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Biomedical subjects

C Lopez

Publications and source records attributed to C Lopez.

At least 127 records · Page 7Linked to original sources

High cytotoxic activity against herpes simplex virus type 1 infected targets found in murine peritoneum.

Unelicited murine peritoneal cells (PC) were found to efficiently lyse the natural cytotoxic (NC) cell target, WEHI-164, as well as herpes simplex virus-type 1 (HSV-1)-infected WEHI-164 and 3T3 cells but not the natural killer (NK) target, YAC-1. Lysis by PC of HSV-1-infected WEHI-164 and 3T3 cells required longer culture times than splenic cell lysis of YAC-1 cells. The PCs which lysed these targets were found to be slightly adherent to nylon wool but non-phagocytic, and were not augmented by preincubation with interferon. Also, PC effectors lacked Qa-5 and asialo GM1 markers which are found on splenic NK cells which lysed YAC-1 targets. We found that there was no correlation between peritoneal NC activity and genetic resistance to HSV-1.

Animals↗

Metastasis to the parotid gland from colorectal adenocarcinoma.

This manuscript presents only the fifth reported case in the literature of colorectal carcinoma with metastasis to the parotid gland. A 66-year-old white woman, referred to Roswell Park Memorial Institute, presented with a left parotid mass and a past history of undergoing right hemicolectomy for an adenocarcinoma of the ascending colon with synchronous liver metastases. The clinical presentation and treatment of the patient are discussed with a review of the literature.

Adenocarcinoma↗

Antiviral activity of 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodocytosine against human cytomegalovirus in human skin fibroblasts.

2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodocytosine (FIAC) was shown to be a selective anti-human cytomegalovirus agent in vitro with a 50% antiviral effective dose of 0.6 microM (J. M. Colacino and C. Lopez, Antimicrob. Agents Chemother. 26:505-508, 1983) and a 50% cell growth inhibitory dose of 8 microM. Antiviral activity was more readily reversed with 10-fold excess thymidine, whereby the 50% effective dose was increased to 11.3 microM. FIAC-induced cytotoxicity was more readily reversed with 10-fold excess of deoxycytidine, whereby the 50% inhibitory dose was increased to greater than 100 microM. Thymidine was unable to reverse completely the antiviral activity of FIAC. Although, the extent of phosphorylation of thymidine, deoxycytidine, and deoxyuridine was 6-, 4-, and 4-fold greater, respectively, in human cytomegalovirus-infected cell lysates than in uninfected cell lysates, the extent of phosphorylation of FIAC was only 1.3-fold greater in human cytomegalovirus-infected cell lysates than in uninfected cell lysates. By comparison, the extent of FIAC phosphorylation was 500 times greater in herpes simplex virus type 1-infected cells than in uninfected cell lysates. Methotrexate was 400 times more effective against human cytomegalovirus replication than it was against herpes simplex virus type 1 replication, indicating that thymidylate synthetase may be important for human cytomegalovirus replication. However, 10 microM FIAC did not inhibit thymidylate synthetase activity in uninfected or virus-infected cells as determined by their metabolism of [6-3H]deoxyuridine in the presence or absence of drug. FIAC at 1 microM suppresses and FIAC at 10 microM completely inhibits human cytomegalovirus DNA replication as indicated by Southern blot analysis. This inhibition was reversible. FIAC incorporation into the DNA of human cytomegalovirus strain AD169-infected cells was stimulated relative to that in nondividing, uninfected cells.

Antiviral Agents↗

Recurrent Salmonella typhimurium bacteremia associated with the acquired immunodeficiency syndrome.

Seven Haitian and one white patient with the acquired immunodeficiency syndrome and Salmonella typhimurium bacteremia were identified over a 28-month period. In three patients bacteremia developed concurrently with an opportunistic infection associated with the acquired immunodeficiency syndrome. The remaining five patients had their initial episodes of bacteremia 3 to 11 months before the diagnosis of the acquired immunodeficiency syndrome. These five patients had signs suggestive of the syndrome, plus evidence of disordered cellular immune function (lymphopenia, anergy, decreased T-helper cells, decreased proliferative responses, and a deficiency in mononuclear-cell alpha interferon production). Salmonella typhimurium bacteremia in the appropriate clinical setting may be an opportunistic pathogen associated with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Human natural killer cells limit replication of herpes simplex virus type 1 in vitro.

Studies were undertaken to determine whether natural killer (NK) cells could inhibit the replication of herpes simplex virus type 1 (HSV-1) in culture. In the absence of effector cells, HSV-1 was found to replicate in fibroblasts with up to a 100-fold increase in virus titer from 4 to 16 hr after incubation at 37 degrees C. Human peripheral blood mononuclear cells were found to limit virus replication in a dose-dependent manner, with the greatest inhibition being observed at the highest concentration evaluated: i.e., an effector:target ratio of 800:1. The antiviral effect was not observed when nonactivated or virus-activated mononuclear cells were added to the virus preparations at the end (instead of the beginning) of the assay period, indicating that the observed effect was not due to a nonspecific toxicity of soluble factors released from freeze-thawed effectors. Neither was inhibition of HSV-1 replication due to the generation of interferon (IFN) during the NK assay, because the addition of anti-IFN did not abrogate the antiviral effect. Thus, the inhibition of viral replication was most likely due to a cytotoxic effector rather than to release of soluble factors. The effector cells responsible for limiting HSV-1 replication were shown to be NK cells by a number of criteria. Mononuclear cells from both HSV-1 seropositive and seronegative donors limited virus replication; their activity could be boosted by pretreatment of effector cells with IFN; the effector cells which limited virus replication were found in Percoll gradient fractions enriched for large granular lymphocytes; and the effector cells shared the cell surface phenotype of NK cells--they were enriched in populations depleted of T cells by panning with Leu-4 and were depleted of activity by treatment with the anti-NK antibody Leu-11b plus complement. We conclude that human NK cells are capable of recognizing and lysing HSV-1-infected target cells before infectious virus progeny are generated. These results suggest that NK cells, acting early in the course of an infection, might serve to limit HSV-1 replication and therefore reduce the virus load in the host before the development of the adaptive immune response and clearance of the infection.

Antibody-Dependent Cell Cytotoxicity↗

Advanced leiomyosarcoma of the stomach.

Retrospective studies of twelve patients with advanced gastric leiomyosarcomas were undertaken to evaluate radical surgical resection and combined modality treatment with regard to the patient survival and symptom palliation. All but one patient were found to have metastases or involvement of adjacent organs at the initial operation. Despite radical resection, multidrug chemotherapy, and radiation therapy, no patient survived beyond the third year. Patients with objective response to chemotherapy and radiation and chemotherapy had a mean survival of 27 months, while those who did not respond survived only 7 months. The longest survival among untreated group was 8 months. Successful palliation of advanced gastric leiomyosarcoma requires early diagnosis, surgical resection and multimodal therapy.

Adult↗

Pedunculated primary hepatocellular carcinoma.

A case report and two additional cases of pedunculated, primary hepatocellular carcinoma (PHCC) are added to those previously reviewed, and are compared with the more typical presentations of PHCC. Distinct differences include lesser associations with hepatitis B and alpha fetal protein among the pedunculated lesions. More importantly, this unique form of PHCC carries a much higher resectability rate that hopefully can be translated into longer survival in this subgroup.

Aged↗

Cavernous hemangioma of the anus.

Vascular tumors of the large bowel can be divided into malignant and benign lesions. The benign lesions can be divided into capillary and cavernous hemangiomas. Large-bowel hemangiomas are rare lesions, with the majority of cases reported in the rectum and rectosigmoid regions. Few cases of isolated anal hemangiomas are found in the literature. A case of an asymptomatic anal cavernous hemangioma, palpable on routine rectal examination and subsequently removed at proctosigmoidoscopy, is described.

Aged↗

Endobronchial metastasis from colorectal carcinoma.

A case report and review of the literature concerning endobronchial metastasis from colorectal carcinoma is discussed. Careful attention to the past history of the patient, presenting symptoms and laboratory evaluation, may lessen the diagnostic difficulty in differentiating a centrally located bronchogenic carcinoma from a metastasis to a major bronchus. In the majority of cases, the primary colorectal tumor will precede the pulmonary abnormality. The most frequently manifested symptoms are cough and hemoptysis. Radiologic findings usually consist of a collapsed lung, lobe or segment secondary to the bronchial obstruction. There appears to be equal predilection for metastatic involvement of either the right or left bronchial segments. Bronchial biopsies and comparison with the previous histology of the primary colorectal tumor are mandatory.

Adenocarcinoma↗

Evaluation of bladder washings and urine cytology in the diagnosis of bladder cancer and its correlation with selected biopsies of the bladder mucosa.

We report a prospective study of 136 patients with biopsy proved bladder tumor who underwent 311 evaluations with cystoscopy, urinary cytology, bladder washing and, when indicated, bladder biopsies. Cytology results from bladder washings were superior to routine urinary cytology studies in detecting abnormal cells. Also, there was a significant increase in the number of positive cytology studies in bladder washings from patients with no evidence of tumor by cystoscopy but who had biopsy proved dysplasia. Multiple selective bladder biopsies showed a higher incidence of mucosal abnormalities if the primary tumor was of a higher grade.

Biopsy↗

Nucleosides. 129. Synthesis of antiviral nucleosides: 5-alkenyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracils.

Synthesis of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracils containing a vinyl (4a), 2-halovinyl (4b-d), or ethyl substituent at C-5 was achieved. These nucleosides were found to be about a log order less active than 2'-fluoro-5-iodo-ara-C (FIAC) against HSV-1, but they are much less cytotoxic against normal human lymphocytes than FIAC. Nucleosides 4a and 4e showed good activity against HSV-1 (ED50 = 0.16 and 0.24 microM, respectively) and HSV-2 (ED50 = 0.69 and 0.65 microM) with very little cytotoxicity (ID50 greater than 100 microM).

Animals↗

Deficiency of interferon-alpha generating capacity is associated with susceptibility to opportunistic infections in patients with AIDS.

Acquired immune deficiency syndrome (AIDS) is a newly described syndrome in which patients are susceptible to certain malignancies and opportunistic infections (OI) usually found only in immunosuppressed individuals. Patients with AIDS have been found to have deficiencies of virtually all of their host defense systems. In this report, the natural resistance systems have been discussed. Although a deficiency of NK-cell function has been found in many patients with AIDS, this deficiency failed to distinguish patients susceptible to OI or malignancy from male homosexual controls. A deficiency of interferon-alpha generation by mononuclear cells upon exposure to HSV-1 infected fibroblasts was the best correlate with susceptibility to OI in AIDS patients. This deficiency failed to correlate with serum levels of acid-labile interferon-alpha in these patients. Although the interferon generating deficiency may be caused by the infections in these patients, it is more likely that the deficiency lays the groundwork for the establishment of the opportunistic infections.

Acquired Immunodeficiency Syndrome↗

A human monoclonal antibody to cytomegalovirus (CMV).

We report the development of a human monoclonal antibody to cytomegalovirus (CMV) produced from a human X human hybridoma. This hybrid was developed by fusion of an EBV-transformed cell line making antibody to CMV and a human lymphoblastoid cell line WI-L2. The antibody is directed to a CMV-specific antigen primarily in the nucleus of CMV-infected human fibroblasts. It cross-reacts with at least 10 different strains of CMV and may provide a method for the rapid in vitro diagnosis of CMV infections. The production of CMV-specific human man monoclonal antibodies from human-human hybridomas for future therapeutic use is now technically feasible with this specific method of production.

Antibodies, Monoclonal↗

Metabolic competition studies of 2'-fluoro-5-iodo-1-beta-d-arabinofuranosylcytosine in vero cells and herpes simplex type 1-infected vero cells.

2'-Fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine (FIAC) is a potent antiviral agent with minimal cytotoxicity. In Vero cells, incorporation of labeled dCyd and dThd into the acid-insoluble DNA fraction was, respectively, competitively and noncompetitively inhibited by FIAC. In herpes simplex type 1 (HSV-1) infected Vero cells, these inhibition patterns became noncompetitive. The inhibition constants of FIAC on dThd and dCyd incorporation into the acid-insoluble fraction during a 15-min period were greater than 30 microM which were much higher than the antiviral concentration of FIAC (ED90 = 0.003-0.013 microM) for continuous exposure. Incorporation of dUrd into acid-insoluble DNA was inhibited by 10 microM FIAC in HSV-1-infected Vero cells, but not in uninfected cells. The radioactivity of [2-14C]FIAC was incorporated into the acid-insoluble DNA fraction, and this incorporation in uninfected cells was strongly inhibited by 10 microM dCyd but not by dThd. By contrast, the incorporation in HSV-1-infected Vero cells was strongly inhibited by 10 microM dThd but not by dCyd. These data indicate that FIAC behaves metabolically like dThd, dUrd, or 5-iodo-dUrd in HSV-1-infected cells but like dCyd in noninfected cells. Thus, combined use of dCyd and FIAC may reduce cytotoxicity of FIAC or incorporation of FIAC into host cell DNA without affecting its antiviral activity. This finding is of significance since, for practical reasons, incorporation of FIAC into host cell DNA needs to be reduced as much as possible.

Animals↗