Cyrille Bader

Urolithiasis in Patients with End Stage Renal Failure

Renal stones from 30 chronic hemodialysis patients were subjected to morphological study by means of microscopic examination and to constitutional analysis with infrared spectrophotometry. In 29 patients calculi could be classified into 3 main types: 1) protein stones made of pure proteins or with a protein core and less than 30% calcium oxalate (9 cases, or 30%)--they were observed predominantly in patients with primary glomerular disease, 2) oxalo-protein stones with a core of calcium oxalate and a total stone content of more than 30% calcium oxalate (15 cases, or 50%)--they appeared to be related to metabolic factors, such as high urinary oxalate and low urinary citrate concentration, and to iatrogenic factors, namely vitamin D3 and calcium salt supplementation, and 3) aluminum-magnesium urate stones, probably induced by aluminum overload (6 cases, or 20%). Thus, our study indicates that a significant proportion (70%) of stones formed by hemodialysis patients may be due to metabolic and iatrogenic factors. Our data suggest that accurate analysis of such stones provides useful information on pathogenetic factors and consequently may give clues to their prophylaxis.

Comparative effects of 17β-estradiol, progestin R5020, tamoxifen and RU38486 on lactate dehydrogenase activity in MCF-7 human breast cancer cells

The effects of 17 beta-estradiol (estradiol), synthetic progestin R5020 and their antagonists, tamoxifen (Tam) and synthetic RU38486 on lactate dehydrogenase (LDH) activity in MCF-7 human breast cancer cells during the growth period were studied. A specially developed quantitative cytochemical assay was used; LDH activity is expressed per cell, and is thus independent of the positive and negative growth effects of the hormones and antagonists. Estradiol and R5020 stimulated LDH activity after similar exposures (6-48 h) and the stimuli were concentration dependent over the range 10(-7) M to 10(-10) M. As for the antagonists, RU38486 stimulated LDH activity in much the same way as estradiol and R5020; Tam alone, on the other hand, does not stimulate LDH, but when added to estradiol, Tam inhibits estradiol mediated LDH activation. When present at half-stimulant concentration, estradiol + R5020 and estradiol + RU38486 exhibit additive effects on LDH activity. Thus LDH appears to be an interesting tool for the study of hormone and antagonist effects in MCF-7 breast cancer cells.

In vitro relative biological activities of (1--34)N-terminal synthetic fragments of human parathyroid hormone in the human renal cortical adenylate cyclase assay.

Two sequences differing in the amino acids at 3 positions have been reported for the (1-34)N-terminal fragment of human parathyroid hormone by Brewer et al. [ 1,2] and subsequently by Niall et al. [3,4] (fig.1). These two structures have been shown to be biologically active in both in vivo and in vitro assay systems [S-9] . Nevertheless due to the different assay conditions used in these studies, it is at present difficult to assess the relative biological activities of the two sequences. We have reported a comparative study of their relative biological activities in the in vitro renal cortical adenylate cyclase activation assay system [lo]. The Niall sequence was shown to be more active than the Brewer sequence on bovine and porcine kidney membranes. Nevertheless this study as well as others [9,11,12] showed also that the biological response depends on the species origin of the membrane. Thus in order to further assess the relative biological activities of these two hormone sequences we studied their relative biological potency in the same, isologous in vitro assay system using human kidney membranes and compared them with a glandular extract of human parathyroid. Our results show unambiguously that the behaviour of the Niall sequence is very close to that of the natural glandular extract and suggest that this sequence is more likely the active natural hormone.

Liquid scintillation counting for measurement of tritiated uptake in lymphocyte transformation in vitro: A new direct-suspension procedure

Liquid scintillation counting of trichloracetic acid extracts of [3H] TdR-labelled lymphocytes has been studied by a direct suspension method without previous solubilization. In this new method, mixing of the labelled powder in water suspension with Scintillator Emulsifying Mixture (SEM) results in a firm gel whose mechanical properties provide an heterogeneous sample ready for counting. Counting efficiency and stability of such samples are related to the amount of labelled cells. Comparative studies with standard hyamine procedure have shown that this simple and rapid method gives reliable results.

Part 1. A Refined Etiological Classification of Calcium Oxalate Urolithiasis Based on Calculi Studies

Current etiological classifications of calcium-oxalate urolithiasis do not reflect the various pathological situations that may be implicated. An etiological classification using morpho-constitutional analysis (MCA) of the calculi was studied. This analysis combines structural and infrared studies of the surface, the section, and the nucleus of the calculi (Adv. Nephrol.l5:2l9 (1986)).

Part II: Morpho-Constitutional Analysis (MCA) of Calculi in Hyperparathyroidism, Distal Renal Tubular Acidosis, and Primary Hyperoxaluria

Calculi from patients with primary hyperarathyroidism (PHP, n=55), distal renal tubular acidosis (dRTA, n=19), and primary hyperoxalosis (PHO, n=40) were analyzed by morpho-constitutional analysis (MCA) (Adv. Nephrol.15: 219 (1986). The table shows the MCA of calculi in patients with PHP, dRTA and PHO.

CALCIUM-INDUCED MODULATION OF THE TUBULIN POOL IN PARATHYROID GLANDS

Participation of cytoplasmic microtubules has been implicated in various secretory processes such as release of hormone from secretory cells and secretion or movement of granular products (see ref. 1, 2 for review). The great bulk of these works is based on the inhibitory effects of colchicine (3) and vinca-alkaloids (4). The mechanism of action has been attributed to the ability of these agents to bind to tubulin, the protein subunit of the cellular microtubules, and as a consequence, to prevent microtubule assembly. With these techniques it has been shown that colchicine and vinca-alkaloids may affect Parathyroid Hormone (PTH) secretion in in vitro culture of Parathyroid Glands (PTG) (5, 6). It has been suggested that these effects may indicate a role of microtubules in the sequence of events leading to release of PTH. Nevertheless although ultrastructural studies of PTG have demonstrated the presence of microtubules (6, 7, 8, 9), anatomical evidence to support a mechanism by which microtubules might affect intracellular processing of PTH are rare. On the other hand in in vivo studies the precise site of action of colchicine is difficult to ascertain because it has been shown that this product may produce hypocalcemia (10) and may inhibit bone resorption (11). Moreover recent studies have shown that the renal handling of phosphate and its regulation by PTH may depend on cytoplasmic microtubules, which have been described in proximal renal tubule cells (12). To further assess the presence of a microtubular system (MTS) in PTG and its possible functional significance, we initiated the following studies which extend previous work in our laboratory (13) in order to demonstrate tubulin in PTG on a biochemical basis. After demonstration of a specific Colchicine Binding Protein (Co1BP) in PTG, the tubulin pool size level in PTG slices incubated in vitro in various extracellular calcium concentrations was assayed.