Serotyping for homotransplantation V. Evaluation of a matching scheme

An attempt was made to determine whether 36 long-term kidney homograft recipients and their donors were compatible for 7 major leukocyte groups. It was found that 21 of these recipients were surviving 2 to 3 years in spite of incompatibility for 1 or 2 major leukocyte antigens. Survival of mismatched grafts does not itself indicate that the antigens being measured are not transplantation antigens, for it was shown that the 15 recipients with no groups of mismatch were clinically superior to those with group incompatibilities. Moreover, histopathologic scores given to biopsy specimens taken 2 to 3 years after transplantation were significantly correlated with the number of group mismatches. Because the leukocyte groups were determined by cytotoxicity reactions of peripheral blood lymphocytes, the results may have been influenced considerably by chimerism in chronically dialyzed uremic patients or change in lymphocyte antigenicity or susceptibility to lysis upon prolonged immunosuppressive treatment. Although the possibility of these complications could not be ruled out in all instances, it was shown that 52 dialyzed uremic patients and 49 patients who had been treated with immunosuppression for over 1 year did not possess more or less antigens than a random population of normal individuals. It is concluded that: (1) the major leukocyte antigens are histocompatibility antigens, and (2) since survival can be attained at times despite mismatches for these groups, the antigens are of intermediate strength and kidney homograft rejection may occur if excessive numbers of antigens are incompatible or if particular combinations of antigens are mismatched. © 1966 by The Williams and Wilkins Co

Factors determining short- and long-term survival after orthotopic liver homotransplantation in the dog

Without azathioprine therapy, the operative risk with orthotopic liver transplantation is small. Twenty-two of 23 animals survived 2 days or more, and 19 for 6 days or longer. All eventually died of rejection within 10 days. Changes in homograft histology and function were similar to those previously reported, with cellular infiltration and hepatocyte necrosis which was heavily concentrated in the centrilobular areas. In individual experiments, there was little evidence of immunologically induced segmental hepatic arterial or portal venous occlusion; hepatocyte loss was homogeneous, and fibrinoid vascular lesions were uncommon. There was, however, some evidence of damage to the sinusoidal endothelium by adherent mononuclear cells. The changing character of the mononuclear infiltration of the homograft was reflected by widespread proliferation of similar cells in the host lymphoid tissue. Specific changes in other host organs were not noted. Some of the biochemical and histologic alterations caused by unmodified rejection can also be produced by azathioprine. In 18 nontransplanted dogs, acute rises in SGOT, SGPT, and alkaline phosphatase, unaccompanied by hyperbilirubinemia, were noted within a few days after beginning administration of this agent. Although these abnormalities tended to regress within the 40 day period of observation, more than two thirds of the livers showed histologic evidence of centrilobular hepatocyte damage or necrosis-often with intrahepatic cholestasis, but always without mononuclear cell infiltration. The hepatotoxicity was not prevented by methionine. Weight loss and progressive anemia also occurred. Lymphoid tissue was depleted. The mortality from the toxicity study was 33 percent. The use of azathioprine to mitigate rejection increased the early mortality after homotransplantation, 32 of 116 dogs dying within the first week (28 percent), most commonly of pulmonary complications. The 84 animals living longer than 7 days had a greatly potentiated homograft survival, exceeding 25 days in 44 dogs, and 50 days in 24. Fifteen animals are still alive from 62 to 324 days postoperatively. Six dogs had all drugs stopped after 116 to 123 days. Only 1 has had a clinically evident late rejection and 5 are still alive from 63 to 204 days later. Three of these animals had repeat biopsies 77 to 182 days after cessation of therapy; one homograft which was normal at 4 months remained so 6 months later, another had an improved histologic appearance, and the third had deteriorated. The longest mean survival was in those animals receiving adjuvant therapy with L-methionine or S35-methionine, but the variability of the results was so great that a statistically significant advantage of these agents could not be demonstrated. Soon after operation red cell survival was decreased, but in chronic survivors there was no evidence of a grafthost reaction. There was great variability in the vigor of rejection, ranging from the uncontrollable (29 percent) to the clinically undetectable (23 percent). Most of the animals (49 percent) had some biochemical evidence of rejection which proved to be spontaneously reversible, to a greater or lesser degree, since intensification of immunosuppressive therapy was not required. These findings correlate well with the histologic studies. In virtually all animals, azathioprine delayed the onset of rejection but in those dying in the second and third postoperative weeks, the pathologic stigmas of rejection were very similar to the untreated controls. As in the untreated animals, the number of proliferating large pyroninophilic cells in the host's lymphoid tissues was roughly proportional to the number of mononuclear cells invading the homograft liver. After this time, the predominant histologic features in most animals were those of repair and regeneration, with either absent or relatively minor degrees or continuing destruction. Since the major rejection damage was centrizonal, the healing was most prominent in these areas with interconecting fibrosis around the central veins, centrilobular bile canalicular dilatation and cholestasis, and pseudolobule formation. In some of the homografts, increased connective tissue was also present in the portal tracts, but in others including the longest survivor there were no residual abnormalities whatever. In azathioprine-treated animals, damage to the vessels in the homograft portal tracts was found in only one liver. With electron microscopy there was some evidence of damage to the sinusoidal endothelium by adherent mononuclear cells, a finding which could be analogous to that described by Kountz and co-workers11 in the peritubular capillaries of renal homografts. If immunologically mediated hemodynamic alterations play an important role in liver homograft rejection by interrupting the blood supply to the hepatocytes, it seems most likely that they occur at this intrasinusoidal capillary level rather than in the larger vessels. © 1965

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception

The Hubbard model within the equations of motion approach

The Hubbard model has a special role in Condensed Matter Theory as it is considered as the simplest Hamiltonian model one can write in order to describe anomalous physical properties of some class of real materials. Unfortunately, this model is not exactly solved except for some limits and therefore one should resort to analytical methods, like the Equations of Motion Approach, or to numerical techniques in order to attain a description of its relevant features in the whole range of physical parameters (interaction, filling and temperature). In this manuscript, the Composite Operator Method, which exploits the above mentioned analytical technique, is presented and systematically applied in order to get information about the behavior of all relevant properties of the model (local, thermodynamic, single- and two- particle ones) in comparison with many other analytical techniques, the above cited known limits and numerical simulations. Within this approach, the Hubbard model is shown to be also capable to describe some anomalous behaviors of the cuprate superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference

Molecular Longitudinal Tracking of Mycobacterium abscessus spp. during Chronic Infection of the Human Lung

<div><p>The <i>Mycobacterium abscessus</i> complex is an emerging cause of chronic pulmonary infection in patients with underlying lung disease. The <i>M. abscessus</i> complex is regarded as an environmental pathogen but its molecular adaptation to the human lung during long-term infection is poorly understood. Here we carried out a longitudinal molecular epidemiological analysis of 178 <i>M. abscessus</i> spp. isolates obtained from 10 cystic fibrosis (CF) and 2 non CF patients over a 13 year period. Multi-locus sequence and molecular typing analysis revealed that 11 of 12 patients were persistently colonized with the same genotype during the course of the infection while replacement of a <i>M. abscessus sensu stricto</i> strain with a <i>Mycobacterium massiliense</i> strain was observed for a single patient. Of note, several patients including a pair of siblings were colonized with closely-related strains consistent with intra-familial transmission or a common infection reservoir. In general, a switch from smooth to rough colony morphology was observed during the course of long-term infection, which in some cases correlated with an increasing severity of clinical symptoms. To examine evolution during long-term infection of the CF lung we compared the genome sequences of 6 sequential isolates of <i>Mycobacterium bolletii</i> obtained from a single patient over an 11 year period, revealing a heterogeneous clonal infecting population with mutations in regulators controlling the expression of virulence factors and complex lipids. Taken together, these data provide new insights into the epidemiology of <i>M. abscessus</i> spp. during long-term infection of the CF lung, and the molecular transition from saprophytic organism to human pathogen.</p></div

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Electrophysiological dynamics of Chinese phonology during visual word recognition in Chinese-English bilinguals

Silent word reading leads to the activation of orthographic (spelling), meaning, as well as phonological (sound) information. For bilinguals, native language information can also be activated automatically when they read words in their second language. For example, when Chinese-English bilinguals read words in their second language (English), the phonology of the Chinese translations is automatically activated. Chinese phonology, however, consists of consonants and vowels (segmental) and tonal information. To what extent these two aspects of Chinese phonology are activated is yet unclear. Here, we used behavioural measures, event-related potentials and oscillatory EEG to investigate Chinese segmental and tonal activation during word recognition. Evidence of Chinese segmental activation was found when bilinguals read English words (faster responses, reduced N400, gamma-band power reduction) and when they read Chinese words (increased LPC, gamma-band power reduction). In contrast, evidence for Chinese tonal activation was only found when bilinguals read Chinese words (gamma-band power increase). Together, our converging behavioural and electrophysiological evidence indicates that Chinese segmental information is activated during English word reading, whereas both segmental and tonal information are activated during Chinese word reading. Importantly, gamma-band oscillations are modulated differently by tonal and segmental activation, suggesting independent processing of Chinese tones and segments

Politeness and compassion differentially predict adherence to fairness norms and interventions to norm violations in economic games

Adherence to norms and interventions to norm violations are two important forms of social behaviour modelled in economic games. While both appear to serve a prosocial function, they may represent separate mechanisms corresponding with distinct emotional and psychological antecedents, and thus may be predicted by different personality traits. In this study, we compared adherence to fairness norms in the dictator game with responses to violations of the same norms in third-party punishment and recompensation games with respect to prosocial traits from the Big Five and HEXACO models of personality. The results revealed a pattern of differential relations between prosocial traits and game behaviours. While norm adherence in the dictator game was driven by traits reflecting good manners and non-aggression (i.e., the politeness aspect of Big Five agreeableness and HEXACO honesty-humility), third-party recompensation of victims—and to a lesser extent, punishment of offenders—was uniquely driven by traits reflecting emotional concern for others (the compassion aspect of Big Five agreeableness). These findings demonstrate the discriminant validity between similar prosocial constructs and highlight the different prosocial motivations underlying economic game behaviours