CHILD syndrome caused by a deletion of exons 6-8 of the NSDHL gene.

The X-linked dominant CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) is a rare developmental defect characterized by a strictly lateralized inflammatory nevus. In the majority of cases, the right side of the body is affected. Ipsilateral hypoplastic lesions may involve the brain, skeletal structures, lungs, heart or kidneys. We describe a case of CHILD syndrome involving the left side of the body. Absence of metacarpal, metatarsal and phalangeal bones of the left hand and foot resulted in oligodactyly, with only 3 fingers and 1 toe. An ipsilateral inflammatory epidermal nevus with hyperkeratosis, parakeratosis, acanthosis and perivascular lymphohistiocytic infiltrate was strictly confined to the left half of the patient's body. The phenotype was shown to be associated with a deletion of exons 6-8 of the X-linked NSDHL gene, confirming that CHILD syndrome is due to loss of function of an enzyme involved in cholesterol biosynthesis.

Ethnicity and glutathione S-transferase (GSTM1/GSTT1) polymorphisms in a Brazilian population.

The distribution of polymorphisms related to glutathione S-transferases (GST) has been described in different populations, mainly for white individuals. We evaluated the distribution of GST mu (GSTM1) and theta (GSTT1) genotypes in 594 individuals, by multiplex PCR-based methods, using amplification of the exon 7 of CYP1A1 gene as an internal control. In São Paulo, 233 whites, 87 mulattos, and 137 blacks, all healthy blood-donor volunteers, were tested. In Bahia, where black and mulatto populations are more numerous, 137 subjects were evaluated. The frequency of the GSTM1 null genotype was significantly higher among whites (55.4%) than among mulattos (41.4%; P = 0.03) and blacks (32.8%; P < 0.0001) from São Paulo, or Bahian subjects in general (35.7%; P = 0.0003). There was no statistically different distribution among any non-white groups. The distribution of GSTT1 null genotype among groups did not differ significantly. The agreement between self-reported and interviewer classification of skin color in the Bahian group was low. The interviewer classification indicated a gradient of distribution of the GSTM1 null genotype from whites (55.6%) to light mulattos (40.4%), dark mulattos (32.0%) and blacks (28.6%). However, any information about race or ethnicity should be considered with caution regarding the bias introduced by different data collection techniques, specially in countries where racial admixture is intense, and ethnic definition boundaries are loose. Because homozygous deletions of GST gene might be associated with cancer risk, a better understanding of chemical metabolizing gene distribution can contribute to risk assessment of humans exposed to environmental carcinogens.

Ethnicity and glutathione S-transferase (GSTM1/GSTT1) polymorphisms in a Brazilian population

The distribution of polymorphisms related to glutathione S-transferases (GST) has been described in different populations, mainly for white individuals. We evaluated the distribution of GST mu (GSTM1) and theta (GSTT1) genotypes in 594 individuals, by multiplex PCR-based methods, using amplification of the exon 7 of CYP1A1 gene as an internal control. In São Paulo, 233 whites, 87 mulattos, and 137 blacks, all healthy blood-donor volunteers, were tested. In Bahia, where black and mulatto populations are more numerous, 137 subjects were evaluated. The frequency of the GSTM1 null genotype was significantly higher among whites (55.4 percent) than among mulattos (41.4 percent; P = 0.03) and blacks (32.8 percent; P < 0.0001) from São Paulo, or Bahian subjects in general (35.7 percent; P = 0.0003). There was no statistically different distribution among any non-white groups. The distribution of GSTT1 null genotype among groups did not differ significantly. The agreement between self-reported and interviewer classification of skin color in the Bahian group was low. The interviewer classification indicated a gradient of distribution of the GSTM1 null genotype from whites (55.6 percent) to light mulattos (40.4 percent), dark mulattos (32.0 percent) and blacks (28.6 percent). However, any information about race or ethnicity should be considered with caution regarding the bias introduced by different data collection techniques, specially in countries where racial admixture is intense, and ethnic definition boundaries are loose. Because homozygous deletions of GST gene might be associated with cancer risk, a better understanding of chemical metabolizing gene distribution can contribute to risk assessment of humans exposed to environmental carcinogens.

[Molecular biomarkers in cancer: implications for epidemiological research and public health]. / Biomarcadores moleculares em câncer: implicações para a pesquisa epidemiológica e a saúde pública.

Identification of molecular biomarkers is a common result of current cancer epidemiological research. Both genetic and molecular epidemiology have enjoyed impressive developments in recent decades, with important repercussions on traditional epidemiological approaches. In this paper we evaluate the new frontiers of cancer epidemiology, incorporating both genetic and molecular biology approaches. We examine the current knowledge of molecular biomarkers for exposure and susceptibility to cancer, the role of gene mutations in carcinogenesis, and their application to epidemiological studies. By exploring the status of relevant biomarkers, these approaches become effective in evaluating exposure and susceptibility and show enormous potential for elucidating mechanisms of carcinogenesis and the effect of risk factors in cancer. However, these approaches are necessarily more invasive and raise several ethical issues for consideration by both researchers in public health and society as a whole.

Frequency of oral mucosa micronuclei in gas station operators after introducing methanol.

Methanol has been proposed in different countries as an alternative automotive fuel to be used as an additive to, or replacement for, gasoline or ethanol. Utilization of methanol is increasing exposure to low levels of methanol vapors in the environment and more specifically in occupational settings such as gas stations. Pump operators are exposed to relatively high levels of fuel vapors, the consequences of which have not been fully examined. In this study, the micronucleus assay in squamous oral cells was performed on pump operators of 28 gas stations in three different periods in the city of São Paulo, Brazil. The frequency of micronuclei (MN) was evaluated before and 1 year after a mixed fuel called MEG, which contains 33% methanol, 60% ethanol and 7% gasoline, was introduced. The third evaluation, 3 years later, represents a period where the number of cars using alcohol fuel had decreased drastically and the pump operator exposure to MEG became very low. The frequency of MN observed in 76 employees in 1992 (mean = 3.62 +/- 0.39) was significantly increased (P < 0.001) as compared with 76 operators exposed in 1989 (mean = 1.41 +/- 0.26) and 129 exposed in 1995 (mean = 1.20 +/- 0.15). These differences were also significant when compared with control groups not exposed professionally to motor fuel. These findings could indicate a mutagenic hazard of the MEG occurring in those with occupational exposure.

Nervous system cancer mortality in an industrialized area of Brazil 1980-1993.

OBJECTIVES: The industrialization process and nervous system cancer (NSC) mortality in a urban region of Brazil. METHOD: From registries of the State System of Data Analysis Foundation (SEADE), 103 males deaths by NSC (ICD-9) in Baixada Santista (BS), from 1980 to 1993 were selected. Mortality ratios were calculated comparing the standardized mortality rate for ages over 10 years old (G1) and for the age group from 35 to 64 years old, in the industrialized and non-industrialized areas in three periods: 1980-1993, 1980-86, 1987-93. RESULTS: A statiscally significant high mortality was observed in the industrialized area, for ages over 10 in all periods and only from 1980 to 1993 for ages from 34 to 64. The highest mortality ratio occurred from 1980-86 for ages over 10 - 4.12 (CI 1.79-9.42). CONCLUSION: High mortality was probably related to the environmental and occupational exposure to many organic and inorganic chemical substances, considered carcinogenics, such as aliphatic and aromatic hydrocarbons, organochlorinated, formaldehyde, nitrogenated compounds and heavy metals, found in the port and industrial complex. We discuss the importance of case-control studies in characterizing the association of these and other risk factors in the determination of NSC.

Cytochrome P450-2E1 and glutathione S-transferase mu polymorphisms among Caucasians and mulattoes from Brazil.

The variable interindividual ability to metabolize environmental toxicants, also known as metabolic polymorphism, may be of substantial importance in the modulation of cancer risk. The ethnic distribution of these polymorphisms could be interesting in order to establish an association with cancer risk or even to establish selective advantage of some genotypes. Cytochrome P450 2E1 (CYP2E1) is a secondary enzyme that can metabolize ethanol, and glutathione S-transferase (GSTM1) is thought to be involved in the detoxification of epoxides and polycyclic aromatic hydrocarbons. Mutation in these genes was investigated in a random sample of healthy subjects from São Paulo, Brazil, which included 206 Caucasians and 86 mulattoes. Pst I restriction fragment length polymorphism (RFLP) in the 5'-flanking region of the CYP2E1 gene has been identified in 10.2% of Caucasian individuals and in 11.6% of mulattoes. For GSTM1 the frequency of the null genotype was significantly higher in Caucasian individuals (60.2%) than in mulattoes (41.9%). Allele frequencies were (1) CYP2E1 locus: P = 0.949, q = 0.051, se(p) = se(q) = 0.011 among Caucasians; and p = 0.942; q = 0.058; se(P) = se'(q) = 0.018 among mulattoes; and (2) GSTM1 locus: p = 0.224, q = 0.776, se(p) = se(q) = 0.022 among Caucasians; and p = 0.353; q = 0.647; se(p) = se(q) = 0.041 among mulattoes.

HMGIC expression in human adult and fetal tissues and in uterine leiomyomata.

The high-mobility-group (HMG) protein gene, HMGIC, is localized to chromosome 12, band q15, a region often rearranged in benign mesenchymal tumors, including uterine leiomyomata. Although some evidence suggests a role in regulation of cell proliferation, the precise function of HMGIC in the development or progression of these tumors remains unclear. We investigated HMGIC expression in 17 fetal tissues (adrenal, aorta, bone, brain, heart, intestine, kidney, liver, lung, muscle, ovary, placenta, skin, spleen, stomach, testis, and uterus) and 10 adult tissues (aorta, brain, cerebellum, fat, kidney, liver, lung, lymph node, myometrium, and spinal cord) by Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. Comparisons between HMGIC gene expression in tumor samples from 11 uterine leiomyomata and 7 normal matched myometrium or in vitro cell cultures (chorionic villi, placenta, myometrium, leiomyoma, and skin) were also performed. The gene was expressed in all fetal tissues tested but only in adult lung and kidney. HMGIC was also expressed in leiomyoma tumor samples containing t(12;14) and in all in vitro cell cultures. The pattern of HMGIC expression suggests that this gene is important in rapidly proliferating human fetal tissues. Restoration of expression in leiomyomata required dysregulation of HMGIC. Transcripts of HMGIC can also be detected after in vitro cell culture, suggesting that HMGIC expression may be affected by factors present in culture media and serum. Genes Chromosomes Cancer 25:316-322, 1999.

Chromosomal aberrations in peripheral lymphocytes of abstinent alcoholics.

The frequency of structural and/or numerical chromosomal aberrations in human metaphasic cells of lymphocyte cultures from abstinent alcoholics who were abstinent for 1 month up to 32 years was compared with those from controls not selected for alcohol consumption. Cytogenetic analyses revealed a significant increase of the frequencies of cells with structural aberrations in the abstinent alcoholics (7.1%), compared with controls (2.4%). The frequency of numerical aberrations showed a significant regression on ages in abstinent alcoholics and controls. These results suggest specific action of chronic alcohol consumption impairing biological repair with aging. The increased frequency of chromosome-type aberrations associated with alcohol consumption, even after long withdrawal, could be due to an action of ethanol or its metabolites on primordial leukopoietic cells.

Utilization of citogenetic technics in paternity investigation

Th joint analysis of several genetic markers in casesof paternity investigation renders possible a cumulative probability of 99.7% of change of esclusion of a flasely accused father. The role of heteromorphism of the Y chromosome size was appraised in this work, with more than one genetic marker, in 20 expertise examinations in paternity investigation, where the children were male. The results found with found with this method, in association with the research on erythrocytic and leucocytic antigens showed the exclusion of two falsely accused men. Cytogenetic analysis with Giemsa stain in combination with leukocyte (HLA system) and erithrocyte antigens investigation demonstrated the exclusion of two men falsely accused

Utilization of cytogenetic technics in paternity investigation.

The joint analysis of several genetic markers in cases of paternity investigation renders possible a cumulative probability of 99.7% of chance of exclusion of a falsely accused father. The role of heteromorphisms of the Y chromosome size was appraised in this work, with more than one genetic marker, in 20 expertise examinations in paternity investigation, where the children were male. The results found with this method, in association with the research on erythrocytic and leucocytic antigens showed the exclusion of two falsely accused men. Cytogenetics analysis with Giemsa stain in combination with leukocyte (HLA system) and erythrocyte antigens investigation demonstrated the exclusion of two men falsely accused.

[Sex determination in blood stains through identification of Y-chromatin: medico-legal application]. / Diagnóstico do sexo em crostas de sangue através da identificação da cromatina Y: aplicação médico-legal.

The Y-chromatin is visualized in human interphase nuclei, corresponding to the distal portion of the Y-chromosome, which shows marked fluorescence after staining with quinacrine. This report describes the results of sex determination on blood smears fixed in methanol and blood stains left at room temperature for 13 weeks (1st report), and for 10 months (2nd report). Blind trials showed that a reliable sex determination of blood stains on glass left for at least six months is possible. The application of this method in forensic practice is discussed.