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Biomedical subjects

C Giordano

Publications and source records attributed to C Giordano.

At least 73 records · Page 4Linked to original sources
PubMed1996

N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester: a novel, high selective and optimal chromogenic active site titrant for human and bovine alpha-, beta- and gamma-thrombin.

The serine proteinase catalyzed hydrolysis of N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p- nitrophenyl ester (Eoc-D-Phe-Pro-azaLys-ONp) was investigated at pH 6.2 and 21.0 degrees C. The results are consistent with the minimum three-step catalytic mechanism. The acylation step is rate limiting for human (Lys 77 species) and porcine plasmin, and for bovine beta-trypsin, the deacylation rate being limiting, on the other hand, for human and bovine alpha-, beta- and gamma-thrombin. Moreover the M(r) 33,000 species of human urokinase and the neuraminidase-treated porcine pancreatic beta-kallikrein-B do not catalyze the hydrolysis of the tripeptide. According to the specificity properties of the serine proteinases considered. Eoc-D-Phe- Pro-azaLys-ONp shows the characteristics of a novel, high selective and optimal chromogenic active site titrant for human and bovine alpha-, beta- and gamma-thrombin.

Animals↗
PubMed1996

In vitro T cell activation in elderly individuals: failure in CD69 and CD71 expression.

A large number of T cell dysfunctions have been observed in the elderly. The most widely observed is the inability of these cells to proliferate at a level comparable to T cells from young individuals after stimulation by mitogens. To better characterize T cell impairment, we have focused on the in vitro T cell activation, analyzing by flow cytometry the activation molecules CD69 and CD71 on mitogen-stimulated lymphocytes from young and elderly subjects. The results show that the percentages of CD69+ and CD71 + T cells were significantly decreased in cultures from elderly subjects when compared to values obtained culturing cells from young individuals. The differences observed seem not due to differences in CD4 and CD8 rates in the "old' cells that underwent activation, since, following activation, the pattern of CD4 and CD8 phenotypes was the same in both groups of subjects. Signals from CD69 are relevant in controlling cytokine gene expression because its stimulation leads to interleukin-2 production and increases its receptor expression. The interaction of this cytokine with its cellular receptor is an essential requirement for T lymphocytes to express CD71 and to start proliferation. Thus, a key role in the age-associated impairment of T cell activation could be played by an ineffective modulation of CD69 expression suggesting a defect in the signal transduction pathway of the T cell receptor-CD3 complex in elderly.

Adult↗
PubMed1996

Spinal cord compression resulting from Burkitt's lymphoma in children.

We report seven cases of spinal cord compression resulting from Burkitt lymphoma in boys aged 15 years and below. This became manifest clinically as acute or rapidly progressive spinal cord compression. All the patients showed total paraplegia with a sensory loss at thoracic level and sphincter disturbances. Four patients were operated on, the operation permitting exeresis of an epidural tumor. In three cases surgery was followed by chemotherapy. One patient was treated exclusively with chemotherapy. Owing to the effectiveness of chemotherapy, surgery should be considered only in cases of rapid deterioration or for diagnostic purposes.

Adolescent↗
PubMed1996

Depression of CD4 T cell subsets and alteration in cytokine profile in boutonneuse fever.

Interferon (IFN)-gamma, interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-alpha were significantly increased in sera from Sicilian patients with acute boutonneuse fever (BF) compared with those of healthy controls. IFN-gamma levels dropped sharply within the second week after infection. IL-6, IL-10, and TNF-alpha levels gradually declined; in convalescent patients only were they in the normal range. In contrast, peripheral blood mononuclear cells (PBMC) stimulated in vitro with phytohemagglutinin (PHA) produced low levels of IL-10 and IFN-gamma in acute BF that were compatible with the reduction in the levels of CD4+, CD4+/CD45RO+, and CD4+/CD45RA+ cells. In vitro production of TNF-alpha and IL-6 from PBMC stimulated with PHA was not significantly modified during the various phases of the infection compared with control PBMC, which could be due to the persistence of high levels of CD14+ monocytes compensating for the decrease in CD20+ B cells.

Adult↗
PubMed1996

Correlation between glomerular morphology and renal haemodynamic response to amino-acid administration in patients with IgA nephropathy.

RATIONALE: To establish relationship, if any, between renal morphology and renal haemodynamic response to amino acids. DESIGN AND METHODS: We investigated the correlation between renal haemodynamic regulation and morphology in a group of 15 patients with primary IgA nephropathy (IgAN) (age 26 +/- 2 years, BMI 24.4 +/- 1, GFR 64 +/- 5 ml/min, RPF 377 +/- 34 ml/min, FF 0.17 +/- 0.02). Twelve normal subjects (age 30 +/- 3 years, BMI 24 +/- 1, GFR 82 +/- 6 ml/min, RPF 421 +/- 42 ml/min, FF 0.19 +/- 0.02) were studied as controls. IgA patients were divided into two groups according to the histological staging of glomerular lesions: group I (n = 7) stage II, and group II (n = 8) stage III-IV. RESULTS: In the basal state GFR was similar in the two groups and averaged 64 +/- 9 and 64 +/- 6 ml/min respectively. In contrast, FF was significantly lower in group II (0.14 +/- 0.01) (P < 0.05) in comparison to group I (0.21 +/- 0.03) and controls (0.19 +/- 0.02). In order to evaluate the renal functional reserve, all study groups underwent to an intravenous amino-acid infusion designed to increase plasma amino acid levels twofold (total from 2096 +/- 145 to 4301 +/- 221 mumol/l in IgA nephropathy patients and from 2272 +/- 83 to 3844 +/- 238 mumol/l in controls). In response to amino-acid infusion, GFR rose significantly in group I (GFR 20 +/- 2% and RPF 37 +/- 4% versus basal) and controls (GFR 20 +/- 2% and RPF 20 +/- 3% versus basal) (both P < 0.01 vs basal). In contrast, in patients with more severe glomerular lesions (group II) neither GFR nor RPF rose significantly (GFR -1 +/- 4% and RPF -8 +/- 6% versus basal) (P NS versus basal, P < 0.01 versus group I and controls). CONCLUSIONS: The data show that in IgA nephropathy: severe forms of glomerular lesions are associated with a complex alteration of glomerular haemodynamic regulation, characterized by lower basal FF and loss of haemodynamic response to hyperaminoacidaemia.

Adult↗
PubMed1996

Blood pressure and progression of renal failure in the elderly.

There are a lack of studies about elderly patients with chronic renal failure (CRF). We studied 22 patients, aged 64 to 74 years, who were diagnosed with hypertensive nephropathy (HN), defined as a diastolic blood pressure (DBP) < 95 mm Hg and a basal creatinine clearance (CCr) of 52 +/- 6 ml/min/1.73 m2. During the minimum two-year follow-up, the progression of renal failure (RF) was analyzed by the plotted slope of CCr versus time. Patients were divided into two groups, each administered one of two different drugs, Ca antagonists (group I) and angiotensin converting enzyme (ACE) inhibitors (group II). The DBP in both groups was lowered by the end of the study. The mean arterial pressure (MAP) was less in group I (97.35 +/- 5.98 mm Hg) than in group II (108.3 +/- 9.95 mm Hg). The decline in renal function was a mean rate of -0.62 +/- 0.36 ml/min/month in group I and -1.03 +/- 0.17 ml/min/month in group II. In conclusion, we show that patients who were on ACE inhibitors exhibited a greater MAP and a greater decline in renal function compared with the patients who were on Ca antagonist therapy. We also found that patients who were younger than 70 years old had better control of their blood pressure rates and less of a rate of decline in renal function than their older counterparts.

Aged↗
PubMed1996

[Pancreatic harvesting from multiorgan donors for islet transplantation].

The result of human islet isolation procedures to transplant in type I insulin-dependent diabetic patients is significantly conditioned by the technique used for pancreas procurement from multiorgan donor. In fact, during multiorgan procurement, an improper handling of the gland could result in edema or degranulation of the acinar tissue, detrimental for the islet purification step. The surgical technique used by our surgical team, includes some important refinements to obtain the largest quantity and the best quality of purified endocrine material.

Adolescent↗
PubMed1995

In vivo and in vitro cytokine profiles and mononuclear cell subsets in Sicilian patients with active visceral leishmaniasis.

Sera from Sicilian patients with confirmed visceral leishmaniasis (Leishmania donovani infantum) were analysed at the moment of the diagnosis, during the course of the disease and after clinical recovery, for the concentration of IL-10, IFN-gamma, IL-4 and IL-2. The results show high concentrations of IL-10 and IFN-gamma in the sera at the beginning of infection that return to the normal range following successful chemotherapy. By contrast, PBMC stimulated in vitro with Ag and mitogen produced low levels of IL-10 and IFN-gamma when collected at the time of the diagnosis and normal levels when assayed after recovery. IL-2 was undetected in the sera and was significantly reduced in the supernatants of actively infected patients, returning to the normal level after recovery. IL-4 was absent in the sera and in high concentrations in the supernatants in all the phases of the disease. The levels of CD4+ and CD8+ T cells were within the normal range, but acute VL patients had markedly reduced levels of memory T cells (CD3+/CD45RO+) compared with healthy controls. These cells returned to the normal levels following successful chemotherapy. T cells are strongly activated in acute VL patients as indicated by the elevated number of CD3+ HLA-DR+ and by the increase in HLA-DR antigen on these cells. There was a significant reduction in the cell membrane DR antigen of the monocytes (CD 14+) during the acute phase of the disease, but it returned to the normal range after clinical recovery. These findings therefore suggest that in Sicilian patients with active VL the cytokine profile is not clearly characterized by Th2 phenotype as in mice, and both Th1-like and Th2-like cells appear to proliferate and to be activated. Furthermore, IL-10, rather than IL-4, could play an important part in the inhibition of IFN-gamma-induced macrophage activation and could reflect the levels of HLA-DR antigen expressed by the monocytes.

Animals↗
PubMed1995

Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from newly-diagnosed IDDM patients.

The bcl-2 gene product has been shown to regulate apoptotic cell death, and its dysregulation has been shown to induce several abnormalities in the immune system. No data exist regarding bcl-2 expression in autoimmune diseases, such as human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein expression by testing T lymphocytes from 15 newly-diagnosed (< 3 weeks) IDDM patients in comparison to 10 age-matched control subjects. The expression of bcl-2 on CD3+ lymphocyte subsets was investigated after membrane permeabilization by two- or three-colour immunofluorescence. When the percentage and mean fluorescence intensity (MFI) of bcl-2+/CD3+ cells from normal individuals and patients were compared, we found that bcl-2 expression within the CD3+ and CD4+ CD45R0+ T-cell populations was reduced significantly in IDDM patients (46.8 +/- 15.4 vs 79.6 +/- 11.7; 25.7 +/- 3.8 vs 47.15 +/- 5.7, respectively; p < 0.001). To establish whether low bcl-2 expression in T cells from newly-diagnosed patients reflects their susceptibility to death by an apoptotic process, we also evaluated DNA staining with propidium iodide in CD3+ lymphocyte suspension after a (24-72 h) culture period (spontaneous apoptosis). We found that IDDM patients have higher levels of spontaneous apoptosis (mean +/- SEM: 24 h = 4.6 +/- 0.8; 48 h = 9.9 +/- 1; 72 h = 12.8 +/- 1.1) than control subjects (24 h = 1.8 +/- 0.4; 48 h = 4.6 +/- 0.4; 72 h = 5.7 +/- 0.3; p < 0.02-0.001). Our study suggests that recent onset IDDM is characterised by reduced bcl-2 expression, which in turn may be associated with the increased spontaneous apoptosis we observed.

Adolescent↗
PubMed1995

Defective expression of the apoptosis-inducing CD95 (Fas/APO-1) molecule on T and B cells in IDDM.

Triggering of CD95 (Fas/APO-1) cell surface receptors regulates the elimination of autoreactive T and B lymphocytes through a mechanism of cell suicide called apoptosis. Three different mutations involving CD95 or its ligand are responsible for induction of autoimmunity in susceptible mouse strains. To determine whether a defect involving the CD95 receptor is associated with human insulin-dependent diabetes mellitus (IDDM), we have studied the expression of CD95 on peripheral blood mononuclear cells from IDDM patients at different stages of the disease. Three-colour flow cytometry and mean fluorescence analysis showed that T and B lymphocytes from newly diagnosed IDDM and patients with long-standing disease, and subjects at high risk of developing the disease were highly defective in CD95 expression (p < 0.001), whereas monocytes from all the groups studied expressed normal amounts of CD95 molecules on their cell surface. T-cell subset analysis showed that the impairment of CD95 expression in IDDM patients and high-risk subjects involved both CD3+ CD4+ (p < 0.001) and CD3+ CD8+ cells (p range: < 0.01-0.001), suggesting that this alteration concerns both helper and cytotoxic T cells. Moreover, after activation in vitro with anti-CD3 monoclonal antibody, T cells from newly diagnosed IDDM patients maintained a reduced CD95 expression during the entire cell culture period (24-72 h) in comparison to the control population (p < 0.001). In conclusion, we found a reduced expression of the apoptosis-inducing CD95 receptor on T and B lymphocytes of individuals with clinical and preclinical IDDM. We hypothesize that this defective expression may impair the capacity of autoreactive lymphocytes to undergo CD95-mediated apoptosis, contributing to the lack of control on beta-cell specific B- and T-cell clones.

Adult↗
PubMed1995

T-cell activation in HLA-B8, DR3-positive individuals. Early antigen expression defect in vitro.

The HLA-B8, DR3 haplotype is overrepresented in several autoimmune diseases, implying that genes predisposing to these disorders are linked to this haplotype. In the patients affected by these diseases, as well as in healthy HLA-B8, DR3 individuals, various dysfunctions reflecting an impairment of T-cell activation have been found. To better characterize T-cell impairment of HLA-B8, DR3-positive healthy individuals, we analyzed the surface expression of early (CD69) and late (CD71) activation phenotypes. MNC cultures were stimulated with PHA and used for T-cell phenotyping by flow cytometry analysis. The results showed that the percentage of CD69+ T cells was significantly decreased in MNC from HLA-B8, DR3+ subjects. This defect was detected in cell cultures from all subjects studied, but it attained significance only in females in the early hours after stimulation. The difference in CD69 expression between HLA-B8, DR3-positive individuals and -negative ones was not due to differences in CD4 and CD8 ratios in the HLA-B8, DR3 cells that underwent activation, as following activation the pattern of CD4 and CD8 antigen expression was the same in both groups of subjects. Concerning the late antigen CD71, no significant difference in percentage was observed between T lymphocytes from HLA-B8, DR3+ and HLA-B8, DR3- subjects at all the times studied. The analysis of the requirements for CD69 expression has suggested that sustained PKC activation and an increase of intracellular CA2+ could be responsible for TCR/CD3-mediated CD69 induction. Thus, present data suggest a defect in the signal transduction pathway of the TCR/CD3 complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Follicular thyroid cells of autoimmune thyroiditis may coexpress ICAM-1 (CD54) and its natural ligand LFA-1 (CD11a/CD18).

The leukocyte functional associated antigen-1 (LFA-1)-intercellular adhesion molecule-1 (CD11a-CD18/CD54) intercellular adhesion system plays a crucial role in several immunologic phenomena, including adhesion between lymphocytes and epithelial cells. In previous studies evidence for CD54 expression on thyroid follicular cells in Hashimoto's thyroiditis was provided. In this study we evaluated the possible expression of CD11a and CD18 antigens on thyrocytes of patients with Hashimoto's thyroiditis and on thyrocytes of patients with Graves' disease and simple goiter as controls; we used both alkaline phosphatase immunostaining and indirect immunofluorescence on cryostatic tissue sections. The results showed that LFA-1 (both CD11a and CD18) positivity on thyroid follicles may occur in glands of patients with Hashimoto's disease, with a pattern very similar to that of CD54: this was observed in five of seven specimens. Conversely, no positivity was observed in tissues from patients with Graves' disease or goiter: notably, isolated follicular cells from Graves' goiter tissues are induced in culture to express CD54, but not LFA-1. Using double-staining techniques, we were able to show that in specimens from patients with Hashimoto's disease, the same follicular structures coexpressed LFA-1 and CD54. Such a coexpression of the two ligands further emphasizes the possible role of this adhesion system in the pathogenesis of epithelial damage, through bidirectional interactions between thyroid epithelial cells and infiltrating LFA-1 or CD54-positive mononuclear cells.

Adult↗
PubMed1995

[Prognostic factors in the radio-surgical treatment of laryngeal carcinoma].

We examined a homogeneous group of 116 patients with laryngeal and hypopharyngeal carcinomas, treated with surgery followed by radiotherapy according to the conventional procedure. The tumors occurred in the larynx in 88 cases (75.86%) and in the hypopharynx in 28 (24.14%); correlations between overall survival and disease-free survival on the one hand, and clinical and histological parameters on the other hand were established with a multivariate analysis using the Cox method. After 5 years 75.86% of the patients were alive. This variable was negatively influenced by pN (pN0 89.8%, pN1 76.2%, pN2 69%); pT (pT3 82.5%, pT4 62.5%), by vascular embolization (90% of patients alive with no vascular embolization versus 69.7% with vascular embolization), by the grade of peritumoral inflammation (64.3% of patients alive with slight peritumoral inflammation, 69.2% with medium-grade inflammation and 87.3% with strong inflammation), and finally by a great number of plasma cells and few granulocytes; 78.44% of these patients remained disease-free. This variable was negatively affected by pN (pN0 91.8%, pN1 76.2%, pN2 60%), patients' age and extracapsular spread (85.5% of disease-free patients with no extracapsular spread, vs. 51.55% with extracapsular spread); and positively influenced by basal cell differentiation (95% of disease-free patients versus 71.8%). Overall and disease-free survival rates which differed at the beginning, coincided after two years because of local recurrences. On the basis of these results we conclude that the correct assessment of morphologic variables should be considered as a useful tool for treatment planning.

Adult↗
PubMed1995

[Nasal patency patterns observed during working hours in a group of technicians habitually exposed to formaldehyde].

Formaldehyde is a substance which is widely used in several work fields, including many medical and biological sectors. It appears that formaldehyde exposure may cause bronchial asthma. Little information is available, however, with regard to upper aereal tracts. The nose is a target organ of major importance for a large range of professional and extra-professional environmental pollutants. In particular, cases of professional rhinitis brought about by exposure to disinfectants have been reported in Literature. In the light of general knowledge related to the close correlation between upper and lower airways, and to the lack of information concerning the effects of short-term formaldehyde exposure on the upper aereal tract, the Authors decided that investigation of such exposure might prove interesting as well as worthwhile. A group of fifteen technicians who work in three different pathology departments and who had been exposed to formaldehyde for at least one year were studied. The purpose of the study was to assess possible alteration in nasal resistances at the end of a normal work shift. The subjects under study were observed according to a procedure which included several clinical, allergological, serological and functional evaluations carried out on specific days of the week. A control group, consisting of eight asymptomatic, non-atopic subjects who had never been exposed to inhalation of irritants was also monitored in the same way. Conclusions were drawn after considering some important variables such as exposure time, possible anatomical alterations of the nose, the presence of respiratory allergies and smoking habits. It was apparent that professional formaldehyde exposure typical of that experienced by technicians working in pathology departments induced a short-term irritant effect on the upper aereal tract, which, even though subclinical, is revealed by a statistically significant increase in nasal resistance. This effect seems to be favoured (at statistically not significant levels) by atopy, cigarette smoking and anatomical alterations of the nose. Our data seem to exclude a chronic cumulative effect of formaldehyde exposure.

Adult↗
PubMed1994

HIV-associated lymphoma in Africa: an autopsy study in Cote d'Ivoire.

HIV infection predisposes to the development of non-Hodgkin lymphoma (NHL). The frequency of NHL among HIV-positive adults and children in sub-Saharan Africa is not known. In 1991-1992, a representative autopsy study of HIV infection was performed in Abidjan, Côte d'Ivoire. Of 247 HIV-positive adult (> 14 years) medical patients dying in hospital, 2.8% had NHL, 1.6% with visceral NHL and 1.2% with primary cerebral lymphoma. The estimated crude incidence of NHL among HIV-positive adults in Abidjan was 84/100,000 per year, 10-fold greater than the expected pre-AIDS incidence of NHL but less than the incidence observed among HIV-positive adults in industrialised countries. None of 78 autopsied HIV-positive children (median age = 17 months) had NHL. HIV infection augments the incidence of NHL among adults in Africa, but short survival with advanced HIV disease probably prevents the major increase in HIV-associated NHL seen in industrialised countries. Survival of HIV-positive children in Africa appears too short to permit the significant development of additional NHL; classic Burkitt lymphoma is not an AIDS-associated tumour in Africa.

Adolescent↗
PubMed1994

Defective T cell receptor/CD3 complex signaling in human type I diabetes.

The autoimmune process leading to the destruction of pancreatic beta-cells is mediated by T lymphocytes. Peripheral T cells from subjects with preclinical and clinical type I diabetes respond weakly in vitro to lectin stimulation. We, therefore, investigated in a group of newly diagnosed diabetic patients the presence of a defect in the signal transduction pathway of the T cell receptor (TcR)/CD3 complex. Following stimulation with anti-CD3-coupled beads, the proliferative response in diabetic T cells was significantly decreased in comparison with that from normal T cells. Interestingly, addition of either recombinant interleukin (IL)-2 or phorbol 12-myristate 13-acetate to the cell culture was able to completely restore impaired anti-CD3-induced proliferation in diabetic T cells, suggesting the presence of a defect through the TcR/CD3 pathway, located upstream of protein kinase C (PKC) activation and resulting in low IL-2 production and proliferation. Intracellular Ca2+ measurements by Fluo-3 labeling and flow cytometry analysis on diabetic and control T cells after anti-CD3 stimulation gave comparable results, indicating that this defect does not involve events leading to intracellular Ca2+ mobilization. In contrast, anti-CD3 stimulation of diabetic T cells resulted in a marked impairment of PKC translocation and CD69 antigen expression, as assessed by peptide substrate phosphorylation and by flow cytometry analysis, respectively. Taken together, our data clearly show the presence in individuals at the onset of the disease of an in vitro defect in the signal transduction pathway of the TcR/CD3 complex, resulting in ineffective PKC activation which is not able to induce normal IL-2 production and proliferation of diabetic T cells.

Antigens, CD↗