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Biomedical subjects

W Clark

Publications and source records attributed to W Clark.

At least 73 records · Page 4Linked to original sources
PubMed1993

The amateur Radio Emergency Service (ARES) and the National Disaster Medical System (NDMS).

The rescue, treatment, and evacuation of thousands of patients from a natural disaster or armed conflict that is coordinated by the National Disaster Medical System must be performed in accordance to health care standards recognized in this country. Without an effective communication system, morbidity and mortality will needlessly rise. A medical communication protocol that addresses this problem is proposed.

Communication↗
PubMed1993

Gene-regulatory properties of Myc helix-loop-helix/leucine zipper mutants: Max-dependent DNA binding and transcriptional activation in yeast correlates with transforming capacity.

Max is a basic helix-loop-helix/leucine zipper (bHLH/LZ) protein that forms sequence-specific DNA-binding complexes with the c-Myc oncoprotein (Myc). Using Saccharomyces cerevisiae, we have shown that the Max bHLH/LZ domain enables Myc to activate transcription through CACGTG and CACATG sequences in vivo, and that the number and context of such sites determines the level of activation. In addition, we have used yeast to investigate the role of the Myc helix-loop-helix (HLH) and leucine zipper (LZ) motifs in mediating Max-dependent DNA-binding and transcriptional activation in vivo using HLH/LZ mutants generated by site-directed mutagenesis. The results show that, while both motifs are essential for Myc to activate transcription, helix 2 of the HLH together with the contiguous LZ suffice to mediate complex formation with Max, whilst helix 1 is essential for sequence-specific DNA binding of Myc-Max complexes. Furthermore, the ability of Myc HLH/LZ mutants to bind DNA and activate transcription in collaboration with Max correlates closely with their neoplastic transforming activity in higher eukaryotic cells.

Base Sequence↗
PubMed1992

A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group.

Sixty-three patients with crescentic glomerulonephritis (cellular crescents in greater than 50% of glomeruli) were considered for a prospective randomized trial comparing intravenous methylprednisolone, prednisone, and azathioprine with and without plasma exchange. Of 32 patients who fulfilled the inclusion criteria for this study, 16 were randomly assigned to receive drug therapy (control) and 16 to receive plasma exchange as well. The randomization was stratified for initial need of dialysis, and the presence of oliguria and sclerosis. Renal pathology was similar in the two groups of patients. There was no significant difference in the number of patients initially on dialysis who were able to discontinue it during the study (2/7 control v 3/4 plasma exchange), whereas no control but two plasma exchange-treated patients started dialysis during the study. Serum creatinine at randomization was similar in the two groups: 769 +/- 486 mumol/L (8.7 +/- 5.5 mg/dL) in the control group versus 643 +/- 275 mumol/L (7.3 +/- 3.1 mg/dL) in the plasma exchange group. There was no significant difference between the two groups in mean serum creatinine, change in serum creatinine, change in reciprocal, or change in logarithm of serum creatinine at 1, 3, 6, or 12 months following randomization. Power calculation, assuming a 20% difference would be clinically relevant, was 0.94 at 12 months. There was significant morbidity in both groups; there were two deaths within 1 year of randomization, both of pulmonary infection and both in the plasma exchange group. We conclude that plasma exchange offers no additional therapeutic benefit to patients with idiopathic rapidly progressive glomerulonephritis (RPGN) who are not dialysis-dependent at presentation.

Adult↗
PubMed1992

Sequelae of haemolytic uraemic syndrome.

Twenty two patients with previous episodes of haemolytic uraemic syndrome (HUS) were investigated for evidence of deficits in cognitive, behavioural, and academic function. Patients were pair matched with 22 controls for age (+/- 1 year), gender, and socioeconomic status. HUS patients had numerically lower cognitive and achievement scores and higher behavioural problem ratings than their controls on every measure. None of the group differences was significant at the 0.01 level. Significance values between 0.10 and 0.01 were obtained for the Wechsler full scale and verbal intelligence quotient scores and for several of the achievement measures and behaviour ratings. These results were conservatively interpreted as trends and are considered to provide preliminary indications of a post-HUS deficit in behaviour, verbal intelligence, and the verbally based skills of reading comprehension and vocabulary. The findings provide interim guidelines for follow up care but require confirmation and elaboration in a larger study.

Achievement↗
PubMed1991

EGF and TGF-alpha in wound healing and repair.

Wound healing is a localized process which involves inflammation, wound cell migration and mitosis, neovascularization, and regeneration of the extracellular matrix. Recent data suggest the actions of wound cells may be regulated by local production of peptide growth factors which influence wound cells through autocrine and paracrine mechanisms. Two peptide growth factors which may play important roles in normal wound healing in tissues such as skin, cornea, and gastrointestinal tract are the structurally related peptides epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). EGF/TGF-alpha receptors are expressed by many types of cells including skin keratinocytes, fibroblasts, vascular endothelial cells, and epithelial cells of the GI tract. In addition, EGF or TGF-alpha are synthesized by several cells involved in wound healing including platelets, keratinocytes, and activated macrophages. Healing of a variety of wounds in animals and patients was enhanced by treatment with EGF or TGF-alpha. Epidermal regeneration of partial thickness burns on pigs or dermatome wounds on patients was accelerated with topical application of EGF or TGF-alpha, and EGF treatment accelerated healing of gastroduodenal ulcers. EGF also increased tensile strength of skin incisions in rats and corneal incisions in rabbits, cats, and primates. Additional research is needed to better define the roles of EGF, TGF-alpha and their receptor in normal wound healing, to determine if alterations have occurred in the EGF/TGF-alpha system in chronic wounds, and optimize vehicles for effective delivery of peptide growth factors to wounds.

Amino Acid Sequence↗
PubMed1990

Weekly food servings and participation in social programs among low income families.

Low income families were interviewed to determine factors related to the number of family food servings per week. A multiple regression model indicated that participation in WIC (supplemental food program for women, infants and children), household size, and number of different income sources were associated with more family food servings per week. Number of food servings per week decreased the last week of the month most often in families with younger members.

Diet↗
PubMed1990

High alveolar surface tension increases clearance of technetium 99m diethylenetriamine-pentaacetic acid.

The effect of high alveolar surface tension on alveolar epithelial permeability was studied in anesthetized closed-chest mongrel dogs. Alveolar surface tension was elevated by displacement of pulmonary surfactant from the alveolar hypophase by the aerosolized detergent dioctyl sodium sulfosuccinate (OT). After measurement of baseline hemodynamics, arterial blood gases, and airway pressure, the dogs were separated into groups: Group I inhaled a 1% solution of OT (15 mg/kg) in a vehicle of equal parts saline and ethanol; group II inhaled the same volume of vehicle without OT. The pulmonary clearance of technetium 99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) (half-time in minutes) was studied immediately after aerosol (OT and vehicle) delivery and compared with that of historical control values. No change was seen in arterial blood gases and airway pressure after vehicle inhalation, whereas OT caused a marked fall in arterial oxygen tension and increase in airway pressure. Vehicle inhalation effected only a slight increase in DTPA clearance, whereas OT significantly reduced half-time over control and group II. These data suggest that high alveolar surface tension increases alveolar epithelial permeability.

Aerosols↗
PubMed1990

Prevention of CTL and NK cell-mediated cytotoxicity by microencapsulation.

Graft rejection represents one of the major barriers preventing successful pancreatic islet transplantation. Microencapsulation of isolated islets has been proposed as a potential method of overcoming this problem. We present here for the first time evidence that the biocompatible semi-permeable capsule membrane prevents cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell-mediated cytotoxicity. The ability of the microcapsule to immunoisolate pancreatic and tumor cell (EL-4 and YAC-1) targets from these two mechanisms of the immune rejection response was assessed using a 51chromium-release assay. Significant cell lysis occurred when target cells were incubated with free effector cells, or with NK effector cells co-encapsulated with NK-sensitive target cells (via the release of NK cytotoxic factors (NKCF)). This effect was not observed with encapsulated effector cells alone. These results clearly demonstrate the efficacy of the microcapsule in protecting target cells against both specific cytotoxicity by CTL's, and nonspecific killing by NK cells. They also provide a method for the in vitro evaluation of the immunoprotective properties of the various new capsular materials, in terms of the effector limb or destructive phase of the allograft rejection response.

Animals↗
PubMed1989

Analysis of Adh gene regulation in Drosophila: studies using somatic transformation.

We have used in vitro mutagenesis and somatic transformation [Sofer and Martin, 1987a; Martin et al., 1986] to investigate the role of cis-acting sequences in the control of alcohol dehydrogenase gene expression in larvae of Drosophila melanogaster. Two sets of experiments were carried out. In the first, a series of deletions were constructed in the region upstream of the proximal transcriptional start site. In the second, one or both introns were removed from within the structural gene. These constructs (on circular plasmids) were injected into Adh-null embryos and ADH activity was assayed in third instar larvae of the injected generation. The first set of experiments indicated that there are at least three distinct regulatory regions essential for larval activity located in the 5' flanking region of the gene. One, in an area that includes the TATA box, was found to be necessary but not sufficient for larval ADH activity. Two others, further upstream, seemed to have enhancer-like properties because their absence could be compensated by a second copy of the Adh gene on the same plasmid molecule. The second set of experiments showed that neither the tissue distribution nor amount of ADH activity was affected by the removal of one or both introns from the Adh gene.

Alcohol Dehydrogenase↗
PubMed1989

Islet transplantation for the cure of diabetes.

This symposium format was similar to that used in the Kroc Foundation Meetings that Josiah Brown organized previously. As it had been at the Kroc Meetings, this memorial symposium dedicated to Dr. Brown was very successful in terms of the quality of the presentations, updating the most critical findings in islet transplantation and fostering the free exchange of provocative opinions. All participants well recognized that there has been tremendous advancement in islet isolation techniques, understanding of the immunological mechanisms underlying islet rejection, and the development of methods of immunomodulation to overcome rejection-related problems. Progress in these areas is one more step toward the final goal of providing new treatment for diabetics.

Animals↗
PubMed1989

Presbycusis.

Explore the source record for details and available documents.

Aged↗
PubMed1987

Base sequence effects in double helical DNA. I. Potential energy estimates of local base morphology.

A series of potential energy calculations have been carried out to estimate base sequence dependent structural differences in B-DNA. Attention has been focused on the simplest dimeric fragments that can be used to build long chains, computing the energy as a function of the orientation and displacement of the 16 possible base pair combinations within the double helix. Calculations have been performed, for simplicity, on free base pairs rather than complete nucleotide units. Conformational preferences and relative flexibilities are reported for various combinations of the roll, tilt, twist, lateral displacement, and propeller twist of individual residues. The predictions are compared with relevant experimental measures of conformation and flexibility, where available. The energy surfaces are found to fit into two distinct categories, some dimer duplexes preferring to bend in a symmetric fashion and others in a skewed manner. The effects of common chemical substitutions (uracil for thymine, 5-methyl cytosine for cytosine, and hypoxanthine for guanine) on the preferred arrangements of neighboring residues are also examined, and the interactions of the sugar-phosphate backbone are included in selected cases. As a first approximation, long range interactions between more distant neighbors, which may affect the local chain configuration, are ignored. A rotational isomeric state scheme is developed to describe the average configurations of individual dimers and is used to develop a static picture of overall double helical structure. The ability of the energetic scheme to account for documented examples of intrinsic B-DNA curvature is presented, and some new predictions of sequence directed chain bending are offered.

Base Composition↗