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At least 235 records · Page 13Linked to original sources
PubMed2003

Genetic background of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: association of HLA-DRB1*0901 with microscopic polyangiitis.

OBJECTIVE: To examine association of 8 candidate genes with susceptibility to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japanese patients. Little is known on the genetic background of AAV in Japanese patients mainly because of the difficulty in collecting a sufficient number of samples for the genetics study. METHODS: Sixty-nine patients, including 50 with microscopic polyangiitis (MPA), were recruited in a multicenter study. Among them, 64 patients were positive for myeloperoxidase (MPO)-ANCA. Associations of HLA-DRB1, tumor necrosis factor-alpha promoter (TNF), TNF receptor 2 (TNFR2), Fcgamma receptor IIa (FCGR2A), IIb (FCGR2B), IIIa (FCGR3A), IIIb (FCGR3B), and CTLA-4 (CTLA4) polymorphisms were examined in a case-control analysis. RESULTS: A significant association of HLA-DRB1*0901 with MPA (p = 0.0037, OR 2.44, 95% CI 1.33-4.46), as well as with MPO-ANCA positivity (p = 0.0014, OR 2.44, 95% CI 1.41-4.22), was detected. There was no difference in the TNF promoter haplotype frequencies between patients with MPA and controls, excluding the possibility that the association of DRB1*0901 was secondarily caused by linkage disequilibrium with TNF. No association was observed for TNFR2, FCGR, or CTLA4 with MPA, nor with the presence of MPO-ANCA, although the combined genotype FCGR2A-131H/H and 3A-176F/F was increased in patients with MPA (p = 0.025). CONCLUSION: There was an association of HLA-DRB1*0901 with MPA and MPO-ANCA positive vasculitis in Japanese patients.

Adult↗
PubMed1981

The influence of genetic background on the expression of mutations at the diabetes locus in the mouse. III. Effect of H-2 haplotype and sex.

The expression of the mouse mutation, diabetes (db), was examined on eight different inbred genetic backgrounds. The influence of H-2 haplotype and sex was examined. Mice of both sexes in two diabetes (db) strains (C57BL/6J, 129/J) having the H-2b haplotype were resistant to the diabetogenic action of the mutant gene. On the contrary, two H-2d congenic diabetes stocks (C57BL/KsJ, DBA/2J) exhibited severe diabetes associated with beta-cell necrosis. However, diabetes resistance was not restricted to mice with H-2b haplotype since the congenic diabetes MA/J stock (H-2k) was also resistant. Similarly, diabetes susceptibility was not restricted to mice with the H-2d haplotype, since males, but generally not females, in the congenic CBA/Lt-db/db and C3HeB/FeJ-db/db stocks (both H-2k) also exhibited a severe diabetes. Males of the congenic SWR/J-db stock (H-2q) had a diabetes of intermediate severity. Female diabetes mice with H-2k and H-2q haplotypes exhibited a sustained hypertrophy and hyperplasia of beta-cells and were able to control hyperglycemia better than males. Thus, while the H-2b haplotype remains associated with resistance, and the H-2d haplotype with susceptibility to induction of genetic diabetes, the diabetes stocks with H-2k haplotype clearly illustrate the importance of non-H-2, but sex-associated, genetic modifiers.

Animals↗
PubMed1997

Genetic background of the differences in timing of meiotic maturation in mouse oocytes: a study using recombinant inbred strains.

Recombinant inbred strains of mice derived from CBA and KE strains were used for studying the genetic background of the duration of the first meiotic cycle which differs in oocytes from progenitor strains. Oocytes were screened in vitro for the timing of germinal vesicle breakdown as well as for the timing of first polar body extrusion, and the approximate duration of the first meiotic M-phase was calculated. Although oocytes from progenitor strains did not differ in the duration of germinal vesicle breakdown, this characteristic segregated in recombinant strains showing involvement of at least two genes. Because of the similar duration of germinal vesicle breakdown in CBA and KE oocytes, the difference in timing of first polar body extrusion (9 h and 12 h for CBA and KE, respectively) reflects the difference in the duration of the first meiotic M-phase. The timing of germinal vesicle breakdown and the duration of M-phase in recombinant strains were negatively correlated (P < 0.01); in general, the more time needed for breakdown of the germinal vesicle, the shorter the M-phase. The timing of first polar body extrusion varied among strains: in some it was similar to one of the parental strains; in others it was intermediate between the two, which again shows the involvement of at least two genes in the control of this character. The linkage analysis suggests that one of the putative genes influencing the timing of first polar body extrusion may be situated near the Gpi-1 locus on chromosome 7, that is, in the region containing the locus for cyclin E. The possible involvement of cyclin E in the control of the timing of first meiosis in mouse oocytes is discussed.

Animals↗
PubMed2006

Genetic background differences between FVB and C57BL/6 mice affect hypnotic susceptibility to pentobarbital, ketamine and nitrous oxide, but not isoflurane.

BACKGROUND: Pharmacogenomics has allowed us to identify the mechanisms underlying much of the inherited variability in drug response. There have been several reports of strain-dependent anesthetic actions in rodents, indicating that significant genetic differences exist in the hypnotic and antinociceptive effects of various anesthetics. METHODS: Loss of righting reflex was used to compare the hypnotic action of pentobarbital, ketamine, nitrous oxide and isoflurane between two genetically different populations of mice, C57BL/6 with black hair and Friends virus B (FVB) with white hair. RESULTS: C57BL/6 mice were more susceptible than FVB mice to the hypnotic effects of ketamine, pentobarbital and nitrous oxide. However, the sensitivity to isoflurane did not differ between C57BL/6 and FVB mice. CONCLUSION: Genetic background affects the hypnotic susceptibility to some anesthetic agents in mice. Our results indicate that there may be a different genetic basis for the operation of hypnosis between isoflurane and other anesthetics, such as pentobarbital, ketamine and nitrous oxide.

Anesthetics, Dissociative↗
PubMed1999

Tissue plasminogen activator (tPA) deficiency exacerbates cerebrovascular fibrin deposition and brain injury in a murine stroke model: studies in tPA-deficient mice and wild-type mice on a matched genetic background.

Although the serine protease, tissue plasminogen activator (tPA), is approved by the US Food and Drug Administration for therapy to combat focal cerebral infarction, the basic concept of thrombolytic tPA therapy for stroke was challenged by recent studies that used genetically manipulated tPA-deficient (tPA-/-) mice, which suggested that tPA mediates ischemic neuronal damage. However, those studies were potentially flawed because the genotypes of tPA-/- and wild-type control mice were not entirely clear, and ischemic neuronal injury was evaluated in isolation of tPA effects on brain thrombosis. Using mice with appropriate genetic backgrounds and a middle cerebral artery occlusion stroke model with nonsiliconized thread, which does lead to microvascular thrombus formation, in the present study we determined the risk for cerebrovascular thrombosis and neuronal injury in tPA-/- and genetically matched tPA+/+ mice subjected to transient focal ischemia. Cerebrovascular fibrin deposition and the infarction volume were increased by 8.2- and 6. 7-fold in tPA-/- versus tPA+/+ mice, respectively, and these variables were correlated with reduced cerebral blood flow up to 58% (P<0.05) and impaired motor neurological score by 70% (P<0.05). Our findings indicate that tPA deficiency exacerbates ischemia-induced cerebrovascular thrombosis and that endogenous tPA protects the brain from an ischemic insult, presumably through its thrombolytic action. In addition, our study emphasizes the importance of appropriate genetic controls in murine stroke research.

Animals↗
PubMed2001

Genetic background in patients with acute myocardial infarction.

The renin-angiotensin system is believed to play important roles in the development of acute myocardial infarction, and gene polymorphisms may also be involved. To investigate the genetic background in patients with acute myocardial infarction, we performed a case control study in a Japanese population. The study included 150 patients with acute myocardial infarction and 150 healthy, age- and sex-matched controls. We examined polymorphisms of angiotensin II type 1 receptor (1 166 A / C), type 2 receptor (3123 C / A), and bradykinin B2 receptor (-58 T / C) in these subjects. The allelic frequencies of angiotensin II type I receptor C and angiotensin II type 2 receptor A were significantly higher in the acute myocardial infarction subjects than in the control subjects, and this tendency was more significant in the younger patients. The combined ratios of angiotensin II type 1 receptor C and type 2 receptor A alleles in patients under 64 years old were significantly higher than in their older counterparts. However the total numbers of conventional coronary risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) in individual subjects were not significantly different between younger and older patients. These polymorphisms were found to be involved in the development of acute myocardial infarction, particularly in the younger patients, and it was concluded that the incidence of acute myocardial infarction might be reduced by management from the genotypes.

Aged↗
PubMed2006

A Wolbachia-associated fitness benefit depends on genetic background in Drosophila simulans.

The alpha-proteobacteria Wolbachia infect a number of insect species and influence host reproduction to favour the spread of infected females through a population. The fitness effect of this infection is important in understanding the spread and maintenance of Wolbachia within and among host populations. However, a full elucidation of fitness effect requires careful control of host genetic background. Here, I transferred a single clone of Wolbachia (the wHa strain) into three genetically distinct isofemale lines of the fly Drosophila simulans using microinjection methodology. These lines carried one of the three described mitochondrial haplogroups (siI, siII or siIII) and differ in nuclear genome as well. Population cage assays showed that wHa-infected siIII flies enjoyed a dramatic fitness benefit compared to uninfected siIII. In contrast, wHa did not affect the fitness of siI or siII flies. This study points to the importance of host-by-symbiont interaction terms that may play an important role in organismal-fitness.

Animals↗
PubMed1980

Influence of age and genetic background on in vivo fatty acid synthesis in obese (ob/ob) mice.

The relationship of developing obesity and hyperinsulinaemia to fatty acid synthesis in whole body and major tissues has been studied in two strains of genetically obese (ob/ob) mice using in vivo incorporation of 3H2O into fatty acids. Rates of fatty acid synthesis were not increased in pre-weaning C57BL/6J obese mice even though hyperinsulinaemia and obesity occurred. Post-weaning, rates of fatty acid synthesis increased to 5 weeks of age in adipose tissue, liver and carcass, the latter being the major site of synthesis. Synthesis then declined in carcass and adipose tissue, but remained unchanged in liver at 3 months. Increased fatty acid synthesis developed earlier in Imperial College obese mice as compared to the C57BL/6J strain and total rates of synthesis were 3--5 times greater. Adipose tissue was the major site of synthesis in Imperial College obese mice, while carcass was of only minor importance. Thus genetic background and age strongly affected rates of fatty acid synthesis and also the extent to which various tissues contributed.

Adipose Tissue↗
PubMed2003

Heterogeneity of interleukin 5 genetic background in atopic dermatitis patients: significant difference between those with blood eosinophilia and normal eosinophil levels.

BACKGROUND: Blood eosinophil levels in patients with atopic dermatitis vary widely during exacerbation of the disease. We considered that in addition to environmental factors, the genetic background involved with elevating blood eosinophil levels might be heterogeneous among atopic dermatitis patients. OBJECTIVE: We attempted to determine whether a polymorphism of the interleukin (IL)5 gene plays a role in atopic dermatitis, particularly in those patients with blood eosinophilia. Due to the close relation of blood eosinophilia to high IgE productivity, we also assessed these polymorphisms in patients with high IgE concentrations. METHODS: We determined the genotype of the IL5 polymorphism -703C/T in 451 atopic dermatitis patients and 116 normal subjects. The patients were classified into three groups by blood eosinophil levels; less than 7%, from 7 to 15%, and more than 15%, as well as by serum IgE concentrations; less than 500 IU/ml, from 500 to 2000 IU/ml, and more than 2000 IU/ml. RESULTS: IL5 -703C/T was not significantly associated with either total atopic dermatitis patients or individual patients who had both blood eosinophilia and high IgE productivity. However, the distribution of the IL5 -703C/T genotype was significantly different between patients with either blood eosinophilia or high IgE productivity and those without either condition (P=0.0476, P=0.0088, respectively). CONCLUSION: These results suggest that the IL5 gene may play a role in blood eosinophilia associated with atopic dermatitis. We also considered that the IL5 -703C/T gene polymorphism does not have a direct relationship to disease specificity.

Adolescent↗
PubMed2002

Mapping of genes controlling aluminum tolerance in rice: comparison of different genetic backgrounds.

Aluminum toxicity is the main factor limiting the productivity of crop plants in acid soils, particularly in the tropics and subtropics. In this study, a doubled-haploid population derived from the rice ( Oryza sativa L.) breeding lines CT9993 and IR62266 was used to map genes controlling Al tolerance. A genetic linkage map consisting of 280 DNA markers (RFLP, AFLP and SSR) was constructed to determine the position and nature of quantitative trait loci (QTLs) affecting Al tolerance. Three characters - control root length (CRL), Al-stressed root length (SRL) and root length ratio (RR) - were evaluated for the DH lines and the parents at the seedling stage in nutrient solution. A total of 20 QTLs controlling root growth under Al stress and control conditions were detected and distributed over 10 of the 12 rice chromosomes, reflecting multigenic control of these traits. The two QTLs of largest effect, qALRR-1-1 and qALRR-8 for root length ratio (a measurement of Al tolerance) were localized on chromosomes 1 and 8, respectively. Three other QTLs in addition to qALRR-8 were apparently unique in the CT9993 x IR62266 mapping population, which may explain the high level of Al tolerance in CT9993. Comparative mapping identified a conserved genomic region on chromosome 1 associated with Al tolerance across three rice genetic backgrounds. This region provides an important starting point for isolating genes responsible for different mechanisms of aluminum tolerance and understanding the genetic nature of this trait in rice and other cereals.

Aluminum↗
PubMed2003

Genetic background determines phenotypic severity of the Plp rumpshaker mutation.

The rumpshaker mutation of the proteolipid protein (Plp) gene causes dysmyelination in man and mouse. We show that the phenotype in the mouse depends critically on the genetic background in which the mutation is expressed. On the C3H background there is normal longevity whereas changing to a C57BL/6 strain results in seizures and death at around postnatal day 30. The more severe phenotype is associated with less myelin and reduced levels of major myelin proteins. There are also more apoptotic cells, including oligodendrocytes, increased numbers of proliferating cells, increased numbers of NG2+ oligodendrocyte progenitors and increased microglia compared to the milder phenotype. The number of mature oligodendrocytes is similar to wild-type in both strains of mutant, however, suggesting that increased oligodendrocyte death is matched by increased generation from progenitors. The dichotomy of phenotype probably reflects the influence of modifying loci. The localization of these putative modifying genes and their mode of action remain to be determined.

Animals↗
PubMed2001

Innate resistance to Babesia infection is influenced by genetic background and gender.

Infection of severe combined immunodeficient mice with Babesia sp. strain WA1 was studied to assess the contributions of innate and adaptive immunity in resistance to acute babesiosis. The scid mutation showed little effect in genetically susceptible C3H mice and did not decrease the inherent resistance of C57BL/6 mice to the infection, suggesting that innate immunity plays a central role in determining the course of Babesia infection in these strains. In contrast, the scid mutation dramatically impaired resistance in moderately susceptible BALB/c mice, suggesting that acquired immunity may play an important secondary role. In comparison to their female counterparts, male mice of different genetic backgrounds showed increased resistance to the infection, indicating that the gender of the host may influence protection against babesiosis.

Animals↗
PubMed1984

Effects of starvation and refeeding on the excretion of urinary steroid metabolites in mice with different genetic background.

Gas chromatographic steroid metabolic profiling procedures have been applied to investigations of the effects of starvation and refeeding in mice. Urinary steroid metabolites were quantitatively followed during the starvation-refeeding experiments for mice with different genetic backgrounds. Some quantitative alterations were noted for certain congenic strains of mice. The metabolites which exhibited such quantitative variations were tentatively identified by means of combined gas chromatography-mass spectrometry.

Animals↗
PubMed1989

Clastogenic effects of benzo[a]pyrene in postimplantation embryos with different genetic background.

Certain strains of mice vary in their enzyme inducibility by polycyclic hydrocarbons, i.e., the strain C57 shows high and the strain DBA shows low inducibility of aryl hydrocarbon hydroxylase (AHH) by benzo[a]pyrene (BaP). The effect of this genetically determined difference on the clastogenic response to BaP was studied in 11 day old embryos after transplacental treatment. The four possible crosses, C57 and DBA inter se, C57 X DBA and DBA X C57, were used to determine the influence of the genetic background on the aberration yields in the embryos. Constitutive and induced AHH levels were measured in liver, bone marrow, and placenta of the pregnant females and in their embryos. Enzyme inducibility was high in tissues of C57 dams and in their homozygous or heterozygous embryos. In contrast, induction of AHH activity was low in tissues of DBA females and their homozygous embryos. The high BaP-induced AHH activity found in heterozygous embryos of DBA dams is in agreement with the dominant mode of inheritance for high AHH inducibility. The cytogenetic results showed that the clastogenic response was lowest in homozygous C57 embryos and highest in hybrid embryos independent of the genetic constitution of the dams. Homozygous DBA embryos showed an intermediate aberration yield. The AHH inducibility by BaP did not correlate quantitatively with the induced aberration rates. However, the data suggest that BaP activation in embryonic tissue on day 11 of pregnancy is sufficient to account for the clastogenicity in the fetuses. It is concluded that the genetic endpoint chromosomal breakage is not only determined by the formation of active BaP metabolites but also by genetically controlled detoxification of BaP, repair process, and the rate of transformation of primary DNA lesions into true DNA discontinuities.

Animals↗
PubMed2002

Sensorimotor functions in transgenic mice expressing the neurofilament/heavy-LacZ fusion protein on two genetic backgrounds.

NFH-LacZ transgenic mice are characterized by expression of a non-endogenous fusion protein between a truncated form of mouse NFH (neurofilament of heavy molecular weight) and the complete Escherichia coli beta-galactosidase protein. These transgenic mice were compared to their respective controls on two background strains (C3H and FVB) in several sensorimotor tests. NFH-LacZ mice were deficient in tests requiring balance and equilibrium in a manner generally independent of genetic background. In particular, NFH-LacZ mice fell more quickly than controls from two stationary beams and had fewer rears in an open-field. The transgenic mice were also impaired during the initial trials of sensorimotor learning on the rotorod. We conclude that despite the absence of overt signs of sensorimotor weakness in their home cage, the disruption of the NFH gene, causing neurofilament accumulations in the cell body and diminished axonal calibers of motoneurons, is sufficient to cause motor deficits that resemble the early stages of amyotrophic lateral sclerosis.

Animals↗
PubMed1986

Importance of follow-up of family history for understanding the genetic background of cancer.

The details of family histories naturally change as time passes. Thus, the family histories at the time of first consultation are incomplete, particularly in the cases of younger cancer patients whose disease is indicated as having a genetic background on the basis of epidemiological studies. The necessity for follow-up of the family history is illustrated by presenting some clinical cases as examples.

Female↗
PubMed1985

The genetic background modulates the effect of the beige gene on susceptibility to cytomegalovirus infection in mice.

Homozygous beige (bg/bg) mice were more susceptible to the development of fatal disease induced by murine cytomegalovirus (MCMV) than their bg/ + littermates. However, the increase in susceptibility depended on the genetic background of the strain carrying the bg gene. C57BL/6, SB/Le, DBA/2, and CBA bg/bg mice showed, respectively, 2.5-, 3.2-, 9.5-, and 18.6-fold increases in susceptibility compared with the corresponding bg/+ animals. Beige mice showed higher liver titres of MCMV than bg/ + by the 2nd or 3rd day after infection, and tissue damage was also greater. Splenic NK cells were not detected in uninfected bg/bg mice, and after virus inoculation the increment in cytotoxicity was greater in bg/ + than in bg/bg mice. However, cytotoxicity towards WEHI-164 cells was not impaired in bg/bg mice and was not augmented by MCMV. Interferon titres were also not impaired by the beige mutation. Of the strains examined, CBA had the highest endogenous levels of NK cells and were most genetically resistant to MCMV. Thus, our observation that the beige gene had the greatest effect on susceptibility in this strain suggests that NK cells are important mediators of genetically determined resistance to MCMV.

Animals↗
PubMed1999

Genetic background determines the nature of immune responses and experimental immune-mediated blepharoconjunctivitis (EC).

PURPOSE: Experimental immune-mediated blepharoconjunctivitis (EC) was induced in Lewis rats by immunization with ovalbumin (OVA) in complete Freund's adjuvant (CFA) or aluminum hydroxide [Al(OH)3]. To investigate the affect of genetic factors on the susceptibility of EC, we tested different strains of rats for the development of EC. METHODS: Lewis and Brown Norway (BN) rats were immunized once with 100 microg of OVA in CFA or Al(OH)3. Three weeks later they were challenged with OVA in eye drops; 24 hours after the challenge they were sacrificed and their eyes, blood, and lymph nodes were harvested for histological studies, measurement of OVA-specific antibodies (IgG, IgG1, IgG2a, IgE), and proliferation or cytokine assay, respectively. ELISA was used to detect OVA-specific IgG; passive cutaneous anaphylaxis was used for detecting IgE. RESULTS: EC, OVA-specific IgG, and cellular immunity were induced in Lewis rats by using either adjuvant, whereas IgE was not produced by either adjuvant. In contrast, IgE was produced in BN rats using either adjuvant, whereas cellular immunity was evoked only when CFA was used. Less cellular infiltration as well as cellular proliferation was detected in BN rats immunized with Al(OH)3. In both strains, Al(OH)3 induced a higher IgG1/IgG2a ratio than did CFA. More interferon-gamma by stimulation with OVA was noted in Lewis rats compared to BN rats, whereas interleukin-4 was detected only in BN rats. CONCLUSIONS: The severity of EC evaluated by cellular infiltration was dependent on OVA-specific cellular immunity. Genetic background is more important than adjuvants in determining the nature of EC and immunity.

Aluminum Hydroxide↗