Search PubMed⌕ Search

Biomedical subjects

D J Morris

Publications and source records attributed to D J Morris.

At least 127 records · Page 7Linked to original sources
PubMed1991

The "mineralocorticoid-like" actions conferred on corticosterone by carbenoxolone are inhibited by the mineralocorticoid receptor (type I) antagonist RU28318.

We have previously demonstrated, in adrenalectomized male rats, that the liquorice derivative carbenoxolone (CS) can confer mineralocorticoid (MC)-like activity upon the glucocorticoid corticosterone (B) and amplify the Na(+)-retaining actions of aldosterone (Aldo) and deoxycorticosterone (DOC). The purpose of the present study was to determine whether the MC-like effects of B and the amplified actions of ALDO and DOC in the presence of CS are mediated via the occupation of type I (MC) receptors. In adrenalectomized male rats, B (100 micrograms/rat) alone produced a significant kaliuresis, but no antinatriuresis. This kaliuresis was blocked by the type I (MC) receptor antagonist RU28318 (300 micrograms/rat). In the presence of CS (2.5 mg/rat), B produced a significant Na+ retention, and the kaliuretic activity of B was significantly enhanced. This CS-induced antinatriuresis produced by B was significantly reduced by RU28318, as was the amplified kaliuresis. The MC effects of either Aldo (0.05 micrograms/rat) or DOC (5 micrograms/rat) alone were, as expected, reduced by RU28318 (300 micrograms/rat). As previously reported, CS amplified only the Na(+)-retaining actions of Aldo and DOC, and it was also possible to reduce these amplified effects with RU28318. The present study demonstrates that in the presence of CS, the MC actions of B, Aldo, and DOC are mediated to a large extent via the occupation of type I (MC) receptors.

Adrenalectomy↗
PubMed1991

5 alpha-dihydrocortisol in human aqueous humor and metabolism of cortisol by human lenses in vitro.

Glucocorticoids have long been implicated in the etiology of primary open-angle glaucoma (POAG) and cataract. Cortisol metabolites have biologic activity and may affect aqueous humor dynamics. This study was done to determine whether these metabolites are found in human aqueous humor and can be produced by ocular tissues. Radioimmunoassays (RIA) were developed for 5 alpha-dihydrocortisol (5 alpha-DHF) and 5 beta-dihydrocortisol (5 beta-DHF). These assays, as well as a cortisol RIA, were used to quantify these three steroids in 20 surgically derived aqueous humor specimens from patients with and without POAG. The mean concentrations of cortisol and 5 alpha-DHF were 2.5 and 1.3 ng/ml, respectively. In the small group studied, there was no statistically significant difference between the aqueous humor steroid levels in patients with and without POAG. The amount of 5 beta-DHF was at the lower limits of detection of the assay system and could not be uniquivocally shown. Human lenses metabolized cortisol in vitro to 5 alpha-DHF and 3 alpha,5 alpha-tetrahydrocortisol (3 alpha,5 alpha-THF). There was no 5 beta-DHF or cortisone formed. The 5 alpha-DHF and 3 alpha,5 alpha-THF were identified by their positions on thin-layer chromatography, their retention times on high-performance liquid chromatography, and recrystallization with authentic standards to constant specific activity. The data suggest that the lens is the source of 5 alpha-DHF in aqueous humor.

Aged↗
PubMed1990

Diagnosis of cytomegalovirus infection in cyclosporin-treated renal allograft recipients.

The relative merits of antibody response and virus shedding as markers of cytomegalovirus (CMV) infection among cyclosporin-treated renal allograft recipients were analysed. CMV-specific antibody was assayed by IgG-specific radioimmunosorbent test (RIST) and by complement fixation test (CFT). CMV shedding was assayed by virus isolation and by the rapid test immediate early nuclear antigen detection (IENAD). RIST and CFT detected seroconversion in similar numbers of patients, but the former test was the more sensitive when CMV antibody was sought in pretransplant sera to differentiate primary from recurrent infection. IENAD detected or excluded CMV shedding for more urine specimens than virus isolation (462/515 [90%] vs. 366/515 [71%]), but the reverse applied to saliva specimens (33/57 [58%] vs. 54/57 [95%]). The high specificity of IENAD allowed positive results by IENAD to be accepted when virus isolation failed to provide a result. IENAD was, however, less sensitive than virus isolation even when specimens yielding CMV by IENAD, but no result by virus isolation, were included in the analysis (27/44 [61%] vs. 38/44 [86%]). Assays of both antibody response and virus shedding were required to maximise the diagnosis of recurrent CMV infections, but the former assay detected all primary CMV infections. The diagnostic implications of these results are discussed.

Antibodies, Viral↗
PubMed1990

The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats.

Ingestion of licorice or treatment with chemical derivatives of glycyrrhetinic acid (GA), an active principle of licorice, can cause hypertension, sodium retention, and hypokalemia. Although GA has been shown to inhibit 11 beta-hydroxysteroid dehydrogenase, it may not be the only hepatic enzyme affected by this licorice derivative. Therefore, we studied the effects of GA on other major hepatic steroid-metabolizing enzymes from adrenalectomized male rats using aldosterone as the substrate; namely, delta 4-5 alpha- and delta 4-5 beta-reductases and 3 alpha- and 3 beta-hydroxysteroid dehydrogenases (3 alpha- and 3 beta-HSD). From these in vitro studies, we demonstrated that GA does not affect either microsomal 5 alpha-reductase or cytosolic 3 alpha-HSD activity. However, GA is a potent inhibitor of cytosolic 5 beta-reductase; the K(is) and K(ii) were calculated from enzyme kinetic analysis to be 6.79 and 5.41 microM, respectively, using the Cleland equation, indicating that GA is a noncompetitive inhibitor of aldosterone. In addition, GA specifically inhibited microsomal 3 beta-HSD enzyme activity by what appears to be a competitive inhibition mechanism, causing a build-up of the intermediate, 5 alpha-dihydroaldosterone (DHAldo). Thus, this study has indicated that GA has a profound effect on hepatic ring A-reduction of aldosterone. Inhibition of 5 beta-reductase and 3 beta-HSD results in decreased synthesis of both 3 alpha, 5 beta-tetrahydroaldosterone (THAldo) and 3 beta, 5 alpha-THAldo and, hence, accumulation of aldosterone and 5 alpha-DHAldo, both potent mineralocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Synthesis of 6 beta-hydroxyaldosterone by A6 (toad kidney) cells in culture.

Incubation of aldosterone with confluent layers of A6 (toad kidney) cells leads to its hydroxylation at the 6 beta-position. 6 beta-Hydroxyaldosterone is the major metabolite when the incubation is carried out at pH 6.8, whereas the product comprises 6 beta-hydroxy-17-isoaldosterone accompanied by some 6 beta-hydroxyapoaldosterone at pH 7.4. All products were identified by high-field 1H nuclear magnetic resonance spectroscopy. Control experiments indicated that the side-chain isomerization to form the 17-iso and apo derivatives occurs after the cytochrome P 450-dependent synthesis of 6 beta-hydroxyaldosterone.

Aldosterone↗
PubMed1990

Ribavirin response in measles pneumonia.

A 9-year-old boy with Hodgkin's disease developed measles 1 month after completing eight courses of intensive anti-cancer chemotherapy. The atypical nature of the rash and the absence of Koplik's spots indicated a high risk of progression to fatal giant cell pneumonia. Seven days nebulised and intravenous ribavirin therapy produced apparent recovery. Two weeks later the child presented with measles giant cell pneumonia diagnosed on open lung biopsy. Ribavirin therapy was again successful. The role of ribavirin in the treatment of measles in immunocompromised children is discussed.

Child↗
PubMed1990

Comparison of polyethylene glycol precipitation and ultracentrifugation for recovery of cytomegalovirus from urine prior to detection of DNA by dot-blot hybridisation.

Polyethylene glycol (PEG) precipitation provided a useful alternative to ultracentrifugation for recovering cytomegalovirus (CMV) from clinical specimens prior to DNA hybridisation studies. The conditions for use of PEG are described. In a study of 61 urine samples from patients suspected of CMV infection 18 yielded a positive DNA hybridisation result. Fifteen were positive after both concentration procedures, two after PEG precipitation only and one after ultracentrifugation only. The DNA hybridisation results are discussed in the light of the results of virus isolation by cell culture.

Chemical Precipitation↗
PubMed1990

Screening of bone marrow and kidney transplant donors and recipients for cytomegalovirus antibody by commercial latex agglutination or competitive enzyme-linked immunosorbent assays.

A commercial competitive enzyme-linked immunosorbent assay and a sensitive in-house radioimmunosorbent test detected cytomegalovirus (CMV) antibody in similar numbers of serum specimens (66 and 67 of 152, respectively) obtained from bone marrow and renal transplant donors and recipients. In contrast a commercial latex agglutination assay for CMV antibody apparently gave false positive results when testing serum specimens obtained from organ donors. The implications for CMV screening of organ transplant donors and recipients are discussed.

Antibodies, Viral↗
PubMed1990

Immunoradiometric assay for cytomegalovirus-specific IgG antibodies: assay development and evaluation in blood transfusion practice.

An immunoradiometric assay (radio-immunosorbent test; RIST) for the detection of IgG antibodies to human herpesvirus 4 [human cytomegalovirus (CMV)] has been developed. The technique utilizes CMV antigen passively adsorbed to a polyvinyl microtitration plate and a radiolabelled murine monoclonal anti-human IgG antibody to detect binding of human antibody to the 'solid phase' reagent. The assay was optimized, and its specificity confirmed by testing paired acute and convalescent sera from patients with acute CMV or other human herpesvirus infections. To determine the assay's sensitivity 1433 blood donor sera were examined. The RIST was more sensitive than a standard complement fixation (CFT), in that 53% of these sera were positive by RIST and 48% positive by CFT. There were 1303 concordant results, 88 sera positive only by RIST and 19 sera were only positive by CFT. These discrepant results remained after an attempt to exclude false positive reactivity; their significance is discussed. Use of a monoclonal anti-human IgG antibody in the RIST reduced non-specific binding to the control uninfected cell antigen such that blood donor sera could be tested in the assay using only a CMV antigen without generating an unacceptable false positive rate.

Animals↗
PubMed1990

Donor seropositivity and prednisolone therapy as risk factors for cytomegalovirus infection and disease in cyclosporin-treated renal allograft recipients.

We attempted to assess the importance of blood transfusion, donor seropositivity, and prednisolone therapy as risk factors for cytomegalovirus infection in cyclosporin-treated renal allograft recipients. Primary infection was diagnosed in 27 of 86 patients (31 per cent) and recurrent infection in 27 of 79 patients (34 per cent). Receipt of banked blood from unselected donors after transplantation did not increase the incidence of primary infection in the few transfused patients. Kidney donor seropositivity and maintenance prednisolone in addition to cyclosporin were associated with increases in the incidence of primary or recurrent infection, respectively. Cytomegalovirus infection was clinically mild. Presumed bacterial pneumonias occurred in three patients with recurrent cytomegalovirus infection. The absence of severe cytomegalovirus disease probably reflected the minimal use of prednisolone. Matching of seronegative donors with seronegative recipients seemed unjustifiable in cyclosporin-treated renal transplant patients.

Adult↗
PubMed1990

The production of human parvovirus capsid proteins in Escherichia coli and their potential as diagnostic antigens.

We have expressed a number of polypeptides derived from the capsid proteins of the human parvovirus B19 in Escherichia coli. These include native VP1 (84K) and VP2 (58K) proteins and also fusions to beta-galactosidase containing differing amounts of the amino terminus of the VP1/2 polypeptide. Although each of these was expressed at high levels and the majority were produced as full-length proteins, only one was soluble. This soluble polypeptide, p132, is a beta-galactosidase fusion protein that includes 145 amino acids from B19 which are entirely derived from the region unique to VP1. Despite containing such a small portion of VP1, which itself constitutes only 4% of total capsid protein, p132 reacted with all our known anti-B19 IgM-positive human serum samples. We conclude that this region contains epitopes which must be prominently exposed on the intact virus. We have demonstrated the use of this recombinant antigen in a simple diagnostic assay for B19-specific antibodies which can be used for initial screening of human serum samples. In a survey of 103 serum specimens, our ELISA positively identified all samples (19/19) which were positive by IgM antibody capture radioimmunoassay. The recombinant p132 antigen is efficiently produced and readily purified from E. coli, and its use as a diagnostic antigen should increase the availability of routine clinical testing for human parvovirus infection.

Antigens, Viral↗