Search PubMed⌕ Search

Biomedical subjects

R Stuart

Publications and source records attributed to R Stuart.

At least 37 records · Page 2Linked to original sources
PubMed1990

Role of cytosolic factors in the transport of proteins across membranes.

In a review article published in 1986 we emphasized that an unfolded conformation is a prerequisite for the transport of precursor proteins across membranes, and that cytosolic factors exist whose function is to maintain what we termed the transport-competent conformation of precursor proteins. Subsequent observations in a number of different in vitro systems related both the competent conformation and the cytosolic factors to the recent observations on the ATP-requirements for protein transport. Here we review the currently available data on such factors, and their ATP-requirements, for prokaryotic as well as eukaryotic organisms. Furthermore, we discuss possible models for their action and relate them to the so-called molecular chaperones. These were originally defined as being involved in the proper folding and assembly of oligomeric protein complexes, but have since been shown in addition to facilitate the transport of proteins across membranes.

Biological Transport↗
PubMed1989

Accumulation of tetrahydrofolates in human plasma after leucovorin administration.

Reduced folates in plasma after i.v. and oral leucovorin administration were estimated by a ternary complex assay based on the incorporation of CH2FH4 into a stable complex with Lactobacillus casei thymidylate synthase and [3H]FdUMP. Each of the reduced folates, CH2FH4, FH4, and 5CH3FH4, could be quantitatively recovered from plasma by this approach even in the presence of high concentrations of the parent compound leucovorin. Examination of the accumulation kinetics of these reduced folates showed that after i.v. administration of 20 mg D,L-leucovorin to a healthy volunteer, FH4 and, to a lesser extent, CH2FH4 accumulated to maximal levels very early (less than 15 min), with a subsequent depletion that had a half-life of approximately 30 min. Accumulation of FH4 reached a peak level that was 12% of the maximal level of 5CH3FH4 achieved and more than 3 times greater than the pretreatment level of this common, circulating reduced folate form. Similar accumulation patterns were observed in a female patient with metastatic colonic cancer who was undergoing methotrexate (MTX)/fluorouracil therapy followed by i.v. leucovorin (15 mg). FH4 also accumulated, but to a lesser extent and over a longer period of time, when the same dose of leucovorin given orally. When several similar doses of leucovorin were given prior to the experimental dose, greater accumulation and duration of the FH4 response was observed. We propose that accumulation of FH4 and CH2FH4 could provide a circulating source of the reduced folate thought to be the active form for both high-dose MTX with leucovorin rescue and enhancement of fluorouracil activity.

Administration, Oral↗
PubMed1986

Urinary profiles of organic acids and volatile metabolites during the starvation process in rats.

Capillary gas chromatographic procedures were used to quantify the volatile and acidic compound profiles in the urinary samples of Sprague-Dawley rats during the starvation and refeeding periods. Numerous metabolites, identified through mass spectrometry, showed significant variations due to these physiological processes. Correlations are attempted with the previously studied biochemical processes in diabetic animals.

Acids↗
PubMed1986

Quantitative alterations in the metabolism of carbonyl compounds due to diet-induced lipid peroxidation in rats.

Following the dietary induction of lipid peroxidation in rats (verified by the levels of malonaldehyde and glutathione peroxidase), the urinary carbonyl compounds were followed chromatographically. Through a headspace gas chromatographic procedure, increases of several aldehydes and furan derivatives were noticed. Liquid chromatography of the dinitrophenylhydrazone derivatives of urinary carbonyls provided a more definitive experiment, in which the increased-peroxidation animals could be compared to those maintained on a control diet. Several carbonyl metabolites, identified by mass spectrometry, were elevated following the lipid peroxidation induction.

Animals↗
PubMed1983

Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia.

We performed a prospective randomized trial of antithoracic duct lymphocyte globulin (ATDLG), HLA-haploidentical marrow, and androgen (regimen ABA) versus androgen alone (concurrent STANDARD care controls) in 42 newly diagnosed individuals with severe aplastic anemia. ABA patients also were matched with patients from our preceding study (historical STANDARD care controls). Supportive care and pretreatment patient characteristics were the same in all groups. By life table analysis, 76% of patients receiving ABA are alive at 2 yr compared to 31% of the concurrent control group (p less than 0.002 versus ABA) and 19% of the historical controls (p less than 0.0001 versus ABA) given STANDARD care. ABA patients had greater hematologic improvement than either control group (p less than 0.001). However, improvement with ABA was often incomplete. Toxicity of ATDLG was considerable but manageable. Further studies to determine the mechanism of action and active component(s) of ABA are indicated.

Androgens↗
PubMed1980

Goose fatty acid synthetase mRNA.

The fatty acid synthetase of animal tissues consists of two identical subunits (Mr = 250,000), each of which is a multienzyme protein containing domains for the acyl carrier peptide and the seven different catalytic activities required for the conversion of acetyl-CoA and malonyl-CoA to palmitate. Total poly(A+) RNA was isolated from goose uropygial gland and translated in a cell-free rabbit reticulocyte system. The translation products contained a polypeptide having the same molecular weight as the native synthetase subunits; this protein was specifically recognized by anti-synthetase antibodies and could be competed by excess native synthetase for antibody binding. Fractionation of the poly(A+) RNA by sucrose gradient centrifugation showed that synthetase mRNA is very large, repeatedly exhibiting a sedimentation coefficient of 35 S. Gel electrophoresis of this purified mRNA fraction following glyoxylation showed the presence of several species of RNA, one of which correlated well with the in vitro translation of the synthetase. This mRNA species has a molecular weight of 2.95 X 10(6), which is large enough to code for a protein with a molecular weight of 250,000. These results confirm the multifunctional nature of the synthetase and indicate that the synthetase subunit must arise as a single polypeptide chain synthesized from one contiguous mRNA.

Animals↗
PubMed1980

John Marsh.

Explore the source record for details and available documents.

History, Modern 1601-↗
PubMed1976

Renomedullary interstitial cell lesions and hypertension.

The notion that renomedullary nodules of the kidney arise as a response to hypertension was tested. Heart weight, ratio of heart weight to body weight, and blood pressure in 160 patients in whom such nodules were found at autopsy were compared with similar measurements in 160 patients without nodules. There were no significant differences between the two groups, and it was concluded that there was no evidence to support the idea that the renomedullary nodule represents a response to hypertension.

Autopsy↗