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Biomedical subjects

D G Williams

Publications and source records attributed to D G Williams.

At least 145 records · Page 8Linked to original sources
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

Cortical infarction in rabbits with serum sickness following Cyclosporin A therapy.

Rabbits given acute serum sickness (ASS) and treated with Cyclosporin A (CyA) developed glomerular capillary thrombosis and cortical infarction. These lesions were associated with severe endothelial injury and platelet-fibrin-leucocyte thrombi. They were not seen in untreated rabbits with ASS, nor in normal rabbits given CyA alone in equivalent doses. A similar renal lesion has been reported in patients receiving CyA following bone marrow transplantation.

Animals↗
PubMed1983

Systemic lupus erythematosus and IgA deficiency.

A survey of 138 patients with systemic lupus erythematosus (SLE) (113 with nephritis) was carried out following the finding of a patient with membranous nephropathy and IgA deficiency who later developed SLE. Two hundred random hospital patients and 143 patients with idiopathic glomerulonephritis were also studied. One patient with minimal change nephrotic syndrome had IgA deficiency, but the other 342 patients had normal IgA concentrations. In the SLE group, in contrast, 4 patients had IgA deficiency and another patient prolonged IgA deficiency following phenytoin treatment. These and other published data suggest that the association of IgA deficiency is about 20 times more common in patients with SLE and nephritis than in the general population. This association may be a manifestation of defective T-cell regulation, a failure to eliminate immune complexes in the absence of IgA, or both.

Adolescent↗
PubMed1982

Thiamine, riboflavin and pyridoxine deficiency in psychiatric in-patients.

One hundred and seventy-two successive admissions to a district general hospital psychiatric unit were examined. Routine psychiatric, drug and dietary histories were taken and signs of avitaminosis B specifically noted. Red cell transketolase (for thiamine deficiency), glutathione reductase (for riboflavin deficiency) and aspartate transaminase (for pyridoxine deficiency) were measured. Of the patients, 53 per cent were deficient in at least one vitamin, 12 per cent in more than one (30 per cent in thiamine, 27 per cent in riboflavin and 9 per cent in pyridoxine). Schizophrenics and alcoholics were significantly over-represent in those patients low in thiamine and in more than one vitamin. Patients with an affective disorder had low riboflavin and low pyridoxine. It is suggested that affective changes are characteristic of riboflavin and pyridoxine deficiency.

Aspartate Aminotransferases↗
PubMed1982

Anti-ssDNA and antinuclear antibodies in human malaria.

The incidence of serum antinuclear antibodies and serum antibodies to single stranded (ss) and double stranded (ds) DNA was investigated following acute malaria in 58 Caucasians visiting tropical countries but resident in Britain and in 24 Ghanaians resident in Ghana. In Caucasians this infection was associated with a significant increase in the incidence of speckled antinuclear antibodies (38% compared to 3% in controls; P less than 0.001) and a significant rise in antibody levels against ssDNA (14% compared to 5%; P less than 0.05), but no rise in antibodies against dsDNA. Acute malaria in Ghanaians was associated with an incidence of 25% of antinuclear antibodies and 4% of antibodies to ssDNA; these were similar to those found in healthy Ghanaians who are chronically exposed to malaria. Antibodies against dsDNA were not detected. The incidence of antinuclear antibodies and levels of anti-ssDNA antibodies was higher in the Ghanaian healthy population than in normal Caucasians. These observations indicate that malaria is associated with the development of antinuclear and anti-ssDNA antibodies. Ghanaian patients with a tropical splenomegaly syndrome or with a nephrotic syndrome, both of which conditions are suspected of having a malarial aetiology, had serum levels of anti-ssDNA higher than healthy controls. This observation adds further circumstantial evidence to the role of malaria in causing anti-DNA antibodies.

Adult↗
PubMed1982

Corynebacterium hofmannii infection after renal transplantation.

A case of malakoplakia affecting the entire urinary tract is described. The patient had received a cadaveric renal transplant and had required particularly heavy immunosuppression because of recurrent rejection episodes. Heavy hematuria developed, and this was followed by obstruction at the vesico-ureteric junction. Despite adequate drainage via a nephrostomy, the graft ceased functioning, and was explanted. Although appropriate antibiotics were given, the patient died. The organism responsible for triggering the malakoplakia was Corynebacterium hofmannii, and this is only the third report of this organism as a human pathogen. However, other coryneform bacteria have been reported as being pathogenic in immunosuppressed subjects, and should be sought when more common organisms cannot be cultured in such patients showing signs of infection.

Adult↗
PubMed1982

Significance of mesangial IgM deposition in "minimal change" nephrotic syndrome.

During a 6-year period, 64 patients with a nephrotic syndrome, shown histologically to result from minimal change nephropathy, were studied for a mean of 4.5 years. Fifty of the patients showed no glomerular immunoglobulin on immunofluorescent or immunoperoxidase study, but 14 had mesangial deposits of IgM. The onset characteristics, response to treatment, and long-term course were similar in the two groups. We conclude that IgM deposition in the mesangium in patients with minimal change nephrotic syndrome is of no prognostic value, and our data do not suggest that this group of patients, although a histopathologic entity, represent a clinically distinct group.

Adolescent↗
PubMed1982

Impaired lymphocyte transformation in minimal change nephropathy in remission.

A group of 37 patients with minimal change nephropathy (MCN) in remission for a mean period of 4.9 years (range 0.25-10) and on no current treatment were found to have a lymphocyte response to the mitogen Concanavalin A which was significantly lower than normal (P less than 0.001). This reduction in lymphocyte transformation was mainly due to the 24 patients who had received in addition to steroids a course of cyclophosphamide from 1 to 12 years (mean 6.7 years) previously (P less than 0.005 when compared t normal). Although the lymphocyte response of the remaining group of 13 patients who had not been treated with cyclophosphamide was not significantly lower than normal, there were three whose lymphocyte response to Concanavalin A was below the normal range. Our findings indicate that remission of MCN may be accompanied by a persistence of the abnormal lymphocyte function which is present during the nephrotic phase, and that cyclophosphamide may cause or add to this defect by a long-term effect on lymphocytes.

Adolescent↗
PubMed1982

Effects of high-dose i.v. steroid (pulse) therapy on acute serum sickness in rabbits.

We investigated the effect of high doses (50 mg/kg/day) of i.v. methylprednisolone ("pulses") on a model of acute serum sickness in rabbits, using bovine serum albumen as antigen and endotoxin as an adjuvant. The pulses were given on 2 consecutive days at one of the following times during antigen elimination: Days 1 and 2, Days 5 and 6, and Days 8 and 9. Methylprednisolone did not alter antibody production, or the size of circulating immune complexes. Pulses given at any period inhibited the fibrinoid necrosis associated with arteritis, but did not otherwise lessen the histopathological changes. Pulses given on Days 1 and 2 or at the end of immune elimination on Days 8 and 9 increased proteinuria and haematuria, and tended to increase histopathological changes, whereas pulses given at the onset of immune elimination on Days 5 and 6 in contrast reduced haematuria, but had a variable effect on proteinuria and organ damage. In this model high-dose steroids produced no consistent amelioration of the disease, apart from reduced fibrinoid necrosis, and at some times there was a tendency for the disease to be exacerbated.

Animals↗
PubMed1981

Gel-electrophoretic identification of hen brain neurotoxic esterase, labelled with tritiated di-isopropyl phosphorofluoridate.

The particulate fraction from hen brain was labelled with [3H]di-isopropyl phosphorofluoridate (DiPF) and separated by polyacrylamide-gel electrophoresis. Four radioactive protein bands (1--4) of molecular weights 155000, 92000, 60000, and 30000 were resolved. Most of the labelling of bands 2, 3 and 4 was inhibited by preincubation with Paraoxon. The residue in band 4 was sensitive to pH 5.2. Successive treatments with Paraoxon and pH 5.2 resulted in the abolition of bands 3 and 4. Bands 1 and 2 contained one and two polypeptides respectively, whose labelling was sensitive to Mipafox, but one, in band 2, was sensitive to higher concentrations of Paraoxon. The concentrations of the other two polypeptides were 6.7 and 1.95 pmol of DiPF bound/g of brain in bands 1 and 2 respectively. Both were as sensitive to Mipafox as neurotoxic esterase and were also sensitive to phenyl benzylcarbamate. 4-Nitrophenyl di-n-pentylphosphinate given in vivo inhibited neurotoxic esterase and the labelling of the band-1 polypeptide by 82% and 84% respectively, but inhibited the labelling of the band 2 polypeptide by 51%. The phosphinate in vitro produced 98% inhibition of the labelling of the band-1 polypeptide, with only 26% inhibition of the band-2 polypeptide, under conditions sufficient to inhibit neurotoxic esterase totally. Both neurotoxic esterase and the band-1 polypeptide were found in the forebrain at 1.74-fold their concentration in the rest of the brain, whereas the band-2 polypeptide was uniformly distributed. The evidence indicates that the Mipafox-sensitive polypeptide in band 1 is the [3H]DiPF-labelled active-site subunit of neurotoxic esterase. The catalytic-centre activity of the enzyme for phenyl valerate hydrolysis was found to be 2.6 x 10(5) min-1.

Animals↗
PubMed1981

Dianthins, ribosome-damaging proteins with anti-viral properties from Dianthus caryophyllus L. (carnation).

1. Dianthin 30 and dianthin 32, two proteins isolated from the leaves of Diathus caryophyllus (carnation), were purified to homogeneity by chromatography on CM-cellulose. 2. The mol.wt. of dianthin 30 is 29 500 and that of dianthin 32 is 31 700. Both dianthins are glycoproteins containing mannose. 3. Dianthins inhibit protein synthesis in a lysate of rabbit reticulocytes, with an ID50 (concentration giving 50% inhibition) of 9.15 ng/ml (dianthin 30) and 3.6 ng/ml (dianthin 32). They act by damaging ribosomes in a less-than-equimolar ratio. Protein synthesis by intact cells is partially inhibited by dianthins at a concentration of 100 microgram/ml. 4. Dianthins mixed with tobacco-mosaic virus strongly decrease the number of local lesions on leaves of Nicotiana glutinosa.

Antiviral Agents↗
PubMed1981

Long-term impairment of suppressor-cell function by cyclophosphamide in minimal-change nephropathy and its association with therapeutic response.

Lymphocyte suppressor-cell function was studied by induction with concanavalin A in 31 patients with minimal-change nephropathy (MCN) in remission. 21 patients had been treated with cyclophosphamide 0.5--12.0 years previously (mean 6.5 years) and had been in remission for 0.5--9.0 years (mean 5.1 years). The remaining 10 patients had never received cyclophosphamide and had been in remission for 1--10 years (mean 5.3 years). The cyclophosphamide-treated group had significantly less suppressor-cell function than either the controls or the non-cyclophosphamide-treated group, the latter being not significantly different from normal. When patients who had received cyclophosphamide were divided into those who had relapsed after taking this drug (10 patients) and those who had not (11 patients), suppressor-cell function was significantly impaired in the non-relapsing group. This association of impaired suppressor-cell function with failure to relapse may indicate that suppressor cells have a pathogenetic role in MCN and that the therapeutic effect of cyclophosphamide in this disease is to diminish their function. Alternatively, the impaired suppressor-cell function in the non-relapsing group may be simply a marker of effective treatment with cyclophosphamide. The finding of long-term suppression of lymphocyte function after cyclophosphamide coupled with this drug's risks of causing malignancy and gonadal dysfunction reinforces the need for caution in its use in MCN.

Adolescent↗