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Biomedical subjects

J A Bruijn

Publications and source records attributed to J A Bruijn.

At least 19 recordsLinked to original sources
PubMed1999

Prevention of renal allograft rejection in primates by blocking the B7/CD28 pathway.

BACKGROUND: There is accumulating evidence that blockade of the costimulatory pathways offers a valid approach for immune suppression after solid organ transplantation. In this study, the efficacy of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) in combination with cyclosporine (CsA) to prevent renal allograft rejection was tested in non-human primates. METHODS: Rhesus monkeys were transplanted with a partly major histocompatibility complex-matched kidney on day 0. Anti-CD80 and anti-CD86 mAbs were administered intravenously daily for 14 days starting at day - 1. CsA was given intramuscularly for 35 days starting just after transplantation. The kidney function was monitored by determining serum creatinine levels. RESULTS: The combination of anti-CD80 and anti-CD86 mAbs completely abrogated the mixed lymphocyte reaction. Untreated rhesus monkeys rejected the kidney allograft in 5-7 days. Treatment with anti-CD80 plus anti-CD86 mAbs resulted in a significantly prolonged graft survival of 28+ 7 days (P=0.025). There were no clinical signs of side effects or rejection during treatment. Kidney graft rejection started after the antibody therapy was stopped. The anti-mouse antibody response was delayed from day 10 to 30 after the first injection. No difference in graft survival was observed between animals treated with CsA alone or in combination with anti-CD80 and anti-CD86 mAbs. However, treatment with anti-CD80 and anti-CD86 mAbs reduced development of vascular rejection. CONCLUSIONS: In combination, anti-CD80 and antiCD86 mAbs abrogate T-cell proliferation in vitro, delay the anti-mouse antibody response in vivo, and prevent graft rejection and development of graft vascular disease in a preclinical vascularized transplant model in non-human primates.

Animals↗
PubMed1999

Cellular localization and tissue distribution of polycystin-1.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of fluid-filled cysts in both kidneys, in addition to a variety of extra-renal manifestations. The PKD1 gene product, polycystin-1, encodes a novel protein with a putative role in cell-cell/cell-matrix interactions. The present study we focused on the (sub)cellular localization of polycystin-1 in cultured cells, and on its tissue distribution in various organs. In Madin Darby canine kidney (MDCK) cells, several polyclonal antibodies showed intense staining at the sites of interaction between adjacent cells, which remained after Triton extraction. Weak cytoplasmic staining was observed. No signal was detected at the free borders of cell aggregates, supporting a role for polycystin-1 in cell-cell interactions. At the tissue level, polycystin-1 expression was observed in specific cell types in tissues with known manifestations of the disease, but also in tissues of organs which have not been reported to be affected in ADPKD. Expression was frequently seen in epithelia, but also in endocrine cells (pancreatic islets, parathyroid-producing cells, clusters in the adenohypophysis, clusters in the adrenal gland, and Leydig cells in the testis). In addition, expression was observed in myocardium and more weakly in myocytes of cardiac valves, of the cerebral arteries, and of skeletal muscles.

Animals↗
PubMed1999

Sequential development of anti-GBM nephritis and ANCA-associated Pauci-immune glomerulonephritis.

The medical history is presented of a 23-year-old man experiencing three episodes of pulmonary-renal syndrome. On the first occasion, a diagnosis of anti-glomerular basement membrane (GBM) disease (with linear deposition of immunoglobulin G [IgG] along the GBM) was made, whereas anti-neutrophil cytoplasmic autoantibodies were also present in serum. On the third occasion, 5 years later, p-ANCA-associated vasculitis (with pauci-immune crescentic glomerulonephritis) was diagnosed, whereas anti-GBM antibodies were absent. The current literature on ANCA-positive anti-GBM disease is briefly reviewed. A substantial proportion (20% to 30%) of patients with histologically and serologically proven anti-GBM nephritis display the presence of ANCA as well. In this group of patients with dual antibodies, clinical and histological findings suggest that ANCA are not merely epiphenomena, but are of pathogenetic importance and might be responsible for an initial vasculitic insult to the kidney with resultant secondary anti-GBM nephritis. The clinical course in our patient lends further support to this concept. Histological demonstration of anti-GBM nephritis followed by ANCA-associated pauci-immune glomerulonephritis in a single patient has not been reported before.

Adult↗
PubMed1999

The pathogenesis of progressive renal failure.

All glomerular kidney disorders with the exception of minimal change disease are characterized by a progressive decline of renal function in association with progressive glomerulosclerosis and tubulointerstitial fibrosis of the kidneys involved. This almost universal association seems to suggest that the progressive loss of kidney function results from a fibrogenic pathogenetic mechanism that serves as a final common pathway with the initial insult to the glomerulus initiating a cascade of events including an early inflammatory phase followed by a fibrogenic response in the glomerular and the tubulointerstitial compartments of the kidneys. The present review will address the pathogenesis of this fibrogenic process covering the interplay between glomerular and tubulointerstitial events, the roles of recruited and resistant cells, cytokines, growth factors and the extracellular matrix.

Cytokines↗
PubMed1999

Idiotype usage by polyclonally activated B cells in experimental autoimmunity and infection.

Both in animal models and in human systemic lupus erythematosus (SLE) the occurrence of nephritogenic autoantibodies bearing dominant idiotypes has been described. In this study we investigate the relation between the induction pathway of polyclonal B cell activation and the production and glomerular deposition of nephritogenic antibodies with shared dominant idiotype(s). Polyclonal B cell activation was induced in several experimental models characterized by glomerular immune deposit formation. We monitored the occurrence of dominant idiotypes among immunoglobulins deposited in the glomeruli. In addition, we studied the species specificity of the dominant idiotypes, by monitoring their presence in kidney sections of patients with an immunologically mediated kidney disease. Anti-idiotype antisera against two monoclonal anti-DNA autoantibodies were used, derived from MRL-lpr/lpr mice, i. e. clone H241 and clone H130. Autoantibodies with the H241 idiotype were present in immune complex depositions in all experimental models but not in humans. We therefore conclude that the presence of this dominant idiotype is independent of the induction pathway of polyclonal B cell activation. However, autoantibodies bearing the H130 idiotype were only detected in kidney sections of mice with spontaneous lupus.

Animals↗
PubMed1999

Haematopathology of 'Sjögren-mice': histopathological changes in spleens after semiallogeneic cell transfer.

Haematopoietic transplantation chimeras may be readily produced in adult mice, using F1-hybrids of selected inbred strains as recipients and mice from one of the parental strains as donors. We transplanted spleen cells from BALB/c donors into nonirradiateded F1-hybrids of BALB/c and CBA/H-T6. Both female and male recipients developed a primary Sjögren's syndrome-like exocrinopathy without signs of kidney disease. At long-term follow-up, 7(1/2) months after cell transfer, lymph nodes were enlarged, and spleens were diminished and irregular in shape. In general, changes in haematopoietic organs were more prominent in males. The results verify that although hybrid mice of either sex develop glandular manifestations comparable with primary Sjögren's syndrome, when the immune system is stimulated by semiallogeneic immunocytes, the evoked reactions in haematopoietic tissues show gender difference.

Animals↗
PubMed1999

Depressed in-patients respond differently to imipramine and mirtazapine.

Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression. After a previous report of a marked difference in the response to mirtazapine compared to imipramine, we report here an analysis of different symptom clusters. One hundred seven consecutive in-patients with major depression (Diagnostic and Statistical Manual III-R, DSM-III-R) and a Hamilton Rating Scale for Depression (HRS-D) score of 18 points or more were randomly assigned to double-blind treatment. Two and four weeks after predefined blood levels had been obtained, the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine, the latter being in excess of the 15-45 mg/day range currently advised. Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients (79%) who were not receiving any co-medication. Imipramine was more effective against the clusters related to core symptoms of depression: "depression and guilt", "retardation", and "melancholia", respectively. Mirtazapine showed a biphasic response with regard to the clusters "sleep" and "anxiety/agitation", respectively, which consisted of a marked response after two weeks of predefined blood level, but with a waning of this effect at four weeks. Imipramine produced a more gradual response on these clusters, which was more pronounced at four weeks than with mirtazapine. Two aspects of the present study could be related to this finding: blood level control resulted in optimal treatment with imipramine but not mirtazapine, and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication. These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in-patients.

Adrenergic alpha-Antagonists↗
PubMed1999

Role of tubular cells in progressive renal disease.

It is generally accepted that the progressive loss of kidney function results from a pathogenic process that is independent of the original etiology, functioning as a final common pathway. Part of this response is characterized by triggering of interstitial infiltration and induction of tubular damage. As a consequence, tubular epithelial cells (TEC) can become activated and begin to express several inflammatory mediators. In the present review, we will summarize the potential role of TEC in progressive renal disease. Much emphasis will be put on studies using in vitro cultured TEC. These studies have provided more insight into the different signals involved in the regulation of the production of inflammatory mediators like complement, cytokines and chemokines, as well as progression factors like growth factors and matrix component by TEC.

Animals↗
PubMed1999

Recurrence of IgA nephropathy after renal transplantation.

With time recurrence of IgA nephropathy in renal allografts may be found in most, if not all patients. However, at the present graft loss due to recurrent IgA nephropathy appears to be of limited importance as compared to other causes. No definite risk factors for recurrent disease and/or graft failure have been identified yet. Although recurrence rates appear to be higher in allografts from living related donors, graft loss rates due to IgA nephropathy are not significantly different. More important, sporadic cases of IgA nephropathy should be excluded in all living related donors.

Biopsy↗
PubMed1998

Complete withdrawal of immunosuppression in kidney allograft recipients: a prospective study in rhesus monkeys.

BACKGROUND: We previously reported the successful withdrawal of immunosuppression in kidney-allografted rhesus monkeys. Recipients had received pretransplant blood transfusions and cyclosporine (CsA) immunosuppression for 6 to 12 months. One animal is still alive at more than 15 years after transplantation. Our hypothesis was that the sharing of a single DR antigen between blood donor and recipient, and the sharing of the same DR antigen with the kidney donor, may be beneficial to allograft survival. We now report on the results from a prospective study. METHODS: The animals received three pretransplant blood transfusions from a single donor sharing one DR antigen with the recipient. Subsequently, a life-supporting kidney from a donor sharing the same DR antigen was transplanted. CsA was given for at least 6 months after transplantation. RESULTS: Two animals rejected their graft at 5-8 weeks after cessation of CsA treatment. One animal is still alive at 700 days after transplantation. This animal showed MLR nonreactivity to its kidney donor, similar to the animal at more than 15 years after transplantation. CONCLUSION: These results demonstrate that withdrawal of immunosuppression may be a realistic option in kidney graft patients under careful immunological monitoring of donor-specific immunity.

Animals↗
PubMed1998

[A successful treatment of drug-resistant depression with electroconvulsive therapy].

A woman aged 56 had been treated at the age of 23 for a psychotic depression with vital characteristics in the context of a bipolar disorder. The treatment included electroconvulsive therapy (ECT). From the age of 47, she suffered relapses; drug treatment proved inadequate. For the last 3 years, ECT was administered, which resulted in a good condition. ECT is an effective treatment in patients with depression resistant to medication. However, in spite of continuation pharmacotherapy, the proportion of patients relapsing within 6 months after successful ECT is large. For these patients, continuation ECT may be an efficacious method.

Adult↗
PubMed1998

Association between leukocyte infiltration and development of glomerulosclerosis in experimental lupus nephritis.

Mice with chronic graft-versus-host disease (GvHD) induced by injection of DBA/2 lymphocytes into (DBA/2 x C57BL/10) F1 hybrids (DBA/2 GvHD) develop a lupus-like glomerulonephritis with global glomerulosclerosis 12 weeks after induction of the disease. In two other strain combinations with similar H-2 incompatibilities [BALB/c into BALB/c x BL10 (BALB/c GvHD) and BALB.D2 into BALB.D2 x BL10 (BALB.D2 GvHD)], GvHD induction leads to lupus nephritis without global glomerulosclerosis. This study investigated the identity of kidney-infiltrating leukocytes and their involvement in the development of glomerulosclerosis in these three strain combinations. In mice with DBA/2 GvHD, a significant increase in glomerular CD11a-positive cells was found 4 weeks after disease induction. Mice with BALB/c or BALB.D2 GvHD did not show an increase in glomerular CD11a-positive cells at any time point. In the interstitium, CD11a-positive cells were observed 4 weeks after disease induction only in mice with DBA/2 GvHD. In mice with BALB.D2 GvHD, no increase was found in interstitial CD11a-positive cells. In mice with BALB/c GvHD, interstitial CD11a-positive cells were found from week 4 onward. Further immunohistochemical analysis of the glomerular CD11a-positive cells in mice with DBA/2 GvHD showed that these cells were neither polymorphonuclear leukocytes (PMN), nor CD3-positive (T cells), B220-positive (B cells), or F4/80-positive (macrophages). They were all CD45-positive (leukocytes) and MHC class II-positive. In conclusion, we have shown in this model of chronic lupus nephritis that glomerular influx of as yet unidentified CD11a-positive leukocytes is associated with the development of glomerulosclerosis.

Animals↗
PubMed1998

Differential expression of collagen IV isoforms in experimental glomerulosclerosis.

Expansion of the glomerular mesangial matrix (MM), thickening of the glomerular basement membrane (GBM), and eventually the development of glomerulosclerosis are often seen in immunologically mediated kidney diseases. In addition to quantitative changes in the extracellular matrix (ECM), qualitative changes in ECM molecules may contribute to alterations in the composition of the glomerular matrix. The expression of collagen IV, alpha 1-5(IV) mRNA, and polypeptides was therefore investigated during the development of chronic graft-versus-host disease (GvHD) in mice, a model for lupus nephritis, and in chronic serum sickness (CSS) in rats, a model for membranous nephropathy. Immunohistochemical studies showed increased mesangial expression of alpha 1 and alpha 2 early in the disease, but only late in the GBM. In contrast, alpha 3 and alpha 4 increased in the GBM during disease, but not in the MM. The mRNA levels for all collagen IV chains were increased in isolated glomeruli before morphological alterations were detectable. The mRNA increase was earlier and more profound for alpha 3, alpha 4 and alpha 5 than for alpha 1 and alpha 2. Expression of alpha 3(IV) was greatest in GvHD, whereas expression of alpha 4 was greatest in CSS. As determined by in situ hybridization (ISH), alpha 1 mRNA was observed dispersed in the glomerulus, but alpha 3, alpha 4, and alpha 5 mRNAs were mainly located in cells at the periphery of the glomerular tuft. The changes in the relative abundance of collagen IV mRNA in disease states may perturb the collagen IV network, altering glomerular structure and function, and may thereby play a central role in the development of glomerulonephritis and glomerulosclerosis.

Animals↗
PubMed1998

The role of EDTA in provoking allergic reactions to subcutaneous infusion of apomorphine in patients with Parkinson's disease: a histologic study.

One of the formulations of apomorphine, used in clinical practice, contains sodium edetate (EDTA). EDTA is a chelator which indirectly prevents oxidation of apomorphine. A clinical and histologic study in four patients revealed that apomorphine with EDTA caused severe subcutaneous nodules, histologically characterized by an inflammatory infiltrate with a large amount of eosinophils, indicating a cell-mediated allergic reaction. After withdrawal of EDTA, this allergic component completely disappeared, which was accompanied clinically by less extensive nodule formation with a softer consistency. It is therefore recommended that EDTA be excluded from apomorphine formulations.

Abdominal Muscles↗
PubMed1998

Experimental glomerulonephritis is attenuated by CD8+ T cell chimerism and prevented by Mls-1-incompatible thymocytes.

Chronic graft-versus-host disease (GvHD) in mice is a model resembling glomerulonephritis in human systemic lupus erythematosus. In the present study congenic mouse strains were used to investigate the pathogenetic role of (1) donor T cell subset chimerism and (2) donor thymocytes in this model. In GvHD employing minor lymphocyte-stimulating-1 (Mls-1)-compatible donors and recipients, full-blown immune complex glomerulonephritis was associated with a low-donor CD8(+) T cell chimerism. Injection of lymphocytes from Mls-1-negative donors (Mls-1(b)) into Mls-1-positive recipients (Mls-1(a)) induces a type of GvHD characterized by rapid self-limitation accompanied by the immediate inhibition of donor T cell chimerism and the absence of glomerulonephritis. However, omission of thymocytes from the donor inoculate does result in glomerular depositions containing immunoglobulins. These results suggest that donor CD8(+) T cell chimerism is associated with attenuation of immune complex glomerulonephritis, whereas Mls-1-incompatible donor T cell precursors prevent the disease.

Animals↗
PubMed1998

Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane.

In diabetic nephropathy, expression of glycosaminoglycan side chains of heparan sulphate proteoglycan in the glomerular basement membrane is reduced proportionally to the degree of proteinuria. We performed a cross-sectional study to evaluate whether non-vascular basement membranes also show a decrease in heparan sulphate side chain staining in patients with diabetic nephropathy. We evaluated the skin basement membrane for extracellular matrix components in the following groups: control subjects (n = 16); patients with Type 1 diabetes and normoalbuminuria (n = 17), microalbuminuria (n = 7), and macroalbuminuria (n = 16); patients with Type 1 diabetes and diabetic nephropathy undergoing renal replacement therapy (n = 13); and non-diabetic patients undergoing renal replacement therapy (n = 21). The following antibodies were used for this immunohistochemical study: monoclonal antibodies against the heparan sulphate side chain (JM403) and core protein (JM72) of the glomerular heparan sulphate proteoglycan; polyclonal antibodies against the core protein (B31); polyclonal antibodies against collagen types I, III, and IV, fibronectin, and laminin; and monoclonal antibodies against the noncollagenous domain of alpha1(collagen IV) and alpha3(collagen IV), against transforming growth factor beta(2G7), and against advanced glycosylation end products (4G9). Expression of heparan sulphate side chains was reduced in the skin basement membrane of patients with overt diabetic nephropathy, of those with Type 1 diabetes undergoing renal replacement therapy, and those with non-diabetic renal failure. Increased intensity of staining was found for collagen type I and advanced glycosylation end products in patients with diabetic nephropathy. Changes in the extracellular matrix of the skin basement membrane seem to be similar to those in the glomerular basement membrane. These findings support the suggestion that patients with diabetic nephropathy also have altered heparan sulphate and collagen staining in extrarenal basement membranes. However, patients with non-diabetic renal failure also had reduced expression of heparan sulphate in the skin basement membrane, suggesting that this finding is not specific for diabetic nephropathy.

Adult↗