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Biomedical subjects

J Green

Publications and source records attributed to J Green.

At least 361 records · Page 20Linked to original sources
PubMed1993

Activation of FNR-dependent transcription by iron: an in vitro switch for FNR.

FNR is an iron-binding transcriptional regulator of Escherichia coli which controls the expression of target genes in response to anaerobiosis. The mechanism used by FNR to sense and respond to anaerobiosis is unknown but it is thought to involve iron. In vitro transcription analyses have shown that iron-deficient FNR is unable to activate transcription from the FF-melR promoter, but activity could be restored by preincubation with Fe2+ and beta-mercaptoethanol. The reactivation of FNR was prevented and reversed by chelating agents, and this reactivation thus provides an artificial in vitro switch for FNR-dependent transcriptional activation.

Bacterial Proteins↗
PubMed1993

A role for iron in transcriptional activation by FNR.

FNR is a transcriptional regulator which controls the expression of target genes in response to anoxia in Escherichia coli. The mechanism by which FNR senses and responds to anaerobiosis is unknown but indirect evidence suggests that an iron cofactor is involved. Using KMnO4 as a probe for DNA melting at active promoters, footprinting studies have now shown that the ferrous iron chelator, ferrozine, inhibits open complex formation in vivo, and that FNR with a high iron-content is essential for open complex formation in vitro. Since open complex formation is an essential pre-requisite for transcription, it is concluded that transcriptional activation by FNR is mediated by a ferrous iron cofactor.

Anaerobiosis↗
PubMed1993

Giardiasis in lambs at pasture.

Faecal samples from a group of lambs at pasture were screened at weekly intervals for nine weeks for the presence of Giardia species using a modified zinc sulphate flotation method. Fifty-nine of 86 lambs (68.6 per cent) excreted giardia cysts on one or more occasions. They were first detected at approximately three weeks of age and the highest incidence of excretion of cysts occurred when the lambs reached a mean age of 37 days. The lambs had diarrhoea but it was attributed to the presence of Eimeria ovinoidalis.

Animals↗
PubMed1993

Evidence against a relationship between fatty acid ethyl ester synthase and the Pi class glutathione S-transferase in humans.

Recently, Bora et al. (Bora, P. S., Bora, N. S., Wu, X., and Lange, L. G. (1991) J. Biol. Chem. 266, 16774-16777) reported the cloning and expression of a human fatty acid ethyl ester synthase III (FAEES-III) cDNA that has only four amino acid substitutions compared with human glutathione S-transferase (GST) GSTP1-1, and, when expressed in MCF-7 cells, the protein has both FAEES and GST activities. By site-directed mutagenesis of a GSTP1 cDNA, we have constructed a clone that encodes the FAEES-III protein described by Bora et al. (1991). The recombinant FAEES-III protein was expressed in Escherichia coli and has been shown to be devoid of FAEES and GST activities. The recombinant FAEES-III protein does not bind to a glutathione agarose affinity matrix, presumably because two of the substituted amino acids, Trp-39-->Cys and Gln-52-->Glu, are thought to contribute to the GST glutathione binding site. One of the base substitutions in the FAEES-III cDNA encodes an extra SacI site not found in the GSTPI cDNA. Polymerase chain reaction amplification of human genomic DNA has identified the GSTPI gene, but no DNA from the proposed FAEES gene with a diagnostic SacI site has been detected. Evaluation of the hybridization pattern of HindIII genomic restriction fragments has identified fragments that contain the GSTPI gene and a pseudogene (Board et al. 1992), and there do not appear to be any hybridizing fragments that could contain the FAEES-III gene. Our results do not provide any evidence in support of a relationship between FAEES-III and GST, and the cDNA reported by Bora et al. (1991) may have resulted from a cloning artifact.

Acyltransferases↗
PubMed1993

Serum screening for Down's syndrome: some women's experiences.

OBJECTIVES: To describe the experiences of a small group of women who had positive results after serum screening for Down's syndrome. DESIGN: Semistructured telephone interviews and correspondence with women after a positive screening result (four women) negative amniocentesis results (eight), or termination of a pregnancy with a confirmed abnormality (eight). SUBJECTS: 20 women who contacted Support After Termination For Abnormality about their experiences of serum screening for Down's syndrome. MAIN OUTCOME MEASURES: Women's knowledge and understanding of the test; staff misconceptions; communication of results; how women coped with the diagnostic process; attitudes to the test and to termination of abnormal fetuses. RESULTS: All women were made anxious by their positive screening test, no matter how they were told. The women's experiences suggested that medical staff were unclear about the implications of screening tests and how to interpret risk. Even after receipt of negative amniocentesis results some women remained anxious. Staff did not always recognise women's concerns while awaiting amniocentesis results. CONCLUSIONS: The way in which serum screening is being implemented does not always meet the needs of women with positive results. Some of the problems were not specific to screening for Down's syndrome. When screening tests are introduced policies should be adopted to ensure appropriate support for participants.

Adaptation, Psychological↗
PubMed1993

Elevated proliferating cell nuclear antigen levels in immature thymocytes. Dissociation from cell cycle progression.

Entry into and progression through the cell cycle is associated with a tightly regulated program of gene expression in mature T cells. One such gene product, proliferating cell nuclear Ag (PCNA), is the auxiliary protein of DNA polymerase delta, and is induced during late G1 and early S phase after stimulation of resting (G0) cells. Blockade of PCNA production has been found to inhibit cell division suggesting that PCNA plays an important role in cell proliferation. The extent to which PCNA and other proliferation-related gene products are similarly regulated in thymocytes has been largely undetermined. Here, we report that immature double positive (CD4+CD8+) thymocytes express high levels of PCNA protein and mRNA relative to mature single positive (CD4+CD8- or CD4-CD8+) thymocytes or peripheral blood T cells. Elevation of PCNA expression among double positive thymocytes is not the result of increased numbers of cycling cells in this subpopulation, being specifically observed in double positive thymocytes with normal diploid DNA content and resting (G0) levels of RNA. Unlike mature thymocytes and T cells, mitogenic stimulation did not induce an increase in PCNA expression in double positive thymocytes. These data indicate that immature thymocytes express high levels of PCNA in the absence of cell cycle progression, thus providing evidence for differential regulation of proliferation related pathways during lymphoid development. Altered expression patterns of these genes in immature vs mature thymocytes may contribute to the process of thymic selection.

Animals↗
PubMed1993

Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction.

A growing body of evidence points to a role for epidermal keratinocytes as active participants in immunologic reactions. Inasmuch as certain T cell-mediated skin diseases, such as psoriasis and atopic dermatitis, are triggered by microbial infection, we asked whether multipassaged human keratinocytes could provide the costimulatory signals necessary to induce autologous T cell proliferation in response to bacterial-derived super-antigens. On exposure to IFN-gamma, keratinocytes are induced to express HLA-DR and HLA-DQ class II MHC Ag, and the lymphocyte function-associated Ag-1 counter-receptor intercellular adhesion molecule-1 (ICAM-1). This change in keratinocyte phenotype is accompanied by the ability of these cells to support T cell proliferation induced by two different bacterial-derived superantigens, staphylococcal enterotoxins A and B. Superantigen-driven proliferation in the presence of IFN-gamma-treated keratinocytes was significantly inhibited (70-90% reduction) by mAb against the LFA-1 alpha- or beta-chain or ICAM-1. Proliferation was not inhibited by mAb against the CD28 ligands BB-1 or B7, even though these keratinocytes express BB-1. In addition to previous defined roles for class II MHC Ag, stimulation of LFA-1 on the T cells by ICAM-1 on the keratinocytes also plays an important costimulatory role in this superantigen-mediated response. The accessory cell capability of keratinocytes was not unique to superantigen driven responses as PHA, as well as anti-CD3 mAb also induced vigorous T cell proliferation when IFN-gamma-treated keratinocytes were added. However, IFN-gamma-treated keratinocytes consistently failed to provoke an allogeneic response. These data demonstrate that 1) keratinocytes can serve as accessory cells for T cell proliferation using a variety of different stimuli, 2) the LFA-1/ICAM-1 interaction plays a major role in keratinocyte-mediated costimulation, and 3) previous reports in which IFN-gamma-treated keratinocytes failed to support T cell proliferation to nominal or alloantigens, may reflect impaired Ag presentation via class II MHC molecules, rather than lack of necessary costimulatory signals. These findings highlighting the accessory cell function of keratinocytes may have implications for our understanding of the pathogenesis of immunologic disorders of the skin.

Antibodies, Monoclonal↗
PubMed1993

Testing for fetal abnormality in routine antenatal care.

The detection of fetal abnormality is a major component of routine antenatal care. A variety of techniques are now in use, although these are constantly being modified in the pursuit of more accurate and earlier detection. In this paper we draw attention to the distinction between screening and diagnostic tests, and describe the techniques which have been most commonly used in the UK: serum-screening for neural tube defects; screening for Down's syndrome; ultrasound scanning; amniocentesis and chorionic villus sampling.

Chromosome Aberrations↗
PubMed1993

Activated keratinocytes present bacterial-derived superantigens to T lymphocytes: relevance to psoriasis.

In the past, epidermal keratinocytes were felt to be primarily concerned with the barrier function of skin. During inflammatory and immune-mediated skin diseases, keratinocytes were only portrayed as being passive/inert targets for noxious agents produced by infiltrating leukocytes. This innocent bystander and/or 'brick and mortar' conceptualization of the keratinocyte must now be significantly modified to take into account the growing body of experimental in vitro and in vivo results that substantiate re-classification of keratinocytes as fully fledged members of the immune system (i.e. immunocytes). Because keratinocytes produce important primary cytokines, adhesion molecules, and mononuclear cell chemotactic factors; as well as functioning as accessory cells for resting T lymphocytes, they can initiate and perpetuate the inflammatory and immunological reactions in the skin which contribute to the pathobiology of psoriasis. This review will emphasize the dynamic contribution that epidermal keratinocytes make to cutaneous immunohomeostasis, with particular focus on the potential role of bacterial derived superantigens and their ability to stimulate resting T cell proliferation when presented by cytokine-activated keratinocytes.

Adult↗
PubMed1993

Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy.

The aim of this study was to determine the usefulness of recombinant human granulocyte colony stimulating factor (r-metHuG-CSF) following conventional chemotherapy for small cell lung cancer. 130 previously untreated patients were randomised to receive either r-metHuG-CSF (230 micrograms/m2) or placebo on days 4-17 following CDE (cyclophosphamide, doxorubicin and etoposide) chemotherapy. Over all cycles, 53% of 64 patients on placebo and only 26% of 65 patients on r-metHuG-CSF had at least one experience of neutropenia with fever defined as a neutrophil count less than 1.0 x 10(9)/l and a temperature > or = 38.2 degrees C (P < 0.002). It resulted in a reduction in the requirement for parenteral antibiotics from 58% in placebo patients compared with 37% in the r-metHuG-CSF group (P < 0.02), and a significant reduction in the incidence of infection-related hospitalisation. Chemotherapy doses were reduced by 15% or more at least once in 61% of the placebo group compared with 29% in the r-metHuG-CSF group (P < 0.001). 47% of the patients treated with placebo and 29% of the patients treated with r-metHuG-CSF experienced at least one cycle with a delay of 2 days or more in the administration of chemotherapy (P < 0.04). r-metHuG-CSF was well tolerated. There were no significant differences between the two groups in terms of response or survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Sociodemographic determinants in the hospitalization decision: evaluation of an emergency department interhospital transfer policy.

STUDY OBJECTIVES: To evaluate an emergency department's "treat and transfer" policy during a two-month period of reduced inpatient capacity by determining the number and characteristics of transferred patients not admitted as planned to the receiving hospital. DESIGN: Matched case-control analysis. SETTING: Public hospital adult ED. TYPE OF PARTICIPANTS: Patients transferred to other hospitals for admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twelve percent of patients (16 of 135) were not admitted after transfer during the first month, and 8% during the two-month period. Only IV drug use was found to be significantly associated with an increased risk of discharge without admission (odds ratio = 9.5; 95% confidence interval, 1.9 to 47.8). CONCLUSION: Patients transferred from the public hospital ED resulted in admission to the receiving hospital in 92% of transfers. A history of IV drug use was the only characteristic found to be associated with discharge without admission to the accepting hospital.

Adolescent↗
PubMed1993

Investigation of motivational and behavioural factors influencing men who have sex with other men in public toilets (cottaging).

One-hundred-and-thirty-four individuals engaging in cottaging returned postal questionnaires. The sample was mainly urban and gay identified. Cottagers reported that cottaging was one way of meeting partners amongst a range of others they used. Most enjoyed it and felt in control of their cottaging. The majority of cottagers engaged in safer sexual activity, but there were a significant number who engaged in unsafe sexual activity last time they cottaged. Of those who had been voluntarily tested in the past and reported their serostatus, 23% were seropositive. Unsafe sexual activity was unrelated to whether tested or not, known serostatus or knowledge of the risks of transmission.

Adult↗
PubMed1993

Effect of timing of antihypertensive therapy on glomerular injury: comparison between captopril and diltiazem.

Recent studies have suggested that the progression of experimental chronic renal disease may be prevented by early use of antihypertensive drugs. It is unclear, however, whether such therapies may also affect established and progressive renal disease. In the present study we compared the effects of captopril (CEI) and diltiazem (CCB), started either at week 10 or at week 24 on the evolution of adriamycin nephropathy (AN). Rats were studied at weeks 7, 16, 24, 32, and 38 of the disease. None of the treatments influenced the development of nephrotic range proteinuria. The use of CCB from week 10 was even associated with increased proteinuria. The moderate hypertension of ADR rats was reduced to the same degree with both drugs. Inulin clearance (GFR) was significantly reduced in all ADR rats. However, in ADR rats treated with CEI from week 10 and in those treated with CCB from week 24, the GFR was relatively higher. Glomerular injury, evaluated by semiquantitative methods, was not ameliorated by CEI treatment. Earlier CCB treatment (week 10) worsened glomerular lesions, whilst CCB treatment initiated at week 24 reduced significantly the degree of mesangial expansion and focal glomerular sclerosis. We conclude that, in addition to their common antihypertensive action, the specific effect of drug therapy seems to be crucially time dependent.

Animals↗
PubMed1993

Home exercises are as effective as outpatient hydrotherapy for osteoarthritis of the hip.

Hydrotherapy for OA of the hip has rarely been evaluated in controlled studies. Forty-seven patients with OA of the hip were followed for 18 weeks. Patients were randomly allocated either to a regimen of home exercises or to twice weekly hydrotherapy for 6 weeks in addition to home exercises. There was an improvement seen in both subjective and objective measures in both groups with treatment. There was no significant difference between the two groups. Response to treatment appeared independent of age, sex and radiological severity. We conclude that for most patients, a carefully graded and supervised regimen of home exercises is beneficial and there is little benefit in adding hydrotherapy to this regimen.

Aged↗