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L A Goldsmith

Publications and source records attributed to L A Goldsmith.

At least 37 records · Page 2Linked to original sources
PubMed1997

Genetic skin diseases with altered aging.

Integration, homeostasis, and redundancy of function are hallmarks of important biological processes. Individual gene defects may overcome and override normal homeostatic systems and lead to dramatic, recognizable phenotypes by profoundly altering 1 or more physiological systems. Classical human geneticists interested in a monogenetic disease began at the level of altered function and struggled to determine the genomic defect of that disease. In the past 1 1/2 decades, many monogenetic defects have been identified by positional cloning, and the abnormal gene has been characterized. A challenge for current investigators is to understand how a genetic defect, identified by a DNA mutation, leads to the altered phenotype. This effort is not trivial, since there are multiple metabolic and structural consequences of a single altered gene. Further complexity results from individual genetic changes being modified by the genetic diversity of the human host. Pleiotropy refers to the phenomenon of multiple phenotypic effects of a single gene.

Aging↗
PubMed1996

Full proceedings from the National Conference to Develop a National Skin Cancer Agenda. American Academy of Dermatology and Centers for Disease Control and Prevention, Washington, D.C., April 8-10, 1995.

National efforts to reduce skin cancer incidence and mortality require scientifically coordinated efforts. This report summarizes the first American Academy of Dermatology/Centers for Disease Control and Prevention national conference to develop a skin cancer agenda. Leading experts in dermatology, public health, medicine, health education, nursing, behavioral sciences, environmental health and epidemiology identified and prioritized skin cancer control issues in five key areas. Discussion centered around strategies for reducing UV exposure and increasing public and professional awareness of skin cancer. Panelists in five sessions developed consensus on several public and professional recommendations and a series of research strategies.

Health Education↗
PubMed1996

Skin effects of air pollution.

The skin is a target organ for pollution and also allows the penetration of exogenous agents into the body. About 700,000 new cases of skin cancer were diagnosed in 1993, and 9100 people died of cancer; 76% of the deaths were due to melanoma. Skin cancers are most closely associated with exposure to UVB (290 to 320 nm) irradiation. For every 1% decrease in ozone there is a 2% increase in UVB irradiance, and therefore a 2% increase in skin cancer is predicted. Therefore the atmospheric pollution by ozone-depleting chemicals is a major concern to dermatologists. In addition to being a target organ and site of neoplasms and contact allergens, the skin is the site of significant absorption of environmental pollutants. In the case of chloroform, the percutaneous absorption is equivalent to the respiratory uptake, emphasizing how important it is to recognize skin absorption in toxicologic exposures.

Air Pollutants↗
PubMed1996

Localization of the Darier disease gene to a 2-cM portion of 12q23-24.1.

Positional cloning with microsatellite markers allowed further localization of the Darier disease gene to a 2-cM interval of chromosome 12, 12q23-24.1, between the polymorphic loci D12S234 and D12S129. A region this size is suitable for construction of a contig to identify the Darier disease gene. Use of a polymorphic intronic marker for nitric oxide synthetase 1 gene, which maps to the same chromosomal area as the Darier gene, allowed exclusion of that gene as the Darier disease gene.

Chromosome Mapping↗
PubMed1996

A model for keratinocyte gene therapy: preclinical and therapeutic considerations.

Gene transfer to the skin is essential for correcting genetic disorders and studying skin biology. Previous attempts at in vivo gene transfer have employed replication-deficient adenovirus injected subcutaneously and plasmid DNA propelled by a gene gun. In this report, we used mouse skin as a model and evaluated the efficiency of these two methods. Using the luciferase reporter gene, we found that adenovirus injected subcutaneously transduced primarily cells in the dermis. However, particle bombardment of skin by gene gun delivered the reporter gene mainly into the epidermis. When mouse skin was bombarded with a DNA construct expressing human TGF-alpha, the epidermis of the treated mice showed localized epidermal acanthosis and hypergranulosis, which resembled the histological phenotype of previously described transgenic mice overexpressing TGF-alpha in the epidermis. These results suggest that the gene gun may be an effective tool for epidermal gene transfer and could be potentially useful in determining in vivo effects of growth factors and cytokines on the epidermis.

Adenoviruses, Human↗
PubMed1995

Golfer's nails.

Explore the source record for details and available documents.

Adult↗
PubMed1995

Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis.

OBJECTIVE: To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death. METHODS: A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used. RESULTS: Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage. CONCLUSION: Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines.

Clinical Protocols↗
PubMed1995

Biological monitoring of iodine, a water disinfectant for long-term space missions.

In order to establish guidelines for exposure of astronauts to iodine, used as a water disinfectant in space, we studied the usefulness of hair, saliva, and urine for biological monitoring in humans and in the human hair/nude mouse model. The monitoring of iodine in patients that received 150 mCi of Na131I (carrier-free) showed similar patterns of elimination for blood, saliva, and urine. The mean correlation coefficient (r) between iodine elimination for blood/saliva was 0.99, for blood/urine, 0.95, and for saliva/urine, 0.97. The absolute value of iodine concentrations in urine revealed marked variability, which was corrected by adjusting for creatinine levels. The autoradiographic studies of human hair demonstrated that iodine is rapidly incorporated into external layers of the hair root and can be removed easily during washing. These data were confirmed after iodine exposure using the human hair/nude mouse model. Hair does not provide satisfactory information about exposure due to unstable incorporation of iodine. The most useful medium for biological monitoring of astronauts exposed to high doses of iodine in drinking water is urine, when adjusted for creatinine, and saliva, if quantitative evaluation of flow rate is provided.

Animals↗
PubMed1995

The latest fashions in skin disease.

The complex nature of epidermal tissue homeostasis is borne out by the range of diseases affecting this tissue. Indeed, mutations in proteins involved in intracellular integrity and cell-cell or cell-matrix adhesion can cause disease in an appropriate epidermal compartment. The most important realization in epidermal disease in the last two years has been that point mutations in key structural genes can result in filaments collapsing, cell cytolysis, or cell adhesion defects; and that these defects can result in severe human skin disease. Now that these associations have been made, the important next step will be to alleviate the suffering of these patients. Animal models will be an important part of these investigations; many molecules including growth factors, oncogenes, and cell adhesion molecules have been targeted to the epidermis of transgenic mice to investigate their role in disease. Such animal models should also elucidate the causes of diseases like psoriasis, a very common skin disease, the molecular basis of which remains elusive. Gene therapy involving the replacement of defective genes or local delivery of therapeutic molecules will be one of the main goals in alleviating these known epidermal diseases. Such protocols in the epidermis are aided by the relative accessibility of the skin and the presence of the "stem cells" in relatively accessible compartments. Indeed, as the last few years have shed much light on the genetic causes of epidermal disease, it is hoped that the next several years will prove as illuminating in the alleviation of these diseases.

Animals↗
PubMed1994

Apoptosis in human skin development: morphogenesis, periderm, and stem cells.

During human skin development, embryonic- and fetal-specific periderm cells and incompletely keratinized cells are replaced by keratinocytes that differentiate while stratifying to form the fully functional epidermis. Proliferating basal cells of fetal skin also develop into epidermal appendages such as hair follicles and glands. We demonstrate that programmed cell death, not emphasized in conventional epidermal biology, has an important function in establishing the final architecture of the human epidermis and its appendages. Immunohistochemical localization of transglutaminases in fetal periderm, intermediate epidermal cells, and within appendages coincides with DNA fragmentation indicating that apoptosis is involved in deletion of these stage-specific cells and remodeling of appendages. The data also suggest that terminal differentiation of epidermal cells might be a specialized form of apoptosis. The pattern of expression of bcl-2, a gene associated with survival of some cells, is exclusive of the distribution patterns of markers of the cell death pathway. Bcl-2 protein is correlated with specific morphogenetic events in hair follicles and eccrine sweat glands, and its presence in single cells of the hair follicle bulge suggests that Bcl-2 may be a stem cell marker.

Adult↗
PubMed1994

Melanocytic nevi in Turner syndrome.

One morphologic feature of Turner syndrome is increased numbers of melanocytic nevi; however, little attention has been given to their characterization. The development of a melanoma in one of our patients with Turner syndrome prompted this study. We prospectively examined 10 patients with the disease, confirmed by karyotype. All patients underwent full body skin examination noting the number, size, distribution, and degree of clinical atypia of melanocytic nevi. Representative and unusual lesions were photographed. An average of 115 nevi were seen, with the majority measuring 1 to 5 mm. Most were located on the back and extremities. Clinical atypia was uncommon. Our patients had larger numbers of benign-appearing nevi than the general population. Large numbers of melanocytic nevi is a risk factor for melanoma, suggesting that these patients have an increase in one risk factor. Longitudinal studies are indicated to clarify this issue; nevertheless, we recommend periodic skin examinations and the regular use of sunscreens for individuals with Turner syndrome.

Adolescent↗
PubMed1993

Homeobox genes and skin development: a review.

Homeobox (HOX) genes are a gene family that encode information critical for the normal embryologic development of many different organisms, including vertebrates. HOX genes encode transcriptional regulatory factors that bind to multiple different genes and thereby determine the developmental fate of a cell. The role of HOX genes in the development of skin is undetermined but, based on information from other organisms and recent experimental data from skin models, it is likely that this class of genes is important for the normal development of skin adnexae, pigmentary system, and stratified epidermis during embryogenesis. The purpose of this review is to briefly summarize what is known about HOX genes and to familiarize the reader with recent insights into how HOX genes may function in skin development.

Animals↗
PubMed1993

Molecular biology of the skin introduction: approaches and principles.

This issue of Seminars in Dermatology describes our current understanding of the molecular nature of skin diseases. Some would say it is hubris to even contemplate this charge considering the rapid progress in molecular genetics. We implore the gods protecting the nucleotides to look kindly on our efforts. This introductory article discussed some general methodological considerations and techniques and provides a glossary of common terms used in molecular biology, useful for understanding this issue of Seminars in Dermatology. This article is aimed at neophytes to enhance their ability to enter the magical realm of the gene. The articles in this issue describe diseases with a defined defect at the DNA level or diseases in which there is a rapid closing in on the basic defect.

Genetic Techniques↗
PubMed1993

Mendelism in early 20th-century American dermatology.

Now, almost a century ago since Mendel's work was rediscovered, is a propitious time to review the appearance of mendelian concepts in American dermatology. In our world of instantaneous and sometimes overwhelming dissemination of new information and the apparent rapid incorporation of new knowledge into our specialty, it is useful to examine how heredity was incorporated in the dermatologic literature in the first 25 years of the 20th century. The dermatologic literature serves as a surrogate for the thought of the era.

Dermatology↗