[Long course metastasis in renal adenocarcinoma. Adrenal gland involvement]. / Enfermedad mestastásica de larga evolución en el adenocarcinoma renal. Afectación suprarrenal.

OBJECTIVES: To report two cases of metachronic adrenal metastasis (one contralateral and the other bilateral) from renal cell carcinoma with long survival. METHODS: Two patients with clear cell renal carcinoma that developed metastasis to the adrenals are described. Each patient had undergone three operations for solitary metastasis during the 8-years follow-up. The indications for the surgical management of solitary metastasis, morbidity, prognosis and recent investigational treatment possibilities reported in the literature are analyzed. RESULTS: Resection of the renal cell carcinoma achieved a survival of more than 8 years with a good quality of life and no significant surgical complications. The outcome, however, is poor. CONCLUSIONS: Although there was no lymph node involvement and the tumor was localized to the renal parenchyma, one patient developed solitary lung metastasis and contralateral adrenal metastasis 4 and 8 years after the initial diagnosis, respectively. In the other case, contralateral adrenal metastasis appeared three years later. The possibility of long-term metastasis to the adrenal gland should be taken into account due to renal vein involvement. Preservation of the adrenal gland at the initial surgery (lower pole tumor) led to adrenal metastasis 8 years after the initial diagnosis. The prognosis is poor in both cases and the situation is discouraging for the urologist.

[Painful erections related to sleeping]. / Erecciones dolorosas relacionadas con el sueño.

Case report of sleep-related painful erections in a 34 year-old male with grade C3 HIV infection. Due to severe impairment of the patient's general condition, no proper diagnostic studies were performed to gain deeper knowledge of the symptom's pathological etiology. Empirical therapy was started based on evidence from the literature consulted, and the results seen were optimal. This paper contributes a brief review of a condition infrequently seen by the vast majority of urologists.

[Disjunction patterns: the morphological and ultrastructural bases of bladder instability in the male]. / Patrones de disyunción: bases morfológicas y ultraestructurales de la inestabilidad vesical del varón.

OBJECTIVE: To apply the new protocols and recent contributions on detrusor ultrastructural morphology in order to standardize criteria and evaluate our findings relative to the ultrastructural morphology, the presence of a dysfunction pattern, changes in nerve supply and formation of a chained cellular syncytium in hyperactive detrusor bladder instability in the male. METHODS: We studied 480 ultrastructural preparations of detrusor muscle from 32 male patients with bladder outlet obstruction with and without urodynamically demonstrated bladder hyperactivity. Bladder biopsies were obtained from the anterior aspect of the bladder and prepared according to the standard procedures for ultrastructural study. Semiquantitative nerve supply ultrastructural patterns, syncytial composition, and complete and incomplete disjunction were analyzed. RESULTS: Lower urinary tract obstruction was demonstrated in all patients; 6 of these patients had involuntary phasic detrusor contractions during filling. No significant decrease in nerve supply was found in isolated obstruction or in bladder hyperactivity. No axonal degeneration was observed in any of the patients and the myelin sheath structure was normal. Nerve effector endings were also normal. Four patients with hyperactive detrusor showed complete and two incomplete disjunction pattern. Incomplete disjunction pattern was also demonstrated in two patients with isolated obstruction. CONCLUSIONS: The change in the properties of the detrusor muscle in the unstable bladder is due to a complete reduction in excitatory nerve relation to smooth muscle. Having established the concept of common final myogenic pathway that explains involuntary detrusor contraction, complete dysfunction ultrastructural patterns have been defined with univocal relation to hyperactive detrusor. These patterns indicate the existence of a syncytium of chained muscle cells with changes in the excitation threshold that are absent in the normal stable detrusor. Two ultrastructural components sustain this hypothesis: 1) the major loss observed in intermediate cellular unions that are thought to mediate in the mechanical coupling of cellular contraction and 2) the presence in all the microscopic fields of abutments in the narrow cellular unions like gap-junctions, which mediate the electrical coupling. In the present study we have found this pattern in 4 out of 6 patients with hyperactive detrusor, and congruent with other studies, the incomplete disjunction pattern could be the prelude of bladder hyperactivity.

[Valsalva minimal leak point pressure: a useful approximation to type III female urinary incontinence]. / Presión mínima de escape con Valsalva: una útil aproximación a la incontinencia urinaria femenina tipo III.

OBJECTIVE: It has been reported that anatomic female urinary incontinence with complex sphincteric malposition can coexist with intrinsic damage of the sphincter itself. In this study we analyzed the utility of measuring minimum abdominal pressure at standardized bladder capacities that causes urinary incontinence in order to quantify intrinsic sphincteric damage in female urinary incontinence. METHODS: The study comprised 50 women with urinary incontinence aged 36-78 years (mean 59.4), ICS standardized complete urodynamic study was performed. Minimum leak point pressure with Valsalva maneuver in decumbent and standing positions was determined during the filling phase of cystomanometry and it was defined as a measure of the abdominal pressure expressed as total baldder pressure without involuntary detrusor activity and exercised at standardized bladder capacities that originates objective urinary incontinence. Minimum leak point pressure for each bladder capacity was evaluated. Leak point pressures below 60 cm H2O indicate intrinsic sphincteric damage; pressures between 60 and 90 cm H2O indicate intrinsic damage and malposition or urethral hypermobility may coexist, and leak pressures over 90 cm H2O are related to complex sphincteric malposition. RESULTS: 5 women showed severe sphincteric deficiency (type III) and urinary incontinence was demonstrated with 50 ml bladder capacity and 30 cm H2O of abdominal pressure without detrusor activity. Thirty-five women (70%) had type II urinary incontinence. Of these, 10 (28.5%) showed intrinsic sphincteric damage in addition to malpositioning of the sphincteric complex at leak point pressures between 60 and 90 cm H2O. The rest of the women showed Blaivas' type 0 and I urinary incontinence. CONCLUSIONS: Valsalva minimum leak point pressure is a reproducible, reliable, useful and easily measured parameter in diagnosing female stress urinary incontinence. It allows approximation of the abdominal pressure to the level at which urinary leakage is produced during the filling phase of cystomanometry and gives us an idea of the extent of the intrinsic sphincteric damage, if any. Not only is sphincter damage demonstrated in type III urinary incontinence, but that it may also coexist to a varying degree with complex sphincteric malposition.

Permeability to inhibitors of protein synthesis in virus infected cells.

Infection of HeLa cells with different viruses induces permeabilization of the cell membrane to protein toxins such as alpha-sarcin. This phenomenon occurs with HeLa, KB, BHK-21 and L929 cells and EMC, SFV, VSV and Polio virus and is dependent on the ability of the virus to infect the cells. Inhibitors of endocytosis and lysosomotropic agents do not affect this process. Cells become sealed to the toxin approximately four hours after the infection. Sulfhydryl reagents impair cellular permeabilization to alpha-sarcin.

Permeability to alpha sarcin in virus-infected cells.

Incubation of HeLa cells with Encephalomyocarditis virus (EMC) induces permeability of the cell membrane to protein toxins, such as alpha sarcin. To induce permeability to this toxin only 5 min incubation of cells with virus is needed. On the other hand, less than 1 min exposure of the susceptible cells to alpha sarcin produces maximal inhibition of protein synthesis. EMC virus treated with UV-light, although unable to replicate, can still induce the entrance of alpha sarcin into HeLa cells, but the virion loses this capacity after heating at 60 degrees C for 10 min. These findings suggest that an integral viral genome is not necessary to make the cells permeable to alpha sarcin, and that a virion protein might be involved in this phenomenon. Although human interferon prevents productive EMC infection, it does not affect the virus-induced entrance of alpha sarcin into the cells. The plasma membrane of cells that have been treated with virion particles can recover its initial lack of permeability to alpha sarcin after 2 h at 37 degrees C. Poliovirus modifies membrane permeability in human HeLa cells, but it has no effect on mouse L cells. This fact suggests that viral attachment to specific cell surface receptors is necessary to induce permeability, since receptors to poliovirus are only present in primate cells.

Site of action of ricin on the ribosome.

The extent of the inhibitory effect of ricin in polyphenylalanine synthesis by eukaryotic ribosomes is strongly dependent upon the concentration of ribosomes and the elongation factors EF 1 and EF2. Maximal inhibition by ricin, in this assay is observed when either ribosomes or the two elongation factors are added under limiting conditions, whereas ricin-treated ribosomes support protein synthesis at saturating concentrations of elongation factors and ribosomes. Similarly, the enzymatic binding of Phe-tRNA to ribosomes is drastically blocked in ricin-treated ribosomes when low EF 1 concentrations are added to the reaction mixture, but there is no inhibition when EF 1 is at saturating concentrations. Furthermore, formation of the complex EF 2-guanosine triphosphate-ribosome, using free ribosomes pretreated with ricin, is strongly inhibited at limiting concentrations of EF2, but is not affected at saturating concentrations of this factor. However, ricin does not inhibit the EF 2-dependent translocation of peptidyl-tRNA by polysomes, although the toxin is very active in preventing amino acid incorporation by polysomes. Our results suggest that the damaging effect of ricin on the ribosome causes a decreased affinity for both elongation factors EF 1 and EF 2. Thus, the toxin inhibits the enzymatic binding of aminoacyl-tRNA to ribosomes. The lack of inhibition of translocation by ricin suggests that the toxin cannot interact with ribosomes with substrate bound to the acceptor site. Essentially similar results are observed with ricin, abrin, ricin A chain, abrin A chain, and ricinus agglutinin A chain. A possible effect of the toxins on initiation and/or termination is further discussed.

Protective effect of elongation factor 2 on the inactivation of ribosomes by the toxic lectins abrin and ricin.

The inactivation of rabbit reticulocyte ribosomes by abrin and ricin A-chains was studied by incubating ribosomes with the A-chains and testing, after various periods of time, aliquots of the ribosomes for their ability to polymerize phenylalanine. The presence of elongation factor 2 (EF-2) reduced the rate of inactivation of ribosomes by the A-chains. The protective effect of EF-2 was strongly enhanced by GTP and, to a lesser extent, also by GDP or dGTP. Other nucleotides had no demonstrable effect. Much less protection was found after binding of Phe-tRNA to ribosomes in the presence of EF-1 (enzymic binding) or in the presence of high Mg2+ concentration (non-enzymic binding). The data indicate that when EF-2 binds to the ribosomes it completely or partially covers the target site for abrin and ricin A-chains. The possibility that EF-1 also binds to this site is discussed.

Antibiotics and compounds affecting tanslation by eukaryotic ribosomes. Specific enhancement of aminoacyl-tRNA binding by methylaxnthines.

The mode and site of action of inhibitors of translation (initiation, elongation and termination of protein synthesis) in eukaryotic systems is reviewed. The isolation and characterization of a factor is described that binds Ac-Phe-tRNA to form a complex made up of binding factors, Ac-Phe-tRNA, and ribosome. The binding of Ac-Phe-tRNA probably occurs at the ribosomal site involved in the binding of the initiator substrate Met-tRNAF. The effect of inhibitors of the intitiation phase of protein synthesis on the nonenzymic Ac-Phe-tRNA binding to ribosomes is investigated. The two sites translocation model for translation in eukaryotic cells is presented and the effects of inhibitors on the various steps of protein synthesis are determined empirically. The site of action of inhibitors of peptide bond formation at the ribosomal peptidyl transferase center is elucidated. The action of inhibitors of translocation is sutdied in model cell-free systems from human cells. In addition, a number of methylxanthines are shown to enhance the elongation phase in polypeptide synthesis by stimulating the enzymic binding of aminoacyl-tRNA. The effect of caffeine, theophylline and its derivatives are shown to be fairly specific and dependent on the ribosome concentration. Aminophylline is shown to have a similar effect but also enhances aminoacyl-tRNA synthetase activity at low Mg++ concentrations, probably displacing the optimal concentration of Mg++ in the reaction. This second effect of aminophylline appears to be due to the ethylenediamine moiety of aminophylline since it is also observed in the presence of different polyamines but not in the presence of caffeine or theophylline.

Ribosome inactivation by the toxic lectins abrin and ricin. Kinetics of the enzymic activity of the toxin A-chains.

A sensitive test system for toxin-treated ribosomes was worked out by treating rabbit reticulocyte ribosomes with abrin A-chain, ricin A-chain or ricinus agglutinin A-chain, adding neutralizing amounts of specific antitoxins and testing for polyphenylalanine-synthesizing activity in a system where the concentration of elongation factors and ribosomes were varied. The strongest inhibition was obtained in the presence of low concentrations of elongation factor (EF-2). The activity of the ribosomes decreased with time of incubation with the toxin A-chains. Addition of anti-toxins stopped further inactivation. In systems containing untreated and toxin-treated ribosomes the ability to polymerize phenylalanine was proportional to the concentration of untreated ribosomes. There was a linear relationship between toxin A-chain concentration and the number of ribosomes inactivated per minute. The inactivation rate increased with temperature, and the estimated activation energy was 10.6 kcal (44.3 kJ). Linewaver-Burk plots of the data obtained by incubating various ribosome concentrations with toxins indicated a molecular activity of about 1500 ribosomes/minute for abrin and ricin A-chains and 100 ribosomes/minute for ricinus agglutinin A-chain. The apparent Michaelis constant was 0.1-0.2 muM for all three A-chains. The activity of the A-chains in the intact cell is discussed.

Effects of ricin on the ribosomal sites involved in the interaction of the elongation factors.

The effects of ricin on the different steps of the elongation cycle of protein synthesis in a rabbit reticulocyte cell-free system are studied in this paper. The toxin most probably acts by catalytically inactivating the ribosomes, since a single molecule of the toxin can inactivate 300 ribosomes for poly(U)-directed phenylalanine incorporation. The effect of the toxin on the ribosome is irreversible. Ricin specifically inhibits elongation-factor-1-dependent aminoacyl-tRNA binding to ribosomes but has no effect on the non-enzymic binding of aminoacyl-tRNA. Ricin also inhibits formation of the complex elongation-factor-2 - ribosome - nucleotide with GTP, GDP or GMP-P(CH2)P. However, the toxin has no effect on translocation. These apparently conflicting results are discussed in this study.