Factors Associated with Frailty Syndrome in Older Adults.

OBJECTIVE: Frailty is a common geriatric syndrome, characterized by a decrease in energy reserve and stress resistance, resulting in an accumulated decline of multiple physiological systems and greater vulnerability. Frailty syndrome has a multifactorial etiology involving a biological basis associated with sociobehavioral factors. We verify the association of frailty syndrome with family functionality level, nutritional status and medication adherence in older adults. DESIGN: Observational and analytical study. SETTING AND PARTICIPANTS: Conducted at ambulatory the university hospital, with patients aged 60 years or older. MEASUREMENTS: Cognitive function was measured using the Mini-Mental State Examination (MMSE); nutritional status was evaluated using the Mini Nutritional Assessment (MNA) and Body Mass Index, BMI; the 5-item FRAIL scale was used for frailty screening; family functioning was assessed using the Family APGAR Index, which evaluates Adaptability, Partnership, Growth, Affection, and Resolve; Self-reported medication adherence was measured by the eight-item Morisky Medication Adherence Scale (MMAS-8). RESULTS: The study involved 308 older adults, with a mean age of 70.40 years, There was an association between frailty and highly dysfunctional family with an OR of 5.9 (95% CI 1.9-18.5)(p<0.05), nutritional risk assessed by BMI, where low weight presented an OR of 2.5 (95% CI 1.1-5.8) and obesity an OR of 2.8 (95% CI 1.1-7.0)(P <0.05) and a nutritional risk assessed by MNA with an OR 6.3(95% CI 1.9-20.4) and low medication adherence with an OR of 8.9 (95% CI, 3.6-21.6)(P = 0.01). CONCLUSION: Frailty syndrome is associated with high levels of family dysfunction, nutritional risk and poor medication adherence amongst older people.

Endogenous sex hormones are not associated with subclinical atherosclerosis in menopausal women.

AIM: The aim of this paper was to compare the carotid intima-media thickness (IMT) in pre- and postmenopausal women and to evaluate the association between endogenous sex hormones, body fat distribution, and insulin resistance and the IMT. METHODS: This cross-sectional study included 145 women aged 45-65 yr, comprising 56 premenopausal (FSH<20IU/mL and regular menstrual cycles) and 89 postmenopausal (FSH>40IU/ml and amenorrheic). All patients were evaluated for lipid profile, estradiol and testosterone, insulin ratio (G/I), HOMA-IR, and ultrasound measurement of IMT. Each variable was assessed for correlation with IMT using the univariate model. RESULTS: No difference was observed in IMT between pre- and postmenopausal women. A positive and statistically significant correlation was found between IMT and FSH levels (rs=0.21, P<0.009) and HOMA (rs=0.16, P<0.04). A positive and statistically significant correlation was observed between testosterone and waist (rs=0.3, P<0.04). No correlation was found between IMT and time of menopause (r=0.02, P=0.19). CONCLUSION: Estradiol and testosterone are not associated with subclinical atherosclerosis in menopausal women. A positive correlation between IMT and FSH may reflect an association between low estrogen and IMT. Abdominal fat can be an important link between androgenic levels and cardiovascular risk.

Nutritional status, dietary intake and serum levels of vitamin C upon diagnosis of cancer in children and adolescents.

INTRODUCTION: The prevalence of malnutrition upon diagnosis, together with reduced food intake secondary to disease and treatment, make the periodic assessment of nutritional status (including the intake of antioxidant nutrients) of considerable importance to the follow up of patients with cancer. OBJECTIVES: Assess the nutritional status and frequency of inadequate vitamin C levels among children and adolescents with cancer at the beginning of treatment and determine associated factors. METHODS: A cross-sectional study was carried out with 30 patients under 18 years. Nutritional status was assessed using laboratory methods and anthropometric measurements. Vitamin C adequacy was assessed through its serum concentration and dietary intake. RESULTS: In the sample, 10% were short for their age and 13.3% were underweight. The triceps skinfold measurement revealed fat depletion in 68% and the arm muscle circumference measurement revealed muscle depletion in 32.0%. Seventy percent of the patients had vitamin C deficiency and had greater weight loss, lower Z scores for all anthropometric indicators analyzed, lower serum albumin and higher C-reactive protein than those without vitamin C deficiency, but these differences were not statistically significant. CONCLUSIONS: Children with cancer may have nutritional deficits upon diagnosis. Further studies are needed on the association between serum levels of antioxidant and nutritional status in order to offer safe, effective nutritional support.

The stress kinase mitogen-activated protein kinase kinase (MKK)7 is a negative regulator of antigen receptor and growth factor receptor-induced proliferation in hematopoietic cells.

The dual specificity kinases mitogen-activated protein kinase (MAPK) kinase (MKK)7 and MKK4 are the only molecules known to directly activate the stress kinases stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) in response to environmental or mitogenic stimuli. To examine the physiological role of MKK7 in hematopoietic cells, we used a gene targeting strategy to mutate MKK7 in murine T and B cells and non-lymphoid mast cells. Loss of MKK7 in thymocytes and mature B cells results in hyperproliferation in response to growth factor and antigen receptor stimulation and increased thymic cellularity. Mutation of mkk7 in mast cells resulted in hyperproliferation in response to the cytokines interleukin (IL)-3 and stem cell factor (SCF). SAPK/JNK activation was completely abolished in the absence of MKK7, even though expression of MKK4 was strongly upregulated in mkk7(-/-) mast cell lines, and phosphorylation of MKK4 occurred normally in response to multiple stress stimuli. Loss of MKK7 did not affect activation of extracellular signal-regulated kinase (ERK)1/2 or p38 MAPK. mkk7(-/-) mast cells display reduced expression of JunB and the cell cycle inhibitor p16INK4a and upregulation of cyclinD1. Reexpression of p16INK4a in mkk7(-/-) mast cells abrogates the hyperproliferative response. Apoptotic responses to a variety of stimuli were not affected. Thus, MKK7 is an essential and specific regulator of stress-induced SAPK/JNK activation in mast cells and MKK7 negatively regulates growth factor and antigen receptor-driven proliferation in hematopoietic cells. These results indicate that the MKK7-regulated stress signaling pathway can function as negative regulator of cell growth in multiple hematopoietic lineages.

Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap.

The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell-dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.

CD45: new jobs for an old acquaintance.

Identified as the first and prototypic transmembrane protein tyrosine phosphatase (PTPase), CD45 has been extensively studied for over two decades and is thought to be important for positively regulating antigen-receptor signaling via the dephosphorylation of Src kinases. However, new evidence indicates that CD45 can function as a Janus kinase PTPase that negatively controls cytokine-receptor signaling. A point mutation in CD45, which appears to affect CD45 dimerization, and a genetic polymorphism that affects alternative CD45 splicing are implicated in autoimmunity in mice and multiple sclerosis in humans. CD45 is expressed in multiple isoforms and the modulation of specific CD45 splice variants with antibodies can prevent transplant rejections. In addition, loss of CD45 can affect microglia activation in a mouse model for Alzheimer's disease. Thus, CD45 is moving rapidly back into the spotlight as a drug target and central regulator involved in differentiation of multiple hematopoietic cell lineages, autoimmunity and antiviral immunity.

Regulation of T cell activation, anxiety, and male aggression by RGS2.

Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Galpha protein subunits in vitro, negatively regulating G protein-coupled receptor signaling. The physiological role of mammalian RGS proteins is largely unknown. The RGS family member rgs2 was cloned as an immediate early response gene up-regulated in T lymphocytes after activation. To investigate the role of RGS2 in vivo, we generated rgs2-deficient mice. We show that targeted mutation of rgs2 in mice leads to reduced T cell proliferation and IL-2 production, which translates in an impaired antiviral immunity in vivo. Interestingly, rgs2(-/-) mice also display increased anxiety responses and decreased male aggression in the absence of cognitive or motor deficits. RGS2 also controls synaptic development and basal electrical activity in hippocampal CA1 neurons. Thus, RGS2 plays an important role in T cell activation, synapse development in the hippocampus, and emotive behaviors.

Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

Glucocorticoid production in the murine thymus.

Glucocorticoid hormones are known to act as important modulatory factors in the development of autoimmune diseases, and to play an important role in thymic T-cell selection. There seems to be a finely balanced equilibrium between the apoptosis-inducing effects of glucocorticoid and T cell receptor ligand binding. Here we are investigating whether glucocorticoid-induced T cell apoptosis is mainly dependent on circulating glucocorticoid levels or if the thymus itself is able to produce glucocorticoids. To this end, we attempted to demonstrate enzyme activities of the whole set of steroidogenic enzymes for the synthesis of glucocorticoids in murine thymic tissue. We isolated steroidogenic organelles from thymic tissue, incubated these with radioactive (precursor) steroids in vitro, and visualized the resulting products by thin-layer chromatography. Our results show that the thymus possesses all enzymes and cofactors required for glucocorticoid production. However, an intact thymic architecture is necessary for glucocorticoid production, since 11beta-hydroxylase was not detected in irradiated thymi or in a thymic epithelial cell line. The results of these experiments show that the whole glucocorticoid metabolism takes place within the thymus. This finding provides the biochemical basis for the in situ effects of glucocorticoid hormones on thymocyte development and selection.

Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration.

Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kgamma were generated. We show that PI3Kgamma controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kgamma-deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPCR) agonists and chemotactic agents. PI3Kgamma links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3Kgamma regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.

Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b.

The signalling thresholds of antigen receptors and co-stimulatory receptors determine immunity or tolerance to self molecules. Changes in co-stimulatory pathways can lead to enhanced activation of lymphocytes and autoimmunity, or the induction of clonal anergy. The molecular mechanisms that maintain immunotolerance in vivo and integrate co-stimulatory signals with antigen receptor signals in T and B lymphocytes are poorly understood. Members of the Cbl/Sli family of molecular adaptors function downstream from growth factor and antigen receptors. Here we show that gene-targeted mice lacking the adaptor Cbl-b develop spontaneous autoimmunity characterized by auto-antibody production, infiltration of activated T and B lymphocytes into multiple organs, and parenchymal damage. Resting cbl-b(-/-) lymphocytes hyperproliferate upon antigen receptor stimulation, and cbl-b(-/-) T cells display specific hyperproduction of the T-cell growth factor interleukin-2, but not interferon-gamma or tumour necrosis factor-alpha. Mutation of Cbl-b uncouples T-cell proliferation, interleukin-2 production and phosphorylation of the GDP/GTP exchange factor Vav1 from the requirement for CD28 co-stimulation. Cbl-b is thus a key regulator of activation thresholds in mature lymphocytes and immunological tolerance and autoimmunity.

CD28 costimulation is crucial for the development of spontaneous autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a severe central nervous system disease. Experimental autoimmune encephalomyelitis (EAE) mimics MS in mice. We report that spontaneous development of EAE in RAG-1-deficient mice transgenic for a myelin basic protein (MBP)-specific TCR (TgMBP+/RAG-1-/-) requires expression of the T cell costimulatory molecule CD28. Surprisingly, T cells from CD28-/-TgMBP+/RAG-1-/- mice proliferate and produce IL-2 in response to MBP1-17 peptide in vitro, excluding clonal anergy as the mechanism of CD28-regulated pathogenesis. Proliferation of autoaggressive T cells was dependent on the concentration of the MBP peptide, as was the development of MBP-induced EAE in CD28-deficient PL/J mice. These results provide the first genetic evidence that CD28 costimulation is crucial for MBP-specific T cell activation in vivo and the initiation of spontaneous EAE.

OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis.

The tumour-necrosis-factor-family molecule osteoprotegerin ligand (OPGL; also known as TRANCE, RANKL and ODF) has been identified as a potential osteoclast differentiation factor and regulator of interactions between T cells and dendritic cells in vitro. Mice with a disrupted opgl gene show severe osteopetrosis and a defect in tooth eruption, and completely lack osteoclasts as a result of an inability of osteoblasts to support osteoclastogenesis. Although dendritic cells appear normal, opgl-deficient mice exhibit defects in early differentiation of T and B lymphocytes. Surprisingly, opgl-deficient mice lack all lymph nodes but have normal splenic structure and Peyer's patches. Thus OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.

Thymic epithelial cells synthesize a heparan sulfate with a highly sulfated region.

Epithelial cells are important components of the thymus microenvironment and are involved in thymocyte differentiation. The production and secretion of sulfated glycosaminoglycans by these cells grown in culture were investigated using labeling with radioactive 35S-Na2SO4 and 3H-glucosamine. The major glycosaminoglycans synthesized by these cells are heparan sulfate and hyaluronic acid. The structure of the heparan sulfate was investigated by the pattern of degradation products formed by deaminative cleavage with nitrous acid. The ratio 35S-sulfate/ H-glucosamine is high in the segments of the heparan sulfate released during the deaminative cleavage with nitrous acid but low in the resistant portion of the molecule. Thus, the heparan sulfate synthesized by the thymic epithelial cells contains a highly sulfated region. Digestion with heparitinase reveals that this highly sulfated region is a heparin-like segment of the molecule. The heparan sulfate is rapidly incorporated into the cell surface but its secretion to the extracellular medium requires a longer incubation period. Finally, heparin was used to mimic the possible effect of this heparan sulfate with a highly sulfated region, as ascertained by its ability to modulate thymocyte adhesion to thymic epithelial cells. Since heparin actually enhanced thymocyte adhesion, it is suggested that the heparan sulfate described herein, secreted by the thymic epithelium, may play a role upon intrathymic heterotypic cellular interactions.

Thymic heterotypic cellular complexes in gene-targeted mice with defined blocks in T cell development and adhesion molecule expression.

Thymocytes form unique multicellular complexes with epithelial cells (thymic nurse cells, TNC) and rosettes (ROS) with macrophages, epithelial cells and dendritic cells. To investigate the role of differentiation checkpoints in the formation of the thymic heterotypic complexes in vivo, we used mutant mice which have genetically defined blocks at early and late stages of T cell development. We show that RAG-1-/-, TCRbeta-/- , and p56lck-/- mice lack thymocyte ROS formation with epithelial cells, macrophages, or dendritic cells. TNC formation was not affected by TCRbeta and p56lck gene mutations but partially decreased in RAG-1-/- mice, indicating that TNC are the earliest thymocyte-stromal cell complexes formed in development, whereas ROS only appear after thymocytes have rearranged and expressed a functional TCRbeta chain. Genetic blocks in CD8 lineage commitment (CD8-/- and IFN regulatory factor-1-/- mice) and positive and negative T cell selection (CD45-/-, TCRalpha-/-, and CD30-/- mice) did not affect thymocyte-stromal cell complexes. Surprisingly, CD4-/- mice, but not MHC class II-/- mice, had significantly reduced numbers of TNC and ROS, in particular, a severe defect in ROS formation with thymic dendritic cells. The CD4-/- block in ROS and TNC formation was rescued by the introduction of a human CD4 transgene. Moreover, we show that the adhesion receptors CD44 and LFA-1 cooperate in the formation of the thymic microenvironment. These results provide genetic evidence on the role of defined stages in T cell development and adhesion molecules on thymocyte/stromal cell interactions in vitro.

The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling.

Ship is an Src homology 2 domain containing inositol polyphosphate 5-phosphatase which has been implicated as an important signaling molecule in hematopoietic cells. In B cells, Ship becomes associated with Fcgamma receptor IIB (FcgammaRIIB), a low affinity receptor for the Fc portion of immunoglobulin (Ig)G, and is rapidly tyrosine phosphorylated upon B cell antigen receptor (BCR)-FcgammaRIIB coligation. The function of Ship in lymphocytes was investigated in Ship-/- recombination-activating gene (Rag)-/- chimeric mice generated from gene-targeted Ship-/- embryonic stem cells. Ship-/-Rag-/- chimeras showed reduced numbers of B cells and an overall increase in basal serum Ig. Ship-/- splenic B cells displayed prolonged Ca2+ influx, increased proliferation in vitro, and enhanced mitogen-activated protein kinase (MAPK) activation in response to BCR-FcgammaRIIB coligation. These results demonstrate that Ship plays an essential role in FcgammaRIIB-mediated inhibition of BCR signaling, and that Ship is a crucial negative regulator of Ca2+ flux and MAPK activation.

Cohort study on canine emigration and Leishmania infection in an endemic area for American visceral leishmaniasis. Implications for the disease control.

American visceral leishmaniasis is a main public health matter in Brazil. Since dogs have been incriminated as the main urban reservoir of AVL agent Leishmania chagasi, a cohort study aimed at understanding the dynamics of the canine infection was carried out in Jequié--an endemic community in the Northeast of Brazil. The inhabited urban and periurban areas of Jequié were divided into 140 clusters of 0.25 km2. All 1681 dogs domiciled in 34 randomly selected clusters were screened for Leishmania antibodies in an enzyme-linked immunosorbent assay. After the seropositive dogs were painlessly eliminated, a cohort of 1286 seronegative dogs was followed up for 18 months, yielding a total of 1739.7 dog-years. The overall incidence of Leishmania infection, as assessed by the detection of Leishmania antibodies in blood samples collected every six months, was 6.55 cases/100 dog-years (95% confidence interval; CI 6.04-7.26). Two subsets of clusters, with 0.70 and 1.35 relative risks of infection, were identified. The annual emigration rate was 2.26 cases/100 dog-years (95% CI 1.86-2.66). The implications of these findings for the control of American visceral leishmaniasis are discussed.

Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes.

The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH2 terminal kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/-) chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross-linking. SEK1(-/-) peripheral T cells showed decreased proliferation and IL-2 production after CD28 costimulation and PMA/Ca2+ ionophore activation. Although CD28 expression was absolutely crucial to generate vesicular stomatitis virus (VSV)-specific germinal centers, SEK1(-/-)RAG2(-/-) chimeras mounted a protective antiviral B cell response, exhibited normal IgG class switching, and made germinal centers in response to VSV. Interestingly, PMA/Ca2+ ionophore stimulation, which mimics TCR-CD3 and CD28-mediated signal transduction, induced SAPK/JNK activation in peripheral T cells, but not in thymocytes, from SEK1(-/-) mice. These results show that signaling pathways for SAPK activation are developmentally regulated in T cells. Although SEK1(-/-) thymocytes failed to induce SAPK/JNK in response to PMA/Ca2+ ionophore, SEK1(-/-)RAG2(-/-) thymocytes proliferated and made IL-2 after PMA/Ca2+ ionophore and CD3/CD28 stimulation, albeit at significantly lower levels compared to SEK1(+/+)RAG2(-/-) thymocytes, implying that CD28 costimulation and PMA/Ca2+ ionophore-triggered signaling pathways exist that can mediate proliferation and IL-2 production independently of SAPK activation. Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL-2 production and T cell proliferation.

Murine thymic nurse cells and rosettes: analysis of adhesion molecule expression using confocal microscopy and a simplified enrichment method.

Thymic nurse cells (TNC) and T-cell stromal rosettes (ROS) are two in vivo models for stromal cell-thymocyte interactions. We describe a simplified enrichment method for TNC and ROS that overcomes the necessity for large amounts of tissue. The complexes were further analyzed with confocal microscopy, and three subunits of ROS were defined on the basis of their central cell phenotype, i.e., macrophage, dendritic, or epithelial cell rosettes. Because adhesion molecules are proposed to play a crucial role in T-cell development, we investigated CD44, LFA-1, and ICAM-1 expression in such complexes. The epithelial component of TNC expresses CD44 and ICAM-1, whereas intra-TNC thymocytes are LFA-negative. With regard to ROS, all subsets expressed CD44, and macrophage and dendritic cell ROS were also ICAM-1-positive and LFA-1-positive. The current protocol opens the possibility for further in vivo analysis of stromal cell-thymocyte interactions, e.g., for studies of scarce gene mutant mice.

Development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens.

Chickens of the Obese strain (OS) are known to develop spontaneous autoimmune thyroiditis (SAT) in the first 2-3 weeks post-hatching, but onset and severity of SAT for this period among sublines of OS chickens has not yet been analysed in detail. In the present paper, we described the kinetics of SAT in age-matched OSB13B13C, OSB5B5C, OSB15B15INN and OSB5B5INN chicken sublines. The results revealed no thyroid infiltration in OS fetuses at 20th ED of the analysed sublines. Mononuclear cell infiltration of thyroid was first noted in 2-4-day-old chickens, followed by aggravation of thyroiditis in 4-week-old OSB13B13C and OSB15B15INN chickens and in 5-week-old OSB5B5C birds. Interestingly, two subpopulations of OSB5B5INN chickens were found with different kinetics of SAT development: one with degree of SAT lower than 40%, was designated "low responders" and the other, with similar degrees of SAT as the other three sublines, was characterized as "high responders". Our results allow an age-dependent prediction of SAT development among OS chickens and the rational design of animal experiments, particularly for assessing the relevance of therapeutic interventions.