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Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 163 records · Page 9Linked to original sources
PubMed1993

Transient lateral patellar dislocation: diagnosis with MR imaging.

OBJECTIVE: Transient lateral patellar dislocation is frequently difficult to diagnose accurately on the basis of clinical findings. Accordingly, we studied the MR findings in 26 cases to determine if MR imaging is useful in establishing the diagnosis. MATERIALS AND METHODS: A retrospective review of 1450 MR examinations of acutely injured knees was performed to determine the MR findings resulting from transient lateral patellar dislocation. A distinctive constellation of MR findings reflecting the known mechanism of injury indicative of transient lateral patellar dislocation was found in 26 patients. Patellar dislocation was not clinically suspected before imaging in 19 (73%) of these 26 patients; most patients had been referred for suspected injury of the cruciate ligaments or menisci. Axial, sagittal, and coronal MR images were obtained in all patients, and all had clinical follow-up. Correlation of MR findings with surgical findings was possible in six. RESULTS: Specific components of the constellation of MR findings included disruption or sprain of the medial retinaculum in 25 (96%) of 26 patients, lateral patellar tilt or subluxation in 24 patients (92%), lateral femoral condyle contusion in 21 patients (81%), osteochondral injury in 15 patients (58%), and joint effusion in all 26 patients (100%). Concomitant injury to major ligaments or menisci was present in eight (31%). CONCLUSION: Our findings suggest that patients with transient lateral patellar subluxation have a distinctive constellation of MR findings that can be used to distinguish this entity from other common knee injuries.

Adolescent↗
PubMed1993

Legionella pneumophila induced tumor necrosis factor production in permissive versus nonpermissive macrophages.

The ability of an opportunistic intracellular bacterial pathogen, Legionella pneumophila, to induce tumor necrosis factor (TNF) in macrophages from susceptible A/J or resistant BDF1 and BALB/c mice was determined. Cultures of peritoneal elicited macrophages from these mouse strains produced TNF in response to the Legionella. The TNF levels produced by the macrophages stimulated with either heat-killed Legionella vaccine or lipopolysaccharide were similar and dose dependent, although the amount of TNF produced by macrophages from permissive A/J mice was 2- to 4-fold higher than that produced by macrophages from the nonpermissive mice. Similar differences in TNF levels occurred when macrophages from either permissive or non-permissive mice were infected with viable Legionella. The TNF levels produced by the A/J mouse macrophages increased as a function of time after infection, with a peak of activity on Day 1 or 2, depending upon the initial concentration of the bacteria. Infection of the A/J mouse macrophages with avirulent Legionella resulted in induced levels comparable to those induced by a virulent strain. Although it is widely believed that TNF production by mouse macrophages is related to resistance to infections, the results of this study did not show a relationship between TNF production by macrophages in vitro and resistance versus susceptibility of the macrophage donor mouse strain to Legionella infection.

Animals↗
PubMed1993

Differential effects of ethanol on permissive versus nonpermissive macrophages infected with Legionella pneumophila.

The effect of ethanol treatment was studied in terms of effect on permissive versus nonpermissive macrophages for growth of Legionella pneumophila, which is an intracellular bacterium causing pneumonia in immunocompromised patients. It was found that ethanol treatment of permissive macrophages from L. pneumophila-susceptible A/J mice evinced a decrease in replication of the bacteria compared with nontreated infected macrophages. Whereas there was more than a 100-fold increase in Legionella growth over a 48-hr culture period in infected A/J mouse macrophages, treatment of the macrophages with 0.5% ethanol depressed the ability of the macrophages to be infected by Legionella approximately 45%. A lower concentration of ethanol had a lesser effect but still resulted in inhibition of the ability of the cells to replicate Legionella. In contrast to ethanol-induced inhibition of the A/J mouse macrophages to replicate Legionella, macrophages from Legionella-resistant BALB/c mice, which only minimally replicated Legionella (i.e., only a 2-fold increase or less over a 48-hr replicated Legionella (i.e., only a 2-fold increase or less over a 48-hr period), treatment with ethanol resulted in their greater replication of the Legionella. This effect was most marked with the 1.0% concentration of ethanol after 7 days of pretreatment, while the 0.5% and 0.1% concentrations of alcohol caused less enhancement of bacterial growth in the cells, but these concentrations still had a significant enhancement effect. Thus, ethanol had differing effects on growth of the opportunistic intracellular bacterium Legionella in macrophages from permissive versus nonpermissive mice. Studies on the mechanisms involved are in progress.

Animals↗
PubMed1993

Delta 9-tetrahydrocannabinol injection induces cytokine-mediated mortality of mice infected with Legionella pneumophila.

Delta 9-Tetrahydrocannabinol (THC) injection modulates immune cell function, but the significance of this in altering host resistance to infection is not understood. In addition, exposure to THC and other drugs of abuse during infection is associated with an acute mortality syndrome. We examined the effect of THC injection on the survival of mice infected with Legionella pneumophila (Lp). Mice given two injections of THC (8 mg/kg)-one 24 hr before and the second 24 hr after a sublethal Lp infection-experienced acute collapse and death. The drug injection after infection caused death; deaths occurred within 30 min after the injection, and neither one nor two drug injections before infection resulted in death. The THC-induced mortality resembled cytokine-mediated shock in both kinetics and symptoms; therefore, sera from drug-treated animals were measured for the acute-phase cytokines tumor necrosis factor (TNF) and interleukin 6 (IL6). The level of each cytokine was significantly elevated by THC treatment, suggesting a role in the observed mortality. To directly test this role, mice were administered a single injection of either anti-TNF alpha, anti-IL6, or a mixture of anti-IL1 alpha and -IL1 beta antibodies 1 hr before the second THC injection. Results showed that each antibody treatment protected the mice, with anti-IL6 being the most effective. Fluctuations in blood granulocytes levels also supported a role of acute-phase cytokines in THC-induced mortality. These results show that THC injection increases the blood levels of acute-phase cytokines in infected animal and that these elevated levels, at least in part, account for the mortality induced by THC injection.

Acute-Phase Proteins↗
PubMed1992

A homolog of the proteasome-related RING10 gene is essential for yeast cell growth.

Proteasomes are intracellular protein complexes displaying multiproteolytic activities. These complexes have been implicated in the antigen degradation process that generates peptides associated with the major histocompatibility complex (MHC) class-I molecule. RING10 and RING12 are genes encoded by the class-II region of the human MHC that have sequence homology to proteasome-encoding genes. We have identified a yeast gene, called PRG1, that encodes a protein predicted to contain 55.6% sequence identity to 80% of the RING10 gene product. Genomic disruption of PRG1 revealed that it is essential for yeast cell growth. These data strongly indicate that the antigen-processing system present in vertebrates evolved from a basic cellular process present in all organisms.

Amino Acid Sequence↗
PubMed1992

Differing macrophage and lymphocyte roles in resistance to Legionella pneumophila infection.

Similar to guinea pig macrophages and human monocytes, macrophages from the peritoneal cavity of thioglycolate pretreated A/J mice are permissive for growth of Legionella pneumophila. In contrast, macrophages from BDF1 mice are not permissive for L. pneumophila. Lymphocytes from A/J and BDF1 mice proliferated in response to Legionella Ag but guinea pig lymphocytes did not. Also, splenocyte cultures from A/J mice treated with either Con A or Legionella vaccine produced supernatants which induced A/J macrophages to restrict Legionella growth, but guinea pig splenocyte culture supernatants obtained after stimulation with L. pneumophila vaccine did not induce Legionella growth restriction activity by guinea pig macrophages. Murine rIFN-gamma but not rIFN-alpha markedly inhibited growth of Legionella in A/J mouse macrophages and monoclonal anti-IFN-gamma antibody neutralized the anti-Legionella activity of culture supernatants from A/J mouse splenocytes responding to Legionella Ag. From these data, IFN-gamma appears to be an important factor in anti-Legionella activity of Ag-activated mouse splenocyte culture supernatants. Cyclosporin A, when given to either A/J or BDF1 mice, reduced the proliferation responses of splenocytes to T cell mitogens and also decreased the IFN production of A/J spleen cells to Legionella Ag. In addition, drug treatment decreased the resistance of A/J mice to Legionella infection as shown by an increase in the number of viable bacteria in the liver. However, injection of drug treated mice with lymphokine-rich splenocyte culture supernatant reconstituted the resistance of these animals. These results suggest an important role for lymphocyte activation and lymphokine production in the resistance of A/J mice to Legionella infection. The greater resistance of BDF1 mice, however, may result from nonpermissive macrophages and responsive lymphocytes. In the case of guinea pigs, susceptibility to Legionella infections may result from both the permissive nature of the macrophages and the relatively unresponsive nature of the lymphocytes in these animals.

Animals↗
PubMed1992

Clinical pharmacology of adinazolam and N-desmethyladinazolam mesylate following single intravenous infusions of each compound in health volunteers.

The tolerability, pharmacokinetics and pharmacodynamics of adinazolam and N-desmethyladinazolam (NDMAD) were assessed following intravenous infusions of 5, 10, 15, and 20 mg adinazolam mesylate, 10, 20, 30 and 40 mg NDMAD mesylate, and placebo. Six subjects per dose level received treatments in a double-blind crossover design. No clinically significant changes were seen in blood pressure, pulse, respiration, or clinical laboratory parameters. Untoward effects typical of benzodiazepines were observed almost exclusively after NDMAD administration. Adinazolam and NDMAD pharmacokinetics were dose-independent. NDMAD clearance was 50% of the value for adinazolam. Adinazolam and NDMAD administrations increased uric acid clearance and decreased plasma uric acid. Adinazolam administration had no significant effect on psychomotor performance. NDMAD administration produced dose related decreases in performance; 286 ng/ml NDMAD produced a 50% decrease in DSST. These results confirm that adinazolam and NDMAD both produce uricosuria and definitively show that adinazolam is devoid of benzodiazepine-like effects at therapeutic concentrations; NDMAD mediates these effects. Uricosuric activity is present for both compounds, but the relative potencies are still unknown.

Adolescent↗
PubMed1992

The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state.

We gave 12 healthy male volunteers 1 mg of alprazolam or placebo on three occasions after a standard breakfast in a double-blind, randomized, single-dose, three-way crossover study. The three trials were: (a) oral alprazolam and sublingual placebo; (b) oral placebo and sublingual alprazolam; (c) placebo by both routes. Plasma alprazolam concentrations during 24 h after each dose were measured by electron-capture gas-liquid chromatography. Peak plasma concentrations were reached later after sublingual than oral dosage (2.8 vs 1.8 h, P less than 0.01). Other kinetic variables were not significantly different: peak plasma concentration, 11.3 vs 12.0 ng.ml-1; elimination half-life, 12.5 vs 11.7 h; and total area under the plasma concentration versus time curve, 197 vs 186 h.ng.ml-1. Pharmacodynamic measures showed that sublingual and oral alprazolam both produced sedation, fatigue, impaired digit symbol substitution, slowing of reaction time, and impairment of the acquisition and recall of information. These changes were initially observed at 0.5 h after dosage and lasted up to 8 h. In general the two routes were significantly different from placebo but not from each other.

Administration, Oral↗
PubMed1992

Delta 9-tetrahydrocannabinol suppresses concanavalin A induced increase in cytoplasmic free calcium in mouse thymocytes.

It has been shown that delta-9-tetrahydrocannabinol (THC) suppresses thymocyte, lymph node, and splenic lymphocyte proliferation in response to a mitogenic stimulus. It has also been reported that increases occur in the cytosolic free calcium concentration (Ca2+) in mitogen treated lymphocytes. In an attempt to understand a portion of the molecular basis of the THC induced suppression of lymphocyte proliferation, we have examined the effects of THC on the Concanavalin A (Con A) induced cytosolic free Ca2+ mobilization in mouse thymocytes measured by fluorescent Ca2+ probes and spectrofluorometry. The results show that a 10 minute pretreatment with THC suppresses the normal rise in intracellular free Ca2+ in response to Con A. A THC concentration of 4 micrograms/ml (13 microM) was suppressive and the drug vehicle, DMSO, had no effect. In addition, we found that THC pretreatment did not inhibit the binding of FITC labeled Con A to the thymocytes suggesting that the drug did not interfere with lectin binding to the cell surface. To further define the nature of the Ca2+ response affected by THC, mouse thymocytes containing fura-2 were exposed to Con A either in the presence or absence of Ca(2+)-containing medium. It was observed that THC abrogated both intracellular release (measured in Ca(2+)-free medium) as well as extracellular Ca2+ influx. These results suggest that a portion of the proliferation defect in THC treated lymphocytes may be related to a drug induced inhibition of Ca2+ mobilization that normally occurs following mitogen treatment.

Aminoquinolines↗
PubMed1992

Splenocyte blastogenesis suppressed in rats implanted with an osmotic pump.

Rats implanted subcutaneously with an empty osmotic pump connected by a polyethylene catheter to a jugular vein for 5 to 10 days evinced a decreased splenocyte responsiveness to blastogenic stimulation in vitro to bacterial lipopolysaccharide, a known B cell stimulator, as well as to the plant mitogens pokeweed mitogen (PWM), a known stimulator of T and B cells, and Concanavilan A, a known T cell stimulator. The surface of the implanted pumps became infiltrated with lymphoid cells, especially macrophages. Suppression of blastogenic responsiveness after implantation for 10 days with an empty pump or even a pump dispensing pyrogen free saline only in a continuous manner was nearly as marked as that which occurred at 2-5 days after continuous infusion with endotoxin. These depressed blastogenic responses, although less, were also evident when rats were implanted with a catheter into a jugular vein connected by means of a swivel to either an empty pump or one dispensing pyrogen free saline. Suppression of blastogenic responsiveness was not related to alteration in serum complement or corticosteroid levels. Since administration of immunomodulatory substances systemically to individuals often involves implantation of an osmotic pump, investigation into the mechanisms of lymphoid cell suppression associated with an implanted pump itself has potential significance.

Animals↗
PubMed1992

Inhibition by delta-9-tetrahydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages.

Suppression by delta-9-tetrahydrocannabinol (THC) of tumor necrosis factor (TNF) production by macrophages has not been reported previously. The present study evaluated the effect in vitro of THC on soluble TNF-alpha production by cultured murine peritoneal macrophages. THC at 5 or 10 micrograms/ml added to medium [RPMI 1640 containing 10 ng LPS/ml, mouse IFN-gamma (100 u/ml), and 0.5% bovine serum albumin (BSA)] used to induce TNF significantly decreased TNF-alpha production by BALB/c mouse macrophages. Macrophages pretreated with THC at 0.1, 0.5, or 1.0 micrograms/ml in protein-free medium for 3 h at 37 degrees C, prior to TNF induction, also showed a decreased ability to produce TNF-alpha in a dose-dependent manner. Increasing the protein concentration from 0.5 to 5% BSA in the medium which was used to induce TNF prevented the inhibitory activity of THC. Human peripheral blood adherent cells treated with THC-containing medium produced less TNF-alpha than controls that were not exposed to THC. Thus, our data provide evidence that THC can inhibit TNF production by mouse and human macrophages. The drug's activity is concentration dependent and is related to the amount of serum protein in the medium used to induce this cytokine.

Animals↗
PubMed1992

Cocaine augments proliferation of human peripheral blood T-lymphocytes activated with anti-CD3 antibody.

Previously we observed that cocaine can suppress the phytohemagglutinin-induced proliferation of cultured, purified human T-lymphocytes. However, because the receptor activation pathways stimulated by this mitogen are not fully understood, we decided in the present study to examine the effects of cocaine on T-lymphocyte cultures stimulated with the anti-CD3 antibody which is known to stimulate these cells through the T-cell receptor complex. The results show that cocaine augments T-lymphocyte proliferation to anti-CD3 stimulation at drug concentrations observed in the blood of cocaine abusers. This augmentation was dose dependent reaching a plateau at a concentration above 0.75 microM. The amount of interleukin-2 (IL-2), as measured by ELISA, in the supernatants of T-cell cultures and the level of cytosolic free-calcium (Ca2+) mobilization in the T-cells were also increased at approximately the same concentrations that increased proliferation. Cocaine treatment alone had no effects on proliferation, IL-2 production, or Ca2+ mobilization. These results suggest that cocaine augments proliferation of human T-lymphocytes when the cells are activated through the T-cell receptor complex by increasing cytosolic Ca2+ mobilization and subsequent IL-2 production.

Adjuvants, Immunologic↗
PubMed1992

Differing effects of delta-9-tetrahydrocannabinol (THC) on murine spleen cell populations dependent upon stimulators.

Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, can suppress the immune response, both in vitro and in vivo. In the present study, THC was found to either up-regulate or down-regulate lymphocytes depending on the method of stimulation. When the mitogens concanavalin A (Con A) or phytohemagglutinin (PHA) were used to stimulate THC-treated splenocytes, a down-regulation of lymphocyte proliferation occurred, which reflected lower T-cell numbers in general and Ly2 positive cells specifically. When splenocytes were stimulated directly by using anti-CD3 antibody it was found that low concentrations of THC enhanced lymphocyte proliferation, T-cell numbers in general, and Ly2 cells specifically. These results emphasize that THC can either enhance or suppress aspects of the immune response, depending on the specific immune stimulants used and the specific parameter of immunity measured.

Adjuvants, Immunologic↗