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Biomedical subjects

D R Turner

Publications and source records attributed to D R Turner.

At least 91 records · Page 5Linked to original sources

Molecular basis of X-ray-induced mutation at the HPRT locus in human lymphocytes.

Human lymphocytes lacking functional HPRT enzyme after a dose of 300 rad X-radiation were cloned and the monoclonal populations expanded so that sufficient genomic DNA was obtained for Southern analysis. A total of 33 mutant clones were analysed. Wild-type clones showed no evidence of changes to the HPRT gene resolvable by Southern banding patterns whereas 17 of 33 mutant clones showed changes. The alterations observed included total gene deletions (3 clones) and partial gene deletions with or without the appearance of novel bands (12 clones). Two clones showed the appearance of novel bands only. There were no changes observed in 16 of the 33 mutant clones. Three clones showed changes inconsistent with deletion of portions of the gene. In these clones inversion seems to have been the most likely cause of the mutation. The spectrum of gene alterations following ionizing radiation appears different to that previously observed for spontaneous mutations. Consequently, ionizing radiation or radiomimetic agents would appear to be aetiologic, at the most, for only a minor proportion of in vivo somatic mutations.

Base Sequence↗

The Goodpasture antigen in Alport's syndrome: studies with a monoclonal antibody.

A mouse monoclonal antibody (MCA-P1), which recognizes an antigenic determinant in human glomerular basement membrane against which autoantibodies are directed in Goodpasture's syndrome, was used in indirect immunofluorescence studies to investigate glomerular basement membrane structure in Alport's syndrome. We found reduced or absent binding of MCA-P1 to glomerular and distal tubular basement membranes in renal biopsy tissue from ten patients with Alport's syndrome. Antiglomerular basement membrane antibody eluted from the kidneys of a patient who had died from Goodpasture's syndrome was used to confirm these findings. In contrast, there was bright linear fluorescence of MCA-P1 on glomerular and tubular basement membranes of normal renal material and renal biopsy tissue obtained from patients with a variety of glomerulonephritides. These results suggest an abnormality or a variable quantity of the immunoreactive autoantigen in the glomerular basement membrane of patients with Alport's syndrome. Furthermore, MCA-P1 may be of value in the diagnostic interpretation of renal biopsies from patients with familial nephritis.

Anti-Glomerular Basement Membrane Disease↗

The influence of tumour cell DNA abnormalities on survival in colorectal cancer.

The cellular DNA content was measured from paraffin-embedded material in 134 colorectal cancers from patients in whom the outcome was known. Seventy-two (55 per cent) were found to contain cells with abnormal DNA (DNA aneuploid). The presence of such a population of cells was not related to pathological stage or histological grade. However, only 14 (19 per cent) patients with DNA aneuploid tumours survived 5 years compared with 27 (43 per cent) of patients with diploid tumours (chi 2 = 8.0, P = 0.005). Stepwise logistic analysis showed cellular DNA content to be an important prognostic factor in colorectal cancer, independent of pathological stage and histological grade.

Aneuploidy↗

Persistent renal damage following pre-eclampsia: a renal biopsy study of 13 patients.

Renal biopsy material was examined from 13 patients who had a history of pre-eclampsia and who were biopsied after delivery. The characteristic 'endotheliosis' associated with pre-eclampsia appeared to resolve at varying rates and was not seen in biopsies taken more than 1 month after delivery. Four of the biopsies showed residual focal segmental glomerular lesions which are described. Focal global glomerular sclerosis (eight biopsies), focal interstitial scarring (seven biopsies) and arteriolo-sclerosis (nine biopsies) were also identified. These findings support those earlier reports which indicated that pre-eclampsia is capable of producing persistent renal damage in a small but significant percentage of cases.

Adolescent↗

Anaesthetic problems associated with Weaver's syndrome.

A child of 14 months with the clinical features of Weaver's Syndrome presented for surgery twice within a period of 6 weeks. The prime anaesthetic difficulty associated with this case, namely a difficult airway, and other problems related to Weaver's syndrome, are discussed.

Anesthesia, General↗

Reflections on notochordal differentiation arising from a study of chordomas.

This study of thirteen cases of chordoma serves to emphasize the occurrence of three different histological patterns; classical, seven; chondroid, three; and intermediate or mesenchymal, three. The study also suggests that more adequate sampling of these tumours detects the chondroid variant more readily. These varying patterns of differentiation in tumours of notochordal origin suggest that the parent tissue may have the potential to develop along similar lines in the embryo. Thus mesenchymal and cartilaginous tissue formed from notochordal cells could contribute to the formation of the nucleus pulposus and inner portion of the intervertebral disc cartilages. This concept contrasts with the previously held view that the notochord atrophies at an early stage in embryonic development.

Adult↗

Immunohistochemical localization of Y hapten and the structurally related H type-2 blood-group antigen on large-bowel tumours and normal adult tissues.

The monoclonal antibody C14/1/46/10 which defines the Y hapten carbohydrate antigen (Brown et al., 1983) was shown, by the indirect immunoperoxidase technique, to stain tissue sections of 96% of colo-rectal adenocarcinomas and 100% of colo-rectal adenomas. In contrast, a monoclonal antibody defining the related H type-2 blood-group antigen was found to stain 86% of adenocarcinomas and 32% of adenomas. In adenocarcinomas the percentage of cells stained for both antigens was, on average, greater in group O than in group A patients. In adenomas a focal pattern of expression was observed, for both Y hapten and H type-2 antigen, that was characteristic of group A but not group O adenocarcinomas. In the normal mucosa of the distal colon, whilst H type-2 antigen was absent, Y hapten was found in the immature cells of the crypt bases. A comparison of the cellular phenotypes present in adenocarcinomas, adenomas and normal mucosa of the distal colon supports the adenoma-carcinoma sequence hypothesis for the genesis of colo-rectal carcinomas. In normal adult tissues Y hapten was predominantly found on epithelial cells whilst nervous tissues, muscles and connective tissues were negative. The expression of Y hapten in several positive tissues was dependent upon secretor status. A comparison of the expression of Y hapten and H type 2 antigen on normal adult tissues revealed that all of the permutations of expression of these two structurally related antigens were possible.

ABO Blood-Group System↗

A comparison of human pulmonary arterial and venous prostacyclin and thromboxane synthesis--effect of a thromboxane synthase inhibitor.

The amounts of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) produced by the endothelial surfaces of paired samples of human pulmonary arteries and veins, obtained from patients undergoing thoracic surgery, were measured. The amounts of 6-keto-PGF1 alpha and TxB2 produced by arteries compared with veins were not different. However, both arteries and veins produced more 6-keto-PGF1 alpha than TxB2, the ratio being approximately 7.5:1 for both. 6-keto-PGF1 alpha synthesis by arteries was significantly correlated with that produced by veins but the relative amounts of TxB2 were not correlated. 6-keto-PGF1 alpha synthesis was correlated with TxB2 synthesis for veins but not for arteries. 8 of the 12 arterial samples exhibited some degree of intimal fibrosis. Incubation with the thromboxane synthase inhibitor, dazoxiben , caused a significant inhibition of vascular TxB2 synthesis and a significant increase in 6-keto-PGF1 alpha synthesis. In 3 of the 5 cases the increase in 6-keto-PGF1 alpha was too large to be explained by the fall in TxB2.

6-Ketoprostaglandin F1 alpha↗

Bopindolol: a new long acting beta-receptor antagonist; its effects on haemodynamics, and on the renin response to tilting.

Oral administration of single doses of bopindolol (1-4mg) caused significant reductions in the rises of systolic blood pressure and heart rate produced by exercise; only the reduction in the rise of heart rate was significantly dose-related. Resting heart rate was reduced by bopindolol. There were small effects on resting blood pressure. Bopindolol caused a significant attenuation of the rise in plasma renin activity produced by passive head-up tilting to 75-85 degrees. Bopindolol produced a dose-related attenuation of the increase in pulse rate evoked by passive tilting. All effects 1-4 were maintained for at least 24 h. There was no measurable effect on plasma potassium concentration, peak flow rate or forced expiratory volume (FEV1).

Adolescent↗

Nonoccupational exposures to indoor air pollutants: a survey of state programs and practices.

A national survey of health department activities in 1982 revealed that 32 states (63 per cent) had a program or person(s) responsible for evaluating exposures to one or more nonoccupational indoor air pollutants (NIAPs). Only four states (8 per cent) had existing or proposed NIAP exposure standards. Twenty-nine (57 per cent) of the states had a program to evaluate nonoccupational exposures to formaldehyde, but these varied widely. There is a need for coordinated, consistent approaches to defining and controlling emerging environmental public health problems such as indoor air pollution.

Air Pollutants↗

Vasculitis affecting the kidney: presentation, histopathology and long-term outcome.

Fifty-three patients who by clinical and/or histological criteria were judged to have vasculitis affecting the kidney were reviewed. Patients with systemic lupus or Schönlein-Henoch purpura were excluded. Segmental necrotising glomerulitis was taken as a manifestation of vasculitis ('microscopic polyarteritis'). Those patients in whom vasculitis was confined to glomerular capillaries were compared with those who in addition had vascular lesions outside the glomeruli. The two groups were found to have identical clinical features. Clinical presentation was predominantly extrarenal, and exclusively renal in only two. Three patients were classified histologically as Wegener's granulomatosis, four had malignant tumours and two relapsing polychondritis. Hepatitis B surface antigen was absent in all of 37 patients tested. Renal disease presented with microscopic haematuria and minor proteinuria in the majority (32) but 16 patients presented with rapid deterioration of renal function, including seven with anuria. Histologically 42 patients showed segmental necrotising glomerulitis ('microscopic polyarteritis'), six diffuse proliferative glomerulonephritis,and in five only minor or ischaemic glomerular changes were present. Crescents were found in 41/42 of those with segmental necrotising glomerulitis, nd involved more than 50 per cent of glomeruli in 15 patients. Immunohistochemical studies were generally negative except the fibrin. Electron microscopy showed no evidence of immune deposits in necrotising glomerulitis, but these were present in 2/6 patients with diffuse proliferative glomerulonephritis. Overall prognosis was poor, 35 patients having died, 20 early in the course of the disease and 15 later. Oligoanuria and extensive crescent formation were adverse signs. Survivals were 54, 38 and 34 per cent at one, five and 10 years respectively. Of those who survived the initial illness, 12 were stable with apparently inactive disease, whilst 16 continued to show clinical signs of activity and required treatment. A variety of treatments was employed including oral and intravenous corticosteroids, immunosuppressive agents, anticoagulants; only one patient was treated by plasmapheresis. It is difficult to draw any firm conclusions as to the efficacy of treatment and survival rates remain unsatisfactory.

Acute Disease↗

Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long-term prognosis.

Of 104 patients with idiopathic mesangiocapillary glomerulonephritis studied for at least two years, 69 patients had type I disease and 35 had type II. Forty-five patients were children, and 59 were adults. Type II mesangiocapillary glomerulonephritis was more common in children than in adults, but no other clinical feature distinguished the two types at onset. Complement studies revealed that patients with type II had lower serum C3 concentrations and more frequently showed C3-splitting activity (C3 nephritic factor) in the serum. Children had hypertension or a lowered glomerular filtration rate less frequently at onset than did adults, but children had a higher incidence of a hematuric onset; C3 nephritic factor was also more frequent in the children. During a follow-up period of two to 21 years (mean eight years), only seven patients (five with type I and two with type II) showed clinical remission, whereas 38 percent of patients with type I and 49 percent of patients with type II died or required dialysis; a further 23 percent of patients with type I and 16 percent of patients with type II had continuing disease and reduced glomerular filtration rate. Only the presence and persistence of a nephrotic syndrome in type I predicted renal failure. In both types, the presence of sclerosis or crescents in the initial renal biopsy specimen was associated with a poorer prognosis, but no other feature was of major prognostic value.

Adolescent↗

Late onset systemic lupus erythematosus and lupus-like disease in patients with apparent idiopathic glomerulonephritis.

We report 17 patients who presented with either apparent idiopathic glomerulonephritis (16 patients) or post-streptococcal glomerulonephritis (one patient). Doubts arose about the nature of these patients' disease, either because their initial renal histology was suggestive of systemic lupus erythematosus (SLE) in the absence of its clinical or serological features, or because they developed with time the clinical or serological features of SLE. Three patients had a positive antinuclear antibody (ANA) test at the onset of their illness, but normal levels of serum binding of double-stranded DNA (dsDNAB). In another four patients the dsDNAB was slightly raised but with a negative ANA. On renal biopsy the predominant appearance was membranous glomerulonephritis (GN) in 10, subendothelial mesangiocapillary GN (MCGN) in three, and focal segmental glomerulosclerosis in two; one patient each had a focal proliferative GN and a diffuse endocapillary GN. On 1 micron renal sections stained with toluidine blue, 10 patients had immune deposits at multiple sites within the glomeruli. Over a period of one to 14 years, six patients developed extrarenal features suggestive of SLE, nine a positive ANA, and 12 increased serum levels of dsDNAB. Five patients became hypocomplementaemic. Cryoglobulins were isolated from the sera of 10 out of 12 patients; seven contained DNA. Separated cryoglobulin IgG from eight patients showed antibody activity directed against both ss and dsDNA in four, and against dsDNA only in three. On the basis of the clinical, histological and serological observation during follow-up five patients were reclassified as definite SLE, four as probable SLE and two as possible SLE. Rarely, SLE may present with nephritis as the sole disease manifestation, antedating other clinical features and even immunological markers of the disease by years. In addition, some patients with a glomerulonephritis may show clinical and immunological, or histological features of SLE, but do not fit accepted definitions of the disease.

Adolescent↗

Rapidly progressive glomerulonephritis with extensive glomerular crescent formation.

Thirty-nine patients with severe crescentic glomerulonephritis and rapidly progressive renal failure were reviewed. Nineteen patients had a focal necrotizing glomerulonephritis, they usually presented with signs of multi-system disease, and eight had histologically-proven microscopic polyarteritis. A second group of 20 patients presented with an acute nephritic syndrome, often with nephrotic features, and had only minor prodromal symptoms. Renal biopsy material showed various forms of proliferative glomerulonephritis in addition to crescents. The most important prognostic feature at admission was renal function: only four of 21 patients who required dialysis recovered any renal function. The prognosis was worse for those with necrotizing glomerulonephritis, of whom two-thirds had oliguria on admission. All patients who were not oliguric, and some with oliguria, were treated with high doses of corticosteroids, usually accompanied by azathioprine and anticoagulants. Seventeen of 18 patients who were not oliguric initially retained or regained renal function, although three subsequently went into renal failure, and three others died of non-renal causes. At the most recent review, 25 of the 39 patients were either dead (16 patients) on dialysis or transplanted (nine patients). Ten were alive with diminished renal function, one had normal renal function but persisting proteinuria, and three were well. Prompt treatment may have contributed to these favourable results in a very severe disease.

Adolescent↗

A study of cytoplasmic oestrogen receptors in patients with breast cancer in a district general hospital.

The tumors of 61 patients suffering from primary adenocarcinoma of the breast were assayed for oestrogen receptors (ER), using the dextran-coated charcoal method. A statistically significant relationship (P less than 0.05) was found to exist between ER status and the histological grade of the tumour. No relationship was found between ER status and either tumour size or the pathological state of the axillary lymph nodes. It is concluded that it is a practical proposition to establish an ER assay service in a district general hospital, with subsequent benefits for the individual patient.

Adenocarcinoma↗

Ageing in vivo does not alter the kinetics of DNA strand break repair.

The alkaline elution technique has been used to measure the apparent rate constant for repair of DNA strand breaks induced by X-radiation in human transformed lymphocyte DNA. Repair follows first-order kinetics and is essentially complete within 60 min. Although biological variation is observed there is no significant change in rate of repair with age of lymphocyte donor. In light of this it is unlikely that age-associated changes in DNA which have been widely observed arise from a changed persistence of strand breaks.

Adolescent↗