Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ahb/Ahb homozygous and the Ahb/Ahd heterozygous inbred mouse strains from the (C57BL/6)(DBA/2)F1 X DBA/2 backcross are genetically responsive to 3-methylcholanthrene. They both also develop, within 6 hours after a large intraperitoneal dose of acetaminophen, an irreversible opacity in the anterior portion of the lens. Such cataract formation does not occur in similarly treated nonresponsive inbred strains or nonresponsive Ahd/Ahd individuals from the same backcross. Differences in acetaminophen metabolism and toxicity are associated with the Ah locus in the mouse, and differences in heritability at the Ah locus exist in the human. Our ophthalmologic findings may be important clinically to certain patients receiving either a single large overdose of this drug or high doses over a long period.
 ...
PMID:Ah locus: genetic differences in susceptibility to cataracts induced by acetaminophen. 64 13

The susceptibility of cataract Shionogi (CTS) mice as young as 8 to 10 weeks of age to passive anaphylactic shock mediated by anti-benzylpenicilloyl IgE and IgG1 monoclonal antibodies was compared with those of other strains of the same age including sister strains such as nonobese-diabetic (NOD) and nonobese-nondiabetic (NON). When the animals had been treated with killed Bordetella pertussis organisms, potent sensitization, enough to cause lethal shock, was produced by either monoclonal antibody preparation in CTS, NOD, C57BL/6J and DS/Shi strains, but not at all in C3H/He, DBA/2 and BALB/c strains. In the NON strain, lethal shock was elicited in the animals sensitized with the IgG1 antibody but not in those sensitized with the IgE antibody. Without the pertussis pretreatment, sensitization sufficient to cause lethal shock was produced at a high frequency by the IgG1 antibody in CTS and NOD mice but not in the other strains. When the IgE antibody was used, lethal shock was not observed in any of the mouse strains tested except for one CTS mouse. These results indicate that CTS as well as NOD are highly susceptible strains, and that IgG1 antibody is more effective than IgE antibody for producing systemic sensitization for anaphylactic shock. In addition to these findings, the results revealed an age-dependent potentiation of anaphylactic shock in CTS mice. The IgE antibody-mediated lethal shock was produced in all the aged animals of this mouse strain tested without the Bp treatment, but not in aged NOD and NON mice.
 ...
PMID:High susceptibility of cataract Shionogi (CTS) mice to passive anaphylactic shock mediated by allogeneic IgE and IgG1 monoclonal antibodies. 187 60

The mutagenic effectiveness of ethylnitrosurea (ENU) was assessed in treated spermatogonia of DBA/2 mice. In a total of 17,515 offspring examined following 160 mg ENU/kg body weight treatment of parental males, 26 forward specific-locus mutations, 2 reverse specific-locus mutations and 9 dominant cataract mutations were recovered. ENU increased the mutation rate to all 3 genetic endpoints. However, ENU was less effective in treated DBA/2 mice than in the standard experimental protocol employing treated hybrid (102 X C3H)F1 male mice. This observed difference for a direct-acting mutagen such as ENU may result from differences in the detoxification of ENU or from differences in the DNA-repair capabilities of strain DBA/2. The first documented reverse mutation of the b allele is reported. The reversion was shown to be due to an AT to GC transition. To date, in addition to the reverse mutation of the b allele, 5 independent ENU-induced mutations recovered in germ cells of the mouse have been molecularly characterized and all have been shown to be base substitutions at an AT site. This is in contrast to the expected mechanism of ENU mutation induction due to O6-ethylguanine adduct formation which results in a GC to AT base-pair substitution and emphasizes the complexities of mutagenesis in germ cells of mammals.
 ...
PMID:The induction of forward and reverse specific-locus mutations and dominant cataract mutations in spermatogonia of treated strain DBA/2 mice by ethylnitrosourea. 207 72

The polycyclic aromatic hydrocarbon naphthalene is bioactivated by cytochromes P450 to an electrophilic epoxide intermediate, which subsequently is metabolized to naphthoquinones (NQ) and possibly to a free radical intermediate. These reactive intermediates may bind covalently to lenticular tissues, cause oxidant stress and/or lipid peroxidation, thereby initiating cataracts. To evaluate this hypothesis, male C57BL/6 or DBA/2 mice were treated with naphthalene or one of several naphthoquinone and naphthol metabolites, in the presence or absence of modulators of chemical bioactivation and detoxification. In C57BL/6 mice, cataracts were caused by naphthalene (500-2000 mg/kg ip) in a dose-dependent fashion. The incidence of naphthalene-induced cataracts was decreased by pretreatment with the P450 inhibitors SKF 525A and metyrapone, the antioxidants caffeic acid and vitamin E, the glutathione (GSH) precursor N-acetylcysteine, and the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (p less than 0.05). Naphthalene cataractogenicity was enhanced by pretreatment with the cytochrome P450 inducer phenobarbital and the GSH depletor diethyl maleate (DEM) (p less than 0.05), and was unaffected by pretreatment with the prostaglandin synthetase inhibitors aspirin or naproxen, or the epoxide hydrolase inhibitor trichloropropene oxide. Cataracts were initiated by 1,2-NQ and 1,4-NQ (5-250 mg/kg ip) in a dose-dependent fashion, with a molar potency about 10-fold higher than that for naphthalene. NQ cataractogenicity was enhanced by pretreatment with DEM (p less than 0.05). 1-Naphthol (56 to 562 mg/kg ip) demonstrated a cataractogenic potency intermediary to that for naphthalene and NQ. DBA/2 mice treated with naphthalene (2000 mg/kg ip), 1,4-NQ (65-250 mg/kg ip), 1,2-NQ (30-250 mg/kg ip), or DEM followed by 1,4-NQ (125 mg/kg ip) did not develop cataracts. These results suggest that naphthalene cataractogenesis in C57BL/6 mice requires P450-catalyzed bioactivation to a reactive intermediate, which may be the NQ and/or a free radical derivative, either of which is dependent upon GSH for detoxification.
 ...
PMID:In vivo murine studies on the biochemical mechanism of naphthalene cataractogenesis. 274 33

Unilateral cataracts were investigated in 750 day-old BALB/c, C57BL/6 and DBA/2 mice, and the six reciprocal crosses between these strains. This abnormality of the lens appears to be inherited additively in the cross DBA/2xBALB/c (with incomplete penetrance in DBA/2 and F1 mice) but as a completely recessive character in the cross DBA/2xC57BL/6. The mode of inheritance may depend on the genetic background against which this phenotype is expressed, unless this abnormality is inherited as a threshold character. Aged DBA/2 mice may constitute a useful model for senile unilateral cataract, probably caused by early uveitis.
 ...
PMID:A note on the genetics of a unilateral senile cataract in mice. 280 46

Acetaminophen has been shown to be cataractogenic in mice and rabbits. C57BL/6 and DBA/2 mice respectively are genetically susceptible and resistant to the induction of cytochrome P-448 by 3-methylcholanthrene (3-MC). This isoenzyme is thought to bioactivate acetaminophen to a toxic reactive intermediate. These two murine strains also are correspondingly susceptible and resistant to acetaminophen cataractogenesis. To evaluate the potential role of enzymatic bioactivation as a determinant of acetaminophen cataractogenesis, C57BL/6 and DBA/2 mice were treated with acetaminophen, 300 or 400 mg/kg intraperitoneally (ip), with or without pretreatment 48 hr earlier using 3-MC, 200 mg/kg ip. Lenticular cataracts were evaluated using the unaided eye and a slit lamp, and hepatotoxicity was evaluated by determination of peak plasma concentration of alanine aminotransferase (ALT). Plasma concentrations of acetaminophen and metabolites, particularly the glutathione (GSH)-derived conjugates (cysteine and mercapturic acid) reflecting enzymatic bioactivation, were measured by high-performance liquid chromatography. Cataracts developed only in C57BL/6 mice pretreated with 3-MC, occurring in 1 of 5 and 5 of 5 animals treated respectively with 300 and 400 mg/kg of acetaminophen. Comparing these two groups of induced C57BL/6 mice, production of the cysteine conjugate of acetaminophen was 2.5-fold higher with the 400 mg/kg dose of acetaminophen (p less than 0.05). Compared to their respective dose-matched, noninduced controls, cysteine conjugate production in the 300 and 400 mg/kg dose groups of induced C57BL/6 mice respectively was 3-fold and 4-fold higher (p less than 0.05). No DBA/2 mice developed cataracts. No mercapturic acid conjugate was detectable in the plasma of DBA/2 mice, and production of the cysteine conjugate was not altered in this strain by increasing the dose of acetaminophen or by pretreatment with 3-MC. The mean peak plasma concentration of the cysteine conjugate, reflecting acetaminophen bioactivation, was 5-fold higher in animals developing cataracts compared with those without cataracts (p less than 0.001). Plasma concentrations of unmetabolized acetaminophen were similar in all groups and unrelated to the development of cataracts. All mice of both strains pretreated with 3-MC showed evidence of hepatotoxicity, indicating a dissociation between hepatotoxic and cataractogenic susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Metabolic evidence for the involvement of enzymatic bioactivation in the cataractogenicity of acetaminophen in genetically susceptible (C57BL/6) and resistant (DBA/2) murine strains. 340 97

In the study of the lens of a congenital cataractous mouse mutant (CAT), it has been shown that a loss of growth regulation at the cellular level causes gross lens abnormalities. The phenotypic characteristics of the cataractous mouse lens are similar to those seen in human congenital cataract and thus serves as a model system for medical research. In this present investigation, we have demonstrated that the abnormalities of the congenital cataractous lens can be rescued by forming chimaeras between DBA/2 (a noncataractous strain of mouse) and the CAT mutant. This report describes the histological, cellular and biochemical analysis of the resultant chimaeric eyes, and discusses possible mechanisms by which these results were achieved.
 ...
PMID:Rescue of developmental lens abnormalities in chimaeras of noncataractous and congenital cataractous mice. 366 66

Strain BALB/c and DBA/2 mice were chosen to investigate the effects of genetic background on the radiation-induced mutation rate since they exhibit differences in their radiation sensitivity. Males were exposed to 3 + 3-Gy X-irradiation and mated to untreated specific locus Test-stock females. Offspring resulting from treated spermatogonia were screened for induced specific locus forward and reverse mutations and dominant cataract mutations. Since BALB/c mice are homozygous brown and albino, specific locus forward mutations could be screened at 5 of the 7 specific loci (a, d, se, p, s), while reverse mutations could be screened at the b and c loci. Strain DBA/2 is homozygous non-agouti, brown and dilute. Therefore, specific locus forward mutations could be screened at 4 loci (c, se, p, s) and reverse mutations were screened at the a, b and d loci. Results indicate no effect of genetic background on the sensitivity to mutation induction of specific locus forward mutations, while for the dominant cataract alleles strain DBA/2 exhibited a higher mutation rate than either strain BALB/c or similarly treated (101/El X C3H/El)F1 mice. If, by confirmation, these differences should be demonstrated to be real, it is interesting that strain DBA/2 should exhibit a greater sensitivity to radiation-induced dominant mutations. First, strain DBA/2 was chosen as radiation resistant or repair competent. The observation that DBA/2 exhibited a higher sensitivity to radiation-induced mutation may indicate a role for repair, albeit misrepair, in the mutation process. Second, that the effect of genotype was only observed for the mutation rate to dominant cataract alleles may reflect a difference in the spectrum of DNA alterations which result in dominant or recessive alleles. A dominant allele is more likely misinformation, such that as heterozygote it interferes with the wild-type allele. By comparison, a recessive allele may result from any DNA alteration leading to the loss of a functional gene product. One reverse mutation at each of the a and d loci was recovered in the present experiments. The similarities of the present results for radiation-induced reverse mutations with the extensive data on the spontaneous reverse mutation rates are interesting. Reverse mutations were recovered only at the a and d loci. Further, the reverse mutations recovered at the a locus were to alternate alleles (at, Aw or Asy) while true reverse mutations were apparently recovered at the d locus.
 ...
PMID:Radiation-induced forward and reverse specific locus mutations and dominant cataract mutations in treated strain BALB/c and DBA/2 male mice. 382 62

The ocular histopathological response of C3-depleted and normal DBA/2J mice was compared after corneal scarification and experimental infection with topically applied Pseudomonas aeruginosa. Normal, non-C3-depleted mice were capable of mounting a vigorous polymorphonuclear leukocyte response at 24 h after bacterial challenge and eventually restored corneal clarity. In contrast, C3-depleted animals responded at 24 h to the ocular bacterial challenge with a decreased number of polymorphonuclear leukocytes migrating into the cornea. Additionally, the eyes of C3-depleted mice exhibited persistence of bacteria, cataract of the ocular lens, and loss of vision.
 ...
PMID:Effect of C3 depletion on experimental Pseudomonas aeruginosa ocular infection: histopathological analysis. 669 7

Male mice of the genotypes AKR, BALB/c, (102/ElxC3H/El)F1 or DBA/2 were exposed to 3 + 3 Gy irradiation with a 24 h fractionation interval and mated to untreated Test-stock females. The offspring were screened for activity alterations of 10 erythrocyte enzymes as well as recessive specific-locus and dominant cataract mutations. The observed mutation rates per locus per gamete x 10(-5) for treated spermatogonia were 6.8, 4.9, 2.5 and 1.3 for enzyme-activity mutations, 8.6, 24.1, 22.8 and 31.4 for specific-locus mutations, and 0.7, 0.9, 0.6 and 2.5 for cataract mutations, respectively. Some variability from strain to strain in the frequency of radiation-induced mutations was observed. However, there was no consistent effect of genotype on the frequency of induced mutations and it is concluded that no effect of genetic background exists for the four genotypes tested. There is good agreement between the observed enzyme-activity mutation rate in children of survivors of the atomic bombings and the expected mutation rate based on results with mice. Results are therefore consistent with an estimation of human radiation-induced genetic risks based upon an extrapolation of experimental results in the mouse.
 ...
PMID:Estimates of the radiation-induced mutation frequencies to recessive visible, dominant cataract and enzyme-activity alleles in germ cells of AKR, BALB/c, DBA/2 and (102xC3H)F1 mice. 796 68


1 2 Next >>