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M L Williams

Publications and source records attributed to M L Williams.

At least 181 records · Page 10Linked to original sources
PubMed1987

Effects of cholesterol sulfate on lipid metabolism in cultured human keratinocytes and fibroblasts.

Effects of cholesterol sulfate on acetate incorporation into lipid fractions were examined in normal human fibroblast and keratinocyte cultures. Inhibition of sterologenesis in normal fibroblast cultures by cholesterol sulfate was less profound than that produced by either lipoprotein-containing serum or 25-hydroxycholesterol. Cholesterol sulfate also inhibited sterologenesis in low density lipoprotein receptor-deficient fibroblasts and inhibited both sterologenesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in keratinocytes. Cholesterol sulfate increased incorporation of acetate into fatty acid-containing lipids in preconfluent cultures of both cell types in lipoprotein-depleted media. Similar effects were not observed either in response to lipoprotein-containing serum or 25-hydroxycholesterol. Cholesterol sulfate had no effect on oleic acid incorporation into diglycerides, triglycerides, or phospholipid fractions; neither did it inhibit acid lipase activity; nor did it inhibit fatty acid oxidation, indicating that cholesterol sulfate does not inhibit catabolism of acyl lipids. Because cholesterol sulfate had similar effects on fatty acid metabolism in steroid sulfatase-deficient fibroblasts lines, desulfation to cholesterol is not a prerequisite. Cholesterol sulfate did not significantly affect incorporation of oleic acid into sterol esters in fibroblast cultures, but in contrast, inhibited sterol esterification in keratinocyte cultures. These data suggest a novel role for cholesterol sulfate as a modulator of cellular lipid biosynthesis.

Acetates↗
PubMed1987

The extracellular matrix of stratum corneum: role of lipids in normal and pathological function.

The mammalian stratum corneum, formerly treated as a homogeneous film, is now more properly viewed as a two-compartment system. The cornified cell is protein-enriched and lipid-depleted, lying embedded in an expanded extracellular matrix of highly nonpolar lipids. Because of its strategic location between the cornified layer, this lipid matrix is responsible for many phenomena related to the permeability barrier, as well as cohesion and desquamation. Thus, manipulation of this compartment could lead to enhanced drug delivery and improved lubrication, as well.

Alkanes↗
PubMed1987

Genetically transmitted, generalized disorders of cornification. The ichthyoses.

In this review, we have attempted to classify the genetically transmitted, generalized disorders of cornification according to available genetic, clinical, and biochemical data (Table 1). Admittedly, the list is long and sure to be lengthened, but this manner of delineation is required to uncover the underlying biochemical causes of the DOC. Grouping diseases according to artificial and outmoded standards clearly impedes this effort, as well as undermines a scholarly approach to patients, because important information about disease expression, differences in inheritance patterns, and subtle, but important, differences in responsiveness to therapy may be obscured by classification of an entity on the basis of overly simplified diagnostic criteria. Thus, clinicians should be wary of classification schemes based solely upon phenotypic similarities, because they may not be based upon valid genetic or biochemical criteria. Clearly, the classification offered in this article must be considered provisional, and it should be modified as new information is acquired. Despite our desire to recognize and codify distinct genetic disorders, this has not been possible in all cases, such as in DOC 17 (chondrodysplasia punctata syndromes), which almost certainly includes more than one genetic entity.

Chromosome Aberrations↗
PubMed1987

Ichthyosis induced by cholesterol-lowering drugs. Implications for epidermal cholesterol homeostasis.

Ichthyosis and other disorders of cornification may occur as side effects of treatment with several hypocholesterolemic agents. Recent progress in understanding of the functional role of lipids in stratum corneum provides a new pathophysiologic basis for these earlier clinical observations. In stratum corneum, lipids are segregated within intercellular membranes, where they appear to regulate permeability barrier function and desquamation. Cholesterol is an important constituent of these membranes and may be essential to both of these functions. Perturbation of barrier function induces cholesterologenesis locally within the epidermis. Polar sterol metabolites, such as cholesterol sulfate, may also regulate epidermal sterologenesis under normal or pathologic circumstances. Cholesterol homeostasis may also modulate desquamation. For example, hairless mice fed azacosterol hydrochloride (20,25-diazacholesterol) develop a generalized scaling disorder without loss of barrier function. In these mice, total stratum corneum sterol content is markedly decreased, and topical or systemic repletion with cholesterol can correct the scaling abnormalities.

Animals↗
PubMed1986

A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies.

We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Predominant risk factors included oxytocin stimulation of labor, dysfunctional labor, abnormal fetal heart rate, or meconium-stained amniotic fluid. This prospective alternate-month clinical trial took place over a 36-month period during which 34,995 women gave birth. In alternate months, either 7 (for "selective monitoring") or 19 (for "universal monitoring") fetal monitors were made available in the labor and delivery unit. During the "selective" months, 6420 of 17,409 women (37 percent) were electronically monitored, as compared with 13,956 of 17,586 women (79 percent) during the "universal months." Universal monitoring was associated with a small but significant increase in the incidence of delivery by cesarean section because of fetal distress, but perinatal outcomes as assessed by intrapartum stillbirths, low Apgar scores, a need for assisted ventilation of the newborn, admission to the intensive care nursery, or neonatal seizures were not significantly different. We conclude that not all pregnancies, and particularly not those considered at low risk of perinatal complications, need continuous electronic fetal monitoring during labor.

Adult↗
PubMed1986

Single-centre randomised trial of ritodrine hydrochloride for preterm labour.

106 women between 24 and 33 weeks' gestation and in preterm labour, rigidly defined to include cervical dilatation plus regular uterine contractions, were randomly allocated to receive either intravenous ritodrine hydrochloride or no tocolytic treatment. Ritodrine treatment significantly delayed delivery for 24 hours or less but did not significantly modify the ultimate perinatal consequences of preterm labour.

Adult↗
PubMed1986

Cholesterol sulfate uptake and outflux in cultured human keratinocytes.

Cholesterol sulfate-cholesterol homeostasis in the epidermis may be important for normal desquamation. Recent evidence from cell-culture studies indicates that cholesterol sulfate inhibits sterologenesis by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis. For cholesterol sulfate in the stratum corneum to function as a feedback regulator of epidermal sterologenesis, it must have the capacity enter cells. In these studies, uptake and outflux of cholesterol sulfate was examined in cultured human foreskin keratinocytes, and compared with uptake and outflux of cholesterol and 25-hydroxycholesterol, as well as with sterol uptake by another cell type, the skin fibroblast. The uptake of the free (not lipoprotein-associated) form of all three sterols was not consistent with a receptor-mediated process. Although the cholesterol sulfate uptake was approximately three-fold less than that of 25-hydroxycholesterol, it was nearly seven-fold greater than that of cholesterol itself. Whereas 25-hydroxycholesterol was rapidly washed out of keratinocytes in outflux experiments, both cholesterol and cholesterol sulfate tended to remain cell-associated. These studies demonstrate that cholesterol sulfate is readily taken up by keratinocytes, in which it may be in a position to modulate cellular lipid metabolism.

Cells, Cultured↗
PubMed1986

Interactions of cholesterol and cholesterol sulfate with free fatty acids: possible relevance for the pathogenesis of recessive X-linked ichthyosis.

Whereas the stratum corneum contains large amounts of unesterified cholesterol and minimal amounts of cholesterol sulfate, in recessive X-linked ichthyosis (RXLI), levels of cholesterol decrease while cholesterol sulfate content increases. To study the molecular basis for abnormal shedding in RXLI, we compared the interaction of cholesterol and cholesterol sulfate with the free fatty acid, hexadecanoic acid, by differential scanning calorimetry (DSC). While cholesterol and the free fatty acid formed a eutectic mixture, such an interaction did not occur upon mixing of cholesterol sulfate with hexadecanoic acid. In addition, and unexpectedly, free cholesterol appeared to undergo progressive autoxidation during repeated DSC measurements at only slightly supraphysiologic temperatures. These studies may provide a molecular mechanism for the abnormal desquamation that occurs in RXLI. The regular formation of oxidation products of cholesterol observed here, if matched by equivalent molecular events in vivo, may have important implications for epidermal pathophysiology.

Calorimetry, Differential Scanning↗
PubMed1986

Glucose threshold for macrosomia in pregnancy complicated by diabetes.

We analyzed 205 diabetic women treated with insulin during pregnancy to assess the effects of several maternal factors on the development of fetal macrosomia. A total of 95 women were selected for study because they had clearly defined gestational criteria, two or more daytime glucose profiles during the third trimester, and no other complications known to affect fetal growth. The incidence of macrosomia was not found to increase significantly until the mean glucose concentration reached 130 mg/dl; macrosomia occurred in 65% of mothers with glucose values greater than or equal to 130 mg/dl compared with 27% in those with lower values. Other factors strongly associated with fetal macrosomia were maternal weight and insulin dosage. Multiple logistic analysis was performed to control for each risk factor and to obtain estimates of the relative risk for macrosomia. The risk of macrosomia was two times greater in women with mean glucose concentrations greater than or equal to 130 mg/dl, approximately threefold in women whose weight exceeded 80 kg, and one and one half times greater in women with insulin dosages more than 80 units/day. We conclude that several maternal factors in addition to glucose concentration play important roles in the development of fetal macrosomia among diabetic women and that the glucose concentration threshold for macrosomia may exceed 130 mg/dl.

Adult↗
PubMed1986

Morphologic and microbiologic features of Pseudomonas aeruginosa pneumonia in normal hamsters.

A model of pneumonia due to Pseudomonas aeruginosa was produced in hamsters by an intratracheal bolus instillation of microorganisms. Sequential lung changes from 4 hr through 11 days were studied by morphologic and microbiologic methods. Hamsters inoculated with greater than 10(6) pseudomonads survived but consistently had histologic evidence of mild bronchopneumonia 24 hr postinoculation, whereas a severe bronchopneumonia and a 100% mortality were elicited with a 10(8) inoculum of organisms in 0.5 ml phosphate-buffered saline (PBS). An inoculum of 10(7) pseudomonads/0.5 ml PBS was then used to define the changes in the bacterial population in Pseudomonas pneumonia and to obtain serial histopathologic observations. Quantitative lung cultures obtained within 1 hr postinoculation demonstrated a mean of 10(6) colony forming units per lung, and none of the hamsters were bacteremic. However, by 24 hr bacterial counts had increased and all animals were bacteremic. Bacterial proliferation continued through 48 hr; however, the number of bacteremic animals had decreased. By 72 hr, bacterial counts had decreased with total Pseudomonas clearance noted by 120 hr. A striking polymorphonuclear leukocyte-rich alveolar exudate was present by 12 hr. Pseudomonas "vasculitis" was evident by 24 hr. The evolution of this vascular lesion correlated with the bacteremic state of the hamsters. By 11 days, resolution of the pneumonic process was seen. The macroscopic and microscopic features of this hamster model of Pseudomonas pneumonia are very similar to those reported in infected patients.

Animals↗
PubMed1986

Patterns of medical services utilization by infants discharged from a neonatal intensive care unit.

A decreasing neonatal mortality rate has increased the number of infants who survive their stay in a neonatal intensive care unit only to need continued medical care. Medical services utilization by families with high-risk infants has been widely studied, but research is sparse on high-risk infants who do not receive follow-up care through medical specialists' services or speciality clinics. After dividing medical services utilization into four patterns, ranging from use of only primary care to use of three kinds of medical services, the authors analyzed a set of predictors of utilization. The factors most likely to affect pattern of utilization significantly are related to health need and illness level. The infants with more serious medical conditions diagnosed at birth were found to use the most follow-up services. No effects of location of residence or social class were found, which suggests that families had no significant problems of access to medical care services for their infants in the defined region of the study.

Child Health Services↗
PubMed1985

Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and sterol synthesis by cholesterol sulfate in cultured fibroblasts.

Although widely distributed throughout mammalian tissues, the biological function of cholesterol sulfate remains largely unknown. In these studies we have demonstrated that cholesterol sulfate suppresses de novo sterol synthesis in cultured human fibroblasts. It was further shown in these cultured cells that cholesterol sulfate is a potent inhibitor of the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34), the rate-limiting enzyme in cholesterol biosynthesis and the site at which exogenous cholesterol suppresses endogenous cholesterol synthesis. Because cholesterol sulfate inhibited sterologenesis in steroid-sulfatase deficient fibroblasts derived from patients with recessive X-linked ichthyosis, it was inferred that cholesterol sulfate per se and not cholesterol liberated by intracellular desulfation was the inhibitor in these studies. Cholesterol sulfate may be an endogenous regulator of mammalian cholesterol biosynthesis.

Cell Division↗
PubMed1985

Heterogeneity in autosomal recessive ichthyosis. Clinical and biochemical differentiation of lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma.

Nonbullous congenital ichthyosiform erythroderma (CIE) and classic lamellar ichthyosis (LI) can be distinguished by clinical, histopathologic, and biochemical findings reported herein. Whereas all patients with CIE (n = 12) had fine white scales, they were heterogeneous with respect to degree of erythroderma, ectropion, and prognosis. In contrast, all patients with LI (n = 6) had large, dark, platelike scales, severe ectropion that showed no improvement with age, and minimal erythroderma. Although the stratum corneum of patients with LI was two to three times thicker than that of those with CIE, the latter group demonstrated more acanthosis, parakeratosis, hypergranulosis, and less prominent dermal capillaries. Studies of scale-lipid content have indicated biochemical correlates of this clinical heterogeneity. These clinical, histologic, and biochemical findings provide useful guidelines to differentiate CIE from LI and strongly suggest that autosomal recessive primary ichthyosis comprises two distinct diseases.

Adolescent↗
PubMed1985

Ichthyosis and neutral lipid storage disease.

Four members of a consanguineous middle eastern family had a lipid storage disease characterized by congenital ichthyosiform erythroderma, neurosensory deafness, cataracts, mild myopathy, and leukocyte vacuoles. These patients are similar to several others recently reported and represent a unique disorder of lipid metabolism. The clinical and biochemical manifestations of this lipid storage disease are reviewed. Evidence is presented that the disorder is inherited as an autosomal recessive trait, and that heterozygotes may be detected by the presence of vacuoles within circulating eosinophils.

Adolescent↗