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Biomedical subjects

K Walker

Publications and source records attributed to K Walker.

At least 91 records · Page 5Linked to original sources

Analyses of anti-human CD monoclonal antibodies for cross reactions with swine cell antigens.

For the First International Swine CD Workshop an effort was made to include commercially available anti-human CD monoclonal antibodies (mAb) that had been prescreened to determine whether they were cross-reactive with swine cell CD antigens. Thus before the actual workshop began, ten companies were contacted to determine whether they would participate in this effort. Four companies (Dako Corporation, Carpenteria, CA; T Cell Sciences, Cambridge, MA; Bioproducts for Science, Indianapolis, IN; PharMingen, San Diego, CA) provided a total of 38 mAb for tests of cross-reactions with swine cell antigens. Two companies (Coulter, Hialeah, FL and Becton Dickinson, San Jose, CA) declined to participate because of the low likelihood of positive cross-reactions. Several other companies (Behringewerke, Marburg, Germany; Boehringer Mannheim, Indianapolis, IN; Biosource International, Camarillo, CA; Applied Immune Sciences, Menlo Park, CA) were interested but either had problems in preparing the mAb in time for US importation or in providing the quantities necessary free to the workshop. The studies described below verify that few anti-human CD mAb exhibit consistent, predictable cross-reactions on pig cells; of the seven mAb that showed reactivity on swine cells only one mAb, Dako's anti-CD18, showed consistent reactivity with every pig tested and at the expected intensity level.

Animals↗

Workshop studies on monoclonal antibodies reactive against porcine myeloid cells.

Investigators from eight laboratories analyzed the reactivity of 22 monoclonal antibodies (mAb) against porcine myeloid cells. Based on binding data, clustering analysis and inhibition studies, workshop mAb 74-22-15 (003) and 6F3 (007) were assigned a swine workshop cluster number 3 (SWC3). These mAb recognized macrophages and neutrophils; neutrophils; a monocyte/macrophage-specific mAb was not identified by this workshop.

Animals↗

Confronting 'reality': nursing, science and the micro-politics of representation.

In an age where previous frames of reference lose their certainty nurses are finding themselves rethinking their relations to the 'real'. In this paper I interrogate an empirical 'text' of a local nursing cultural practice through a poststructural critique of the ways in which language, discourses, representation and experience intersect to construct 'reality' for us with specific consequences. I do this in an attempt to disclose the micro-politics at work in the processes of signifying and thus representing nursing to a world of potential students. The discourses of science and caring find themselves exposed in particular representational technologies and practices that mark nursing's collusion with the 'truths' of science at the expense of those we loosely name 'caring'. This cultural theoretical work constitutes a provisional and historical fragment of analysis designed to trouble the relations we often unwittingly sustain with dominant 'regimes of truth'.

Adolescent↗

AggR, a transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAggEC) has been associated with persistent pediatric diarrhea in the developing world, yet the pathogenetic mechanisms of EAggEC infection are unknown. Our previous data have suggested that aggregative adherence of some EAggEC strains to HEp-2 cells is mediated by flexible, bundle-forming fimbriae, which we have termed aggregative adherence fimbriae I (AAF/I). Genes sufficient to confer expression of AAF/I are located on the 60-MDa plasmid of EAggEC 17-2; AAF/I genes are present as two unlinked plasmid regions (regions 1 and 2), separated by 9 kb of DNA. Here we report the complete DNA sequencing of region 2 and the identification of an open reading frame which is involved in the expression of AAF/I. One open reading frame of 794 bp encodes a protein (designated AggR) with a predicted molecular size of 29.4 kDa, which shows a high degree of amino acid sequence identity to CfaR and other members of the AraC class of gene regulators. The cloned aggR gene (or, alternatively, a cloned cfaR gene) was sufficient to complement a region 1 clone to confer AAF/I expression. To further substantiate the role of aggR in the regulation of AAF/I, we constructed a 289-bp in-frame aggR deletion and replaced the native gene in 17-2 by allelic exchange, using the temperature-sensitive vector pIB307. The resulting aggR deletions were negative for AAF/I expression, but expression was restored when the aggR gene (cloned into pBluescript II SK) was reintroduced into the aggR mutant. RNA slot blot experiments using a probe for the putative AAF/I pilin subunit (aggA) revealed that aggR operates as a transcriptional activator of aggA expression. aggA::phoA fusions were constructed in 17-2 and in 17-2 delta aggR. AggR was found to promote expression of the aggA gene under a variety of conditions of temperature, osmolarity, oxygen tension, and medium. At acid pH, aggA expression was maximal and was regulated by both AggR-dependent and AggR-independent mechanisms.

Alkaline Phosphatase↗

Preliminary evidence on the question of gender differences in language testing of older people.

The effect of gender on the outcomes of language assessments in older people is relatively unknown. This study compared the performance of groups of normal older men and women on three different batteries of language and memory tests. No significant mean score difference was found. All three batteries therefore show no strong quantitative gender bias and can be applied equally to older men and women with communication difficulties. Although no quantitative gender difference was found, the data suggested two possible areas for further investigation (error types and interpersonal styles) which may have clinical implications.

Aged↗

Research with/in nursing: 'troubling' the field.

Nursing and research coexist in a 'troubled' relationship. The culture of nursing and the discourses of research together generate tensions and conflicts which often work to constrain nurses' attempts to engage in research activity. In this paper I attempt to expose possible reasons why this might be so. Drawing on critical feminist post-structuralist theories and recent empirical research with clinical nurses some of the 'challenges' to thinking and doing research in nursing are given voice and brought to critical expression.

Cultural Characteristics↗

The counterpart relationship: a model for clinical nurse specialists in international nursing practice.

The proposed counterpart relationship model can be an effective tool in blending role functions to provide culturally sensitive nursing care in international settings. The authors explore their experience in developing a counterpart relationship where the CNS enters into a mutually collaborative relationship with a host counterpart from a cultural base different from the CNS's. The goal is to improve the level of health care provided to a specific cultural group and to transition the responsibilities of the CNS to the host counterpart.

Global Health↗

Isolation of glucagon antagonists by random molecular mutagenesis and screening.

Glucagon has an important role in the regulation of glucose homeostasis, and glucagon antagonists may be effective therapeutic agents in the control of diabetes mellitus. We were able to identify a number of analogs with antagonist activity by creating libraries of mutant glucagon coding sequences, expressing them in a yeast (Saccharomyces cerevisiae) secretion system, and screening for clones that produce analogs that inhibit the glucagon stimulation of rat hepatocyte membrane adenylate cyclase. These libraries were constructed by allowing random misincorporation during the synthesis of oligonucleotides that contained the complete coding sequence for mammalian glucagon or for an analog (desHis1-glucagon) that had partial antagonist activity. We developed and used a simplified screening assay to test culture broths from > 3500 individual transformant yeast clones for their ability to inhibit glucagon-dependent adenylate cyclase activity. Ultimately, > 20 different analogs with antagonist activity were identified by recovering and sequencing plasmid DNA from yeast strains that were positive in the screening assay. Interestingly, several analogs were identified repeatedly in independent yeast clones and certain amino acid substitutions occurred in more than one analog. This clustering of randomly isolated mutations clearly delineates the regions of the glucagon molecule that are important for designing improved glucagon antagonists. A subset of the antagonists identified in yeast broth were produced by peptide synthesis to confirm their activities as pure compounds.

Adenylyl Cyclases↗

Tumor markers CA 19-9 and CA 195 are also useful as markers for cystic fibrosis.

When monoclonal kits are used we can no longer detect highly elevated serum concentrations of carcinoembryonic antigen in cystic fibrosis (CF) patients as we could earlier (Pediatr Res 10:223-236, 1975). Instead, we find increased concentrations of CA 19-9 or CA 195 in the CF sera. The serum levels of CA 19-9 not only reflect the pulmonary condition of CF patients but also respond well to antibiotic therapy. Several lines of evidence suggest that the elevated serum concentration of CA 19-9 is derived from sputum and corresponds with the amount of sputum in the lung. Correlations between CA 19-9 and CA 195 in random and serial specimens from both patients with CF and patients with pancreatic carcinoma suggest that all sera contain heterogeneous, Lewis blood group-related epitopes and the proportions of various epitopes are different among individual patients. When monitored on multiple tumor markers, the pattern of CF is different from that of pancreatic carcinoma although both usually show elevated CA 19-9. Our study indicates that both CA 19-9 and CA 195 can be used as sensitive markers for the early detection of exacerbation in CF patients.

Adolescent↗

Changes in the CA 19-9 antigen and Lewis blood group with pulmonary disease severity in cystic fibrosis.

The altered carbohydrate structure of sputum from patients with cystic fibrosis (CF) has been thought to be due to the inflammatory airway response. Carcinoembryonic antigen (CEA) and CA 19-9 detect sialosylated carbohydrates in mucus. The epitope of CA 19-9 is part of the Lewis A (Le(a)) blood group antigen. Serum concentrations of CEA and CA 19-9 were determined by radioimmunoassay in 41 CF patients, aged 6-34 years; 16 were asymptomatic Outpatients, and 25 had been admitted for pulmonary exacerbations. There was no difference in CEA between groups. The CA 19-9 serum concentration was elevated in 90% of patients who had at least one of the two Lewis antigens. The CA 19-9 concentration of Inpatients with exacerbations was 2.7 times that of stable Outpatients (263 +/- 44 versus 99 +/- 13 U/mL; P less than 0.02). CA 19-9 correlated significantly with age (r = 0.35, P less than 0.05), Brasfield score (r = 0.39, P less than 0.015), pulmonary function tests, cough severity (r = 0.50, P less than 0.001) and NIH clinical score (r = 0.57, P less than 0.001). CA 19-9 concentration of Inpatients decreased by 44% from admission to discharge (302 +/- 45 to 169 +/- 39, P less than 0.02). Fourteen of 25 (56%) of the Inpatients were Le(a) positive versus only 3/15 (20%) of Outpatients who had milder lung disease (P less than 0.002). Of the Inpatients, 25% with more advanced lung disease were Le(a+b+), a rare blood group in the normal population, and one not observed in the Outpatients with milder disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ethanol flush for the prevention of catheter occlusion.

Catheter occlusion by lipid material has been associated with the use of compounded nutrient solutions containing lipid. We have studied the incidence of catheter occlusion when either a saline or an ethanol flush has been used prior to the application of a heparin lock following an overnight infusion of such nutrients. Lipid occlusion occured in 13 of 23 catheters when a saline flush preceeded the application of a heparin lock, whereas the use of a 20% ethanol solution before the application of the heparin lock resulted in only 2 occlusoins in 28 catheters (p < 0.001). In addition there was significantly longer catheter survival in the ethanol group (p < 0.01). It is concluded that an ethanol flush may significantly reduce the incidence of catheter occlusion during the use of lipid mixes.

Journal Article↗

A nationwide quality assurance program can describe standards for the practice of pathology and laboratory medicine.

An important component of quality assessment is the analysis of peer group comparisons, although little data are available for evaluation. We developed and tested six interinstitutional quality indicators related to Pathology and Laboratory Medicine among 36 institutions. Results showed that the mean frequency of intraoperative frozen section consultations (6.0%), sensitivity of fine needle aspiration cytology diagnosis (87%), nosocomial infections (5.0%) and average cross-match to transfusion ratio (2.1%) was comparable with previous studies, but the range of values was large. The median stat laboratory turnaround time of approximately 1 hr for CSF cell count, glucose, protein and gram smear was considerably longer than expected from previous investigations, and was longer for larger institutions. Analysis of serious laboratory reporting errors showed the lowest number detected by individuals working in transfusion medicine, and highest numbers among hematology workers. We conclude that interinstitutional comparison of data from quality assurance programs can be used to describe performance standards related to the quality and effectiveness of care.

Biopsy, Needle↗

Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.

It has been reported recently that the wild-type p53 gene product can positively regulate the expression of a test gene adjacent to the enhancer-promoter elements of the murine muscle-specific creatine kinase (MCK) gene. This discussion reports the identification of a wild-type p53 protein-specific DNA-binding element located within the p53-responsive region of the MCK enhancer-promoter element. This p53 protein/DNA-binding element has been defined by DNase I footprint analysis, which identified a 50-bp region. This 50-bp sequence was sufficient to confer wild-type p53 responsiveness on a heterologous minimal promoter. The mutant forms of p53 protein are much less capable of stimulating this DNA element. This study has identified the first example of a naturally occurring wild-type p53-specific DNA-binding element that is able to mediate positive regulation of a test gene. The results suggest a biological function in gene regulation for the wild-type p53 protein that is lost or altered in the mutant p53 proteins.

Animals↗

Indomethacin worsens and a leukotriene biosynthesis inhibitor accelerates mucosal healing in rat colitis.

The implication of leukotrienes as mediators of inflammation and recent evidence that prostaglandin analogues provide a beneficial effect during experimental colitis led to the speculation that (i) leukotrienes may be injurious and (ii) prostaglandins may be protective to colonic mucosa. Using a 2% acetic acid induced rat colitis model, we administered specific cyclooxygenase (indomethacin) and leukotriene biosynthesis inhibitors (MK-886) to examine the effect of endogenous prostaglandins and leukotrienes on colonic macroscopic injury, mucosal inflammation as measured by myeloperoxidase activity, net in vivo intestinal fluid absorption, and colonic PGE2 and LTB4 levels as measured by in vivo rectal dialysis. Indomethacin treatment prior to induction of colitis reduced endogenous mucosal PGE2 levels and exacerbated macroscopic ulceration and net fluid absorption. Addition of the exogenous PGE1 analogue misoprostol to the indomethacin-exacerbated colitis completely healed colonic macroscopic ulceration and inflammation but only partially improved fluid absorptive injury. The specific leukotriene biosynthesis inhibitor MK-886 administered prior to induction of colitis healed macroscopic ulceration and inflammation but not fluid absorptive injury. This mucosal reparative effect of MK-886 occurred at a dose that reduced colonic LTB4 synthesis while concomitantly enhancing PGE2 levels. Combining MK-886 with misoprostol treatment improved not only macroscopic ulceration and inflammation but also provided a synergistic effect that maintained net colonic fluid absorption at noncolitic control levels. These studies suggest that, during the induction of experimental colitis, endogenous prostaglandins play a pivotal role in providing a mucosal healing effect, and that leukotriene biosynthesis inhibitor may manifest part of its beneficial effect by shifting arachidonic acid metabolism towards production of prostaglandins.

Acetates↗

Two weeks of oral synthetic E2 prostaglandin (Enprostil) improves the intestinal morphological but not the absorptive response in the rat to abdominal irradiation.

Enprostil, a synthetic E2 prostaglandin, was administered in a dose of 5 micrograms/kg body weight by gastric tube to rats for 14 days following abdominal irradiation with a single dose of 600 cGy from a 137Cs source. Enprostil prevented the body weight loss and the reduced food intake observed in irradiated animals given placebo, and also prevented the irradiation-associated decline in the mucosal weight and surface area of the ileum. Enprostil given to nonirradiated animals reduced the maximal transport rate (Vmax) and the apparent Michaelis constant (Km*) for the ileal uptake of D-glucose, but did not prevent the irradiation-associated decline in the ileal uptake of glucose. Thus, there is a dissociation of the effects of Enprostil on the morphological and the absorptive properties of the intestine. It is concluded that a 2-week course of a daily oral dose of E2 prostaglandin begun shortly after a single exposure to nonlethal abdominal irradiation prevents the radiation-associated reduction in the intestinal mucosal surface area and the animal's body weight, but does not prevent the malabsorption of glucose.

Animals↗

Malignant melanoma in a Hispanic male with nevus of Ota.

Nevus of Ota is uncommon in the non-Oriental population. We report a case of malignant melanoma with metastasis to the genitourinary tract in a Hispanic male with nevus of Ota. Thirty-six prior cases of nevus of Ota with malignant melanoma reported in the English language are reviewed. Sixty-eight percent were women; 76% were Caucasians. Metastatic disease was reported in 16%. Three patients had liver metastases. Our case was the first involving the genitourinary tract. All but one patient with metastatic disease died within 1 month of presentation. Despite the increased frequency of nevus of Ota in the Japanese, only 4 cases of malignant melanoma have been reported. Nevus of Ota would appear to be a risk factor for developing malignant melanoma in the Caucasian population.

Brain Neoplasms↗

Verapamil alters eicosanoid synthesis and accelerates healing during experimental colitis in rats.

In inflammatory bowel disease, prostaglandins are mucosal protective whereas leukotrienes are proinflammatory. Recent evidence suggests that the formation and action of leukotrienes are calcium-dependent, whereas the formation and action of prostaglandins are not. To examine the possibility that, because of differential regulation of arachidonic acid metabolism, calcium channel blockade might alter mucosal eicosanoid synthesis and accelerate healing during inflammatory bowel disease, we treated a 4% acetic acid-induced colitis model with verapamil and/or misoprostol and determined the effects on colonic macroscopic injury, mucosal inflammation as measured by myeloperoxidase activity, in vivo intestinal fluid absorption, and mucosal prostaglandin E2 and leukotriene B4 (LTB4) levels as measured by in vivo rectal dialysis. In colitic animals, verapamil treatment significantly improved colonic fluid absorption and macroscopic ulceration. This mucosal-protective effect of verapamil occurred in the presence of a twofold reduction in mucosal LTB4 synthesis. In noncolitic animals, verapamil alone had no effect on in vivo fluid absorption, macroscopic ulceration, or myeloperoxidase activity but did induce a threefold reduction in LTB4 synthesis in addition to shifting arachidonic acid metabolism towards a sixfold stimulation of prostaglandin E2 synthesis. Our results show that, when administered before the experimental induction of colitis, the calcium channel blocker, verapamil, has a mucosal-protective effect that occurs as a consequence of reduced mucosal leukotriene synthesis and increased prostaglandin synthesis. This differential regulation of arachidonic acid metabolism may play an important role in the development of novel therapeutic agents for inflammatory bowel disease.

Animals↗

Treatment of gastric lymphoma.

A review of 52 patients with gastric lymphoma at the Texas A&M University College of Medicine Affiliated Scott and White Memorial Hospital (Temple, TX). was performed to determine the influence of different treatment modalities. Thirty-one patients had a potentially curative resection, while 21 underwent a palliative procedure or biopsy alone. Overall 5-year survival was 73.4 per cent after curative resection and 38.3 per cent for lesser operative procedures (P less than .005). Adjuvant radiation was given to 14 patients after curative resection with a 5-year survival rate of 71.5 per cent compared to 82.4 per cent in the 17 patients treated by curative resection alone (nonsignificant). Patients who underwent palliative surgery or biopsy who received postoperative radiation therapy had a 38.0 per cent 5-year survival rate compared to a 0.0 per cent 5-year survival rate in patients who received no therapy (P = .18). The authors conclude that curative resection is the treatment of choice for gastric lymphoma, but radiation therapy may offer some benefit when complete resection is not feasible.

Actuarial Analysis↗