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Biomedical subjects

A Ricci

Publications and source records attributed to A Ricci.

At least 19 recordsLinked to original sources
PubMed1998

High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: implications for protocol design of therapeutic antigen-specific vaccination strategies.

Human melanoma cells express several antigens which are recognized by autologous and specific CTL clones in association with HLA-class-I molecules. Many of these antigens represent suitable targets for tumor immunotherapy, since their expression in human melanoma cells is common and highly specific. In order to achieve real clinical success with therapeutic vaccination strategies, one important requirement is the expression of the target antigen by all the tumor lesions of a patient. We have studied this issue by assessing, through an RT-PCR approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic lesions (82%), the homogeneity in the pattern of gene expression within the cluster was complete. Heterogeneity within the same cluster was observed in only 3 out of 17 clusters (18%) and represented only minor features. Our data reveal that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic lesions express the same pattern of antigen-coding genes. These observations have 2 main clinical implications: (i) the antigenic characterization of one single and easily accessible lesion allows identification of optimal targets for an active antigen-specific immunotherapy treatment; (ii) almost all the metastatic lesions are expected to be hit by the immune response eventually induced against the tumor antigen. Moreover, these data suggest that active specific immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in high-risk AJCC-stage-III-melanoma patients.

Antigens, Neoplasm↗
PubMed1998

Percent achieved of predicted peak exercise oxygen uptake and kinetics of recovery of oxygen uptake after exercise for risk stratification in chronic heart failure.

To investigate whether percent achieved of predicted peak exercise oxygen uptake (%VO2max) and recovery of oxygen consumption after exercise may provide prognostic information in chronic heart failure (CHF), we prospectively studied 196 patients with mild to moderate CHF. The following variables were examined: age, etiology of CHF, functional class, ejection fraction (EF), peak exercise oxygen uptake normalized for body weight (VO2max), %VO2max, time to reach 50% of the peak oxygen uptake after exercise (T1/2VO2max), presence of nonsustained ventricular tachycardia (NSVT) and inability to take ACE-inhibitors. VO2max was the most powerful predictor of cardiac death (P<0.0001). Other independent predictors of death were EF, T1/2VO2max, NSVT and inability to take ACE-inhibitors. The discriminatory accuracy of VO2max for cardiac death was not significantly greater than that of %VO2max. In conclusion, the determination of %VO2max does not enhance risk stratification in CHF whereas the kinetics of oxygen consumption after exercise can provide prognostic information.

Exercise Test↗
PubMed1998

Response to long-term hGH therapy in two children with Schwachman-Diamond syndrome associated with GH deficiency.

Schwachman-Diamond syndrome is a rare congenital disorder characterized by pancreatic insufficiency, metaphyseal anomalies, recurrent infections, hematologic abnormalities, and growth retardation. Slow growth in these patients has been attributed to nutritional deficits, recurrent infections, and skeletal anomalies. Two cases of Schwachman-Diamond syndrome associated with growth hormone deficiency have been previously reported. We report here on 2 additional cases with this unusual association. Therefore, growth failure in Schwachman-Diamond syndrome should not be assumed to be due to chronic illness or recurrent infections; other etiologies for growth failure should be sought. However, the presence of metaphyseal disorders probably interferes with the long-term efficacy of growth hormone substitutive therapy.

Adolescent↗
PubMed1998

Density and localization of calcium channels of the L-type in human pulmonary artery.

The pharmacological profile and the anatomical localization of Ca2+ channels of the L-type were investigated in the human pulmonary artery to identify possible mechanisms involved in the regulation of the pulmonary vascular tone. Analysis was performed on slide-mounted frozen sections of human pulmonary artery using radioligand binding assay techniques associated with light microscope autoradiography. [3H]-Nicardipine was used as ligand. Human renal and right coronary arteries also were used as systemic reference arteries. Binding of [3H]-nicardipine to sections of human pulmonary artery was time-, temperature- and concentration-dependent, saturable and reversible. In the human pulmonary artery, the apparent equilibrium dissociation constant (Kd) was 0.12+/-0.02 nM and the maximum density of binding sites (Bmax) was 38.15+/-2.25 fmol/mg tissue. Kd values were 0.3+/-0.01 nM and 0.5+/-0.02 in the human renal artery and right coronary artery respectively. Bmax values were 248+/-16 fmol/mg tissue and 173+/-9.5 fmol/mg tissue in the human renal artery and right coronary artery respectively. The pharmacological profile of [3H]-nicardipine binding to sections of human pulmonary artery was consistent with the labeling of Ca2+ channels of the L-type. It was similar in the pulmonary artery and in the human renal and right coronary arteries. Light microscope autoradiography revealed a high density of [3H]-nicardipine binding sites within smooth muscle of the tunica media of human pulmonary artery as well as of human renal and right coronary arteries. A lower accumulation of the radioligand occurred in the tunica adventitia. No specific binding was noticeable in the tunica intima. Our data suggest that human pulmonary artery expresses Ca2+ channels of the L-type sensitive to dihydropyridines. These sites have similar affinity and lower density than those expressed by systemic arteries. The presence of Ca2+ channels of the L-type in human pulmonary artery suggests that their pharmacological manipulation may be considered in the treatment of pulmonary hypertension.

Aged↗
PubMed1998

Frequency of breast biopsy and breast cancer diagnosis in central Connecticut--trends from 1993 to 1997.

The frequency of diagnosed breast cancer at Hartford Hospital has risen 75% from 1993 to 1997 (153 vs 87 cases during January-March 1997 as compared to January-March 1993). During the same intervals the frequency of breast biopsies performed also increased 45% (455 vs 312 biopsies). The rate of "positive" biopsies has increased slightly (27.9%, 28.3%, 31.5%, 30.7%, and 33.6% for the first three months of each year 1993 to 1997, respectively). When stratified into thirds based on decreasing practice activity of Hartford Hospital surgeons with regard to breast surgery, the "positive" biopsy rates were 28.7%, 31.2%, and 33.0% respectively. Local breast cancer incidence is rising, however surgeons are not "overusing" breast biopsy as compared to recent past practice despite the fact that many more breast biopsies are now being performed.

Biopsy, Needle↗
PubMed1998

Double heterozygosity for mutations in the BRCA1 and BRCA2 genes in a breast cancer patient.

BACKGROUND: Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 confer substantial increased lifetime risk for breast cancer, and in the case of BRCA1, for ovarian carcinoma as well. These two genes alone account for the vast majority of hereditary breast cancer families. Numerous mutations have been described in each gene, the majority of which are small insertions or deletions resulting in expression of a truncated protein. MATERIALS AND METHODS: Several common mutations can be detected using a polymerase chain reaction-mediated, site-directed mutagenesis assay, which transforms the amplicon derived from either the wild-type or mutant allele by adding or removing a restriction endonuclease site. We screened 49 putative sporadic breast tumors using this methodology, targeting four BRCA1 mutations (185delAG, 5382insC, R1443X, and E1250X) and a single BRCA2 mutation (6174delT). RESULTS: Using the polymerase chain reaction-mediated, site-directed mutagenesis assay, we identified two mutations, namely, a 185delAG mutation (BRCA1) and a 6174delT mutation (BRCA2). Interestingly, these two mutations were found in the same sample. None of the remaining 48 breast tumors showed evidence of these mutations. Allele-specific oligonucleotide probes were then employed in conjunction with the Universal GeneComb Test Kit, which confirmed the presence of mutations. CONCLUSIONS: Our data suggest that the common germline BRCA1 and BRCA2 mutations are infrequently encountered in sporadic breast cancers. The one case with dual BRCA1 and BRCA2 mutations suggests that this tumor may be hereditary in origin, despite the lack of a positive family history. Double heterozygosity for mutations in BRCA1 and BRCA2 may have increasingly significant implications with regard to predisposition to breast cancer.

BRCA2 Protein↗
PubMed1997

Age-related changes of the noradrenergic innervation of rat tracheo-bronchial tree and pulmonary vasculature.

Age-related changes of the noradrenergic innervation of the tracheo-bronchial tree and of pulmonary vasculature were investigated in male Wistar rats of 3 months (young), 12 months (adult) and 24 months (old/aged), using catecholamine histofluorescence techniques associated with image analysis and by high pressure liquid chromagraphy with electrochemical detection. In young rats, blue-green fluorescent nerve fibres supply tracheo-bronchial smooth muscle and tracheal and bronchial glands, which are innervated by a delicate network of nerve fibres rich in varicosities. Pulmonary artery and vein are sparsely innervated. They are supplied with nerve fibres distributed in the vasa vasorum or the adventitia and the outer tunica media. The higher noradrenaline concentrations were found in the trachea and extraparenchymal bronchi, followed by pulmonary vein and pulmonary artery. The density and pattern of noradrenergic innervation of the tracheo-bronchial tree, or of the pulmonary vasculature, were similar in young and adult rats. In aged rats, a loss of noradrenergic innervation involving primarily the supply to the smooth muscle of the tracheo-bronchial tree was observed. Histofluorescence techniques demonstrated a higher sensitivity than noradrenaline assay in detecting changes of the sympathetic innervation of the tracheo-bronchial tree and of the pulmonary vasculature. The possible significance of reduced noradrenergic innervation of the tracheo-bronchial tree in aged rats is discussed.

Adrenergic alpha-Agonists↗
PubMed1997

Age-related changes of sulphide-silver staining in the rat hippocampus.

The influence of ageing on sulphide-silver positive zinc stores was assessed in the stratum radiatum of the CA1-CA3 sub fields of the rat hippocampus and in the molecular layer of the dentate gyrus using a silver amplification histochemical technique associated with microdensitometry. The volume of areas examined for microdensitometry was evaluated as well by quantitative image analysis. Male Sprague-Dawley rats aged 3 months (considered to be young), 12 months (considered to be adult) and 24 months (considered to be old) were used. Microdensitometric analysis of values of sulphide-silver staining corrected for the volume of hippocampal areas investigated revealed no age-dependent changes of staining in the CA1 sub field of the hippocampus. In the CA2 sub field a decrease of sulphide-silver staining was noticeable in aged rats in comparison with younger cohorts. A progressive reduction in the intensity of sulphide-silver staining was observed in the CA3 sub field of the hippocampus. In the molecular layer of the dentate gyrus, the intensity of staining was decreased in adult and old rats in comparison with young animals. These findings indicate a different sensitivity to ageing of histochemically detectable zinc stores of rat hippocampus. The possibility of a specific sensitivity to senescence of different zinc-containing pathways of the hippocampus is discussed.

Aging↗
PubMed1997

Pharmacological characterisation and autoradiographic localisation of a putative dopamine D3 receptor in the rat kidney.

The pharmacological profile and the microanatomical localisation of a putative dopamine D3 receptor in the rat renal cortex were investigated using radioligand binding assay and light microscope autoradiography techniques. [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetraline ([3H]7-OH-DPAT) was used as a ligand. [3H]7-OH-DPAT was bound specifically to sections of renal cortex. The binding was time-, temperature- and concentration-dependent, of high affinity and guanine nucleotide-insensitive. The dissociation constant (Kd) value was 0.57 +/- 0.02 nM and the maximum density of binding sites (Bmax) was 62.4 +/- 3.5 fmol/mg tissue. The pharmacological profile of [3H]7-OH-DPAT binding to sections of rat renal cortex suggests the labelling of a dopamine D3 receptor. Light microscope autoradiography revealed the accumulation of the radioligand primarily within cortical tubules and to a lesser extent in the glomerular tuft. In glomeruli, binding sites were found mainly in mesangium and mesangial cells. The demonstration of a putative dopamine D3 receptor in slide-mounted sections of rat renal cortex suggests that appropriate radioligand binding assay techniques combined with autoradiography, may contribute to characterise peripheral dopamine receptor subtypes.

Animals↗
PubMed1997

Dopamine D4 receptor in human peripheral blood lymphocytes: a radioligand binding assay study.

The expression of dopamine D4 receptor was investigated in human peripheral blood lymphocytes with a radioligand binding assay technique, using [3H]clozapine as radioligand. [3H]Clozapine was specifically bound to human peripheral blood lymphocytes. The binding was time-, temperature-, and concentration-dependent and of high affinity, with a dissociation constant (K(d)) value of 0.34 +/- 0.02 nM and a maximum density of binding sites (B(max)) value of 27 +/- 1.4 fmol/10(6) cells. The pharmacological profile of [3H]clozapine binding to human peripheral blood lymphocytes was similar to that found in Chinese hamster ovary (CHO) cells transfected with the D4 clone (D4.2 variant). The above results are consistent with molecular biology studies demonstrating the expression of a dopamine D4 receptor in immune cells and in human peripheral blood lymphocytes. The availability of a rapid and sensitive radioligand binding assay technique for the dopamine D4 receptor in human peripheral blood lymphocytes may contribute to better define the role of this dopamine receptor subtype in neurological and psychiatric disorders.

Adult↗
PubMed1997

Trk-like proteins during the post-hatching growth of the avian bursa of Fabricius.

Neurotrophins are growth factors acting on responsive cells through membrane receptors identified as Trk tyrosine kinase proteins (A, B and C). Trks are present in the mammalian lymphoid organs, and indirect evidence suggests that they are also present in the avian bursa of Fabricius. This study was designed to analyze (a) the occurrence and localization of Trk proteins in the bursa of Fabricius; and (b) whether the post-hatching growth of the organ (from hatching to 75 days) involves cells expressing Trk proteins. We used pigeon bursae of Fabricius, and rabbit polyclonal antibodies against specific epitopes of TrkA, TrkB and TrkC. Cytokeratins and vimentin were studied in parallel with label non-lymphoid cells of the bursal follicles. Immunoreactivity (IR) for all assessed antigens was found in specific non-lymphoid cells. From hatching to 15 days, TrkB-like IR was found outside the follicles in cells localized beneath the follicle associated (FAE) and interfollicular (IFE) epithelium. Between 30-75 days TrkB-like IR labelled the medullary secretory dendritic cells (SDC). The density of SDC displaying IR increased up to 60 days. TrkA-like and TrkC-like IR was primarily observed in FAE and IFE, but also in the medullary reticular epithelial cells (REC) up to 15 days. The present results provide evidence of the occurrence, localization and post-hatching changes in Trk proteins in avian bursa of Fabricius. Trks were localized on non-lymphoid cells which participate in providing the adequate microenvironment for B lymphocyte maturation. Furthermore, the cell segregation in the expression of Trks suggests specific roles for their ligands in controlling the function of medullary SDC and REC, hence bursal lymphoid follicle physiology.

Animals↗
PubMed1997

Pulmonary alveolar microlithiasis: review of Italian reports.

Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology, characterized by the presence of calcific concretions in the alveolar spaces. A familial occurrence is frequently found so that an inherited trait is thought to be involved. The chest X-ray is characterized by a 'sandstrom' picture while the clinical state undergoes to a slow and progressive impairment resulting in respiratory failure at the end stage. We have reviewed the Italian literature of the past 50 years detecting 48 case-reports of PAM (19 males and 29 females). Only 20 out of them were documented in international journals. A familial occurrence of 43.7% was found and 18 patients were under age fifteen. There was a prevalence in the female sex (60.4%) and in the second decade of life. Chest X-ray was the most important tool to diagnose PAM revealing the characteristic picture in all patient. Bronchoalveolar lavage (BAL) and open lung biopsy respectively show the characteristic calcospherites in the recovered fluid (BALF) and in the alveolar spaces. About 300 cases of PAM are reported in the international literature. We believe these data are probably underestimated because many case-reports are not published in international literature.

Adolescent↗
PubMed1997

Use of [3H]-clozapine as a ligand of the dopamine D4 receptor subtype in peripheral tissues.

1. Molecular biology studies have documented the presence of peripheral dopamine D4 receptors. This site has not been characterized yet with classical radioligand binding assay techniques because of the lack of selective radioligands. 2. The atypical neuroleptic clozapine labelled with tritium ([3H]-clozapine) has been proposed and sold as a radioligand for brain dopamine D4 receptors. However, the selectivity of [3H]-clozapine for D4 receptor subtypes, and its specificity for brain dopamine receptors, have been questioned. 3. In this study dopamine D4 receptors were assayed in peripheral organs known to express them, such as rat atria and kidney, by using a radioligand binding assay technique with [3H]-clozapine as the radioligand. Parallel experiments were performed using Chinese hamster ovary (CHO) cells transfected with the D4 receptor clone (variant D4.2). 4. [3H]-Clozapine was bound to sections of rat atria and kidney. After appropriate blockade of sites other than dopamine receptors to which it can bind (i.e. muscarinic cholinergic, serotonergic and alpha-adrenergic receptors), the radioligand was bound to a site displaying a pharmacological profile similar to that expressed by CHO cells transfected with the D4 receptor. 5. The above findings indicate that with appropriate protocols, [3H]-clozapine may represent a radioligand for peripheral dopamine D4 receptors.

Animals↗
PubMed1997

Activated eosinophils in esophagitis in children: a transmission electron microscopic study.

BACKGROUND: Esophagitis in infants and children is often characterized by eosinophilic inflammation. The underlying pathophysiologic mechanisms leading to this type of inflammation, and the role of eosinophils in the clinical expression of esophagitis, are unknown. The purpose of this study was to demonstrate the ultrastructural activation state of eosinophils in esophagitis in infants and children. METHODS: Standard transmission electron microscopy was used to examine endoscopic esophageal biopsy material from patients with and without esophagitis, as defined by standard histologic criteria. RESULTS: Twelve esophagitis and three control cases were studied. In patients with esophagitis, electron microscopy revealed numerous eosinophils throughout the mucosa and invariably demonstrated signs of activation, including inversion of core-to-matrix densities and lucency of granule core protein. Eosinophils in an activated state were seen in active diapedesis through vascular endothelium into the mucosa. Eosinophils were sometimes seen in proximity to lymphocytes. Biopsies of control patients did not demonstrate eosinophils. CONCLUSIONS: Eosinophils present in esophagitis are activated by electron microscopic criteria, and can been seen in an activated state entering into the mucosa. This suggests that eosinophils play an active role in the pathophysiology of this disorder, and that proinflammatory factors are present that selectively recruit and activate eosinophils in esophagitis in children.

Adolescent↗
PubMed1997

Dopamine D3 receptor in peripheral mononuclear cells of essential hypertensives.

Dopamine D3 receptor was studied in peripheral mononuclear cells of high-normal, stage 1, stage 2, and stage 3 essential hypertensives using a radioligand binding assay technique with [3H]-7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT) as a radioligand. A group of de novo Parkinsonian patients was also examined as a reference group of impaired dopaminergic function. [3H]-7-OH-DPAT was bound specifically to human peripheral mononuclear cells in a manner consistent with the labeling of a dopamine D3 receptor. No changes in free dopamine, norepinephrine, epinephrine and aldosterone levels, renin activity, dissociation constant of [3H]-7-OH-DPAT binding, or the pharmacological profile of [3H]-7-OH-DPAT binding were found between normotensive control subjects and essential hypertensives or Parkinsonians. The density of peripheral mononuclear cell [3H]-7-OH-DPAT binding sites increased in essential hypertensives parallel to blood pressure value augmentation. A higher density of [3H]-7-OH-DPAT binding sites was found in Parkinsonians. In these patients, the density of [3H]-7-OH-DPAT binding sites was similar to that observed in high-normal subjects and in stage 1 essential hypertensives. The increased density of peripheral mononuclear cell dopamine D3 receptor in hypertension as well as in Parkinson's disease may represent an upregulation mechanism consequent to impaired dopaminergic function. In view of the difficulty in identifying markers of peripheral dopamine function, analysis of dopamine D3 receptor in peripheral mononuclear cells may help evaluate whether the dopaminergic system is involved in hypertension.

Adult↗
PubMed1997

[Prevalence of venous diseases. The San Valentino screening and prevalence study].

The PAP/PEA (Prevalence of Early Atherosclerosis) study aims to define the prevalence of subclinical atherosclerosis in a typical population of central Italy. A concomitant study evaluates the prevalence of venous diseases. The first group of 850 patients evaluated, indicated the prevalence of superficial ve-nous disease, the prevalence of deep venous thrombosis and pulmonary embolism and the prevalence of the most common venous malformations. Also the costs of venous problems was considered. In conclusion some 12% of the evaluated population sample (male population 46%) had or had been affected in the past by a venous problem and 50% of them had been under some form of treatment.

Adolescent↗