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Biomedical subjects

T Sawa

Publications and source records attributed to T Sawa.

At least 145 records · Page 8Linked to original sources

Dephostatin, a novel protein tyrosine phosphatase inhibitor produced by Streptomyces. I. Taxonomy, isolation, and characterization.

A novel inhibitor of protein tyrosine phosphatase, dephostatin, was isolated from the culture broth of a strain of Streptomyces. The active principle was extracted from the broth filtrate with ethyl acetate and purified by silica gel chromatography and by HPLC. Dephostatin inhibited protein tyrosine phosphatase prepared from a human neoplastic T-cell line with an IC50 at 7.7 microM. The inhibitory pattern of dephostatin was competitive against the substrate. Dephostatin inhibited the growth of Jurkat cells.

Cell Division↗

Isolation and structure determination of novel phosphatidylinositol turnover inhibitors, piericidin B5 and B5 N-oxide, from Streptomyces sp.

In the course of a screening program for inhibitors of epidermal growth factor (EGF)-induced phosphatidylinositol turnover in human epidermoid carcinoma cell line A431, we discovered two novel compounds of the piericidin family from the culture broth and mycelia of a Streptomyces strain MJ288-OF3. We named them piericidin B5 and B5 N-oxide. By NMR and mass spectrometric analyses, the molecular formulas of piericidin B5 and B5 N-oxide were determined to be C27H41NO4 (MW 443) and C27H41NO5 (MW 459), respectively. Piericidin B5 and B5 N-oxide inhibited phosphatidylinositol turnover of A431 cells with IC50S of 10.0 micrograms/ml and 1.1 micrograms/ml, respectively.

Anti-Bacterial Agents↗

Correlation between DNA ploidy and clinical features in smooth muscle tumors of the gastrointestinal tract.

Paraffin-embedded tissue samples from 51 surgically resected, gastrointestinal smooth muscle tumors (10 leiomyomas, 5 leiomyoblastomas and 36 leiomyosarcomas) were assayed for nuclear DNA content, and the results were examined for correlation with clinico-pathological variables (tumor size, cellularity and mitosis) and prognosis. Twenty-four (47%) of the 51 tumors, consisting of 3 (30%) of the 10 leiomyomas, 2 (40%) of the 5 leiomyoblastomas and 19 (53%) of the 36 leiomyosarcomas, were identified as aneuploid. A close correlation was found between the mitotic index and the tumor size ( = 0.528; P < 0.001). The DNA ploidy pattern of the leiomyosarcoma was closely correlated with the patient survival periods (P = 0.06). The estimated median survival period was 73 months for patients with diploid tumors, and 51 months for those with aneuploid tumors. The 10-year survival rate for aneuploid tumors was lower than that for diploid tumors (P < 0.001). The measurement of DNA content may provide an index of prognostic value in gastrointestinal leiomyosarcomas.

Adult↗

[Hemodynamics and respiratory function in heart failure].

We discussed the pathophysiology of left-sided heart failure with special reference to the pulmonary "venous" system and further discussed the relationship between the capacitance of the pulmonary "venous" system and the pulmonary function. The slope of the pressure-volume line (compliance) in the pulmonary "venous" system was flat in NYHA class II and III patients as compared to class I. Elevated pulmonary "venous" pressure leads to a decrease in the compliance of the pulmonary "venous" system and consequently to a decrease in the static pulmonary compliance and this causes a respiratory dysfunction and an increase in the ventilation-perfusion imbalance. These changes may finally lead to an increase in the work of breathing, resulting in clinical symptoms such as dyspnea.

Heart Failure↗

[Utilization of Lotus 1-2-3 for on-line data logging system from clinical monitors].

We contrived to obtain digital output data from clinical monitors using "Lotus 1-2-3" and its on-line data logging add-in software "1-2-3 DataLogger". Easy macroprogramming of Lotus 1-2-3 enabled us to obtain digital data automatically into the worksheet of Lotus 1-2-3 from the monitors. Data taken up into the worksheet could be analysed readily using graphic function or calculation of Lotus 1-2-3.

Anesthesiology↗

[The influence of pulmonary "venous" compliance on the static pulmonary compliance: a study of patients with left-sided heart disease with normal respiratory function].

In heart diseases, such as mitral stenosis and angina pectoris, the static pulmonary compliance has been reported to be decreased. By definition, the pulmonary "venous" system consists of the pulmonary veins and the left atrium. It plays an important role as the reservoir for the left ventricle. In this laboratory, the pulmonary "venous" compliance (Cp"v") has been evaluated as delta V/delta P of a short segment of the P"V" volume-pressure curve. To evaluate the influence of Cp"v" on the static pulmonary compliance and to speculate about the mechanisms of the reduction in static pulmonary compliance in left-sided heart disease, hemodynamic data and static pulmonary compliance (Cst) were measured in 27 patients with left-sided heart disease. Cst was measured with esophageal balloon technique in a sitting position. The static volume-pressure curve was fitted by a sigmoid model: V = Vm/(1 + e(A-P)/kappa), where kappa is a shape constant and an index of the lung stiffness. The pulmonary blood volume (PBV) was estimated with our own method, using radionuclide (RN) angiocardiography. The mean pulmonary artery wedge pressures (PAW) were measured using a floating catheter. Cp"v" was calculated as the delta V/delta P from the increment of pulmonary "venous" volume (delta V) and that of PAW (delta P) that occurred during passive elevation of the legs. Pulmonary arterial compliance (Cpa) was obtained from an analysis of the diastolic decline in pulmonary arterial pressure wave forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

[A case of gastric cancer with multiple liver metastases showing marked efficacy of preoperative and postoperative chemotherapy with CDDP, MMC and UFT(PMU), or CDDP, MMC, UFT and etoposide (PMUE)].

The patient, a 65-year-old male with far advanced gastric cancer of H3N4 (Stage 4), was assumed inoperable on admission and chemotherapy using CDDP, MMC and UFT(PMU) was carried out. As a result, the levels of AFP and CEA were reduced notably, and PR effects were recognized in liver and lymphnode metastatic lesion. Thus, 2 months later, reduction surgery was performed, during which primary lesion was resected and a reservoir tube for chemotherapy was placed in the common hepatic artery. Subsequently, the chemotherapy with Etoposide added to PMU(PMUE) was continued by utilization of a reservoir, so that liver metastasis decreased more than 90% from the maximum. However, metastasis lesions of left lobe of the liver had enlarged with reincrease of AFP and CEA since 6 months after the operation. A month later left lobectomy of the liver was performed. Residual metastases of the liver were then enlarged. PMUE with Ca antagonist was used with little effect then. The patient died of liver failure 15 months after initial admission.

Adenocarcinoma, Papillary↗

Specific base recognition of oligodeoxynucleotides by capillary affinity gel electrophoresis using polyacrylamide-poly(9-vinyladenine) conjugated gel.

Poly(9-vinyladenine) was synthesized and utilized as an affinity macroligand entrapped within the gel matrix. Base-specific separation of oligodeoxynucleotides was achieved with high resolution and high speed by electrophoresis, using capillaries filled with conjugated polyacrylamide-poly(9-vinyladenine) gel. Oligothymidylic acids were selectively separated from the mixture of oligothymidylic and oligodeoxyadenylic acids by utilizing a specific hydrogen bonding between poly(9-vinyladenine) and oligothymidylic acids. Migration time and resolution of oligodeoxynucleotides were influenced by several parameters, such as the size of poly(9-vinyladenine), capillary temperature, and concentrations of poly(9-vinyladenine) and urea. Some guidelines are presented, based on the theoretical formulation of the effect of these parameters, in order to find optimum electrophoretic conditions. Analytical capillary affinity gel electrophoresis was developed for the selective and sensitive base recognition of oligodeoxynucleotides with efficiencies as high as several 10(6) plates/m by using a urea-gel capillary with poly(9-vinyladenine) and temperature-programming.

Adenine↗

High-performance affinity chromatography of oligonucleotides on nucleic acid analogue immobilized silica gel columns.

The nucleic acid analogues poly(9-vinyladenine) (PVAd), poly(9-adenylethyl methacrylate) and poly(thymylethyl methacrylate) (PTM) were chemically bonded to porous silica gel, which had been pretreated with 3-trimethoxysilylpropyl methacrylate, by free radical copolymerization to produce novel packing materials for affinity chromatographic columns. The columns separated nucleosides and nucleotide dimers on the basis of hydrophobic interaction using an aqueous buffer and complementary hydrogen bonding interaction in methanol as an eluent. The PVAd- and PTM-silica gel columns gave a nucleobase-selective separation of oligonucleotides differing in length from mixtures of oligoadenylic and oligouridylic acids. On the PVAd-silica gel column terminal phosphate isomers of oligouridylic acid up to seven mer were resolved and the elution order of the isomers was different from that on an ODS column.

Chromatography, Affinity↗

Effect of intra-hepatoarterial infusion of MMC and CDDP for gastric cancer patients with liver metastases.

The influence of operative treatment and chemotherapy on the prognosis in 93 gastric cancer patients with liver metastasis was studied. Chemotherapy included the systemic administration of mitomycin C (MMC) (39 patients), an intra-hepatoarterial infusion of MMC (MMC IAC group) (19 patients) and an intra-hepatoarterial infusion of MMC and cisplatin (CDDP) (MMC + CDDP IAC group) (24 patients). Either MMC or MMC and CDDP were given in 1-4 courses every 3-4 weeks from the first one to two post operative weeks. The response rate was 4 per cent (1/23), 29 per cent (5/17) and 73 per cent (17/23) for MMC systemic administration, MMC IAC and MMC + CDDP IAC, respectively, with a significantly high rate of effectiveness for the MMC + CDDP IAC. In addition, regarding the median survival period, the MMC + CDDP IAC group showed 11.8 months, as compared with 2.9 months for other chemotherapeutic treatments, indicating a good prognosis regardless of any possible resection of the primary lesion. A Cox proportional hazard model revealed the treatment by MMC + CDDP IAC alone to be a significant independent factor. These results indicated that MMC + CDDP intra-arterial chemotherapy is an effective approach to gastric cancer with liver metastasis.

Adult↗

Cerebral extracellular glucose and lactate concentrations during and after moderate hypoxia in glucose- and saline-infused rats.

To assess the effect of a glucose infusion on brain extracellular fluid (ECF) during systemic hypoxia, changes in glucose and lactate concentrations in cerebral ECF during and after moderate hypoxic hypoxia were measured in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were given either saline (n = 6) or 50% glucose solution (n = 6) for 3 h, starting 60 min before the onset of hypoxia. Hypoxia was produced by circulating 7% O2 gas in a plastic chamber for 90 min. In saline-infused animals, brain ECF glucose concentrations decreased slightly during hypoxia, although blood glucose concentrations did not change. Blood lactate concentrations increased to 6.28 +/- 0.91 mM, at 60 min after the onset of hypoxia (P less than 0.05). Brain ECF lactate concentrations increased to 3.53 +/- 0.20 mM and remained constant during 60 min of steady-state hypoxia (P less than 0.05) and decreased to the basal level within 60 min after the end of hypoxia. When sodium lactate solution was infused intravenously for 90 min (n = 4), blood lactate concentrations increased to a level as high as those found during hypoxia. However, the brain ECF lactate concentration increased only to 1.86 +/- 0.09 mM. In glucose-infused animals, the blood glucose concentration reached 339.1 +/- 32.3 mg/dl at the end of the glucose infusion, and the brain ECF glucose concentration increased to 54.7 +/- 7.3 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of glucose infusion on cerebral cortical glucose and lactate concentrations during endotoxemia in rats.

Hypoglycemia has been observed in several species before death from endotoxemia. Although several studies have emphasized the importance of maintaining brain glucose at normal concentration during endotoxemia, the effect of glucose infusion on cerebral glucose metabolism has not been studied. Accordingly, the effects of glucose infusion on interstitial glucose and lactate concentrations in the cerebral cortex during endotoxemia were studied in 22 Wistar rats. Cerebral glucose and lactate were measured at 30-min intervals for 4 h using microdialysis. Animals were divided into four groups: 1) saline-infused control (n = 5); 2) saline-infused endotoxemia (n = 7); 3) glucose-infused control (n = 5); and 4) glucose-infused endotoxemia (n = 5). In groups 2 and 4, endotoxemia was induced by intravenous injection with E. coli lipopolysaccharide B (5 mg.100 g-1). One hour after endotoxin administration, saline or 50% glucose was infused at a flow rate of 0.5 ml.100 g-1.h-1 for 3 h. Endotoxin induced a significant increase (P less than 0.05) in blood glucose in the saline-infused rats, which survived for 4 h (n = 5), from 91.6 +/- 15.4 mg.100 ml-1 at baseline to 136.3 +/- 23.3 mg.100 ml-1 (149%) at 1 h, followed by a gradual decrease (to 63% of the basal concentration at 4 h). Similar changes were observed in brain glucose (14.9 +/- 1.9 mg.100 ml-1 baseline, 175% of baseline at 2 h, and 57% of baseline at 4 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lactate in rat skeletal muscle after hemorrhage measured by microdialysis probe calibrated in situ.

The interstitial lactate concentration in rat skeletal muscle was measured in the normal state and after hemorrhage using a microdialysis probe, and the values calculated by in vitro and in vivo calibration were compared. After withdrawal of 30% of the estimated total blood volume, the lactate concentration in the dialysate gradually increased and then maintained an almost constant level. It was found that interstitial lactate levels of skeletal muscle calculated by the in vitro calibration method were not significantly different from those calculated by in vivo calibration in both the normal state and after hemorrhage. These data indicate that the absolute lactate concentration in the muscle interstitium in the normal state and after acute hemorrhage can be practically measured by a microdialysis probe calibrated in vitro. From the comparison of lactate concentrations in blood and in the muscle interstitium, it was suggested that rat skeletal muscle functions as a lactate consumer, rather than as a lactate producer, after acute hemorrhage.

Acute Disease↗

TA-3037A, a new inhibitor of glutathione S-transferase, produced by actinomycetes. I. Production, isolation, physico-chemical properties and biological activities.

TA-3037A, a new inhibitor of glutathione S-transferase was discovered in the fermentation broth of Streptomyces sp. TA-3037. It was purified by chromatography followed by solvent extraction and then isolated as yellow needles. TA-3037A has the molecular formula of C16H11NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 4.9 microM.

Cells, Cultured↗