PubMed Health⌕ Search

Biomedical subjects

A Dash

Publications and source records attributed to A Dash.

At least 19 recordsLinked to original sources
PubMed2003

Effect of hydrogen peroxide on amino acid concentrations in bovine retina and vitreous humor, ex vivo.

In a previous study, we showed evidence that oxidative stress induced by hydrogen peroxide (H2O2) can inhibit the release of [3H]-D-aspartate from the bovine isolated retina, in vitro. The aim of the present study was to investigate the effect of H2O2 on glutamate and glycine levels in the bovine retina and vitreous humor, ex vivo. Furthermore, we examined whether inhibition of catalase activity with 3-amino-triazole had any effect on the concentrations of these amino acids in the posterior segment of the bovine eye. Whole eye organ cultures were prepared by incubating tissues in oxygenated Krebs solution at 37 masculine C for 30 min. After incubation, H2O2 (1-100 microM) or sterile distilled water was injected intravitreally into each eye. Thirty minutes after injection, the retina and vitreous humor were removed for analysis of glutamate and glycine by high performance liquid chromatography (HPLC) with fluorescence detection. Exogenously applied H2O2 (1-100 microM) caused a concentration-related decrease in both glutamate and glycine levels in the bovine retina. Furthermore, while H2O2 (1-10 microM) caused a concentration-dependent decrease in glycine levels in the vitreous humor, it had no significant effect on glutamate levels. The catalase inhibitor, 3-amino-triazole (10 mM), caused a significant reduction in both glutamate and glycine levels in the bovine retina, ex vivo. Likewise, 3-AT caused an attenuation in both glutamate and glycine concentration in the vitreous humor. We conclude that oxidative stress induced by H2O2 can alter the release and/or availability of amino acids in the posterior segment of bovine eyes.

Amino Acids↗
PubMed2001

Molecular genetics of acute myeloid leukaemia.

Elucidation of the molecular genetic basis of leukaemias has relied on the cloning and characterization of recurring chromosomal translocations. A common theme in acute myeloid leukaemia (AML) associated with balanced reciprocal translocations is the involvement of transcription factors as one or both of the fusion partners. Transcription factors commonly involved in chromosomal translocations include core binding factor (CBF), retinoic acid receptor alpha (RARalpha), ETS family of transcription factors and homeobox gene (HOX) family members. In addition, the recruitment of transcriptional co-activators and co-repressors by these transcription factors suggests that these proteins also may play a critical role in leukaemogenesis. In support of this hypothesis' at least three fusions associated with leukaemias and involving transcriptional co-activators CBP and p300 have been recently cloned. However expression of transcription factor fusion proteins is not sufficient to induce a leukaemic phenotype, as evidenced in part by the long latencies required for disease development in the murine models of the disease. An emerging paradigm is the co-operation between constitutively activated tyrosine kinase molecules, such as FLT3, and transcription factor fusions in the pathogenesis of AML. In such a model, the activated tyrosine kinase confers proliferation and/or anti-apoptotic activity to the hematopoietic cells, while the transcription factor fusion impairs normal differentiation pathways with limited effect on cellular proliferation.

Acute Disease↗
PubMed2001

Malignant Sertoli cell tumour--a case report.

Sertoli cell tumours are rare sexcord stromal tumours of testis. Malignant behaviour is observed in one tenth of such tumours. A malignant sertoli cell tumour is reported here in a 70 years old man. The tumour was of large size and showed necrosis, marked celllar pleomorphism, and mitotic figures.

Aged↗
PubMed1997

Dexamethasone augmentation in treatment-resistant depression.

A total of 10 patients who fulfilled DSM-III-R criteria for major depression were recruited to the study, each of whom had failed to respond to a 6-week course of treatment with either sertraline or fluoxetine. Each subject had baseline serum cortisol measurements together with a Hamilton depression (HAMD) score. All patients were started on dexamethasone (3 mg daily) for 4 days, while remaining on their antidepressant treatment. Further Hamilton ratings were made on days 5 and 21. Six patients showed a significant improvement, whilst two showed a minimal response. A good clinical response was associated with a high baseline cortisol level.

1-Naphthylamine↗
PubMed1996

The gene 59 protein of bacteriophage T4. Characterization of protein-protein interactions with gene 32 protein, the T4 single-stranded DNA binding protein.

The gene 59 protein (gp59) of bacteriophage T4 stimulates the activities of gene 41 protein (gp41), the T4 replicative DNA helicase, by promoting the assembly of gp41 onto single-stranded (ss)-DNA molecules that are covered with cooperatively bound gene 32 protein (gp32). This helicase-ssDNA assembly process, which is important for the reconstitution of the primosome component of the T4 DNA replication fork, appears to require both gp59-gp41 and gp59-gp32 protein-protein interactions. In this study we characterize the physical and functional interactions of gp59 with gp32, the T4 ssDNA-binding protein. Experimental results presented herein indicate: 1) that gp59 binds specifically to both free and ssDNA-bound gp32 molecules; and 2) that in both cases binding involves contacts between gp59 and the acidic C-terminal domain of gp32 (the so-called "A-domain"). We further show that single-stranded DNA molecules coated with (gp32-A), a truncated form of gp32 lacking the A-domain, are refractory to gp59-dependent helicase assembly. The data indicate that specific contacts between gp59 molecules and the A-domains of gp32 molecules are essential for gp59-dependent assembly of gp41 onto gp32-ssDNA complexes. Our results are consistent with a model in which gp59 binds to gp32 molecules within the gp32-ssDNA complex and therein forms a target site for helicase-ssDNA assembly.

Adenosine Triphosphatases↗
PubMed1995

Relationship between disease activity and anti-neutrophil cytoplasmic antibody concentration in long-term management of systemic vasculitis.

Autoantibodies directed against neutrophil cytoplasmic antigens (ANCA) are valuable in the diagnosis of primary systemic vasculitis, and immunofluorescence studies suggest that changes in ANCA concentration reflect changes in disease activity. We used enzyme-linked immunosorbent assays to examine retrospectively the relationship between ANCA concentration and disease activity in 56 patients with systemic vasculitis. We included patients with Wegener's granulomatosis, microscopic polyangiitis, idiopathic rapidly progressive glomerulonephritis, and Churg-Strauss syndrome, and examined separately the initial treatment period (mean length of follow-up, 26 months) and long-term management (mean length of follow-up, 59 months). Levels of ANCA decreased during induction therapy with prednisolone and cyclophosphamide, with or without plasma exchange. During follow-up, 27 relapses were documented in 20 patients (10 with Wegener's granulomatosis, nine with microscopic polyangiitis, and one with Churg-Strauss syndrome), occurring between 4 and 183 months (mean, 62 months) after initial presentation. Patients in whom ANCA were detectable 1 year or more after treatment were at particular risk of clinical relapse. Proteinase 3-directed ANCA appeared to be associated with a higher rate of relapse (44% of patients relapsed) than myeloperoxidase-directed ANCA (13% of patients relapsed). Twenty-four of the 27 relapses occurred in the presence of detectable ANCA; in 21 of these, ANCA concentration was high or rising. The temporal relationship between changes in ANCA concentration and clinical relapse varied considerably between patients; in seven patients, ANCA remained at high levels for many months (range, 14 to 67 months) before eventual relapse. One patient showed high concentrations of ANCA over a period of 11 years without relapse. In five patients, increases in the ANCA level were not temporally associated with relapse (although four of these patients relapsed on other occasions.) We conclude that monitoring ANCA by enzyme-linked immunosorbent assays is of value in the long-term management of patients with Wegener's granulomatosis, microscopic polyangiitis, idiopathic rapidly progressive glomerulonephritis, and Churg-Strauss syndrome. Increases in ANCA and persistently high levels point to the risk of relapse and indicate the need for frequent clinical review and continuing maintenance immunosuppression. However, our results suggest that ANCA assays should always be used in conjunction with other indices of disease activity and should not be the sole basis for changing therapy.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

Recovery from neuromuscular blockade: residual curarisation following atracurium or vecuronium by bolus dosing or infusions.

We conducted a survey of the incidence of Postoperative Residual Curarisation (PORC) in two groups of patients following the use of atracurium or vecuronium. In the first group (B) the neuromuscular blocking drugs were administered by bolus dosing, and in the second group (I) by continuous fusion. On arrival in the recovery room, neuromuscular function was assessed both by compound evoked electromyogram (EMG) in a train of four pattern and also clinically, by the ability to sustain a headlift for > 5 seconds, and to cough. Results were obtained from 150 patients (100 in group B and 50 in group I). The incidence of PORC, as defined by a train of four ratio of < 0.7, on arrival in the recovery room was 12% in group B, and 24% in group I. Clinical criteria of adequate neuromuscular reversal revealed different results, with the majority of patients being unable to perform either clinical test on arrival in recovery. Those patients in whom a peripheral nerve stimulator was used intra-operatively did not have a reduced incidence of PORC. We have demonstrated that PORC is still a common occurrence even with intermediate duration of action neuromuscular blocking drugs.

Adolescent↗
PubMed1994

Expression of HSP70 mRNA in the embryonic chicken lens: association with differentiation.

The heat shock protein, HSP70 is constitutively expressed in the embryonic chicken lens. The present study investigates the localization of HSP70 mRNA in the lens as a function of developmental age to determine whether the state of proliferation or differentiation of the cells is correlated with expression of this gene. Using reverse transcription and quantitative PCR for HSP70 mRNA in RNA samples derived from microdissected regions of the lens, we have found that the concentration of HSP70 mRNA is highest in the annular pad cells at 6 days of development, and in the annular pad and fiber cells at 14 and 19 days of development, suggesting that expression is associated with fiber cell formation. This association was confirmed by studies of HSP70 transcription and HSP70 mRNA levels in cultured explants of 6 day embryonic chicken lens epithelia differentiating in culture. Nuclear run-on transcription experiments indicated that transcription of HSP70 is elevated after 5 and 24 hr of differentiation in vitro. Other genes whose transcription was monitored, c-myc and delta-crystallin, showed distinct patterns of transcriptional regulation, indicating that the changes in HSP70 transcription are specific. RNA extracted from cultured explants at these same times showed increased levels of a 3.4 kb mRNA which hybridized at high stringency to a chicken HSP70 cDNA probe. These results demonstrate that HSP70 mRNA in the embryonic chicken lens is associated primarily with cells in the early stages of fiber formation, and that increased transcription of this gene is part of the differentiation process.

Animals↗
PubMed1994

Effect of oral theophylline on resting energy expenditure in normal volunteers.

BACKGROUND: The aim of this study was to investigate the contribution of regular treatment with oral theophylline to the increase in resting oxygen consumption observed in patients with chronic airflow limitation who are receiving bronchodilator therapy. METHODS: Resting oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 10 normal subjects (six men, age 21-48 years, weight 50-85 kg) before and after 11 days of treatment with either placebo or theophylline in a double blind manner, in twice daily oral doses ensuring trough serum concentrations between 8.4 and 13.5 mg/l. An open canopy method was used to measure VO2 and VCO2 and in all test conditions this was extended for 60 minutes after an inhalation of 800 micrograms of salbutamol super-imposed on the background placebo or theophylline treatment. RESULTS: Resting VO2 and heart rate were increased during theophylline treatment compared with placebo by 6.5% and 8.4% respectively. Salbutamol inhalation transiently increased VO2, VCO2, and heart rate in all tests but this was not modified by background theophylline treatment. CONCLUSION: Oral theophylline treatment causes a sustained increase in resting oxygen consumption and heart rate but does not modify the metabolic response to acutely inhaled salbutamol.

Adult↗
PubMed1993

Relationship between disease activity and ANCA level by ELISA in the long-term management of vasculitis.

Solid-phase immunoassays were used to examine the relationship between ANCA concentration and disease activity during follow-up of 63 patients with systemic vasculitis. ANCA levels fell with induction therapy. Relapses during long-term follow-up were generally associated with high or rising ANCA concentrations, although the temporal relationship between clinical relapse and changes in ANCA was variable.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1987

Fast liver catabolism of C1q in patients with paraproteinaemia and depletion of the classical pathway of complement.

The main clinical features in four patients with IgG1k paraproteinaemia and acquired complement deficiency included xanthomatous skin lesions (in three), panniculitis (in three) and hepatitis (in two). Hypocomplementaemia concerned the early classical pathway components--in particular C1q. Metabolic studies employing 125I-C1q revealed a much faster catabolism of this protein in the four patients than in five normal controls and three patients with cryoglobulinaemia (mean fractional catabolic rates respectively: 23.35%/h; 1.44%/h; 5.84%/h). Various experiments were designed to characterize the mechanism of the hypocomplementaemia: the patients' serum, purified paraprotein, blood cells, bone marrow cells, or xanthomatous skin lesions did not produce significant complement activation or C1q binding. When three of the patients (two with panniculitis and hepatitis) were injected with 123I-C1q, sequential gamma-camera imaging demonstrated rapid accumulation of the radionuclide in the liver, suggesting that complement activation takes place in the liver where it could produce damage.

Adult↗
PubMed1987

A single autoantigen in Goodpasture's syndrome identified by a monoclonal antibody to human glomerular basement membrane.

A mouse monoclonal antibody (P1) to the autoantigenic component of human glomerular basement membrane (GBM) was used to study the immunochemistry and tissue distribution of the Goodpasture antigen and the specificity of the human autoimmune response in Goodpasture's syndrome (anti-GBM disease). In solid phase assays, monoclonal antibody P1 bound to collagenase-solubilized human GBM (the ligand used in assays for human autoantibody), but not to other biochemically defined components of basement membrane. On Western blotting, P1 bound to the same 6 bands in solubilized GBM (between 26 and 58 kilodaltons with major bands at 26 and 54 kilodaltons) that were recognized by sera from all 42 patients studied with anti-GBM disease. Preincubation with sera from 8/8 patients blocked the subsequent binding of P1 from 83 to 89% on densitometer scanning of the Western blot; and preincubation with P1 blocked the binding of sera from 6/6 patients from 58 to 89%. Indirect immunofluorescence and immunoperoxidase studies revealed that the pattern of binding of P1 was identical to that of antibody eluted from the kidneys of a patient with Goodpasture's syndrome; there was linear binding to GBM, Bowman's capsule, and distal tubular basement membrane. In addition, P1 bound to basement membranes in lung and choroid plexus, and to membranes of the lens capsule, choroid, and retina of the eye and cochlea, but not to other organs studied. It is concluded that there is a single major autoantigenic component of human GBM (the Goodpasture antigen), which is present on fragments of different molecular weight in the collagenase digest. This antigen is distributed throughout well-defined basement membranes known to be involved in both Goodpasture's and Alport's syndromes. Human anti-GBM antibodies bind to the same (or closely related) determinants which are recognized by P1, demonstrating that the autoimmune response in Goodpasture's syndrome is of highly restricted specificity.

Anti-Glomerular Basement Membrane Disease↗
PubMed1983

Urticaria and vasculitis: a continuum of histological and immunopathological changes.

Histopathological criteria were used to classify twenty-four patients with chronic urticaria into three groups, which were then studied to establish whether circulating immune complexes (CICs), complement activation and deposition of immunoreactants are confined to patients with urticarial vasculitis. Group I (three patients) had classical urticarial vasculitis, and two of these patients showed hypocomplementaemia with evidence of C3 conversion and deposition of immunoreactants in lesional and uninvolved skin. Ten patients (group 2) with a dense perivascular mixed-cellular infiltrate had normal or raised complement levels and infrequent evidence of C3 conversion. Immunoreactants were detected only in their lesional skin. Eleven patients (group 3) had only a sparse perivascular infiltrate. In this group, complement was normal and immunofluorescence was essentially negative. Cryoglobulins were detected in group I patients only. Monoclonal rheumatoid factor and C1q binding were positive in all group I patients, half the group 2 patients and none of the group 3 patients. This study suggests that urticaria and urticarial vasculitis form a disease continuum, and identifies a group of patients with features intermediate between urticarial vasculitis and ordinary urticaria.

Adult↗
PubMed1983

Production of a monoclonal antibody to autoantigenic components of human glomerular basement membrane.

We describe a mouse monoclonal antibody which reacts on immunoblotting with those components of collagenase digested human glomerular basement membrane (GBM) that are also recognized by autoantibodies in sera from patients with anti-GBM nephritis. Competition between the monoclonal antibody and anti-GBM autoantibodies was demonstrated in a solid phase radioimmunoassay, suggesting that both are directed against the same autoantigen.

Animals↗
PubMed1981

Complement-mediated solubilization in patients with systemic lupus erythematosus, nephritis or vasculitis.

Solubilization of an immune precipitate by serum is a complement function mediated by the alternative pathway and enhanced by the classical pathway--it therefore provides the basis of a simple quantitative assessment of the integrity of complement function. Using a preformed radiolabelled precipitate of BSA-alpha BSA Ab, the solubilization capacity of serial sera from 75 patients with various immune complex diseases or diseases associated with hypocomplementaemia was investigated to correlate this assay of complement function prospectively with disease activity and with measurements of circulating immune complexes (CIC). Reduction in solubilization, defined by more than 25% of values in a given patient being below the normal range, was found in 11 of 12 patients with active SLE, two of 19 patients with active systemic vasculitis, three of three patients with post-streptococcal glomerulonephritis and in three of six patients with nephrotic syndrome due to other types of nephritis. In serial studies, solubilization correlated with disease activity in patients with SLE (P less than 0.005), systemic vasculitis (P less than 0.05) and post-streptococcal glomerulonephritis (P less than 0.05). CIC were found more frequently than abnormalities in solubilization; however, the solubilization assay identified a population of patients with CIC more likely to have active disease. This simple assay of complement function provides data on an aspect of immune complex disease not readily apparent from standard estimations of circulating immune complexes, and appears to be a better measure of their potential phlogistic effects.

Adult↗