Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genetic Determinism”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1982

The effect of a saccharose-rich diet on carbohydrate and lipid metabolism of streptozotocin-diabetic rats and genetically determined 'diabetic' mice (gg-diab).

Streptocotocin-diabetic rats were fed with a saccharose-rich diet (68 per cent saccharose) for 37 weeks. Serum levels of insulin, triglycerides, and cholesterol were determined thereafter as well as the lesions of kidneys by histologically evaluation. For the second series of experiments, genetically determined diabetic mice (transient hyperglycemia, low k-value, but no glucosuria), were fed with the saccharose-rich diet for eight weeks. Thereafter the serum levels of insulin, triglycerides, and cholesterol were determined as well as secretion and biosynthesis of insulin of isolated pancreatic mouse islets. The metabolic parameters and the determination of the kidney lesions revealed that saccharose-feeding deteriorates the diabetic state of streptocotocin-diabetic rats: the levels of serum glucose, urine volume and urinary glucose rose rapidly in the saccharose-fed diabetic rats. These animals showed significantly higher levels of triglycerides and cholesterol after 18 and 37 weeks compared with diabetic rats fed a control diet (68 per cent starch). The kidney lesions became still more severely expressed by saccharose-rich diet. On the other hand, no major differences in the serum parameters of saccharose- or starch-fed genetically determined mice could be noticed: no manifestation of diabetes could be provoked in these latent-diabetic mice.

Animals↗
PubMed1992

Relation between chloroguanide bioactivation to cycloguanil and the genetically determined metabolism of mephenytoin in humans.

It has been suggested recently that the bioactivation of chloroguanide hydrochloride (proguanil) to its active antimalarial metabolite cycloguanil cosegregates with the genetically determined polymorphism of mephenytoin hydroxylation. We determined the chloroguanide to cycloguanil ratio in urine after oral administration of a single dose of 200 mg proguanil either alone or together with 100 mg racemic mephenytoin or 40 mg dextromethorphan in a randomized crossover study performed in 24 healthy subjects. The mephenytoin hydroxylation index was also determined after administration of 100 mg racemic mephenytoin either alone or together with 200 mg proguanil. Two subjects were poor metabolizers and one subject was an intermediate metabolizer of mephenytoin. These three subjects had chloroguanide to cycloguanil ratios of more than 50. The 21 subjects with the extensive metabolizer phenotype for mephenytoin hydroxylation had chloroguanide to cycloguanil ratios of less than 10. The chloroguanide to cycloguanil ratio was not significantly altered by mephenytoin or dextromethorphan coadministration. The trend toward a correlation between chloroguanide/cycloguanil ratio and log mephenytoin hydroxylation index did not reach statistical significance. Inclusion of the dextromethorphan metabolic ratio into the model did not improve the relationship. These findings confirm that the bioactivation of chloroguanide to cycloguanil cosegregates with the genetically determined activity of the CYP2C family. However, the chloroguanide to cycloguanil ratio and the mephenytoin hydroxylation index do not similarly reflect the variable activity of CYP2C.

Adult↗
PubMed1986

Analysis of the genetic determinants coding for the S-fimbrial adhesin (sfa) in different Escherichia coli strains causing meningitis or urinary tract infections.

Recently we have described the molecular cloning of the genetic determinant coding for the S-fimbrial adhesin (Sfa), a sialic acid-recognizing pilus frequently found among extraintestinal Escherichia coli isolates. Fimbriae from the resulting Sfa+ E. coli K-12 clone were isolated, and an Sfa-specific antiserum was prepared. Western blots indicate that S fimbriae isolated from different uropathogenic and meningitis-associated E. coli strains, including O83:K1 isolates, were serologically related. The Sfa-specific antibodies did not cross-react with P fimbriae, but did cross-react with F1C fimbriae. Furthermore the sfa+ recombinant DNAs and some cloned sfa-flanking regions were used as probes in Southern experiments. Chromosomal DNAs isolated from O18:K1 and O83:K1 meningitis strains with and without S fimbriae and from uropathogenic O6:K+ strains were hybridized against these sfa-specific probes. Only one copy of the sfa determinant was identified on the chromosome of these strains. No sfa-specific sequences were observed on the chromosome of E. coli K-12 strains and an O7:K1 isolate. With the exception of small alterations in the sfa-coding region the genetic determinants for S fimbriae were identical in uropathogenic O6:K+ and meningitis O18:K1 and O83:K1 strains. The sfa determinant was also detected on the chromosome of K1 isolates with an Sfa-negative phenotype, and specific cross-hybridization signals were visible after blotting against F1C-specific DNA. In addition homology among the different strains was observed in the sfa-flanking regions.

Adhesins, Escherichia coli↗
PubMed1982

Transduction of the genetic determinant for streptolysin S in group A streptococci.

The genetic determinant for streptolysin S production (SLS+) was successfully transduced to two naturally occurring nonhemolytic strains of group A streptococci (Streptococcus pyogenes), an M-type 18 strain associated with an outbreak of rheumatic fever and an M-negative variant of a type 49 strain isolated from a skin lesion. Attempts to transduce this determinant to a nonhemolytic M-type 68 strain and a nonhemolytic T-type 12 strain were not successful. Transduction was accomplished with a double temperature-sensitive mutant bacteriophage. Cellular antigenic characters and the phage sensitivity of the transductants remained unaltered. The donor strain also transduced streptomycin resistance well when the nonhemolytic type 49 strain was used as a recipient. There was no evidence of cotransduction of the determinants for streptolysin S and streptomycin resistance.

Antigens, Bacterial↗
PubMed1992

Genetically determined differences in drug metabolism as a risk factor in drug toxicity.

Drug metabolizing enzymes are of paramount importance in drug detoxification as well as chemical mutagenesis, carcinogenesis and toxicity via metabolic activation. Thus genetically determined differences in the activity of these enzymes can influence individual susceptibility to adverse drug reactions, drug induced diseases and certain types of chemically induced cancers. The genetic polymorphisms of three human drug metabolizing enzymes, namely N-acetyltransferase and two cytochrome P-450 isozymes (P-4502D6: debrisoquine/sparteine polymorphism, P-4502C8-10: mephenytoin polymorphism) have been firmly established. Based on the metabolic handling of certain probe drugs, the population can be divided into two phenotypes: the rapid acetylator/extensive metabolizer and slow acetylator/poor metabolizer. These polymorphisms have provided useful tools to study the relationship between genetically determined differences in the activity of drug metabolizing enzymes and the risk for adverse drug reactions and certain types of chemically-induced diseases and cancers. With regard to the susceptibility of the two phenotypes, drug mediated toxicity for the following scenarios can be anticipated. (1) The toxicity of the drug is caused by the parent compound and the elimination of the drug proceeds exclusively via the polymorphic enzyme. No alternate pathways of biotransformation are available. Thus the slow acetylator/poor metabolizer phenotype will be more prone to such a type of toxicity since, at the same level of exposure, this phenotype will accumulate the drug as a result of impaired metabolism (e.g. isoniazid polyneuropathy, perhexiline polyneuropathy, pesticide induced Parkinsons disease). (2) The polymorphic pathway is a major route of detoxification. Impairment of this pathway shifts the metabolism to an alternate pathway via which a reactive intermediate is being formed. In such a situation the slow acetylator/poor metabolizer phenotype constitutes a major risk factor for toxicity (e.g. isoniazid hepatotoxicity). (3) The toxicity is mediated by a reactive intermediate generated by a polymorphic enzyme. Hence extensive metabolizers are at a much higher risk than poor metabolizers to develop toxicity or cancer (e.g. bronchial carcinoma in smokers, not chemically induced aggressive bladder cancer).

Animals↗
PubMed1983

Mutagenesis of extrachromosomal genetic determinants for exfoliative toxin B and bacteriocin R1 synthesis in Staphylococcus aureus after plasmid transfer by protoplast fusion.

In previous studies, we have shown that a 27-megadalton plasmid (pRW002) in Staphylococcus aureus contains genetic determinants for exfoliative toxin B (ET B) and bacteriocin (Bac R1) synthesis and Bac R1 resistance. Attempts to transform or transduce this plasmid to S. aureus or Bacillus subtilis recipients were not successful. However, genetic transfer of the plasmid was possible after polyethylene glycol-induced fusion of S. aureus protoplasts containing pRW002 and S. aureus protoplasts lacking this plasmid. Some of the resulting fusants lost the ability to make ET B, Bac R1, or both products. Fusants that were Bac R1-, Bac R1s, ET B- all lacked the 27-megadalton pRW002 plasmid. The largest class of fusants was Bac R1+, Bac R1r, ET B-. Immunodiffusion analyses of ET B extracts from 28 fusants showed that four ET B+ strains were cross-reacting mutants that produced ET B protein that was serologically related to, but not identical to, the wild-type toxin. Results indicated that genetic transfer of pRW002 after protoplast fusion induced molecular rearrangements that resulted in mutation of the genetic determinants for ET B and Bac R1 synthesis. Recombination of chromosomal genes was enhanced after CaCl2 was added to the protoplast-fusion mixture.

Bacterial Toxins↗
PubMed2006

Pathology and genetics of multiple system atrophy: an approach to determining genetic susceptibility spectrum.

Recent advances in the molecular pathology and genetics of multiple system atrophy (MSA) indicate that the disease involves plural pathogenic mechanisms. The determination of the morphological spectrum of MSA using quantitative pathological analysis points to the need for further investigation to determine the population-bound phenotype distribution of MSA. These notions support the hypothesis that a spectrum of genetic susceptibility factors underlies MSA pathogenesis. A possibly effective strategy for determining this genetic susceptibility spectrum is to perform an association study of important genes for neurodegenerative diseases, which are prevalent in a population, using linkage disequilibrium mapping in MSA patients with well-characterized morphological phenotypes.

Genetic Predisposition to Disease↗
PubMed2006

Genetic determinants of carotid ultrasound traits.

Atherosclerosis is a complex disease with various intermediate phenotypes that are themselves complex and influenced by many factors. Through the use of carotid ultrasound techniques, the intermediate stages of vascular disease can be imaged and studied for association with potential genetic determinants. In this article we review the most recent available data (reports published since 2004) on the genetic determinants of atherosclerosis, as measured by one-, two-, and three-dimensional ultrasonography of the carotid arteries. In general, associations are disparate and modest. For intima-media thickness, promising associations have been found for both TNFRSF1A R92Q and PPARG P12A, but associations also differed in the same individuals depending on the specific ultrasound trait studied (eg, linear intima-media thickness versus total plaque volume in carotid arteries). Some of the challenging issues for future studies include accounting for gene-environment interactions, sex-specific associations, and the distinctiveness of different carotid ultrasound measures.

Carotid Artery Diseases↗
PubMed1998

Genetic determinants of Pseudomonas aeruginosa colonization in cystic fibrosis patients in Canada.

The present study was aimed at analyzing whether the rate of colonization and the age at colonization with Pseudomonas aeruginosa was genetically determined in cystic fibrosis (CF) patients. These two variables were calculated among 127 CF patients whose genotypes were known and who were monitored at the Clinique de Fibrose Kystique in Saguenay Lac-Saint-Jean. No statistically significant differences were found in the rate or the age at colonization when the patients were grouped by genotype; however, this result could be due to the small number of patients in each genotype group. The rate of colonization was significantly lower among CF patients carrying the A455E mutation, a "mild" allele with respect to exocrine pancreatic function, than among those carrying either the deltaF508 or the 621 + IG- > T mutation, both of which are "severe" alleles. The results confirm previous reports that the rate of colonization with Pseudomonas aeruginosa is, at least in part, genetically determined.

Adolescent↗
PubMed2005

Genetically determined resistance to lethal levels of copper by Daphnia longispina: association with sublethal response and multiple/coresistance.

The development of resistance to toxicants has been reported for a wide range of organisms. Two questions were addressed in the present study: Are genetically determined resistance responses at lethal levels (min to h) of copper associated with responses at extreme lethal (h to d) and sublethal levels and does genetically determined resistance to lethal levels of copper confer resistance to lethal levels of other chemicals? Twelve cloned lineages of Daphnia longispina, differing in their resistance to copper, were exposed to sublethal concentrations of copper and to lethal concentrations of copper, zinc, cadmium, hydrogen ions, and a pyrethroid insecticide (deltamethrin). Three kinds of toxicity assays were carried out: Survival time (death occurs in min to h; only for metals and hydrogen ions), cumulative mortality (death occurs in h to d; for all tested chemicals), and feeding depression assays (only for copper). A correlation between different levels of toxicity was observed only for extreme and moderate lethal responses to copper, and no correlation was found between lethal and sublethal levels of copper. Multiple resistance to lethal levels of toxicants was observed only for the pair copper/zinc.

Animals↗
PubMed2004

Mapping of genetic determinants of the sympathoneural response to stress.

Activation of the sympathoadrenal system (SAS, comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defense mechanism as well as a contributor to several cardiovascular diseases. There is variability in the SAS response to stress, although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hypertriglyceridemic (hHTg) rat, are hyperresponsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats (n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma norepinephrine (NE) and epinephrine (Epi) levels, indices of activation of the sympathoneural and adrenal medulla components, respectively, measured in the resting state and in response to an immobilization stress. Responses were assessed early (20 min) and late (120 min) after the application of the stress. A genome scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak LOD scores of 4.17 and 3.52, respectively) influencing both the early and late plasma NE response to stress were found on chromosome 10. Together, the QTLs accounted for approximately 20% of the total variation in both the early and late NE responses in the F(2) rats. Interestingly, the QTLs had no effect on plasma Epi response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the SAS response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases.

Animals↗
PubMed1986

Congenital scoliosis in monozygotic twins. Genetically determined or acquired in utero?

The term "congenital scoliosis" contributes little to our understanding of aetiology, for "congenital" simply means "to be born with" and is applicable to deformities present at birth whether these are genetically determined or acquired in utero. The presentation of monozygotic twins, one of whom has congenital scoliosis (vertebral anomalies) while the other is normal, provides a rare opportunity to study the cause of this deformity. Three pairs of monozygotic twins, previously unreported, are presented with a review of the previous literature. These cases add weight to the argument that congenital scoliosis may be acquired in utero rather than being genetically determined.

Adolescent↗
PubMed1998

Genetically determined neuropathies.

There have been major advances in the understanding of the genetically determined neuropathies in recent years. The underlying genetic defects are now known for many of the demyelinating hereditary motor and sensory neuropathies, and linkage data are available for some of the axonal hereditary motor and sensory neuropathies. This has important implications for both diagnosis and genetic counselling in this group of conditions. The genetic defect in most cases of familial amyloid polyneuropathy is also now known. In the most common form of familial amyloid polyneuropathy (FAP), transthyretin-related FAP, liver transplantation has been established as the first definitive treatment for a hereditary neuropathy and should be considered especially in young adult patients. This review will concentrate on the advances in the molecular genetics of the hereditary motor and sensory neuropathies, the hereditary sensory and autonomic neuropathies and the familial amyloid polyneuropathies with particular emphasis on the difficulties in classifying the first group.

Adult↗
PubMed2005

Effects of psycho-social stress during pregnancy on neuroendocrine and behavioural parameters in lactation depend on the genetically determined stress vulnerability.

The neuroendocrine consequences of repeated exposure of the pregnant mother to relevant stressors have been studied in the offspring, but not in the mothers. As these stress effects might depend on the genetically determined stress susceptibility of the dams, here, we investigated the effects of daily exposure to psycho-social stressors (maternal defeat by an aggressive lactating resident and restraint) between pregnancy days 4 and 18 in female rats selectively and bidirectionally bred for high (HAB) or low (LAB) anxiety-related behaviour. ACTH and corticosterone secretory responses to a mild stressor were found to be low in unstressed lactating HAB and LAB dams (day 8 of lactation) indicating an intact physiological attenuation of the HPA axis at this time. Pregnancy stress significantly increased the reactivity of the hypothalamo-pituitary-adrenal (HPA) axis in lactating HAB, but not LAB rats, reflecting impaired attenuation of the HPA axis selectively in pregnancy-stressed HAB dams. The high and low anxiety phenotypes were consistent in lactation and not significantly altered by pregnancy stress, despite an elevated level of arousal in pregnancy-stressed HAB dams. In general, HAB dams showed signs of a more protective maternal behaviour compared to LAB dams: (i) in the home cage, HAB dams spent more time in direct pup contact (day 1 of lactation), (ii) during two forms of the pup retrieval test, differing in the level of challenging the dam, HAB dams retrieved the pups faster, and (iii) during the maternal defence test, they were more aggressive towards a virgin intruder compared to LAB and NAB dams. Pregnancy stress did not alter any of these behavioural measures, except an increase in the speed of pup collection in a novel environment in HAB dams and increased maternal aggression in LAB dams. The results indicate a robust behavioural phenotype of HAB and LAB dams with respect to anxiety and maternal behaviour which was found to be almost unchanged by exposure to pregnancy stress. However, the finding of differential effects of pregnancy stress on the attenuation of the reactivity of the HPA axis in lactation makes HAB and LAB rats a potential animal model for studying genetically determined differences in stress vulnerability and stress-induced maladaptation of the HPA axis post-partum.

Adaptation, Physiological↗
PubMed1987

[Genetic determinants of antibiotic resistance in enterobacteria].

Antibiotic resistance of enterobacterial strains from population isolated in Krasnodar region is rather often controlled by the "plasmid" genes. The conclusion is based on using the colony hybridization with [32P]-DNA fragments of plasmids, carrying the genetic determinants of antibiotic resistance, as a method for antibiotic resistance, genes screening. Kanamycin resistance in the majority of strains is coded by APH (3') II gene, streptomycin resistance by APH (3") gene, chloramphenicol resistance by CATI, sulphonilamide resistance by DHPS type II gene. Tetracycline resistance of the studied enterobacterial strains is not connected with the widespread genetic determinants of a new class tetracycline resistance.

Drug Resistance, Microbial↗
PubMed1999

Genetic determination of variation and covariation of peak bone mass at the hip and spine.

The likelihood of low trauma fracture in the elderly is highly predictable by peak bone mass (PBM) at age approximately 25-50 yr. We estimated the magnitude of genetic determination of the variation and covariation of PBM of the spine and hip (adjusted by age, gender, and ethnicity) in 47 independent healthy full-sib pairs and 27 healthy mother-offspring pairs. For the spine and hip, the narrow-sense heritabilities (h(2)) (mean +/- SE) were 0.76 +/- 0.34 and 0.84 +/- 0.36, respectively, when estimated from full sibs, and 0.86 +/- 0.38 and 0.84 +/- 0.39, respectively, when estimated from parent-offspring. Some genetic loci underlying PBM variation at the hip and spine are the same or closely linked, as is reflected by the high genetic correlation of 0.95 +/- 0.05 between them when estimated from full sibs, and 0.57 +/- 0.27 when estimated from parent-offspring, respectively. Generally, common familial environmental effects shared by relatives may bias these estimates. However, these effects may be small, since our results reported herein and those in other earlier studies indicate that common familial environmental effects are probably negligible in causing similarity of bone mass among family members. The correlation of bone mass among randomly sampled couples living in the same household is small and nonsignificant as measured either by densitometry at the radius and ulna or by quantitative ultrasound at the patella. The problem of shared environmental effects notwithstanding, we conclude that much of the PBM variation and covariation at the hip and spine is determined genetically.

Absorptiometry, Photon↗
PubMed1991

[Genetic determination of rheumatoid arthritis].

The study on the nature of genetic determination of the definite rheumatoid arthritis (RA) and its forms was carried out, based on the material comprising clinical data on 189 probands and their 1st and 2nd degree relatives (713 subjects) which is contained in the computer Family Data Bank at the Department of Epidemiology and Genetics of this institute. The heritability coefficient "in narrow sense" (80%) obtained within the framework of the multifactorial threshold model confirmed once more important role of genetic factors in the appearance of the disease. The study of genetic heterogeneity within the framework of the Ch. Smith's and T. Reich's models failed to reveal any independent genetically RA forms. An assumption of the essential role of the genes localized in the X chromosome, based on diverse susceptibility of sexes, received no conformation. It has been shown that the RA distribution in the population and families may well be described by means of a variant of the single autosomal two-allele locus model with incomplete and differentiated for two sexes penetrance. The model parameters obtained, a particular penetrance of the mutant homozygote in both sexes equalling 100%, and penetrance of the normal homozygote equalling 0 in men and reaching 0 (0.028%) in women testify to a very essential influence of the major gene on determination of RA.

Arthritis, Rheumatoid↗