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Biomedical subjects

P Capuano

Publications and source records attributed to P Capuano.

9 recordsLinked to original sources

NaPi-IIa and interacting partners.

Regulation of renal proximal tubular reabsorption of phosphate (Pi) is one of the critical steps in Pi homeostasis. Experimental evidence suggests that this regulation is achieved mainly by controlling the apical expression of the Na+-dependent Pi cotransporter type IIa (NaPi-IIa) in proximal tubules. Only recently have we started to obtain information regarding the molecular mechanisms that control the apical expression of NaPi-IIa. The first critical observation was the finding that truncation of only its last three amino acid residues has a strong effect on apical expression. A second major finding was the observation that the last intracellular loop of NaPi-IIa contains sequence information that confers parathyroid hormone (PTH) sensitivity. The use of the above domains of the cotransporter in yeast two-hybrid (Y2H) screening allowed the identification of proteins interacting with NaPi-IIa. Biochemical and morphological, as well as functional, analyses have allowed us to obtain insights into the physiological roles of such interactions, although our present knowledge is still far from complete.

Animals↗

T-cell activity in HLA-associated autoimmune diseases.

BACKGROUND: The existence of T-helper-1 (Th1) and T-helper-2 (Th2) subsets has been implicated in the regulation of several immune responses, and alterations in the Th1/Th2 balance have been involved in autoimmunity. The present study investigates the relative influence of Th1 and Th2 patterns in autoimmune responses in patients with HLA-associated autoimmune diseases. METHODS: This study concerns 849 patients of both sexes, suffering from several autoimmune diseases. Tissue typing for HLA antigens of Class I (A, B, C) and Class II (DR, DQ) was carried out in all patients by conventional serologic methods, comparing results with frequencies detected in a normal population. Many immunological tests were also done. In particular, lymphocyte subsets (CD4+, CD8+, CD3-HLA-DR+, NK cells, sIg + B cells) were detected with monoclonal antibodies by a fluorescent cytometer. The changes in frequencies of T cell subsets were used to calculate the possible incidence of two effector phenotypes (TE-1; TE-2). RESULTS: The results of the immunogenetic analysis confirmed the significant HLA-associations in several diseases. The essential T-cell changes were also exposed, thus defining the incidence of T-cell phenotypes (TE-1 = 56.3%; TE-2 = 34.8%). This finding suggested a major impact of cell-mediated immunity, as compared with that of antibody-mediated immunity. CONCLUSIONS: The anomalies of Th1/Th2 balance can impact autoimmune disease, and in many cases a Th2 response can prevent Th1-mediated autoimmunity, which is the most evident phenomenon in several HLA-associated diseases.

Autoimmune Diseases↗

Cytotoxic effector function in HLA-associated autoimmune diseases.

BACKGROUND: The mechanisms by which cytotoxic-T-lymphocytes (CTLs) and natural killer (NK) cells recognize and kill target cells are the subject of intense research. Previous observations in patients with HLA-associated autoimmune diseases show a major impact of cell-mediated immunity as compared to antibody-mediated immunity. This study analyzes the possible co-operation of NK cells in the autoimmune process, comparing their increase to that of cytotoxic-T-lymphocytes. METHODS: This research examines the incidence of CD8+ T cells and NK cells increases in 1065 patients with various autoimmune diseases. Tissue typing for HLA antigens was carried out in all patients by conventional serologic methods. Lymphocyte subsets (CD4+, CD8+, CD3-HLA-DR+, NK cells, sIg+ B cells) were detected with monoclonal antibodies by a fluorescent cytometer. Results were statistically compared to normal control values by the Student's "t"-test. RESULTS: The analysis of results shows the incidence of CTLs and NK cell increases in patients with different autoimmune syndromes. In some diseases (uveitis, multiple sclerosis, and other neurological autoimmune disorders) raised frequencies of NK cell increase are most evident. These results suggest some possible relationships between CTLs and NK cells in the pathogenesis of the autoimmune process. CONCLUSIONS: The present results show that CTLs and NK cells are implicated in immune dysregulation, which characterizes the complex pathogenesis of autoimmune diseases.

Autoimmune Diseases↗

Immunogenetics of inflammatory bowel disease.

BACKGROUND: This study investigates the association of HLA antigens to inflammatory bowel disease (IBD), which is reminiscent of the simultaneous or subsequent presence of ulcerative colitis (UC) and Crohn's disease (CD) found in these patients, showing also the concomitant association of other autoimmune conditions. The aim of this study is to confirm the autoimmune origin of IBD and the immunogenetic basis of the disease. METHODS: The study concerns 18 consecutive patients of both sexes, aged 20 to 62 years, sharing the clinical criteria of IBD indicated by previous authors. Tissue typing for HLA antigens of Class I (A; B; C); and Class II (DR; DQ) was carried out by conventional serologic methods, comparing alleles frequencies with those of normal controls random selected by the chi-square test. The main immune functions and other laboratory tests were also done in all patients, to define the concomitant autoimmune condition. RESULTS: Immunogenetic analysis shows the significant increase in two HLA antigens: HLA-DR2 (50.0% vs 25.5% of controls); HLA-DR7 (44.4% vs 21.1% of controls). In particular, the association of HLA-DR7 to IBD is reminiscent of that found in a personal series of 54 patients with primary celiac disease (55.5% vs 21.1% of controls). The findings on immune functions show the high frequency of anomalies of cell-mediated immunity (62.5%) and humoral immunity (88.8%), associated with decrease in complement and increase in immune-complexes. These alterations were always correlated with the presence of HLA-DR2 and/or HLA-DR7. CONCLUSIONS: This study on immunogenetics of ibd does not separate UC and CD on genetic grounds, thus suggesting that common HLA Class II genes may predispose to an altered regulation of immunologic mechanisms in these disorders.

Journal Article↗

Prenatal diagnosis and hemodynamic evaluation of Klippel-Trenaunay-Weber syndrome.

Klippel-Trenaunay-Weber syndrome is a rare congenital soft-tissue anomaly which is characterized by the presence of multiple hemangiomata, arteriovenous fistulas and limb hypertrophy. We report the ultrasound findings in two cases of early prenatal diagnosis at 17 and 18 weeks of gestation. The pathogenesis of the syndrome and involvement of the cardiovascular system are discussed.

Adult↗

[Immunologic functions after laparoscopic cholecystectomy].

Trauma and surgical procedures can induce immune depression, related to the prevalent impairment of cell-mediated immunity, which may predispose to infections. The early recovery following laparoscopic cholecystectomy without infectious complications seems to be related to a lesser degree of surgical trauma and to only minimal impairment of immune functions. The present study was conducted in 20 patients with symptomatic gallstone disease, all undergoing laparoscopic cholecystectomy. Blood samples taken before operation and at 3 and 6 days postoperatively were tested for lymphocyte subsets (CD4+, CD8+, CD19+, CD57+), blood chemistry parameters (IgG, IgA, IgM, CH-50, C3, C4) and haemochrome. A group of 10 normal volunteers, matched for age and sex, were also examined twice at an interval of 48 h. Student's "t"-test was used for statistical comparisons. The findings showed only minimal changes in immune functions after operation (slight increase in CD57+ cells, and very slight decreases in IgM and C4 factor) and a slow reduction of serum haemoglobin levels as compared with preoperative values. All parameters returned to baseline levels within 6 days of the operation. This study demonstrates that laparoscopic cholecystectomy does not significantly affect immune functions, suggesting that immunity is preserved in the postoperative period.

Adult↗

[The importance of intracellular pH in the regulation of cell function].

Cell life is possible only if intracellular pH (pHi) oscillations are kept within a very narrow range. Measurement of pHi is therefore a very important parameter when examining cell and organ functions. Several methods have been used to monitor pHi; these include fluorescent dyes and pH sensitive electrodes. In addition, many instruments have been applied to the detection of pHi in living organs even at the level of single cells: NMR and confocal microscopy are just an example. Transport proteins located on the cell membrane and intracellular vesicles are responsible for maintaining the correct pHi. In renal tubular cells these include the sodium hydrogen exchanger (NHE), the sodium-dependent and independent chloride-bicarbonate exchanger (Cl--HCO3-), the sodium bicarbonate co-transport (Na+-HCO3-), the ATP-coupled proton pump (H+-ATPasi) and the ATP-dependent proton-potassium pump (H+-K+-ATPasi). All these carriers have been cloned and it is now clear that there are several isoforms with specific properties. The function of these proteins is closely linked to several hormone blood levels, systemic acid-base status, protein diet content as well as other factors. In addition, these carriers are not homogeneously distributed along the nephron and are sensitive to specific stimuli like interstitial osmolality and luminal fluid flow rate. Finally, it has been recently demonstrated that the pHi may be involved in numerous aspects of cell function, such as metabolism, apoptosis, malignancy and it is implicated in the pathogenesis of particular forms of renal stones (Dent's disease).

Angiotensin II↗