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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 361 records · Page 20Linked to original sources

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↗

A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty.

A single point mutation that encodes an aspartic acid (Asp578) to glycine substitution in the LH/CG receptor (LH/CGR) gene, D578G, was recently found in American patients with familial male-limited precocious puberty and in a Japanese patient with a sporadic form of the disorder. Transfection of the mutant, compared to the wild-type, LH/CGR complementary DNA into COS-7 cells results in higher basal cAMP production, but a normal agonist-induced response; the mutation is, therefore, proposed to constitutively activate Leydig cells and elevate serum testosterone, despite low levels of gonadotropin. In the current study we examined two additional Japanese patients with male-limited precocious puberty without a family history of the disease. We describe a heterozygous cytosine (C) to thymine (T) transition at nucleotide 1715 in both; the mutation encodes an alanine to valine substitution in codon 572 of transmembrane helix 6, A572V. Transfected into COS-7 cells, the A572V mutant exhibited the same constitutively high basal cAMP levels and normal agonist-induced cAMP response as the D578G mutant. We conclude that the constitutively higher cAMP levels caused by the A572V mutation led to Leydig cell activation and male-limited precocious puberty, as in the previously described D578G mutation. As the mother of one of the two patients had the same heterozygous mutation, this patient represents the first recognized case of inherited male-limited precocious puberty in the Japanese population. The previously described D578G mutant did not increase basal or agonist-induced inositol phosphate production in transfected COS-7 cells, or the number of LH/CGRs or their affinity for LH/CG. In contrast, transfection of the A572V mutation in COS-7 cells exhibited significantly higher inositol phosphate levels basally and at 10(-11) mol/L hCG, but significantly lower inositol phosphate levels at 10(-7) mol/L hCG. These data suggest that the A572V mutation of the LH/CGR may have effects on the guanine nucleotide binding protein which activates phospholipase C (Gq) coupling and phospholipase-C activation in addition to its effects on Gs coupling and activation of adenylyl cyclase. A572V-transfected cells also exhibited a higher affinity, despite an apparent decrease in the number of binding sites, for [125I]hCG, compared to transfectants with the wild-type LH/CGR. We hypothesize that these differences between the A572V and D578G mutations reflect a greater impact of the A572V mutation on receptor conformation.

Base Sequence↗

Effects of aprindine on electrophysiological properties of the atrial muscle in man.

The effects of aprindine on atrial vulnerability were studied in 11 patients; 9 with paroxysmal atrial fibrillation (PAF), and 2 with Wolff-Parkinson-White syndrome, aged 19 to 69 (55.9 +/- 16.5; mean +/- SD). Before and 10 min after the intravenous injection of aprindine (1.5 mg/kg), programmed extrastimulation was performed from the right atrial appendage. Atrial vulnerability was assessed by evaluating the repetitive atrial firing zone (RAFZ), conduction delay zone (CDZ), maximum conduction delay (Max. CD) and fragmented atrial activity zone (FAAZ). After the injection, the duration of the P wave and QTc interval was significantly prolonged without any change in blood pressure or heart rate. RAF was observed in 8 patients under control conditions. However, after the injection of aprindine, the RAFZ completely disappeared in 2 patients, was narrowed in 4, and became wider in 1. AF was induced in the remaining patient. The zone significantly reduced (p < 0.01) without any change in CDZ or Max. CD. While FAA was observed in 5 patients under control conditions, it completely disappeared in 2 patients, was narrowed in 1, and did not change in the remaining 7 after the injection of aprindine. In patients whose RAFZ narrowed after administration of aprindine, the wavelength, as determined from the atrial effective refractory period and conduction velocity, was augmented. These results indicate that aprindine suppresses atrial vulnerability with an augmentation of the wavelength. However aprindine exaggerated atrial vulnerability in some patients, such that atrial fibrillation was induced.

Action Potentials↗

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↗

Cytosolic free calcium elevation in vascular smooth muscle cells induced by cerebrospinal fluid from patients with subarachnoid hemorrhage--biochemical nature of the calcium-mobilizing factor.

The present study was undertaken to characterize the biochemical nature of the factor in cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) that induces a transient elevation of cytosolic free calcium in cultured vascular smooth muscle cells. Cell-free CSF collected from patients on days 7-10 after SAH was treated in three different ways: heating, ultrafiltration, and salting out with ammonium sulfate. The effects of the resultant solutions on the level of cytosolic free calcium in cultured vascular smooth muscle cells were then examined. Heated CSF and ultrafiltrated solution containing substances with molecular weights of less than 10,000 caused no significant elevation of cytosolic free calcium. Proteins precipitated by 50-75% saturated ammonium sulfate caused an increase in the level of cytosolic free calcium and also produced a rapid accumulation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. The results indicate that the factor responsible for the increase in cytosolic free calcium in cultured vascular smooth muscle cells is a protein with a molecular weight of more than 10,000, and the factor stimulates receptor-mediated phosphoinositide breakdown.

Calcium↗

RES-701-2, -3 and -4, novel and selective endothelin type B receptor antagonists produced by Streptomyces sp. I. Taxonomy of producing strains, fermentation, isolation, and biochemical properties.

RES-701-2, -3 and -4, novel cyclic peptide endothelin antagonists, were isolated from the culture broths of Streptomyces sp. RE-701 and RE-896, RES-701s selectively inhibited the ET-1 binding to endothelin type B receptor (ETB receptor) with IC50 values ranging from 5 to 20 nM. Taxonomy of the producing strains, fermentation, isolation and biochemical properties of RES-701s are described.

Amino Acid Sequence↗

[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↗

[Varicella pneumonia with multiple nodular shadows after allogeneic bone marrow transplantation in chronic myeloid leukemia].

A 30-year-female with chronic myelogenous leukemia received allogeneic bone marrow transplantation (BMT). On day 104, low-grade fever, cough, and general malaise developed, resulting in hospitalization 10 days later. Chest X ray revealed diffuse infitrates, suggesting cytomegalovirus interstitial pneumonia. Ganciclovir (DHPG) was given daily and all symptoms disappeared three days later. However, a very few vesicular lesions appeared on her trunk and her two children had chickenpox at that time. Chest CT was taken and disclosed diffuse nodular shadows. Clinical course and chest CT suggested varicella pneumonia. DHPG administration was stopped and acyclovir PO started to be given. She was discharged in excellent condition. In this report, we show a rare case of varicella pneumonia after allogeneic BMT and efficacy of DHPG for the treatment of varicella pneumonia.

Acyclovir↗

Alterations in DNA and cell membranes in an initiation process of carcinogenesis by N-nitrosourea.

We examined DNA alkylation of rat organs (liver, stomach, kidney, lung, and brain) treated with a tissue specific carcinogen, N-methyl-N'-(beta-naphthyl)-N-nitrosourea (MNaNU) (200 mg/kg wt.). There is no correlation between the level of O6-methylguanine (O6-MeG) and formation of tumors with these organs. Fourier-transform infrared (FT-IR) spectra of the treated tissues were compared with those obtained form the non-treated organs in the region between 1000 and 1350 cm-1. The infrared spectra of the treated stomach which is a target organ for induction of tumors showed the formation of hydrogen bonding in carbohydrates, disturbance of nucleic acid structures, and presence of disordered states in the membranes. Further, the stomachs were divided into the forestomachs (target tissue) and glandular stomachs, and their FT-IR spectra were also examined. Using 1134 cm-1 band due to the C-H plane bending of the naphthyl ring of MNaNU, we estimated approximately 0.82 mg of MNaNU would persist in the forestomach of one rat at 6h after administration. The present results demonstrate importance of pharmacokinetics and receptor sites in cell membrane in addition to DNA alkylation for carcinogenesis by directly acting N-nitroso compounds.

Alkylating Agents↗

Vitellogenin gene of the silkworm, Bombyx mori: structure and sex-dependent expression.

Vitellogenin of Bombyx mori is a precursor of major yolk protein synthesized in the female fat body at larval-pupal ecdysis. The gene for B. mori vitellogenin is composed of seven exons interspersed by six introns. Developmental profile of the primary transcript of the gene indicated that the biosynthesis of B. mori vitellogenin is regulated transcriptionally in a sex- and stage-dependent manner in the fat body. The Arg-X-Arg-Arg sequence, which conforms to the recognition site of mammalian furin, occurs in a region just upstream of the putative proteolytic cleavage site of B. mori previtellogenin.

Aedes↗

High conservation of subunit composition of RNA polymerase I(A) between yeast and mouse and the molecular cloning of mouse RNA polymerase I 40-kDa subunit RPA40.

Mouse RNA polymerase I (or A) was purified from an ascites cell line MH134 to virtual homogeneity using a novel purification procedure and examined for subunit composition. In marked contrast to older purifications that reported 5-8 subunits, polymerase I was found to have 11 subunits with remarkable correspondence to those of yeasts. The cDNA encoding a 40-kDa subunit of this enzyme, designated RPA40, was isolated. It predicts a polypeptide of 355 amino acids (M(r) = 40,065) and is encoded by a single copy gene. Protein sequence analysis reveals that RPA40 is the homolog of yeast RPC40, having homology to alpha subunit of Escherichia coli RNA polymerase, yeast RPB3, and human RPB33 RNA polymerase II subunits. The high conservation of this subunit among distant eukaryotes and different RNA polymerases suggests functional importance of this protein as a core subunit.

Amino Acid Sequence↗