Search PubMed⌕ Search

Biomedical subjects

C Esposito

Publications and source records attributed to C Esposito.

At least 109 records · Page 6Linked to original sources
PubMed1996

Does the presence of ANCA in patients with ulcerative colitis necessarily imply renal involvement?

BACKGROUND: ANCA are thought to play a pathogenic role in renal vasculitis. ANCA may also be detected in patients with diseases not usually associated with renal pathology, such as ulcerative colitis. Our study was conducted to determine if the presence of ANCA in patients with ulcerative colitis is associated with renal pathology. METHODS: Eight ANCA-positive and five ANCA-negative patients with a histological and endoscopic diagnosis of active ulcerative colitis were investigated. Repeated complete urinalyses and determination of microalbuminuria and creatinine clearance were performed. Serum IgG and IgA ANCA were evaluated in all patients by indirect immunofluorescence and ELISA, and when detected the antibodies were further characterized by alpha granules preparation, myeloperoxidase, lactoferrin, and cathepsin G. RESULTS: In both ANCA-positive and ANCA-negative patients renal function was normal or near normal and urinalyses (including microalbuminuria) failed to disclose any abnormalities. ANCA exhibited a perinuclear pattern in all ANCA-positive patients. Interestingly, none of the ANCA-positive patients had antibodies to myeloperoxidase or to alpha granules which are usually found in the sera of patients with ANCA-associated vasculitis, and only one had antibodies to lactoferrin. The ANCA specificity remained undetermined in the remaining seven patients. At the end of the 1-year observation period, all ANCA-positive patients remained ANCA-positive without developing symptoms, signs or laboratory abnormalities consistent with renal involvement. CONCLUSIONS: Renal damage was not observed in ANCA-positive patients with ulcerative colitis even after 1 year of follow-up, suggesting that the ANCA found in these patients do not share the antigenic targets with the ANCA commonly found in renal vasculitis. Therefore the potential of ANCA of inducing renal lesions (if any) is dependent on their own antigenic specificity.

Adolescent↗
PubMed1996

Effects of hypercholesterolemia of renal hemodynamics: study in patients with nephrotic syndrome.

Experimental and clinical studies have demonstrated a positive relationship between hyperlipidemia and rate of progression of renal disease, suggesting that lipids can induce or aggravate glomerular injury mainly by interacting with mesangial cells. Nevertheless, recently has been demonstrated that increased cholesterol levels can also induce endothelial cell dysfunction. Thus, since endothelium is known to play a major role in modulating the vascular tone, we have tested the possibility that hypercholesterolemia impairs the renal hemodynamics in patients with active nephrotic syndrome and elevated serum cholesterol levels. In this single-blind, nonrandom study, 12 patients were treated with pravastatin (group T, treated, n = 12) and 8 with placebo (group C, controls, n = 8). The controls were studied after the pravastatin group had been completed. Before starting the treatment the patients underwent basal determinations including routine laboratory investigations and PAH and inulin clearances. The same determinations were repeated after 48 h, and 6 and 12 weeks from the beginning of the treatment. The study at 48 h was performed to see if pravastatin had a direct, cholesterol-independent effect on renal function. The following basal results were reported (mean +/- SEM; group T vs. group C): serum cholesterol (mmol/l) 9.7 +/- 0.4 vs. 9.1 +/- 0.3 (NS); proteinuria (g/24 h): 6.2 +/- 0.2 vs. 7.0 +/- 0.7 (NS); PAH clearance (ml/min): 353 +/- 21 vs. 385 +/- 31 (NS); inulin clearance (ml/min): 62.5 +/- 7.7 vs. 67 +/- 9.3 (NS). After 48 h, no changes were observed in both groups. Subsequently, in group T, the following percentage changes of basal levels were observed: serum cholesterol -21.4 +/- 3.2% at 6 weeks (p < 0.05) and -34.9 +/- 3.2% at 12 weeks (p < 0.01); inulin clearance +3 +/- 3.7% at 6 weeks (NS) and +9.3 +/- 2.9% at 12 weeks (p < 0.05); PAH clearance +7 +/- 3.1% at 6 weeks (p < 0.05) and +21.2 +/- 5.5% at 12 weeks (p < 0.01). By contrast, no significant changes of these parameters occurred in group C at any time, so that the percent changes of baseline values of CPAH were significantly greater in group T (at 6 weeks: p < 0.05; at 12 weeks p < 0.005). These results indicate that the reduction of cholesterol is associated with a significant increase in renal plasma flow, thus, suggesting that hypercholesterolemia may actually impair the renal hemodynamics. We speculate that this effect may contribute to increase the risk of ischemic acute renal failure in nephrotic patients and, along with changes induced in the mesangium by other mechanisms, to contribute to the progression of renal disease.

Adult↗
PubMed1996

Are acantholysis and transglutaminase inhibition related phenomena?

BACKGROUND: The loss of intercellular cohesion among keratinocytes (acantholysis) may be considered the histologic marker of pemphigus. Many drugs, especially thiol drugs, proved to be able to provoke in vitro acantholysis by biochemical mechanisms interfering with the disulfide and thiol group balance. As to nonthiol drugs, the pathomechanism of acantholysis is still unexplained. OBJECTIVE: To explain the molecular mechanism of enalapril-induced acantholysis a potential link between transglutaminase (TGase) activity and the effects of this drug was investigated. METHODS: TGase activity in extracts from human breast skin cultured in the presence of thiopronine, captopril and enalapril were evaluated in vitro. The acantholytic potential of cystamine, a known TGase inhibitor, was also investigated. RESULTS: Enalapril, the most powerful acantholytic drug in vitro, was found to inhibit both the purified enzyme and the TGase activity in the extracts from cultured human breast skin explants. Kinetic studies showed that enalapril inhibition was competitive with respect to the amino acceptor substrate and uncompetitive with respect to the amino donor substrate. Moreover, an acantholytic effect of cystamine on explants of normal human skin was shown. CONCLUSIONS: These results suggest that acantholysis and the inhibition of TGase activity could be two related phenomena.

Acantholysis↗
PubMed1996

Effect of galactose on alpha-crystallin.

Chromatographic separation of alpha-crystallin incubated with [3H]-labelled galactose showed the radioactivity to be concentrated in the low molecular mass subunits (20 and 40 kDa). The effect of glycation on the structural organization of alpha-crystallin was evaluated by FPLC analysis of native (pH 6.8 and 8.2) and glycated protein in dissociating conditions. Results suggest that the glycation acts on the protein surface by altering its charge distribution.

Animals↗
PubMed1996

Serial morphometric analysis of sclerotic lesions in primary "focal" segmental glomerulosclerosis.

The possibility of missing the diagnosis of focal segmental glomerulosclerosis (FSGS) has been primarily attributed to the focal distribution of the sclerotic lesions, but this assumption has not been verified by any serial morphometric analysis of renal biopsy specimens. The aim of this study is to assess the size and the distribution of sclerotic lesions in primary FSGS and to establish the minimum number of glomeruli and sections necessary for the diagnosis. Fourteen biopsies from adult nephrotic patients with primary FSGS were carefully selected from a group of 41 biopsies, to minimize the possibility of finding and misinterpreting nonspecific glomerular scars, and were serially cut to obtain 1485 consecutive 2 microns-thick sections that, after PAS staining, showed 182 glomeruli. Fifty-seven glomeruli were "complete", i.e., they emerged after the first section and disappeared before the last section. The percentage of glomeruli with sclerotic lesions was 31.5% in the starting section, 71.8% after the observation of all serial sections, and 81.7% when only the complete glomeruli were considered. The morphometric analysis on complete glomeruli revealed that the volume of the sclerotic lesions averaged just 12.5% +/- 2.2 SE of the entire glomerular volume, and the statistical analysis revealed that the minimum number of glomeruli needed in the starting section to exclude sclerotic lesions is eight (P < 0.01) or nine (P < 0.001). If fewer glomeruli are seen, it is necessary to cut 2 microns-thick serial sections, but to examine just one of every 11 (P < 0.001), the number of sections to examine being proportional to the number of glomeruli found. In conclusion, this study shows that the distribution of sclerotic lesions in primary FSGS is not focal, but diffuse; however, because of the small size of the sclerotic lesions, the probability of missing the diagnosis is statistically relevant when fewer than eight glomeruli are found in the starting section, unless a serial morphological analysis, even on a reduced number of sections, is made.

Adult↗
PubMed1996

Molecular analysis of glomerular diseases in renal biopsies: initial results of a collaborative international study. The International Study Group for Molecular Study of Kidney Biopsies.

An accurate assessment of which patient with glomerular disease will progress to end-stage renal failure would be an important addition to establishing prognosis and evaluating therapeutic strategies. We previously found the development of glomerular scarring in animal models was preceded by an increase in glomerular type IV collagen mRNAs and that the level of scarring predicted the rate of progression. The purpose of this study was to determine whether these findings apply to human glomerular diseases using microdissected glomeruli and assessment of mRNA by competitive PCR. After showing that the levels of type IV collagen mRNAs were elevated in sclerotic glomeruli isolated from nephrectomies, we undertook this preliminary cross-sectional study of type IV collagen subchain mRNAs in renal biopsies in two of the leading causes of glomerulosclerosis, diabetic nephropathy, and membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels were altered in disease-specific ways. The relative levels of the individual alpha-chains of type IV collagen depended on the anatomic site of the glomerular lesions. The alpha 2 type IV/alpha 3 type IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with those obtained from experimental animals, suggest that a dysregulation of basement collagen synthesis underlies progressive glomerular scarring. If these conclusions are verified in prospective studies it will be feasible to assess the risk of developing progressive glomerulosclerosis in the individual patient and to quantitatively assess therapeutic responses in a timely manner.

Aged↗
PubMed1995

Neurokinin receptors could be differentiated by their capacity to respond to the transglutaminase-synthesized gamma-(glutamyl5)spermine derivative of substance P.

Four different gamma-(glutamyl5)amine derivatives of substance P (SP) were synthesized in vitro in the presence of purified guinea pig liver transglutaminase and Ca2+. The 1,3-diaminopropane, spermidine, spermine (Spm), and monodansylcadaverine adducts of the neuropeptide were purified by HPLC on a reversed-phase column and characterized by fast atom bombardment mass spectrometry. The gamma-(glutamyl5)Spm derivative of SP (Spm-SP) was found to be able, like the parent neuropeptide, to provoke rabbit aorta relaxation, to decrease rat arterial blood pressure, and to inhibit collagen-induced platelet aggregation. Unlike SP, only a weak inflammatory response was observed when Spm-SP was injected in the rat hind limb. All these effects were found to be prevented by N omega-nitro-L-arginine methyl ester, a well-known nitric oxide synthesis inhibitor. In contrast, Spm-SP was completely ineffective in contracting guinea pig ileal segments, thus confirming our preliminary observations indicating that Spm-SP does not evoke SP-like spasmogenic effects on isolated smooth muscle preparations. The specificity of the effects due to the selective introduction of a Spm moiety at the glutamine5 level was demonstrated by the SP agonist pharmacological profile of the other gamma-(glutamyl5)amine derivatives tested. These results suggest that neurokinin receptors could be differentiated by their capacity to respond to Spm-SP.

Animals↗
PubMed1994

Segmental dilatation of the ileum in a newborn with Bochdaleck's hernia.

Congenital segmental dilatation of intestine is a very rare pathology and up to date less than 50 cases have been reported in literature. Herein we report a case of segmental dilatation of ileum associated to diaphragmatic hernia. The main clinical and pathogenetic aspects are discussed, and the theory of a ganglionic dysplasia as a cause of congenital segmental dilatation is here confirmed.

Dilatation, Pathologic↗
PubMed1994

Pediatric endoscopic surgery: pride and prejudice.

82 endoscopic surgical procedures (abdominal: 77; thoracic: 5) were performed by the same surgeon on 75 children aged from 1 month to 17 years (median 8.1 years) during the two-year period from January 1991 to December 1992. Due to the multispecialization of the Children's Hospital, a variety of pathologies were explored or treated with appendectomy accounting for 33% (27/82). There were no perioperative deaths. Three major complications occurred (1 post-appendectomy peritonitis, 1 hemorrhage during splenectomy and 1 post-operative occlusion). 14 patients required conversion to open surgery. Indications for endoscopic exploration of advanced lesions, prospective indications, and policy when confronted with a healthy appendix are discussed.

Abdomen↗
PubMed1994

Suppression of rat epididymal sperm immunogenicity by a seminal vesicle secretory protein and transglutaminase both in vivo and in vitro.

The pretreatment of epididymal spermatozoa with SV-IV, one of the major secretory protein produced by the epithelium of adult rat seminal vesicles, was found to markedly decrease their ability to induce in vivo peritoneal macrophage activation, measured as class II major histocompatibility complex surface antigen expression, superoxide anion production, phagocytic activity, and antigen presentation. In addition, the treatment of spermatozoa with SV-IV produced a significant decrease of their immunogenicity evaluated in vitro by [3H]thymidine incorporation in splenocyte/spermatozoon co-culture. The concurrent presence of SV-IV and transglutaminase, an enzyme secreted in large amounts from the rat anterior prostate, amplified these phenomena. The suppression of the epididymal sperm immunogenicity is suggested to be of crucial importance for the prevention of the immune response to the sperm introduced in the immunocompetent female genital tract during coitus.

Animals↗
PubMed1994

Biological activities of CNBr fragments of a major protein secreted from the rat seminal vesicle epithelium.

Two fragments of SV-IV, one of the major proteins secreted from the rat seminal vesicle epithelium, were produced in vitro by protein cleavage with CNBr at level of the single methionine residue (Met-70) occurring in its polypeptide chain. After their purification by reversed-phase chromatography, SV-IV/A (1-70 fragment) and SV-IV/B (71-90 fragment) were assayed as transglutaminase substrates, and their anti-inflammatory, anti-thrombotic and immunosuppressive properties were evaluated in comparison with native SV-IV. Both fragments retained the SV-IV ability to act as transglutaminase substrates in vitro; fast atom bombardment mass spectrometry analyses of the reaction products pointed to Gln-9 and Gln-86 as acyl donor sites, and to Lys-59, -79 and -80 as acyl acceptor sites. In contrast, only SV-IV/A was shown to possess, like SV-IV, the property of inhibiting both the intensity of the carrageenin-induced rat foot edema and the platelet aggregation induced in vivo by different agents. Finally, the two protein fragments were found to be completely unable to inhibit both the mitogen-induced proliferation of human T cells and the mixed lymphocyte reaction.

Amino Acid Sequence↗
PubMed1994

[Kidney injuries in children].

Over the past 4 years 18 children were observed at the La Timone-Enfants Hospital in Marseille with renal lesions consequent to nonpenetrating abdominal traumas. Hematuria was reported in 14 cases (7 macroscopic and 7 microscopic) and all cases suffered from abdominal and/or lumbar pain. In relation to the diagnostic iter used: 18 echographies, 15 urographies, 13 TAC, 2 ascendant pyelographies, 2 scintigraphies with DMSA, 1 echo-Doppler and one angiography were performed. Renal lesions were classified as: 8 type 1, 5 type 2, 4 type 3, 1 type 4. Four cases were operated and one case underwent percutaneous drainage of an urohematoma. Following an analysis of these case and a revision of the literature, the authors emphasise that the evolution and progress in the diagnosis and treatment of this important aspect of traumatic pathology in children enables an almost complete recovery of kidney function in almost all cases.

Abdominal Injuries↗
PubMed1993

Human-immunodeficiency-virus transmembrane glycoprotein gp41 is an amino acceptor and donor substrate for transglutaminase in vitro.

Recombinant gp41, the transmembrane glycoprotein of the human-immunodeficiency-virus (HIV) envelope, is an amino acceptor and donor substrate for transglutaminase in vitro. Gln51, Gln52, Gln66 and Lys77 residues were suggested as reactive sites, recognized by the enzyme, for possible cross-linking reactions with gp120, CD4 or other receptor(s) occurring on the surface of HIV-target cells. Soluble CD4, even though unable to function as an amino-acceptor transglutaminase substrate, becomes active in the presence of gp41, negatively influencing the enzyme-catalyzed incorporation of the polyamine spermidine into the transmembrane protein. These results suggest a possible role for transglutaminase in virus entry into host cells, via receptor-mediated endocytosis, and/or in HIV-induced CD4+ T-cell depletion via apoptosis.

Amino Acid Sequence↗