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Biomedical subjects

D Frederick

Publications and source records attributed to D Frederick.

26 records · Page 2Linked to original sources
PubMed1987

Intrapulmonary growth of Staphylococcus aureus in rats during induced atelectasis.

Intrinsic pulmonary antibacterial defenses are mediated by alveolar macrophages and by noncellular factors. Mechanical ventilation in the resting tidal volume range leads to alterations in the physical characteristics of alveolar surfactant, alveolar instability, regional hypoxia, and systemic hypoxemia. While a number of experimental manipulations diminish the activity of the intrinsic antibacterial defense system, the effects of mechanical ventilation per se have not been systematically evaluated previously. We found that normal rats ventilated without sighing (periodic large breaths) manifested severe defects in pulmonary clearance of Staphylococcus aureus during 6-h experiments, such that growth of the inoculum occurred. Addition of a timer-controlled mechanism to cause the animals to sigh every 2 min, without other modifications in the experimental conditions, caused significant improvement in clearance. Analysis of cellular response, compartmentalization of viable bacteria, surfactant quantities and sedimentation characteristics, and protein influx indicated that the defect in clearance paralleled alterations in the physical state of surfactant and alveolar stability but was not strongly correlated with alterations in the other parameters we measured. The data show that defective pulmonary bacterial clearance is rapidly induced by measures which alter alveolar stability and suggest that intrinsic pulmonary defenses require maintenance of normal air-liquid interfaces for optimal function.

Animals↗
PubMed1986

Corticosteroids in COPD. A clinical trial and reassessment of the literature.

A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects.

Aged↗
PubMed1984

Physician maldistribution in cross-cultural perspective: United States, United Kingdom, and Sweden.

Physician maldistribution is a widely recognized problem facing virtually all health care systems. In this study, information from three health care systems--the United States, the United Kingdom, and Sweden--was used to address two questions: How do organizational features of health care systems affect their ability to deal with the problem of physician maldistribution? What are the effects of physician distribution on the health status of populations? It was found, first, that all three systems perceived similar problems of physician maldistribution and drew on a repertoire of similar solutions, none of which was altogether responsive to the problem. Second, the relationship of physician distribution to health status was found to be ambiguous, with some evidence that physician/population ratios may affect some health measures but not others.

Cross-Cultural Comparison↗
PubMed1982

Metallothionein mRNA induction in mouse small bowel by oral cadmium and zinc.

Induction of metallothionein mRNA was investigated in organs of mice receiving oral zinc and cadmium. The low molecular weight, heat stability, and 30% cysteine content of metallothionein facilitated its detection in cell-free translation products analyzed by Sephadex G-50 chromatography and by gel electrophoresis. Native and heat-denatured [35S]cysteine-labeled polypeptides directed by poly(A)+ mRNA from organs of mice exposed orally to 3 mg CdCl2 or 15 mg ZnCl2 were compared with those of control mice. Although parenteral administration of CdCl2 (30 micrograms) did not elicit a measurable metallothionein mRNA accumulation in gut, oral administration of this metal induced intestinal metallothionein mRNA to high levels; translatable metallothionein mRNA was not detected in control organs. Five hours after oral CD or Zn, metallothionein constituted 12-17% of [35S]cysteine directed into protein by gut mRNA, and metallothionein mRNA was induced to similar levels in liver, kidney, and spleen of the same mice. After oral Zn, metallothionein mRNA levels in proximal jejunum were twice those in other regions of intestine. Metallothionein mRNA accumulates rapidly in small bowel after oral Zn and Cd; simultaneous induction in other mouse organs indicates a systemic response.

Animals↗
PubMed1975

Methylated messenger RNA in mouse kidney.

Polyadenylated messenger RNA from mouse kidney labeled in vivo exhibited a pattern of methylation distinct from that of rRNA and tRNA. After mice were given L-[methyl-3H]methionine, 4% of the polyribosomal RNA label was bound to oligo (dT)-cellulose; 20-24% of orotate- or adenine-labeled polyribosomal RNA eluted in the poly(A)+ RNA fraction under similar conditions. [3H]Methyl radioactivity was not incorporated into low molecular weight (5-5.8 S) rRNA, indicating the extent of nonmethylpurine ring labeling was negligible. [3H]Methyl-labeled poly(A)+ RNA sedimented heterogeneously in sodium dodecyl sulfate containing gradients similarly to poly(A)+ mRNA labeled with [3H]orotic acid. Based on an average molecular length of 2970 nucleotides, renal mRNA was estimated to contain 8.6 methyl moieties per molecule. Analysis of alkaline-hydrolyzed RNA sampled by DEAE-Sephadex-urea chromatography provided estimates of the relative amounts of base and ribose methylation. Although 83% of the [3H]methyl radioactivity in rRNA was in the 2'-0-methylnucleotide fraction, no methylated dinucleotides were found in mRNA. In poly(A)+ mRNA 60% of the [3H]methyl label was in the mononucleotide fraction; the remainder eluted between the trinucleotide and tetranucleotide markers and had a net negative charge between -4 and -5. The larger structure, not yet charcterized, could result from two or three consecutive 2'-0-ribose methylations and is estimated to contain 2.6 methyl residues. Alternatively, the oligonucleotide could be a 5'-terminal methylated nucleotide species containing 5'-phosphate(s) in addition to the 3'-phosphate moiety resulting from alkaline hydrolysis. Either structure could have a role in the processing or translation of mRNA in mammalian cells.

Animals↗
PubMedDate not supplied

Tc-99m-labeled tropanes as dopamine transporter imaging agents.

The development of novel Tc-9m-labeled tropane derivatives as dopamine transporter imaging agents is reported. A series of neutral and lipophilic conjugated complexes, containing N-(alkylthiolato)-tropane, aminobis(ethylthiolato), and a [99mTc]TcO3+ center core, were prepared and evaluated as central nervous system (CNS) dopamine transporter imaging agents in rats. One of the compounds, [99mTC]technetium, [methyl 3-(4-chlorophenyl)-8-(2-mercaptoethyl-8-azabicyclo [3.2.1]octane-2-carboxylato-S][[2,2'-(methylimino)bis[eth anethiolato]] (2-)-N,S,S']oxo (25), displayed low initial uptake in rat brain (0.1% at 2 min post i.v. injection); the striatal/cerebellar (ST/CB) ratio reached 3.50 at 60 min after an i.v. injection. The specific uptake can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, N-methyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; i.v. 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.0. In contrast, the specific uptake in striatum was not affected by pretreating rats with a noncompeting ligand, haldol (i.v., 1 mg/kg). In vitro autoradiography of rat brain sections exhibited elevated labeling in striatum, major islands of Calleja, and olfactory tubercle regions, where dopamine neurons are known to be concentrated. This series of compounds is the first example of technetium-99m labeled CNS receptor-specific imaging agents and may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS abnormality in conjunction with single photon emission computed tomography.

Animals↗