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Biomedical subjects

M Introna

Publications and source records attributed to M Introna.

103 records · Page 6Linked to original sources
PubMed1983

Effect of a streptococcal preparation (OK432) on natural killer activity of tumour-associated lymphoid cells in human ovarian carcinoma and on lysis of fresh ovarian tumour cells.

The streptococcal preparation OK432 was studied for its effects on natural killer (NK) activity of peripheral blood lymphocytes (PBL) from normal donors and from ovarian cancer patients, and of tumour-associated lymphocytes (TAL) from peritoneal effusions. OK432 augmented NK activity against the susceptible K562 line and induced killing of the relatively resistant Raji line. Freshly isolated ovarian carcinoma cells were relatively resistant to killing by unstimulated PBL and TAL. OK432 induced significant, though low, levels of cytotoxicity against 51Cr-labelled ovarian carcinoma cells. Augmentation of killing of fresh tumour cells by OK432 was best observed in a 20 h assay and both autologous and allogeneic targets were lysed. PBL were separated on discontinuous Percoll gradients. Unstimulated and OK432-boosted activity were enriched in the lower density fractions where large granular lymphocytes (LGL) and activity against K562 were found. Thus, OK432 augments NK activity of PBL and TAL in human ovarian carcinomas and induces low, but significant, levels of killing of fresh tumour cells. Effector cells involved in killing of fresh ovarian tumours copurify with LGL on discontinuous gradients of Percoll.

Adult↗
PubMed1983

Defective natural killer activity within human ovarian tumors: low numbers of morphologically defined effectors present in situ.

Tumor-associated lymphocytes (TAL) were isolated from 17 ascites and 7 solid ovarian carcinomas. TAL had defective natural killer (NK) activity against K562. Large granular lymphocytes, the morphologically identified effectors of NK activity, were poorly represented in TAL from ovarian carcinomas as compared to peripheral blood lymphocytes from the same patients or from normal donors. Similar results were obtained when effectors of NK activity were identified with an anti-NK (HNK-1) monoclonal antibody. When four TAL preparations were separated on discontinuous Percoll gradients, they were able to be enriched for NK activity and large granular lymphocyte morphology in the lower density fractions as observed with blood. These observations suggested that a low concentration of the relevant effector cells was the major factor determining the defective NK cytotoxicity of lymphoid cells associated with these human neoplasms.

Antibodies, Monoclonal↗
PubMed1982

Interferon effect on cytotoxicity of peripheral blood and tumor-associated lymphocytes against human ovarian carcinoma cells.

A study was done to investigate the tumoricidal activity of peripheral blood lymphocytes (PBL) and tumor-associated lymphoid cells (TAL) against freshly isolated tumor cells in human ovarian carcinoma. TAL and carcinoma cells were purified by density and velocity sedimentation on discontinuous Ficoll-Hypaque gradients and fetal bovine serum. Purified carcinoma cells from 23 ascitic and 3 solid tumors were used as targets in a 4- or a 20-hour 51Cr release assay. K562 cells were used to measure natural killer (NK) activity. Freshly purified ovarian carcinoma cells were relatively resistant to lysis by normal unstimulated PBL. Cytolytic activity of ovarian cancer PBL and TAL did not exceed that of control PBL: Only one PBL preparation had high levels of cytotoxicity (36.2 and 42.9% specific lysis after 4 and 20 hr at an effector-to-target cell ratio of 50:1) against autologous cancer cells but not against allogeneic targets (less than 5% specific lysis). TAL and, to a lesser extent, ovarian cancer PBL showed impaired NK activity against K562 compared to the activity seen in controls. In vitro exposure to partially purified human fibroblast interferon (IFN) (1,000 U/ml for 1-18 hr) augmented NK activity against K562 of PBL and TAL. When ovarian carcinoma cells were used as targets, IFN enhanced the cytotoxicity of normal PBL in a 4- and 20-hour assay; stimulation by IFN was less frequently observed with ovarian cancer PBL and TAL in a 4-hour assay, but after 20 hours effector cells from tumor-bearing subjects showed IFN-boosted cytotoxicity against carcinoma cells similar to the degree of cytotoxicity seen in controls. IFN enhanced the cytotoxicity of PBL and TAL against both autologous and allogeneic carcinoma cells. Thus PBL and TAL are rarely cytotoxic against 51Cr-labeled fresh autologous carcinoma cells, but in vitro exposure to IFN induced low levels of killing of ovarian tumor cells.

Cells, Cultured↗
PubMed1982

Natural cytotoxic activity in human lungs.

Disease-free surgical lung specimens from 13 patients with neoplastic or infectious diseases and from three subjects with non-neoplastic, non-infectious pathology were mechanically disaggregated. Natural cytotoxicity was tested against 51Cr-labelled K562 target cells. Unseparated lung cells had little cytotoxicity against K562 cells. Removal of plastic and nylon-wool-adherent cells resulted in cell preparations (morphologically 80% lymphoid) with increased cytolytic activity against K562 but cytotoxicity levels were considerably lower than those of blood lymphocytes tested in parallel. Similar results were obtained when phagocytic adherent cells were removed with carbonyl iron. The NK-resistant murine TU5 and human Raji lines were not affected by lung effector cells. In vitro exposure to partially purified fibroblast interferon enhanced the cytotoxicity of unseparated or non-adherent lung cells. Thus, unlike in mouse pulmonary tissue, low levels of natural cytotoxic activity are associated with the humans lung.

Cell Survival↗
PubMed1982

Inhibition of natural killer activity by human bronchoalveolar macrophages.

Mononuclear phagocytes were isolated by adherence from peripheral blood, peritoneal exudates, early lactation milk, ovarian carcinomatous ascites and bronchoalveolar lavages. Their capacity to modulate natural killer (NK) activity was assessed by mixing them with blood lymphocytes and by measuring lysis of 51Cr-labeled K562 cells. Unlike other mononuclear phagocyte populations, alveolar macrophages caused a marked dose-dependent inhibition of NK activity. Significant inhibition (40%) of the expression of cytotoxicity was evident at a ratio of alveolar macrophages to lymphoid cells of 0.12:1, and more than 80% suppression was usually observed at a ratio of 0.5:1. Blood monocytes, peritoneal and milk macrophages were consistently inactive up to the highest ratio tested, 2:1. Inhibition of the expression of NK activity by alveolar macrophages was observed at lymphocyte to K562 ratios ranging from 6:1 to 100:1 and over a 4 h or 20 h 51Cr release assay. Alveolar macrophages also inhibited interferon-stimulated cytotoxicity. Alveolar macrophages are unique among the mononuclear phagocyte populations studied in their capacity to inhibit the expression of NK activity effectively, and they could play a role in determining the low levels of NK activity associated with human pulmonary tissue.

Ascitic Fluid↗
PubMed1981

Inhibition of human natural killer activity by cyclosporin A.

The effect of in vitro exposure to cyclosporin A on human natural killer (NK) activity was investigated using peripheral blood lymphocytes as effectors and 51Cr-labeled K562 cells as targets. After preincubation of the effectors with the drug for 20 hr, a dose-dependent reduction of NK activity was observed at concentrations ranging from 0.1 to 10 micrograms/ml. Exposure to the drug during the 20-hr preincubation and the 4-hr 51Cr-release assay resulted in greater impairment of NK cytotoxicity than preincubation alone, whereas the drug, present only during the assay, had no effect on cytolytic activity. Inhibition of NK activity required a minimal exposure time to the drug of 8 hr. The inhibitory effect of cyclosporin A on NK activity was rapidly reversible as, after a 20-hr incubation with 19 micrograms/ml, complete recovery of cytotoxicity was already observed after a further 4-hr culture in medium. Partially purified human fibroblast interferon augmented NK activity even in the presence of high concentrations (10 micrograms/ml) of cyclosporin A.

Cells, Cultured↗
PubMed1981

Inhibition of natural killer activity by tumor-associated lymphoid cells from ascites ovarian carcinomas.

Tumor-associated lymphocytes (TAL) were isolated from ascites ovarian tumors by stepwise application of density and velocity sedimentation on discontinuous Ficoll-Hypaque gradients and fetal bovine serum. TAL had low levels of natural killer (NK) activity compared to levels of peripheral blood lymphocytes (PBL) from the same patients or control subjects. When TAL were mixed with PBL, significant inhibition of NK activity was observed in 7 of 27 patients tested, with the suppression levels ranging from 14 to 60%. Inhibition of PBL NK activity was observed at the ratio of TAL to PBL of 1:1 or 2:1. Suppression of NK activity was detected with effector-to-target cell ratios ranging from 6:1 to 25:1 and at incubation time from 4 to 20 hours in the cytolysis assay. Tumor-associated macrophages from 6 patients were tested for suppression of NK activity. Only with 1 donor was a 17% inhibition observed at a ratio of macrophages of PBL of 1:1. Thus suppression by mature plastic adherent macrophages does not play a major role in the determination of the low levels of NK in human ascites ovarian tumors and the inhibitory activity of suppressor TAL, which had a minor contamination (less than 5%) with mononuclear phagocytes. When TAL from 1 patient with suppressive activity were passed through nylon wool, inhibition of NK activity was observed with both adherent and nonadherent cells.

Cell Separation↗
PubMedDate not supplied

Outbreak of persistent, unexplained, generalized lymphadenopathy with immunological abnormalities in drug addicts in Milan.

Persistent unexplained lymphadenopathy (LAS) with intermittent fever, weight loss, night sweats and malaise was observed from March to October 1983 in 16 of 133 intravenous drug addicts who had been followed for at least two years in a Center for Drug Addicts Assistance in Milan, Italy. All the subjects lived in a restricted suburban area and indulged in frequent toxicomanic practices and mutual sexual intercourse. The subjects showed immunological alterations such as lymphopenia (50%), decreased T helper/T suppressor ratio (93%), both these abnormalities (43%), decreased T helper cells (75%), increased T suppressor cytotoxic cells (81%), decreased natural killer (NK) activity (77%), anergy (50%) or hypoergy (43%) to recall skin testing and elevated levels of IgG (87%). Anti-HTLV III antibodies were found in 14 of 16 (87%) patients with LAS and in 3 of 11 (27%) symptom-free drug addicts belonging to the same group. It will be important to assess in the future whether this clinical and immunological picture results in acquired immunodeficiency syndrome in an area so far untouched by this disease.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Scleroderma fibroblasts constitutively express the long pentraxin PTX3.

OBJECTIVE: PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein) and of an unrelated N-terminal domain. Unlike the classical pentraxins, PTX3 is expressed in response to IL-1beta and TNF-alpha but not to IL-6. The present study was designed to investigate the expression of PTX3 in normal and scleroderma fibroblasts. METHODS: Normal and SSc fibroblasts were cultured in the presence and absence of inflammatory cytokines. PTX3 mRNA expression in fibroblasts was evaluated by Northern analysis. PTX3 protein levels in fibroblast culture medium were estimated by ELISA. RESULTS: Normal fibroblasts were induced to express high levels of P7X3 mRNA by IL-1beta and TNF-alpha but not by other cytokines or growth factors. Scleroderma fibroblasts, unlike normal fibroblasts, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in SSc fibroblasts was not modified by anti-TNF-alpha antibodies or IL-1 receptor antagonist. In contrast, IFN-gamma and TGF-beta inhibited the constitutive but not the stimulated expression of PTX3 in SSc fibroblasts. CONCLUSIONS: PTX3 is a main feature of activated scleroderma fibroblasts.

C-Reactive Protein↗