Relationship between brain atrophy estimated by a longitudinal computed tomography study and blood pressure control in patients with essential hypertension.
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To evaluate the relationship between blood pressure control and the progression of brain atrophy in the elderly, patients with essential hypertension and brain atrophy were longitudinally evaluated using computerized tomography (CT). The study evaluated 48 patients with essential hypertension aged 46-78 years, and 30 sex- and age-matched normotensive control subjects. The extent of brain atrophy as determined by caudate head index (CHI), the inverse cella media index (iCMI), and Evans' ratio (ER) was estimated twice at an interval of 5-9 years (mean, 6.9 years). The mean annual increases in CHI (deltaCHI), iCMI (delta iCMI), and ER (deltaER) were evaluated. Mean blood volume in the common carotid artery (BF) and the decrease in BF per year (deltaBF) were also determined. The deltaCHI, delta iCMI, and deltaER increased with age in the hypertensive subjects as well as the control group across all age groups evaluated. The deltaCHI, delta iCMI, and deltaER were significantly greater in the patients with essential hypertension in their 50 s as compared with the controls. In patients with essential hypertension aged 65 years or older, the deltaCHI, delta iCMI, and deltaER were significantly lower in the group in whom the blood pressure was controlled within the range of borderline hypertension than the groups in which it was controlled in the range of normal or mild hypertension. In the younger patients under the age of 65 with essential hypertension, blood pressure control did not affect the deltaCHI, delta iCMI, and deltaER. The deltaCHI, delta iCMI, and deltaER were significantly correlated with deltaBF in both groups. These findings indicate that control of systolic blood pressure within the range of borderline hypertension may delay the progression of brain atrophy in elderly patients with essential hypertension. (+info)
Nucleo-cytoplasmic interactions that control nuclear envelope breakdown and entry into mitosis in the sea urchin zygote.
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In sea urchin zygotes and mammalian cells nuclear envelope breakdown (NEB) is not driven simply by a rise in cytoplasmic cyclin dependent kinase 1-cyclin B (Cdk1-B) activity; the checkpoint monitoring DNA synthesis can prevent NEB in the face of mitotic levels of Cdk1-B. Using sea urchin zygotes we investigated whether this checkpoint prevents NEB by restricting import of regulatory proteins into the nucleus. We find that cyclin B1-GFP accumulates in nuclei that cannot complete DNA synthesis and do not break down. Thus, this checkpoint limits NEB downstream of both the cytoplasmic activation and nuclear accumulation of Cdk1-B1. In separate experiments we fertilize sea urchin eggs with sperm whose DNA has been covalently cross-linked to inhibit replication. When the pronuclei fuse, the resulting zygote nucleus does not break down for >180 minutes (equivalent to three cell cycles), even though Cdk1-B activity rises to greater than mitotic levels. If pronuclear fusion is prevented, then the female pronucleus breaks down at the normal time (average 68 minutes) and the male pronucleus with cross-linked DNA breaks down 16 minutes later. This male pronucleus has a functional checkpoint because it does not break down for >120 minutes if the female pronucleus is removed just prior to NEB. These results reveal the existence of an activity released by the female pronucleus upon its breakdown, that overrides the checkpoint in the male pronucleus and induces NEB. Microinjecting wheat germ agglutinin into binucleate zygotes reveals that this activity involves molecules that must be actively translocated into the male pronucleus. (+info)
Partial remission phase of diabetes in children younger than age 10 years.
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There is renewed interest in the phase of partial remission in recently diagnosed diabetes because of the potential for pharmacological and immune intervention to preserve beta cell function. 95 children younger than 10 years were investigated to assess the influence of age, sex, diabetic ketoacidosis (DKA), admission at diagnosis, and ethnicity on the frequency of remission and insulin requirements during the first two years after diagnosis. Partial remission was defined as a requirement of insulin < 0.5 U/kg body weight/day. There was partial remission in 41 patients, with no differences for children aged 2-4 years and those aged 5-9 years. None of the five children aged < 2 years remitted. Forty five of 95 children were admitted to hospital at diagnosis, of whom 26 of 45 had DKA (blood pH < 7.25). In this number of children we were unable to show a statistical difference in the rate of remission with respect to DKA, admission to hospital at diagnosis, sex, or South Asian ethnic background. There were no differences in insulin requirements between the different groups by the end of two years and at that time seven of the children required insulin < 0.5 U/kg/day. The results suggest that even in preschool children there is potential for attempting to preserve beta cell function. (+info)
Female gonadal hormones differentially modulate cocaine-induced behavioral sensitization in Fischer, Lewis, and Sprague-Dawley rats.
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Evidence suggests the existence of genetic differences in cocaine sensitization in male rats. The present study was undertaken to investigate cocaine sensitization in female rats of genetically distinct inbred (Fischer 344 and Lewis) and outbred (Sprague-Dawley) strains. All female rats were bilaterally ovariectomized and randomly assigned to one of four experimental groups: 1) estradiol benzoate group, 2) progesterone group, 3) estradiol benzoate-plus-progesterone group, and 4) ovariectomized group. Additional controls included sham-operated female rats, female rats that received a single oil injection, and female rats that received repeated oil injections. To determine gender-related differences in the acute and chronic effects of cocaine, data obtained from female rats were compared with those from strain- and weight-matched male rats. Estradiol benzoate-plus-progesterone female rats showed greater locomotor effect in response to an acute dose of cocaine and had more robust sensitization in response to repeated cocaine than did male rats. The bilateral removal of ovaries abolished cocaine sensitization. In all strains of rats studied, progesterone alone did not alter the ovariectomy-induced attenuation of cocaine behavior, but estrogen alone restored cocaine-induced behavioral sensitization. There were significant strain effects on the degree of gonadal hormonal-induced modulation of cocaine sensitization in female rats. Female Lewis rats were extremely sensitive to repeated-cocaine effects, whereas the Fischer 344 female rats showed only marginal effects. The Sprague-Dawley rats ranked intermediate in their behavioral sensitivity. The present study strongly supports the hypothesis that female rats are more sensitive to both acute and chronic behavioral effects of cocaine than are male rats and that the effects are strain dependent. It also shows that estrogen plays an important role in the increased sensitivity of female rats to cocaine sensitization. Together, these data indicate significant interactions between ovarian steroid hormones and genetic factors in cocaine-induced behavioral effects. (+info)
Sex dependence of human intracranial gliomata.
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The age and sex distribution of 1223 cases of intracranial gliomata, diagnosed in the geographical area covered by the Mersey Regional Cancer Registry over the period 1961-70, are analysed. In children and adults, the intracranial gliomata predominates in males, the tumour incidence figures indicating a ratio of 3 : 2. For young adults, the tumour incidence increases with age and is approximately the same in males and females. It is not until the age group 45-49 years is reached that the tumour incidence in males is higher. The peak tumour incidence occurs at the same age in both sexes (60-64 years) and thereafter incidence declines with age. These results are compared with previously published human data, and with the findings of experimental studies in the rat. Factors including naturally occurring changes in the hormone levels are discussed, in an attempt to explain the observed age-related sex differences. (+info)
Dietary determinants of colorectal proliferation in the normal mucosa of subjects with previous colon adenomas.
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Dietary determinants of colorectal mucosa proliferation were studied in 69 subjects previously operated for at least two sporadic colon adenomas. Information on recent dietary habits was collected by a validated food frequency questionnaire, and proliferation was measured by [3H]thymidine incorporation in colorectal biopsies by determining the labeling index (LI) and the percentage of LI in the upper part of the crypt, two parameters that are increased in subjects at high risk of colon cancer. The LI was significantly higher in women as compared with men (P = 0.01). Diet showed several associations with colorectal mucosa proliferation: (a) subjects in the highest tertile of fish consumption had a significantly lower LI (P = 0.0013) compared with those in the lower tertiles [5.20 +/- 1.87 versus 6.80 +/- 2.18 (mean +/- SD)]; (b) subjects with a low red meat consumption had lower proliferation in the upper part of the crypt [2.38 +/- 2.10, 5.30 +/- 4.62, and 5.89 +/- 4.82 in the low, middle, and high tertile of consumption, respectively (mean +/- SD); P = 0.0093]; (c) according to estimated nutrient intakes, the LI was lower in subjects reporting a high intake of starch (P = 0.006) and higher in subjects with a low intake of beta-carotene (P = 0.002). The results show that subjects reporting a diet rich in fish, starch, and beta-carotene and low in red meat had lower colorectal mucosa proliferation and a normal pattern of proliferation along the crypt. Given the correlation between colorectal proliferative activity and colon cancer risk, such a dietary pattern might be beneficial for subjects at high risk of colon cancer. (+info)
Serum levels of ochratoxin A in healthy adults in Tuscany: correlation with individual characteristics and between repeat measurements.
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Ochratoxin A (OTA), a mycotoxin widely contaminating staple foods and beverages, has been classified as a "possible human carcinogen (Group 2B)" by the IARC. Serum levels of OTA were measured in a group of 138 healthy adults (age, 35-65 years) living in the area surrounding Florence (Tuscany, central Italy) and detected in all but four samples (97%). After the exclusion of one subject with a peak value of 57.2 ng/ml, OTA levels ranged between 0.12 and 2.84 ng/ml, with mean and median values of 0.56 and 0.48 ng/ml, respectively. OTA levels were significantly higher in men than in women (0.64 versus 0.50) and correlated positively with height. A strong association was found with the season in which blood samples were obtained, with summer values higher than autumn values. On the other hand, OTA levels tended to be negatively associated with blood pressure, either systolic or diastolic; no association was evident with age, weight, body mass index, and smoking history. The associations with height and season persisted in a multivariate regression analysis. A subgroup of subjects provided a repeat blood sample approximately 1 year later. The Spearman correlation coefficient between 68 pairs of original and repeat measurements was practically null (r = 0.05). Only two subjects (2.9%) had OTA levels of >1 ng/ml on both occasions. These results suggest that OTA contamination is widespread in foods consumed by this population, in agreement with previous reports from Italy and other countries. A strong seasonal variation, which possibly differs from year to year, was observed. OTA serum levels are a short-term biomarker with a high within-subject variability; therefore they have limited use at the individual level but can be used to characterize populations or subgroups of subjects. Additional analyses are needed to explore the dietary determinants of OTA levels in this population. (+info)
Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans.
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Since little is known about chromosomal locations harboring type 2 diabetes-susceptibility genes, we conducted a genomewide scan for such genes in a Mexican American population. We used data from 27 low-income extended Mexican American pedigrees consisting of 440 individuals for whom genotypic data are available for 379 markers. We used a variance-components technique to conduct multipoint linkage analyses for two phenotypes: type 2 diabetes (a discrete trait) and age at onset of diabetes (a truncated quantitative trait). For the multipoint analyses, a subset of 295 markers was selected on the basis of optimal spacing and informativeness. We found significant evidence that a susceptibility locus near the marker D10S587 on chromosome 10q influences age at onset of diabetes (LOD score 3.75) and is also linked with type 2 diabetes itself (LOD score 2.88). This susceptibility locus explains 63.8%+/-9.9% (P=. 000016) of the total phenotypic variation in age at onset of diabetes and 65.7%+/-10.9% (P=.000135) of the total variation in liability to type 2 diabetes. Weaker evidence was found for linkage of diabetes and of age at onset to regions on chromosomes 3p, 4q, and 9p. In conclusion, our strongest evidence for linkage to both age at onset of diabetes and type 2 diabetes itself in the Mexican American population was for a region on chromosome 10q. (+info)