Search PubMed⌕ Search

Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 181 records · Page 10Linked to original sources
PubMed1992

Pharmacokinetics and pharmacodynamics of oral diazepam: effect of dose, plasma concentration, and time.

Eleven healthy subjects received single oral doses of placebo, 2 mg diazepam, 5 mg diazepam, and 10 mg diazepam in a randomized four-way crossover study. Plasma diazepam levels, the Digit Symbol Substitution Test (DSST), and fraction of total electroencephalographic (EEG) amplitude falling in the sigma plus beta (13 to 31 Hz) frequency range were determined during the 12 hours after drug administration. Peak plasma diazepam concentration and area under the 12-hour curve were proportional to dose; time of peak was independent of dose. Baseline percentage of EEG amplitude falling in the 13 to 31 Hz range averaged 15.7% and did not differ among the four trials. The percentage of EEG amplitude falling in the 13 to 31 Hz range did not change over baseline with placebo or 2 mg diazepam but was increased 1/4 to 2 1/2 hours after 5 mg diazepam, (maximum, +7.3%) and 3/4 to 12 hours after 10 mg diazepam (maximum, +15.2%). The increase in the percentage of EEG amplitude falling in the 13 to 31 Hz range was highly correlated with plasma diazepam concentration. DSST scores for placebo and 2 mg diazepam were nearly identical. DSST decrements with 5 and 10 mg diazepam paralleled and were correlated with the changes in the percentage of EEG amplitude falling in the 13 to 31 Hz range and with plasma diazepam levels. Thus the EEG analysis provides objective quantitation of benzodiazepine central nervous system effects, in turn reflecting plasma levels and other clinical measures.

Administration, Oral↗
PubMed1992

Granulocyte-colony stimulating factor facilitates the restoration of resistance to opportunistic fungi in leukopenic mice.

Administration of recombinant human granulocyte-colony stimulating factor (G-CSF), which induces hemopoietic precursor cells to proliferate and differentiate into neutrophils, protected leukopenic mice infected with opportunistic fungi. Mice were injected with cyclophosphamide and were then subcutaneously (s.c.) or intravenously (i.v.) administered 15-120 micrograms G-CSF kg-1 day-1 for 3 days. The number of peripheral blood neutrophils in the G-CSF treated mice was significantly increased 48 h after G-CSF administration. All leukopenic mice infected with either Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus were significantly protected by treatment with the G-CSF. Moreover, G-CSF treatment caused a decrease in the number of viable yeasts in kidneys of Candida infected mice. These data suggest that prophylactic therapy with G-CSF may be useful against fungal infections in an immunocompromised host.

Animals↗
PubMed1992

Further characterization of the biological and pathogenic properties of erythromelalgia-related poxviruses.

Six isolates of erythromelalgia-related poxvirus (ERPV) were characterized with respect to host range, c.p.e. and inclusions, pock formation on chorioallantoic membrane (CAM), morphogenesis, serological reactivity, pathogenesis in animals and DNA restriction fragment profile. The results suggest that ERPV is either a new member of the Orthopoxvirus genus or a subspecies of ectromelia virus. Evidence is provided that (i) ERPV has a wide host range in vitro in which characteristic viral c.p.e. and inclusion bodies are induced; (ii) ERPV, unlike ectromelia virus, causes the formation of tiny greyish-white pocks on CAM both at 34 degrees C and 39 degrees C; (iii) eosinophilic A-type inclusions of ERPV do not contain viral particles; (iv) ERPV isolates are neutralized by both rabbit anti-vaccinia virus and mouse anti-ectromelia virus sera, but not vice versa; (v) young rabbits are not susceptible to ERPV by skin and/or corneal scratch infection even though ERPV is lethal for mice by intraperitoneal inoculation; (vi) the HindIII and SalI fragment profiles of ERPV P-4 DNA are similar to, but obviously different from, those of Chinese ectromelia virus. These biological and pathogenic characteristics of ERPV are distinguishable from those of other members of the genus Orthopoxvirus currently described in the literature.

Animals↗
PubMed1992

Environmental risk factors in endemic pemphigus foliaceus (Fogo selvagem). "The Cooperative Group on Fogo Selvagem Research".

Endemic pemphigus foliaceus or Fogo selvagem (FS) is an epidermal organ-specific autoimmune disease mediated by autoantibodies. Individuals at risk are peasants who live and work on farms located in the interior of certain endemic states of Brazil. This case-control study compares a group of 52 FS patients with 52 patients suffering from other dermatoses admitted and followed at the hospital for pemphigus (Hospital do Penfigo) in the city of Goiania, state of Goias. Patients and controls matched 1:1 by age, sex, and occupation were examined by two dermatologists at the time of admission and asked to respond to a prepared questionnaire. This questionnaire concerned current and past (1 and 5 years) exposure to environmental risk factors. The following risk factors were assessed: black fly bites, presence of rodents at home, exposure to cereal dust, exposure to fumes or dust released by tree and shrub removal, and exposure to insecticides. Relative risks were estimated from tabulated data by the odds ratio and tested for significance by the chi-square test. The 95% confidence interval for the odds ratio was also calculated for each of the risk factors. The only risk factor showing an odds ratio significantly different from one was exposure to simuliidae bites (odds ratio 4.7, p less than 0.001). This study reinforces the hypothesis that chronic exposure to black fly antigens may precipitate IgG4 antibody formation in predisposed individuals. These antibodies in turn may cross-react with epidermal antigens and cause acantholysis and the clinical expression of the disease known as FS.

Adolescent↗
PubMed1992

Pregnant women with endemic pemphigus foliaceus (Fogo Selvagem) give birth to disease-free babies.

Endemic pemphigus foliaceus (PF), also known as Fogo Selvagem (FS), is an organ-specific autoimmune disease mediated by autoantibodies. These autoantibodies are disease specific, predominantly restricted to the IgG4 subclass, and pathogenic, as demonstrated by passive transfer studies. In contrast to pemphigus vulgaris, neonatal skin disease does not appear to occur in babies born to mothers with non-endemic PF or FS. In the present study we have examined 19 mother/neonate pairs where the mother had documented FS. Mothers and neonates were examined soon after delivery and tested by immunofluorescent (IF) techniques for FS autoantibodies either in circulation (mothers' sera or babies' cord blood) or bound to the neonatal epidermis. All neonates included in this study were born with normal skin. Twelve biopsies from 17 neonates showed negative direct IF using both FITC-antihuman IgG or monoclonal anti-IgG subclass antibodies. In five biopsies the epidermal ICS of the babies showed weak staining. In 10 of the 19 cord sera tested, FS IgG autoantibodies were undetectable; in nine, these autoantibodies were present in low titers (less than 1:40). The sera of the mothers showed higher titers of FS autoantibodies, and IgG4 was the predominant IgG subclass autoantibodies. It appears that human placenta may modulate the expression of disease in the newborn by operating as a "biologic immunoadsorbent" of pathogenic autoantibodies.

Adult↗
PubMed1992

MRI in migraineurs.

Forty-six migraineurs and 69 age- and sex-matched controls referred for MRI scans of the brain were evaluated for the incidence of intracranial pathology. Axial long TR/short TE and long TR/long TE and sagittal short TR/short TE scans were performed in all patients. Enhancement with Gd-DTPA was performed in all controls and in nine migraineurs. Six of 46 (13%) of the migraineurs had white matter lesions versus three of 69 (4.3%) of the controls. The white matter lesions in migraineurs were seen in a younger age group than in the controls. These findings agree with recent MRI studies. Ischemia or an immune-based white matter demyelination are possible mechanisms for the white matter lesions.

Adolescent↗
PubMed1992

Genetic control of macrophage susceptibility to infection by Legionella pneumophila.

Legionella pneumophila readily grows in cultures of thioglycollate (TGC)-induced macrophages (MPs) from A/J mice, but not in MPs from BALB/c mice or other mouse strains. In the present study, the growth of Legionella pneumophilia in MPs from A/J and BALB/c mice, as well as hybrids of the two strains and back-crossed mice, was investigated to determine whether the permissiveness of growth of these bacteria was due to an inherited trait of the MPs. The MPs from all A/J mice supported the growth of Legionella, regardless of whether they were obtained from TGC or casein injected donors, but the cells from the mice given TGC supported growth of L. pneumophila much better than cells from mice injected with casein. Furthermore, MPs obtained from all BALB/c mice treated with either TGC or casein were nonpermissive for the growth of L. pneumophila. MPs from approximately 46% of the back-crossed ACF1 to A/J mice were permissive for L. pneumophila growth, while MPs from all ACF1 to back-crossed BALB/c mice were found to be nonpermissive. MPs from approximately 19% of ACF2 mice were permissive for L. pneumophila. Killing activities of MPs using temperature sensitive mutants of Salmonella typhimurium were variable and did not correlate with permissiveness or nonpermissiveness for growth of L. pneumophila.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cyclic AMP inhibition of lipopolysaccharide-induced restriction of Legionella pneumophila growth in macrophage cultures.

The mechanism of the effects of lipopolysaccharide (LPS) on macrophages in terms of replication of intracellular facultative bacteria is unclear. It was found in the present study that the anti-Legionella pneumophila activity induced by LPS in macrophages from susceptible A/J mice was reversed in vitro by dibutyryl cyclic AMP (DcAMP). A 24-h pretreatment of murine thioglycolate-elicited macrophages with LPS resulted in an enhanced ability of these cells to inhibit the intracellular growth of L. pneumophila. This anti-L. pneumophila activity of macrophages induced by LPS was inhibited when DcAMP (10(-3) to 10(-5) M) was present during preincubation with LPS. The addition of DcAMP to the cultures was more effective before LPS treatment than after treatment. The effect of DcAMP was dose dependent. The secretion and production of acid phosphatase by LPS-activated macrophages were also inhibited by the addition of DcAMP before LPS treatment. Furthermore, the anti-L. pneumophila activity of macrophages induced by LPS could also be reversed in vitro by treatment with prostaglandin E2, colchicine, isoproterenol, theophylline, or hydrocortisone, all of which are known to increase the intracellular levels of cyclic AMP in various tissues. These observations indicate that the anti-L. pneumophila activity induced by LPS treatment can be modified by mechanisms involving cyclic nucleotide metabolism.

Animals↗
PubMed1992

Differential morphologic and metabolic alterations in permissive versus nonpermissive murine macrophages infected with Legionella pneumophila.

Legionella pneumophila infection of macrophages from permissive guinea pigs and from A/J mice compared with infection of cells from nonpermissive BDF1 mice was studied by electron microscopy. The cells from the BDF1 mice were nonpermissive for legionella growth in vitro and showed few if any bacteria in phagosomes by electron microscopic examination. Similar electron micrographic examination of macrophages from A/J mice permissive for legionella growth showed numerous intact intracellular bacteria within 24 to 48 h of culture and the transition of intracellular bacteria from localization in a few large vacuoles early in the course of infection to later localization in areas surrounded and studded by ribosomes. These electron microscopic observations were similar to those seen in the case of guinea pig macrophages infected with legionellae. Biochemical studies of macrophages from permissive versus nonpermissive animals showed little or no differences in respiratory burst and lysosomal enzyme activity for macrophages from all animals tested. However, when zymosan was used as a stimulant, macrophages from the nonpermissive mouse strain produced a larger amount of H2O2 and O2- than did cells from permissive guinea pigs or A/J mice. However, legionella vaccine itself induced no detectable or very little H2O2 and O2- in macrophages tested from any source. These results suggest that permissiveness of A/J mouse macrophages to legionella growth may involve mechanisms similar to those occurring in guinea pig macrophages in terms of morphologic and possibly even biochemical events. The relatively higher production of reactive oxygens by BDF1 mouse macrophages in response to zymosan correlated with nonpermissiveness for legionella growth, although further analysis is necessary to link these observations.

Animals↗
PubMed1992

Infection of macrophages with Legionella pneumophila induces phosphorylation of a 76-kilodalton protein.

Infection of peritoneal macrophages from susceptible A/J mice with Legionella pneumophila induced phosphorylation of a 76-kDa protein. The phosphorylation occurred when macrophages were infected with a virulent strain of L. pneumophila but did not occur when they were infected with an avirulent strain or with other bacteria such as either Pseudomonas aeruginosa or Salmonella typhimurium. Also, no phosphorylation of this protein was observed when macrophages were stimulated with either lipopolysaccharide or phorbol myristate acetate. However, phosphorylation did occur in macrophages infected with a virulent strain of L. pneumophila and treated with either erythromycin to inhibit growth or with cytochalasin D to inhibit uptake of L. pneumophila by macrophages. These results support the view that phosphorylation of this protein occurs during the early phases of interaction between L. pneumophila and macrophages. The role of this specific protein in the recognition, intracellular uptake, and growth of L. pneumophila in permissive macrophages remains to be clarified.

Animals↗
PubMed1992

An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1.

We isolated and molecularly cloned a human immunodeficiency virus type 1 (HIV-1) strain (89.6) which is unusual because it is both macrophage-tropic and extremely cytopathic in lymphocytes. Moreover, this is the first well-characterized infectious molecularly cloned macrophage-tropic HIV-1 strain derived from peripheral blood. HIV-1 89.6 differs markedly from other macrophage-tropic isolates within the envelope V3 region, which is important in determining cell tropism and cytopathicity. HIV-1 89.6 may thus represent a transitional isolate between noncytopathic macrophage-tropic viruses and cytopathic lymphocyte-tropic viruses.

Amino Acid Sequence↗
PubMed1992

Anterior cruciate ligament injury: MR imaging diagnosis and patterns of injury.

The anterior cruciate ligament (ACL) is an important stabilizer of knee motion. Injury of the ACL can lead to substantial disability; an accurate diagnosis of ACL injury is vital in both short-term and long-term patient care. Magnetic resonance (MR) imaging has emerged as the study of choice to evaluate the status of the ACL and other associated structures in the knee. Sagittal MR images have been commonly used in the evaluation of the ACL. However, the authors believe that coronal and axial imaging planes can add useful information about ACL injury and, thus, lead to improved accuracy and confidence regarding diagnosis. Multiplanar imaging can readily demonstrate meniscal, ligamentous, and bone marrow injuries that commonly occur with the most frequent mechanisms of ACL injury. These mechanisms, in order of frequency, include internal rotation and valgus stress, hyperextension, and varus stress with external rotation. An understanding of these mechanisms is helpful in the MR diagnosis of ACL injury.

Anterior Cruciate Ligament Injuries↗
PubMed1992

Contrasting effects of THC on adult murine lymph node and spleen cell populations stimulated with mitogen or anti-CD3 antibody.

Marijuana, and specifically its psychoactive component, THC, can up or down regulate lymphocyte proliferation in murine spleen cells depending in part on the method used to stimulate the cells. This study identifies a difference in THC induced disregulation using cells derived from two different secondary lymphoid organs, the spleen and the lymph node. It was found that THC treatment of mitogen (concanavalin A or phytohemagglutinin) stimulated cells derived from either organ resulted in suppression of the proliferative response. In contrast, spleen cells stimulated with anti-CD3 antibody and treated with low doses of THC displayed an enhanced proliferation whereas the response in lymph nodes did not change. The cell type involved with this THC immunoenhancement in spleen cells was found to be the Ly2 cell. Further differences in the THC modulation of Ly2 spleen cells as compared to lymph node cells were noted following stimulation with PHA. Proliferation of Ly2 cells of splenic origin was inhibited with low doses of THC whereas the Ly2 cells of lymph node origin were more resistant to this drug induced suppression. This study, therefore, demonstrates differences in the immunomodulatory capability of THC dependent upon the organ source of the lymphocytes.

Animals↗
PubMed1992

Continuous infusion of endotoxin depresses splenic blastogenesis.

Continuous infusion of a sublethal dose of bacterial endotoxin into rats via an implanted osmotic pump markedly affected the blastogenic responsiveness of spleen cells to specific endotoxin as well as to the nonspecific mitogens Con A, PHA or PWM. There was also a marked alteration in lymphoid cell type and number in the spleen of the rats after continuous infusion of endotoxin, with a marked increase in plasma cell infiltration and germinal center formation. There was no significant alteration in glucocorticoid steroid levels. Control rats given saline only for a period of seven days via an implanted pump showed no or minimal effect for the first 5 days and then a delayed depression of blastogenic responses to LPS and to Con A, but this time lag contrasted markedly to the much earlier unresponsiveness of splenocytes from rats infused with endotoxin. Only a slight to moderate cellular infiltration occurred in the spleen of control rats implanted with a pump infusing saline only or an empty pump. Thus endotoxin infusion in a continuous manner via an implanted pump accounted for the early and marked suppression of responsiveness, as well as alteration in spleen size and cellularity.

Animals↗
PubMed1992

Enhanced growth of Legionella pneumophila in tetrahydrocannabinol-treated macrophages.

Legionella pneumophila is an opportunistic intracellular pathogen that infects macrophages, both in vivo and in vitro. Tetrahydrocannabinol is a major psychoactive component of marijuana and can affect the functional activity of macrophages. In the present study, it was found that the treatment of macrophage cultures from permissive A/J mice with THC enhanced the growth of Legionella in these cells. Legionella grew much better in macrophages treated with low doses of THC, which caused no alteration in the number or viability of macrophages, as compared with growth in untreated cells. Furthermore, lipopolysaccharide-treated A/J mouse macrophages restricted the growth of Legionella, but this growth restriction was overcome by the addition of THC to LPS-treated macrophage cultures after infection. Thus, it is apparent that THC has the ability to enhance the growth of the intracellular opportunistic pathogen Legionella that grows in A/J mouse macrophages.

Animals↗
PubMed1992

Continuous endotoxin infusion suppresses rat spleen cell production of cytokines.

Endotoxin, i.e., lipopolysaccharides, was continuously infused into rats at a nonlethal dose by means of an implanted osmotic pump for up to 2 weeks. The pump was connected to the jugular vein by a polyethylene catheter. Administration of endotoxin via the pump compromised the ability of spleen cells to produce the lymphokines interleukin 1 and tumor necrosis factor after stimulation in vitro with endotoxin. In addition, the ability of the spleen cells to produce alpha/beta-interferon in response to endotoxin in vitro was also examined, as was the capability of the spleen cells to produce gamma-interferon following stimulation with concanavalin A. Suppression of the expected interleukin 1 and tumor necrosis factor production by spleen cells from rats continuously infused with endotoxin was observed. There was also a moderate effect on interferon production, but this was much less. These results provide further findings indicating the unresponsiveness of spleen cells to lipopolysaccharides, as well as to a nonspecific plant mitogen, following continuous infusion of endotoxin into rats via an implanted osmotic pump. Additional studies are needed to determine the mechanisms involved in such suppression.

Animals↗
PubMed1992

Enhanced growth restriction of Legionella pneumophila in endotoxin-treated macrophages.

Macrophages from A/J mice are permissive for growth of Legionella pneumophila, an intracellular opportunistic pathogen that grows preferentially in macrophages. Macrophages from other mouse strains are highly resistant to growth of Legionella. In the present study, it was found that macrophages from A/J mice are readily activated by pretreatment with lipopolysaccharide (LPS), so that the cells do not permit Legionella to replicate in vitro, as occurs when untreated macrophages from A/J mice are cultured with these organisms for 48 hr. The augmentation of Legionella growth inhibition by LPS-activated macrophages from nonpermissive BDF1 mice also occurred. After in vitro infection, there was a 1000-fold increase in the number of Legionella in A/J macrophages and approximately a 10-fold increase in BDF1 macrophages, but LPS treatment of macrophages from either strain resulted in marked growth restrictions. This suppression was both dose dependent as well as dependent upon the time of addition of the LPS to the macrophages. Furthermore, the lipid A component of LPS was found to be as effective as the intact LPS in activating macrophages to inhibit the intracellular growth of Legionella. Further studies concerning the mechanisms involved are clearly warranted and in progress.

Animals↗