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At least 973 records · Page 54Linked to original sources
PubMed1960

Genetic studies of influenza viruses. I. Viral morphology and growth capacity as exchangeable genetic traits. Rapid in ovo adaptation of early passage Asian strain isolates by combination with PR8.

The passage of newly isolated, filamentous Asian (A2) influenza viruses in the presence of non-infective PR8 (A) virus results in the rapid emergence of virus of Asian (A2) antigenicity but PRS-like growth capacity and spherical morphology. Evidence is presented that this effect results from genetic interaction of the infective Asian and non-infective PR8 viruses rather than from spontaneous change of the Asian strain. It is concluded that influenza viral morphology, growth rate and growth capacity are associated genetic traits which distinguish unadapted from adapted strains, and which are transferable by recombination. A pragmatic consequence of these experiments is the fact that conditions have been defined for the rapid adaptation of early passage influenza virus isolates to the chick embryo allantoic sac. Such adaptation is attended by an increase in viral yield which has obvious implications for vaccine production during future epidemics with new antigenic types.

Animals↗
PubMed2004

Reconstructing pathways in large genetic networks from genetic perturbations.

I present an algorithm that determines the longest path between every gene pair in an arbitrarily large genetic network from large scale gene perturbation data. The algorithm's computational complexity is O(nk(2)), where n is the number of genes in the network and k is the average number of genes affected by a genetic perturbation. The algorithm is able to distinguish a large fraction of direct regulatory interactions from indirect interactions, even if the accuracy of its input data is substantially compromised.

Algorithms↗
PubMed1996

The genetic and non-genetic toxicity of the fungicide Vinclozolin.

The mutagenic/cocarcinogenic potential of the fungicide Vinclozolin was assessed by a comprehensive examination of toxicity mechanisms at both the genetic and the metabolic level. Vinclozolin did not induce any significant increase in chromosomal aberrations in human pheripheral blood lymphocytes cultured in vitro, both in the presence and in the absence of metabolic activation. However, significant dose-related increases in micronucleated erythrocytes (up to 4-fold over the control) were found in the bone marrow cells of mice 24 h after treatment with the fungicide over a range of concentrations from 312.5 to 1250 mg/kg. The morphology and the size of micronuclei induced was suggestive of a predominantly clastogenic mode of action. Several cytochrome P450 (CYP)-dependent reactions have been monitored in liver, kidney and lung microsomes of male and female Swiss Albino CD1 mice in order to ascertain certain toxic non-genetic properties (related to carcinogenesis) of Vinclozolin. It was found to be a selective inducer towards CYP 3A (liver, kidney) and 2E1 (liver), as exemplified by the significant increases of the demethylation of aminopyrine (APND, up to 2.3-fold, female liver), and hydroxylation of p-nitrophenol (pNPH, up to 5.6-fold, male liver). In general, however, Vinclozolin has a complex pattern of induction and suppression of CYP-dependent enzymes, as shown from the reduced expression of various monooxygenases depending upon dose, sex or organ considered. For example, pNPH activity was suppressed in kidney (up to 48% loss, averaged between male and female), whereas ethoxycoumarin O-deethylase was reduced in lung up to 53% in male (at the highest dose). These data were sustained by means of Western immunoblotting using rabbit polyclonal antibodies anti-CYP 3A and 2E1. Northern blotting analysis using CYP 3A1/2 and 2E1 cDNA biotinylated probes showed that the expression of such isozymes is regulated at the mRNA level. Taken together, the findings indicate the clastogenic activity and the possible cotoxic, cocarcinogenic and promoting potential of Vinclozolin.

Animals↗
PubMed2004

Measuring the genetic damage in cancer patients during radiotherapy with three genetic end-points.

In this paper the genetic damage for three genetic end-points was studied in cancer patients during radiotherapy using the micronucleus test, comet assay and hprt gene mutation test. The subjects were from: (i) a group of 24 patients suffering from various types of cancers; (ii) a group of 23 controls matched according to age, sex and smoking. Blood samples were collected from the controls and from the cancer patients prior to radiotherapy and after cumulative radiation doses of 10, 30 and 50 Gy. The results of the micronucleus test indicated that the mean micronuclei rate (MNR) and mean micronucleated cells rate (MCR) in the cancer patients prior to radiotherapy were 12.46 and 11.29 per thousand, respectively, which were significantly higher than those (6.65 and 5.96 per thousand) in controls (P < 0.01). However, the results of the comet assay and hprt gene mutation test showed no significant difference between untreated cancer patients and controls (P > 0.05). The mean MNR/MCR at 0, 10, 30 and 50 Gy in cancer patients increased with the cumulative dose, being 12.46, 35.83, 64.63 and 85.00 per thousand for MNR and 11.29, 31.25, 53.63 and 67.28 per thousand for MCR, respectively. Similar results were obtained in the comet assay and hprt gene mutation test. Meanwhile, it was found that there was inter-individual variability in response to radiotherapy among patients.

Adult↗
PubMed1994

What can the molecular genetics of hypertensive rats teach us about the genetics of hypertension in humans?

Recent progress in molecular genetics has raised expectations that the application of powerful new techniques to established animal models of hereditary hypertension may provide important new insights in the genetic basis of human hypertension. Whereas these methods provide exciting opportunities, we shall have to revise many traditional and established strategies used in hypertension research to recognize their full potential. Although it is probably naive to anticipate the quick identification of genes involved in the pathogenesis of human hypertension from this research, these methods, if applied wisely, are likely to render important conceptual insights into the nature not only of hypertension and cardiovascular disease but of polygenic disorders in general.

Animals↗
PubMedDate not supplied

Revised sections F7.5 (quantitative amino acid analysis) and F7.6 (qualitative amino acid analysis): American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories, 2003.

Determination of plasma amino acid levels has become a key piece of information in the diagnosis and clinical management of a group of metabolic genetic disorders. Appropriate laboratory methodologies have been published for amino acid analysis, yet there is a need for direction for the laboratory in performing this testing. The following guidelines were generated by a working group of the American College of Medical Genetics Laboratory Quality Assurance Committee. Based upon a body of knowledge and professional experience, these guidelines and standards are to be the benchmark for performance of amino acid analysis for clinical interpretation.

Amino Acids↗
PubMed1995

Genetically modified human epidermis overexpressing PDGF-A directs the development of a cellular and vascular connective tissue stroma when transplanted to athymic mice--implications for the use of genetically modified keratinocytes to modulate dermal regeneration.

We investigated the hypothesis that keratinocyte-produced platelet-derived growth factor-AA (PDGF-AA) is involved in epidermal-dermal interactions and that PDGF-AA is an important mediator of the temporal and spatial events of tissue repair. Retroviral-mediated gene transfer was used to introduce the gene encoding human PDGF-A into cultures of human diploid keratinocytes. Genetic modification boosted the endogenous in vitro level of PDGF-AA secretion by over 300 fold. When PDGF-secreting cells were transplanted as epithelial sheets to athymic mice, modified keratinocytes underwent terminal differentiation and generated a stratified epithelium comparable to unmodified cells. Seven days after grafting the newly synthesized connective tissue layer subjacent to the PDGF-A-modified grafts was significantly thicker, was rich in mononuclear cells and fibroblasts, and had increased numbers of blood vessels when compared to control grafts of unmodified cells. These results suggest that PDGF-AA secreted by the epidermis is an important mediator of epithelial-mesenchymal interactions and helps to promote growth and vascularization of the underlying dermal tissue. Further, these data demonstrate the feasibility of using genetically modified cells to modulate tissue regeneration.

Animals↗
PubMed1983

Genetic control of murine antibody-dependent cell-mediated cytotoxicity. Partial identity with the genetic control of NK activity.

We have observed that the intensity of the direct antibody-dependent cell-mediated cytotoxicity (ADCC) response after an inoculation of foreign tumour cells varies with the strain of mice studied. The inoculation of a human lymphoblastoid cell-line into CBA/J, BALB/c, or DBA/2 mice gives rise to a good cytotoxic response by the host K cells armed with specific antibodies. In contrast, A/J, B10.A, C57BL/6 and B10.S mice respond poorly under the same conditions. The high response is dominant in F1 hybrids between high and low responders and is also expressed among F2 backcrosses with the H-2 phenotype of low responders, suggesting that non-H-2 genes are also implicated in the regulation of ADCC. The genetic control is not exerted at the level of antibody secretion but at that of K-cell activity, since sera from high or low responders are equally effective in arming an ADCC reaction, whereas K cells from low-responder strains are less efficient than those from high-responder strains. The natural killer (NK) activity of the same strains has been screened. The results show a good correlation with some high- and low-responder strains, such as CBA and DBA/2 or A/J and SJL, respectively, but not with C57BL/6, B10.S or B10.A strains. Thus, in addition to common genes controlling both lytic functions, there are specific genetic factors influencing the balance between NK and K cells. These findings confirm the general view that NK and K cells represent only partially identical subsets.

Animals↗
PubMedDate not supplied

The limits of genetic influence: a behavior-genetic analysis of infant-caregiver relationship quality and temperament.

This report presents data on 9-month-old twin pairs (n(MZ)=172; n(DZ)=333) from the Early Childhood Longitudinal Study, demonstrating that the role of genetic variation among infants is trivial and the shared and nonshared environment is substantial in accounting for the observed quality of infant-caregiver relationships. In contrast, maternal reports of temperament were best accounted for by genetic variation and nonshared environmental influences. Interestingly, however, shared environmental effects were documented for observations of temperament. Consistent with a growing database, the current study calls into question the ubiquity of heritability effects in all domains of psychological inquiry. It also bolsters consensus in the field of developmental psychology that shared environmental effects are not as elusive as had once been thought.

Adult↗
PubMed2006

Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology.

This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed.

Animals↗
PubMed2003

Genetics and susceptibility to toxic chemicals: do you (or should you) know your genetic profile?

This review is based on a symposium/roundtable session, sponsored by the Division of Toxicology of the American Society for Pharmacology and Experimental Therapeutics, that was held at the 2002 Experimental Biology meeting in New Orleans, LA. The focus is on the role of pharmacogenomics in determining individual susceptibility to chemically induced toxicity. An individual's risk of disease from exposure to toxic chemicals is determined by a complex interplay between genetics, physiology, and concurrent or prior exposures to drugs and other chemicals. The first section of the review defines the basics of pharmacogenetics and pharmacogenomics and assesses the current state of the science. Selected applications to specific enzyme systems are summarized by way of example. New, state-of-the-art approaches to studying genetic determinants of susceptibility, including analytical methods and transgenic technology, are then discussed. Finally, ethical and legal concerns with the application of this knowledge and methodology to human health will be discussed.

Animals↗
PubMed1998

Comparison of Randomly Amplified Polymorphic DNA with Amplified Fragment Length Polymorphism To Assess Genetic Diversity and Genetic Relatedness within Genospecies III of Pseudomonas syringae.

Recently, DNA pairing analyses showed that Pseudomonas syringae pv. tomato and related pathovars, including P. syringae pv. maculicola, form a genomic species (Pseudomonas tomato) (L. Gardan, H. L. Shafik, and P. A. D. Grimont, p. 445-448, in K. Rudolph, T. J. Burr, J. W. Mansfield, D. Stead, A. Vivian, and J. von Kietzell, ed., Pseudomonas syringae Pathovars and Related Pathogens, 1997). The genetic diversity of 23 strains belonging to this genomic species and 4 outgroup strains was analyzed with randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphic (AFLP) techniques. Simple boiling of P. syringae cells was suitable for subsequent DNA amplification to obtain reliable patterns in RAPD and AFLP analyses. In general, the grouping of P. syringae strains by both analysis techniques corresponded well with the classification obtained from an RFLP analysis of ribosomal DNA operons, DNA pairing studies, and an analysis of pathogenicity data. However, two strains of P. syringae pv. maculicola produced distinct DNA patterns compared to the DNA patterns of other P. syringae pv. maculicola strains; these patterns led us to assume that horizontal transfer of DNA could occur between bacterial populations. Both techniques used in this study have high discriminating power because strains of P. syringae pv. tomato and P. syringae pv. maculicola which were indistinguishable by other techniques, including pathogenicity tests on tomato, were separated into two groups by both RAPD and AFLP analyses. In addition, data analysis showed that the AFLP method was more efficient for assessing intrapathovar diversity than RAPD analysis and allowed clear delineation between intraspecific and interspecific genetic distances, suggesting that it could be an alternative to DNA pairing studies. However, it was not possible to distinguish the two races of P. syringae pv. tomato on the basis of an analysis of the data provided by either the AFLP or RAPD technique.

Journal Article↗
PubMed1999

Genetic analysis of Borrelia garinii OspA serotype 4 strains associated with neuroborreliosis: evidence for extensive genetic homogeneity.

Infection with Borrelia garinii outer surface protein (Osp) A serotype 4 strains has been correlated with the development of neuroborreliosis in Lyme borreliosis patients in Europe. OspA serotype 4 isolates have been recovered primarily from human cerebrospinal fluid, suggesting a tropism for this environment. Previous studies with monoclonal antibodies directed against OspA and OspC demonstrated that OspA serotype 4 strains are antigenically closely related. In view of the pronounced antigenic and genetic variability that has been noted in the Osps of other Borrelia isolates, we sought to determine if OspA serotype 4 strains represent a recently emerged clonal lineage of B. garinii. Toward this goal, a representative group of OspA serotype 4 strains was analyzed for traits that typically exhibit hypervariability among isolates that cause Lyme borreliosis. The following criteria were assessed: (i) ospC sequences, (ii) plasmid composition, (iii) genomic restriction fragment length polymorphism (RFLP) patterns, and (iv) the RFLP patterns of the upstream homology box (UHB) element which flanks members of the UHB gene family at their 5' end. Collectively, these analyses demonstrate genetic homogeneity, suggesting that OspA serotype 4 strains are a recently emerged clonal lineage with an apparent tropism for the central nervous system.

Antigens, Bacterial↗
PubMed1975

Genetic control of fatty acid metabolism, especially study of genetic control of cholesterol.

The serum cholesterol of 1431 inhabitants over 10 years old in the general population was estimated by the method of Autoanalyzer. The correlation coefficients of the serum total cholesterol between parent and child and between siblings were obtained from other samples which completely excluded consanguinity. The genetic study of 41 pedigrees of familial hypercholesterolemia with xanthoma which described the cholesterol value of parent and child in Japan and other countries was done, and the following results were obtained. 1) Cholesterol is a quantitative character, therefore it will be controlled genetically by polygene. 2) It was presumed that the mode of inheritance of type II hypercholesterolemia (with or without xanthoma) was also controlled by polygene. 3) The correlation coefficients of cholesterol between parent and child and between siblings were found to be 0.26004, 0.27998, respectively. 4) The heritability of cholesterol was found to be 0.5995.

Adolescent↗
PubMed1998

Genetic and non-genetic basis of essential hypertension: maladaptation of human civilization to high salt intake.

The relation between salt intake and hypertension has long been controversial. Available evidence provides conflicting results. However, biological and evolutionary insights into the structure and principle function of the kidney and the blood pressure sustaining machinery, with the extracellular fluid volume and the renin-angiotensin system acting as a central player, clearly indicate that salt has been a precious commodity in the terrestrial animal kingdom and that essential hypertension may be a consequence of the kidney's maladaptation to excess salt intake, which is specific to recent human civilization. This review provides a hypothesis to explain how and why hypertension develops and attempts to define the roles of genetic, non-genetic, and environmental factors in its pathogenesis.

Adaptation, Physiological↗
PubMed1987

Genetic control of immune response to pseudorabies and atrophic rhinitis vaccines: II. Comparison of additive direct and maternal genetic effects.

Data from 52 litters farrowed in two seasons of a cross-fostering experiment were analyzed to estimate variances and covariances for additive direct and maternal genetic effects on immune response to pseudorabies virus and B. bronchiseptica vaccine. Twenty purebred boars and 44 sows of the Duroc, Landrace and Yorkshire breeds were used. Immune response was measured after vaccine challenge. A modified-live pseudorabies (PR) vaccine was administered to piglets at 28 d of age; response was measured by log2 serum neutralization titers at 56 d. An inactivated B. bronchiseptica bacterin was administered at 28, 42 and 112 d. Antibody levels were measured relative to positive and negative controls at 28, 56 and 119 d by using an enzyme-linked immunosorbent assay (ELISA). Results from this study for heritability were .18 +/- .09 for PR titer and .15 +/- .07 and .52 +/- .15 for 56- and 119-d ELISA values, respectively. The variability due to nurse environment (maternal genetic variance and common environmental variance) as a percentage of phenotypic variance was 11.1% for PR titers and 29.6 and 8.8% for 56- and 119-d ELISA values, respectively. The heritabilities estimated in this study indicate that, if improved immune response to vaccines is desired, selection may be useful. However, the importance of maternal environment would make early selections less accurate than selections based on immune response measured later in life.

Animals↗
PubMed1992

Multiple metabolic syndrome: aspects of genetic epidemiology and molecular genetics.

Epidemiological studies have documented the association between cardiovascular disease and high blood pressure, dyslipidaemia, impaired glucose tolerance, non-insulin-dependent diabetes mellitus (NIDDM), and central obesity. In fact, several of these abnormalities, often all of them, can be identified in the very same individuals, constituting the entity of the multiple metabolic syndrome. Furthermore, many of these abnormalities seem to run in families. These findings raise important questions about the genetic epidemiology of the disease and about the molecular genetic background of the most likely common nominator of this syndrome, namely insulin resistance. Therapeutic actions must also be carefully considered to avoid the encouragement of some abnormalities while treating others.

Apolipoproteins E↗