Biomedical subjects
Publications and source records attributed to P Anderson.
Today's work environment requires improved employee performance levels in order to satisfy pressures for cost containment and efficient case management techniques. Effective use of performance appraisals can play a highly valuable role in accomplishing these requirements. Design and use of an active appraisal system is discussed in this article.
A renal biopsy from a 36-year-old man with AIDS showed a severe tubulointerstitial nephritis with intranuclear inclusions in epithelial cells. Electron microscopy revealed the characteristic findings of a polyomavirus (PyV) infection, and immunofluorescence indicated the presence of BK virus (BKV) antigen. Inoculation of rhesus monkey kidney cell cultures both with urine and with buffy coat blood cells resulted in a cytopathic response which was subsequently confirmed to be due to BKV. Further characterization of the viral DNA from the kidney by PCR amplification and Southern blot analysis with PyV and strain-specific primers and probes indicated that the virus was closely related to the BK(Dun) strain but different in its apparent sequence arrangement. Subsequent cycle sequencing showed a dinucleotide mutation of TG-->AA which substitutes hydrophilic Gln for hydrophobic Leu in a sequence homologous to an origin DNA-binding domain of simian virus 40 T antigen. It is suggested that the mutation and a coding region rearrangement of this strain of BKV designated BKV(Cin) has the potential to alter viral DNA replication and enhance pathogenicity.
A number of different designs of cells have been developed for the study of dissolution processes in packed apatite powders. Basic design requirements were that no deleterious processes, such as high temperature sintering or binding agents, were involved, and that there was maximum opportunity for experimental study. One design used alternating filter paper discs and apatite layers (typically 42 mg). At the end of an experiment, the cell could be disassembled and infrared spectra and X-ray powder diffraction patterns made of individual layers. Cells without filter paper discs were also made, but terminal sampling at well-defined depths was more difficult or impossible. The cells were constructed from poly(methylmethacrylate) so the course of dissolution could be monitored by radiography. Subsurface loss of apatite was almost always seen after from 2 weeks to 8 months exposure to buffer solutions at pH 3.0-5.5. The greatest loss of apatite was typically 0.4-2 mm below the surface, which is at a larger distance than usually seen for dental enamel. This may be attributable to the low packing density (typically 35-60 vol%) found in the present systems compared with enamel.
Ryanodine receptor channels regulate contraction of striated muscle by gating the release of calcium ions from the sarcoplasmic reticulum. Ryanodine receptors are expressed in excitable and non-excitable cells of numerous species, including the nematode C. elegans. Unlike vertebrates, which have at least three ryanodine receptor genes, C. elegans has a single gene encoded by the unc-68 locus. We show that unc-68 is expressed in most muscle cells, and that the phenotypic defects exhibited by unc-68 null mutants result from the loss of unc-68 function in pharyngeal and body-wall muscle cells. The loss of unc-68 function in the isthmus and terminal bulb muscles of the pharynx causes a reduction in growth rate and brood size. unc-68 null mutants exhibit defective pharyngeal pumping (feeding) and have abnormal vacuoles in the terminal bulb of the pharynx. unc-68 is required in body-wall muscle cells for normal motility. We show that UNC-68 is localized in body-wall muscle cells to flattened vesicular sacs positioned between the apical plasma membrane and the myofilament lattice. In unc-68 mutants, the vesicles are enlarged and densely stained. The flattened vesicles in body-wall muscle cells thus represent the C. elegans sarcoplasmic reticulum. Morphological and behavioral phenotypes of unc-68 mutants suggest that intracellular calcium release is not essential for excitation-contraction coupling in C. elegans.
The mineral content of dental enamel is commonly measured by X-ray attenuation experiments. Most studies have used contact microradiography in which intensities are measured with photographic film which is convenient and gives high spatial resolution. However photon counting intensity measurements are to be preferred in many experiments (longitudinal and scanning microradiography, and microtomography), as illustrated here, because they have a larger dynamic range and greater sensitivity to small intensity changes. Additionally, the detector and specimen are well separated which allows the pseudo-continuous study of de- and remineralization. The mineral content is often quoted as 95 wt% or 87 vol% hydroxyapatite for permanent human enamel. This determination from attenuation experiments requires accurate values of elemental mass attenuation coefficients and a number of assumptions. The effects of possible choices of these are considered and it is shown that the most important is the density of enamel mineral used in conversion of wt% to vol%. If the density is taken as 2.99 g cm(-3), as recently suggested (J.C. Elliott, Dental Enamel, Ciba Foundation Symposium 205, Wiley, Chichester, pp. 54-72, 1997), instead of 3.15 g cm(-3) as for hydroxyapatite, the calculated vol% is approximately 93 instead of approximately 87.
PURPOSE/OBJECTIVES: To describe the process of establishing a multisite team to conduct research with a multicultural focus on fatigue. DATA SOURCES: Articles, book chapters, personal experience. DATA SYNTHESIS: Teamwork facilitated development of a productive professional working group, sharing of resources, and data collection culminating in a research proposal for studying cancer-related fatigue in a multicultural population. CONCLUSIONS: Establishing a common goal by investing time, committing to the process, and establishing trust was the secret to effective team functioning. IMPLICATIONS FOR NURSING PRACTICE: The prospect of multi-institutional collaboration has implications for oncology nurses in the areas of research and practice. Goals that could not be achieved easily in the setting of a single institution are reached more easily with multisite collaboration and teamwork.
Public health policy should aim to reduce the harm done by alcohol use, whilst recognizing its real and perceived benefits. The reduced risk of coronary heart disease (CHD) with the consequent reduction of mortality for some people in older age is one such benefit. The increased risk of sudden coronary death from acute alcohol intoxication is one such harm. A number of policies have been demonstrated to be effective in the reduction of the harm done by alcohol use, at least in industrialized countries. These are: enforcement of a minimum drinking age; drink-drive deterrence; enforced prevention of intoxication in public drinking places; controls on access to alcohol, including restrictions on numbers of licensed premises and hours and days of sale; and taxation policy to regulate the affordability of alcohol. Many of these strategies seem unlikely to have a direct effect on drinking relevant for reduced risk of CHD, but are likely to have a direct beneficial effect on drinking relevant for sudden coronary death. The level of alcohol consumption associated with the lowest mortality rate for a population will vary depending on patterns of ill health and causes of death. In countries with high rates of CHD the per capita level may be in the order of about three litres of absolute alcohol per year among drinking adults. In countries with low rates of CHD, the level is likely to be substantially lower. Many countries in which alcohol is readily available are consuming at a level substantially above three litres per capita of drinking adults per year and in these countries public health policy should continue to advise action to reduce per capita consumption.
CD94 (Kp43) is a member of the human C-type lectin superfamily encoding type II membrane glycoproteins expressed on NK cells and a subset of T cells. Ligation of CD94 has been shown to either potentiate or inhibit NK cell proliferation and cytolytic effector function. Here we show that CD94 ligation triggers apoptosis in IL-2-primed NK cells. Evidence for CD94-induced apoptosis includes: 1) chromatin condensation as measured by increased fluorescence of Hoechst dye, 2) induction of DNA fragmentation, and 3) characteristic morphology by transmission electron microscopy. IL-2 priming (at least 12 h) is required for activation-induced NK cell death triggered by CD94. Activation-induced NK cell death triggered by CD94 ligation is extremely rapid (DNA fragmentation is first observed at 120 min). Unlike activation-induced T cell death, it is not inhibited by neutralizing Abs reactive with TNF-alpha or Fas ligand. Our results suggest that CD94 may play a role in the elimination of activated NK cells during the transition from the innate to the Ag-specific immune response.
Albuterol is a beta2-adrenergic agonist commonly used as a bronchodilator for the treatment of patients with asthma. We have developed an assay to determine plasma levels as low as 50 pg/ml of albuterol by gas chromatography-mass spectrometry (GC-MS). This assay utilizes isotopically labeled albuterol ([13C]albuterol) as an internal standard. In this assay albuterol and the internal standard are recovered from 1 ml of plasma using solid-phase extraction. The samples are then derivatized to trimethylsilyl ethers using N,O-bis(trimethylsilyl)trifluoro-acetamide with 1% trimethylchlorosilane. The samples are then analyzed by GC-MS with selected-ion monitoring (SIM) for the ions m/z 369.15 and 370.15. The method has been validated for a concentration range of 50-10000 pg/ml in plasma.
OBJECTIVE: To examine the association between malnutrition and microcephaly in the first two years of life. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Royal Darwin Hospital (a tertiary referral centre); 157 of 165 previously studied Aboriginal children aged under two years who were admitted with diarrhoea between May 1990 and April 1991. Birth weight, birth length, birth head circumference, admission head circumference and admission nutritional status were examined. Nutritional status was categorised according to World Health Organization (WHO) criteria for wasting (thinness) and stunting (shortness). Microcephaly on admission was defined as a head circumference less than the second percentile on Australian reference charts. Small-for-gestational-age (SGA) and birth microcephaly were defined as being less than the tenth percentile for an Australian hospitalised population, corrected for gestational age at confinement. Low birth weight (LBW) was defined as less than 2500 g. MAIN OUTCOME MEASURE: Microcephaly on admission. RESULTS: Of the 157 children, 76 (48%) were wasted, 36 (23%) stunted and 37 (24%) microcephalic on admission. A total of 26 (17%) children had been of LBW, 17 (11%) SGA and 21 (13%) microcephalic at birth. On univariate analysis, microcephaly on admission was associated with wasting (crude odds ratio [OR], 3.91; 95% confidence interval [CI], 1.6-9.7; P < 0.005), but not stunting. There were no significant associations between microcephaly on admission and LBW, being SGA, microcephaly at birth, age or sex. With multivariate analysis, birth head circumference was significantly associated with microcephaly on admission (adjusted OR, 3.62; 95% CI, 1.28-10.23; P < 0.05), as was wasting (adjusted OR, 4.38; 95% CI, 1.88-10.20; P < 0.001). CONCLUSIONS: Wasting was significantly associated with microcephaly, independent of intrauterine growth retardation (as measured by being SGA) and LBW. As malnutrition in critical periods of both intra- and extrauterine development may have irreversible effects on intellectual potential and behaviour, the emphasis on improved nutrition must begin during pregnancy, and should continue in infancy and early childhood.
Proteins cleaved by interleukin-1 beta converting enzyme family proteases during apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus (SLE). We have tested the possibility that proteins phosphorylated in cells undergoing apoptosis are also targets for autoantibody production in patients with autoimmune disease. Sera from 9/12 patients containing antinuclear antibodies (10/12 meeting diagnostic criteria for SLE or a lupus overlap syndrome), precipitated new phosphoproteins from lysates derived from Jurkat T cells treated with apoptotic stimuli (i.e., Fas-ligation, gamma irradiation, ultraviolet irradiation), but not with an activation (i.e., CD3-ligation) stimulus. Sera derived from individual patients precipitated different combinations of seven distinct serine-phosphorylated proteins. None of these phosphoproteins were included in precipitates prepared using sera from patients with diseases that are not associated with autoantibody production or using serum from rheumatoid arthritis patients. Protein phosphorylation precedes, or is coincident with, the induction of DNA fragmentation, and is not observed when apoptosis is inhibited by overexpression of bcl-2. Serum from four patients precipitated a serine/threonine kinase from apoptotic cell lysates that phosphorylates proteins of 23-, 34-, and 46-kD in in vitro kinase assays. Our results suggest that proteins phosphorylated during apoptosis may be preferred targets for autoantibody production in patients with SLE.
Charcot spine, also known as neuropathic spinal arthropathy, is a late complication of traumatic spinal cord injury that can produce pain and further disability. We report five cases of Charcot spine occurring in patients with previous traumatic spinal cord injury that we have identified at our institution from 1985 to 1994. All patients had complete paraplegia with levels of neurologic injury ranging from T7 to T12. Common presenting symptoms included back pain, loss of spasticity, change in bladder function, and audible noises with motion. The diagnosis of Charcot spine was made from 6 to 31 years after original spinal cord injury. In four cases where a surgical fusion had been performed, the Charcot joint developed within two spinal segments below the caudal end of the fusion. Radiological studies, especially plain films and computed tomography, were helpful in making the diagnoses. Immobilization of the affected joint is an essential element of treatment. Surgical repair and stabilization were performed in four patients and has been recommended to the other patient. Early diagnosis and proper treatment is important in preventing the progression of this disorder.
Various approaches to the management of the impalpable testis in cases of cryptorchidism have been advocated. The authors' experience over the past 13 years was reviewed to try to determine an optimal approach. Of 1,305 patients with undescended testicles seen between February 1982 and December 1995, 157 boys (12.03%) had impalpable testes with 17 having bilateral impalpable testes for a total of 174 impalpable testes. A hernia sac was present in 155 impalpable testes with a testicle present in all cases. No hernia sac was found in 19 impalpable testes, five of which had no testicle present. This was confirmed by either open exploration or laparoscopy. One hundred forty-eight boys underwent groin exploration as initial treatment, 13 of these had bilateral impalpable testes. In addition to the five absent testicles with no hernia sac, one patient with a hernia sac and no testicle evident benefited from subsequent laparoscopy to identify an intraabdominal testicle. All other patients underwent routine orchidopexy or orchidectomy (one case with grossly malformed testicle). Nine boys underwent laparoscopy as initial treatment, four of these had bilateral impalpable testes. Two abnormal testicles were found and removed. Groin exploration and subsequent orchidopexy was definitive treatment in all other cases. The association of a hernia sac with an impalpable undescended testicle is very significant (P < .00001 Fisher's Exact test). The absence of a sac therefore may reflect an alternate diagnosis. When no sac is found with a testicle in the groin, this may represent an ectopic testicle. When no sac is found with no testicle, this may represent a vanishing testicle. From this experience the authors conclude that groin exploration should be the initial approach to impalpable testes. The presence of a hernia sac with an absent testicle demands further exploration; the absence of a hernia sac with an absent testicle suggests a vanishing testicle and may need no further exploration.
The cytoplasmic life of an mRNA revolves around the regulation of its localization, translation and stability. Interactions between the two ends of the mRNA may integrate translation and mRNA turnover. Regulatory elements in the region between the termination codon and poly(A) tail - the 3' untranslated region - have been identified in a wide variety of systems, as have been some of the key players with which these elements interact.
Homelessness is a growing problem in the United States, with population numbers ranging from 300,000 to several million. This article reviews five studies that focused on identification and assessment of cardiovascular risk factors in the homeless population. A case study presents the successful outcome of a homeless male with several risk factors. Assessment and intervention by a nurse practitioner led to his re-entry into the domiciled population. Implications for clinical practice and recommendations for further research are discussed.
The European Conference, Health, Society and Alcohol held in Paris, 12-14 December 1995, was a meeting point between science and policy. Science informed the policy process. As a tool for policy implementation, the Conference adopted the European Charter on Alcohol, a set of ethical principles and strategies for action. Of a number of important issues that frame policy, three deserve mention. First, market forces, as opposed to health and social policy decisions are increasingly influencing the policy debate. Second, existing policy options to reduce alcohol-related harm are unlikely to lead to an increased risk of coronary heart disease among older age groups. And third, policy developments and changes in drinking patterns in countries of southern Europe are an important driving force in European policy on alcohol.
Host protection against pneumococcal disease i primarily mediated by phagocytosis. We developed and standardized an opsonophagocytic assay using HL-60 cells (human promyelocytic leukemia cells). Fifty-five serum samples were analyzed for the presence of functional antibody against seven pneumococcal serogroups or serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) by using differentiated HL-60 cells (granulocytes) and peripheral blood leukocytes (PBLs). Six of the 55 serum samples were from unvaccinated adult volunteers, 31 serum samples were from adults who received one dose of the 14-valent or the 23-valent polysaccharide vaccine, and 18 serum samples were from 16-month-old infants who received four doses of an investigational 7-valent polysaccharide-protein conjugate vaccine. The results of an opsonophagocytic assay with HL-60 cells correlated highly with those of an assay with PBLs as effector cells (median r for seven serotypes = 0.87: P < 0.01). Opsonophagocytic titers were compared with the immunoglobulin G antibody concentrations determined by enzyme-linked immunosorbent assay (ELISA). The r values for serogroups or serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F were 0.61, 0.60, 0.67 0.90, 0.61, 0.39, and 0.57, respectively, when HL-60 cells were used as effector cells and 0.56, 0.47, 0.61, 0.90, 0.71, 0.31, and 0.62, respectively, when PBLs were used. The assay requires small amounts of serum (40 microliters per serotype), making this test suitable for assaying infant sera. Culturable cells aid in assay standardization and likely reduce donor-to-donor variability. This standardized assay, in combination with the standardized ELISA, can be used to evaluate current and developing pneumococcal vaccines, in which functional opsonophagocytic antibody activity may correlate with protection against pneumococcal disease.
All cells are constantly exposed to conflicting environment cues that signal cell survival or cell death. Survival signals are delivered by autocrine or paracrine factors that actively suppress a default death pathway. In addition to survival factor withdrawal, cell death can be triggered by environmental stresses such as heat, UV light, and hyperosmolarity or by dedicated death receptors (e.g., FAS/APO-1 and tumor necrosis factor [TNF] receptors) that are counterparts of growth factor or survival receptors at the cell surface. One of the ways that cells integrate conflicting exogenous stimuli is by phosphorylation (or dephosphorylation) of cellular constituents by interacting cascades of serine/threonine and tyrosine protein kinases (and phosphatases). Survival factors (e.g., growth factors and mitogens) activate receptor tyrosine kinases and selected mitogen-activated, cyclin-dependent, lipid-activated, nucleic acid-dependent, and cyclic AMP-dependent kinases to promote cell survival and proliferation, whereas environmental stress (or death factors such as FAS/APO-1 ligand and TNF-alpha) activates different members of these kinase families to inhibit cell growth and, under some circumstances, promote apoptotic cell death. Because individual kinase cascades can interact with one another, they are able to integrate conflicting exogenous stimuli and provide a link between cell surface receptors and the biochemical pathways leading to cell proliferation or cell death.