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Biomedical subjects

S Uthayakumar

Publications and source records attributed to S Uthayakumar.

At least 19 recordsLinked to original sources
PubMed2000

Is it evidence-based practice? Prophylactic antibiotics for termination of pregnancy to minimize post-abortion pelvic infection?

Sexually transmitted infections (STIs) causing upper genital tract problems after termination of pregnancy (TOP) is well recognized. We undertook this study to assess the local prevalence of Chlamydia trachomatis infection and to estimate the potential benefits of introducing screening. The prevalence rate of C. trachomatis was 6%. Nine sexual contacts of the index cases were identified. They were symptom free, but all had non-specific urethritis (NSU). Four of them were positive for C. trachomatis. We conclude that screening for chlamydial infection is essential and routine prophylactic antibiotic cover may not be beneficial.

Abortion, Induced↗
PubMed1999

Cell surface and substrate distribution of the 67-kDa laminin-binding protein determined by using a ligand photoaffinity probe.

BACKGROUND: Peptide 11, a nine-amino acid sequence from the beta1 chain of laminin-1, has been reported to inhibit tumor cell invasion of basement membranes, and to reduce tumor lung colonization (Iwamoto et al.: Science 238:1132-1134, 1987; Landowski et al.: Clin Exp Metastasis 13:357-372, 1995). The peptide is a ligand for the 32/67-kDa laminin-binding protein (LBP); however, the mechanism by which the 67-kDa LBP promotes invasion is unknown. METHODS: We have synthesized a highly specific probe for the 67-kDa LBP by adding a biotinylated residue, and replacing the required tyrosine in peptide 11 with the photoactivatable bezophenone crosslinker, 4-benzoyl-L-phenylalanine. This probe was used to follow the distribution of the 67-kDa LBP by gel electrophoresis, fluorescence-activated cell scanning, and confocal microscopy techniques. RESULTS: A single crosslinked protein, consistent with the high molecular weight form of the LBP, was found on Western blots of membrane detergent extracts from cells treated with the ligand probe. A CHO cell line, manipulated to overexpress the laminin-specific alpha6beta1 integrin, exhibited increased invasiveness, and expressed more cell surface 67-kDa LBP. Membrane-associated 67-kDa LBP was found in the vicinity of focal adhesion plaques and also associated with the matrix substrate. Studies on conditioned medium indicated that the matrix-associated LBP derived from material that was shed from the cells, with more being shed from the more invasive CHO variants. CONCLUSIONS: These results demonstrate the utility of this novel probe in diverse experimental protocols, and suggest that shedding of the 67-kDa LBP may have a role in promoting tumor cell invasion.

Animals↗
PubMed1998

Bacterial vaginosis and cervical intraepithelial neoplasia--cause or coincidence?

Evidence regarding a causal relationship between bacterial vaginosis and cervical intraepithelial neoplasia has so far been incomplete and conflicting. To determine whether bacterial vaginosis is associated with cervical intraepithelial neoplasia a retrospective study was conducted at the Genitourinary Medicine Clinic at Southlands Hospital, Shoreham-by-Sea, UK. Three hundred patients who presented to the clinic with a first diagnosis of genital warts in the absence of other sexually transmitted diseases were recruited. Results of cervical cytology and where abnormal, histology on colposcopically directed punch biopsies were collected. Bacterial vaginosis was diagnosed by the detection of clue cells on Gram-staining of a high vaginal swab, positive amine test, vaginal pH above 4.5 and the presence of characteristic vaginal discharge. Odds ratio showed an increased prevalence of cervical intraepithelial neoplasia associated with bacterial vaginosis. The results suggest that a prospective cross sectional study should be performed to formally test the hypothesis that bacterial vaginosis predisposes to cervical intraepithelial neoplasia.

Journal Article↗
PubMed1997

The prevalence of skin disease in HIV infection and its relationship to the degree of immunosuppression.

A cross-sectional study of human immunodeficiency virus (HIV) positive patients who attended the HIV clinic in Brighton over a 4-month period was carried out to describe the prevalence and severity of skin manifestations in HIV-positive patients and to elucidate their association with the peripheral CD4 cell count and with the HIV disease stage. The subjects were consecutively examined by an experienced dermatologist. Skin manifestations were classified into infections, dermatoses, pruritus and neoplasm. A severity index was derived by scoring each condition as either absent, mild, moderate or severe. One hundred and fifty-one patients were enrolled with a mean age of 38.3 years. One hundred and thirty-nine were homo/bisexual men; 58 were asymptomatic and 35 had acquired immune deficiency syndrome (AIDS); 37 had CD4 counts below 200. Skin conditions were present in 138 of the 151 subjects (91.4%). The total number of events was 331. The most frequent problem was infection followed by dermatoses, pruritus and malignancy. The most frequent condition was seborrhoeic eczema followed by tinea and xerosis. We have demonstrated a statistically significant association between CD4 count, disease stage and skin manifestations in HIV-positive individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Immunization with recombinant p17/p24:Ty virus-like particles in human immunodeficiency virus-infected persons.

In studies of the natural history of human immunodeficiency virus type 1 (HIV-1) infection, it has been repeatedly shown that higher-titer antibody responses to the HIV gag p24 protein correlate with less rapid disease progression. In HIV-negative persons, immunization with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) induced humoral and cellular immune responses to p24. This construct was therefore studied as a potential immunotherapeutic agent with the objective of augmenting the immune response to p24 in a double-blind placebo-controlled trial involving 74 p24 antibody-positive, asymptomatic HIV-1-infected subjects with CD4 cell counts > 350/mm3. Immunization with p24-VLP was generally well tolerated. Immunization with p24-VLP did not increase p24 antibody levels and had no effect on CD4 cell counts or virus load. The failure to increase p24 antibody titers cannot entirely be explained by the subjects' immunodeficiency because most generated an antibody response to Ty, a yeast component of the immunogen.

AIDS Vaccines↗
PubMed1996

Randomized cross-over comparison of liposomal daunorubicin versus observation for early Kaposi's sarcoma.

OBJECTIVES: To evaluate single-agent liposomal daunorubicin chemotherapy in the management of early HIV-related Kaposi's sarcoma (KS). DESIGN: Randomized cross-over comparison of liposomal daunorubicin versus observation. SETTING: Study conducted at single site in tertiary referral HIV unit. PATIENTS: Twenty-nine HIV-seropositive men with < 20 cutaneous KS, no visceral involvement and CD4 cell counts < 400 x 10(6)/I were randomized. Adequate haematological, hepatic and renal function was required for entry. A left ventricular ejection fraction of > 45% was necessary for eligibility. INTERVENTIONS: Patients were randomized to 12 weeks observation or 12 weeks of liposomal daunorubicin 40 mg/m2 every 2 weeks. After 12 weeks, or at disease progression, patients were crossed over to receive the alternative arm. MAIN OUTCOME MEASURES: Disease evaluation was according to AIDS Clinical Trials Group criteria for response assessment and toxicity was recorded using the World Health Organization standardized grading. RESULTS: Response rate to initial liposomal daunorubicin was six out of 15 (40%) and none experienced a spontaneous response during the observation arm. Six patients (40%) randomized to the initial chemotherapy arm progressed during chemotherapy, while 10(72%) in the observation arm progressed. Neutropenia was the main toxicity associated with liposomal daunorubicin and was documented following 20 out of 139(14%) treatment cycles. CONCLUSIONS: Liposomal daunorubicin is a well tolerated and efficacious treatment for early KS; however, the duration of response is brief.

AIDS-Related Opportunistic Infections↗
PubMed1995

Control pathways of the 67 kDa laminin binding protein: surface expression and activity of a new ligand binding domain.

A number of papers have been published on the clinical correlation of the expression of the 67 kDa laminin binding protein (LBP) with the metastatic potential of solid tumors. Both mRNA and protein expression levels have been reported, but both the relationship between them and the molecular nature of the 67 kDa surface product remain unclear. We have utilized a homotypic overexpression system to investigate the cell surface presentation of the 67 kDa LBP and the contribution of this protein to the invasive phenotype of cultured cell lines. We report here that the cellular mRNA levels do not directly reflect the levels of the 67 kDa LBP observed on the cell surface in this overexpression system. Methotrexate amplification of transfected plasmids expressing the 67 kDa LBP leads to an initial elevation of both the LBP mRNA and surface protein levels. This is accompanied by an altered, more flattened, cell morphology. Later, apparent adaptation of the cells to methotrexate is accompanied by a down-regulation of the surface expression of the protein. mRNA levels, however, remain elevated. A nine amino acid sequence, CDPGYIGSR (peptide 11), within the beta chain of laminin 1 has been identified as a probable binding domain for the 67 kDa LBP. Previous studies have identified a region of the 67 kDa LBP which may be involved in laminin interaction, although not necessarily via the peptide 11 domain. We have identified a second site within the amino acid coding sequence of the 67 kDa LBP which also shows biological activity both in vitro and in vivo. A peptide with this sequence, LBP residues 205-229, binds laminin-1 in a peptide 11 inhibitable manner. The receptor-derived peptide modulates invasion of basement membrane matrix in vitro and inhibits experimental lung colony formation when injected along with B16BL6 mouse melanoma cells. However, pretreatment of the melanoma cells with the peptide enhances lung colony formation. Thus, the interaction of the 67 kDa LBP with basement membrane matrix appears to involve a complex series of events including multiple adhesive sites and tight regulation of cell surface expression.

Amino Acid Sequence↗
PubMed1995

Cell surface accumulation of overexpressed hamster lysosomal membrane glycoproteins.

We cloned and sequenced cDNAs encoding two lysosomal membrane glycoproteins, lgp-A and lgp-B, from Chinese hamster ovary cells. The deduced amino acid sequences of these proteins are similar to those of the other known members of this conserved family (also known as "LAMP" proteins). We used the cDNAs to generate stable lines of hamster lgp-expressing mouse NIH-3T3 cells, rat NRK cells, and monkey CV-1 cells. We also generated hybridomas that secrete antibodies specific for hamster lgp-A and lgp-B, enabling us to distinguish foreign from endogenous lgps in a wider variety of transfected cell lines. One line of mouse NIH-3T3 cells that expresses hamster lgp-B was studied in detail. Whereas most of the hamster lgp-B appeared to be transported to lysosomes in these cells, butyrate-induced overexpression resulted in the accumulation of a significant proportion of the total on the plasma membrane. In addition, overexpression of this foreign lgp-B also resulted in the appearance of the endogenous mouse lgp-A and lgp-B on the plasma membrane. Characterization of this accumulation suggested that it resulted from competition for one or more limited components in the transport pathway(s) to lysosomes. Endocytosis from the plasma membrane appeared to be one step that was saturable.

3T3 Cells↗
PubMed1993

Holter ST monitoring early after acute myocardial infarction: mechanisms of ischaemia in patients treated by thrombolysis.

OBJECTIVE: To investigate the mechanisms of Holter ST shift in patients with acute myocardial infarction treated by thrombolysis. DESIGN: Prospective observational study. SETTING: A London district general hospital. SUBJECTS: The study group consisted of 94 patients with acute myocardial infarction treated by thrombolysis. INTERVENTIONS: All underwent early 48 hour Holter ST monitoring and elective coronary arteriography. MAIN OUTCOME MEASURES: Relation of Holter ST shift to multivessel coronary disease, coronary patency, collateralisation, and morphology of the infarct related lesion. RESULTS: There was a trend towards an increased prevalence of Holter ST shift in patients with patency of the infarct related artery and those with multivessel disease. This was only significant in patients with three vessel disease, a significantly higher proportion of whom had > 3 episodes of ST shift (41% v 14%; p = 0.02) or a total duration of ST shift > 1 hour (35% v 13%; p = 0.04) than those with less extensive coronary disease. Holter ST shift occurred in a significantly higher proportion of patients with complex lesion morphology (Ambrose type 2 or 3) compared with those with lesions of Ambrose morphology type 1 or 2 (60% v 33%; p = 0.05). CONCLUSION: Holter ST shift detected early after thrombolysis is an ischaemic phenomenon with a complex pathophysiology. It reflects both remote ischaemia in patients with multivessel disease, and dynamic ischaemic processes related to complex lesion morphology in those with a patent infarct related artery.

Adult↗
PubMed1992

The histocompatibility antigen in asbestos related disease.

Thirty nine phenotypes of human leucocyte antigens (HLA)-A-B-DR and DQ were obtained from 99 asbestos workers (one woman and 98 men). Presence or absence of antinuclear antibodies and rheumatoid factor was determined in 91 of them. Workers were divided into five groups: asbestos workers with no apparent disease (AW; n = 17), diffuse benign pleural disease (PD; n = 31), asbestosis (AS; n = 24), asbestosis with lung cancer (AS-CA; n = 14), and mesothelioma (M; n = 13). Compared with AW, several trends of differences of HLA antigen prevalence were found in patients with asbestos related disease, but these did not achieve statistical significance when p was corrected (pcorr) by number of analyses undertaken. Analysis of the results obtained in previous studies together with the results of this study showed that compared with AW, AS patients had decreased prevalence of HLA-DR5 (pcorr < 0.02). Reasons for the differences in results of previous studies and statistical methods commonly used to compare prevalences of HLA antigen are discussed.

Adult↗
PubMed1990

Evaluation of a novel solid-phase immunoassay, Clearview Chlamydia, for the rapid detection of Chlamydia trachomatis.

Clearview Chlamydia (Unipath Limited, Bedford, United Kingdom) is a rapid immunoassay for the direct detection of Chlamydia trachomatis antigen. This assay was evaluated against the tissue culture method by using 376 paired endocervical specimens. The Clearview assay had a sensitivity of 93.5% and a specificity of 99% when it was compared with the tissue culture method. This assay does not require specialized equipment or trained personnel and yields results within 30 min from the time that a specimen is collected.

Bacteriological Techniques↗
PubMed1986

Asbestos fibres in bronchoalveolar lavage fluid from asbestos workers: examination by electron microscopy.

The uncoated and coated fibre load in bronchoalveolar lavage (BAL) fluid was assessed using light microscopy, scanning electron microscopy, and x ray microanalysis in 15 subjects with previous, unprotected exposure to asbestos, including three with clinical and radiological evidence of asbestosis, and in 13 urban dwelling control subjects with no known occupational exposure to asbestos. The mean ferruginous body count per ml BAL fluid in asbestos exposed subjects as determined by light microscopy was 52 (range 0-333). No ferruginous bodies were detected in control subjects. The mean fibre count per ml BAL fluid in asbestos exposed subjects as determined by electron microscopy was 793 (133-3700), significantly greater than 239 (44-544) in controls (p less than 0.05). Electron microscopic counts correlated with duration of previous exposure to asbestos (r = 0.47, p less than 0.05) and with percentage neutrophil counts (r = 0.53, p less than 0.025). There was no relation between electron microscopic fibre counts and light microscopic ferruginous body counts. In 11 asbestos exposed cases x ray microanalysis confirmed the presence of asbestos and in six the asbestos fibre type was clearly identified. Of five subjects showing no asbestos bodies by light microscopy, all showed fibres by electron microscopy, and in three cases the presence of asbestos was confirmed by microanalysis. Among control subjects, fibres were either large organic fibres or smaller particles which microanalysis showed were not asbestos. In only one control case were a few fibres identified which were confirmed as asbestos fibres on microanalysis. Electron microscopic examination of BAL fluid may confirm past exposure to asbestos and probably gives a crude quantitative estimate of asbestos load.

Adult↗
PubMed1985

Asbestosis: assessment by bronchoalveolar lavage and measurement of pulmonary epithelial permeability.

Thirty two patients with asbestosis were assessed by means of bronchoalveolar lavage (27 patients) and the half time clearance from lungs to blood (T1/2LB) of an inhaled aerosol of diethylenetriamine pentacetate (DTPA) labelled with technetium 99m (32 patients). T1/2LB was also measured in 20 non-smoking normal individuals and 17 smokers without a history of exposure to asbestos. Thirteen patients (46%) showed an increase in the percentage of neutrophils with or without an increase in the percentage of eosinophils and eight (29%) showed an increased percentage of lymphocytes. The number of neutrophils plus eosinophils expressed as a percentage of the total count was positively correlated with the length of the history of disease (r = 0.53, p less than 0.025) and greater percentages were associated with more severe impairment of lung function. Smokers had lower percentages of lymphocytes than non-smokers (p less than 0.002) and showed increased proportions of neutrophils and eosinophils more often than non-smokers (p less than 0.05). In 18 non-smokers with asbestosis the mean T1/2LB was 33.8 (range 10.0-62.0) minutes, significantly less than 57.2 (30.5-109) minutes in 20 non-smoking normal subjects (p less than 0.002). In non-smokers shorter T1/2LB correlated with a longer time since first exposure to asbestos (r = -0.65, p less than 0.005), longer duration of exposure (r = -0.70, p less than 0.001), and a shorter time since last exposure (r = 0.59, p less than 0.01). Shorter T1/2LB was also associated with increased inflammatory activity as shown by higher bronchoalveolar lavage cell counts (r = -0.53, p less than 0.025) and higher combined percentages of neutrophils, eosinophils, and lymphocytes (r = -0.47, p less than 0.05). The techniques of bronchoalveolar lavage and measurement of inhaled solute clearance may be useful in assessing inflammatory activity in asbestosis.

Adult↗