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Biomedical subjects

C Lopez

Publications and source records attributed to C Lopez.

At least 109 records · Page 6Linked to original sources

Natural killer cell function and interferon generation in patients with primary immunodeficiencies.

Patients with primary immunodeficiency disorders were evaluated for three aspects of natural defense: natural killer (NK) cells which lyse HSV-infected fibroblasts [NK(HSV-FS)], NK cells which lyse K562 tumor targets [NK(K562)], and interferon-alpha generation. In addition, capacity to make interferon upon challenge with other commonly used inducers was also evaluated. Most patients with severe combined immunodeficiency disease (SCID) and deficits of both T- and B-cell function demonstrated normal NK function with one or both targets. Six of eight SCID patients generated interferon-alpha at or below the lower limit of normal while only two made clearly normal levels. Six of 10 patients with Wiskott-Aldrich syndrome (WAS) had normal NK(K562) and five of 10 generated normal levels of interferon-alpha but all had severely deficient NK(HSV-FS). Patients with Bruton's agammaglobulinemia demonstrated normal NK and interferon generation, as did patients with common variable immunodeficiency, even when subdivided into patients with T-cell proliferative deficiencies and those with only hypogammaglobulinemia. Natural defense parameters may help categorize patients with SCID and WAS and help define these heterogeneous diseases.

Agammaglobulinemia↗

Rectification of the remnants of the leaflets--a new surgical technique to avoid periprosthetic leaks in aortic valve replacement.

During the last 12 years, we have used a modified suture technique for aortic valve replacement in 450 patients in order to avoid periprosthetic leaks. There were 420 survivors, and reoperation for periprosthetic leaks was necessary in no instance. The "secret" of our technique consists of the uniform distribution of the tensile forces among all sutures, eliminating uneven stresses that favors tearing of the tissues or rupture of the stitches.

Adolescent↗

Enzymology and pathogenicity in mice of a herpes simplex virus type 1 mutant resistant to 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodocytosine.

The deoxypyrimidine nucleoside analog 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodocytosine (FIAC) is a potent and selective inhibitor of herpes simplex virus type 1 in vitro (C. Lopez, K. A. Watanabe, and J. J. Fox, Antimicrob. Agents Chemother. 17:803-806, 1980). Isopycnographic analysis demonstrated that 1 microM FIAC inhibited herpes simplex virus DNA replication by more than 95% but inhibited cellular DNA replication by only 32%. Mutant herpes simplex virus type 1 selected resistant to FIAC displayed linked resistance to other nucleoside analogs, including arabinosylthymine and acyclovir. Lysates derived from Vero cells infected with FIAC-resistant virus showed markedly lower levels of thymidine kinase activity and were unable to phosphorylate selectively arabinosylthymine or FIAC, in contrast to lysates from cells infected with wild-type herpes simplex virus type 1. Finally, drug-resistant virus displayed a 6,000-fold decrease in pathogenicity when inoculated intraperitoneally into genetically susceptible A/J mice. These results indicate that resistance to deoxypyrimidine nucleoside analogs is due, at least in part, to alterations in viral thymidine kinase and is accompanied by decreased pathogenicity in vivo.

Animals↗

Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity.

We evaluated the cellular immunity of 408 clinically stratified subjects at risk for acquired immune deficiency syndrome (AIDS), to define the role of interferon-alpha production deficits in the pathogenesis of opportunistic infections (OI). We followed 115 prospectively for up to 45 mo. Onset of OI was associated with, and predicted by, deficiency both of interferon-alpha generation in vitro, and of circulating Leu-3a+ cells. Interferon-alpha production is an index of the function of certain non-T, non-B, large granular lymphocytes (LGL) that are independent of T cell help. Leu-3a+ cell counts are a marker of T cell function. OI did not usually develop until both of these mutually independent immune functions were simultaneously critically depressed, leading to a synergistic interaction. These data suggest that the AIDS virus affects a subset of LGL, and that cytokine production by these cells is an important component of the host defense against intracellular pathogens that becomes crucial in the presence of severe T cell immunodeficiency.

Acquired Immunodeficiency Syndrome↗

Characterization of a new primary human pancreatic tumor line.

A primary human pancreatic tumor line (BxPC-3) has been established from a biopsy specimen of a histologically confirmed adenocarcinoma of the body of the pancreas. Tumorigenicity was proven by xenograft in athymic nude mice. Upon re-establishment of tumor xenografts in tissue culture, the epithelial tumor cells retained their original morphology. Histopathologically, the tumors grown in nude mice exhibited the original characteristics of the primary adenocarcinoma in the patient, producing traceable mucin and displaying moderately well to poorly differentiated adenocarcinomas with occasional lymphocytic infiltrations at the tumor peripheries. Furthermore, the tumor xenografts differentially expressed carcinoembryonic antigen, human pancreas cancer-associated antigen, and human pancreas-specific antigen. Karyotyping and glucose-6-phosphate dehydrogenase isoenzyme characterization revealed that this tumor line was of human origin and devoid of HeLa cell contamination. The BxPC-3 tumor line has been maintained for more than four years in our laboratory and represents a valuable model for primary human pancreatic cancer.

Adenocarcinoma↗

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↗