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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 343 records · Page 19Linked to original sources

Prevention of bone loss by percutaneous estradiol implants in ovariectomized rats.

This study was conducted to investigate whether hydroxyapatite (HAP) is appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-HAP disks containing low, medium or high doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. All rats were sacrificed 90 days after surgery. At the end of the experiment, bone mineral density of the lumbar spine was measured by dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2-HAP devices was determined by an HPLC method. Estradiol release from the HAP devices followed almost a zero-order kinetics. Estradiol remained intact in E2-HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the spine of OVX rats in a dose-dependent manner.

Animals↗

Crystallization and preliminary crystallographic analysis of a 2,3-dihydroxybiphenyl dioxygenase from Pseudomonas sp. strain KKS102 having polychlorinated biphenyl (PCB)-degrading activity.

Crystals have been obtained for a 2,3-dihydroxybiphenyl dioxygenase (conventionally called BphC) from a polychlorinated biphenyl (PCB)-degrader, Pseudomonas sp. strain KKS102. The crystals were grown using both ammonium sulfate and MPD as the precipitating agents. The crystals belonged to a tetragonal space group (I422) and diffracted to 2.5 A.

Crystallization↗

Cardiovascular actions of frog urotensin II in the frog, Rana catesbeiana.

The effects of synthetic frog urotensin II on cardiac output and arterial blood pressure and on the motility of isolated vascular smooth muscle were investigated in the bullfrog, Rana catesbeiana. Bolus injections of frog urotensin II (100 nmol/kg) into the left systemic arch produced a rapid and sustained fall in blood flow through the right branch of the truncus arteriosus (to 62 +/- 5% of preinjection values; n = 8). The response exhibited strong tachyphylaxis. There were no significant effects on heart rate and central arterial blood pressure but the fact that a fall in cardiac output was not accompanied by a fall in pressure suggests that the peptide produced an increase in peripheral vascular resistance. Rings of vascular smooth muscle from the proximal and distal regions of the left and right systemic arches responded to urotensin II with sustained and concentration-dependent contractions. The tissues from the different regions did not significantly differ in their maximum response and sensitivity to the peptide (EC50 values from 4.6 x 10(-9) to 6.5 x 10(-9) M; n = 6). Acetylcholine (3 x 10(-8) to 3 x 10(-6) M) significantly (P < 0.05) relaxed the rings in an endothelium-dependent manner but urotensin II did not produce relaxation at any concentration tested. The contractile effect of urotensin II (10(-7) M) was not affected by preincubation of the rings with atropine, tetrodotoxin, and somatostatin-14 but indomethacin produced a significant (P < 0.05) decrease in the amplitude of the contractions of the systemic arch (to 18 +/- 2% of control values; n = 6). Arachidonic acid (10(-5) M) also produced a sustained contraction of the rings. The data suggest an involvement of prostaglandin synthesis in the contractile action of urotensin II on isolated frog vascular smooth muscle but, unlike in mammals, urotensin II does not stimulate nitric oxide synthesis in this tissue.

Acetylcholine↗

Somatostatin-, vasoactive intestinal peptide-, and granulin-like peptides isolated from intestinal extracts of goldfish, Carassius auratus.

Three new peptides were originally isolated from intestinal extracts of goldfish. They were structurally related with somatostatin, vasoactive intestinal peptide (VIP), and granulin (GRN) and thus termed goldfish somatostatin (gSS-28), gVIP, and gGRN, respectively. The primary structures of these peptides were determined as: SVESSNHLPA 10RERKAGCKNF20YWKGFTSC for the gSS-28; HSDAVFTDNY10SRYRKQMAAK20KYLNSVLA-NH2 for the gVIP, and VIHCDSSTIC10 PDGTTCCLSP20YGVWYCCPFS30MGQCCRDGIH40CCRHGYHCDS50TSTHCLR for the gGRN. The amino acid sequence of the gSS-28 was more similar (79-86% similarity) to somatostatins obtained in anglerfish, flounder, and sculpin, but far (21% similarity) from the catfish somatostatin, whereas goldfish and catfish belong to the same superorder. The structure of the gVIP was closely related to that of the cod VIP; only one residue (Tyr13) being substituted for Phe13 in the cod VIP. Comparing amino acid sequences of VIPs obtained in various vertebrates, the primary structure of this peptide was revealed to be relatively well conserved among vertebrates. In addition, the dose-response curve for the effect of gVIP on the short-circuit current (Isc) across the eel intestine was similar to that of human VIP, suggesting that VIPs in vertebrates have similar effect. The amino acid sequence of gGRN was 96% identical to that of carp GRN-1; only two residues (Ser6-Ser7) being substituted for Ala6-Ala7 in the carp GRN-1. The physiological significance of these peptides is discussed.

Amino Acid Sequence↗

Removal of LDL from plasma by adsorption reduces adhesion molecules on mononuclear cells in patients with arteriosclerosis obliterans.

BACKGROUND: There is increasing evidence that immune processes are important in the development of atherosclerosis. We investigated whether low density lipoprotein (LDL) adsorption therapy affected serum cytokine levels and the expression of adhesion molecules on peripheral blood mononuclear cells (lymphocytes and monocytes) in patients with arteriosclerotic obliterance (ASO). METHODS AND RESULTS: LDL adsorption therapy was repeated ten times over a period of three months in ten ASO patients. The total serum cholesterol and LDL cholesterol levels were significantly reduced at the end of therapy. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured serum levels of inflammatory cytokines (interleukin-1 beta (IL-1 beta), IL-6 and tissue necrosis factor alpha (TNF-alpha)) and expression of adhesion molecules (lymphocyte function-associated antigen 1 alpha (LFA-1 alpha), LFA-1 beta, CD2, very late antigen (VLA)-4, VLA-5 and CD44) on mononuclear cells in the same patients and a group of healthy subjects. Serum levels of all inflammatory cytokines were markedly higher in ASO patients compared with healthy subjects, but there was no significant difference in the level before and after LDL adsorption. VLA-4 expression on CD3+ cells, but not of other adhesion molecules, was markedly higher in ASO patients compared with healthy subjects. LDL adsorption caused a significant reduction in CD2, VLA4 and VLA-5 expression on CD3+ cells. Furthermore, VLA-4 and VLA-5 expression on monocytes diminished significantly after LDL adsorption. CONCLUSIONS: Our results indicate that LDL adsorption-induced immunoregulation is mediated by an indirect stimulatory effect on the immune system. The results suggests that improved peripheral circulation produced by LDL adsorption may reflect improved immune dysfunctions of atherosclerotic lesions in ASO patients.

Aged↗

Effect of adrenomedullin on aldosterone secretion by dispersed rat adrenal zona glomerulosa cells.

Adrenomedullin, a novel hypotensive peptide, was discovered in human pheochromocytoma. Although adrenomedullin exists also in normal adrenal medulla and several other organs, its effect on steroidogenesis in adrenal cortex has not been studied. We examined the effect of adrenomedullin on aldosterone secretion by the dispersed rat adrenal zona glomerulosa cells. Adrenomedullin (10(-12)-10(-7) M) did not affect basal aldosterone secretion. Adrenomedullin dose dependently inhibited aldosterone secretion stimulated by 10(-9) M angiotensin II and 10 mM potassium, whereas 10(-9) M ACTH-stimulated aldosterone was not significantly inhibited by adrenomedullin. N6,O2'-dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP, 10(-5)-10(-3) M) and Ca+ ionophore A23187 (10(-8)-10(-6) M) stimulated aldosterone secretion dose dependently, and A23187-stimulated secretion was significantly inhibited by adrenomedullin (10(-8) M), but db-cAMP-stimulated secretion was not inhibited by adrenomedullin. Our data suggest the possibility that adrenomedullin is a novel inhibitory peptide of aldosterone secretion induced by increasing concentration of intracellular free calcium.

Adrenocorticotropic Hormone↗

Effects of washing acid injuries to the skin with water: an experimental study using rats.

A skin acid injury model has been constructed using SD rats and 1N HCl. The changes over time, with particular attention to subcutaneous tissue pH, were recorded and included a comparative study of the effect of washing with water at 1, 3 and 10 min after injury, on subcutaneous tissue pH. After inflicting an acid injury, the subcutaneous tissue pH of control animals reached its minimum value at the seventh minute, and had not recovered to the pre-experimental level by the 60th minute. In the group of rats which was washed at 1 min, the pH did not drop below 7.5, it remained virtually unchanged. In the group washed at 3 min, the pH declined slightly, but subsequent to washing, the pH increased gradually. In the group washed at 10 min, the changes in pH were almost the same as those in the untreated group. These results indicated that if washing was carried out before the subcutaneous tissue pH level reached a minimum value, any remaining acid on the skin surface could be washed away, effectively suppressing the subsequent fall in pH.

Animals↗

Kallikrein generates angiotensin II but not bradykinin in the plasma of the urodele, Amphiuma tridactylum.

Incubation of heat-denatured plasma from the urodele, Amphiuma tridactylum (three-toed amphiuma) or from the anurans Rana ridibunda (European green frog) and Rana catesbeiana (American bullfrog) with either glass beads, porcine pancreatic kallikrein or trypsin did not generate bradykinin-like immunoreactivity. However, peptides were generated in kallikrein-treated amphiuma plasma that contracted vascular rings from the bullfrog systemic arch and had a spasmogenic action on the bullfrog urinary bladder. These peptides which were not generated in trypsin-treated plasma, were purified to homogeneity by reverse-phase HPLC and their primary structures established as: Asp-Arg-Val-Tyr-Val-His-Pro-Phe ([Asp1,Val5]angiotensin II) and Asn-Arg-Val-Tyr-Val-His-Pro-Phe ([Asn1,Val5]angiotensin II). Incubation of synthetic [Asn1,Val5]angiotensin II with amphiuma plasma resulted in deamidation to [Asp1,Val5]angiotensin II. The data suggest, therefore that amphiuma plasma contains an L-asparagine amidohydrolase (asparaginase), as previously described for the eel. Although bradykinin-related peptides have been isolated from frog skin, this study provides evidence tha the kallikrein-kinin system may be absent from the blood of amphibia.

Amino Acid Sequence↗

Incidence and predictors of diabetes in Japanese-American men. The Honolulu Heart Program.

Reports on the incidence and predictors of diabetes in minority populations are infrequent. The 6-year cumulative incidence of diabetes between 1965 and 1974 was estimated among 7210 Japanese-American men aged 45 to 68 years who were enrolled in the Honolulu Heart Program and were free of clinically recognized diabetes at baseline. The incidence of "possible" diabetes (based on history, medication, or hospital diagnosis) was 12.8% and the incidence of "probable" diabetes (based on diabetic medication) was 5.7%. Estimates of incidence in subjects with a nonfasting glucose concentration less than 225 mg/dL 1 hour after a 50-g load were 9.7 and 4.0%, respectively. Multivariate adjusted odds ratios (ORs) for probable diabetes in all subjects comparing the upper quintile with the lower four quintiles combined for continuous variables indicated statistically significant direct associations with body mass index (OR, 1.69; 95% confidence interval (CI), 1.31 to 2.18), 1-hour postchallenge glucose level (OR, 5.79; 95% CI, 4.58 to 7.33), triglyceride levels (OR, 1.47; 95% CI, 1.14 to 1.91), systolic blood pressure (OR, 1.36; 95% CI, 1.05 to 1.76), and parental history of diabetes (OR, 1.73; 95% CI, 1.29 to 2.33), and an inverse association with physical activity (OR, 0.49; 95% CI, 0.34 to 0.72), using logistic regression models including these variables as well as age, subscapular/triceps skinfold ratio, and hematocrit simultaneously. Associations were similar but slightly weaker in men with glucose levels less than 225 mg/dL and in those who remained free of cardiovascular disease. When older men (55 to 68 years old) were compared with younger (45 to 54 years old) men, associations among the older group were stronger for body mass index, physical activity, and systolic blood pressure and they were weaker for glucose levels, triglyceride values, and parental diabetes. Results suggest that body mass index, physical inactivity, glucose level, and parental diabetes appear to be independent risk factors for diabetes, while triglyceride and systolic blood pressure levels may be markers for an adverse cardiovascular risk factor profile associated with diabetes and may reflect an insulin resistance syndrome.

Adult↗

Development of a rat model for orthotopic liver transplantation for hepatocellular carcinoma.

BACKGROUND: Surgical resection is of limited benefit in hepatocellular carcinoma accompanied by severe liver cirrhosis or multicentric hepatic cancer. The long-term survival of patients with advanced hepatocellular carcinoma after transplantation is quite poor. We have studied the characteristics, natural course, and cause of diethylnitrosamine-induced liver cancer in rats and have shown it to be a good model of liver cancer in human beings. Therefore we performed orthotopic liver transplantation (OLT) in rats with diethylnitrosamine-induced liver cancer to study the patterns of recurrence. METHODS: Diethylnitrosamine 100 parts per million in drinking water was administered daily for 4 months to male inbred LEW rats. A laparotomy was performed 120 or 134 days after commencing the oral diethylnitrosamine to confirm the induction of cancer confined grossly to the liver. The livers were resected, and orthotopic transplantation with livers of normal LEW rats was performed. RESULTS: By day 150 all the rats in the non-OLT group died of intraabdominal hemorrhage caused by spontaneous rupture of liver cancer (mean survival time +/- SD, 138.2 +/- 5.3 days; n = 14). However, the OLT (day 120) group recovered their body weight comparatively early after transplantation and survived a maximum of 218 days until death from recurrence (203.8 +/- 21.3 days; n = 4). A significant extension in survival time was observed (p < 0.01). In autopsies performed at the time of death, metastatic liver cancer was observed in the transplanted livers with two showing metastases to the lung. The cause of death was cancer in all the rats. However, the OLT (day 134) group all died of major complications of severe pneumonia and disseminated intravascular coagulation within 2 weeks of OLT (141.3 +/- 5.0 days; n = 4). CONCLUSIONS: After liver transplantation to rats with hepatocellular cancer confined to the liver, recurrence was observed at a comparatively early stage in all transplant recipients. Although a significant prolongation of survival was noted, they all died of cancer. The timing of transplantation is also an important factor. This experimental liver transplantation model of progressive rat liver cancer will be useful in the study of primary liver cancer in human beings.

Animals↗

Global structure-acute toxicity relationships for mice using structural parameter ratios: new approach to molecular design and screening.

A method for a preliminary survey of the relationship between molecular structure and performance was described using 1506 random data of structure-acute toxicity for mice (intravenously dosed). The structural patterns of the weakest toxic structures (111) were extracted from the data and the patterns discriminated for 64.2% of the other structures (1395). As for the 826 structures of strongest toxicity, 78.3% were discriminated by these structural patterns. These results were obtained by using structural parameter ratios to describe the structural patterns and the exhaustive elimination process to select the best parameter ratio from many candidates. The results were summarized in the form of a chart which can be used for practical screening for the weakest toxic structures.

Animals↗

Cytotoxicity of CPT-11 for gastrointestinal cancer cells cultured on fixed-contact-sensitive plates.

The cytotoxicity of SN-38, the major metabolite of CPT-11 (7-ethyl-10-[4-(1-piperidino)-1- piperidino]carbonyloxycamptothecin, was compared among gastrointestinal carcinomas of every organ, and between primary and metastatic lesions of every organ-originated gastrointestinal carcinoma, by an in vitro anticancer drug sensitivity test using fixed-contact-sensitive plates. The rates of cases having a high response (percent survival 75% or lower) to SN-38 but a low response (percent survival above 75%) to cisplatin, mitomycin C (MMC), adriamycin (ADM) and 5-fluorouracil (5-FU) were 14.6, 19.4, 15.6 and 27.0%, respectively. While, the rates of cases having a high response to cisplatin, MMC, ADM and 5-FU but a low response to SN-38 were 7.3, 2.8, 9.4 and 13.5%, respectively. Each of the former rates were higher than each of the latter rates. In particular, the former rate for MMC was significantly higher than the latter rate (p = 0.04). Two cases with colon cancer showed a high response only to SN-38. The percent survival of primary lesions in colon cancer was significantly lower than that in stomach cancer. The rates of hepatocellular carcinoma cases having a high response to SN-38 but a low response to cisplatin, MMC, ADM and 5-FU were 16.7, 16.7, 0 and 25%, respectively. Only one case had a high response to 5-FU but a low response to SN-38. The percent survival of metastatic lesions in pancreatic cancer was significantly lower than that of primary lesions. From this study, we recommend the further clinical trial of CPT-11 for colon and hepato-cellular cancers.

Animals↗

Prevention of vascular graft infection by sisomicin incorporated into fibrin glue.

To examine the efficacy of sisomicin (SISO) incorporated into fibrin glue (FG) for the prevention of graft infection in animal models, the susceptibility to infection of Dacron grafts (control) and SISO-FG Dacron grafts following the inoculation of Staphylococcus aureus or S. epidermidis was compared. The results showed that SISO-FG Dacron grafts displayed resistance to graft infection.

Animals↗

Anterior chest wall axillary artery to contralateral axillary vein graft for vascular access in hemodialysis.

Patients with end-stage renal failure and peripheral vascular disease pose a difficult management problem in establishing long-term angioaccess for hemodialysis. In 4 patients with access problems, we created axillary artery to contralateral axillary vein Goretex grafts. The grafts were cannulated regularly for periods ranging from 29 to 66 months without difficulty. There was one episode of thrombosis and one of congestive heart failure. The mean venous pressure was 120 mm Hg with a mean arterial flow of 220 ml/min. This type of vascular access can provide adequate blood flow in difficult patients and maintain efficient dialysis. It should be a useful addition to the armamentarium of the vascular surgeon.

Adult↗

Electrophysiological effects of MS-551 in humans: a class III antiarrhythmic agent.

To investigate the clinical effects of MS-551, a Class III antiarrhythmic agent, 11 patients underwent electrophysiological study. MS-551 was given intravenously as an initial dose of 0.2 or 0.3 mg/kg for 5 minutes followed by the continuous infusion at 0.2 or 0.3 mg/kg for 30 minutes, respectively, in all patients. The rate corrected QT interval increased significantly from 3 minutes after the beginning of MS-551 infusion. The sinus heart rate decreased significantly by 8% at 10 minutes after the drug administration (P < 0.025). Mean PR and QRS intervals, and blood pressure were not significantly affected by the drug. Mean PA, AH, and HV intervals during sinus rhythm were also not affected. The effective refractory periods (ERPs) of the atrium and ventricle were significantly prolonged by 13% from 202 +/- 24 ms to 231 +/- 26 ms (P < 0.0005), and by 7% from 238 +/- 11 ms to 257 +/- 13 ms (P < 0.002), respectively, by MS-551. The ERP of the atrioventricular node and sinoatrial nodal recovery time were not changed significantly by the drug. This is a report of the effects of MS-551 in humans. This agent could be useful for treatment of tachyarrhythmias by prolongation of ERPs of the atrium and ventricle without significant variations of blood pressure and intracardiac conduction times. It is noteworthy that MS-551 slightly but significantly decreased heart rate.

Aged↗

Multiple Polychlorinated Biphenyl Transformation Systems in the Gram-Positive Bacterium Rhodococcus sp. Strain RHA1.

The cloned bphA gene of the polychlorinated biphenyl (PCB) degrader Rhodococcus sp. strain RHA1 was expressed in Rhodococcus erythropolis IAM1399 cells, resulting in the transformation of di-, tri-, and tetrachlorobiphenyls. Disruption of the bphA1 gene in RHA1 resulted in a lack of growth on biphenyl and a loss of PCB transformation activity. However, the bphA1 insertion mutant of RHA1, designated RDA1, retained the ability to transform PCB congeners when grown on ethylbenzene as its carbon source. It also transformed 4-chlorobiphenyl to 4-chlorobenzoate, although it was suspected to be deficient in bphB and bphC gene activities as well as bphA. This suggested that an alternative PCB degradation system distinct from the one encoded by the cloned bph genes was present.

Journal Article↗

Characterization of biphenyl catabolic genes of gram-positive polychlorinated biphenyl degrader Rhodococcus sp. strain RHA1.

Rhodococcus sp. strain RHA1 is a gram-positive polychlorinated biphenyl (PCB) degrader which can degrade 10 ppm of PCB48 (equivalent to Aroclor1248), including tri-, tetra-, and pentachlorobiphenyls, in a few days. We isolated the 7.6-kb EcoRI-BamHI fragment carrying the biphenyl catabolic genes of RHA1 and determined their nucleotide sequence. On the basis of deduced amino acid sequence homology, we identified six bph genes, bphA1A2A3A4, bphB, and bphC, that are responsible for the initial three steps of biphenyl degradation. The order of bph genes in RHA1 is bphA1A2A3A4-bphC-bphB. This gene order differs from that of other PCB degraders reported previously. The amino acid sequences deduced from the RHA1 bph genes have a higher degree of homology with the tod genes from Pseudomonas putida F1 (49 to 79%) than with the bph genes of Pseudomonas sp. strains KF707 and KKS102 (30 to 65%). In Escherichia coli, bphA gene activity was not observed even when expression vectors were used. The activities of bphB and bphC, however, were confirmed by observing the transformation of biphenyl to a meta-cleavage compound with the aid of benzene dioxygenase activity that complemented the bphA gene activity (S. Irie, S. Doi, T. Yorifuji, M. Takagi, and K. Yano, J. Bacteriol. 169:5174-5179, 1987). The expected products of the cloned bph genes, except bphA3, were observed in E. coli in an in vitro transcription-translation system. Insertion mutations of bphA1 and bphC of Rhodococcus sp. strain RHA1 were constructed by gene replacement with cloned gene fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

A Novel Transformation of Polychlorinated Biphenyls by Rhodococcus sp. Strain RHA1.

We have characterized a biphenyl degrader, Rhodococcus sp. strain RHA1. Biphenyl-grown cells of strain RHA1 efficiently transformed 45 components in the 62 major peaks of a polychlorinated biphenyl (PCB) mixture of Kanechlors 200, 300, 400, and 500 within 3 days, which includes mono- to octachlorobiphenyls. Among the intermediate metabolites of PCB transformation, di- and trichlorobenzoic acids were identified. The gradual decrease of these chlorobenzoic acids during incubation indicated that these chlorobenzoic acids would also be degraded by this strain. The effect of the position of chlorine substitution was determined by using PCB mixtures that have chlorine substitutions mainly at either the ortho or the meta position. This strain transformed both types of congeners, and strong PCB transformation activity of RHA1 was indicated. RHA1 accumulated 4-chlorobenzoic acid temporally during the transformation of 4-chlorobiphenyl. The release of most chloride in the course of 2,2(prm1)-dichlorobiphenyl degradation was observed. These results suggested that RHA1 would break down at least some PCB congeners into smaller molecules to a considerable extent.

Journal Article↗