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F Mampaso

Publications and source records attributed to F Mampaso.

At least 37 records · Page 2Linked to original sources
PubMed1999

Changes in the pattern of fibronectin mRNA alternative splicing in acute experimental mesangioproliferative nephritis.

Fibronectins (FN) regulate cell migration, proliferation, and matrix formation during tissue injury. In humans, up to 20 different FN isoforms are generated by alternative splicing in three regions called EIIIA, EIIIB, and V, which have been implicated in the process undergoing wound healing and embryonic development. Specifically, EIIIA- and EIIIB-containing isoforms have been implicated in the regulation of cell proliferation and migration, whereas FN isoforms containing the full-length V region (named V120) are ligands to the VLA-4 integrin. To study the changes in the expression of FN isoforms in the anti-Thy-1 nephritis, an acute and self-resolutive model of mesangioproliferative nephritis, we analyzed the FN splicing patterns by means of ribonuclease protection assays. At Day 7 after anti-Thy-1 monoclonal injection, time of the maximal matrix expansion and glomerular hypercellularity, EIIIA+, EIIIB-, and V120 FN mRNA isoforms were increased. In accordance with the mRNA studies, FN proteins, including the EIIIA and V120 regions, increased in the mesangium of nephritic rats, as assayed by immunohistochemistry. Coinciding with the EIIIA and V120 isoforms up-regulation, there was an increase in mesangial cell proliferation and in the number of VLA-4+ infiltrating cells. At Day 14, in parallel with a remission of the above-mentioned changes, there was a decline in the mRNA and protein FN isoforms increased in the previous phase. The marked and reversible changes in the pattern of FN isoforms and their temporal association with other indicators of glomerular injury suggest that certain FN isotypes are important and coordinated components of the mechanisms attempting to reverse glomerular damage.

Acute Disease↗
PubMed1998

Delayed graft function does not reduce the survival of renal transplant allografts.

BACKGROUND: The aim of the present study was to investigate the effect of delayed graft function (DGF) in graft outcome when adjusted by the presence of acute rejection in the first month after transplantation. METHODS: A total of 437 cadaveric renal transplant patients on cyclosporine and steroids were included in the study. Variables related to donor, recipient, and graft were prospectively collected. RESULTS: The incidence of DGF was 44.4%. When patients dying with a functioning graft were censored, graft survival rates at 1 and 6 years were similar in patients with immediate function to those with DGF, when rejection was not present (96% and 81% vs. 95% and 83%, respectively). Rejection negatively influenced graft survival rates at 1 and 6 years, both in patients with immediate graft function (80% and 73%, P<0.05 vs. no DGF/no rejection) and more deeply in those with associated DGF (77% and 62%, P<0.001 vs. no DGF/no rejection). Rejection was more frequently diagnosed in patients with DGF than in those with immediate graft function (50% vs. 39.9%, P<0.05). Length of hospitalization was longer and the number of needle core biopsies was higher in patients with DGF or rejection. The presence of both complications had an additive effect. CONCLUSIONS: This study showed that DGF did not adversely affect kidney graft survival in patients without rejection. However, it increased the length of hospitalization and the number of graft biopsies, thus increasing the cost of transplantation. Moreover, rejection was more frequent in patients with DGF, and it had a negative impact on graft outcome. Because the association of DGF and rejection gave the poorest outcome, an effort should be made to prevent both complications.

Adolescent↗
PubMed1998

Differential effects of antibodies to vascular cell adhesion molecule-1 and distinct epitopes of the alpha4 integrin in HgCl2-induced nephritis in Brown Norway rats.

Four distinct epitopes (A, B1, B2, and C) have been functionally defined on the human alpha4 integrin. In this study, two cross-reactive antihuman alpha4 monoclonal antibodies (mAb) (HP2/1 and HP2/4 specific for epitopes B1 and B2, respectively) were used to functionally characterize the rat VLA-4 subunit and to define similar functional epitopes in this rodent species. It was found that B1 and B2 anti-alpha4 mAb completely block adhesion to fibronectin, but the inhibition of adhesion to vascular cell adhesion molecule-1 (VCAM-1) with HP2/1 mAb was lower than with HP2/4 mAb. It was also observed that epitope B2 HP2/4 mAb induced homotypic aggregation in rat lymphocytes, whereas epitope B1 HP2/1 mAb did not. Using the HgCl2 model of nephritis, this study shows the protective effect of both anti-alpha4 mAb against infiltration of the renal interstitium by leukocytes. Nevertheless, HP2/1 mAb, but not HP2/4 mAb, virtually abolished the anti-glomerular basement membrane antibody synthesis and glomerular deposits. These findings indicate the dual but independent role played by alpha4 integrins in both extravasation of leukocytes and in the production of antibodies. Finally, this study demonstrates that anti-rat VCAM-1 mAb showed a positive reactivity of the renal vascular endothelium and, most importantly, that administration of anti-VCAM-1 antibodies completely abrogated the interstitial cell infiltrates without affecting anti-glomerular basement membrane antibody production. These results confirm the important role played by VLA-4/VCAM-1 pathway in leukocyte infiltration, and further support the dual and independent role of alpha4 integrins in both renal infiltration and autoantibody synthesis in this model of renal disease.

Analysis of Variance↗
PubMed1997

Role of leucocyte adhesion molecules in aminonucleoside of puromycin (PAN)-associated interstitial nephritis.

Rats receiving a single dose (10 mg/l00 g body wt) of PAN develop severe proteinuria and acute interstitial nephritis. To investigate the mechanisms involved in interstitial leucocyte accumulation, we examined the expression of adhesion molecules on kidney tissue sections as well as on endothelial cell cultures. We also performed in vivo treatments with antibodies against adhesion molecules. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) was found on day 7 of the disease, when interstitial nephritis was first detected. Also, rat endothelial cells in culture showed maximal expression of ICAM-1 in the presence of 10(-9) - 10(-11) M PAN. Adhesion of peripheral blood mononuclear cells (PBMC) on kidney sections from PAN-treated rats was highest on day 7 (3.05 +/- 0.7 (mean +/- s.e.m.); controls 0.75 +/- 0.5). Such increased adhesion was notably blocked after PAN-treated rat kidney sections were incubated with anti-ICAM-1 MoAb (0.9 +/- 0.4). In addition, adhesiveness of PBMC to PAN-stimulated endothelial cells in culture was enhanced (25 +/- 2.5%; non-stimulated cells 13 +/- 3.1%). The addition of specific MoAbs against ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) produced a high blockage of adhesiveness induced by exposure to PAN (inhibition 58 +/- 3%; non-stimulated cells 40 +/- 7%). Simultaneous administration to PAN-treated rats of anti-LFA-1 and anti-ICAM-1 MoAbs reduced the number of interstitial cells by 70% compared with the 30% of reduction obtained when anti-very late antigen-4 (VLA-4) MoAb and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies were used. Our results suggest that the LFA-1/ICAM-1 pathway plays a principal role in the interstitial nephritis occurring in rats with PAN-nephrosis.

Animals↗
PubMed1996

Soluble adhesion molecules in renal transplantation.

Serum levels of sICAM-1 and sVCAM-1 adhesion molecules as well as TNF cytokine were measured in 50 kidney transplant recipients [14 patients with stable graft function, 18 patients with acute rejection, 10 patients with CsA toxicity, 6 patients with ATN, and 2 patients with cytomegalovirus (CMV) disease] during the first 3 postoperative weeks. All the patients studied showed, on the first posttransplant day, elevated serum levels of sICAM-1 (260 +/- 53 ng/mL). Interestingly, all the patients with good graft function presented thereafter a reduction of sICAM-1 serum levels close to the normal values (185.2 +/- 40 ng/mL). In contrast, the group of patients with acute allograft rejection showed significantly increased serum levels of sICAM-1 (371.5 +/- 86 ng/mL; p < 0.001), 3-4 days before diagnosis of acute rejection. Although sVCAM-1 levels were increased in both acute graft rejection (2263 +/- 106) and CsA toxicity (1650 +/- 315) patients, such increase was not significant among either group of patients when the group with CsA toxicity was compared with either ATN (1320 +/- 204) or stable renal function (1089 +/- 167). No statistical differences in the levels of TNF were demonstrated between the different groups of patients studied. Our findings demonstrate that quantitative determination of serum sICAM-1 may be of predictive clinical value in transplanted patients with acute renal allograft rejection.

Cyclosporine↗
PubMed1996

Membranous nephropathy: recurrence after kidney transplantation.

BACKGROUND: It is supposed that about 5% of dialysis patients had membranous nephropathy as a cause for their renal failure. Despite of this prevalence, only 33 cases of recurrent membranous nephropathy after kidney transplantation have been reported in the English literature. METHODS: Among 509 recipients of renal allografts, membranous glomerulonephritis was the cause of renal failure in five patients, who received six transplants. RESULTS: Recurrence of the disease was observed in three allografts (50%) in three patients, all of them were on treatment with cyclosporin and low-dose prednisone. Proteinuria appeared at 2, 5 and 19 months after grafting. One patient experienced a spontaneous remission after 12 months and he is free from proteinuria and with good renal function after 5 years. The remaining two patients presented progressive renal function deterioration and returned to haemodialysis 24 and 17 months after th appearance of proteinuria. In these patients increasing the immunosuppression did not produce any beneficial effect. One of those patients underwent a second transplant; recurrence of the membranous nephropathy has not been observed after 3 years of follow-up. CONCLUSIONS: In this study three new cases of recurrence of membranous nephropathy are reported. One patient experienced a spontaneous remission of proteinuria. Recurrence of membranous nephropathy in renal allograft was very high in our series. Its appearance was associated with poor prognosis of the graft in most patients, although spontaneous remission of proteinuria is possible.

Adult↗
PubMed1995

Passive dual immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta maximally ameliorates acute aminonucleoside nephrosis.

Rats receiving a single dose (10 mg/100 g) of aminonucleoside of puromycin (PAN) develop heavy proteinuria and acute interstitial nephritis (AIN). Whole isolated glomeruli from rats injected with PAN secreted both TNF-alpha and IL-1 beta cytokines. TNF-alpha secretion was first and maximally detected on day 3, whereas IL-beta activity was found on day 7, when rats were heavily proteinuric and AIN developed. In vivo treatment with either anti-TNF-alpha or anti-IL-1 beta antibodies produced a drastic and simultaneous reduction in both levels of proteinuria and intensity of interstitial cell infiltrate. These effects improved when both antibodies were administered together. Our studies demonstrate the effectiveness of immunosuppressive therapy against these two cytokines in rats with PAN-induced nephrosis.

Animals↗
PubMed1994

Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin.

HgCl2 induces the synthesis of anti-GBM Abs with the development of glomerular and interstitial nephritis, as well as proteinuria, in the Brown Norway rat. The development of this autoimmune disease is a consequence of the appearance of an autoreactive T cell subset-inducing activation of B cells. The administration to mercury-treated rats of the mouse anti-human VLA alpha 4 HP2/1 mAb, which cross-reacts with the rat homologue integrin, completely abrogated the interstitial cell infiltrates. As demonstrated by peripheral blood analysis, this effect is not a result of the depletion of circulating leukocytes or leukocyte subsets. Interestingly, the administration of Abs specific for the alpha 4 integrin also highly reduced anti-GBM Ab synthesis, thus preventing detectable glomerular deposits and proteinuria. Our results confirm that in vivo alpha 4 functions in adhesive interaction of circulating leukocytes and vascular endothelium, and is centrally important in the extravasation and migration of T lymphocytes to sites of tissue injury. We also found a complete absence of interstitial cell infiltrates, together with a positive glomerular IgG lineal deposition pattern, when anti-GBM Abs were passively transferred to rats pretreated with anti-alpha 4 mAb, thus indicating an independent role of alpha 4 integrin in both extravasation of immune cells and production of autoantibodies. Furthermore, these in vivo findings provide preliminary evidence for the participation of the VLA-4 integrin in mediating the intercellular interaction of leukocytes regulating the production of Abs, most likely through the existence of additional yet unknown ligand(s).

Animals↗
PubMed1994

Swine-reconstituted SCID mice as a model for African swine fever virus infection.

Injection of swine peripheral blood mononuclear cells into mice with severe combined immunodeficiency (SCID), resulted in the stable long-term establishment of a functional swine immune system (SCID-sw). Swine immunoglobulins were present in the serum of SCID-sw mice and swine cells were detected in the blood as well as in lymph nodes and spleen using monoclonal antibodies raised against cell subpopulations. Swine lymphocytes from reconstituted SCID mice responded in vitro to specific antigens or mitogens. When SCID-sw mice were challenged with African swine fever (ASF) virus, ASF virus-infected cells were detected in blood and spleen, and antiviral antibodies and virus-specific T cells were generated.

African Swine Fever Virus↗
PubMed1994

Recurrence of focal-segmental glomerulosclerosis in kidney transplant patients on ciclosporin.

Two patients on maintenance hemodialysis after terminal renal failure due to nephrotic syndrome and biopsy-proven focal-segmental glomerulosclerosis received three cadaver renal allografts. Immediate recurrence of nephrotic syndrome was observed. In two transplants immunosuppression consisted of ciclosporin A and low-dose steroids. One patient was unsuccessfully treated with immunoadsorption after the second transplant. All grafts were lost because of uncontrolled nephrotic syndrome. Renal allograft biopsy specimens showed findings indicating recurrence of the original disease.

Adolescent↗