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Biomedical subjects

J D Gangemi

Publications and source records attributed to J D Gangemi.

At least 37 records · Page 2Linked to original sources
PubMed1991

Phosphonylmethoxyalkyl purine and pyrimidine derivatives for treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS.

Murine acquired immunodeficiency syndrome (MAIDS) was induced in C57BL/6 mice following infection with the LP-BM5 retrovirus complex. Infected mice developed splenomegaly, lymphadenopathy and loss of B- and T-cell functions 100 days after virus inoculation. Mice with AIDS were highly susceptible to opportunistic murine cytomegalovirus (MCMV) and herpes simplex virus (HSV-1) infections. The therapeutic activities of two phosphonylmethoxyalkyl derivatives, 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and (S)-1-(3-hydroxy-2-phosphonylmethoxy-propyl)cytosine (HPMPC), were evaluated in MAIDS immunosuppressed mice infected with MCMV or HSV-1. MCMV infection resulted in extensive viral replication in lung, liver and spleen and death occurred five to twelve days post-infection. Treatment with either HPMPC or ganciclovir (DHPG) reduced mortality and viral replication in target organs; however, HPMPC was as effective as DHPG at one-fifth the DHPG dose. Moreover, when a single dose (100 mg/kg) of HPMPC was administered 24 h prior to MCMV infection, it suppressed virus replication at seven and 14 days post-infection, thus resulting in a significant prolongation of life. PMEA was effective against opportunistic HSV-1 infections, but appeared to be less effective than HPMPC against MCMV infections. These results indicate that MAIDS can be used as a model for evaluating antivirals in an immunocompromised host, and suggest that both PMEA and HPMPC may be useful in the treatment of opportunistic CMV and HSV-1 infections.

Adenine↗
PubMed1990

Use of human monocytes in the evaluation of antiviral drugs: quantitation of HSV-1 cytopathic effects.

An assay for the evaluation of antiviral and immunomodulator potency was developed using pure populations of cultured human monocytes. The assay involved culturing of human monocytes until they were fully susceptible (15-20 days) to lytic infection with HSV-1. When susceptible cells were cultured with recombinant interferon-alpha or a synthetic interferon inducer such as polyinosinic:polycytidylic acid prior to infection, a significant enhancement in resistance to the cytopathic effects of HSV-1 was observed. Likewise, a dose dependent reduction in cell lysis was observed when acyclovir was added immediately after virus infection. Monocyte resistance to HSV-1 was determined by the retention of pinocytic activity as determined by the uptake of neutral red dye. Relative pinocytic activity was quantitated using a simple colorimetric procedure. This antiviral assay can be completed in 48 h; is easy to perform, highly sensitive and reproducible.

Acyclovir↗
PubMed1989

Antiviral activity of a novel recombinant human interferon-alpha B/D hybrid.

The antiviral potential of a novel cross-species active, recombinant human interferon-alpha B/D hybrid (rHuIFN-alpha B/D), was evaluated for its efficiacy in cultured human monocytes and in several murine models of viral disease. When examined in 14-day-old human monocyte cultures, rHuIFN-alpha B/D was highly effective in preventing viral replication and cell destruction caused by herpes simplex virus type 1 (HSV-1/VR3). The effect observed with 100 units of this hybrid IFN was as good or higher than that observed with equivalent amounts of rHuIFN-alpha A or IFN-gamma. In addition, a single dose (5 X 10(7) U/kg) of rHuIFN-alpha B/D administered several hours after intranasal infection with HSV-1/VR3 suppressed pulmonary virus replication and prevented death due to interstitial pneumonia. Similarly, mice infected with a more aggressive strain of HSV-1 (McIntyre) were protected when this IFN preparation was administered at the time of virus infection and 1 day later. The anti-retroviral activity of rHuIFN-alpha B/D was examined in two murine leukemia retroviral models, Rauscher (RMLV) and Friend (FMLV), and a murine model of acquired immunodeficiency (LP-BM5). Treatment of RMLV or FMLV infected mice significantly prolonged mean survival times and the number of long-term FMLV survivors. These therapeutic effects were demonstrated when IFN was administered on the day of virus infection or as late as 3 days following infection. Transient reversal of the immunosuppressive effects induced by LP-BM5 infection was observed when rHuIFN-alpha B/D treatment was initiated at the time of virus infection. Moreover, when rHuIFN-alpha B/D was used together with azidothymidine (AZT), the effect of the combination was better than either drug alone.

Antiviral Agents↗
PubMed1989

Significant differences in therapeutic responses to a human interferon-alpha B/D hybrid in Rauscher or Friend murine leukemia virus infections.

Treatment of mice infected with Rauscher (RMLV) or Friend (FMLV) murine leukemia viruses at an early stage of disease (beginning at day 0 and continuing every other day for 21 days) with 5 x 10(7) units/kg body weight of a cross-species-active recombinant human interferon-alpha B/D hybrid (rHuIFN-alpha B/D) was more effective in FMLV than in RMLV infections. In contrast, treatment with 5 x 10(7) units/kg body weight of IFN beginning as late as 15 days postinfection and continuing every other day for 21 days was more effective in RMLV than in FMLV infections. These differences were consistent with observed changes in circulating white blood cells, spleen weight, and reverse transcriptase levels. Additionally, biweekly long-term administration (beginning at day 0) of 5 x 10(6) units/kg of rHuIFN-alpha B/D (an ineffective treatment in short-term therapy) significantly prolonged the mean survival time of RMLV-infected mice, but only weakly prolonged that of FMLV-infected mice.

Animals↗
PubMed1989

9-(2-Phosphonylmethoxyethyl)adenine in the treatment of murine acquired immunodeficiency disease and opportunistic herpes simplex virus infections.

The murine model of acquired immunodeficiency disease was used to evaluate both the antiretroviral and antiherpetic activities of the acyclic nucleotide analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The antiretroviral activity of PMEA was compared with that of azidothymidine (AZT) in mice receiving the drug either immediately after infection or at late times in disease progression. Both AZT (oral, 30 mg/kg) and PMEA (parenteral, 25 and 5 mg/kg) were effective in slowing the development of disease when administered daily beginning on the day of infection. In contrast, neither drug alone was effective in modifying disease outcome when administered several weeks after viral infection. Human recombinant alpha interferon (rhuIFN alpha-B/D at 5 x 10(7) U/kg) was also ineffective when administered late in the course of disease. However, when administered in combination, both alpha interferon and PMEA (25 mg/kg) were able to suppress disease progression even when treatment was initiated as late as 3 weeks postinfection. Mice that were immunocompromised due to LP-BM5 virus infection were highly susceptible to acute (lethal) infection with herpes simplex virus type 1, whereas their immunocompetent littermates were not. PMEA was as effective as acyclovir in the treatment of opportunistic herpes simplex virus type 1 infections in LP-BM5 virus-infected mice. Thus, like AZT, PMEA was effective against retrovirus infection, and, like acyclovir, PMEA was effective against herpes simplex virus type 1 infection. This gives PMEA the unique potential of being useful in the treatment of opportunistic herpes simplex virus infections as well as the underlying retroviral disease.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Therapeutic efficacy of liposome-encapsulated ribavirin and muramyl tripeptide in experimental infection with influenza or herpes simplex virus.

Large, negatively charged, multilamellar liposomes were examined for their ability to improve the therapeutic activity of the broad-spectrum antiviral agent ribavirin (RIB) and the synthetic immunostimulant muramyl tripeptide (MTP-PE) in the treatment of viral pneumonitis. Liposome-encapsulated MTP-PE (L-MTP-PE) was superior to free MTP-PE in activating alveolar macrophages and in protecting mice against intranasal challenge with 10 LD50 (50% lethal dose) of herpes simplex virus type 1 (HSV-1). Mice treated with liposome-encapsulated or free MTP-PE had no detectable viremia and had lower pulmonary titers of virus than controls. Liposome-encapsulated RIB (L-RIB; 3 mg per mouse), administered several hours after infection, was more effective than was free RIB (10 mg per mouse) in protecting mice against intranasal challenge with 10 LD50 of influenza virus, but neither L-RIB nor free RIB protected mice against HSV-1 infection. In contrast, combination therapy with both L-RIB and L-MTP-PE was more effective than either agent used alone.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

An ultrastructural examination of murine alveolar macrophages following intranasal administration of propionibacterium acnes.

Light and electron microscopic analysis of murine lungs or isolated pulmonary cells was performed three days after intranasal administration of the bacterial immunostimulant, Propionibacterium acnes (P. acnes). Our observations indicated that pulmonary alveolar and airway macrophages (PAMs) were the only cells with P. acnes bacilli in their cytoplasm. Bacilli were not observed in pulmonary interstitial macrophages, granulocytes, lymphocytes or pulmonary parenchymal cells such as type I and type II pneumocytes. Because of the morphological heterogeneity of PAMs observed in control and experimental animals, it was not possible from these studies to be certain about the relative abundance or complexity of lysosomes, endoplasmic reticulum, Golgi and other organelles in the two groups. However, we noted that it was not uncommon to observe in the same PAM, profiles of P. acnes and a well developed Golgi complex and endoplasmic reticulum. These P. acnes--associated morphological alterations occurred at a time when functional activities (e.g., phagocytosis, cytostasis) of PAMs were enhanced.

Animals↗
PubMed1986

Role of pulmonary macrophages in resistance to experimental metastasis.

Intranasal inoculation of C3H/HeN mice with Propionibacterium acnes activates pulmonary macrophages but not splenic or peritoneal macrophages. When mice so treated were injected IV with tumor cells, no protection against the challenge was seen. Conversely, inoculation of C3H/HeN mice with P. acnes by the IP route activated splenic and peritoneal macrophages but not pulmonary macrophages. When mice with activated splenic and peritoneal macrophages were challenged with an IV injection of tumor cells, the mice demonstrated an increased resistance to the formation of pulmonary tumors. Thus, activation of splenic and peritoneal macrophages correlated better with protection against IV tumor challenge than activation of pulmonary macrophages. Experiments were done that demonstrated that the effect was not due to the augmentation of NK cell activity. The data are consistent with the conclusion that activated pulmonary macrophages alone are not effective in conferring resistance to pulmonary tumor nodule formation in this tumor model.

Animals↗
PubMed1986

Suppressive effects of 3-methylcholanthrene on the in vitro antitumor activity of naturally cytotoxic cells.

Transient suppression of splenic natural killer (NK), natural cytotoxic (NC), and peritoneal macrophage cytotoxicity was observed following a single injection of 3-methylcholanthrene (3-MC) into C3H/HeN mice. Natural killer cell activity was depressed by 30-60% 4-6 d after injection of 1.0 mg 3-MC. Levels of NK reactivity returned to normal 8 d post 3-MC injection, and no suppression of natural killing was seen when tested 6 wk after 3-MC treatment. 3-MC did not affect Propionibacterium acnes augmentation of NK cell activity when tested both 6 d and 6 wk after carcinogen injection. The results indicate that the observed suppression of naturally cytotoxic cells may not be important in allowing 3-MC-induced tumors to grow, since suppression is not long-lasting. Therefore, any effect on tumor growth mediated by a suppression of naturally cytotoxic cells would have to be exerted at the earliest stages of tumor development.

Animals↗
PubMed1985

Phagocytic activity of alveolar macrophages in patients with bronchogenic carcinoma.

Human bronchoalveolar cells were obtained by lavage during diagnostic fiberoptic bronchoscopy of 21 patients suspected of having lung malignancies. Of these patients 11 were diagnosed as having primary lung cancer (Group I) and included individuals with squamous cell carcinoma, adenocarcinoma, undifferentiated large and oat cell carcinoma at varying locations and TNM stages, 4 patients demonstrated nonprimary metastatic carcinoma (Group II), and 6 patients did not reveal detectable tumors by bronchoscopy or follow-up (Group III) and were included as study controls. We examined the ability of pulmonary alveolar macrophages (PAMs) lavaged from patients in each of the three study groups to phagocytose opsonized sheep red blood cells. Phagocytic activity varied among patients in the same and different study groups; however, no significant differences were observed in the phagocytic or tumoristatic activities of PAMs recovered from tumor-bearing and nontumor-bearing lung regions of the same patient. Moreover, lavage fluids collected from tumor-bearing regions did not suppress the phagocytic activity of PAMs collected from control lungs nor lung regions contralateral to the tumor-bearing lung. The data do not support the view that bronchial neoplasms or their secreted products suppress phagocytic functions of alveolar macrophages.

Adult↗
PubMed1985

Bronchoalveolar lavage and the immunology of primary lung cancer.

Bronchoalveolar lavage (BAL) is a powerful tool with which the immunology of the lung in health and disease can be studied. This technique has been successfully used to characterize localized humoral and cell-mediated responses in sarcoidosis and a number of other interstitial pneumonitides. In contrast, BAL in patients with lung cancer has resulted in some confusion regarding the extent and type of local and systemic immunity in these patients. This review summarizes some of the data obtained from these patients via BAL, but does not attempt to explain the reported discrepancies. The objective of this review is rather to identify gaps which exist in our knowledge of the environmental factors influencing pulmonary immunity in primary lung cancer.

Antibodies, Neoplasm↗
PubMed1984

Ceftriaxone levels in blood and tissue during cardiopulmonary bypass surgery.

One gram of ceftriaxone was given intravenously to 15 patients approximately 2 h before cardiopulmonary bypass surgery. Ceftriaxone levels in plasma (mean +/- standard deviation) were 60.4 +/- 18.8 micrograms/ml (range, 17.0 to 96.0 micrograms/ml) at the beginning of bypass, 44.2 +/- 16.6 micrograms/ml (range, 9.4 to 78.6 micrograms/ml) at the end of bypass, and 19.6 +/- 9.6 micrograms/ml (range, 4.2 to 47.1 micrograms/ml) the following morning, 18.1 to 24.7 h after infusion of ceftriaxone. Concentrations in the sternal bone were 4.7 +/- 2.1 micrograms/g (range, 1.0 to 10.1 micrograms/g; tissue-to-plasma ratios, 0.066 +/- 0.036). Concentrations in the atrial appendage were 7.7 +/- 1.8 microgram/g (range, 3.6 to 10.2 micrograms/g; tissue-to-plasma ratios, 0.143 +/- 0.062). These data suggest that a single dose of ceftriaxone might be useful for prevention of infection due to susceptible pathogens.

Aged↗
PubMed1983

Opsonization of alphaviruses in hamsters.

Immune elimination of alphaviruses in immunized hamsters appears to involve formation of virus/antibody aggregates which are subsequently cleared from the circulation by cells of the reticuloendothelial system (RES). Virulent strains of Venezuelan (VEE) and Western equine encephalitis (WEE) viruses which were cleared slowly from the circulation of nonimmune hamsters, were cleared rapidly when inoculated into the blood of immunized hamsters. Likewise, when these viruses were mixed with specific hamster immune serum prior to inoculation, they were efficiently cleared from the circulation of nonimmune hamsters. Virus, mixed with specific immune serum, or inoculated into immunized hamsters, formed virus/antibody aggregates, as demonstrated by density gradient centrifugation, filtration through polycarbonate membranes, precipitation with Staphylococcus protein A, and electron microscopy. Cleared virus was concentrated primarily in liver and spleen, as confirmed by autoradiography. Immune clearance of virulent VEE was demonstrable within 5 to 6 days following immunization of hamsters with live attenuated VEE vaccine, strain TC-83. In these hamsters, a close association was established between formation of virus/antibody aggregates, rapid clearance, and survival of challenged hamsters. Adsorption of virus to hamster macrophages in culture was enhanced by immune serum in the presence of complement. These results are compatible with the hypothesis that immune clearance of virus in the intact hamster involves a complement-dependent interaction of virus/antibody complexes with cells which possess Fc and complement receptors. The clearance of immune complexes by the RES serves to amplify the protective effect of neutralizing antibody alone.

Adsorption↗
PubMed1983

Enhancement of natural resistance to influenza virus in lipopolysaccharide-responsive and -nonresponsive mice by Propionibacterium acnes.

Lipopolysaccharide-responsive C3H/HeN mice were rendered resistant to a mouse-adapted strain of influenza (Aichi, H(3)N(2)) virus when Propionibacterium acnes was given either intranasally or intraperitoneally several days before virus infection. The time of P. acnes treatment was important since no protection was demonstrated when this agent was given either on the same day as or several days after virus challenge. In contrast, lipopolysaccharide-nonresponsive C3H/HeJ mice were not protected when P. acnes was administered intranasally at any time before infection; however, protection was demonstrated when P. acnes was given by the intraperitoneal route. Depending on the route of inoculation, P. acnes induced several distinctive immunological responses in the lungs of both C3H/HeN and C3H/HeJ mice. Intranasal inoculation was more effective in activating pulmonary macrophages in C3H/HeN than in C3H/HeJ mice. In contrast, intraperitoneal inoculation activated pulmonary natural killer cells in both mouse lines but did not activate pulmonary macrophages.

Adjuvants, Immunologic↗
PubMed1983

Comparison of cefamandole and cefazolin during cardiopulmonary bypass.

In a randomized comparison, concentrations of cefazolin were found to exceed those of cefamandole in serum, atrial appendage, and sternal bone in patients undergoing cardiopulmonary bypass. No postoperative infections and no antibiotic-related complications occurred in either patient group.

Aged↗
PubMed1981

Polypeptide synthesis catalysed by components of Pichinde virus disrupted by detergent.

Pichinde virus preparations were investigated for ribosomal components and associated activities. After detergent treatment and fractionation, viral components were assayed for polypeptide synthesis, elongation of nascent polypeptide chains, and mRNA activity. It was demonstrated that these subviral particles could synthesize polypeptides when exogenous mRNA template, aminoacyl--tRNAs, translation factors, GTP and appropriate cations were added. Undisrupted, whole virions could not synthesize polypeptide; disruption and subsequent centrifugation of subviral ribosomes was a prerequisite for the biosynthetic activity described.

Arenaviridae↗