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Biomedical subjects

R E Williams

Publications and source records attributed to R E Williams.

At least 19 recordsLinked to original sources
PubMed1992

Parathyroid hormone stimulates protein kinase C but not adenylate cyclase in mouse epidermal keratinocytes.

Intact human parathyroid hormone, hPTH [1-84], and the hPTH [1-34] fragment stimulated membrane-associated protein kinase C (PKC) activity in immortalized (but still differentiation-competent) murine BALB/MK-2 skin keratinocytes. Unexpectedly, the hormone and its fragment did not stimulate adenylate cyclase. The failure of PTH to stimulate adenylate cyclase activity was not due to the lack of a functioning receptor-cyclase coupling mechanism because the cells were stimulated to synthesize cyclic adenosine monophosphate (cyclic AMP) by the beta-adrenergic drug isoproterenol. Thus, skin keratinocytes seem to have an unconventional PTH receptor that is coupled to a PKC-activating mechanism but not to adenylate cyclase. These observations suggest that normal and neoplastic skin keratinocytes respond to the PTH-related peptide that they make and secrete.

Adenylyl Cyclases↗
PubMed1992

Maximal exercise response of paraplegic wheelchair road racers.

The maximal metabolic responses of 11 paraplegic wheelchair road racers were evaluated with 2 wheelchair exercise protocols: increasing speed and increasing resistance. The maximal heart rates, minute ventilations and oxygen uptakes were similar for the 2 tests, indicating that either protocol is suitable for maximal wheelchair dynamometer exercise tests for groups. The resulting data were then compared to published data on maximal arm exercise by athletic and non athletic paraplegics and ambulatory males of the same age group. The combined mean values for both exercise tests of maximal oxygen consumption rate (VO2max = 37.4 ml/kg/min), minute ventilation (VE = 109.4 l/min), respiratory exchange quotient (RQmax = 1.18) and heart rate (187 beats/min) are in the mid range of reported data on wheelchair athletes. The mean RQ and heart rate values were similar to those achieved by ambulatory individuals performing maximal exercise tests. The mean VO2max of 37.4 ml/kg/min in our subjects is comparable to that achieved by sedentary ambulatory males of this age group. The data and the comparison to published data suggest several conclusions: in some parameters elite male paraplegic road racers have maximal values similar to those of ambulatory males, and in others they have maximal values substantially lower than might be expected; there is considerable variability among paraplegics in the metabolic responses to maximal exercise, most likely related to differences in cardiovascular fitness; and paraplegics can improve their cardiovascular fitness by training.

Adult↗
PubMed1992

Re-examining crude coal tar treatment for psoriasis.

Two separate, double-blind, randomized, half-and-half body comparisons, each involving 20 in-patients with psoriasis, were conducted to compare the effect of different concentrations of crude coal tar in yellow soft paraffin. The therapeutic effect of 1% crude coal tar used twice daily for 10 days was significantly less than that achieved with an incremental regimen starting at 5% and increasing by 5% every second day to a maximum of 25%. No such difference was seen when a steady concentration of 5% was compared with the same incremental regimen. We conclude that there appears to be no benefit from exceeding a concentration of 5% crude coal tar in yellow soft paraffin in the treatment of patients with psoriasis and that the plateau in the dose-response curve for the action of crude coal tar in psoriasis begins at a point between 1 and 5%.

Administration, Topical↗
PubMed1992

Staphylococcus aureus and intra-nasal mupirocin in patients receiving isotretinoin for acne.

Thirty patients commencing isotretinoin for acne were entered into a double-blind, randomized, placebo-controlled trial to investigate the effect of pulsed intra-nasal mupirocin ointment on Staphylococcus aureus colonization and isotretinoin-related side-effects. In both mupirocin and placebo groups there was an increase in isolation of S. aureus throughout the period of treatment with isotretinoin from the anterior nares, facial skin and lips. However, these increases were significantly less in the mupirocin-treated group. A high proportion of all patients suffered inflammatory side-effects of isotretinoin such as cheilitis and nasal vestibulitis, with their maximum severities being recorded 2 months after starting isotretinoin. In spite of the smaller increase in S. aureus colonization in the mupirocin-treated group no difference was demonstrated in either the incidence of specific S. aureus infections (e.g. furunculosis) or the prevalence of isotretinoin-related inflammatory side-effects. Furthermore, no relationship between the presence of S. aureus and the severity of inflammatory side-effects was shown. Streptococcus species were isolated on four separate occasions from four different patients during the study but their pathogenicity was unclear. These findings suggest that although pulsed intra-nasal mupirocin produces a significant reduction in isotretinoin-related staphylococcal colonization, its routine use cannot be justified on the basis of clinical benefit.

Acne Vulgaris↗
PubMed1992

Effects of high-probability requests on the acquisition and generalization of responses to requests in young children with behavior disorders.

The failure to respond to requests in young children often is maintained by the reactions of the adults that encounter this behavior. This failure to respond to requests has been identified as a primary reason for the children's exclusion from community, social, and instructional opportunities. Numerous interventions that target the failure to respond have consisted of punishment and reinforcement procedures. More recently, antecedent interventions have focused on changing the context in which a request is delivered. In the current study, high-probability requests were provided as an antecedent to delivering a low-probability request. The requests were delivered by multiple trainers in an attempt to produce generalized appropriate responding to adults who did not use the high-probability sequence. Results showed an immediate increase in appropriate responding in 2 children when the intervention was delivered. In addition, when the intervention was implemented by more than one adult, spontaneous increases in responding also were observed toward adults who had never implemented the request sequence. Improvements in responding to requests were maintained after the intervention was discontinued.

Aggression↗
PubMed1992

Assessing treatment effects through changes in perceptions and cognitive organization.

This investigation tested the Associative Group Analysis (AGA) for its analytic sensitivity in assessing perceptions and attitudes and in mapping changes in cognitive organization indicative of substance abuse. Based on inferences drawn from the distributions of thousands of spontaneous, free associations elicited by strategically selected stimulus themes, AGA offers an unstructured approach to assess images and meanings, and to map systems of mental representation evasive to the more direct methods of using questions or scales. This article compares pretreatment and posttreatment samples, tracing the psychosocial effects of treatment. The investigations focus on variables related to substance abuse such as self-image, social nexus, and perceptions of illicit substances. The results indicate a sensitive approach, useful in treatment evaluation.

Cognitive Behavioral Therapy↗
PubMed1991

The direct measurement of protein kinase C (PKC) activity in isolated membranes using a selective peptide substrate.

A protein kinase C (PKC)-selective peptide substrate was used to develop a method for measuring PKC activity directly and quantitatively in isolated cell membranes without prior detergent extraction and reconstitution of the enzyme with phosphatidylserine and TPA in the presence of excess Ca2+. This simple and rapid method can reliably measure changes in membrane-associated PKC activity induced by various bioactive compounds such as hormones and growth factors. Also, this method, which measures PKC activity in its native membrane-associated state, has the advantage of being able to distinguish between active and inactive PKC associated with cell membranes.

Amino Acid Sequence↗
PubMed1991

The effects of fifth graders' socially directed behavior on motor and social responses of children with severe multiple handicaps.

Two elementary-aged boys with severe, multiple handicaps participated in social play activities with nonhandicapped fifth graders. Increases in all participants' socially directed behavior were observed consistent with teachers' instructions to play together. In addition to social behavior increases, both boys with handicaps showed increases in targeted motor responses when interacting with the fifth graders. Donald, for example, substantially increased the amount of extended arm reaching and grasping/manipulating. David increased the amount of time he kept his head in either a full or partially upright position. The results of the investigation are considered in terms of extending the positive outcomes of handicapped-nonhandicapped peer social interactions.

Adolescent↗
PubMed1991

Local forearm vasodilation with intra-arterial administration of enalaprilat in humans.

To determine whether converting enzyme inhibitors could produce peripheral vasodilation through a local mechanism, we infused enalaprilat, 2 micrograms/min/dl forearm volume (FAV), into the brachial artery of normal subjects and measured changes in forearm blood flow (FBF) with strain-gauge plethysmography. Enalaprilat produced a peak increase in FBF of 2.82 +/- 0.54 ml/min/dl FAV (78% increase) at 1 minute (p less than 0.01 versus vehicle) and an increase of 1.11 +/- 0.28 ml/min/dl FAV at 4 minutes (p less than 0.05 versus vehicle). Blood pressure and plasma renin activity measured at the completion of infusion did not change. Intravenous enalaprilat infusion at the same dose in seven additional normal subjects did not increase FBF. Pretreatment of seven subjects with 75 mg oral indomethacin attenuated the peak response to enalaprilat (4.13 +/- 1.52 versus 0.58 +/- 0.32 ml/min/dl; p less than 0.05). We conclude that intra-arterial enalaprilat produces an increase in FBF in normal subjects. This peripheral vasodilation is caused by a local effect independent of circulating renin-angiotensin system inhibition. This response is attenuated by indomethacin, suggesting that prostaglandins contribute to the vasodilator response.

Blood Pressure↗
PubMed1991

Treatment with deferoxamine during ischemia improves functional and metabolic recovery and reduces reperfusion-induced oxygen radical generation in rabbit hearts.

BACKGROUND: Iron may play a central role in oxygen radical generation during myocardial ischemia and after reperfusion. Because conditions during ischemia may also liberate iron, we hypothesized that administration of the iron chelator deferoxamine during ischemia would result in improved functional and metabolic recovery after postischemic reperfusion. METHODS AND RESULTS: Isolated, perfused rabbit hearts were studied by phosphorus-31 nuclear magnetic resonance spectroscopy. The hearts received one of three treatments: deferoxamine at the onset of 30 minutes of global ischemia (n = 9), deferoxamine as a bolus followed by a continuous 15-minute infusion begun at reflow (n = 9), or standard perfusate (n = 7). Hearts treated with deferoxamine during ischemia showed better recovery of developed pressure than did control hearts (63.2 +/- 7.5% versus 41.2 +/- 2.9% of baseline) (p = 0.02) and better recovery of myocardial phosphocreatine content (92.4 +/- 10.3% versus 68.2 +/- 4.5% of baseline, p less than 0.05). These functional and metabolic benefits were comparable to those obtained with deferoxamine treatment during early reperfusion. In 15 additional hearts, intraischemic treatment with deferoxamine resulted in no reduction in oxygen radical concentrations as measured on frozen tissue by electron paramagnetic resonance spectroscopy at end ischemia, but the treatment eliminated the reperfusion-induced increase of free radical generation observed in control hearts (2.9 +/- 0.01 versus 7.0 +/- 0.07 microM, p less than 0.001). The magnitude of reduction was similar to that when deferoxamine was given at the onset of reflow (2.4 +/- 0.02 microM, p less than 0.001 versus control). CONCLUSIONS: These results demonstrate improved functional and metabolic recovery of myocardium treated with deferoxamine during ischemia, accompanied by a reduction in reperfusion-induced oxygen free-radical generation to the same degree as reflow treatment, confirming the importance of iron in the pathogenesis of myocardial reperfusion injury.

Animals↗
PubMed1991

Endothelium-dependent vasodilation is attenuated in patients with heart failure.

BACKGROUND: Endothelial cells produce a number of substances, collectively termed endothelium-derived relaxing factor (EDRF), that promote local relaxation of vascular smooth muscle. Although studies have demonstrated defects in endothelium-dependent vasodilation in animal models of hypertension, atherosclerosis, and heart failure, there are only limited data from human subjects because of the difficulty in obtaining fresh vascular segments. METHODS AND RESULTS: To address the hypothesis that endothelium-dependent vasodilation is attenuated in patients with heart failure, we measured forearm blood flow responses to the intra-arterial administration of methacholine, a known stimulus of EDRF release through muscarinic receptors. In 14 normal subjects, a dosage range of methacholine increased forearm blood flow by 5.26 +/- 0.63, 10.50 +/- 0.63, and 13.22 +/- 0.86 ml/min/100 ml forearm volume (FAV); these responses were 1.98 +/- 0.46, 5.48 +/- 0.79, and 8.50 +/- 1.53 ml/min/100 ml FAV in 14 patients with heart failure. When pooled over all doses, the responses were strikingly less in the patients with heart failure (5.32 +/- 0.31 versus 9.52 +/- 0.60 ml/min/100 ml FAV; p = 0.0003). In a second study, the average difference in forearm blood flow responses between patients with heart failure and normal subjects with methacholine was significantly greater than the average difference between the groups with nitroprusside (4.04 +/- 1.10 versus 2.20 +/- 0.71 ml/min/100 ml FAV; p = 0.04). The decreased methacholine responses in the patients with heart failure were not related to age (r = 0.39; p = NS) or etiology because there was no difference in the responses between patients with ischemic heart disease and those with idiopathic cardiomyopathy. CONCLUSIONS: These data suggest that endothelium-dependent vasodilation is attenuated in patients with heart failure. Although the mechanisms of the decreased endothelium-dependent responses in heart failure are not known, this impaired local vasodilation may contribute to abnormalities in vasoconstriction that are characteristic of heart failure.

Adult↗
PubMed1990

Human granulocyte colony-stimulating factor: biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines.

Human granulocyte colony-stimulating factor (G-CSF) is a regulatory glycoprotein that stimulates the production of neutrophilic granulocytes from committed hematopoietic progenitor cells both in vitro and in vivo. In this report, we show that biosynthetic (recombinant) human G-CSF enhances colony formation by normal human bone marrow and the human myeloid leukemic cell lines, HL-60 and KG-1, as well as nonhematopoietic small cell lung cancer lines, H128 and H69. G-CSF also modulates multiple differentiated functions of human neutrophils, including enhanced oxidative metabolism in response to f-Met-Leu-Phe (f-MLP), increased antibody-dependent cell-mediated cytotoxicity (ADCC), and augmented arachidonic acid release in response to ionophore and chemotactic agents. These effects are all maximal at a concentration of 100 to 500 pmol/L. Using 125I-labeled recombinant human G-CSF, high affinity binding sites were identified on human neutrophils, the myeloid leukemia cell lines KG-1 and HL-60, and the small cell carcinoma cell lines, H128 and H69. G-CSF receptor numbers ranged between 138 and 285 sites per cell with a kd of 77 to 140 pmol/L, consistent with the concentrations of G-CSF that elicit biologic responses in vitro. Decreased specific binding of 125l-G-CSF by human neutrophils was consistently observed in the presence of excess unlabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF), suggesting competition or down modulation by GM-CSF of the G-CSF receptor.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

An analysis of the regions of the myelin basic protein that bind to phosphatidylcholine.

The interactions of phosphatidylcholine (PC) to regions of the myelin basic protein (MBP) was examined. In solid phase binding assays the nature of the binding of unilamellar vesicles of 14C-labeled phosphatidylcholine to bovine 18.5 kDa MBP, its N- and C-terminal peptide fragments, photooxidized 18.5 kDa MBP and the mouse 14 kDa protein, with an internal deletion of residues 117-157, was studied. The data were analyzed by computer-generated Scatchard plots in which non-specific binding was eliminated. Non-cooperative, low affinity binding of PC vesicles to MBP was observed, and this binding found to be sensitive to pH and ionic changes. At an ionic strength of 0.1 and pH 7.4, the binding of PC to the 14 kDa mouse MBP exhibited a Kd similar to that obtained with both the N-terminal and photooxidized 18.5 kDa bovine MBP. The studies indicated that the sites of PC interaction with MBP are located in the N-terminal region of the protein. The C-terminal region appeared to modulate the strength of the interaction slightly. Under similar conditions, lysozyme did not bind PC liposomes, and histone bound them nonspecifically.

Animals↗
PubMed1990

Assessment of a contact-plate sampling technique and subsequent quantitative bacterial studies in atopic dermatitis.

The aerobic bacterial flora of 20 patients with atopic dermatitis and 19 control subjects was extensively sampled using the Williamson and Kligman scrub technique and a contact-plate method (cysteine lactose electrolyte deficient media). Comparison of the two quantitative techniques showed that the contact plate is a reliable and convenient alternative to the scrub technique for the quantification of Staphylococcus aureus, micrococci and coagulase negative staphylococci. Quantification of bacterial flora using both techniques showed high rates of colonization by S. aureus on both involved and clinically normal skin of patients with atopic dermatitis. A linear increase in S. aureus counts with increasing severity of dermatitis was found. In contrast, diphtheroids showed a trend of decreasing isolation rates and counts as the severity of the dermatitis increased. Isolation rates and absolute counts for micrococci/coagulase negative cocci were unaffected by the severity of the dermatitis.

Adult↗
PubMed1989

Role of the maleyl-albumin receptor in activation of murine peritoneal macrophages in vitro.

It has been previously demonstrated that maley-lated-BSA (maleyl-albumin) induces functional activation in murine peritoneal macrophages. Furthermore, maleyl-albumin has been shown to interact with two distinct sites on human monocytes; one site is the scavenger receptor, a 260-kDa oligomeric protein which recognizes modified forms of low density lipoprotein (LDL), and the second is a lower affinity site which has yet to be structurally characterized. In the present study, we wished to quantitatively assess the number and character of maleyl-albumin-binding sites on murine peritoneal macrophages and to determine which site or sites are involved in signaling the macrophage to undergo extensive functional development. Binding studies. demonstrate at least two distinct receptors for maleyl-albumin on murine peritoneal macrophages. Scatchard analyses of the binding isotherms reveal two sites characterized by dissociation constants (Kd) of 17.6 nM and 4.9 microM and maximal binding of 1.2 x 10(5) and 1 x 10(6) sites/cell, respectively. The contribution of the scavenger receptor, determined by binding analyses of malondialdehyde-LDL, is described by two sites with Kd of 39.4 pM and 9.6 nM, and maximal binding of 2.7 x 10(3) and 1.9 x 10(4) sites/cell, respectively. Maleyl-albumin blocks binding of malondialdehyde-LDL, whereas modified LDL fails to inhibit binding of maleyl-albumin. Maleyl-albumin, at concentrations producing lower affinity binding, stimulates tumor cytolysis, expression of mRNA encoding TNF, and suppression of INF-gamma-induced expression of Ia Ag. Malondialdehyde-LDL fails to elicit these responses. We conclude that macrophage activation produced by maleyl-albumin is mediated by interaction with the low affinity, high capacity binding site for maleyl-albumin rather than the scavenger receptor.

Albumins↗
PubMed1989

Overlapping direct repeats stimulate deletions in specially designed derivatives of plasmid pBR325 in Escherichia coli.

Current misalignment mutagenesis models have identified certain sequences such as direct and inverted repeats, which can stabilize transient misalignments on single-stranded DNA, as major structural parameters for deletions. We have constructed derivatives of the plasmid pBR325 to investigate further the relative roles of such sequences under controlled conditions. The plasmid derivatives pOCE15, pRS1 and pRS4, were obtained by cloning fragments of the same approximate size (60-64 bp) but different sequence into the unique EcoR1 site of the chloramphenicol acetyl transferase (cat) gene of plasmid pBR325. The insert of pOCE15 is a perfectly palindromic lac operator fragment. Both pRS1 and pRS4 carry the same non-palindromic fragment but differ from each other in the sequence at the right (3') end of the insert. Plasmid pRS4 differs from pRS1 by a 9-bp duplication containing an additional EcoR1 site at the 3' end of the insert. This arrangement yields overlapping imperfect 17-18 bp and perfect 11 bp direct repeats at the deletion termini and creates multiple opportunities for the stabilization of misaligned intermediates. The deletion rate, measured from the reversion of chloramphenicol sensitivity (Cms) to resistance (Cmr), was always highest in pRS4, intermediate in pOCE15 and lowest in pRS1, with an approximate ratio of 100:10:1. We have also obtained evidence for the participation of RecA in the genesis of deletions in these pBR325-derived plasmids.

Base Sequence↗