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Biomedical subjects

Y Hino

Publications and source records attributed to Y Hino.

At least 19 recordsLinked to original sources

Workplace exposure to environmental tobacco smoke and high density lipoprotein cholesterol among nonsmokers.

There are few epidemiologic studies among adult nonsmokers on the effects of workplace environmental tobacco smoke on high density lipoprotein cholesterol (HDL-C). The authors investigated this relation, using data from health examinations conducted in 1995 on 3,062 Japanese nonsmokers in a total of 27 municipal offices with few smoking restrictions. Multiple regression analysis with adjustments for age, body mass index, alcohol drinking, and sports activities showed that in women, and in men lacking both alcohol consumption and sports activities characteristics, there were inverse linear relations between workplace smoking indices and HDL-C levels. Multivariate logistic regression showed that nonsmoking women in the upper two thirds of offices ranked by smoking intensity had an increased risk of low HDL-C levels (<45 mg), taking those in the lowest third of offices as reference (the medium third: odds ratio = 1.7; 95% confidence interval: 1.2, 2.5; the highest third: odds ratio = 1.6; 95% confidence interval: 1.1, 2.4). The results indicated that workplace environmental tobacco smoke exposure is associated with HDL-C among nonsmokers. However, the lack of data on home exposure limits causal inferences about the effects of workplace exposure.

Adult

Dominant negative forms of Akt (protein kinase B) and atypical protein kinase Clambda do not prevent insulin inhibition of phosphoenolpyruvate carboxykinase gene transcription.

Transcriptional regulation of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in hepatic gluconeogenesis, by insulin was investigated with the use of adenovirus vectors encoding various mutant signaling proteins. Insulin inhibited transcription induced by dexamethasone and cAMP of a chloramphenicol acetyltransferase (CAT) reporter gene fused with the PEPCK promoter sequence in HL1C cells stably transfected with this construct. A dominant negative mutant of phosphoinositide (PI) 3-kinase blocked insulin inhibition of transcription of the PEPCK-CAT fusion gene, whereas a constitutively active mutant of PI 3-kinase mimicked the effect of insulin. Although a constitutively active mutant of Akt (protein kinase B) inhibited PEPCK-CAT gene transcription induced by dexamethasone and cAMP, a mutant Akt (Akt-AA) in which the phosphorylation sites targeted by insulin are replaced by alanine did not affect the ability of insulin to inhibit transcription of the fusion gene. Akt-AA almost completely inhibited insulin-induced activation of both endogenous and recombinant Akt in HL1C cells. Furthermore, neither a kinase-defective mutant protein kinase Clambda (PKClambda), which blocked insulin-induced activation of endogenous PKClambda, nor a dominant negative mutant of the small GTPase Rac prevented inhibition of PEPCK-CAT gene transcription by insulin. These data suggest that phosphoinositide 3-kinase is important for insulin-induced inhibition of PEPCK gene transcription and that a downstream effector of phosphoinositide 3-kinase distinct from Akt, PKClambda, and Rac may exist for mediating the effect of insulin.

Cell Line

Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1).

The roles of Akt (protein kinase B) and the atypical lambda isoform of protein kinase C (PKClambda), both of which act downstream of phosphoinositide 3-kinase, in the activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1) in response to insulin were investigated. A mutant Akt (Akt-AA) in which the phosphorylation sites targeted by growth factors are replaced by alanine was shown to inhibit insulin-induced activation of both Akt and glycogen synthase in L6 myotubes. Expression of a mutant Akt in which Lys179 in the kinase domain was replaced by aspartate also inhibited insulin-induced activation of glycogen synthase but had no effect on insulin activation of endogenous Akt. A kinase-defective mutant of PKClambda (lambdaDeltaNKD), which prevents insulin-induced activation of PKClambda, did not affect the activation of glycogen synthase by insulin. Insulin-induced phosphorylation of 4E-BP1 was inhibited by Akt-AA in Chinese hamster ovary cells. However, lambdaDeltaNKD had no effect on 4E-BP1 phosphorylation induced by insulin. These data suggest that Akt, but not PKClambda, is required for insulin activation of glycogen synthase and for insulin-induced phosphorylation of 4E-BP1.

Amino Acid Sequence

Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1.

The complete sequence of the genome of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1, which optimally grows at 95 degrees C, has been determined by the whole genome shotgun method with some modifications. The entire length of the genome was 1,669,695 bp. The authenticity of the entire sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2,694 open reading frames (ORFs) were assigned. By similarity search against public databases, 633 (23.5%) of the ORFs were related to genes with putative function and 523 (19.4%) to the sequences registered but with unknown function. All the genes in the TCA cycle except for that of alpha-ketoglutarate dehydrogenase were included, and instead of the alpha-ketoglutarate dehydrogenase gene, the genes coding for the two subunits of 2-oxoacid:ferredoxin oxidoreductase were identified. The remaining 1,538 ORFs (57.1%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs suggested that a considerable member of ORFs were generated by sequence duplication. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 47 tRNA genes including 14 genes with intron structures. All the assigned ORFs and RNA coding regions occupied 89.12% of the whole genome. The data presented in this paper are available on the internet homepage (http://www.mild.nite.go.jp).

Archaea

Alteration of perceived fragrance of essential oils in relation to type of work: a simple screening test for efficacy of aroma.

The perceptional change of fragrance of essential oils is described in relation to type of work, i.e. mental work, physical work and hearing environmental (natural) sounds. The essential oils examined in this study were ylang ylang, orange, geranium, cypress, bergamot, spearmint and juniper. In evaluating change in perception of a given aroma, a sensory test was employed in which the perception of fragrance was assessed by 13 contrasting pairs of adjectives. Scores were recorded after inhaling a fragrance before and after each type of work, and the statistical significance of the change of score for 13 impression descriptors was examined by Student's t-test for each type of work. It was confirmed that inhalation of essential oil caused a different subjective perception of fragrance depending on the type of work. For example, inhalation of cypress after physical work produced a much more favorable impression than before work, in contrast to orange, which produced an unfavorable impression after physical work when compared with that before work. For mental work, inhalation of juniper seemed to create a favorable impression after work, whereas geranium and orange both produced an unfavorable impression then. From these studies, together with those conducted previously with lavender, rosemary, linalool, peppermint, marjoram, cardamom, sandalwood, basil and lime, we thus concluded that the sensory test described here might serve not only as a screening test for efficacy of aroma but also as a categorized table for aroma samples which can act as a reference to each other.

Adult

Associations between self-assessed masticatory disability and health of community-residing elderly people.

OBJECTIVE: To examine the relationship between the self-assessed masticatory disability and the health of community-residing older people. METHODS: Of 1473 randomly selected people aged 65 years and older living in Settsu, Osaka Prefecture, in October 1992, data on general health status, history of health management, psychosocial conditions, and dental conditions were obtained from 1405 people by interviews made during home visits. Follow-up for 54 months was completed for 1306 subjects (93.0%; 1072 living, 234 deceased). RESULTS: Being over 75 years of age, having poor general health and poor dental status, not using dental health checks, not using general health checks, not participating in social activities, not feeling that life is worth living (no "ikigai"), and feeling anxious about the future were univariately and significantly associated with self-assessed masticatory disability. Logistic regression analyses indicated that being older than 75 years, having poor general health and poor dental status, not using dental health checks, and not participating in social activities were independently associated with self-assessed masticatory disability. The Cox proportional hazards model showed that being male, over 75 years of age, and in poor general health, as well as not using general health checks, and not participating in social activities were independently associated with mortality. Self-assessed masticatory disability was univariately and significantly related to mortality, but by itself was not a significant risk factor for mortality, because of the potential influence of other variables. CONCLUSIONS: Certain health and psychosocial factors are closely associated with self-assessed masticatory disability among older people. Further investigations are needed to determine whether masticatory disability is a significant risk factor for mortality.

Aged

Intraosseous epithelioid malignant peripheral nerve sheath tumor of the phalanx. Case report.

We report the first case of intraosseous epithelioid malignant peripheral nerve sheath tumor (MPNST) occurring in the phalanx. The patient was a 50-year-old Japanese man with an intramedullary lytic lesion of the proximal phalanx. Microscopically, the tumor was composed of epithelioid cells or polygonal cells, forming large cell nests with central necrosis. Most tumor cells were diffusely and strongly immunopositive for S-100 protein and vimentin, and negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, alpha-smooth muscle actin, and HMB-45. Laminin-positive material was discontinuously demonstrated between the individual tumor cells. Electron microscopy showed prominent external lamina. Our case indicated that laminin is useful for differentiating epithelioid MPNST from metastatic carcinoma and malignant melanoma.

Bone Neoplasms

Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation and activation of endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be inhibited by a dominant-negative mutant of the serine-threonine kinase Akt, suggesting that Akt is necessary for insulin-induced phosphorylation and activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS) that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273 was replaced by alanine was not phosphorylated either in response to insulin in intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which alanine was substituted for either serine-296 or serine-421, each of which lies within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein kinase, were phosphorylated by Akt in vitro or in response to insulin in intact cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when expressed in adipocytes. These results suggest that PDE3B is a physiological substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is important for insulin-induced activation of PDE3B.

3',5'-Cyclic-AMP Phosphodiesterases

Changes in endothelium-derived vascular regulatory factors during dobutamine-stress-induced silent myocardial ischemia in patients with Kawasaki disease.

The changes in endothelium-derived vascular regulatory factors during dobutamine (DOB)-induced myocardial ischemia (MI) were investigated in 21 patients with Kawasaki disease aged from 11 months to 18 years. They were classified into an ischemia group (8 patients) and a non-ischemia group (13 patients) based on the results of 99mTc myocardial scintigraphy and DOB stress 99mTc myocardial scintigraphy. In the ischemia group, MI was relatively mild, because there were ischemic changes on the electrocardiogram and no significant symptoms during DOB stress. Catheters were positioned near the orifice of the coronary artery (Ao) and at the coronary sinus (CS). Hemodynamics and the blood concentrations of lactic acid and endothelin-1, as well as NO3-, 6-keto-prostaglandin F1alpha, and thromboxane B2, (which are inactive metabolites of nitric oxide, prostaglandin I2 and thromboxane A2, respectively), were measured at rest and after DOB stress (maximum dose: 30 microg x kg(-1) x min(-1)). The CS/Ao ratio was determined for all parameters. The rate-pressure product, an index of work load, and the cardiac index were significantly increased by DOB stress in both groups. Coronary angiography showed no vasospasm of the epicardial coronary arteries before or after DOB stress in either group. The plasma concentrations of endothelin-1 and 6-keto-prostaglandin F1alpha were significantly increased after DOB stress in the ischemia group, but the serum concentration of NO did not increase. The lack of an increase in NO production during DOB stress may have contributed to the worsening of MI in patients with Kawasaki disease.

Adolescent

[Research on the contents of material safety data sheets].

The Material Safety Data Sheet (MSDS) system for the safe management of chemical substances was officially promulgated in 1993 and has been gradually put into practice through administrative guidance in Japan. However, little research has been done on the quality of such data sheets provided from various sectors of industries. We examined two sets of MSDSs obtained from a refractory ceramic plant. In the first survey in 1995, the set of MSDSs was from July, 1992 to March, 1994; and in the second survey in 1997, the set was from April, 1994 to November, 1996. The number of MSDSs examined in these two surveys was 159 and 81, respectively. The number of MSDSs in which "Hazard Identification" was indicated was 100 (63%) in the 1995 survey and 75 (93%) in the 1997 survey. The number of those in which "Toxicological Information (Stability and Reactivity)" was indicated was 81 (51%) and 80 (99%), respectively. The description rates for the essential items, including the above two, were found to be improving.

Data Collection

Complete sequence and gene organization of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3.

The complete sequence of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3, has been determined by assembling the sequences of the physical map-based contigs of fosmid clones and of long polymerase chain reaction (PCR) products which were used for gap-filling. The entire length of the genome was 1,738,505 bp. The authenticity of the entire genome sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2061 open reading frames (ORFs) were assigned, and by similarity search against public databases, 406 (19.7%) were related to genes with putative function and 453 (22.0%) to the sequences registered but with unknown function. The remaining 1202 ORFs (58.3%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs in the genome provided evidence that a considerable number of ORFs were generated by sequence duplication. By similarity search, 11 ORFs were assumed to contain the intein elements. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 46 tRNA genes including two with the intron structure. All the assigned ORFs and RNA coding regions occupied 91.25% of the whole genome. The data presented in this paper are available on the internet at http:@www.nite.go.jp.

Chromosomes, Archaeal

A de novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic long QT sydrome. Mutations in brief no. 140. Online.

Two missense mutations and a nine-nucleotide deletion of the cardiac sodium channel (SCN5A) gene have been shown to cause long QT syndrome (LQTS) in several familial cases. We identified a novel missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic LQTS. We used polymerase chain reaction, single-strand conformation polymorphism analysis and DNA sequence analysis to identify a mutation of the SCN5A gene in the patient. A single nucleotide substitution of guanine to adenine, in codon 1612, changed the coding sense of the SCN5A from arginine to glutamine (R1623Q) in the S4 segment of domain IV which is a highly conserved region of the SCN5A. This mutation was not identified in the unaffected biological parents and brother of the patient, and 100 normal, unrelated individuals. This finding is the first evidence of a de nova mutation in SCN5A associated with LQTS.

Amino Acid Substitution

Body mass decrease after initial gain following smoking cessation.

BACKGROUND: Although smoking cessation is strongly associated with subsequent weight gain, it is not clear whether the initial gain in weight after smoking cessation remains over time. METHOD: Cross-sectional analyses were made, using data from periodic health examinations for workers, on the relationship between body mass index (BMI) and the length of smoking cessation. In addition, linear regression coefficients of BMI on the length of cessation were estimated according to alcohol intake and sport activity, to examine the modifying effect of these factors on the weight of former smokers. RESULTS: Means of BMI were 23.1 kg/m2, 23.3 kg/m2, 23.6 kg/m2 for light/medium smokers, heavy smokers and never smokers, respectively. Among former smokers who had smoked > or = 25 cigarettes a day, odds ratio (OR) of BMI >25 kg/m2 were 1.88 (95% confidence interval [CI] : 1.05-3.35), 1.32 (95% CI : 0.74-2.34), 0.66 (95% CI: 0.33-1.31) for those with 2-4 years, 5-7 years, and 8-10 years of smoking cessation, respectively. The corresponding OR among those who previously consumed <25 cigarettes a day were 1.06 (95% CI: 0.58-1.94), 1.00 (95% CI: 0.58-1.71), and 1.49 (95% CI: 0.95-2.32). CONCLUSIONS: The results suggest that although heavy smokers may experience large weight gain and weigh more than never smokers in the few years after smoking cessation, they thereafter lose weight to the never smoker level, while light and moderate smokers gain weight up to the never smoker level without any excess after smoking cessation.

Adult

Relation between intellectual dysfunctioning and mortality in community-residing older people.

OBJECTIVE: To examine the relationship between intellectual dysfunctioning and mortality in a community-residing older population. DESIGN: Of the 1473 randomly selected people aged 65 years and older living in Settsu, Osaka Prefecture, in October 1992, 1405 were contacted. Data for assessment of intellectual dysfunctioning were obtained from 1383 people (98.4%), who constituted the study cohort. Follow-up for 42 months was completed for 1300 subjects (94.0%; 1117 living, 183 deceased). MEASURES: Data on general health status, history of health management, psychosocial conditions, and intellectual dysfunctioning were collected by means of interviews during home visits at the time of enrollment. Intellectual dysfunctioning was determined with the assessment instrument developed by the Social Survey Division of the Office of Population Censuses (OPCS) in Great Britain. RESULTS: The Kaplan-Meier analysis indicated that the estimated survival rates for men and women decreased with a decline in intellectual function in two age groups: 65 to 74 and 75 years and older. For both sexes, the log rank test showed that the curves among the four groups based on intellectual dysfunctioning (intact, mild, moderate, and severe) achieved statistical significance for the age group of 75 years and older. For both age groups and each of the levels of intellectual dysfunctioning, the estimated survival rate for men was lower than that for women. Application of the Cox proportional hazards model resulted in unadjusted hazard ratios of mild, moderate, and severe intellectual dysfunctioning for mortality of 1.68, 2.44, and 5.37, respectively. Multivariate analysis on the other hand, yielded adjusted hazard ratios of mild, moderate, and severe intellectual dysfunctioning of 1.19, 1.12, and 1.74, respectively, leaving severe dysfunctioning as the only statistically significant factor associated with mortality. Other factors such as sex, age, general health status, history of management, and psychosocial conditions were controlled. CONCLUSION: Intellectual dysfunctioning, as measured by an assessment instrument developed by OPCS, represents an increased risk factor for mortality among community-residing older people.

Activities of Daily Living

Requirement of atypical protein kinase clambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes.

Phosphoinositide (PI) 3-kinase contributes to a wide variety of biological actions, including insulin stimulation of glucose transport in adipocytes. Both Akt (protein kinase B), a serine-threonine kinase with a pleckstrin homology domain, and atypical isoforms of protein kinase C (PKCzeta and PKClambda) have been implicated as downstream effectors of PI 3-kinase. Endogenous or transfected PKClambda in 3T3-L1 adipocytes or CHO cells has now been shown to be activated by insulin in a manner sensitive to inhibitors of PI 3-kinase (wortmannin and a dominant negative mutant of PI 3-kinase). Overexpression of kinase-deficient mutants of PKClambda (lambdaKD or lambdaDeltaNKD), achieved with the use of adenovirus-mediated gene transfer, resulted in inhibition of insulin activation of PKClambda, indicating that these mutants exert dominant negative effects. Insulin-stimulated glucose uptake and translocation of the glucose transporter GLUT4 to the plasma membrane, but not growth hormone- or hyperosmolarity-induced glucose uptake, were inhibited by lambdaKD or lambdaDeltaNKD in a dose-dependent manner. The maximal inhibition of insulin-induced glucose uptake achieved by the dominant negative mutants of PKClambda was approximately 50 to 60%. These mutants did not inhibit insulin-induced activation of Akt. A PKClambda mutant that lacks the pseudosubstrate domain (lambdaDeltaPD) exhibited markedly increased kinase activity relative to that of the wild-type enzyme, and expression of lambdaDeltaPD in quiescent 3T3-L1 adipocytes resulted in the stimulation of glucose uptake and translocation of GLUT4 but not in the activation of Akt. Furthermore, overexpression of an Akt mutant in which the phosphorylation sites targeted by growth factors are replaced by alanine resulted in inhibition of insulin-induced activation of Akt but not of PKClambda. These results suggest that insulin-elicited signals that pass through PI 3-kinase subsequently diverge into at least two independent pathways, an Akt pathway and a PKClambda pathway, and that the latter pathway contributes, at least in part, to insulin stimulation of glucose uptake in 3T3-L1 adipocytes.

3T3 Cells

Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.

A wide variety of biological activities including the major metabolic actions of insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, the downstream effectors of the various signaling pathways that emanate from PI 3-kinase remain unclear. Akt (protein kinase B), a serine-threonine kinase with a pleckstrin homology domain, is thought to be one such downstream effector. A mutant Akt (Akt-AA) in which the phosphorylation sites (Thr308 and Ser473) targeted by growth factors are replaced by alanine has now been shown to lack protein kinase activity and, when overexpressed in CHO cells or 3T3-L1 adipocytes with the use of an adenovirus vector, to inhibit insulin-induced activation of endogenous Akt. Akt-AA thus acts in a dominant negative manner in intact cells. Insulin-stimulated protein synthesis, which is sensitive to wortmannin, a pharmacological inhibitor of PI 3-kinase, was abolished by overexpression of Akt-AA without an effect on amino acid transport into the cells, suggesting that Akt is required for insulin-stimulated protein synthesis. Insulin activation of p70 S6 kinase was inhibited by approximately 75% in CHO cells and approximately 30% in 3T3-L1 adipocytes, whereas insulin-induced activation of endogenous Akt was inhibited by 80 to 95%, by expression of Akt-AA. Thus, Akt activity appears to be required, at least in part, for insulin stimulation of p70 S6 kinase. However, insulin-stimulated glucose uptake in both CHO cells and 3T3-L1 adipocytes was not affected by overexpression of Akt-AA, suggesting that Akt is not required for this effect of insulin. These data indicate that Akt acts as a downstream effector in some, but not all, of the signaling pathways downstream of PI 3-kinase.

3T3 Cells