Progress in sequencing the mouse genome.
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Access to Information↗
Biomedical subjects
J Rodgers
Publications and source records attributed to J Rodgers.
Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice.
Stimulation of the acute phase response during infection of mice with Trypanosoma brucei brucei (T. b. brucei) was investigated in an experimental model of the post-treatment reactive encephalopathy (PTRE), a common side-effect of anti-trypanosome therapy. Plasma levels of the acute phase proteins (APP), haptoglobin (Hp) and serum amyloid P (SAP) increased by day 7 post-infection, but by day 20 had fallen to an intermediate level. This was accompanied by induction of the cytokines, interleukin (IL)-6 and tumour necrosis factor-alpha (TNFalpha) in both liver and brain. Treatment of mice on day 21 with a subcurative dose of diminazene aceturate (Berenil), a procedure known to induce a mild PTRE, cleared the parasite from the circulation with plasma APP and liver expression of mRNA for IL-6 and TNFalpha returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFalpha was detected in the brains of animals with developing PTRE although TNFalpha was not significantly greater than in the control group. A further subcurative dose of Berenil, leading to a more severe PTRE, was associated with elevated serum concentrations of Hp and SAP, increased TNFalpha mRNA in the liver and detectable IL-6 and TNFalpha mRNA in the brain. mRNA for IL-1alpha was expressed in brain and liver samples from all animals. A severe PTRE caused a systemic acute phase response which was not apparent with a mild PTRE. The pattern of cytokine mRNA induction was similar following both drug treatments. However, the difference in APP production could be caused by a breakdown in the blood-brain barrier during severe PTRE allowing cytokine synthesised in the brain to enter the circulation and maintain a systemic response.
Acute-Phase Proteins↗
The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis.
This article is a transcription of an electronic symposium sponsored by the Brazilian Society of Neuroscience and Behavior (SBNeC). Invited researchers from the European Union, North America and Brazil discussed two issues on anxiety, namely whether panic is a very intense anxiety or something else, and what aspects of clinical anxiety are reproduced by animal models. Concerning the first issue, most participants agreed that generalized anxiety and panic disorder are different on the basis of clinical manifestations, drug response and animal models. Also, underlying brain structures, neurotransmitter modulation and hormonal changes seem to involve important differences. It is also common knowledge that existing animal models generate different types of fear/anxiety. A challenge for future research is to establish a good correlation between animal models and nosological classification.
Anti-Anxiety Agents↗
Preregistration nursing education in Australia, New Zealand, the United Kingdom, and the United States of America.
The debate concerning nurses' diverse entry into practice was enlivened in 1995, when the American Nurses Association reaffirmed its contention that a baccalaureate degree was necessary for professional nursing practice. This debate may be informed by an appreciation of the educational routes taken by other countries that have changed from hospital-based to college-based nursing education. This paper describes and analyzes preregistration nursing education in Australia, New Zealand, the United Kingdom, and the United States, from the late nineteenth century to the present. Nurses in Australia and New Zealand are currently educated entirely at the baccalaureate level. In the United Kingdom, nursing education is in the process of becoming completely university-based, resulting in a diploma or degree. In the United States, the majority of nurses graduate from two-year associate degree programs. This level of education, briefer than in the other countries described, potentially limits nurses' professional contributions.
Australia↗
Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia.
This multicenter trial evaluated the safety and efficacy of escalating doses of Niaspan (niacin extended-release tablets) and placebo (administered once-a-day at bedtime) in patients with primary hyperlipidemia on the percent change from baseline in levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Extended-release niacin was initiated at a dose of 375 mg/day, raised to 500 mg/day, and further increased in 500-mg increments at 4-week intervals to a maximum of 3,000 mg/day. A total of 131 patients (n = 87, extended-release niacin; n = 44, placebo) were treated for 25 weeks with study medication after a 6-week diet lead-in/drug washout phase and 2-week baseline LDL cholesterol stability phase. Significant decreases from baseline in levels of LDL cholesterol and apolipoprotein B became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or =0. 05), reaching 21% and 20%, respectively, at the 3,000-mg/day dose. Significant increases from baseline in levels of high-density lipoprotein cholesterol became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or = 0.05), reaching 30% at the 3,000-mg dose. Significant decreases from baseline in triglycerides and lipoprotein(a) occurred at the 1,000-mg dose and were apparent at all subsequent doses (p < or =0.05), reaching 44% and 26%, respectively, at the 3,000-mg dose. The most common adverse events were flushing and gastrointestinal disturbance. Transaminase increases were relatively small, and the proportion of patients who developed liver function abnormalities on extended-release niacin was not significantly different from placebo. Thus, extended-release niacin was generally well tolerated and demonstrated a dose-related ability to alter favorably most elements of the lipid profile.
Adult↗
Cognitive performance amongst recreational users of "ecstasy".
RATIONALE: Previous work has suggested that memory impairments have been associated with the recreational use of "ecstasy". This previous work, however, has not taken into consideration the additional use of cannabis amongst those examined. Cannabis use has also been associated with memory impairment. There is therefore a clear need to explore the impact of both of these illicit substances upon memory ability. OBJECTIVES: To determine whether recreational use of ecstasy impairs memory and attentional ability and to explore the impact of the concomitant use of cannabis upon these cognitive functions. In addition, an exploration of subjective accounts of cognitive ability was undertaken to determine whether objective impairments were perceived by users in everyday functioning. METHODS: Cognitive functioning was examined in three groups of young people: 15 regular users of ecstasy; 15 regular users of cannabis who had never taken ecstasy and 15 control subjects who had never taken any illicit substances. The Weschler Memory Scale (revised) and a computerised reaction time task were administered on a day when the subjects claimed to be drug free. In addition, subjects completed a biographical questionnaire and the Cognitive Failures Questionnaire (CFQ) in order to assess subjective accounts of cognitive slips. RESULTS: Performance was similar across all three groups for measures of visual reaction time, auditory reaction time, complex reaction time, visual memory and attention and concentration. Significant impairment was found on measures of verbal memory in both cannabis users and ecstasy users. A significant impairment in performance was found on measures of delayed memory for the ecstasy users compared to both the cannabis group and the control group. Despite these findings, no differences in subjective ratings of cognitive failures were found between the groups. CONCLUSIONS: The present study provides additional evidence for longterm neuropsychological sequelae associated with the use of ecstasy, particularly with regard to delayed memory ability.
Adult↗
Biomarker distribution after injection into the canine prostate: implications for gene therapy.
OBJECTIVE: To evaluate the distribution of biomarkers after transrectal injection into the canine prostate and to report a method for enhancing the distribution of gene expression. MATERIALS AND METHODS: Carbon black was first used to evaluate the histopathological distribution in canine prostate of single or multiple injections via the transurethral, transperineal and transrectal routes. The distribution of canarypox virus (ALVAC) vector-delivered gene expression was then compared using both fluid-phase injection techniques and delivery in a solid carrier composed of a gelatine sponge matrix. RESULTS: After transurethral administration, carbon black was detected as scattered particles in ducts and acini, mostly in the periphery of the gland. Direct transrectal injection of carbon black resulted in a localized collection at the site of injection, with only a minimal peri-acinar distribution. Transrectal injection of the fluid-phase (virus suspended in diluent) ALVAC vector encoding the beta-galactosidase gene resulted in a similar distribution, with limited gene expression at the site of injection and in the needle track. Delivery of the same number of virus particles in the gelatine sponge matrix resulted in qualitatively greater gene expression. CONCLUSIONS: Direct injection of the canine prostate with biomarkers, including viral vectors, in the fluid-phase results in very localized gene expression, while the distribution was more widespread after delivery in a gelatine sponge matrix.
Animals↗
Immunization with f-Met peptides induces immune reactivity against Mycobacterium tuberculosis.
OBJECTIVE: To determine whether synthetic peptides containing an amino terminal formyl-methionine residue and corresponding to the sequence of several proteins produced by Mycobacterium tuberculosis, would elicit an immune response in mice. DESIGN: Peptides corresponding to the amino termini of 8 M. tuberculosis proteins and initiating with formyl methionine residues were synthesized. The ability of these peptides to bind to the mouse non-classical MHC class I molecule H-2M3a was determined by flow microfluorimetry. These peptides were used to pulse dendritic cells that were then injected into normal mice. These mice were subsequently challenged with aerosolized M. tuberculosis and, 30 days later, the number of viable bacteria in the lungs was determined. RESULTS: Four of the 8 synthetic peptides bound to H-2M3a and stabilized its expression on the cell surface. Injection of mice with dendritic cells pulsed with H-2M3a binding peptides elicited non-MHC restricted cytotoxic T lymphocytes that killed peptide pulsed target cells and macrophages infected with M. tuberculosis. Immunization of mice with syngeneic dendritic cells pulsed in vitro with 2 of these peptides led to retardation of the growth of M. tuberculosis following aerosol challenge. CONCLUSION: Peptides that bind to non-polymorphic class I molecules can elicit immune reactivity directed towards M. tuberculosis.
Animals↗
Dietary antioxidant depletion: enhancement of tumor apoptosis and inhibition of brain tumor growth in transgenic mice.
Apoptosis, or regulated cell suicide, eliminates unwanted and damaged cells, including precancerous and cancerous cells. Since reactive oxygen species (ROS) act as essential apoptotic mediators, we reasoned that increasing the ROS level might enhance apoptosis and thereby slow down tumor growth. Here, using a defined transgenic brain tumor model with known tumor apoptosis rates, we test the impact of antioxidant-depleted diet, capable of increasing ROS levels, or antioxidant-enriched diets on tumor growth. Dramatically increased apoptosis occurs within tumors, but not in normal tissues of antioxidant-depleted mice. The presence of detectable increased oxidant stress within tumors indicates that the likely mechanism of enhanced tumor apoptosis is via ROS and DNA oxidative impairment. Importantly, due to the ROS-enhanced apoptosis, tumor growth is inhibited in mice fed an antioxidant-depleted diet. In clear contrast, an antioxidant-rich diet had no impact on tumor growth.
Animals↗
Assessing primary care content: four conditions common in community health center practice.
Under managed care, community health center (CHC) care patterns will be increasingly subject to outside scrutiny. This article discusses results of medical records reviews assessing quality of care at CHCs for acute otitis media, diabetes, asthma, and hypertension. As a group, these safety net providers meet or exceed prevailing practice across other health care settings; however, there is substantial variation among sites. Regression analyses indicate that the individual CHC used by a patient is the most consistent determinant of whether a patient receives recommended care. Drawing on these results, the article explores approaches for improving care and discusses the implications for performance measurement among CHCs and other safety net providers.
Adolescent↗
Wrestling with typology: penetrating the "black box" of managed care by focusing on health care system characteristics.
The health care system has undergone a fundamental transformation undermining the usefulness of the typology of the health maintenance organization, the independent practice association, the preferred provider organization, and so forth. The authors present a new approach to studying the health care system. In matrix form, they have identified a set of organizational and delivery characteristics with the potential to influence outcomes of interest, such as access to services, quality, health status and functioning, and cost. The matrix groups the characteristics by domain--financial features, structure, care delivery and management policies, and products--and by key roles in the health care system--sponsor, plan, provider intermediary organization, and direct services provider. The matrix is a tool for researchers, administrators, clinicians, data collectors, regulators, and other policy makers. It suggests a new set of players to be studied, emphasizes the relationships among the players, and provides a checklist of independent, control, and interactive variables to be included in analyses.
Data Collection↗
Haptoglobin, the acute phase response and natural human immunity to trypanosomes.
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Acute-Phase Reaction↗
Attentional ability among survivors of leukaemia.
Attentional ability in 19 survivors of acute lymphoblastic leukaemia and 19 sibling controls was assessed using a neuropsychological model of attention. Analysis revealed that children who had received treatment for leukaemia exhibited significantly poorer performance on measures of the "focus encode" and "focus execute" elements of attention and on measures of the ability to respond to external cues and feedback. No significant differences in performance were found for measures of sustained attention and the ability to shift attention. These results indicate that children who have received treatment for leukaemia may experience highly specific attentional deficits that could have an impact on academic performance, particularly mathematical and reading skills. It is suggested that this underlying attentional deficit might be the source of the neuropsychological sequelae associated with the disease. Future attempts at remediation should incorporate activities specifically designed to ameliorate focusing difficulties.
Antineoplastic Agents↗
State health expenditure accounts: purposes, priorities, and procedures.
This article reports on the State Health Expenditure Account (SHEA) project which developed procedures States can use in tracking their health care expenditures. The purposes, priorities, and concepts of SHEAs were designed to meet the needs of State policymakers. The resulting methods are discussed and illustrated using calculations of SHEAs for California. Contrasts with the National Health Expenditure (NHE) framework are provided. Recommendations for cooperation between the Health Care Financing Administration (HCFA) and the States that would facilitate the adoption and estimation of SHEAs are offered. Details of the methods used for the California estimates can be found in the Technical Note of this article.
Accounting↗
Zinc-induced inactivation of the yeast ZRT1 zinc transporter occurs through endocytosis and vacuolar degradation.
The ZRT1 gene encodes the transporter responsible for high affinity zinc uptake in yeast. ZRT1 is transcribed in zinc-limited cells and its transcription is repressed in zinc-replete cells. In this report, we describe a second, post-translational mechanism that regulates ZRT1 activity. In zinc-limited cells, ZRT1 is a stable, N-glycosylated plasma membrane protein. Exposure to high levels of extracellular zinc triggers a rapid loss of ZRT1 uptake activity. Our results demonstrate that this inactivation occurs through zinc-induced endocytosis of the protein and its subsequent degradation in the vacuole. Mutations that inhibit the internalization step of endocytosis also inhibited zinc-induced ZRT1 inactivation and the major vacuolar proteases were required to degrade ZRT1 in response to zinc. Furthermore, immunofluorescence microscopy showed that ZRT1 is localized to the plasma membrane in zinc-limited cells and that the protein is transferred to the vacuole via an endosome-like compartment upon exposure to zinc. ZRT1 inactivation is a relatively specific response to zinc; cadmium and cobalt ions trigger the response but less effectively than zinc. Moreover, zinc does not alter the stability of several other plasma membrane proteins. Therefore, zinc-induced ZRT1 inactivation is a specific regulatory system to shut off zinc uptake activity in cells exposed to high extracellular zinc levels thereby preventing overaccumulation of this potentially toxic metal.
Carrier Proteins↗
Regulation of zinc homeostasis in yeast by binding of the ZAP1 transcriptional activator to zinc-responsive promoter elements.
Zinc homeostasis in yeast is controlled primarily through the regulation of zinc uptake. Transcription of the ZRT1 and ZRT2 zinc transporters increases in zinc-limited cells, and this induction is dependent on the ZAP1 gene. We hypothesized previously that ZAP1 encodes a zinc-responsive transcriptional activator. Expression of ZAP1 itself increases in zinc-limited cells. This response is also dependent on ZAP1 function through a potential positive autoregulatory mechanism. In this report, we describe the characterization of zinc-responsive elements (ZREs) in the promoters of the ZRT1, ZRT2, and ZAP1 genes. A ZRE consensus sequence, 5'-ACCYYNAAGGT-3', was identified and found to be both necessary and sufficient for zinc-responsive transcriptional regulation. We also demonstrate that ZREs are DNA binding sites for ZAP1. First, a dominant ZAP1 mutation, ZAP1-1(up), which causes increased expression of ZAP1-regulated genes in zinc-replete cells, exerted its effects specifically through the ZREs. Second, electrophoretic mobility shift assays and in vitro DNase I footprint analyses indicated that ZAP1 binds to ZREs in a sequence-specific fashion. These studies demonstrate that ZAP1 plays a direct role in controlling zinc-responsive gene expression in yeast by binding to zinc-responsive elements in the promoters of genes that it regulates.
Alleles↗
Do people shift their use of health services over time to take advantage of insurance?
This paper provides a test of the hypothesis that people shift their consumption of health services to time periods when they have more generous insurance coverage, in order to take advantage of third-party payment. We use data from the Survey of Income and Program Participation to compare utilization rates for people in transition between being insured and being uninsured to those of people who are continuously insured and continuously uninsured. We find little support for the hypothesis that people anticipate changes in their insurance status and arrange their health care consumption accordingly.
Data Collection↗
A chemical gas incident in London: how well prepared are London A & E departments to deal effectively with such an event?
This study aimed to investigate the preparedness of inner London Accident and Emergency (A & E) departments in the event of a major chemical incident. The dimensions of preparedness studied were procedures, facilities and equipment, protective clothing, knowledge, and attitudes towards chemical incidents. A review of the relevant literature will be published in issue 6/3 of this journal, July 1998.
Attitude of Health Personnel↗