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Biomedical subjects

G Cambridge

Publications and source records attributed to G Cambridge.

At least 55 records · Page 3Linked to original sources
PubMed1992

Analysis of antibody reactivity in the sera of 42 patients with paraproteinaemia.

The clinical expression of disease in patients with conditions in which autoimmunity is thought to contribute to the pathogenesis of disease is the result of an unfortunate combination of predisposing and environmental factors. The presence of autoantibodies showing a variety of antigen specificities in sera from many of these patients has been closely correlated with particular spectra of organ involvement or tissue destruction. Their precise role in the disease process is as yet unclear. Sera from patients with paraproteinaemia also often contain autoantibodies to a variety of cell components, although symptoms of autoimmune disease are rarely found in this group of individuals. In this study of 42 sera from patients with paraproteinaemia we have confirmed the presence of autoantibodies in 33% (13/42) of samples. Amongst the autoantibodies detected were those to human neutrophils (3), U1RNP (8) and cardiolipin (4). In five sera, the immunoglobulin class of autoantibody did not correlate with that of the monoclonal band. This study extends previous reports of the repertoire of autoantibodies present in sera from patients with paraproteinaemia.

Antibodies, Anticardiolipin↗
PubMed1992

Production of human monoclonal antibodies to myeloperoxidase.

Two mouse-human heterohybridomas secreting human antibodies to myeloperoxidase (MPO) were derived from the peripheral blood of a patient who developed microscopic polyarteritis as the result of long-term treatment with hydralazine. Forty-five immunoglobulin-secreting lines were obtained from the fusion of patient lymphocytes with the CB-F7 heteromyeloma cell line. Of these, two antibodies, one IgG and one IgM, bound to myeloperoxidase in solid phase ELISA and gave a perinuclear staining pattern on ethanol-fixed human neutrophil cytospin preparations. The staining patterns were similar to those seen with serum from the patient. Antigen-inhibition studies revealed that the affinity of the IgG monoclonal antibody was 28 times higher (k = 1.4 x 10(-7)) than the IgM antibody (k = 5 x 10(-5)). Cross-inhibition studies further suggested that the two monoclonal antibodies recognized the same epitope on MPO. Of the other secreting cell lines, none produced antibody which reacted with the panel of autoantigens used for testing. Neither mononuclear antibody reacted with this panel indicating that they were not simply polyreactive natural autoantibodies. These are the first human monoclonal antibodies to native myeloperoxidase to be reported.

Animals↗
PubMed1991

Development of a co-culture system with induced HepG2 cells and K562 cells for examining drug metabolism in vitro. Studies with cyclophosphamide, ondansetron and cisplatin.

We have established a cell co-culture system for assessing potential cytotoxic effects of drugs and their metabolites in vitro. Human hepatoma cells (HepG2) were cultured for 7 days in modified Earle's medium in order to induce their drug metabolising (primarily mixed function oxidase) enzymes. K562 human erythroleukemic cells in Transwells, were used as indicator cells for the cytotoxic effects of cyclophosphamide (CYP) and Ondansetron (OND) and/or their metabolites, produced by induced HepG2 cells in the co-cultures. CYP was found to be approximately 1000 times more toxic to K562 cells when cultured in the presence of induced HepG2 cells. OND, a selective 5-HT3 receptor antagonist which is used as an anti-emetic during chemotherapy, was not found to be cytotoxic in the co-cultures at concentrations as high as 100 microM. Since OND has been particularly useful in relieving vomiting induced by cisplatin (cisPt) chemotherapy, we also examined the effect of cisPt on K562 cells in the presence and absence of OND, and found no evidence that OND significantly enhances the cytotoxic effect of cisPt on these cells alone or in co-cultures with induced HepG2 cells. The induced HepG2 co-culture system uses cells of human origin and clearly has considerable potential for examining the effects of drugs and their metabolites on indicator cells derived from a tissue of choice. This system may be particularly useful in the assessment of metabolism and toxicity of new drugs intended for human use.

Antiemetics↗
PubMed1991

Interleukin-2 nephrotoxicity assessed in vitro.

Immunotherapy with interleukin-2 (IL-2) is complicated by many side effects of which nephrotoxicity is the most limiting. We have examined IL-2 nephrotoxicity in vitro using the pig kidney cell line LLC-PK.1 model system. Human recombinant IL-2 (HrIL-2) was toxic to LLC-PK.1 cells at concentrations comparable to those seen in the serum of patients undergoing cancer immunotherapy. Many of the side effects of IL-2 immunotherapy are due to IL-2-induced synthesis of tumour necrosis factor-alpha (TNF-a) and can be alleviated by co-administration of steroids. However, HrIL-2 nephrotoxicity in vitro was unaffected by addition of dexamethasone to cultures and LLC-PK.1 cells were found to be resistant to the anti-proliferative effects of TNF-a. These results suggest that the nephrotoxic effect of HrIL-2 is due to a direct toxic effect on kidney cells.

Animals↗
PubMed1989

The detection and enumeration of cytokine-secreting cells in mice and man and the clinical application of these assays.

An in vitro assay for the detection and enumeration of mouse and human cytokine-secreting cells is described and some ways in which it may be used diagnostically are indicated. The assay is an extension of the ELISA plaque assay or ELISPOT assay and uses pairs of antibodies to capture and then visually develop secreted lymphokines. In this way, it is possible to enumerate the specific cytokine-secreting cells. This assay may provide a valuable tool in the clinical investigation of the mechanisms of disease development and tissue destruction.

Animals↗
PubMed1989

Cyclosporin in juvenile dermatomyositis.

Juvenile dermatomyositis in fourteen children who had not responded fully to steroids and other immunosuppressants and who had had chronic active disease for an average of 3 years was successfully treated with cyclosporin. Twelve patients had serious complications of the disease or of previous treatment. The response to cyclosporin included recovery of muscle strength and function and resolution of complications. It was possible to stop steroids or to reduce the steroid dose, which had previously been difficult, in all fourteen patients. In general, a low dose of cyclosporin (2.5-7.5 mg/kg daily) was sufficient and no serious side-effects were seen.

Child↗
PubMed1989

Relation between lymphocytotoxic antibodies, anti-DNA antibodies and a common anti-DNA antibody idiotype PR4 in patients with systemic lupus erythematosus, their relatives and spouses.

Forty-two patients with systemic lupus erythematosus (SLE), 65 of their healthy relatives and 20 spouses were studied for the presence of lymphocytotoxic antibodies (LCA), anti-lymphocyte antibodies (ALA), antibodies to DNA and a common idiotype (Id) PR4. Seventy-one per cent of the patients had positive levels of LCA, and in 34% the PR4 Id was detected; normal levels were found in their families. Anti-PR4, an anti-Id, failed to block the lymphocytotoxic activity in those nine patients who both carried the Id and had LCA. This indicates that the Id was not present on LCA. There was no correlation between anti-DNA antibodies and LCA, suggesting that different mechanisms are involved in their expression.

Antibodies, Antinuclear↗
PubMed1988

In vitro response to influenza immunisation by peripheral blood mononuclear cells from patients with systemic lupus erythematosus and other autoimmune diseases.

Reduced in vitro anti-influenza antibody response by peripheral blood mononuclear cells (PBMs) after vaccination was confirmed in a group of 28 patients with systemic lupus erythematosus (SLE), and also in 16 patients with some other autoimmune syndromes. This group of patients with SLE had higher serum anti-DNA binding, but there was no evidence of increased autoantibody production after vaccination, nor any clinical or laboratory evidence of flares in disease activity that are sometimes seen to follow intercurrent infection. Although a reduced in vitro antibody response may, to some extent, reflect redistribution of antibody producing cells, there appears to be more generalised impairment of the immune response in these patients, which cannot be accounted for by steroid/immunosuppressive therapy.

Adult↗
PubMed1987

Cellular infiltrates in human skeletal muscle: exercise induced damage as a model for inflammatory muscle disease?

The type and distribution of mononuclear cell infiltrates in muscle biopsies taken from 9 subjects at differing times after exercise in which the muscle is stretched (eccentric exercise) has been characterised. The appearances are compared to those seen in muscle from patients with inflammatory muscle disease. After exercise infiltrating cells were seen in perivascular, perimysial and endomysial regions, the extent being greater in the later biopsies (9-14 days). The predominant cell type was the macrophage (46-100% of all infiltrating cells), the remainder were T lymphocytes with a predominance of the CD4 positive helper/inducer subset. Approximately one third of the T cells expressed DA2 (class 2) antigen indicating that they were activated. Very few B lymphocytes and no Leu7 positive cells were seen. There was evidence of class 1 expression on some of the damaged muscle fibres. The appearance of the experimentally damaged muscle in normal subjects was very similar to untreated polymyositis suggesting that a proportion of the infiltrating cells seen in this disease may be present as part of a natural response to damage rather than being its cause.

Adult↗
PubMed1986

Licensed to kill.

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Cytotoxicity, Immunologic↗
PubMed1985

Natural history of left ventricular function in neonatal Coxsackie myocarditis.

Three neonates are described who had severe congestive cardiac failure following Coxsackie-B virus infection. Overall left ventricular function was depressed and accompanied by regional differences in wall motion. Recovery has been gradual, and after 40 or more months of follow-up, all three infants still have evidence of myocardial damage. This provides further evidence linking myocarditis with dilated cardiomyopathy.

Coxsackievirus Infections↗
PubMed1983

Myocarditis in siblings leading to chronic heart failure.

Two brothers, aged 7 and 9, presented 4 years apart with progressive heart failure following a probable viral infection. Electrocardiograms of both showed widespread precordial Q waves. Cardiac catheterization in each case revealed almost equal right atrial, right ventricular and pulmonary artery pressures and poorer contraction of the right than left ventricle. High neutralizing antibody titres to Coxsackie B4 virus were found in the siblings and their mother. Widespread post-myocarditic scarring of both ventricles was found at autopsy on the elder brother. These findings provide further evidence that Coxsackie myocarditis accounts for some cases of dilated cardiomyopathy and suggest that familial factors may be important.

Adolescent↗
PubMed1979

Antibodies to Coxsackie B viruses in congestive cardiomyopathy.

Fifty patients with congestive cardiomyopathy have been studied for evidence of previous Coxsackie B virus infection and compared with age- and sex-matched controls who had been admitted to hospital for investigation of other cardiac diseases. High neutralisation titres (greater than or equal to 1024) to Coxsackie B viruses were more common among the controls. On subdividing the patients according to their length of symptomatic history before study, high titres were more common only in those with a short history (less than or equal to 1 year). High titres were more common when there had been a febrile illness at the onset of symptoms. Endomyocardial biopsies of 18 patients disclosed no evidence of myocarditis, or, in 12 cases, of viral involvement. Although the evidence remains circumstantial, these results support the theory that Coxsackie B viruses may cause congestive cardiomyopathy and encourage further research into the mechanisms of myocardial cell damage by these visuses.

Adult↗
PubMed1976

Cell-mediated immune response to influenza virus infections in mice.

The local and systemic cell-mediated immune (CMI) responses to influenza virus infection in mice were examined by leukocyte migration inhibition and lymphocyte-mediated cytotoxicity tests. Mice were inoculated intranasally with 5 50% lethal doses of the A/WSN (H0N1) strain of influenza virus. Cells from the lymph nodes draining the upper and lower respiratory tract were used to measure the local response, and the spleen was the source of cells used for systemic determinations. The local response by pulmonary lymph node cells was greater and appeared earlier than was observed systemically in the spleen. The specificity of the CMI response was investigated by using a heterologous virus strain, A/Jap (H2N2), and recombinants A/Jap-NWS (H2N1) and A/NWS-Jap (H0N1), obtained from a cross between A/Jap (H2N2) and a virus, A/NWS (H0N1), with surface antigenic specificity similar to that of the inoculated virus. From the results of both tests used as correlates of CMI, it appeared that the response was specific against the hemagglutinin component of the inoculated virus. No reactivity was observed against the heterologous virus A/Jap (H2N2) nor against the recombinant A/Jap-NWS (H2N1) bearing the same neuradminidase as that of the inoculated virus.

Animals↗