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Biomedical subjects

S Mizushima

Publications and source records attributed to S Mizushima.

At least 37 records · Page 2Linked to original sources

Preventive nutritional factors in epidemiology: interaction between sodium and calcium.

1. It is generally believed, though difficult to prove, that diet plays a role in the risk of various diseases. Components of difficulties include several issues such as dietary assessment method, regression dilution bias, multicolinearity and interaction among nutrients. 2. The present study focuses on colinearity and interaction between sodium and calcium, which should be cautiously examined in nutritional epidemiological studies in relation to blood pressure and bone mineral density. 3. The World Health Organization's International Cooperative Cardiovascular Diseases and Alimentary Comparison study showed significant multicolinearity among urinary sodium, calcium and urea nitrogen as well as urinary calcium and magnesium. Urinary sodium and calcium had significant correlation (r = 0.438, P < 0.05, n = 48) by cross-centre analysis. 4. Interaction between sodium and calcium on bone mineral density is studied using the data set from bone mineral density screening for 1658 females, aged 20-40 years, in Yokohama, Japan. Among those who have lower calcium intake (< 600 mg/day), higher calcium intake (%) from small fish, which is likely to be associated with a high salt diet, related to significantly lower mineral bone density. 5. Interaction between sodium and calcium on bone mineral density among young Japanese females is suggested. Moderate sodium restriction is needed for prevention of not only cardiovascular diseases but also osteoporosis.

Blood Pressure↗

Dietary soybeans intake and bone mineral density among 995 middle-aged women in Yokohama.

To investigate relationship of dietary factors, especially source of calcium intake, to bone mineral density (BMD) among Japanese middle-aged women, a total of 995 healthy women age of 40 to 49 (mean +/- SD, 45 +/- 3), who lives in Yokohama-city, were recruited through convenience sampling by the municipal information paper and health announcement at each 18 public health center in 18 wards for the three-day course on prevention of osteoporosis from October 1996 to March 1998. The BMD of the 2nd metacarpal bone was measured using Computed X-ray Densitometry (CXD) method, by a trained radiologist. Dietary intake of calcium was assessed by self-reporting food frequency questionnaire on calcium dietary sources such as milk, dairy products, small fish, vegetables, and soybeans and carefully checked by trained dietician. An independent gradient of non-adjusted and adjusted BMD for age and weekly calcium intake, through soybeans intake frequency (p = 0.03) was noted. This study suggest soybeans, through possible beneficial effects of vitamin-K, soyprotein, and isoflavonoid, may affect BMD of middle aged women.

Adult↗

Sexual behaviour of commercial sex workers and their clients in Cambodia. Japan-Cambodia Collaborating Research Group.

OBJECTIVE: This study surveyed the sexual behaviour of commercial sex workers and their clients in an attempt to identify factors of transmission of STDs (including HIV/AIDS) and to control their epidemics in Cambodia and South-East Asia. DESIGN: Cross-sectional study. SETTING: Trained questioners asked items of the questionnaires to each objective subject in December 1996. Data were analysed to show the descriptive status by risk group of each person. PARTICIPANTS: 200 direct commercial sex workers, 220 indirect commercial sex workers, and 211 clients in Phnom Penh. RESULTS: Prostitution was widely accepted by both young males and females, and this was an easy way for young girls to obtain money. Although commercial sex workers and clients were knowledgeable about prevention methods against STDs, they seldom used condoms. Some commercial sex workers had been infected with STDs many times, and many of them incompletely treated the diseases by themselves. Social support from governmental and non-governmental organisation was poor. CONCLUSIONS: It is very important to support both commercial sex workers in practicing preventive methods against STDs and also visiting physicians when they notice symptoms of STDs. It is strongly recommended that not only governmental but also non-governmental organisations should be more active in this area.

Acquired Immunodeficiency Syndrome↗

[Epidemiological study on HIV/AIDS in Cambodia seroprevalence of HIV/STD among commercial sex workers].

OBJECTIVE: To describe epidemiological features of HIV prevalence among female commercial sex workers (CSWs) in Cambodia, a cross-sectional study using a questionnaire study and serological tests was carried out from December 1997 to January 1998. We report the main results of the analyses of serological tests in this article. METHODS: Two hundred ninety six CSWs working in Sisophon and Poi Pet, located in northwest Cambodia, Bantey Mean Chey province, were recruited for interview based on a questionnaire on sexual behavior, and serological tests. The blood samples were examined for HIV antibody, Chlamydia trachomatis IgG antibody, TPHA, Hepatitis B surface antigen, and Hepatitis B surface antibody. The relationship between HIV and the other STD's was analyzed by using logistic regression analysis. RESULTS: The HIV seroprevalence rate was 43.9% (130 out of 296). The seropositive rate of Chlamydia trachomatis IgG antibody (C.T.-IgG-Ab) was 73.3% (217 out of 296). Logistic regression analysis showed a significant association between C.T.-IgG-Ab positive and HIV prevalence. (Odds Ratio: 5.33; 95% Confidence Interval, 2.82-10.07). CONCLUSIONS: This study suggests that the existence of Chlamydia trachomatis is closely related with HIV prevalence among CSWs in Cambodia. Other STDs may also increase susceptibility to male-to-female sexual transmission of HIV. This suggests that appropriate prevention against STDs will be needed for the control of HIV prevalence in Cambodia.

Acquired Immunodeficiency Syndrome↗

Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5).

A cDNA encoding the human homolog of the tumor necrosis factor receptor-associated factor 5 (TRAF5) protein has been molecularly cloned from a cDNA library of Human Daudi B cell line. The sequence analysis revealed that the cDNA encoded a protein of 557 aa residues with a calculated molecular weight of 64,236. The encoded protein has typical structural characteristics shown in the TRAF family of proteins and binds to the cytoplasmic region of lymphotoxin-beta receptor more efficiently than to that of CD40 and CD30. The TRAF5 gene was mapped to the human chromosome 1q32.3-q41.1. Overexpression of human TRAF5 activates NF kappa B transcription factor in human 293T kidney cells. These results suggest that the human TRAF5 protein could be involved in the signal triggered by various members of the tumor necrosis factor receptor (TNFR) superfamily including CD40, CD30 and lymphotoxin-beta receptor.

Amino Acid Sequence↗

Dietary magnesium intake and blood pressure: a qualitative overview of the observational studies.

Published reports of 30 separate sets of analyses from 29 observational studies relating dietary intake of magnesium to blood pressure (BP) were identified through a comprehensive search using MEDLINE and BIDS-EMBASE. Three studies were prospective, 24 cross-sectional (25 reports), of which four also contained a longitudinal component, and two were obtained from baseline data in a trial. Various dietary methodologies were used: 24-h dietary recall (n = 12), food-frequency questionnaire (8), food record (7), and duplicate diet (2). Twelve reports compared magnesium intake or BP level between subgroups. Seven showed a negative association between magnesium intake and BP level, and five reported no association. From 18 of the 30 sets of analyses either a regression estimate or a Pearson correlation coefficient was reported. Many reports also allowed identification of subgroups by sex, age and race. Ninety population samples and subgroups could thus be identified from the 30 reports. All 11 Pearson-r correlation coefficients reported for systolic BP (SBP) (three significant, P < 0.05) and 10 (out of 12) Pearson-r correlation coefficients reported for diastolic BP (DBP) (four significant) were negative. Seven reports (13 subgroups for SBP, 11 subgroups for DBP) gave partial regression coefficients after adjustment; 10 (seven significant) and eight (six significant) were negative for SBP and DBP, respectively. For 13 subgroups in five papers, Pearson-r correlation coefficients were reported after adjustment for confounding factors. Eight (out of 13) showed a negative relationship for SBP and DBP. This review points to a negative association between dietary magnesium intake and BP. A systematic quantitative overview is needed to reconcile the inconsistencies of the results of individual studies and to quantify the size of such relationship.

Adolescent↗

Amino-terminal region of SecA is involved in the function of SecG for protein translocation into Escherichia coli membrane vesicles.

Protein translocation across the cytoplasmic membrane of Escherichia coli is accomplished by concerted actions of the translocation ATPase SecA and the membrane-embedded SecE/Y/G complex. SecA interacts with preproteins and undergoes ATP-driven cycles of membrane insertion-deinsertion. To address how SecA interacts functionally with other components in the translocation machinery, we characterized a SecA mutant lacking amino-terminal 8 amino acid residues (SecA N-8). Although the absence of the 8 residues did not grossly affect the interaction of SecA with a preprotein, ATP, or phospholipids, nor did it affect the intrinsic ATPase activity, it gave differential effects on the translocation of different preproteins. It also affected the translocation ATPase activity, the ability of membrane insertion, and the topology inversion of SecG coupled with the membrane insertion-deinsertion of SecA. Most noteworthy, SecA N-8 was pronouncedly defective in the translocation of proton motive force-dependent preproteins, in which SecG might have a role. We propose that the amino-terminal region of SecA is important for the functional interaction with SecG.

Adenosine Triphosphatases↗

Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction.

Recently a point mutation of guanine to thymine at nucleotide position 1917 in the endothelial nitric oxide synthase (eNOS) gene has been reported to be associated with coronary artery spasm. In addition, a significant association of the 4a/b polymorphism in intron 4 of the eNOS gene with coronary artery disease has been reported. However, the implications of these polymorphisms with respect to acute myocardial infarction (AMI) remain to be established. We conducted a case-control study of 226 patients with AMI and 357 healthy gender- and age-matched control subjects. In the former group, coronary angiograms were evaluated according to angiographic criteria based on the number of diseased vessels (>/=75%) and the number of stenotic lesions (>/=50%). Homozygosity for the Glu-Asp298 polymorphism existed in 5 of 226 patients with AMI (2.2%) but not in any of the 357 control subjects (P=.0085). However, when we evaluated the coronary angiograms of 226 case patients, there was no difference in the number of diseased vessels or the number of stenotic lesions between the patients with this homozygote and those without it. By contrast, there was no evidence of a significant increase in the risk of AMI or the severity of coronary atherosclerosis among individuals with the a/a genotype of the eNOS4a/b polymorphism. Our results imply that patients who are homozygous for the Glu-Asp298 polymorphism may be genetically predisposed to AMI; however, this mutation apparently is not related to the severity of coronary atherosclerosis. Further studies are needed to confirm our results and characterize the molecular mechanisms by which eNOS is involved in susceptibility to AMI.

Case-Control Studies↗

Gene expression of the two heavy chains and one light chain forming the inter-alpha-trypsin-inhibitor in human tissues.

Human inter-alpha-trypsin-inhibitor (ITI) is a serine proteinase inhibitor with a molecular weight of 220 kDa which consists of 3 different polypeptides. The constitutive components are 2 heavy chains (H1 and H2 chains) and 1 light chain (L chain), and its inhibitory activity is considered to be derived from this L chain. It has also been reported that this L chain is almost identical to the trypsin inhibitor (UTI) occurring in human urine. We examined the gene expression of the ITI constitutive peptides in human tissues using the reverse transcription (RT) -PCR technique. As a result, the genes of the H1 chain were found to be expressed in various tissues, particularly strongly in the liver. On the other hand, the genes of the H2 chain were found to be strongly expressed in the adrenal glands, brain, kidneys, and lungs, as well as the liver. Further, the PCR amplification product of the L chain was strongly detected not only in the liver but also in the pancreas, kidneys, lungs, stomach and testes. These results suggest the possibility that the major tissue which produces ITI is the liver, and the H chains and L chain (UTI) are produced as a component of ITI- related proteins in other tissues as well as in the liver.

Alpha-Globulins↗

[Relationship between dietary calcium and bone mineral density before menopause].

To study the relationship between dietary calcium intake and bone mineral density (BMD) among young Japanese females, we recruited 1298 females under 40 years living in Yokohama city for BMD measurement by Computed X-ray densitometer (CXD method) and dietary questionnaire. 1. The average of BMD was 2.75 mm/AI and was highest in the 35 to 39 year old group. 2. Calcium intake (Ca) and protein intake (Protein) were highest in 35 to 39 year old group. 3. BMD, Ca, and Protein were significantly higher in those who had regular dietary habits than those with irregular habits. 4. Among those who had lower Ca, (less than 600 mg per day), the amount of small fish consumed whole was negatively correlated with BMD (p = 0.035), and those with higher consumption of small fish than average had significantly (p = 0.018) lower BMD than those with lower small fish consumption adjusting for age and Ca and protein intake. These findings imply a possibility that small fish accompanied by higher salt intake may influence BMD adversely in this population by an interaction with calcium urinary excretion, which has been suggested by experimental and epidemiologic studies. Dietary composition of Ca may be important for prevention of osteoporosis.

Absorptiometry, Photon↗

In vitro analysis of the stop-transfer process during translocation across the cytoplasmic membrane of Escherichia coli.

In this study, using a derivative of proOmpA containing an artificial stop-transfer sequence (proOmpA2xH1), we analyzed the process of stop-transfer during translocation across the cytoplasmic membrane of Escherichia coli. ProOmpA2xH1 did not interfere with the transit of wild-type proOmpA. When proOmpA2xH1 was anchored in the membrane, membrane-inserted SecA was deinserted with the reversion of the inverted topology of SecG. Cross-linking experiments revealed that the anchored proOmpA2xH1 that does not interact with either SecY or SecA. These results, taken together, suggest that proOmpA2xH1 leaves the translocation pathway by means of a specific interaction between the stop-transfer sequence and the translocational channel.

Adenosine Triphosphate↗

The hydrophobic region of signal peptides is involved in the interaction with membrane-bound SecA.

The positive charges of signal peptides are important for the interaction with SecA, a translocation ATPase. To examine whether or not the hydrophobic region of signal peptides also interacts with SecA, we constructed model preproteins, proOmpF-Lpps, possessing no positively charged amino acid residues at the amino-terminus and different numbers of alanine/leucine residues in the hydrophobic region of signal peptides. When the hydrophobic stretch was sufficiently long, amino-terminal positively charged residues were not required for the translocation of preproteins across the cytoplasmic membrane of Escherichia coli both in vitro and in vivo. Chemical cross-linking between SecA and preproteins possessing no positively charged residues at the amino-terminus was observed only in the presence of liposomes containing acidic phospholipids. The degree of cross-linking increased as the length of the hydrophobic stretch increased irrespective of whether positively charged residues were present or not. A preprotein possessing no positively charged residues at the amino-terminus, which is competent in the presence of liposomes, competitively inhibited the cross-linking of wild-type proOmpF-Lpp with SecA under the same conditions. It is concluded that both the amino-terminal positive charges and central hydrophobic domains are involved in the interaction with SecA in the initial stage of translocation in addition to their possible roles in transmembrane movement of preproteins.

Adenosine Triphosphatases↗

Short hydrophobic segments in the mature domain of ProOmpA determine its stepwise movement during translocation across the cytoplasmic membrane of Escherichia coli.

Based on the finding that a series of engineered proOmpAs containing disulfide-bridged loops of different sizes at different positions exhibits a discontinuous mode of polypeptide transit across the cytoplasmic membrane of Escherichia coli, we suggested previously that the translocation of preproteins takes place at every 30 amino acid residues (Uchida, K., Mori, H., and Mizushima, S. (1995) J. Biol. Chem. 270, 30862-30868). In the present study, we investigated the molecular mechanism underlying this stepwise translocation. Deletion or relocation of hydrophobic segments of the mature domain of proOmpA (H1, residues 233-237; H2, residues 261-265) significantly altered the pattern of the stepwise translocation. The stepwise mode of polypeptide insertion was also observed with reconstituted proteoliposomes comprising purified SecA, SecY, and SecE. Cross-linking experiments involving a photoactivable cross-linker revealed that SecY and SecA are the components which interact with the hydrophobic segment of proOmpA. The present results indicate that the hydrophobic segments of the mature domains of preproteins interact with membrane embedded translocase during polypeptide transit across the membrane, which causes a discontinuous mode of polypeptide movement.

Adenosine Triphosphatases↗

The hydrophobic region of signal peptides is a determinant for SRP recognition and protein translocation across the ER membrane.

Newly recognized mammalian secretory proteins such as preprolactin are translocated across the endoplasmic reticulum (ER) in a signal recognition particle (SRP)-dependent manner. Recent studies revealed that there are two recognition steps for signal peptides during this translocation. The first step is recognition by SRP, which results in elongation arrest, and the second step is interaction between signal peptides and the translocation channel embedded in the ER membrane. To determine the roles of the hydrophobic region of signal peptides in the recognition by SRP and the membrane-embedded translocation machinery, we constructed chimeric proteins consisting of the mature region of preprolactin and signal peptides containing different numbers of leucine residues. The translocation of these chimeric proteins was completely dependent on SRP, and the efficiency increased as the number of leucine residues increased up to 10 and then decreased. Although the efficiency of elongation arrest also increased as the number of leucine residues increased up to 10, it only slightly decreased as the number increased up to 20. Similar results were obtained when the hydrophobic region was replaced by alternate leucine and alanine residues, except that the most efficient translocation occurred when the number was 14. Taken together, the present results suggests that the total hydrophobicity of the hydrophobic region of signal peptides is a determinant for recognition by both SRP and the membrane-embedded translocation machinery, although the specificities of the two signal recognition steps are slightly different from each other.

Amino Acid Sequence↗

Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese.

To clarify the role of genetic factors in atherosclerotic plaque formation in the carotid artery and magnetic resonance imaging abnormalities in the brain, we investigated the association of these abnormalities with the angiotensin-converting enzyme (ACE) genotype. One hundred sixty-nine subjects (age, 59.2+/-0.8 years, mean+/-SE) admitted to our hospital for health checkups underwent brain magnetic resonance imaging to evaluate lacunar infarction. B-mode ultrasound examinations of the carotid arteries were performed to detect atherosclerotic plaque. The I/D polymorphism of the ACE gene was determined by the polymerase chain reaction method. Multivariate regression analysis was performed to assess the effects of the following variables on the presence of plaque, mean plaque thickness, and number of plaques: fibrinogen, sex, age, body mass index, mean blood pressure, glycosylated hemoglobin, LDL cholesterol, HDL cholesterol, hematocrit, and the D allele of the ACE gene. The frequency of carotid atherosclerotic plaque was significantly (P=.034) higher in subjects with the D allele than in those without this allele. However, the frequency of lacunar stroke was similar in these groups. A multivariate regression analysis showed that the presence of plaque was independently associated with the D allele (odds ratio=3.27, P=.016). However, mean plaque thickness and the number of plaques were not associated with the D allele. The D allele of the ACE gene may be involved in the presence of carotid plaque but not in the extent of this plaque or asymptomatic lacunar stroke in Japanese subjects.

Aged↗

[Diagnostic value of serum soluble interleukin-2 receptor levels in interstitial pneumonia of the patients with hematological disorders].

Serum levels of soluble interleukin-2 receptor (SIL-2R) and C-reactive protein (CRP) were measured in 12 patients with interstitial pneumonia (IP) and 10 patients with bacterial pneumonia (BP) of hematological malignancies. Mean SIL-2R levels (U/ml) were 394 +/- 140 in normal controls, 755 +/- 320 in BP, and 2328 +/- 943 in IP. A significantly higher level was found in IP than BP (p < 0.05). Moreover, the SIL-2R/CRP ratio which was over 260 in all cases of IP completely distinguished IP from BP. Levels of SIL-2R rose before the onset of IP and were closely associated with clinical course in most cases. From these results, measurement of serum SIL-2R may be useful for the diagnosis and monitoring of the clinical course of IP complicated with hematological diseases.

C-Reactive Protein↗