of myocardial contrast echocardiography and coronary angiography for assessing the acute protective effects of collateral recruitment during occlusion of the left anterior descending coronary artery at the time of elective angioplasty.

To assess the immediate change in collateral flow distribution within the occluded myocardium and the acute protective effects on myocardial ischemia after coronary occlusion, myocardial contrast echocardiography (MCE) was performed in 15 patients with normal left ventricular function undergoing elective coronary angioplasty of the left anterior descending artery, and the results were compared with those obtained from coronary angiography (CA). The sonicated or nonsonicated contrast material was injected into the right coronary artery before and during coronary occlusion and collaterals were graded on a 4-point scale (none = 0 to good = 3). Development of subjective anginal symptoms, ST-segment shift and wall motion abnormality during coronary occlusion were graded on a 4-point scale (none = 0 to severe = 3). Both MCE and CA detected a significant development in collateral flow during coronary occlusion. There was no significant correlation between MCE and CA collateral grades before or during coronary occlusion. The collateral flow assessed with MCE was inversely but significantly correlated with development of subjective anginal symptoms (r(s) = -0.70, p <0.01), ST-segment shift (r(s) = -0.78, p < 0.005) or wall motion abnormality (r(s) = -0.91, p < 0.001) during coronary occlusion. In contrast, the angiographic collateral flow was not correlated with development of anginal symptoms (r(s) = -0.46, p = 0.10), ST-segment shift (r(s) = -0.41, p = 0.14), or wall motion abnormality (r(s) = -0.26, p = 0.35). The present study suggested that the acute protective effects of coronary collaterals during coronary occlusion were closely associated with myocardial perfusion rather than the angiographic epicardial collateral vessel filling, and thus MCE was useful in assessing the acute protective effects of coronary collaterals during coronary occlusion.

Aged↗
PubMed1997

Fibroblasts spread on immobilized fibrin monomer by mobilizing a beta1-class integrin, together with a vitronectin receptor alphavbeta3 on their surface.

Human and murine fibroblasts were found to spread far more avidly on fibrin monomer monolayers than on immobilized fibrinogen, indicating that removal of fibrinopeptides by thrombin is a prerequisite for the fibrin-mediated augmentation of cell spreading. In fact, cell spreading was not efficiently augmented on monolayers of a thrombin-treated dysfibrinogen lacking the release of fibrinopeptide A due to an Aalpha Arg-16 --> Cys substitution. Since a synthetic Arg-Gly-Asp (RGD)-containing peptide inhibited the fibrin-mediated cell spreading, subsequent dissociation of the carboxyl-terminal globular domain of the Aalpha-chains appears to render the RGD segments accessible to the cell-surface integrins. In support of this, fibrin-augmented cell spreading was inhibited by an antibody recognizing a 12-kDa peptide segment with gamma Met-89 at its amino terminus, which is located in close association with the RGD segment at Aalpha 95-97 in the helical coiled-coil interdomainal connector. The fibrin-mediated augmentation of cell spreading was inhibited not only by an antibody against human vitronectin receptor (LM 609) but also by an antibody against the beta1 subunit of integrin (mAb13), suggesting that the beta1-class integrin together with a vitronectin receptor, alphavbeta3, is mobilized onto the surface of fibroblasts upon contact with the fibrin monomer monolayer.

Animals↗
PubMed1997

Evolution of a multigene family that encodes the Kunitz chymotrypsin inhibitor in winged bean: a possible intermediate in the generation of a new gene with a distinct pattern of expression.

Winged bean Kunitz chymotrypsin inhibitor (WCI) accumulates in an organ-specific and temporally regulated manner. The protein is encoded by a multigene family that includes at least four putative inhibitor-coding genes and three pseudogenes. The structure of the WCI genes indicates that an insertion at a 5' proximal site occurred after duplication of the ancestral WCI gene and that several gene conversion events subsequently contributed to the evolution of this gene family. Analysis of the promoter activity of the 5' regions of the WCI genes in transgenic tobacco showed that only the 5' regions of the WCI-3a and WCI-3b genes, which encode the major WCI protein in winged bean, promoted the organ-specific and temporally regulated expression of a reporter gene. The 5' region of a pseudogene, the WCI-P1 gene which contains frameshift mutations, exhibited constitutive promoter activity in tobacco, an indication that the 5' region of the WCI-P1 gene might spontaneously have acquired new regulatory sequences during evolution. Since gene conversion is a relatively frequent event and since the homology between the WCI-P1 and WCI-3a/b genes is disrupted at a 5' proximal site by remnants of an inserted sequence, the WCI-P1 gene appears to be a possible intermediate that could be converted into a new functional gene with a distinct pattern of expression by a single gene-conversion event.

Base Sequence↗
PubMed1997

Monocytes modulate the fibrinolytic balance of endothelial cells.

Cultured endothelial cells (ECs) produced a constitutive plasminogen activator inhibitor-I (PAI-1), whereas primary culture of monocytes from blood did not produce a detectable amount of PAI-1. Addition of monocytes to ECs caused the accumulation of a large amount of PAI-1 in the supernatant in a dose- and time-dependent manner. Having almost no effect on the production of tissue-type plasminogen activator (t-PA), monocytes decreased the potential fibrinolytic activity of ECs. The 6 hours conditioned medium obtained from the coculture system between monocytes and either ECs or paraformaldehyde-fixed ECs had almost the same effect on the other ECs to produce PAI-1 and t-PA as monocytes that were direct contact with ECs. In addition, this effect was specifically inhibited by using two antibodies against interleukin-1 beta and tumor necrosis factor-alpha. These results indicate that interleukin-1 beta and tumor necrosis factor-alpha induced by the coculture are mostly responsible for decreasing the fibrinolytic activity of ECs.

Cells, Cultured↗
PubMed1997

Localization of plasminogen activators and their inhibitor in squamous cell carcinomas of the head and neck.

BACKGROUND: Plasminogen activators (PAs) and their inhibitors are thought to play an important role in tumor invasion and metastasis. However, there have been few reports in which histologic localization of PAs has been demonstrated in head and neck tumors. METHODS: We examined the patterns of expression of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and vitronectin in head and neck squamous cell carcinomas using immunohistochemical techniques. We also studied the correlation between the immunohistologic expression of these fibrinolytic proteins and the clinical staging of the tumor. RESULTS: Of 28 tumor specimens, 15 (54%) showed immunoreactivity for u-PA; 8 (36%), for t-PA; and 23 ( 82%), for PAI-1. There was a significant correlation between PAI-1 expression and the extent of the primary tumor. CONCLUSIONS: The present study demonstrates the existence and possible pathophysiologic significance of u-PA and PAI-1 in squamous cell carcinomas of the head and neck.

Carcinoma, Squamous Cell↗