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We first prove that a Riemannian manifold ( M , g ) (M,g) with globally constant additive Weyl invariants is locally homogeneous. Then we use this result to show that a manifold ( M , g ) (M,g) whose Laplacian commutes with all invariant differential operators is a locally homogeneous space.

La apolipoproteína (apo) AI es el constituyente proteico principal de las lipoproteínas de alta densidad (HDL) plasmáticas teniendo una función primordial en el transporte reverso de colesterol, sin embargo, y en el otro extremo del espectro bioquímico, las amiloidosis debidas a apoAI están asociadas al plegamiento anómalo y depósitos insolubles de la proteína causando serio daño tisular y falla orgánica dependiendo de la mutación. La primera forma de amiloidosis apoAI que se describió es la provocada por apoAI Arg26Gly, induciendo neuropatía periférica y muerte por insuficiencia renal. El mecanismo que desencadena la formación de estos depósitos y el daño tisular no es claro, sugiriendo en base a datos nuestros y de otros grupos dos posibilidades; 1) que la proteína en su conformación amiloidogénica es la responsable de activar señales pro-inflamatorias y 2) ambientes inflamatorios son los responsables del procesamiento patológico de apoAI., Facultad de Ciencias Médicas

Cellular membranes are heterogeneous in composition, and the prevailing theory holds that the structures responsible for this heterogeneity in vivo are small structures (10-200 nm), sterol- and sphingolipid-enriched, of different sizes, highly dynamic denominated rafts. Rafts are postulated to be platforms, which by sequestering different membrane components can compartmentalize cellular processes and regulate signaling pathways. Despite an enormous effort in this area, the existence of these domains is still under debate due to the characteristics of the structures itself: small in size and highly mobile, which from the technical point of view implies using techniques with high spatial and temporal resolution. In this report we measured rapid fluctuations of the normalized ratio of the emission intensity at two wavelengths of Laurdan, a membrane fluorescent dye sensitive to local membrane packing. We observed generalized polarization fluctuations in the plasma membrane of intact rabbit erythrocytes and Chinese hamster ovary cells that can be explained by the existence of tightly packed micro-domains moving in a more fluid background phase. These structures, which display different lipid packing, have different sizes; they are found in the same cell and in the entire cell population. The small size and characteristic high lipid packing indicate that these micro-domains have properties that have been proposed for lipid rafts., Instituto de Investigaciones Bioquímicas de La Plata

Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe atherosclerosis. Results showed that both variants share common structural properties including decreased stability compared to Wt apoA-I and a more flexible structure that gives rise to formation of partially folded states. Interestingly, however, distinct features appear to determine their pathogenic mechanisms. ApoA-ILys107-0 has an increased propensity to aggregate at physiological pH and in a pro-inflammatory microenvironment than Wt apoA-I, whereas apoA-IGly26Arg elicited macrophage activation, thus stimulating local chronic inflammation. Our results strongly suggest that some natural mutations in apoA-I variants elicit protein tendency to aggregate, but in addition the specific interaction of different variants with macrophages may contribute to cellular stress and toxicity in hereditary amyloidosis., Facultad de Ciencias Médicas

La ricerca si sofferma sulle relazioni tra organi politici a cui è attribuito il ruolo di rappresentanza, di mediazione di interessi e di indirizzo e controllo nei confronti di chi amministra e organi amministrativi a cui sono attribuiti i poteri gestori relativi alla traduzione delle finalità dell’azienda pubblica in obiettivi operativi, alla scelta delle combinazioni dei fattori produttivi e al coordinamento dell’organismo personale. Con l’emanazione del D.Lgs. 150/09 si ricerca una maggiore responsabilizzazione della dirigenza ed il miglioramento delle prestazioni e si favorisce l’introduzione di un sistema premiante che rapporti la componente retributiva di risultato alla quantità e alla qualità delle prestazioni piuttosto che un sistema prevalentemente sanzionatorio. In particolare l’obiettivo della ricerca è quello di verificare se, negli enti locali, il Decreto Legislativo 150/09 ha prodotto effetti nell’ambito del rapporto tra organi politici e organi amministrativi.

Numerosos estudios sugieren que las vías de señalización y por ende la funcionalidad celular dependen de la organización de dominios en la membrana, que a su vez está determinada por la composición lipídica de la misma. El colesterol (Col) interviene en la regulación de la fluidez al particionar de manera selectiva en dominios específicos de la membrana, y se ha demostrado que su homeostasis es crucial para la viabilidad celular. Además, se sabe que el exceso de Col puede resultar citotóxico. Este lípido no puede ser degradado o utilizado como combustible, por lo que su exceso debe ser removido por aceptores o almacenado en compartimientos intracelulares. Las lipoproteínas de alta densidad (HDL) y en particular su apolipoproteína mayoritaria, la apoA-I, cumplen un rol fundamental en el transporte reverso del Col, que consiste en transportar el excedente desde los tejidos periféricos hacia el hígado para su eliminación en forma de sales biliares, o para ser redirigido desde los hepatocitos hacia los tejidos esteroidogénicos.

A fin de poder llevar a cabo las distintas funciones biológicas, es esencial que las proteínas conserven su conformación nativa. Algunas proteínas son estructuralmente inestables, y entonces pequeños cambios en el microambiente en el que se encuentran pueden ser clave para alterar el equilibrio hacia una conformación patológica. Las amiloidosis se caracterizan por la presencia de depósitos extracelulares de proteínas que adoptan estructura fibrilar. La apolipoproteína A-I humana no está normalmente asociada a esta patología, aunque fueron detectados agregados de la misma con la secuencia nativa en placas ateroscleróticas seniles. A pesar de ser frecuente, se conoce relativamente poco de la patogénesis y significancia de la agregación patológica de la apoA-I.

A fin de poder llevar a cabo las distintas funciones biológicas, es esencial que las proteínas conserven su conformación nativa. Algunas proteínas son estructuralmente inestables, y entonces pequeños cambios en el microambiente en el que se encuentran pueden ser clave para alterar el equilibrio hacia una conformación patológica. Las amiloidosis se caracterizan por la presencia de depósitos extracelulares de proteínas que adoptan estructura fibrilar. La apolipoproteína A-I humana no está normalmente asociada a esta patología, aunque fueron detectados agregados de la misma con la secuencia nativa en placas ateroscleróticas seniles. A pesar de ser frecuente, se conoce relativamente poco de la patogénesis y significancia de la agregación patológica de la apoA-I., Facultad de Ciencias Médicas

Numerosos estudios sugieren que las vías de señalización y por ende la funcionalidad celular dependen de la organización de dominios en la membrana, que a su vez está determinada por la composición lipídica de la misma. El colesterol (Col) interviene en la regulación de la fluidez al particionar de manera selectiva en dominios específicos de la membrana, y se ha demostrado que su homeostasis es crucial para la viabilidad celular. Además, se sabe que el exceso de Col puede resultar citotóxico. Este lípido no puede ser degradado o utilizado como combustible, por lo que su exceso debe ser removido por aceptores o almacenado en compartimientos intracelulares. Las lipoproteínas de alta densidad (HDL) y en particular su apolipoproteína mayoritaria, la apoA-I, cumplen un rol fundamental en el transporte reverso del Col, que consiste en transportar el excedente desde los tejidos periféricos hacia el hígado para su eliminación en forma de sales biliares, o para ser redirigido desde los hepatocitos hacia los tejidos esteroidogénicos., Universidad Nacional de La Plata

Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis., Facultad de Ciencias Médicas

Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis.

We prove that it is possible to associate to each infinitesimal model on a Euclidean vector space V a locally homogeneous Riemannian manifold. As an application, we characterize, in the space of the algebraic curvature tensors on V, the orbits which can occur for locally homogeneous Riemannian manifolds.

The relationship between social and life conditions on the one hand and the presence of depression on the other was analysed in a population of institutionalized elderly subjects. The influence of health status on psychological condition and the presence of endocrinological changes in hormones associated with chronic stress were investigated in depressed elderly people. One hundred and thirty-seven elderly people (mean age 82.4 ± 7.7) were studied and 60 of them underwent a thorough psychiatric examination. The overall prevalence of depression-not previously diagnosed in all but one patient—was 76.6%; 23.3% were severely depressed. Neither gender nor the presence of organic disease differentiated the depressed from the non-depressed. The only two life and social variables associated with depression among the many items analysed were the length of institutionalization and the period of retirement. It was observed that a higher cortisol level in the severely depressed group showed a positive correlation between plasma (and urine) cortisol level and Hamilton Rating Scale for Depression (HRSD) score. A relationship between immunological impairment and depression in old age has been reported elsewhere; it is suggested that these findings could be partly mediated by the observed endocrinological changes.

Si bien las amiloidosis severas no suelen ser patologías prevalentes, el plegamiento anómalo de proteínas está involucrado a procesos crónicos de inflamación. Los niveles de apolipoprotein A-I (apoA-I) humana se correlacionan inversamente con el riesgo de sufrir enfermedades cardiovasculares por su participación en el transporte reverso de colesterol; sin embargo, depósitos de la forma nativa de la proteína se encuentran asociados a placas seniles, y algunas mutaciones puntuales inducen en paciente la formación de depósitos asociados a placas ateromatosas o disfunción renal., Facultad de Ciencias Médicas

In this work a physical modelling framework is presented, describing the intelligent, non-local, and anisotropic behaviour of pedestrians. Its phenomenological basics and constitutive elements are detailed, and a qualitative analysis is provided. Within this common framework, two first-order mathematical models, along with related numerical solution techniques, are derived. The models are oriented to specific real world applications: a one-dimensional model of crowd-structure interaction in footbridges and a two-dimensional model of pedestrian flow in an underground station with several obstacles and exits. The noticeable heterogeneity of the applications demonstrates the significance of the physical framework and its versatility in addressing different engineering problems. The results of the simulations point out the key role played by the physiological and psychological features of human perception on the overall crowd dynamics., 26 pages, 17 figures

An excess of intracellular free cholesterol (Chol) is cytotoxic, and its homeostasis is crucial for cell viability. Apolipoprotein A-I (apoA-I) is a highly efficient Chol acceptor because it activates complex cellular pathways that tend to mobilize and export Chol from cellular depots. We hypothesize that membrane composition and/or organization is strongly involved in Chol homeostasis. To test this hypothesis, we constructed a cell line overexpressing stearoyl coenzyme A (CoA) desaturase (SCD cells), which modifies plasma membrane (PM) composition by the enrichment of monounsaturated fatty acids, and determined this effect on membrane properties, cell viability, and Chol homeostasis. PM in SCD cells has a higher ratio of phospholipids to sphingomyelin and is slightly enriched in Chol. These cells showed an increase in the ratio of cholesteryl esters to free Chol; they were more resistant to Chol toxicity, and they exported more caveolin than control cells. The data suggest that cell functionality is preserved by regulating membrane fluidity and Chol exportation and storage.

Aggregates of the amyloid-beta peptide (Abeta) play a central role in the pathogenesis of Alzheimer's disease (AD). Identification of proteins that physiologically bind Abeta and modulate its aggregation and neurotoxicity could lead to the development of novel disease-modifying approaches in AD. By screening a phage display peptide library for high affinity ligands of aggregated Abeta(1-42), we isolated a peptide homologous to a highly conserved amino acid sequence present in the N-terminus of apolipoprotein A-I (apoA-I). We show that purified human apoA-I and Abeta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by Abeta. Significantly, Abeta/apoA-I complexes were also detected in cerebrospinal fluid from AD patients. Interestingly, apoA-I and apoA-I-containing reconstituted high density lipoprotein particles protect hippocampal neuronal cultures from Abeta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates Abeta aggregation and Abeta-induced neuronal damage and that the Abeta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of Abeta toxicity.

We studied the role of a central domain of human apolipoprotein AI (apoAI) in cholesterol mobilization and removal from cells. In order to check different protein conformations, we tested different sized and cholesterol-content reconstituted apoAI particles (rHDL). Meanwhile cholesterol-free discs were active to induce mobilization, only small cholesterol-containing rHDL were active. To test the influence of a central domain in such events, we used two apoAI variants: one, with its central Y helix pair replaced by the C-terminal domain, and the other having a lysine deleted in central region. The helix-swapping variant decrease the cholesterol pool available to acyl-CoA cholesterol acyl transferase and increase mobilization of newly synthesized cholesterol. Instead, the deletion mutant had no effect on both events. We conclude that the central domain of apoAI is involved in cholesterol cell traffic and solubilization, and that a Y-type charge distribution in polar face may be required, as well as a correct helices-polar face orientation.

Renal stone disease often begins by renal colic. In order to manage this event adequately, several goals should be pursued: first, attenuate pain; second, favour progression and spontaneous expulsion of stones; third, prevent from obstructive and infectious complications. All of the aforementioned points pertain to medical management of this disease. Concerning prevention, it is widely agreed that pathogenesis of kidney stones is a consequence of abnormalities in urine environment, leading to a disequilibrium between promoters and inhibitors of crystallization. Therefore, the rationale for therapy is to make urine less conductive to stone formation, by both decreasing state of saturation and increasing inhibitory potential. In only some types of stone-forming salts it is possible to obtain undersaturation with the solid phase. Indeed, uric acid stones can be chemically dissolved by using alkali and allopurinol. To a lesser extent, this also applies to cystine stones, with the use of thiols and alkali. In these subsets, the aforementioned tools are also effective to prevent new stone formation. Much more challenging appears the treatment of calcium containing stones. About 10% of such stones is caused by systemic disorders and, in these cases, the prevention of new stones is successfully accomplished by curing the underlying disease. For instance, parathyroidectomy cures calcium nephrolithiasis in case of hyperparathyroidism. However, the majority of patients with calcium stones are idiopathic stone-formers, in whom metabolic abnormalities often occur, namely, hypercalciuria, hyperoxaluria, hypocitraturia. The correction of these abnormalities by using thiazide diuretics, alkaline citrates, potassium phosphate and bisphosphonates is based on the prevailing metabolic defect. Among the most recent available tools, Oxalobacter Formigenes and probiotics have been proposed to treat primary or secondary hyperoxalurias. In general, the treatment of stone disease reduces its recurrence rate, but only seldom results in stable remission. Anyway, less stones mean reduction of the need for urological procedures and the associated infective or obstructive complications. Of course, medical prevention implies financial efforts, but a careful cost to benefit analysis demonstrates that these are well justified.

A theorem of I. M. Singer [9] states that a Riemannian manifold is locally homogeneous if and only if the Riemannian curvature tensor and its covariant derivatives are the same at each point up to some orderkM + 1.

The occurrence of chronic renal insufficiency was investigated in 171 patients with severe idiopathic calcium stone disease. Ninety healthy subjects matched for age and sex were used as controls. The patients were thereafter subclassified into two subgroups, assuming a GFR of 80 ml/min/1.73 m2 body surface area as a cut-off value: the normal GFR, 141 patients, and the impaired GFR, 30 patients. The normal GFR group included more males and the patients were younger both at onset and at presentation. In the impaired GFR group the disease lasted longer, but the overall stones and the stone recurrence rate were as high as those of the normal GFR patients. The single stone episodes were more severe in the former group as suggested by the occurrence of more surgery and complications. The GFR level was in part predicted by the age of patients; however, stone disease was shown to induce a clear-cut influence in accelerating the natural worsening of GFR with age. The onset of renal insufficiency causes multiple changes in renal pathophysiology, which result in a sharp decrease in the urine saturation with respect to calcium salts. These changes account for the decrease in the stone recurrence rate in the impaired GFR group. Thus, unless factors independent of or complicating the calcium stone disease supervene, the renal insufficiency of treated patients remains mild and relently progressive.

We give examples of Lorentz manifolds modelled on an indecomposable Lorentz symmetric space which are geodesically complete and not locally homogeneous.

Shrimp High Density Lipoprotein-beta-Glucan Binding Protein (HDL/BGBP) has been studied by its role in nutrition and innate defense. Although the mechanisms of lipid loading are still unknown, HDL-BGBP binds and aggregates phospholipids vesicles in vitro. To gain insights into the HDL-BGBP mechanism of interaction with membranes, we have used fluorescence spectroscopy and electron microscopy. Data show that HDL-BGBP does not induce membrane fusion, leakage nor lipid exchange, although microstructural changes are clearly observed. This work supports a model where protein aggregation leads to liposome clustering. Such interaction may be a critical factor for the activation of the shrimp blood cell in vivo.

Apolipoprotein A-I (apoA-I) interaction with specific cell lipid domains was suggested to trigger cholesterol and phospholipid efflux. We analyzed here apoA-I interaction with dimyristoylphosphatidylcholine/ distearoylphosphatidylcholine (DMPC/DSPC) bilayers at a temperature showing phase coexistence. Solid and liquid-crystalline domains were visualized by two-photon fluorescence microscopy on giant unilamellar vesicles (GUVs) labeled with 6-dodecanoyl-2-dimethylamino-naphthalene (Laurdan). A decrease of vesicle size was detected as long as they were incubated with lipid-free apoA-I, together with a shape deformation and a relative enrichment in DSPC. Selective lipid removal mediated by apoA-I from different domains was followed in real time by changes in the Laurdan generalized polarization. The data show a selective interaction of apoA-I with liquid-crystalline domains, from which it removes lipids, at a molar ratio similar to the domain compositions. Next, apoA-I was incubated with DMPC/DSPC small unilamellar vesicles, and products were isolated and quantified. Protein solubilized both lipids but formed complexes relatively enriched in the liquid component. We also show changes in the GUV morphology when cooling down. Our results suggest that the most efficient reaction between apoA-I and DMPC/DSPC occurs in particular bilayer conditions, probably when small fluid domains are nucleated within a continuous gel phase and interfacial packing defects are maximal., Instituto de Investigaciones Bioquímicas de La Plata

Colorectal cancer is one of the most common cancers in developed countries. Increasing numbers of early stage colorectal cancers and precancerous adenomatous lesions, polypoidal type lesions, and flat and depressed type lesions can be visualised and treated endoscopically thanks to endoscopic ultrasonography, high magnification chromoendoscopy and other technical advances. Polypectomy is generally considered for protuberant lesions, with both sessile and pedunculate morphology, and endoscopic mucosal resection (EMR) is indicated for superficial, flat or depressed types of lesions. Endoscopic therapy for colonic adenoma with dysplasia and early colorectal cancer is more advantageous than the conventional operative treatment, in that it is a relatively non-invasive and less costly method. However, endoscopic therapy is completely ineffective in lesions with lymph node or distant metastasis. Therefore, it is becoming more and more important to understand the correct indications and limitations of endoscopic polypectomy/mucosectomy as well as complication rates and the correct follow-up schedule.

Plasma membrane (PM) is a dynamic barrier which translates the outside signals to the cell. We are interested in how changes in the PM (composition, organization etc) influence cell homeostasis and vice versa. For this purpose we constructed two permanent Chinese Hamster Ovary (CHO KI) cell lines with permanent modifications in the PM lipid composition. The first line (SCD), over expressing Stearoyl CoA desaturase resulted in an increase of monounsaturated fatty acids at the PM phospholipids. The second cell line over expressing both Δ5 and Δ 6 desaturases (Δ 5/ Δ 6-cells), turned into a rise of poly unsaturated fatty acids and lower ratio cholesterol/phospholipids.Laurdan Generalized Polarization (Laurdan GP) microscopy and two-photon excitation, used to measure membrane packing (fluidity) in the PM of alive cells, showed for the SCD similar fluidity than control cells, indicating a metabolic compensation due to a relative increase in cholesterol content induced by the mutation. For the second cell line (Δ5/Δ6-cells) this compensation process did not occurred and the membrane fluidity increased compared with the control.The MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) reduction assay showed an increased viability in the two mutant cells as compared with the control. Cholesterol removal mediated by apolipoprotein A-I was measured by scintillation counting and showed to be reduced both cell lines. Together, our results indicate that PM lipid composition determines cholesterol partition, the feasibility of cholesterol to be exported and thus regulates its toxicity and homeostasis. Acknowledgements: This work was supported by US grant P41-RRO3155 to SAS and Argentinean grants ANPCyT (PICT 2106-2008) and CONICET (PIP 112-200801-00953) to MAT.

Two new Cys mutants of proapolipoprotein A-I, D9C and A232C, were created and expressed in Escherichia coli systems. Specific labeling with the thiol-reactive fluorescence probe, 6-acryloyl-2-dimethylaminonaphthalene (acrylodan), was used to study the structural organization and dynamic properties of the extreme regions of human apolipoprotein A-I (apoA-I) in lipid-free and lipid-bound states. Spectroscopic approaches, including circular dichroism and various fluorescence methods, were used to examine the properties of the mutant proteins and of their covalent adducts with the fluorescence probe. The mutations themselves had no effect on the structure and stability of apoA-I in the lipid-free state and in reconstituted HDL (rHDL) complexes. Furthermore, covalent modification with acrylodan did not alter the properties of the apoA-I variants in the lipid-bound state nor in the lipid-free A232C mutant, but it affected the structure and local stability of the lipid-free protein in the D9C mutant. Fluorescence results using the acrylodan probe confirmed a well-organized structure in the N-terminal region of apoA-I. Also, they suggested a three-dimensional structure in the C-terminal region, stabilized by protein-protein contacts. When Trp residues and acrylodan were used as donor-acceptor pairs for fluorescence resonance energy transfer (FRET), average distances could be measured. Both intensity and lifetime changes of the Trp emission indicated a protein folding in solution that brings the C-terminus of the protein near the Trp residues in the N-terminal half of the sequence. Also, the N- and C-terminal domains of apoA-I appeared to be near each other in rHDL having two apoA-I per particle.

Little research within the field of developmental or educational psychology has addressed teachers' perceptions of the characteristics of children who interact in different types of peer organizations. This study was designed to examine teachers' perceptions of the characteristics of boys and girls who interact in groups or in dyads. Participants (teachers and children) were recruited from 10 classes from all grade levels of 2 elementary schools. The children were asked to name those in their classes who played together frequently. On the basis of participants' responses, 2 categories of target children were identified: those who played with at least 3 other children (group) and those children who played with 1 other child (dyad). Two teachers then rated each target child on 6 characteristics. The results indicated that, compared with children who played in dyads, target children who played in groups were rated by teachers as being more competitive, receiving more attention from peers, valuing their friends more, and being more emotionally expressive. No differences were found between target children who played in groups or dyads in empathy or self-confidence. In addition, no interaction between sex and type of social organization was found for any of the measures. Results are discussed in terms of the relation between social organization and functions of peer relations.

Between peripheral blood and tissue-infiltrating lymphocytes there is an intermediate compartment, the blood of the organ-draining vessels, which could show unusual features. The aim of the present study was to analyse the characteristics of the lymphocytes from the stomach-draining vessels and the cytokine secretion by these lymphocytes. The CagA-mediated lymphocyte activation in Helicobacter pylori-infected subjects and the humoral response to this antigen were evaluated and correlated with clinical data.We studied lymphocyte proliferation either with mitogens or with the CagA antigen and cytokine production and IgG anti-CagA by means of an enzyme-linked immunosorbent assay in peripheral blood and gastric-vein blood obtained during surgical intervention.We showed higher proliferative response and cytokine production in lymphocytes from the gastric vein. The mitogenic response to the CagA antigen was highly specific but poorly sensitive for the H. pylori infection in both the compartments. The overall cytokine profile in our patients affected by non-ulcer disease was of the Th0 type.Gastric-vein-derived lymphocytes seem to show unusual features, as they behave like peripheral blood lymphocytes but show higher responses to all the tested stimuli. It is possible that the interaction of the lymphocytes with the mucosal environment could activate the synthetic mechanisms, making the cells more 'responsive' to the stimulation. The CagA antigen is able to induce a specific T-lymphocyte response and is therefore a valid candidate antigen for the development of a vaccine.

In this paper, the clinical and metabolic patterns of nephrolithiasis in different ages of adulthood are studied.Eight-hundred patients observed at the Mauriziano Hospital between 1990 and 1995, were classified into 3 groups, on the basis of age at the onset of disease: A: 20 through 39 years; B: 40 through 59; C: 60 years and over.Calcium-oxalate stones had a lower recurrence in C (19.1%) and B (31.5%) than in A (41.7%). Pure uric acid stones recurred in 18.9% of C, 16.7% of B and 4.3% of A. The prevalence of hypercalciuria was higher in A (50.3%) than in B (35.9%) and C (36%); so did hypocitraturia. Hyperuricuria was lower in A (5%, p0.05) than in B (9.4%) and C (10%). Low urine pH (5.5) was 13% in A, 21.3% in B, 38% in C. Prevalence of hyperoxaluria was about 14% in all groups. The whole prevalence of secondary forms of stone disease was 13% in A, 12% in B and 30% in C. Differences among groups were mainly due to prevalence of urological abnormalities and urinary tract infection. In patients without metabolic disturbances. urological abnormalities or urinary tract infections altogether, were 4.6% in A; 5.2% in B; 33% in C. Urological approach removed 8% of stones in A, 5.6% in B and 10.2% in C.Higher morbidity in younger patients could be due to a lower prevalence of easier-passing uric acid stones. The higher occurrence of urological disturbances and struvite stones in the elderly could explain the higher morbidity in this group.

Academic stress is a good model of psychological stress in humans for studying psychoneuroimmune correlations. We looked for correlations between psychological scores, immune tests and plasma levels of cortisol and neuropeptide Y (NPY). A group of medical students were evaluated at the beginning of the academic year (Baseline) and the day before an examination (Stress). They underwent evaluation by The Profile of Mood States (POMS), The Malaise Inventory, The Self Efficacy Scale and A Global Assessment of Recent Stress (GARS). The lymphocyte subsets, the lymphocyte proliferative response and the cytokine production were also evaluated. We detected modifications of some psychological test scores between the Baseline and Stress evaluation, a significant reduction of lymphocyte proliferation, IL-2 production and percentage of the lymphocyte CD19, and an increase in plasma cortisol levels during stress. The lymphocyte proliferation negatively correlated with the POMS score as well as the percentage of CD16+ cells with NPY plasma levels. NPY levels were not different from Baseline. The emotional and mood states seem to influence immunity. Copyrightz1999S.KargerAG,Basel

The effects of aging on the activation of the cytoplasmic tyrosine protein kinase p56 lck have been investigated in PBL from adult and elderly subjects upon activation with mitogens or different co-stimuli. Results show that the amount and phosphorylation of p56 lck are reduced in PBL from elderly as compared to adult subjects. This finding suggests that alterations in p56 lck may contribute to the age-associated loss of some T cell functions, such as proliferation and IL-2 production, which are found decreased in PBL from old individuals. However, p56 lck seems irrelevant to the production of IFN- γ and IL-4 which were both found increased in the PBL from old subjects, as expected from the relative expansion of memory versus naive T cell subpopulations in aging.