Antihypertensive effect of thymectomy in Lyon hypertensive rats. Vascular reactivity, renal histology, and sodium excretion.

The aim of this study was to search for the possible mechanisms involved in the antihypertensive effect of neonatal thymectomy that we previously observed in Lyon hypertensive (LH) rats. To that end, we studied in LH and normotensive control (LN) rats the consequences of neonatal thymectomy on vascular reactivity, renal structure, and pressure-natriuresis. The increase in pressor responses to angiotensin I and phenylephrine noted in LH rats as compared to LN animals was abolished by neonatal thymectomy. Histological study showed that kidneys from LH rats exhibited arterial wall hypertrophy, segmental hyalinization of the glomeruli, and were infiltrated by mononuclear cells. All these features of kidney injury were reduced in neonatally thymectomized LH rats. Lastly, the responses of isolated perfused kidneys from LH rats to stepwise reductions in renal perfusion pressure differed from those of LN rats by decreased renal perfusion flow and natriuresis. Neonatal thymectomy tended to improve sodium excretion in parallel with a slight decrease in renal vascular resistances. It is concluded that the normalization of vascular responsiveness to vasoconstrictor factors, the alleviation of renal lesions and, to a lesser extent, the moderate improvement of pressure natriuresis may account, at least in part, for the antihypertensive effect of neonatal thymectomy in LH rats.

A new method of preparation of segmental pancreatic grafts for transplantation: trials in dogs and in man.

A new method of eliminating the exocrine function of the pancreas by obstruction of pancreatic duct with neoprene was investigated in dogs and applied to three cases of human segmental pancreatic transplantation. Neoprene is a liquid synthetic rubber which flocculates with changes in pH. In animals, progressive fibrosis of the pancreatic tissue occurs after injection of neoprene in the main pancreatic duct, leaving islets well vascularized and functioning for prolonged periods. Using this technique, three severely diabetic patients received a cadaver segmental pancreatic allograft. Blood sugar returned to normal levels within the first hours or days after operation. All three grafts continue to function 1.5, 2, and 8 months, respectively, following transplantation. If these results are confirmed by further clinical experience, this method may be of considerable assistance in the treatment of severe diabetes by pancreatic transplantation.

Treatment of post-transplant lymphomas with anti-B-cell monoclonal antibodies.

The treatment of post-transplant lymphomas still needs major improvements in order to put the patient in remission and to retain graft function. Chemotherapy is far too toxic in these patients. A more specific treatment such as anti-B-cell monoclonal antibody is very promising. The cytotoxic effect of antibody relies mainly on complement-induced and antibody-dependent cellular cytotoxicity; apoptosis may also induce tumor cell death. B-cell antigens expressed on the cell surface are the targets of antibody attack; some specificities may be chosen because of their level of expression or because of signaling induced within the cell. Anti-B-cell antibodies can be produced by genetic engineering in order to be humanized or to carry bispecific Fabs. The efficacy and safety of anti-B-cell monoclonal antibodies (mAbs) in transplant patients have been proven with different antibodies such as anti-CD21/CD24 mAb, anti-CD38 mAb and anti-CD20 mAb. In a retrospective analysis of different centers in France, rituximab (anti-CD20 mAb, Roche Products) achieved an overall 69% remission rate in 34 organ and bone-marrow transplant patients. But the conditions of use of antibody must be better defined, particularly with regard to the immunosuppressive therapy, the type of tumor and the dose of antibody. We must also improve our understanding of the in vivo mechanisms of action of antibody to develop more efficient antibody constructs.

Nephrotic syndrome in procainamide induced lupus nephritis.

We report a case of the nephrotic syndrome occurring in a patient with procainamide induced LE. It was associated with bilateral pleural effusions, pericarditis, fever, positive LE cell preparation and a high titer of antinuclear antibodies. No anti-DNA antibodies were found. Renal biopsy showed mesangial proliferation with few IgM and C3 deposits and interstitial infiltrates; electron microscopy revealed subendothelial deposits. Clinical improvement occured after steroid therapy and there was no recurrence 24 months after withdrawal of prednisone.

Immunohistochemical localization of type IV collagen fibronectin and laminin in the juxtaglomerular apparatus of the rat kidney.

The juxtaglomerular apparatus (JGA) is a complex structure containing several components: the vessels, the extraglomerular mesangium and the distal tubule. These structures include cellular elements and an extracellular matrix (ECM). Collagenous (type IV collagen) and noncollagenous components of the basement membranes were studied. The localization of type IV collagen and of two extracellular glycoproteins (laminin and fibronectin) was investigated using immunofluorescent and immunoperoxidase labelled antibodies. Type IV collagen and laminin have the same localization on the JGA basement membranes. On the other hand, fibronectin is limited to the entrance of the glomerular stalk. On electron microscopy, type IV collagen is found in the basement membrane while fibronectin is restricted to certain areas of the extracellular matrix. These findings confirm data concerning the distribution of these three components in basement membranes and allow a better understanding of the histoarchitecture of the juxtaglomerular apparatus.

[Development of early kidney lesions in genetically hypertensive, normotensive and hypotensive rats]. / Evolution des lésions rénales précoces chez les trois souches de rats génétiquement hypertendus, normotendus et normotendus-bas.

Morphological changes were studied in 3 different strains of rats genetically hypertensive (LH) normotensive (LN), or with low blood pressure (LL). Renal lesions were evaluated at 3, 5, 9, and 21 weeks of age, when blood pressure was significantly different between the 3 groups and the difference increased up to 21 weeks of age. Small histological changes could be detected in the LH groups as early as the fifth week (2 cases out of 8). However the differences between hypertensive rats and normo or hypotensive rats were obvious only at 9 weeks progressively increasing up to the 21th week. The juxta glomerular apparatus was mainly affected with hypertrophy and hyalinisation and hyaline deposits within the wall of the afferent arteriole and lacis cells. The lesions were constant although focal and of moderate intensity. They were frequently associated with segmental hyalinisation of the glomerulus and slight tubular and interstitial changes. The comparative study between three strains of rats shows that the renal vascular lesions appear early but after the onset of hypertension.

[Late diagnosis of cystinosis in 2 brothers: histological and ultrastructural renal study]. / Cystinose à revelation tardive chez deux frères. Etude histologique et ultrastructurale rénale.

Cystinosis was discovered by chance in two adolescent boys who had proteinuria with minor tubular abnormalities. Renal biopsies were examined by light microscopy, electron microscopy and immunofluorescence. There were few histological changes but crystals were present in the epithelial cells of the glomerulus and occasionally in the tubules. A further unusual feature was the detection of IgA deposits in the mesangium.

IL-1 production by human thymic dendritic cells: studies on the interrelation with DC accessory function.

Thymic dendritic cells (DC) have been proposed to play a critical role in the generation of immunocompetent T lymphocytes. Since IL-1 is widely considered to be an important second signal in T cell stimulation, we have studied the ability of isolated human thymic DC to produce IL-1. Using the EL4/CTLL conversion assay standardized with recombinant IL-1 beta (rIL-1 beta), we demonstrate that upon LPS-stimulation thymic DC produce small amounts of IL-1 as compared to peripheral blood monocytes (PBM). In contrast with PBM, DC IL-1 production is not influenced by indomethacin. IL-1 activity was detected in the supernatants of DC cultures from all thymuses tested, although quantitative variability was noted among individual thymic donors. The specificity of the active factor was confirmed by neutralization assays with anti-IL-1 beta mAb. On the other hand, we demonstrate that rIL-1 beta cannot substitute for nor amplify the accessory function of thymic DC and that anti-IL-1 beta mAb fails to block the DC accessory function. Thus we conclude that IL-1 beta might not be a major factor for the efficient DC accessory function toward mature thymocytes recently demonstrated in our laboratory. Of interest, IL-1 beta was also detected in the supernatants of DC-thymocyte cocultures in the absence of mitogenic factor, suggesting that thymocyte contacts can constitute a sufficient signal to induce DC to produce IL-1. These observations indicate that human thymic DC represent an intrathymic source of IL-1 whose role in thymocyte proliferation or maturation remains to be understood.

Simultaneous staining of nuclear DNA and blood group cell surface antigens on cells from bladder irrigation fluid.

Simultaneous staining of nuclear DNA and blood group cell-surface antigens is proposed as a means of studying the prognosis of superficial bladder cancer. The quality of the results obtained on urothelial cells from bladder irrigation fluid, as shown by fluorescence microscopy, suggests that this staining technique may be suitable for flow cytometry.

Revelation of AB cell surface antigens on bladder-washing specimens with the immunofluorescence technique. An approach to automated cytology.

Revelation of AB cell surface antigens is possible with the immunofluorescence technique on urothelial cells from bladder irrigation fluid. Normal urothelial cells show a heterogeneous expression varying with cell type and cell viability. However, the loss of any antigenic reactivity of some cells seems to be directly related to their neoplastic features. Flow cytometry appears to be the most appropriate technique to provide the necessary objectivity for this type of study.

Cyclosporine A nephrotoxicity: evidence for mesangial foam-cells in dogs.

Nephrotoxicity of cyclosporine A was studied in dog after 3 weeks' administration of the drug at high doses (20 mg/kg/day). Cyclosporine A concentrations measured in different organs revealed a high ratio between renal tissue and plasma. Renal histopathology showed non-specific tubular lesions and glomerular modifications. There were lipids in the mesangial cells which took on a foamy aspect. Ultrastructural study and lipid staining confirmed these findings, and non-specific esterase reaction revealed no macrophagic infiltration. Using anti-CSA antibodies it was not possible to demonstrate CSA in the mesangial cells. This alteration has never been described before in CSA therapy and its meaning is not clear; however, it does suggest that there occur modifications in the lipid metabolism or in the phagocytic function of the mesangial cells when cyclosporine A is administered over long periods.

Clinically occult bladder cancer diagnosis. Trial using ultraviolet cystoscopy.

Ultraviolet cystoscopy was used to demonstrate flat cancerous and precancerous bladder lesions by two techniques based on different principles: the loss of epithelium blood group antigenic expression using immunofluorescence reaction, and submucosa neoangiogenesis after fluorescein intravenous injection. The results obtained with these two techniques were disappointing, but do not preclude the use of ultraviolet cystoscopy in this type of study.

[Macrophage infiltration in human glomerulonephritis: histochemical study by the non-specific esterase method]. / Infiltration macrophagique au cours des glomérulonéphrites humaines: etude histochimique par la méthode de l'activité des estérases non spécifiques.

Detection of glomerular macrophages in glomerulonephritis (GN) was attempted in 77 renal biopsies by measuring non-specific esterase (NSE) activity. Macrophage infiltration was at its highest in two cases of cryoglobulinemia (NSE index greater than 10) both associated with a diffuse proliferative GN. In 15 cases of lupus, macrophage infiltration was low or absent (NSE index 0.44). In diffuse proliferative GN (24 cases) only GN with extracapillary proliferation had an NSE index greater than 1. In GN with predominant IgA (23 cases), apart 2 cases of extracapillary forms, there was no notable macrophage infiltration. There is a relation between monocytes and the localization and the quantity of glomerular deposits. The NSE index is higher in the case of large sub-endothelial deposits of immunoglobulins, C3 and/or fibrin.