PubMed Health⌕ Search

Biomedical subjects

W Clark

Publications and source records attributed to W Clark.

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

Sensitive assays for hepatitis A antibodies.

Two commercial assay kits for detecting antibody to hepatitis A virus (anti-HAV) have been modified in order to increase their sensitivity. These modifications are made by less dilution of the test serum, in the case of Abbott HAVAB-M assay, or by an increase in the volumetric ratio of the test serum to the labeled anti-HAV in the case of the Abbott HAVAB assay. These modifications result in 5- to 20-fold increases in test sensitivity and enable the detection of anti-HAV at 2-3 weeks following vaccination. The earlier detection of anti-HAV is important to vaccine development in assuring the presence of antibody levels in travelers sooner after vaccination.

Adult↗
PubMed1993

Changes in the level of perforin and its transcript during effector and target cell interactions.

Perforin is a cytoplasmic granule protein expressed in cytotoxic lymphocytes, and is capable of lysing target cells. This protein is induced as cytotoxic T cells are activated, and the mRNA expression is modulated by various stimulators. These observations suggest possible changes in the level of perforin transcripts and protein when killer lymphocytes meet specific target cells leading to target cell death. To address this question, we examined three murine T-cell clones and primary human NK cells in perforin expression. When the cytotoxic lymphocytes were exposed to sensitive targets, perforin mRNA disappeared within 5 to 30 min and appeared within an hour thereafter. Among the murine T cell clones, L3 and OE4 showed two phases of mRNA decrease while human NK cells and the third murine T cell clone, AB.1, showed only one phase of mRNA loss during a 240 min period. The data indicate that when cytotoxic lymphocytes receive signals from a sensitive target, the cells rapidly degrade previously accumulated perforin mRNA and synthesize new transcripts. Interestingly, heat shock protein 70 mRNA was induced as the perforin mRNA levels recovered, while P55 Il-2 receptor mRNA was downregulated within 5 min after exposure to targets. The perforin protein level also rapidly decreased immediately after the interaction with the target, followed by a recovery, and then another decrease as seen in primary human NK cells, OE4 and L3 cells. However, in the AB.1 clone, no change in perforin content was detectable, despite the loss of perforin mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prevention of scrapie transmission in sheep, using embryo transfer.

Reciprocal embryo transfers were made between scrapie-inoculated and scrapie-free sheep (Cheviot and Suffolk breeds) to measure scrapie transmission via the embryo (using offspring from embryos of scrapie-inoculated donors and scrapie-free recipients) and via the uterus (using offspring from embryos of scrapie-free donors and scrapie-inoculated recipients taken by cesarean section). Two control groups of offspring, 1 from scrapie-free parents (negative) and 1 from scrapie-inoculated parents (positive), also were included. All sheep were observed for clinical signs of scrapie until death or for a minimum of 60 months. Final diagnosis was made on the basis of histopathologic findings or results of mouse inoculation and/or proteinase-K-resistant protein analysis. Thirty to 61% of the scrapie-inoculated donor/recipient sheep within groups developed scrapie within 8 to 44 months after inoculation. None of the scrapie-free donor/recipients, including those gestating embryos from scrapie-inoculated donors, developed scrapie. Also, none of the offspring observed to > or = 24 months of age from reciprocal cross, via embryo (0/67), or via the uterus (0/25), or from the negative-control group (0/33) developed scrapie. Fifty-six of the offspring via embryo, 19 of these via the uterus, and 31 negative controls survived to > or = 60 months of age. Of the 21 sheep in the positive-control group, 2 (9.5%) developed scrapie, 1 at 31 months of age and 1 at 42 months of age. In the Cheviot offspring, the percentage of sheep carrying the short incubation allele ranged from 24 to 44% and the percentage in the Suffolk offspring ranged from 61 to 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Evaluating needle exchange: are there negative effects?

OBJECTIVE: We analyzed data on all drug-treatment admissions in San Francisco County over a 4-year period (n = 35,460) to evaluate the potential negative effects of the San Francisco needle-exchange program. METHODS: Admissions in the 2 years preceding implementation of the exchange program (1987-1988) were compared with admissions in the 2 years following implementation (1989-1990). RESULTS: No negative consequences of needle exchange were detected. Specifically, the presence of the exchange program was not associated with (1) increases in injection drug use, (2) increases in needle-sharing behavior, or (3) changing drug-use behavior from non-injection to injection. We also compared high-drug-use neighborhoods with and without local needle-exchange sites. Neighborhoods without needle-exchange sites showed a greater increase in proportion of admissions for injection drug use, and in frequency of injection, over time. CONCLUSIONS: Because of methodological limitations, our findings are preliminary. Longitudinal studies comparing needle-exchange and non-exchange cohorts are needed to further evaluate effects of this intervention.

Adult↗
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↗