Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming

Naive T cells are stimulated by antigen-presenting dendritic cells (DCs) in secondary lymphoid organs, but whether other types of cell participate in T cell priming is unclear. Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs. Recruitment of NK cells is also induced by some, but not all, adjuvants and correlates with the induction of T helper cell type 1 (T(H)1) responses. NK cell depletion and reconstitution experiments show that NK cells provide an early source of interferon-gamma (IFN-gamma) that is necessary for T(H)1 polarization. Taken together, our results identify an induced pathway of NK cell migration in antigen-stimulated lymph nodes and a mechanism by which some adjuvants may facilitate T(H)1 responses.     

Migration of human blood dendritic cells across endothelial cell monolayers: adhesion molecules and chemokines involved in subset-specific transmigration

Distinct subsets of dendritic cells (DCs) are present in blood, probably "en route" to different tissues. We have investigated the chemokines and adhesion molecules involved in the migration of myeloid (CD11c(+)) and plasmacytoid (CD123(+)) human peripheral blood DCs across vascular endothelium. Among blood DCs, the CD11c(+) subset vigorously migrated across endothelium in the absence of any chemotactic stimuli, whereas spontaneous migration of CD123(+) DCs was limited. In bare cell migration assays, myeloid DCs responded with great potency to several inflammatory and homeostatic chemokines, whereas plasmacytoid DCs responded poorly to all chemokines tested. In contrast, the presence of endothelium greatly favored transmigration of plasmacytoid DCs in response to CXCL12 (stromal cell-derived factor-1) and CCL5 (regulated on activation, normal T expressed and secreted). Myeloid DCs exhibited a very potent transendothelial migration in response to CXCL12, CCL5, and CCL2 (monocyte chemoattractant protein-1). Furthermore, we explored whether blood DCs acutely switch their pattern of migration to the lymph node-derived chemokine CCL21 (secondary lymphoid-tissue chemokine) in response to microbial stimuli [viral double-stranded (ds)RNA or bacterial CpG-DNA]. A synthetic dsRNA rapidly enhanced the response of CD11c(+) DCs to CCL21, whereas a longer stimulation with CpG-DNA was needed to trigger CD123(+) DCs responsive to CCL21. Use of blocking monoclonal antibodies to adhesion molecules revealed that both DC subsets used platelet endothelial cell adhesion molecule-1 to move across activated endothelium. CD123(+) DCs required beta(2) and beta(1) integrins to transmigrate, whereas CD11c(+) DCs may use integrin-independent mechanisms to migrate across activated endothelium.     

A multimedia database system for thermal ablation therapy of brain tumors

A prototype multimedia medical database is described for supporting thermal ablation therapy of brain tumors. Its design is motivated by the major need to manage and access multimedia information on the progress and reaction of tumors to various therapy protocols. The database links images to patient data in a way that permits the user to view and query medical information using alphanumeric, temporal, and feature-based predicates. Visualization programs permit the user to view or annotate the query results in various ways. These results support the wide variety of data types and presentation methods required by neuroradiologists to manage thermal ablation therapy data. The database satisfactorily meets the requirements defined by thermal ablation therapy. A similar approach is being undertaken for supporting different therapies of other types of tumors, thus showing the generality of our approach.     

Association of a functional serotonin transporter gene polymorphism with binge eating disorder.

The pathophysiological mechanisms underlying binge eating disorder (BED) are poorly understood. There is evidence that abnormalities in brain serotonin (5HT) play an important role in binge eating behavior, therefore genes involved in 5HT transmission, such as the 5HT transporter (5HTT) gene, may contribute to the biological vulnerability to BED. We examined whether the polymorphism of the promoter of the 5HTT gene, consisting of a long (L) and a short (S) variant, was associated with BED. Seventy-seven obese or non-obese women with BED, and 61 normal weight control women were genotyped at the 5HTT gene linked polymorphism (5HTTLPR). Statistical analysis showed that both the LL genotype and the L allele of the 5HTTLPR were significantly more frequent in BED subjects. Moreover, the L allele was associated with a moderate but significant risk to develop BED (OR = 2.01, CI = 1.33-3.57). Although these data should be regarded as preliminary because of the small size of our sample, they suggest that the 5HTTPRL may contribute to the genetic susceptibility to BED.     

Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis

Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens.     

Fast,persistent, Ca2+-dependent K+ current controls graded electrical activity in crayfish muscle

The early outward current in opener muscle fibres of crayfish (Procambarus clarkii) was studied using the two-electrode voltage-clamp technique. This current was abolished in Ca²⁺-free and 5 mM Cd²⁺ solutions, and was blocked by extra- or intracellular tetraethylammonium, indicating that it was a Ca²⁺-dependent K⁺ current [I _K(Ca)]. I _K(Ca) was voltage dependent, apamin insensitive and sensitive to charybdotoxin (CTX), which, in addition to its tetraethylammonium sensitivity, suggests that the channels mediating I _K(Ca) behave in a BK type manner. I _K(Ca) activation was extremely fast, reaching a maximum within 5 ms, and the inactivation was incomplete, stabilizing at a persistent steady-state. I _K(Ca) was insensitive to intracellular ethylenebis(oxonitrilo)tetraacetate (EGTA), but was abolished by injection of the faster Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid (BAPTA), suggesting that voltage-dependent Ca²⁺ channels and those mediating I _K(Ca) should be clustered closely on the membrane. Under two-electrode current-clamp recording mode, low amplitude, graded responses were evoked under control conditions, whereas repetitive all-or-none spikes were elicited by application of CTX or after loading the cells with BAPTA. We conclude that I _K(Ca) activates extremely quickly, is persistent and is responsible for the generation and control of the low amplitude, graded, active responses of opener muscle fibres.     

A dominant ovarian follicle induces unilateral changes in the origin of the blood supply to the tubal corner of the uterus

BACKGROUND: The blood supply to the tubal corner of the uterus may originate from the uterine and ovarian arteries. The border of supply from the arteries has been found to move in young women; the change seemed dependent on ovarian steroid production. The present work investigated whether the border of supply could differ between the two sides of the uterus in the same woman having one dominant follicle (>10 mm). METHODS: Vagina was flushed with saline of room temperature in 15 women with a dominant follicle >10 mm. The temperature was measured in the mid-uterine lumen and in the tubal corner of the uterus at 2, 5 and 7 min after starting cooling. The investigation was repeated 30 min later measuring the temperature in the other tubal corner. RESULTS: The temperature decrease was, as found in previous investigations, more pronounced in the uterine cavity than in the tubal corners. However, a difference was found between the two tubal corners. At all measurement times the decrease was significantly smaller in the tubal corner corresponding to the dominant follicle than in the contralateral side. CONCLUSIONS: In our model, 'cold' is transferred from the vaginal venous blood to the uterine artery and the cooling defines the supply area of the uterine artery. Therefore, the results indicate that the area of supply from the ovarian artery in the tubal corner ipsilateral to the dominant follicle is greater than that in the contralateral side. It is possible to speculate that this difference is related to the hormonal production of the dominant follicle.     

Neural regions essential for writing verbs

Functional imaging data collected during cognitive tasks show which brain regions are active during those tasks, but do not necessarily indicate which regions are essential for those tasks. Here, in a study of two cases of selectively impaired written naming of verbs after focal brain ischemia, we combined imaging and behavioral testing to unambiguously identify brain regions that are crucial for a specific cognitive process. We used magnetic resonance perfusion imaging to show that the selective impairment in each case was due to hypoperfusion (low blood flow) in left posterior inferior frontal gyrus (PIFG) and precentral gyrus (PrG); the impairment was immediately reversed when blood flow was restored to these regions, indicating that parts of the left frontal lobe are crucial for representing and processing verbs.     

Association between A218C polymorphism of the tryptophan-hydroxylase-1 gene,harm avoidance and binge eating behavior in bulimia nervosa

Genes involved in serotonin transmission are likely involved in the biological predisposition to bulimia nervosa. We investigated whether the A218C polymorphism of the tryptophan-hydroxylase-1 gene was associated to bulimia nervosa and/or to some phenotypic aspects of the disorder. One hundred eighty Caucasian women (91 patients with bulimia nervosa and 89 healthy controls) were enrolled into the study. They underwent a blood sample collection for A218C polymorphism of the tryptophan-hydroxylase-1 genotyping and a clinical evaluation assessing comorbidity for Axis I and II psychiatric disorders, harm avoidance personality dimension and bulimic symptoms. The distribution of both tryptophan-hydroxylase-1 A218C genotypes and alleles did not significantly differ between patients and controls. Bulimic women with the AA genotype exhibited a more severe binge eating behavior and higher harm avoidance scores than those with CC genotype. These findings support the idea that tryptophan-hydroxylase-1 A218C polymorphism does not play a part in the genetic susceptibility to bulimia nervosa, but it seems to be involved in predisposing bulimic patients to a more disturbed eating behavior and higher harm avoidance.