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Biomedical subjects

C May

Publications and source records attributed to C May.

At least 55 records · Page 3Linked to original sources
PubMed1998

Development of a toxin-binding agent as a treatment for tunicaminyluracil toxicity: protection against tunicamycin poisoning of sheep.

OBJECTIVE: To assess the ability of certain derivatives of beta-cyclodextrin to treat sheep affected by tunicaminyluracil toxicity, using tunicamycin poisoning as a model system. DESIGN: Controlled treatment trial. ANIMALS: One hundred and sixty Merino wethers were used in the studies. PROCEDURE: Groups of sheep were experimentally poisoned with tunicamycin. Derivatives of beta-cyclodextrin, with or without magnesium sulphate and magnesium gluconate, were administered to treatment groups daily for 2 to 3 days. Treatment groups were compared with untreated groups in terms of survival. RESULTS: A significant increase in survival was observed following treatment of tunicamycin-affected sheep with hydroxypropyl-beta-cyclodextrin (HP beta-CD) and magnesium sulphate in solution (P < 0.05). In subsequent trials, formulation of the cyclodextrin in the form of a magnesium gluconate gel suspension demonstrated significant protection (P < 0.01) and was equally as effective as the cyclodextrin in solution, but required half the frequency of administration, even when the treatment was not commenced until 24 h after the final toxin dose. Beta-cyclodextrin-epichlorohydrin copolymer also improved the survival rate. After toxin administration, the sheep lost significantly less weight if treatment with HP beta-CD was commenced early (P < 0.001). CONCLUSION: Protection studies using these two beta-cyclodextrin derivatives suggest that they may be effective in increasing the survival of sheep poisoned by tunicamycin and warrant further testing in field outbreaks of annual ryegrass toxicity.

Animals↗
PubMed1997

The professional imagination: narrative and the symbolic boundaries between medicine and nursing.

The sociology of nursing, despite decisive interventions by recent commentators, continues to take as its main focus the subordination of nursing to biomedicine. This view reflects analytic stability, as well as institutional inertia. Far less attention has been paid by sociologists to the ways in which nursing is constructing its difference from medicine, and the exercise of the professional imagination that this involves. This paper suggests a strategy by which this might be remedied, which would focus on professional narratives.

Delivery of Health Care↗
PubMed1997

Regulatory interactions of transcription factor YY1 with control sequences of the E6 promoter of human papillomavirus type 8.

Human papillomavirus type 8 (HPV-8) is a strictly cutaneous oncogenic virus known to induce malignant skin lesions in epidermodysplasia verruciformis patients. Our study shows that sequences surrounding transcription start sites of the HPV-8 oncogene E6 (nt 175-179) and comprising the presumable CCAAC and TATA boxes of the E6 promoter P175 contain a cluster of four motifs similar to the DNA recognition site of the multifunctional cellular transcription factor yin-yang 1 (YY1). Using DNase I footprinting and gel retardation tests it could be demonstrated that three of these motifs indeed act as YY1 binding sites. To test their functional relevance for P175 activity, engineered YY1 binding site mutants were analysed in the context of a P175 test vector using transient expression assays with human keratinocytes. YY1 turned out to exert both positive and negative effects upon the activity of the HPV-8 E6 promoter; binding of YY1 to a site upstream of the promoter's cap-position (BS1) activated transcription, whereas the downstream site (BS2) mediated repression. The second downstream YY1 binding site (BS3) seemed to play an auxiliary role, enhancing the negative effect of YY1 BS2. These observations define YY1 as an important cellular protein involved in the control of E6 oncogene expression of the skin-specific 'high risk' HPV-8 and emphasize the potential regulatory role of sequences located downstream of the transcription start site.

DNA-Binding Proteins↗
PubMed1997

Cell-type-specific separate regulation of the E6 and E7 promoters of human papillomavirus type 6a by the viral transcription factor E2.

Gene expression of human papillomaviruses (HPV) is tightly controlled by cellular factors and by the virally encoded E2 protein through binding to distinct sites within the regulatory noncoding region. While for the high-risk genital papillomaviruses a single promoter drives the expression of all early genes, a second promoter present in the E6 open reading frame of the low-risk HPV type 6 (HPV6) would allow an independent regulation of E6 and E7 oncogene expression. In this report, we provide the first evidence that E2 regulates both early promoters of HPV6 separately and we show that promoter usage as well as E2 regulation is cell type dependent. Among the different epithelial cell lines tested, only RTS3b cells allowed an expression pattern similar to that observed in naturally infected benign condylomas. While the E6 promoter was repressed by E2 to 50% of its basal activity, the E7 promoter was simultaneously stimulated up to fivefold. Activation of the E7 promoter was mediated predominantly by the binding of E2 to the most promoter-distal E2 binding site. Repression of the E6 promoter depended on the presence of two intact promoter-proximal binding sites. Mutation of both of these repressor binding sites reversed the effect of E2 on the E6 promoter from repression to activation. In contrast, in HT3 cells we observed an E2-mediated activation of the E6 promoter in the context of the wild-type noncoding region. This indicated that repression of the E6 promoter by binding of E2 to both promoter-proximal binding sites did not function in the cellular environment provided by HT3 cells. These data suggest that the separate regulation of the E6 and E7 promoters of HPV6 is mediated through successive occupation of binding sites with different affinities for E2 depending on the intracellular concentration of E2 and on the cellular environment provided by the infected cell.

Animals↗
PubMed1997

Transgenic mice expressing the tyr22 variant of murine DHFR: protection of transgenic marrow transplant recipients from lethal doses of methotrexate.

Expression of the arg22, drug-resistant variant of dihydrofolate reductase (DHFR) in hematopoietic cells has been demonstrated to confer resistance to methotrexate (MTX) in mice, even though this variant suffers from low catalytic activity. The recently reported tyr22 variant has the advantage of higher catalytic activity combined with significant resistance to MTX. To evaluate the resistance conferred by tyr22-DHFR in vivo, we generated several transgenic mouse lines carrying a tyr22-DHFR minigene regulated by its natural promoter. The transgene copy number in 11 lines ranged from 6 to 68 copies and ribonuclease protection analysis demonstrated that 4 of these lines expressed significant transgenic DHFR mRNA at 20 to 68% of the endogenous DHFR mRNA level. Marrow from 4 of the 11 lines conferred significant increases in MTX-resistance in comparison with normal marrow when transplanted into lethally irradiated recipients. The ability of the tyr22-DHFR transgenic marrow to confer MTX-resistance to bone marrow transplant (BMT) recipients did not correlate with the level of mRNA expression or the number of transgene copies. However, two lines (lines 11 and 15) that were most effective in maintaining normal hematocrit levels in BMT recipients receiving 1 mg/kg/day MTX exhibited the greatest ability to form MTX-resistant hematopoietic progenitor colonies in vitro. Furthermore, MTX dose escalation studies demonstrated that line 11 marrow conferred resistance in BMT recipients receiving up to 6 mg/kg/day MTX. Southern blot analysis of the BMT recipients 7 months posttransplantation showed a preponderance of transgenic donor-derived cells in bone marrow and spleen, as well as a surprisingly high level in the small intestine. These results indicate that tyr22-DHFR is likely to be superior to arg22-DHFR in conferring MTX-resistance in BMT recipients, illustrating its usefulness for chemoprotection during MTX chemotherapy and also potentially for in vivo selection of transduced cells in gene therapy trials.

Amino Acid Substitution↗
PubMed1997

Wavelet transforms for electrocardiogram processing.

Wavelet transforms were used to remove noise and detect characteristic points for feline and human electrocardiograms. The electrocardiograms contained both 60 Hz line noise and wideband noise. Noise was removed from the signals using both Fourier and wavelet techniques. For the Fourier technique, the signals were notch filtered at 60 Hz, and then low-pass filtered. To remove noise using wavelet techniques, the signals were wavelet-transformed and then soft thresholding was performed on each of the resulting details. The two methods of removing noise were then compared to illustrate the advantages of the wavelet approach. Wavelet transforms were also used to detect a characteristic point on each beat. An algorithm was written to find this point, calculate the instantaneous heart rate, and then plot heart rate variability.

Animals↗
PubMed1996

Cucumber T-complex protein. Molecular cloning, bacterial expression and characterization within a 22-S cytosolic complex in cotyledons and hypocotyls.

T-complex protein (TCP) found in mammalian cells and yeast has been proposed as cytosolic folding machinery. We report here the cloning and initial characterization of a plant TCP cDNA. CSTCP-1 cDNA prepared from mRNA of cotyledons of germinating cucumber seeds encodes a polypeptide composed of 535 amino acid residues. The 59157-Da protein exhibits only 28% identity to both TCP-1p from yeast or and its homolog in Arabidopsis thaliana. Antibodies raised against the bacterially expressed plant protein were used to analyze the intracellular localization of TCP in two different plant tissues: fat-degrading non-dividing cotyledons and meristematic hypocotyls during seed germination. Cell fractionations included differential centrifugation and sedimentation of large complexes at 23000O x g for 4h. The latter fraction was further fractionated by sedimentation velocity centrifugation. This enrichment was required to detect by Western blotting cytosolic 59-kDa species as constituents of 22-S particles. From hypocotyls, a preparation of T-complex was obtained which consisted almost exclusively of proteins in the molecular range of 57-62 kDa. Likewise, the radioactive Cucumis sativus TCP-1 synthesized from CSTCP-1 mRNA in vitro using reticulocyte lysate was shown to migrate as a 61-kDa species.

Amino Acid Sequence↗
PubMed1996

More semi than structured? Some problems with qualitative research methods.

Qualitative research techniques have become a favoured tool of academic nursing research in recent years. Although there is now a significant body of methodological literature intended to train students in these techniques, the limits of qualitative research techniques are rarely discussed. This research note discusses the limits on claims than can be made about the utility of such techniques.

Anthropology, Cultural↗
PubMed1996

Ascertaining dementia by expert panel in epidemiologic studies of nursing home residents.

A new method for ascertaining dementia in epidemiologic research and the results of a study to evaluate it are described. The method relies on an expert panel of clinicians reviewing clinically relevant information collected by lay evaluators to arrive at a diagnosis based on DSM-III-R criteria. The approach was developed to study dementia in a statewide sample of over 2400 new admissions to 59 nursing homes in Maryland. Expert panel ascertainment of dementia was compared to that obtained by direct clinical evaluation for 100 nursing home residents. Agreement between the panel and direct assessment was 76% (kappa = 0.59) using a three-category classification of dementia, no dementia, and indeterminate. This ascertainment strategy provides an alternative to methods currently in use and is particularly well-suited for populations with a high prevalence, in those dispersed over large geographic areas, and when timely, cost-effective evaluations are required.

Aged↗
PubMed1996

Interleukin-2 secretion by transduced and unselected BDL-2 lymphoma results in increased survival in mice with previously established disseminated disease.

The transfer and expression of cytokine genes into malignant cells to provide a more effective tumor response has shown promise. The majority of murine models in which tumor vaccination strategies have been tested have utilized selected and expanded clones of tumor cells, which is impractical clinically. In a model of murine B lineage lymphoma (BDL-2), we compared the effectiveness of tumor vaccines composed of a) a BDL-2 clone established by G-418 resistance following transduction with the LIL2SN retrovirus and screened for maximal IL-2 secretion, b) a syngeneic fibroblast line transduced with LIL2SN and screened for G-418 resistance and IL-2 expression, which was co-injected with the parental line, and c) a heterogeneous (unselected) population of BDL-2 cells transduced with the MFG/IL2 virus, reported to provide enhanced expression of cytokine genes and minimize the need for selection. Testing of splenocytes derived from vaccinated animals reveals that injections of BDL-2 expressing IL-2 results in an increased capacity of splenocytes to kill BDL-2 in vitro, compared to vaccination of BDL-2 alone or in combination with IL-2 secreting fibroblasts. We show that a vaccine composed of MFG/IL2 transduced, unselected BDL-2 cells is equivalent or superior to a clone derived from LIL2SN transduction in prolonging survival of animals with previously established tumor. These studies provide evidence that transduction of tumor with MFG based vectors without in vitro selection leads to expression of high levels of IL-2 and can impact the survival of animals with disseminated tumor.

Animals↗
PubMed1996

Methotrexate dose-escalation studies in transgenic mice and marrow transplant recipients expressing drug-resistant dihydrofolate reductase activity.

Methotrexate (MTX) dose-escalation studies were conducted in two inbred lines of FVB/N transgenic mice expressing distinct drug-resistant dihydrofolate reductases (DHFRs) and in animals transplanted with transgenic marrow. Survival of animals expressing a tryptophan-31 variant DHFR transgene was only slightly improved over that of normal animals, and survival of tryptophan-31 variant DHFR marrow transplant recipients was indistinguishable from that of normal animals (at a MTX dose of 4 mg/kg i.p. daily). In contrast, extended survival was observed for animals expressing an arginine-22 variant (Arg22) DHFR transgene, with the last three of eight animals in this group succumbing at a final MTX dose of 14 mg/kg i.p. daily. Survival was slightly reduced for normal animals transplanted with Arg22 marrow. Interestingly, demise of animals in both Arg22 groups was not associated with the profound drop in hematocrit levels usually observed in MTX-treated animals. These animals were instead characterized by severe atrophy of the gastrointestinal tract, whereas hematocrit levels and marrow histology were relatively normal. Kidney pathology (mesangiocapillary glomerulopathy) was also observed in Arg22 marrow recipients but not in Arg22 transgenics, consistent with expression of the drug-resistance gene in kidney tissues of the transgenics, as demonstrated by ribonuclease protection analysis. Immediate dose-response studies in Arg22 marrow transplant recipients defined a maximum tolerated dose of 4 mg/kg/day MTX, 2 to 3 times that of animals transplanted with normal marrow or of normal untransplanted animals. These results define the extent of chemoprotection afforded by drug-resistant DHFR expression and serve to identify alternate sites of toxicity in animals administered the higher levels of MTX afforded by drug-resistant DHFR expression in the marrow.

Animals↗
PubMed1996

The biopsychosocial model of general practice: rhetoric or reality?

BACKGROUND: For more than 20 years, general practitioners have been encouraged to adopt a 'biopsychosocial' model of health care, that is, encompassing physical, psychological and social aspects. AIM: A study was undertaken to explore the extent to which general practitioners' views about the acceptable boundaries of their work are consistent with a biopsychosocial model. METHOD: A semi-structured postal questionnaire was sent to all 494 members of the Royal College of General Practitioners in Mersey Region who were general practitioner principals. The general practitioners were asked to list up to three topics presented by patients that they considered to be appropriate, and up to three topics that they considered to be inappropriate, to a general practitioner's knowledge and skills. The general practitioners were asked to rate, on a five-point scale of appropriateness, each of a list of 12 topics about which patients might have problems and present. Responses were analysed by sex and age of respondents. RESULTS: The response rate was 42%. Acute physical problems were most often listed appropriate by respondents, followed by chronic physical and psychological problems. The topics most often considered inappropriate were bureaucracy and social issues. Among the list of 12 specified topics, respondents considered terminal care and hypertension to be more appropriate than housing issues, spiritual worries, welfare rights or political issues. The sex of respondents did not relate to differences in results. Respondents aged 35 years and over generally considered topics presented by their patients to be more appropriate than did their younger colleagues. CONCLUSION: The general practitioner respondents in this study appeared to hold the view that general practitioners should work to a bio(psycho) rather than a biopsychosocial model of health care.

Attitude of Health Personnel↗