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D Mancini

Publications and source records attributed to D Mancini.

At least 55 records · Page 3Linked to original sources
PubMed1996

Indirect recognition of donor HLA-DR peptides in organ allograft rejection.

To determine whether indirect allorecognition is involved in heart allograft rejection T cells obtained from peripheral blood and graft biopsy tissues were expanded in the presence of IL-2 and tested in limiting dilution analysis (LDA) for reactivity to synthetic peptides corresponding to the hypervariable regions of the mismatched HLA-DR antigen(s) of the donor. Serial studies of 32 patients showed that T cell reactivity to donor allopeptides was strongly associated with episodes of acute rejection. The frequency of allopeptide reactive T cells was 10-50-fold higher in the graft than in the periphery indicating that T cells activated via the indirect allorecognition pathway participate actively in acute allograft rejection. In recipients carrying a graft differing by two HLA-DR alleles the response appeared to target only one of the mismatched antigens of the donor. Indirect allorecognition was restricted by a single HLA-DR antigen of the host and directed against one immunodominant peptide of donor HLA-DR protein. However, intermolecular spreading was demonstrated in patients with multiple rejection episodes by showing that they develop allopeptide reactivity against the second HLA-DR antigen. These data imply that early treatment to suppress T cell responses through the indirect pathway of allorecognition, such as tolerance induction to the dominant donor determinant, may be required to prevent amplification and perpetuation of the rejection process.

Cells, Cultured↗
PubMed1996

Heterogenous point mutations in the BRCA1 breast cancer susceptibility gene occur in high frequency at the site of homonucleotide tracts, short repeats and methylatable CpG/CpNpG motifs.

Heterogeneous mutations in the BRCA1 tumour suppressor gene are responsible for a large percentage of inherited breast cancers as well as breast/ovarian cancers in families with a high incidence of both cancer types. Over a hundred BRCA1 mutations have been reported, but little is known of the mechanism(s) responsible for BRCA1 mutagenesis. To determine the significance of specific nucleotide sequences at mutational sites within the BRCA1 gene, we assessed how frequently independent BRCA1 mutations occur at the site of short direct repeats, single nucleotide repeats (homonucleotides) and at CpG and CpNpG motifs. We found that homonucleotide and short direct repeats are commonly associated with small deletions and insertions. Substitution mutations are frequently associated with homonucleotide repeats and with methylatable CpG dinucleotides and CpNpG trinucleotides. Our methylation and sequencing experiments show that CpG and certain CpNpG motifs are methylated, supporting the hypothesis that DNA methylation specificity at these sites may be an important contributor to BRCA1 mutagenesis. We suggest that BRCA1 mutations are acquired by replication errors and are retained by cells through an intricate balancing of replication and repair mechanisms. Such mutations may provide a proliferative advantage for a cell, leading to the tumour phenotype.

BRCA1 Protein↗
PubMed1996

Changes in myofibrillar protein composition of human diaphragm elicited by congestive heart failure.

We describe the changes in proportions of myofibrillar proteins elicited by chronic congestive heart failure in the costal diaphragm (DIA) of humans using one and two-dimensional electrophoretic techniques. Three myosin heavy chain (MHC) isoforms were found in the DIA from control subjects: slow MHC I (43 +/- S.E. 2%), fast MHC IIa (41 +/- 2%) and fast MHC IIb (17 +/- 1%). In heart failure DIA, the percentage of MHC I was increased to 57 +/- 2%, while that of MHC IIb was decreased to 8 +/- 2 (P < 0.001 for both cases). Similarly, this DIA had higher molar ratios (%) of the slow myosin light chain isoforms (i.e. 1sa, 1sb, and 2s), and lower molar ratios of the fast isoforms (i.e. 1f, 2f, and 3f) than control DIA. Heart failure DIA also contained lower proportions of both alpha-tropomyosin and fast isoforms of troponin-T, I and C than control DIA. These results indicate that heart failure elicits fast-to-slow transformations of both myosin and regulatory proteins of human costal DIA. These changes can be viewed as an increase in slow-twitch characteristics of the DIA and differ from the adaptations elicited by heart failure in limb muscles.

Diaphragm↗
PubMed1996

Fracture after cardiac transplantation: a prospective longitudinal study.

Cardiac transplantation is associated with increased prevalence of vertebral fractures, but the natural history of and risk factors for fracture after this life-saving procedure are unclear. We evaluated 47 patients (34 men and 13 postmenopausal women) before transplantation with spinal radiographs, determination of bone density by dual energy x-ray absorptiometry, and measurement of biochemical indexes of mineral metabolism. During the first year after transplantation, incident fractures were documented radiographically. Associations among demographic characteristics, bone density, biochemistries, and fracture risk were evaluated with logistic regression analysis. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), 17 patients (7 women and 10 men) sustained a total of 34 fractures. Most fractures involved the spine, and 85% of the patients who experienced fracture did so within 6 months of transplantation. Fifty-four percent of the women and 29% of the men experienced fracture. Femoral neck bone mineral density was significantly lower in women who experienced fracture than in those who did not (0.604 +/- 0.11 vs. 0.760 +/- 0.12 g/cm2; P < 0.04), but did not differ in men according to fracture outcome. The amount of bone loss at the femoral neck by 6 months after transplantation was significantly greater in men with fracture than in men without fracture (12.0 +/- 6.4% vs. 6.8 +/- 5.3%; P < 0.04), but did not differ in women according to fracture outcome. Pretransplant 1,25-dihydroxyvitamin D levels were significantly lower (25 +/- 9 vs. 39 +/- 17 pg/mL; P < 0.007) and intact PTH levels tended to be higher in men who did not experience fracture (37 +/- 15 vs. 69 +/- 46 pg/mL; P < 0.06). Individual pretransplant bone density measurements demonstrated substantial overlap between patients who did and did not experience fracture, and normal bone density did not necessarily protect against fracture after transplantation. We conclude that fractures are a common and early complication of cardiac transplantation. No pretransplant measurement has yet been identified that reliably predicts fracture after transplantation in the individual patient.

Bone Density↗
PubMed1991

Effect of antitumor surgery on soluble interleukin-2 receptor serum levels.

Surgically induced immunosuppression may play a role in cancer, because of the possible existence of micrometastases at the time of surgical removal of tumors. Antitumor immune reactions are mediated by interleukin-2 (IL-2). IL-2 acts on a specific IL-2 cell surface receptor; moreover, a soluble form of IL-2 receptor (sIL-2R) can be released in the blood. This study was carried out to evaluate the effect of surgery on sIL-2R serum levels in patients with operable solid tumors. A total of 48 patients with cancer and 11 controls who underwent major surgery for non-neoplastic disease were evaluated before and 7 days after surgery. Serum mean levels of sIL-2R were significantly higher after than before surgery in both the cancer and control groups. No correlation was seen between surgery-induced changes in sIL-2R and in T lymphocyte subsets. Because of its capacity of binding to IL-2, the increased blood concentrations of sIL-2R could reduce the IL-2 availability and negatively affect antitumor immune reactions.

Breast Neoplasms↗
PubMed1991

Bilateral bronchoalveolar lavage in progressive systemic sclerosis: interlobar variability, lymphocyte subpopulations, and functional correlations.

Bilateral bronchoalveolar lavage (BAL) was carried out in right middle and left upper lobes of 22 nonsmoking females suffering from progressive systemic sclerosis in order to assess interlobar differences and functional correlation of the BAL composition. The patients' age ranged from 20 to 66 years, and the mean disease duration was 10.4 years. The most frequent finding was a mild BAL lymphocytosis (right in 11 of 22 patients; left in 8 of 22), but eosinophilic (right in 11 of 22; left in 5 of 22 patients) and neutrophilic (right in 9 of 22 patients; left in 1 of 22) alveolitis was recognized as well. Differential counts suggestive of alveolitis limited to one of the lavaged lobes were demonstrated in about one fourth of the cases. Including increased cellularity among the criteria of pathological BAL fluid composition, 14% of the subjects showed bilateral BAL results within the normal range. OKT8-positive lymphocytes were significantly increased in 3 patients, but the mean values were not. Total lung capacity, vital capacity, and forced expiratory volume in 1 s correlated inversely with BAL neutrophil (p less than 0.05) and granulocytic (p less than 0.01) differential counts; the strongest, positive correlation was demonstrated regarding the lymphocyte/granulocyte ratios (p less than 0.0005). In conclusion, several patterns of alveolitis as well as a bilaterally normal BAL composition were found in our series; moreover, even if inhomogeneous alveolitis did occur, a single lavage performed in the right middle lobe correctly detected or excluded the presence of an alveolitis in 95% of our patients.

Adult↗
PubMed1989

Effect of exercise duration on density and coupling of beta-adrenergic receptors on human mononuclear cells.

The effect of maximal exercise on lymphocyte beta-adrenergic receptors was examined in 26 normal subjects. Exercise increased O2 consumption (Vo2) from 5 +/- 1 to 50 +/- 4 ml.min-1.kg-1, plasma norepinephrine level from 188 +/- 28 to 2,682 +/- 160 pg/ml, and plasma epinephrine level from 94 +/- 72 to 857 +/- 180 pg/ml. The density of beta-adrenergic receptors on lymphocytes obtained at rest was 31 +/- 3.7 fmol/mg protein; exercise increased the density of receptors by 86 +/- 33% (range 0-257%) to 58.3 +/- 1.5 fmol/mg protein but did not alter the affinity of the receptor for [125I]iodopindolol or the coupling of the receptor to the guanine nucleotide-binding regulatory protein. The density of beta-adrenergic receptors increased progressively throughout exercise and paralleled the increase in heart rate. The magnitude of the change in the density of beta-adrenergic receptors did not correlate with the magnitude of the increase in heart rate, Vo2, or plasma levels of catecholamines. The density of receptors was still elevated 15 min after completion of exercise but fell below base line 1 h after peak exercise to 18.2 +/- 6.7 fmol/mg protein (P less than 0.05 vs. base-line levels). These results demonstrate that exhaustive exercise results in a progressive increase in the number of beta-adrenergic receptors on lymphocyte membranes, followed by a reduction in the density of receptors during the recovery phase of exercise. Despite a significant increase in the level of plasma catecholamines, the receptor remains coupled to the guanine nucleotide-binding regulatory protein.

Adult↗
PubMed1988

CI-930, a new cardiotonic and vasodilating agent: hemodynamic comparison to dobutamine and long-term clinical effects.

The hemodynamic and clinical effects of parenteral and oral CI-930, a new phosphodiesterase type III inhibitor with combined vasodilator and inotropic properties, were studied in 12 patients with severe congestive heart failure refractory to therapy including captopril. The maximum response to dobutamine was also determined. Intravenous CI-930 increased cardiac index from 1.73 +/- 0.48 to 2.38 +/- 0.55 L/min/m2, and reduced pulmonary capillary wedge pressure from 19.2 +/- 7.9 to 12.5 +/- 6.4 mm Hg, mean right atrial pressure from 7.5 +/- 6.3 to 3.6 +/- 4.0 mm Hg, and systemic vascular resistance from 2288 +/- 860 to 1711 +/- 611 dynes . sec . cm-5 (p less than 0.001 for all). Heart rate and mean systemic arterial pressure were unchanged. The increment in cardiac index produced by dobutamine was higher than for CI-930, 2.68 +/- 0.55 vs 2.38 +/- 0.55 L/min/m2, p less than 0.001. However, reduction in pulmonary capillary wedge pressure tended to be less with dobutamine, 15.7 +/- 7.9 vs 12.5 +/- 6.4 mm Hg (NS). Hemodynamic benefits of oral CI-930 were equivalent to that of the parenteral drug. Duration of action was 9 to 12 hours. Chronic therapy resulted in subjective improvement in approximately 50% of patients. Exercise capacity, assessed by maximum oxygen consumption, was unchanged, 8.4 +/- 3.3 vs 9.8 +/- 3.4 ml/kg/min (NS). No overt laboratory manifestations of toxicity were observed.

Cardiotonic Agents↗
PubMed1985

Intravenous use of amrinone for the treatment of the failing heart.

Amrinone, a new nonadrenergic, nonglycosidic agent with combined positive inotropic and vasodilating properties, was approved recently for parenteral use in the treatment of left ventricular failure. Its mechanism of action is mediated primarily by selective phosphodiesterase fraction III inhibition, although at high doses alterations of calcium transport may occur. Acute hemodynamic changes produced by amrinone include augmentation of cardiac output and decreases in pulmonary capillary wedge pressure, right atrial pressure and systemic vascular resistance. Heart rate and blood pressure remain unaltered. Myocardial oxygen consumption declines concomitantly with the decrease in systolic wall tension. The efficacy of amrinone is comparable to that of dobutamine and dopamine. Synergistic interactions with catecholamines and vasodilators are described. Adverse effects are minimal, with dosage limited predominantly by decreases in filling pressures.

Aminopyridines↗
PubMed1985

Systemic and regional hemodynamic effects of captopril and milrinone administered alone and concomitantly in patients with heart failure.

The effects of milrinone and captopril on ventricular performance, renal blood flow, and femoral vein oxygen content were compared in 11 patients with severe chronic heart failure. The increase in stroke volume index was greater with milrinone than with captopril (28 +/- 7 vs 24 +/- 7 ml/m2; p less than .05), while pulmonary capillary wedge pressures fell similarly (19 +/- 10 vs 21 +/- 7 mm Hg). Mean systemic arterial pressure decreased significantly from 84 +/- 10 to 73 +/- 11 mm Hg (p less than .05) with captopril but did not with milrinone. Neither drug changed heart rate significantly. Although milrinone produced a greater improvement in ventricular performance than captopril, renal blood flow increased similarly with both drugs from 289 +/- 78 to 417 +/- 111 ml/min (p less than .05) and from 278 +/- 77 to 441 +/- 115 ml/min (p less than .05), respectively. Femoral vein oxygen content was increased by milrinone from 7.9 +/- 2.6 to 9.8 +/- 3.0 ml/100 ml (p less than .05) and was not changed by captopril. In seven additional patients, intravenous milrinone, administered at the peak effect of captopril, further augmented stroke volume index from 24 +/- 6 to 32 +/- 6 ml/m2 (p less than .05) and tended to reduce pulmonary capillary wedge pressure further from 20 +/- 8 to 18 +/- 9 mm Hg (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Calcitonin secretion and bone disease severity in hypercalcaemic hyperparathyroidism.

Calcitonin (CT) plasma levels and urinary hydroxyproline (OHPr) excretion were studied in twenty-eight patients (eleven males and seventeen females) with primary hyperparathyroidism in order to ascertain the effect of CT secretion on the severity of bone disease. The results show that in primary hyperparathyroidism plasma CT levels are increased in about 50% of patients independent of sex. Plasma CT levels were correlated with serum calcium values in males but not in females. Urinary OHPr excretion values appeared higher in those patients which showed lower CT plasma levels. In this latter group the incidence of undetectable CT plasma values was higher in females. The results suggest that in patients with primary hyperparathyroidism the persistent challenge of CT secreting parafollicular cells due to chronic hypercalcemia, may induce a decrease in their functional reserve, and that the bone involvement may have a greater incidence and more severe course in females, due at least in part, for their inability to increase CT secretion as much as males, due to an intrinsic sex-related lower CT secretory reserve.

Adolescent↗
PubMed1981

Incidence of normocalcemic hyperparathyroidism in idiopathic hypercalciuria: evaluation by dietary calcium deprivation test.

Calcium metabolism was studied in 37 patients with "idiopathic hypercalciuria" on a home diet and after 10 days of low calcium dietary intake (less than 400 mg/24h). After low calcium intake, urinary calcium excretion returned to within normal limits in 70% of the cases. In the group of patients which failed to respond to calcium restriction, TmPO4/GFR values were reduced and, furthermore, in 20% of them plasma iPTH and urinary cAMP levels were increased. These data seem to indicate that: the incidence of absorptive hypercalciuria is higher than hypercalciuria of renal origin; normocalcemic hyperparathyroidism due to primary calcium leak is present only in a limited number of cases, consequently, hypercalciuria secondary to renal phosphate leak is a rather frequent occurrence.

Calcium↗
PubMed1979

[Evaluation of intestinal absorption of calcium by means of double-isotope methods and oral administration of the tracer].

The percent intestinal absorption of calcium was measured in normal volunteers and in patients with idiopathic hypercalciuria employing the deconvolution method, the ratio of the two administered isotopes at equilibrium and the percent of dose present in plasma 2 hr after oral administration of the tracer. Comparison of results obtained showed that the technique based on the ratio between the two radioisotopes overestimates intestinal absorption by about 9% with respect to values calculated with the deconvolution method, but gives results comparable to those determined by oral administration of the isotope. The percent dose of the tracer 2 h after i.v. administration is closely correlated with the size of the miscible calcium pool. A less significant correlation exists between the size of the pool and percent of the dose 2 h after oral administration.

Administration, Oral↗
PubMed1979

[Studies of the half-life of plasma parathyroid hormone: rate of disappearance of immunoreactive fragments of the hormone after surgical removal of the parathyroid adenoma in primary hyperparathyroidism].

The disappearance rate of immunoreactive plasma parathyroid hormone (iPTH) was studied, employing two different antisera, following removal of parathyroid adenoma in patients with primary hyperparathyroidism. One antisera contained antibodies against both the NH2 region and the COOH terminal of the molecule (antiserum 211/32, Wellcome Laboratories), the other contained antibodies against antigenic sites of the terminal COOH portion (Immuno Nuclear Corporation antiserum). The iPTH plasma level dropped in all patients following removal of the adenoma. The half-life was longer than that of the native hormone and shorter than that of the terminal fragment with both antisera, being 38.8 min for the 211/32 and 32.9 min for the I.N.C. antiserum. Whilst this finding might be expected for the 211/32 antiserum, on account of its characteristics, it is difficult to offer an explanation for the observed half-life of the I.N.C. anti serum which is specific for the terminal COOH region. These results appear to suggest that the terminal COOH fragment may be further metabolized and that its longer half-life, observed by other authors, is due to the antisera used recognizing the antigenic sites in a fragment smaller than the terminal COOH portion of the molecule, rather than to the effective half-life of the entire fragment.

Adenoma↗
PubMed1979

[Values and limitations of the radioimmunological determination of plasma parathyroid hormone in the study of the functional activity of the parathyroid glands].

Aim of the present study was to establish the limits and difficulties prevailing in RIA of PTH due to different specificity of antisera. Studies were carried out on normal volunteers and 36 patients with primary hyperparathyroidism (HPT) employing two different assay techniques a) 211/32 antiserum from Wellcome Lab. and b) Immuno Nuclear Corporation Kit. Plasma iPTH values were higher in most primary HPT patients than in normal subjects with both techniques. It is possible nevertheless to differentiate the primary HPT patients with normal plasma iPTH values from normal subjects by correlating plasma iPTH values with corresponding serum calcium values.

Humans↗