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M B Pepys

Publications and source records attributed to M B Pepys.

At least 235 records · Page 13Linked to original sources
PubMed1982

Isolation of human C-reactive protein and serum amyloid P component.

Procedures are described for the isolation in high yield of consistent, highly purified preparations of human C-reactive protein (CRP) and serum amyloid P component (SAP). CRP was obtained from malignant ascitic and pleural fluids by calcium-dependent affinity chromatography on pneumococcal C-polysaccharide covalently coupled to cyanogen bromide-activated Sepharose. It was then gel filtered on Ultrogel AcA44 (acrylamide-agarose beads) in the presence of calcium ions, combining molecular sieve chromatography with removal of contaminating SAP by its affinity of agarose. Residual trace contaminants were removed by immunoabsorption with anti-normal human serum and anti-SAP antibodies insolubilised on Sepharose and/or by absorption with Sepharose-Con A to remove glycoproteins and Blue-Sepharose to remove albumin. After a final gel filtration step on Sephacryl S-300 35-45% of the initial CRP was recovered in pure form according to biochemical and immunochemical criteria. SAP was isolated from normal serum by calcium-dependent affinity chromatography on unsubstituted Sepharose beads, followed by solid-phase immunoabsorption of contaminants and finally gel filtration on Sephacryl S-300. At least 50% of the SAP in the starting material was recovered in pure form according to biochemical and immunochemical criteria. Ready availability of such preparations facilitates biochemical, biophysical and particularly biological studies of these plasma proteins.

Amyloid↗
PubMed1982

Enumeration of lymphocyte populations in whole peripheral blood of patients with antibody-mediated nephritis during treatment with cyclosporin A.

Lymphocyte populations identified by surface markers were enumerated in whole peripheral blood of 3 patients with Goodpasture's syndrome (mediated by anti-glomerular basement membrane antibody) whilst on treatment with cyclosporin A (CSA). The whole blood method, using alkaline phosphatase-labelled reagents, permits precise enumeration of the relative and absolute numbers of lymphocyte subsets in the circulation. Using conventional rabbit and monoclonal mouse anti-human T-cell antibodies, a small decrease in the percentage of T-lymphocytes was noted following the start of CSA treatment. The absolute T-cell count fell, but only to just below normal. There was no marked or consistent effect on the percentages or absolute numbers of B-cells, C3b-receptor or Fc(gamma)-receptor bearing lymphocytes. These results are compatible with a mechanism of immunosuppression by CSA in which there is selective inhibition of a relatively minor subset of T-lymphocytes.

Adolescent↗
PubMed1982

Serum amyloid P-component and C-reactive protein in serum of healthy Icelanders and members of an Icelandic family with macroglobulinaemia.

Serum levels of amyloid P-component (SAP) and C-reactive protein (CRP) were determined in 260 asymptomatic Icelanders of both sexes and various age groups and in 60 members of a family with macroglobulinaemia. In the normal group the SAP levels were normally distributed but slightly higher than in a comparable British group. Elevated levels of SAP and CRP were found in four elderly sibs of the macroglobulinaemia family. Two of them had benign monoclonal macroglobulinaemia (BMM), one had Waldenström's macroglobulinaemia and one increased polyclonal IgA. In addition, a notable small increase (2-20 micrograms/ml) in the levels of CRP was found in 6 children and 3 grandchildren of two elderly sibs with BMM. This increase in serum CRP levels was also found in five of six family members when investigated four years later. The HLA haplotypes present in the family members, including B7, are not closely associated with the various abnormal protein changes detected in the elderly sibs of the second generation or their descendents. Likewise, the increased levels of SAP, CRP or IgM are not associated with any particularly type of the genetic protein markers of blood group systems tested.

Adolescent↗
PubMed1982

Serum levels of C-reactive protein in Crohn's disease and ulcerative colitis.

Prospective measurements were made of serum C-reactive protein levels and erythrocyte sedimentation rate in sixty-four patients with Crohn's disease and fifty with ulcerative colitis. The results were related to clinical assessment of disease activity. C-reactive protein levels were raised in both groups but were significantly higher in Crohn's disease than ulcerative colitis for all categories of disease severity: with mild disease the median and range of C-reactive protein concentration were 4, 0-65 mg/l in Crohn's disease v. 0, 0-15 mg/l in ulcerative colitis, P less than 0.01; in moderate disease the values were 15, 1-100 mg/l v. 3, 0-29 mg/l respectively, P less than 0.05 and in cases of severe disease, 85, 15-183 mg/l v. 12, 2-33 mg/l respectively, P less than 0.001. Erythrocyte sedimentation rate was also higher in Crohn's disease but did not closely reflect disease activity in individual patients. C-reactive protein levels corresponded closely with clinical and pathological indices of relapse, remission and response to therapy in patients with Crohn's disease. The precise assay of serum C-reactive protein provides an objective criterion of inflammatory activity, which may be useful in the assessment, management and study of Crohn's disease.

Adolescent↗
PubMed1982

The membrane phenotype of T-prolymphocytic leukaemia.

Cells from 13 cases of T-prolymphocytic leukaemia (T-PLL) were studied with a battery of immunological techniques in order to define their membrane phenotype. All cases were E-rosette positive and were negative with OKT6, anti-HLA-DR, anti-Ig and M-rosettes; in 3, 20-30% of the cells had receptors for C3b. 7 cases had predominantly a 'helper/inducer' T-subset phenotype, (OKT4+, OKT8-) and 4 had a 'suppressor/cytotoxic' phenotype (OKT8+, OKT4-). Cells in 2 cases coexpressed OKT4 and OKT8 in 48% and 95% of prolymphocytes and in another, both OKT4 and OKT8 were negative. Terminal transferase (TdT) was negative by IF in all the cases, but a low positive level was detected biochemically in one. Although T-PLL appears to be heterogenous in respect of membrane phenotype, the observation of unexpected features in 8 of the cases raises the possibility that it may originate in a cell of intermediate maturation between late thymocytes and mature T-lymphocytes. These features plus the clinical manifestation of the disease - typical morphology, splenomegaly, lymphadenopathy, skin lesions, high WBC and aggressive clinical course - help define T-PLL as a distinct clinicopathological entity.

Aged↗
PubMed1982

C-reactive protein in childhood dermatomyositis.

Serum levels of C-reactive protein (CRP) were determined in 9 patients with childhood dermatomyositis. Four children were seen during clinical relapse and all had serum CRP levels less than 1 mg/l. In addition direct immunofluorescent staining of muscle biopsies from 4 patients showed no evidence of CRP deposition in muscle tissue. Such patients appear to be able to produce CRP in response to acute infections, and it is suggested therefore that the pathological process in childhood dermatomyositis may not induce a significant CRP response.

Adolescent↗
PubMed1982

Enumeration of lymphocyte populations defined by surface markers in the whole blood of patients with Crohn's disease.

The proportions and absolute numbers of different lymphocyte populations were determined using alkaline phosphatase-labelled reagents in the whole peripheral blood of 22 patients with Crohn's disease. Monoclonal mouse anti-T cell antibody (OKT3) was used to identify T cells, polyvalent F(ab')2 anti-human immunoglobulin for B cells, C3b for C3b-receptor bearing cells, and soluble IgG antibody-antigen complexes for Fc(gamma)-receptor bearing cells. Endogenous myeloperoxidase served to distinguish monocytes. Application of this methodology to whole blood avoids the inevitable loss of cells which accompanies separation of mononuclear cells from blood and therefore permits precise enumeration of lymphocyte populations in the circulation. No significant difference from healthy adult controls was observed in any of the lymphocyte subsets tested.

Adult↗
PubMed1982

Measurement of serum C-reactive protein concentration in myocardial ischaemia and infarction.

Serum C-reactive protein (CRP) and creatine kinase (CK) MB levels were measured prospectively in patients with definite myocardial infarction, patients with spontaneous or exercise-induced angina, subjects undergoing coronary arteriography, and patients with non-cardiac chest pain. All individuals with infarction developed raised CRP levels and there was a significant correlation between the peak CRP and CK MB values. The CRP, however, peaked around 50 hours after the onset of pain at a time when the CK MB, which peaked after about 15 hours, had already returned to normal. In 20 patients who recovered uneventfully, CRP levels fell, returning to normal about seven days after infarction in four cases who were followed to this point. In eight complicated cases, including four who died within the first 10 days, the CRP level remained high. Angina alone or coronary arteriography did not cause a rise in the CRP or CK MB concentrations. Increased CRP production is a non-specific response to tissue injury and raised CRP levels in cases of chest pain with a normal CK MB indicated a pathological process other than myocardial infarction. Regular monitoring of CRP levels may also assist in early recognition of intercurrent complications occurring after myocardial infarction.

Angina Pectoris↗
PubMed1982

Correlation in rheumatoid arthritis of concentrations of plasma C3d, serum rheumatoid factor, immune complexes and C-reactive protein with each other and with clinical features of disease activity.

The concentrations of C3d in the plasma and of C-reactive protein (CRP), immune complexes and rheumatoid factor in the serum were measured in 99 patients with rheumatoid arthritis. Most patients had raised levels, the values of which correlated with disease activity assessed according to a newly described index based on multivariate analysis of subjective, semi-objective and objective features of the disease. There were also significant correlations between the values for plasma C3d and circulating immune complexes, immune complexes and rheumatoid factor, serum CRP and immune complexes, and serum CRP and plasma C3d. Measurement of plasma C3d provides a useful means of detecting in vivo complement activation, which may be involved in the pathogenesis of rheumatoid arthritis, but neither C3d levels nor any of the other variables correlated as closely with disease activity as did the serum CRP concentration.

Adult↗
PubMed1982

Role of the acute phase response in the Shwartzman phenomenon.

Following elicitation of the local Shwartzman reaction by intradermal injection of Salmonella enteritidis lipopolysaccharide (LPS) in mice, there was a marked acute phase response which was monitored by measuring the serum levels of serum amyloid P component (SAP) and C3. Prednisolone therapy had no effect on either the cutaneous lesion or the accompanying acute phase response. Also, in vivo complement depletion with cobra factor did not affect the lesion or the SAP response despite gross reduction in serum C3 levels. In contrast, administration of colchicine at the same time as LPS suppressed both the acute phase response and the Shwartzman reaction. Inhibition of the cutaneous reaction by colchicine was abrogated by injecting mice with casein, and unrelated acute phase stimulus, the day before challenge with LPS. These observations suggest that acute phase proteins may participate in pathogenesis of the Shwartzman phenomenon.

Amyloid↗
PubMed1982

Isolation and characterization of C-reactive protein and serum amyloid P component in the rat.

C-reactive protein (RP) and serum amyloid P component (SAP) have been identified for the first time in rat serum and isolated by calcium-dependent affinity chromatography. Rat CRP closely resembled human CRP in its amino acid composition, in having five subunits per molecule and in its electron microscopic appearance as a pentameric annular disc. It differed, however, from all other mammalian CRP's characterised hitherto in being a glycoprotein bearing a single complex oligosaccharide on each polypeptide subunit. Furthermore one pair of tis subunits per molecule was linked by a interchain disulphide bridges whereas in other animals the subunits of both CRP and SAP are all non-covalently associated. The serum concentration of CRP in normal healthy laboratory rats and in specific pathogen-free rats was 300-600 micrograms/ml which is much greater than has been described in any other species and exceeds even maximal acute phase levels of CRP in man. Following injections of casein or croton oil, serum CRP levels rose to a maximum of about 900 micrograms/ml. Rat CRP bound to pneumococcal C-polysaccharide (CPS( but, in marked contrast to the behaviour of CRP from man, rabbit and marine teleost fish, it did not precipitate with CPS solutions, agglutinate CPS-coated sheep erythrocytes or initiate complement activation. Rat SAP, like SAP of other species, was a glycoprotein but unlike them it was composed only of a single pentameric disc not two such discs interacting face-to-face. The normal level of SAP in rat serum was 20-50 micrograms/ml, very similar to the levels seen in man, and it did not behave as an acute phase reactant in response to casein or croton-oil injections. In this respect it resembled human SAP but differed from murine SAP which is a major acute phase reactant.

Amino Acids↗
PubMed1982

Familial amyloidosis of Ostertag.

A 23 year old Englishman presented with keratoconjunctivitis sicca and was found to have systemic amyloidosis. Five members of his family in two generations also had non-neuropathic amyloid particularly affecting the kidneys. This conforms to the Ostertag type of hereditary amyloidosis. Amyloid deposits in the proband showed permanganate-sensitive Congophilia and positive immunofluorescence staining for P component, but were negative for amyloid A and prealbumin. These observations suggested that the fibril protein in this patient was immunochemically distinct from the amyloid fibrils characterized hitherto.

Adult↗