Number of glomeruli in normal and hypertrophied kidneys of mice and guinea-pigs.

1. In mice and guinea-pigs, the number of glomeruli was counted in kidneys during normal growth and in hypertrophy induced by unilateral nephrectomy. 2. In mice, the number of glomeruli increased sharply during the first 2 weeks in life, and more slowly afterwards. Unilateral nephrectomy, when performed during this period of natural increase, induced the formation of supplementary nephrons in the contralateral kidney. 3. In guinea-pigs, the number of glomeruli was almost complete at birth. No evidence of a supplementary increase in the number of nephrons was found in hypertrophied kidneys following unilateral nephrectomy. 4. These results, together wit previous data obtained in the rat, suggest that the ability to induce new nephrons after unilateral nephrectomy in different species would depend more on the state of kidney maturity at birth than on differences in the renal mechanisms which lead to hypertrophy.     

Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy

Background Differences between major allergens from distinct grass species remain to be investigated, both in terms of structure and antigenicity. Methods Group 1 and 5 allergens purified from five common Pooideae species were analysed by mass spectrometry (MS). Major histocompatibility complex (MHC) class II‐restricted T cell epitopes were identified using predictive algorithms and human leucocyte antigen (HLA)‐binding assays. CD4⁺ T cell reactivity and IgE binding were assessed based on the induction of CD154 expression in peripheral blood mononuclear cells and using competitive ELISA assays, respectively. Results MS analysis of group 5 pollen allergens reveals considerable intra‐ and inter‐species variability in amino acid sequence, with 30–50 predominant isoforms found for each species. Differences in the amino acid sequence as well as N‐ and O‐glycosylation contribute to the variability of group 1 allergens, yielding 5–10 main isoforms, depending on the species. Out of 14 MHC class II‐restricted T cell epitopes identified within group 1, only one is conserved among the five grass species. Significant differences in binding affinities for HLA‐DR molecules result in variable CD4⁺ T cell recognition of group 1 and 5 allergens purified from the various species. Up to 38% and 85% of patients exhibit seric IgE responses to species‐restricted (or semi‐restricted) epitopes associated with group 1 or 5 allergens, respectively. Conclusion Major pollen allergens from distinct grass species bear both shared and species‐restricted T and B cell immune epitopes. When compared with single extracts, a five grass pollen extract is thus more suitable for specific immunotherapy, as it contains a broader repertoire of the IgE epitopes to which patients are sensitized. Cite this as: H. Chabre, B. Gouyon, A. Huet, V. Baron‐Bodo, E. Nony, M. Hrabina, F. Fenaille, A. Lautrette, M. Bonvalet, B. Maillère, V. Bordas‐Le Floch, L. Van Overtvelt, K. Jain, E. Ezan, T. Batard and P. Moingeon, Clinical & Experimental Allergy, 2010 (40) 505–519.     

Immunohistochemical and biochemical evidence for a cardiovascular mineralocorticoid receptor.

The presence of mineralocorticoid receptors (MRs) and their physicochemical characteristics were investigated in the heart and blood vessels of rabbits. Immunohistochemical methods using the monoclonal anti-idiotypic antibody H10E, which interacts with the steroid binding domain of MRs, revealed the presence of immunoreactive material in the heart and large blood vessels. In the heart, a positive staining was observed in myocytes and endothelial cells of atria and ventricles. In vessels, MRs were detected in the aorta and pulmonary artery. They were localized in endothelial and vascular smooth muscle cells. No staining was present in the small vascular bed, arterioles, and capillaries. In all these studies, the mineralocorticoid specificity of the staining was assessed by in situ competition experiments with aldosterone and RU486, a glucocorticoid antagonist. The presence of MRs in the heart and vessels was further demonstrated by specific aldosterone binding to one class of high affinity binding sites in the cytosol of the adrenalectomized rabbit heart (Kd, 0.25 nM; maximum MR concentration, 15-20 fmol/mg protein), whose mineralocorticoid specificity has been clearly established by competition studies. Sedimentation gradient analyses revealed that the cardiovascular MR is an 8.5S hetero-oligomer that includes the heat shock protein 90. The physicochemical characteristics of the cardiovascular MRs are virtually identical to those of the renal MRs. Altogether, our results clearly demonstrate the presence of MRs in the cardiovascular system. This supports the possibility of direct aldosterone actions in the heart and blood vessels.     

Aldosterone binding in isolated tubules I. Biochemical determination in proximal and distal parts of the rabbit nephron

Microbiochemical methods were applied to proximal tubules (PCT) and a mixture of distal and cortical collecting tubules (D + C) of rabbit kidney in order to define aldosterone binding sites. For each experiment, after incubation of kidney pyramids with [3H]aldosterone ([3H]A), either alone or in the presence of an excess unlabeled A, 100-150 mm of both categories of tubules were microdissected using collagenase. Specific binding was determined on the nuclear fraction of each sample. Aldosterone concentrations ranged from 2 X 10(-9) to 4.5 X 10(-8) M. No specific binding was detectable in PCT. Specific binding in D + C increased rapidly as a function of [3H]A concentration up to 5 X 10(-9) M and then more slowly. No plateau was reached. Both the absence of saturation of the binding curve and the curvilinear aspect of the Scatchard plot suggested the presence of two binding sites, one of high affinity, presumably a mineralocorticoid site, and the other of lower affinity, possibly a glucocorticoid site. These experiments suggest that the distal structures of the nephron, located in the cortex, are the main sites of binding of aldosterone and contain a high number of specific binding sites for this hormone.     

Atypical urticaria disclosing acute basophilic leukemia. Apropos of a case associated with hyperhistaminemia

Acute basophilic leukaemia (ABL) is a rare disease characterized by high fever, anaemia and haemorrhagic diathesis. Its prognosis is somber and its response to therapy mediocre. Death is mainly due to cerebral or digestive hemorrhage and coronary disease. In a very small number of cases ABL, like all diseases accompanied by an increase in basophils, may be associated with hyperhistaminemia responsible for cutaneous and gastric symptoms.     

Cutaneous manifestations in chronic lymphocytic leukemia

Cutaneous lesions arising during the course of chronic lymphocytic leukemia (CLL), generally of the B-cell type, are frequent. Three types of cutaneous manifestations must be differentiated: (1) specific lesions, (2) cutaneous manifestations closely related to the disease but without a leukemoid infiltrate and (3) associations with various dermatologic conditions. The various clinical features are discussed.