Changes in the body composition of the domestic shorthaired cat during growth and development.
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Absorptiometry, Photon↗
Biomedical subjects
P Anderson
Publications and source records attributed to P Anderson.
Prevention policies.
Alcohol is a special commodity because of its dependence producing properties and the extent and severity of problems associated with its use, many of which are preventable. The elements of a comprehensive preventive policy include: controls to raise the price of alcohol; controls on the availability of alcohol, particularly minimum age limits for the purchase of alcohol and limits to the hours and days of sale of alcohol and numbers of outlets; controls on the use of alcohol, particularly restricting drinking and driving; product safety standards, particularly information on the alcohol content of beverages, controls on marketing, particularly restrictions on advertising and sponsorship and; education and information programmes, including those based at a community level to promote support for prevention policies and those based in schools and primary health care.
Adolescent↗
Contamination levels and doses to staff arising from the use of Technegas.
The aim of this work was to assess the levels of airborne activity and contamination arising from Technegas ventilation scintigraphy and to estimate doses to staff. The maximum air concentration was below the 99Tcm-derived air concentration limit and considerably lower than reported levels for conventional radioaerosols. The level of contamination on staff gloves and aprons exceeded the body surface contamination limit in 63 and 9% of cases, respectively. Levels of contamination and air concentration were generally higher if the patient had difficulty with the administration procedure. Room surface contamination was very low. In 24% of cases activity was detectable on staff (either in the hair or nose) using gamma camera imaging. Annual skin doses from these sources are calculated to be below the limit for deterministic effects. Whole body effective doses are calculated to be similar to those received by staff performing other nuclear medicine studies. However, care should be exercised to keep exposure from both airborne and fixed sources to a minimum and a regular review of contamination levels is recommended. We recommend the wearing of gloves for all Technegas administrations and disposable hats and masks may be considered in certain cases.
Air Pollutants, Occupational↗
Research in general practice for smokers and excessive drinkers in Australia and the UK. I. Interpretation of results.
This review examines the role of the general practitioner in assisting patients to stop smoking and in reducing levels of excessive drinking. After over a decade of clinical trials, we discuss what interventions work in general practice and interpret the results of clinical trials conducted predominantly in Australia and the UK. Studies have generally found a superiority of GPs' brief advice over non-intervention groups. Very brief GP advice results in smoking abstinence rates from 5% to 10%, reduction in alcohol consumption of around 25-35% and reduction in proportions of excessive drinkers of around 45%. The greater investment of GPs' time and the more comprehensive interventions which include follow up usually resulted in higher abstinence rates among smokers from between 20% to 36%, and reduction in proportions of excessive drinkers of up to 60-70%. The contributions of the adjuncts nicotine chewing gum, follow up visits and the personalization of health effects are discussed. It is difficult to make comparisons between studies and we examine some of the reasons. The predictors of successful outcome are presented as they are of particular interest to GPs in terms of targeting health promotion activities.
Alcoholism↗
Research in general practice for smokers and excessive drinkers in Australia and the UK. II. Representativeness of the results.
This paper reviews some of the issues related to the appropriateness of generalizing the results from clinical trials which have been conducted in general practice for smokers and excessive drinkers. We discuss the representativeness of the results related to the method of recruitment of general practices and patients to the study populations. We examine methodological issues and reasons associated with general practitioners' and patients' non-compliance with maintaining the research protocols and intervention requirements which relate to the practiceworthiness and the future uptake of interventions. When assessing the applicability of interventions to general practice, there are three basic research questions which should be looked at quite separately that relate to: efficacy, effectiveness and implementation.
Alcoholism↗
Research in general practice for smokers and excessive drinkers in Australia and the UK. III. Dissemination of interventions.
This article reviews the main methods of dissemination of interventions to doctors for the benefit of patients who are smokers and excessive drinkers. Firstly, the modes of delivery of interventions are discussed such as: postal delivery, face-to-face strategies such as an educational facilitator, courier, training workshops, reinforcement contact after training, and teaching in medical school. Secondly, we examine GPs' delivery of interventions working in association with others such as with: the health visitor, health facilitator, practice nurse, and specialist clinic. Thirdly, we discuss the debate about the public health impact of GP interventions for smokers, which is about rates of recruitment of patients to programs and about the most effective interventions that will continue to be used by GPs. Fourthly, doctors underutilize their opportunities to identify and intervene with smokers and excessive drinkers and we explore many of the barriers to intervention. Finally, there are several new initiatives in general practice that require research including: matching GPs to specific treatments, comparing the uptake and continued use of different levels of interventions, evaluating the most effective ways of delivering interventions to GPs, and the training of doctors in the intervention methods.
Alcoholism↗
Overview: public health, health promotion and addictive substances.
All of the dependence-producing substances are capable of causing harm but in most cases the harm is preventable. This paper seeks to develop some of the themes raised by the five substance-based prevention papers by presenting an outline of the Ottawa Charter for Health Promotion. The Ottawa Charter provides a strategic framework for prevention and covers public health policy, trade issues, availability, price, advertising and types of supportive environments and responses. It is suggested that an effective approach to the prevention of harm from dependence-producing substances would involve a planned response which included alcohol, tobacco and drugs. Such a response would also emphasize financial and economic consequences of drug use, and would seek to strengthen or develop links with partners outside the immediate health care arena.
Combined Modality Therapy↗
Plasma acetylsalicylic acid and salicylic acid levels during aspirin provocation in aspirin-sensitive subjects.
The ability of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit the cyclo-oxygenase which catalyzes formation of prostaglandins appears to be central to the mechanisms involved in aspirin sensitivity. We have investigated whether the plasma levels of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) at the time of intolerance reactions correspond with the concentrations required for enzyme inhibition in vitro. Twelve aspirin-sensitive and 15 aspirin-tolerant subjects were followed during provocation with aspirin. ASA and SA concentrations in plasma were determined by HPLC. After oral provocation (up to 460 mg cumulative dose), the levels of ASA and SA in plasma were equivalent in aspirin-sensitive and aspirin-tolerant subjects. For the aspirin-sensitive subjects, at the time of adverse reaction, the concentration range was 2.9-33.3 microM for ASA and 18.1-245 microM for SA. Oral provocation with sodium salicylate yielding 10-fold higher SA levels did not elicit intolerance reactions. Statistically significantly lower levels of ASA and SA (P < or = 0.01) evoked airway obstruction, as compared with merely extrapulmonary symptoms. Bronchial absorption of aspirin was found after inhalation of lysine-aspirin and was comparable in asthmatic and nonasthmatic subjects. In three aspirin-sensitive subjects who developed airway obstruction, the plasma levels for ASA and SA were 0.9-2.6 microM and 0.0-6.7 microM, respectively. In conclusion, the plasma levels of ASA reached at the time of a positive reaction are of the magnitude known to inhibit cyclo-oxygenases. Neither differences in bioavailability of ASA nor the formation of SA seems to contribute to the aspirin-elicited reactions.
Administration, Oral↗
Imprecise excision of the Caenorhabditis elegans transposon Tc1 creates functional 5' splice sites.
Imprecise excision of the Caenorhabditis elegans transposon Tc1 from a specific site of insertion within the unc-54 myosin heavy chain gene generates either wild-type or partial phenotypic revertants. Wild-type revertants and one class of partial revertants contain insertions of four nucleotides in the unc-54 third exon (Tc1 "footprints"). Such revertants express large amounts of functional unc-54 myosin despite having what would appear to be frameshifting insertions in the unc-54 third exon. We demonstrate that these Tc1 footprints act as efficient 5' splice sites for removal of the unc-54 third intron. Splicing of these new 5' splice sites to the normal third intron splice acceptor removes the Tc1 footprint from the mature mRNA and restores the normal translational reading frame. Partial revertant unc-54(r661), which contains a single nucleotide substitution relative to the wild-type gene, is spliced similarly, except that the use of its new 5' splice site creates a frameshift in the mature mRNA rather than removing one. In all of these revertants, two alternative 5' splice sites are available to remove intron 3. We determined the relative efficiency with which each alternative 5' splice site is used by stabilizing frameshifted mRNAs with smg(-) genetic backgrounds. In all cases, the upstream member of the two alternative sites is used preferentially (> 75% utilization). This may reflect an inherent preference of the splicing machinery for the upstream member of two closely spaced 5' splice sites. Creation of new 5' splice sites may be a general characteristic of Tc1 insertion and excision events.
Alternative Splicing↗
In vitro cultivation of exoerythrocytic stages of the simian malaria parasites Plasmodium fieldi and Plasmodium simiovale in rhesus monkey hepatocytes.
Exoerythrocytic stage parasites of Plasmodium fieldi and Plasmodium simiovale, 2 simian malaria parasites related to the human malaria parasite Plasmodium ovale, were cultured in vitro by inoculating primary cultures of hepatocytes from rhesus monkeys (Macaca mulatta) with sporozoites. Less than 1% of sporozoites developed into schizonts for either species. Structure and size of the liver stages in both species were similar to previous in vivo descriptions, and the time required for in vitro maturation correlated well with the prepatent periods described for each species. Such monkey models could be very useful in conducting scientific investigations on the pre-erythrocytic stages of P. ovale-like malaria parasites.
Animals↗
Developmental regulation of a mucinlike glycoprotein selectively expressed on natural killer cells.
Natural killer (NK) cells are CD3:TCR-, CD16+, CD56+ large granular lymphocytes capable of recognizing and eliminating a variety of virus-infected, malignant, and antibody-coated target cells. Two functionally distinct populations of peripheral blood NK cells can be differentiated by their surface expression of an isoform of the neural cell adhesion molecule (CD56). CD56bright NK cells have the attributes of an undifferentiated cell, in that they proliferate in response to exogenous cytokines, but exert poor cytolytic activity. CD56dim NK cells have the attributes of a more differentiated cell, in that they proliferate poorly in response to exogenous cytokines, but are potent cytolytic effector cells. Here we describe the molecular characterization of a NK cell restricted epitope (PEN5) that is selectively expressed on the functionally differentiated CD56dim NK cells. PEN5+ NK cells proliferate poorly in response to interleukin 2 (IL-2), but are potent cytolytic effectors, whereas PEN5- NK cells proliferate in response to IL-2, but are poor cytolytic effectors. Biochemical and immunochemical analyses reveal the PEN5 epitope to be an unusual sulfated poly-N-lactosamine carbohydrate related to keratan sulfate glycosaminoglycans. Immunoprecipitates prepared using a monoclonal antibody reactive with PEN5 include two polydisperse membrane-bound glycoproteins, PEN5 alpha (120-170 kD) and PEN5 beta (210-245 kD). Enzymatic deglycosylation reduces the apparent molecular weight of both PEN5 isoforms by 80-90%, and classifies PEN5 beta as a mucinlike glycoprotein. The surface expression of the PEN5 epitope is downmodulated by stimuli that induce NK cell proliferation, and it is absent from leukemic NK cells of patients with granular lymphocyte proliferative disorder. Taken together, these results indicate that PEN5 is a developmentally regulated poly-N-lactosamine epitope associated with a mucin-type glycoprotein, whose expression is restricted to the population of nonproliferative NK cells fully committed to cytolytic effector function.
Amino Sugars↗
Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma.
An impaired immune response is frequently observed in cancer patients and tumor-bearing mice. T-cells from mice with an experimental colon carcinoma were recently shown to express T-cell receptors that completely lacked the signal-transducing molecule CD3 zeta. Here, we have investigated the expression of the signal-transducing molecule zeta on lymphocytes from 14 patients with colorectal carcinomas using flow cytometric analysis of permeabilized cells with a monoclonal antibody (TIA-2; IgG1) specific for the cytoplasmic domain of the zeta chain as well as with immunoprecipitation and analysis on diagonal gel electrophoresis. We demonstrate that T-cells isolated from the tumors of the patients express significantly less CD3 zeta than T-cells in the peripheral blood of the same patients and that the peripheral blood of the patients express decreased levels of zeta chains, as compared to the levels found in lymphocytes from healthy controls. This decreased expression was also observed on zeta chains associated with the low affinity Fc receptor for IgG found in tumor-infiltrating NK cells (Fc gamma RIIIA alpha; CD16).
Colorectal Neoplasms↗
Occipitocervical arthrodesis using contoured plate fixation. An early report on a versatile fixation technique.
A simple, inexpensive, and rigid technique for occipitocervical fixation was evaluated in 14 patients with occipitocervical instability. Posterior arthrodeses of the occipitocervical region were performed using pelvic reconstruction plates and screws as internal fixation devices. At follow-up, which averaged 11.7 months, all patients had fused with minimal complications. This versatile technique, readily adapted to complex deformities and extensible for subaxial fixation, was reviewed.
Adult↗
Failure to induce long-term depression by an anti-correlation procedure in area CA1 of the rat hippocampal slice.
We have independently in our two laboratories re-examined the report by Stanton and Sejnowski (Nature, 339, 215-218, 1989) that single stimuli to a test pathway in area CA1 of the hippocampal slice, when delivered between short bursts of stimuli to a second, convergent pathway, produce an associative long-term depression (LTD) in the test pathway. While robust associative LTP was observed when stimuli to the two inputs were correlated in time, the anti-correlation procedure failed to induce LTD; rather, a trend towards potentiation was observed. This result was obtained using both submerged and interface chambers, and in two different strains of rat. A transient depression lasting for a few minutes could usually be elicited by strong tetanic stimulation; this depression was not restricted to activated pathways.
Animals↗
Local control of T2/3 transitional cell carcinoma of bladder is correlated to differences in DNA supercoiling: evidence for two discrete tumor populations.
Single cell tumor suspensions were prepared from biopsy and urine samples from 48 patients with muscle invasive transitional cell carcinoma of the bladder. Prior to therapy, samples were irradiated in vitro with the condensation of DNA supercoils measured by the light scattered within a flow cytometer. Six months after completing a course of radiotherapy, the in vitro data were correlated with the presence or absence of local disease. After 12-Gy irradiation, nucleoid extraction and staining with 50 micrograms/ml ethidium bromide, 2 predominant forms of supercoiling behavior were seen. Nucleoids scattered either approximately 10% (Type I) or 35% (Type II) more light than unirradiated controls. Those patients with residual disease showed more Type I behavior (21 of 25; 84%) than those patients clear of disease (9 of 23; 39%) (P = 0.02). It is proposed that the ability of these tumor samples to adopt positive supercoiling after irradiation is related to a stronger association between individual DNA loops and their attachment to the nuclear matrix. This difference in nucleoid response within these tumor samples may be related both to intrinsic cellular radiosensitivity and, subsequently, to clinical radiocurability.
Adult↗
Association of a 70-kDa tyrosine phosphoprotein with the CD16: zeta: gamma complex expressed in human natural killer cells.
The CD16: zeta: gamma receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fc gamma domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of zeta and gamma are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the zeta subunit and the phospholipase C gamma-1 and gamma-2 isoforms. Here we show that CD16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16: zeta: gamma receptor complex, results in the tyrosine phosphorylation of a 70 kDa zeta-associated protein (pp70). Similarly, a 70-kDa zeta-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa zeta-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16: zeta: gamma complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.
Humans↗
Effect of a short course of rapamycin, cyclosporin A, and donor-specific transfusion on rat cardiac allograft survival.
The interactions of rapamycin (Rapa), CsA, and donor-specific transfusion (DST) were examined in an ACI to Lewis rat heterotopic cardiac allograft model. Survival data were truncated at 175 days for the purpose of statistical comparisons. Vehicle (Veh)-treated animals rejected at a mean of 7.3 +/- 0.2 days. Treatment with a DST on the day before transplantation (d-1) resulted in a decreased survival of 5.5 +/- 0.3 days (P < 0.05). An 8-day course of low-dose CsA (d-1 to d6) in Veh-treated animals prolonged allograft survival to 10.3 +/- 0.5 days (P < 0.05). The addition of a DST d-1 to the Veh/CsA-treated animals resulted in a synergistic prolongation of survival to 45.7 +/- 12.5 days (P < 0.05). Rapa proved to be a potent immunosuppressive agent in this model, with an 8-day course of Rapa (d-1 to d6) at 0.5 mg/kg/day (R1) or 1.5 mg/kg/day (R2), resulting in mean allograft survivals of 24.2 +/- 5.0 and 67.3 +/- 20.9 days, respectively (P < 0.05 vs. Veh or Veh/CsA). Rapa demonstrated synergy with CsA by further prolonging allograft survival to 115.9 +/- 27.9 days (R1/CsA, P < 0.05 vs. Veh/CsA, R1) and 164.6 +/- 10.4 days (R2/CsA, P < 0.05 vs. Veh/CsA). The extended graft survival using a combination of Rapa and DST, compared to Rapa alone, did not prove to be statistically significant. When all three treatments were combined (Rapa/DST/CsA), no significant benefit to survival was seen over Veh/DST/CsA (45.7 +/- 12.5 days vs. R1/DST/CsA, 81.9 +/- 18.4 days; R2/DST/CsA, 98.5 +/- 21.3 days; P > 0.05). If Rapa was withheld until postoperative day 1 (Rapa, 1.5 mg/kg/day on d1 to d6/DST/CsA), enhancement of the DST/CsA effect was seen with a mean survival of 170.2 +/- 4.8 days (P < 0.05). This suggests that the timing of Rapa administration may significantly impact its interaction with DST/CsA treatment and merits further investigation.
Animals↗
mRNA surveillance by the Caenorhabditis elegans smg genes.
mRNAs that contain premature stop codons are unstable in most eukaryotes, but the mechanism of their degradation is largely unknown. We demonstrate that functions of the six C. elegans smg genes are necessary for rapid turnover of nonsense mutant mRNAs of the unc-54 myosin heavy chain gene. Nonsense alleles of unc-54 express mRNAs that are unstable in smg(+) genetic backgrounds but have normal or near normal stability in smg(-) backgrounds. smg mutations also stabilize mRNA of unc-54(r293), a small deletion that removes the unc-54 polyadenylation site and expresses an aberrant mRNA. Most unc-54 nonsense mutations are recessive in both smg(+) and smg(-) genetic backgrounds. However, four specific alleles are recessive when smg(+) and dominant when smg(-). These smg-dependent dominant alleles express nonsense mutant polypeptides that disrupt thick filament and/or sarcomere assembly. All four alleles are predicted to express nonsense fragment polypeptides that contain most of the myosin globular head domain without an attached rod segment. By degrading messages that contain premature stop codons, the smg genes eliminate mRNAs that encode potentially toxic protein fragments. We propose that this system of mRNA turnover protects cells from their own errors of transcription, mRNA processing, or mRNA transport.
Animals↗