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Biomedical subjects

M Abbate

Publications and source records attributed to M Abbate.

At least 37 records · Page 2Linked to original sources
PubMed1998

The LNLS soft X-ray spectroscopy beamline.

The soft X-ray spectroscopy beamline installed at a bending-magnet source at the LNLS is described. The optics are designed to cover energies from 800 to 4000 eV with good efficiency. The focusing element is a gold-coated toroidal mirror with an angle of incidence of 17 mrad. The UHV double-crystal monochromator has three pairs of crystals, Si (111), InSb (111) and beryl (101;0), that can be selected by a sliding movement. The UHV workstation is equipped with an ion gun, an electron gun, an electron analyser, LEED optics, an open channeltron and a photodiode array. This beamline is intended for photoemission, photoabsorption, reflectivity and dichroism experiments.

Journal Article↗
PubMed1998

Experimental Goodpasture's syndrome in Wistar-Kyoto rats immunized with alpha3 chain of type IV collagen.

BACKGROUND: Glomerulonephritis and lung hemorrhage of autoimmune Goodpasture syndrome develop due to immune reactions against epitope(s) of the non-collagenous (NC1) domain of alpha3-chain of type IV collagen [alpha3(IV) NC1]. Whether thymic mechanisms have a role in the loss of tolerance to the Goodpasture epitope has not been established. We studied the renal and pulmonary effects of immunization with different forms (monomer, dimer, or hexamer) of alpha3(IV) NC1 collagen in Wistar-Kyoto (WKY) rats, and assessed whether the intrathymic inoculation of the antigen may protect against anti-GBM disease. METHODS: WKY rats were immunized with bovine alpha3(IV) monomer, dimer, or hexamer, or with alpha3(IV) NC1 synthetic peptide. Renal function, kidney and lung immunohistology, and circulating and tissue bound antibodies to type IV collagen chains were analyzed. Effects of intrathymic inoculation of antigen on subsequent disease induction were analyzed in WKY rats given alpha3(IV) NC1 dimer or GBM preparation intrathymically 48 hours before immunization. RESULTS: Proteinuria, linear IgG deposition in GBM, and crescentic glomerulonephritis developed in WKY rats immunized with alpha3(IV) NC1 dimer or hexamer. Lesions were dose-dependent upon injections of 10 to 100 microgram dimer. The alpha3(IV) NC1 monomer induced less severe proteinuria and no crescents. Pulmonary hemorrhage was detectable in 35% of rats immunized with 25 to 100 microgram alpha3(IV) NC1 dimer; alpha3(IV) synthetic peptide (36 carboxyl terminal) did not induce disease. Rats injected intrathymically with up to 100 microgram alpha3(IV) NC1 dimer or with GBM 48 hours before immunization were not protected against subsequent development of proteinuria and glomerulonephritis. CONCLUSIONS: These findings document that glomerulonephritis and lung hemorrhage can be elicited in WKY rats by immunization with alpha3(IV) NC1. Failure of the intrathymic inoculation of antigen to prevent disease suggests that immunological tolerance cannot be achieved by this intervention, in contrast to other autoimmune conditions, and may imply independent roles for cellular and humoral nephritogenic pathways in anti-GBM nephritis.

Animals↗
PubMed1998

Pharmacologic control of angiotensin II ameliorates renal disease while reducing renal TGF-beta in experimental mesangioproliferative glomerulonephritis.

We evaluated the effect of blocking angiotensin II (AngII) on the development of proteinuria and glomerular injury in antithymocyte serum (ATS) glomerulonephritis. Disease was induced in Sprague-Dawley rats by a single intravenous injection of rabbit ATS. Three groups of rats were considered: group 1 (n = 13), ATS rats with no therapy; group 2 (n = 13), ATS rats treated with angiotensin-converting enzyme inhibitor (40 mg/L lisinopril in the drinking water); and group 3 (n = 13), ATS rats treated with AngII receptor antagonist (50 mg/L L-158,809 in the drinking water). Treatment started 3 hours after ATS injection and lasted 4 days. An additional group of control rats (group 4, n = 13) received preimmune serum. At day 4, ATS rats developed proteinuria (46+/-5 mg/d v control 12+/-1 mg/d; P < 0.01), which was prevented by both lisinopril and L-158,809 (14+/-0.2 mg/d and 15+/-1.6 mg/d, respectively, P < 0.01 v ATS). Systolic blood pressure was comparable in ATS rats and in controls (119+/-4 mm Hg v 120+/-2 mm Hg). Systolic blood pressure values were significantly decreased after either lisinopril or L-158,809 (104+/-3 mm Hg and 101+/-5 mm Hg, respectively; P < 0.01 v ATS). Serum creatinine levels were similar in all groups. Quantitation of proliferating cells and macrophages by analysis of proliferating cell nuclear antigen-positive and ED1-positive cells/glomerular cross-section showed a marked increase in proliferating cell nuclear antigen-positive cells in glomeruli of ATS rats over controls (12.6+/-0.5 cells/glomerular cross-section v 1.9+/-0.2 cells/glomerular cross-section; P < 0.01), which was significantly (P < 0.01) prevented by both treatments (lisinopril, 5.7+/-1.0 cells/glomerular cross-section; L-158,809, 4.8+/-1.5 cells/glomerular cross-section). The increase in ED1-positive cells (10+/-0.7 cells/glomerular cross-section v controls, 1.8+/-0.2 cells/glomerular cross-section; P < 0.01) was also significantly (P < 0.01) reduced by lisinopril and L-158,809 (4.1+/-0.7 cells/glomerular cross-sections and 2.6+/-0.6 cells/glomerular cross-section, respectively). Blocking of AngII activity prevented almost completely the formation of microaneurysms in ATS rats (percent of glomeruli with microaneurysms: ATS, 11.5%+/-3.5%; ATS + lisinopril, 0.4%+/-0.2%; ATS + L-158,809, 0.8%+/-0.8%; controls, 0%). Because AngII is a potent inducer of renal transforming growth factor-beta (TGF-beta), a cytokine involved in the regulation of cell proliferation, matrix deposition, and monocyte migration (which is overexpressed in the kidney of ATS rats), we then evaluated the effect of AngII inhibitors on renal gene expression of TGF-beta1 and on urinary TGF-beta1. TGF-beta1 mRNA levels in kidneys of ATS rats were 3.6-fold higher than those of controls and were reduced by 46% and 32% after treatment with lisinopril and L-158,809, respectively. Urinary TGF-beta1 excretion increased in ATS (37.3+/-6.0 ng/d v controls, 13.8+/-3.4 ng/d; P< 0.01) but was normalized by lisinopril and L-158,809 (7.6+/-1.9 ng/d and 6.4+/-0.4 ng/d, respectively; P < 0.01). Thus, in ATS, blocking AngII synthesis prevents proteinuria and reduces glomerular cell proliferation and inflammatory cell infiltration, possibly by reducing excessive renal TGF-beta synthesis. These findings may be relevant for future strategies in the treatment of human mesangioproliferative glomerulonephritis.

Angiotensin II↗
PubMed1998

In progressive nephropathies, overload of tubular cells with filtered proteins translates glomerular permeability dysfunction into cellular signals of interstitial inflammation.

Progression to end-stage renal failure is the final common pathway of many forms of glomerular disease, independent of the type of initial insult. Progressive glomerulopathies have in common persistently high levels of urinary protein excretion and tubulointerstitial lesions at biopsy. Among the cellular mechanisms that may determine progression regardless of etiology, the traffic of excess proteins filtered from glomerulus in renal tubule may have functional importance by initiating interstitial inflammation in the early phase of parenchymal injury. This study analyzes the time course and sites of protein accumulation and interstitial cellular infiltration in two different models of proteinuric nephropathies. In remnant kidneys after 5/6 renal mass ablation, albumin and IgG accumulation by proximal tubular cells was visualized in the early stage, preceding interstitial infiltration of MHC-II-positive cells and macrophages. By double-staining, infiltrates developed at or near tubules containing intracellular IgG or luminal casts. This relationship persisted thereafter despite more irregular distribution of infiltrate. Similar patterns were found in an immune model (passive Heymann nephritis), indicating that the interstitial inflammatory reaction develops at the sites of protein overload, regardless of the type of glomerular injury. Osteopontin was detectable in cells of proximal tubules congested with protein in both models at sites of interstitial infiltration, and by virtue of its chemoattractive action this is likely mediator of a proximal tubule-dependent inflammatory pathway in response to protein load. Protein overload of tubules is a key candidate process translating glomerular protein leakage into cellular signals of interstitial inflammation. Mechanisms underlying the proinflammatory response of tubular cells to protein challenge in diseased kidney should be explored, as well as ways of limiting protein reabsorption/deposition to prevent consequent inflammation and progressive disease.

Albumins↗
PubMed1997

Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.

Mononuclear cell infiltration in glomeruli and renal interstitium is a prominent feature of some types of glomerulonephritis, including lupus nephritis. The mechanism(s) underlying monocyte influx into the kidney is not fully understood. Recently, monocyte chemoattractant protein-1 (MCP-1) has been identified as a chemotactic factor involved in the recruitment of monocytes/macrophages in the glomeruli of rats with mesangioproliferative as well as anti-glomerular basement membrane glomerulonephritis. In the study presented here, renal MCP-1 mRNA expression in New Zealand Black x New Zealand White (NZB/W) F1 mice, a model of genetically determined immune complex disease that mimics systemic lupus in humans, was investigated. Northern blot analysis revealed a single 0.7 kb MCP-1 transcript of very low intensity in kidneys from 2-month-old NZB/W mice that had not yet developed proteinuria nor renal damage. Message levels, which increased markedly with the progression of nephritis and in association with mononuclear cell infiltration, were 10- and 15- fold higher in 8-10-month-old mice than in 2-month-old mice. By in situ hybridization, increased expression of MCP-1 mRNA was demonstrated in glomeruli and, even more striking, in tubular epithelial cells. Western blot analysis demonstrated increased expression of MCP-1 protein in kidneys of 10-month-old NZB/W mice, consistent with MCP-1 mRNA data. When NZB/W mice were treated with cyclophosphamide up to 12 months of age, expression of MCP-1 in the renal tissue remained low, the influx of inflammatory cells did not appear, and glomerular and tubular structures remained well preserved. These data suggest that elevated MCP-1 might act as a signal for inflammatory cells to infiltrate the kidney in lupus nephritis.

Animals↗
PubMed1997

[Reintervention in mitral valve prostheses. Analysis of risk factors].

From 1980 to 1996, 111 patients (83 females, 28 males, mean age 51.47 +/- 15.73 years, range 1-76) underwent mitral valve replacement. Seventy-five patients underwent replacement of a biological valve and 36 of a mechanical valve. Three patients underwent a third operation. Seventy prostheses were replaced because of a structural dysfunction. Other causes of valve failure were: 24 thrombosis (23 mechanical and 1 biological), 10 endocarditis (7 mechanical, 3 biological) and 4 leakages (3 mechanical and 1 biological). One patient who had recurrent anticoagulant-related haemorrhage underwent reoperation to replace his mechanical valve with a biological prosthesis. Two patients had their valve replaced because of mismatch between size of the valve and body surface area. Thirteen operations were performed on emergency and 29 on urgency. There were 22 in-hospital deaths with a hospital mortality of 19.82%. Fourteen deaths (63.63%) occurred in patients operated on emergency or urgency. All deceased patients were in NYHA functional class III or IV. Our data suggest that risk of reoperation on mitral prosthesis is highly influenced by the preoperative functional class. In spite of the fact that replacement of biological valves should be more elective than that of mechanical valves, we did not find any difference between the two groups of patients.

Adolescent↗
PubMed1996

Acceleration of recovery in acute renal failure: from cellular mechanisms of tubular repair to innovative targeted therapies.

Kidney repair from injury is a major focus of interest for research, both clinical and basic, in the field of acute renal failure. This is so because very little progress has been made during the past several years to improve mortality in hospitalized patients with acute renal failure despite the unique potential of the kidney for complete structural and functional recovery. Novel therapeutic options have recently emerged from the knowledge of molecular mechanisms of tissue injury after ischemia, including pathways of endothelial-leukocyte interaction and epithelial cell aggregation mediated by integrin molecules. These strategies are promising because they may target early mechanisms of leukocyte infiltration and tubular obstruction. However, it seems clear that additional interventions should address the reparative program that potentially leads to the full restoration of kidney structure and function. Thus, acceleration of repair from acute renal failure is achieved experimentally by growth factors which besides different renal actions seem to have in common the ability to stimulate proliferation of surviving tubular epithelial cells. We direct attention to cellular processes which characterize, and possibly have role in, renal repair from acute tubular injury as potential targets of therapy. In addition to proliferation, they include epithelial differentiation and apoptosis. Further investigation in the biology of repair should set the stage for rational design of targeted therapies which may accelerate the pace of recovery and hopefully decrease mortality in such a dramatic and potentially reversible setting.

Acute Kidney Injury↗
PubMed1995

LLC-PK1 cell growth is repressed by WT1 inhibition of G-protein alpha i-2 protooncogene transcription.

The temporal expression of the early growth response gene (EGR-1) is one molecular mechanism for both maximal activation of the G alpha i-2 gene and accelerated growth in mitotically active predifferentiated LLC-PK1 renal cells. These events are dependent on an enhancer area in the 5'-flanking region of the G alpha i-2 gene that contains an EGR-1 motif (5'-CGCCCCCGC-3'). However, acquisition of the polarized phenotype in LLC-PK1 cells is accompanied by loss of EGR-1 expression and occupancy of the EGR-1 site by nuclear binding proteins other than EGR-1. We now demonstrate that one of these binding proteins is the Wilms' tumor suppressor (WT1). Furthermore, the temporal expression of WT1 in LLC-PK1 cells acquiring the polarized phenotype represses both G alpha i-2 gene activation and growth in these cells. These findings suggest the existence of differentiation-induced pathways in LLC-PK1 cells that alternatively abrogates EGR-1 and promotes WT1 gene expression, thereby modulating a target protooncogene G alpha i-2 that is participatory for growth and differentiation in renal cells. These studies emphasize the usefulness of the LLC-PK1 renal cell as a model to elucidate normal programs of genetic differentiation in which WT1 participates.

Animals↗
PubMed1995

Glomerulonephritis: from new knowledge on the mechanisms of tissue damage to novel therapies.

Remarkable progress has been made in the past two years in the investigation of immunological events and effector mechanisms which lead to glomerular inflammation and tissue damage, suggesting a number of areas in which therapeutic modulation is possible. We review recent advances in the two major areas of investigation in this field: the nephritogenic response to glomerulonephritis and local inflammatory reaction, and the novel therapeutic perspectives that have emerged from insights into the biology and pathology of the immune and inflammatory response.

Animals↗
PubMed1995

[Diagnostic accuracy of transesophageal echocardiography in the diagnosis of aortic dissection: comparison with computerized axial tomography].

This study was designed to assess the sensibility, specificity and diagnostic accuracy of transesophageal echocardiography (TEE) and X-ray contrast enhanced computed tomography (CT) in the diagnosis of aortic dissection and its complications. Fifty patients with clinically suspected aortic dissection were examined. Imaging results were validated in each case by intraoperative and/or autopsy findings and/or the results of cineangiography. The Stanford and DeBakey classifications were used to differentiate the dissection type; the patients were also subdivided by TEE according to a modified DeBakey classification. The sensibility of TEE to detect aortic dissection was 100%, significantly higher (p < 0.05) than that of CT for type A dissections (77.2%). The two imaging procedures did not statistically differ (NS) in the detection of type B dissection (CT sensibility 87.5%). The specificity of TEE for the detection of type A aortic dissection was 94%; it was not significantly higher (NS) than that of CT (CT specificity 86.6%). Both TEE and CT had no false negative findings in the diagnosis of type B aortic dissection (100%; TEE vs CT, NS). TEE was reliable in the correct identification of the primary entry site in the ascending aorta (80%), the arch (62.5%) and descending aorta (71.4%), and also in the involvement of coronary arteries (62.5%), and aortic arch branch vessels (71.4%); CT scanning was not effective in detecting any of these complications. Aortic regurgitation was accurately identified by TEE in each case. Both TEE and CT scanning correctly identified thrombosis of the false lumen and pericardial effusion. Intraoperative TEE documented in all patients postrepair persistence of the intimal flap in aortic segments that were not operated; flow in the false lumen was detected in 46.6% of the patients; in 26.6% of them secondary tears, not seen before surgical treatment, were detected. In conclusion, TEE allows a bedside, safe and accurate diagnosis and classification of aortic dissection. It also provides the diagnostic information necessary for the therapeutical decision making. Intraoperative TEE allows improvement in preoperatory diagnosis and gives important information for the management of the patient immediately after cardiopulmonary bypass and in the follow-up.

Adult↗
PubMed1995

[Value of intraoperative transesophageal echocardiography during repair of thoracic aorta dissection].

The study was designed to assess the diagnostic accuracy and usefulness of intraoperative transesophageal echocardiography (TEE) during repair of aortic dissection. To this end, 32 patients with ascending aortic dissection, undergoing replacement of the ascending aorta, were examined. The diagnosis was validated in each case by intraoperative and/or autopsy findings. The accuracy of TEE was studied in three different periods of surgical operation: before cardiopulmonary bypass (TEE pre-CPB), during CPB (TEE-CPB) and after CPB (TEE post-CPB). In comparison with TEE performed in the intensive care unit 70 +/- 40 min before surgery, TEE pre-CPB showed a higher diagnostic accuracy (100 vs 96%) in classification of the dissection type, a higher sensibility in the identification of intimal tears (83 vs 75%), involvement of the coronary arteries (71 vs 62%) and of aortic arch branches (81 vs 71%); there was no statistically significant difference in the detection of the aortic valve involvement (100 vs 100%). TEE-CPB showed normal perfusion of the true lumen in all but one patient, in whom TEE-CPB showed retrograde perfusion of the false lumen, promptly resolved by fenestration of the false lumen. TEE post-CPB showed persistence of the intimal flap in non repaired segments in all the patients with type I aortic dissection: in 60% of them there was no communication between the true and false lumen; in 40% of them there was a communication between the two lumina, which was proximal in 25% and distal in 15%; all patients did not show thrombosis of the false lumen. TEE post-CPB allowed also the evaluation of flow in left aortic arch branch vessels in 77% of the patients and in the coronary arteries in 70%, and showed well functioning prosthesis in all patients. In each case aortic regurgitation was mild; however, one case had severe insufficiency which was corrected at the time of surgery with annuloplasty. Ejection fraction was normal in 45% of the patients, whereas it was decreased in the remaining patients. Intraoperative TEE during repair of aortic dissection is accurate and useful: it allows improvement in preoperative diagnosis just before CPB, optimizing surgical technique; it gives also important information for the management of patients immediately after CPB and for the follow-up.

Adult↗