On the part played by the socket in tooth support

Transducers of movement were used to detect the direction and amount of displacement of the alveolar margins of fifteen teeth in two adult monkeys. Controlled horizontal and intrusive thrusts were applied manually. Bone displacement started in response to forces appreciably less than 100 g and occurred in a linear manner with forces up to 1 kg. Horizontal forces of more than about 50 g tended to cause the labial and lingual alveolar plates to be displaced in the same direction as the applied force. The distance the bone was displaced and subsequently recoiled was less than the displacement and recoil of the root in the linear phase of movement. This implies increasing tissue compression on the side to which the tooth was moved and decreasing pressure in the membrane on the other side with elastic deformation of the socket. Intrusive force caused dilatation of the socket. The conclusion is reached that force to a tooth cause compression and tension in the periodontal membrane.     

Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients

The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline). Using microarrays, we diagnosed rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28 mixed (no borderline). Molecular assessment confirmed most conventional diagnoses (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors, particularly in mixed rejection, and improved prediction of failure. ABMR was strongly associated with increased graft loss, but TCMR was not. ABMR became common in biopsy specimens obtained >1 year post-transplant and continued to appear in all subsequent intervals. TCMR was common early but progressively disappeared over time. In 108 biopsy specimens obtained 10.2–35 years post-transplant, TCMR defined by molecular and conventional features was never observed. We conclude that the main cause of kidney transplant failure is ABMR, which can present even decades after transplantation. In contrast, TCMR disappears by 10 years post-transplant, implying that a state of partial adaptive tolerance emerges over time in the kidney transplant population.     

Enhancement of the Solubility and Efficacy of Poorly Water-Soluble Drugs by Hydrophobically-Modified Polysaccharide Derivatives

Purpose This work was intended to develop and evaluate a new polymeric system based on amphiphilic carboxymethylpullulans (CMP₄₉C₈ and CMP₁₂C₈) that can spontaneously self-assemble in aqueous solutions and efficiently solubilize hydrophobic drugs. Methods The self-assembling properties of CMP₄₉C₈ and CMP₁₂C₈ were characterized by fluorescence spectroscopy and surface tension measurements. The solubilization of benzophenone and docetaxel was assessed from surface tension measurements, UV spectrometry and HPLC assays. The in vitro cytoxicity of CMP₄₉C₈ solutions and the docetaxel commercial vehicle (Tween 80?/Ethanol–water) were evaluated in the absence and in the presence of docetaxel. Results Compared to CMP₁₂C₈, CMP₄₉C₈ in aqueous solutions appeared to self-organize into monomolecular aggregates containing hydrophobic nanodomains, and to significantly increase the apparent solubility of benzophenone. Docetaxel solubility could also be improved in the presence of CMP₄₉C₈ but to a lower extent due to the surface properties of the drug. Nevertheless, in vitro, the cytotoxicity studies revealed that against cancer cells, the CMP₄₉C₈-docetaxel formulation was equipotent to the commercial docetaxel one. Furthermore, in the absence of the drug, CMP₄₉C₈ appeared less cytotoxic against macrophages than the Tween? 80/Ethanol–water. Conclusions CMP₄₉C₈ is a good candidate for solubilizing hydrophobic drugs and could be applied to docetaxel formulations.     

Stratification of Wilms tumor by genetic and epigenetic analysis

Somatic defects at five loci, WT1, CTNNB1, WTX, TP53 and the imprinted 11p15 region, are implicated in Wilms tumor, the commonest childhood kidney cancer. In this study we analysed all five loci in 120 Wilms tumors. We identified epigenetic 11p15 abnormalities in 69% of tumors, 37% were H19 epimutations and 32% were paternal uniparental disomy (pUPD). We identified mutations of WTX in 32%, CTNNB1 in 15%, WT1 in 12% and TP53 in 5% of tumors. We identified several significant associations: between 11p15 and WTX (P=0.007), between WT1 and CTNNB1 (P less than 0.001), between WT1 and pUPD 11p15 (P=0.01), and a strong negative association between WT1 and H19 epimutation (P less than 0.001). We next used these data to stratify Wilms tumor into three molecular Groups, based on the status at 11p15 and WT1. Group 1 tumors (63%) were defined as 11p15-mutant and WT1-normal; a third also had WTX mutations. Group 2 tumors (13%) were WT1-mutant. They either had 11p15 pUPD or were 11p15-normal. Almost all had CTNNB1 mutations but none had H19 epimutation. Group 3 tumors (25%) were defined as 11p15-normal and WT1-normal and were typically normal at all five loci (P less than 0.001). We also identified a novel clinical association between H19 epimutation and bilateral disease (P less than 0.001). These data provide new insights into the pattern, order, interactions and clinical associations of molecular events in Wilms tumor.     

Clinical assessment of renal function

The kidney carries out many key functions in the body, including the maintenance of fluid, acid–base and electrolyte homeostasis, the removal of nitrogenous waste, the production of erythropoietin, the hydroxylation of vitamin D and an important influence on regulation of blood pressure. This perhaps explains the increased risk of morbidity and mortality postoperatively in patients with acute or chronic renal impairment. Identification of these patients preoperatively allows the assessment of risk to both the kidneys and other organs. Protective measures can then be used in these patients with close monitoring to minimize poor outcomes. Clinical assessment of kidney function involves a thorough history and physical examination, with supplementary blood and radiological investigations.     

EEG spectral dynamics during discrimination of auditory and visual targets

This study measured the changes in the spectrum of the EEG (electroencephalogram) and in the event-related potentials (ERPs) as subjects detected an improbable target in a train of standard stimuli. The intent was to determine how these measurements are related, and to what extent the ERPs might represent phase-locked changes in EEG rhythms. The experimental manipulations were the stimulus modality (auditory or visual), the discriminability of the target, and the presence or absence of distraction. The ERPs showed sensory-evoked potentials that were specific to the modality and a target-evoked P300 wave that was later in the visual modality than in the auditory, and later and smaller when the discrimination was more difficult. The averaged EEG spectrograms showed that targets increased the frontal theta activity, decreased posterior and central alpha and beta activity, and decreased the central gamma activity. The scalp topography of the changes in the alpha and beta activity indicated a posterior desynchronization specific for the visual task and occurring with both targets and standards and a more widespread desynchronization for targets in either modality. Increased phase synchronization occurred during the event-related potentials, but modeling demonstrated that this can be seen when an evoked potential waveform is simply added to the background EEG. However, subtracting the spectrogram of the average ERP from the average spectrogram of the single trials indicated that phase-resetting of the background EEG rhythms can occur during the ERP. The idea that the ERPs and the EEG rhythms "share generators" can explain these findings.     

Multiple frontal systems controlling response speed

This study evaluated a model of attention that postulates several distinct component processes, each mediated by specific neural systems in the human frontal lobes. A series of reaction time (RT) tests (simple, choice, and prepare) examined the hypothesis that different attentional processes are related to distinct regions within the frontal lobes. These tests were given to 38 patients with frontal lesions and 38 age-matched control subjects. Lesions were localized both by general regions (superior medial, inferior medial, left and right lateral) and by individual architectonic areas. Lesions in the superior medial (SM) frontal lobes, particularly involving areas 24 and 32 on the right, were associated with slow RT in all tests and with failure to decrease RT after a warning signal. Lesions in the right lateral (RL) frontal lobe, centred in area 9/46v, prevented the decrease in RT with increasing foreperiod that was seen in normal subjects and in patients with lesions elsewhere in the frontal lobes. The ability to energize a response for rapid RT, either generally or specifically following a warning stimulus, is sensitive to lesions of the right SM. Monitoring of stimulus occurrence and response behaviour in order to enhance the speed of response to upcoming stimuli is sensitive to RL lesions.