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Biomedical subjects

M Browning

Publications and source records attributed to M Browning.

At least 19 recordsLinked to original sources
PubMed2003

Systemic neutrophil activation in acute preschool viral wheeze.

BACKGROUND: In preschool children, attacks of wheeze are usually triggered by viral colds. The inflammatory substrate in preschool viral wheeze (PVW) is unclear, but epidemiological data suggest that most PVW is not caused by allergic inflammation. We therefore speculated that the neutrophils are an important effector cell. Systemic neutrophil activation is the first stage for the development of pulmonary neutrophilia. Markers of neutrophil activation are shedding of the adhesion molecule L-selectin from the cell surface, upregulation of Mac-1 expression, and an increase in serum soluble L-selectin. AIMS: To obtain evidence for systemic neutrophil activation during PVW. METHODS: Preschool children (1-5 years) admitted to hospital with acute PVW (n = 20) and normal controls (n = 18) were studied. Adhesion molecule expression on CD16 positive neutrophils was determined in both groups and expressed as molecules of equivalent fluorochrome (MEF). Serum soluble L-selectin was analysed by ELISA. RESULTS: Compared with controls, children with PVW had reduced neutrophil L-selectin expression (median MEF (IQR): 69 (11 to 96) units versus 136 (109 to 163) units, p < 0.001) and higher serum soluble L-selectin (2.8 (2.3 to 3.1) versus 2.4 (2.2 to 2.6) micro g/ml, p = 0.04). There was no significant difference in neutrophil Mac-1 expression. CONCLUSION: Systemic neutrophil activation is associated with acute PVW.

Acute Disease↗
PubMed2001

Rheumatoid arthritis: a primary care approach.

PURPOSE: To provide primary care providers with guidelines on the evaluation, diagnosis and management of patients with rheumatoid arthritis (RA). DATA SOURCES: Research-based articles in the medical literature, review articles, and clinical practice is a chronic inflammatory disease that affects mainly synovial joints. Diagnosis is based primarily on clinical examination. Clinical criteria developed by the American Rheumatism Association can help the primary care provider recognize this potentially devastating disease and facilitate early referral to a rheumatologist for treatment. IMPLICATIONS FOR PRACTICE: Patients with RA should be treated early and aggressively. Laboratory tests are not essential to confirm the diagnosis of RA. The clinical usefulness of the rheumatoid factor could be increased by restricting the test to patients who have a high probability of RA based on clinical symptoms.

Antirheumatic Agents↗
PubMed2000

Identification of diminished tissue culture invasiveness among multiple antibiotic resistant Salmonella typhimurium DT104.

Salmonella infections continue to cause gastrointestinal and systemic disease throughout the world. Salmonella typhimurium further poses a major health concern due to its apparent enhanced ability to acquire multiple antibiotic resistance genes. Currently it is unclear if multiresistant S. typhimurium are more or less pathogenic than non-resistant counterparts. Using an in vitro invasion assay, we evaluated the relative pathogenicity of over 400 multiresistant S. typhimurium isolates. Our studies failed to identify any <<< >>> isolates. However, we identified 12 isolates exhibiting invasive phenotypes that were constrained relative to controls. These <<< >>> strains were found in a variety of phagetypes all possessing at least a hexaresistant profile. Further studies revealed that the alterations in invasion were not due to changes in adherence. Limited studies exploring in vivo virulence revealed a mildly decreased ability to cause murine lethality for the hypoinvasive strain examined. These results indicate that the ability to cause disease is not increased but is rather mildly attenuated for certain isolates of multiresistant S. typhimurium.

Animals↗
PubMed2000

Definition of peptide binding motifs amongst the HLA-A*30 allelic group.

HLA class I molecules present endogenously processed peptide ligands for surveillance by the T-cell receptor. This potentially immunogenic surface of HLA and peptide is a consequence of the polymorphism found within the HLA molecule and its preference for ligand binding together with peptide conformation within the binding groove. To investigate the relation between the polymorphic differences between some closely related HLA alleles and their effect on peptide preference, transfectants were established, each containing one of four allelic variants of HLA-A*30. Peptides from all four transfectants were eluted, and both individual ligands and peptide pools were sequenced. The data shows two distinct peptide motifs which distinguish A*3001 from the other three known A*30 variants. Differences in preferences at minor positions within the peptide sequence were noted between A*3002, A*3003 and A*3004, providing additional evidence of the implications of sequence polymorphism to HLA function.

Alleles↗
PubMed1999

Pathogenicity of Bacillus thuringiensis variety kurstaki to Ixodes scapularis (Acari: Ixodidae).

Pathogenicity of the entomopathogenic bacterium Bacillus thuringiensis variety kurstaki de Barjac & Lemille was tested against the black-legged tick, Ixodes scapularis Say. Engorged larvae dipped in a solution of 10(8) spores per milliliter showed 96% mortality 3 wk after infection. The LC50 value for engorged larve (concentration required to kill 50% of ticks) was 10(7) spores per milliliter. B. thuringiensis shows considerable potential as a microbial control agent for the management of I. scapularis.

Animals↗
PubMed1997

Implementation of an osteoporosis research program with a mobile dual-energy X-ray absorptiometry unit: the Montana/Wyoming experience.

To expedite recruitment, and subject participation, for a large clinical osteoporosis therapy trial utilizing the bisphosphonate ibandronate, an integrated network of 13 satellite clinical sites was developed, linked by a mobile clinic vehicle transporting a dual-energy X-ray absorptiometry (DXA) unit. A predominantly rural area of the United States (Montana, northern Wyoming) was accessed for the project, due to the large pool of potential subjects living in this area who were not yet involved in osteoporosis clinical studies. The results of the project to date (through 10 months) confirm the feasibility of such a study design, with 1774 subjects screened by DXA for the study, and 280 (15.8%) accepted. The mobile DXA unit has functioned according to specifications for a stationary DXA machine, with the stability of spine phantom measurements over 10 months assessed as a coefficient of variation of 0.46%. The success of the project validates the concept of performing clinical osteoporosis therapy trials in previously underutilized rural community settings, facilitated by a satellite site network and mobile clinic.

Absorptiometry, Photon↗
PubMed1997

HLA and cancer: implications for cancer immunotherapy and vaccination.

Both animal models and studies in humans indicate that the immune response has enormous potential for the treatment of cancer, and that HLA plays a central role in this. This role is likely to become increasingly important in years to come, as effective strategies for immunotherapy of cancer are developed. In the last few years, much of the focus of tumour immunology has been on the identification and characterization of tumour-associated antigens that represent HLA-restricted tumour-specific targets. In the next few years the emphasis is likely to change, such that the HLA type and antigen profile of an individual's tumour may define the most appropriate form of therapy for the patient. The ability of tumour cells to down-regulate or lose expression of some or all HLA molecules may prove to be a major barrier to the effectiveness of such treatments. The next few years should show whether the potential of the advances in tumour immunology made over the last decade can be realized, or whether the application of these advances as therapeutic strategies falls short of their promise.

Antigens, Neoplasm↗
PubMed1997

Does being unusual and dangerous mean you are mad?

This article is, essentially, an examination of what the medical profession and society generally mean by the term 'mad', and what relevance 'madness' has to modern psychiatry. It suggests that 'madness' differs from 'mental illness' and that psychiatry only deals with the latter. It concludes that for any rigorous, rational approach to psychiatry to be attempted an accepted framework of what constitutes mental illness must be used. This is the important role of ICD 10 and DSM IV which help to ensure that psychiatrists do not act as 'moral gaolers of the state'.

Humans↗
PubMed1997

Pathogenicity of the entomopathogenic fungus Metarhizium anisopliae (Deuteromycetes) to Ixodes scapularis (Acari: Ixodidae).

The entomopathogenic fungus Metarhizium anisopliae is highly pathogenic to the black-legged tick, Ixodes scapularis. Spore concentrations of 10(8)/ml for engorged larvae and 10(7)/ml for engorged females resulted in 100% tick mortality, 2 wk postinfection. The LC50 value for engorged larvae (concentration to kill 50% of ticks) was 10(7) spores/ml. Metarhizium anisopliae shows considerable potential as a microbial control agent for the management of Ixodes scapularis.

Animals↗
PubMed1996

Mechanisms of loss of HLA class I expression on colorectal tumor cells.

For several years this laboratory has studied the expression of HLA class I on established colorectal tumor cell lines and on fresh tumors. We review here the mechanisms by which colorectal tumor cells may lose surface expression of HLA class I molecules. Several independent mechanisms have been identified, including loss or mutations in beta 2-microglobulin genes, loss of HLA heavy chain genes, selective lack of expression of HLA alleles, and regulatory defects in HLA expression including loss of expression of the peptide transporters associated with antigen processing (TAP). The data suggest that colorectal tumor cells may evade tumor specific, HLA restricted immune attack by loss of HLA class I expression through a number of mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Emergency hormonal contraception usage in genitourinary medicine clinic attenders.

OBJECTIVE: To assess the indications for usage of emergency hormonal contraception amongst a population of London genitourinary medicine clinic attenders. METHODS: In a prospective study, 150 consecutive women receiving emergency hormonal contraception (EHC) were enrolled. The attending doctor completed a questionnaire of patient details and prescribed EHC with prophylactic prochlorperazine. Follow-up was arranged three weeks later, at which time outcomes and side-effects of therapy were recorded. For those women who did not reattended as planned case notes were reviewed at three months. RESULTS: Of 150 women surveyed, 100 (66%) reported contraceptive method failure, 48 (32%) had used no contraception at the time of last sexual intercourse and two requested EHC after sexual assault. Ninety three (62%) reported condom failure, 7 (5%) oral contraceptive pill failure. Seventy five (50%) had used EHC before (range 1-10 times). Seventy one (47%) women reattended within three months. Five (3.3%) of the 150 women were pregnant; none of these cases had experienced nausea or vomiting whilst taking EHC. Side-effects were reported by 22 (31%) of the 71 patients who reattended. Nine (6%) women had been followed-up in the family planning advisory clinic. Of the 71 women who reattended, 39 (55%) reported that their preferred future method of contraception would be condoms. Of the 150 women 19 (13%) underwent tests for sexually transmissible infections within one month of presentation. CONCLUSIONS: EHC usage in this population was associated with a failure rate of at least 3.3% and an overall side effect rate of 31%. Despite requests for emergency contraception because of condom failure many elected to continue using condoms as their preferred method of contraception. The majority of women (53%) did not return for follow-up or family planning advice, and so we believe that future contraceptive plans must be addressed at the time EHC is prescribed.

Adolescent↗
PubMed1995

Mechanisms of allele-selective down-regulation of HLA class I in Burkitt's lymphoma.

Burkitt lymphomas (BL) that arise in HLA-AII-positive individuals are characterized by selective loss/down-regulation of the HLA AII polypeptide. We have investigated the molecular basis of such down-regulation by comparing 5 pairs of BL lines and Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) derived from the normal B cells of the same individuals. The presence of apparently intact HLA AII genes was confirmed in all 5 BL/LCL pairs by polymerase chain reaction (PCR) typing and by Southern-blot hybridization with HLA A locus-specific probes. Northern-blot analysis with locus- and allele-specific probes revealed a significantly lower expression or absence of AII-specific mRNA in all 5 BL lines compared to the corresponding LCLs. Up-regulation of AII-specific mRNA was achieved by IFN alpha treatment of 2 BL lines with low HLA AII expression (BL-28 and BL-72) while the treatment had no effect in 3 BL lines (WWI-BL, WW2-BL and BL41) that did not express the endogenous gene. HLA AII expression was restored by transfection of the gene in WWI-BL whereas transfectants of BL-41 remained AII-negative. An HLA-AII-promoter-driven chloramphenicol acetyl transferase reporter gene (pAIICAT) was active in WWI-BL but not in BL-41. HLA-AII was expressed in hybrids of BL-41 with an AII-positive LCL, while expression of the endogenous HLA AII gene could not be restored by fusion of BL-41 with an AII-negative LCL, although an adequate set of transcription factors was present in the hybrid. Our results suggest that genetic defects and lack of transcription factors may contribute to the selective down-regulation of HLA AII in BL cells.

Alleles↗
PubMed1995

Identification of conserved antigenic components for a cytotoxic T lymphocyte-inducing vaccine against malaria.

Several cellular and humoral mechanisms probably play a role in natural immunity to Plasmodium falciparum malaria, but the development of an effective vaccine has been impeded by uncertainty as to which antigens are targeted by protective immune responses. Experimental models of malaria have shown that cytotoxic T lymphocytes (CTL) which kill parasite-infected hepatocytes can provide complete protective immunity against certain species of Plasmodium in mice, and studies in The Gambia have provided indirect evidence that CTL play a protective role against P falciparum in humans. By using an HLA-based approach, termed reverse immunogenetics, we have previously identified peptide epitopes for CTL in liver-stage antigen-1 and the circumsporozoite protein of P falciparum. We have extended this work to identify CTL epitopes for HLA class I antigens that are found in most individuals from Caucasian and African populations. Most of these epitopes are in conserved regions of P falciparum. CTL peptide epitopes were found in a further two antigens, thrombospondin-related anonymous protein and sporozoite threonine and asparagine rich protein, indicating that a subunit vaccine designed to induce a protective CTL response may need to include parts of several parasite antigens. However, CTL levels in both children with malaria and in semi-immune adults from an endemic area were low suggesting that boosting these low levels by immunisation might provide substantial or even complete protection against infection and disease.

Adult↗
PubMed1995

Comparison of serum CA 72-4 and CA 19-9 levels in gastric cancer patients and correlation with recurrence.

BACKGROUND: This longitudinal prospective study evaluates the serum levels of the tumor markers CA 72-4 and CA 19-9, alone or in combination, in gastric cancer patients. PATIENTS AND METHODS: Serum tumor markers CA 72-4 and CA 19-9 were measured in 52 patients who had gastric adenocarcinomas and 32 with benign gastric disorders. Serial measurements of these markers were carried out in 30 cancer patients at a median follow-up time of 38 months. RESULTS: CA 72-4 and CA 19-9 had sensitivities of 42% and 46% for the preoperative detection of gastric cancer. Sensitivity for the two combined was 63%. CA 72-4 provided 100% specificity, compared to 72% for CA 19-9. Postoperatively, 17 cancer patients remained disease-free. Sixteen of these maintained normal levels of CA 72-4, and 10 of CA 19-9. Thirteen patients developed recurrent disease. In 9, serum CA 72-4 levels rose from near-normal after surgery and reached diagnostic values approximately 6 months before clinical diagnosis of recurrence. Only 3 patients exhibited such a pattern with CA 19-9. CONCLUSIONS: CA 72-4 is a reliable marker in gastric cancer. Postoperative serial sampling of CA 72-4 may facilitate early identification of recurrences.

Adenocarcinoma↗
PubMed1994

Activity of extracts of Kigelia pinnata against melanoma and renal carcinoma cell lines.

Serial dilutions of standardised water, ethanol, and dichloromethane extracts of the stembark and fruits of Kigelia pinnata were tested for their growth inhibitory effects against four melanoma cell lines and a renal cell carcinoma line (Caki-2) using two different (MTT and SRB) assays. Lapachol, a possible constituent of these extracts, together with known therapeutic antineoplastic agents, was also tested in the same way. The IC50 of each extract was measured after extracts were diluted to 100 micrograms/ml in 1% ethanol or water. Significant inhibitory activity was shown by the dichloromethane extract of the stembark and lapachol (continuous exposure). Moreover, activity was dose-dependent, the extract being less active after 1 h exposure. Chemosensitivity of the melanoma cell lines to the stembark was greater than that seen for the renal adenocarcinoma line. In marked contrast, sensitivity to lapachol was similar amongst the five cell lines. Lapachol was not detected in the stembark extract.

Antineoplastic Agents, Phytogenic↗