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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 19 recordsLinked to original sources

Low serum cholesterol and mortality. Which is the cause and which is the effect?

BACKGROUND: Many studies have reported an association between a low or lowered blood total cholesterol (TC) level and subsequent nonatherosclerotic disease incidence or death. The question of whether low TC is a true risk factor or alternatively a consequence of occult disease at the time of TC measurement remains unsettled. To shed new light onto this problem, we analyzed TC change over a 6- year period (from exam 1 in 1965 through 1968 to exam 3 in 1971 through 1974) in relation to subsequent 16-year mortality in a cohort of Japanese American men. METHODS AND RESULTS: The study was based on 5941 men 45 to 68 years of age without prior history of coronary heart disease, stroke, cancer, or gastrointestinal-liver disease at exam 1 who also participated in exam 3 of the Honolulu Heart Program. The association of TC change with mortality end points was investigated with two different approaches (continuous and categorical TC change) with standard survival analysis techniques. Falling TC level was accompanied by a subsequent increased risk of death caused by some cancers (hemopoietic, esophageal, and prostate), noncardiovascular noncancer causes (particularly liver disease), and all causes. The risk-factor-adjusted rate of all-cause mortality was 30% higher (relative risk, 1.30; 95% CI, 1.06 to 1.59) among persons with a decline from middle (180 to 239 mg/dL) to low (< 180 mg/dL) TC than in persons remaining at a stable middle level. By contrast, there was no significant increase in all-cause mortality risk among cohort men with stable low TC levels. Nonillness mortality (deaths caused by trauma and suicide) was not related to either TC change or the average of TC levels in exams 1 and 3. CONCLUSIONS: These results add strength to the reverse-causality proposition that catabolic diseases cause TC to decrease.

Aged

Amino acid sequence of spinach ferredoxin:thioredoxin reductase catalytic subunit and identification of thiol groups constituting a redox-active disulfide and a [4Fe-4S] cluster.

Ferredoxin:thioredoxin reductase is a [4Fe-4S] protein involved in the light regulation of carbon metabolism in oxygenic photosynthesis. This enzyme catalyses the reduction of thioredoxins with light-generated electrons. Ferredoxin:thioredoxin reductase is composed of two dissimilar subunits, a catalytic subunit, and a variable subunit. The catalytic subunit of spinach ferredoxin:thioredoxin reductase, which contains the redox-active disulfide bridge, was sequenced by conventional protein sequencing techniques and the functional roles of all eight cysteine residues were examined by chemical modifications. The polypeptide chain with a calculated molecular mass of 12,959 Da consists of 113 amino acids and has a calculated isoelectric point of 5.30. Six of the eight cysteine residues are clustered as Cys-Pro-Cys and Cys-His-Cys groups. Cys19 and Cys27 are free cysteines with no catalytic function, Cys54 and Cys84 constitute the redox-active disulfide bridge of the active site, and the remaining four, Cys52, Cys71, Cys73, and Cys82 bind the Fe-S cluster.

Amino Acid Sequence

Relationship between peritoneal collagen type IV concentrations and the presence of disseminated metastases in gastric cancer.

OBJECTIVE: To predict disseminated microscopic foci or occult micrometastases in the peritoneal cavity in patients with gastric cancer. DESIGN: Randomly selected patients with gastric cancer had peritoneal washings performed at the beginning of laparotomy. PATIENTS: Thirty-nine patients with gastric carcinoma and 10 patients with other benign disease as a control group. SETTING: Inpatients in a surgical department. INTERVENTIONS: The concentration of collagen type IV in the irrigated peritoneal fluid was measured radioimmunologically. Intraoperative peritoneal cytologic examination and measurements of carcinoembryonic antigen (CEA) levels were also performed. MAIN OUTCOME MEASUREMENTS: Results of the quantitative analyses of the collagen type IV concentrations as related to the clinicopathological characteristics and comparison of these results with regard to those of the peritoneal cytologic examination and CEA and collagen type IV levels. RESULTS: There were eight patients with elevated collagen type IV concentrations. They had carcinomas with serosal invasion (pT3 and pT4) and metastatic spread (pN2, M1). Patients with clinically evident peritoneal disseminated metastases had significantly higher collagen type IV concentrations compared with those without metastases. The collagen type IV levels were more sensitive than peritoneal cytologic examination or CEA values in detecting disseminated metastases. There was an early peritoneal recurrence in the form of ovarian metastases in one patient with negative cytologic results and an elevated collagen type IV level. Linear regression analysis showed a statistically significant correlation between the collagen type IV and CEA levels. CONCLUSION: Quantitative detection of abnormal collagen type IV levels may be useful for predicting the presence of disseminated metastases in patients with gastric cancer.

Adult

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

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

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

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

Distribution and correlates of insulin in elderly men. The Honolulu Heart Program.

The role of insulin in cardiovascular disease is uncertain, and studies in elderly or minority populations are infrequent. Fasting and 2-hour insulin concentrations and their cross-sectional associations with cardiovascular risk factors were examined in 3562 elderly (aged 71 to 93 years) Japanese American men from the Honolulu Heart Program who were reexamined between 1991 and 1993. Insulin distributions were skewed (mean and median: 16.8 and 12 microU/mL for fasting; 117.2 and 93 microU/mL for 2-hour); fasting but not 2-hour insulin levels declined significantly with age (P < .0001 and P = .54, respectively). Factors most strongly correlated with insulin included measures of obesity, fat distribution, and levels of triglyceride, glucose (r = .38 to r = .50 fasting, r = .21 to r = .27 2-hour), and HDL cholesterol (r = -.41 and r = -.22, respectively). Other correlates included fibrinogen, hematocrit, heart rate, blood pressure, cigarettes per day (all positive), alcohol, physical activity, and forced vital capacity (negative). Associations were also evident across risk factor quintiles. Insulin levels were significantly elevated in men with hypertension and diabetes. In multiple linear regression analyses, log10 fasting insulin was positively and independently associated with body mass index, triglycerides, glucose, fibrinogen, hematocrit, heart rate, diabetes, and hypertension and negatively associated with HDL cholesterol, physical activity, and forced vital capacity. In general, results were similar for log10 2-hour insulin and when subjects who fasted < 12 hours or had diabetes were excluded. Substitution of medication use and blood pressure for hypertension indicated independent associations of medication use but not blood pressure with insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Role of cathepsin B as prorenin processing enzyme in human kidney.

Renin is synthesized from an inactive precursor, prorenin, through cleavage at a pair of basic amino acids catalyzed by prorenin processing enzyme (PPE). A lysosomal protease, cathepsin B, has been suggested to be a strong candidate for PPE. However, there still remains a possibility that other protease(s) can also catalyze prorenin processing. We studied the subcellular distribution of PPE in human renal cortex using pure recombinant prorenin as a PPE assay substrate. PPE and renin activities, and cathepsin B activity and protein were colocalized in the lysosomal fraction. The PPE activity was completely inhibited by a cathepsin B specific inhibitor, CA074. Taken together with the immunohistochemical data showing that cathepsin B and PPE are colocalized in dense secretory granules of juxtaglomerular cells of kidney, we conclude that cathepsin B is the authentic PPE in human kidney.

Catalysis

Highly increased insulin secretion in a patient with postprandial hypoglycemia: role of glucagon-like peptide-1 (7-36) amide.

The mechanism(s) of an inappropriate secretion of insulin is poorly understood. We report a case of reactive hypoglycemia associated with an unusually exaggerated insulin secretion. The patient, a 32-year-old man, developed frequent episodes of postprandial hypoglycemia after interferon treatment was begun for chronic type C hepatitis. Oral glucose challenge test confirmed the patient's extremely high plasma IRI response, i.e., more than 1000 microU/ml, and that of plasma C-peptide 56.9 ng/ml at 90 min, followed by symptomatic hypoglycemia (plasma glucose 34 mg/dl) at 240 min. The plasma proinsulin level also was high, but the molar ratio of immuno reactive insulin (IRI)/plasma C-peptide and IRI/proinsulin was within the normal range. Antibodies to insulin or insulin-receptor were negative. Plasma IRI response was apparently greater when the glucose was given orally than when given intravenously. The response of plasma glucagon-like-peptide (GLP)-1 to oral glucose was quite high (from baseline of 45.5 to 303.2 pmol/L) and showed a close parallel with the change in the plasma IRI concentration. The greatly enhanced insulin secretion leading to reactive hypoglycemia in this patient may therefore be attributed to the increased secretion of GLP-1.

Adult

Activation of phosphoinositide-specific phospholipase C by transferrin in porcine cerebral arterial smooth muscle cells.

The effect of transferrin on phosphoinositide metabolism was investigated in smooth muscle cells isolated from the porcine basilar artery. Ferric iron-bound transferrin induced a rapid increase in the level of inositol phosphates, the metabolic products of phosphoinositides through the phospholipase C pathway. Neither transferrin free of ferric iron nor ferric iron alone caused the activation of phospholipase C. This study suggests that ferric iron-bound transferrin is capable of eliciting receptor-mediated signal transduction in porcine cerebral arterial smooth muscle cells, which could result in the contraction of smooth muscle cells. Transferrin may be involved with the cerebral arterial narrowing in pathological conditions such as subarachnoid hemorrhage.

Animals

[Antitumor effect of MMC mixed in Beriplast P].

We attempted to mix an anticancer drug. MMC, with a fibrinogen preparation, Beriplast P (B. P.). First, we examined how MMC was gradually released from its mixture. As the result, its release depended on the MMC concentration in B. P., and the release rate of 1.0 mg MMC from 100 microliters B. P. was 1.6 mg/30 min. Second, we examined the safety of the conjugated drug for normal tissue, because MMC is one of anticancer drugs causing serious damage to normal tissue. When the conjugation of 100 microliters B. P. and below 1.6 mg MMC was coated within one square centimeter, the drug was safe for the endothelium of artery and vein, and the intestinal wall. Third, we attempted an experiment on both the antitumor effect and the role of survival prolongation of the conjugated drug in a mouse carrying a malignant tumor. MMC conjugated with Beriplast P had a highly antitumor effect, which caused necrosis in the cancer cells in unstable conditions. Also, its conjugation drug could inhibit the growth of cancer cells in stable conditions, and prolonged the survival period. From these results, the mixture of MMC and B. P. was found to possess an MMC releasing effect, was safe for normal tissues, and showed high antitumor effect with prolongation of the survival period.

Animals

[Immunopotentiation by OK-432 ointment to apply to the mouse abdominal skin].

The immunopotentiating effect of a streptococcal preparation, OK-432 (Picibanil), mixed with an ointment based Lanolin, was examined. The mixture was applied to mouse abdomen. The effect of OK-432 ointment was compared with those of OK-432 ip and sc. The leucocyte count in the abdominal cavity increased in 3.6 x 10(6) and 12.5 x 10(6) on the 3rd day after ointment application and ip injection of 5 KE OK-432, respectively. The result indicated that OK-432-Lanolin applied to the abdominal skin wall affected the abdominal cavity. IL-6 and IFN-gamma in the abdominal cavity increased in 1.4 ng and 9 ng, respectively, after applying 5 KE OK-432 ointment. From these results the treatment with OK-432 ointment on the abdominal skin exhibited an immunomodulatory effect on the abdominal cavity.

Abdomen

Antihypertensive effect of levcromakalim in patients with essential hypertension. Study by 24-h ambulatory blood pressure monitoring.

Levcromakalim (BRL 38227, CAS 94535-50-9) is a new antihypertensive drug with vasodilator activity due to activation of potassium channels in vascular smooth muscle. In this study, we treated 14 patients with essential hypertension on an out-patient basis to investigate the antihypertensive effect of levcromakalim by 24-h blood pressure monitoring for a 12-weeks treatment period. Levcromakalim significantly lowered blood pressure for 24 h without affecting standard deviation, range of variation and pulse rate. When 24-h monitoring period was divided into daytime (6:00-22:00) and nighttime (22:30-5:30), there were no statistically significant differences in magnitude of fall in blood pressure at night between baseline and end of treatment values. Four patients (28.5%) reported 6 adverse events, including headache, facial hot flushes, oedema and floating feeling. All symptoms were mild or moderate. These data show that levcromakalim controls ambulatory blood pressure both in the daytime and nighttime without changing the circadian rhythm of blood pressure, and suggest that levcromakalim will be an efficacious and safe antihypertensive drug.

Adult

[Treatment with percutaneous transluminal balloon venoplasty for superior vena cava syndrome after permanent pacemaker implantation].

Superior vena cava (SVC) syndrome after transvenous implantation of a permanent pacemaker is relatively uncommon. We present a woman whose neck and face became swollen two years after implantation of a two-chamber pacemaker. Computed tomography and digital subtraction angiography revealed severe SVC stenosis. Percutaneous transluminal venoplasty (PTV) was performed to relieve the stenosis. PTV was effective to improve the swelling of her neck and face. PTV seems to be a good method to relieve SVC stenosis after implantation of a pacemaker.

Adult