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Biomedical subjects

M W Long

Publications and source records attributed to M W Long.

62 records · Page 4Linked to original sources

U.S. Public Health Service Cooperative trial of three rifampin-isoniazid regimens in treatment of pulmonary tuberculosis.

A total of 822 patients with newly diagnosed pulmonary tuberculosis were assigned randomly to one of 3 daily rifampin-isoniazid (RIF-INH) regimens: 450, 600, or 750 mg of RIF in combination with 300 mg of INH. After an initial 20 weeks of therapy with RIF-INH, patients recieved 300 mg of INH and 15 mg of ethambutol (EMB) per kg of body weight for either 12 or 18 months after their sputum cultures became negative. The rate of bacteriologic conversion of sputum among the 3 RIF-INH regimens was compared for 552 patients who completed the 20 weeks of RIF-INH therapy. Apporximately 60 per cent of these patients also completed their assigned INH-EMB therapy and were examined for relapse for at least one year after therapy was stopped. There was no significant difference in the rate of sputum conversion or rate of relapse between the group of patients who received 600 mg of RIF and those who received 750 mg of RIF. However, the 450-mg RIF regimen was significantly less effective than the other 2 regimens, as manifested by a lower rate of sputum conversion and a higher rate of treatment failures. Further analysis showed that RIF dosages of less than 9 mg per kg of body weight per day may be inadequate for treatment of pulmonary tuberculosis. The acceptability of these regimens was high, and the incidence of adverse reactions requiring discontinuation of RIF-INH therapy was quite low (3.3 per cent). A large proportion of patients (44 per cent) developed increased concentrations of transaminase during therapy with RIF-INH. These abnormalities were usually transient and, in most cases, of no clinical significance. In the relapse analysis, 12 months of chemotherapy after sputum conversion was shown to be as effective as 18 months of therapy after conversion of these RIF-containing regimens.

Adolescent↗

Thrombocytosis-induced suppression of small acetylcholinesterase-positive cells in bone marrow of rats.

Transfusion of platelet concentrates was used to establish a thrombocytosis of approximately three times normal platelet levels in male rats. This thrombocytosis resulted in a rebound thrombocytopenia to 60% of normal counts. Examination of the small acetylcholinesterase (ACh-E) positive cells of the marrow at this time showed a reduction to 50% of normal levels without significant changes in control animals. A second group of experiments indicated that this suppression developed as early as the third day posttransfusion, persisted until day 7, and returned to baseline levels by day 9. Incorporation of 75SeM indicated that the reduction in platelet count was due to decreased platelet production. Little or no changes were observed in the hematocrit or WBC. This evidence supports the hypothesis that these cells are early cells in the megakaryocytic series. They are the earliest cells of the series seen to be affected by thrombocytosis. Feedback control by platelets or platelet extracts of this cell population may represent one level of regulation of megakaryopoiesis.

Acetylcholinesterase↗

Acetylation rates and monthly liver function tests during one year of isoniazid preventive therapy.

A blind, prospective evaluation of the incidence and course of isoniazid-associated liver injury was made in 358 hospitalized men. The men were psychiatric patients during one year of tuberculosis preventive therapy. Blood samples were obtained at monthly intervals from the patients, the majority of whom were taking isoniazid. When the data were analyzed at the end of the year, a strikingly increased incidence of abnormal serum transaminase (SGOT) and bilirubin values was found among the isoniazid recipients. However, most subjects demonstrating biochemical evidence of hepatic injury recovered completely while continuing to take isoniazid and did not progress to clinically overt hepatitis. The mechanism underlying this adaptation to isoniazid injury is unknown. No serum antibodies against isoniazid could be demonstrated, and no correlation was found between the presence of antinuclear antibodies or elevated isoniazid plasma concentrations and the occurrence of hepatic injury. These data support the view that hepatotoxic metabolities of isoniazid may be responsible for the liver injury.

Acetylation↗

Osteogenesis and bone-marrow-derived cells.

This paper addresses some of the important aspects of stem cell commitment to the bone cell lineage examining the various types of precursor cells, their responses to cytokines and other extracellular influences, and recent observations on the biochemical and molecular control of lineage-specific gene expression. The process of osteopoiesis involves the proliferation and maturation of primitive precursor cells into functional osteoblasts. The bone cells purportedly originate from mesenchymal stem cells that commit to the osteogenic cell lineage becoming osteoprogenitor cells, preosteoblasts, osteoblasts, and osteocytes. Further understanding of this developmental process requires that lineage-specific markers be identified for the various populations of bone cells and their precursors, that cell separation techniques be established so that cells of the osteogenic lineage can be purified at different stages of differentiation, and that these isolated cells are studied under serum-free, chemically defined conditions.

Animals↗

Haemonectin, a bone marrow adhesion protein specific for cells of granulocyte lineage.

There is substantial evidence that the haematopoietic microenvironment is crucial to the growth and differentiation of haematopoietic cells. This microenvironment is composed of stromal cells, soluble factors and extracellular matrix (ECM). We have shown that a complex extract of bone marrow ECM can stimulate the growth and differentiation of haematopoietic cells in vitro. Furthermore, the use of inhibitors or stimulators of ECM synthesis in long-term marrow culture affects cell proliferation. On a molecular level, however, the interactions between ECM and haematopoietic cells are not well understood. We have investigated the adhesion between specific bone marrow ECM components and haematopoietic cells, and found a protein, 'haemonectin', of relative molecular mass 60,000 in bone marrow ECM which is a lineage- and organ-specific attachment molecule for cells of granulocyte lineage. This specificity distinguishes haemonectin from previously described adhesion proteins which have a wider tissue distribution and cell type specificity.

Antigens, Surface↗