Correlation between CT and anatomopathological staging of kidney cancer.

Our Moroccan context is experiencing an increase in the frequency of renal tumors. This trend can be explained by the generalization of the use of imaging, in particular abdominal ultrasound, which has become almost systematic among general practitioners (Godley and Ataga, 2000 [1]). The specificity of kidney cancer is anatomopathological heterogenicity: histological type, nuclear grade, tumor stage, these elements constitute the most important prognostic factors. Renal biopsy appears to be a safe and reliable solution with a low risk of tumor seeding and complications, however it cannot provide all the detailed histological information needed. Hence the interest in the abdominal scanner. The abdominal scanner is the reference examination for the evaluation of renal tumors, it diagnoses the tumor, specifies these characteristics, it assesses the loco regional, venous extension. The objective of our study is to correlate pathological and CT findings of 70 kidney cancer in order to determine the reliability of CT in kidney cancer and its extension.

[Predictors of catheter-related bladder discomfort]. / Facteurs prédictifs de l'inconfort lié à la sonde vésicale.

INTRODUCTION: Establish a descriptive epidemiological profile of patients with Catheter Related Bladder Discomfort (CRBD) and identify its predictive factors. MATERIAL AND METHOD: Between June 2019 and December 2019, 300 patients have been evaluated. Different parameters were taken into account including: sex, age, body mass index (BMI), historical health data, duration and indications of the urinary catheterization, type of the transurethral catheter used, lubrication of the catheter and the existence of CRBD. We grouped our patients according to the intensity of CRBD syndrome. The various factors likely to be correlated with the occurrence of CRBD were subject of a univariate then multivariate analysis. RESULTS: 300 patients were included. The average age was 49 years (133 men and 167 women). 68 patients (22.6%) had history of urinary catheterization. 19% of patients were catheterized for acute urinary retention, while 81% were catheterized before surgery. The average duration of the urinary catheterization was 2.5 days. 54% showed CRBD symptoms, including more than 92% on the first day of the urinary catheterization. The significant risk factors in multivariate analysis were: the caliber of the catheter ≥18 Fr, the absence of lubrication, laparotomy, age <50 years, Cesarean and urinary catheterization medical history. CONCLUSION: This study identified various factors incriminated in the occurrence of CRBD. The role of the hospital practitioner is to prevent this syndrome by reducing predictive factors, particularly the technical ones. LEVEL OF EVIDENCE: 3.

Hyperandrogenism-Insulin Resistance-Acanthosis Nigricans Syndrome.

Introduction. Female hyperandrogenism is a frequent motive of consultation. It is revealed by hirsutism, acne or seborrhea, and disorders in menstruation cycle combined or not with virilisation signs. Several etiologies are incriminated but the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome is rare. Observation. A 20-year-old girl, having had a five-year-old secondary amenorrhea. The exam revealed a patient, normotensive with a body mass index at 30 kg/m(2) and a waist measurement of 120 cm, a severe hirsutism assessed to be 29 according to Ferriman Gallwey scale, virilisation signs of male morphotype, clitoridic hypertrophy and frontal alopecia, and an acanthosis nigricans behind the neck, in the armpits and elbows. The assessment carried out revealed testosteronemia at 1.28 ng/mL, which is more than twice the upper norm of the laboratory. Imaging studies were negative for both ovarian and adrenal masses. The retained diagnosis is HAIR-AN syndrome probably related to ovarian hyperthecosis and she was provided with androcur 50 mg/day and estradiol pills 2 mg/day and under hygiene-dietetic conditions. Conclusion. This case proves that HAIR-AN syndrome could be responsible for severe hyperandrogenism with virilisation signs. It must be retained after discarding the tumoral causes and when there are signs of insulin resistance.

Thyroid Hemiagenesis Associated with Hashimoto's Thyroiditis.

Thyroid hemiagenesis is a rare congenital anomaly resulting from failure of one thyroid lobe development. We report a 23-year-old female presented with Hashimoto's thyroiditis in left lobe, associated with hemiagenesis of right lobe and isthmus which was previously diagnosed as Graves' hyperthyroidism, but developed further into Hashimoto's thyroiditis after being treated with antithyroid drugs. The symptoms of hyperthyroidism in the current case led to the diagnostic confirmation by scintiscanning of an absent lobe. The antithyroid pharmacotherapy by thiamazole was used. However, due to symptoms of hypothyroidism, it was discontinued two months later, so thyroid hormone substitution was reintroduced. Antithyroid antibody studies and ultrasonography documented the presence of Hashimoto's thyroiditis.

[Ketosis-prone atypical diabetes mellitus: report of two cases]. / Diabète atypique avec tendance à la cétose ou diabète "Africain": à propos de deux cas.

An atypical presentation of diabetes mellitus was described in black subjects, initially in adolescents by Winter et al. then, in adult populations. The principal characteristics of "African" diabetes are an acute onset with severe hyperglycemia and ketosis, and a clinical course of type 2 diabetes mellitus. In the subsequent clinical course after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. In the subsequent clinical course after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. The molecular mechanisms underlining the insulin secretory dysfunction are still to be understood and may involve glucolipotoxicity processes. The HLA alleles associated with susceptibility to type 1 diabetes were reported of high frequency in some populations with this form of diabetes, in the absence of makers of pancreatic beta cell autoimmunity. The aim of the present review is to discuss two cases of African diabetes and review the specific diagnostic, metabolic, pathogenic and management features of this atypical diabetes.

[Cushing's syndrome due to a pulmonary carcinoid]. / Syndrome de Cushing révélateur d'un carcinoïde pulmonaire.

Cushing paraneoplasic syndrome is a rare cause of hypercorticism. We report a case of 35 year-old man presenting with Cushing's syndrome characterized by severe signs of hypercorticism and hypokalemia. Endocrine investigations were suggestive of an hypercortisolism linked to an ectopic adrenocorticotropic (ACTH) secretion, both at baseline (mean ACTH levels=275 pg/ml, urinary free cortisol excretion=3.898 mmol/24 h) and after pharmacodynamic testing (lack of inhibition of ACTH by dexamethasone). Thoracic tomodensitometric examination revealed a 15 mm tumor corresponding to a neuroendocrine pulmonary carcinoid with positive immunostaining for chromogranin A. Postoperative ACTH measurement was undetectable, plasma cortisol and free urinary cortisol were also decreased after tumor resection suggesting complete tumor removal. This case report illustrates the characteristics of paraneoplasic Cushing syndrome due to ACTH secreting pulmonary neuroendocrine carcinoid.

Hypomethylation of DNA and resistance to apoptosis in tonsillar hypertrophy in children.

We analyzed the hypomethylation of DNA and the sensitivity to apoptosis of tonsillar cells and peripheral blood lymphocytes (PBL) in twenty children with either recurrent tonsillitis (RT) or tonsillar hypertrophy (TH). We found no significant differences in DNA methylation of PBL obtained from RT and TH groups. Hypomethylation of DNA extracted from tonsillar tissue was higher in TH than in RT and was associated with lower spontaneous and thapsigargin-induced apoptosis. By contrast, RT showed a low level of DNA hypomethylation and was associated with high sensitivity to spontaneous and thapsigargin-induced apoptosis.

[Tuberculous osteoarthritis of the foot in the diabetic: not unrecognize this diagnostic trap. About one case]. / Ostéoarthrite tuberculeuse du pied chez le diabétique : piège diagnostique à ne pas méconnaître. A propos d'une observation.

Osteoarticular tuberculosis is the fourth leading extrapulmonary localization of tuberculosis. The disease has a progressive course and is often diagnosed in the stage of bone destruction, causing an important diagnostic problem in diabetics with nervous osteoarthropathy. We report the case of a 23-year-old patient with multicomplicated diabetes type 1, treated for pulmonary tuberculosis who consulted after a trauma distended the left ankle. Bone biopsy was performed because of the diagnostic doubt between diabetes and infectious osteoarthropathy. Pathology reported active tuberculosis. Osteoarticular tuberculosis is still a severe disease because of the functional prognosis that requires early diagnosis, a difficult task in some conditions particularly in the diabetic where the disease may mimic nervous osteoarthropathy. Bone biopsy should be performed if there is a doubt.

[Primary lymphoma of the thyroid gland]. / Lymphome malin primitif de la thyroïde.

Malignant primary lymphoma of the thyroid gland is a rare disease generally occurring women in the 6(th) or 7(th) decade of life. The principal clinical sign is giant goiter rapidly leading to sings of compression, raising the question of differential diagnosis with anaplastic cancer. The radiological findings in our patient were suggestive of malignancy due to the locoregional invasion. Immunohistochemistry study of the surgical specimen was required to reach the definitive diagnosis of thyroid gland primary lymphoma. Diagnosis of malignant primary lymphoma of the thyroid gland made at the stage of extensive locoregional extension compromises prognosis. Our patient died after one session of chemotherapy.

[Incidence of factors favoring recurrent foot ulcers in diabetic patients]. / Etude de la fréquence et des facteurs favorisant les récidives des ulcères de pied chez les patients diabétiques.

BACKGROUND: Patients with foot ulcers have a high risk of relapse and amputation. Several studies have reported that 28 to 51% of amputated diabetics will have a second amputation of the lower limb within five years of the first amputation. The purpose of this study was to assess the incidence of factors favoring relapse within two years. MATERIAL AND METHODS: One hundred ten diabetic patients were treated for foot lesions in the Casablanca Ibn Rochd university hospital between 1997 and 2000. Ninety of these patients attended review consultations. RESULTS: There were 42 cases of relapse (46.6%). Male gender predominated in the relapse patients with a sex ratio of 3.2. Mean age at relapse was 55 years; 71.5% of the patients had type 2 diabetes. Lesions observed were neuropathic ulcer (n=23), arterial ulcer (n=6), infected wounds (n=13). Revealing factors were burns and wounds. The main risk factors were neuropathy (n=23, 52%), neuroarteriopathy (n=12, 31%), peur arteriopathy (n=6, 12%). Patients who relapsed (n=42) were significantly different from patients who did not relapse (n=48) for gender, presence or absence of neuropathy, and presence or absence of arteriopathy. DISCUSSION: Secondary preventive measures against these risk factors, medical care, and specialized follow-up were satisfactory in these patients. our findings illustrate the importance of specialized management of diabetic patients with foot lesions. Adequate care of the lesions and preventive measures against risk factors are needed.

The N-terminal adenosine triphosphate binding domain of Hsp90 is necessary and sufficient for interaction with estrogen receptor.

To understand how the molecular chaperone Hsp90 participates in conformational maturation of the estrogen receptor (ER), we analyzed the interaction of immobilized purified avian Hsp90 with mammalian cytosolic ER. Hsp90 was either immunoadsorbed to BF4 antibody-Sepharose or GST-Hsp90 fusion protein (GST.90) was adsorbed to glutathione-Sepharose. GST.90 was able to retain specifically ER, similarly to immunoadsorbed Hsp90. When cells were treated with estradiol and the hormone treatment was maintained during cell homogenization, binding, and washing steps, GST.90 still interacted efficiently with ER, suggesting that ER may form complexes with Hsp90 even after its activation by hormone and salt extraction from nuclei. The GST.90-ER interaction was consistently reduced in the presence of increasing concentrations of potassium chloride or when cytosolic ER-Hsp90 complexes were previously stabilized by molybdate, indicating that GST.90-ER complexes behave like cytosolic Hsp90-ER complexes. A purified thioredoxin-ER fusion protein was also able to form complexes with GST.90, suggesting that the presence of other chaperones is not required. ER was retained only by GST.90 deletion mutants bearing an intact Hsp90 N-terminal region (1-224), the interaction being more efficient when the charged region A was present in the mutant (1-334). The N-terminal fragment 1-334, devoid of the dimeric GST moiety, was also able to interact with ER, pointing to the monomeric N-terminal adenosine triphosphate binding region of Hsp90 (1-224) as the region necessary and sufficient for interaction. These results contribute to understand the Hsp90-dependent process responsible for conformational competence of ER.

Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90.

Heat shock protein (hsp)90 functions in a complex chaperoning pathway where its activity is modulated by ATP and by interaction with several co-chaperones. One co-chaperone, p23, binds selectively to the ATP-bound state of hsp90. However, the isolated ATP-binding domain of hsp90 does not bind p23. In an effort to identify the p23-binding domain, we have constructed a series of hsp90 deletion mutants fused with glutathione-S-transferase (GST). Full-length GST-hsp90 is able to bind p23, and also, to chaperone assembly of progesterone receptor complexes. Truncations from the C terminus of GST-hsp90 reveal a C-terminal boundary for the p23-binding domain at approximately residue 490. This fragment contains, in order, the ATP-binding domain, a highly charged region, and 203 residues beyond the charged region. p23 binding is unaffected by deletion of the charged region, indicating that two noncontiguous regions of hsp90 are involved in p23 binding. These regions are only effective when hsp90 is in a dimeric state as shown by loss of p23 binding upon removal of GST or as shown by use of FK506-binding protein12-hsp90 constructs that form dimers and bind p23 only in the presence of a bivalent drug. Thus, p23 binding requires an hsp90 dimer with close proximity between N-terminal regions of hsp90 and a conformation specified by ATP.

The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone.

Heat shock protein 90 (Hsp90), one of the most abundant chaperones in eukaryotes, participates in folding and stabilization of signal-transducing molecules including steroid hormone receptors and protein kinases. The amino terminus of Hsp90 contains a non-conventional nucleotide-binding site, related to the ATP-binding motif of bacterial DNA gyrase. The anti-tumor agents geldanamycin and radicicol bind specifically at this site and induce destabilization of Hsp90-dependent client proteins. We recently demonstrated that the gyrase inhibitor novobiocin also interacts with Hsp90, altering the affinity of the chaperone for geldanamycin and radicicol and causing in vitro and in vivo depletion of key regulatory Hsp90-dependent kinases including v-Src, Raf-1, and p185(ErbB2). In the present study we used deletion/mutation analysis to identify the site of interaction of novobiocin with Hsp90, and we demonstrate that the novobiocin-binding site resides in the carboxyl terminus of the chaperone. Surprisingly, this motif also recognizes ATP, and ATP and novobiocin efficiently compete with each other for binding to this region of Hsp90. Novobiocin interferes with association of the co-chaperones Hsc70 and p23 with Hsp90. These results identify a second site on Hsp90 where the binding of small molecule inhibitors can significantly impact the function of this chaperone, and they support the hypothesis that both amino- and carboxyl-terminal domains of Hsp90 interact to modulate chaperone activity.

Hsp90 chaperone activity requires the full-length protein and interaction among its multiple domains.

Hsp90 is an abundant and ubiquitous protein involved in a diverse array of cellular processes. Mechanistically we understand little of the apparently complex interactions of this molecular chaperone. Recently, progress has been made in assigning some of the known functions of hsp90, such as nucleotide binding and peptide binding, to particular domains within the protein. We used fragments of hsp90 and chimeric proteins containing functional domains from hsp90 or its mitochondrial homolog, TRAP1, to study the requirements for this protein in the folding of firefly luciferase as well as in the prevention of citrate synthase aggregation. In agreement with others who have found peptide binding and limited chaperone ability in fragments of hsp90, we see that multiple fragments from hsp90 can prevent the aggregation of thermally denatured citrate synthase, a measure of passive chaperoning activity. However, in contrast to these results, the luciferase folding assay was found to be much more demanding. Here, folding is mediated by hsp70 and hsp40, requires ATP, and thus is a measure of active chaperoning. Hsp90 and the co-chaperone, Hop, enhance this process. This hsp90 activity was only observed using full-length hsp90 indicating that the cooperation of multiple functional domains is essential for active, chaperone-mediated folding.

[Screening for diabetic retinopathy with ophthalmoscopy: the contribution of non-ophthalmologist practitioners seems possible]. / Dépistage de la rétinopathie diabétique par l'ophtalmoscopie: la contribution du médecin non ophtalmologiste paraît possible.

Diabetic retinopathy is a severe and frequent complication of diabetes. Screening and early treatment of retinal lesions avoid blindness, but diagnosis is often established too late. The purpose of our study was to compare the concordance between the results of examination of fundus oculi whether performed by a previously trained non ophthalmologist physician at diabetes day center or during a routine ophthalmology consultation. Results were classified a posteriori in order to have binary response (presence of the lesion, absence of the lesion). Ninety six eyes were examined. Results of these examinations were compared using the kappa test agreement (kappa). The concordance was good for the majority of retinal lesions. The concordance in the results suggests that the contribution of non ophthalmologist physicians to the screening of diabetic retinopathy is possible and could facilitate the selection of patients who require specialized and elaborate ophthalmologic exploration.

Presence of an aromatase inhibitor, possibly heat shock protein 90, in dominant follicles of cattle.

In cattle, it has been suggested that follicular fluid has direct modulatory effects on follicular growth and maturation. In the first part of this study, an in vitro test using aromatase activity of follicular wall fragments as an end point was validated for cattle follicles and was used to test whether follicular fluid (from dominant or non-dominant follicles) modulates aromatase activity. Fluid from dominant follicles at a concentration of 24 or 12% (obtained during the luteal and follicular phases, respectively) significantly inhibited aromatase activity. Inhibitory activity was low or absent in fluid from non-dominant follicles. FSH-stimulated aromatase activity was also reduced by fluid from dominant follicles, but not to a greater extent than in basal conditions. Finally, charcoal-treated fluid from dominant follicles retained its inhibitory activity. In contrast, ovarian venous serum draining a dominant follicle had no activity at the three concentrations tested (6, 12 and 24%). In the second part of the study, identification of the compounds involved in this modulatory activity was attempted using SDS-PAGE. Comparison of the fluorographs from de novo synthesized proteins stored in follicular fluid (inhibitory medium) with those secreted in incubation medium (inactive medium) demonstrated that one protein (90 kDa, pI 5.8) was significantly (P < 0.05) more abundant in fluid from dominant follicles (2.0 +/- 0.09%) than in the culture medium (1.3 +/- 0.1% of the total proteins). This protein had characteristics similar to those of heat shock protein 90 (hsp 90). Therefore, in the final part of the study, the presence of hsp 90 in ovarian cells and follicular fluid was investigated using immunohistochemistry and western blot analysis. After immunohistochemistry, a positive signal was detected mainly in the granulosa cells of larger follicles and to a smaller extent in thecal cells and oocytes. Western blot analysis also demonstrated the presence of hsp 90 in follicular wall fragments and fluid. When blotting was achieved on a sample of follicular fluid resolved by two-dimensional PAGE, the spot detected had a similar location to that at 90 kDa and pI 5.8. Addition of purified hsp 90 to bovine follicles in vitro depressed aromatase activity by altering the K(m) value (and possibly the Vmax value) of the enzyme. It is proposed that hsp 90 is a functional regulator of follicular maturation through its action on aromatase.

Heat-induced oligomerization of the molecular chaperone Hsp90. Inhibition by ATP and geldanamycin and activation by transition metal oxyanions.

It has been previously reported that heat shock protein 90 (Hsp90) oligomerizes at high temperatures and displays concomitantly a novel chaperone activity (Yonehara, M., Minami, Y., Kawata, Y., Nagai, J., and Yahara, I. (1996) J. Biol. Chem., 271, 2641-2645). In order to better define these oligomerization properties at high temperatures and to know whether they are influenced by modulators of Hsp90 function, heat-induced oligomerization of highly purified dimeric Hsp90 has been investigated over a wide range of temperature and protein concentrations by native polyacrylamide gel electrophoresis and size exclusion chromatography. Whereas below 50 degreesC, the dimeric form is maintained over a large range of concentrations, at the critical temperature of 50 degreesC, a sharp transition from dimeric to higher order oligomeric species takes place within minutes, in a highly ordered process, suggesting that a conformational change, leading to the appearance of a new oligomerization site, occurs in Hsp90 dimer. Moreover, at and above the critical temperature, the extent of oligomerization increases with Hsp90 concentration. Formation of high order oligomers at high temperatures is sensitive to modulators of Hsp90 function. ATP and geldanamycin, both known to bind to the same pocket of Hsp90, are inhibitors of this process, whereas molybdate, vanadate, and Nonidet P-40, which are thought to increase surface hydrophobicity of the protein, are activators. Thus, oligomerization of Hsp90 at high temperatures may be mediated through hydrophobic interactions that are hindered by ligands and favored by transition metal oxyanions. The fact that the heat-induced oligomerization of Hsp90 is affected by specific ligands that modulate its properties also suggests that this process may be involved in cell protection during heat shock.

The molecular chaperone Hsp90 can negatively regulate the activity of a glucocorticosteroid-dependent promoter.

Hsp90, a molecular chaperone required for the functioning of glucocorticosteroid receptor (GR), ensures, by direct interaction, the conformational competence of the steroid-binding pocket. In addition to having this positive function, Hsp90 maintains steroid receptors in an inactive form in the absence of hormone. However, neither the participation of Hsp90 once the pathway has been activated by the ligand nor the importance of increased Hsp90 levels in determining the amplitude of the response has ever been assessed directly. Here, by increasing the Hsp90/GR ratio in the nuclear compartment, we found an attenuation of the response to glucocorticosteroids that was not due to a nonspecific or toxic effect of the Hsp90 modified by nuclear targeting. Since this negative effect was more pronounced at high levels of hormone, when receptor and Hsp90 are maximally dissociated, the possibility of an interaction between Hsp90 and GR, already activated to a DNA-binding form, was directly investigated. Indeed GR, after in vivo activation by ligand, was still able to reassociate with Hsp90, suggesting that this interaction plays a role in vivo, possibly in receptor recycling. Moreover, the GR binding to its DNA response element was inhibited by an excess of Hsp90, pointing to a function of Hsp90 in the nuclear compartment. It is thus proposed that an increased Hsp90/GR ratio influences the responsiveness to ligand at a step that is after receptor activation. This increased ratio may be of pathophysiological relevance in the different circumstances that lead to an elevated level of nuclear Hsp90.

Production and characterization of a monoclonal antibody able to discriminate galectin-1 from galectin-2 and galectin-3.

Antisera raised against galectin-1 exhibit crossreactivities with other galectins or related molecules. In order to overcome this problem, a monoclonal antibody to human brain galectin-1 was obtained by selecting clones without reactivity toward galectin-3. This mAb specifically bound galectin-1 of various animal origins but neither galectin-2 nor galectin-3. Western-blotting analysis of soluble human brain extracts after 2D gel electrophoresis revealed only the two most acidic isoforms of galectin-1. The ability of this mAb to bind galectin-1/asialofetuin complexes indicates that its epitope is not localized in the carbohydrate recognition domain of galectin-1. This particularity induces with efficiency its monospecificity.