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Biomedical subjects

J C Roberts

Publications and source records attributed to J C Roberts.

At least 127 records · Page 7Linked to original sources
PubMed1966

Nonphosphorylating respiration of mitochondria from brown adipose tissue of rats.

Mitochondria from brown adipose tissue of cold-acclimated rats (6 degrees C) oxidize alpha-ketoglutarate at a rate twice that of controls (26 degrees C). In both groups, however, the phosphorus: oxygen ratio with alpha-ketoglutarate never exceeded unity, and it is essentially zero with either succinate or alpha-glycerophosphate. Adenosine triphosphatase activity of these mitochondria is very low and it is not stimulated by 2,4-dinitrophenol. In addition, both respiration and phosphorylation are unaffected by adenosine diphosphate, 2,4-dinitrophenol, bovine serum albumin, or glutathione. Endogenous respiration of tissue slices is not stimulated by 2-4-dinitrophenol. It is suggested that brown fat mitochondria are not capable of oxidative phosphorylation, but do phosphorylate at the substrate level. Since these findings provide an unusual example of electron transport by means of an energetically nonconservative pathway, their significance to thermogenesis by brown adipose tissue is particularly emphasized.

Adenine Nucleotides↗
PubMedDate not supplied

Using starburst dendrimers as linker molecules to radiolabel antibodies.

Starburst dendrimers, spherical polymers constructed from methyl acrylate and ethylenediamine, were successfully used to covalently couple synthetic porphyrins to antibody molecules. The dendrimers, as linker molecules, have great potential for increasing the specific activity of radiolabeled antibodies for tumor therapy and diagnosis.

Antibodies↗
PubMedDate not supplied

The case for perfusion fixation of large tissue samples for ultrastructural pathology.

We present the case for the perfusion fixation of large, freshly isolated tissue samples of liver and lung from dog, rat, and mouse. Individual lobes of liver and lung were fixed by vascular perfusion using a technique that is simple and quick to perform and results in a reproducibly high standard of ultrastructural preservation compared to immersion fixation. A major advantage to the use of this technique lies in the ability to provide tissue samples for diagnostic ultrastructural pathology and toxicological pathology while avoiding the need for whole-organ or whole-body perfusion fixation. This advantage therefore permits the use of fresh tissue from the same organ for other investigative purposes (e.g., drug metabolism studies and pharmacokinetics), thereby allowing correlation of structure and function. The advantages of perfusion fixation compared to immersion fixation are discussed, and potential applications for tissue preparation of postmortem specimens and also for scanning electron microscopy are indicated.

Animals↗
PubMedDate not supplied

Effects of thiols on topoisomerase-II alpha activity and cell cycle progression.

Thiol containing compounds exhibiting antioxidant properties are currently being evaluated for use in cytoprotection and chemoprevention. Many of these have also been found to be effective in inhibiting cell cycle progression and cellular proliferation. N-Acetyl-L-cysteine (L-NAC), along with its nonmetabolically active stereoisomer N-acetyl-D-cysteine (D-NAC), together with captopril and dithiothreitol (DTT) were investigated to assess their effects on cell cycle progression as determined by flow cytometry. Topoisomerase-IIa (topo-II alpha) activity, an enzyme involved in DNA synthesis, was also monitored as a function of drug dose using a kinetoplast DNA (kDNA) decatenation assay. Chinese hamster ovary (CHO) AA8 cells were exposed to each thiol at concentrations ranging from 4 microM to 4 mM for a period of 3 h. Following the removal of the thiols, cell cultures were followed for an additional 5 h to assess changes in cell cycle progression. L-NAC, which also serves as a precursor for glutathione (GSH) synthesis, effectively inhibited topo-IIa activity by at least 50% at all concentrations tested. Associated with this reduction in enzyme activity was a sixfold increase in the relative number of cells accumulating in G2phase. D-NAC, which is unable to participate in GSH synthesis, was only half as effective as L-NAC at each concentration tested in inhibiting topo-IIa activity as well as perturbing cell progression through G2. In comparison, captopril, an inhibitor of angiotensin converting enzyme (ACE), had little effect on the progression of cells into G2 phase. In contrast to the repressive effects of L-NAC and D-NAC, it enhanced topo-IIa activity over control values by approximately 20%. DTT, a well characterized thiol known to be capable of reducing disulphides in proteins, was observed to be relatively ineffective in either perturbing cell cycle progression or affecting topo-IIa activity. This suggests an involvement of a mechanism(s) in addition to thiol mediated affects on reduction/oxidation processes. The inhibitory effects of L-NAC and D-NAC on topo-IIa activity, in contrast to the other two thiols, may be due in part to the presence of amine groups which could allow for their participation in polyamine related processes. The difference in the magnitude of the effect exhibited by L-NAC, as compared to D-NAC, on the repression topo-IIa activity also suggests a role for GSH in this process. Inhibition of cellular progression and proliferation by thiols can therefore be mediated by diverse mechanisms which include both cycle-phase specific (i.e. L-NAC and D-NAC) and non cell cycle specific (i.e. captopril) processes.

Acetylcysteine↗
PubMedDate not supplied

Mononuclear-cell peptide mediation of chromaffin-cell epinephrine secretion.

Previously, we have shown that novel mononuclear-cell-derived factor(s) [molecular weight (MW) < 3,000] stimulate the release of epinephrine (EPI) from adrenal medullary chromaffin cells to levels comparable to that of maximal cholinergic stimulation. The present study provides evidence that the observed bioactivity is due to the action of a single peptide of 627 Da apparent MW. The peptide nature of the bioactive component was suggested by a decreased bioactivity after acid hydrolysis as well as altered bioactivity subsequent to peptidase (carboxypeptidase Y, leucine aminopeptidase) treatment. The bioactive conditioned-medium (CM) peptide(s) were isolated and further characterized using SDS-PAGE analysis. SDS-PAGE separation of G-25 Sephadex purified CM shows that bioactivity resides in a single peptide band. Additional studies revealed that CM also mediates norepinephrine release from sympathetic ganglia cells. Regulation of peptide production was shown to involve negative feedback in that incubation with mononuclear cells with EPI prevented further bioactive peptide release. This feedback inhibition was partially blocked by the beta-adrenergic receptor antagonist propranolol. These findings suggest a novel and potentially important mechanism by which the immune system can alter neuroendocrine function.

Adrenal Medulla↗
PubMedDate not supplied

Surface failure of commercial and experimental restorative resins.

A single-pass test was used to study the surface failure of commercial and experimental restorative resins and composites. The surface failure observed for unfilled diacrylate resins was more severe than that seen for an unfilled acrylic resin. Addition of nonsilanated filler to the diacrylate resins increased the resistance to penetration but did not dramatically change the mode of surface failure. The surface failure of the commercial composite resins, which contain silanated filler, was ductile in mode and the resistance to penetration of the diamond slider was the highest of the materials studied. The wear of restorative resins and composites is determined, therefore, by resistance to penetration as well as mode of deformation during sliding.

Acrylic Resins↗