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Biomedical subjects

M Mariani

Publications and source records attributed to M Mariani.

At least 217 records · Page 12Linked to original sources
PubMed1990

Genetic polymorphisms in the Croatian ethno-linguistic minority of Italy.

Phenotype and gene frequencies of twelve genetic markers (ABO, RH, MNS, ACP1, ESD, PGD, PGM1, PGM2, HB, ALB, CP and HP) of the three Croatian communities (Acquaviva Collecroce, Montemitro and S. Felice del Molise) living in Southern Italy are reported. From the comparison with the surrounding Italian population and with Balkan populations, some instances of still incomplete genetic admixture can be inferred (ABO*A and O, ESD, PGD and PGM1).

Adolescent↗
PubMed1990

[Doppler echocardiography in the functional evaluation of patients with pure mitral valve stenosis].

To evaluate the utility of echo-Doppler (ED; PW, CW and color), 67 patients affected by pure mitral stenosis (20 M, 47 F, mean age 52 years) were submitted to ED examination. Right and left cardiac catheterization were performed in 20 patients within 24 hours before ED. Mitral area obtained by Doppler method (Hatle's formula) correlated highly with both echo-2 dimensional and hemodynamic area (r = 0.93, p less than 0.001; r = 0.95, p less than 0.001 respectively). It was possible to calculate systolic pulmonary pressure, in patients with tricuspid incompetence, (43.9 +/- 14.9 mmHg, range 25-80) which correlated significantly (r = 0.95, p less than 0.001) with hemodynamic data (40.2 +/- 12.7 mmHg, range 20-70). The left atrial-left ventricular pressure gradient was 15.6 +/- 6.9 mmHg, range 6-32; the mean pressure gradient was 8.4 +/- 3.7 mmHg, range 3-17; the pressure half time 170.2 +/- 62.3 ms, range 83-330. We observed different types of direction of transmitral jets: centrally directed (n = 34); forward antero-lateral wall (n = 28); toward interventricular septum (n = 5). The transmitral jets presented 4 different appearances: scimitar-shaped (n = 28); candle flame (n = 24); mushroom (n = 9); double-jets (n = 6). No correlation was observed between the different types of transmitral jets (direction and appearance) and the parameters obtained by Doppler (PW and CW): velocities, pressure half-time, gradients. Thus, Doppler echocardiography permits a complete anatomic and functional evaluation of patients with pure mitral stenosis. We have not observed any correlation between the hemodynamic data and the different types of transmitral jets visualized by color Doppler.

Echocardiography, Doppler↗
PubMed1990

[Hemorrhages of the upper gastrointestinal tract. A comparison of the diagnostic accuracy between endoscopic and radiological examinations].

One hundred and forty-eight patients admitted for upper gastrointestinal hemorrhage, but excluding esophageal varices, underwent optic fibre gastroscopy at the time of admission and were then examined using a barium meal after a 24-48 h interval. The aim of the study was to compare the sensitivity, specificity and diagnostic accuracy of the two tests. A correct diagnosis was obtained using both procedures in 58.2% of cases. Endoscopy provided an accurate diagnosis in 35.1% of patients, whereas gastrointestinal x-rays showed the exact site of the lesion in only 6.7% of cases. Endoscopy had a sensitivity of 92.5% compared with 60.7% for the barium meal. Endoscopy also had a higher level of specificity (100%) versus the barium meal (33.3%). The results obtained from the pathological examination of specimens confirmed the accuracy of endoscopy. In conclusion, early endoscopy is a reliable procedure in the emergency assessment of the hemorrhaging patient; routine x-ray examination does not appear to add additional information and may be reserved for subsequent use if endoscopy gives doubtful or misleading indications of the site of bleeding.

Barium Sulfate↗
PubMed1990

Gene transfer by retrovirus-derived shuttle vectors in the generation of murine bispecific MAbs.

This report deals with the use of gene transfer by retrovirus-derived shuttle vectors in a novel model aimed at the generation of hybrid hybridomas secreting bispecific monoclonal antibodies (biMAbs). Following this approach, two genes conferring dominant resistance trait to the neomycine analogue geneticin (G418) and to methotrexate (MTX) respectively, were infected in two established hybridoma lines, each producing a well characterized MAb. The vectors used here were replication-deficient, being dependent on the complementation of helper virus provided by packaging lines. The infection procedure involved co-cultivation of the hybridomas with irradiated packaging cell lines, previously transfected with the vectors and producing the recombinant retroviruses, not inclusive of helper virus in their genome. The packaging lines used were psi2 ecotropic cells made able to produce high titers of virus. Further, the vector pMV7 was carrying G418 resistance while the pSDHT render the cells able to survive MTX. Easy and fast transfer of the dominant selection markers yielded lines of hybridomas to be fused according to the conventional somatic fusions. The resulting double hybridomas were tested for the production of hybrid molecules retaining parental specificity and successively underwent extensive cloning. The purification system featuring the most efficiently between the true biMAbs and the parental immunoglobulins (or other combination products) proved to be HPLC on hydroxylapatite column. The method described above was successful in producing two biMAbs targeting simultaneously molecules expressed on cytotoxic cells (such as CD3 on T-lymphocytes and CD16 on NK cells) and the melanoma-associated antigen Ep2.

Animals↗
PubMed1989

Type 1 fiber abnormalities in skeletal muscle of patients with hypertrophic and dilated cardiomyopathy: evidence of subclinical myogenic myopathy.

Abnormalities of skeletal muscle have been described in patients with dilated and hypertrophic cardiomyopathy. Eleven patients with dilated and eight with hypertrophic cardiomyopathy without overt symptomatic skeletal myopathy underwent extensive neuromuscular studies. Quantitative electromyography showed abnormal reduction of motor unit potential duration, indicative of myogenic myopathy, in four patients (36%) with dilated and in three (37%) with hypertrophic cardiomyopathy. Values were 21% to 40% (mean 28%) lower than those in age-matched normal control subjects. The presence of normal nerve conduction velocities and of normal motor unit fiber density in all patients indicated lack of neurogenic abnormalities. Skeletal muscle biopsy was performed in five patients with dilated and in four with hypertrophic cardiomyopathy. In all nine patients light and electron microscopy showed central hyporeactive cores, selective atrophy and mitochondrial abnormalities of type 1 fibers but not of type 2 fibers. The degree of impairment of left ventricular function in patients with electromyographic abnormalities was similar to that of those without (percent fractional shortening at two-dimensional echocardiography 21 +/- 9 versus 25 +/- 10, ejection fraction at angiography 39 +/- 13% versus 42 +/- 13% and left ventricular end-diastolic pressure 21 +/- 6 versus 21 +/- 8 mm Hg) as well as symptom duration (9 +/- 4 versus 12 +/- 8 months). Thus, subclinical electromyographic alterations indicative of myogenic myopathy are frequent in patients with dilated and hypertrophic cardiomyopathy and are unrelated to the degree of impairment of left ventricular function. The concomitant histologic alterations, characterized by selective type 1 atrophy, are similar to those observed in congenital and idiopathic myopathies, but different from those described in secondary heart failure.

Adult↗
PubMed1989

Sarcoplasmic reticulum function in the "stunned" myocardium.

Transient ischemia does not induce myocardial necrosis but may be associated with prolonged contractile dysfunction ("stunned" myocardium). It has been suggested that alteration of the excitation-contraction coupling system (sarcoplasmic reticulum) could be responsible for this phenomenon. We tested this hypothesis by characterizing sarcoplasmic reticulum (SR) function in an isolated rat heart model of "stunned" myocardium (hearts reperfused after 10 min of normothermic global ischemia). At the end of the ischemic period oxalate-supported Ca-uptake was depressed either in the whole homogenate or in isolated SR (to 47% and 22% of control values, respectively). During reperfusion Ca-uptake of the whole heart homogenate recovered almost completely whereas slight but significant depression persisted in isolated SR (48 +/- 2 vs 67 +/- 4 nmol/min x mg, P less than 0.01). In the presence of ruthenium red or ryanodine, two inhibitors of SR Ca-release channels, Ca-uptake was stimulated. Both in the whole heart homogenate and in isolated SR, such stimulation was remarkably smaller after reperfusion than in control conditions (P less than 0.001) suggesting reduced conductivity state of the SR Ca-release channels. Ca-stimulated, magnesium-dependent ATPase activity was remarkably reduced during ischemia and postischemic reperfusion induced only incomplete recovery (93 +/- 18 vs 169 +/- 14 nmol ATP/min x mg protein, P less than 0.05). We conclude that complex modifications of SR function occur in the "stunned" myocardium and could contribute to the contractile impairment found in this condition.

Animals↗
PubMed1989

Protection of isolated rat heart from oxidative stress by exogenous creatine phosphate.

The influence of exogenous creatine phosphate (CP) on peroxidative heart injury was investigated in two experimental models: isolated working rat hearts and myocardial membrane preparations. In the first model the addition of 190 microM hydrogen peroxide to the perfusion buffer caused a marked decrease of aortic flow, minute work and peak aortic pressure, and leakage of intracellular enzymes. In the presence of 10 mM CP the hemodynamic damage produced by the same concentration of hydrogen peroxide was significantly lower and enzyme release was also remarkably reduced. The protection was concentration-dependent and the whole structure of the molecule was required since creatine was found to be ineffective. In the absence of hydrogen peroxide, CP and creatine did not affect heart performance. In microsomal membrane preparations CP decreased the formation of thiobarbituric acid-reactive material (malonaldehyde) induced by hydrogen peroxide in the presence of ferrous ions. This protection was concentration-dependent and occurred at physiological concentrations of CP. Also in this experimental model creatine had no effect and creatine plus inorganic phosphate was much less active than CP. The influence of CP on oxidative heart stress could account for the beneficial effect of this substance in different models of ischemic injury.

Animals↗
PubMed1989

The adenosine hypothesis revisited: relationship between purine release and coronary flow in isolated rat heart.

We evaluated the adenosine hypothesis through a new approach, based on the study of the relationship between coronary flow or resistance and purine release, which is an accurate index of myocardial adenosine release. Isolated rat hearts were perfused at different work loads, in hypoxic conditions and after a short period of global ischaemia. When the results of all experiments were considered together, purine release was significantly but weakly related to coronary flow and coronary resistance (r = 0.416 v coronary flow, r = 0.378 v the reciprocal of coronary resistance, p less than 0.01). Closer relationships were obtained within the three subgroups: the correlation coefficients increased to 0.819 and 0.835 (p less than 0.001) in the hearts perfused at different work loads with normal oxygen supply, to 0.701 and 0.757 (p less than 0.02 and p less than 0.01) in the hypoxic hearts, and to 0.897 and 0.978 (p less than 0.02 and p less than 0.01) in the hearts recovering from ischaemia. The relationships between purine release and coronary flow or resistance were significantly different in the three subgroups (p less than 0.001): at any value of purine release coronary resistance was highest during hypoxia and lowest after ischaemia, while the opposite was true for coronary flow. We suggest that the adenosine hypothesis is converted into a "weaker" statement: adenosine is involved in the adjustment between heart performance and coronary resistance but other factors contribute to the regulation of coronary flow, and/or affect the response to adenosine.

Adenosine↗
PubMed1988

Differential lysis of melanoma clones by autologous recombinant interleukin 2-activated lymphocytes. Relationship with spontaneous resistance to doxorubicin (Dx).

To investigate whether human melanoma cells intrinsically resistant to autologous LAKs do exist, and whether a relationship between the level of lysis of LAKs and spontaneous drug resistance can be identified at the clonal level, we studied 44 clones obtained from a metastatic melanoma lesion. The antigenic phenotype of clones revealed a marked heterogeneity in the expression of HLA antigens of classes I and II. The clones were subsequently tested for sensitivity to autologous LAK and for spontaneous resistance to Dx. No clone resistant to autologous LAK was found, although a considerable range of lysis was noted with a normal frequency distribution. Growth in agar of the 2 clones in which lysis was least pronounced (6 and 26) was completely inhibited after co-culture with LAKs, indicating a lack of absolute resistance to these effectors. Spontaneous resistance to Dx, evaluated as ID50, revealed instead that the majority of clones had a low ID50. The frequency distribution of clones showed a left-skewed curve. The percentage of specific 51Cr-release and the ID50 for Dx could be correlated in 25 clones by linear regression. Sensitivity to LAK did not correlate with HLA classes I or II or melanoma-associated antigen expression. These results support the contention that increased LAK sensitivity of tumor cells is associated with drug resistance.

Antigens, Neoplasm↗
PubMed1988

Effects of treatment with embryonic and uterine tissue homogenates on Lewis lung carcinoma development.

Based on the hypothesis that the development of cancer is actively inhibited during embryonic life, the effects on tumor growth of homogenates of different tissues (embryos, uteri at ninth day of pregnancy, non-pregnant uteri and normal liver) were investigated in syngeneic C57BL/6 female mice. Primary tumor growth and spontaneous pulmonary metastasis formation were completely suppressed in the group of mice treated with pregnant uteri homogenates. Embryos, non-pregnant uteri and normal liver homogenates were ineffective.

Animals↗
PubMed1988

Susceptibility of human and murine drug-resistant tumor cells to the lytic activity of rIL2-activated lymphocytes (LAK).

This article surveys the available data on the sensitivity of drug-resistant tumor cells to recombinant interleukin 2 (rIL2)-activated lymphocytes (LAK). In our own study, three different experimental systems were used: 1. in vitro treatment of tumor cells with an anticancer drug followed by the use of surviving cells as targets of LAK; 2. use of pairs of drug-resistant and drug-sensitive cell sublines; 3. analysis of several tumor clones obtained from the same tumor. The antitumor activity of LAK was evaluated both by the 51Cr release and the human tumor clonogenic assay (HTCA). In all the experimental systems used, drug-resistant tumor cells were found to be significantly lysed by LAK, with a consistent trend towards a higher susceptibility than their drug-sensitive counterparts. A positive correlation between the sensitivity to LAK and the ID50 for doxorubicin (Dx) was found in 44 melanoma clones analyzed, suggesting that spontaneously drug-resistant clones have a higher sensitivity to LAK than the drug-sensitive clones. Drug-resistant cells were also more sensitive to antibody and complement-mediated lysis, whereas the higher lysis of drug-resistant tumor cells exerted by LAK was maintained in a lectin dependent cytotoxicity assay. These data offer a rationale for combining chemotherapy with adoptive immunotherapy in the treatment of cancer. Moreover, studying the reasons for the higher LAK sensitivity of drug-resistant tumor cells may provide insights into the mechanisms by which tumor cells can resist LAK action.

Animals↗
PubMed1988

Lack of cross-resistance of a doxorubicin-resistant B16 melanoma line with 4'-deoxy-4'-iodo-doxorubicin.

A B16 melanoma cell line in which resistance to doxorubicin (Dx) had been induced by in vitro exposure to the drug, was found not to be cross-resistant with 4'-deoxy-4'-iodo-doxorubicin (4'-I-Dx), a new Dx derivative. Dx was 200 times less active in resistant than in sensitive cells, whereas the iodo derivative compound had the same level of activity in both cell lines. Cytotoxicity of Dx was dependent on concentration and on length of treatment, whereas that of 4'-I-Dx was correlated only with drug concentration. In an effort to explain this different behavior, intracellular retention and distribution of the two drugs was examined. Uptake and efflux of 4'-I-Dx in sensitive and resistant cells were similar, and cellular retention of the drug was 5-25 times higher than that of Dx. In addition, intracellular distribution of the iodo-derivative compound was similar in both cell lines, whereas more nuclear Dx was found in sensitive than in resistant cells. These differences may explain not only the lack of cross-resistance, but also the different cytotoxic behavior, of 4'-I-Dx.

Animals↗
PubMed1988

Doxorubicin cellular pharmacokinetics and DNA breakage in a multi-drug resistant B16 melanoma cell line.

Mechanisms of anthracycline resistance have been investigated in a B16 murine melanoma cell subline selected by continuous in vitro exposure to increasing concentrations of doxorubicin (DX). Altered drug pharmacokinetics were observed in resistant B16 cells as compared to the sensitive counterpart. In fact, cellular DX uptake - as determined by a fluorescence method - was lower in resistant than in sensitive cells. Furthermore, drug efflux rate was shown to be higher in resistant than in sensitive cells; treatment of cells with the metabolic inhibitor sodium azide decreased drug efflux rate in resistant but not in sensitive cells, suggesting the presence of an energy-dependent drug extrusion mechanism in the resistant B16 cells. However, since drug-induced cell killing did not correlate with cellular DX contents in sensitive and resistant cells, drug resistance of B16 subline could not be completely explained by the observed differences in drug pharmacokinetics. Since drug-induced DNA breaks have been related to drug cytotoxicity, DNA cleavage was also measured by alkaline elution methods. The number of DNA breaks produced by DX was decreased in resistant cells as compared to sensitive cells at the same cellular drug accumulation. The results are consistent with the view that anthracycline resistance may be multifactorial and probably arises following multiple biochemical changes.

Animals↗
PubMed1988

Verapamil potentiation of doxorubicin resistance development in B16 melanoma cells both in vitro and in vivo.

The effect of the combined administration of doxorubicin (DX) and verapamil (VRP) on the induction of DX resistance of B16 melanoma cells, was investigated both in vitro and in vivo. Cells grown in the presence of increasing concentrations of DX and of 1 microM VRP, tested at several passages, were more resistant than cells grown with DX alone. The treatment of B16 melanoma bearing mice with the maximal tolerated dose of DX (12 mg kg-1 i.v.) and of VRP (25 mg kg-1 i.p.) selected a line (B16-DX. VRP) completely resistant to DX after 17 transplants, while treatment with DX alone selected a DX resistant line after 27 transplants. Lung metastases were significantly lower in the B16-DX. VRP line compared to the original B16 melanoma. The results suggest that the association of VRP with DX increases the rate of resistance development to DX.

Animals↗
PubMed1988

Relation between lymphocyte subpopulations and pineal function in patients with early or metastatic cancer.

It has been demonstrated that melatonin and other pineal hormones play a role in the neuroendocrine control of immunity. Anomalies of both pineal and immune functions have been reported in cancer. Pineal and lymphocyte functions, however, have never been simultaneously evaluated in oncologic patients. This preliminary study was carried out in order to analyze the melatonin-lymphocyte relationship in human neoplasms. In a first investigation, we evaluated melatonin serum levels and lymphocyte subpopulations on venous blood samples collected during the morning from 46 healthy controls and from 27 cancer patients, 13 of whom had metastases, while the other 14 were without metastases. Moreover, melatonin levels were high in 10 oncological patients and within the normal range in the other 17 cases. B lymphocyte (B), total T lymphocyte (T3), T helper/inducer (T4) and T suppressor/cytotoxic (T8) mean percentages and T4/T8 mean ratios did not significantly differ, either between patients with high and normal melatonin levels, or between metastatic and nonmetastatic cancer patients. In a second study, we evaluated the effects of a prolonged treatment with melatonin (20 mg/daily intramuscularly at 3:00 p.m. for 2 months) on 8 patients with advanced cancer, in whom conventional antitumor therapies had failed. Mean percentages of B, T3, T4, T8 lymphocytes and T4/T8 mean ratios were not significantly different before or after melatonin treatment. In only one patient did the T4/T8 ratio decrease after therapy; in this case only, a stabilization of the disease was obtained, while in all 7 other patients the neoplastic disease progressed also during melatonin treatment, even if an evident improvement of the performance status was seen as it was in most cases. These results seem to exclude that melatonin may influence lymphocyte functions in cancer. Longitudinal studies and further data, however, will be needed to clarify this question.

Adult↗