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Biomedical subjects

T J Hamblin

Publications and source records attributed to T J Hamblin.

At least 163 records · Page 9Linked to original sources

The effect of plasma exchange on the in vitro monocyte function of patients with immune complex diseases.

In vitro function tests were performed on peripheral blood monocytes isolated from patients with putative immune complex diseases undergoing therapeutic plasma exchange. Bacterial killing by monocytes improved significantly after plasma exchange (pre: 29 +/- 5%; post: 39 +/- 3%). The intracellular content of the acid hydrolase N-acetylglucosaminidase (NAG) after in vitro culture rose significantly following plasma exchange (pre: 48.3 +/- 21 nmol mg protein-1 hr-1; post: 76.6 +/- 30.6), although the amount of NAG released into the supernatant was unchanged. Plasma exchange also resulted in reduced levels of immune complexes (IC) and clinical improvement in most patients. The beneficial effect of plasma exchange in patients with IC diseases may be partly due to removal of IC which are known to influence the functional activity of cells of the mononuclear macrophage series.

Acetylglucosaminidase↗

A human b-cell lymphoma synthesizing and expressing surface mu-chain in the absence of detectable light chain.

Lymph node cells obtained from a case of non-Hodgkin's lymphoma, of follicular center cell histology, were seen by immunofluorescence to express immunoglobulin mu heavy chains but no detectable light chain on their surfaces. Antibody specific for determinants expressed only on uncombined mu-chain reacted with these cell surfaces, but not with normal or neoplastic cells expressing surface IgM. Analysis of radioiodinated surface material revealed mu-chains which, without reduction, migrated on SDS-gel electrophoresis as normal mu-chain monomers, and again failed to detect light chains. Lysates of cells incubated with 3H-leucine revealed the synthesis of mu-chains but not of light chains. The labeled mu-chains were not secreted into the culture supernatant, a finding confirmed in parallel cultures by radioimmunoassay. The findings are discussed with particular reference to current concepts of the "mu-chain only" phenotype.

Adult↗

Coincident chronic lymphocytic leukemia and osteosclerotic multiple myeloma.

We report the first occurrence of chronic lymphatic leukemia (CLL) and osteosclerotic multiple myeloma (MM) in the same patient. The surface Ig of the CLL and the monoclonal serum Ig had different heavy and light chain classes, and CLL lymphocytes failed to secrete the monoclonal Ig in short-term culture. We conclude that they were entirely separate malignancies occuring together by chance.

Bone Marrow Examination↗

Extracellular idiotypic immunoglobulin arising from human leukemic B lymphocytes.

The peripheral blood lymphocytes of nine out of nine patients with typical surface Ig-positive chronic lymphocytic leukemia but no paraprotein visible on serum electrophoresis have been shown by radioimmunoassay to export small amounts of pentameric IgM during culture (in the range of 2.4-7.2 ng/10(7) cells per h); three out of nine also exported monomeric IgD (0.7-1.4 ng/10(7) cells per h). Immunoglobulin turned over on the cell surface did not appear to contribute to material in the culture fluid, except possibly as vesicle-bound Ig. In three cases, which included two of the IgD producers, anti-idiotypic antibody raised against the cell surface Fab mu was used to demonstrate the idiotypic nature of the exported Ig. Anti-idiotypic antibody was also used to measure levels of idiotypic Ig in the sera of these three patients as a proportion of the total Ig. Total serum IgM was depressed in all three patients, and the idiotypic IgM represented 43%, 65%, and 96% of the IgM. The findings suggest that in typical chronic lymphocytic leukemia involving B lymphocytes, the export of a small amount of idiotypic Ig by the neoplastic cells in a common or even usual occurrence.

Antibodies, Anti-Idiotypic↗

Preliminary experience in treating lymphocytic leukaemia with antibody to immunoglobulin idiotypes on the cell surfaces.

Tumour-specific antiserum was raised in sheep against idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes from a patient with chronic lymphocytic leukaemia (prolymphocytic variant). The complement-activating IgG1 subclass of the anti-idiotype was prepared from the serum in monodisperse form for infusion. Two treatments of 480 and 1200 mg caused the white-cell count to fall by one-third and one-half respectively. However, there was a rapid resurgence, so that by 8 days after each treatment the counts were restored to approximately 85% of their former levels. No change was noted in the size of spleen or lymph nodes. Each treatment probably destroyed 4-8 X 10(11) cells, some 10% of the total tumour load. The antibody was rapidly consumed, and there was evidence of heavy utilization of complement.

Aged↗

Anti-keratin antibodies in rheumatoid arthritis.

A naturally occurring antibody that reacts with the keratinised tissue of animal oesophagus was found in the serum of 75 out of 129 patients (58%) with classical or definite rheumatoid arthritis (RA) but not in sera from 105 healthy people. Detection of the antibody, which is unrelated to rheumatoid factor, is more specific for RA than the reaction in the sheep-cell agglutination test but less sensitive.

Adolescent↗

Plasmapheresis in Crohn's disease.

6 patients with Crohn's disease for 1-14 years have been treated with plasmapheresis for periods of up to 6 months. The symptoms of the one newly diagnosed patient were controlled by plasmapheresis alone, and 5 steroid-dependent patients were able to reduce their steroid requirements. During the study period, 13 clinical relapses were managed without increasing steroid dosage. There was evidence of circulating soluble immune complexes in all the patients and these levels were lowered by plasmapheresis. A possible role of plasmapheresis in the management of Crohn's disease is discussed.

Adult↗

Anti-idiotype sera raised against surface immunoglobulin of human neoplastic lymphocytes.

The idiotypic determinants of surface immunoglobulins on B-cell lymphomas and lymphocytic leukemias represent tumor-specific antigens, individually unique for each tumor. As such they have both diagnostic and therapeutic potential, particularly for those neoplasms with no serum monoclonal immunoglobulin arising from synthesis of the protein for export. We describe the raising in animals of anti-idiotype sera directed against two examples of a nonexporting neoplasm, human chronic lymphocytic leukemia. The procedure involves exposing the cells to papain so as to remove the Fab fragments (containing the idiotypic determinants) from the surface immunoglobulin, recovering the Fab on cellulose immunosorbent particles, and immunizing animals with the immunosorbent-Fab complex.

Aged↗

The immune response to phichi174 in man. IV. Primary and secondary antibody production in patients with chronic lymphatic leukaemia.

Ten patients with chronic lymphatic leukaemia (CLL) were injected with the antigen phichi174 intravenously on two occasions to test their capacity for antibody production. Nine out of ten patients failed to develop a primary response, and five out of ten failed to develop a secondary response. Only one out of the ten of the secondary responses fell within the normal range. There was evidence of defective switching from IgM to IgG antibody in two out of three cases in which the immunoglobulin class of antibody in the secondary response was determined. The severity of the immunoparesis in CLL is related to the severity of the disease.

Aged↗