Search

Detailed epidemiological investigations on the relationship of environmental factors, especially occupational and microbiological factors, to the development of idiopathic dilated cardiomyopathy (IDC) are scarce.A multi-hospital case-control study was conducted in 38 hospitals throughout Japan in order to survey IDC cases and age, sex-matched outpatient controls at each hospital. Crude and adjusted odds ratios (ORs) by various environmental factors were calculated in 135 pairs of cases and controls. Univariate analyses revealed significantly increased ORs for lower education, passive smoking in the workplace, cold and/or hot workplace, symptoms of fatigue and history of bacterial infection; in contrast, decreased ORs were associated with a history of rubella and gastroduodenal diseases. Based on multivariate adjusted analyses, lower education (OR 1.96, 95% confidence interval (CI) 1.13-3.40), cold or hot workplace (OR 1.84, 95%CI 1.08-3.12) and history of measles (OR 1.78, 95%CI 1.01-3.08) exhibited a significant positive relationship with IDC risk. History of rubella (OR 0.17, 95%CI 0.06-0.52) and gastroduodenal diseases (OR 0.14, 95%CI 0.07-0.29) were inversely related to the risk.Some occupational and microbiological factors appear to relate independently to the development of IDC and further investigation is required to establish their respective mechanisms.

A cross-sectional study on 6,676 workers consisting of 4,243 males and 2,433 females aged 20-58 yr in a metal product factory was conducted to elucidate the relationship between work characteristics, e.g. job demand/control/support, sedentary job, overtime work and shift work, and waist to hip ratio (WHR) as well as body mass index (BMI) taking alcohol consumption, smoking, exercise and other psychosocial factors such as education and marital status into account. By a stepwise multiple regression analysis, BMI was associated with shift work, marital status and sedentary job for males, and with exercise but inversely associated with education for females. WHR was also associated with shift work, alcohol consumption, marital status and sedentary job but inversely associated with exercise for males, and with sedentary job, marital status and education but inversely associated with smoking for females. These results suggest that work characteristics such as sedentary job and shift work should also be considered when trying to prevent increases in BMI and WHR.

Evidence regarding the relationship between childhood obesity and adult obesity in Japan is limited. This study was conducted to determine the relationship between childhood mass index (BMI) at 3 months, 12 months, 3 years and 20 years in a general population.Data obtained from men and women aged 20 years (born between 1968-1974), who had received medical examinations in Ishikawa Prefecture, Japan, were linked to data of medical examinations of the same individuals as infants (3 months, 12 months, and 3 years). The relationship between childhood BMI (or Kaup index) and adult BMI was analyzed for a total of 2,314 participants (1,080 men and 1,234 women), whose data could be followed for 20 years.BMI at 20 years displayed significant positive correlations with BMI at 3 months, 12 months, and 3 years; this correlation was strongest with respect to BMI at 3 years (r = 0.33, p0.001 in men; r = 0.42, p0.001 in women). In terms of percentages of obese participants (BMI 25 kg/m2 or over) at 20 years in accordance with BMI categories at each age, the rates were 4.6% in men and 1.0% in women with a BMI less than 15 kg/m2 at 3 years, but 29.1% and 29.5%, respectively, with a BMI of 18 kg/m2 or over (6.3 and 29.5 times higher, respectively). Percentages of obese participants at 20 years were highest in those exhibiting an above average BMI at 3 years, regardless of the BMI at 3 months.Body mass in young adults is strongly related to body mass in childhood, especially with that at 3 years. About 30 percent of obese children at 3 years remain obese into adulthood. These results are of interest with respect to assessment of future risk of adulthood obesity at medical examinations for infants in Japan.

We studied the molecular mechanism through which the fungal beta-lactone, hymeglusin, potently and specifically inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase. [(14)C]Hymeglusin covalently bound to purified rat liver and to recombinant hamster cytosolic HMG-CoA synthases. The enzyme activity was completely inhibited at a binding ratio of 1.6-2.0 mol [(14)C]hymeglusin/mol HMG-CoA synthase. Incubating the enzyme with 2 mM iodoacetamide (IAA) or 2 mM N-ethylmaleimide (NEM) but not with 1.0 mM diisopropyl fluorophosphates (DFP) completely inhibited the binding, suggesting that hymeglusin binds to a Cys residue of HMG-CoA synthase. Recombinant hamster HMG-CoA synthase labeled with [(3)H]hymeglusin was digested with V8 protease, and the [(3)H]peptide was purified by high performance liquid chromatography (HPLC). The sequence of the peptide was Ser-Gly-Asn-Thr-Asp-Ile-Glu-Gly-Ile-Asp-Thr-Thr-Asn-Ala-[(3)H]hymeglusyl Cys-Tyr-Gly-Gly-Thr-Ala-Ala-Val-Phe-Asn-Ala-Val-Asn-, which corresponds to the active site sequence (from Ser 115 to Asn 141) of hamster HMG-CoA synthase. These findings showed that hymeglusin inhibits hamster cytosolic HMG-CoA synthase by covalently modifying the active Cys 129 residue of the enzyme.

A 36-year-old man was admitted to our hospital complaining of cough, dyspnea on exertion, skin eruptions, and joint pain. Characteristic skin lesions such as erythema around the nails, telangiectasis, and edema of the eyelids were observed in this patient. He had never complained of muscle symptoms, and his laboratory examinations showed no elevation of either CPK or aldolase. From several lines of evidence including the skin biopsy findings, amyopathic dermatomyositis was diagnosed. Chest X-ray films showed subpleural funicular opacities and consolidation in both lower lung fields. Lung biopsy specimens taken under video-assisted thoracoscopic surgery revealed nonspecific interstitial pneumonia, group II. Oral prednisolone treatment was initiated at 60 mg daily together with oral cyclosporin A (100-150 mg daily). The minimum serum concentration of cyclosporin A was maintained between 100 and 200 ng/ml. Respiratory symptoms gradually improved, and the oral prednisolone dose was tapered off. Pulmonary function and chest CT findings showed marked improvement.

The purpose of the present study was to examine, in the aging people, racial and gender differences in the morphology of corneal endothelium as well as the incidence of cornea guttata in two Asian subject groups, one in Singapore and the other in Japan. Four hundred and sixty-five Chinese Singaporeans and 299 Japanese subjects (residents of Monzen-machi, Ishikawa Prefecture) aged 50 years and older were recruited for the study. Corneal endothelial abnormalities were diagnosed with slit-lamp biomicroscopy and specular microscopy. Primary cornea guttata appeared as beaten metal appearance in slit-lamp images and dark regions in specular images. In addition to cornea guttata, corneal endothelial morphology was also analysed with specular microscopy. The mean cell density was 2,808/mm2 in the Japanese subjects which was significantly higher than the 2,718/mm2 seen in the Singaporeans (p < 0.001). The incidence of cornea guttata was significantly higher in the Singaporeans than in the Japanese individuals and also higher in women than in men of both racial groups. These differences support not only a racial and a gender factor but also a possible environmental influence.

To clarify the effects of nutrient/food intake and lifestyle, especially exercise, on calcaneal bone mass in both male and female high school students.A total of 798 healthy Japanese high school students (281 boys and 517 girls) were recruited, and their calcaneal bone was assessed by ultrasound using Lunar Achilles. The subjects were thereby divided into a lower bone mass group and a normal bone mass group according to stiffness at the cut-off level of 90 for the boys, and 77 for the girls. Information on lifestyle including frequency of food consumption and regular exercise during the period at junior high school and high school was collected by questionnaire. Nutrient intake was assessed by a semi-quantitative food frequency questionnaire.1. The intake of total energy and fat in the lower bone mass group was lower than in the normal bone mass group in both sexes. 2. The frequency of subjects not consuming milk in the lower bone mass group was higher than in the normal bone mass group in both sexes. In the boys, the frequency of the subjects who liked to eat green vegetables in the lower bone mass group was lower in the normal bone mass group. 3. The mean stiffness for subjects undertaking exercise during junior high school was higher than in subjects not exercising, even after adjustment for age in both sexes. The frequency of subjects with a habit of sun bathing in the lower bone mass group was significantly lower than in the normal bone mass group in the girls. 4. An analysis using a logistic model was performed to select the factors related to lower bone mass without being confounded with other factors. Lower energy intake in boys and lower fat intake, no exercise during high school life and no milk consumption in girls were each independently related to lower bone mass.These results suggest that nutrition and exercise habit affect calcaneal bone mass in high school students of both sexes, especially milk consumption being an important factor related to bone mass in girls.

Expression of retroviral Gag protein in yeast has previously shown Gag targeting to the plasma membrane but little or no production of Gag virus-like particles (VLPs). Here we show that, after removal of the cell wall, the expression of HIV type 1 Gag protein in Saccharomyces cerevisiae spheroplasts allowed simultaneous budding of VLPs from the plasma membrane. Our data show that ( i ) the VLPs released from yeast spheroplasts were spherical and had morphological features, such as membrane apposed electron-dense layers, characteristic of the immature form of HIV particles; ( ii ) the VLPs were completely enclosed in the plasma membrane derived from yeast, which is denser than that of higher eukaryotic cells; ( iii ) the VLP Gag shells remained intact after treatment of nonionic detergent; and ( iv ) the VLPs were released soon after removal of the cell wall and accumulated up to 300 μg/liter of culture. Our results also show that VLP production was abolished by amino acid substitution of the Gag N-terminal myristoylglycine and impaired when Gag C-terminal deletions were extended beyond the nucleocapsid domain. These results were consistent with those obtained previously in higher eukaryotic expression systems, suggesting that similar Gag domains were used for VLP assembly. We suggest that the system described here offers significant advantages for studying host factors required for VLP budding. The system also may be available for production of vector virus-free VLPs for practical applications such as vaccine development.

Objective: To estimate the total number of patients with idiopathic cardiomyopathy in Japan and the prevalence of the disorder. Design: A nationwide epidemiological survey. Setting: Hospitals selected randomly from among all hospitals in Japan. Patients: Patients presenting with any of the three types of idiopathic cardiomyopathy: dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. Main outcome measures: The total number of patients in Japan was estimated using the sampling and response rates in each stratum with respect to hospital size. The second survey was conducted for patients reported in the first survey in order to obtain detailed information, including age, sex, and specific clinical data. Results: Estimated patient totals and 95% confidence intervals (CI) were 17 700 (95% CI 16 500 to 18 800) for dilated cardiomyopathy, 21 900 (95% CI 20 600 to 23 200) for hypertrophic cardiomyopathy, and 300 (95% CI 250 to 350) for restrictive cardiomyopathy. Crude prevalence per 100 000 population was estimated as 14.0 for dilated cardiomyopathy, 17.3 for hypertrophic cardiomyopathy, and 0.2 for restrictive cardiomyopathy; crude incidence per 100 000 person-years was estimated as 3.58, 4.14, and 0.06, respectively. Conclusions: The total number and prevalence of patients with idiopathic cardiomyopathy in Japan are estimated for the first time in a nationwide survey. The prevalence of dilated cardiomyopathy in Japan appears to be about half that of Western populations, while that of hypertrophic cardiomyopathy is about the same.

To discover the role of the kidney in tryptophan degradation, especially tryptophan to niacin, rat kidneys were injured by feeding a diet containing a large amount of adenine. The kidney contains very high activity of aminocarboxymuconate-semialdehyde decarboxylase (ACMSD), which leads tryptophan into the glutaric acid pathway and then the TCA cycle, but not to the niacin pathway. On the other hand, kidneys contain significant activity of quinolinate phosphoribosyltransferase (QPRT), which leads tryptophan into the niacin pathway. The ACMSD activity in kidneys were significantly lower in the adenine group than in the control group, while the QPRT activity was almost the same, however, the formations of niacin and its compounds such as N1-methylnicotinamide and its pyridones did not increase, and therefore, the conversion ratio of tryptophan to niacin was lower in the adenine group than in the control group. The contents of NAD and NADP in liver, kidney, and blood were also lower in the adenine group. The decreased levels of niacin and the related compounds were consistent with the changes in the enzyme activities involved in the tryptophan-niacin metabolism in liver. It was concluded from these results that the conversion of tryptophan to niacin is due to only the liver enzymes and that the role of the kidney would be extremely low.

To determine whether birth weight and childhood growth, especially rate of height increase, are independently related to major cardiovascular disease risk factors in adult life, the authors conducted a 20-year follow-up study in a Japanese population, using the record-linkage method. From medical checkup data for babies and for residents aged 20 years in Ishikawa, Japan, the authors obtained 20-year follow-up data (1985-1994) on 4,626 participants (2,198 men and 2,428 women) born in 1965-1974. Using multiple linear regression analysis, the authors estimated that a 1-standard-deviation higher birth weight was significantly associated with systolic blood pressure that was lower by 1.6 mmHg in men and by 1.0 mmHg in women, and with a serum cholesterol level that was lower by 0.07 mmol/liter in men and by 0.04 mmol/liter in women, after adjustment for current weight and rate of height increase. Moreover, after adjustment for birth weight and current weight, a 1-standard-deviation higher rate of height increase from age 3 years to age 20 years was significantly associated with systolic blood pressure that was lower by 0.7 mmHg in men and by 0.5 mmHg in women, and with serum cholesterol that was lower by 0.09 mmol/liter in men and by 0.05 mmol/liter in women. The results suggest that lower birth weight and lower rate of height increase during childhood are independently associated with increases in blood pressure and serum cholesterol in adult life.

To investigate the relationship between microalbuminuria and hypertension in nondiabetic subjects, we selected 245 Japanese men aged 35 to 69 years on the basis of the results of a 75 g oral glucose tolerance test. Prevalence of hypertension (blood pressure levels > or =140/90 mm Hg or treatment of hypertension) in microalbuminuria-positive (0.03 to 0.3 g/d) subjects was significantly higher than that in microalbuminuria-negative (

This article presents an evaluation of the factor structures of the Japanese version of the Maslach Burnout Inventory (MBI). The MBI is a widely used psychometric instrument for measuring 'burnout' developed by Maslach and her co-workers. The MBI consists of four subscales: Emotional Exhaustion, Personal Accomplishment, Depersonalization, and Involvement. The MBI was translated into Japanese along with a back-translation and was administered to a sample of 267 nurses. Various psychometric analyses showed that the Japanese version of the MBI has high reliability for the 22 items scored for the frequency dimension. The factor analysis using principal factoring with an oblique rotation resulted in three factor structures that had different implications from the MBI: Emotional Exhaustion/Depersonalization, Personal Accomplishment, and Physical Exhaustion. The correlationship between the MBI and the General Health Questionnaire (GHQ), measures of depression, showed that burnout was a unique phenomenon.

Previous studies have shown that single amino acid changes in the amino-terminal matrix (MA) domain, p17, of the human immunodeficiency virus type 1 Gag precursor Pr55, can abrogate virion particle assembly. In the three-dimensional structure of MA such mutations lie in a single helix spanning residues 54 to 68, suggesting a key role for this helix in the assembly process. The fundamental nature of this involvement, however, remains poorly understood. In the present study, the essential features of the MA helix required for virus assembly have been investigated through the analysis of a further 15 site-directed mutants. With previous mutants that failed to assemble, residues mapped as critical for assembly were all located on the hydrophobic face of the helix and had a key role in stabilizing the trimeric interface. This implies a role for the MA trimer in virus assembly. We support this interpretation by showing that purified MA is trimeric in solution and that mutations that prevent virus assembly also prevent trimerization. Trimerization in solution was also a property of a larger MA-capsid (CA) Gag molecule, while under the same conditions CA only was a monomer. These data suggest that Gag trimerization driven by the MA domain is an intermediate stage in normal virion assembly and that it relies, in turn, on an MA conformation dependent on the hydrophobic core of the molecule.

The stimulatory effects of several DNA-binding basic proteins (histone and protamine) and HIV-1 Rev with arginine (Arg)-rich clusters on the activity of casein kinase II (CK-II) were investigated in vitro. It was found that recombinant Rev (rRev) and the synthetic oligo-fragments corresponding to the amino acid sequences of its Arg-rich cluster stimulate CK-II activity in a dose-dependent manner. The activated CK-II phosphorylates several cellular and viral proteins in HIV-1 infected human MOLT-4 cells, and also phosphorylates HIV-1 structural proteins, including recombinant reverse transcriptase (rRT). These phosphorylations are selectively inhibited by CK-II inhibitors, such as quercetin, oGA (a glycyrrhetinic acid derivative) and NCS-chrom (an enediyne containing antibiotic). The data presented here suggest that HIV-1 Rev acts as an effective potent activator of CK-II, which may be a cellular mediator promoting HIV-1 replication in virus-infected cells.

To investigate the relation between occupation and the development of non-insulin-dependent diabetes mellitus (NIDDM), we undertook a 10-year follow-up survey of male employees of a zipper and aluminum sash factory in Japan. Of 1,218 employees we followed 1,087 subjects. We classified the subjects into five occupations: managers, technical workers, clerical workers, workers in transport, and laborers. NIDDM incidence was 3.1% for 10 years. The age-adjusted incidence of the workers in transport was the highest and that in laborers was the lowest. We used a multiple logistic analysis for adjustment with baseline characteristics such as age, BMI, fasting plasma glucose, and family history of diabetes mellitus. Adjusted relative risk of the workers in transport compared with the laborers was significantly high (3.95). Our work suggests that occupation is related to the development of NIDDM.

Background Yeast is recognized as a generally safe microorganism and is utilized for the production of pharmaceutical products, including vaccines. We previously showed that expression of human immunodeficiency virus type 1 (HIV-1) Gag protein in Saccharomyces cerevisiae spheroplasts released Gag virus-like particles (VLPs) extracellularly, suggesting that the production system could be used in vaccine development. In this study, we further establish HIV-1 genome packaging into Gag VLPs in a yeast cell system. Results The nearly full-length HIV-1 genome containing the entire 5′ long terminal repeat, U3-R-U5, did not transcribe gag mRNA in yeast. Co-expression of HIV-1 Tat, a transcription activator, did not support the transcription. When the HIV-1 promoter U3 was replaced with the promoter for the yeast glyceraldehyde-3-phosphate dehydrogenase gene, gag mRNA transcription was restored, but no Gag protein expression was observed. Co-expression of HIV-1 Rev, a factor that facilitates nuclear export of gag mRNA, did not support the protein synthesis. Progressive deletions of R-U5 and its downstream stem-loop-rich region (SL) to the gag start ATG codon restored Gag protein expression, suggesting that a highly structured noncoding RNA generated from the R-U5-SL region had an inhibitory effect on gag mRNA translation. When a plasmid containing the HIV-1 genome with the R-U5-SL region was coexpressed with an expression plasmid for Gag protein, the HIV-1 genomic RNA was transcribed and incorporated into Gag VLPs formed by Gag protein assembly, indicative of the trans-packaging of HIV-1 genomic RNA into Gag VLPs in a yeast cell system. The concentration of HIV-1 genomic RNA in Gag VLPs released from yeast was approximately 500-fold higher than that in yeast cytoplasm. The deletion of R-U5 to the gag gene resulted in the failure of HIV-1 RNA packaging into Gag VLPs, indicating that the packaging signal of HIV-1 genomic RNA present in the R-U5 to gag region functions similarly in yeast cells. Conclusions Our data indicate that selective trans-packaging of HIV-1 genomic RNA into Gag VLPs occurs in a yeast cell system, analogous to a mammalian cell system, suggesting that yeast may provide an alternative packaging system for lentiviral RNA.

Recombinant baculoviruses now represent a mature technology in which vector development, particularly for the control of expression level, has reached a plateau. However, other aspects of expression, such as the production of multiple proteins, improved product purification or maximizing protein processing, remain areas for novel vector and host cell development. This year has seen these topics come to the fore in descriptions of new expression systems.

To determine whether blood pressure is associated with 24-h urinary C-peptide excretion in subjects with varying degrees of glucose tolerance, we studied 247 Japanese men aged 30-69 who had never been treated with antihypertensive medications or with insulin. Plasma glucose and insulin responses during a 75-g oral glucose tolerance test, blood pressure and body mass index were obtained and urinary C-peptide excretion, in total and per kg body weight, were examined by 24-h urine collection. In monovariate analyses, urinary C-peptide excretion per kg body weight increased significantly as the blood pressure level rose (p0.05). After adjustment for age and body mass index by analysis of covariance, this relationship remained significant (p0.05), where adjusted mean values (+/- SEM) of urinary C-peptide per kg body weight were 1.56 +/- 0.05 microgram/24h/kg in the normotensive group and 2.04 +/- 0.17 microgram/24h/kg in the hypertensive (stage 2-4) group. When stratified simultaneously by glucose tolerance status and blood pressure level, adjusted mean values of urinary C-peptide per kg body weight were significantly higher in diabetic hypertensives than in diabetic normotensives. These results suggest that increase in 24-h urinary C-peptide excretion, i.e. 24-h insulin secretion, might contribute to an elevation of blood pressure both in normal and diabetic individuals.

To clarify the effect of environmental cadmium (Cd) exposure on the life prognosis of inhabitants living in a Cd-polluted area, the standardized mortality ratio (SMR) according to cause of death in urinary β 2-microglobulin (β2-MG)-positive subjects (≥1000 μg/gCr) was compared to that of the Japanese general population and β2-MG-negative subjects (β 1000 μg/gCr).The SMR for all causes of death of both sexes was higher than that of the Japanese general population and β 2-MG-negative subjects. Among women, the SMR for malignant neoplasms was higher than that of β 2-MG-negative subjects. For cardiovascular disease and cerebrovascular disease, especially heart failure and cerebral infarction, SMRs were significantly higher in both sexes. The SMR for renal diseases was significantly high in the men and tended to be high in the women.These results suggest that the prognosis of urinary β 2-MG-positive subjects with Cd-induced renal tubular dysfunction is unfavorable, with higher mortality rates due to renal diseases, cerebral infarction and heart failure contributing to this. Although the increase of the mortality rate was slight, Cd might affect cancer mortality in women.

Seven internal deletions within the p24 domain of the human immunodeficiency virus type 1 Gag precursor have been assessed for their effect on Gag particle formation following their expression using recombinant baculoviruses. In addition, each deleted molecule was assessed for its ability to bind soluble p24 antigen in vitro. The mutants fell into three different phenotypic groups: (i) three mutants that had no effect on either p24 binding or Gag particle assembly, (ii) three mutants that abolished both features and (iii) one mutant that bound p24 in vitro but failed to assemble particles. Mutations that abolished both in vitro p24 binding and particle assembly mapped to the C terminus of p24 confirming this region as critical for virion assembly. We suggest the division of virion assembly into at least two distinct phases and suggest a model in which the critical sequences mapped to date are combined with available structural information.

Objective: To determine whether blood pressure within the normal range is associated with plasma insulin concentration in a japanese population with normal glucose tolerance. Methods: We studied 491 normotensive japanese men with normal glucose tolerance, who had never been treated with antihypertensive medications. Plasma glucose and insulin response during a 75-g oral glucose-tolerance test, blood pressure, body mass index, serum lipids, alcohol consumption and smoking status were obtained. The subjects were divided into quartiles according to mean blood pressure level (

We compared thyroid hormone levels of inhabitants (19 men and 16 women) of the cadmium (Cd)-polluted Kakehashi River basin in Ishikawa Prefecture, with those of subjects (23 men and 47 women) living in a non-polluted area. In addition, we investigated the relationships between the thyroid hormone levels and indices of renal dysfunction induced by Cd exposure. The following results were obtained: 1) The free T4 level of females was significantly lower than that of controls. 2) The T3 level of inhabitants of both sexes was significantly higher than that of controls. 3) The level of free T4 among females became lower with the increases of urinary beta 2-microglobulin (beta 2-MG), urinary protein, urinary sugar, urinary amino acids and serum creatinine (Cr) levels, and with decreases of creatinine-clearance (CCr) and %TRP. 4) We could not find any relationship between the increase of T3 and the indices of renal dysfunction induced by Cd exposure in either sex.

To assess the influence of environmental cadmium (Cd) exposure on long-term outcome, a follow-up study was conducted from 1981-1982 to March 1991 on 3178 inhabitants living in the Cd-polluted Kakehashi River basin. The standardized mortality ratios of the urinary beta 2-microglobulin (beta 2-MG)-, protein-, and amino acid-positive subjects of both sexes and the urinary glucose-positive female subjects were higher than those of the subjects with urinary-negative findings or the general Japanese population during the observation period. After adjusting for age using Cox's proportional hazards model, significant associations were found between mortality and urinary indices. In multiple comparisons using all of the indices, urinary protein and beta 2-MG in the women and urinary protein in the men were the factors most contributing to the mortality rates. In the urinary protein-negative female group as well, a significant association was found between urinary beta 2-MG and mortality. These results suggest that the prognosis of subjects with Cd-induced renal dysfunction is unfavorable, with the mortality rate increasing even in the early stage of proximal tubular dysfunction. Urinary protein and urinary beta 2-MG are important prognostic factors, with the latter, in particular, considered to be useful as an early index predictive of premature mortality.

A nutritional survey and questionnaire regarding dietary habits were administered to 649 men ranging in age from 35 to 64 years receiving a one-day health screening examination. First, comparisons of nutrient intake based on the nutrient rate of the Recommended Dietary Allowances for Japanese (RDA), and the total score on the questionnaire regarding dietary habits according to the RDA rates of total energy and calcium (Ca) were investigated. Then, the comparisons of intake of food groups, intake of nutrients and the total score on the questionnaire regarding dietary habits according to potassium/energy (K/E) ratio and phosphorus/calcium (P/Ca) ratio were determined. Last, differences between comparisons with the nutrient rates of RDA and comparisons with K/E ratio and P/Ca ratio were investigated. The following results were obtained: 1. Even in the group with RDA rates of total energy or Ca of > or = 90% and < or = 110% the RDA rates of some other nutrients were out-side the appropriate range. 2. In the group with high K/E ratios, as compared to the group with low ratios, the intake of potatoes, pulses, fruits, green/yellow vegetables, other vegetables, soy sauce, other beverages, fish/shellfish, and milk products showed high values, while cereals and fats/oils showed low values. For this reason, in the former group as compared to the latter, the intake and RDA total energy rate showed low values whereas the intake and RDA rates of nutrients such as Ca, Fe, and vitamin A were low. 3. In the group with high P/Ca ratios, as compared to the group with low ratios, the intake of beer and meats showed high values while that of pulses, green/yellow vegetables, and milk products showed low values. For this reason, in the former group as compared to the other groups, despite the fact that the intake and RDA total energy rate tended to be higher, the intake of nutrients such as Ca, P, K, and vitamin A showed lower values. 4. The RDA rates of all of the nutrients of group with a high K/E ratio and the group with a low P/Ca ratio generally showed largely appropriate values. 5. These results suggest that indices reflecting the balance of minerals such as the K/E and P/Ca ratios more objectively reflect the quality of nutrition than comparisons based on the RDA rates of total energy and specific-nutrient.

Karasek 1) suggested that the work environment could be defined by two important elements, the psychological job demands (demand) placed on the worker and the decision latitude (control) permitted in deciding how to meet these demands. The demand-control (DC) model of job stress was therefore proposed. The DC model is one of the most popular models in the domain of job stress and employee well being 2) . Although there has been an increase in the number of overseas studies on the DC model, reports in Japan are much less common. We targeted the Japanese population to examine associations between job demand, control and the depressive state.

Human immunodeficiency virus 1 (HIV-1) nucleocapsid protein p15 was produced as a fusion protein with glutathione S-transferase (GST) in Escherichia coli. Rapid purification of GST::p15 in an active form by one-step glutathione-agarose chromatography was accomplished in the presence of an antioxidant. Recombinant p15 fused to GST was shown to stimulate the dimerization of viral RNA. HIV-1 reverse transcriptase-catalyzed in vitro synthesis of minus-strand cDNA from synthetic human tRNA(Lys3UUU) and natural bovine tRNA(Lys3SUU) primer molecules was enhanced by GST::p15. GST produced in E.coli revealed no effect with respect to RNA dimerization and cDNA synthesis, demonstrating that both activities reside in the p15 portion of the fusion protein.

The external glycoproteins of human immunodeficiency virus type 1 (HIV-1) (gp120) and HIV-2 (gp105) are responsible for binding the cellular receptor CD4. The proteins are functionally identical although their affinity for CD4 varies, with gp120 binding 10- to 20- fold more efficiently than gp105. To investigate the structural requirements for CD4 binding in each molecule we have constructed a number of hybrid glycoproteins in which sequences are exchanged between the two molecules via conserved residues and subsequently tested for their ability to bind to CD4. We found that two constructs in which the V1/V2 or V3 loops of gp105 are exchanged for those of gp120 continue to bind to CD4. Surprisingly, however, all other domain exchange mutants failed to bind to CD4 suggesting that long-range interactions within the molecule are sequence-specific. Mixing mutant molecules in vitro did not rescue CD4 binding. However, coexpression of a number of mutant glycoprotein pairs within the same cell produced complementation of CD4 binding ability; complementing molecules were shown to be heteromeric in structure. Alignment of the molecules within each complementation group allowed the interactive sequences necessary for receptor binding to be determined. These sequences constitute a novel target for the disruption of gp120 function.

A non-glycosylated form of the HIV-1 envelope protein gp120 and four truncated derivatives have been expressed as non-fused secreted products in the periplasmic space of E. coli . We show that the full length molecule, whilst folded and soluble, fails to bind to CD4 consistant with other work that suggests an essential role for carbohydrate in gp120 function. In addition, when used in conjunction with the truncated derivatives, rapid epitope mapping of anti-gp120 monoclonal antibodies is achieved using both Western-blot and ELISA formats.

Neurovirulence of the Onderstepoort strain of canine distemper virus (CDV) adapted to human neural cell lines was determined by the intracerebral inoculation of DDD mice at 3 and 5 weeks of age. Intensity of neurovirulence was estimated by histopathological changes in the central nervous system and clinical symptoms. The original virus propagated in Vero cells induced leptomeningoencephalitis, whereas neuroblastoma-adapted virus induced nerve cell degeneration and mild encephalitis with relatively low morbidity and fatality. In contrast, the viruses adapted to glioblastoma and oligodendroglioma caused high morbidity and fatality. The latter two viruses induced necrotizing encephalopathy including edema and hyperemia. In addition, the glioblastoma-adapted virus induced formation of giant cells. The oligodendroglioma-adapted virus caused demyelination and spongy state associated with degeneration of glial cells and axons. These observations are discussed in regard to a possible correlation between the neurovirulence of CDV in mice and its tropism for neural cells in vitro.

A copper decoration method was employed to visualize the conducting defects in Langmuir-Blodgett (LB) films under an optical microscope. The resulting copper decoration patterns strictly reflected the morphology of the LB films.

Expression of human immunodeficiency virus Gag protein and the N-terminal matrix (MA) domain in Escherichia coli yielded spherical structures in the cytoplasm. When human N-myristoyltransferase was coexpressed, both Gag and MA were fully myristoylated and spherical structures were relocated in close proximity to the cytoplasmic membrane. However, neither myristoylated Gag nor MA exhibited tight binding to E. coli membrane, suggesting that myristoylation in E. coli did not confer membrane affinity on Gag despite the relocation. Our data also suggest that the morphogenetic pathway of Gag particles in prokaryotic cells differs from that in eukaryotic cells despite biochemical similarities of in the form of Gag expressed.