Alterations of body mass index and body composition in atomic bomb survivors.

OBJECTIVE: Obesity, underweight, sarcopenia and excess accumulation of abdominal fat are associated with a risk of death and adverse health outcomes. Our aim was to determine whether body mass index (BMI) and body composition, assessed with dual-energy X-ray absorptiometry (DXA), are associated with radiation exposure among atomic bomb (A-bomb) survivors. DESIGN: This was a cross-sectional study conducted in the Adult Health Study of the Radiation Effects Research Foundation. SUBJECTS: We examined 2686 subjects (834 men and 1852 women), aged 48-89 years (0-40 years at A-bomb exposure), for BMI analysis. Among them, 550 men and 1179 women underwent DXA in 1994-1996 and were eligible for a body composition study. RESULTS: After being adjusted for age and other potential confounding factors, A-bomb radiation dose was associated significantly and negatively with BMI in both sexes (P=0.01 in men, P=0.03 in women) and appendicular lean mass (P<0.001 in men, P=0.05 in women). It was positively associated with trunk-to-limb fat ratio in women who were less than 15 years old at the time of exposure (P=0.03). CONCLUSIONS: This is the first study to report a significant dose response for BMI and body composition 50 years after A-bomb radiation exposure. We will need to conduct further studies to evaluate whether these alterations affect health status.

Genetic parameters for preweaning and early growth traits in Berkshire pigs when creep feeding is used.

The objective of this study was to find optimal traits for inclusion in selection criteria by estimating genetic parameters for direct genetic, maternal genetic, and common environmental effects for growth traits before 60 d of age and for the number of teats under an open breeding population, and to evaluate genetic relationships for traits at 60 d of age. Records of 2,344 male and 2,204 female purebred Berkshire pigs were analyzed. For BW at 14 d of age and for weaning weight, the heritabilities of a direct genetic effect were greater than those of a maternal genetic effect. This result is contrary to previous results showing a gradual decrease in the maternal genetic effect and an increase in the direct genetic effect up to weaning. The positive genetic correlations between direct and maternal genetic effects for BW at 14 d of age and weaning weight are clearly contrary to other reports. This phenomenon seems to be caused by creep feeding begun just after the birth of the piglets and maintained throughout the preweaning period in this Berkshire population.

Prevalence of adult-onset multifactorial disease among offspring of atomic bomb survivors.

The first study to examine whether parental radiation exposure leads to increased heritable risk of common adult-onset multifactorial diseases (i.e., hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, and stroke) was conducted among 11,951 participants in the clinical examination program out of a potential of 24,673 mail survey subjects who were offspring of survivors born from May 1946 through December 1984. Logistic regression analyses demonstrated no evidence of an association between the prevalence of multifactorial diseases in the offspring and parental radiation exposure, after adjusting for age, city, gender and various risk factors. The odds ratio (OR) for a paternal dose of 1 Gy was 0.91 [95% confidence interval (CI) 0.81-1.01, P = 0.08], and that for a maternal dose of 1 Gy was 0.98 (95% CI 0.86-1.10, P = 0.71). There was no apparent effect of parental age at exposure or of elapsed time between parental exposure and birth, but male offspring had a low odds ratio (OR = 0.76 at 1 Gy) for paternal exposure, but cautious interpretation is needed for this finding. The clinical assessment of nearly 12,000 offspring of A-bomb survivors who have reached a median age of about 50 years provided no evidence for an increased prevalence of adult-onset multifactorial diseases in relation to parental radiation exposure.

Laparoscopic cholecystectomy in a patient on continuous ambulatory peritoneal dialysis.

The patient was a 72-year-old man who was receiving continuous ambulatory peritoneal dialysis (CAPD) with a diagnosis of chronic renal failure. Although his response to dialysis therapy was favorable, right hypochondralgia and fever occurred, and gallstones were detected by abdominal ultrasonography and computed tomography. Drip-infusion cholangiography (DIC) revealed neither dilation nor calculus in the common bile duct. The patient was diagnosed as having acute cholecystitis and cholecystolithiasis and, in consideration of his general condition, laparoscopic cholecystectomy was carried out. Pneumoperitoneum was performed through a CAPD tube, and a 10 mm-trocar was carefully introduced through a supraumbilical incision so as not to injure the CAPD tube. Since intraoperative cholangiography showed a condition similar to preoperative DIC, only cholecystectomy was undertaken. The postoperative course was uneventful, with neither postoperative hemorrhage nor leakage of dialysate from the wound.

Antiarrhythmic effects of magnesium on rat papillary muscle and guinea pig ventricular myocytes.

1. Despite widespread use of magnesium ion (Mg2+) for antiarrhythmic purposes, little direct information is available regarding its antiarrhythmic mechanisms. To elucidate the possible cellular mechanism, the effects of Mg2+ on early afterdepolarization (EAD), delayed afterdepolarization (DAD), triggered activity (TA), transient inward current (TI) and aftercontraction (AC) were examined in various cardiac preparations. The effects of Mg2+ on myoplasmic Ca2+ concentration were also studied. 2. The effects of Mg2+ on AC, induced by overdrive stimulation, were studied in isolated rat ventricular papillary muscle superfused with low K+ solution. In enzymatically isolated guinea pig myocytes, EAD, DAD and/or TA were induced after overdrive stimulation under conditions of superfusion with low K+ solution, using the whole-cell current-clamp method, and TI was also induced by the whole-cell voltage-clamp method. 3. Immediately after changing the solutions, containing varying concentrations of Mg2+, the effects of Mg2+ were examined. In addition, effects of Mg2+ on Ca transient were studied, using fura-2. 4. We found that: (1) in the rat papillary muscle, 10 mM Mg2+ effectively inhibited AC, which was produced after stimulation at both 3.3 Hz and 5 Hz, although 5 mM Mg2+ was without effect in the case of AC induced after 5-Hz stimulation; (2) in the myocytes, 5 mM Mg2+ did not inhibit DADs, EADs and TA, but 10 mM Mg2+ inhibited them completely; (3) the amplitude and frequency of TI decreased significantly in the presence of 10 mM Mg2+; and finally (4) 10 mM Mg2+ inhibited the Ca transient underlying DAD and/or TA. 5. The findings suggest, but do not prove unequivocally, that Mg's actions are probably due to a combination of a shift of the threshold of various ion channels to less negative potentials, a decrease in Ca2+ influx via Ca channels, a block of several K channels, and/or a block of Na-Ca exchanger. In conclusion, the present study indicates that extracellular Mg2+, via whatever mechanism, exerts antiarrhythmic activities.

Effects of KT-362, a sarcolemmal and intracellular calcium antagonist, on calcium transients of cultured neonatal rat ventricular cells: a comparison with gallopamil and ryanodine.

We evaluated the effects of KT-362 (5-[3-([2-(3,4-dimethoxyphenyl)-ethyl]amino)-1-oxopropyl]-2,3,4,5, -tetrahydro-1,5-benzothiazepine fumarate), a putative intracellular calcium antagonist, on the intracellular free calcium concentration ([Ca2+]i) of cultured neonatal rat ventricular cells using microfluorometry of fura-2. The effects were compared with those of gallopamil (D-600), a sarcolemmal calcium channel antagonist, and ryanodine, a modulator of sarcoplasmic reticulum (SR) function. KT-362 decreased both systolic [Ca2+]i (sCa) and diastolic [Ca2+]i (dCa) in cell aggregates, in a concentration (1, 3, 10, and 30 microM) and stimulation frequency (0.2, 0.5, and 1.0 Hz) dependent manner. The time to peak of the Ca2+ transient was significantly prolonged by KT-362 at a concentration of 30 microM, while the half-life of the Ca2+ transient was prolonged at concentrations of > or = 10 microM. Gallopamil (1 microM) decreased both sCa and dCa in a frequency (0.2, 0.5, and 1.0 Hz) dependent fashion, as was the case for KT-362, but did not change the time course of Ca2+ transients. Ryanodine (10 microM) prolonged the time to peak and half-life of the Ca2+ transient, as was also the case for KT-362, while the effect of ryanodine on dCa differed from that of KT-362. Finally, the effect of KT-362 on Ca2+ transients could be mimicked by simultaneous application of gallopamil and ryanodine. These results suggest that KT-362 is a novel compound that exerts depressant effects on both sarcolemmal Ca2+ channels, and perhaps Ca2+ release channels of the sarcoplasmic reticulum, in cultured neonatal rat ventricular cells.

Mechanical stretch increases intracellular calcium concentration in cultured ventricular cells from neonatal rats.

We investigated the effects of mechanical stretch on intracellular calcium concentration ([Ca2+]i) of cultured neonatal rat ventricular cells using microfluorometry with fura-2. Myocytes were cultured on laminin-coated silicon rubber and stretched by pulling the rubber with a manipulator. Myocytes were either mildly stretched (to less than 11.5% of control length), moderately so (to 115%-125% of control length), or extensively (to over 125% of the control length). "Quick stretches" (accomplished within 10s) of moderate to extensive intensities produced a large transient increase of [Ca2+]i in the early phase of stretch (30 s-2 min), followed by a small but sustained increase during the late phase of stretch (5-10 min). The initial transient increase in [Ca2+]i after the "quick stretch" was preserved in the presence of gallopamil (10(-7) M) or ryanodine (10(-5) M), but was absent in Ca(2+)-free medium or in the presence of gadolinium (10(-7) M). The late or steady state [Ca2+]i increase was observed in the presence of gadolinium, gallopamil, or ryanodine but was abolished in Ca(2+)-free medium. A steady-state increase in [Ca2+]i was also evoked by "slow stretch" in which cells were slowly pulled to the final length within 1-2 min. As the presence of external Ca2+ was indispensable, increased trans-sarcolemmal Ca2+ influx appears to be involved in both initial and steady-state increases in [Ca2+]i. The initial increase in [Ca2+]i after the "quick stretch" can be attributed to the activation of gadolinium-sensitive, stretch-activated channels.

Electrocardiographic diagnosis of left circumflex artery occlusion and the occlusion site.

In patients with a posteroinferior acute myocardial infarction and both ST depression (in lead V1 or V2) and ST elevation in the inferior leads, it is difficult to differentiate a left circumflex artery occlusion from a right coronary artery occlusion. Furthermore, there is no useful method to identify the obstruction site in the left circumflex artery. In a study of 52 patients with single-vessel left circumflex artery disease, ST elevation in V6 was found to be a useful indicator for left circumflex artery occlusion in such patients. Furthermore, the sum of the ST changes in leads a VF and V2 is useful for identifying the occluded site in the left circumflex artery.

A comparative study of effects of isoproterenol and dihydroouabain on calcium transients and contraction in cultured rat ventricular cells.

We investigated the effects of isoproterenol, a beta-adrenergic agonist, and dihydroouabain, a Na+,K(+)-pump inhibitor, on Ca2+ transients and contraction of cultured rat ventricular cells and compared the effects with those of altered external ion concentrations, with special reference to the changes in diastolic intracellular free calcium concentration ([Ca2+]i). We measured [Ca2+]i of cultured cell aggregates, stimulated at 1.0 Hz, with the use of dual-wavelength microfluorometry of fura-2, at room temperature (24-26 degrees C). The contraction was measured as a shortening of the aggregates using a photodiode array placed on a video monitor. Isoproterenol increased the magnitude of contraction and the peak amplitude of the Ca2+ transient, in a concentration (10(-9)-10(-6) M)-dependent manner, but did not change the diastolic Ca2+ level. Isoproterenol at 10(-7) M or higher significantly shortened the duration of contraction and half decay time of a Ca2+ transient yet it did not change the time to peak. Dihydroouabain (10(-7)-10(-5) M) increased the contraction and elevated both systolic and diastolic calcium levels but it did not alter the duration of contraction, the time to peak and the half decay time. The effects of dihydroouabain on Ca2+ transients were mimicked by lowering [K+]o (0.4 mM), by lowering [Na+]o (74 mM) or by elevating [Ca2+]o (3.6 or 5.4 mM). Ryanodine (10(-5) M), by itself, decreased systolic Ca2+ transient amplitude, increased diastolic Ca2+ levels and prolonged the time to peak and the half decay time. In the presence of ryanodine, isoproterenol increased both systolic and diastolic [Ca2+]i. Thus, most procedures that increased the systolic Ca2+ transient amplitude increased the diastolic Ca2+ levels as well, and enhanced the contraction. The only exception was isoproterenol that markedly increased the systolic Ca2+ transient amplitude without affecting the diastolic Ca2+ level, a finding in keeping with the observation that isoproterenol stimulates Ca2+ uptake by the sarcoplasmic reticulum.

[Antiarrhythmic effects of magnesium on single ventricular myocytes].

Despite magnesium ions (Mg)'s widespread use for antiarrhythmic purposes, little is known concerning its antiarrhythmic mechanisms. We, therefore, examined Mg effects on delayed afterdepolarization (DAD), early afterdepolarization (EAD), triggered activity (TA) and aftercontraction (AC), using isolated ventricular cells and/or ventricular papillary muscle. In the experiments using the multicellular preparation, ACs were measured, with the use of a strain gauge. ACs were induced in isolated rat papillary muscle superfused with low K+ (0.5 mM) medium, after a train stimulation (2-5 Hz, 10-30 beats). In the experiments concerning cardiac myocytes, the effects of Mg on transient inward current (TI), which is responsible for DAD, were studied using a whole-cell voltage-clamp method applied on isolated guinea pig ventricular cells. And action potentials were also induced by current clamp (10 ms) and the effects of Mg on DAD, EAD and TA were examined. TI, DAD, EAD and TA were induced by use of pipette solution with high Ca2+ (0.7 mM) and low EGTA (0.1 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effects of alpha-tocopherol and coenzyme Q10 on warm ischemic damages of the rat kidney.

Studies were done on the protective effects of alpha-tocopherol and coenzyme Q10 (CoQ10) on warm ischemic damage to the rat kidney. Administration of alpha-tocopherol (10 mg/kg body wt/day) for 7 days or a single i.p. injection of CoQ10 (6 mg/kg body wt) increased the survival rate from 0 to 46.7% of the rats subjected to warm ischemia for 120 min. The administration of alpha-tocopherol and CoQ10 increased adenosine triphosphate (ATP) in the renal tissue from 0.53 +/- 0.18 to 0.92 +/- 0.29, and from 0.64 +/- 0.26 to 1.00 +/- 0.54 mumol/g wet weight, respectively, 4-hr reperfusion after 120 min of warm ischemia. Serum creatinine levels of the surviving rats after 120 min of warm ischemia was 9.98 +/- 0.19 mg/100 ml in the control group and 5.84 +/- 0.95 and 7.27 +/- 1.62 mg/100 ml, respectively, in alpha-tocopherol and CoQ10 administered group, when determined 2 days after the operation. These results indicate that alpha-tocopherol and CoQ10 have a protective effect on warm ischemic damage to the rat kidney, demonstrated by an increase in ATP resynthesis after reflow following warm ischemia and by the maintenance of a lower serum creatinine level. This effect was accompanied by an increase in the survival rate of ischemic rats.