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Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 235 records · Page 13Linked to original sources
PubMed1990

Macrophage-tropic strains of human immunodeficiency virus type 1 utilize the CD4 receptor.

To characterize the role of CD4 in human immunodeficiency virus type 1 (HIV-1) infection of macrophages, we examined the expression of CD4 by primary human monocyte-derived macrophages and studied the effect of recombinant soluble CD4 and anti-CD4 monoclonal antibodies on HIV-1 infection of these cells. Immunofluorescence and Western blot (immunoblot) studies demonstrated that both monocytes and macrophages display low levels of surface CD4, which is identical in mobility to CD4 in lymphocytes. Recombinant soluble CD4 and the anti-CD4 monoclonal antibody Leu3a blocked infection of macrophages by three different macrophage-tropic HIV isolates, and the cytopathic effects of HIV-1 infection were similarly prevented. Dose-response experiments using a prototype isolate which replicates in both macrophages and T lymphocytes showed that recombinant soluble CD4 inhibited infection of macrophages more efficiently than in lymphocytes. These results indicate that CD4 is the dominant entry pathway for HIV-1 infection of macrophages. In addition, recombinant soluble CD4 effectively blocks HIV-1 infection by a variety of macrophage-tropic strains and thus has the potential for therapeutic use in macrophage-dependent pathogenesis in HIV disease.

Antibodies, Monoclonal↗
PubMed1990

MR imaging of the normal and abnormal clivus.

We retrospectively reviewed 330 T1-weighted sagittal images, 80 T2-weighted sagittal images, and 83 gadopentetate-dimeglumine-enhanced scans of normal adults to determine the MR appearance of the normal adult clivus. MR images of 21 patients with an abnormal clivus (19 with tumor invasion and two with marrow reconversion) were also evaluated retrospectively and compared with those of the control group to assess MR features distinguishing the two groups. Our study revealed that a normal adult clivus consisted of low- and high-intensity portions mixed in various proportions on T1-weighted images. The low-intensity portion was isointense or hyperintense relative to the pons and always contained foci of bright signal intensity. The low-intensity tumor of a pathologic clivus tended to be hypointense relative to the pons (17/19), and was completely devoid of foci of bright signal intensity. The normal adult clivus was approximately isointense relative to the pons on T2-weighted images. Clival tumors were grossly hyperintense relative to the pons on T2-weighted images in 11 of 17 patients. In the remaining six patients, either a portion of or the entire lesion was isointense relative to the pons and, therefore, was not detectable on T2-weighted images. A normal adult clivus can enhance to some degree (19/83). Clival tumors were found to enhance intensely. A clivus of very low signal intensity (signal void) on T1- or T2-weighted images was always abnormal. The clivus with marrow reconversion was uniformly hypointense relative to the pons on T1-weighted images and isointense relative to normal marrow on T2-weighted images. The intensity patterns of the normal clivus on T1- and T2-weighted MR images change predictably with advancing age. Intensity patterns of abnormal clivi differ from those of normal clivi. When contrast material is used, normal and abnormal clivi generally show different patterns of enhancement.

Adult↗
PubMed1990

The premature infant home intervention program.

The Premature Infant Home Intervention Program, a collaborative effort of the Visiting Nurse Association of Cleveland and Rainbow Babies and Children's Hospital of Cleveland, is designed to provide family support and medical surveillance for high-risk premature infants, to ensure post-discharge wellbeing, and improve survival outcome during the first years of life.

Community Health Nursing↗
PubMed1990

Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis.

Low dose methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis. Current product recommendations accompanying MTX preparations advise against concurrent usage of nonsteroidal antiinflammatory drugs (NSAID), and adverse pharmacokinetic interactions have been reported with this combination. Six patients who were receiving MTX were studied with both oral and parenteral MTX, 10-25 mg/dose, without NSAID and with ibuprofen (2400 mg/day) and flurbiprofen (300 mg/day) for 6 weekly doses. Serum MTX levels were obtained at frequent intervals. Serum was separated and MTX analyzed using a radioimmunoassay (RIA). There was no observable interaction between MTX and either ibuprofen or flurbiprofen, with respect to the area under the curve per unit dose, Cmax, Cmax/dose, Tmax, and serum half-life. The pharmacokinetic indices were not significantly influenced by the route of administration.

Administration, Oral↗
PubMed1990

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Adult↗
PubMed1990

Alteration of rat splenocyte blastogenesis and interleukin-1 production following slow infusion of human tumor necrosis factor-alpha.

The bolus injection of tumor necrosis factor (TNF)/cachectin into rats has been reported to induce shock and tissue injury similar to catabolic states seen in cachexia. In the present study, we administered TNF/cachectin to rats by either bolus injection or slow infusion and analyzed the influence on splenocyte mitogen-induced proliferation and interleukin-1 (IL-1) production. Also, TNF administration was compared with lipopolysaccharide (LPS) injection and saline injection. Serum TNF levels were elevated by 30 min following the start of slow infusion, peaked at around 90 min, and remained elevated throughout the 3-h sampling. However, analysis of serum TNF following a bolus injection showed that TNF peaked earlier (30 min) but then declined over the next 2.5 h. LPS infusion resulted in a serum TNF peak at 60-90 min with a rapid decline to near baseline by the end of the 3-h sampling. Spleens were removed from rats following either 3 h of infusion or 3 h following bolus injection, and single-cell suspensions were prepared and analyzed in culture for lymphocyte proliferation to either concanavalin-A (con-A) or pokeweed mitogen (PWM). Adherent spleen cell cultures were also tested for IL-1-forming capacity in response to LPS. The slow infusion of TNF had a suppressive effect on splenic T lymphocyte responsiveness to con-A. This suppressive effect was not observed in the response to the T cell-dependent B cell mitogen PWM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types.

To characterize the host range of different strains of HIV-1, we have used four types of cells, primary monocyte-derived macrophages (MDM), primary PBL, a promonocyte cell line (U937), and a CD4+ T cell line (SUP-T1). These cells were infected with three prototype strains of HIV-1, a putative lymphocyte-tropic strain (IIIB), and two putative monocyte-tropic strains (SF162 and DV). Infections were monitored by assays for infectious virus, for cell-free and cell-associated viral antigen (p24), and for the proportion of cells infected by immunohistochemical staining. It was concluded that: (a) the use of four different cell types provides a useful biological matrix for distinguishing the tropism of different strains of HIV-1; this matrix yields more information than the infection of any single cell type. (b) A monocyte-tropic strain of HIV-1, such as strain SF162, shows a reciprocal host range when compared with a lymphocyte-tropic strain such as IIIB; strain SF162 replicates well in primary MDM but not in U937 or SUP-T1 cells, while strain IIIB replicates well in both U937 and SUP-T1 cells but not in MDM. (c) Both lymphocyte-tropic and monocyte-tropic strains of HIV-1 replicate well in PBL. (d) The promonocyte cell line, U937, and the T cell line, SUP-T1, differ markedly from primary cells, such as MDM and PBL, in their ability to support the replication of different strains of HIV-1; these cell lines cannot be used as surrogates for primary cells in host range studies of HIV-1 strains.

Antibodies, Monoclonal↗
PubMed1989

Enhancement of human monocyte function against Candida albicans by the colony-stimulating factors (CSF): IL-3, granulocyte-macrophage-CSF, and macrophage-CSF.

The effect of IL-3, granulocyte-macrophage (GM)-CSF and macrophage (M)-CSF on Candida albicans growth inhibition by human peripheral blood monocytes was investigated. By using a radiolabel microassay developed in our laboratory that makes use of the incorporation of [3H]glucose into residual C. albicans, we demonstrated that rGM-CSF and rIL-3 effectively enhanced human monocyte-mediated anticandidal activity. Incubation for 24 h with either GM-CSF or IL-3 significantly enhanced monocyte antifungal responses down to 0.01 U/ml. M-CSF, at higher concentrations of 10 U/ml, could also enhance monocyte function but to a smaller degree. None of the CSF interfered directly with fungal growth, even up to 1000 U/ml. Because IFN-gamma is also a known monocyte activator, its effect on monocytes was also assessed. Monocytes were first cultured in medium for several days and then further incubated with each of the cytokines. Monocytes aged in medium were found to lose their spontaneous anticandidal activity. Such aged monocytes did not develop anticandidal activity in response to IFN-gamma but did in response to GM-CSF or IL-3. To further elucidate this difference, fresh monocytes were continuously cultured with or without cytokines for 1 to 5 days before assessing their anticandidal activity. Monocytes cultured in IFN-gamma progressively lost their activity by 2 days but monocytes in GM-CSF or IL-3 maintained their high level of anticandidal activity throughout the whole length of culture. Therefore, GM-CSF and IL-3 not only enhanced fresh monocyte anticandidal activity, but maintained monocyte function for a longer period. These results suggest that GM-CSF and IL-3 may act on monocytes via a different pathway than does IFN-gamma.

Candida albicans↗
PubMed1989

Interleukins 1 and 2 production and responsiveness in the early stages of retroviral infections of mice.

Infection of BALB/c mice with the Friend leukemia complex (FLC) or its helper F-MuLV produced no major changes of IL 1 production and responsiveness but caused profound derangements of IL 2 homeostasis. IL 2 production by spleen cells was severely decreased from the early stages postinfection (pi). By Day 8 the effects of the two viral preparations were similar. Reminiscent of the kinetics of immunosuppression produced by the two viruses, subsequently the effects diverged: in the case of FLC, IL 2 accumulation became progressively lower, while F-MuLV-infected spleen cells produced approximately half the normal levels of IL 2 irrespective of time pi. At Day 8 pi unstimulated spleen cells absorbed enhanced amounts of IL 2, but failed to proliferate in response to it. Unfractionated and adherent spleen cells from infected mice (but not cell-free virus or culture fluids) inhibited the proliferative response of CTLL-2 cells to IL 2, suggesting a "suppressor" function for infected macrophages. Exogenous IL 2 failed to bring in vitro antigen or mitogen responsiveness of infected spleen cells to the levels seen with control cells and did not affect FLC-induced leukemogenesis in vivo.

Animals↗
PubMed1989

Lysis of mycobacteria-infected monocytes by IL-2-activated killer cells: role of LFA-1.

Mycobacterium avium-intracellulare (MAI) is a ubiquitous soil contaminant that rarely causes disseminated disease in adults regardless of immunological status. In AIDS patients, however, this organism invades virtually every tissue and organ, and most conventional chemotherapeutic agents are usually ineffective against MAI. We report here that monocytes, in which MAI has established an intracellular parasitic stage, are under the control of natural killer (NK) cells. Autologous large granular lymphocytes (LGL), purified from human peripheral blood leukocytes, were capable of efficiently lysing autologous MAI-infected monocytes in a 5-hr 51Cr release assay. More importantly, interleukin 2 (IL-2) was able to activate the LGL to a higher degree of lysis of infected monocytes. LGL cultured in medium alone could not kill normal monocytes, but showed some degree of lysis of MAI-infected cells. IL-2 activated killer (LAK) cells, on the other hand, lysed normal monocytes to a moderate degree and this activity was makedly enhanced if the monocytes were infected with MAI. The sensitivity of monocytes was directly proportional to the inoculating number of bacteria, indicating that increased bacterial burden would enhance susceptibility to LAK-mediated lysis. Finally, the addition of monoclonal antibodies to LFA-1 (both alpha and beta chains), but not LFA-2 or LFA-3, blocked lysis of both infected and uninfected monocytes when added directly to the cytotoxicity assays, indicating that this adhesion protein is involved in the lysis of autologous, infected monocytes. Thus, NK/LAK cells may be important in containment of infection by lysis of infected monocytes before the bacteria can multiply and spread to other sites.

Antigens, Differentiation↗
PubMed1989

In vitro stimulation of rat liver retinyl ester hydrolase by ethanol.

Retinyl ester hydrolase (REH), the enzyme which converts retinyl esters to retinol, was partially characterized from whole liver homogenates of rats using an HPLC method with quantitation of retinol product. Optimal results were obtained by incubation of 1 mg of whole homogenate protein with 900 microM all-trans-retinyl palmitate and 275 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate in a 0.1 M Tris-maleate buffer, pH 7.0, for 1 h at 37 degrees C. The enzyme assay proved to be sensitive and reproducible, with an interanimal coefficient of variation of 13% (n = 7). Because ethanol has been shown to mobilize vitamin A from the liver, we tested its effect on REH activity at several concentrations. In concentrations ranging from 0.01 to 0.5 M, ethanol added in vitro caused a concentration related increase in REH activity (from 20 to 86% above baseline activity). This increase was specific to ethanol as acetaldehyde, 1-propanol, and t-butanol either did not change or significantly decreased REH activity over the range of concentrations tested. The range of concentrations of ethanol causing stimulation in our assays was within the range of concentrations seen in the blood of rats after acute ethanol ingestion. Stimulation of REH activity could explain, in part, the well-known effects of ethanol on mobilization of vitamin A from liver stores.

Acetaldehyde↗
PubMed1989

The effects of flurbiprofen, aspirin, cimetidine, and antacids on the gastric and duodenal mucosa of normal volunteers. An endoscopic and photographic study.

This 7-day, single blind, randomized endoscopic tolerance study compared daily doses of 100, 150 and 200 mg flurbiprofen with 2600 mg aspirin. After seven days the flurbiprofen 100 and 150 mg groups had significantly less gastric irritation than the flurbiprofen 200 mg and aspirin groups. Flurbiprofen showed a linear dose-response relationship with respect to gastric injury and serum drug levels. Four subjects each on aspirin and flurbiprofen with the most severe injuries continued on their medications plus cimetidine and antacids for four more weeks. Both drug groups showed clinical improvement in the gastroduodenal area. In conclusion, flurbiprofen and aspirin therapy can be tolerated in the presence of gastroduodenal irritation by concomitantly administering cimetidine and antacids.

Adult↗
PubMed1989

Impaired absorption of tetracycline by colestipol is not reversed by orange juice.

Nine volunteers received a 500 mg oral dose of tetracycline hydrochloride in three trials: A: With 180 ml water; B: With 30 gm colestipol in 180 ml water; C: With 30 gm colestipol in 180 ml orange juice. Tetracycline concentrations in multiple urine samples collected during 48 hours after each dose were determined by high pressure liquid chromatography. The three trials did not differ significantly in 48 hour cumulative urine volume (3086 vs 3207 vs 3194 ml for Trials A, B, and C). However, the three trials differed significantly in 48 hour excretion of tetracycline (F = 28.2; P less than .001). During Trial A, mean excretion was 237 mg; this was significantly (P less than .05) reduced to 109 mg in Trial B and 104 mg in Trial C. However, Trials B and C were not different. Thus, coadministration of tetracycline with colestipol significantly impairs tetracycline absorption by more than 50%. Mixing colestipol with orange juice does not alter colestipol-induced impairment of tetracycline absorption.

Adult↗
PubMed1989

Induction of interferon-gamma and tumor necrosis factor by Legionella pneumophila: augmentation of human neutrophil bactericidal activity.

We have previously reported that Legionella pneumophila antigens can induce interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) in vitro and in vivo in mice. Furthermore, treatment of murine polymorphonuclear leukocyte (PMN) cultures with these cytokines resulted in augmented killing of the bacteria in vitro. The purpose of the present study was to determine if these findings could be extended to human responses. Here we report that Legionella antigens induced IFN-gamma and TNF in nonimmune human leukocytes cultures, and that these cytokines were able to stimulate the bactericidal activity of isolated PMN against L. pneumophila in vitro. Furthermore, optimal production of IFN-gamma was found in cultures which were enriched for large granular lymphocytes (LGL). The phenotype of IFN-producing cells was determined to be CD11+, CD16+, CD2+, and negative for CD4, CD8, CD14, and Leu 7. Additionally, Legionella-infected monocytes were found to produce TNF in a dose-dependent response to the number of infecting bacteria, and the addition of recombinant IFN-gamma to infected monocytes resulted in augmented production of TNF in a synergistic manner. Finally, treatment of PMN with recombinant IFN-gamma and recombinant TNF augmented their bactericidal activity against Legionella in a dose-dependent response. Thus, cytokines which can be induced by L. pneumophila antigens are able to stimulate PMN function in vitro, suggesting that resistance to infection results from a complex interaction of cytokines and cell responses.

Antibodies↗
PubMed1989

Friend leukemia complex infection of mice as an experimental model for AIDS studies.

It is now clear that AIDS results from a complex pathogenesis where virus-induced cytopathology represents only one of the contributing factors, while the others remain elusive. For this and other reasons there is much interest in the mechanisms whereby other classically immunodepressive noncytocidal retroviruses, such as viruses of the murine Friend leukemia complex (FLC), affect the immune system. FLC-induced immunosuppression has already provided important leads to the understanding of the mechanisms whereby retroviruses immunosuppress their hosts. It is expected that further investigation of the model will prove useful in several areas of AIDS research, including the development of efficacious drug therapies.

Acquired Immunodeficiency Syndrome↗