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Biomedical subjects

T Koyano

Publications and source records attributed to T Koyano.

At least 19 recordsLinked to original sources
PubMed2003

Suppression of TGF-beta signaling by conophylline via upregulation of c-Jun expression.

In the course of screening for inhibitors of transforming-growth factor-beta (TGF-beta) functions we found that conophylline, a vinca alkaloid, inhibited TGF-beta-induced apoptosis in rat hepatoma cells. Because conophylline also inhibited TGF-b-induced promoter activity in mink lung cells, we studied the mechanism of the inhibition in this cell line. Conophylline did not inhibit nuclear translocation of Smad2. Instead, we found that conophylline increased the expression of c-Jun, which had been earlier shown to interact with the corepressor TGIF to suppress the transcriptional activity dependent on Smad2. Conophylline attenuated the interaction between the Smad2 complex and p300 but enhanced that between the Smad2 complex and TGIF. In cells overexpressing c-Jun, suppression of promoter activity induced by TGF-beta and the enhancement of the association of the Smad2 complex with TGIF were also observed. Thus, our data suggest that inhibition of TGF-beta-induced promoter activity by conophylline can be attributed to its potency in modulating the interaction of downstream transcriptional factors via upregulation of c-Jun expression.

Animals↗
PubMed2003

Induction of insulin production in rat pancreatic acinar carcinoma cells by conophylline.

We set up a screening system to detect low-molecular-weight compounds that induce insulin expression in pancreatic acinar carcinoma AR42J cells. They can differentiate into insulin-producing cells with neuron-like morphological change when treated with activin A. We employed this morphological change for the screening of beta-cell inducers among various signal transduction inhibitors. As a result, a vinca alkaloid, conophylline, induced neurite formation at 0.1 approximately 0.3 microg/ml in 72 h, like activin A. Conophylline-treated cells were found to express insulin as measured at both mRNA and protein levels. By RT-PCR analysis, conophylline-treated cells were shown to express neurogenin3 strongly. They also expressed Beta2/NeuroD and Nkx2.2, but not Pax4 and PP. Although activin A induces nuclear translocation of Smad2, conophylline did not. But the latter induced p38 activation, like activin A, as detected by phosphorylation. Pretreatment with a p38-specific inhibitor, SB203580, lowered the conophylline-induced insulin production. Therefore, p38 activation would be involved in the differentiation of AR42J cells into insulin-producing cells. Studies on structure-activity relationship with conophyllidine, conofoline, conophyllinine, and related monomer alkaloids showed that the dimeric aspidosperma structure with the dihydrofuran unit in its center was essential for the differentiation-inducing activity.

Animals↗
PubMed2001

Surgical approach for repair of descending thoracic aortic aneurysms and postoperative respiratory function.

Good exposure and the minimization of lung and thorax injuries are important objectives of surgery for descending thoracic aortic aneurysm (DTAA). In this study, three surgical approaches for DTAA were compared to assess postoperative respiratory function. The subjects were 21 patients with DTAA, three of whom had a thoracoabdominal aneurysm. The mean age was 61 years, and there were 12 men and 9 women. The causes of aneurysm were atherosclerosis in 16 patients, chronic dissection in 4, and traumatic pseudoaneurysm in 1. All the patients underwent femoro-femoral partial cardiopulmonary bypass. The DTAA was replaced with a prosthetic graft in 18 patients and repaired with a patch graft in 3. Three approaches were selected, namely, posterolateral thoracotomy (PL group, n = 12), median sternotomy combined with anterolateral thoracotomy (M group, n = 5), and spiral incision (S group, n = 4). There were no significant differences in operation time, cardiopulmonary bypass time, intraoperative blood loss volume, or water balance. The duration of respiratory support and intensive care unit stay were significantly (P < 0.05) longer in the M group than in the other two groups. The alveolararterial oxygen difference (AaDO2) and respiratory index (RI) levels immediately after surgery were also significantly (P < 0.05) higher in the M group than in the PL group. There were no significant differences in AaDO2 and RI levels 12 and 24h after surgery among the three groups. These results suggest that posterolateral thoracotomy is a desirable surgical approach for DTAA repair in view of the fact that it has the least effect on postoperative respiratory function.

Adult↗
PubMed2001

New multiflorane-type triterpenoid acids from Sandoricum indicum.

Three new 12beta-hydroxymultiflorane triterpenoid acids, sandorinic acids A-C (1-3), were isolated from the stem bark of Sandoricum indicum together with five known triterpenes (4-8). The structures of 1-3 were elucidated by spectral data interpretation. Compounds 1-8 were evaluated for their inhibiting activity against several tumor cell lines and for their effects on lymphocyte proliferation.

Animals↗
PubMed2001

Unusual annular erythema associated with myelodysplastic syndrome.

We report a case of unusual annular erythema associated with myelodysplastic syndrome (MDS). A 58-year-old male with MDS developed annular erythema on his back, scaly erythema on the dorsa of hands, and exudative erythema on his eyelids. Histological examination revealed a mononuclear cell infiltrate around vessels and follicles in the mid- to lower dermis. He had no history of treatment with granulocyte-colony-stimulating factor (G-CSF). Serum granulocyte-macrophage-colony-stimulating factor (GM-CSF) level was slightly elevated (5.84 pg/ml, normal < 2.0 pg/ml), whereas other cytokines including G-CSF, IL-6, and IL-8 were within normal limits. Skin manifestations were much improved by systemic mepitiostane, and serum GM-CSF level returned to normal levels.

Aged↗
PubMed2001

Reconstruction of heavily calcified aorta and its visceral branches without extracorporeal circulation.

A 61-year-old Japanese female was referred to our hospital for surgical treatment of a localized heavily calcified abdominal aorta. Preoperative angiograms and computed tomograms revealed severe stenosis of the aorta, resembling a slit. Bypass grafting between the thoracic and abdominal aorta was successfully performed together with the reconstruction of the celiac artery, superior mesenteric artery, and bilateral renal arteries without extracorporeal circulation. Postoperative angiograms showed patency of the graft and branches. A localized heavily calcified abdominal aorta is relatively rare, and the cause of this entity might be Takayasu's aortitis.

Aged↗
PubMed2001

The characteristics of screened patients with abdominal aortic aneurysm.

BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has not yet been established in Japan. We therefore report the characteristics of a screened population and discuss the implications of screening using ultrasound in Japan. METHODS: The subjects in our screening group were composed of 4428 participants who were 60 years of age or older. Aneurysm was detected in 16 cases, 15 males and 1 female, the detection rate being 0.4% in total and 0.9% in the males. We compare the characteristics of screened patients (n = 16) with non-screened patients operated on for abdominal aortic aneurysm (n = 166). RESULTS: There were no significant differences in the mean age or in the female ratio between the screened and non-screened groups (71 vs 70 y/o, 6% vs 13%, respectively). Solitary iliac aneurysms were significantly (p < 0.05) more frequent in the screened than in the non-screened group (19% vs 3%). The size of aneurysm in the screened group was significantly (p < 0.05) smaller compared with the non-screened group. Sixty-three per cent of the screened group and only 8% of the non-screened group had an aneurysm less than 40 mm in size. Aneurysm was palpable in only 31% of those of the screened group. There were no significant differences between the groups in the frequency of arteriosclerotic risk factors such as hypertension, ischaemic heart disease, diabetes mellitus, peripheral vascular disease and smoking habits. Surgical treatment was selected in 7 out of 16 screened patients. The remaining 9 patients with small-sized abdominal aortic aneurysms have been carefully followed up. CONCLUSIONS: Screening for abdominal aortic aneurysm using ultrasound is advisable especially for male participants and for the detection of iliac aneurysms. This screening procedure is useful for early detection because the screened aneurysm is generally small-sized and impalpable.

Aged↗
PubMed2000

A new bioactive steroidal saponin, furcreastatin, from the plant Furcraea foetida.

Microbial and plant secondary metabolites were screened for compounds that are selectively cytotoxic to mutant p53-expressing mouse fibroblasts. As a result, furcreastatin, a novel steroidal saponin, was isolated from an EtOH extract of the leaves of Furcraea foetida. Furcreastatin consisted of hecogenin as the aglycone and a hexasaccharide containing D-galactose, L-rhamnose and four D-glucose residues. The structure was determined to be (3 beta,5 alpha,25R)- 3-hydroxyspirostan-12-one 3-O-[alpha-L-Rhap-(1-->4)-beta-D-Glcp-(1-->3)-¿beta-D-Glcp-(1-->3) -beta-D- Glcp-(1-->2)¿-beta-D-Glcp-(1-->4)-beta-D-Galp] by extensive NMR spectroscopic studies. Furcreastatin decreased the viability of mutant p53-over-expressing cells with an ED50 of 4.0 micrograms/mL, and decreased that of the parental cell-line with an ED50 of 9.6 micrograms/mL.

3T3 Cells↗
PubMed2000

Accuracy of carboxyhemoglobin dilution method for the measurement of circulating blood volume.

PURPOSE: The management of circulating blood volume (BVc) is crucial in intensive care unit (ICU) patients. The purpose of this study was to verify the accuracy and precision of the carbon monoxide-labeled hemoglobin (CO-Hb) dilution method (CO method) by comparing it with the 51Cr-labeled erythrocyte dilution method (51Cr method) for the measurement of BVc. METHODS: A prospective study was performed in 18 patients who underwent coronary artery bypass grafting (CABG) under mild hypothermic cardiopulmonary bypass (CPB). The BVc was measured by both the CO method and the 51Cr method at 24 hr after ICU admission in order to verify the accuracy and precision of the CO method. Paired data were assessed in absolute terms, and percentage errors were calculated by the degree of agreement. RESULTS: Small mean differences and standard deviations between the CO method and the 51Cr method (-70.2 +/-184.8 mL) and small percentage errors (-0.49+/-1.29%) indicated the accuracy and precision of the CO method, and a close correlation was observed (r = 0.97). CONCLUSION: The CO method can measure BVc with a similar degree of accuracy as the 51Cr method. It is simple, repeatable and safe without the risk of exposure to radioactivity in the ICU.

Blood Volume↗
PubMed2000

Changes in gastric intramucosal pH and circulating blood volume following coronary artery bypass grafting.

PURPOSE: To determine the changes in gastric intramucosal pH (pHi) following coronary artery bypass grafting (CABG) in comparison with systemic hemodynamic variables and circulating blood volume (BVc). METHODS: Twenty patients who underwent CABG under mild hypothermic cardiopulmonary bypass (CPB) were included. Hemodynamic variables and the values of pHi were obtained at 3,6, 12 and 24 hr after admission to the intensive care unit (ICU). The pHi was measured by gastric tonometric catheter. The BVc was measured by carbon monoxide (CO)-labeled hemoglobin (CO-Hb) dilution method (CO method) at 6 and 24 hr after ICU admission. RESULTS: Systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) decreased with time. Systemic oxygen delivery index (DO2I) and systemic oxygen consumption index (VO2I) showed a gradual increase during the study period. By contrast, pHi decreased to the lowest value (7.26+/-0.05) at six hours and returned to normal levels (7.34+/-0.04) at 24 hr after ICU admission. Changes in BVc between six and 24 hr ranged from -242 ml to 978 ml (mean, 334+/-338 ml). The pHi increased in patients whose BVc increased by > 300 ml. Mean fluid balance was negative in this period (-386+/-667 ml; range, -1786 - + 423 ml). CONCLUSION: The pHi showed the lowest value at six hours and returned to normal at 24 hr after ICU admission. The pHi increased with the decrease in vascular resistance and with the increases in BVc in this period. The improvement of pHi, an indicator of splanchnic perfusion, appears to be related to systemic vasodilatation and an increase in BVc.

Aged↗
PubMed2000

Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa.

Sphingomyelinase is considered to be involved in the regulation of apoptosis and cell growth. In the course of our screening for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, alpha-mangostin, cowanin, and cowanol, from the bark of Garcinia speciosa. These compounds competitively inhibited bovine brain-derived acidic sphingomyelinase with IC(50) values of 14.1, 19.2, and 10.9 microM, respectively and inhibited the acidic sphingomyelinase more effectively than the neutral sphingomyelinase of bovine brain. alpha-Mangostin inhibited the acidic sphingomyelinase in the most selective manner. alpha-Mangostin was chemically modified and its structure-activity relationships are discussed.

4-Chloro-7-nitrobenzofurazan↗
PubMed2000

[MRSA septicemia caused by an infected pacemaker lead: a case report with a review of Japanese literatures].

A 50-year-old woman was admitted to our hospital because of MRSA septicemia caused by a contaminated permanent pacemaker lead. A pacemaker system was successfully removed under cardiopulmonary bypass support. Postoperative antibiotics was administered for 7 weeks. Total removal of a pacemaker system under cardiopulmonary bypass support is the treatment of choice in a case with pacemaker infection associated with MRSA septicemia.

Aminoglycosides↗
PubMed2000

Postoperative oxygenation following coronary artery bypass grafting. A multivariate analysis of perioperative factors.

BACKGROUND: Pulmonary oxygenation is generally temporarily impaired following cardiac surgery. We studied the factors influencing postoperative oxygenation using multivariate analysis. METHODS: This study was retrospectively performed in University hospital. Fifty patients undergoing solitary coronary artery bypass grafting were included in this study. Patients were divided into two groups by mean age; older group (n=25) and younger group (n=25). Alveolar-arterial oxygen difference (A-aDO2) and respiratory index (RI) were measured at 3 hours after surgery and on postoperative day 1. Statistical analysis was performed using forward selection stepwise regression of 12 perioperative variables. RESULTS: In all patients, A-aDO2 and RI significantly (p<0.01) increased after surgery and remained high on POD1. In stepwise regression analysis, preoperative A-aDO2 and RI were significant factors in the equations for postoperative A-aDO2 and RI in general, which was the most important factor in the older group. In the older group, preoperative A-aDO2 or RI and water balance were significant (p<0.05) factors which were responsible for half the oxygenation impairment just after surgery, and PCWP showed a significant (p<0.01) negative correlation with both A-aDO2 and RI on POD1. In the younger group, PCWP was a significant (p<0.01) factor for A-aDO2 and CVP and CI were significant for RI on POD1. CONCLUSIONS: Postoperative oxygenation was mainly influenced by the preoperative respiratory condition, especially in old patients, indicating that preoperative management by a physiotherapist may be necessary. Pleurotomy also had a negative influence. Careful intraoperative and postoperative volume control is important in old patients.

Adult↗
PubMed1999

Spatiotemporal patterns of activity in an intact mammalian network with single-cell resolution: optical studies of nicotinic activity in an enteric plexus.

Multiple Site Optical Recording of Transmembrane Voltage (MSORTV) has been used to measure, continuously and simultaneously, the spontaneous electrical activity from all of the neurons in individual ganglia or up to five interconnected ganglia of the submucous plexus of the guinea pig small intestine. These are the first optical recordings of electrical activity with single-cell resolution from a mammalian nervous system. They are used to investigate the effects of acute and chronic application of nicotine on the firing patterns of this neural network containing important cholinergic components. After washout of acutely applied nicotine, the firing rates of selected neurons were dramatically elevated. These results suggest that nAChRs that reversibly desensitize after exposure to nicotine may be responsible for the enhancement of activity that is observed after a brief application of this agonist. In addition, immunostaining with monoclonal antibodies was used to localize alpha3/alpha5, alpha7, and beta2 nAChR subunits, and the results demonstrate the prevalence of alpha3/alpha5. It is this alpha3-containing nAChR subtype that probably accounts for most of the excess activity elicited by nicotine application.

Animals↗
PubMed1999

Postoperative brain complications following retrograde cerebral perfusion.

This study was undertaken to investigate the neurological risk factors associated with the retrograde cerebral perfusion (RCP) technique, by examining the relationship between intraoperative parameters and post-operative brain complications. A total of 12 patients who underwent surgery for thoracic aortic aneurysms using the RCP technique were included in this study. Profound hypothermia was induced through cardiopulmonary bypass which was established with a femoral arterial cannula and bicaval return. During RCP, a venous drainage cannula from the superior vena cava (SVC) was switched over to the arterial return circuit, and oxygenated blood was retrogradely infused through the SVC. The perfusion flow rate was maintained at 273 +/- 113 ml/min and the SVC pressure was maintained at 15 +/- 6 mmHg. The RCP time was 68 +/- 27 min with a range of 27-130 min, and the lowest rectal temperature was 16 +/- 1 degrees C. The total elapsed time until emergence from anesthesia after the operation was 12 +/- 6 h. The operation time correlated with the awakening time (r = 0.729, P = 0.0088). Longer RCP times of up to 101 and 130 min tended to result in post-operative brain damage. The lowest rectal temperature also correlated with the awakening time (r = 0.697, P = 0.0149), and an inverse correlation between the SVC pressure and the awakening time was observed (r = -0. 727, P = 0.0091). These findings demonstrate the importance of reducing both the RCP and operation times to decrease the incidence of brain damage. If carried out under optimal conditions, including perfusion pressure and brain temperature, RCP could be marginally prolonged safely without causing major neurological complications.

Aged↗
PubMed1999

Cardioprotective effects of Lazaroid U-74389G on ischemia-reperfusion injury in canine hearts.

BACKGROUND: Lazaroid, an inhibitor of iron-mediated lipid peroxidation, has been shown to reduce free radical-mediated injury after ischemia and reperfusion. The effect of Lazaroid U-74389G was investigated on ischemia-reperfusion injury of the heart through preservation and transplantation (Tx) in dogs. METHODS: Eleven pairs of adult mongrel dogs weighing 8.5 to 12 kg formed the recipient-donor combinations. Following electromechanical arrest of the heart using cardioplegia, the coronary vascular beds were washed out with a cold University of Wisconsin solution followed by 12-hour preservation and orthotopic Tx. Experimental animals were divided into 2 groups; 6 pairs formed the control group, and 5 formed the Lazaroid-treated group in which Lazaroid U-74389G at 10 mg/kg was administered intravenously 30 minutes before reperfusion of the heart. The cardiac function including cardiac output, left ventricular (LV) pressure, and LV dp/dt was assessed 2 hours after Tx by comparing it with the recovery rates (%) from cardiac function of donor dogs. Each transplanted heart was harvested for histological study. RESULTS: The recovery of cardiac function after Tx was significantly better in the Lazaroid-treated group than in the control group. Histologically, myocardial damage, evaluated by both light and transmission electron microscopy, was less evident in the Lazaroid-treated group than in the control group. CONCLUSION: Early cardiac function following Tx was significantly better and histological damage was less in the Lazaroid-treated group than in the control group, suggesting that Lazaroid U-74389G is effective in preventing ischemia-reperfusion injury after preservation and Tx.

Adenosine↗
PubMed1999

Reversal of multidrug resistance by kopsiflorine isolated from Kopsia dasyrachis.

Kopsiflorine, an indole alkaloid of the aspidofractinine-type isolated from Kopsia dasyrachis, was examined for its effect in enhancing drug cytotoxicity in multidrug-resistant tumor cells. The cytotoxicity of vincristine was enhanced in a concentration-dependent manner by kopsiflorine in drug-resistant KB cells (VJ-300). Kopsiflorine alone had no effect on the growth of drug sensitive or resistant cells, but the intracellular accumulation of vincristine was enhanced by kopsiflorine in VJ-300 cells. Kopsiflorine (10 micrograms/ml) significantly inhibited the binding of [3H]azidopine to P-glycoprotein in VJ-300 cells. The results suggest that kopsiflorine interacts directly with P-glycoprotein and inhibits the efflux of antitumor agents in drug-resistant cells.

Drug Resistance, Multiple↗