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Biomedical subjects

M B Gorin

Publications and source records attributed to M B Gorin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Long-term tamoxifen citrate use and potential ocular toxicity.

PURPOSE: To estimate the prevalence of abnormalities in visual function and ocular structures associated with the long-term use of tamoxifen citrate. METHODS: A single-masked, cross-sectional study involving multiple community and institutional ophthalmologic departments was conducted with a volunteer sample of 303 women with breast cancer currently taking part in a randomized clinical trial to determine the efficacy of tamoxifen (20 mg/day) in preventing recurrences. Participants included women who had never been on drug (n=85); women who had taken tamoxifen for an average of 4.8 years, then been off the drug for an average of 2.7 years (n=140); and women who had been on tamoxifen continuously for an average of 7.8 years (n=78). Women were evaluated by questionnaire, psychophysical testing, and clinical examination to determine any abnormalities in visual function and the comparative prevalences of corneal, lens, retinal, and optic nerve pathology. RESULTS: There were no cases of vision-threatening ocular toxicity among the tamoxifen-treated participants. Compared with nontreated participants, the tamoxifen-treated women had no differences in the activities of daily vision, visual acuity measurements, or other tests of visual function except for color screening. Intraretinal crystals (odds ratio [OR]=3.58, P=.178) and posterior subcapsular opacities (OR=4.03, P=.034) were more frequent in the tamoxifen-treated group. CONCLUSIONS: Women should have a thorough baseline ophthalmic evaluation within the first year of initiating tamoxifen therapy and receive appropriate follow-up evaluations.

Aged↗
PubMed1998

A practice-based survey of familial age-related maculopathy.

PURPOSE: We evaluated the efficacy of a practice-based survey of age-related maculopathy (ARM) to identify potential families for molecular genetic studies. Demographic and ophthalmic features of the eligible study population were compared with responders and with individuals who reported a positive family history of ARM. METHODS: Individuals seen within a three-year period in a comprehensive ophthalmic practice were identified through billing codes. Clinical records were reviewed, coded, and merged with questionnaire responses. Patient identifiers were removed prior to analyses. RESULTS: There were no significant differences between the respondents and the eligible cohort with respect to gender, age, or type of macular degeneration. Comparable percentages of younger and older individuals with ARM reported positive family histories. The distribution of atrophic macular degeneration, choroidal neovascular membranes, and milder forms of the disease among the individuals reporting positive family histories corresponded to the distribution of the entire eligible cohort of patients. CONCLUSIONS: This recruitment strategy for ARM families is cost-effective and confirmed a high prevalence of familial ARM. The respondents are representative of the general ARM population. This approach is applicable for other ophthalmic genetic conditions.

Aged↗
PubMed1998

Linkage analysis of X-linked cone-rod dystrophy: localization to Xp11.4 and definition of a locus distinct from RP2 and RP3.

Progressive X-linked cone-rod dystrophy (COD1) is a retinal disease affecting primarily the cone photoreceptors. The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus. We have refined the COD1 locus to a limited region of Xp11.4, using two families reported elsewhere and a new extended family. Genotype analysis was performed by use of eight microsatellite markers (tel-M6CA, DXS1068, DXS1058, DXS993, DXS228, DXS1201, DXS1003, and DXS1055-cent), spanning a distance of 20 cM. Nine-point linkage analysis, by use of the VITESSE program for X-linked disorders, established a maximum LOD score (17.5) between markers DXS1058 and DXS993, spanning 4.0 cM. Two additional markers, DXS977 and DXS556, which map between DXS1058 and DXS993, were used to further narrow the critical region. The RP3 gene, RPGR, was excluded on the basis of two obligate recombinants, observed in two independent families. In a third family, linkage analysis did not exclude the RPGR locus. The entire coding region of the RPGR gene from two affected males from family 2 was sequenced and was found to be normal. Haplotype analysis of two family branches, containing three obligate recombinants, two affected and one unaffected, defined the COD1 locus as distal to DXS993 and proximal to DXS556, a distance of approximately 1.0 Mb. This study excludes COD1 as an allelic variant of RP3 and establishes a novel locus that is sufficiently defined for positional cloning.

Alleles↗
PubMed1997

Spectrum of malignancy and premalignancy in Carney syndrome.

Carney syndrome is a rare, autosomal dominant, multi-system disorder comprising 8 well-characterized findings, only 2 of which need be present for a definitive diagnosis. Benign neoplasms are frequent, but malignancies are thought to be uncommon. We have studied a family to clarify the diagnosis and spectrum of clinical manifestations of the syndrome and to develop guidelines for management. The proposita, a 34-year-old woman had classic findings of Carney syndrome, invasive follicular carcinoma of the thyroid gland, Barrett metaplasia of the esophagus, neoplastic colonic polyps, bipolar affective disorder, and atypical mesenchymal neoplasm of the uterine cervix distinct from the myxoid uterine leiomyoma usually seen in this syndrome. Although thyroid gland neoplasm is rare in Carney syndrome, this patient's most aggressive manifestation was her thyroid carcinoma. The diagnosis of Carney syndrome was established in her 9-year-old son and is a probable diagnosis in her 12-year-old daughter. Endocrine manifestations were prominent in the family with at least 9 relatives in 3 generations affected with various endocrine abnormalities. The findings in this family indicate that the spectrum of manifestations in this pleiotropic gene apparently includes a malignant course with premalignant and endocrinologic disorders not previously recognized.

Adult↗
PubMed1997

A gene responsible for the pigment dispersion syndrome maps to chromosome 7q35-q36.

OBJECTIVES: To demonstrate the inheritance of the pigment dispersion syndrome in 4 families and to determine the location of a gene responsible for this syndrome. PATIENTS: Fifty-four members of 4 families affected by the pigment dispersion syndrome and pigmentary glaucoma. All 4 families are white. Two of the pedigrees are of Irish descent, and 2 are of mixed western European descent that includes some Irish ancestry. INTERVENTIONS: Individuals from 4 pedigrees affected by the pigment dispersion syndrome and their spouses were clinically examined for evidence of the pigment dispersion syndrome. DNA samples from patients and appropriate family members were used for a genome screen using microsatellite repeat markers distributed throughout the human genome. Genotypes were used for linkage analysis to identify markers segregating with the disease trait. RESULTS: Twenty-eight patients showed clinical evidence of the pigment dispersion syndrome. Of these, 14 also had elevated intraocular pressures requiring medical or surgical treatment or both. Significant linkage was observed between the disease phenotype and markers located on the telomere of the long arm of human chromosome 7 (i.e., 7q35-q36). The maximum 2-point lod score (i.e., Zmax) for a single pedigree (i.e., PDS5) was 5.72 at theta = 0 for markers D7S2546 and D7S550. An analysis of affected recombinant individuals demonstrated that the responsible gene is located in a 10-centimorgan interval between markers D7S2462 and D7S2423. CONCLUSIONS: The pigment dispersion syndrome was found to be inherited as an autosomal dominant trait in 4 affected pedigrees. The gene responsible for the syndrome in these 4 families maps to the telomeric end of the long arm of chromosome 7 (i.e., 7q35-q36). Locating a gene responsible for this condition is the first step toward the isolation of the gene itself. Characterization of the responsible gene will help elucidate the pathophysiology of this disease and potentially will lead to new methods of diagnosis and treatment.

Adolescent↗
PubMed1996

New polymorphic markers in the vicinity of the pearl locus on mouse chromosome 13.

We have used a Mus domesticus/-Mus spretus congenic animal that was selected for retention of Mus spretus DNA around the pearl locus to create a highly polymorphic region suitable for screening new markers. Representation difference analysis (RDA) was performed with either DNA from the congenic animal or C57BL/6J as the driver for subtraction. Four clones were identified, characterized, and converted to PCR-based polymorphic markers. Three of the four markers equally subdivide a 10-cM interval containing the pearl locus, with the fourth located centromeric to it. These markers have been placed on the mouse genetic map by use of an interspecific backcross panel between Mus domesticus (C57BL/6J) and Mus spretus generated by The Jackson Laboratory.

Animals↗
PubMed1996

Recurrence of a choroidal neovascular membrane in a patient with punctate inner choroidopathy treated with daily doses of thalidomide.

PURPOSE: To determine whether thalidomide therapy can prevent a recurrence of a choroidal neovascular membrane in a patient with punctate inner choroidopathy. METHODS: Case report. In a 38-year-old woman with bilateral punctate inner choroidopathy, thalidomide therapy was initiated three days after laser photocoagulation of a choroidal neovascular membrane. RESULTS: The patient had a recurrence of the choroidal neovascular membrane eight months after the start of thalidomide therapy. CONCLUSIONS: The failure of thalidomide to prevent a recurrence of a choroidal neovascular membrane in this patient suggests that this medication may have only a limited benefit in preventing recurrences of choroidal neovascular membranes.

Adult↗
PubMed1996

An integrated genetic map of the pearl locus of mouse chromosome 13.

We have used a Mus domesticus/spretus congenic animal and two interspecific backcross panels to map genetically 30 sequence-tagged sites (STSs) and 13 genes to the vicinity of the pearl locus on mouse chromosome 13. The STSs defining the mapped region are from D13Mit9 to D13Mit37, spanning 10.6 cM. Genes mapped to this region include Versican (Cspg2), GTPase activating protein (Rasa), dihydrofolate reductase (Dhfr), arylsulfatase (As-1), thrombin receptor (Cf2r), hexosaminidase b(Hexb), 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr), microtubule associated protein 5/1b (Mtap5), phosphodiesterase (Pde), phosphatidylinositol 3' kinase (Pik3rl), rat integrin a1-subunit (Itga1), collagen receptor a2-subunit (Itga2), and 5-hydroxytryptamine 1a receptor (Htr1a). This high resolution genetic map of the pearl region of chromosome 13 establishes the order of multiple markers, including genes whose human homologs are located within a limited region of human chromosome 5, with respect to the phenotypic anchor marker pearl.

Animals↗
PubMed1996

Tamoxifen-associated eye disease. A review.

PURPOSE: The oral antiestrogen tamoxifen has demonstrated efficacy in the treatment of metastatic breast cancer and as adjuvant therapy in early-stage disease. Clinical trials of tamoxifen in chemoprevention of breast cancer among high-risk women have focused attention on potential adverse effects of long-term tamoxifen use, including the possibility of ocular toxicity. This review evaluates the published case reports, clinical series, and clinical trial data on ocular toxicities attributed to tamoxifen. Clinical issues of surveillance, differential diagnosis, and management of tamoxifen-related eye disease are discussed. DESIGN: National Library of Medicine online bibliographic services were used to identify case reports and clinical studies of ocular adverse effects that occurred in patients receiving tamoxifen published through the fall of 1994. The medical literature relevant to issues raised by the reports and studies was similarly identified and reviewed. RESULTS: Case reports and case series identify crystalline retinal deposits, macular edema, and corneal changes as potential tamoxifen ocular toxicities. Extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen. Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms. CONCLUSION: Ocular toxicity is uncommon in the current clinical setting of long-term, low-dose tamoxifen use. Physicians should be aware of the potential for ocular toxicity among patients receiving the drug and should assure appropriate surveillance and prompt evaluation of visual complaints.

Aging↗
PubMed1996

Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients.

Usher syndrome type 1b (USH1B) is an autosomal recessive disorder characterized by congenital profound hearing loss, vestibular abnormalities, and retinitis pigmentosa. The disorder has recently been shown to be caused by mutations in the myosin VIIa gene (MYO7A) located on 11q14. In the current study, a panel of 189 genetically independent Usher I cases were screened for the presence of mutations in the N-terminal coding portion of the motor domain of MYO7A by heteroduplex analysis of 14 exons. Twenty-three mutations were found segregating with the disease in 20 families. Of the 23 mutations, 13 were unique, and 2 of the 13 unique mutations (Arg212His and Arg212Cys) accounted for the greatest percentage of observed mutant alleles (8/23, 31%). Six of the 13 mutations caused premature stop codons, 6 caused changes in the amino acid sequence of the myosin VIIa protein, and 1 resulted in a splicing defect. Three patients were homozygotes or compound heterozygotes for mutant alleles; these three cases were Tyr333Stop/Tyr333Stop, Arg212His-Arg302His/Arg212His-Arg302His, and IVS13nt-8c-->g/Glu450Gln. All the other USH1B mutations observed were simple heterozygotes, and it is presumed that the mutation on the other allele is present in the unscreened regions of the gene. None of the mutations reported here were observed in 96 unrelated control samples, although several polymorphisms were detected. These results add three patients to single case reported previously where mutations have been found in both alleles and raises the total number of unique mutations in MYO7A to 16.

Alleles↗
PubMed1995

Sequence analysis and exclusion of phosducin as the gene for the recessive retinal degeneration of the Abyssinian cat.

Phosducin was evaluated as a candidate gene for the recessive retinal degeneration in the Abyssinan cat, rdAc, using reverse transcription and polymerase chain amplification. The nucleotide sequence of the cat phosducin coding region was determined except for 23 bp at the 5' end. Single-strand conformation analysis of a silent polymorphism within the coding region established the nonlinkage of the phosducin gene with the rdAc locus.

Amino Acid Sequence↗
PubMed1995

A peripherin/retinal degeneration slow mutation (Pro-210-Arg) associated with macular and peripheral retinal degeneration.

BACKGROUND: Mutations in the peripherin/retinal degeneration slow (RDS) gene have been identified in patients with retinitis pigmentosa and pattern macular dystrophy. The authors initially examined a large family affected with both peripheral and macular degeneration, inherited as an autosomal dominant trait. Screening for peripherin/RDS mutations identified a previously unreported nucleotide alteration in all of the affected individuals. Two additional families later were found to have this same mutation. METHODS: DNA samples from the members of three unrelated families were screened for peripherin/RDS mutations by denaturing gradient gel electrophoresis of the polymerase chain reaction-amplified peripherin/RDS coding sequences. The sequence change that was detected was further characterized by DNA sequencing. Family members were examined and evaluated with psychophysical and electrophysiologic methods. RESULTS: A proline to arginine mutation in codon 210 of peripherin/RDS was found in all clinically affected individuals. Macular changes included extensive geographic atrophy, pigment epithelial changes, and/or drusen. The proline to arginine mutation was not found among 100 healthy individuals, making it unlikely to be a nondisease-causing polymorphism. CONCLUSIONS: The authors identified a novel peripherin/RDS gene mutation associated with autosomal dominant retinal degeneration in patients from three different families. The largest family showed a broad variability in the expressivity of the mutation. The overlap of clinical features with those of age-related maculopathy highlights the need to consider photoreceptor-specific genes as potential factors in the etiology of the latter condition.

Adolescent↗
PubMed1995

Prevalence of lens changes in Ukrainian children residing around Chernobyl.

The objective of this study is to determine the prevalence and characteristics of lens changes in the eyes of a pediatric population, 5-17 y old, living in the permanent control zone around the Chernobyl nuclear reactor and to compare these findings with those from an unexposed control population. A total of 1,787 children are reported on (996 exposed and 791 unexposed). Over three-quarters of the subjects examined in this study show a form of minor change, termed focal lens defect, in the cortical and/or nuclear portions of the lens of the eye. The exposed group shows a small (3.6%), but statistically significant excess (p = 0.0005) of subclinical posterior subcapsular lens changes similar in form to changes identified in atomic bomb survivors. These posterior subcapsular changes tend to occur in boys 12-17 y old and in exposed children who report consuming locally grown mushrooms on a regular basis.

Adolescent↗
PubMed1994

Clinical diversity and chromosomal localization of X-linked cone dystrophy (COD1).

X-linked progressive cone dystrophy (COD1) causes progressive deterioration of visual acuity, deepening of central scotomas, macular changes, and bull's-eye lesions. The cone electroretinography (ERG) is variably abnormal in affected males, and the rod ERG may also be abnormal. The clinical picture of heterozygous females ranges from asymptomatic to a widespread spectrum of cone-mediated dysfunction. A prior linkage study demonstrated linkage between the COD1 locus and the marker locus DXS84, assigned to Xp21.1, with no recombination. In the present study, we have clinically characterized a large four-generation family with COD1 and have performed a linkage analysis using seven polymorphic markers on the short arm of the X chromosome. No recombination was observed between the disease and the marker loci DXS7 and MAOA, suggesting that the location of COD1 is in the region Xp11.3, distal to DXS84 and proximal to ARAF1.

Child↗
PubMed1994

Efficient strategies for genomic searching using the affected-pedigree-member method of linkage analysis.

The affected-pedigree-member (APM) method of linkage analysis is a nonparametric statistic that tests for nonrandom cosegregation of a disease and marker loci. The APM statistic is based on the observation that if a marker locus is near a disease-susceptibility locus, then affected individuals within a family should be more similar at the marker locus than is expected by chance. The APM statistic measures marker similarity in terms of identity by state (IBS) of marker alleles; that is, two alleles are IBS if they are the same, regardless of their ancestral origin. Since the APM statistic measures increased marker similarity, it makes no assumptions concerning how the disease is inherited; this can be an advantage when dealing with complex diseases for which the mode of inheritance is difficult to determine. We investigate here the power of the APM statistic to detect linkage in the context of a genomewide search. In such a search, the APM statistic is evaluated at a grid of markers. Then regions with high APM statistics are investigated more thoroughly by typing more markers in the region. Using simulated data, we investigate various search strategies and recommend an optimal search strategy that maximizes the power to detect linkage while minimizing the false-positive rate and number of markers. We determine an optimal series of three increasing cut-points and an independent criterion for significance.

Female↗
PubMed1993

Sequence-specific scission of DNA by RNAs linked to a chemical nuclease.

RNAs linked to the chemical nuclease 1,10-phenanthroline-copper cut double-stranded DNA of complementary sequence. This cleavage reaction is applicable to all sequences and can be used to measure the distance between marker genes in base pairs, map the size of a transcription unit and define positions of chromosomal breakpoints.

Copper↗