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Biomedical subjects

C Lopez

Publications and source records attributed to C Lopez.

At least 163 records · Page 9Linked to original sources
PubMed1981

Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions.

Four homosexual men presented with gradually enlarging perianal ulcers, from which herpes simplex virus was cultured. Each patient had a prolonged course characterized by eight loss, fever, and evidence of infection by other opportunistic microorganisms including cytomegalovirus, Pneumocystis carinii, and Candida albicans. Three patients died; Kaposi's sarcoma developed in the fourth. All were found to have depressed cell-mediated immunity, as evidenced by skin anergy, lymphopenia, and poor or absent responses to plant lectins and antigens in vitro. Natural-killer-cell activity directed against target cells infected with herpes simplex virus was depressed in all patients. The absence of a history of recurrent infections or of histologic evidence of lymphoproliferative or other neoplastic diseases suggests that the immune defects were acquired.

Adult↗
PubMed1981

Marrow transplantation for juvenile osteopetrosis.

Two children with the juvenile form of osteopetrosis were treated with marrow transplants from their HLA identical siblings. Following transplantation each child exhibited extensive bone reabsorption with a marked augmentation of osteoclastic function attributable to donor osteoclasts, including remodeling of bone with expansion of intramedullary hematopoiesis and correction of associated abnormalities of thymic factor and natural killer cells. Osteopetrosis ultimately recurred in one patient in whom engraftment of donor hematopoietic elements was not achieved. Our studies indicate that marrow transplantation will correct osteopetrosis but that permanent reconstitution necessitates sustained engraftment of marrow precursors of cells with osteoclastic activity.

Bone Marrow Transplantation↗
PubMed1980

Resistance to HSV-1 in the mouse is governed by two major, independently segregating, non-H-2 loci.

Earlier studies showed that genetic resistance of adult, inbred strains of mice to Herpes Simplex Virus-type 1 (HSV-1) is a dominant genetic trait. The present studies were undertaken to determine the number of genetic loci involved and whether they were found within the major histocompatibility complex, H-2, of the mouse. Challenge with HSV-1 of progeny of mice backcrossed to moderately susceptible BALB/c mice, of progeny of mice backcrossed to very susceptible A/J strain mice, and of progeny of the F-2 cross using (C57BL/6 x A/J)F1 mice indicated that two major loci were responsible for resistance. The backcrosses to BALB/c mice suggested that additional genes on this background enhanced resistance, while further backcrosses with the A/J mice indicated that other genes on the A/J background (or the lack thereof) reduced resistance. Studies with congenic mice showed that genes within the H-2 did not influence resistance or susceptibility.

Animals↗
PubMed1980

Herpes infections in the immunosuppressed host.

Very recent studies indicate that a primitive immune system plays an important role in resisting herpesvirus infections in the mouse. This system appears to be reflected by the NK cell assay and preliminary data suggest that this test reflects resistance in man to herpesvirus infections. We propose that ths system may be responsible for resistance to reactivated herpesvirus infections and its suppression might result in clinically apparent disease. Studies in our laboratory are currently aimed at evaluating this possibility.

Adolescent↗
PubMed1980

2'-fluoro-5-iodo-aracytosine, a potent and selective anti-herpesvirus agent.

A newly synthesized pyrimidine analog, 2'-fluoro-5-iodo-aracytosine (FIAC), suppressed by 90% the replication of various strains of herpes simplex virus types 1 and 2 at concentrations of 0.0025 to 0.0126 microM. Cytotoxicity was minimal, as determined by trypan blue dye exclusion with norman Vero, WI-38, and NC-37 cell proliferation; the 50% inhibitory dose was 4 to 10 microM in a 4-day assay. When compared with other antiviral drugs, FIAC was active at much lower concentrations than arabinosylcytosine, iododeoxyuridine, and arabinosyladenine. It was slightly more active against herpes simplex virus type 1 than acycloquanosine and slightly more toxic to normal cells. FIAC was about 8,000 times more active against the replication of wild-type herpes simplex virus type 1 than against a mutant strain lacking the expression of virus-specified thymidine kinase. Since FIAC appears to be preferentially phosphorylated by the viral enzyme, this is probably responsible, at least in part, for the selectivity of its antiviral actions. Although FIAC appears to be an arabinosylcytosine analog, its antiviral activity was not reversed by deoxycytidine. The minimal cytotoxicity exhibited by FIAC for normal cells, however, was reversed by equimolar concentrations of deoxycytidine. Thymidine, which reversed the antiviral activity, was effective only when used in great excess.

Antiviral Agents↗
PubMed1980

Marrow-dependent cells depleted by 89Sr mediate genetic resistance to herpes simplex virus type 1 infection in mice.

Adult mice resistant to infection with 10(6) plaque-forming units of a virulent strain of herpes simplex virus type 1 were treated with 89Sr to abrogate marrow-dependent cell functions. Treated mice were found to be much more susceptible to the herpes simplex virus type 1 infection than untreated mice. The virus persisted in the visceral tissues of 89Sr-treated mice for 3 or more days postinfection but not in those of untreated mice. The virus also spread to the spinal cords of treated but not untreated mice. A marrow-dependent cell appeared to mediate resistance to herpes simplex virus type 1 by controlling the infection early after inoculation and not allowing the infection spread to the central nervous system.

Animals↗
PubMed1979

Association between pre-transplant natural kill and graft-versus-host disease after stem-cell transplantation.

Natural killer activity against herpes simplex virus type 1 infected fibroblasts NK(HSV-1) was studied prospectively in patients undergoing allogenic bone-marrow or fetal-tissue stem-cell transplantation. Thirteen patients showed evidence of engraftment and survived long enough to develop graft-versus-host disease (GvHD). Of this group, all of the seven having normal NK(HSV-1) activity before transplantation acquired GvHD and the six having low NK(HSV-1) had no evidence of GvHD. These results were independent of mode of preparation of patients for transplantation, source of stem cells used, or cytomegalovirus infections, and they suggest that this assay reflects a host-determined function capable of stimulating GvHD.

Anemia, Aplastic↗
PubMed1979

Nucleosides. 110. Synthesis and antiherpes virus activity of some 2'-fluoro-2'-deoxyarabinofuranosylpyrimidine nucleosides.

A series of 5-substituted 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosines 7a-d and their corresponding uracils 9a-d,f were prepared by condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinosyl bromide (5) with appropriately trimethylsilylated pyrimidines followed by saponification of the protected nucleosides 6 or 8. 1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (7e) was obtained by iodination of 7a. Iodination of 8a followed by removal of the protecting acyl-protecting groups afforded the 5-iodo nucleoside 9e. Several of these 2'-fluoro-substituted nucleosides completely obviated replication of herpes simplex virus type 1 (HSV-1) in monolayers of Vero cells at concentrations of 10-100 microgram/mL. The 5-iodocytosine analogue 7e was the most effective, showing 99.5% suppression of viral replication even at concentrations of 0.1 microgram/mL. The cytotoxicity of 7e to L5178Y or P815 cells in culture was minimal. A comparison of the efficacy of 7e against HSV-1 with other known nucleoside antiviral agents indicates that further in vitro and in vivo evaluation of 7e is warranted.

Antiviral Agents↗
PubMed1979

Replication of herpes simplex virus type 1 in macrophages from resistant and susceptible mice.

Studies were carried out to determine whether the in vitro capacity of adherent peritoneal cells to replicate herpes simplex virus type 1 (HSV-1) might correlate with the in vivo susceptibility of mice genetically resistant, moderately susceptible, or very susceptible to HSV-1 infection. Unstimulated and proteose peptone-stimulated monolayers restricted viral replication when infected immediately, but replicated HSV-1 when infected after 3 to 7 days of culture. Macrophages from resistant C57Bl/6 mice restricted HSV-1 replication significantly better than cells from susceptible mice. This function did not segregate with resistance, since macrophages from resistant F1 mice failed to restrict HSV-1 replication. Induction of peritoneal exudate cells with thioglycolate yielded cells capable of replicating HSV-1 when infected immediately after plating and after 4 days of culture.

Animals↗
PubMed1979

Natural killing of herpes simplex virus type 1-infected target cells: normal human responses and influence of antiviral antibody.

Studies of a mouse model of genetic resistance to herpes simplex virus type 1 (HSV-1) indicate that the marrow-dependent effector cell of allogeneic resistance plays an important role in natural resistance to this virus infection. Since the marrow-dependent effector cell appears to be closely related to the natural killer (NK) cells, an NK assay with HSV-1-infected fibroblasts [NK(HSV-1)] has been developed to study this resistance mechanism in humans. Incubation of effector and target cells for 12 to 14 h gave the greatest percent specific release (%SR) and kept spontaneous (51)Cr release from infected target cells below 35%. Patients with Bruton's agammaglobulinemia demonstrated significant kill indicating antiviral antibody was not necessary. Seropositive individuals gave a 9% greater%SR than seronegative individuals. Depletion of B-cells consistently diminished NK (HSV-1) for seropositive individuals and augmented kill for seronegative individuals. Although antiviral antibody produced in culture may contribute to NK (HSV-1), depletion of B-cells allowed quantitation of NK (HSV-1) to the exclusion of most of the antibody-dependent kill. The NK cells detected by this assay showed many of the properties reported for NK cells with K562 targets. Two patients with severe herpesvirus infections demonstrated NK (HSV-1) responses greater than 2 standard deviations below the normal mean. Since normal individuals with virus infections have higher rather than lower natural kill, the low NK (HSV-1) may reflect their susceptibility to the virus infection.

Antibodies, Viral↗
PubMed1979

Suppression of the immune response in tumor-bearing mice. I. Response to virus-producing tumor cells and non-virus-producing tumor cells.

Spleen cells from mice inoculated with syngeneic murine sarcoma virus (MuSV)-transformed tumor cells suppressed the mixed leukocyte reaction. Mice inoculated with virus-producing tumor cells demonstrated two types of suppression. First, an early suppression was shown to be mediated by an adherent suppressor T-cell on the basis of its sensitivity to Thy 1.2 antiserum plus complement and the absence of the early suppression in T-cell-deficient nude mice. This suppression may have been induced in response to viral antigens associated with cell surface antigens (modified self-antigens) or viremia, because it was not induced by a non-virus-producing tumor cell line. Second, a late suppression was also seen in tumor-bearing BALB/c mice. This suppression was shown to be T-cell-independent by its presence in nude mice and by its resistance to gamma-irradiation and Thy 1.2 antiserum plus complement. In addition, the late suppression was present in mice inoculated with a nonproducer clone of MuSV-transformed cells. This finding suggests that viral antigens and/or viremia is not required for induction of the late suppression.

Animals↗
PubMed1979

Suppression of the immune response in tumor-bearing mice. II. Characterization of adherent suppressor cells.

Adherent spleen cells from late (greater than or equal to 18 days post inoculation) tumor-bearing BALB/c mice suppressed lymphoproliferative and effector immunity as evaluated by the mixed leukocyte culture and cell-mediated lympholysis assays. Procedures that eliminated T-cells or B-cells while enriching for macrophage populations significantly augmented the suppression, whereas removal of phagocytic and adherent cells abrogated the suppressive effect. We concluded that the cells responsible for suppression of cell-mediated immune responses in late tumor-bearing mice were of the monocyte-macrophage series. Furthermore, the suppressive influence was not due merely to the increased number of macrophages in tumor-bearing animals. Experiments clearly showed that the splenic macrophages, even at low concentrations, demonstrated a suppressive function.

Animals↗
PubMed1978

Immunological nature of genetic resistance of mice to herpes simplex virus type 1 infection.

Treatment of mice genetically resistant to HSV-1 with agents which impair T-cell or macrophage function markedly diminished resistance. Bone marrow transplantation of genetically susceptible mice with marrow from resistant F1 mice produced chimeras resistant to HSV-1. Resistance thus appears to be immunological in nature. Striking similarities were found between resistance to HSV-1 and allogeneic resistance.

Animals↗