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Biomedical subjects

V Parsons

Publications and source records attributed to V Parsons.

At least 19 recordsLinked to original sources
PubMed2000

Transcriptional regulation of 2',3'-cyclic nucleotide 3'-phosphodiesterase gene expression by cyclic AMP in C6 cells.

It was recently shown that the two transcripts encoding the isoforms of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP1 and CNP2) are differentially regulated during the process of oligodendrocyte maturation. In oligodendrocyte precursors, only CNP2 mRNA is present, whereas in differentiating oligodendrocytes, both CNP1 and CNP2 mRNAs are expressed. This pattern of CNP expression is likely due to stage-specific transcriptional regulation of the two CNP promoters during the process of oligodendrocyte differentiation. Here, we report the influence of increased intracellular cyclic AMP (cAMP) levels on the transcription of both CNP1 and CNP2 mRNAs in rat C6 glioma cells. We found that the transcription of CNP1 mRNA was significantly increased in comparison with that of CNP2 mRNA in cells treated with cAMP analogues to elevate intracellular cAMP levels. This up-regulation of CNP1 expression (a) is due to an increase of transcription, (b) requires de novo protein synthesis, and (c) requires the activity of protein kinase A. These results are physiologically significant and support the idea that a cAMP-mediated pathway is part of the molecular mechanisms regulating the expression of CNP1 in oligodendrocytes. The regulation of CNP1 promoter activity by cAMP was then investigated in stably transfected C6 cell lines containing various deletions of the CNP promoter directing the bacterial chloramphenicol acetyltransferase gene. We showed that the sequence between nucleotides -126 and -102 was essential for the cAMP-dependent induction of CNP1 expression. Gel retardation analysis showed that two protein-DNA complexes are formed between this sequence and nuclear factors from C6 cells treated or not treated with cAMP. This suggests that the induction of CNP1 mRNA transcription is not mediated by changes in binding of nuclear factors that interact directly with the -126/-102 sequence. Sequence analysis of this region revealed the presence of a putative activator protein-2 (AP-2) binding site. It is interesting that mutagenesis of this region resulted in a significant reduction in transcriptional responses to cAMP, implying a possible role for the AP-2 factor in the expression of CNP1. In addition, we have shown that putative binding sites for activator protein-4 and nuclear factor-1 adjacent to the AP-2 site are required for efficient induction of CNP1 expression by cAMP. Taken together, our results show that the cAMP-dependent accumulation of CNP1 mRNA appears to depend on the synergistic interaction of several regulatory elements.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1998

Identification of a 37 kDa plant protein that interacts with the turnip mosaic potyvirus capsid protein using anti-idiotypic-antibodies.

Experimental data are provided for the presence of a plant protein that interacts with the capsid protein (CP) of turnip mosaic potyvirus (TuMV). The receptor-like protein was identified by exploiting the molecular mimicry potential of anti-idiotypic antibodies. A single-chain Fv molecule derived from the monoclonal antibody 7A (Mab-7A), which recognizes the CP of TuMV, was produced in Escherichia coli and the recombinant protein was used to raise rabbit antibodies. The immune serum reacted with Mab-7A but not with a monoclonal antibody of the same isotype, indicating that anti-idiotypic antibodies were produced. These anti-idiotypic antibodies recognized a 37 kDa protein from Lactuca sativa. Complex formation between the anti-idiotypic antibodies and the plant protein was inhibited by the CP of TuMV which indicates that the plant protein interacts with the viral protein. The 37 kDa protein was localized in chloroplasts and was detected in other plant species.

Animals↗
PubMed1994

Outcome of renal transplantation in hepatitis BsAg-positive patients.

Renal transplantation of patients with previous or ongoing hepatitis B virus infection has been tempered with a concern that immunosuppression may lead to viral replication and progressive liver damage. However, renal transplantation as therapy for end-stage renal failure in these patients improves quality of life and reduces the risk of body fluid exposure to their carers. To assess the long-term outcome of renal transplantation in hepatitis-BsAg-positive patients a retrospective study was carried out on the patients transplanted in this unit since 1969. Seventy-six patients received 98 grafts up to December 1991; follow-up was available on 68. Thirty-one of the 68 patients died; the causes of death were infective 23, cardiovascular 6, liver failure 4, pancreatitis 2, aspiration 1, GI haemorrhage 1, and stopped therapy 1. Serological markers of hepatitis B virus infection did not correlate with outcome. The risk of developing liver failure after renal transplantation appears small in the hepatitis-BsAg-positive patients and no patient should be denied a renal transplant on the basis of serological tests.

Adolescent↗
PubMed1994

Systemic bone changes accompanying early rheumatoid arthritis in patients treated with nonsteroidal antiinflammatory drugs alone.

Seventeen patients suffering from early rheumatoid disease (mean duration, 3.5 years) and treated with nonsteroidal antiinflammatory drugs alone had evidence of systemic bone changes. Transiliac bone biopsies, compared with age and gender-matched controls, demonstrated reduced bone volume and increased eroded surface. In addition, the metacarpal indices were reduced in the rheumatoid patients and correlated with the iliac crest bone volume. These changes, found distal from sites of synovitis, suggest that in this group of rheumatoid patients there were systemic changes of bone metabolism. No biochemical abnormalities of calcium homeostasis were found. Collectively, present observations may be a reflection of the rheumatoid disease process itself.

Adult↗
PubMed1993

Biochemical markers of bone turnover in women with surgically treated carcinoma of the breast.

Biochemical markers of bone turnover were measured in fasting urine and blood samples obtained from 38 postmenopausal women with previous surgical treatment of breast cancer combined with adjuvant chemotherapy, tamoxifen, or placebo. Significantly elevated urinary pyridinoline as nmol mmol-1 creatinine (47.5 and 42.5 in tamoxifen and placebo treated patients compared with 26.3 in normal controls, both P < 0.001) and deoxypyridinoline (11.9 and 10.5 compared with 6.3, P < 0.001 and P = 0.002 respectively) were found with unchanged urinary hydroxyproline, serum alkaline phosphatase and procollagen I carboxyterminal peptide (PICP). These findings suggest enhanced bone resorption resulting from the humoral osteoclast activating effect of the previous breast cancer or underlying carcinoma recurrence. Alternatively the raised pyridinium excretion might indicate an altered crosslinking composition of bone collagen. No specific effect on bone metabolism was found with tamoxifen treatment as all measured parameters were similar in both tamoxifen ex-users and non-users. This confirmed the safety of tamoxifen therapy with respect to bone.

Aged↗
PubMed1993

Successful control of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis using magnesium carbonate and calcium carbonate as phosphate binders.

To avoid the use of aluminium as a phosphate binder, patients on CAPD who were stable were dialysed against a peritoneal dialysis fluid which was magnesium free. A mixture of calcium and magnesium carbonate was used as a phosphate binder over a period in excess of 1 year. Vitamin D analogues were used in the majority. Results show satisfactory control of hyperparathyroidism with mean parathyroid hormone concentration for the group of 121 pg/ml (normal < 100 pg/ml), calcium concentration of 2.41 mmol/l, magnesium 0.97 mmol/l, phosphate 1.36 mmol/l and aluminium 0.35 mmol/l (normal < 0.2 mumol/l). These results were as good as and better in some respects than a minority using calcium carbonate alone or remaining on aluminium hydroxide, the latter remaining on Mg-containing CAPD fluid.

Calcium↗
PubMed1992

Arteriovenous fistulas in renal transplants: color Doppler ultrasound observations.

One hundred twenty-six new renal transplants were scanned regularly with color Doppler ultrasound (CDU). In 22 (17.5%) of the grafts there was evidence of postbiopsy arteriovenous (AV) fistula during the first 6 months postoperatively. In 14 cases the fistula closed spontaneously. In the remaining eight, the fistula was still present up to 24 months later (four cases) or until the graft failed (four cases). Additionally, 163 established grafts were scanned for evidence of vascular abnormality. AV fistulas were observed in 15 grafts (8%). Circulatory complications of fistulas observed include vascular steal and a possible association with graft vein and artery stenosis.

Arteriovenous Fistula↗
PubMed1992

Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.

Bone Density↗
PubMed1991

Treatment of rapidly progressive glomerulonephritis by extracorporeal immunoadsorption, prednisolone and cyclophosphamide.

Ten patients with rapidly progressive glomerulonephritis and acute renal failure were treated with extracorporeal immunoadsorption, prednisolone, and cyclophosphamide. Three patients had systemic lupus erythematosus, five had microscopic polyarteritis and two had Wegener's granulomatosis. All ten patients were dialysis-dependent prior to immunoadsorption. Nine of ten patients rapidly regained renal function and seven continue to have independent renal function between 9 and 30 months after immunoadsorption. Three patients at presentation were not dialysis dependent. Despite treatment with methylprednisolone, cyclophosphamide, and oral prednisolone, renal function continued to deteriorate and they required dialysis. Immunoadsorption was then started without alteration in baseline immunosuppression. Within a mean of 4.6 days, range 3-7 days, renal function improved and the patients no longer required dialysis. Antineutrophil cytoplasmic antibodies and double-stranded DNA antibodies were rapidly removed by immunoadsorption. Only one patient with systemic lupus erythematosus and two with microscopic polyarteritis had significant resynthesis of antibody at 1 month post-immunoadsorption. Renal biopsy before and after immunoadsorption and immunosuppressive therapy showed resolution of glomerular crescents and no evidence of active disease. Immunoadsorption coupled with prednisolone and cyclophosphamide may be of value in the treatment of rapidly progressive glomerulonephritis.

Adult↗
PubMed1990

Incidence of thin membrane nephropathy: morphometric investigation of a population sample.

To explore the incidence of thin membrane nephropathy (thin basement membrane syndrome, benign familial haematuria), glomerular basement membrane thickness was assessed by light and electron microscopy and by morphometry in a series of newly transplanted allograft kidneys, in lieu of normal kidney specimens. Five of the 76 donors possessed an abnormally thin basement membrane, similar to that observed in thin membrane nephropathy, while in two others the measurements fell in the overlap range between thin and normal. Seven donors therefore had a definite or possible basement membrane lesion. After taking account of an additional series of controls, unrelated to transplantation, it is suggested that the incidence of this abnormality in the general population lies between 5.2% and 9.2%. Circumstances did not allow any association between a thin basement membrane and haematuria or other clinical manifestations to be detected.

Adolescent↗
PubMed1990

Hyperparathyroid bone disease in diabetic renal failure.

Hyperparathyroid bone disease is a common complication of end stage renal failure, particularly in patients on maintenance haemodialysis. Several studies have, however, shown a near absence of hyperparathyroid bone disease in diabetic patients who have been receiving haemodialysis for periods of up to 4 years. We have studied biochemical indices of mineral metabolism in 54 consecutive pre-dialysis patients with moderate to severe renal impairment. Deteriorating renal function was associated with developing hypocalcaemia and hyperphosphataemia. Hypocalcaemia was strongly related to increased severe alkaline phosphatase activity (p less than 0.001), suggesting the development of hyperparathyroidism. Five patients with hypocalcaemia and increased alkaline phosphatase were studied in detail. All had elevated serum concentrations of parathyroid hormone and histological signs of hyperparathyroidism on bone biopsy. Three of the patients had low serum 25 hydroxyvitamin D levels with associated osteomalacia, the other 2 patients were notable for their long duration of renal failure. In the long-term (greater than 4 years) we also observed the development of hyperparathyroidism in a small group of diabetic patients maintained on haemodialysis. We conclude that diabetic patients are not uniquely protected against renal osteodystrophy. Although the prevalence of hyperparathyroidism may be lower in diabetic patients than in those with other types of renal disease, the same factors which predispose to bone disease in non-diabetic patients (long duration of renal failure, low serum 25 hydroxyvitamin D and long periods on haemodialysis) also operate in the diabetic population.

Adult↗
PubMed1989

Effect of graft perfusion with two CD45 monoclonal antibodies on incidence of kidney allograft rejection.

In a blind trial, 77 patients were randomised to receive first cadaver kidney allografts that had been perfused either with a pair of CD45 monoclonal antibodies (mAbs), in an attempt to reduce the immunogenicity of passenger leucocytes, or with control human albumin solution. No complications of mAb perfusion were observed. Patient and allograft survival were similar in both groups. Rejection episodes were recorded in 7 (18%) of the patient with mAb perfused allografts compared with 24 (63%) of the controls.

Animals↗
PubMed1989

Carnitine and weakness in haemodialysis patients.

Weakness in haemodialysis patients has been attributed to several factors including carnitine deficiency. Malnutrition, neuropathy, uraemic myopathy and parathyroid hormone excess may all be important. Six haemodialysis patients were shown to have reduced muscle power compared with a normal population, and to be malnourished by dietary assessment, and features of their weakness were investigated. Total carnitine was normal in plasma but elevated in muscle, with an excess of esterified carnitine in both plasma and muscle and diminished free plasma carnitine. Muscle biopsy showed no features of carnitine deficiency and electromyography showed a non-specific neuropathy with additional myopathic changes in some. Dietary supplementation with L-carnitine (2 g/day) for 6 weeks in a placebo-controlled trial showed a redistribution of carnitine fractions but no subjective or objective improvement in muscle function. There was no improvement in the plasma lipid profile. The weakness of haemodialysis patients is multifactorial. We have not demonstrated total carnitine depletion in either muscle or plasma, and oral supplementation of L-carnitine has no demonstrable effect in this group.

Administration, Oral↗
PubMed1989

Success of communication about renal transplantation between patient and doctor.

Four hundred patients in 12 renal units, half of them with attached transplant units, answered a questionnaire by post or in clinics about the successes and failures of the communication process that concerned their treatment by dialysis and transplantation. Eighty per cent wanted more information, whatever their mode of treatment, those with successful transplants being more satisfied with the information given than those with failed transplants (60% vs 35%). Patients with a failed transplant were more enthusiastic about a second transplant than those still waiting for their first (80% vs 70%). Answers still show some anxiety about transplantation in 20% of patients. Free comments not elicited by questions revealed lack of information about the major implications of transplantation and drugs used in treatment. It is suggested that written information must be backed up by personal enhancement of the stages a patient passes through. Patients' Associations provide a valuable way of giving information.

Choice Behavior↗