Structural organization of glutamate dehydrogenase. 2. Inactivation and dissociation of immobilized hexamer induced by urea

The urea-induced inactivation and dissociation of catalytically active hexamer of glutamate dehydrogenase (L-glutamate-NAD(P)-oxidoreductase, EC 1.4.1.3) from bovine liver were studied using radioactive phosphopyridoxyl derivative of the enzyme immobilized on cyanogen bromide-activated Sepharose CL-4B. It is shown that at neutral pH (7.0-7.8) urea causes dissociation of glutamate dehydrogenase to directly yield catalytically inactive immobilized monomers rather than hexamer's stable fragments at the same time. At pH 8.9 or 5.6 the urea-induced is accompanied by the formation of conformationally stable immobilized dimers or trimers, respectively. The trimers are catalytically active, whereas the dimers did not exhibit any enzymatic activity. The data obtained led to suggestion that the hexamer consists of three either equivalent dimers (3 alpha 2) or of two equivalent trimers (2 alpha 3).     

Analysis of compressive creep behavior of the vertebral unit subjected to a uniform axial loading using exact parametric solution equations of Kelvin-solid models--Part II. Rhesus monkey intervertebral joints

The simulation of long-term creep response behavior, observed on 54 Rhesus monkey intervertebral joints subjected to a constant axial compressive stress, is attempted by two- and three-parameter-solid models utilizing the Burns- Kaleps 'exact analysis scheme'. Model parameters identified by the analysis of each specimen's experimental strain data were optimized via a computer program and the mechanical properties (Young's moduli and the viscosity coefficient) appropriate to each model were calculated for individual spinal segments. Simulation results for the two-parameter-solid (one- Kelvin -unit) model demonstrate its general ineptness in predicting the observed strain-time behavior of normal spinal sements . The three-parameter-solid model yielded excellent results in the simulation of observed spinal segment compressive creep phenomena. It produced an average error between the model predicted and experimental strain values that ranged from a low of 0.4000% to a high of 3.290% for the 54 Rhesus monkey intervertebral joints, with a collective average error for all specimens of only 1.363%.     

Analysis of compressive creep behavior of the vertebral unit subjected to a uniform axial loading using exact parametric solution equations of Kelvin-solid models--Part I. Human intervertebral joints

The creep response phenomena observed on 47 human intervertebral discs subjected to a constant axial compressive stress was analytically studied by two-, three- and four-parameter-solid models employing the Burns- Kaleps 'exact analysis scheme'. The mechanical properties (Young's moduli and viscosity coefficients) associated with each model were calculated for each of the 47 disks, with superior results obtained for the latter two models. Results for the two-parameter-solid model suggest its possible usefulness in simulating creep response that is characteristic of disk degeneration. Results for the three- and four-parameter-solid models were excellent, with an average error for the model predicted strain, epsilon(ti)cal, values from the experimentally measured, epsilon(ti)exp, values of 2.314% for the former model and 4.446% for the latter model on the 47 human spinal segments analyzed. The three-parameter-solid model was most sensitive in its predictability of strain behavior for ti greater than 1 min; whereas the four-parameter-solid model demonstrated greater simulation sensitivity in the 0 less than ti less than or equal to 1 min range.     

Conditioned alimentary motor reflexes in cats following destruction of the scorpula]

Bilateral ablation of the putamen results in temporary disappearance of natural as well as artificial conditioned motor reflexes in cats. Further training is necessary for their reestablishment. Restored conditioned reflexes appear with a long latency. After partial bilateral ablation of the putamen, animals that have been trained not only to press a pedal, but also to make a choice between a right or left feeding tray, lose the latter ability. After the reestablishment of conditioned reflexes, the animal makes a correct choice of side only in 68--70% of cases. After total bilateral ablation of the putamen the animals lose artificial conditioned reflexes. The results suggest that the putamen has a close relation to the mechanisms of learning and memory.     

Biodeterioration of Mayan buildings at uxmal and tulum,Mexico

Uxmal and Tulum are two important Mayan sites in the Yucatan peninsula. The buildings are mainly composed of limestone and grey/black discoloration is seen on exposed walls and copious greenish biofilms on inner walls. The principal microorganisms detected on interior walls at both Uxmal and Tulum were cyanobacteria; heterotrophic bacteria and filamentous fungi were also present. A dark‐pigmented mitosporic fungus and Bacillus cereus, both isolated from Uxmal, were shown to be acidogenic in laboratory cultures. Cyanobacteria belonging to rock‐degrading genera Synechocystis and Gloeocapsa were identified at both sites. Surface analysis previously showed that calcium ions were present in the biofilms on buildings at Uxmal and Tulum, suggesting the deposition of biosolubilized stone. Apart from their potential to degrade the substrate, the coccoid cyanobacteria supply organic nutrients for bacteria and fungi, which can produce organic acids, further increasing stone degradation.     

The differentiation of rhythmogenic characteristics of the ureter's different regions in guinea pigs

Characteristics of rhythmogenic pacemakers of the ureter's perirenal middle and peribladder region morphologically and electrophysiologically are analysed in guinea pigs both in presence of spreading activity and breach of conductivity. It was shown that the action potential's amplitude of the middle region is the highest and duration of the spike activities from perirenal zone is maximal and all three regions are characterised by different functional conditions.     

Effect of histamine on spontaneous rhythmogenesis of the guinea pig ureter

Histamine changed characteristics of the perinephric spontaneous spike activity and of the spreading electrical wave. It was shown that histamine could activate latent pacemakers of the ureter's middle area. Morphological picture of the histamine effect was also shown.     

Electrophysiological pacemaking properties of the ureter peribladder area in cats and rats

The rhythm generated by the peribladder area was found to be slower than that generated by the basis perirenal pacemaker in cats and rats. The antiperistaltic waves' frequency of the peribladder area was the lowest within the range of all the recorded rhythms.     

Conditional Survival in de novo Metastatic Urothelial Carcinoma

Background

Second-line therapy is frequently utilized for metastatic urothelial carcinoma, but there are limited data to guide this approach. While an assessment of overall survival based on registry data may not capture the impact of second- and third-line therapies on clinical outcome, this may be reflected in relative conditional survival (RCS).

Methods

Patients with stage IV urothelial carcinoma diagnosed from 1990–2010 were identified from the Surveillance, Epidemiology and End Results (SEER) dataset. The association of clinicopathologic variables with disease specific survival (DSS) was explored through univariate and multivariate analyses. DSS in subgroups divided by time period (1990–2000 v 2001–2010) was compared using the Kaplan-Meier method and log-rank test. One-year RCS at annual landmarks up to 5 years was compared in subgroups divided by time period.

Results

Of 261,987 patients diagnosed with urothelial carcinoma from 1990–2010, 3,110 patients met criteria for the current analysis. Characteristics of patients diagnosed between 1990 and 2000 (n = 810) and 2001 to 2010 (n = 2,300) were similar and there was no significant difference in DSS between the two groups. On multivariate analysis, older age (age ≥ 80) was associated with shorter DSS (HR 1.79, 95%CI 1.48–2.15), but no association was found between time period of diagnosis and outcome. One-year RCS improved substantially through successive annual landmarks up to 5 years, but no differences were seen in subgroups divided by time of diagnosis.

Conclusions

No difference in RCS was observed amongst patients with stage IV urothelial carcinoma diagnosed from 1990–2000 and 2001–2010. A lack of difference in RCS (more so than cumulative DSS) may reflect a lack of progress in salvage therapies for the disease.