Biomedical subjects

T Shimamoto

Publications and source records attributed to T Shimamoto.

At least 37 records · Page 2Linked to original sources

PubMed2001

Antitumor effects of a novel phenoxazine derivative on human leukemia cell lines in vitro and in vivo.

2-Amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx) was synthesized by reacting 2-amino-5-methylphenol with bovine hemolysates. Because Phx is a phenoxazine derivative like actinomycin D, we examined its effects on the proliferation of the human leukemia cell lines K562, HL-60, and HAL-01. Phx inhibited proliferation and induced apoptosis in all of the leukemia cell lines we tested, in a dose-dependent manner. We further investigated the antitumor effect of this compound on HAL-01-bearing nude mice. Treatment with Phx markedly reduced the tumor growth rate in the experimental group, as compared with the control group. Moreover, Phx was found to have few adverse effects on weight loss and WBC count. In addition, we examined the effects of Phx on human normal hematopoietic progenitor cells by a clonogenic assay, and we observed less suppression of normal progenitor cells than of leukemic progenitors. These results suggest that Phx may be used to treat patients affected by different types of leukemia.

Animals↗

PubMed2001

[Characteristics of heterosexually acquired AIDS in Japan. An inter-country comparison using AIDS Surveillance data].

OBJECTIVES: To identify epidemiological characteristics of heterosexually acquired AIDS in Japan, with emphasis on potential influence on future trends. METHODS: National AIDS Surveillance data in Japan were compared with those in the UK and US, where detailed information is available from well-established surveillance procedures. Data on AIDS cases diagnosed until the end of 1996, particularly those acquired heterosexually, were analyzed by year of diagnosis, gender and age group. RESULTS: The number of heterosexually acquired AIDS cases in Japan has continued to increase, while those in the UK and US leveled out or decreased recently. The increase during a two-year period after reaching a certain number of cases per year was found to be 2.3-fold in Japanese, 2.4-fold in UK whites and 5-fold in US whites. The male to female ratio (M/F) for heterosexually acquired AIDS was 6.3 among Japanese, while the ratio was 1.1 and 0.5 in the UK and US, respectively. The age distribution at AIDS diagnosis demonstrated a peak from 35 to 54 years of age among Japanese males, as compared to 30 to 34 among males in the UK and the US. No significant difference was apparent in the age distribution among females in the three countries. CONCLUSIONS: The relatively small number of AIDS cases in Japan is attributable to the late introduction of HIV and the limited chance of heterosexual transmission from homosexual/bisexual men and injecting drug users. In addition, transmission has probably most often occurred between middle-aged Japanese males and non-Japanese females. As there is a growing risk of HIV infection among Japanese females and young Japanese males, new prevention strategies targeting these groups are urgently required.

Acquired Immunodeficiency Syndrome↗

PubMed2001

[Trends in the incidence of cardiovascular diseases and risk factors among urban and rural Japanese males].

OBJECTIVES: To examine long-term trends in the incidence of coronary heart disease, stroke, and their risk factors among Japanese populations, we explored 32 years of surveillance data for male residents in urban and rural areas in Japan. METHODS: The surveyed populations were 40-79 year-old male residents in M community (population over 40 years old in 1995 was 11,121) of Y City in Osaka (urban area; Osaka) and I town (n = 3,571) in Akita prefecture (rural area; Akita). Incidence rates of coronary heart disease (myocardial infarction, angina pectoris), sudden cardiac death, percutaneous transluminal coronary angioplasty (PTCA) and stroke per 1,000 person-years were calculated for 1964-71, 1972-79, 1980-87 and 1988-95. Risk factors were evaluated by cross-sectional surveys conducted in the median years for each period. Dietary intake was examined by the 24-hour recall method in the latter three periods. RESULTS: Age-adjusted incidence of coronary heart disease per 1,000 men increased progressively from 0.27 in 1964-71 to 0.90 in 1988-95 (P = 0.222 for trend) among 40-59 year old residents in Osaka. Among their 60-79 year old counterparts, though the incidence was 2.62-3.11 and did not change over the periods studied, the combined rates for coronary heart disease and men who had a PTCA reached 3.79 in 1988-95. In contrast, the incidence of coronary heart disease among Akita residents did not change over time and stroke declined 70 percent between 1964-71 and 1988-95 (P < 0.001) in both 40-59 and 60-79 year age group: The decrease in cerebral infarction was less marked between 1980-87 and 1988-95 among 60-79 year old individuals. Significant increases in diastolic blood pressure, total serum cholesterol, body mass index, salt intake and total fat percent of total energy in Osaka, were associated with the elevation in the incidence of coronary heart disease. In Akita, blood pressure leveled off over the study period, but decreased less during the last decade whereas the prevalence of obesity increased. CONCLUSION: Trends in cardiovascular diseases and their risk factors differ among different geographical areas. The present long-term study, in particular, demonstrated an increase in the incidence of coronary heart disease among urban Japanese male residents in Osaka between the 1960s and the 1990s.

Adult↗

PubMed2001

Hypermethylation of p16(INK4a) and p15(INK4b) genes in non-small cell lung cancer.

Hypermethylation of CpG island is a common mechanism by which tumor suppressor genes are inactivated. The tumor suppressor genes p16(INK4a) and p15(INK4b) are important components of the cell cycles. We have studied the feasibility of detecting tumor-associated aberrant p16(INK4a) and p15(INK4b) methylation in non-small cell lung cancer (NSCLC) using methylation-specific PCR. We found a high frequency of hypermethylation of the p16(INK4a) gene in 17 of 45 cases of NSCLC. In this study, there was no difference between the clinicopathological features or overall survival of patients with and without p16(INK4a) methylation. On the other hand, p15(INK4b) promoter hypermethylation is rare (5/45) in lung cancer and occurs in association with p16(INK4a) methylation. The overall survival of patients with p15(INK4b) methylation was markedly shortened in this series. We also analyzed cells in bronchial washings, and p16(INK4a) methylation was detected in 4 of 17 cases of NSCLC. Moreover, 1 of 10 plasma samples from patients with NSCLC was positive for p16(INK4a) methylation. Our results suggest a possible prognostic role of p15(INK4b) methylation in NSCLC, and that the detection of aberrant p16(INK4a) methylation in both bronchial washings and plasma may be useful for cancer diagnosis.

Adult↗

PubMed2001

Adult T-cell leukemia showing different immunophenotypes in invaded organs.

We report here a case of adult T-cell leukemia (ATL) who presented acute renal failure and skin eruption. Renal and skin biopsies showed diffuse invasion of ATL cells. Furthermore, the surface phenotype of tumor cells taken from the bone marrow (BM) or peripheral blood (PB)(CD4-CD8-) differed from that of cells taken from the kidney or skin (CD4+CD8-). These findings suggested that CD4-CD8-ATL cells in the BM and PB had differentiated to CD4+CD8- cells in the kidney and skin.

Acute Kidney Injury↗

PubMed2000

Plasma fibrinogen and coronary heart disease in urban Japanese.

There is little information on the relation of plasma fibrinogen concentration to the risk of coronary heart disease in Asians, including Japanese, whose plasma fibrinogen concentration has been reported to be low by Western standards. The authors conducted a prospective study with 4.8 years of follow-up of 11,977 men and women aged 21-89 years (mean value of fibrinogen = 267 mg/dl) living or working in Osaka, Japan, in 1990-1996 to examine the relation of plasma fibrinogen with the incidence of coronary heart disease (myocardial infarction and angina pectoris). Mean fibrinogen concentration was 293.6 mg/dl for men who developed coronary heart disease (n = 35) compared with 261.6 mg/dl for men free of coronary heart disease (n = 8,094; difference, p < 0.01), and 355.2 mg/dl for women who developed coronary heart disease (n = 6) compared with 276.8 mg/dl for women free of coronary heart disease (n = 3,842; difference, p < 0.01). With a Cox proportional hazards model to adjust for cardiovascular risk factors, the relative risk for the highest fibrinogen quartile (> or =295 mg/dl) compared with the lowest (<228 mg/dl) was 4.8 (95% confidence interval: 1.4, 16.8, p = 0.01) for coronary heart disease, and 3.8 (95% confidence interval: 1.1, 13.4, p = 0.04) for myocardial infarction. Plasma fibrinogen is useful to predict the risk of coronary heart disease among urban Japanese, whose mean plasma fibrinogen is relatively low.

Adult↗

PubMed2000

Characterization of human herpesvirus 7 U27 gene product and identification of its nuclear localization signal.

A monoclonal antibody, 5H4, that recognizes human herpesvirus 7 (HHV-7) was used in Western analysis to probe HHV-7-infected SupT1 cells. This antibody recognizes a 40-kDa virus-specific polypeptide that is expressed in the absence of viral DNA synthesis. By screening a lambdagt11 HHV-7 cDNA library, the gene encoding the protein was identified as the U27 open reading frame previously reported [J. Virol. (1996) 70, 5975-5989]. Immunofluorescent studies showed a punctate nuclear localization of the protein in both HHV-7-infected cells and transfected cells. A computer program predicted two classic nuclear localization signals (NLSs) in the middle and C-terminal regions of the protein. A C-terminal deletion mutant of the protein could not enter the nucleus, whereas green fluorescent protein or maltose binding protein fused to the C-terminal region of the protein was transported into the nucleus. These findings demonstrate that the predicted C-terminal, but not middle, NLS of the protein actually function as NLS. In addition, nuclear transport of a maltose binding protein-fusion protein containing the C-terminal NLS of the U27 protein was inhibited by both wheat germ agglutinin and a Q69L Ran-GTP mutant, indicating that the U27 protein is transported into the nucleus from the cytoplasm by means of classic nuclear transport machinery. Interestingly, this NLS motif is highly conserved at the C-termini of all herpesvirus DNA polymerase processivity factors that have been examined.

Amino Acid Sequence↗

PubMed2000

Structure of transcripts and proteins encoded by U79-80 of human herpesvirus 6 and its subcellular localization in infected cells.

We analyzed the U79-80 gene of human herpesvirus 6 (HHV-6), which is predicted to be a positional homolog of the UL112-113 gene of human cytomegalovirus (HCMV). The U79-80 gene encoded a family of nuclear proteins of 36, 41, 44, and 59 kDa. These proteins had common amino termini and were generated by complex alternative splicing. Transcripts from U79-80 appeared as early as 3 h postinfection and could be detected in the presence of phosphonoformate. U79-80 proteins were seen as early as 8 h postinfection and could be detected in the presence of phosphonoformate but not in the presence of cycloheximide combined with actinomycin D treatment. The U79-80 proteins were localized to the nucleus of infected cells, where they were detected as a speckled or punctuate pattern. Moreover, the U79-80 proteins colocalized with the components of the viral DNA replication machinery and appeared to distribute adjacent to or touching nuclear domain 10, where viral DNA replication occurs. From the sequence analysis of genomic DNA, the predicted amino acid similarity between U79-80 and UL112-113 was lower than between other genes, but the characteristics of the transcripts and proteins encoded by U79-80 were similar to those of UL112-113. These results suggest that the U79-80 proteins have a role in viral DNA replication and are functional homologues of the UL112-113 proteins.

Amino Acid Sequence↗

PubMed2000

MEIS1 and HOXA7 genes in human acute myeloid leukemia.

Co-activation of Meisl with Hoxa7 or Hoxa9 homeobox genes by retroviral gene insertion has recently been reported to be leukemogenic in murine myeloid leukemia. In this study we determined their expression in human leukemia. Most human myeloid leukemia cell lines co-expressed MEIS1 with HOXA7 and HOXA9. Among patients with acute leukemia, 50% of AML patients expressed MEIS1, while the majority of ALL patients were negative. A total of 89.5% of patients expressing MEIS1 co-expressed HOXA7. In unadjusted models, poorer response to chemotherapy was associated with expression of HOXA7 regardless of MEIS1 status and older patients were more likely to express either gene.

Cell Line↗

PubMed2000

Overexpression of the homeobox gene DLX-7 inhibits apoptosis by induced expression of intercellular adhesion molecule-1.

OBJECTIVE: DLX genes constitute a subfamily of divergent homeobox genes. We have previously reported that inhibition of DLX-7 expression by an antisense oligonucleotide caused apoptosis in the K562 erythroleukemia cell line, which highly expresses DLX-7. In this study, we have constructed an expression vector encoding human DLX-7, and examined the effects of overexpression of DLX-7 in the IL-3-dependent lymphoid precursor cell line Ba/F3. METHODS: DLX-7 expression vector was electroporated into Ba/F3 cells, and generate a DLX-7 expressing Ba/F3 cells. Northern blot analysis was performed to determine DLX-7 gene expression. WST-1 assay was used to cell proliferation assay. To detect apoptosis, we performed TUNEL assay. Expression of cell surface adhesion molecules was examined by FACS analysis. RESULTS: Growth properties of DLX-7-transfected Ba/F3 cells in the presence of IL-3, did not differ from those of control Ba/F3 cells. However, in the absence of IL-3, DLX-7-transfected cells abrogated growth dependence on cytokines due to inhibition of apoptosis. Because adhesion properties of DLX-7-transfected cells increase, we examined expression of adhesion molecules in these cells. Expression of intercellular adhesion molecule (ICAM)-1 and ICAM-2 were markedly upregulated in DLX-7-transfected cells. Both anti-ICAM-1 antibody and anti-LFA-1 antibody blocked the aggregation of DLX-7-transfected cells. Moreover, in the absence of IL-3, cytokine-independent cell growth was blocked by anti-ICAM-1 antibody. CONCLUSION: These results indicate that DLX-7 overexpression blocks apoptosis and that ICAM-1 expression induced by DLX-7 contributes to this antiapoptotic effect.

Animals↗

PubMed2000

Angiotensinogen T174M and M235T variants, sodium intake and hypertension among non-drinking, lean Japanese men and women.

OBJECTIVE: To examine the interaction of sodium intake with genetic variations of the angiotensinogen gene and hypertension. DESIGN: A community-based case-reference study. SETTING: Two rural Japanese communities. PARTICIPANTS: Non-overweight and non-drinking Japanese men and women: 229 hypertensives and 229 age-, sex- and community-matched normotensives aged 32 to 83 years. METHODS: Polymorphisms of the angiotensinogen gene detected by an allele-specific polymerase chain reaction. A priori hypothesis is individuals with 174M (threonine-to-methionine substitution) or 235T (methionine-to-threonine substitution) allelic variations may have an elevated risk of hypertension when they have a high sodium intake, estimated by 24-h urine collection and a dietary questionnaire. RESULTS: The genotypic frequency of the haplotype including both the 174M and 235T alleles was higher among hypertensives than among normotensives (23 versus 14%, P= 0.02). The frequency of the 174M allele was specifically higher among hypertensives than normotensives (12 versus 7%, P=0.01), and the odds ratio of hypertension associated with the 174M (versus 174T) allele was 1.8 [95% confidence interval (CI) 1.1-3.0, P=0.01]. The frequency of the 235T allele did not vary between the two groups (80 versus 82%, P= 0.40). The relationship between the 174M allele and hypertension was more evident among persons who had higher urinary sodium excretion (> = 166 mmol/day) than those with lower excretion (< 166 mmol/day): odds ratio 2.5 (95% CI, 1.2-5.2), P=0.01 versus 1.5 (95% CI, 0.7-3.1), P= 0.31; P for interaction = 0.04, and this trend was primarily observed for early-onset hypertension (< 55 years at onset). A similar but nonsignificant association was observed when stratified using present and past sodium intake scores derived from questionnaires. CONCLUSION: Angiotensinogen genotype may affect the development of early-onset hypertension among Japanese, particularly in those who have a high sodium intake.

Adult↗

PubMed2000

Expression of human herpesvirus 6B rep within infected cells and binding of its gene product to the TATA-binding protein in vitro and in vivo.

We have characterized the human herpesvirus 6B (HHV-6B) rep gene, which is a homologue of the adeno-associated virus type 2 rep and is unique in the herpesvirus family. Three transcripts, 9.0, 5.0, and 2. 7 kb (the major transcript), were detected by Northern blotting using an HHV-6B rep probe under late conditions. We investigated the expression kinetics of the rep gene using cycloheximide (CHX) and phosphonoformic acid (PFA), which are inhibitors of protein synthesis and viral DNA synthesis, respectively. The 5.2-kb transcript was mainly detected in the absence of protein biosynthesis upon infection, and none of the 9.0-, 5.0-, and 2.7-kb transcripts detected under the late conditions were detected in the presence of CHX and PFA. Sequences obtained from a cDNA library showed that the 5.0- and 2.7-kb transcripts were spliced from two and three exons, respectively, and the 2.7-kb transcript was more abundant. Immunohistochemistry using an antibody raised against the HHV-6 rep gene product (REP) revealed that REP was mainly present in the nucleus of MT-4 cells within 24 h after infection with HHV-6B. Using pull-down assays, coimmunoprecipitation, and a mammalian two hybrid system, we showed that HHV-6 REP binds to a transcription factor, human TATA-binding protein, through its N-terminal region.

Animals↗

PubMed2000

Synthesis and serotonin 2 (5-HT2) receptor antagonist activity of 5-aminoalkyl-substituted pyrrolo[3,2-c]azepines and related compounds.

A series of 5-aminoalkylpyrrolo[3,2-c]azepine derivatives was synthesized and their serotonin 2 (5-HT2) receptor antagonist and antiplatelet aggregation activities were evaluated. 5-HT2 receptor antagonist activity was largely determined by the nature of the substituent at the 8-position as well as the aminoalkyl group at the 5-position of the pyrrolo[3,2-c]azepine ring. Compound 18a, 5-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-8-hydroxy-1-methyl- 1,4,5,6,7,8-hexahydropyrrolo[3,2-c]azepin-4-one, was recognized as having potent 5-HT2 receptor antagonist activity with weak alpha1 adrenoceptor blocking activity and no significant D2 receptor binding affinity, while the corresponding isomeric pyrrolo[3,4-c]azepine derivative (22) displayed only weak 5-HT2 receptor antagonist activity. After racemic 18a was resolved directly via diastereomeric salt formation, each enantiomer was evaluated precisely. The 5-HT2 receptor antagonist activity of 18a was found to reside primarily in (-)-18a (which was about 14-fold more potent than (+)-18a in isolated guinea pig arteries). Consequently, (S)-(-)-18a (SUN C5174) displayed the overall best profile with potent 5-HT2 receptor antagonist activity (pA2=8.98+/-0.06) and high selectivity versus other receptors. SUN C5174 showed a marked inhibitory effect on the platelet aggregation induced by serotonin in combination with collagen and adenosine diphosphate (ADP) in canine or human platelet-rich plasma (IC50=6.5 to 16 nM). Moreover, this compound significantly inhibited the mortality rate in mouse acute pulmonary thromboembolytic death induced by collagen and serotonin at oral doses of 0.3 mg/kg or higher. SUN C5174 is currently undergoing clinical evaluation.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed2000

Transport of pyruvate in Saccharomyces cerevisiae and cloning of the gene encoded pyruvate permease.

Pyruvate uptake in Saccharomyces cerevisiae was not observed at 0 degrees C and was prevented by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). The initial uptake rate of S. cerevisiae kyokai No. 901 was maximum at pH 6 and Km = 4.1 mM. It seemed that lactate inhibited the pyruvate uptake competitively from the results of the Lineweaver-Burk plots. The inhibition constant (Ki) in the presence of 3 mM lactate was 1.6 mM. The pyruvate uptake was inhibited by D-glucose and deoxyglucose, but not by L-glucose, acetate or ethanol. Mutants of laboratory strain No. 5022 ((a) his(2,6), ura3) deficient in pyruvate uptake were isolated from fluoropyruvate resistant mutants. Transformation of the mutant with a yeast genomic library allowed the isolation of the gene JEN1 (YKL217w), which restored pyruvate uptake. Disruption of JEN1 abolished the uptake of pyruvate and gained the resistance against fluoropyruvate. The results indicate that no other monocarboxylate permease is able to efficiently transport pyruvate in S. cerevisiae.

Biological Transport↗

PubMed2000

Validity and reliability of the Japanese version of the selected anger expression scale and age, sex, occupation and regional differences in anger expression among Japanese.

To examine the reliability and construct validity of the Japanese version of the Anger Expression Scale among four Japanese communities, and to examine distributions of anger expression scores according to sex, age, occupation, and community, we performed a cross-sectional study among 1,802 men and 3,229 women aged 20-70 in four geographic populations in 1995-97. We handed a self-administered questionnaire, which was selected from the Spielberger Anger Expression Scale, to the participants in the risk factor surveys and measured anger-in and anger-out as the anger expression scale. These scales had high internal consistency (Cronbach's alpha coefficient was 0.97-0.98 for anger-out and 0.77-0.86 for anger-in) and were of almost the same structure as the original. The Pearson correlation coefficients for the anger expression scale examined in 1995 and 1996 were 0.69 for anger-out and 0.57 for anger-in (both p < 0.001). The mean scores of both anger-out and anger-in were inversely associated with age. The mean anger-out score was higher for men than for women (p < 0.001), whereas the mean anger-in score did not vary significantly between the sexes. Furthermore, the mean scores of anger-out and anger-in varied among populations and occupational groups. The present study suggests that the Japanese version of the selected Anger Expression Scale is an acceptable scale for evaluating anger expression among Japanese.

Adult↗

PubMed2000

Telomere dynamics and genetic instability in disease progression of chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is characterized by a Philadelphia (Ph) translocation creating a novel BCR-ABL oncoprotein, and CML patients have a chronic phase for several years followed by an intractable blast cell proliferation, called blast transformation. In the blast phase, more than 60% of patients show additional cytogenetic changes, e. g., double Ph, +8, i(17q). In this review, we would like to address genetic changes, including genome instability, cytogenetic changes, and telomere dynamics that relate to karyotypic instability. In the chronic phase, approximately 60% of CML patients show reduced telomere length without highly elevated telomerase activity or microsatellite alterations, indicating that telomere reduction may be linked to cell replication. Therefore, the Ph translocation might be a first event to immortalize cell proliferation. In the blast phase, 50% of CML patients have high levels of elevated telomerase activity and the same number of patients had microsatellite changes. Of note is that most patients with telomerase up-regulation in the blast phase had additional cytogenetic changes and >60% of them showed microsatellite changes at least at one locus. In contrast, most patients without telomerase activity did not show microsatellite changes. These findings may indicate that telomerase up-regulation in the blast phase of CML patients is closely associated with microsatellite changes (representative of genome instability), while blast cells in the remaining patients (30%) maintain their proliferative capability without microsatellite changes and telomerase up-regulation. This further suggests that there is also an unknown mechanism for genome stability without the process of telomerase up-regulation in some patients with CML in blast crisis.

Cell Transformation, Neoplastic↗

PubMed2000

Effects of shift work on 24-hour ambulatory blood pressure and its variability among Japanese workers.

OBJECTIVES: This study examined the effects of rotating shift work on blood pressure in a comparison of ambulatory blood pressure and long-term changes in blood pressure between shift and day workers. METHODS: Ambulatory blood pressure was measured for 24-hour periods at an interval of 30 minutes for 27 shift workers and 26 day workers when they worked during the day. Blood pressure was compared between these 2 groups of workers for 4 time categories (awake, sleep, nonwork awake, and work periods). Their long-term blood pressures, recorded in annual surveys, were reviewed for long-term changes. These comparisons were adjusted for the effects of body mass index, alcohol intake, anger expression, and physical activity. RESULTS: On the average, sleep time was shorter and the anger-in (ie, anger suppressed) score was higher for the shift workers than for the day workers, but body mass index and alcohol intake did not differ between the 2 groups. Even after adjustment for these co-variables, the mean systolic blood pressure during the 24-hour, awake, and work periods were higher among the shift workers than among the day workers. The 24-hour standard deviations of the systolic blood pressures were also higher for the shift workers than for the day workers. Among the shift workers, but not among the day workers, a significant long-term increase was observed in systolic blood pressure measured in the annual surveys. CONCLUSIONS: These results suggest that shift work may increase systolic blood pressure levels among Japanese men.

Adult↗

PubMed2000

Prospective study on alcohol intake and risk of subarachnoid hemorrhage among Japanese men and women.

BACKGROUND: Few prospective data are available to evaluate potential risk factors of subarachnoid hemorrhage among the Japanese, although several prospective studies conducted in the United States and in Europe have shown a positive relationship between alcohol intake and the risk of subarachnoid hemorrhage. METHODS: A 9.4 year follow-up study was conducted on 12,372 men and women age 40 to 69 years who had no history of stroke, in six communities in Japan. The incident cases of subarachnoid hemorrhage were confirmed with computed tomography findings and/or clinical findings. Alcohol intake and other cerebrovascular risk factors were measured at the baseline examination. A Cox proportional hazard analysis was used to estimate the relative risks and 95% confidence intervals of the incidence of subarachnoid hemorrhage. RESULTS: During the follow-up assessment, 71 cases of subarachnoid hemorrhages occurred. For men, heavy drinking appeared to be an independent risk factor for subarachnoid hemorrhage; multivariate-adjusted relative risk was 4.3 (95% confidence interval [CI]: 1.1-16.8; p = 0.04). Among women, no excess risk was found for heavy drinking, probably due to the small number of heavy drinkers (n = 15). The combination of heavy drinking with smoking or hypertension increased the risk of subarachnoid hemorrhage substantially for men; the multivariate-adjusted relative risk was 6.0 (95% CI: 1.8-20.1;p = 0.004) for heavy drinking smokers and 13.0 (95% CI: 3.9-43.9; p < 0.001) for heavy drinking hypertensives. CONCLUSIONS: A reduction in alcohol intake, smoking cessation, and control of hypertension are important in preventing subarachnoid hemorrhage among Japanese men.

Adult↗