Biomedical subjects

Ikuo Saito

Publications and source records attributed to Ikuo Saito.

At least 37 records · Page 2Linked to original sources

PubMed2005

Status of home blood pressure measured in morning and evening: evaluation in normotensives and hypertensives in Japanese urban population.

To assess home blood pressure status in a Japanese urban population, we analyzed home blood pressure values in normotensive subjects determined by casual blood pressure (< 140/90 mmHg), hypertensive subjects without medication (> or = 140/90 mmHg) and treated hypertensive patients. The subjects (468 male, 232 female; mean age 41 years old) were recruited from a company located in Tokyo. Home blood pressure was measured with a semi-automatic device (Omron HEM-759P). Subjects were instructed to perform triplicate morning and evening measurements on 7 consecutive days. In the treated hypertensive group (n = 70), there was a significant difference between morning (139 +/- 12/88 +/- 9 mmHg) and evening (130 +/- 12/79 +/- 8 mmHg) home blood pressure. In the normotensive group (n = 558), however, only the diastolic blood pressure (DBP) component of the home blood pressure was significantly different between morning (115 +/- 13/72 +/- 9 mmHg) and evening (114 +/- 12/68 +/- 8 mmHg). In the nontreated hypertensive group (n = 72), casual blood pressure (145 +/- 14/92 +/- 9 mmHg) was higher than morning (138 +/- 16/89 +/- 11 mmHg) and evening (134 +/- 16/83 +/- 11 mmHg) home blood pressure, but no difference was seen between morning and evening systolic blood pressure (SBP). According to the reference value of the Japanese Society of Hypertension 2004 (SBP > or = 135 mmHg and/or DBP > or = 85 mmHg), 7.2% (systolic) and 8.7% (diastolic) of subjects in the normotensive group were classified as hypertensive by home blood pressure. Casual blood pressure in the treated hypertensive group was normal in 64.3% for SBP and 70.0% for DBP. However, their morning SBP (32.9%), morning DBP (40.0%), evening SBP (10.0%), and evening DBP (17.1%) were classified as hypertensive by home blood pressure. Furthermore, patients who were taking antihypertensive drug(s) only in the morning (n = 52) showed higher morning SBP (6 mmHg, p = 0.086) and morning DBP (6 mmHg, p = 0.005) than patients taking drug(s) by other administration schedules (n = 18), but no difference in evening home blood pressure was observed. In conclusion, a proportion of the subjects defined as normotensive by casual blood pressure were classified as hypertensive by home blood pressure in the present urban population. Furthermore, morning home blood pressure control in the treated hypertensive group classified as under control by casual blood pressure was insufficient, especially in patients who were taking medication only in the morning.

Adult↗

PubMed2004

Ubc9 and Protein Inhibitor of Activated STAT 1 Activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated Human CYP11B2 Gene Transcription.

Aldosterone synthase (CYP11B2) is involved in the final steps of aldosterone biosynthesis and expressed exclusively in the adrenal zona glomerulosa cells. Using an electrophoretic mobility shift assay, we demonstrate that COUP-TFI binds to the -129/-114 element (Ad5) of human CYP11B2 promoter. Transient transfection in H295R adrenal cells demonstrated that COUP-TFI enhanced CYP11B2 reporter activity. However, the reporter construct with mutated Ad5 sequences showed reduced basal and COUP-TFI-enhanced activity, suggesting that binding of COUP-TFI to Ad5 is important for CYP11B2 transactivation. To elucidate molecular mechanisms of COUP-TFI-mediated activity, we subsequently screened for COUP-TFI-interacting proteins from a human adrenal cDNA library using a yeast two-hybrid system and identified Ubc9 and PIAS1, which have small ubiquitin-related modifier-1 (SUMO-1) conjugase and ligase activities, respectively. The coimmunoprecipitation assays confirmed that COUP-TFI forms a complex with Ubc9 and PIAS1 in mammalian cells. Immunohistochemistry showed that Ubc9 and PIAS1 are markedly expressed in rat adrenal glomerulosa cells. Coexpression of Ubc9 and PIAS1 synergistically enhanced the COUP-TFI-mediated CYP11B2 reporter activity, indicating that both proteins function as coactivators of COUP-TFI. However, sumoylation-defective mutants, Ubc9 (C93S) and PIAS1 (C351S), continued to function as coactivators of COUP-TFI, indicating that sumoylation activity are separable from coactivator ability. In addition, chromatin immunoprecipitation assays demonstrated that ectopically expressed COUP-TFI, Ubc9, and PIAS1 were recruited to an endogenous CYP11B2 promoter. Moreover, reduction of Ubc9 or PIAS1 protein levels by small interfering RNA inhibited the CYP11B2 transactivation by COUP-TFI. Our data support a physiological role of Ubc9 and PIAS1 as transcriptional coactivators in COUP-TFI-mediated CYP11B2 transcription.

Animals↗

PubMed2004

High throughput multiple combination extraction from large scale polymorphism data by exact tree method.

Single nucleotide polymorphisms (SNPs) are increasingly becoming important in clinical settings as useful genetic markers. For the evaluation of genetic risk factors of multifactorial diseases, it is not sufficient to focus on individual SNPs. It is preferable to evaluate combinations of multiple markers, because it allows us to examine the interactions between multiple factors. If all the combinations possible were evaluated round-robin, the number of calculations would rapidly explode as the number of markers analyzed increased. To overcome this limitation, we devised the exact tree method based on decision tree analysis and applied it to 14 SNP data from 68 Japanese stroke patients and 189 healthy controls. From the obtained tree models, we succeeded in extracting multiple statistically significant combinations that elevate the risk of stroke. From this result, we inferred that this method would work more efficiently in the whole genome study, which handles thousands of genetic markers. This exploratory data mining method will facilitate the extraction of combinations from large-scale genetic data and provide a good foothold for further verificatory research.

Adult↗

PubMed2004

Inverse association between serum adiponectin level and transaminase activities in Japanese male workers.

BACKGROUND/AIMS: Since a novel polypeptide named adiponectin was shown to prevent the development of steatosis and steatohepatitis in animal models, we studied whether it was also possible in a clinical situation. METHODS: Associations between serum adiponectin levels and serum transaminase activities were studied in 791 Japanese males who were not heavy drinkers, and had no autoimmune or HBV- or HCV-induced liver diseases. RESULTS: Various markers of metabolic diseases including levels of body mass index (BMI), serum triglyceride, total cholesterol, and insulin resistance assessed by the homeostasis model were significantly higher in subjects with increased transaminase activities when compared to those with normal activities. Single regression analyses demonstrated that the logarithmic serum adiponectin level was inversely correlated with the levels of logarithmic serum AST (r=-0.229, P<0.0001), ALT (r=-0.305, P<0.0001), and gammaGTP (r=-0.278, P<0.0001). Even in multiple regression analyses in which subjects' age and levels of BMI, serum triglyceride, total cholesterol, and insulin resistance were adjusted, the inverse correlations were significant (P=0.0426, 0.0332, and 0.0011, respectively). CONCLUSIONS: Hypoadiponectinemia may worsen liver diseases associated with metabolic diseases in clinical cases. In addition to aggravation of insulin resistance and hyperlipidemia, some hypoadiponectinemia specific mechanisms may stand behind the association.

Adiponectin↗

PubMed2004

Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population.

Leptin plays an important role in the regulation of body weight and is known to circulate in both free and bound forms. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. Clinical studies have shown that soluble leptin receptor (sOB-R) levels are lower in obese individuals. In the present study, we measured the serum sOB-R level in 419 healthy Japanese subjects (198 men and 221 women, aged 30 to 65 years, body mass index [BMI] 21.7 +/- 2.6 [SD] kg/m2) and in 150 type 2 diabetic patients (96 men and 54 women, BMI 24.3 +/- 3.8 kg/m2). We investigated the relationships between serum sOB-R level and BMI, blood pressure, homeostasis model assessment-insulin resistance index (HOMA-IR), serum leptin and adiponectin levels, lipid profile, and leptin receptor (LEPR) gene Lys109Arg and Gln223Arg polymorphisms. Serum leptin and sOB-R levels were measured by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), respectively. The serum sOB-R level in men was significantly higher than that in women. The serum sOB-R level was negatively correlated with BMI, fasting insulin, HOMA-IR, and serum leptin level and positively correlated with high-density lipoprotein (HDL)-cholesterol and serum adiponectin levels. The correlations between serum sOB-R level and fasting insulin, HOMA-IR, serum leptin, adiponectin, and HDL-cholesterol levels were significant even after adjustment for age, sex, and BMI in healthy subjects. There was no association between serum sOB-R level and the LEPR polymorphisms examined. These findings suggest that the serum sOB-R level is negatively correlated with HOMA-IR and serum leptin level and positively correlated with HDL-cholesterol level and serum adiponectin level, independent of age, sex, and BMI, in the Japanese population.

Adiponectin↗

PubMed2004

Proteasome-mediated mineralocorticoid receptor degradation attenuates transcriptional response to aldosterone.

The ubiquitin-proteasome pathway regulates the turnover of many nuclear hormone receptors, such as the estrogen receptor. For estrogen receptor, proteasome inhibition decreases ligand-mediated transcription. We provide evidence that the mineralocorticoid receptor (MR) is degraded by the ubiquitin-proteasome pathway in a ligand-dependent manner and that proteasomal inhibition results in increased accumulation of the MR with enhancement of transcriptional response to aldosterone. Examination of the primary sequence of human and rat MR has identified two candidate PEST degradation motifs. Mutation of lysine 715 and/or 367 within this PEST element failed to prevent degradation of MR protein or transcriptional activity mediated by aldosterone, indicating that other lysine residues are targeted by proteasomal degradation of MR. These findings demonstrate a coupling between MR up-regulation and transcriptional hyperactivity.

Aldosterone↗

PubMed2004

FHL2, UBC9, and PIAS1 are novel estrogen receptor alpha-interacting proteins.

Estrogen plays important roles in the pathophysiology of atherosclerosis and cardiovascular diseases mediated by estrogen receptor alpha (ERalpha). To elucidate the molecular mechanisms, we screened ERalpha-interacting proteins from a human heart cDNA library using a yeast two-hybrid system, and identified the four and a half of LIM-only protein 2 (FHL2). FHL2 interacted with ERalpha in the presence of 17beta-estradiol, but not of tamoxifen or raloxifene in yeast. FHL2 mainly interacted with N-terminal A/B domain of ERalpha but not C-terminal ligand-binding domain. However, overexpression of full-length FHL2 did not affect ERalpha-dependent transcriptional activities of a reporter containing 3 copies of estrogen response element in COS-1 cells. Since tissue distribution of FHL2 was highly restricted to the heart, the function of FHL2 may be observed in a cell type- or promoter-specific manner. We have also detected strong interactions of ERalpha with Ubc9 and PIAS1 in yeast. Ubc9 and PIAS1, small ubiquitin-related modifier-1 (SUMO-1) conjugating enzyme and ligase, respectively, markedly interacted with ERalpha in a 17beta-estradiol-dependent manner. These proteins mainly interacted with the DNA-binding and ligand-binding domains of ERalpha. Overexpression of Ubc9 or PIAS1 potentiated ERalpha-mediated transcriptional activities in COS-1 cells in a dose-dependent manner, indicating that both Ubc9 and PIAS1 function as coactivators of ERalpha. In addition, the SUMOylation-defective mutant, Ubc9 (C93S) continued to enhance ERalpha-dependent transcriptional activities. These findings suggest that coactivator abilities and SUMOylation capacities of Ubc9 and PIAS1 are separable and distinct. The present studies indicate that ERalpha exhibit tissue-specific functions utilizing multiple tissue-restricted receptor-interacting proteins.

Animals↗

PubMed2004

COUP-TF and transcriptional co-regulators in adrenal steroidogenesis.

Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) and steroidogenic factor-1 (SF-1) play key roles in the transcriptional regulation of steroidogenic P450 genes. Transfection studies showed that SF-1 activated bovine CYP17 promoter activity, whereas COUP-TFs repressed it from the CRS2 element in a mutually exclusive manner in mouse adrenocortical Y-1 cells. COUP-TFI and SF-1 competitively bind to the Ad5 element of the human CYP11B2 gene promoter. Unexpectedly, overexpression of COUP-TFI increased the CYP11B2 promoter activity, whereas overexpression of SF-1 repressed it in human adrenocortical H295R cells. In cortisol-producing adrenal cortical adenomas, down-regulation of nuclear receptors, including COUP-TFs was found. We therefore screened for COUP-TFI-interacting proteins using a yeast two-hybrid system and have identified Ubc9 and PIAS1, SUMO-1 conjugating enzyme and ligase, respectively. Coexpression of Ubc9 and PIAS1 synergistically enhanced COUP-TFI-mediated trans-repression of CYP17 gene as well as transactivation of CYP11B2 gene. The SUMOylation-defective mutants of these proteins continued to function as co-regulators of COUP-TFI. These findings indicate that Ubc9 and PIAS1 can function as transcriptional co-regulators of COUP-TFI to modulate adrenal cortical steroidogenesis in a SUMOylation-independent manner.

Adrenal Cortex↗

PubMed2004

Associations between serum leptin levels and transaminase activities and the status of lifestyle in Japanese workers.

BACKGROUND: Leptin has been implicated in the pathogenesis of various liver diseases. In this study, associations between serum leptin levels and serum transaminase activities and the statuses of various lifestyles, including that of ethanol consumption, were studied. METHODS: Associations between these factors were statistically examined in 122 Japanese men on the basis of the data taken from their health checkups. Individuals with cirrhosis, hepatitis virus infection, and autoimmune liver diseases were excluded. RESULTS: Spearman's simple regression analyses demonstrated that serum leptin levels correlated with serum activities of aspartate aminotransferase (r = 0.174, p = 0.0382) and alanine aminotransferase (ALT; r = 0.336, p < 0.0001) but not with serum gamma-glutamyl transpeptidase activity (r = 0.155, p = 0.0656). In multiple regression analysis in which subjects' age, levels of serum triglyceride, and insulin resistance index were adjusted, the logarithmic serum leptin level was significantly associated with logarithmic ALT activity (p = 0.004) but not with logarithmic aspartate aminotransferase activity (p = 0.134). ANOVA showed no significant association between serum leptin levels and total lifestyle status assessed by Breslow's index. Multiple logistic regression analysis showed that normal body mass index and proper exercise were factors accounting for maintaining a normal leptin level, whereas the ethanol consumption level did not affect the serum leptin level. No significant association between ethanol consumption and serum leptin level was confirmed by single regression analysis as well as by Spearman's simple regression test. CONCLUSION: Increased serum leptin is related to morbid conditions increasing ALT. Because the association between the degree of ethanol consumption and the serum leptin level was not significant, the reported association between the serum leptin level and alcoholic liver disease should, at least, not be a feature of its early stage.

Adult↗

PubMed2004

Adiponectin, an adipocyte-derived protein, predicts future insulin resistance: two-year follow-up study in Japanese population.

It has been reported that the serum adiponectin level was negatively correlated with body mass index (BMI), insulin resistance index, and triglycerides and was positively correlated with high-density lipoprotein cholesterol in several cross-sectional studies. However, the causal relationship has not been elucidated. We investigated whether the baseline adiponectin level could predict subsequent changes in insulin resistance, lipid profile, or body weight in a 2-yr longitudinal study. This study included 590 male Japanese subjects, aged 30-65 yr, who received annual health checkups in both 2000 and 2002. Blood pressure, heart rate, and anthropometric and metabolic parameters, including serum insulin and adiponectin levels, were determined. The insulin resistance index was calculated based on homeostasis model assessment. Baseline adiponectin level was not correlated with the subsequent change in lipid profile or BMI in 2 yr after adjustment for each baseline value. However, the baseline adiponectin level was negatively correlated with subsequent changes in insulin and insulin resistance index based on homeostasis model assessment, even after adjustment for change in BMI (r = -0.162 and r = -0.140, respectively). These findings suggest that the serum adiponectin concentration predicts subsequent changes in insulin resistance, but not in lipid profile or body weight.

Adiponectin↗

PubMed2004

Associations among lifestyle status, serum adiponectin level and insulin resistance.

OBJECTIVE: The aim of this study was to determine whether lifestyle status affects the insulin resistance index or serum adiponectin level, which may be responsible for the development of insulin resistance syndrome that sometimes indicates lifestyle-related diseases. METHODS: A cross-sectional study was performed. PATIENTS: Seven hundred thirty-eight males aged 30 to 65 years who had regular health checkups in our office were enrolled. Each subject's lifestyle status, level of serum adiponectin, and serum insulin level were assessed by a self-administered questionnaire based on Breslow's lifestyle index, enzyme-linked immunosorbent assay, and radioimmunoassay, respectively. Moreover, their insulin resistance indexes were assessed by the homeostasis model. RESULTS: One-way ANOVA demonstrated an inverse correlation between Breslow's index and the logarithmic insulin resistance index (p<0.0001), and a tendency of a correlation between Breslow's index and the logarithmic serum adiponectin level (p=0.0681). Multiple logistic regression analyses demonstrated that, among the seven lifestyle items in Breslow's index, body mass index of more than 26.1 kg/m2 and insufficient exercise style had 8.9 times and 2.1 times the risks for insulin resistance and the former also had 3.2 times the risk for hypoadiponectinemia. Partial correlation coefficients of these correlations were 0.336 (p<0.0001), 0.107 (p=0.0013), and 0.165, (p<0.0001), respectively. CONCLUSION: Unhealthy lifestyles may cause hypoadiponectinemia and insulin resistance followed by insulin resistance syndrome, i.e. lifestyle-related diseases. These findings present reasonable explanations for the relationships between lifestyles and lifestyle-related diseases. Improvement of unhealthy lifestyles, especially the control of body weight, may have beneficial effects against the development of lifestyle-related diseases.

Adiponectin↗

PubMed2004

Potential errors resulting from sex and age difference in assessing family history of coronary heart disease.

BACKGROUND: Coronary heart disease occurs nearly exponentially with age and differently between men and women. Therefore, difference in sex and age of family members yields errors in assessing the family history as a risk factor. The influence of sex and age on the positivity of family history was assessed numerically. METHODS: Through questionnaires filled in by the parents of 2316 high school students, information was obtained on the past history of coronary heart disease among students' parents, grandparents, uncles, and aunts. The sex- and age-specific proportion of a positive history was calculated from the past history among the 24,071 family members. The influence of sex and age on a positive history was estimated as odds ratios by logistic regression analysis of the past history. RESULTS: The odds ratios obtained for sex and age difference were 1.61 (95% confidence interval: 1.42-1.83) and 1.07 (95% confidence interval: 1.06-1.07), respectively. This indicated that a positive history was 1.61 times higher among male members than among female members of the same age, and that a positive history increased by (1.07)y, where y was age difference by year. CONCLUSIONS: Potential errors resulting from disregarding the sex and age of family members can be substantial, judging from the above numerical figures. Some measures to control for the sex and age of family members are required in assessing family history of coronary heart disease.

Adult↗

PubMed2004

Effects of leptin receptor gene 3'-untranslated region polymorphism on metabolic profiles in young Japanese men.

We investigated the effects of leptin receptor gene 3'-untranslated region (3'-UTR) polymorphism on clinical and metabolic parameters in 221 young Japanese men aged 21 to 28 years. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify a pentanucleotide (CTTTA) insertion in 3'-UTR of the leptin receptor gene. Body mass index, blood pressure, plasma glucose, insulin, leptin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, free fatty acids, uric acid, apolipoprotein A-I (apoA-I), and cholesteryl-ester transfer protein levels were measured. There was only 1 homozygote and 38 heterozygotes for the 3'-UTR insertion allele among the 221 subjects. The insertion allele frequency was 0.090. Plasma HDL-cholesterol and apoA-I levels were significantly lower (p = 0.015 and p = 0.032 by Mann-Whitney U test, respectively) in homozygous or heterozygous carriers of the insertion allele than in subjects homozygous for the normal allele. There were no differences in other parameters measured. Furthermore, when the subjects were divided into three groups according to HDL-cholesterol level, the percentage of insertion allele-positive subjects was significantly lower in the highest HDL-cholesterol group (chi(2) = 8.42, p = 0.015). These findings suggest that serum HDL-cholesterol and apoA-I levels are influenced by the leptin receptor gene 3'-UTR polymorphism in young Japanese men.

3' Untranslated Regions↗

PubMed2003

Promoting nerve regeneration through long gaps using a small nerve tissue graft.

BACKGROUND: If nerve tissue is capable of inducing regeneration, as suggested by the neurotropism theory, then even small pieces of nerve tissue should have the potential to induce nerve regeneration. Therefore, long gaps might presumably be bridged via the neurotrophic potential of small pieces of nerve tissue grafted into the middle of the nerve gap. It is necessary to confirm the validity of the neurotropism theory and to also explore the potential usefulness of small nerve grafting through long gaps. METHODS: A small piece of nerve tissue was grafted into a silicone tube bridging a relatively long nerve gap in an attempt to promote nerve regeneration. A 15-mm gap was created in the left sciatic nerve of 31 Wistar rats (8 weeks of age). The experimental groups included one with nonvascularized nerve tissue grafted into a silicone tube with no distal nerve suturing (NV-A), another with vascularized nerve tissue grafted into a silicone tube with no distal nerve suturing (V-A), a third group with nonvascularized nerve tissue grafted into a silicone tube with distal nerve suturing (NV-P), a fourth group with vascularized nerve tissue grafted into a silicone tube with distal nerve suturing (V-P), and a group with no nerve segment grafted into the silicone tube (control). Electrophysiologic and histologic examinations were performed 10 weeks after the operation. RESULTS: No regeneration was obtained in the control group. Nerve regeneration was evident at the proximal end of the tube in the NV-A, V-A, NV-P, and V-P groups, and at the distal end in the NV-P and V-P groups. The degree of distal regeneration was extremely slight in the NV-A and V-A groups. An electrophysiologic examination performed in the NV-P and V-P groups revealed better results in the latter group. CONCLUSION: Small nerve grafts are capable of inducing nerve regeneration even over a long nerve gap, by grafting nerve tissue into the middle of the lesion using a silicone tube.

Animals↗

PubMed2003

Regulation of differential COUP-TF-coregulator interactions in adrenal cortical steroidogenesis.

Hyperfunctioning adrenocortical adenomas produce excessive amounts of various corticosteroids due to dysregulated expression of steroidogenic enzymes. Since no genetic mutations in steroidogenic enzyme genes have been identified as yet, the dysregulated expression at the transcription level may be crucial. Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) and steroidogenic factor-1 (SF-1) play key roles in the transcriptional regulation of steroidogenic P450 genes. Transfection studies showed that SF-1 activated and COUP-TFs repressed the transcription of bovine CYP17 gene promoter from the CRS2 element in a mutually exclusive manner in Y-1 cells. The results indicate that COUP-TFs negatively regulate the transcriptional activity of SF-1, a steroidogenic cell-specific activator of various steroidogenic P450 genes. Expression of both COUP-TFI and COUP-TFII was significantly decreased in the cortisol-producing adenomas, in which CYP17 was drastically overexpressed, indicating that decreased expression of COUP-TFs play a key role in overexpression of CYP17 in this type of tumors. We then screened for COUP-TFI-interacting proteins from a cortisol-producing adenoma cDNA library using a yeast two-hybrid system and identified a novel RING finger-containing protein which can function as a coregulator for COUP-TFI. Notably, COUP-TFI activated rather than repressed several target genes including the human CYP11B2 gene promoter, the results of which were opposite to those of the CYP17 promoter. The bifunctional activities of COUP-TFI may be derived from the promoter context and our newly identified COUP-TFI coregulator.

Adrenal Cortex↗

PubMed2003

Correlation between insulin resistance and gamma-glutamyl transpeptidase sensitivity in light drinkers.

BACKGROUND: Our previous studies suggested that serum gamma-glutamyl transpeptidase (GGTP) level was correlated with insulin resistance level estimated by the homeostasis model assessment in teetotalers and occasional drinkers. In the surveys, strong correlation between GGTP and triglyceride also was observed. This study examined whether the correlation held true for regular drinkers. METHODS: Seven hundred and seventeen male subjects in annual health checkups were divided into three groups according to their drinking styles and further divided into four subgroups according to their serum GGTP levels. In the other surveys, they were ranked by their amount of ethanol consumption. The correlation between GGTP and insulin resistance level was studied in each group. RESULTS: Single regression analysis and analysis of variance showed that GGTP level was significantly correlated with insulin resistance level as determined by the homeostasis model assessment, as well as with triglyceride level regardless of subjects' drinking styles. The associations were confirmed by multiple regression analyses in which age, levels of uric acid, total cholesterol, high-density lipoprotein cholesterol, and body mass index were adjusted, at least in nondrinkers or light drinkers. However, the multiple regression analyses indicated that the association between GGTP and insulin resistance level was not significant in subjects who take ethanol more than five times per week. The studies according to the amount of subjects' ethanol consumption indicated that the association between GGTP and insulin resistance was significant in the subjects who take ethanol up to 280 g/week. CONCLUSION: Individual variation in insulin resistance status may contribute to individual variations of sensitivity of GGTP to ethanol intake, at least in light drinkers.

Adult↗

PubMed2003

Nuclear receptors and co-regulators in adrenal tumors.

We have reported that excessive steroid hormone production in adrenal cortical tumors results from the disordered expression and activity of specific steroidogenic enzymes. Since no genetic mutations in these steroidogenic enzymes have as yet been identified, disordered expression at the transcription level may be crucial for excessive hormone production in adrenocortical tumors. Nuclear receptors SF-1 and COUP-TF/DAX-1 have been shown to activate and repress, respectively, the transcription of CYP17 gene in a mutually exclusive manner in Y-1 cells. Interestingly, the expression of COUP-TF and DAX-1 is significantly decreased in the cortisol-producing adenomas, in which CYP17 is overexpressed. Conversely, DAX-1 is highly expressed in deoxycorticosterone-producing adenomas, where CYP17 expression is almost absent. These expression profiles indicate the possibility that COUP-TF and DAX-1 play important roles in the transcriptional repression of CYP17 in adrenal tumors. To clarify the mechanisms of COUP-TF-mediated repression, we therefore screened for COUP-TF-interacting proteins using a yeast two-hybrid system from a cortisol-producing adenoma cDNA library. We then cloned a novel COUP-TF-interacting protein-1 (CIP-1), which interacts with COUP-TFI, COUP-TFII, and SF-1. Functionally, CIP-1 can act as a transcriptional co-repressor for COUP-TF repression activity. CIP-1 expression profiles parallel those of COUP-TFI in steroidogenic tissues, strongly suggesting that, together, COUP-TFI and CIP-1 play an important role in steroidogenesis.

Adenoma↗

PubMed2003

Effect of education through a periodic newsletter on persistence with antihypertensive therapy.

Sufficient persistence with therapy is important to achieve the desired benefits of antihypertensive therapy. This study was designed to describe the rates of persistence with antihypertensive therapy for 1 year and to assess the effect of patient education by a periodic newsletter on persistence rates in general practice in Japan. Information on 5,324 patients who received the newsletter once a month for 1 year (intervention group; 53.9% of those originally registered) and 666 patients who did not receive the newsletter (control group; 94.3% of those originally registered) was obtained from a physician questionnaire (response rate: 54.3%). The rate of persistence with antihypertensive therapy in the intervention group was similar to that in the control group (91.7% vs. 90.7%, respectively). The patient questionnaire (response rate: 28.2%) indicated that most patients consistently read the newsletter and found it useful in understanding the management of hypertension. The results of this 1-year study showed that about 90% of patients persisted with therapy for 1 year. Although most of them evaluated the newsletter favorably, no clear effect of the newsletter on their persistence with therapy was revealed. However, these results do not rule out a possible effect of education on persistence with therapy over the long-term, and thus there is need of a longer-term study employing follow-up questionnaires.

Aged↗