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Biomedical subjects

R J Howard

Publications and source records attributed to R J Howard.

At least 343 records · Page 19Linked to original sources
PubMed1980

A trial of vidarabine for cytomegalovirus infection in renal transplant patients.

Vidarabine was evaluated in renal transplant patients as a potential therapeutic agent in cytomegalovirus (CMV) infection. Four patients received vidarabine on an open protocol, then ten additional patients were enrolled in a double-blind protocol. Among the nine patients who received vidarabine, no notable clinical improvement occurred in either the vidarabine- or placebo-treated groups. Thus, vidarabine showed no therapeutic effect in the treatment of CMV infections at the dosages used. Four patients showed dramatic CNS deterioration within several days of the onset of vidarabine therapy. Tremors and myoclonus were common, and one patient had unusual brain pathologic changes with widespread neuronal chromatolysis. The pathologic findings in the brain in the other three patients were complex and included intracerebral hemorrhage, Fabry's disease, coccidioidomycosis meningitis, and cerebral vascular occlusion. Thus, there was no conclusive proof that vidarabine contributed to the sudden neurologic deterioration of these patients.

Adult↗
PubMed1979

Identification of differences between the surface proteins and glycoproteins of normal mouse (Balb/c) and human erythrocytes.

The topography of the external surface of the Balb/c mouse erythrocyte has been investigated and compared to the human erythrocyte by using a series of protein radiolabeling probes. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the pattern of Coomassie Blue stained proteins was very similar for mouse and human erythrocyte ghosts, as was the distribution of radioactivity in protein bands after lactoperoxidase catalyzed radioiodination. The mouse erythrocyte glycoproteins identified by periodic-acid-Schiff and 'Stains-All' reagents, sialic acid analysis of gel slices, binding of 125I-wheat germ agglutinin and 125I-concanavalin A to the gels, and glycoprotein radiolabeling techniques, differed markedly from the sets of proteins labeled by radioiodination, and also differed from the human erythrocyte glycoproteins. Instead of the PAS I to PAS IV series of sialoglycoproteins characteristic of human erythrocytes, the mouse erythrocyte possesses a broad band of sialoglycoproteins with several peaks ranging in mol wt from 65,000 to 32,000. The same group of sialoglycoproteins were labeled by the periodate/B3H4-technique specific for terminal sialic acid, and the galactose oxidase/B3H4-method (plus neuraminidase) specific for galactosyl/N-acetylgalactosaminyl residues penultimate to sialic acid. These results emphasize the necessity to employ a variety of protein radiolabeling probes based on different labeling specificities, to study the membrane topography of cells which are poorly understood compared to the human erythrocyte membrane.

Animals↗
PubMed1979

Disseminated histoplasmosis in renal transplant recipients.

Five cases of disseminated histoplasmosis complicating renal transplantation are reported. Nine previously reported cases from the literature are reviewed. In this setting disseminated histoplasmosis usually presents as a nonspecific systemic febrile illness that may be fulminant or more subacute. Five of 14 patients presented with skin lesions; only one patient presented with primary pulmonary symptoms of cough and dyspnea. Three of our patients and three others previously reported on survived the infection and maintained good function in the transplanted kidney despite prolonged therapy with amphotericin B. Immunosuppression was the only predisposing factor that could be identified with certainty in the five patients reported on herein. However, in two of the five patients the onset of disseminated histoplasmosis coincided with a well documented cytomegalovirus infection; the viral infection may have been a factor predisposing to infection in these two cases.

Adult↗
PubMed1979

Plasmodium berghei - infected red cells sorted according to DNA content.

A cell-sorting method is described for the analysis and separation of red blood cells in Plasmodium berghei-infected mouse blood based on their DNA content. This method involves a selective uptake of the bis-benzimidazole dye 33258 Hoechst, a DNA-binding dye, by red blood cells containing parasites. Infected blood is incubated at 37 degrees C with the dye then washed at 4 degrees C to remove unbound dye. Uninfected cells are then non-fluorescent at the characteristic wavelengths for 33258 Hoechst excitation and emission, whereas parasitized cells display fluorescence intensities in approximately direct proportion tothe number of parasite nuclei (i.e. amount of parasite DNA) within the cell and can be sorted accordingly. Providing cells were incubated in a complex nutrient medium during dye uptake at 37 degrees C, the sorted parasite-infected cells produced lethal P. berghei infections when injected into BALB/c mice. The dye-labelling technique is simple and sufficient red blood cells at various stages of infection can be collected for biochemical or immunochemical studies by cell sorting.

Animals↗
PubMed1979

Optimal conditions for lactoperoxidase catalyzed radioiodination of external proteins on mouse erythrocytes.

Optimal conditions were established for specific labelling of the surface proteins of mouse erythrocytes using lactoperoxidase-catalyzed radioiodination. The levels of H2O2 and I-, and cell concentrations required for restriction of haemoglobin labelling to less than 5% of the total 125I-protein, were different for radioiodination employing direct H2O2 addition or generation of H2O2 with glucose oxidase plus glucose. Preparation of mouse erythrocyte ghosts by hypotonic lysis caused loss of some minor labelled proteins present on intact cells and shifts to lower molecular weights of others. It is therefore important to solubilize labelled cells directly in electrophoresis buffer to avoid artifactual degradation of labelled proteins. The extent of labelling internal cell proteins was measured by a procedure suitable for the comparison of a large number of samples: solubilized radioiodinated erythrocytes were electrophoresed on 14% acrylamide gels and the radioactivity determined in the haemoglobin band which migrates separately from other proteins. The major labelled protein on the mouse erythrocytes had an apparent molecular weight of 92,000, and may be analogous to Band 3 of the human erythrocyte.

Animals↗
PubMed1979

Immunoprecipitation of biosynthetically-labelled products in the identification of antigens of murine red cells infected with the protozoan parasite, Plasmodium berghei.

In this methodological paper an immunoprecipitation technique has been optimised for the identification of antigens of Plasmodium berghei-infected blood which react with antibody specificities in a host-protective antiserum. Extracted 3H-leucine biosynthetically-labelled products of infected blood were sequentially reacted and precipitated with sera from mice which had been exposed to P. berghei but which were either non-protected or protected against lethal infection, protection having been shown to be transferable to naive recipients with the appropriate serum. As analysed by polyacrylamide gel electrophoresis under reducing conditions, a small number of molecular species was detected in immunoprecipitates using host-protective sera which were apparently not quantitatively precipitated out of the complex mixture of labelled products of infected blood using sera from non-protected mice.

Animals↗
PubMed1979

100 HLA-identical sibling transplants. Prognostic factors other than histocompatibility.

Analysis of 100 patients receiving HLA identical sibling transplants was performed. Excellent graft survival demonstrated in the group attests to the importance of matching serological determined antigens. There seems to be a modest beneficial effect on antilymphoblast globulin in low dosage, but not in high doses. Insulin dependent diabetes mellitus results in a significant negative influence on patient survival and graft function in the male recipient but not in the female. A particularly striking point that emerges is the potential hazard in incorrectly treating for rejection. Rejection occurs very rarely in these patients; in a patient with deteriorating renal function, etiologies other than rejection should be vigorously sought (including transcutaneous biopsy) prior to initiation of rejection therapy.

Adult↗
PubMed1979

Ten year experience with renal transplantation in juvenile onset diabetics.

Between 1968 and 1978, 305 juvenile onset diabetic patients with uremia and 462 nondiabetic uremic patients of similar age received primary renal allografts at the University of Minnesota. Two hundred eight of the diabetic patients are alive and 190 have functioning renal grafts three months to ten years after transplantation. Cumulative patient survival rates at two years for diabetic recipients of kidneys from HLA identical siblings, other related and cadaver donors are 90, 73 and 68%, respectively, the corresponding graft functional survival rates are 90, 67 and 55%. For nondiabetic patients receiving kidneys from the same donor categories the corresponding patient survival rates are 97, 86 and 75%, while the graft functional survival rates are 94, 77 and 64%. The differences in patient and graft survival between diabetic and nondiabetic recipients are statistically significant only for the patients receiving grafts from HLA-nonidentical related donors. For all recipients under the age of 30, there are no statistically significant differences in patient and graft survival. Regardless of the age of the patient or the source of the kidney, the survival of diabetic patients treated with transplantation at our institution is better than the use of chronic hemodialysis, alone. Technical complications do not occur more frequently in diabetic transplant recipients. Cardiovascular disease is responsible for most of the late deaths in these diabetic patients. Amputations of digits or extremities have been required in 15% of the diabetic patients. On the positive side, the vision of 88% of these recipients remained stable or had improved visual acuity, and 82% of the diabetic patients were actively rehabilitated after transplantation. Kidney transplantation is the treatment of choice for end-stage renal failure in diabetic patients, just as it is for most uremic patients.

Adult↗
PubMed1979

Prognosis after renal transplantation: cumulative influence of combined risk factors.

Seven hundred sixty-seven primary renal allografts from a single center were divided into subgroups according to combinations of several major risk factors: donor source and histocompatibility match, age, and presence or absence of diabetes. The relative effect of diabetes on patient and graft survival decreased as histocompatibility differences increased. The influence of recipient age, however, dramatically decreased as histocompatibility differences decreased. In all groups donor source and histocompatibility match had the strongest relative effect in determining subsequent 2-year patient and graft survival.

Adolescent↗
PubMed1979

Encephalomyocarditis virus-induced diabetes mellitus treated by islet transplantation.

There is considerable evidence that at least some cases of juvenile onset diabetes mellitus in humans are a result of viral infection. Viral-induced diabetes in mice may provide an experimental counterpart more similar to the clinical situation than chemical-induced diabetes. Our experiments in such mice indicate that islet transplantation is effective in ameliorating viral-induced diabetes and is encouraging for ultimate clinical application of islet transplantation to juvenile onset insulin-dependent diabetics. In addition, our results show that islets in ectopic sites outside of the pancreas are resistant to damage induced by primary viral infection. The mechanism of this resistance is obscure and will be the subject of future investigations.

Animals↗
PubMed1979

Plasmodium-infected blood cells analyzed and sorted by flow fluorimetry with the deoxyribonucleic acid binding dye 33258 Hoechst.

Red cells from Plasmodium berghei infected mouse blood can be sorted on the basis of their DNA content with the bisbenzimidazole dye 33258 Hoechst. The optimal conditions for dye uptake have been established and with these conditions uninfected cells are nonfluorescent and can be completely separated from infected cells which exhibit fluorescence in almost direct proportion to the number of parasite nuclei (i.e. DNA) they contain. The number of fluorescent cells detected and their fluorescence intensity is shown to be dependent on the dye concentration and the incubation medium being used. At least a proportion of the infected cells sorted from each fluorescence peak in the cell distribution retain their infectivity in vivo with some, but not all, conditions of labeling. This technique is being used to separate minor cell populations from infected blood for biochemical and immunochemical analyses and to screen human samples for malaria infected cells.

Animals↗