Role of IL-2 in rat fetal thymocyte development

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR- P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.      

Inflammatory mediators in late antigen-induced rhinitis

To investigate the mechanisms responsible for the late-phase response in patients with allergies, we measured four biochemical mediators (histamine, tosyl-L-arginine methyl ester [TAME]-esterase, kinin, and prostaglandin D2) in nasal secretions after nasal challenge with pollen antigen in 12 patients with allergy. Nine patients had an immediate response and a recurrence of symptoms 3 to 11 hours after challenge. The clinical symptoms during recurrence were accompanied by a second increase in levels of histamine, TAME--esterase, and kinin over base-line values, although kinin levels were lower than during the immediate response. In contrast, although the levels of prostaglandin D2 were significantly increased during the immediate response, they did not increase above base line during the late response. Rechallenge with allergen 11 hours after the initial provocation, however, was associated with reappearance of all four biochemical mediators, including prostaglandin D2. We conclude that the late response to nasal challenge with allergen is accompanied by a second increase in the concentrations of histamine and TAME--esterase but differs from the immediate response in the lack of prostaglandin D2 production and in the amount of kinin generated. Since histamine is released only by mast cells and basophils and prostaglandin D2 is not produced by basophils, we suggest that these cells are partly responsible for the late-phase response.     

Graded modality-specific specialisation in semantics: A computational account of optic aphasia

A long-standing debate regarding the representation of semantic knowledge is whether such knowledge is represented in a single, amodal system or whether it is organised into multiple subsystems based on modality of input or type of information. The current paper presents a distributed connectionist model of semantics that constitutes a middle ground between these unitary- versus multiple-semantics accounts. In the model, semantic representations develop under the pressure of learning to mediate between multiple input and output modalities in performing various tasks. The system has a topographic bias on learning that favours short connections, leading to a graded degree of modality-specific functional specialisation within semantics. The model is applied to the specific empirical phenomena of optic aphasia--a neuropsychological disorder in which patients exhibit a selective deficit in naming visually presented objects that is not attributable to more generalised impairments in object recognition (visual agnosia) or naming (anomia). As a result of the topographic bias in the model, as well as the relative degrees of systematicity among tasks, damage to connections from vision to regions of semantics near phonology impairs visual object naming far more than visual gesturing or tactile naming, as observed in optic aphasia. Moreover, as in optic aphasia, the system is better at generating the name of an action associated with an object than at generating the name of the object itself, because action naming receives interactive support from the activation of action representations. The ability of the model to account for the pattern of performance observed in optic aphasia across the full range of severity of impairment provides support for the claim that semantic representations exhibit graded functional specialisation rather than being entirely amodal or modality-specific.     

Assessment of right ventricular systolic function using tricuspid annular-plane systolic excursion in Nigerians with systemic hypertension

Aim

Right ventricular (RV) systolic function in patients with hypertensive heart disease (HHD) is not well characterised. The primary aim of this study was to assess the systolic function of the right ventricle in patients with HHD using tricuspid annular-plane systolic excursion (TAPSE).

Methods

The study was cross-sectional in design and carried out in Kano, Nigeria. Patients were recruited if they had HHD on echocardiography and were at least 15 years of age. Patients with other cardiac pathologies such as ischaemic and valvular heart diseases were excluded. Patients were considered to have abnormal RV systolic function if they had reduced values of TAPSE (< 15 mm). A p-value of < 0.05 was considered statistically significant.

Results

A total of 186 patients were serially recruited over seven months. Of these, 131 (70.4%) had normal RV systolic function (group 1) and 55 patients (29.6%) had abnormal function (group 2). Group 2 patients were older (p = 0.002) and had a higher prevalence of peripheral oedema (p = 0.002), moderate to severe dyspnoea, higher heart rate and lower left ventricular ejection fraction (p < 0.001). Atrial arrhythmias were also more prevalent among group 2 patients (p < 0.05). The best correlate to TAPSE was the septal mitral annularplane systolic excursion (r = +0.541, p < 0.001). Several variables such as age predicted the presence of reduced TAPSE.

Conclusion

The study found that almost one-third of patients with HHD in Kano had RV systolic dysfunction as defined by reduced TAPSE, and these patients had a greater prevalence of factors associated with morbidity and mortality.     

Serum concentrations of oestradiol-17beta, progesterone, relaxin and chorionic gonadotrophin during blastocyst implantation in natural pregnancy cycle and in embryo transfer cycle in the rhesus monkey

The present study was undertaken to assess the temporal association between the profiles of serum concentrations of oestradiol-17beta, progesterone, chorionic gonadotrophin (CG) and relaxin in pregnancies established naturally, and after embryo transfer, as well as in failed pregnancies in rhesus monkeys. In naturally mated cycles (group 1) a conception rate of 75% was obtained. In group 1, the mean day of CG detection in serum was 11.5 +/- 1.9 day post-ovulation, and for relaxin, 9.0 +/- 2.5 day post-ovulation. In group 2, embryo transfer to synchronous, non-mated surrogate recipients was performed; seven embryo transfer cycles yielded three pregnancies which were allowed to continue to term and normal infants were delivered. In embryo transfer cycles the mean day of CG detection was 14.8 +/- 1.8 day post- ovulation, and for relaxin, 11.4 +/- 2.6 day post-ovulation. A delay of about 3 days was observed in the appearance in circulation of CG (P < 0.05) and also of relaxin (P < 0.05) between natural mated and embryo transfer conception cycles. Significant differences (P < 0.05 for progesterone and P < 0.03 for oestradiol) were obtained for the areas under the curves for progesterone and oestradiol between days 12 and 16 in conception cycles compared with failed pregnancies. These data provide the first observation of the normal hormonal signals associated with maternal recognition of transferred embryos during the peri- implantation period, and suggest that the use of such an experimental primate embryo transfer model may help to elucidate components of maternal and embryonic signal-response mechanisms during embryo implantation.      

<Emphasis Type=Italic>CYP2C19</Emphasis> and <Emphasis Type=Italic>ABCB1</Emphasis>gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background  

Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.