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Self-reported prevalence of non-insulin-dependent diabetes mellitus in the 1st (Issei) and 2nd (Nisei) generation of Japanese-Brazilians over 40 years of age.

The immigration of Japanese people to Brazil began in 1908 with two major waves, from 1925 to 1940 and from 1952 to the 1960s. Brazil has the largest population (about 1,288,000) of Japanese origin outside Japan with varying age groups. A mortality study revealed that diabetes as an underlying cause of death was higher in the first-generation Japanese than in Japan (3.4 vs. 1.9 per 100,000 for men, and 7.2 vs. 1.9 for women). The self-reported prevalences of known diabetes in subjects aged 40 years or older were obtained by questionnaires from three sources. In six Japanese cultural associations in Säo Paulo city, the prevalences were 9.7% and 6.9% for the first generation (mean age 61.5 years) and for the second generation (mean age 40.0 years), respectively. Age-adjusted prevalences, according to the Brazilian population in the 1980 national census, were 6.9% and 8.1% for the first and second generations. According to a study carried out as a part of a socioeconomic census of the Japanese population in Brazil, the prevalences of diabetes were 7.4% and 5.2%, and the age-adjusted prevalences were 5.3% and 5.8% in the first and second generations, respectively. Another study carried out for employees of a bank, owned by Japanese-Brazilian community members, revealed crude prevalences of diabetes in the first and second generations of 7.1% and 4.2%, and age-adjusted prevalences of 7.3% and 8.2%, respectively. These data indicate an increased prevalence of diabetes in this population compared to Japan, suggesting the importance of environmental factors in the pathogenesis of diabetes.

Adult↗

Empirical tests of the intrinsic pseudorandom number generator on IBM-compatible microcomputers.

This paper reports results of frequency and serial correlation tests, for 30 different seeds and two different seeding mechanisms (the RANDOMIZE statement and the RND function), of a Microsoft pseudorandom number generator available on IBM-compatible (and some IBM) microcomputers. The generator is shown to perform well on these screening tests, in comparison to previously reported results for the Microsoft generator available on IBM-PC microcomputers. However, the generator seeding mechanisms--the RANDOMIZE statement and the RND function--exhibit anomalies similar to those of the IBM-PC generator, and could result in seeding which is inconsistent with the desire of the user. Furthermore, the differences in the randomness characteristics of sequences of numbers generated by IBM and IBM-compatible microcomputers have serious implications regarding the true compatibility of the two types of microcomputers.

Mathematical Computing↗

Stimulated rat mast cells generate histamine-releasing peptide from albumin.

Media conditioned by compound 48/80-stimulated rat mast cells generated immunoreactive histamine-releasing peptide (HRP) when incubated at physiological pH with bovine serum albumin and the carboxypeptidase inhibitor, O-phenanthroline. The generation of immunoreactive HRP (IR-HRP) was time (after 3 h the concentration of IR-HRP was 20 nM), temperature, and pH dependent and was prevented by omitting albumin, by using media conditioned by nonstimulated mast cells, or by pretreatment of mast cells with disodium cromoglycate, an inhibitor of mast cell secretion. The amount of IR-HRP generated increased linearly with the number of mast cells stimulated and varied directly with the concentration of conditioned media. After removal of the media from stimulated mast cells, the remaining cell pellet retained its ability to generate IR-HRP for up to 8 h. Stimulation of mast cells by either neurotensin or substance P, or of sensitized cells by anti-IgE serum, also produced conditioned media that generated IR-HRP. The amount of IR-HRP formed by various conditioned media or by stimulated cell pellets was dependent upon the concentration of O-phenanthroline used. Including the chymase inhibitor, chymostatin, prevented the formation of IR-HRP in a dose-dependent manner. HPLC analysis showed four peaks of IR-HRP. The major one coeluted with synthetic HRP. These results indicate that the peptide, HRP, can be generated by stimulated mast cells incubated in the presence of albumin. They suggest that a chymase-like enzyme secreted by the mast cell is able to cleave albumin to yield HRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Three-generation reproduction study on carmine of cochineal in the rat.

Carmine was fed continuously to male and female rats over three generations at dietary concentrations that provided intakes of 50, 150 or 500 mg carmine/kg body weight/day. In adult animals of all generations there were no effects of treatment on body-weight gain, food and water intakes or fertility. At autopsy the weights and the gross and microscopic appearance of the organs were normal. In the teratological investigations, examination of the foetal skeletons of the F3 generation revealed a slightly more advanced stage of ossification in all treated groups compared to those of the control. Survival, growth and development of offspring were similar in each group apart from a slight delay in the time of tooth eruption in the 150- and 500-mg/kg groups of the first and second generations. This was not seen in the final generation. It is concluded that carmine had no untoward effects on the growth and fertility of adult rats, or on the ante- and postnatal development of their offspring when given continuously at doses of up to 500 mg/kg body weight/day in the diet throughout all phases of mating, gestation, lactation, weaning and adult life over three successive generations.

Abnormalities, Drug-Induced↗

Dietary two-generation reproduction study of thiabendazole in Sprague-Dawley rats.

The potential reproductive toxicity of the fungicide and anthelmintic thiabendazole (TBZ) was assessed in Sprague-Dawley rats for two generations. Doses of 10, 30 or 90 mg/kg/day were administered by way of the diet beginning at 8 wk of age for the F0 generation and postnatal wk 4 for the F1 generation and continuing until the animals were killed. Concentrations of TBZ in the diet were adjusted weekly, except during the gestation and lactation intervals when concentrations were held constant. There were no TBZ-related deaths or adverse physical signs during the study. TBZ-related effects consisted of decreases in average body weight gains and food consumption in the middle and high dose groups. In both the F0 and F1 generations during the premating and post-cohabitation periods, the effects in the middle-dose group were observed only in males and were generally slight in magnitude (food consumption 3-5% below control, weight gain 7-18% below control), whereas the effects in the high dose group occurred in both sexes and were slight to moderate in magnitude (food consumption 9-13% below control, weight gain 13-46% below control). During gestation of the F0 females there were slight decreases in average weight gain and food consumption (8% and 4-16% below control, respectively); a similar effect on food consumption, but not weight gain, occurred in the F1 generation. There were no effects on F0 or F1 reproductive performance (including indices of mating, fecundity, fertility, length of gestation, litter size, birth weight, and post-implantation survival), nor were any histomorphological changes observed in the reproductive tissues of animals in the high dose group. There was no evidence of developmental toxicity in the TBZ-exposed F1 or F2 generations, except for slight decreases in average pup weights between postnatal days 4 and 21 in the high dose group (5-10% below control). The NOAEL (no-observed-adverse-effect level) for all developmental, growth, survival and reproductive performance parameters assessed in this study was 10 mg/kg/day.

Animals↗

Acoustic generation of intra-arterial contrast boluses.

Microbubbles generated by ultrasonic cavitation in vivo might be useable as flow indicators in some situations instead of injectable contrast agents. Knowledge of those vascular microbubble-generating ultrasonic fields which produce from negligible up to significant damage will help improve guidelines for more effective, safer diagnostic and therapeutic ultrasound. Microbubble boluses have been generated by a 1.8-MHz, focused sound field in the in vivo canine abdominal aorta. Spatial peak acoustic intensities of 19,000 W cm-2 generated microbubble boluses when exposure was longer than 12 ms, whereas intensities greater than 4300 W cm-2 generated a bolus when exposure was for 250 ms. The onset time of these boluses (less than one cardiac cycle) is unachievable with intravenous contrast injection. With optimized waveforms and focusing, acoustic bolus generation may prove to be an effective, minimally invasive method for fast performance of certain selective angiography.

Acoustics↗

Relation between thyroid peroxidase, H2O2 generating system and NADPH-dependent reductase activities in thyroid particulate fractions.

In thyroid gland, iodination takes place on the apical plasma membrane and requires the presence of the thyroid peroxidase and H2O2 generating system. H2O2 generation and NBT (nitro blue tetrazolium) reductase activity (both of which are NADPH-dependent) as well as peroxidase activity were compared for their respective orientations in membrane vesicles. The possible role of NADPH-NBT reductase activity in H2O2 generation was also examined. Results favor the conclusion that thyroid peroxidase is oriented towards the luminal side of the vesicles, whereas the NADPH site of NADPH oxidase-dependent H2O2 generation is located on the external side of the same or of different vesicles. Furthermore, it is shown that different NADPH-NBT reductase activities are present on both the outer and inner surfaces of the membrane vesicles, and that none of these activities is able to produce either H2O2 or O-2. The idea that a multi-component complex is involved in H2O2 generation is discussed, and a model is proposed which takes into account the possible spatial separation of the thyroid peroxidase site from the NADPH site of this H2O2 generation system on the apical membrane of the thyrocyte.

Animals↗

Effects of fatty acids on superoxide radical generation in leukocytes.

Acetylated ferricytochrome c was employed for the detection of superoxide radicals (O-2) generated both in intact cells and in subcellular fractions of leukocytes. Certain saturated fatty acids, myristate in particular, induced the production of O-2 in leukocytes, suggesting a correlation between the formation of O-2 and the hydrophobic interaction of fatty acids with the leukocyte plasma membrane. As compared with O-2 radical generation from phagocytizing leukocytes a greater stimulation of O-2 formation was observed in cells in which myristate was added. The enhanced activity which generated O-2 in the cell-free system was located in a particulate fraction but not in the cytosol. The rate of O-2 generation in the particulate fraction was higher in the presence of NADPH than in the presence of NADH. The effects of reagents such as KCN, 2,4-dichlorophenol and aminotriazole on the O-2 generation in this fraction are examined and the nature of the O-2 generating system is discussed.

Amitrole↗

Free radical and enzymatic mechanisms for the generation of protein bound reducing moieties.

We have previously shown that exposure of many proteins, and free aromatic amino acids (particularly tyrosine) to free radical fluxes generates a stable activity capable of reducing protein bound and free transition metal ions. Here we define the capacity of several radical generating systems (gamma irradiation of water, UV irradiation, metal-dependent sugar autoxidation and Haber-Weiss systems) to produce protein-bound reducing moieties (PBRedM), and also reducing derivatives of tyrosine. Under the defined conditions of the gamma radiolysis system, reductive activity was generated under both oxic and anoxic irradiations and specific gassing regimes as well as the inclusion of specific radical scavengers established that hydroxyl radicals were responsible. When BSA was irradiated anoxically in the presence of formate a reductive activity related to the exposure of protein thiol groups was generated; all other reductive activities we detected were not thiol-related. Incubations of tyrosinase with BSA or insulin also generated reductive activity. All the conditions we have studied can convert tyrosine into DOPA and we suspect that protein-bound DOPA is the main reductive activity generated on proteins.

Amidines↗

Generation of retinal cells in the wallaby, Setonix brachyurus (quokka).

We have examined the generation of retinal cells in the wallaby, Setonix brachyurus (quokka). Animals received a single injection of tritiated thymidine between postnatal days 1-85 and retinae were examined at postnatal day 100. Retinae were sectioned, processed for autoradiography and stained with Cresyl Violet. Ganglion cells were labelled by injection of horseradish peroxidase into the optic tracts and primary visual centres. Other cells were classified according to their morphology and location. Retinal cell generation takes place in two phases. During the first phase, which concludes by postnatal day 30, cells destined to lie in all three cellular layers of the retina are produced. In the second phase, which starts by postnatal day 50, cell generation is almost entirely restricted to the inner and outer nuclear layers. Cells produced in the first phase are orthotopic and displaced ganglion cells, displaced and orthotopic amacrine cells, horizontal cells and cones. Glia in the ganglion cell layer, orthotopic amacrine cells, bipolar and horizontal cells. Muller glia, and rods are generated in the second phase. Cells became heavily labelled with tritiated thymidine in the central retina before postnatal day 7, over the entire retina (panretinal) by postnatal day 7 and from postnatal day 18, only in the periphery. The second phase of cell generation is initiated at P50, in a region extending from the optic nerve head to mid-temporal retina. Subsequently, cells are generated in annuli, centred on mid-temporal retina, which are seen at progressively more peripheral locations. Therefore, cell addition to the inner and outer nuclear layers continues for longer in peripheral than in mid-temporal retina. We suggest that such later differential cell addition to the inner and outer nuclear layers contributes to an asymmetric increase in retinal area. This non-uniform growth presumably results in more expansion of the ganglion cell layer peripherally than in mid-temporal retina and may play a role in establishing density gradients of ganglion cells.

Animals↗

Mechanisms of supraspinal correction of locomotor activity generator.

In experiments on immobilized decerebrate cats, data about reorganization of efferent activity parameters of the forelimb and hindlimb locomotor generators evoked by electrical stimulation of descending systems were obtained. The generators controlling both forelimb and hindlimb locomotor movements were found to be characterized by the existence of stable states at which total influence of different descending systems on these generators was extremely limited. These data enable us to conclude that the sense of activity reorganization in locomotor generators of both forelimb and hindlimb under the influence of descending system signals is in bringing the motor program to a dynamic relation with supraspinal inflow, where a sufficient degree of limitation and balancing of the influences of corresponding descending systems on the interneuronal nets, determining time and phase characteristics of these generators, is ensured. Possible mechanisms of realization of this interaction between descending signals and locomotor activity generators are discussed.

Animals↗

Motor program for pedal waves during Aplysia locomotion is generated in the pedal ganglia.

The activity in the nerves innervating the foot of Aplysia was examined during pedal wave generation. Cyclic patterned discharges (i.e. bursting) in the pedal nerves was associated with the pedal wave. Individual units exhibited bursting during pedal wave generation. but fired tonicly when the pedal wave was absent. Bursting in the nerves persisted after the foot was deafferented, confirming previous behavioral results that pedal waves were the result of a centrally generated motor program. Deafferentation caused increased burst durations and decreased spike frequencies within each burst. This suggests that sensory input from the foot excites the oscillator which underlies pedal wave generation and serves to increase the amplitude of the oscillations. Bursting in the nerves persisted after surgically isolating the pedal ganglia, showing that the neural circuitry necessary for pedal wave generation resides in the pedal ganglia. After isolating the pedal ganglia, bursts in the nerves were longer, less vigorous and less frequent. This suggests that input from the other central ganglia affects both the amplitude and the period of the oscillator. The firing of units in homologous pedal nerve branches, showed similar, but not identical patterns with the pedal commisure intact. Individual homologous units differed in both absolute timing and frequency of firing. After cutting the commissure, synchronization of activity in the homologous nerves was lost. This indicates that bilateral coordination of the pedal wave motor programs generated in each pedal ganglion is maintained via the pedal commissure. The possible mechanisms involved are considered.

Afferent Pathways↗

Zirconium molybdate gel as a generator for technetium-99m--I. The concept and its evaluation.

A new 99mTc generator for the preparation of radiopharmaceuticals has been developed. Its elution characteristics and chemical stability merit its consideration as a replacement for present generators. The 99Mo is present as a zirconium molybdate gel, the high molybdate content of which allows the use of (n, gamma) 99Mo. The resulting generator is as effective and as convenient to use as chromatographic generators that are based on fission product 99Mo. Laboratory evaluations of the concept at low levels of radioactivity described in this paper show that the gel can be prepared in a form which is stable when used in a generator and from which TcO4- can be eluted in yields of 80-85%. The influence of formulation variables on gel properties was established. The performance of this generator using 99Mo with specific activities between 4 and 13 GBq g-1 is described in a further paper.

Chemical Precipitation↗

Two-generation reproduction study of sulfur mustard in rats.

Comprehensive data are not available to evaluate the potential risk to reproduction from exposure to sulfur mustard (HD), [bis(2-chloroethyl) sulfide]; thus, the reproductive effects of HD were evaluated in Sprague-Dawley rats. Groups, of rats (27 females and 20 males/group/generation) were gavaged with 0, 0.03, 0.1, or 0.4 mg/kg HD 5 d/week for 13 weeks prior to mating and throughout gestation, parturition, and lactation in a 42-week, 2-generation study. Growth of adult F1 rats of both sexes was reduced by the 0.4 mg/kg exposure. There were no significant effects on reproductive function or pregnancy outcome in either generation, except for an altered sex ratio in the 0.4 mg/kg group. Although not different at birth, growth of the 0.4 mg/kg F1 and F2 offspring was depressed during lactation. A dose-related lesion of the squamous epithelium of the forestomach was observed in adults of both sexes and both the F1 and F2 generation. For a given treatment, the incidence was approximately the same for each sex at each generation. When animals were pooled by sex and generation, approximately 70% (66 out of 94) of the low dose group had only mild microscopic lesions, 72% (68 out of 94) of the intermediate dose group had moderate lesions, and 81% (76 out of 94) of the high group had marked lesions. The lesion, acanthosis, was characterized by thickening of the squamous musoca with varying degrees of hyperkeratosis. Benign neoplasms of the forestomach were found in about 10% of the intermediate and high dose groups in both F0 and F1 generations. Based on these results, the No-Observable-Adverse-Effect-Level (NOAEL) is 0.1 mg/kg/d.

Animals↗

Age-related changes in antioxidant enzymes and prooxidant generation in tissues of the rat with special reference to parameters in two insect species.

The objective of this study was to explore the relationship between partially reduced oxygen species and the aging process. Effect of age on antioxidant defenses and prooxidant generation was evaluated by comparing the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, and rates of mitochondrial O-2 and H2O2 generation in the liver, heart, and brain of 3-month and 18-month-old Sprague-Dawley rats. In addition, comparisons of antioxidant defenses and mitochondrial prooxidant generation were made between short-lived insects and the rat tissues. Results indicated that antioxidant enzymes exhibit a mixed pattern of age-related alterations. In each organ of the rat examined, activities of some enzymes were up with age and of others down with age. The overall magnitude of decline in antioxidant defenses observed here and elsewhere in the literature was deemed to be unlikely to be functionally significant. In contrast, the rate of mitochondrial O-2 and H2O2 generation increased in various tissues of the rat. Antioxidant defenses in insects were comparable to tissues in the rat but rates of O-2 and H2O2 generations were notably higher. Results are interpreted to suggest that rates of prooxidant generation may be more crucial than antioxidant levels as possible longevity determinants.

Aging↗

Prostaglandin F2 alpha rises in response to hydroxyl radical generated in vivo.

Free radicals and some free fatty acids, such as arachidonic acid metabolites, have been hypothesized to be contributors to secondary damage to the spinal cord upon injury. These two types of species may form a feedback loop in which generation of one type leads to formation of the other. In this study, to determine whether hydroxyl radical causes generation of arachidonic acid metabolites in vivo, we generated hydroxyl radical, a most reactive oxygen radical, in the rat spinal cord and measured resulting changes in levels of prostaglandin F2 alpha, an arachidonic acid metabolite that rises following traumatic injury. The hydroxyl radical was generated in the rat spinal cord by administering H2O2 through one microdialysis fiber and FeCl2/EDTA through a parallel fiber. The prostaglandin F2 alpha in the collected microdialysates was measured by HPLC as its 3-bromomethyl-6,7-dimethoxy-1-methyl-2-(1H)-quinoxalinone derivative. Prostaglandin F2 alpha dramatically increased in response to hydroxyl radical generation, but declined substantially after 3 h of exposure. Prostaglandin F2 alpha was undetectable when either H2O2 or FeCl2/EDTA was administered alone in control experiments, demonstrating that its formation was caused by generated hydroxyl radical.

Animals↗

HPLC-chemiluminescence and thermospray LC/MS study of hydroperoxides generated from phosphatidylcholine.

Lipid hydroperoxides generated from phosphatidylcholine (PC) by two commonly employed phosphatidylcholine hydroperoxide (PCOOH) generation methods were examined by HPLC-chemiluminescence (CL) and thermospray LC/MS assay. This HPLC-CL assay is specific for hydroperoxides. In the HPLC-CL chromatograms, a major peak eluted at 4.7 min for the samples generated by the photooxidation of PC in the presence of methylene blue. The direct LC/MS analysis of the hydroperoxides contained in this peak determined that the hydroperoxides are mono- and di-PCOOH. Quantitation showed that over 90% of the hydroperoxides generated by photooxidation are PCOOH. In contrast, a different major peak appeared at 3.7 min for the hydroperoxides generated by the incubation of PC with the azo compound AMVN. We determined by LC/MS analysis that the hydroperoxides contained in this peak were not equivalent to either mono- or di-PCOOH. Indeed, 70%-95% of the hydroperoxides generated by AMVN incubation were not PCOOH, but rather a large portion were AMVN-derived hydroperoxides. The hydroperoxides contained in the 4.7-min peak (i.e., PCOOH) were preferentially responsive to cytochrome c-luminol CL cocktail (about 100-fold more responsive than the hydroperoxides in the 3.7-min peak), whereas the hydroperoxides in the 3.7-min peak (including AMVN-derived hydroperoxide) were preferentially responsive to microperoxidase-isoluminol CL cocktail (about 20-fold more responsive than the PCOOH), suggesting a substrate specificity for the CL cocktail.

Chromatography, High Pressure Liquid↗

The effects of generation and gender on the joint distributions of lipid and apolipoprotein phenotypes in the population at large.

The generation and gender effects on the joint distributions of total plasma cholesterol (Total-C), ln triglycerides (lnTrig), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), apolipoproteins AI (Apo AI), AII (Apo AII), and E (lnApo E) were studied in 184 male grandparents (MGP), 242 female grandparents (FGP), 237 male parents (MP), 235 female parents (FP), 202 male children (MC), and 200 female children (FC). Homogeneity of variance tests revealed that lipid variances were gender and/or generation specific while apolipoprotein variances were homogeneous across strata. In the absence of heterogeneity of variance, significant heterogeneity in LDL:lnTrig and lnTrig:Apo AII covariation was found between genders in the parental generation. In the presence of heterogeneity of variance, significant heterogeneity of correlation between genders and/or across generations was found for the HDL-C:LDL-C, Total-C:LDL-C, Total-C:lnTrig, lnTrig:LDL-C, Total-C:lnApo E and HDL-C:lnApo E bivariate distributions. Analyses of principal components revealed that the generation and gender specific cohorts have similar eigenvalues but distinct eigenvectors for the first two principal components underlying the seven dimensional lipid and apolipoprotein distribution. We conclude that the amount of variability explained by the first two principal components is the same across cohorts but how the interindividual variability is distributed among the lipid and apolipoprotein traits is generation and gender specific. This study documents the role that variance and covariance might play in determining risk of disease for special subgroups of the population at large. It also demonstrates how variances and covariances between risk factors traits characterize life processes of aging and sexual dimorphism. This study argues that future biometrical genetic and epidemiological studies of coronary artery disease must take into account age and gender effects on interindividual variability and covariability of risk factors.

Adult↗