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Biomedical subjects

R L Friedman

Publications and source records attributed to R L Friedman.

70 records · Page 4Linked to original sources
PubMed1983

Acute and chronic effects of serotonin (5HT) antagonists on serotonin binding sites.

The administration of 14 daily doses of cyproheptadine, BC-105, metergoline and methysergide induced a marked decrease in the number (Bmax) of 3H-spiroperidol binding sites (5HT2 sites) in frontal cortex, when assayed 48 h after the last dose; the apparent affinity (KD) of 3H-spiroperidol was not changed. The same treatment schedules failed to modify the KD and Bmax values for 3H-5HT binding to the 5HT1 site in the hippocampus. Cyproheptadine, BC-105 and methysergide, but not metergoline, decreased the density of 5HT2 sites in frontal cortex 48 h after a single dose. Additional studies of the decrease in 3H-spiroperidol binding after in vivo treatment with cyproheptadine showed that the extent of binding loss was unaltered by repeated washing. Furthermore, cyproheptadine added in vitro to membranes isolated from frontal cortex inhibited the binding of 3H-spiroperidol in a competitive manner; Scatchard plots were linear with the same maximum binding (Bmax) and different slopes. Therefore, these preliminary studies suggest that the loss of 5HT2 binding sites after in vivo treatment with cyproheptadine and with other 5HT antagonists may reflect an adaptive response. This apparent paradoxical effect suggests that the action of these drugs at the 5HT2 binding sites should be reevaluated.

Animals↗
PubMed1983

Cloning of cDNA sequences of human adenosine deaminase.

Cloned cDNA sequences of human adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) have been isolated from a cDNA library constructed in bacteriophage lambda gt10. The cDNA for the library was prepared from poly(A)+ RNA isolated from a human T-lymphoblast cell line, CCRF-CEM. The library was initially screened by differential plaque hybridization to labeled cDNA prepared from human T- and B-lymphoblast cell lines with a 21-fold difference in levels of translatable ADA mRNA. Two recombinants containing cloned cDNA sequences for ADA were identified by hybridization-selected translation. Both recombinants contained approximately 1,600 base pairs of inserted human DNA. Restriction maps of the two inserts were not identical. One contained approximately 40 base pairs of additional DNA toward the center of the cDNA. The cloned cDNA specifically hybridized to five fragments generated by HindIII digestion of human genomic DNA. It also hybridized to human lymphoblast RNA species 1.6 and 5.8 kilobases in length. The cDNA was used as a probe to estimate ADA mRNA levels in human lymphoblast cell lines. ADA mRNA levels correlate closely with levels of ADA catalytic activity and ADA protein in cell lines containing structurally normal ADA. A leukemic T-lymphoblast line produced 6 to 9 times as much ADA protein and ADA mRNA as transformed B-lymphoblast lines. Two mutant B-lymphoblast lines from patients with hereditary ADA deficiency contained unstable ADA protein but had 3 to 4 times the normal level of ADA mRNA.

Adenosine Deaminase↗
PubMed1982

The effects of Legionella pneumophila toxin on oxidative processes and bacterial killing of human polymorphonuclear leukocytes.

The effect of Legionella pneumophila toxin on selected functions of human polymorphonuclear leukocytes was investigated. Amounts of L. pneumophila toxin that had no effect on leukocyte viability or phagocytosis significantly decreased hexose monophosphate shunt activity and O2 consumption during phagocytosis and bacterial iodination and killing in a dose-dependent fashion. The mechanism of action of this toxin appears to be unique among bacterial products thus far studied.

Bacterial Toxins↗
PubMed1982

Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats.

A chronic pulmonary infection model in rats was employed to assess the role of individual Pseudomonas aeruginosa exoproducts in disease due to this organism. Groups of rats were inoculated transtracheally with agar beads in which were embedded approximately 10(4) colony-forming units of P. aerugijnosa PAO and the PAO derivatives PR1, T1, E64, and a mixture of T1 and E64 in equal numbers (10(4)). Eight animals from each group were sacrificed at 3, 9, and 30 days after challenge, and their lungs were examined for histopathological changes, bacterial numbers, and the presence of P. aeruginosa exoproducts. The Tox- mutant T1 and the PR1 mutant, which produces enzymatically inactive toxin A, were both found to be less virulent in the rat lung model than was the toxigenic parental strain PAO. Pathological changes seen in animals infected with these mutants were restricted to intra- and peribronchial inflammation, whereas the toxigenic parental strain caused parenchymal changes, including a dense mononuclear-cell infiltration in the alveolar spaces in addition to intra- and peribronchial inflammation. Additionally, mutant E64, which produces a temperature-sensitive elastase, was also found to be less virulent in the rat lung model than was the parental strain. These data demonstrate that both active toxin A and elastase are required for maximum virulence of P. aeruginosa in this model.

Bacterial Toxins↗
PubMed1981

Effect of formalin toxoiding on Pseudomonas aeruginosa toxin A: biological, chemical, and immunochemical studies.

We investigated the effect of Formalin toxoiding on the biological, chemical, and immunological activities of Pseudomonas aeruginosa toxin A. Formalin treatment alone resulted in a 1,000-fold decrease in toxin-induced cell cytotoxicity and altered the antigenicity of the toxin A molecule without adversely affecting enzymatic activity. Competitive blocking experiments indicated that Formalin-mediated detoxification proceeded via alterations in a region of the toxin molecule other than the active site of the enzyme. The addition of lysine to Formalin-toxin mixtures not only increased the rate and extent of detoxification and antigenic alteration, but also completely destroyed enzymatic activity. The immunogenicities of different toxoids varied substantially. Upon dialysis and storage, Formalin-derived toxoids underwent partial toxic reversion, whereas a Formalin-lysine-derived toxoid did not. The sodium dodecyl sulfate-polyacrylamide gel patterns of Formalin- and Formalin-lysine-treated toxins indicated that these treatments caused the formation of a heterogenous group of high-molecular-weight species and produced substantial changes in the electrophoretic mobility of toxin A.

ADP Ribose Transferases↗
PubMed1980

Isolation and characterization of a Pseudomonas aeruginosa mutant producing a nontoxic, immunologically crossreactive toxin A protein.

Nitrosoguanidine mutagenesis of Pseudomonas aeruginosa strain PAO-1 yielded a mutant strain, PAO-PR1, which produced a protein that was immunologically indistinguishable from native toxin A and was nontoxic for cultured Chinese hamster ovary cells. In contrast to native toxin, the cell-associated and extracellular crossreactive material (CRM), designated "CRM protein," possessed no adenosine diphosphate-ribosylating activity. This CRM protein comigrated with native toxin A on sodium dodecyl sulfate/polyacrylamide gels, could be immunoprecipitated with antitoxin from culture supernatants of strain PAO-PR1, and gave a reaction of identity in immunological assays. Equivalent amounts of toxin A antigen and CRM protein antigen were produced in liquid culture by their respective strains as quantitated in a radioimmunoassay for toxin A. These data suggest that mutant strain PAO-PR1 possesses one or more missense mutations within the structural gene for toxin A that adversely affect enzymatic activity, thereby rendering the molecule nontoxic.

Bacterial Toxins↗
PubMed1980

Role of Kupffer cells, complement, and specific antibody in the bactericidal activities of perfused livers.

The relative roles of Kupffer cells, complement, and specific antibody in liver antimicrobial activities were investigated by using a rat liver perfusion model. Normal livers trapped an average of 60% of Salmonella typhimurium in a single pass and in the presence of plasma killed more than 60% of these organisms in 30 min. Livers depleted of Kupffer cell function by silica treatment had significantly less bactericidal ability (ca. 15%) in the presence of plasma, showing that viable Kupffer cells are required for optimal antimicrobial activity. To determine the importance of complement in Salmonella killing, plasma complement activity was inhibited by heating at 57 and 50 degrees C, zymosan absorption, chelation with disodium ethylenediaminetetraacetate (EDTA) and depletion of rat C3 by using specific immunoabsorbent. All treatments significantly reduced bactericidal activity in the perfused liver. Chelation of plasma with EDTA had no effect, suggesting that the alternate and not the classical pathway for complement activation was involved. Immune plasma alone was bactericidal. When immune plasma was heated, zymosan absorbed, or chelated with EDTA, bactericidal activity was inhibited in the perfused liver, but bacterial trapping increased. These results suggest that complement is required for bactericidal activity in perfused livers and that specific antibody only enhances bacterial trapping.

Animals↗
PubMed1979

The development and evaluation of a small ready-reference library collection for a rural practice: a case study.

A demonstration core collection of twenty-four ready-reference sources and five journals was selected cooperatively by a solo practitioner in rural Menifee County, Kentucky, and the University of Kentucky Medical Center Library Field Librarian to fit the ready-reference and current awareness information needs of a primary care solo rural practice in eastern Kentucky. The collection selections were systematically assessed by the physician to determine their utility in filling the practitioner's information needs with regard to his particular situation in terms of medical experience and level of training, available library and educational resources, and the type of health problems seen in his practice. This assessment showed that the Rural Demonstration Library Collection completely filled the information needs of the physician 66% of the time materials were consulted and filled his immediate information needs either completely or partially 82% of the time the collection was searched. This demonstration has shown that, under a specific set of circumstances, a librarian and a solo rural practitioner can effectively work together in identifying health sciences materials which fit the information needs of a solo rural practitioner. It suggests that cooperation between a librarian and a physician is important in meeting information needs.

Book Collecting↗
PubMed1977

Hepatic clearance of Salmonella typhimurium in silica-treated mice.

Scanning electron microscopy demonstrates that crystalline silica destroys liver Kupffer cells but has no other obvious deleterious effects on the liver. Silica-treated livers still retain the ability to trap large numbers of bacteria perfused through the portal vein even though the rate of clearance is well below normal. In vivo, silica treatment decreases the rate of bacterial clearance from the blood, alters the in vivo organ distribution of cleared bacteria, and decreases the mean lethal dose of Salmonella typhimurium over 100-fold. Cumulatively, the data indicate that silica treatment enhances susceptibility to gram-negative infection, probably by destruction of macrophages.

Animals↗
PubMedDate not supplied

Reasons for intracranial hypertension and hemodynamic instability during acute elevations of intra-abdominal pressure: observations in a large animal model.

In previous studies we reported that an acute elevation in intra-abdominal pressure (IAP) is responsible for the elevation in intracranial pressure (ICP) and mean blood pressure (MBP). Thus far, the reasons for the increased ICP during an acute elevation in IAP and the combined effects of increased IAP and ICP on hemodynamics have not been reported. Five large animals (swine) were studied. Each animal served as its own control. A subarachnoid screw was placed for ICP monitoring. The jugular vein, femoral vein, and femoral artery were cannulated. ICP, MBP, central venous pressure above (CVPA) and below (CVPB) the diaphragm, and PaC02 were monitored after a pneumoperitoneum with C02 was established at 5, 15, and 30 mm Hg of IAP. Cavography was performed to evaluate the morphology of the inferior vena cava at different increments of IAP. Measurements were obtained in reverse Trendelenburg (group 1), supine (group 2), and Trendelenburg (group 3) positions. Multiple regression analysis was used to examine the effects of IAP and positioning in separate models with different blood pressures as dependent variables. Increased IAP significantly increased CVPA, CVPB, ICP, and MBP. There were no changes in cerebral perfusion pressure. The change in position (from group 1 to group 3) significantly increased CVPA and decreased the CVPB. Cavograms performed on animals in the supine position with increased IAP showed a narrowing of the IVC at the level of the diaphragm. Increases in IAP will increase ICP and MBP without altering the cerebral perfusion pressure. A mechanical effect mediated by compression of the inferior vena cava at the level of the diaphragm with increased central venous pressure and decreased drainage from the lumbar plexus and central nervous system is responsible for this effect.

Abdomen↗
PubMedDate not supplied

alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences.

Complementary DNAs corresponding to the interferon (IFN)-induced messenger RNAs for histocompatibility locus antigens (HLA), metallothionein-II (MT2), 2',5'-oligoadenylate synthetase and about eight other proteins of unknown sequence have been isolated recently, and by interferon regulation of transcription has been demonstrated for several of the eight mRNAs, with a significant increase apparent in as little as 5 min. We now show that IFN-alpha treatment results in a three- to fivefold increase in the transcription of MT2 and HLA class I genes in human T98G neuroblastoma cells. Furthermore, comparison of regions upstream of the MT2A gene, two HLA genes and one HLA class II gene reveals a homologous sequence of approximately 30 base pairs (bp) which may be involved in regulating transcription of interferon-induced genes. Transcription of the mRNA for human MT2A is induced by glucocorticoids or metal ions and the regulatory elements have been mapped by promoter-fusion experiments. We now show that the rate of transcription of MT2A is the same on treatment with interferon or dexamethasone, but that the mRNA accumulates much faster with dexamethasone, indicating that post-transcriptional events are important in the latter case.

Base Sequence↗
PubMedDate not supplied

Hamstring muscle injuries among water skiers. Functional outcome and prevention.

Water skiing is associated with severe injuries to the proximal hamstring muscles. We wanted to define the mechanism of injury, describe the associated pathologic changes, determine the functional limitations of patients, and suggest measures to prevent injury. Twelve patients with water skiing-related hamstring injuries were included. Six patients were experienced skiers and six were novices. The mechanism of injury was identical in five of six novice skiers. Each sustained the injury while attempting to get up on one or two skis from a submerged position. In contrast, the expert skiers all sustained injury secondary to a fall while skiing. Physical examination documented evidence of complete or partial avulsion of the proximal hamstring muscle origins in all patients. In addition, six patients had magnetic resonance imaging or computed tomography scans that confirmed the location and extent of the tear. Convalescence ranged from 3 months to 1.5 years before the patient could return to vigorous activities. Seven patients (58%) returned to most of their preinjury sports, albeit at a lower level. Five patients (42%), all with complete disruptions, were unable to run or participate in sports requiring agility. Two of these patients required delayed surgical repairs because of persistent functional limitations.

Adolescent↗