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Biomedical subjects

M L Williams

Publications and source records attributed to M L Williams.

At least 109 records · Page 6Linked to original sources
PubMed1994

Trichothiodystrophy: clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings.

Trichothiodystrophy (TTD), an autosomal recessive disorder characterized by sulfur-deficient brittle hair, identifies a group of genetic disorders with an altered synthesis of high-sulfur matrix proteins and a defect in excision repair of ultraviolet damage in fibroblasts of most TTD patients. In contrast to patients with xeroderma pigmentosum (XP), TTD patients do not have an increased frequency of skin cancers. TTD patients may be grouped into four categories: 1) those without photosensitivity and without a defect in excision repair of UV damage; 2) those without photosensitivity and with an excision-repair defect in the same gene as in XP-D (complementation group D); 3) those with photosensitivity and with the XP-D repair defect; 4) those with photosensitivity and with a repair defect distinct from that in XP-D. We present a brother and sister in the third category of TTD. Clinically, the patients have brittle hair, short stature, ichthyosis, photosensitivity, nail and dental dysplasias, cataracts, mental retardation, and pyramidal tract abnormalities. Diagnosis was made by hair mount, which shows the characteristic banding pattern with polarizing microscopy, and by hair amino acid analysis, which demonstrated decreased high-sulfur matrix proteins. Fibroblasts cultured from skin biopsies had a marked DNA excision repair defect similar to the repair defect seen in XP-D. We have documented a unique dysmyelinating disorder on magnetic resonance imaging of the brain that might explain their mental retardation, marked hyperactivity, and neurologic deficits. Following the discovery that the human excision repair cross complementing rodent ultraviolet group 2 (ERCC2) gene is able to correct the ultraviolet sensitivity of XP-D cell strains, the ERCC2 cDNA from previous TTD patients was sequenced and shows frameshifts, deletions and point mutations in the ERCC2 gene. Molecular analysis of our patients is in progress. Molecular analysis of the defects in ERCC2 in clinically distinct patients with XP,XP/Cockayne's syndrome, and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders.

Brain↗
PubMed1994

An experimental test of retention in residential and outpatient programs.

Previous studies of residential and outpatient drug treatment programs have found that retention is higher in residential than in outpatient programs. This study attempts to verify previous findings by conducting an experiment that controls for ecological, self-selection, and program content biases. The Houston Recovery Campus is a research-focused, multiple-provider drug treatment facility for the indigent of Harris County, Texas. During the study period, 646 applicants were randomly assigned to two comparable 28-day programs. The first program was a residential program; the second was an outpatient day treatment program. Twenty-eight day retention rates were significantly higher for the residential program (76%) compared to the day treatment program (64%).

Adult↗
PubMed1994

Illicit drug injectors in three Texas cities.

In three Texas cities illicit drug injectors not in treatment were located by outreach and interviewed with a standard questionnaire. In all the cities the drug injectors were predominantly undereducated and unemployed young men from minority groups. In Dallas and Houston most were Black, while in San Antonio most were Hispanic. The most frequently reported primary drug in Houston was cocaine, but in Dallas and San Antonio it was heroin. The high needle risk for AIDS and the low rates of positive HIV antibody tests in these samples present a special window of opportunity for prevention of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Melanoma risk factors and atypical moles.

Despite important advances in the treatment of melanoma, the prognosis for advanced disease remains discouraging. This fact, in combination with a worldwide epidemic of melanoma among persons of white skin type, has focused attention on identifying melanoma in its early, surgically curable stages. Attention has also been directed toward pinpointing which persons are at increased risk for melanoma to reduce risk where possible and to aid early diagnosis. Essentially all epidemiologic studies have identified an increased number of melanocytic nevi as an important risk factor in the development of melanoma, but controversy has arisen concerning the risk associated with certain types of nevi, particularly "dysplastic" nevi. We review melanoma risk factors and examine the relationship between melanocytic nevi and melanoma to clarify for primary care physicians what is "known" (non-controversial) and what is "unknown" (controversial). We propose a working definition of an atypical mole phenotype and outline an approach to managing high-risk patients.

Female↗
PubMed1994

MR of neurocutaneous melanosis.

PURPOSE: To describe the MR findings of neurocutaneous melanosis in the brain and correlate these with the known pathology and proposed embryologic basis of this disorder. METHODS: The brain (seven patients) and spine (three patients) MR scans of seven patients with neurocutaneous melanosis were retrospectively reviewed. In two patients, findings were confirmed at surgery. The pattern of central nervous system involvement was also correlated with known pathologic studies regarding frequency and location of melanotic deposits. RESULTS: Five patients had regions of T1 shortening in the cerebellum; three of these also had T2 shortening. Five patients had regions of T1 shortening in the anterior temporal lobes. Other areas of involvement included the pia mater over the cerebellum (two patients), pons (one patient), medulla (one patient), and left parietal lobe (one patient). Only two lesions showed enhancement, edema, or necrosis; both were proved malignant melanomas at biopsy. No pial enhancement was detected. CONCLUSION: Neurocutaneous melanosis appears to involve the brain in specific locations that can be detected on MR imaging. Knowledge of these locations can aid in differentiating metastases, secondary to malignant degeneration of the large cutaneous nevi, from melanotic deposits that are a part of the disease. Identification of malignant degeneration of the melanotic deposits is difficult; at present, it depends on the identification of growth, edema, or necrosis of the deposits.

Adolescent↗
PubMed1993

Dermatitis in treated maple syrup urine disease.

Two children who had classic maple syrup urine disease developed an eruptive dermatitis when plasma isoleucine levels, leucine levels, or both fell below normal during periods of protein restriction. The dermatitis was resistant to topical corticosteroid therapy. Rapid resolution occurred after treatment with isoleucine and leucine dietary supplements.

Dermatitis↗
PubMed1993

High-affinity fatty acid-binding activity in epidermis and cultured keratinocytes is attributable to high-molecular-weight and not low-molecular-weight fatty acid-binding proteins.

Fatty acid-binding proteins (FABPs) are abundant low-molecular-weight cytosolic proteins in tissues involved in fatty acid (FA) metabolism. Because epidermis is also an active lipogenic tissue, we examined cytosols from murine and porcine epidermis and cultured human keratinocytes and fibroblasts for FABPs. High-affinity FA-binding activity was present in both epidermis and differentiated keratinocytes, whereas no high-affinity FA-binding activity was found in cultured human fibroblasts or undifferentiated keratinocytes. By column chromatography, a single binding peak was identified in the high (90-100 kDa)-molecular-weight range and no binding activity was evident in the low (14-15 kDa)-molecular-weight range, where conventional FABPs elute. Moreover, rabbit anti-rat heart FABP, anti-rat intestine FABP, and anti-rat liver FABP antisera did not identify proteins in the 14-15-kDa range in murine epidermal cytosol by Western immunoblots, whereas the anti-rat-heart antibody recognized a protein of approximately 32 kDa. Isoelectric focusing of differentiated keratinocyte cytosol demonstrated a single FA-binding peak having a pI of approximately 4.0. Analysis of this binding peak by SDS-PAGE revealed peptides of approximately 66 and 38 kDa. These findings suggest the possibility that the FA-binding protein in keratinocyte cytosol normally exists as a heterodimer. Western immunoblots of both differentiated keratinocyte cytosol and keratinocyte-conditional media stained with a rabbit anti-human serum albumin antibody identified a protein of approximately 67 kDa, but the electrofocused fraction did not react with this antibody. Thus, epidermis and differentiated keratinocytes possess high-affinity cytosolic FA-binding activity that cannot be ascribed either to conventional low-molecular-weight FABPs or to albumin.

Binding, Competitive↗
PubMed1993

Lipid supplemented medium induces lamellar bodies and precursors of barrier lipids in cultured analogues of human skin.

Barrier function of cultured skin substitutes (CSS) is required for their effective use in clinical treatment of skin wounds, and for percutaneous absorption in vitro. Arachidonic, palmitic, oleic, and linoleic free fatty acids, in conjunction with the antioxidant alpha-tocopherol acetate (lipid supplements, "LS"), were added to nutrient media of CSS to provide precursors of epidermal barrier lipids. CSS were composed of human keratinocytes (HK), fibroblasts (HF), and collagen-glycosaminoglycan substrates, and were incubated for 14 d submerged or lifted to the air-liquid interface in media based on MCDB 153 +/- LS. Duplicate samples (30 cm2) were harvested and the epidermal analogue was analyzed for total protein, total DNA, total lipid, lipid fractions including acylglucosylceramide (AGC), and presence of lamellar bodies. Significant increases (p < 0.05) were detected between CSS incubated in +LS medium for total lipid, total DNA, ceramide, glucosylceramide, triglycerides, and diglycerides. AGC and lamellar bodies were detected only in epithelia of CSS incubated in +LS medium. These data show that free fatty acids, vitamin E, and lifting of CSS promote increased epithelial morphogenesis compared to CSS cultured submerged without lipid supplements. Presence of lamellar bodies and AGC suggests enhanced production in vitro of barrier-associated epidermal lipids.

Cell Cycle↗
PubMed1993

Glucocorticoids accelerate fetal maturation of the epidermal permeability barrier in the rat.

The cutaneous permeability barrier to systemic water loss is mediated by hydrophobic lipids forming membrane bilayers within the intercellular domains of the stratum corneum (SC). The barrier emerges during day 20 of gestation in the fetal rat and is correlated with increasing SC thickness and increasing SC lipid content, the appearance of well-formed lamellar bodies in the epidermis, and the presence of lamellar unit structures throughout the SC. Because glucocorticoids accelerate lung lamellar body and surfactant maturation in man and experimental animals, these studies were undertaken to determine whether maternal glucocorticoid treatment accelerates maturation of the epidermal lamellar body secretory system. Maternal rats were injected with betamethasone or saline (control) on days 16-18, and pups were delivered prematurely on day 19. Whereas control pups exhibited immature barriers to transepidermal water loss (8.16 +/- 0.52 mg/cm2 per h), glucocorticoid-treated pups exhibited competent barriers (0.74 +/- 0.14 mg/cm2 per h; P < 0.001). Glucocorticoid treatment also: (a) accelerated maturation of lamellar body and SC membrane ultrastructure; (b) increased SC total lipid content twofold; and (c) increased cholesterol and polar ceramide content three- to sixfold. Thus, glucocorticoids accelerate the functional, morphological, and lipid biochemical maturation of the permeability barrier in the fetal rat.

Animals↗
PubMed1993

Preservation of permeability barrier ontogenesis in the intrauterine growth-retarded fetal rat.

The epidermal permeability barrier is provided by intercellular lipids forming multiple membrane bilayers in the stratum corneum. In the fetal rat, the barrier to transepidermal water loss forms during the 20th d of gestation and is accompanied by 1) increasing stratum corneum thickness; 2) increasing stratum corneum lipid content, particularly nonpolar ceramide and cholesterol content; and 3) the formation of lamellar unit structures throughout the stratum corneum interstices. In this report, we demonstrate that among pups of 20 d gestational age increasing barrier competence is correlated with increasing fetal weight. It has been previously demonstrated that fetal rats subjected to intrauterine growth retardation (IUGR) exhibit a thinner stratum corneum and decreased content of differentiation-specific epidermal structural proteins. To determine whether IUGR fetal rats also exhibit immaturity of barrier function and the barrier membrane system, maternal rats underwent unilateral uterine vessel ligation on d 17 or 18 of gestation and IUGR and control littermates were harvested on d 20, 21, or 22 of gestation for determination of transepidermal water loss. Despite significant somatic growth retardation and a thinner stratum corneum, barrier function in IUGR fetal rats did not significantly differ from that in control littermates at any gestational age. In both IUGR and control fetal rat epidermis at 21 d gestational age, lipids were deposited in a membrane pattern as visualized by nile red fluorescence microscopy and formed lamellar unit membrane structures throughout the stratum corneum intercellular domains as observed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A preliminary ethnographic decision tree model of injection drug users' (IDUs) needle sharing.

This article presents a preliminary ethnographic decision tree model of the needle sharing and HIV risk decision-making processes common to injection drug users (IDUs) in Houston, Texas. Ethnographic tree decision modeling is a rigorous qualitative method used to understand and predict how and why people in certain groups do things the way they do. The model was developed from data collected from focus group and individual interviews and naturalistic observations. The research participants were White, African-American and Latino male and female IDUs. The model presents IDUs' needle-sharing routines or scripts based on several prioritized criteria. The model supports other researchers' findings that social roles play an important part in shaping IDUs' needle sharing. Yet, the model attempts to specify the different kinds of roles and relationships. The model suggests that social roles IDUs play and the status hierarchy between roles are the translation mechanisms that organize IDUs' social relationships into drug and HIV risky activities.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Pathobiology of the stratum corneum.

The epidermis is a dynamic system whose metabolic activity is regulated in large part by the integrity of the permeability barrier. This barrier resides in the stratum corneum and comprises a unique 2-compartment system of structural protein-enriched corneocytes embedded in a lipid-enriched intercellular matrix. Lipid extraction or metabolic imbalances, such as essential fatty acid deficiency, produce barrier abnormalities that in turn result in epidermal hyperproliferation, scaling, and inflammation. When the barrier remains intact, lipid imbalances, such as an abnormal cholesterol sulfate:cholesterol ratio in recessive X-linked ichthyosis, can lead to abnormal corneocyte adhesion (visible scale). Both cellular and intercellular proteins also participate in normal desquamation, and protein abnormalities may provoke abnormal scaling (such as filaggrin in ichthyosis vulgaris). Thus, perturbations of the stratum corneum may be the catalyst for a number of skin diseases, rather than the end result of processes that are initiated in subjacent skin layers.

Cell Membrane Permeability↗