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Biomedical subjects

M L Barr

Publications and source records attributed to M L Barr.

At least 73 records · Page 4Linked to original sources

Effects of a 2.15-micron laser on human atherosclerotic xenografts in vivo.

The thulium-holmium-chromium:yttrium-aluminum-garnet (THC:YAG) laser has a tissue effect similar to that of the CO2 laser, with the advantage of transmissibility through flexible fibers. The authors used a human-rabbit xenograft model to evaluate the thrombotic and healing responses of atherosclerotic vessels subjected to laser energy. Occluded atherosclerotic human coronary artery segments were recanalized in vitro by use of the THC:YAG laser. Destruction of plaque by the laser was achieved with minimal collateral thermal damage. These vascular segments were then transplanted into the rabbit abdominal aorta. The authors observed that the luminal surface of the lased vessels was more thrombogenic than that of the nonlased control vessels. However, occlusion of the lased vessels did not occur. Repair of laser-treated tissue progressed until a mature, nonthrombogenic fibrin-platelet aggregate was adherent to the luminal wall. Overall, the lased vessels behaved in a fashion similar to the nonlased control vessels. On the basis of these results, the authors believe that the THC:YAG laser may have use in human angioplasty.

Angioplasty, Laser↗

Humoral immune responses after cardiac transplantation: correlation with fatal rejection and graft atherosclerosis.

Although the advent of cyclosporine has allowed dramatic improvement in survival rates after heart transplantation, long-term outcome remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic cardiac transplants despite cyclosporine administration. The hypothesis of our study is that human heart transplant recipients given treatment with cyclosporine are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 118 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with positive sera on at least three separate samplings at minimal intervals of 1 week were considered to be antibody producers (Ab+), and those with less than three positive sera samplings were considered nonproducers (Ab-). Donor lymphocytes were not available for most recipients for the assessment of the specificity of antibodies produced. Seventy-six of 118 patients (64%) were Ab+. One-year, 3-year, and 5-year actuarial survival rates were 81%, 70%, and 53%, respectively, for Ab+ patients compared with corresponding rates of 93%, 90%, and 90%, respectively, in Ab- patients (p less than 0.01). Graft atherosclerosis confirmed by coronary angiography or autopsy developed in 12 Ab+ patients (16%), compared with 1 of 42 Ab- patients (2.3%) (p less than 0.05). These data show that almost two thirds of heart transplant recipients produce anti-HLA antibodies after grafting that correlate strongly with adverse outcome. Immunotherapies directed at control of deleterious humoral immune responses need to be developed.

Actuarial Analysis↗

Very rapid lactate measurement in ischemic perfused hearts using 1H MRS continuous negative echo acquisition during steady-state frequency selective excitation.

Using 1H MRS continuous negative echo acquisition during steady-state frequency selective excitation (CASTLE) myocardial lactate accumulation was followed in a globally ischemic perfused rat heart model. 1H MRS CASTLE derived lactate determinations were verified biochemically and were measured during ischemia and reperfusion (both in the absence and in the presence of a known inhibitor of glycolysis). In addition, using the Bloch equations modified for the effect of diffusion in the presence of a magnetic field gradient the theoretical dependency of measurements made with CASTLE upon T1, T2 and the flip angle alpha were demonstrated. It was found that 1H MRS CASTLE allowed for rapid identification of the lactate -CH3 resonance in an isolated perfused heart with little shimming required, and excellent water and lipid suppression. Measurements of lactate using this technique reflected a true difference in myocardial lactate as evidenced by biochemical analysis and the expected changes in tissue lactate that accompanied reperfusion and ischemia in the presence of a glycolytic inhibitor. Theoretical calculation demonstrated that the dependency of the relative signal intensity obtained with 1H MRS CASTLE was a complex function of T1, T2, and alpha. These calculations also demonstrated the theoretical feasibility of applying 1H MRS CASTLE to localized spectroscopy using a surface coil.

Animals↗

Acute reoxygenation injury in the isolated rat heart: role of resident cardiac mast cells.

Leukocyte-mediated myocardial reperfusion injury is characterized by the progressive migration and accumulation of polymorphonuclear leukocytes within the myocardium. In this study, we hypothesized that leukocytes normally resident to the myocardium also contribute to myocardial injury in the absence of migration and accumulation of peripheral polymorphonuclear leukocytes. In isolated crystalloid-perfused rat hearts, we found numerous resident cardiac leukocytes that were identified primarily as macrophages and mast cells, the latter staining avidly for peroxidase. When hypoxic perfused hearts (60 minutes, n = 16) were reoxygenated there was a prompt release of this peroxidase activity, the extent of which correlated closely with the degree of myocardial injury (total creatine kinase release, r = 0.96). When reoxygenation associated mast cell degranulation was prevented in six additional hypoxic hearts using 10 microM Lodoxamide Tromethamine, peroxidase release was reduced 7.8-fold (p less than 0.001) and creatine kinase release (injury) was reduced 5.9-fold (p less than 0.001). These results demonstrate that the isolated crystalloid-perfused rat heart is not a leukocyte-free preparation and suggest that mast cells resident to the heart play an important role in acute reoxygenation injury.

Acute Disease↗

Long-term studies on rhesus monkeys (Macaca mulatta) immunized against Plasmodium knowlesi.

Studies carried out on four rhesus monkeys (Macaca mulatta) that had been vaccinated against Plasmodium knowlesi show that the immunized animals were protected against a challenge with a heterologous strain of P. knowlesi. This protection was shown to be present even 4 years after the immunization schedule has been completed. The effect could not be attributed toprevious infections with the parasite, since four control rhesus monkeys that had recovered from one to four challenges with P. knowlesi died when exposed to the heterologous strain. Data obtained from the lymphocyte transformation test and the radioimmunoassay are also presented.

Animals↗

Delayed dermal hypersensitivity in rhesus monkeys (Macaca mulatta) immunized against Plasmodium knowlesi.

Eighteen Rhesus monkeys were immunized with a fresh or lyophilized antigen preparation obtained from erythrocytes infected with Plasmodium knowlesi. Sixteen of these monkeys showed a positive delayed hypersensitivity response when subsequently skin tested with the immunizing antigen. Ten of the 16 positive reactors survived a P, knowlesi challenge, the remaining 6 showed several indications of protection. None of the 18 control monkeys gave a positive skin reaction or survived the challenging inoculum. Macro- and microscopical evidence suggests that the dermal reaction is of a delayed type. Preliminary biochemical analysis of the antigen used in this experiment is included and its significance is discussed. Hematological data is also presented.

Animals↗

Ultrastructural study of Plasmodium knowlesi antigen used in vaccination of rhesus monkeys.

Material from various steps obtained in the French pressure cell technic of preparing antigen from Plasmodium knowlesi-infected red cells, was examined by elctron microscopy. A positively charged colloidal iron solution was used to differentiate between membranes of host red cells and parasites. Red cell membranes take the stain, wheras parasite membranes do not. This antigen which has been used previously to protect monkeys against P. knowlesi appears to consist almost entirely of membrane-bounded vesicles. Some of these vesicles contain a fine granular material, whereas others appear empty. The antigen failed to stain with the positively charged iron solution, which suggests that it is free of contamination by host cell membrane.

Animals↗

The sex chromosomes in evolution and in medicine.

The recent emergence of human cytogenetics has a firm foundation in studies on other forms of life. Historical highlights are Mendel's studies on the garden pea (published in 1865 but lost in an obscure journal until 1900); formulation of cytogenic postulates by Sutton and Boveri (1902-1903); Bridges' discovery of chromosome abnormalities in Drosophila (1916), followed by numerous similar studies in plants; and demonstration of the chromosomal basis of the syndromes of Down, Klinefelter and Turner in man (1959).The sex chromosomes (XX and XY) evolved from a pair of undifferentiated autosomes of a premammalian ancestor, the X chromosome changing less than the Y as they evolved. Eleven numerical abnormalities of the sex chromosomes are known in man, and knowledge of their effects on development is accumulating. The abnormal complexes range in size from the XO error of Turner's syndrome to the XXXXY error of a variant of Klinefelter's syndrome.

Adult↗