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Biomedical subjects

P Grimes

Publications and source records attributed to P Grimes.

At least 19 recordsLinked to original sources
PubMed1997

Genetic mapping of a mouse ocular malformation locus, Tcm, to chromosome 4.

The Tcm mutation in the mouse is an autosomal dominant ocular malformation manifesting as microphthalmia, iris dysplasia, cataract, and coloboma. As a first step to cloning the Tcm gene, we report the localization of the Tcm mutation with respect to known microsatellite markers. Backcross progeny carrying the Tcm mutation were produced by mating Tcm/+ heterozygous mice to normal C57BL/6 partners. Genomic DNA from each mouse was subjected to PCR analysis to identify simple sequence length polymorphisms. Our results locate Tcm to Chr 4 and suggest candidate genes responsible for the Tcm phenotype. Finally, ocular histopathology was done in 3-week-old animals to define the extent of the malformation.

Abnormalities, Multiple↗
PubMed1997

The mouse Cat4 locus maps to chromosome 8 and mutants express lens-corneal adhesion.

Cat4 is the second largest allelism group in the collection of mouse dominant eye mutations recovered in Neuherberg and carriers express anterior polar cataract, central corneal opacity, and lens-corneal adhesions. We have mapped the Cat4 locus of the mouse to central Chromosome (Chr) 8 at position cM 31. Histological characterization of Cat4(a) heterozygotes and homozygotes indicates failure of separation of the lens vesicle from the surface ectoderm. Human anterior segment ocular dysgenesis (ASOD) is autosomal dominant, carriers express an eye phenotype similar to that of Cat4(a) carriers, and it has been mapped to a region of 4q homologous to mouse central Chr 8. Thus, on the basis of phenotype and map position, Cat4 may be a mouse model of human ASOD. The genes Junb, Jund1, Mel, and Zfp42 are discussed as possible candidates for Cat4.

Animals↗
PubMed1996

The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney.

We describe a new mouse frameshift mutation (Pax2(1Neu)) with a 1-bp insertion in the Pax2 gene. This mutation is identical to a previously described mutation in a human family with renal-coloboma syndrome [Sanyanusin, P., McNoe, L. A., Sullivan, M. J., Weaver, R. G. & Eccles, M. R. (1995) Hum. Mol. Genet. 4, 2183-2184]. Heterozygous mutant mice exhibit defects in the kidney, the optic nerve, and retinal layer of the eye, and in homozygous mutant embryos, development of the optic nerve, metanephric kidney, and ventral regions of the inner ear is severely affected. In addition, we observe a deletion of the cerebellum and the posterior mesencephalon in homozygous mutant embryos demonstrating that, in contrast to mutations in Pax5, which is also expressed early in the mid-hindbrain region, loss of Pax2 gene function alone results in the early loss of the mid-hindbrain region. The mid-hindbrain phenotype is similar to Wnt1 and En1 mutant phenotypes, suggesting the conservation of gene regulatory networks between vertebrates and Drosophila.

Abnormalities, Multiple↗
PubMed1993

Adrenergic innervation of the choroid and iris in diabetic rats.

We compared the distribution and density of ocular adrenergic nerves in rats after 3 to 13 months of streptozotocin diabetes and in age-matched control animals to learn whether diabetic sympathetic neuropathy is evident in the eye as it is in other organs. An aqueous aldehyde method for histochemical demonstration of catecholamines provided a clear and complete view of the adrenergic innervation in whole flat preparations of choroid and iris. In the choroid, a dense plexus of varicose nerve fibers invested all of the branching arterial blood vessels. A less dense network of nerves was present in the choroidal stroma between the arteries, but there was no obvious association of nerves with the venules draining choroidal capillaries. Using a stereological method to measure the density of the adrenergic plexus of choroidal arteries, we found the mean innervation density to be normal in diabetic animals sampled at 3, 9, and 13 months after onset of hyperglycemia. Microscopic examination also failed to reveal diabetes-associated changes in the diffuse stromal nerves of the choroid or in the rich adrenergic innervation of the iris. Diabetes of relatively long duration, therefore, does not obviously affect the density or distribution pattern of catecholamine-containing nerves supplying the rat eye.

Adrenergic Fibers↗
PubMed1993

Management of vitiligo.

Vitiligo is a disease of unknown origin that causes destruction of melanocytes in the skin, mucous membranes, the eyes, and occasionally in hairbulbs and in the ears. The loss of melanocytes alters both structure and function of these organs. The goals of therapy are multifold. The primary goal is to restore melanocytes to the skin so that the epidermis has a normal morphology. Such repigmented skin regains its normal immune/inflammatory functions.

Administration, Cutaneous↗
PubMed1986

Acute reversible cataract induced by xylazine and by ketamine-xylazine anesthesia in rats and mice.

Combined administration of ketamine and xylazine is used increasingly for safe, effective anesthesia of small laboratory animals. We found that rats injected systemically with ketamine and xylazine at doses recommended for effective anesthesia developed acute reversible lens opacities. Mice given the same drug doses were similarly affected. Testing of each drug alone demonstrated that xylazine was the causative agent. The appearance of cataract was associated to varying degree with proptosis, suppression of the blink reflex, corneal surface drying, and mydriasis. All of these ocular effects, including cataract also could be induced locally by topical application of xylazine to one eye, with untreated contralateral eyes showing no drug effects. A possible cause of xylazine-induced transient lens opacification is trans-corneal water loss and alteration of aqueous humor composition due to corneal exposure. Additional action on aqueous humor formation and the lens itself may be due to the alpha-2-adrenoceptor nature of xylazine. Whatever the cause of cataract induction, the occurrence of this phenomenon during ketamine-xylazine anesthesia appears to be associated with marked changes in the physiological state of the eye. Therefore, the side-effects of anesthetic drug combination should be considered prior to its use on animals for studies of ocular physiology.

Acute Disease↗
PubMed1980

Hepatic function in mononucleosis induced by Epstein-Barr virus and cytomegalovirus.

We evaluated serial enzyme and bilirubin determinations as aids to diagnosis of Epstein-Barr virus-induced infectious mononucleosis (121 cases) and the heterophil-negative mononucleosis-like illness due to cytomegalovirus (33 cases). Laboratory evidence for either type of mononucleosis includes mild to moderate hepatic dysfunction, with aspartate aminotransferase activity increased, but lower than commonly encountered in active viral hepatitis. Of the enzymes commonly assayed in evaluating liver function, aspartate aminotransferase activity was the most commonly abnormal: in 96.7% of those with Epstein-Barr virus disease and 87.9% with cytomegalovirus disease. Values for alkaline phosphatase were increased in 94.2% of the Epstein-Barr virus cases and 63.6% of the cytomegalovirus cases, and gamma-glutamyltransferase values were increased in 90.9% and 75.8%, respectively. We conclude that, in serially studied patients, normal results for liver-function studies or very high aspartate aminotransferase activities (greater than 1000 U/L) eliminate, for practical purposes, both Epstein-Barr virus and cytomegalovirus as diagnostic considerations.

Adolescent↗
PubMed1976

Inhibition of cell division in rat lenses by prostaglandin E1.

Prostaglandin E1 (PGE1) suppresses mitotic activity in the epithelial cells of rat lenses maintained in organ culture. At a concentration of 5 x 10(-5)M, PGE1 caused gradual inhibition of mitosis which was first evident after six hours of incubation and was maximum at 50 per cent of control values after 16 and 24 hours in culture. During this period prostaglandin-treated lenses showed no change in the number of cells labeled with H3-thymidine, but the amount of radioactive precursor incorporated per cell was reduced by almost half. At a higher concentration (1 x 10(-4)M) PGE1 evoked a transient mitotic inhibition within the first few hours of culture, but caused cell damage after 24 hours of incubation; a lower dose (1 x 10(-5M) had no influence on mitotic activity.

Animals↗