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Biomedical subjects

T Knapp

Publications and source records attributed to T Knapp.

18 recordsLinked to original sources

The specialty of the treating physician affects the likelihood of tumor-free resection margins for basal cell carcinoma: results from a multi-institutional retrospective study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy. Surgical experience and physician specialty may affect the outcome quality of surgical excision of BCC. METHODS: We performed a multicenter retrospective study of BCC excisions submitted to the respective Departments of Pathology at 4 major university medical centers. Our outcome measure was presence of histologic evidence of tumor present in surgical margins of excision specimens (incomplete excision). Clinician experience was defined as the number of excisions that a clinician performed during the study interval. The analytic sample pool included 1459 tumors that met all inclusion and exclusion criteria. Analyses included univariate and multivariate techniques involving the entire sample and separate subsample analyses that excluded 2 outlying dermatologists. RESULTS: Tumor was present at the surgical margins in 243 (16.6%) of 1459 specimens. A patient's sex, age, and tumor size were not significantly related to the presence of tumor in the surgical margin. Physician experience did not demonstrate a significant difference either in the entire sample (P <.09) or in the subsample analysis (P >.30). Tumors of the head and neck were more likely to be incompletely excised than truncal tumors in all the analyses (P <.03). Compared with dermatologists, otolaryngologists (P <.02) and plastic surgeons (P <.008) were more likely to incompletely excise tumors; however, subsample analysis for plastic surgeons found only a trend toward significance (P <.10). Dermatologists and general surgeons did not differ in the likelihood of performing an incomplete excision (P >.4). CONCLUSION: The physician specialty may affect the quality of care in the surgical management of BCC.

Aged↗

A genetically encoded, fluorescent indicator for cyclic AMP in living cells.

Cyclic AMP controls several signalling cascades within cells, and changes in the amounts of this second messenger have an essential role in many cellular events. Here we describe a new methodology for monitoring the fluctuations of cAMP in living cells. By tagging the cAMP effector protein kinase A with two suitable green fluorescent protein mutants, we have generated a probe in which the fluorescence resonance energy transfer between the two fluorescent moieties is dependent on the levels of cAMP. This new methodology opens the way to the elucidation of the biochemistry of cAMP in vivo.

Adrenergic alpha-Agonists↗

John Dewey's unknown critique of marginal utility doctrine: instrumentalism, motivation, and values.

During the late nineteenth century, marginal utility theory became the dominant ideology of the new academic discipline of economics. This article explicates and discusses previously unexamined lecture notes prepared in 1913 by John Dewey on marginal utility doctrine. After briefly characterizing the state of marginal utility doctrine, Dewey's criticisms are shown to derive from his instrumentalism and general theory of value. In Dewey's view, marginalism privatized value and by doing so induced moral agnosticism, a condition of permanently suspended judgment regarding individual and social needs that was likely to undermine the foundations of a democratic community since it immunizes value against collective appraisal by public bodies. Moreover, while marginal utility theory represented a serious concerted attempt to deal with substantive problems of value in economics and the economy, to Dewey it was ultimately a form of apologetics for the existing mode of social relations.

Economics↗

Briefly noted

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Journal Article↗

News and notes

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Journal Article↗

MR imaging of symptomatic osteochondromas with pathological correlation.

OBJECTIVE: To demonstrate the value of MR imaging in the diagnosis and differentiation of the various symptomatic complications of osteochondromas, providing pathological correlation with emphasis on the usefulness of MR imaging as a single imaging modality in these patients. DESIGN: We retrospectively reviewed all MR examinations of clinically symptomatic osteochondromas (30 patients) performed at our institution between March 1990 and October 1997. PATIENTS: Thirty patients had clinically symptomatic osteochondromas during the study period. Twenty patients were male and 10 were female. There were five cases of multiple osteochondromatosis. Pathological correlation was available in 24 patients. RESULTS AND CONCLUSION: Symptomatic complications included fracture (7%), osseous deformity limiting range of motion (23%), vascular injury (7%), neurological compromise (10%), bursa formation (27%) and malignant transformation (27%). MR imaging was able to diagnose or suggest the etiology for the clinical symptomatology in all cases, demonstrating that it is an ideal imaging modality in the diagnostic evaluation of symptomatic complications of osteochondromas and often avoids the need for further imaging.

Adolescent↗

A genome-wide functional assay of signal transduction in living mammalian cells.

We describe a genome-wide functional assay for rapid isolation of cell clones and genetic elements responsive to specific stimuli. A promoterless beta-lactamase reporter gene was transfected into a human T-cell line to generate a living library of reporter-tagged clones. When loaded with a cell-permeable fluorogenic substrate, the cell library simultaneously reports the expression of a large number of endogenous genes. Flow cytometry was used to recover individual clones whose reporter-tagged genes were either induced or repressed following T-cell activation. Responsive clones were expanded and analyzed pharmacologically to identify patterns of regulation associated with specific genes. Although demonstrated using T cells, the genomic assay could be applied to map downstream transcriptional consequences for any propagating cell line in response to any stimulus of interest.

Cell Separation↗

Collagen-induced secretion-dependent phase of platelet aggregation is inhibited by the snake venom metalloproteinase jararhagin.

Jararhagin, a 52 kDa metalloproteinase from Bothrops jararaca snake venom, belongs to the family of enzymes with an N-terminal Zn2+-containing enzymatic domain, a disintegrin-like domain and a cysteine-rich C-terminal domain. Both jararhagin and jararhagin C, a 28 kDa-protein from the same venom identical to the disintegrin-like domain of jararhagin, inhibit collagen-induced platelet aggregation. In this study, jararhagin and synthetic linear peptides based on the disintegrin-like domain of jararhagin overlapping with the RGD sequence of venom disintegrins, were shown for the first time to inhibit the release of 5-hydroxytryptamine (5-HT) from platelets preloaded with [14C]5-HT and stimulated with collagen. The normal phosphorylation of the 21-kDa myosin light chain (p21) in response to the stimulation indicated that jararhagin and the peptides did not interfere with platelet shape change. The selective inhibition of the secretion-dependent phase of the platelet response to collagen by the enzyme and its peptides was confirmed by the defective phosphorylation of pleckstrin, a 47-kDa platelet protein (p47) involved in dense granule secretion.

Amino Acid Sequence↗

The influence of silicone implantation on type II collagen-induced arthritis in mice.

OBJECTIVE: To determine whether silicone implantation exacerbates autoimmune disease in a murine experimental model of arthritis. METHODS: DBA/1 mice were implanted with silicone in the form of an elastomer, gel, or oil, and immunized with type II collagen. The influence of silicone implantation on collagen-induced arthritis and the immune response to type II collagen were determined by comparison against control mice receiving sham implantation. Adjuvant effects of silicone implantation were examined by measuring cytokine levels in implanted animals and assessing autoantibodies against proteins extracted from recovered silicone implants. RESULTS: No adverse influence of silicone implantation on the clinical aspects of collagen-induced arthritis was observed. Further, polydimethylsiloxane silicone oil failed to serve as an adjuvant in the immune or arthritogenic response to type II collagen in mice. Cytokine analysis indicated that tumor necrosis factor alpha levels were lower and interleukin-2 levels were higher in silicone-implanted mice. The development of arthritis increased protein binding to implanted elastomers and gel, and autoantibodies against silicone-bound proteins were present in sera from arthritic mice and absent in sera from nonarthritic mice. CONCLUSION: The data suggest that silicone implantation may result in autoantibodies against silicone-bound proteins, and the presence of arthritis may either provoke or increase the level of such autoantibodies. However, silicone implantation did not increase the incidence or severity of disease compared with sham-operated controls. Thus, it appears that autoantibodies against silicone-bound proteins may not have pathologic significance in this experimental model of arthritis.

Animals↗

What psychology students know and believe about Charles Darwin.

204 introductory and 154 advanced students in psychology were asked about their knowledge of Charles Darwin and endorsement of belief statements about the status of evolutionary theory. Advanced students had higher scores than introductory students on three of six multiple-choice knowledge items and differed from them on all six statements of belief as assessed by chi 2. Advanced students appear to know more about evolutionary theory but may be less inclined to endorse its relevancy to psychology.

Biological Evolution↗

Imipramine for the treatment of cocaine and methamphetamine dependence.

At the Drug Detoxification, Rehabilitation, and Aftercare Program of the Haight-Ashbury Free Clinics, we conducted a double-blind, controlled, randomized clinical trial of imipramine in the treatment of cocaine and methamphetamine abusers. The purpose of the trial was to test the efficacy of imipramine as a treatment for stimulant dependence and to establish the feasibility of conducting a controlled clinical trial at the clinic under conditions that approximated usual clinical practice. Subjects were randomly assigned to receive either 10 or 150 mg/day of imipramine. Imipramine 10 mg/day was the control condition. Subjects could receive study medication for up to 180 days. One-hundred eighty-three subjects participated in the study: 151 were cocaine dependent and 32 were methamphetamine dependent. In addition to receiving study medication, all subjects were assigned to intensive drug abuse counseling, which included an HIV education component. Using an intention-to-treat analysis, we found that retention in treatment was significantly longer for subjects who were treated with 150 mg of imipramine compared to control. However, we found no consistent differences between the two groups of subjects in Beck Depression Inventory scores, stimulant craving, self-report of time since last use of stimulants, or percent of urinalyses positive for stimulants. The feasibility of conducting a controlled, randomized clinical trial of medication for treatment of drug abuse was established for this community clinic setting.

Cocaine↗

Molecular biological approaches to the study of vectors in relation to malaria control.

To a large extent, control of malaria vectors relies on the elimination of breeding sites and the application of chemical agents. There are increasing problems associated with the use of synthetic insecticides for vector control, including the evolution of resistance, the high cost of developing and registering new insecticides and an awareness of pollution from insecticide residues. These factors have stimulated interest in the application of molecular biology to the study of mosquito vectors of malaria; focussing primarily on two aspects. First, the improvement of existing control measures through the development of simplified DNA probe systems suitable for identification of vectors of malaria. The development of synthetic, non-radioactive DNA probes suitable for the identification of species in the Anopheles gambiae complex is described with the aim of defining a simplified methodology which is suitable for entomologist in the field. The second aspect to be considered is the development of completely novel strategies through the genetic manipulation of insect vectors of malaria in order to alter their ability to transmit the disease. The major requirements for producing transgenic mosquitoes are outlined together with the progress which has been made to date and discussed in relation to the prospects which this type of approach has for the future control of malaria.

Animals↗

Cloning of a polymorphic DNA fragment from the genome of Leishmania donovani.

Recombinant DNA clones, containing highly repetitive DNA sequences, have been isolated from a Leishmania donovani genomic DNA library prepared in the replacement vector lambda gt.WES.lambda B. Two clones, probably telomeric in location, have been characterised and show a restriction fragment size polymorphism. Evidence is presented which suggests that L. donovani is diploid for this cloned genomic locus.

Animals↗

The tubulin genes of Trypanosoma cruzi.

The organization of the alpha- and beta-tubulin genes in the genome of Trypanosoma cruzi have been analysed by Southern blotting using tubulin probes derived from Trypanosoma brucei. The tubulin array appears to be more complex in this organism than in other members of the same family. Some tubulin genes are tightly clustered in an alternating (alpha-beta)n array with a basic repeat unit length of 4.3 kb. However, other pairs of alternating alpha- and beta-tubulin sequences appear to be physically separated from the basic group. This finding indicates that the tubulin gene cluster present in T. cruzi is less perfectly conserved than in T. brucei. T. (Herpetosoma) rangeli is similar to T. (Schizotrypanum) cruzi in its tubulin gene organization whereas most of these genes are tandemly clustered in the genome of T. (Trypanozoon) evansi, with a basic repeat unit length of 3.6 kb as previously described for T. (Trypanozoon) brucei. Two overlapping recombinant clones containing T. cruzi tubulin sequences have been isolated from a genomic cosmid library of T. cruzi epimastigotes using the T. brucei tubulin probes. Partial sequencing of the T. cruzi beta-tubulin gene has confirmed its identity and shows more than 70% homology with the sea urchin, chicken and T. b. rhodesiense beta-tubulin reported gene sequences. Analysis of tubulin gene organization through the parasite life cycle does not show evidence of major rearrangements within the repeat unit. Several T. cruzi strains and cloned lines whilst sharing the 4.3-kb tubulin repeat unit, exhibited very variable tubulin gene organization with tubulin probes. These striking differences in the organization of this structural gene among T. cruzi strains and cloned lines suggest that the heterogeneity previously reported in parasite populations may be related to a very dynamic, diploid genome.

Animals↗

The impact of medical, reeducational, and psychological variables on rehabilitation outcome in amputees.

178 male unilateral above-knee amputees (cause of amputation: war injury or accident) participated in the study. Medical reeducational, social, vocational, and psychological predictor variables as well ad medical, social, vocational, and psychological outcome variables were assessed by means of interviews, expert ratings, questionnaires, and by ratings from the amputees partners. A series of risk factors for poor rehabilitation was specified by means of discriminant and correlational analyses. Optimization of medical/reeducational care, helping the amputee to gain insight into the necessity of amputation, making available to him a person to confide in with personal problems, and helping him to overcome social withdrawal seem to be the most important measures to prevent poor rehabilitation outcome.

Adolescent↗

A controlled trial of imipramine for the treatment of methamphetamine dependence.

At the Drug Detoxification Program of the Haight Ashbury Free Clinics, we conducted a randomized clinical trial of imipramine in the treatment of methamphetamine dependence. The purposes of the trial were to test the efficacy of imipramine as a treatment for methamphetamine dependence and to establish the feasibility of conducting a controlled clinical trial at the Clinic. Thirty-two subjects were randomly assigned to receive either 10 or 150 mg/day of imiprine for 180 days. Imipramine 10 mg/day was the control. Subjects received intensive counseling. Retention in treatment was significantly longer for subjects who were treated with 150 mg of imipramine compared to control (median days: 33.0 vs. 10.5). There were no consistent differences in percent of urine samples positive for methamphetamine, Beck Depression Inventory scores, or craving. Determination of the full extent of imipramine's utility in the treatment of methamphetamine dependence awaits a larger trial.

Adult↗