Flow cytometric characterization and clinical outcome of CD4+ T-cell lymphoma in dogs: 67 cases.

BackgroundCanine T-cell lymphoma (TCL) is conventionally considered an aggressive disease, but some forms are histologically and clinically indolent. CD4 TCL is reported to be the most common subtype of TCL. We assessed flow cytometric characteristics, histologic features when available, and clinical outcomes of CD4+ TCL to determine if flow cytometry can be used to subclassify this group of lymphomas.ObjectiveTo test the hypothesis that canine CD4+ T-cell lymphoma (TCL) is a homogeneous group of lymphomas with an aggressive clinical course.AnimalsSixty-seven dogs diagnosed with CD4+ TCL by flow cytometry and treated at 1 of 3 oncology referral clinics.MethodsRetrospective multivariable analysis of outcome in canine CD4+ TCL including patient characteristics, treatment, and flow cytometric features.ResultsThe majority of CD4+ TCL were CD45+, expressed low class II MHC, and exhibited an aggressive clinical course independent of treatment regimen (median survival, 159 days). Histologically, CD4+ TCL were classified as lymphoblastic or peripheral T cell. Size of the neoplastic lymphocytes had a modest effect on both PFI and survival in this group. A small number of CD4+ TCL were CD45- and class II MHC high, and exhibited an apparently more indolent clinical course (median survival not yet reached).Conclusions and clinical importanceAlthough the majority of CD4+ TCL in dogs had uniform clinical and flow cytometric features and an aggressive clinical course, a subset had a unique immunophenotype that predicts significantly longer survival. This finding strengthens the utility of flow cytometry to aid in the stratification of canine lymphoma

Phase transitions in K₁₋x(NH₄)xH₂PO₄ single crystals

An apparatus for growing single crystals from aqueous solution by the slow evaporation method was constructed. Mixed crystals of K₁₋x (NH₄) x H₂PO₄ (KADP) with (NH₄)H₂PO₄ (ADP) fractions of 0.021 and 0.12 were successfully grown. Their composition was determined by means of the x-ray powder diffraction method. This analysis also suggests that those crystals are a mixture of two phases even at room temperature. The details of the structure of the additional phase could not be determined. -- The dielectric constant ε of the mixed crystals as well as pure KH₂PO₄ (KDP) was measured along the polar axis in the temperature range from 20 K to 300 K. The frequency range of the applied electric field was from 100 Hz to 10 MHz. The data were analyzed by means of the standard Landau theory of phase transitions with coupling terms reflecting the interaction between the electric and elastic degrees of freedom. The temperature dependence of ε follows a typical Curie-Weiss behavior in the range of approximately 30 K above Tc for all crystals studied. The value of the critical temperature decreases with increasing ammonium ion content in agreement with previously published results. The analysis of the frequency dependence of the dielectric susceptibility clearly indicates the existence of two dispersion processes: resonant and relaxational. The former is attributed to the piezoelectric activity of all the crystals studied. The latter is the result of the response of the permanent dipole moments present in ferroelectric crystals to the applied electric field. In the case of mixed crystals the relaxational dispersion is characterized by a distribution of relaxation times. Its mean relaxation time as well as its width increases with decreasing T. This is a typical behavior for mixed crystals for which the two end members of the solid solution in their pure form undergo ferroelectric and antiferroelectric phase transitions, respectively. This behavior is a result of competing long range interactions. -- New results for the temperature dependence of the CE/66 and CE/11 elastic constants of the crystals were obtained by means of the Brillouin spectroscopy. In addition to that the soft acoustic mode behaviour was also studied by means of the piezoelectric resonance method. Both of them gave qualitatively similar results which also correlate very well with the dielectric measurements. All major differences could be explained by assuming an inhomogeneous distribution of the ammonium ions in the KDP matrix. The Brillouin results were also analyzed by means of the Landau theory. It approximates very well the temperature dependence of the CE/66 elastic constant in the paraelectric phase region for all crystals studied. The measured values of CE/66 below Tc are in general lower than those predicted by the model. The greater the NH₄ content the bigger the discrepancy. -- Moreover, the analysis of the temperature dependence of the CE/66 elastic constant indicates the existence of a new phase in the mixed materials. Its stability region broadens with increasing NH₄ concentration. For the crystal with the highest ammonium concentration studied it coincides with the dielectric plateau region between 70 K and 55 K. At temperatures below the plateau region the K₀.₈₈(NH₄)₀.₁₂H₂PO₄ sample scattered the laser light very strongly. This is most likely caused by defects and sample inhomogeneities but annealing the sample for two hours at 400 K does not result in any significant change

STUDIA UNIWERSYTECKIE MŁODZIEŻY JAKO DROGA KSZTAŁTOWANIA JE J DOJRZAŁOŚCI SPOŁECZNEJ

Bromberek Benon, Studia tmiwersyteckie młodzieży jako droga kształtowania jej dojrzałości społecznej (University studies of young people as a way of formation of their social maturity), „Neodidagmata” XX, Poznań 1991, Adam Mickiewicz University Press, pp. 81-99. ISBN 83-232-0302-4. ISSN 0077-653X. Received: June 1986. The author of this article makes an attempt at answering the following question, on the basis of results of studies conducted with application of various techniques on a sample of 2253 students of the University of Poznań: what was demographic make-up in the whole cycle of five-years studies; motives of undertaking a continuation of university studies; the level of preparation for university studies represented by the interviewed young people and the expectations of these people which they manifested; the course of studies, thus the results they obtained during their studies (interpreted both quantitatively and qualitatively); plans for the future life and their attitude to the selected values. The analysis conducted and the conclusions which are its results show the young students from the University of Poznań (in the years 1976-1980) within an aspect of their demographic and psychosocial features pointing to their dynamics during the course of studies and significance in the process of studies and socialization

Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy

BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL. Blood was drawn on day zero and 14 days post treatment. Lymphocyte proliferation was quantified by (3)H-thymidine uptake assay (results expressed as counts per minute). The mRNA expression was studied by RT-PCR and serum levels of cytokines were quantified by ELISA and a cytokine bead array system. RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone. The mRNA expression of proinflammatory cytokines TNF-α (p < 0.05), cyclins G (p < 0.01) and E (p < 05) were decreased, and of TGF-β (p < 0.03) and p21 (p < 0.05) were increased in patients treated with this combination. Circulating levels of IFN-γ (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-β (p < 0.04) was observed in patients treated with TAC and SRL combination. CONCLUSION: These novel findings demonstrate that addition of SRL to TAC therapy enhances immuno modulation and causes increased immunosuppression providing a rationale for this concomitant therapy

In a Bilingual Mood: Mood Affects Lexico-Semantic Processing Differently in Native and Non-Native Languages

Positive and negative moods tend to have differential effects on lexico-semantic processing in the native language (L1). Though accumulating evidence points to dampened sensitivity to affective stimuli in the non-native language (L2), little is known about the effects of positive and negative moods on L2 processing. Here, we show that lexico-semantic processing is differently affected by positive and negative moods only in L1. Unbalanced Polish–English bilinguals made meaningfulness judgments on L1 and L2 sentences during two EEG recording sessions featuring either positive- or negative-mood-inducing films. We observed a reduced N1 (lexical processing) for negative compared to positive mood in L2 only, a reduced N2 (lexico-semantic processing) in negative compared to positive mood in L1 only, a reduced N400 (lexico-semantic processing) for meaningless compared to meaningful L1 sentences in positive mood only, and an enhanced late positive complex (semantic integration and re-analysis) for L2 compared to L1 meaningful sentence in negative mood only. Altogether, these results suggest that positive and negative moods affect lexical, lexico-semantic, and semantic processing differently in L1 and L2. Our observations are consistent with previous accounts of mood-dependent processing and emotion down-regulation observed in bilinguals

Controlling stimulus ambiguity reduces spurious creative ideation variance in a cyclic adaptation of the alternative uses task

In the alternative uses task (AUT), a well-established creativity assessment, participants propose alternative uses for common items (e.g., a brick) within a 2–3 min timeframe. While idea evaluation is likely involved, the emphasis is strongly on idea generation. Here, we test the value of presenting a word overlapping an image compared to a word only prompt, and we introduce a cyclic adaptation of the AUT explicitly calling on participants to choose their best idea. In Experiment 1, as compared to word only, word + image prompts increased idea fluency but reduced idea originality and variability within a group of native Polish speakers. Thus, word + image prompts improve AUT baselining. In Experiment 2, different participants produced as many ideas as possible within two minutes (List) or their single best idea at the end of each of three 30 s ideation cycles (Cycle). Although originality did not differ between List and Cycle overall, the first three ideas in List were rated as less creative than the ideas in Cycle. Overall, we conclude that using disambiguating images reduces spurious interindividual variability in the AUT while introducing idea evaluation in the task allows us to assess creativity beyond idea generation

Brain potentials reveal reduced sensitivity to negative content during second language production

Prior research suggests that bilinguals show reduced sensitivity to negative content when operating in the second language (L2). The available evidence, however, is limited to language comprehension. We tested the production of emotional words in Polish (L1)–English (L2) bilinguals in two EEG studies that manipulated emotional cueing. In Experiment 1 (neutral context), white or black circles indicated whether participants should read aloud (shadow) or translate a subsequently presented word. N400 amplitudes were selectively reduced for negative L2 words regardless of the task. In Experiment 2 (emotional context), we used black or white emojis, either sad or neutral, as cues. The previous interaction between word valence and language of operation vanished, but late positive potential amplitudes elicited by negative words were larger for translation from L2 to L1 (i.e., production in Polish) than L1 to L2. These results validate and extend to production previous findings of attenuated emotional response in L2 comprehension

Exercise-induced pulmonary haemorrhage impairs racing performance in thoroughbred racehorses

REASONS FOR PERFORMING STUDY : Exercise-induced pulmonary haemorrhage (EIPH) occurs commonly in Thoroughbred racehorses worldwide. While EIPH is believed to be an important cause of impaired performance in these horses, there is limited evidence from sufficiently powered studies to evaluate this association. OBJECTIVES : To evaluate whether EIPH is associated with finishing position, distance finished behind race winners and differences in race earning among Thoroughbred horses racing in South Africa. STUDY DESIGN : Prospective cross-sectional study. METHODS : One thousand Thoroughbred horses racing in South Africa were enrolled prior to a single race and underwent tracheobronchoscopic examination within 2 h of racing. Three observers, blinded to the horses’ identity and race performance, independently evaluated EIPH occurrence and severity using video recordings of the examination. Data were analysed using multivariable logistic and linear regression while controlling for important horse and race factors as potential confounding variables. RESULTS : Overall, 68% of horses had evidence of EIPH (grade ≥1). Horses without evidence of EIPH (severity grade 0), when compared with horses with any evidence of EIPH (grade ≥1), were >2 times more likely to win races (odds ratio = 2.3; 95% confidence interval 1.4–3.7; P = 0.001), finished an average of one length ahead of horses with EIPH (P = 0.03), and were 2.5 times more likely to be in the highest decile in race earnings (odds ratio = 2.5, 95% CI 1.5–4.1, P<0.001). However, no association was identified regarding finishing in the top 3 positions or earning money when analysed as a continuous variable or analysed as any winnings vs. none. CONCLUSIONS : Exercise-induced pulmonary haemorrhage was associated with impaired performance in Thoroughbred racehorses not medicated with furosemide and not using nasal dilator strips. These findings provide strong corroboration of previous research indicating that the occurrence of EIPH has a major impact on the ability of Thoroughbred racehorses to compete successfully as elite athletes.Equine Research Centre, Faculty of Veterinary Science, University of Pretoria, and by the Thoroughbred Racing Trust of South Africa.http://onlinelibrary.wiley.com/journal/10.1001/(ISSN)2042-33062016-05-31hb201

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations. GBA1 is a gene of high clinical and therapeutic interest. Damaging biallelic protein-coding variants cause Gaucher disease and monoallelic variants confer risk for PD and dementia with Lewy bodies, likely by reducing the function of glucocerebrosidase. Interestingly, the African ancestry-specific GBA1 risk variant is a noncoding variant, suggesting a different mechanism of action. Using full-length RNA transcript sequencing, we identified partial intron 8 expression in risk variant carriers (G) but not in nonvariant carriers (T). Antibodies targeting the N terminus of glucocerebrosidase showed that this intron-retained isoform is likely not protein coding and subsequent proteomics did not identify a shorter protein isoform, suggesting that the disease mechanism is RNA based. Clustered regularly interspaced short palindromic repeats editing of the reported index variant ( rs3115534 ) revealed that this is the sequence alteration responsible for driving the production of these transcripts containing intron 8. Follow-up analysis of this variant showed that it is in a key intronic branchpoint sequence and, therefore, has important implications in splicing and disease. In addition, when measuring glucocerebrosidase activity, we identified a dose-dependent reduction in risk variant carriers. Overall, we report the functional effect of a GBA1 noncoding risk variant, which acts by interfering with the splicing of functional GBA1 transcripts, resulting in reduced protein levels and reduced glucocerebrosidase activity. This understanding reveals a potential therapeutic target in an underserved and underrepresented population