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PubMedDate not supplied

T and B cell repertoire in gastric lymph follicles in children with Helicobacter pylori infection.

Helicobacter pylori infection has been implicated in the development of gastrointestinal malignancy in adults and children. The histopathological processes that lead to such development are unknown. We compared the immune cell repertoire of mucosal lymph follicles in children with H. pylori infection to B cell type mucosal associated lymphoid tissue (MALT)-lymphoma of adults. The B and T cell populations residing within the lymph follicles and/or within B cell type MALT lymphoma were characteriZed by an immunohistochemical technique, utilizing B and T cell markers including: CD3, CD4, CD8 (T cells); CD20, CD40, GD74, BLA36, CD80, CD86 (B cells). Stain intensity was compared between the samples. T cell repertoire was observed within the lymph follicles, but not in the B cell MALT-lymphoma specimens. No significant difference was observed between the staining of CD40, CD74, CD8, and BLA36. The B cell markers, CD80 and CD86, were found within the centrocytic zone of the lymph follicle. In the B cell repertoire, no significant difference was observed between the lymph follicles of children with H. pylori infection and the adult MALT-lymphoma specimens except in CD20. B and T cells were in close anatomical proximity, enabling them to interact and exchange immunological information.

Antigens, CD↗
PubMed1996

Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts.

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.

Antigens, CD↗
PubMed1997

Stabilization of invariant chain mRNA by 12-O-tetradecanoylphorbol-13-acetate is blocked by IFN-gamma in a murine B lymphoma cell line.

Activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) increased steady-state levels of mRNA encoding the major histocompatibility complex (MHC) class II antigen I-A beta and the class II antigen-associated invariant chain (Ii, CD74) in A20 B lymphoma cells and in normal mouse B cells. The increase in Ii mRNA levels appeared to be due to a slight increase in the rate of gene transcription and an increase in the stability of Ii mRNA. The half-life of Ii mRNA increased from 12 h to >24 h following treatment with TPA, as determined by Northern blot analysis following actinomycin D treatment or by the [3H]-uridine pulse-chase method. Interferon-gamma (IFN-gamma), which has been well characterized as a cytokine that induces class II antigens and the Ii, increased Ii expression slightly in A20 cells. However, cotreatment of cells with TPA and IFN-gamma resulted in a block in the TPA-induced increase in Ii expression. Transcription of the Ii gene was minimally affected following treatment with IFN-gamma alone, and cells treated with both TPA and IFN-gamma had the same transcription rate as the control cells. IFN-gamma did, however, block stabilization of Ii mRNA by TPA. Activation of PKC by TPA, which was previously shown to lead to membrane translocation and downregulation, was not inhibited by IFN-gamma. Therefore, IFN-gamma appeared to block a downstream signal transduction pathway activated by PKC that controls stability of Ii mRNA.

Animals↗
PubMed1993

Demonstration of Epstein-Barr viral genomes by in situ hybridization in acquired immune deficiency syndrome-related high grade and anaplastic large cell CD30+ lymphomas.

From September 1984 through December 1991, of those with human immunodeficiency virus infection seen at the acquired immune deficiency syndrome unit of the Centro di Riferimento Oncologico, Aviano, Italy, 71 patients had systemic non-Hodgkin's lymphomas. The most frequent histotypes were small noncleaved cell, anaplastic large cell (ALC) CD30/BerH2+, and large cell immunoblastic. In 22 representative cases of these histotypes, including 9 of small noncleaved cell, 9 of ALC CD30/BerH2+, and 4 of immunoblastic non-Hodgkin's lymphomas, Epstein-Barr virus genetic information was assessed by in situ hybridization and correlated with histologic and immunophenotypic findings. Expression of B-cell associated markers, usually including CD19, CD20, CD22, CDw75, and CD74, was found in 17 of the 22 evaluated cases. All small noncleaved cell and immunoblastic cases and four cases of ALC lymphomas expressed B-cell immunophenotypes, whereas the remaining ALC cases were immunologically undetermined. In situ hybridization detected Epstein-Barr virus in 12 of 22 cases (54.5%). Seven of nine ALC lymphomas were positive, as were three of five small noncleaved cell type (Burkitt's lymphoma), one of four small noncleaved cell type (non-Burkitt's variant), and one of four large cell immunoblastic type. The results of this study indicate that Epstein-Barr virus genomes might be identified in more than 50% of the evaluated high grade non-Hodgkin's lymphomas; this association occurred significantly more often in the small noncleaved cell lymphomas resembling endemic Burkitt's lymphoma (60%) and with ALC CD30/BerH2+ lymphomas (77.8%). These findings support the notion that Epstein-Barr virus may play a role in the development of non-Hodgkin's lymphomas in a proportion of human immunodeficiency virus-infected patients.

Antigens, CD↗
PubMed2000

Expression of accessory molecules for T-cell activation in peripheral nerve of patients with CIDP and vasculitic neuropathy.

Vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP) are neuropathies characterized by a T-lymphocyte infiltrate in the peripheral nerves. The microenvironment in which these T cells become activated, and the molecules and cells that play a role in this process are incompletely understood. Using immunohistochemical analysis, we studied the effect of the presence of adhesion, costimulatory and antigen-presenting molecules on different cell types as a precondition for local T-cell activation in human sural nerve biopsies of seven patients with CIDP, three patients with vasculitic neuropathy and three healthy controls. In biopsies from CIDP and vasculitic neuropathy patients, but not in those from healthy controls, Schwann cells expressed the adhesion/T-cell stimulatory molecule CD58 (LFA-3). The CD58 molecule was also present on endothelial cells of all vasculitic neuropathy patients and one CIDP patient. In biopsies from normal controls and patients, CD54 (ICAM-1) expression was detectable on microvascular endothelial cells. In addition, expression of the costimulatory molecule CD86 was detected on vascular tissue in patients with vasculitic neuropathy. Although macrophages were always present in all subjects, expression of the major histocompatibility complex (MHC)-like molecule CD1a by macrophages was restricted to biopsies from two CIDP patients and one vasculitic neuropathy patient. Unexpectedly, Schwann cells of a single vasculitis patient strongly expressed CD1b, a molecule involved in the presentation of self-glycolipids to T cells. Schwann cells in biopsies from patients and normal controls expressed high levels of the invariant chain, CD74, a molecule involved in the intracellular sorting of MHC class II molecules. There was no evidence for the presence of dendritic cells in sural nerve biopsies. These findings support a model in which T-cell activation can be initiated and/or perpetuated locally in sural nerve biopsies of patients with CIDP and vasculitic neuropathy, and predict an important role for Schwann cells and endothelial cells.

Adult↗
PubMed2001

Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes.

To elucidate the biological dysregulation underlying two forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), we examined global gene expression profiles of inflamed colonic tissue using DNA microarrays. Our results identified several genes with altered expression not previously linked to IBD. In addition to the expected upregulation of various cytokine and chemokine genes, novel immune function-related genes such as IGHG3, IGLL2 and CD74, inflammation-related lipocalins HNL and NGAL, and proliferation-related GRO genes were over-expressed in UC. Certain cancer-related genes such as DD96, DRAL and MXI1 were differentially expressed only in UC. Other genes over-expressed in both UC and CD included the REG gene family and the calcium-binding S100 protein genes S100A9 and S100P. The natural antimicrobial defensin DEFA5 and DEFA6 genes were particularly over-expressed in CD. Overall, significant differences in the expression profiles of 170 genes identified UC and CD as distinct molecular entities. The genomic map locations of the dysregulated genes may identify novel candidates for UC and CD genetic susceptibility.

Adult↗
PubMed2004

A comprehensive screen for chicken proteins that interact with proteins unique to virulent strains of Marek's disease virus.

Genetic resistance to Marek's disease (MD) has been proposed as a method to augment current vaccinal control of MD. Although it is possible to identify QTL and candidate genes that are associated with MD resistance, it is necessary to integrate functional screens with linkage analysis to confirm the identity of true MD resistance genes. To help achieve this objective, a comprehensive 2-hybrid screen was conducted using genes unique to virulent Marek's disease virus (MDV) strains. Potential MDV-host protein interactions were tested by an in vitro binding assay to confirm the initial two-hybrid results. As a result, 7 new MDV-chicken protein interactions were identified and included the chicken proteins MHC class II beta (BLB) and invariant (Ii) chain (CD74), growth-related translationally controlled tumor protein (TPT1), complement component Clq-binding protein (C1QBP), retinoblastoma-binding protein 4 (RBBP4), and alpha-enolase (ENO1). Mapping of the encoding chicken genes suggests that BLB, the gene for MHC class II beta chain, is a positional candidate gene. In addition, the known functions of the chicken proteins suggest mechanisms that MDV might use to evade the chicken immune system and alter host gene regulation. Taken together, our results indicate that integrated genomic methods provide a powerful strategy to gain insights on complex biological processes and yield a manageable number of genes and pathways for further characterization.

Animals↗
PubMed1996

Lymphoid monoclonal antibodies reactive with lung tumors. Diagnostic applications.

In the course of investigating 30 monoclonal antibodies (MAbs) for their potential reactivity with 25 lung tumors of different histologic types, we found that three MAbs commonly used for their specificities for lymphoid markers were highly reactive with non-small-cell carcinomas (NSCLC) and totally nonreactive with small-cell carcinomas (SCLC). Immunostaining was performed by the standard streptavidin-biotin-peroxidase method after microwave antigen retrieval on formalin-fixed, paraffin-embedded tissue sections. LN2 (CD74), LN3 (HLA-DR), and BLA-36, which are commonly used for the identification of B-lymphocytes, strongly immunostained 19 of 25 squamous and adenocarcinomas and none of 34 small-cell carcinomas and carcinoids. Moreover, in combined tumors, these MAbs selectively stained the adenocarcinoma cells but not the adjacent small-cell carcinoma cells. A cocktail mixture of LN2, LN3, and BLA-36 assayed on 24 additional lung tumors produced similar results with even stronger and sharper stainings. Other lymphoid MAbs showed some selective staining but to a lesser degree. Among nonlymphoid MAbs, the results were as expected, with MAbs for cytokeratin (B72.3) and epithelial membrane antigen staining NSCLC but also some SCLC. The MAbs for chromogranin and neuron-specific enolase were not entirely specific, whereas some nerve-cell adhesion molecule MAbs showed good specificity for SCLC. In a field with few specific MAbs, the newly discovered ability of these lymphoid MAbs to discriminate between SCLC and NSCLC may prove useful in the immunohistochemical diagnosis of lung tumors.

Antibodies, Monoclonal↗
PubMed1993

Diagnosis of gastrointestinal T-cell lymphomas in routinely processed tissues.

Diagnosis of primary gastrointestinal T-cell lymphomas is often problematic because lymphoma may not be suspected clinically or on resection, and tissue may not be frozen for immunophenotyping. Furthermore, ulceration and inflammation and the polymorphous character of the lesions makes evaluation difficult. Only approximately 150 cases have been reported, fewer than 20 from North America. We have tried to establish a reliable approach to the diagnosis of gastrointestinal lymphomas of T-cell phenotype in routinely processed tissue. Sections from five primary gastrointestinal T-cell lymphomas were stained with a panel of 13 antibodies reactive in routinely fixed, paraffin-embedded tissue. These included antibodies to pan-T- and pan-B-cell antigens (CD3, CD20), B- and T-cell-associated antigens (CD43, CD45R0; CDw75, CD74), antigens expressed by activated T-cells (HLA-DR, CD30), leukocyte antigens (CD45, CD15), and macrophage markers (MAC-387, HAM-56). All stained positively with T-cell markers MT-1 and Leu-22, four with UCHL-1, and three with anti-CD3 polyclonal antibody. B-cell markers identified by L-26 and LN-1 were negative in all five, whereas LN-2 was expressed in two. Two expressed HLA-DR; all were Ber-H2 negative. Two had an abnormal phenotype: one was Leu-M1 positive, and one LCA negative. Ten B-cell gastrointestinal lymphoma controls were negative for MT-1, Leu-22, and CD3, and nine were negative for UCHL-1. Nine were positive for the B-cell marker L-26, eight for LN-2, and seven for LN-1. All tumors were negative for monocyte-macrophage markers. This antibody panel provides a reliable means for identifying gastrointestinal T-cell lymphomas in paraffin sections. Use of a panel is advisable because of variation in expression and preservation of antigens, and to detect abnormal phenotypes. Application of this approach may facilitate the diagnosis of gastrointestinal T-cell lymphomas both prospectively and in archival material, and thereby encourage studies of the behavior and treatment of these neoplasms.

Aged↗
PubMed1991

Immunohistochemical differential diagnosis between lymphocytoma cutis and malignant lymphoma in paraffin-embedded sections.

A panel of monoclonal antibodies (Leucocyte Common Antigen [CD45], LN-1 [CDw75], LN-2 [CD74], LN-3, L-26, UCHL-1 [CD45RO] and MT-1) which identify B and T cell surface markers were applied to benign lymphocytoma cutis and malignant lymphoma of the skin in paraffin-embedded sections. In five cases of lymphocytoma cutis, both B and T cell markers were positive, consistent with the polyclonality of the proliferative lymphocytes. In contrast, in two cases of B cell lymphoma, only the B cell markers were positive, consistent with the monoclonality. Furthermore, the immunohistochemistry clarified lymph follicle structures of lymphocytoma cutis. These were occasionally not evident in routine hematoxylin and eosin stained sections. Thus an immunologic phenotyping study combined with other appropriate criteria for histologic evaluation and clonal gene rearrangement analysis appears to be useful in distinguishing reactive from neoplastic lymphoid lesions of the skin.

Aged↗
PubMed2006

A cDNA macroarray approach to parasite-induced gene expression changes in a songbird host: genetic response of house finches to experimental infection by Mycoplasma gallisepticum.

In 1994, the bacterial parasite Mycoplasma gallisepticum expanded its host range and swept through populations of a novel host--eastern US populations of the house finch (Carpodacus mexicanus). This epizootic caused a dramatic decline in finch population numbers, has been shown to have caused strong selection on house finch morphology, and presumably caused evolutionary change at the molecular level as finches evolved enhanced resistance. As a first step toward identifying finch genes that respond to infection by Mycoplasma and which may have experienced natural selection by this parasite, we used suppression subtractive hybridization (SSH) and cDNA macroarray approaches to identify differentially expressed genes regulated by the Mycoplasma parasite. Two subtractive cDNA libraries consisting of 16,512 clones were developed from spleen using an experimentally uninfected bird as the 'tester' and an infected bird as 'driver', and vice versa. Two hundred and twenty cDNA clones corresponding 34 genes with known vertebrate homologues and a large number of novel transcripts were found to be qualitatively up- or down-regulated genes by high-density filter hybridization. These gene expression changes were further confirmed by a high throughout reverse Northern blot approach and in specific cases by targeted Northern analysis. blast searches show that heat shock protein (HSP) 90, MHC II-associated invariant chain (CD74), T-cell immunoglobulin mucin 1 (TIM1), as well as numerous novel expressed genes not found in the databases were up- or down-regulated by the host in response to this parasite. Our results and macroarray resources provide a foundation for molecular co-evolutionary studies of the Mycoplasma parasite and its recently colonized avian host.

Animals↗
PubMed1990

Phenotypic and functional changes of tumour cells from patients treated with monoclonal anti-idiotypic antibodies.

In this paper data are presented indicating that immunotherapy with monoclonal anti-idiotypic antibodies (MoAb anti-id) can provoke different responses in the B-cell tumour concerned. With respect to the course of disease during and after immunotherapy, the in vitro findings may very well explain the in vivo observations in the two patients (D.E.F., B.O.R.) with B-cell chronic lymphocytic leukaemia (B-CLL) who were treated with MoAb anti-id. After initial tumour reduction, there was a recurrence of tumour cells with altered functional and phenotypic properties. In both cases the recurring tumour cells still expressed the same idiotype. In one patient (D.E.F.) the phenotypic changes (a surface Ig change from IgM, IgG, IgA, and IgD to weakly positive IgM and IgD) and functional changes (a 10-fold increase in [3H]thymidine uptake and a decreased idiotype secretion in vitro), together with the in vivo findings with respect to the course of disease--at relapse an impressive tumour regrowth rate with constant serum idiotype level--suggest that immunoselection might have taken place favouring the survival and relapse of a less mature, more aggressive tumour cell population with a lower idiotype expression. In the second patient (B.O.R.), the phenotypic changes (an isotype change from IgM and IgD to IgM with the loss of IgD, and a gradual decrease in expression of CD19 and CD24) and functional changes (a 10-fold increase of idiotype secretion in vitro), together with the in vivo finding that the serum idiotype level had increased 25-fold compared with the preimmunotherapy serum level with comparable tumour load, strongly suggest an immunotherapy-induced differentiation of the malignant B cell. We also describe an increased expression of CD74, detected by MoAb BoM22, on the recurring tumour cells of patient B.O.R., whereas the expression of HLA-DP, -DQ and -DR did not change. The significance of this finding is unclear.

Antibodies, Anti-Idiotypic↗
PubMed1998

Phenotypical and functional characterization of Herpesvirus saimiri-immortalized human major histocompatibility complex class II-deficient T lymphocytes.

CD8+ T lymphocytes from two unrelated cases of MHC class II deficiency were immortalized in vitro using Herpesvirus saimiri. In both cases, a lack of expression of surface MHC class II molecules was ascertained, whereas variable defects were shown for MHC class I, CD74 (invariant chain) and LAG-3 (an MHC class II ligand). The functional analysis of both H. saimiri-immortalized T-cell lines revealed the existence of a proliferation impairment in response to anti-CD3 but not to other surface or transmembrane stimuli. Further characterization of this functional defect indicated that it was not associated with impaired early activation events (like calcium flux) but, rather, with certain late events, like the induction of IL-2. H. saimiri-immortalized T cells may be valuable in studying the biological role of MHC class II molecules in activated human T cells.

Cell Transformation, Viral↗
PubMed1995

Reticular crypt epithelium and intra-epithelial lymphoid cells in the hyperplastic human palatine tonsil: an immunohistochemical analysis.

Extensive immunohistochemical analyses of the hyperplastic human palatine tonsil disclosed variegated B cell phenotypes on the lymphoid cells among the crypt epithelium. The reticular epithelial network was evident by cytokeratin immunostaining. The reticular epithelium near the crypt lumen was positive for lysozyme. Secretory component was negative, while HLA-DR was frequently expressed. Intramucosal small lymphocytes, densely distributed in the luminal side, consisted mainly of B cells expressing CD19, CD20, CD21, CD22, CD45R, CD74, DBB42, HLA-DR, HLA-DQ, bcl-2 protein and surface IgM. Some B cells revealed mantle zone phenotypes (surface IgD+, CD5+, CD24+, DBA44+, CD10-, DNA7-). Cells of germinocyte phenotype (CD10+, DNA7+) were sparsely seen. A good number of intramucosal lymphoid cells were further labeled for CD11b, a phenotype of so-called B-1 cells. Plasma cells were clustered within the basal half. IgG was their major immunoglobulin class, followed by IgA, IgM and IgD classes. A smaller number of T cells (CD2+, CD3+, CD5+, CD45RO+, TCR alpha beta+) were identified among the epithelium. CD4+ cells predominated over CD8+ cells. TCR gamma delta+ cells were rare. Macrophages (CD68+), dendritic histiocytes (S-100 protein+, CD1+), and natural killer cells (CD16+ or CD57+) were also dispersed. Another unique feature of this lymphoepithelial complex was the existence of HLA-DR- intramucosal intramucosal microvasculature, where lymphocyte recirculation was suggested. Proliferating cell nuclear antigen was detected commonly in the epithelial cells but rarely in the lymphoid cells. Possible lymphoepithelial interactions and morphologic similarities to the thymic medulla are discussed.

Adolescent↗
PubMed2005

Metastasizing atypical fibroxanthoma (cutaneous malignant histiocytoma): report of five cases.

BACKGROUND: Atypical fibroxanthoma (AFX) is an unusual malignant fibrohistiocytic tumor of sun-damaged skin. When first described, it was felt to be a reactive tumor of low malignant potential. More recently, it has been shown to be a tumor of intermediate malignant potential. OBJECTIVE: To describe five cases of metastatic AFX. RESULTS: Five patients ranging in age from 65 to 85 years old presented with metastatic AFX. Three of the five cases presented with regional lymph node disease. Also, three of the five cases had other aggressive cutaneous malignancies. LN-2 (CD74) staining was positive in three of five primary tumors and two of five metastatic tumors. CONCLUSION: The metastatic potential of AFX may be underestimated. LN-2 staining may be a useful marker in identifying more aggressive tumor behavior.

Aged↗
PubMed1997

Leukemic cells within skin lesions of psoriasis in a patient with acute myelogenous leukemia.

We report on an 81-year-old man with acute myelo-monocytic leukemia (FAB M4) and a long-standing history of psoriasis. Biopsy of psoriatic plaques revealed the coexistence of characteristic histopathologic aspects of psoriasis together with an infiltrate of blasts with features of myelo-monocytes, suggestive of a specific leukemic infiltrate within plaques of psoriasis. Immunohistologic stainings showed positivity of blasts for LN2 (CD74), MT1 (CD43), and lysozyme, consistent with a myeloid lineage of these cells. To the best of our knowledge, this is the first report on the association of psoriasis with myelogenous leukemia. The presence of leukemic cells within psoriatic skin plaques may be explained by non-specific recruitment of recirculating malignant cells to the skin. Alternatively, as psoriasis is an inflammatory disease involving granulocytes among other cell types, it may be hypothesized that leukemic cells retain to some extent their capability to respond to physiologic stimuli and enter the skin in response to specific chemotactic factors.

Aged↗
PubMed1991

Phenotyping of peripheral blood hemopoietic progenitor cells--in vitro cultures using CD34-/CD33-immunomagnetic purging.

In contrast to many detailed studies on the antigenic profile of hemopoietic progenitor cells from human bone marrow, sparse information, so far, has been gathered with regard to the antigen expression of hemopoietic progenitors present in peripheral blood. Previous studies by multiparameter flow-cytometry have revealed substantial differences of the coexpression of the CD33-, CD19-, and CD74- antigens, respectively, on CD34-positive cells from blood versus those from bone marrow, respectively. Immunomagnetic purging with monoclonal antibodies detecting the CD34-, and the CD33- antigen, respectively, has been used to further characterize the expression of these antigens on day 8 and d-14 granulocyte/macrophage and erythroid colonies as grown from circulating progenitor cells. Purging with CD34 monoclonal antibody abrogated all colony formation, whereas purging with CD33 antibody led to differential inhibition of the various progenitors. Purging bone marrow cells with CD34 antibody, an inhibition of only about 25% was observed with regard to erythroid colonies, whereas an inhibition of about 85% was observed for CFU-GM. These findings reinforce the view that circulating progenitor cells represent relatively immature stages of differentiation, when compared to bone marrow progenitors. Particularly, d-8 erythroid colonies from blood do not represent the equivalent of the genuine CFU-E as described from bone marrow, but they seem to be early stages of BFU-E development.

Adult↗
PubMed2005

Molecular correlates of emotional learning using genetically selected rat lines.

The genetic contributions to active avoidance learning in rodents have been well established, yet the molecular basis for genetically selected line differences remains poorly understood. To identify candidate genes influencing this active avoidance paradigm, we utilized the bidirectionally selected Syracuse high- and low-avoidance (SHA and SLA) rat lines that markedly differ in their two-way active avoidance behavior. Rats were phenotyped, rested to allow recovery from testing stress and then hippocampi were dissected for gene expression profiling (Affymetrix U34A chips; approximately 7000 known genes), comparing SLA to SHA. Next, a subset of differentially expressed genes was confirmed by real-time PCR (RT-PCR) in hippocampi. Additional studies at the protein level were performed for some genes. Using triplicate arrays on pooled hippocampal samples, differentially expressed genes were identified by microarray suite 5.0 and robust multi-array average analyses. By RT-PCR analysis in hippocampi, eight genes were nominated as potential candidate genes consistent with the differential expression from the microarray data. Four genes, Veli1 (mlin-7B), SLC3a1, Ptpro and Ykt6p, showed higher expression in SHA hippocampi than SLA. Four genes, SLC6A4, Aldh1a4, Id3a and Cd74, showed higher expression in SLA hippocampi than SHA. The active avoidance behavioral difference between lines probably emerges from 'many small things'. These potential candidate genes generate hypotheses for future testing in human association and rodent studies. Differences in levels of a pleiotropic gene like Ptpro and SLC6A4 suggest that small differences over a lifespan may contribute to large behavioral differences.

Animals↗