Premature separation of centromere and aneuploidy: an indicator of high risk in unaffected individuals from familial breast cancer families?

OBJECTIVES: Injury is the leading cause of death in the male working population of Brazil. An important fraction of these deaths are work related. Very few cohort studies of steel workers, and none from developing countries, have reported on mortality from injuries. This paper analyses mortality from work and non-work related injuries among Brazilian steel workers. METHODS: Deaths during employment from 1 January 1977 to 30 November 1992 were analysed in a cohort of 21,816 male steel workers. Mortality rates specific for age and calendar year among the workers were compared with those of the male population of the state where the plant is located. Work related injuries were analysed by comparing the mortality rates for different subgroups of the cohort. RESULTS: The number of deaths (391) was less than half that expected based on death rates of the general population. Over 60% (242) of deaths were due to injuries. Mortality from most causes was substantially below that in the general population, but that from unintentional injury, was 50% above that of the general population. Standardised mortality ratios (SMRs) were highest for the youngest and the oldest employees and for labourers and clerical workers. Mortality from motor vehicle injury was twice that expected from population rates (SMR = 209, 95% confidence interval (95% CI) 176-244). There was a 67% fall in the age adjusted mortality from occupational injuries in the study period. CONCLUSION: The healthy worker effect in this cohort was greater than that commonly found in studies of occupational groups in developed countries, probably because of a greater socioeconomic gap between employed and unemployed populations in Brazil, and unequal distribution of health care resources. Mortality was especially high for motor vehicle injuries. The fall in mortality from occupational injuries during the study period was probably due to improvement in safety standards, increased automation, and better medical care. There is a need to investigate risk factors for unintentional injuries among steel workers, especially those due to motor vehicle injuries. Prevention of occupational and nonoccupational injuries should be a main priority in Brazil.     

The community-centered board model of managed care for people with developmental disabilities

An asymmetric triazine derivative, HOE 092 V,2-[3,5-alpha-dichloro-4-(4-methyl-sulfonylphenoxy)-phenyl]- 1-methyl-hexahydro-1,2,4-triazine-3,5-dion, was tested in vivo against Glugea anomala parasitizing the connective tissue of sticklebacks (Gasterosteus aculeatus). Naturally infected sticklebacks were incubated in 10-1 plastic aquaria in water containing 0, 2.5, 5, and 10 micrograms HOE 092 V/ml for 2, 3, and 4 h at 22 degrees C. As seen at the ultrastructural level, the drug caused severe damage to all developmental stages of G. anomala except the mature spores. Starting with a dose of 2.5 micrograms/ml, the drug caused significant damage on uni- and multinucleate meronts, sporogonial plasmodia, and sporoblasts. The damage mainly consisted in a decrease in the number of ribosomes, an enlargement of the smooth endoplasmic reticulum and a vacuolization of the cytoplasma. When treatment was done with 5 micrograms for 2 h, multinucleate meronts and sporogonial plasmodia were no longer detectable, and the sporoblasts and the prespore stages except the mature spores had shrunk. After incubation of the infected fish with 10 micrograms HOE 092 V/ml and 4 h exposure, uninucleate meronts were no longer detectable by means of transmission electron microscopy. In the sporoblast mother cells, vacuolization of the cytoplasma and lysis of the nuclei occurred. However, mature spores were not affected. It seems likely that HOE 092 V can be successfully applied in medicinal baths against Microsporidia in fish. The infected fish should be incubated in separate, aerated containers.     

Ultrastructural immunocytochemical localization of neurotensin and the dopamine D2 receptor in the rat nucleus accumbens

The neuroleptic-like effects of neurotensin (NT) are thought to be due to interactions with dopamine (DA) acting primarily at D2 receptors within the nucleus accumbens septi (Acb). Using electron microscopic dual labeling immunocytochemistry, we sought to demonstrate cellular substrates for functional interactions involving NT and DA D2 receptors in the adult rat Acb. Peroxidase reaction product representing D2 receptor-like immunoreactivity (D2-LI) was seen along membranes of Golgi lamellae and multivesicular bodies of perikarya containing immunogold labeling representing NT-LI. Dually labeled somata usually contained highly indented nuclei, a characteristic of aspiny neurons. Dendrites also occasionally colocalized the two immunomarkers. Other somata, dendrites, and all axon terminals were singly labeled with either NT-LI or D2-LI. In distinct sets of terminals, NT-LI was commonly associated with large, dense-cored vesicles, whereas D2-LI was found along the plasmalemma and over nearby small clear vesicles. Each type of terminal comprised approximately 20% of synaptic input to NT-immunoreactive dendrites. Similar proportions of terminals containing NT-LI or D2-LI contacted unlabeled (approximately 55%) or NT-labeled (approximately 35%) dendrites and, occasionally, were observed converging onto common dendrites. Terminals containing NT-LI or D2-LI also were often closely apposed. These findings provide the first ultrastructural evidence that: (1) NT and D2 receptors are colocalized in aspiny neurons and dendrites, (2) NT may produce a direct postsynaptic effect on neurons receiving input from terminals which are presynaptically modulated by DA via D2 receptors, and (3) NT and DA acting at D2 receptors may interact through presynaptic modulation of common axon terminals.     

Sexual disorders: demographic and diagnostic profile during one year of a multidisciplinary project

Taking into consideration a study published 10 years ago on sexual disturbances of students at the University of S?o Paulo, the importance of the subject is discussed, along with the creation in 1993 of the Sexuality Project at the university hospital of the University of S?o Paulo School of Medicine. In its first year, this multidisciplinary project attended 140 patients with sexual dysfunctions (associated or not to other clinical manifestations); the majority were younger than 60 years-old, and 80 percent were male.     

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold {odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6}. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Dental caries in nineteenth century upper Canada

This study examines the presence of dental caries in a large sample of adult skeletons from the 19th century cemetery of St. Thomas' Anglican Church in Belleville, Ontario. The cemetery was used from 1821 to 1874. Caries prevalence and frequencies of diseased and missing teeth were calculated both by observing summary statistics of individual rates and by the total sample of teeth. Postmortem tooth loss is low in this sample and antemortem tooth loss is highest in first mandibular molars, all other molars and then premolars. Age at death, but not sex, was found to be significantly related to the overall Caries Rate while both age and sex were significantly associated with the Diseased-Missing Index. The increase in diseased and missing teeth in older individuals is expected while the sex difference is not explained by simple dietary factors. When compared to reports on British and American samples, caries and antemortem tooth loss in the St. Thomas' sample is most similar to a pre-1850 British group and higher than American samples. Although there is undoubtedly a complex of factors contributing to caries prevalence in this sample, more data are required from large historic samples, particularly from the American northeast and late 19th century Britain, to have a clearer understanding of the influence of diet, cultural, and environmental factors affecting caries rates in historic populations.     

Genetic control of differential baseline breathing pattern

The purpose of the present study was to determine the genetic control of baseline breathing pattern by examining the mode of inheritance between two inbred murine strains with differential breathing characteristics. Specifically, the rapid, shallow phenotype of the C57BL/6J (B6) strain is consistently distinct from the slow, deep phenotype of the C3H/HeJ (C3) strain. The response distributions of segregant and nonsegregant progeny were compared with the two progenitor strains to determine the mode of inheritance for each ventilatory characteristic. The BXH recombinant inbred (RI) strains derived from the B6 and C3 progenitors were examined to establish strain distribution patterns for each ventilatory trait. To establish the mode of inheritance, baseline breathing frequency (f), tidal volume, and inspiratory time (TI) were measured five times in each of 178 mature male animals from the two progenitor strains and their progeny by using whole body plethysmography. With respect to f and TI, the two progenitor strains were consistently distinct, and segregation analyses of the inheritance pattern suggest that the most parsimonious genetic model for response distributions of f and TI is a two-loci model. In similar experiments conducted on 82 mature male animals from 12 BXH RI strains, each parental phenotype was represented by one or more of the RI strains. Intermediate phenotypes emerged to confirm the likelihood that parental strain differences in f and TI were determined by more than one locus. Taken together, these studies suggest that the phenotypic difference in baseline respiratory timing between male B6 and C3 mice is best explained by a genetic model that considers at least two loci as major determinants.     

HLA-B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in mechanisms of HLA class I peptide loading

Tapasin is a resident ER protein believed to be critical for antigen presentation by HLA class I molecules. We demonstrate that allelic variation in MHC class I molecules influences their dependence on tapasin for peptide loading and antigen presentation. HLA-B*2705 molecules achieve high levels of surface expression and present specific viral peptides in the absence of tapasin. In contrast, HLA-B*4402 molecules are highly dependent upon human tapasin for these functions, while HLA-B8 molecules are intermediate in this regard. Significantly, HLA-B*2705 like HLA-B*4402, requires tapasin to associate efficiently with TAP (transporters associated with antigen processing). The unusual ability of HLA-B*2705 to form peptide complexes without associating with TAP or tapasin confers flexibility in the repertoire of peptides presented by this molecule. We speculate that these properties might contribute to the role of HLA-B27 in conferring susceptibility to inflammatory spondyloarthropathies.