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Biomedical subjects

R J Howard

Publications and source records attributed to R J Howard.

At least 325 records · Page 18Linked to original sources
PubMed1981

Cytomegalovirus infection: a quantitative prospective study of three hundred twenty consecutive renal transplants.

The quantitative effects of cytomegalovirus (CMV) infection on morbidity and mortality rates were examined in 320 renal transplant cases. With the use of virus cultures and CMV antibody measurements, all patients were studied, regardless of symptoms, from a time before transplantation to at least 1 year, 11 months after transplantation for a maximum of 5 years, 9 months. The posttransplant risk factors of CMV infection--patient age, type of donor (living-related or cadaver), antigen match between donor and recipient, presence of diabetes, and the presence of pretransplant CMV antibody--were evaluated for their relative effects on patient survival, graft survival, fever, and leukopenia. CMV infection was a significant risk factor for these four events. CMV infection occurred in 181 patients after transplantation and accounted for 25% of the deaths, 20% of the graft failures, 30% of the occurrences of fever, and 35% of the occurrences of leukopenia. Unexpectedly, female recipients were at higher risk than men for the adverse effects of CMV infection. Young patients and those receiving their second transplant were at higher risk of graft loss if they had associated CMV infection. CMV infection was most reliably predicted by the presence of pretransplant antibody, indicating that reactivation of endogenous virus was responsible for most infections. The presence of pretransplant antibody offered a small amount of protection against fever, but no protection against death, graft failure, or leukopenia. Simultaneous episodes of CMV infection and transplant rejection, both common posttransplant events, most often occurred by chance.

Adolescent↗
PubMed1981

Hypertension in a pediatric and adolescent population following kidney transplantation.

The post-renal transplant courses of 53 children and adolescents were evaluated for the prevalence and the etiology of hypertension. The blood pressures were averaged over specific time periods following transplantation and converted to percentile ranks according to standards for age. The number of antihypertensives employed to control blood pressure was assessed. Factors such as sex, obesity, race, donor source, antigen match, steroid administration, rejection, recurrent glomerulonephritis, pre-transplant nephrectomy, renal function and proteinuria were assessed as to their importance in producing hypertension or normotension in the post-transplant period. The average blood pressure was well within acceptable range shortly after transplantation. The patients requiring antihypertensives to control blood pressure dropped by two years post transplant. Chronic rejection was by far the most important factor influencing average blood pressure and the need to employ antihypertensives. Alternate-day prednisone and good graft function were important in establishing the normotensive state.

Adolescent↗
PubMed1980

Changes in the membrane microviscosity of mouse red blood cells infected with Plasmodium berghei detected using n-(9-anthroyloxy) fatty acid fluorescent probes.

A set of n-(9-anthroyloxy) fatty acids (n = 2, 6, 9, 12, 16) have been used as fluorescent probes to examine the lipid environment at different depths in the outer membrane of normal mouse erythrocytes and red blood cells from Plasmodium berghei-infected blood. Fluorescent polarization experiments with normal mouse erythrocytes have demonstrated a typical gradient in microviscosity from the surface to the centre of the bilayer as a consequence of the motional properties of the C-atoms of the phospholipid acyl chains. The fluorescent probes rotate faster in the membrane of purified pluriparasitized cells (greater than 90% purity) than with the remaining fraction of red blood cells from infected blood (20--40% immature, infected red cells, and uninfected red cells), or normal mouse erythrocytes. This increase in fluidity with heavily infected cells occurs predominantly at the centre of the lipid bilayer, rather than at the membrane surface. A comparison of the polarization values of intact and lysed infected cells indicates that the fluorescent fatty acids preferentially label the plasma membrane rather than the internal membranes of infected cells. The results suggest that P. berghei infection causes a change in the composition and/or organization of the outer membrane of pluriparasitized cells which produces a decrease in membrane microviscosity.

Animals↗
PubMed1980

Characterization of surface proteins and glycoproteins on red blood cells from mice infected with haemosporidia: Babesia rodhaini infections of BALB/c mice.

Infection of intact (nu/+) or hypothymic (nu/nu) BALB/c mice with the lethal intra-erythrocytic parasite, Babesia rodhaini, induced several changes in the surface proteins of red cells from infected blood. Lactoperoxidase-catalysed radio-iodination was used to compare the surface proteins on normal mouse erythrocytes and the total red cells from infected blood at different levels of parasitaemia. At very low parasitaemia, when only 2.5% of the red cells contained parasites, we observed significant changes in the profile of radio-iodinated proteins separated by SDS-polyacrylamide gel electrophoresis. These changes included the appearance of a group of high molecular weight proteins, and a protein with an apparent molecular weight (Mr) of 60 000, both of which were absent from normal erythrocytes. The major labelled band on the erythrocyte surface (Mr 92 000) also appeared to be less heavily labelled during infection. The magnitude of these differences in surface proteins increased as the parasitaemia rose, until the new bands dominated the radioactivity profile with blood of greater than 50% parasitaemia. Several control experiments established that the radio-iodinated proteins were surface molecules on intact cells and that artifactual proteolysis did not contribute to the observed differences. The results suggest that changes in the surface proteins occur on all red cells in the blood of infected mice. The results of labelling the surface glycoproteins by oxidation with periodate or galactose oxidase, followed by NaB3H4 reduction, have varied with the isolate of B. rodhaini. With the isolate currently in use, no significant differences were observed in the labelled surface glycoproteins of normal erythrocytes and red cells from infected blood of high parasitaemia, whereas an earlier isolate exhibited a marked decrease of glycoprotein labelling of both infected and uninfected red cells.

Animals↗
PubMed1980

Characterization of surface proteins and glycoproteins on red blood cells from mice infected with haemosporidia: Plasmodium berghei infections of BALB/c mice.

The surface proteins and glycoproteins of red cells from Plasmodium berghei-infected blood have been radio-isotope labelled and compared with those of normal mouse erythrocytes using the following protein labelling probes: lactoperoxidase-catalysed radio-iodination of tyrosyl residues, periodate oxidation and NaB3H4 reduction of sialic acid and oxidation of galactosyl/N-acetylgalactosaminyl residues by galactose oxidase with subsequent NaB3H4 reduction. During P. berghei infection, new tyrosyl-labelled proteins with apparent molecular weights (Mr) of 60 000, 54 000, 40 000 and 27 500 appeared on the surface of most, if not all, red cells in the blood. Purified multinucleate cells (mostly reticulocytes) differed only in that they also had a surface protein with Mr of 83 000. However, this molecule is thought to be specific to mouse reticulocytes rather than derived from parasites. In contrast to the relatively minor changes detected with radio-iodination, striking changes in glycoprotein radio-isotope labelling resulted from infection. All of the red cells in infected blood of greater than 20% parasitaemia lost their periodate-sensitive glycoprotein sialic acid. With some samples there was little change in glycoprotein labelling by the galactose oxidase method, provided neuraminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infected cells which has been inferred in many haemosporidial infections, including malaria.

Animals↗
PubMed1980

Characterization of surface proteins and glycoproteins on red blood cells from mice infected with haemosporidia: Plasmodium yoelii infections of BALB/c mice.

Lactoperoxidase-catalysed radio-iodination was used to compare the surface proteins on red cells from Plasmodium yoelii-infected with normal BALB/c mice. The profile of radio-iodinated proteins separated by SDS-polyacrylamide gel electrophoresis was different for infected blood of similar parasitaemia from mice inoculated with different doses of the parasite. Inoculation with different doses of the parasite. Inoculation with the lower dose resulted in the appearance of a major radio-iodinated protein of apparent molecular weight (Mr) 76 000 which was labelled to a similar extent on uninfected red cells from infected blood and purified multinucleate infected cells. Several minor radio-iodinated bands, with identical mobilities to the minor bands on normal BALB/c erythrocytes, were also present on red cells from this infected blood. In contrast, the higher inoculation dose produced changes in the minor labelled bands, and the band with Mr of 76 000 was absent. In this case, the minor radio-iodinated proteins of the normal BALB/c erythrocyte (with Mr of 65 000, 57 000, 48 000, 38 000 and 32 000) were replaced by a series of bands with Mr of 60 000, 50 000, 43 000 and 28 000 on both uninfected and infected red cells. These differences with inoculation dose may be related to the different duration of these infections, the development of anaemia and the extent of pathological changes at the erythrocyte surface. P. yoelii infection caused a marked loss in periodate-dependent labelling of sialoglycoproteins on most, if not all, red cells in infected blood. There was also a large decrease in galactose oxidase-dependent glycoprotein labelling with or without neuraminidase treatment. These changes in the carbohydrate groups on red cell membrane glycoproteins may be linked to the excessive loss of both uninfected and infected red cells during some malaria infections.

Animals↗
PubMed1980

A difference in surface proteins of Fasciola hepatica larvae from intact and nude mice.

Larvae of the trematode, Fasciola hepatica, dissected from the livers of intact mice at 12 to 14 days of infection, bind anti-immunoglobulins in vitro. This is not so for larvae harvested from the livers of infected hypothymic nude (nu/nu) mice. When attempts were made to confirm the presence of surface Ig using lactoperoxidase-catalysed radioiodination and analysis by SDS-polyacrylamide gel electrophoresis, proteolysis at the time of solubilization markedly affected the profiles obtained. Provided protease inhibitors were present during processing, a mu-like Ig heavy chain and a gamma-like Ig heavy chain could be demonstrated on larvae from nu/+ mice but not on larvae from nu/nu mice.

Animals↗
PubMed1980

Cytoplasmic microtubules and fungal morphogenesis: ultrastructural effects of methyl benzimidazole-2-ylcarbamate determined by freeze-substitution of hyphal tip cells.

The effects of methyl benzimidazole-2-ylcarbamate (MBC), one of only a few agents that are active against microtubules of fungi, were analyzed at the ultrastructural level in freeze-substituted hyphal tip cells of Fusarium acuminatum. Nontreated and control cells had numerous microtubules throughout. After just 10 min of exposure to MBC, almost no cytoplasmic microtubules were present, except near spindle pole bodies. After 45 min of exposure to MBC, no microtubules were present in hyphal tip cells, but they were present in the relatively quiescent subapical cells. These observations suggested that there are different rates of turnover for cytoplasmic microtubules in apical and subapical cells and for microtubules near spindle pole bodies and that MBC acts by inhibiting microtubules assembly. A statistical analysis of the distribution of intracytoplasmic vesicles in thick sections of cells treated with MBC, D2O or MBC + D2O was obtained by use of a high-voltage electron microscope. More than 50% of the vesicles in the apical 30 micrometers of control cells were found to lie within 2 micrometers of the tip cell apex. MBC treatment caused this vesicle distribution to become uniform, resulting in a substantial increase in the number of vesicles in subapical regions. The reduction in the number of cytoplasmic microtubules, induced by MBC, apparently inhibited intracellular transport of these vesicles and rendered random the longitudinal orientation of mitochondria. In most cases, D2O appeared capable of preventing these MBC-effects through stabilization of microtubules. These observations support the "vesicle hypothesis" of tip growth and establish a transport role for cytoplasmic microtubules in fungal morphogenesis.

Benzimidazoles↗
PubMed1980

Kinetics of C Distribution during Photosynthesis by Chloroplast Preparations Isolated from the Siphonous Alga Caulerpa simpliciuscula.

The kinetics of (14)C-labeling of compounds produced during photosynthesis by chloroplast preparations isolated from the green alga Caulerpa simpliciuscula were studied. After 10 minutes photosynthesis sucrose contained more (14)C than any other product, and continued to accumulate radioactivity during the whole hour of incubation. Glucose-6-phosphate and alanine also behaved as end products and continued to accumulate label during the period. In these organelles, glucose-6-phosphate replaced triose phosphate as the main compound exported from the chloroplast during shorter periods of photosynthesis. When either glucose-6-phosphate or 3-phosphoglycerate was supplied to the isolated chloroplasts, they were metabolized, but were not converted to either sucrose or alanine. It is proposed that many of the differences in metabolism which distinguish these algal chloroplasts from those isolated from higher plants are due to their isolation in the form of cytoplasts, i.e. chloroplasts surrounded by a thin layer of extrachloroplastic material which is membrane-bound. The restriction of diffusion of intermediates from the chloroplast by this cytoplast membrane appears to be at least as important as the rather small amount of cytoplasm present in determining the properties observed.

Journal Article↗
PubMed1980

Immediate loss of cell-mediated immunity to murine cytomegalovirus upon treatment with immunosuppressive agents.

Splenic lymphocytes from cytomegalovirus-infected mice lost their in vitro proliferative responses to cytomegalovirus antigen within 3 h after in vivo treatment with antilymphocyte globulin and prednisolone. The response was inhibited when the agents were administered separately or together, and inhibition persisted through a 2-week course of immunosuppression. Circulating specific antibodies were depressed by multiple injections of antilymphocyte globulin alone or with prednisolone, but not by prednisolone alone. Mitogen-induced blast transformation was immediately depressed by immunosuppression with both agents. Although the response to lipopolysaccharide returned briefly, it declined with continuing treatment. Cytomegalovirus infection augmented the depressive effect of immunosuppression on the lipopolysaccharide proliferative response. Prednisolone treatment of infected animals did not affect the concanavalin A response, and lipopolysaccharide stimulation decreased more slowly and to a lesser extent than it did in mice treated with antilymphocyte globulin or both agents. Loss of specific cell-mediated immunity and simultaneous depression of humoral immunity indicated that immunosuppression immediately created an inability to respond to an active cytomegalovirus infection.

Animals↗
PubMed1980

Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation.

Fifty-nine renal transplant recipients with overt CMV disease were treated at the University of Minnesota Health Sciences Center between October 1, 1977 and November 15, 1978. In a group of 141 consecutive transplant patients, the incidence of overt CMV disease was 31%. Fifty-three patients (90%) developed clinical manifestations of CMV disease within 4 months of transplantation, and it was during this time period that overt CMV disease was associated with a significantly increased incidence of transplant nephrectomy and death. Fever was the most common presenting symptom (95% of patients), and overt CMV disease was found to be the single most common cause of fever in all hospitalized transplant recipients. Prolonged fever, diffuse pulmonary infiltrates, gastrointestinal bleeding, pancreatitis, transplant nephrectomy and development of other systemic infections were clinical features used to categorize patients according to disease severity. A number of these features were found to be significantly associated with the diagnosis of overt CMV disease. Twelve patients (20%) developed lethal CMV disease characterized by the presence of most of these features, 6 (10%) had severe disease, 9 (15%) had disease of moderate severity and 32 patients (54%) had mild CMV disease with fever being essentially their only clinical finding. Development of secondary systemic infection was most ominous, and occurred before death in 10 of the 12 patients with lethal CMV disease. The only patients to die with serious bacterial, fungal or protozoan infection during the period of this study had concomitant overt CMV disease. Abnormal liver function tests and leukopenia were common, and the degree of abnormality correlated with the severity of CMV disease. Of the multiple factors analyzed for their influence on the risk of developing overt CMV disease, several factors related to the kidney donor (the relationship of the donor to the recipient, HLA matching and CMV serology) appeared to be most important.

Adolescent↗