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Biomedical subjects

T Koyano

Publications and source records attributed to T Koyano.

66 records · Page 4Linked to original sources

Isolation of a novel substrate-competitive tyrosine kinase inhibitor, desmal, from the plant Desmos chinensis.

In the course of a screening program for tyrosine kinase inhibitors, the chloroform extract of a tropical plant, Desmos chinensis, strongly inhibited the enzyme activity. The active substance was purified by silica gel, gel filtration, and finally crystallized. The structure was elucidated by mass spectrometry and X-ray crystallography to be 8-formyl-2,5,7-trihydroxy-6- methylflavanone, and we named it desmal. Desmal competed with peptide substrate and non-competed with ATP. It inhibited tyrosine kinase in situ in epidermal growth factor (EGF) receptor-overexpressing NIH3T3 (ER12) cells. It also inhibited EGF-induced inositol phosphate formation and morphological changes.

3T3 Cells↗

ATP-regulated K+ channels are modulated by intracellular H+ in guinea-pig ventricular cells.

1. The ATP-regulated potassium channel (K+ATP) was investigated with respect to modulation by intracellular pH (pHi) by using the inside-out membrane patch clamp technique in ventricular cells isolated from the heart of the guinea-pig. Channels which had been closed by internal ATP (0.3-3 mM) were dose-dependently activated by decreasing the pHi over the range of pH 7.6-6.0. However, the channel was conversely inhibited when the pHi was further decreased below 6.0. Inwardly rectifying K+ channels were also decreased in activity when pHi fell from 7.2 to 6.0. 2. The channel activation was also observed with constant concentration of free Ca2+ (1 nM) and Mg2+ (1 mM) in the bathing solution, suggesting that a change in divalent cation concentration is not involved in channel modulation by pHi. 3. When the dose-response relations of the channel activity for ATP concentrations at different pHi were examined, the channel activity obtained at 1 microM ATP was increased by decreasing pH from 7.2 to 6.4. The half-maximal inhibition for ATP concentration at pH 7.2 and 6.4 was 20 and 40 microM, respectively, and the Hill coefficient was 2.5 in both curves. 4. In the absence of ATP, internal H+ was able to reactivate run-down channels but it had less effect on the channel as long as the activity was maintained at a higher level. The increase in the channel activity by H+ was facilitated with a proceeding of the run-down. However, after the channel was completely inactivated by a long exposure of the membrane patch to ATP-free solution, a reduction of pH could not activate the channel. 5. The decrease of pH from 7.2 to 6.4 reduced single channel conductance from 89.0 to 77.7 pS in the absence of Mg2+, whereas it reduced the conductance only at the negative membrane potentials in the presence of 2 mM Mg2+. 6. Mean open and closed times within the burst-like openings of the channel remained unaffected during the change in pHi. 7. We conclude that the cardiac K+ATP channel is modulated by a change in the intracellular pH. The channel modulation consisted of the increase in the channel activity and a decrease in the permeability. The former effect was due to the decrease in the sensitivity of the channel to ATP and the reactivation of the channel which is during the process of run-down in activity.

Adenosine Triphosphate↗

[Familial cases of cutaneous myxomas and spotty pigmentation (Carney's complex)].

In 1985, Carney et al reported a complex of myxomas, spotty pigmentation, and endocrine overactivity and subsequently demonstrated dominant inheritance of the condition. The criteria for diagnosis of the complex is the presence of two or more of the following conditions: (1) cardiac myxoma, (2) cutaneous myxoma, (3) mammary myxoma, (4) spotty mucocutaneous pigmentation, (5) primary pigmented nodular adrenocortical disease (Cushing's syndrome), (6) testicular tumors (sexual precocity), (7) pituitary adenoma secreting growth hormone (acromegaly or gigantism). We encountered a family with an affected mother and daughter. Case 1 was a 43-year-old woman with multiple cutaneous myxomas, mammary myxomas and spotty mucocutaneous pigmentation. Case 2, the 19-year-old daughter of case 1 had multiple cutaneous myxomas and spotty cutaneous pigmentation. These two cases both met the criteria for the diagnosis of the complex. Our report is believed to be the first report on the complex in Japan.

Adult↗

Closed and continuous algae cultivation system for food production and gas exchange in CELSS.

In CELSS (Controlled Ecological Life Support System), utilization of photosynthetic algae is an effective means for obtaining food and oxygen at the same time. We have chosen Spirulina, a blue-green alga, and have studied possibilities of algae utilization. We have developed an advanced algae cultivation system, which is able to produce algae continuously in a closed condition. Major features of the new system are as follows. (1) In order to maintain homogeneous culture conditions, the cultivator was designed so as to cause a swirl on medium circulation. (2) Oxygen gas separation and carbon dioxide supply are conducted by a newly designed membrane module. (3) Algae mass and medium are separated by a specially designed harvester. (4) Cultivation conditions, such as pH, temperature, algae growth rate, light intensity and quantity of generated oxygen gas are controlled by a computer system and the data are automatically recorded. This equipment is a primary model for ground experiments in order to obtain some design data for space use. A feasibility of algae cultivation in a closed condition is discussed on the basis of data obtained by use of this new system.

Biomass↗

Algal phycocyanins promote growth of human cells in culture.

The growth-promoting substances in a non-dialyzable extract of Synechococcus elongatus var. on RPMI 8226 cells (a human myeloma cell line) were separated by gel filtration and ion exchange chromatography. By gel filtration with Sepharose 4B, the dialyzate was separated into two fractions. One fraction was green-colored (P-1) and the other was blue-colored (P-2). The P-2 fraction had a higher growth-promoting activity than P-1. By ion exchange chromatography, the P-2 fraction was separated into two blue-colored fractions of phycocyanin and allophycocyanin. Both biliproteins promoted the growth of RPMI 8226 cells; however, allophycocyanin was more active than phycocyanin.

Cell Division↗

Noninvasive nasal mask BiPAP management for prolonged respiratory failure following cardiovascular surgery.

The purpose of this study was to assess the efficacy of nasal mas bi-level positive airway pressure (BiPAP) support in managing respiratory failure following cardiovascular surgery. A total of 20 patients requiring postoperative prolonged respiratory support of 72 hours or longer were studied. BiPAP support was used for eight patients (BiPAP group); the other 12 patients were managed using ordinary oxygen mask treatment (control group). The mean age of the BiPAP group and control group was 65 and 58 years of age, respectively. The mean period of postoperative endotracheal intubation of the BiPAP group and control group was 12 +/- 5 days and 7 +/- 1 days, respectively. Reintubation was necessary in two patients of the control group. The BiPAP group patients required no reintubation. BiPAP support was discontinued within 48 hours in 6 out of 8 patients. The respiratory rates of control group increased (p < 0.1) 24 hours after extubation, however, the respiratory rates of the BiPAP group remained unchanged. The values of the respiratory index of the BiPAP group improved significantly (p < 0.01) after BiPAP management (from 1.5 +/- 0.2 to 0.9 +/- 0.2). The values of the control group, however, remained unchanged. A-aDO2 and Qs/Qt decreased (p < 0.1) in the BiPAP group. There were no significant differences in central venous pressure or circulatory status between the two groups. In conclusion, BiPAP support is a noninvasive management technique for postoperative respiratory failure and may also prevent prolonged endotracheal intubation.

Aged↗

PEEP therapy for patients with pleurotomy during coronary artery bypass grafting.

Severe pulmonary oxygenation impairment resulting from peripheral lung atelectasis occurred in some patients with pleurotomy during the harvest of the internal mammary artery graft followed by coronary artery bypass grafting (CABG). We studied the efficacy of intraoperative positive end-expiratory airway pressure (PEEP) therapy for the prevention of postoperative pulmonary oxygenation impairment. A total of 66 patients with solitary CABG procedure were included in this study. The pleural cavity was intraoperatively opened in 44 patients and not opened in 22. PEEP therapy was not used in any patient before May 1996 (referred to herein as the former period) and was used more recently in eight patients with pleurotopmy (referred to herein as the latter period). PEEP was initiated immediately after pleurotomy during the harvest of the internal mammary artery graft. Without PEEP therapy, values of PaO2, A-aDO2, and respiratory index (RI) were worse in patients with pleurotomy than in those without pleurotomy. Meanwhile, there were no major differences in these values between patients with or without pleurotomy after the induction of PEEP therapy. Respiratory insufficiency (A-aDO2 > 400 mmHg and RI > 1.5) was detected in six patients with pleurotomy in the former period. Three of these six patients required over 1 week of long-term mechanical respiratory support. No respiratory insufficiency occurred in patients of the latter period. In conclusion, PEEP therapy, which is initiated just after pleurotomy, may prevent oxygen impairment and pulmonary atelectasis after extracorporeal circulation (ECC) and is recommended for patients with pleurotomy, especially for patients with preoperative low respiratory function.

Aged↗

Successful resection of renal cell carcinoma with tumor thrombi extending into the right atrium: a case report.

Renal cell carcinoma (RCC) is often associated with an extension of tumor thrombi into the inferior vena cava (IVC) and occasionally up to the right atrium. RCC with IVC involvement has a relatively favorable prognosis when it is completely resected. We present a successfully resected case of RCC with tumor thrombi extending into the right atrium. We performed radical right nephrectomy with lymph node dissection and removed the tumor thrombi en bloc under total hepatic vascular exclusion with the veno-venous bypass between the IVC and the right atrium using an active centrifugal force pump. The patient has been in good condition for 3 years since surgery with no evidence of recurrence.

Carcinoma, Renal Cell↗

Isolation of a new vinca alkaloid from the leaves of Ervatamia microphylla as an inhibitor of ras functions.

A new vinca alkaloid was isolated from a chroloform extract of Ervatamia microphylla leaves as a potent inhibitor of ras functions. The structure of the new alkaloid was elucidated by spectroscopic analysis to be a dimer of aspidosperma-class indoles. The new inhibitor, named III-121C, induced normal morphology in K-ras(ts)-NRK cells at around 0.3 microgram/ml. It also inhibited DNA, RNA, and protein synthesis weakly at 0.3 microgram/ml. It inhibited the growth of K-ras(ts)-NRK cells with IC50s of 0.29, and 0.20 microgram/ml at 33 degrees C and 39 degrees C, respectively. III-121C is the first vinca alkaloid that inhibits ras functions.

Actins↗

Inhibition of cellular chemotactic invasion by a vinca alkaloid, conophylline.

K-ras-NIH3T3 cells were more invasive than NIH3T3 cells in a chemotactic invasion assay. Conophylline, a new vinca alkaloid isolated as a ras function inhibitor, inhibited the invasion of K-ras-NIH3T3 cells, while it showed no effect on NIH3T3 cells. Conophylline did not increase expression of fibronectin but induced E-cadherin expression in K-ras-NIH3T3 cells. Mouse melanoma B16/F10 is a highly metastatic cell line. Conophylline was found to induce flat morphology in B16/F10 cells and it again inhibited the invasion of the cells to the matrigel membrane. It induced fibronectin expression but not E-cadherin expression in B 16/F10 cells. Thus, conophylline lowered invasiveness of K-ras-NIH3T3 and B 16/F10 cells by reversing neoplastic phenotypes.

3T3 Cells↗