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Biomedical subjects

T Segawa

Publications and source records attributed to T Segawa.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Vascular endothelial growth factor levels in the aqueous and serum in diabetic retinopathy with or without neovascular glaucoma].

We determined the levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in the aqueous and serum in non-insulin dependent diabetic patients with proliferative retinopathy (n = 12) and neovascular glaucoma (n = 11). The aqueous levels of PEGF/VPF were significantly higher in both groups than in 10 diabetics without such complications. The levels were very high in patients with neovascular glaucoma, suggesting that VEGF/VPF is involved in the pathogenesis and progression of diabetic neovascular glaucoma. The serum levels were not significantly related to the presence or the stage of retinopathy. The findings suggest the possibility of treatment of neovascular glaucoma using anti- VRGF/VFP preparations.

Adult↗
PubMed1997

Successful endoscopic injection sclerotherapy for bleeding from bile duct varices.

A 66-year-old man who had undergone hepatic resection and choledochojejunostomy for intrahepatic stones was admitted with dark bloody stools. An endoscopic examination failed to detect the origin of bleeding in the esophagus, stomach, duodenum, or colon. Angiography showed an obstruction of the main trunk of the portal vein and marked cavernous formation of the collateral veins in the hepatoduodenal ligament. The patient was finally found to have variceal bleeding arising from the common bile duct; this was revealed by an endoscopic examination done through a jejunocutaneous fistula created later on. Thereafter, endoscopic injection sclerotherapy was successfully used to treat the hemobilia.

Aged↗
PubMed1997

Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF levels in ocular tissue of 6-, 12-, 18- and 28-week-old Goto-Kakizaki (GK) rats, a well-known model of non-insulin-dependent diabetes, were evaluated by highly sensitive ELISA. VEGF concentrations in the GK rat as well as in non-diabetic Wistar rat significantly decreased from the age of 6 weeks to 18 weeks. However, although VEGF concentrations in the Wistar rat continued to fall significantly from 18 to 28 weeks of age, the levels were maintained between 18 and 28 weeks of age in GK rats. Levels were significantly different between the GK and Wistar rats at 28 weeks of age. Results of immunohistochemical studies of the eyes of Wistar and GK rats at 28 weeks of age suggest diffuse distribution of this cytokine in cells of neural origin. Weak to moderate VEGF immunoreactivity was exhibited mainly in the ganglion cell layer, inner plexiform layer and inner/outer nuclear layers in rats with and without diabetes. However, in the retinal optic nerve fiber layer, retinal pigment epithelium and choroid, strong VEGF immunoreactivity was noted only in the GK rat. In conclusion, increased VEGF production in certain ocular tissue, similar to that in humans, is observed quite early, at least before the appearance of observable retinal changes in the diabetic GK rat. This also suggests that the GK rat can be used as a model of initial or latent phase diabetic retinopathy.

Aging↗
PubMed1997

5-Hydroxytryptamine-induced Ca2+ -independent cGMP formation is mediated by nitric oxide in a nitric oxide synthase-independent manner in NG108-15 cells.

A novel pathway of 5-hydroxytryptamine (5-HT)-induced cGMP formation, which does not require Ca2+ and is distinct from the 5-HT, receptor-mediated pathway, is reported to exist in NG108-15 cells. Although the possible involvement of undefined 5-HT receptors and membrane-bound guanylyl cyclase is suggested. the mechanism is not clarified in detail in this Ca2+ -independent cGMP formation. In the present study, we investigated the activation mechanism of guanylyl cyclase activity. 5-HT-induced Ca2+ -independent cGMP formation was not observed in the cell membrane preparation. In intact cells, the 5-HT-induced Ca2+ -independent cGMP formation was inhibited by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolin-1-oxyl 3-oxide (carboxyPTIO), a nitric oxide (NO)-specific trapper, and by 3,7-bis(dimethylamino)-phenothiazinium chloride (methylene blue), a cytosolic guanylyl cyclase-specific inhibitor, suggesting the involvement of NO and cytosolic guanylyl cyclase. Ca2+ -independent cGMP formation was not inhibited by 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA-AM), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and various arginine-derivative nitric oxide synthase (NOS) inhibitors. Our findings suggest that 5-HT stimulation results in the generation of NO followed by cGMP formation in an NOS-independent manner in NG108-15 cells.

Animals↗
PubMed1996

Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation.

11q23 chromosome aberrations are frequently observed in infantile as well as therapy-related leukemias. The target gene at 11q23, MLL, is disrupted by the translocation and becomes fused to various translocation partner genes such as AF4/FEL, LTG9/AF9 and LTG19/ENL. The resulting chimeric mRNAs are fused in frame and have been predicted to encode leukemia-specific chimeric proteins. In the present study, we raised antibodies against MLL, LTG9 and LTG19 and demonstrated that MLL and chimeric MLL-LTG9 and MLL-LTG19 products are synthesized in vivo and are localized in the nuclei, using immunofluorescence and cell fractionation studies. The truncated N-terminal portion of the MLL product common to the various types of 11q23 translocation was also localized in the nuclei in a similar fashion. Murine 32Dc13 cells stably expressing the truncated N-terminal MLL protein exhibited an inhibition of differentiation and a growth advantage following stimulation by granulocyte-colony stimulating factor, although the IL-3 dependency was not significantly changed in comparison to the parental cells. These results suggest that the N-terminal portion common to various MLL-chimeric products plays an important role in leukemogenesis.

Amino Acid Sequence↗
PubMed1996

Cyclic GMP elevation by 5-hydroxytryptamine is due to nitric oxide derived from endogenous nitrosothiol in NG108-15 cells.

To clarify the involvement of nitric oxide (NO) derived from nitrosothiols (RSNO) in 5-hydroxytryptamine (5-HT)-induced Ca(2+)-independent cGMP formation (CIGF) in NG108-15 cells, we investigated the effects of 5-HT on intracellular contents of RSNO as well as of NO metabolites. 5-HT stimulation resulted in an increase in the intracellular contents of nitrate and cGMP. RSNO was detected in NG108-15 cells and was decreased by 5-HT stimulation. Furthermore, the time course of nitrate increase was coincident with that of RSNO decrease. CarboxyPTIO inhibited 5-HT-induced CIGF, whereas oxyhemoglobin failed to inhibit it. The data suggest that NO is stored in a stable form as RSNO and that 5-HT stimulates NO generation from endogenous RSNO, which is followed by elevation of cGMP via activation of cytosolic guanylyl cyclase by NO in NG108-15 cells. We suggest the existence of a novel 5-HT signal transduction pathway involved in NO generation in NG108-15 cells.

Animals↗
PubMed1996

Mannosylated superoxide dismutase inhibits hepatic reperfusion injury in rats.

Superoxide anion radical (O2-) is one factor related to ischemia/reperfusion injury to the liver. The sites of O2- production and injury have yet to be determined. Superoxide dismutase (SOD), a specific scavenger for O2-, has an inhibitory effect on injury caused by O2-. SOD is of low molecular weight; hence, it has a short half-life in the circulating blood. Mannosylated SOD is taken up in sinusoidal endothelial cells of the liver by receptor-mediated endocytosis. In rats with an occluded inflow against 70% of the liver for 30 min followed by reperfusion there were elevations of serum aspartate aminotransferase and alanine aminotransferase, and lipid peroxide concentrations in liver tissue were significantly inhibited by intravenous administration of mannosylated SOD compared to treatment with normal saline. Electron microscopic examination showed that mannosylated SOD protected against damage to the sinusoidal endothelial cells caused by ischemia/reperfusion and that conventional SOD had no such protective effect. Thus, O2- produced by ischemia/reperfusion apparently damages sinusoidal endothelial cells, and damage to hepatic parenchymal cells is secondary. Mannosylated SOD deserves further study for possible use in surgical resection of the liver and for liver transplantations.

Alanine Transaminase↗
PubMed1994

Stimulation of calcium sequestration by mezerein, a protein kinase C activator, in saponized rabbit platelets.

1. The saponin-permeabilized platelet was used to examine the effect of mezerein, a moderate activator of protein kinase C (C-kinase), on the sequestration of Ca2+ to its intracellular storage sites. 2. We found that the activation of C-kinase by mezerein causes the potentiation of the Ca2+ sequestration. 3. It was suggested that C-kinase in platelets might function as a negative feedback regulator for the agonist-induced Ca2+ mobilization and might be involved in its oscillation.

Animals↗
PubMed1994

Emergency cardiopulmonary bypass support in patients with cardiac arrest caused by myocardial infarction.

Emergency percutaneous cardiopulmonary bypass support (PCPS) was instituted in 3 patients with acute myocardial infarction in cardiac arrest refractory to conventional resuscitation measures. All had severe double or triple vessel disease. Percutaneous transluminal coronary angioplasty (PTCA) was performed in 1 patient and PTCA and directional coronary atherectomy (DCA) were performed in the other 2 patients on combined intraaortic balloon pumping (IABP) and PCPS. Flow rates of 2 to 5 L/min were achieved, with restoration of mean arterial pressure to more than 60 mm Hg during PCPS. The status of all patients was improved hemodynamically with PCPS. One patient died of hemorrhage during PCPS. DCA was successfully performed in the other 2 patients, and PCPS and IABP was discontinued. Time on PCPS ranged from 10 h to 8 days. Time on IABP ranged from 10 days to 2 weeks. These 2 patients died of pneumonia or multiorgan failure after 1.5 months. In conclusion, emergency PCPS is a powerful resuscitative tool that may stabilize the condition of patients in cardiac arrest to allow for definitive intervention.

Aged↗
PubMed1994

[Intraarterial chemotherapy for metastatic renal cell carcinomas: combination with MDR-overcoming agents].

We analyzed the sensitizing activity of five agents, which have been assumed to be MDR-overcoming drugs, in two human renal cell carcinoma cell lines expressing the MDR1 gene at high levels. In addition, we studied the sensitizing activity of cepharanthin, an MDR-overcoming agents, to vinblastine, adriamycin, epirubicin, cisplatin, mitomycin C and etoposide. Based on the results, we treated 6 patients with metastatic renal cell carcinomas (4: bones, 2: contralateral kidneys) by intraarterial injection of vinblastine and adriamycin (or epirubicin) in combination with cepharanthin. Two of the 4 bone metastasis cases responded markedly to the treatment. Renal tubular impairment was observed in one patient who was treated for the contralateral kidney metastasis.

Alkaloids↗
PubMed1993

Extended right lobectomy for Caroli's disease: report of a case and review of hepatectomized cases in Japan.

A 27-year-old man was admitted to Nagasaki University Hospital complaining of fever. Percutaneous transhepatic cholangiography revealed multiple cystic dilatations of the intrahepatic bile ducts of the right lobe, as well as three obvious cystic dilatations and several small dilatations of the intrahepatic bile ducts of the left lobe. An extended right lobectomy was performed. However, the patient later suffered from repeated cholangitis and required the administration of antibiotics as a result of remnant cystic dilatations and stricture of the extrahepatic bile duct following hepatectomy. A slight enlargement of the remnant cystic dilatations, but no new cystic dilatations, were also recognized in the regenerating liver. We reviewed nine cases of hepatectomy for Caroli's disease reported in the Japanese literature, as well as our own case. Among these, four of the seven patients subjected to hepatic resection involving unilateral lobe demonstrated a good recovery. On the other hand, it is difficult to successfully treat Caroli's disease involving both lobes of the liver by hepatic resection.

Adult↗
PubMed1993

Usefulness of sodium chloride as a nondiffusible indicator in the measurement of extravascular lung thermal volume in dogs.

The authors examined the usefulness of sodium chloride as a nondiffusible indicator during the first passage through dogs' lungs, before and after increased-permeability pulmonary oedema produced by an intravenous injection of alloxan. With an injection of a mixture of ice-cold 3 per cent sodium chloride and indocyanine green dye (a nondiffusible reference indicator), the authors simultaneously recorded three dilution curves from the aortic root: dye dilution, thermal and blood electrical conductivity dilution curves in six dogs. The mean transit time of sodium chloride in the conductivity dilution curve was significantly different from, but fairly equal to, that of indocyanine green dye (6.2 +/- 1.4 s (mean +/- SD) against 6.5 +/- 1.4 s (p < 0.01) in the baseline period, and 7.6 +/- 1.9 s against 8.4 +/- 2.1 s (p < 0.01) in the oedema period, respectively). The calculated extravascular lung thermal volume with the thermal and conductivity dilution method (Y, ml kg-1) correlated well with the gravimetrically determined extravascular lung mass in a total of 12 dogs, including six other dogs without intervention (x, g kg-1) (y = 0.72 x +3.03, r = 0.96). The authors conclude that sodium chloride is useful as a nondiffusible indicator in the first passage through the lungs, and that the thermal and conductivity dilution method is also useful for measuring extravascular lung water mass.

Animals↗
PubMed1993

Relationships between serotonin induced elevation of intracellular Ca2+ concentration and stimulation of Ca2+ influx in blood platelets.

Serotonin (5-HT) caused immediate elevation of intracellular Ca2+ concentration ([Ca2+]i) in blood platelets, and it was completely inhibited by 1 mM EGTA. In Ca2+ replenished platelets, however, 2 mM EGTA did not affect the 5-HT induced elevation of [Ca2+]i when EGTA was applied just before or during the stimulation by 5-HT. At the same concentration 5-HT was also found to enhance Ca2+ influx through the activation of 5-HT2 receptor, but with rather longer latent time. From these results it is suggested that 5-HT induced elevation of [Ca2+]i is caused by mobilization of Ca2+ from intracellular Ca2+ storage sites, but not by direct stimulation of Ca2+ influx. Depletion of such Ca2+ stores might impair the effect of 5-HT on [Ca2+]i. Thus, 5-HT induced augmentation of Ca2+ influx might be secondary to replenishment of the depleted Ca2+ stores which was caused by 5-HT induced internal release of Ca2+. It is concluded that the effects of 5-HT on [Ca2+]i and Ca2+ influx in platelets are manifested sequentially or independently.

Animals↗
PubMed1993

Effects of detergents on binding of 5-hydroxytryptamine3 receptor antagonist [3H]GR65630 to rat cortical membranes.

In the absence of detergent, specific binding of [3H]GR65630, a 5-hydroxytryptamine3 (5-HT3) antagonist, determined in the presence of 5-HT3 receptor antagonist ICS205-930, was at most 30% of the total binding. To decrease the level of nonspecific binding, the effects of detergents on [3H]GR65630 binding to rat cortical membranes were investigated. The use of a detergent (0.1% Lubrol PX or Triton X-100) decreased nonspecific binding, increasing the proportion of specific binding to 70% of total binding. In the presence of 0.1% Triton X-100, binding of [3H]GR65630 was rapid, reversible and saturable at 25 degrees C. The rank order of 5-HT3 receptor active drugs in inhibiting [3H]GR65630 binding was quipazine > ICS205-930 > 2-methyl-5-HT = 5-HT > metoclopramide, which confirmed that [3H]GR65630 efficiently labeled 5-HT3 receptors in the presence of Triton X-100. Triton X-100 improved 5-HT3 receptor binding with rat brain membranes.

Animals↗
PubMed1993

Correction for apparent prolongation of mean transit time resulting from response time in a thermodilution system.

We investigated a method of correcting an apparent prolongation in the measured mean transit time (MTT), resulting from the response time of the thermodilution system. We measured the mean response times (MRT) for five commercially available thermistor-tipped catheters by recording their step function response curves. MRT is the sum of the time from the point of step change to the point of the first detection of change in temperature (latency time) plus the time from the first detection to the point of 63.2% of full response (time constant). By using a flow loop model filled with saline through a mixing chamber, we recorded pairs of thermodilution curves simultaneously with pairs of catheters, and studied the influence of MRT on MTT over the constant flow rates of 1-6 L/min. The difference in MRT's (delta MRT, second) between a pair of thermodilution systems correlated with the difference in MTT's (delta MTT, second) between a corresponding pair of thermodilution curves, yielding an equation: delta MTT = 1.07 delta MRT = 0.04 (n = 72, r = 0.95), delta MTT/delta MRT = 1.02 +/- 0.18 (mean +/- SD). We conclude that an apparent prolongation of MTT due to response time is removable by subtracting MRT from measured MTT.

Bias↗
PubMed1993

Effects of acetylsalicylic acid on pulmonary vascular tone and membrane permeability in blood-perfused dog lung.

We studied the effects of acetylsalicylic acid (ASA) on pressor response, microvascular filtration coefficient (Kf), extravascular lung water, and plasma concentrations of cyclooxygenase- and 5-lipoxygenase-derived products in 21 blood-perfused dog lungs with constant flow. The lungs were perfused for 1 h with an intrapulmonary injection of saline as vehicle (n = 5), a low dose of ASA [136 +/- 25 (SD) micrograms/ml perfusate; n = 5], a high dose of ASA (1,006 +/- 278 micrograms/ml perfusate; n = 6), or alloxan (1,000 mg; n = 5). Alloxan significantly increased Kf and extravascular lung water, whereas neither the low nor high dose of ASA increased Kf or extravascular lung water. The ASA-induced increase in vascular resistance did not correlate with the extent of the decrease in perfusate 6-keto-prostaglandin F1 alpha or the ratio of perfusate 6-ketoprostaglandin F1 alpha to thromboxane B2. Moreover, ASA did not enhance the generation of perfusate leukotrienes B4, D4, or E4. We conclude that pulmonary microvascular permeability is unaltered by ASA and that neither the decrease in plasma prostacyclin nor the increase in plasma sulfidopeptide leukotrienes may account for ASA-induced pulmonary vasoconstriction.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

A new antibiotic, cypemycin. Taxonomy, fermentation, isolation and biological characteristics.

A new peptide antibiotic, cypemycin, with a molecular weight of 2,097 (M+H), was isolated from the culture broth of Streptomyces sp. OH-4156. The antibiotic possesses cytocidal activity against P388 leukemia cells in vitro at a concentration of 1.3 microgram/ml (IC50 values), and the antibiotic showed antimicrobial activities against Micrococcus luteus (MIC, 0.2 microgram/ml).

Amino Acid Sequence↗