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Biomedical subjects

M R Mackenzie

Publications and source records attributed to M R Mackenzie.

17 recordsLinked to original sources

[Medical research in Chile: quantitative indicators].

Diverse indicators were used to examine medical research in Chile. According to participation in Fondecyt projects, it was concluded that 420 persons were involved in medical sciences research and that 41.9% of them had no postgraduate title. During the eighties, there was a clear aging of the community dedicated to medical research. The scientific productivity was assessed through the inventory of publications in indexed journals. During the eighties, the number of articles in Clinical Medicine and Biomedical Sciences increased two-fold. The University of Chile published the greatest number of articles, followed by the Catholic University and, with a remarkable lower amount, other Universities. The impact of the published articles in Clinical Medicine and Biomedical Sciences was calculated from the citations that they generated from 1986 to 1988. Likewise, the articles registered in 1985 with the higher citation indexes were identified.

Adult↗

Factors affecting the in vitro evolution of a myeloma cell line.

A continuously growing plasma cell line has been established from the bone marrow of a multiple myeloma patient. Initial growth of the cells was dependent on the presence of bone marrow stromal cells. Following initial outgrowth the cells were maintained by transfer onto non-autocthonous bone marrow stromal cultures. Following approximately one year of continuous growth, a subline was derived which could be grown independently of feeder cells. These stromal-cell-independent myeloma cells nevertheless retained dependence for a growth factor present in stromal-cell-conditioned media. The relevant factor in the conditioned media was determined to be interleukin-6 (IL-6). The cells also ultimately became independent of the conditioned media. These latter cells were shown to contain mRNA for IL-6 and eventually began to secrete IL-6. This cell line has thus progressed from complete dependence on stromal cells to IL-6-dependent growth in the absence of stromal cells to complete self sufficient growth. This in vitro progression may reflect an in vivo pattern of myeloma development.

Bone Marrow↗

Differential diagnosis of monoclonal gammopathy.

With a large segment of the adult population now undergoing routine screening tests on a periodic basis, findings such as rouleaux when the complete blood count is performed or an elevated total protein and globulin fraction on serum chemistries often lead to the performance of a serum protein electrophoresis. When a monoclonal gammopathy is confirmed, the clinician is faced with a broad differential diagnosis that includes a variety of distinct malignant plasma cell disorders and lymphoproliferative diseases, as well as the high incidence of MGUS in the otherwise healthy adult population. Other benign causes of secondary monoclonal gammopathy, such as underlying inflammatory or infectious disorders or drug reactions, may add to the diagnostic dilemma in some patients. By following a systematic plan of laboratory evaluation such as that described here, however, and always keeping the patient's clinical status as a primary focus, the clinician should be able to arrive at a diagnosis and formulate a therapeutic plan in most instances. The most common differential diagnosis, that of MGUS versus PCM, still is difficult in some cases, and it is emphasized that careful follow up over time remains the best method at present for differentiating these two conditions. Once the basic laboratory evaluation of monoclonal gammopathy has been completed, further work-up will need to be individualized. In some cases, the preliminary evaluation will reveal a key feature, such as a monoclonal gammopathy that is IgM, which will lead to a rapid diagnosis of WMG and alert the clinician to investigate other nonroutine aspects of the laboratory evaluation, such as a serum viscosity or specific tests of hemostatic function. In other patients, the initial laboratory evaluation of monoclonal gammopathy may lead to other recommendations, such as lymph node biopsy for evaluation of possible lymphoma, or tissue biopsy to confirm the suspicion of amyloidosis. Overall, the evaluation of monoclonal gammopathy remains a challenging one, but one in which the clinician usually is rewarded with a diagnosis that will allow him to make appropriate management plans for his patient.

Amyloidosis↗

Multiple myeloma: an immunologic profile. Cytotoxic and suppressive effects of the EA rosette-forming cell.

Lymphoid cells bearing receptors for human IgG anti-Rh antibody but not otherwise identifiable as T or B cells were isolated from the peripheral blood of human multiple myeloma patients. These cells do not demonstrate surface immunoglobulin, do not secrete immunoglobulin in culture after stimulation with pokeweed mitogen, and do not possess receptors for the third component of complement. They do not form rosettes with sheep erythrocytes, and do not respond to known T cell mitogens. These cells are not phagocytic and do not possess demonstrable nonspecific esterase. Thus, they must be considered at present, members of the "third population" lymphoid cells. These cells are active in the cytotoxic response by myeloma peripheral blood lymphocytes to myeloma plasma cells accounting for approximately 60% of such activity. They are also responsible for part of the suppression of pokeweed mitogen-stimulated immunoglobulin production, and at equivalent suppressor to target cell ratios are more active than immunoregulatory monocytes. Thus, these cells play an important, not previously widely appreciated role in the pathophysiology of the human myeloma patient.

Antibodies↗

The binding of murine immunoglobulins to staphylococcal protein A.

The binding of murine IgG1, IgG2a, IgG2b, IgG3 protein molecules to Staphylococcal A protein is presented. Differential elution by sodium thiocyanate gradients is described. Proteins of the IgG2 class (either a or b subclass) require between 1.5 and 2.0 M for complete elution, whereas, IgG1 proteins are fully eluted with only 0.5 M NaSCN. These differential elution patterns can be utilized to distinguish between, or prepare proteins of different Ig classes. It is proposed that this quantitative rather than qualitative distinction between Ig subclass binding to Staph A, indicates the existence of multiple binding sites per molecule, with different markers of such sites being present on the heavy chain of the different Ig classes.

Animals↗

Plasma cell antigens in human multiple myeloma.

Tumor-specific antigens capable of eliciting a response from autologous lymphocytes have been described in mouse plasmacytoma systems. This paper presents evidence of similar antigens in human myeloma. Myeloma plasma cells isolated from the bone marrow of 27 patients stimulated autologous and allogeneic peripheral blood lymphocytes (PBL) from myeloma patients in mixed leukocyte culture. Plasma cells isolated fromt the bone marrow of normal patients or patients with benign plasmacytosis failed to stimulate PBL in mixed leukocyte culture. Similar results were found in passive cytotoxicity assays with the use of chinken red blood cells (CRBC) coated with 3M KC1 plasma cell extracts from myeloma patients. PBL from myeloma patients caused 30 to 80 percent chromium-51 release from tanned chromium-labeled plasma cell extract-coated CRBC targets, whereas PBL from normal patients or patients with benign plasmacytosis caused only 10 to 25 percent chromium-51 release. This study indicates the presence of material resembling tumor-specific antigens on human myeloma plasma cells. Immune response to suce antigens is elicited in autologous and allogeneic myeloma patients.

Animals↗

Antiglobulins in endocarditis.

Twenty-five patients with endocarditis and serum antiglobulin activity were studied. The antiglobulins were detected by use of the latex agglutination reaction; only eight sera reacted with sensitized sheep cells and one with human O CD erythrocytes coated with anti-CD (Ripley) antibody. Absorption of the sera with the infecting organisms produced a decrease in antiglobulin activity in 10 of these sera. Absorption with other reference bacteria did not lower the titer of latex agglutination in 9 of 10 of these sera. No inhibition of antiglobulin activity by autologous immunoglobulin G was demonstrable. These findings suggest that some antiglobulins interact with the immunoglobulin G-bacterial complex and are analogous to anti-antibodies.

Animals↗

Anti-antibody activity of a monoclonal macroglobulin.

A monoclonal macroglobulin from a patient with Waldenström macroglobulinemia has been shown to have antiglobulin activity of a new type, namely, that of a true anti-antibody. The protein reacts with human, primate, and rabbit IgM and IgG, only when the target immunoglobulin is complexed to an antigen. The implications of the general findings of antiglobulin activity of monoclonal proteins is discussed in relation to the possible etiology of the disease.

Animals↗