Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module

Mutations in the myotubularin (MTM)-related protein 2 (MTMR2) gene are responsible for the severe autosomal recessive neuropathy Charcot-Marie-Tooth disease type 4B1. MTMR2 belongs to the MTM family of dual-specific phosphatases that use phosphatidylinositol (PI) 3,5-bisphosphate [PI(3,5)P2] and PI 3-phosphate [PI(3)P] as their substrate. Because these substrates are localized in the membrane bilayer, membrane targeting of Mtmr2 is an important regulatory mechanism. In hypoosmotically stressed COS cells with increased levels of PI(3,5)P2, Mtmr2 is bound to the membrane of vacuoles formed under these conditions. Using several mutant forms of Mtmr2, we identified two domains that are necessary for membrane association: (i) A pleckstrin homology-GRAM domain; and (ii) a coiled-coil module. Protein-lipid overlay assays show that the pleckstrin homology-GRAM domain binds to PI(3,5)P2 and PI(5)P, a substrate and a product of the Mtmr2 enzyme, respectively. We also demonstrate that Mtmr2 forms a dimer and that the C-terminal coiled-coil is responsible for homodimerization, in addition to membrane association. Our data indicate that phosphoinositide-protein interactions, as well as protein-protein interactions, are necessary for the correct regulation of MTMR2.     

The role of repeated biopsies in prognosis of prostate cancer

INTRODUCTION: The treatment of prostate cancer is still controversial. One of the most common treatment form is the use of LHRH analogs, but its way of action is still not cleared enough. AIMS: The aim of this study was to determine the predictive value of some histological and immuno-histochemical parameters based on repeated biopsies taken from prostate carcinoma patients. PATIENTS/METHOD: At the time of diagnosis by needle biopsy the TNM stage, serum PSA level, Gleason's grade, apoptotic and mitotic index, as well as Ki67, p53 and bcl2 expression were investigated in 60 prostate carcinoma patients. Anti-androgen therapy supplemented with surgical or chemical castration (with LHRH analogs) was administered. Serum PSA-test and needle biopsy were repeated 13-14 weeks after starting the therapy, simultaneously with determination of the apoptotic and mitotic index, Ki67, p53 and bcl2 expression. RESULTS: Forty-seven patients were alive at the end of the study (average 23.46 +/- 8.6 months) and thirteen patients died (average 25.3 +/- 14.8 months). Initial TNM stage and Gleason's score proved to be of prognostic value. Decrease in mitotic index and increase in apoptotic index during therapy proved to predict favourable long-term response to androgen ablation therapy. Similarly, lower Ki67 and (mutant) p53 expression in the first and also in the second biopsy pointed to a favourable effect of antiandrogen and especially of LHRH analog treatment. Since the ratio between Ki67 percentage and apoptotic index strongly decreased in the survivors upon therapy, changes in Ki67/apoptosis ratio may be recommended as a histologically detectable predictive factor. However, bcl2 expression did not show significant correlation with the outcome of the disease. CONCLUSION: Histological evaluation of parameters such as mitotic and apoptotic index as well as Ki67 and p53 expression in repeated biopsies during treatment may contribute to predicting the value of the actual treatment and may be useful to institute alterations in therapy.     

Tumor-like tracheal and lung diseases in biopsy samples

Tumor like miscellaneous lung diseases are rare conditions. They can be confused with benign and malignant tumors. We describe the clinicopathological features some of this conditions i.e.: two cases of osteoplastic tracheopathy, one inflammatory tracheal polyp, two cases of tumor mimicking foreign body aspiration, and one case of tracheobronchial amyloidosis.     

Bilateral renal cell carcinoma in a horseshoe kidney

We report a case of bilateral renal cell carcinoma in a horseshoe kidney. To the best of our knowledge this is the second reported case in the international literature. We performed different radiological examinations preoperatively to identify of blood supply, because correct preoperative location of vessels is mandatory.     

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.     

Disinhibition der Extensor-Motoneurone nach intercolliculärer Dezerebrierung

Zusammenfassung Trotz kontinuierlicher Anaesthesie und Unterbrechung der Gamma-Spindelschleife löst die natürliche oder elektrische Reizung homonymer Ia-Afferenzen mit konstanter Stärke nach intercolliculärer Dezerebrierung an Extensor-Motoneuronen regelmäßigere Antworten, Verkürzung der Reflexzeit, Zunahme der Entladungsfrequenz, Verstärkung der post-tetanischen Potenzierung und Rekrutierung aus. Da der Grad der recurrenten Hemmung abnimmt, schließen wir, daß die gesteigerte Erregbarkeit der Extensor-Motoneurone im Zustand der Dezerebrierung mit Disinhibition verbunden ist. Die mit einem konstanten Quantum reflexwirksamer Afferenzen erhaltenen Resultate sprechen für unsere Annahme, daß Spastizität nicht hauptsächlich auf fusimotorischer Enthemmung beruht.

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Disinhibition of extensor motoneurones after intercollicular decerebration

Summary Even with continued anesthesia and interrupted gamma-loop intercollicular decerebration leads in extensor motoneurones (excited by electrical or natural stimulation of homonymous Ia-afferents with constant strength) to the following phenomona: more regular responses, shortening of reflex time, increase of discharge frequency, enhancement of post-tetanic potentiation, and recruitment. Because the degree of recurrent inhibition is diminished we conclude that the higher excitability of extensor motoneurones in the decerebrate state is correlated with disinhibition. Furthermore the results obtained with the afferent input for motoneurones kept constant favour our assumption that spasticity is not based merely on the release of fusimotor activity.

     

Can the injured spleen be preserved? Results of 20-year experiments

Researches of different spleen salvaging techniques have begun in 1986 at our department. The early purpose was to develop new spleen preservation surgical techniques, such as spleen autotransplantation and spleen resection. Besides the morphological and radiological examinations we also performed different investigations including hemorheological, hemostaseological and immunological follow-up of the splenic function. From these parameters changes in red blood cell deformability and peripheral phagocyte activity could indicate the possible complications originated from the reduced splenic function. Recent paper takes a survey of these experiences.