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Biomedical subjects

C Castelli

Publications and source records attributed to C Castelli.

At least 73 records · Page 4Linked to original sources
PubMed1990

T lymphocytes can mediate lysis of autologous melanoma cells by multiple mechanisms: evidence with a single T cell clone.

The specificity analysis of a CD3+, WT31+, CD8+ cytotoxic T lymphocyte (CTL) clone (CTL 49), isolated from peripheral blood lymphocytes of a melanoma patient (no. 665) after mixed lymphocyte culture with an HLA-A2+ allogeneic lymphoblastoid cell line (VSKB-LCL), revealed that CTL 49 could lyse, in addition to HLA-A2+ lines, autologous HLA-A2- melanoma (Me665/2) and K562 targets. Killing of VSKB-LCL, but not of Me665/2, could be inhibited by anti-CD3 and by anti-HLA-A2 antibodies or by modulation of the CD3 complex. Cold-target competition studies showed that K562, but not VSKB-LCL, could compete with Me665/2 for lysis by CTL 49. However, unlike K562, Me665/2 could be lysed by CTL 49 in a Ca2(+)-independent fashion in 4 h and 18 h assays. CTL 49 expressed mRNA specific for tumor necrosis factor (TNF alpha) and, to a lesser extent, for lymphotoxin (TNF beta). Exposure of the clone to anti-CD3 antibodies induced the expression of interferon(IFN)-gamma-specific mRNA. Antibodies to TNF alpha, TNF beta and IFN reduced the lysis of Me665/2, but not of K562, by CTL 49 in 18-h cytotoxic assays. Antibodies to TNF alpha and to IFN gamma almost completely inhibited the lysis seen on Me665/2 (but not on K562), in 96-h assays, by supernatants isolated from VSKB-LCL- or anti-CD3-stimulated CTL 49 cells. Taken together, these data indicate that major-histocompatibility-complex-independent lysis of autologous tumor cells and of natural killer reference targets by the same alloreactive T cell clone are activities related at the level of target recognition but distinct at the level of the lytic hit. Thus, efficient lysis of autologous tumor cells results from a complex mechanism based upon direct effector-target interaction as well as on cytokine-mediated cytolytic effects.

Calcium↗
PubMed1990

H-2 class I gene analysis in 3-methylcholanthrene-induced murine fibrosarcomas.

The objective of our study was to determine whether and how frequently MHC class I gene alterations occur in fibrosarcomas induced in BALB/c mice by the carcinogen 3-methylcholanthrene (3-MCA). Southern blot was performed to analyze the genomic organization of class I genes in a panel of twenty tumors of different immunogenic strength used at early in vivo passages. Our results rule out the presence of gross rearrangements or deletions in the H-2 class I genes of the tumors tested and indicate that the frequency of detectable class I alterations giving rise to restriction fragments length polymorphism (RFLP) should be very low.

Animals↗
PubMed1989

Loss of heterozygosity of DQ alpha gene in human malignant melanoma.

DNAs from human melanoma cells, used at early in vitro passage, were evaluated by Southern blot analysis for somatic loss of heterozygosity at the DQ alpha gene. A total of 7 melanomas, 3 primary and 4 metastatic derived from 5 different patients were studied; in one case (pt 665) cell lines were derived from two anatomically different subcutaneous metastasis, whereas in a second case (pt 9923) both the primary tumor and a lymph node metastasis were available. Restriction length polymorphism (RFLP) analysis, performed on autologous peripheral blood lymphocyte (PBL) DNA digested with different enzymes, showed a pattern of bands compatible with the constitutional heterozygous typing at DQ alpha gene in 4 cases whereas 1 case revealed an homozygous typing. When melanoma DNAs were analysed, 1 out of the 4 informative cases (pt 1007) showed a loss of a diagnostic fragment for DQ alpha gene when digested with both Taq I and Bgl I enzymes. These results indicate that class II allelic losses detectable by RFLP can be found on malignant melanoma and add further complexity on the involvement of chromosome 6 whose cytogenetic abnormality are the most consistent in this human neoplasia.

DNA, Neoplasm↗
PubMed1989

P-glycoprotein gene amplification and expression in multidrug-resistant murine P388 and B16 cell lines.

P-glycoprotein gene (mdrl) amplification and expression were examined in murine leukaemia P388/DX and melanoma B16VDXR cell lines, which exhibit a high level of resistance to a selecting agent, doxorubicin, and express a multidrug-resistant phenotype because they are cross-resistant to multiple cytotoxic drugs. The multidrug-resistant phenotype was obtained in different conditions of selection (in vivo and in vitro for P388/DX and B16VDXR, respectively). In both multidrug-resistant cell lines, an increased expression of P-glycoprotein gene (5 kb transcript detected in Northern blots) was observed and the level of P-glycoprotein mRNA correlated with the degree of resistance. In addition, high molecular weight mRNAs homologous to mdrl gene sequence were consistently detected only in P388/DX cells. Overexpression was associated with a high level of gene amplification only in resistant melanoma cells, whereas it occurred in P388/DX cells with a marginal increase in gene copy number. These results, suggesting that different genetic mechanisms could be responsible for P-glycoprotein overexpression, emphasise the complexity of genetic regulation that may affect tumour cell sensitivity to cytotoxic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Rheological profile of nesosteine: a new mucoactive agent.

Nesosteine, a new agent shown to improve physical characteristics of bronchial mucus in animal models, has been studied in chronic bronchitic patients to confirm its effect on viscoelasticity of bronchial secretions. Sputum was collected from hypersecretory bronchitic patients in a stable condition before and after seven days of treatment with nesosteine (900 mg/day) or a placebo. At the end of treatment a significant (p less than 0.05) decrease was found in the viscosity in the nesosteine group: on the contrary, a slight, non-significant increase in viscosity was observed in the mucus samples of the placebo group. The improvement in rheological characteristics of the bronchial mucus in the patients treated with nesosteine was associated with an increase in mucus transport rate (mucociliary clearance) observed in the same samples. The findings indicate that nesosteine reduces mucus viscosity in chronic bronchitic patients and that this change induces also an improvement in mucociliary clearance.

Bronchitis↗
PubMed1988

Differential susceptibility to recombinant interferon-gamma-induced HLA-DQ antigen modulation among clones from a human metastatic melanoma.

Twenty-one clones from an early culture of a histocompatibility leukocyte antigen (HLA) class II negative human metastatic melanoma (Me 9229) were screened for susceptibility to phenotypic modulation induced by recombinant interferon-gamma (rIFN-gamma) by using SPV-L3, a monoclonal antibody to HLA-DQ antigens, in indirect immunofluorescence followed by fluorescence-activated cell sorter analysis. After treatment with 500 U/ml of rIFN-gamma for 3 days one of the clones (9229/18) expressed high levels of DQ antigens, in terms of percentage of positive cells, whereas many other clones were much less susceptible or remained DQ negative. Scatchard analysis of the data of specific binding of 125-I-labeled rIFN-gamma revealed that one clone susceptible (9229/18) and one clone resistant (9229/5) to HLA-DQ modulation expressed similar numbers of interferon-gamma binding sites per cell; dose-response experiments showed that all clones could be induced to express HLA-DR and -DP antigens after exposure to rIFN-gamma. However, the DQ-negative profile of clone 9229/5 was not modified even after incubation with up to 1 X 10(4) U/ml of rIFN-gamma or by extending the culture time in the presence of this lymphokine up to 120 hr. Furthermore, Northern blot analysis indicated a direct correlation between changes in the levels of HLA-DR and -DQ-specific mRNA after rIFN-gamma treatment, and the lack or expression of HLA class II antigens at the cell surface of the two different clones. Karyotype studies did not reveal differences between clones 9229/5 and 9229/18 and Southern blot analysis indicated that both clones had similar EcoRI and HindIII restriction patterns for DR and DQ gene sequences. Finally, strong DQ-specific mRNA signal and antigen expression at the cell surface could be induced even on clone 9229/5 by treating the cells with supernatants from mixed lymphocyte cultures, recently shown to contain a class II-inducing factor different from interferon-gamma. Taken together these results indicate that DQ antigens can be modulated even in clones resistant to rIFN-gamma induction and suggest that the differential susceptibility observed in response to this lymphokine could play a role in the genesis of the phenomenon of intratumor heterogeneity.

DNA, Neoplasm↗
PubMed1987

Ly-5.185 molecule is associated with thymic maturation of lymphocytes but not with their cytotoxic activity.

The Ly-5 system is a composite family of molecules with different molecular weight. Each molecular form is characteristic of a different lymphoid population, in particular a 175,000- to 185,000-dalton doublet is peculiar of thymocytes and peripheral T cells. Athymic nude mice, however, lack the 185,000-dalton form on their lymphocytes. To investigate whether the expression of the 185,000 daltons requires the presence of thymus, we induced nude mice lymphocytes to differentiate into mature T cells in vivo by thymus grafting and, in vitro, into T cytotoxic cells (CTL) by cocultivation with alloantigen plus recombinant interleukin 2 (IL-2). The appearance of the 185,000-dalton form on lymphocytes of thymus-grafted nude mice but not on in vitro activated cytotoxic cells indicates an active role of thymus in the induction of this molecule and suggests that 185,000-dalton form could be a marker of intrathymic differentiation but not of the cytotoxic activity of T cells.

Animals↗
PubMed1985

Disulfide-linked surface molecules of monoclonal antigen-specific suppressor T cells: evidence for T cell receptor structures.

By two-dimensional polyacrylamide gel electrophoresis analysis under nonreducing/reducing conditions, five proteins with interchain disulfide bridges are revealed on the surface of the suppressor T cell lymphoma line LH8-105 obtained by radiation leukemia virus-induced transformation of hen egg-white lysozyme-specific suppressor T lymphocytes. Two disulfide-linked surface proteins expressed by LH8-105 cells have been positively identified by immunoprecipitation with specific antisera. The major labeled membrane protein of LH8-105 cells is the murine leukemia virus env glycoprotein gp70. The second disulfide-linked molecule identified on LH8-105 cells has a molecular mass of 84 kDa under nonreducing conditions and 42 kDa after reduction, and is immunoprecipitated by an antiserum which recognizes the T cell receptor for antigen. A disulfide-linked molecule of a similar molecular mass is also immunoprecipitated from surface-labeled LH8-105 cells by a rabbit antiserum directed against a synthetic peptide predicted from the nucleotide sequence of a cDNA clone encoding the beta chain constant region of a helper T cell hybridoma. Therefore, a dimeric structure comparable to the T cell receptor expressed by cytotoxic and helper T cells is present on the cell surface of these monoclonal antigen-specific suppressor T cells.

Animals↗
PubMed1984

Double-blind clinical evaluation of dimetophrine in chronically reduced arterial tension.

Thirty in-patients with chronically reduced arterial blood pressure and relevant subjective symptoms were treated over a 15-day period with oral doses of either 400 mg dimetophrine twice daily or placebo, according to a prospective, randomized, double-blind design. Systolic and diastolic blood pressures and heart rate were monitored at 5-day interval: subjective specific symptoms (scored 0 to 3 in order of increasing severity), haematology and haematochemistry were recorded before and after treatment. Both systolic and diastolic blood pressures increased significantly after dimetophrine all through the observation period. After 5 days, systolic blood pressure had already reached significantly higher values in comparison with the placebo-treated group, as did diastolic blood pressure by the 10th day. Overall, during the observation period, an increase from 82.7 +/- 1.0 to 112.3 +/- 2.1 mmHg was observed in systolic and from 54.3 +/- 1.3 to 62.7 +/- 1.4 mmHg in diastolic blood pressure with dimetophrine, whereas with placebo, systolic blood pressure increased from 80.4 +/- 1.5 to 93.7 +/- 2.9 mmHg and diastolic blood pressure remained unchanged (53.3 +/- 1.4 mmHg). Concomitantly, heart rate decreased significantly with dimetophrine from 88.1 +/- 2.5 to 77.2 +/- 1.4 beats/min, whereas it remained almost unchanged with placebo (from 83.9 +/- 2.5 to 80.0 +/- 1.9 beats/min). The associated symptoms (asthenia, paleness, drowsiness, fatigue, sweating, vertigo and headache) were largely relieved by dimetophrine (70.0% decrease) but not by placebo (37.4%). All symptoms except drowsiness and vertigo were reduced to a significantly larger extent with dimetophrine than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

[Surgical therapy of the dissection of the ascending aorta. Experience in the use of the G. R. F. biological glue].

Nine patients with dissecting aneurysm of the ascending aorta (type A dissection) were operated upon. Six cases had an acute dissection, whereas three cases had a chronic type of dissection. The ascending aorta was replaced with a Dacron tubular prosthesis after solidification of the external and the internal layers of the two aortic stumps using a G.R.F. biological glue. Early and late results as well as the possible complications during the post-operative course are reported. Furthermore the advantages in using the G.R.F. glue are discussed in details. They are mainly represented by the excellent solidification of the aortic stumps, by the possibility to correct the aortic regurgitation without valve replacement and particularly by a good hemostasis of the surgical sutures.

Adult↗
PubMed1983

[Fixed subvalvular aortic stenosis. Monodimensional echocardiographic findings].

19 patients affected by discrete subvalvular aortic stenosis were studied by M-mode echocardiography. The diagnosis was confirmed by cardiac catheterism and angiocardiography and by anatomic evidence in operative room. The most frequent echocardiographic pattern was the abnormal protosystolic movement of aortic valve leaflets, that was found in all the patients. A discrete linear echo in the outflow tract of the left ventricle was observed in almost half of the cases. In 40% of the cases the left ventricular outflow tract was narrowed. The relations between these echocardiographic patterns and the anatomical kinds of discrete subaortic stenosis are discussed. No correlations were found between echocardiographic patterns and severity of the subaortic stenosis.

Adolescent↗
PubMed1982

[Dyslipidemia and coronary disease. Clinico-coronarographic study].

An inverse relationship between alpha-cholesterol and coronary atherosclerosis was observed in 200 male patients given coronographies. Specifically the lowest alpha-cholesterol levels were observed in patients with the most serious and widespread atherosclerotic lesions. This inverse correlation was maintained at the same level in all age groups.

Adult↗