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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of recombinant tissue factor pathway inhibitors expressed in human SK hepatoma, mouse C127, baby hamster kidney, and Chinese hamster ovary cells.

Recombinant tissue factor pathway inhibitor (rTFPI) has been expressed in four mammalian expression systems using human SK hepatoma, mouse C127, baby hamster kidney (BHK), and Chinese hamster ovary (CHO) cells as hosts. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the immunoaffinity purified rTFPIs all show broad bands and the mean molecular weight of SK hepatoma and C127 rTFPIs (M(r) approximately 38,000) appear larger than those of BHK and CHO rTFPIs (M(r) approximately 35,000). All these proteins inhibit factor Xa and appear to bind factor Xa with 1:1 stoichiometry. The ability of these proteins to inhibit tissue factor-induced coagulation in plasma was examined using a prothrombin time assay. The relative activities of SK rTFPI:C127 rTFPI:BHK rTFPI:CHO rTFPI were found to be 28:15:2.1:1. By Western blot using specific antisera against the amino- and carboxy-termini of TFPI as probes, it is found that all the immunoaffinity purified rTFPIs possess approximately equal amounts of the amino terminus, but the C127 and BHK rTFPIs are deficient in carboxy terminus and the CHO rTFPI is essentially devoid of this region of the protein. Mono S chromatography allowed separation of the full-length and the truncated molecules with high and low anticoagulant activities, respectively. The above results suggest that proteolysis of the carboxy terminus of TFPI occurs to different extent when TFPI is expressed in different cells and that the carboxy terminal region of the TFPI molecule is important for the inhibition of tissue factor-induced coagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Self-administered patient questionnaire for assessing knowledge about joint arthroplasty prior to surgery.

This article assesses the discriminant validity of a questionnaire designed to test patients' knowledge about total joint arthroplasty prior to preoperative educational intervention. The method employed was to compare responses on the test by surgeons, health care workers, and patients and to evaluate whether the test could discriminate among groups. A total of 148 patients, 59 health care workers and 28 orthopedic surgeons completed the questionnaire. The results show that patients are knowledgeable about the benefits of surgery, but are in need of information about surgical risks and complications. The test was able to discriminate between surgeons and the other two groups, but there were few differences between health care workers and patients. Item analysis also demonstrates that the test is reliable. Although the test exhibits acceptable psychometric properties, a major problem in using this test in evaluating educational interventions is the relatively high average score and the potential ceiling effect that prevents measurement of further gains in knowledge. More work is needed on expanding the test to include more items where knowledge of total joint arthroplasty is limited.

Discriminant Analysis↗
PubMed1992

Sources of genotoxicity and cancer risk in ambient air.

Products of incomplete combustion are identified as a major source of carcinogenic risk in urban areas, especially those from small non-industrial sources. The major ubiquitous emission sources outdoors in populated areas are residential home heating and motor vehicles. Indoors the major combustion source is environmental tobacco smoke. Polycyclic organic matter adsorbed onto the particles emitted from incomplete combustion are estimated to make the largest contribution to human genotoxic and cancer risk. Mutagenic emission factors combined with dispersion modelling indicated that automobiles and heating sources were major sources of mutagens. Ambient air studies to apportion the sources of mutagens in non-industrial areas confirmed this prediction. To apportion and estimate the cancer risk of ambient organic matter from particles in vivo animal tumour data, receptor modelling and human exposure data were combined. Tumourigenicity studies of the source apportioned ambient organic matter provided the relative tumour potencies of two ambient samples of different source composition. The human cancer unit risks were developed based on the comparative potency method using tumour data from these ambient samples. Residential wood combustion accounted for 75% of the exposure to particle associated organics, but only 20% of the estimated cancer risk. The remaining 80% of the risk appears to be associated with the mobile source component and atmospheric transformation products from these source emissions.

Air Pollutants↗
PubMed1992

Behavioral consequences of illness: childhood asthma as a model.

Several areas of research on childhood asthma are discussed within a transactional model of asthma. The model emphasizes the multidirectional influences that affect the severity of asthma and associated behavioral disability. The initial focus is on how the clinical presentation and morbidity of asthma are affected both by somatic predisposition and by interactions with multiple internal and external elements. Specific elements include emotional factors, neuroimmunology, temperament, and medication side effects. Second, the impact of asthma on the child, his or her family, and segments of the community are described, as are consequences of the disorder on quality of life. Third, there is a synopsis of preventative interventions for reducing the medical and behavioral impact of childhood asthma. The motif is that the interaction of medical and behavioral procedures can improve the management of asthma while consequences of the disorder are mollified. Finally, as examples of a transactional model of asthma, self-management programs for teaching children to become partners with their physicians in establishing and maintaining control over the disorder are described. A representative of self-management--the ACT (Asthma Care Training) program--is described, along with the impact such programs have on children, their families, and institutions. The conclusion emphasizes that asthma is a complicated and unpredictable disorder that puzzles physicians, behavioral scientists, and patients. Although new treatments may be over the horizon, controlling childhood asthma and its consequences currently rests on the cooperation and increased interaction of medical and behavioral scientists.

Asthma↗
PubMed1992

Malignant melanoma in inflammatory bowel disease.

Malignant melanoma occurred in 11 patients with inflammatory bowel disease (IBD). Six cases occurred in patients with ileocolitis, two in regional enteritis, one in granulomatous colitis, and two in patients with ulcerative colitis. The mean age at development of IBD was 24 yr, and at development of melanoma was 40 yr: the mean duration from onset of IBD to development of melanoma was thus 16 yr. All patients for whom complete information was available, except two, had received steroids and azulfidine for approximately a decade, as well as blood transfusions, usually multiple, and on repeated occasions. Six of the 11 patients had undergone one to seven prior operations (mean 3.5). All patients had wide radical excision of the melanoma, with or without concomitant or subsequent nodal dissection. Two patients (ages 25 and 36 yr) died rapidly from widely disseminated malignant melanoma. These cases may be coincidental, or else there may be an association between IBD and melanoma, related to immunosuppression either from the disease itself, from the medical and surgical therapy, and/or from x-ray exposure.

Adolescent↗
PubMed1991

Medium effects in antibody-catalyzed reactions.

Catalytic antibody technology has been used to explore the contribution of medium effects to the overall rate of an enzyme-catalyzed reaction. An antibody generated against a derivative of 2-acetamido-1,5-napthalenedisulfonate efficiently catalyzes the decarboxylation of 5-nitro-3-carboxybenzisoxazole. This unimolecular reaction is not susceptible to general acid-base catalysis but is highly sensitive to microenvironment; thus, it provides a simple chemical model for biologically important decarboxylations. The 10(4)-fold rate acceleration observed for the antibody reflects the kinetic advantage of the low-dielectric environment of the binding pocket acting to destabilize the substrate by desolvation and to stabilize the charge-delocalized transition state through dispersion interactions. These results are pertinent to an understanding of solvent effects in enzymic reactions in general and suggest approaches for developing antibody catalysts for numerous other reactions that involve large changes in charge distribution as the reaction coordinate is traversed.

Anilino Naphthalenesulfonates↗
PubMed1991

Factors underlying illusory self-assessment of driving skill in males and females.

While it is known that drivers as a group rate their skills as better than the average, the mechanism underlying this illusion is unclear. It is possible, for example, that it is due either to a "positive-self" or "negative-other" bias. A test of these alternative hypotheses revealed that judgments are consistent with a "positive-self" bias. An attempt was made to determine whether the illusion was present in all areas of driving skill or whether there were specific components where the illusion was absent. For men, the bias was present in all the driving components examined. For women, there were several areas where they rated themselves less positively than the men, and four areas where they showed no evidence of any bias. When the effects of driving experience were statistically controlled for, however, these sex differences were found to be substantially reduced.

Adolescent↗
PubMed1991

Advances in drug delivery and targeting.

This review covers a variety of techniques aimed at improving the specificity of delivery of both biologic and cytotoxic agents to tumor tissue while sparing normal tissue. The major areas reported on include further attempts to increase the ability of monoclonal antibodies, both conjugated and unconjugated, to target tumor tissue. It also examines the early clinical trials of liposomes as carriers of both biologics and cytotoxics and the potential problems of this modality. A number of studies in the area of regional drug delivery, including intraperitoneal, intravesical, intra-arterial, and intratumor, highlight the many clinical problems still to be resolved. Improved targeting of antitumor agents to sites of malignant disease appears likely over the next decade judging by the recent developments we review. Although much clinical and laboratory research will be required to achieve this goal, the likely directions appear to be established.

Antibodies, Monoclonal↗
PubMed1991

Quantifying serum antibody class and subclass responses by enzyme immunoassay in humidifier-related disease.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

Air Conditioning↗
PubMed1991

Mobile versus fixed site lithotripsy.

The efficacy of a mobile Dornier HM4 lithotriptor, was compared with that of a fixed site Siemens Lithostar. A total of 115 calculi in 98 patients were treated, 55 on the mobile Dornier and 60 on the Lithostar. The groups were similar except for stone size, the mean of the Lithostar group being 11 mm compared with 7.7 mm in the Dornier group. Fragmentation rates were not significantly different, 88% and 75% on the mobile and fixed site machines, respectively and, at 3 months follow-up 66% and 46% were stone free or with fragments of less than 2 mm. There were no serious complications, and the incidence of mild complications was similar in the two groups. We conclude that the mobile Dornier HM4 is an effective lithotriptor and can offer several advantages over fixed site machines.

Female↗
PubMed1990

Human granulocyte-macrophage colony-stimulating factor plus phorbol myristate acetate stimulate a promyelocytic cell line to produce an IL-1 inhibitor.

We recently described an IL-1 inhibitor found in urine of febrile patients. It is a 26-kDa glycoprotein that acts by blocking the binding of IL-1 to its receptor. In a search for a cell source for the urinary IL-1 inhibitor, we tested three promyelocytic cell lines, H-161, AML-193, and HL-60, for their ability to produce this protein. Under normal culture conditions none of these cell lines produce detectable IL-1 inhibitory activity. The H-161 cells were treated with differentiation-inducing agents, i.e., sodium butyrate, hemin, retinoic acid, DMSO, vitamin D3, and PMA alone or in combination with IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-gamma, granulocyte-CSF, macrophage-CSF, granulocyte/macrophage-CSF (GM-CSF), and Con A and tested for the production of IL-1 inhibitor. Production of IL-1 inhibitor was detected in cell supernatant, when H-161 cells were differentiated to adherent macrophage-like cells under the influence of PMA followed by a second signal provided by GM-CSF. Treatment of the other two cell lines, AML-193 and HL-60, with PMA plus GM-CSF also yielded similar IL-1 inhibitor protein. Partial purified H-161-derived IL-1 inhibitor showed specific binding to IL-1R-bearing cells and blocked the binding of IL-1 to its receptor and is thus similar to the urinary-derived molecule. We conclude the GM-CSF provides a signal to adherent macrophage-like cells to become "inhibitory macrophages" and to produce a competitive inhibitor of IL-1.

Colony-Stimulating Factors↗
PubMed1990

School-based primary prevention: what is an effective program?

Our model makes us pessimistic about quick-fixes. Short-term, narrowly focused programs designed to increase children's knowledge or some limited aspect of their competence are unlikely to be effective in preventing AIDS. Our model suggests that what protects a child from AIDS is not knowledge or isolated social skills but rather the quality of bonds to school, family, and other socialization agents. Ultimately, the school-based route to prevention of AIDS will work only if schools are effective socialization agents: effective in meeting children's needs for autonomy, belonging, and competence, and thereby in helping children build the motivation and social competence they will need to avoid many kinds of high-risk behavior over many years.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Monoclonal antibodies reacting with the interleukin 1 receptor define a multi-molecular complex.

By sequential immunization with a variety of different interleukin (IL) 1 receptor (IL 1R)-bearing cells and by generating a large number of clones from a single fusion experiment, we have managed to produce two monoclonal antibodies which react with the lymphocyte IL 1R. The antibodies also react with the mouse fibroblast line, 3T3, but we have not yet defined their reactivity with cells carrying low-affinity receptors. Immunoprecipitation allows the IL 1R to be isolated from EL4 6.1 cell membrane preparations and shows that the IL 1R exists as a complex. The antibodies clearly interfere with IL 1 responses both in vitro and in vivo. These are the first anti-mouse IL 1R antibodies to be described which clearly and profoundly affect the immune response.

Animals↗
PubMed1990

Phase I and pharmacokinetic study of intraperitoneal thioTEPA in patients with ovarian cancer.

A total of 15 patients with residual ovarian cancer confined to the peritoneal cavity after first-line systemic chemotherapy were treated with triethylene-thiophosphoramide (thioTEPA) in a phase I study. A total of 50 courses of thioTEPA were given intraperitoneally in doses ranging from 30 to 80 mg/m2. The dose limiting toxicity was myelosuppression, which occurred at 80 mg/m2 and was frequently prolonged. Short-lived nausea and vomiting was easily controlled, and there was no local toxicity. Three patients remain free of disease progression at 6, 6 and 12 months. ThioTEPA concentrations were measured by gas chromatography. Peritoneal fluid concentrations declined rapidly in a first-order fashion, with a half-life of 0.96 +/- 0.1 h. A mean of 93% of the drug was absorbed during the 4-h dwell time. Peak plasma levels were achieved 30-60 min after drug instillation and were substantially lower than corresponding peritoneal levels. A pharmacokinetic advantage for intraperitoneal delivery was detected for peak drug concentration (24.9 +/- 8.5) and AUC (9.2 +/- 4.8). Based on this study, the recommended dose for intraperitoneal thioTEPA is 60 mg/m2 every 3-4 weeks. However, the rapid absorption of this drug from the peritoneum, secondary to thioTEPA's small molecular weight and lipophilic nature, suggests that it has only a limited role in intraperitoneal therapy.

Adult↗
PubMed1990

Patterns of fecal coliform contamination in day-care centers.

During a six-month period, on four separate occasions, six licensed day-care centers had cultures taken from environmental surfaces as well as the hands of children and teachers. Fecal coliforms were recovered from 64 (9.5%) of the 675 surfaces sampled. Recovery rate was not influenced by a center's socioeconomic status, time of year, or presence of children who were not toilet trained. Recovery rates did differ significantly in different areas, with the kitchen showing a relatively high recovery rate (19%), and toys and toilets showing remarkably low rates (2% and 4%). Centers with formal hand-washing procedures had lower recovery rates than those without such practices. We also demonstrated a high recovery rate from hands of staff (16%); 6% of children had positive cultures. Contamination of hands and classroom objects is a potential source for the transmission of enteric diseases for children in day-care centers. A program directed at reducing contamination would be important in preventing the spread of diarrheal illness.

Child↗
PubMed1990

Three-year-olds' problems with false belief: conceptual deficit or linguistic artifact?

Researchers are divided over whether young children understand other people's minds. This study reexamines the main technique used to show a basic inability in 3-year-olds to make judgments about a person's thoughts when that person's knowledge happens to be false. 131 children, aged 3, 3 1/2, and 4, were shown the real, unexpected contents of a chocolate box and were required to say what a friend would think was in it and what their own previous expectations had been. Success in this task was compared between the 3 age groups and also according to the specificity of questions asked. It was found, in contrast to previous findings, that test questions that are temporally specific and syntactically straightforward enable most 3-year-olds to attribute false beliefs to others. These results suggest that 3-year-olds' access to information about others' mental states is bounded by the linguistic demands placed upon them, but long before their fourth birthday children have some understanding of others' mind.

Child, Preschool↗