RESUMO
Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele-specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.
Assuntos
Neoplasias Colorretais/genética , Fator de Crescimento Epidérmico/genética , Predisposição Genética para Doença , Polimorfismo Genético , Fator A de Crescimento do Endotélio Vascular/genética , Alelos , Povo Asiático , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Frequência do Gene , Genótipo , Humanos , Malásia/epidemiologia , Razão de ChancesRESUMO
Colorectal cancer (CRC) is one of the most common types of cancer in both developed and developing countries. This disease is triggered by and progresses via the sequential accumulation of multiple genetic alterations. In addition, the interaction between low-penetrance genes and environmental factors can also increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are one of the predisposing factors for CRC, IBD-related genes might, to a certain extent, be associated with cancer initiation. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most well-established gene to be associated with increased susceptibility to Crohn's disease. Thus, various studies have been performed to investigate the potential contribution of this gene to CRC risk. In this study, we aimed to determine the frequency of the Arg702Trp, Gly908Arg, 3020insC, Pro268Ser, and JW1 variants of NOD2/CARD15, and to investigate their association with CRC susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this study. Subsequently, real-time polymerase chain reaction with TaqMan was performed for the genotyping of these NOD2/ CARD15 variants. None of the NOD2/CARD15 variants was statistically associated to CRC susceptibility in our Malaysian population. Our findings were remarkably similar to those of other Asian cohorts, which indicated that these NOD2/CARD15 variants exhibit genetic heterogeneity between Caucasian and Asian populations.
Assuntos
Povo Asiático/genética , Neoplasias Colorretais/genética , Variação Genética , Proteína Adaptadora de Sinalização NOD2/genética , Alelos , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Heterogeneidade Genética , Predisposição Genética para Doença , Genótipo , Humanos , Malásia , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Mutations in the PAX6 gene that cause aniridia have been identified in various ethnicities but not in the Malaysian population. Therefore, the objective of this study was to investigate the PAX6 mutation in a Malaysian family with congenital aniridia. In this study, a complete ophthalmic examination was performed on a Dusun ethnic family with aniridia. Genomic DNA was extracted from the peripheral blood of the subjects and screened for the PAX6 gene mutation using polymerase chain reaction amplification high-resolution melting curve analysis (PCR-HRM) followed by confirmation via direct DNA sequencing. A heterozygous G deletion (c.857delG) in exon 7 causing a frame shift in PAX6 was identified in all affected family members. Genotype-phenotype correlation analysis revealed congenital cataract and all affected family members showed a similar spectrum of aniridia with no phenotypic variability but with differences in severity that were age-dependent. In summary, by using a PCR-HRM approach, this study is the first to report a PAX6 mutation in a Malaysian family. This mutation is the cause of the aniridia spectra observed in this family and of congenital cataract.
Assuntos
Aniridia/genética , Proteínas do Olho/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Polimorfismo Conformacional de Fita Simples/genética , Proteínas Repressoras/genética , Aniridia/patologia , Povo Asiático/genética , Feminino , Estudos de Associação Genética , Humanos , Malásia , Masculino , Mutação , Desnaturação de Ácido Nucleico , Fator de Transcrição PAX6 , LinhagemRESUMO
Allele frequencies of 15 short tandem repeat (STR) loci, namely D5S818, D7S820, D13S317, D16S539, TH01, TPOX, Penta D, Penta E, D3S1358, D8S1179, D18S51, D21S11, CSF1PO, vWA, and FGA, were determined for 154 individuals from the Kadazan-Dusun tribe, an indigenous population of East Malaysia. All loci were amplified by polymerase chain reaction, using the Powerplex 16 system. Alleles were typed using a gene analyzer and the Genemapper ID software. Various statistical parameters were calculated and the combined power of discrimination for the 15 loci in the population was calculated as 0.999999999999999. These loci are thus, informative and can be used effectively in forensic and genetic studies of this indigenous population.
Assuntos
Frequência do Gene/genética , Repetições de Microssatélites , Alelos , Loci Gênicos , Genética Populacional , Humanos , Malásia/etnologia , Reação em Cadeia da PolimeraseRESUMO
We report on the first evidence of intra-community coalitionary lethal aggression in muriquis (Brachyteles). The event occurred in southern muriquis (Brachyteles arachnoides) during a long-term study (>15 years) of two social groups inhabiting mostly pristine Atlantic forest habitat in the Parque Estadual Carlos Botelho, southern São Paulo State, Brazil. The attack took place deep in the core area of the Group Caetê home range. Tense agonistic behaviors and vocalizations preceded the lethal coalitionary attack, and the tension increased over a 36-48 hr period. One adult female and two unidentified individuals also took part in a coalition led by six adult males. The members of the coalition collectively approached, embraced, immobilized and repeatedly bit the entire body of an adult male, resulting in severe bleeding injuries and the victim's death in less than 1 hr after the attack commenced. Combined ecological, behavioral and spatial data related to the event indicate that this was an intra-community attack and suggest social tensions related to mating competition as the proximate trigger of the coalitionary killing. The attack resembled those reported for chimpanzees, with clear numeric superiority and a low risk of injury to aggressors, resulting in the death of a lone conspecific victim. This observation (n=1) is suggestive of a capacity for escalated aggression in muriquis and reinforces arguments for the potential adaptive significance of intra-community aggression in male philopatric societies, as reported for spider monkeys and chimpanzees. These characteristics challenge the view of the muriquis as a peaceful primate and support the general hypothesis that imbalances of power contribute to intra-specific killing in primates, such as chimpanzees and humans.
Assuntos
Comportamento Agonístico/fisiologia , Atelinae/fisiologia , Comportamento Animal/fisiologia , Comportamento Cooperativo , Agressão , Animais , Brasil , Ecossistema , Feminino , Masculino , Predomínio Social , ÁrvoresRESUMO
Wild capuchin monkeys inhabiting dry forest were found to customarily use tools as part of their extractive foraging techniques. Tools consisted of twigs and sticks, often modified, which were used to probe for insects and, most frequently, of stones of a variety of sizes and shapes used for cracking and digging. The use of tools for digging has been thought to be restricted to humans. These monkeys, living in a harsh dry habitat, survive food limitation and foraging time constraints through their extensive tool use.
Assuntos
Comportamento Animal , Cebus/psicologia , Comportamento Alimentar , Alimentos , Animais , Comportamento Apetitivo , Brasil , Meio Ambiente , ÁrvoresRESUMO
The reliability of using the oblique cephalometric radiograph for early prediction of the mesiodistal widths of unerupted lower canines and premolars was investigated. Mandibular models and oblique cephalometric radiographs were obtained for 40 Brazilian children (20 boys and 20 girls), in the mixed dentition phase. Further models were obtained for the same sample when all permanent teeth had erupted. A Student t test showed statistically significant differences of tooth size between the sexes but not between right and left sides. Measurements of the unerupted canines and premolars taken from the 45 degrees cephalometric radiograph were statistically greater than the actual values, although a high correlation was observed between them. Linear regression equations and correction tables were established to compensate for this magnification. The actual values for these teeth were compared with the corrected predicted values from the 45 degrees radiograph and with the predicted values obtained from the methods of Ballard and Wylie, Carey, Moyers, and Tanaka and Johnston. A high correlation was observed only between the actual values and the corrected predicted values from the radiograph. The results indicate that, correcting the magnification, the 45 degrees cephalometric radiographic may be used in predicting unerupted lower canine and premolar widths in Brazilian children.
Assuntos
Dente Pré-Molar/diagnóstico por imagem , Cefalometria/métodos , Dente Canino/diagnóstico por imagem , Dente não Erupcionado/diagnóstico por imagem , Dente Pré-Molar/anatomia & histologia , Brasil , Criança , Dente Canino/anatomia & histologia , Dentição Mista , Feminino , Previsões , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Mandíbula , Odontometria , Ampliação Radiográfica , Reprodutibilidade dos Testes , Fatores Sexuais , Erupção DentáriaRESUMO
The interaction between malnutrition and exposure to a mucosal damaging agent, difluoromethylornithine (DFMO), was examined by monitoring the small-intestinal changes in weanling rats. Malnutrition as induced by the expanded-litter method resulted in severe reduction in body weights in the expanded litters as compared to normal litters. Subsequent treatment of malnourished and well-nourished pups with DFMO for 7 days resulted in decreases in small-intestinal weights and enzyme contents. A 2 factors (well-nourished and malnourished) by 2 factors (DFMO-treated and nontreated) analysis of variance showed no interaction between malnutrition and DFMO treatment in terms of food intake, total mucosal protein, and contents of enterokinase, leucine aminopeptidase and sucrase. Very slight and insignificant interactions (p less than or equal to 0.2) were found for body weights, intestinal weights and total DNA content. Only one parameter studied, the maltase content, showed significant interaction between malnutrition and DFMO treatment (p less than 0.05). Three weeks after the withdrawal of DFMO, essentially all the changes caused by DFMO recovered. But those changes caused by malnutrition did not, such that the malnourished group, whether treated with DFMO or not, still remained significantly less than the control group in their small-intestinal parameters. Analysis of variance showed no interaction between malnutrition and DFMO treatment in the recovery phase. The results suggest that malnutrition is a more important factor in determining the intestinal damage and that malnutrition in the immediate postnatal period does not increase the sensitivity of the small intestine to the damaging effect of DFMO.
Assuntos
Eflornitina/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Distúrbios Nutricionais/complicações , Animais , Animais Lactentes , Divisão Celular/efeitos dos fármacos , Feminino , Glicosídeo Hidrolases/metabolismo , Mucosa Intestinal/enzimologia , Mucosa Intestinal/patologia , Leucil Aminopeptidase/metabolismo , Masculino , Distúrbios Nutricionais/enzimologia , Fosfotransferases/metabolismo , Ratos , Ratos EndogâmicosRESUMO
We evaluated the in vitro and in vivo digestibility and clinical tolerance of three corn syrup sugars (DE10, 15, 24) and one infant formula containing corn syrup sugar as the sole carbohydrate source (DE24). In vitro studies were conducted using human duodenal fluid and jejunal mucosa with normal enzyme activities. In vivo studies included intragastric perfusion studies and tolerance tests using the corn syrup sugars and a clinical formula trial in 32 infants with acute diarrhea. Results of the in vitro studies showed that each of the corn syrup sugars was well hydrolyzed by duodenal fluid and by mixtures of duodenal fluids and mucosal homogenates. Similarly, in vivo studies revealed significant hydrolysis in the proximal intestine, as measured during the perfusion studies, and adequate absorption, as indicated by a rise in serum glucose concentration during tolerance tests. Only patients who had a marginal serum glucose rise after a glucose meal had a blunted rise after a corn syrup feeding. More than 85% of the infants beginning the clinical trial tolerated the formula well and gained weight at or above the expected rate for age during the study interval. These data indicate that, except with severe mucosal injury and secondary monosaccharide intolerance, glucose polymers of the dextrose equivalents tested are suitable carbohydrate sources for infants recovering from acute diarrhea.
Assuntos
Diarreia Infantil/metabolismo , Carboidratos da Dieta/metabolismo , Digestão , Ensaios Clínicos como Assunto , Duodeno/metabolismo , Humanos , Hidrólise , Lactente , Alimentos Infantis/efeitos adversos , Absorção Intestinal , Secreções Intestinais/metabolismo , Jejuno/metabolismo , Zea maysRESUMO
We have described the developmental pattern of the gastrointestinal tract under optimal conditions (i.e., low risk pregnancy and normal labor and delivery at term). The tissues do not develop simultaneously, and morphologic and functional development are not concurrent. An important consideration is the effect of suboptimal or even adverse conditions on the developmental sequence and attainment of maturity. Malnutrition during both the prenatal and postnatal periods may restrict the morphologic and biochemical development of the gastrointestinal tract. Dietary modifications have been shown to alter the developmental pattern of intestinal and pancreatic enzymes in animal models. Drugs and hormonal therapy given during pregnancy and early infancy have been known to cause developmental defects, but the specific effects on the gastrointestinal tract have not been evaluated. For further understanding of digestibility of nutrients and absorption in the perinatal period, these departures from the normal development of the gastrointestinal tract and the mechanisms by which these potential effects occur remain to be described. In view of these undetermined factors, in the case of intolerance or unavailability of milk from the natural mother, feedings should be individualized, with attention to direct measurement of enzyme concentrations, balance studies, or both, especially in the case of extreme prematurity or unusual requirements.
Assuntos
Sistema Digestório/crescimento & desenvolvimento , Cuidado do Lactente , Recém-Nascido , Carboidratos da Dieta/metabolismo , Gorduras na Dieta/metabolismo , Proteínas Alimentares/metabolismo , Digestão , Glucana 1,4-alfa-Glucosidase/metabolismo , Humanos , Alimentos Infantis , Recém-Nascido Prematuro , Absorção Intestinal , Lipase/metabolismo , Concentração Osmolar , Sacarase/metabolismo , Equilíbrio Hidroeletrolítico , alfa-Amilases/metabolismo , beta-Galactosidase/metabolismoRESUMO
The development of glucoamylase activity was compared to that of disaccharidase in the small intestinal mucosa of infants and children. By the age of one month, infants have glucoamylase and disaccharidase levels comparable to those of young adults, indicating that young infants may be able to digest and absorb starches. In infants and children with varying degrees of mucosal injury of the small intestine, the activities of glucoamylase decreased progressively with increasing severity of the villus atrophy. However, the reduction of lactase, palatinase, and sucrase activities was more severe than the loss of activities of glucoamylase and maltase. Thus, children and infants may tolerate polymers of glucose better than disaccharides when they have mucosal injury associated with prolonged diarrhea.