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Biomedical subjects

W H Sherman

Publications and source records attributed to W H Sherman.

29 records · Page 2Linked to original sources

Polyneuropathy in nonmalignant IgM plasma cell dyscrasia: a morphological study.

Six patients had peripheral neuropathy and nonmalignant IgM plasma cell dyscrasia. In two of them, immunological studies indicated that the monoclonal immunoglobulin reacted with myelin-associated glycoprotein, a constituent of peripheral nerve myelin. Sural nerve biopsy specimens from both patients showed morphological signs of primary damage to the myelin sheath. In the other four patients, two of whom had a monoclonal IgMK reactive with chondroitin sulfate C, the axon rather than the myelin sheath was considered the chief site of nerve injury. The morphological findings suggest that the pathogenesis of peripheral neuropathies in IgM plasma cell dyscrasia is heterogeneous. Moreover, the observations are consistent with a pathogenic interaction of the IgM paraprotein with autoantigens in peripheral nerve in some instances.

Aged↗

Monoclonal IgM kappa antibody precipitating with chondroitin sulfate C from patients with axonal polyneuropathy and epidermolysis.

We studied two patients with an axonal type of polyneuropathy, epidermolysis, and IgM kappa plasma cell dyscrasia. The IgM kappa was deposited in the dermis, was absorbed from the serum by axonal micelle preparations, and was precipitated with chondroitin sulfate in highly purified agarose in 0.15 M NaCl with 0.01 M phosphate buffer, pH 7.8. In contrast, we found none of these abnormalities in three patients with IgM plasma cell dyscrasia and demyelinating neuropathy. Of 78 other macroglobulinemic serum samples from patients without neuropathy, 7 precipitated with a sulfated polysaccharide. This reaction occurred at low ionic strength, 0.05 M barbital buffer, pH 8.1, but did not occur in the higher ionic strength of 0.01 M phosphate with 0.15 M NaCl (PBS). The interaction of the IgM with chondroitin sulfate at relatively high ionic strength could cause both the axonal polyneuropathy and the epidermolysis.

Absorption↗

Anti-MAG IgM antibodies in patients with neuropathy and IgM M proteins: detection by ELISA.

In some patients with plasma cell dyscrasia and neuropathy, there are IgM M proteins that react with the myelin-associated glycoprotein (MAG). We used an enzyme-linked immunosorbent assay (ELISA) system to detect anti-MAG IgM antibodies. Reactivity with human MAG by ELISA correlated with demonstration of anti-MAG IgM antibodies by the "immunoblot" technique. Human MAG was more effective than bovine MAG as antigen, and there was no significant reactivity with mouse MAG. The ELISA system is a simple and convenient method for detecting anti-MAG IgM antibodies.

Antibodies, Anti-Idiotypic↗

Identical twin marrow transplantation in multiple myeloma.

We performed the first successful syngeneic bone marrow transplantation (BM Txp) in a patient with multiple myeloma. The patient and his normal identical twin are 50-year-old physicians. Prior to BM Txp, a partial remission was achieved with 1 year of continuous low dosage melphalan and prednisone therapy. Immediately before BM Txp, high dose cyclophosphamide and total body irradiation were administered in an attempt to eradicate the residual tumor. For 17 months after BM Txp, the patient was asymptomatic and hematologically normal although a low concentration of serum monoclonal IgGK persisted. In the 18th month, recurrence of bone pain and increase in the monoclonal IgG signalled exacerbation of the disease. Chemotherapy was resumed and again produced objective and subjective evidence of response. This study demonstrates the feasibility and potential usefulness of syngeneic BM Txp in myeloma.

Blood Grouping and Crossmatching↗

Plasma cell dyscrasia and peripheral neuropathy: identification of the myelin antigens that react with human paraproteins.

In some cases of polyneuropathy and plasma cell dyscrasia, the monclonal antibodies react with human peripheral nerve myelin. To identify the myelin antigens involved, we separated the proteins of human central and peripheral nerve myelin by polyacrylamide gel electrophoresis, transferred the proteins onto nitrocellulose sheets, and used an immunoenzymatic technique to detect the reactive antigens. Serum IgM but not IgG from three patients with neuropathy and complement-fixing anti-human myelin IgM paraproteins immunostained a protein of approximately 100,000 daltons in human peripheral nerve myelin and a protein or closely migrating proteins of similar size in human central nervous system myelin. In a fourth patient, both IgM and IgG immunostained the antigen. Immunostaining was specific for the paraprotein light chain type, and absorption of the patients' sera with human peripheral nerve myelin eliminated the reaction with the central nervous system proteins. No reaction was seen with rabbit peripheral nerve myelin or with membranes prepared from human myotubes, human T cells, or human fibroblasts. Control sera from six patients with neuropathy and IgM paraproteins that did not react with myelin, from four patients with IgM paraproteins but no neuropathy, and from three normal subjects did not immunostain myelin.

Antibodies, Monoclonal↗

Complement-fixing antiperipheral nerve myelin antibodies in patients with inflammatory polyneuritis and with polyneuropathy and paraproteinemia.

Serum from patients with peripheral neuropathies was tested for antiperipheral nerve myelin antibodies by complement fixation. Antibody activity was detected in 5 of 20 patients with acute or chronic remitting polyneuritis and in 4 of 20 patients with polyneuropathy and paraproteinemia but not in patients with other types of neuropathy, neurologic disease, or immunologic disease. In three patients with IgM paraproteinemia, the complement-fixing activity resided in the IgM fraction; in one patient with chronic inflammatory polyneuritis, antibody activity resided in the IgG fraction. In the inflammatory polyneuropathies, antibody titers did not always correlate with disease activity. Sera from patients with remitting polyneuropathies reacted with either human or rabbit peripheral nerve myelin, but sera from patients with paraproteinemia reacted only with human myelin.

Animals↗

Effects of dichloromethylene diphosphonate on skeletal mobilization of calcium in multiple myeloma.

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of oestoclast activity, was evaluated for its ability to decrease the excessive mobilization of skeletal calcium that complicates multiple myeloma. Ten patients with active myeloma, wide-spread bone disease, and hypercalciuria were studied in a double-blind, placebo-controlled, crossover-designed trial in which they took Cl2MDP for eight weeks and placebos for eight weeks. Two patients died during the placebo phase; of eight patients who received Cl2MDP, seven had rapid, sustained, and highly significant (P less than 0.001) decreases in urinary excretion of calcium. Six also had significant decreases in hydroxyproline excretion, and five reported lessening of skeletal pain. On patient did not respond. Although the patients received concurrent chemotherapy during the study, concentrations of myeloma proteins actually increased or decreased only slightly, indicating the declines in hypercalciuria resulted from Cl2MDP and not from improvement in the underlying disease. We conclude that Cl2MDP is a potentially useful inhibitor of osteoclast-mediated bone erosion in multiple myeloma.

Adult↗

Computer-based case tracing (COMTRAC).

To assist clinical assessment and decision making, a computer-based system has been developed to organize key data of individual medical records and display these data in a standard graphic format for each disease. A program for multiple myeloma has been completed and 150 case records entered. The data accessed by computer-based case tracing on all cases of a particular disease are available for cumulative and comparative analyses of different therapeutic regimens.

Data Display↗