Calculation of atmospheric neutrino-induced backgrounds in a nucleon-decay search.
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Biomedical subjects
Publications and source records attributed to D Sinclair.
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A scheme for quantitation of serum and urinary paraproteins is described using isoelectric focusing and scanning densitometry. Paraproteins could be quantified using this system when present at concentrations ranging from 1 mg/ml to 26 mg/ml, depending on the immunoglobulin class. The relevance of these results to monitoring secretory B cell neoplasia and the distinction between monoclonal gammopathy of undetermined significance and myeloma is discussed.
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Immuno-isoelectric focusing (IIEF) showed a 61% incidence of serum paraproteinaemia in 56 patients with chronic lymphocytic leukaemia (CLL). A strong correlation between the serum paraprotein heavy chain isotypes and those of the cytoplasmic heavy chain immunoglobulins was observed with no discrepancy noted in light chain expression. Density gradient ultracentrifugation analysis of selected sera containing monoclonal IgM showed that the IgM paraproteins were mostly 19S, secretory IgM but one patient was found to have both 19S and 8S monoclonal IgM. When the cellular origin of the IgM and IgD paraproteins found in one patient was investigated, both paraproteins were found to share the same idiotype and originate from the neoplastic clone. These findings confirm the view that there is an incomplete maturation block in chronic lymphocytic leukaemia and that in vivo secretion of paraproteins by the neoplastic cells is a relatively common occurrence.
Immuno-isoelectric focusing (IIEF), a technique previously shown to be sensitive for the detection of paraproteinaemia, was used to test 200 individuals over the age of 45, without history of B cell neoplasm, for the presence of serum paraproteinaemia. 11% of these individuals had evidence of paraproteinaemia detectable by IIEF compared with only 2% by zonal and immunoelectrophoresis. A further 12% had oligoclonal immunoglobulins and the remainder had no qualitative abnormality of the immunoglobulin profile. These results are discussed with particular reference to the aetiology, diagnosis and monitoring of potential B cell neoplasm in high risk individuals or groups.
We present results showing that the detectable incidence of Bence-Jones protein in the sera of patients with multiple myeloma is equivalent to the highest detectable incidence of Bence-Jones protein in highly concentrated urine when tested by immuno-isoelectric focusing. In a series of 25 multiple myeloma patients, immuno-isoelectric focusing showed the incidence of Bence-Jones proteinemia to be 68% compared with a detectable incidence of Bence-Jones proteinuria of 32-64% by immunoelectrophoresis and immuno-isoelectric focusing depending upon the urine concentration factor. In view of the variability of factors governing urinary Bence-Jones protein levels, such as renal catabolism, reabsorption and losses during concentration, we suggest that monitoring of serum Bence-Jones protein by immuno-isoelectric focusing should be carried out in conjunction with measurements of urinary Bence-Jones protein in multiple myeloma.
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Immuno-isoelectric focusing is a highly sensitive method of detecting small quantities of monoclonal protein. We have previously reported the first demonstration of serum paraprotein in non-secretory myeloma using this technique (Sheehan et al. 1985). We now report a case of solitary plasmacytoma where this technique revealed a small concentration of serum paraprotein when conventional techniques failed, and discuss the potential value of focusing in plasma cell dyscrasia, with limited tumor cell mass. focusing in plasma cell dyscrasia, with limited tumour cell mass.
The effect of high dosage fentanyl anaesthesia on P50 was studied in patients undergoing coronary bypass surgery. After induction of fentanyl anaesthesia 100 micrograms X kg-1 with pancuronium muscle relaxation P50 changed significantly (P less than 0.005) from 3.40 +/- 0.12 to 3.33 +/- 0.13 kPa. This anaesthesia technique decreases P50 in vivo, but this has more theoretical than practical importance.
A paraprotein band in non-secretory myeloma was shown using a highly sensitive technique of immunoisoelectric focusing. The published work concerning non-secretory myeloma is briefly reviewed.
The limits of detection of four classes of monoclonal immunoglobulin and free light chain in serum by isoelectric focusing and immunoisoelectric focusing have been determined and the sensitivity of these techniques compared with that obtained using immunoelectrophoresis and zonal electrophoresis with immunofixation. Immunoisoelectric focusing was 10-40 times more sensitive than immunoelectrophoresis and could be used to detect concentrations of monoclonal immunoglobulin that were undetectable by zonal electrophoresis with immunofixation. The relevance of this work in monitoring multiple myeloma during treatment and relapse is discussed.
The presence of paraproteins in the sera of 10 patients with chronic lymphocytic leukaemia (CLL) was investigated using immunoisoelectric focusing. Monoclonal immunoglobulins were found in nine of these 10 sera. Five sera contained a single monoclonal IgM paraprotein, one serum contained a single monoclonal IgG paraprotein, while three sera contained more than one monoclonal paraprotein--namely, IgM + IgD, IgM + IgG, and IgM + IgD + IgG. The results indicate that the malignant B cells of CLL may be at a later stage of differentiation than previously assumed and serum monoclonal immunoglobulin could be of value as a tumour marker.
We present a scheme for routine screening of patients' sera for monoclonal immunoglobulin by isoelectric focusing in agarose gels. Using this method combined with immunofixation, we have been able to detect monoclonal immunoglobulin in the sera of patients, and to identify the isotype of the immunoglobulin when conventional techniques such as zonal and immunoelectrophoresis have yielded equivocal results.
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