Paternal height has an impact on birth weight of their offspring in a Japanese population: the Japan Environment and Children's Study.

This study examines the relationship between paternal height or body mass index (BMI) and birth weight of their offspring in a Japanese general population. The sample included 33,448 pregnant Japanese women and used fixed data, including maternal, paternal and infant characteristics, from the Japan Environment and Children's Study (JECS), an ongoing nationwide birth cohort study. Relationships between paternal height or BMI and infant birth weight [i.e., small for gestational age (SGA) and large for gestational age (LGA)] were examined using a multinomial logistic regression model. Since fetal programming may be a sex-specific process, male and female infants were analyzed separately. Multivariate analysis showed that the higher the paternal height, the higher the odds of LGA and the lower the odds of SGA in both male and female infants. The effects of paternal BMI on the odds of both SGA and LGA in male infants were similar to those of paternal height; however, paternal height had a stronger impact than BMI on the odds of male LGA. In addition, paternal BMI showed no association with the odds of SGA and only a weak association with the odds of LGA in female infants. This cohort study showed that paternal height was associated with birth weight of their offspring and had stronger effects than paternal BMI, suggesting that the impact of paternal height on infant birth weight could be explained by genetic factors. The sex-dependent effect of paternal BMI on infant birth weight may be due to epigenetic effects.

Page Kidney Following a Nonepisode Protocol Renal Allograft Biopsy: A Case Report.

Page kidney refers to a clinical condition that is characterized by the acute onset of hypertension and renal dysfunction owing to external compression of the kidney by a hematoma, tumor, lymphocele, or urinoma. We report a case in which Page kidney occurred after a nonepisode protocol renal allograft biopsy. A 31-year-old man with end-stage renal disease received a living related kidney transplant from his father. One year later, a nonepisode protocol renal allograft biopsy was performed. A day later, the patient's serum creatinine level increased to 4.23 mg/dL, and a subcapsular renal hematoma was detected using ultrasonography and computed tomography. Page kidney was diagnosed, and immediate surgical removal of the hematoma was performed. Nine days after the operation, the patient's serum creatinine level had improved to 1.89 mg/dL. Page kidney is a serious but treatable complication of renal allograft biopsies, and clinicians should pay attention to such complications, even in the setting of nonepisode protocol renal allograft biopsies.

Orthotopic Kidney Transplantation in an Elderly Patient With Various Severe Comorbid Conditions: A Case Report.

In recent years, the frequency of high-risk kidney transplantations has increased. We report a case in which a 72-year-old man with various severe comorbidities (prostate cancer, diabetes mellitus, complete atrioventricular block, coronary artery stenosis, severe stenosis of the popliteal arteries, and severe calcification of the iliac arteries) who received an orthotopic kidney transplantation. To prevent the occurrence of acute limb ischemia due to the steal phenomenon (caused by the kidney graft), we decided that a heterotopic kidney transplantation involving the iliac arteries was not an appropriate option. Therefore, as an alternative, left native nephrectomy was performed followed by an orthotopic kidney transplantation to the native renal artery and renal vein through a left subcostal incision. Postoperative ureteral stenosis occurred, and so stent exchange was required every 6 months. Despite the ureteral complication, the patient's serum creatinine level was 1.5 mg/dL at 2 years after the procedure.

Living situations associated with poor dietary intake among healthy Japanese elderly: the Ohasama Study.

BACKGROUND: Rapid increases in life expectancy have led to concurrent increases in the number of elderly people living alone or those forced to change living situations. Previous studies have found that poor dietary intake was common in elderly people living alone. However, there have been few studies about the dietary intake in elderly people living in other situations, particularly those living with family other than a spouse (nonspouse family), which is common in Japan. OBJECTIVE: To examine the differences in dietary intake by different living situations in elderly Japanese people. We analyzed the data of 1542 healthy residents in the town of Ohasama aged 60 years and over who had completed self-administered questionnaires. METHODS: The dietary intake was measured using a validated 141-item food frequency questionnaire. Multiple regression models with robust (White-corrected) standard errors were individually fitted for nutrients and foods by living situation. RESULTS: In men, although the presence of other family was correlated with significantly lower intake of protein-related foods, e.g., legumes, fish and shellfish, and dairy products, these declines were more serious in men living with nonspouse family. Conversely, in men living alone the intake of fruits and vegetables was significantly lower. In women, lower intakes of fruit and protein-related foods were significantly more common in participants living with nonspouse family than those living with only a spouse. CONCLUSION: These findings revealed that elderly people living alone as well as those living with family other than a spouse had poor dietary intake, suggesting that strategies to improve food choices and skills for food preparation could promote of healthy eating in elderly Japanese people.

PP083. Clinic and out-of-clinic blood pressure changes during pregnancy by parity: Boshi study.

INTRODUCTION: Nulliparity is believed to be one of the risk factors for hypertension during pregnancy. However, the relationship between parity and out-of-clinic blood pressure during pregnancy is still unknown. OBJECTIVES: The aim of this study was to evaluate clinic blood pressure and blood pressure measured at home during pregnancy among nulliparous and multiparous women. METHODS: This study was a prospective cohort study. We examined blood pressure measured in the clinic and at home among 530 normotensive pregnant women who received antenatal care at a maternity hospital in Japan. Clinic blood pressures were obtained by duplicate measurements at each antenatal care visit. The participants were also required to measure their own blood pressures every morning at home while they were pregnant. A linear mixed model was used for analysis of the blood pressure course throughout pregnancy [1]. The SAS package (version 9.2) was used for the statistical analyses. RESULTS: A total of 315 nulliparous and 215 multiparous women were entered into this study (mean ages 30.1±4.6years and 33.0±4.1years, respectively). Clinic blood pressure during pregnancy among nulliparous women was significantly higher than that among multiparous women (P=0.02/P<0.0001 for systolic/diastolic blood pressure), whereas there were no significant differences in blood pressure measured at home during pregnancy between them (P=0.42/P=0.22 for systolic/diastolic blood pressure). CONCLUSION: Out-of-clinic blood pressure levels during pregnancy have been shown not to differ between nulliparous and multiparous women, while clinic blood pressure during pregnancy among nulliparous women is higher than that among multiparous women.

High fruit intake is associated with a lower risk of future hypertension determined by home blood pressure measurement: the OHASAMA study.

We investigate associations of fruit and vegetable intake with the risk of future hypertension using home blood pressure in a general population from Ohasama, Japan. We obtained data from 745 residents aged ≥35 years without home hypertension at baseline. Dietary intake was measured using a validated 141-item food frequency questionnaire, and subjects were then divided into quartiles according to the fruit and vegetable intake. Home hypertension was defined as home systolic/diastolic blood pressure of ≥135/85 mm Hg and/or the use of antihypertensive medication. During a 4-year follow-up period, we identified 222 incident cases of home hypertension. After adjustment for all putative confounding factors, the highest quartile of fruit intake was associated with a significantly lower risk of future home hypertension (odds ratio 0.40, 95% confidence interval 0.22-0.74, P=0.004). In conclusion, this study, based on home blood pressure measurement, suggests that higher intake of fruit is associated with a lower risk of future home hypertension.

Home blood pressure measurements associated with better blood pressure control: the J-HOME study.

The usefulness of self-measurements of blood pressure (BP) at home (home BP measurements) in hypertensive patients has been reported by many studies. Several national guidelines recommend the use of home BP measurements to achieve better hypertension control. The objective of this study was to clarify the association between home BP measurements and hypertension treatment among 2363 essential hypertensive patients taking antihypertensive drugs. Compared to the 543 (23.0%) patients who had not taken home BP measurements, the 1820 (77.0%) patients who had taken home BP measurements were significantly older, included a higher proportion of males, included a higher proportion with a family history of hypertension, took a greater number of antihypertensive drugs and alpha blockers and took antihypertensive drugs more often in the evening. Home BP measurements were associated with significantly better control of home and office BP levels. Compared to patients who had not taken home BP measurements, the adjusted odds ratios for good control of morning home BPs, evening home BPs and office BPs in patients who had taken home BP measurements were 1.46 (95% confidential interval (CI) 1.33-1.57), 1.35 (95% CI 1.21-1.47) and 1.23 (95% CI 1.06-1.37), respectively. Home BP measurements were associated with good hypertensive management. Our findings suggest that it is important that physicians recommend home BP measurements to their patients.

Haplotypes of aldosterone synthase (CYP11B2) gene in the general population of Japan: the Ohasama study.

Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone synthase (CYP11B2) has been one of major targets for molecular analyses in association with hypertension. To date, four polymorphic variants of CYP11B2, -344T/C at promoter region, a gene conversion in intron 2, 2713A/G (in exon 3) which converts from Lys to Arg at codon 173 (K173R), and 4986T/C (in exon7) which converts from Val to Ala at codon 386 (V386A), have been identified in Caucasian population. Then, linkage disequilibrium between -344T/C polymorphism and a gene conversion in intron 2 or K173R mutation has been described, suggesting the presence of genetic haplotypes in Caucasians. Since the presence of a gene conversion in intron 2 or V386A mutation was still unknown in the Japanese population, all these polymorphisms were examined together to determine the CYP11B2 haplotypes of Japanese, using DNA samples from 1290 participants of the Ohasama study, who represent the general population of a rural community of northern Japan. Molecular analyses demon- strated the presence of a gene conversion of intron 2, but the absence of V386A mutation in Japanese population. The complete linkage disequilibrium between -344T/C polymorphism and K173R mutation was noted. Although -344T allele was linked either with a gene conversion in intron 2 or with normal intron 2, -344C allele was completely linked with normal intron 2. These results indicate the presence of 3 allelic haplotypes of CYP11B2, -344C with normal intron 2 and 173R, -344T with normal intron 2 and 173K, and -344T with converted intron 2 and 173K, in the general Japanese population. The frequency (total 1.0) was 0.35, 0.53, and 0.12, respectively. The presence of allelic haplotypes is considered to be an additional genetic information to individual polymorphism of CYP11B2 to determine the linkage between CYP11B2 polymorphisms and hypertension.

Aldosterone synthase gene (CYP11B2) C-334T polymorphism, ambulatory blood pressure and nocturnal decline in blood pressure in the general Japanese population: the Ohasama Study.

OBJECTIVE: The C-344T polymorphism in the 5'-flanking region of the aldosterone synthase (CYP11B2) gene has been suggested to be associated with hypertension and disturbed circadian blood pressure (BP) rhythm through its effect on aldosterone synthesis. However, previous findings on this topic have been inconsistent. DESIGN: A cross-sectional study. SUBJECTS AND METHODS: We investigated the CYP11B2 C-344T genotype in 802 subjects, aged 40 and over, in a Japanese community, who gave written informed consent and were monitored for 24 h ambulatory BP. RESULTS: The frequencies of the CC, CT, and TT genotypes in these Japanese subjects were 0.14, 0.44, and 0.42, showing a higher frequency of the T allele (0.64) than in Caucasians. Although there was no significant difference in 24 h ambulatory BP levels among the genotypes, the nocturnal decline in BP was significantly greater in the CC homozygous subjects than in other subjects (P = 0.0065 for systolic and P = 0.031 for diastolic decline in nocturnal BP). Detailed analyses demonstrated that this association was significant only in aged (60 years and over) or male subjects. The prevalence of previous cardiovascular disease was significantly less in these subjects with the CC genotype than in those with the TC and TT genotypes, although age, body mass index, male gender, smoking, use of alcohol and antihypertensive medication did not differ among the three genotypes. There was no significant difference among the three genotypes in biochemical and hormonal parameters. CONCLUSION: Although the C-344 T polymorphism of CYP11B2 did not directly influence the level of 24 h BP, the CC genotype was associated with decreased nocturnal BP in elderly or male Japanese. Since prevalence of previous cardiovascular disease was significantly less in homozygous CC subjects, greater nocturnal BP decline in this genotype appears to be beneficial in the circadian BP rhythm.

The effects of radix Salviae miltiorrhizae on lipid accumulation of peroxidized low density lipoprotein in mouse peritoneal macrophages--lipid analysis and morphological studies.

Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradix Salviae Miltiorrhizae (RSM) to investigate the effects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by using lipid analysis and electron microscopy. Lipid peroxide (LPO) concentrations were increased slightly in the medium after incubation of macrophages with normal LDL (n-LDL), while decreased significantly in the media after incubation of macrophages with pox-LDL. In the three groups with pox-LDL, it could be found that there was a dose-dependent decrease of concentrations of LPO and total cholesterol (TCH) in the two RSM groups, and the decrease in the two RSM groups was much greater than in the group without RSM. RSM accelerated a more decrease of LPO than cholesterol contents in the media containing pox-LDL. The ultrastructural studies also showed that RSM induced the accumulation of lipid droplets in the cytoplasm of mouse peritoneal macrophages. The results suggested that RSM could accelerate the phagocytosis and degradation of pox-LDL by macrophages.

Effects of pressor substances on low density lipoprotein peroxidation by Cu++.

To investigate whether pressor substances accelerate low density lipoprotein peroxidation by Cu++, low density lipoprotein was dialysed against physiological saline containing O-5 mumol/l CuCl2 and/or 1 mumol/l of various pressor substances. Lipid peroxide value of low density lipoprotein changed little with the addition of norepinephrine to the saline, but the addition of norepinephrine to 1 mumol/l CuCl2 accelerated the peroxidation. When low density lipoprotein was dialysed against saline with norepinephrine, epinephrine, serotonin or dopamine, there were no significant differences in the lipid peroxide values of low density lipoprotein. Although the addition of serotonin into the dialyzate did not accelerate the peroxidation of low density lipoprotein due to Cu++, the addition of norepinephrine, epinephrine and dopamine accelerated the Cu(++)-peroxidation with a significant increase in the acceleration rate starting at the 36 hour point. Thus, it is speculated that various stresses stimulating the sympathetic nervous system accelerate the peroxidation of low density lipoprotein and produce peroxidized low density lipoprotein in the blood.

Chemical characterization of peroxidized low-density lipoprotein in plasma and aortic atheroma.

Hydroperoxidized cholesteryl linoleate (HPO-CL, spot X1) was produced by peroxidation of normal LDL isolated from plasma of healthy persons. Spot X stained on thin-layer chromatography plate (silica 60) between triglycerides and free fatty acids. The solvent mixture used consisted of petroleum ether 75, ethyl ether 25, and acetic acid 1. Spot X1 of plasma from healthy subjects stained slightly. It was also identified in plasma LDL of patients with atherosclerotic diseases, and in total lipids extracted from aortic atheroma obtained at autopsy. Whereas spot X1 obtained from plasma LDL of patients with atherosclerotic diseases consisted of HPO-CL, spot X1 obtained from aortic atheroma was reduced HPO-CL (hydroxide CL). Spot X1 of obtained from aortic atheroma was reduced HPO-CL (hydroxide CL). Spot X1 of aortic atheroma did not react to p-methoxydiphenylpyrenylphosphine (MP3)-an agent which shows only positive reaction to hydroperoxide chemical structures-although spot X1 of plasma LDL from atherosclerotic diseases reacted positively to MP3. Moreover, spot X1 obtained from aortic atheroma showed the same Rf value as that of the reduced HPO-CL. The IR profile of spot X1 obtained from aortic atheroma was similar to that of hydroxide CL, although the IR profiled HPO-CL was similar to that obtained from plasma LDL of atherosclerotic patients. In addition, HPO-CL was not recognized in the LDL fraction with clathrin-coated pits from aortic atheroma.

Sodium ionophore converts growth manner of vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVES: Vasoconstrictor peptides such as endothelin (ET) cause hypertrophy of vascular smooth muscle cells (VSMC) in Wistar Kyoto rats (WKY) and hyperplasia in spontaneously hypertensive rats (SHR). They also induce an increase in Na+ concentration ([Na+]i) and activate protein kinase C (PKC) independently. Therefore, we tested the hypothesis that the increase in [Na+]i may be involved in the conversion of growth manner under activated PKC in SHR VSMC. METHODS AND RESULTS: 10(-7) M phorbol ester (TPA) increased the diameter and protein content of VSMC from both strains under 18% serum conditions. Further addition of 10(-6) M gramicidin (Na+ ionophore) converted TPA-induced hypertrophy to hyperplasia, which was due to the quick transition from S to G2/M phase, only in SHR VSMC. Western blot analysis showed that serum- and TPA-induced tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was potentiated by 10(-6) M gramicidin in SHR. [Na+]i, which was measured by sodium-binding benzofuran isophthalate (SBFI), was increased about 35 mM by 10(-6) M gramicidin in both strains, but TPA did not affect basal [Na+]i and the gramicidin-induced increase in [Na+]i. CONCLUSIONS: We conclude that sodium ionophore may convert hypertrophy to hyperplasia synergistically with activated PKC in SHR VSMC, possibly by MAP kinase phosphorylation.

Peroxidized low-density lipoprotein with four kinds of hydroperoxidized cholesteryl linoleate estimated in plasma of young heavy smokers.

AIM: To clarify the mechanisms of vascular complications due to heavy smoking, it was studied whether hydroperoxidized low-density lipoprotein (HPO-LDL) was estimated in plasma of young heavy smokers. METHOD: Plasmas were separated from 15 young male students (HS-M) who smoked more than 30 cigarettes/day over 5 years, and from 10 nonsmoker students (NS-M) too. LDL was isolated by ultracentrifugation. HPO-cholesteryl linoleate (HPO-CL) was identified by thin-layer chromatography (TLC), and lipid peroxide was measured by Determiner LPO (Kyowa Medics Co., Ltd, Tokyo, Japan). The molecular structure of lipid peroxide in LDL was identified using GMS analysis, HPLC chromatography and 1H-NMR analysis. RESULTS: (1) HPO-CL was clearly observed on the TLC in LDL lipids of HS-M but from NS-M it was barely found. (2) Lipid peroxide in LDL separated from HS-M consisted of HPO-CL and reduced HPO-CL. CONCLUSION: Peroxidized LDL was estimated in plasma with young heavy smokers. Because of injurious reactions in vessels of peroxidized LDL, it is considered that heavy smoking is one of the risk factors for vascular complications in heavy smokers.

Batroxobin accelerates lipid accumulation of peroxidized low density lipoprotein in mouse peritoneal macrophages.

Mouse peritoneal macrophages were incubated in DMEM medium with batroxobin (DF-521) to determine the effect of batroxobin on the internalization of peroxidized low-density lipoprotein (pox-LDL) by transmission electron microscopy. Although the morphology of the mouse peritoneal macrophages after incubation with DMEM, normal LDL (n-LDL) and n-LDL plus batroxobin was similar to that of the cells before incubation, they exhibited numerous cytoplasmic lipid droplets after incubation with pox-LDL for 4 h. After addition of batroxobin to the medium containing pox-LDL, the production of lipid droplets in the mouse peritoneal macrophages was tremendously accelerated. Batroxobin accelerates the phagocytosis and degradation of pox-LDL by macrophages.

Transformation of cultured human monocytes by peroxidized low-density lipoprotein.

To study the roles of peroxidized low-density lipoprotein (pox-LDL) during the formation of foam cells from human monocytes, monocytes isolated from normal human blood were incubated with RPMI alone, normal low-density lipoprotein (n-LDL) and copper pox-LDL. The concentrations of total cholesterol (TCH) and lipid peroxide in the human monocyte medium did not change significantly after incubation with RPMI medium alone or n-LDL, but those of TCH decreased slightly after incubation with pox-LDL for 24 h. Triglyceride (TG) concentrations in the culture medium of human monocytes decreased after incubation with all above substances. Ultrastructural studies showed that the monocytes changed to macrophages after incubation with RPMI alone or n-LDL and to foam cells after incubation with pox-LDL for 48 h. We conclude that TGs may be metabolized for ATP production by human monocytes. The energy may play a role in the transformation of monocytes to macrophages, and pox-LDL can induce transformation of monocyte-derived macrophages to foam cells.

The effect of radix Salviae Miltiorrhizae Composita on peroxidation of low density lipoprotein due to copper dichloride.

It is well known that plasma lipoprotein, particularly oxidized LDL, plays an important role in the pathogenesis of atherosclerosis and atherosclerotic diseases. We used oxidized LDL generated by incubating LDL from healthy persons with copper dichloride as a model to investigate the antioxidate property of Radix Salviae Miltiorrhizae Composita (RSMC). On photos, the spot X1 and the spot X2 were clearly found in the control group after the dialysis into copper dichloride for 24 and 48 hours, but they could not found in the RSMC group. The analysis of the constituents of lipids in LDL (by charring method) showed that after dialysis the percentages of the spot X1 and the spot X2 in the RSMC group were significantly lower than those in the control group (P < 0.01). The results suggest that RSMC plays a potential role in antioxidation of lipids or LDL.