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Biomedical subjects

D Marriott

Publications and source records attributed to D Marriott.

43 records · Page 3Linked to original sources
PubMed1985

Specific recognition of calmodulin from Dictyostelium discoideum by the ATP, ubiquitin-dependent degradative pathway.

Calmodulin purified from Dictyostelium discoideum is selectively degraded by rabbit reticulocyte extracts in the presence of ubiquitin and ATP. This protein forms a 1:1 covalent conjugate with ubiquitin. Analyses of the cyanogen bromide fragments of the protein conjugate indicate that lysine 115 on calmodulin is the ubiquitin conjugation site. Bovine brain calmodulin which contains a trimethyllysine residue at this position is not a substrate for conjugation with ubiquitin, and its degradation rate is not affected by ATP and ubiquitin. These results suggest that the trimethyllysine residue in mammalian calmodulin may function in protecting the protein from degradation by the ATP, ubiquitin-dependent pathway. Since there are eight lysine residues in Dictyostelium calmodulin, the specific conjugation of ubiquitin to lysine 115 may provide a good model system to delineate the structural features required for the conjugation and to follow the degradative steps in the pathway.

Adenosine Triphosphate↗
PubMed1985

Metorphamide, a C-terminally amidated opioid peptide, in human adrenal and human phaeochromocytoma.

There appears to be only one possible site for the production of an amidated peptide in the human proenkephalin sequence; this will give rise to the peptide named metorphamide. Since amidation of peptides is commonly an activation step in the synthesis of regulatory peptides, we have examined the levels and form of immunoreactivity to metorphamide in human post-mortem adrenal and phaeochromocytoma extracts. In three out of four post-mortem adrenal extracts, and in each of the two phaeochromocytoma extracts examined, there was 3-4 times more immunoreactivity to the carboxy-terminus of pro-enkephalin, Met-enkephalin(Arg6,Phe7), than to metorphamide. The metorphamide immunoreactivity was shown in each extract to measure only the amidated octapeptide according to gel exclusion and reverse-phase chromatography data. The implications for processing of proenkephalin in human adrenal are indicated.

Adrenal Gland Neoplasms↗
PubMed1983

Acquired immune deficiency syndrome.

The first Australian case of acquired immune deficiency syndrome (AIDS), which occurred in a 27-year-old homosexual man, is reported. The patient, an American citizen now resident in Sydney, presented with life-threatening pulmonary consolidation. AIDS is characterized by severe defects in cell-mediated immunity associated with infections and neoplasms (most commonly Pneumocystis carinii pneumonia and Kaposi's sarcoma). The cause of the syndrome is unknown, but it may be a new infectious agent.

Acquired Immunodeficiency Syndrome↗
PubMed1978

Radionuclide quantitation of left-to-right cardiac shunts in children.

In order to evaluate the clinical usefulness of radionuclide methods measuring the magnitude of left-to-right cardiac shunts, a comparison has been made of the results obtained using these procedures with those estimated by cardiac catheterization. Seventy children in whom the presence or absence of a shunt had been established, were studied. Two methods for radionuclide shunt quantitation, the pulmonary to systemic blood flow ratio (Qp/Qs) of Maltz and Treves and their modified C2/C1, were evaluated. The former was found to be superior and showed a high correlation of shunt size with the catheter results. With attention to the performance of the investigation and in the data analysis, good discrimination can be achieved between normal patients and those with shunts. Because of the atraumatic nature of the investigation, it is concluded that the procedure is of value in the diagnosis of a cardiac murmur, the assessment of postoperative patients and the follow-up of patients known to have a small shunt.

Adolescent↗
PubMedDate not supplied

Efficacy of fluconazole in cryptococcal meningitis.

In this clinical trial, oral fluconazole was used to treat cryptococcal meningitis in 32 patients with Acquired Immune Deficiency Syndrome (AIDS). In 11 patients who received 200 to 400 mg/day of fluconazole as primary therapy, a favorable clinical response was obtained in 67% of all evaluable patients. A negative cerebrospinal fluid (CSF) culture was also reported for 86% of these cases. Fluconazole was used as second-line therapy in an additional 15 patients who were not responsive to therapy with amphotericin B or amphotericin B combined with flucytosine. Positive clinical and mycologic responses were then obtained in more than 60% of these cases. Following successful treatment with fluconazole as either the primary or secondary antifungal agent, 26 patients were evaluated during maintenance therapy with 100 to 200 mg daily of fluconazole to prevent recurrence of disease. The relapse rate was 3.2 cases of cryptococcal meningitis per 1000 patient weeks, with a mean duration of 22 weeks for maintenance therapy. An additional six patients who were also treated with either amphotericin B alone or in combination with flucytosine but were asymptomatic or CSF culture negative when treatment with fluconazole was initiated were evaluated for the safety and efficacy of maintenance therapy. Thus, treatment of fluconazole appears to be efficacious as well as safe. The incidence of superimposed infections associated in these AIDS patients make it difficult to accurately assess any adverse effects.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Managing antituberculosis drug therapy by therapeutic drug monitoring of rifampicin and isoniazid.

BACKGROUND: Current therapeutic regimens with rifampicin and isoniazid have proven successful in treating tuberculosis, however, toxicity, therapeutic failure, relapse and multiple drug resistance are serious concerns. Optimizing drug dose using therapeutic drug monitoring (TDM) may be a better approach than administering therapy as a standard dose. AIMS: To establish and evaluate a TDM service to optimize rifampicin and isoniazid therapy. METHODS: A TDM service for rifampicin and isoniazid was established in November 1998. Drug concentration data were collected, with relevant information to interpret the results. The reason for the request, information on concomitant drug administration and a questionnaire to assess clinical response to the drug results were also obtained. RESULTS: Ninety patient episodes were accepted for study. The rifampicin plasma concentrations showed significant scatter, with 46% of the rifampicin concentrations below the normal range and 2% above the normal range. Similarly, 48% of isoniazid concentrations were below the lower target of the normal range and 29% were above the upper normal limit. There was a greater proportion of isoniazid concentrations above the normal range in female patients. CONCLUSION: Significant pharmacokinetic variability was observed for rifampicin and isoniazid in the patient population studied. Further, a substantial number of plasma concentrations fell outside the suggested normal range for both drugs. Isoniazid plasma concentrations were significantly higher in female patients compared with male patients. Despite these abnormal results, the dose of rifampicin and isoniazid was altered in only 17% of patients, however, many patients received follow-up education because of the drug result. The service was considered valuable by 83% of respondents to the questionnaire. While TDM of rifampicin and isoniazid is a valuable tool to optimize the dose of these drugs in some patients, there is an urgent need for concentration-effect studies and possibly education on the principles and practice of TDM for these drugs.

Adolescent↗