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J P Cosyns

Publications and source records attributed to J P Cosyns.

At least 19 recordsLinked to original sources
PubMed2005

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Age of Onset↗
PubMed2002

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗
PubMed2001

An alternative open reading frame of the human macrophage colony-stimulating factor gene is independently translated and codes for an antigenic peptide of 14 amino acids recognized by tumor-infiltrating CD8 T lymphocytes.

We show that cytotoxic T lymphocytes (CTLs) infiltrating a kidney tumor recognize a peptide encoded by an alternative open reading frame (ORF) of the macrophage colony-stimulating factor (M-CSF) gene. Remarkably, this alternative ORF, which is translated in many tumors concurrently with the major ORF, is also translated in some tissues that do not produce M-CSF, such as liver and kidney. Such a dissociation of the translation of two overlapping ORFs from the same gene is unexpected. The antigenic peptide encoded by the alternative ORF is presented by human histocompatibility leukocyte antigen (HLA)-B*3501 and has a length of 14 residues. Peptide elution indicated that tumor cells naturally present this 14 mer, which is the longest peptide known to be recognized by CTLs. Binding studies of peptide analogues suggest that it binds by its two extremities and bulges out of the HLA groove to compensate for its length.

Amino Acid Sequence↗
PubMed2001

Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs nephropathy?

BACKGROUND: Chinese herbs nephropathy (CHN) is a new type of subacute interstitial nephritis that is attributed to aristolochic acid (AA), which inadvertently has been included in slimming pills. The contribution of other simultaneously prescribed drugs remains disputed. In the present study, the effects of a chronic intake of AA given as a single drug was evaluated through renal histology and function in rabbits. METHODS: Female New Zealand White rabbits were injected intraperitoneally with either 0.1 mg AA/kg or with saline 5 days a week for 17 to 21 months. Body weight, renal function, and urinary excretion of glucose and low molecular weight proteins were monitored prior to sacrifice at the end of the study period. RESULTS: All animals given AA developed renal hypocellular interstitial fibrosis, which was classified into three patterns. Fibrosis was confined to medullary rays (MRs) in pattern I (N = 3), extended to the outer cortical labyrinth (OCL) in pattern II (N = 2), and eventually to the inner cortical labyrinth (ICL) in pattern III (N = 6). Fibrosis in MR and OCL was associated with mainly proximal tubular epithelial cell flattening. All treated animals displayed urothelial atypia. Three of them also developed tumors of the urinary tract. No significant pathologic changes were found in control rabbits. AA-treated animals differed from controls by an impaired growth, increased serum creatinine, glucosuria, tubular proteinuria, and anemia. CONCLUSION: The observed pattern of renal histopathological lesions and disorders of the renal function, as well as urothelial atypia and malignancy, are very reminiscent of CHN. Our observations therefore support a causal role of AA alone in the genesis of this new nephropathy.

Animals↗
PubMed2001

Autosomal-dominant periodic fever with AA amyloidosis: Novel mutation in tumor necrosis factor receptor 1 gene Rapid Communication.

BACKGROUND: The recent identification of genes responsible for syndromes of periodic fever with amyloidosis has opened the way to a molecular diagnosis of hereditary AA amyloidosis. METHODS: A Belgian woman presented for genetic counseling. Three first-degree relatives had a diagnosis of renal amyloidosis with a history of recurrent fever and inflammatory episodes. Medical records and pathological specimens were obtained from all physicians who had been in charge of her three relatives. Immunohistochemical staining was performed on paraffin-embedded material. A mutation search was performed in the MEFV (Mediterranean fever) and tumor necrosis factor receptor 1 (TNFR1 or TNFRSF1A) genes causing familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively. RESULTS: The family history was consistent with autosomal-dominant transmission of periodic fever with arthralgias, abdominal pain, and eventual AA amyloidosis involving the kidneys, digestive tract, and thyroid. Recurrent amyloidosis in kidney graft was demonstrated in one patient and was suspected in the other. A novel heterozygous mutation (C55S) in TNFRSF1A was identified in the affected patient available for genetic testing but not in the asymptomatic woman requiring counseling. No mutation was detected in MEFV. CONCLUSIONS: We report a novel mutation (C55S) in TNFRSF1A, resulting in autosomal-dominant periodic fever and AA amyloidosis. This condition, known as TRAPS, should be added to the differential diagnosis of hereditary renal amyloidosis, with obvious implications for management and genetic counseling.

Adult↗
PubMed2001

Aristolochic acid nephropathy in a Chinese patient: time to abandon the term "Chinese herbs nephropathy"?

The causal role of aristolochic acid (AA) in the so-called Chinese herbs nephropathy (CHN) has been conclusively demonstrated only in the Belgian epidemic. We report a biopsy-proven hypocellular interstitial fibrosing nephropathy in a Chinese patient who had ingested a Chinese herbal preparation bought in Shanghai. The identification of AA in the preparation and of AA-DNA adducts in the kidney tissue unequivocally demonstrates, for the first time, the causal role of AA outside the Belgian epidemic. Because the ingested preparation is very popular in China as an over-the-counter product, our observation raises the possibility that many such cases due to AA might be currently unrecognized in China. AA should be banned from herbal preparations worldwide. All cases of the so-called CHN, in which the causal role of AA has been thoroughly documented, should be further identified as aristolochic acid nephropathy (AAN). The term phytotherapy-associated interstitial nephritis (PAIN) might refer to the other cases associated with phytotherapy without identification, as yet, of the causal agent.

Aristolochic Acids↗
PubMed2001

Myocardial microangiopathy associated with antiphospholipid antibodies.

Myocardial thrombotic microangiopathy is a well described post-mortem finding in patients with the catastrophic antiphospholipid (APL) syndrome. However, it has been only very rarely imaged in living patients. Here, we report two patients with APL antibodies presenting with scintigraphic, electrocardiographic and/or echocardiographic evidence of (sub)acute myocardial ischaemia, despite a normal coronary angiography. Formal proof of a thrombotic microangiopathy was obtained by a kidney biopsy in one patient. We emphasize the value of 99mTc-MIBI (2-methoxy isobutyl isonitrile) exercise stress myocardial scintigraphy for the detection of cardiac microangiopathy associated with the APL syndrome.

Adult↗
PubMed2000

Late-onset renal failure in Senior-Loken syndrome.

We report on four patients, from three different families, with Senior-Loken syndrome (SLS). They were unusual in that they reached end-stage renal failure (ESRF) only during the fifth or sixth decade. SLS is an autosomal-recessive disorder defined by the association of nephronophthisis and retinal dystrophy. Affected individuals invariably progress to ESRF, usually before the age of 20 years. The diagnosis was based on typical clinical presentation and characteristic renal histology, that is, a picture of chronic interstitial nephritis with pronounced thickening and multilayering of tubular basement membranes. Deterioration of renal function was slow, leading to ESRF between the ages of 42 and 56 years. Retinal dystrophy, already symptomatic during childhood in two patients, led to severe visual impairment in all. In contrast with four cases of SLS recently reported in very young patients, the NPH1 gene (the main gene responsible for nephronophthisis) was not deleted in our two tested patients. We conclude that SLS should be considered in adults who suffer from both chronic interstitial nephropathy and retinal degeneration. Whether the SLS is a variant of nephronophthisis and whether early- and late-onset renal failure in SLS is accounted for by genetic or allelic heterogeneity remain to be determined.

Adult↗
PubMed2000

Acute interstitial nephritis and fatal Stevens-Johnson syndrome after propylthiouracil therapy.

We report a case of acute interstitial nephritis and fatal Stevens-Johnson syndrome in a 90-year-old woman with amiodarone-induced hyperthyroidism, who had been treated for 5 weeks with propylthiouracil (PTU). On admission, the patient exhibited acute renal failure and generalized macular purpuric eruption. Acute interstitial nephritis and Stevens-Johnson syndrome were diagnosed and PTU withdrawn. Although renal function recovered after PTU withdrawal and corticosteroid therapy, the patient's condition worsened, and she died after developing multiple organ failure. Acute interstitial nephritis seems to be rarely associated with PTU therapy. Moreover, a literature review suggested that this could represent the first published report of a Stevens-Johnson syndrome developing during PTU therapy.

Acute Disease↗
PubMed1999

Benign monoclonal gammopathy turning to AL amyloidosis after kidney transplantation.

The fate of preexisting benign monoclonal gammopathy after organ transplantation is largely unknown. We report the case of a 47-year-old male kidney graft recipient with a pretransplantation IgG kappa monoclonal gammopathy who developed, 10 years after transplantation, de novo augloid light chain (AL) amyloidosis involving skin and kidney graft. The potential role of heavy immunosuppressive treatment in the development of this complication is discussed. The possible occurrence of AL amyloidosis should be kept in mind when a patient with benign monoclonal gammopathy is evaluated for organ transplantation, as well as when a transplanted patient with pre-existing monoclonal gammopathy develops new onset of proteinuria.

Amyloidosis↗
PubMed1999

Urothelial lesions in Chinese-herb nephropathy.

Rapidly progressive renal fibrosis after a slimming regimen including Chinese herbs containing aristolochic acid (AA) has been identified as Chinese-herb nephropathy (CHN). We reported urothelial atypia in three patients with CHN, with the subsequent development in one patient of overt transitional cell carcinoma (TCC). Therefore, it was decided to remove the native kidneys, as well as the ureters, in all patients with CHN. Nineteen kidneys and ureters removed during and/or after renal transplantation from 10 patients were studied to assess critically urothelial lesions and to characterize the cellular expression of p53, a tumor-suppressor gene overexpressed in several types of malignancies. Multifocal high-grade flat TCC in situ (carcinoma in situ; CiS) was observed, mainly in the upper urinary tract, in four patients, a prevalence of 40%. In one of those patients, a superficially invasive flat TCC of the right upper ureter, as well as two additional foci of noninvasive papillary TCC, were found in the right pelvis and left lower ureter, respectively. This patient also presented recurrent noninvasive papillary TCC of the bladder. Furthermore, in all cases, multifocal, overall moderate atypia was found in the medullary collecting ducts, pelvis, and ureter. All CiS and papillary TCC, as well as urothelial atypia, overexpressed p53. These results show that the intake of Chinese herbs containing AA has a dramatic carcinogenic effect. Carcinogenesis is associated with the overexpression of p53, which suggests a role for a p53 gene mutation. The relationship of this mutation with the reported presence of AA DNA adducts in the kidney remains to be explored.

Adult↗
PubMed1999

Expression of aquaporin-1 in a long-term peritoneal dialysis patient with impaired transcellular water transport.

Aquaporin-1 (AQP1) has been claimed to be the molecular counterpart of the transcellular pathway for free-water movement across the peritoneum during peritoneal dialysis. We report the case of a 67-year-old man, on peritoneal dialysis for 11 years, in whom ultrafiltration failure due to an abolition of the transcellular water transfer (documented by a loss of sodium sieving) was associated with an apparently normal expression of AQP1. We suggest that an alteration of AQP1 structure, rather than of its expression, accounts for this observation.

Aged↗
PubMed1999

Assessing the risk of unsuspected prostate cancer in patients with benign prostatic hypertrophy: a 13-year retrospective study of the incidence and natural history of T1a-T1b prostate cancers.

OBJECTIVE: To determine the incidence and natural history of stage T1a-T1b prostate cancer in patients undergoing surgery for benign prostatic hypertrophy (BPH), and thus evaluate the effect that recent medical and 'minimally invasive' treatments (which provide no prostate sample for pathological examination) might have on the percentage of patients with unsuspected prostate cancer. PATIENTS AND METHODS: A series of 1648 patients undergoing surgery for BPH over a 13-year period were reviewed retrospectively; the period overlapped the introduction of serum prostate specific antigen (PSA) as a detection method. RESULTS: Stage T1 prostate cancer was found in 182 patients (11%), comprising 126 (11%) of 1199 transurethral resections and 56 (12%) of 449 open enucleations. The introduction of systematic PSA assays gradually reduced the mean incidence of T1 cancer from 23% to 7%, with a greater effect on T1b (from 15% to 2%), while the incidence of T1a remained nearly constant (+/-5%). The pathological features of surgical specimens from 43 radical prostatectomies undertaken for T1 tumours were reviewed. Locally advanced disease (stage >/=pT3) was apparent in 13% of T1a and 28% of T1b tumours. Amongst the patients electing for surveillance, only 8% of those with T1a progressed within 30-97 months of follow-up (mean progression time 73 months), whereas 29% of those with stage T1b progressed within 36 months of follow-up (mean progression time 17 months). CONCLUSION: These results show that the use of the PSA assay has decreased but not suppressed the incidence of pT1 prostate cancer, with a greater effect on those tumours at higher risk of progression (T1b). This suggests that the detection of prostate cancer based on PSA and transrectal ultrasonography is appropriate for screening patients and is sufficiently accurate that treatments for BPH that provide no pathological materials can be applied safely.

Aged↗
PubMed1998

Lesions in donor kidneys: nature, incidence, and influence on graft function.

The aim of this study was to assess the influence of kidney-donor transmitted pathology on graft function. Light and immunofluorescent microscopic findings from a surgical biopsy taken prior to transplantation from 114 cadaveric kidney donors were analyzed. Moderate to severe mesangial IgA deposits were considered consistent with IgA nephropathy. Pathological abnormalities were correlated together with donor age, number of mismatches, and type of immunosuppression by multivariate statistical analysis with the serum creatinine values from patients who experienced no acute rejection at 1 year. Serum creatinine values (n = 52) were not correlated with either non-specific light microscopic lesions or immunofluorescent deposits found in the majority of kidney donors or with changes consistent with IgA nephropathy observed in 9% of the cases. There was, however, a correlation with donor age, which was also correlated with the extent of chronic lesions (P < 0.001).

Adolescent↗
PubMed1998

Chinese herbs nephropathy-associated slimming regimen induces tumours in the forestomach but no interstitial nephropathy in rats.

Chinese herbs nephropathy (CHN), a rapidly progressive interstitial fibrosis of the kidney, has been described in approximately 100 young Belgian women who had followed a slimming regimen containing some Chinese herbs. In 4 patients multifocal transitional cell carcinomas (TCC) were observed. Aristolochic acid (AA), suspected as the causal factor of CHN, is a well known carcinogen but its ability to induce fibrosis has never been demonstrated. The objective of this study was to evaluate the latter using doses of AA, durations of intoxication and delays of sacrifice known to yield tumours in rats. We also tested the hypothesis that a possible fibrogenic role of AA was enhanced by the other components of the slimming regimen. Male and female rats were treated orally with 10 mg isolated AA/kg per day for 5 days/week, or with approximately 0.15 mg AA/ kg per day 5 days/week contained in the herbal powder together with the other components prescribed in the slimming pills for 3 months. The animals were killed respectively 3 and 11 months later. At sacrifice, animals in both groups had developed the expected tumours but not fibrosis of the renal interstitium. Whether the fibrotic response observed in man is due to species and/or strain related differences in the response to AA or to other factors, remains to be determined. Interestingly, despite the addition of fenfluramine and diethylpropion, two drugs incriminated in the development of valvular heart disease, no cardiac abnormalities were observed.

Animals↗