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Biomedical subjects

B Walker

Publications and source records attributed to B Walker.

At least 109 records · Page 6Linked to original sources
PubMed1997

Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serum.

To evaluate its role in protection, immune serum was collected from four macaques which were chronically infected with live attenuated simian immunodeficiency virus (SIVmacC8) and had resisted challenge with wild-type SIVmacJ5. The immune serum was transferred to two naive cynomolgus macaques by intraperitoneal injection (11 ml/kg). Four control macaques received an intraperitoneal injection of normal saline. One day later, all macaques were challenged with 10 MID50 of the J5M challenge stock of SIV. After challenge, all macaques became infected as determined by virus co-culture and diagnostic PCR. Virus loads in PBMC at 2 weeks post-challenge were indistinguishable between the two groups of macaques. Thus, the failure of passive immunization to transfer protection indicates that serum components alone are not sufficient to mediate the potent protection obtained using live attenuated vaccines. This is the first time that serum has been transferred from animals known to be protected against superinfection.

Animals↗
PubMed1997

Public health in a managed care environment.

As the health care system moves in a new direction, toward managed care, the critical role of public health in society's efforts to mitigate illness and the realization of health become more apparent. Indeed, the public health problems of this era will not yield to simple solutions. They require a multitude of resources, both human and material, and a myriad of services derived from these resources. Public health's role is to serve as the government's presence in assessing health status, developing policy, evaluating the effectiveness of policy implementation, and assuring access to and quality of comprehensive health services. Increasingly, public health must coordinate a wide array of systems in both the private and public sectors to fulfill its purpose.

Community Health Planning↗
PubMed1997

Cancer risk assessment.

Increasing efforts to reduce the burden of cancer have brought into sharp relief the relevance of cancer risk assessment in preventing the occurrence and, when that is not possible, preventing the progression of the disease. Methods for estimating human cancer risk have evolved steadily over the past few decades as more has been learned about molecular, genetic, and biological aspects of cancer. These methods have been applied with increasing frequency in community-based approaches to reduce the risk of environmentally provoked cancers. At the same time, patients are showing increased interest in estimates of their likelihood of developing cancer during the next 10, 20, or 30 years. This interest is involving more physicians in human cancer risk assessment in clinical counseling settings.

Biomarkers↗
PubMed1997

Founders-Sumner lecture.

The revolution in patient care financing and in the structure and changing scope of the health service system calls for leaders in health care to address existing challenges in the health delivery system. Medical leadership cannot ignore, much less resist, the challenges inherent in the flux and dynamic changes going on in the medical care/health sciences environment. Some of these changes are fueled by fundamental advancements in science and technology. Other developments are fueled by political, demographic, economic and social forces. This article highlights some of these challenges and urges the medical leadership to assume the obligation to assure quality of health-care services and not allow it to be over-shadowed by market forces.

Delivery of Health Care↗
PubMed1997

Do prescribing formularies help GPs prescribe from a narrower range of drugs? A controlled trial of the introduction of prescribing formularies for NSAIDs.

BACKGROUND: Previous studies have suggested that prescribing formularies may promote rational prescribing. The range of drugs prescribed may be one aspect of rational prescribing. AIM: To determine whether the introduction of prescribing formularies helps general practitioners (GPs) to prescribe from a narrower range of non-steroidal anti-inflammatory drugs (NSAIDs). METHOD: General practices in Lincolnshire were offered help in developing prescribing formularies. Ten practices decided to develop a formulary for NSAIDs. Level 3 PACT data were used to determine whether changes in prescribing had occurred with the introduction of the formulary. Matched controls were used to determine whether similar changes had occurred in other practices. RESULTS: Between April and June 1992, and during the same period in 1993, practices that introduced a formulary for NSAIDs reduced the mean number of different drugs used (14.3 versus 13.1, P = 0.04) and increased the percentage of NSAID-defined daily doses coming from the three most commonly used drugs (70.1% versus 74.8%, P = 0.02). Similar changes were not seen in control practices. CONCLUSION: Following the development of a formulary for NSAIDs, practices prescribed from a narrower range of drugs and focused a greater proportion of their prescribing on their three most commonly used drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Murine epidermal growth factor peptide (33-42) binds to a YIGSR-specific laminin receptor on both tumor and endothelial cells.

A laminin-antagonist peptide, comprising amino acids 33-42 of murine epidermal growth factor (mEGF-(33-42)), interacts with a breast cancer- and endothelial cell-associated receptor, which is specific for the laminin B1 chain sequence, CDPGYIGSR-NH2 (Lam.B1-(925-933)), and is immunologically similar to a previously described 67-kDa laminin receptor. In whole cell receptor assays, mEGF-(33-42), Lam. B1-(925-933), and laminin all have IC50 values for displacement of 125I-laminin in the range 1-5 nM. Cell attachment to solid-phase laminin is also blocked by all three ligands, but in contrast to the receptor assays, mEGF-(33-42) or Lam.B1-(925-933), while equipotent with each other, were less effective than laminin. The concentrations of the peptides required to produce half-maximal inhibition of attachment were in the range 230-390 nM, but those for laminin were 1000-fold lower, in the range 0.2-0.3 nM. Like laminin, solid-phase mEGF-(33-42) supports cell attachment, and this ability is blocked by anti-67-kDa receptor antibodies. Modeling studies suggest that both peptides present a tyrosyl and an arginyl residue on the same face of a right-handed helical fold with elliptical cross-section.

Amino Acid Sequence↗
PubMed1996

Molecular architecture of a toxin pore: a 15-residue sequence lines the transmembrane channel of staphylococcal alpha-toxin.

Staphylococcus aureus alpha-toxin is a hydrophilic polypeptide of 293 amino acids that produces heptameric transmembrane pores. During assembly, the formation of a pre-pore precedes membrane permeabilization; the latter is linked to a conformational change in the oligomer. Here, 41 single-cysteine replacement toxin mutants were thiol-specifically labelled with the polarity-sensitive fluorescent probe acrylodan. After oligomerization on membranes, only the mutants with acrylodan attached to residues in the sequence 118-140 exhibited a marked blue shift in the fluorescence emission maximum, indicative of movement of the fluorophore to a hydrophobic environment. Within this region, two functionally distinct parts could be identified. For mutants at positions 126-140, the shifts were partially reversed after membrane solubilization by detergents, indicating a direct interaction of the label with the membrane lipids. Membrane insertion of this sequence occurred together with the final pre-pore to pore transition of the heptamer. Thus residues 126-140 constitute a transmembrane sequence in the pore. With labelled residues 118-124, pre-pore assembly was the critical event to induce the spectral shifts, which persisted after the removal of membrane lipids and hence probably reflects protomer-protomer contacts within the heptamer. Finally, a derivative of the mutant N121C yielded occluded pores which could be opened by reductive reversal of the modification. Therefore this residue probably lines the lumen of the pore.

2-Naphthylamine↗
PubMed1996

MMPI-2 patterns in African-American females.

Researchers have reported conflicting conclusions about the relation of the MMPI (MMPI-2) clinical scale elevations and race. Consequently, this study examined the concurrent validity of the MMPI-2 in evaluating African-American females. Seventy-eight (78) African American college student volunteers were administered the MMPI-2, along with other measures of personality, achievement, and coping style. Scores revealed 76% of the sample had elevated profiles. Subjects were divided into three groups based on frequency of clinical scale code type. Subjects with the 5/9 profile elevations functioned as well as normals on measures of coping skills and mood disorders. Discussion emphasizes the importance of clinical interpretation of MMPI data in research programs and the relationship of the data to coping style.

Adaptation, Psychological↗
PubMed1996

Assessment of urinary gonadotropin in solid carcinomas other than gynecological tumors.

To the already long list of existing tumor markers, a new marker has been recently added, the urinary gonadotropin peptide (UGP). This marker is determined in the urine of cancer patients and is considered to be particularly specific for ovarian carcinomas. The purpose of our study was to assess the specificity of UGP in a variety of malignancies other than ovarian carcinomas, e.g., breast, colonic, lung, and urogenital tumors (n = 50 each). The tumors were compared with benign lesions of the same organs. Urine samples of 50 healthy donors served as controls. The 450 urine samples were tested in duplicate using the UGP EIA-kit from Ciba Corning Diagnostics. All tumors were staged and histologically classified. For normalization in all samples, creatinine levels were determined. UGP was found in all tested tumors, however, with very low sensitivity of 20% in urogenital tumors, 46% in lung, and 30% or 27% in colon and breast carcinomas, respectively. The specificity of UGP was comprised between 100% (breast) and 88%. Clearly elevated UGP-concentrations were seen in postmenopausal women. A comparison of UGP with the optimal markers for each tumor system showed that UGP is not superior to these markers. However, we can confirm UGP as being an optimal marker for gynecological carcinomas.

Adolescent↗
PubMed1996

IL-4 and TNF-alpha-mediated proliferation of the human megakaryocytic line M-O7E is regulated by induced autocrine production of GM-CSF.

In this study, the authors examined the effects of recombinant human interleukin 4 (rhIL-4) and recombinant human tumour necrosis factor alpha (rhTNF-alpha) alone or in combination on proliferation of the human cytokine dependent myeloid cell line, M-O7e. While rhIL-4 or rhTNF-alpha alone induced only a weak proliferative response, a synergistic proliferative signal was clearly evident on stimulation of cells with a combination of both cytokines. The stimulatory effect of rhTNF-alpha is mediated predominantly by the 55-kDa TNF receptor because the agonistic monoclonal antibody htr-9 and the Trp32 Thr86 TNF-alpha mutant protein specific for this receptor type produced similar results to rhTNF-alpha. In contrast, the Asn143 Arg145 TNF-alpha mutant protein specific for the 75-kDa TNF receptor produced only minimal proliferation of M-O7e cells. Using RT-PCR, we found that rhTNF-alpha rapidly and strongly induced granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA production, while rhIL-4 was a slow and less efficient inducer of GM-CSF mRNA. However, there was little evidence of the TNF-alpha/IL-4 combination acting synergistically on GM-CSF mRNA production as the levels of GM-CSF mRNA increased only marginally compared with IL-4 or TNF-alpha alone. Thus, the observed synergistic effect of TNF-alpha/IL-4 costimulation of M-O7e cells seems to be mediated via induction of GM-CSF secretion rather than an enhanced production of GM-CSF mRNA. Higher levels of GM-CSF were detectable in supernatants of cells treated with both rhIL-4 and rhTNF-alpha than in cells stimulated with either cytokine alone. Furthermore, addition of a neutralising antibody against GM-CSF abrogated the observed synergistic effect of rhIL-4 and rhTNF-alpha treatment, indicating that the rhIL-4/TNF-alpha combination acts to significantly increase GM-CSF release which then acts in an autocrine manner to enhance the proliferation of M-O7e cells.

Antibodies, Monoclonal↗
PubMed1996

Staphylococcal alpha-toxin, streptolysin-O, and Escherichia coli hemolysin: prototypes of pore-forming bacterial cytolysins.

Staphylococcal alpha-toxin, streptolysin-O, and Escherichia coli hemolysin are well-studied prototypes of pore-forming bacterial cytotoxins. Each is produced as a water-soluble single-chain polypeptide that inserts into target membranes to form aqueous transmembrane pores. This review will compare properties of the three toxin prototypes, highlighting the similarities and also the differences in their structure, mode of binding, mechanism of pore formation, and the responses they elicit in target cells. Pore-forming toxins represent the most potent and versatile weapons with which invading microbes damage the host macroorganism.

Amino Acid Sequence↗
PubMed1996

Distal vessel atherosclerosis as a cause for false-positive renal scintigraphy.

While captopril-enhanced renal scintigraphy is acknowledged to be a useful screening technique to detect clinically silent obstructive lesions of the main renal arteries, the presence of significant atherosclerosis of distal, smaller renal vessels as a cause of positive scintigraphy scans has not been reported extensively. In a retrospective 2-year analysis of 31 consecutive captopril-enhanced renal scintigrams, we found a total of 13 studies in 11 patients that were classified as "positive" for renal artery stenosis. Of these 11 patients with positive scintigraphic studies, 4 patients underwent 5 renal arteriography procedures; only 1 of these renal arteriograms showed significant stenosis of the main renal artery. In the other 4 cases, an angiographic pattern of diffuse intrarenal distal arterial disease correlated with scintigram lateralization. Angiography was also performed in 4 patients with negative captopril renal scintiscans. In each of these cases the arteriogram was also negative for significant renal artery stenosis, and only 1 patient had diffuse bilateral intrarenal arterial disease. We conclude that distal renal arterial narrowing should be considered in the differential diagnosis of lateralized renal scintigrams. A negative renal scintigraphic study may be more reliable for excluding significant main renal artery obstructive disease.

Adult↗