Renal cortex guanylate cyclase. Preferential enrichment in glomerular membranes.

1. The localisation and some of the properties of rabbit kidney cortex guanylate cyclase (GTP pyrophosphatase lyase (cyclizing) EC 4.6.1.2) have been studied. Upon fractionation of dissociated renal cortex, guanylate cyclase activity was preferentially enriched in fractions of pure glomeruli, where its specific activity was 44.5 times that measured in tubular fragments. Most, if not all, of the glomerular activity was found to be firmly membrane-bound, whereas the guanylate cyclase activity of the tubules was mainly soluble. Therefore, particulate guanylate cyclase activity could serve as marker enzyme for kidney glomeruli. 2. All hormones or hormone-like agents tested were without effect on kidney guanylate cyclase activity. Triton X-100 stimulated both glomerular and tubular activity. 3. Considering the high cyclic GMP forming capacity of kidney glomeruli, part of the cyclic GMP found in urine might be synthetized locally in these structures.

Studies on the different molecular forms of tyrosine aminotransferase from rat liver and hepatoma cells.

In an attempt to clarify the significance of the separable forms of tyrosine aminotransferase, the enzyme from rat liver and from cultured hepatoma cells was studied by carboxymethyl-Sephadex chromatography. Our studies of the form conversion during the purification procedure of the enzyme, where all cellular components were quickly discarded, do not allow us to invoke a specific "converting factor", the existence of which in the particulate fraction has been suggested. Moreover the addition of serine protease inhibitors is not sufficient to prevent the classical conversion. More probably, several factors depending on the environmental conditions might influence different reactions which lead to a preferential conformation of the enzyme in vitro. The difference in the PO4- content of the various enzyme forms and the consecutive differences in negative charge may be the determining factor in the elution pattern of the three forms of the isolated soluble enzyme. This observation raises the possibility that phosphorylation might play a specific role in the regulation of tyrosine aminotransferase synthesis.

Relations between steroid-cell contact, steroid-binding and induction of tyrosine aminotransferase.

The induction of tyrosine aminotransferase by a variety of steroids was studied in cells from a hepatoma tissue culture (HTC). We have defined a class of steroids that induce TAT synthesis to a higher level than optimal inducers described earlier; these are called supra-inducers. When TAT induction is compared with the binding of the steroids to the cytoplasmic receptor or to their binding in the whole cell, a good correlation between binding in vivo of the hormone and its induction capacity can be established, whereas such a correlation was not systematically observed in vitro. A very short exposure of HTC cells to either dexamethasone or corticosterone is sufficient to induce TAT. When the inducer is removed from the culture medium a few minutes after its administration, the intracellular hormone concentration decreases very rapidly but TAT will be synthesized at its maximal rate. Thus the hormones behave as a starting signal for the optimal synthesis of the enzyme, and their presence in the culture medium is not necessary throughout the entire induction period.

Structure-activity relationship of parathyroid hormone: relative sensitivity of rabbit renal microvessel and tubule adenylate cyclases to oxidized PTH and PTH inhibitors.

It has been shown previously that secondary structural changes of bPTH-(1-34) (synthetic amino-terminal (1-34) fragment of bovine parathyroid hormone), obtained by oxidation of the methionines 8 and 18, abolished its hypotensive but not its hypercalcemic action. Hence, it has been postulated that the various physiological effects of the hormone are mediated by different receptors that require different regions or configurations of the peptide. To further examine this hypothesis the relative sensitivity of the PTH-responsive adenylate cyclase of microvessels and tubules isolated from rabbit kidney cortex, to oxidized PTH and PTH inhibitors, was examined. In the presence of GTP, bPTH-(1-34) stimulated both microvessel and tubule adenylate cyclase in a dose-dependent fashion and with analogous affinities (ED50 = 52 nM in the microvessels and 85 nM in the tubules). Hydrogen peroxide treatment of bPTH-(1-34) resulted in the loss of the adenylate cyclase stimulating potency in the microvessels while there was substantial enzyme activation (ED50 = 900 nM) in the tubules. Oxidized PTH inhibited the untreated PTH-stimulated adenylate cyclase, suggesting that oxidized PTH still retains an affinity for vascular receptor sites. Similar treatment of the sulfur-free PTH analog [Nle8,18, Tyr34]bPTH-(1-34)NH2, where methionines have been replaced by norleucine, had little or no effect in both fractions. In the microvessels the synthetic PTH antagonist analogs [Nle8,18, Tyr34]bPTH-(3-34)NH2 and [Tyr34]bPTH-(7-34)NH2, strongly inhibited the adenylate cyclase responses to bPTH-(1-34). No inhibition was seen in the tubules with the same molar ratios of inhibitor to native PTH. Together, these results suggest strongly that the differences in the adenylate cyclase response to various PTH fragments most likely represent a difference in the structural requirements for PTH actions between microvessels and tubules.

The vasodilator action of parathyroid hormone fragments on isolated perfused rat kidney.

The renal vasodilator responses to various fragments of PTH were quantified on a model of isolated perfused rat kidney (IPK), under non-filtering conditions. The 1-34 fragment of bovine PTH, its Nle analogue and rat PTH, injected in sequential cumulative doses, caused concentration-dependent vasodilatation in the vasculature of the IPK which was preconstricted with prostaglandin F2 alpha. The EC50 of PTH for renal vasodilatation ranged from 1 to 2 nM for all PTH fragments and maximum vasodilatation ranged from 33 to 41% of the maximum vasodilatation induced by papaverine. Renal vasodilation was not related to prostaglandin release since similar vasodilatation occurred after the inhibition of prostaglandin synthesis with indomethacin. When PTH was administered in single bolus injections, using a separate kidney for each hormone concentration, rather than repeated injections into the same kidney, higher maximum vasodilatations were obtained (64%). These results most likely reflected tachyphylaxis of the renal vasculature to PTH occurring after repeated exposure of a single kidney to the hormone. The antagonist analogue [Nle8,18, Tyr34]-bPTH-(3-34)A shifted the concentration-related response curve to the right, indicating that the renal vasodilator response to rPTH-(1-34) involved specific vascular receptors.

Hormonal therapy trials in prostatic cancer. An EORTC Genitourinary Group study.

In this paper the authors review the completed and current EORTC Genitourinary Group trials for metastatic carcinoma of the prostate. In terms of time to progression and length of survival, there is no significant difference between any of the effective endocrine treatments that have been studied. The statistical analysis of the different variables used in trials 30,761 and 30,762 determines three risk groups of patients. There is no need for very special laboratory investigations to establish a prognosis. Orchiectomy is the cheapest and safest endocrine treatment in metastatic carcinoma of the prostate.

[Pancreatic metastases of nephro-epitheliomas. Apropos of 2 cases]. / Les métastases pancréatiques des néphro-épithéliomes. A propos de deux observations.

Pancreatic metastasis from clear cell carcinoma of the kidney are exceptional (1 to 3 per cent). Twelve cases have been found in the literature, to which our two observations must be add. Intestinal haemorrhage rule the clinical signs. The complementary arteriography is a very good investigation. Surgery with excision may be effect when a solitary metastasis to the pancreas exist. We can argue about chemotherapy when there is a metastatic dissemination.

[The influence of childbearing on the urinary tract (author's transl)]. / Influence de la gravidité sur les voies excrétrices urinaires.

The study of intravenous pyelograms taken immediately after delivery shows how the ureter has its dynamics modified during pregnancy. The role of parity and of urinary tract infection which sometimes is evidence of a pre-existing urological malformation is demonstrated.

[Current treatments of cancer of the prostate]. / Traitements actuels du cancer de la prostate.

Cancer of the prostate mainly occurs in elderly men and is becoming more frequent as the general European population gets older. Only through continuing progress in the already well developed therapeutic methods will mortality due to this cancer be curtailed. Prognosis of cancer limited to the prostate gland has been improved by radical surgery which reduces morbidity and mortality and advanced radiotherapy techniques. The potentially curable forms, still mainly detected by systematic rectal examination, can be defined better with magnetic resonance imagery and biological markers. Hormonal treatment for more extended or metastatic cancers is now based on several effective, well tolerated products. Chemotherapy has not been able to solve the problem of hormonal escape for which other therapeutic techniques are now under study.

[Treatment of metastatic renal adenocarcinomas with combined recombinant alpha-2a interferon and vinblastine]. / Traitement des adénocarcinomes rénaux métastatiques par l'association interféron recombinant alpha-2a et vinblastine.

The results of treatment of metastatic renal cell carcinoma have so far been very poor. Many phase II studies have shown that interferon alpha therapy is active in a significant proportion of patients (approximately 10 to 15% complete and partial remission). In the hope of improving these results we have conducted a phase I-II study of the combination of interferon alpha-2a and vinblastine in 21 patients with metastatic renal cell cancer. Side-effects were pronounced and the mean tolerated doses were 12.5 x 10(6) U/m2 interferon alpha three times per week and 0.10 mg/kg vinblastine once every three weeks. We observed a 43% response rate, with 1 complete remission, 8 partial remissions, 4 stabilizations and 8 progressions. These very encouraging results need to be confirmed by large scale studies.

[Epidemiology of bladder cancer]. / Epidémiologie du cancer de la vessie.

The urinary bladder cancer mortality varies in different countries. The highest rates are noted in Denmark, UK, Belgium and Italy, the lowest rates in Japan, Singapore and Venezuela. The mortality rates are increasing for both males and females. In France, the highest rates are observed in the South of France contrary to other cancer sites. The highest incidence rates are observed in Europe, in USA and in some countries of Africa. In these same areas, the rates are higher for males and are increasing with time. The mortality is high in the first years after diagnosis. The five-year relative survival rates are 41%, for males and 35% for females. Tobacco, and especially cigarettes, is a well known risk factor. A dose effect relation appears to exist. The occupational risk factors are potentiated by tobacco and modifications are noted and are in relation with new factors. Ground coffee is associated with urinary bladder cancer and appears to be a co-carcinogenic factor with tobacco. Some drugs, such as antimitotics, phenacetin, radiation and urinary bilharziosis, are etiological factors of this cancer. The role of artificial sweeteners, alcohol and nutrition is less well documented.

[A case of hydronephrosis disclosed after traumatic rupture of the kidney pelvis]. / A propos d'un cas d'hydronéphrose découverte lors de rupture traumatique de bassinet.

We report a typical case of traumatic ruptured hydronephrosis (moderate trauma, unknown hydronephrosis). Conservative treatment with pyeloplasty appears to be the best solution in these cases when as is frequently the case the major lesions affect the renal pelvis.

[Radical cystectomy for invasive tumors of the bladder in patients over 70 years of age]. / Cystectomie radicale pour tumeur infiltrante de vessie pour les patients de plus de soixante-dix ans.

The authors present a series of forty patients operated for invasive bladder tumors by radical cystectomy. All patients were older than 70 and had a complicated medical history. Mortality was 1 in 40 and the morbidity was low. The conclusion is that radical cystectomy is a safe procedure in elderly patients.

[Thyroid metastases from a nephro-epithelioma]. / Les métastases thyroïdiennes du néphro-épithéliome.

The authors report a rare case of thyroid metastasis from a nephro-epithelioma, which appeared four years after nephrectomy, and was revealed by a Basedow-type goiter. It was treated by total thyroidectomy. A cervical recurrence was diagnosed in the course of a routine checkup and arteriography. Death occurred 22 years after thyroidectomy and 26 years after nephrectomy. The diagnosis is often only made at necropsy. The slow growth of these metastases does not preclude extended survival after surgical excision, and requires active therapy.

[A case of auto-emasculation]. / A propos d'une observation d'autoémasculation.

We present a case of genital self emasculation in a non-psychotic patient. We discuss here the few problems (surgical, psychiatric, legal and sociologic) that this rare case suggest.

[Effects of an extract of the bark of Pygeum africanum (V.1326) on prostatic secretions in the rat and in man]. / Effets d'un extrait d'écorce de Pygeum africanum (V.1326) sur les sécrétions prostatiques du rat et de l'homme.

Treatment with V.1326 in the rat induces an increase in prostatic secretion. In men with insufficient prostatic secretion, this treatment also induces an increased secretion.

[Transurethral resection of the prostate. Our experience in a series of 244 cases. Mid-term results]. / La résection trans-urétrale de la prostate. Notre expérience sur une série de deux cent quarante-quatre cas. Résultats à moyen terme.

Two hundred and forty four patients were treated by transurethral resection of the prostate (68% for adenomas and 32% for epitheliomas) between June 1980 and August 1982. The indications for surgery are based on obstruction of the urinary outflow tract, and the weight of prostatic tissue, which can best be assessed by ultrasound. TURP is the technique of choice for small and medium-size prostates. Hemorrhage is the most frequent complication at operation. Resorption TURP syndrome is extremely rare if an isotonic liquid is used. Urinary tract infections are best treated preoperatively. 2.6% of the patients suffered from urethral stricture despite the use of a 24 French resectoscope and early removal of the catheter. The greater the surgeon's experience, the lower the incidence of definitive urinary incontinence.

[The upper urinary tract in pregnant women. Physiopathologic, ultrasonic and urographic study]. / Les voies urinaires hautes de la femme enceinte. Etude physiopathologique, échographique et urographique.

This study of the upper urinary tract with the voluntary co-operation of expectant mothers, and based on 316 ultrasound examinations and 138 urographies, confirms the high incidence of uretero-pyelocalyceal dilatations is pregnancy. Compression by the gravidic uterus and the hormonal environment of pregnancy are the best-known etiologies. The frequency of associated urinary infections and the slow regression of the dilatation in the post-partum period (three months) will be noted.

[Our experience with the treatment of urethral stenosis in a series of 90 cases at the Strasbourg Hospital Center]. / Notre expérience du traitement de la sténose de l'urètre sur une série de quatre-vingt-dix cas au Centre Hospitalier de Strasbourg.

Ninety patients presenting with urethral stenosis were treated surgically at the Strasbourg Hospital, involving 100 internal urethrotomies and sixteen urethroplasties. The authors consider that short bulbous stenosis, with no previous treatment, should be treated endoscopically; that, if the stenosis recurs after two internal urethrotomies, or if the stenosis is infected or located in the pendulous or membranous urethra, a urethroplasty is indicated, as in cases of long bulbous stenosis; and that, even though the rate of complications is high following Johansson's urethroplasty, this procedure is indicated in cases of infection. The use of free full-thickness grafts led to a 100% success rate.

[A case of carcinoma of the stomach revealed by a testicular metastasis (author's transl)]. / Cancer de l'estomac révélé par une métastase testiculaire.

A testicular metastasis from a gastric carcinoma is exceptional among the rare secondary localisations of a visceral neoplasm in the testis. It should however be remembered for the testicular tumour sometimes precedes the clinical manifestations of the primary neoplasm. The diagnosis of the testicular metastasis from a gastrict carcinoma can only be made by histological examination and required the use of slides stained with mucicarmine. The method of spread to the testis seems mainly due to inversion of the lymph flow by neoplastic obstruction of the latero-aortic lymph nodes. In the cases reported in the literature, the presence of a testicular metastasis from a carcinoma of the stomach is a factor suggesting a poor prognosis.