B Van Damme

Partial prevention of active Heymann nephritis by lα, 25 dihydroxyvitamin D3

The hormone lα, 25 dihydroxyvitamin D3 (1,25(OH)2DO3 has potent immunosuppressivc effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune‐mediated diseases. To test its in vitro activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with 1,25(OH)2D3 or its synthetic 20‐epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of 1,25(OH)2D3 (0.5 μg/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7–9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH)2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P=0.06) was reached in the 1,25(OH)2D3 groups that developed less proteinuria. The administration of 1,25(OH)2D3 transiently increased the mean serum calcium Concentration with 2.5 mg/dl above the pretreatmcnt values, and the urinary calcium excretion by a factor of 3–5 during the short treatment time. Treatment with the analogue KH 1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH)2D3 in pharmacological doses has immunosupprcssive potency.

Hereditary C6 deficiency in a strain of PVG/c rats.

A chance observation has led to the discovery of a strain of PVG rats (PVG/c−) which are deficient in complement (C) component C6. Analysis of total haemolytic activity (CH50) of PVG/c− serum revealed an absent CH50 activity compared with serum of other rat strains and of a PVG/c rat (PVG/c‐) that showed normal C activity. Thus, the PVG/c− rat was unable to activate the C5b‐9 membrane attack complex. To gain insight into the complement abnormalities, analysis of individual C components was performed. Testing the PVG/c− serum in a C6 haemolytic assay and using deficient human sera showed a deficiency of C6 in the PVG/c− rat. Highly purified human C6 and human sera deficient in other components were able to reconstitute the CH50 activity of the PVG/c+ rat. The possibility that an inactivator of C was present in PVG/c− serum was excluded. The deficiency was found to be inheritable and under the control of an autosomal recessive gene, Furthermore tissue antigens and immunity of the PVG/c+ rat were found to be identical to those determined in the PVG/c+ rat. With regard to their health status, the PVG/c− animals seem to have no disadvantages compared with PVG/c+ rats when held under the same conditions within the protected environment of animal facilities. Taken together, both rat strains provide an unique animal model for studying the biological role of C, particularly the C5b‐9 membrane attack complex in experimental medicine.

Silicon Nephropathy: a Possible Occupational Hazard

A 37-year-old white male, working in a tile factory, presented proteinuria with no obvious tubular dysfunctional. Renal biopsy disclosed a mild focal segmental proliferative glomerulonephritis. Distinct alterations were found by electron microscopy, especially in the proximal tubular cells. Because of a history of heavy dust exposure the silicon content was determined in the kidney biopsy tissue. The finding of 150 mg/kg silicon on tissue dry weight supports the diagnosis of silicon nephropathy.

Localization, Etiology and Impact of Calcium Phosphate Deposits in Renal Allografts

Hypercalcemia, hypophosphatemia and renal phosphate wasting are common after kidney transplantation. Animal data suggest that these alterations in mineral metabolism may contribute to calcium phosphate (CaPhos) deposition in the kidney and renal dysfunction. We tested the hypothesis that CaPhos deposition is highly prevalent in the early posttransplant period and is related to a disturbed mineral metabolism. For this purpose, biomarkers of mineral metabolism and renal calcium and phosphorus handling were prospectively assessed in 201 renal transplant recipients. CaPhos deposits were observed in 4.6, 30.4 and 24.7% of protocol biopsies obtained at the time of engraftment, and 3 and 12 months thereafter, respectively. In multivariate logistic regression analysis, high calcium and low serum phosphorus levels were independently associated with renal CaPhos deposition at month 3. The extent of CaPhos deposition correlated significantly with the severity of mineral metabolism disturbances. Renal function after a mean follow‐up of 33 months was similar in patients with and without CaPhos deposition at month 3. In conclusion, our data demonstrate that CaPhos deposition is highly prevalent in the early posttransplant period and suggest that a disordered mineral metabolism is implicated in its pathogenesis. The clinical relevance of CaPhos deposition remains to be established.

Trisomy 7 and Trisomy 8 in Dividing and Non-Dividing Tumor Cells in Dupuytren’s Disease ☆

Cytogenetic and molecular cytogenetic analysis is reported in a series of 40 tissue samples from 36 patients with Dupuytrens disease, presenting as palmar and/or finger nodules. No consistent structural chromosome changes could be found. Instead, recurrent clonal numerical abnormalities were demonstrated in 22 of 40 tissue nodules, involving trisomies of chromosome 7 or 8 and loss of the Y chromosome. In addition, we showed that trisomy 7 and trisomy 8 were also present in non-dividing cells.

Diabetic cystopathy: neuropathological examination of urinary bladder biopsies

Neuropathological examination of bladder biopsies was done on 14 patients with severe insulin-dependent adult-onset diabetes and compared with the acetylcholinesterase and S100 staining of 38 control specimens. A decrease in acetylcholinesterase activity, due to axonal degeneration was found in all cases. An increase in S100 positivity was found in the majority and is due to Schwann cell proliferation as a regeneration attempt after demyelination or axonal degeneration. When acetylcholinesterase activity decreases and an S100 density increase is found in a patient with diabetes, this combination is highly suggestive of thorough diabetic cystopathy amenable to early symptomatic treatment.

Benefit of anti-TNFalpha treatment for nephrotic syndrome in a patient with juvenile inflammatory bowel disease associated spondyloarthropathy complicated with amyloidosis and glomerulonephritis

Historically, AA amyloidosis accounts for almost half of the deaths among patients with juvenile chronic arthritis, mainly due to complications of end stage renal failure.1 Improved survival has been reported in patients whose underlying inflammatory disorder was brought to remission.2 Tumour necrosis factor (TNFα) blocking agents have been used successfully in the treatment of inflammatory disorders complicated with AA amyloidosis.3–5 We report the effect of TNFα in a case of AA amyloidosis secondary to juvenile spondyloarthropathy. A 26 year old man with juvenile, inflammatory bowel disease associated spondyloarthropathy (HLA-B27+) was admitted to our hospital with proteinuria and ankle oedema. He received combination therapy with methotrexate, sulfasalazine, methylprednisolone, and naproxen. His blood pressure was 130/80 mmHg. Table 1 shows the results of laboratory tests. View this table: Table 1 Laboratory results at the time of admission Ultrasound examination showed an increased bipolar size (130 mm) of both kidneys. A chest x ray examination was normal. A renal …

PLEUROPULMONARY BLASTOMA (PULMONARY BLASTOMA OF CHILDHOOD): GENETIC LINK WITH OTHER EMBRYONAL MALIGNANCIES?

A case of pleuropulmonary blastoma (childhood variant of pulmonary blastoma) was examined using histological, immunohistochemical, ultrastructural and cytogenetic methods. The tumour consisted of undifferentiated ‘blastematous’ areas admixed with zones of rhabdomyoblastic and chondroid differentiation and fascicular areas. Desmin and S‐100 protein immunoreactivity confirmed the myogenic and cartilaginous differentiation. Ultrastructurally only undifferentiated mesenchymal cells were present. The cytogenetic analysis revealed abnormalities of 2q. Involvement of 2q has also been described in hepatoblastoma and embryonal rhabdomyosarcoma. Although further confirmation is needed, our cytogenetic findings in pleuropulmonary blastoma suggest common genetic mechanisms in some paediatric embryonal malignancies.

Cytogenetic characterization of congenital or infantile fibrosarcoma

Chromosome analysis of a congenital or infantile fibrosarcoma from the lower left leg of a 3-week-old baby girl showed only numerical changes involving chromosomes 11, 17 and 20. As three more cases with similar combinations of trisomies of the same chromosomes have been described, this report confirms that adult and congenital fibrosarcoma are cytogenetically different and trisomy 11 may be the key-event.

Neuromuscular choristoma (hamartoma) with smooth and striated muscle component: case report with immunohistochemical and ultrastructural analysis

Benign peripheral nerve tumors with a mesenchymal component are rare and are represented principally by the neuromuscular choristoma. We describe an 11-month-old male infant who presented with a mass arising from the left brachial plexus. The lesion was bound firmly to the involved nerves and consisted histologically and ultrastructurally of bundles of well-differentiated smooth muscle cells intermingled with striated muscle fibers and unmyelinated nerve fibers. In the 13 previously published cases of neuromuscular choristoma, no smooth muscle component was observed. This unique peripheral nerve choristoma with not only striated but also smooth muscle closely resembled neuromuscular choristoma and was considered a variant of it.