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Biomedical subjects

M Kaiser-Kupfer

Publications and source records attributed to M Kaiser-Kupfer.

14 recordsLinked to original sources
PubMed1992

Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences.

Ornithine delta-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate. Inherited deficiency of ornithine delta-aminotransferase results in ornithine accumulation and a characteristic chorioretinal degeneration, gyrate atrophy of the choroid and retina. We have surveyed the ornithine delta-aminotransferase genes of gyrate atrophy patients for mutations. Using a variety of techniques, we discovered and molecularly characterized 21 newly recognized ornithine delta-aminotransferase alleles. We determined the consequences of these and three previously described mutations on ornithine delta-aminotransferase mRNA, antigen, and enzyme activity in cultured fibroblasts. The majority (20/24) of these alleles produce normal amounts of normally sized ornithine delta-aminotransferase mRNA. By contrast, only 2/24 had normal amounts of ornithine delta-aminotransferase antigen. Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine delta-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine delta-aminotransferase and cause gyrate atrophy in these patients.

Alleles↗
PubMed1990

Second eye involvement in age-related macular degeneration: a four-year prospective study.

Age-related macular degeneration (AMD) usually affects both eyes over time. Among patients with advanced AMD in one eye estimates of the risk to the second eye have been diversely reported. Therefore we examined, over a four year period, the rate of second eye involvement in 41 patients with either exudative or advanced atrophic AMD in one eye, and early macular changes in the second eye with best corrected vision of 20/30 or better. The cumulative risk of developing either exudative AMD or atrophic AMD and 20/80 or less vision in the second eye was 23% at four years. The cumulative risk of losing 10 or more letters on the ETDRS visual acuity chart in the second eye was 35% at four years. These results are discussed in relation to previously reported rates of second eye involvement in AMD.

Age Factors↗
PubMed1989

At least two mutant alleles of ornithine delta-aminotransferase cause gyrate atrophy of the choroid and retina in Finns.

Gyrate atrophy of the choroid and retina (GA) is an inherited chorioretinal degeneration caused by deficiency of ornithine delta-aminotransferase (OAT; L-ornithine: 2-oxo-acid aminotransferase; EC 2.6.1.13). GA is one of the "Finnish genetic diseases," a group of several rare monogenic disorders that occur with increased frequency in the Finnish population. Using a combination of RNase A protection, genomic cloning, and polymerase chain reaction amplification of genomic DNA, we found one of two missense mutant OAT alleles to be present in each of 16 Finnish GA pedigrees. The first mutation R180T, in which arginine-180 is replaced by threonine, was present in homozygous form in patients from two pedigrees. The second mutation L402P, in which leucine-402 is replaced by proline, was present in homozygous form in patients from 14 pedigrees. Neither mutation was present in 19 Finnish controls. L402P was not present in 18 non-Finnish GA patients but R180T was found in an American GA patient. We constructed full-length mutant cDNAs by amplifying patient cDNA with the polymerase chain reaction and cloning a restriction fragment containing the mutation into an otherwise normal human OAT cDNA. These mutant cDNAs were then expressed in CHO-K1 cells, which lack endogenous OAT. Both R180T and L402P inactivate OAT. These results show molecular heterogeneity in GA alleles even in the Finnish population.

Alleles↗
PubMed1988

An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration caused by deficiency of the mitochondrial matrix enzyme, ornithine-delta-aminotransferase (OAT). To study the molecular basis of the mutations causing GA, we cloned and sequenced the human OAT cDNA and determined the intron-exon arrangement of the structural gene. Using the cDNA template, we synthesized antisense RNA probes and performed RNase A protection experiments with RNA from four Lebanese GA patients. We found a probe-target mismatch at the 5' end of the first coding exon and amplified this region of the patients' genomic DNA using the polymerase chain reaction. Sequence analysis showed a G----A transition, changing the initiator ATG (methionine) codon to ATA. This mutation segregates with the GA allele in both pedigrees. Initiation of translation at the closest in-frame methionine codon would truncate OAT by 138 amino acids, eliminating the entire mitochondrial leader sequence and 113 amino acids of the mature peptide.

Choroid↗
PubMed1984

Cellular and humoral immune parameters among patients with retinitis pigmentosa and other retinal disorders.

Patients with retinitis pigmentosa, other retinal degenerations and a group of normal volunteers were included in a masked study designed to examine the existence of autoimmune reactions toward retinal antigens and the possible defect in lymphokine production (IL-1, IL-2 and gamma interferon). The results obtained did not show any specific anamnestic response to the retinal S-Ag nor any outstanding defect in gamma interferon production by the lymphocytes of patients with retinitis pigmentosa. It is suggested that a larger masked study be conducted as soon as possible in order to clarify these aspects of immune aberrations in patients with retinitis pigmentosa.

Antibody Formation↗
PubMed1983

Cataract in gyrate atrophy: clinical and morphologic studies.

The clinical appearance of the cataract in nine phakic patients with gyrate atrophy of the choroid and retina is described. The gross and microscopic examination of three cataractous lenses removed from patients 31 years to 47 years of age is reported. Clinically, the lens opacities appeared primarily along the confluence of the sutures posteriorly, interfering with vision because of their location in the visual axis. Histologically the region of the posterior sutures was filled with liquified and degenerated lens material typical of senile cataractous changes. By the second decade, cataract is a uniform finding in patients with gyrate atrophy and appears to be unique as compared with cataracts associated with other forms of retinal degeneration.

Adult↗
PubMed1981

Successful treatment of sudden hearing loss in Cogan's syndrome with corticosteroids.

Cogan's syndrome (CS) is the association of acute nonsyphilitic interstitial keratitis and acute episodes of vertigo, tinnitus, and hearing loss. We have prospectively followed 6 patients with CS who were treated within 4 weeks after the acute onset of hearing loss. Within 1 to 2 weeks after the initiation of corticosteroid therapy, all 6 patients demonstrated improved hearing thresholds for pure tones and supra-threshold speech discrimination results. These patients have been followed an average of 2.5 years (range 0.25-9 years); all have only mild to moderate hearing impairment in the mid (1,000 to 2,000 Hz) and low (250 to 500 Hz) frequency sound ranges. Three of the patients have been tapered off steroids completely with no subsequent permanent decrement of hearing. Thus, early oral corticosteroid administration to patients with sudden hearing loss associated with Cogan's syndrome may preserve auditory function.

Acute Disease↗
PubMed1977

Progressive bilateral essential iris atrophy.

Bilateral progressive essential iris atrophy, more advanced in one eye than in the other, occurred in a 24-year-old white man. Histopathologic examination of the iris from the eye with the more advanced iris atrophy disclosed no vascular abnormalities in that the vessels were patent and appeared normal except for accumulated perivascular connective tissue. Fluorescein angiographic examination of the fellow eye that was undergoing the earliest changes of iris atrophy failed to reveal any vascular abnormalities. However, tonographic examination indicated a markedly decreased outflow facility. There does not appear to be any vascular abnormality involved in the pathogenesis.

Adult↗
PubMed1976

Progressive bilateral essential iris atrophy.

A case of bilateral progressive essential iris atrophy, more advanced in one eye than the other, has been studied. Histopathologic examination of the iris from the eye with the more advanced iris atrophy failed to find any vascular abnormalities in that the vessels were patent and appeared normal except for accumulated perivascular connective tissue. Fluorescein angiographic examination of the right eye which was undergoing the earliest changes of iris atrophy failed to show any vascular abnormalities. However, tonographic examination indicated a markedly decreased outflow facility. There does not appear to be any vascular abnormality involved in the pathogenesis of this case.

Adult↗
PubMed1975

The histopathology of pigmentary dispersion syndrome with glaucoma.

Iris tissue and trabecular meshwork, obtained at time of trabeculectomy, was studied using the light and electron microscope in a 54-year-old woman with pigmentary dispersion syndrome with glaucoma. The specific defect was a loss of the outer epithelial cells of the iris with marked thinning of the remaining outer layers so that the two-cell architecture of the iris epithelium was maintained. In addition, the radial muscle layer was increased in both number and size of muscle fiber. It would appear that the pigmentary dispersion syndrome may represent a congenital or developmental abnormality of the iris epithelium, or both, and that the glaucoma which occasionally occurs in conjunction with this syndrome is of the usual open-angle type.

Atrophy↗