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Biomedical subjects

L Walters

Publications and source records attributed to L Walters.

At least 37 records · Page 2Linked to original sources
PubMed1993

Data monitoring committees: the moral case for maximum feasible independence.

Since data monitoring committees (DMCs) began to be established in the 1970s, they have reviewed the clinical outcome data emerging from ongoing trials. The thesis of this essay is that DMCs most effectively promote the validity and credibility of randomized clinical trials when they perform this function with the maximum feasible independence. The essay argues that four types of individuals and groups should be excluded from the interim monitoring of outcome data: (1) investigators entering patients into a trial; (2) principal investigators or study chairs; (3) representatives of commercial firms connected with a trial; and (4) representatives of regulatory agencies. The role of statistical groups and officials of government funding agencies in the review of outcome data is also discussed.

Clinical Trials as Topic↗
PubMed1992

Fibulin is localized at sites of epithelial-mesenchymal transitions in the early avian embryo.

Fibulin is a 100-kDa calcium-binding, extracellular matrix (ECM), and plasma glycoprotein (Argraves et al., Cell 58, pp. 623-629, 1989; Argraves et al., J. Cell Biol. 111, 3155-3164). Immunoprecipitation analysis showed that antibodies against human fibulin react with an avian isoform (M(r) 100,000). The spatial and temporal distribution of fibulin was examined in the early avian embryo using immunofluorescence microscopy. In stage 15-22 quail embryos fibulin is a constituent of most basement membranes. Areas undergoing epithelial-mesenchymal transitions such as the endocardial cushions, developing myotomes, and neural crest display especially prominent immunostaining. In the early heart fibulin expression was most pronounced in the cardiac jelly at sites where endocardial cushion cells begin the migrations that lead to the formation of valvular and septal primordia. Laser scanning confocal microscopy showed extensive extracellular accumulations of fibulin on the surface of endocardial mesenchyme cells that were motile at the time of fixation (stage 19). These data suggest that enhanced deposition of fibulin at sites of epithelial-mesenchymal transitions may influence cell behavior.

Animals↗
PubMed1992

Zocor, the postmarketing experience.

The aim of this study was to develop and test a descriptive, intensive drug surveillance methodology in order to examine the effectiveness and safety of new drugs in the immediate postmarketing period. The HMG-CoA reductase inhibitor, simvastatin (Zocor), was chosen as the test drug. Data were collected from 100 randomly chosen cardiologists, specialist physicians and general practitioners practising in the six main centres of South Africa. A 66% doctor response rate was achieved and 438 patients were enrolled in the study. The overall effectiveness expressed as a percentage decrease (from baseline) in total cholesterol levels was 20.5% for the 251 patients who started on a 10 mg daily dose of the drug and 27.6% for the 42 patients who started on 10 mg but changed to 20 mg/d. The safety profile of simvastatin was comparable with the premarketing clinical trial data, and patient non-compliance appeared to be dose-related. The methodology employed was found to be suitable for the collection of safety and effectiveness data in the postmarketing period and simvastatin was shown to be effective with few adverse events reported.

Adult↗
PubMed1991

Human gene therapy: ethics and public policy.

The first three human gene transfer/therapy clinical protocols are now underway after having been subjected to an extensive review process by the Recombinant DNA Advisory Committee (RAC) and its Human Gene Therapy Subcommittee. The "Points to Consider" document developed by the RAC established the framework for evaluating genetic intervention protocols. This review process is taking place in a broader social context. Public attitude surveys in this country have indicated a general lack of knowledge in the area of genetic engineering but an acceptance of somatic-cell gene therapy as treatment for disease. Internationally, numerous policy statements on human genetic intervention have been published, all of which support the moral legitimacy of somatic-cell gene therapy for the cure of disease. The debate over the ethical issues related to somatic-cell gene therapy has evolved over a ten-year-period. The time has now come to begin a formal public process for the ethical assessment of germ-line genetic intervention.

Advisory Committees↗
PubMed1990

Fourier transform infrared spectroscopy for the characterization of a model peptide-DNA interaction.

To better understand the structural basis of protein-DNA interactions, the conformational changes that accompany these interactions need to be described. In order to develop a methodological approach to this problem, Fourier transform infrared spectroscopy (FTIR) with derivative resolution enhancement has been used to identify conformational changes that occur when a 29-residue synthetic peptide binds nonspecifically to heterogeneous cellular DNA in aqueous solution. The peptide sequence was chosen de novo, in order to rationally design a peptide model that would allow the relationship between DNA binding and the stability of protein secondary structure to be studied. Peptide at a concentration of 100-200 microM produces 50% saturation of heterogeneous phage DNA sequences as well as of short synthetic oligonucleotides. FTIR spectra reveal significant changes in peptide and DNA upon binding. Second-derivative spectra resolve the amide I band of native peptide into components located at 1627 (beta-strand), 1658 (alpha-helix), and 1681 (turn or beta-strand) cm-1, with a distinct shoulder at 1647 cm-1 (disordered structure). Assignment of the 1681 cm-1 vibration to a turn conformation is supported by uv CD studies, which indicate significant amounts of turn structure in unbound peptide. Ultraviolet CD also confirms the existence of disordered and beta-strand regions in the free peptide. Upon interacting with DNA the band at 1681 cm-1 (turn) is no longer seen; a new band appears at 1675 cm-1; the 1627 cm-1 band (beta-strand) is considerably reduced in intensity; the position of the alpha-helical (1658 cm-1) component remains unchanged; the shoulder at 1647 cm-1 (disorder) disappears. The new vibration at 1675 cm-1 is characteristic of beta-strand structures. The asymmetric stretch (vAS) of the DNA phosphates shifts from 1223 (unbound) to 1229 cm-1 (bound); the relative intensities of vAS and the PO2- symmetric stretch (vS) are altered upon peptide binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
PubMed1990

Avian vasculogenesis and the distribution of collagens I, IV, laminin, and fibronectin in the heart primordia.

The heart-forming regions of the early embryo are composed of splanchnic mesoderm, endoderm, and the associated ECM. The ECM of the heart-forming regions in stage 7-9 chicken embryos was examined using immunofluorescence. Affinity purified antibodies to chicken collagens type I and IV, chicken fibronectin, and mouse laminin were used as probes. We report that (1) the basement membrane of the endoderm contains immunoreactive laminin and collagen IV; (2) the nascent basement membrane of the heart splanchnic mesoderm contains immunoreactive laminin, but not type IV collagen, and (3) the prominent ECM between the splanchnic mesoderm and the endoderm (the primitive-heart ECM) contains collagen IV, collagen I, fibronectin, but not laminin. In addition, we describe microscopic observations on the spatial relationship of cardiogenic cells to the primitive-heart ECM and the endodermal basement membrane.

Animals↗
PubMed1990

Feeling fat: motivations, knowledge, and attitudes of overweight women and men.

This study concerned obesity from the perspective of 47 women and 8 men who considered themselves overweight. They responded to a questionnaire about various aspects of motivation to lose weight, knowledge about obesity, and personal and societal attitudes toward the obese. Although they reduced calorie intake and increased exercise when trying to lose weight, they reported various reasons why their exercise levels were less than optimal. Verbal motivation to lose was only partially reflected in willingness to change lifestyle, even though respondents had spent substantial sums of money on weight-loss attempts. Knowledge about obesity was imperfect, with women and thinner subjects somewhat more knowledgeable. Subjects were aware of and shared some of the negative social stereotypes of the obese, blaming themselves for their overweight. However, most would not trade their obesity for other handicaps found less stigmatizing in other research. As expected, women expressed a greater desire for thinness than men. Implications for health care professionals are discussed.

Adult↗
PubMed1989

Peptide and protein synthesis by segment synthesis-condensation.

The chemical synthesis of biologically active peptides and polypeptides can be achieved by using a convergent strategy of condensing protected peptide segments to form the desired molecule. An oxime support increases the ease with which intermediate protected peptides can be synthesized and makes this approach useful for the synthesis of peptides in which secondary structural elements have been redesigned. The extension of these methods to large peptides and proteins, for which folding of secondary structures into functional tertiary structures is critical, is discussed. Models of apolipoproteins, the homeo domain from the developmental protein encoded by the Antennapedia gene of Drosophila, a part of the Cro repressor, and the enzyme ribonuclease T1 and a structural analog have been synthesized with this method.

Amino Acid Sequence↗
PubMed1989

Distribution of laminin, collagen type IV, collagen type I, and fibronectin in chicken cardiac jelly/basement membrane.

Light microscopic immunolabeling studies were designed to identify and locate structural components within the cell-free extracellular matrix which lies between the embryonic endocardial and myocardial tubes. Affinity-purified antibodies were used to examine stage 15-22 embryonic chicken hearts. Specimens were immunolabeled by using three different methodologies: 1) postembedding labeling of 10 microns cryostat sections, 2) preembedding labeling (en bloc) of whole hearts, and 3) postembedding labeling of ethanol/acetic acid-fixed paraffin sections. Our results establish the spatial distribution of collagen type I and demonstrate for the first time the presence of collagen type IV and laminin in the myocardial-basement-membrane/cardiac jelly.

Animals↗
PubMed1989

Precursors of chondroitin sulfate proteoglycan are segregated within a subcompartment of the chondrocyte endoplasmic reticulum.

Immunocytochemical methods were used at the levels of light and electron microscopy to examine the intracellular compartments of chondrocytes involved in extracellular matrix biosynthesis. The results of our studies provide morphological evidence for the compartmentalization of secretory proteins in the ER. Precursors of the large chondroitin sulfate proteoglycan (CSPG), the major proteoglycan species produced by chondrocytes, were present in the Golgi complex. In addition, CSPG precursors were localized in specialized regions of the ER. Link protein, a separate gene product which functions to stabilize extracellular aggregates of CSPG monomers with hyaluronic acid, was segregated similarly. In contrast, type II procollagen, another major secretory molecule produced by chondrocytes, was found homogeneously distributed throughout the ER. The CSPG precursor-containing ER compartment exhibits a variable tubulo-vesicular morphology but is invariably recognized as an electronlucent, smooth membrane-bounded region continuous with typical ribosome-studded elements of the rough ER. The observation that this ER structure does not stain with antibodies against resident ER proteins also suggests that the compartment is a specialized region distinct from the main part of the ER. These results support recent studies that consider the ER as a compartmentalized organelle and are discussed in light of the possible implications for proteoglycan biosynthesis and processing.

Animals↗
PubMed1988

Ethical issues in the prevention and treatment of HIV infection and AIDS.

The epidemic of infection with the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS) poses a major ethical question: How can we control the epidemic and the harm that it causes without unjustly discriminating against particular social groups and without unnecessarily infringing on the freedom of individuals? This question pertains to three spheres of public policy in the United States: public health, the delivery of health care, and research. In the public health sphere, vigorous educational efforts will be required, as will modified approaches to intravenous drug use, prostitution, and homosexual and bisexual sexual activity. Carefully targeted, voluntary testing and screening programs should be coupled with counseling and with guarantees of confidentiality and nondiscrimination where these are appropriate. Both health care workers and the health care system have a moral obligation to provide care to people with HIV infection, but heroic self-sacrifice should not be required provided that infection control precautions are observed. Patients with neurological involvement and terminally ill patients will benefit from statutes allowing recognition of advance directives about preferred modes of care or nontreatment. There is a moral imperative to perform intensive research directed toward the understanding, treatment, and prevention of HIV infection and AIDS. The research process will raise challenging ethical questions.

Acquired Immunodeficiency Syndrome↗