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Biomedical subjects

M Mariani

Publications and source records attributed to M Mariani.

At least 235 records · Page 13Linked to original sources

Clinical study of melatonin in untreatable advanced cancer patients.

It is known that the pineal gland has some antitumor activity. Melatonin, its most important hormone, has been shown to inhibit tumor growth in vivo and in vitro. Moreover, some investigations have demonstrated an altered melatonin secretion in cancer patients. Despite these interesting data, clinical trials have never been carried out to evaluate the effects of melatonin on human neoplasms. The aim of this study was to draw some preliminary conclusions on melatonin therapy in advanced human neoplasms. Nineteen patients suffering from advanced solid tumors, which did not respond to standard therapies, entered the study. Performance status (PS) was 20 or less in 9 cases, and more than 20 in the other 10. Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period with lower doses in patients who had a remission, a stabilization of disease or an improvement in PS. Among patients with a PS higher than 20, a partial response was achieved in one case with cancer of the pancreas; moreover, 5 of 10 had stable disease, but the other 4 cases had a progression; an evident improvement of PS was obtained in 6 of the 10 cases. In contrast, among patients with a very poor PS, 7 of 9 died within the first 2 months of therapy. This preliminary study would suggest that melatonin may be of some value in treating cancer patients in whom standard antitumor therapies have failed, particularly in improving their PS and quality of life.

Adult↗

Asynergy and left ventricular performance in dilative cardiomyopathy.

The purpose of this work was to evaluate the presence and importance of asynergy in dilative cardiomyopathy. A semiautomatized analysis of left ventriculograms was performed in 18 cases, the morphology of longitudinal and transverse axes time-length curves was evaluated, and mathematical indices of asynchrony and hypokinesis were defined. Ten normal subjects and 9 patients affected by aortic regurgitation were used as controls. In dilative cardiomyopathy, anomalous (polyphasic) time-length curves were present in 55% of the cases, while they were absent in aortic regurgitation and in all normal subjects but one. In addition, the asynchrony index was slightly increased and the hypokinesis index significantly increased (28.8 +/- 7.2% vs. 17.8 +/- 7.1%, p less than 0.001). A negative correlation existed between the asynchrony index and the ejection fraction (r = -0.483, p less than 0.05) and both the ejection fraction and the maximum normalized velocity of contraction were reduced in the patients with the anomalous curves (29.7 +/- 6.9% vs. 46.0 +/- 11.5%, p less than 0.01; 1.66 +/- 0.52 s-1 vs. 2.86 +/- 1.33 s-1, p less than 0.02). It was concluded that asynergy, and especially asynchrony, is frequent in dilative cardiomyopathy and it is strongly associated with a major impairment of overall left ventricular function.

Adolescent↗

Immunogenicity of a free synthetic peptide: carrier-conjugation enhances antibody affinity for the native protein.

The synthetic peptide 166-174 of hCS sequence, corresponding to an antigenic determinant of the protein, was used to elicit MAbs to the native hCS molecule. The synthetic peptide was administered according to different immunization protocols to BALB/c mice, both in the free form or conjugated to carrier proteins. Spleens and popliteal lymph nodes from primed mice were fused with a myeloma cell line to produce MAbs, and selected clones were characterized for isotype and affinity. Spleen fusions gave rise to IgM MAbs, whereas lymph node fusions gave preferentially IgG MAbs. No correlation was found between antibody class and affinity since affinity is highly increased by carrier-conjugation, while it did not enhance IgG production. The free synthetic peptide showed a low immunogenicity: affinities of MAbs produced ranged from 10(5) to 10(7) l/mole, an average 1000-fold lower than the values obtained with carrier-conjugated peptide. In one case, however, carrier conjugation did not give rise to anti-hCS MAbs. Overall, these studies provide a rational approach to the production of anti-protein MAbs by synthetic peptide immunization and offer the opportunity to obtain MAbs of the desired isotype and affinity.

Animals↗

Platelet aggregation behaviour in patients treated with ticlopidine.

Thirty patients (18 women, 12 men) with permanent or paroxysmal atrial fibrillation were treated with a new antiplatelet drug, ticlopidine, in order to study platelet aggregation behaviour, to see whether the drug prevents thromboembolisms and to observe side-effects over a period of 6 months. A further comparative study of the effects of ticlopidine and dipyridamole + aspirin on platelet aggregation was carried out in 20 patients. All appropriate haematological parameters were tested every 3 months, while platelet aggregation curves with ADP were examined also after 15 days. At the end of the period an echocardiogram was performed to check for any sign of thrombosis. The reduction in the aggregation curves was statistically significant for all the ADP stimuli, except at low doses. In the comparison with dipyridamole + aspirin, ticlopidine gave better results; with the former there was no significant reduction in platelet aggregation. A more significant reduction was seen in patients who had showed hyperaggregation at the outset. Bleeding time was increased and platelet adhesivity was reduced. During the 6-month period a slight reduction in white blood cells and a slight increase in creatinine were observed, both remaining within the normal range. Some 33.3% of the patients experienced side-effects. No embolic event or thrombosis in the left atrium was seen. Ticlopidine seems to be an effective antiplatelet drug, especially for patients with hyperaggregation.

Adult↗

Determination of antigen-specific immunoglobulin content in ascitic fluids and antisera.

A rapid and sensitive method is described for the determination of the antigen-specific immunoglobulin contents of ascitic fluids and/or antisera. Immunoglobulins are quantitatively separated from the biological fluid by immunoaffinity chromatography on the insolubilized antigen using the Millipore Millititer filtration system to perform the simultaneous assay of multiple samples. The specific immunoglobulins are then eluted at acidic pH and their concentration is estimated by solid-phase competitive radioimmunoassay. Radioimmunoassay values, corrected for dilutions, give the antigen-specific immunoglobulin concentration of ascitic fluids and/or antisera.

Ascitic Fluid↗

Characterization of a doxorubicin-resistant murine melanoma line: studies on cross-resistance and its circumvention.

A B16 mouse melanoma cell line resistant to doxorubicin was obtained by continuous in vitro exposure to the drug. The ID50 for this line was 200 times higher than that for the parental cell line. The resistant cell line had some biological characteristics similar to those of the sensitive parental cell line, like saturation density and protein content. Differences were found in doubling time which was longer, cloning efficiency which was lower and DNA content which was higher in the resistant as compared to the parental line. Intracellular distribution of doxorubicin was also different having a nuclear-cytoplasmic ratio higher in sensitive than in resistant cells. Melanin content was an unstable feature in the sensitive cell line, whereas melanin was always present in resistant cells. Resistance to doxorubicin was maintained during 50 in vitro passages in the absence of the drug. Cross-resistance was found with vincristine and other anthracyclines, like daunorubicin and 4'-epi-doxorubicin but not with cis-platinum, and a new doxorubicin derivative, 4'-deoxy-4'-iodio-doxorubicin. The B16 line showed a lower resistance index to 4'-deoxy-doxorubicin and 4-demethoxy-daunorubicin (30 and 3 respectively), as compared to doxorubicin. Doxorubicin-resistance was partially circumvented by pretreatment of resistant cells with verapamil, a calcium chelating agent, and by trifluoperazine, a calmodulin-antagonist.

Animals↗

Demonstration of antibodies to human T-lymphotropic retrovirus type III in lymphoadenopathy syndrome patients and in individuals at risk for acquired immune deficiency syndrome (AIDS) in Italy.

An epidemiologic survey of the distribution of lymphoadenopathy syndrome in six Italian cities and its correlation with human T-lymphotropic retrovirus III (HTLV-III) is reported. Serum samples of nine patients with acquired immune deficiency syndrome (AIDS) were tested, 180 from patients with lymphoadenopathy and 349 from individuals belonging to groups such as homosexuals, drug addicts, hemophiliacs, and polytransfused considered at increased risk for AIDS. Prevalence of HTLV-III antibodies was 78% in AIDS patients and 61% in 180 patients with lymphoadenopathy syndrome (variation among drug abusers by city from 51% in Cagliari to 87% in Rome). The percentage of positive sera in individuals at risk for AIDS or lymphoadenopathy ranged from 0% in polytransfused to 8.5% in homosexuals, 14% in drug addicts, and 19.5% in hemophiliacs. No positive sera were found among 660 healthy individuals including relatives of patients with AIDS or lymphoadenopathy or in 342 patients suffering from immunologic or infectious diseases. These results strongly suggest that HTLV-III is the causative agent of AIDS and lymphoadenopathy. Since none of the healthy subjects were positive while a substantial percentage of people at risk for AIDS showed antibodies to HTLV-III, it may be presumed that this infection is also prevalent in the Italian population group in which AIDS and lymphoadenopathy are most likely to develop.

Acquired Immunodeficiency Syndrome↗

An interactive computer program for the determination of the binding constants of monoclonal antibodies by non-linear regression analysis of radioimmunoassay data.

A computer program is presented for non-linear regression analysis of radioimmunoassay data, which allows the determination of the binding parameters of monoclonal antibodies, i.e., affinity constant and number of available binding sites. The program is based on the median method and gives the values of the binding constants and their 95% confidence limits, without the necessity for their preliminary, approximate evaluation. The program may also be used to determine the binding constants for the interaction of receptors with labelled ligands.

Antibodies, Monoclonal↗

Identification of a mixture of two different monoclonal antibodies by nonlinear regression analysis after solid phase radioimmunoassay with labeled antigen.

The results of competitive solid phase radioimmunoassay with labeled antigen, when analyzed by nonlinear regression, may reveal the presence of two different monoclonal antibodies, occasionally produced in a hybridoma culture. In fact, a hybridoma-derived antihuman chorionic somatomammotropin antibody prepared in our laboratories showed an unsatisfactory curve fitting when the experimental data were elaborated on the basis of a monoclonal model. The antibody was subjected to recloning, and gave two separate homogeneous monoclonal antibodies with different affinity constants.

Antibodies, Monoclonal↗