Anti-HIV-1 activity of 3'-azido-3'-deoxythymidine (AZT) in primary mononuclear phagocytes.

Conflicting data have been reported on ability of 3'-azido-3'-deoxythymidine (AZT) to protect mononuclear phagocytes from HIV-1 infection. We compared the antiviral potency of AZT in three types of primary human mononuclear phagocytes: peripheral blood monocytes, monocyte-derived macrophages (in vitro differentiated) and alveolar macrophages (in vivo differentiated). To establish highly-productive virus infection, purified cells (greater than 99%) from healthy donors were challenged with the macrophage-tropic HTLV-IIIBa-L strain at input multiplicities ranging from 0.

Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro.

In studies examining potential interactions between ganciclovir (GCV) and either zidovudine (AZT) or didanosine (DDI) in H9 cells, GCV was found to consistently reduce the anti-human immunodeficiency virus type 1 potency of both AZT and DDI. In the presence of GCV, the 50% effective doses of AZT and DDI were increased three- to sixfold, depending on the molar ratio of drugs and the measure of human immunodeficiency virus type 1 replication (p24 antigen, reverse transcriptase activity, or infectious virus yield). Multiple dose-effect analysis revealed strong antagonism between GCV and either AZT or DDI (combination indices, 2.

In vitro selection and molecular characterization of human immunodeficiency virus-1 resistant to non-nucleoside inhibitors of reverse transcriptase.

Several newly discovered potent and selective non-nucleoside inhibitors of human immunodeficiency virus-1 reverse transcriptase (RT) are undergoing evaluation in clinical trials. We studied the potential for development of viral resistance to one of the prototype compounds, BI-RG-587, a dipyridodiazepinone derivative. Human immunodeficiency virus-1 resistant to BI-RG-587 emerged after only one cycle of in vitro infection in the presence of the drug.

Use of recombinant retroviruses to characterize the activity of antiretroviral compounds.

This report describes the use of a recombinant murine retrovirus encoding beta-galactosidase (PLJ beta-gal retrovirus) to study the antiretroviral activity of zidovudine (AZT) and other nucleoside analogs. The PLJ beta-gal virus permits the rapid and unequivocal identification of individual virus-infected cells arising from a single cycle of viral replication. With this model system, AZT is shown to completely and irreversibly prevent retrovirus infection of proliferating cell lines as measured by a lack of reporter gene expression.

Interleukin-6 expression in primary macrophages infected with human immunodeficiency virus-1 (HIV-1).

We have investigated the effects of human immunodeficiency virus type-1 (HIV-1) infection on constitutive and lipopolysaccharide (LPS)-induced expression of interleukin-6 (IL-6) in cultured blood monocyte-derived macrophages. Highly productive and cytopathic infection of macrophages was established with the macrophage-tropic HIV-1 BaL strain. On Days 14-28 post infection, infected and mock-infected cells were activated with LPS or control medium for 6-24 hours before harvesting culture supernatants and cellular RNA.

Tumor necrosis factor-alpha/cachectin enhances human immunodeficiency virus type 1 replication in primary macrophages.

Macrophages are important target cells for human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 to productively infect macrophages may be influenced by endogenous cytokines that alter the activation state of these cells. In this study, the effect of tumor necrosis factor-alpha/cachectin (TNF alpha), a cytokine with macrophage-activating properties, on HIV-1 replication in primary blood monocyte-derived macrophages was examined.

Altered in vivo activity of liposome-incorporated lipopolysaccharide and lipid A.

We compared the abilities of free and liposome-incorporated Salmonella minnesota wild-type lipopolysaccharide (LPS) and lipid A to activate peritoneal macrophages and induce lethal toxicity in mice. Incorporation of lipid A into multilamellar vesicles resulted in a 100-fold-decreased potency to prime macrophages for phorbol myristate acetate-triggered release of H2O2. In addition, liposome incorporation reduced the lethality of LPS and lipid A at least 10-fold in dactinomycin-sensitized mice.

Incorporation of recombinant gamma interferon into liposomes enhances its ability to induce peritoneal macrophage antitoxoplasma activity.

In this study we compared the ability of free- and liposome-incorporated murine recombinant gamma interferon (rIFN-gamma) to enhance peritoneal macrophage H2O2 release and antitoxoplasma activity in vitro. rIFN-gamma was efficiently (37 to 47%) incorporated into multilamellar vesicles composed of phosphatidylglycerol/cholesterol in a 2:1 molar ratio. The amount of rIFN-gamma incorporated into multilamellar vesicles and added to macrophages (0.

A simple index to estimate the likelihood of bacterial infection in patients developing fever after abdominal surgery.

To identify predictors of bacterial infection in patients developing postoperative fever, we prospectively studied 434 adults who underwent abdominal surgery. Of the 434 study patients, 163 (38%) developed postoperative fever (38.1 degrees C [100.

Arteriolization of venous blood gases: a clue to the diagnosis of cyanide poisoning.

Prompt diagnosis and treatment of cyanide poisoning is essential for a successful therapeutic outcome. We present a patient with acute cyanide poisoning in whom venous blood gases disclosed an abnormally high pO2. Prompt treatment of the patient with the cyanide antidote, sodium nitrite plus sodium thiosulfate, rapidly reversed the cardiovascular and central nervous system manifestations of cyanide toxicity.

Granulocyte-macrophage colony-stimulating factor enhances selective effector functions of tissue-derived macrophages.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is produced by a variety of cells at sites of exposure to antigens. GM-CSF has a stimulatory effect on a number of neutrophil functions, but the effect on macrophage function is less clear. We investigated the effect of purified murine recombinant GM-CSF on murine peritoneal macrophage oxidative metabolism, Fc-dependent phagocytosis, anti-Toxoplasma activity, and expression of class II major histocompatibility antigen (Iad).

Stimulation of macrophage H2O2 release by resident thymocytes: effect of a soluble factor distinct from interferon-gamma.

Activated T cells are known to stimulate macrophage oxidative metabolism and antimicrobial activity through release of interferon-gamma (IFN-gamma). In contrast, the role of nonactivated T cells in regulating macrophage effector functions is less well defined. We have previously reported that a low molecular weight soluble factor derived from resident (nonactivated) thymocytes enhances macrophage receptor-mediated phagocytosis.

Modulation of the biological activity of bacterial endotoxin by incorporation into liposomes.

In an attempt to define the mechanism by which endotoxin induces its biological activity, we studied the effect of the incorporation of lipopolysaccharide and lipid A into phospholipid vesicles (liposomes) on the stimulation of the macrophage cell-line RAW 264.7 and on the coagulation of Limulus amoebocyte lysate. The incorporation of Salmonella minnesota smooth-and rough (Re) lipopolysaccharide or primarily monophosphoryl lipid A into multilamellar and small unilamellar vesicles consisting of phosphatidylcholine, phosphatidylserine and cholesterol (molar ratio 4:1:4) reduced the interleukin 1 inducing potency of these substances about 1000-fold.

A simple index to identify occult bacterial infection in adults with acute unexplained fever.

Patients with acute fever (less than three weeks' duration) and no localizing symptoms or physical findings to suggest a source (unexplained fever) may have self-limited illness or occult bacterial infection requiring prompt treatment. To develop a management strategy for patients with unexplained fever, we studied 880 adults who were evaluated for acute fever in an emergency room. At presentation, 135 (15%) patients had unexplained fever.

Value of the serum bactericidal test in management of patients with bacterial endocarditis.

A review is given of the available clinical data on the prognostic value of the serum bactericidal test in the treatment of patients with bacterial endocarditis. It is concluded that the test, even when performed in a standardized manner, does not provide useful information for the majority of patients with bacterial endocarditis. Until further clinical data are available, routine performance of the test in patients with bacterial endocarditis is not recommended.

Bilateral otitis media and hearing loss in an adult.

Bilateral otitis media, an uncommon entity in adults, may represent the initial manifestation of a life-threatening systemic disease. Prompt recognition and treatment of the underlying disease is needed to preserve auditory function and prevent involvement of other organ systems. We present the case of a thirty-four-year-old male with bilateral serous otitis media and progressive hearing loss, which was refractory to antimicrobial therapy and middle ear drainage.

Detection and immunochemical characterization of a primate type C retrovirus-related p30 protein in normal human placentas.

We find that 12 of 14 specimens of normal human term placentas analyzed by one- or two-dimensional electrophoresis and immunoblotting contain a protein or polypeptide of approximately equal to 30,000 daltons that is antigenically cross-reactive with p30 core protein of the simian sarcoma-associated virus/gibbon ape leukemia virus primate retrovirus group and is physicochemically similar to reference murine and primate type C retrovirus p30s. This finding may lead to an understanding of endogenous type C retrovirus gene expression in humans.

Immunohistologic detection of antigen related to primate type C retrovirus p30 in normal human placentas.

This study reports the immunohistologic detection of SSAV/GaLV type C retrovirus p30-related antigen in unfixed cryostat sections of normal human term placentas by the indirect immunofluorescence method. Goat anti-SSAV p28 serum reacted specifically with 10 of 10 anatomic specimens of human placenta. Goat anti-GaLV p29 serum reacted similarly with 8 of 10 specimens.

Diagnosis and treatment of urethritis in men.

Gonococcal and nongonococcal urethritis are the most common sexually transmitted diseases in men. Failure to control these infections is a result of improper treatment of index cases and their sexual contacts. The proper management of urethritis in men is reviewed.