Loss of Fas (CD95/APO-1) regulatory function is an important step in early MALT-type lymphoma development.

Fas (CD95, APO-1) mutations were found in autoimmune diseases and some lymphomas, suggesting impairment of Fas-mediated cell death signaling that may cause tumor development. Because mucosa-associated lymphoid tissue (MALT)-type lymphoma B cells recognize autoantigens and proliferate in response to antigen and T cell-mediated signals, it is suggestive that autoreactive B cell lymphoma precursor cells may have escaped the Fas-mediated checkpoint that normally operates in healthy individuals. Using different biochemical, molecular, and functional approaches, we analyzed the Fas signaling in malignant B cells from seven MALT-type lymphomas that were additionally characterized for the t(11;18)(q21;q21) and four gastric diffuse large B cell lymphomas (DLBL).

Oral administration of influenza vaccine in combination with the adjuvants LT-K63 and LT-R72 induces potent immune responses comparable to or stronger than traditional intramuscular immunization.

Mucosal immunization strategies are actively being pursued in the hopes of improving the efficacy of vaccines against the influenza virus. Our group investigated the oral immunization of mice via intragastric gavage with influenza hemagglutinin (HA) combined with mutant Escherichia coli heat-labile enterotoxins K63 (LT-K63) and R72 (LT-R72). These oral immunizations resulted in potent serum antibody and HA inhibition titers, in some cases stronger than those obtained with traditional intramuscular administration, in addition to HA-specific immunoglobulin A in the saliva and nasal secretions.

Pathology of lymphoma progression.

Reflecting the stepwise process of oncogenesis, lymphomas may cumulatively develop a more aggressive phenotype during the course of disease, a process referred to as lymphoma progression. Although morphological, clinical and biological aspects of lymphoma progression do not always overlap, changes in lymphoma morphology frequently indicate alterations in the clinical and biological behaviour of the disease. Indolent and aggressive lymphomas in disease progression can either be clonally related or represent clonally unrelated neoplasms.

Primary low-grade B cell non-Hodgkin's lymphoma of MALT type simultaneously arising in the colon and in the lung: report of a case.

zone B cell lymphoma of mucosa-associated lymphoid tissue type according to the Revised European American Lymphoma classification). Other mucosa-associated lymphoid tissue-type lymphomas arise in the salivary glands, thyroid gland, and in the lung (bronchus-associated lymphoid tissue). Here, we report the first case of a monoclonal mucosa-associated lymphoid tissue lymphoma with simultaneous manifestation in the colonic and bronchial mucosa in a 62-year-old patient.

MIDCAB: impact of epicardial stabilization upon outcomes.

Background: Minimally invasive direct coronary artery bypass (MIDCAB) has been criticized as compromising anastomotic patency. Epicardial mechanical stabilization devices purportedly facilitate left internal mammary artery (LIMA) anastomosis, thereby enhancing patency and outcome.

Methods: From June 1996 through January 1999, 39 patients underwent MIDCAB via a small left anterior thoracotomy for revascularization of the left anterior descending coronary artery (LAD) without cardiopulmonary bypass (CPB).

Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells.

Dendritic cells (DC) play a key role in antigen presentation and activation of specific immunity. Much current research focuses on harnessing the potency of DC for vaccines, gene therapy, and cancer immunotherapy applications. However, DC are not readily transfected in vitro by traditional nonviral techniques.

[Genetic and biological features define two types of follicular non-Hodgkin grade 3 lymphoma].

In the REAL classification system, follicular lymphomas (FL) were subdivided into three grades depending on the number of blasts (6). In this study, we were interested in defining biological parameters possibly being important in the delineation of subgroups. Between 1990 and 1998, biological and cytogenetic investigations were performed on 91 FL.

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions.

Surgery for second lung cancers.

Purpose: To evaluate the outcomes of patients surgically treated for their second primary lung cancer.

Method: In a computerized surgical registry of > 800 consecutive patients treated for primary pulmonary carcinoma since 1980, 37 patients presented with a second lung cancer. These patients were analyzed regarding their original treatment, preoperative evaluation, operative procedures, and long-term follow-up.

Torsion of the uterine adnexa. Pathologic correlations and current management trends.

Objective: To evaluate the clinical and pathologic correlates of specimens removed for the diagnosis of adnexal torsion and to evaluate trends in the management of torsion.

Study Design: Cases of ovarian or adnexal torsion (N = 104) were identified retrospectively over a period extending from January 1987 to March 1998 by the coding of ovarian, fallopian tube or adnexal torsion. Statistical evaluation was by chi 2 analysis using the Bonferroni inequality correction when appropriate.

Heterogeneity of the API2-MALT1 gene rearrangement in MALT-type lymphoma.

The translocation t(11;18)(q21;q21), which is the most frequent chromosomal aberration in extranodal marginal zone B cell lymphomas of MALT-type, was characterised in a series of 34 biopsies, including 18 gastric non-Hodgkin's lymphomas (NHL) of MALT-type, six MALT-type NHL of extragastral origin and 10 extranodal large B cell lymphomas (LBL). Based on fluorescence in situ hybridisation, STS-PCR analysis and screening of genomic PAC libraries, a physical map of contiguous DNA probes on chromosome 11 was constructed containing the anti-apoptotic genes API2 and API1 adjacent to the translocation breakpoint. RACE-PCR experiments revealed MALT1 the chromosome 18-derived fusion partner of API2, which has also been reported recently by other groups.

Pathological angioarchitecture in lymph nodes: underlying histopathologic findings.

Pathologic changes of the intranodal angioarchitecture, as displayed by colour Doppler sonography, were used in recent studies to predict malignant infiltration of superficial lymph nodes. We searched for the underlying histopathologic findings in a prospective study including 100 lymph nodes in 86 patients. In the histopathologic specimens, we evaluated tumour infiltration, distribution of intranodal vessels, hilar structures, thickness of the capsule and tissue alterations (necrosis, sclerosis, lipo-/fibromatosis).

Genetically detoxified mutants of heat-labile enterotoxin from Escherichia coli are effective adjuvants for induction of cytotoxic T-cell responses against HIV-1 gag-p55.

There is an urgent need for prophylactic and therapeutic vaccines against human immunodeficiency virus (HIV). Mucosal immunization strategies have great potential to elicit both mucosal and systemic cellular immunity required to protect against HIV-induced acquired immune deficiency syndrome (AIDS). However, mucosal immunizations with soluble protein antigens generally require adjuvants.

Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice.

Intramuscular injection of DNA vaccines elicits potent humoral and cellular immune responses in mice. However, DNA vaccines are less efficient in larger animal models and humans. To gain a better understanding of the factors limiting the efficacy of DNA vaccines, we used fluorescence-labeled plasmid DNA in mice to 1) define the macroscopic and microscopic distribution of DNA after injection into the tibialis anterior muscle, 2) characterize cellular uptake and expression of DNA in muscle and draining lymph nodes, and 3) determine the effect of modifying DNA distribution and cellular uptake by volume changes or electroporation on the magnitude of the immune response.

Recurrent genetic aberrations in thymoma and thymic carcinoma.

Apart from single reported aberrant karyotypes, genetic alterations in thymic epithelial neoplasms have not been investigated so far. In this study, 12 World Health Organization classification type A thymomas (medullary thymomas), 16 type B3 thymomas (well-differentiated thymic carcinomas), and nine type C thymomas, all of them primary thymic squamous cell carcinomas, were analyzed by comparative genomic hybridization and fluorescence in situ hybridization. With the exception of one single case, type A thymomas did not reveal chromosomal gains or losses in comparative genomic hybridization.

Limited sequence heterogeneity of Epstein-Barr virus nuclear antigen 1 in benign and malignant EBV-associated disorders.

Background: The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is essential for replication and maintenance of circular EBV genomes in latently infected B lymphocytes and is the only EBV protein expressed in nearly all cells carrying the virus. EBNA-1 is suggested to be oncogenic in vivo since its expression induces B-cell neoplasia in transgenic mice.

Patients, Materials And Methods: EBV wild-type isolates from ten malignant tumors and from 15 children with various benign EBV-associated disorders were examined for the presence of EBNA-1 variant strains by PCR and sequencing.

Marginal zone B-cell lymphomas (MZBL) arising at different sites represent different biological entities.

Most entities of B-cell malignant non-Hodgkin's lymphomas (NHL) are characterized by typical primary chromosomal changes such as the t(14;18) in follicular lymphoma or the t(11;14) in mantle cell lymphoma. In contrast, marginal zone B-cell lymphomas (MZBL), arising at different nodal and extranodal sites, are poorly characterized on the genetic level. We performed cytogenetic investigations in 20 splenic and in 10 nodal MZBL and analyzed 52 MZBL (including 12 MALT-type lymphomas) for deletions of TP53, D13S25, and RB1 loci by fluorescence in situ hybridization.

Expression of CD94/NKG2A and killer immunoglobulin-like receptors in NK cells and a subset of extranodal cytotoxic T-cell lymphomas.

Thirty-two natural killer (NK) and cytotoxic T-cell lymphomas and 14 noncytotoxic nodal T-cell lymphoma controls were immunostained with the use of monoclonal antibodies reactive against NK-cell receptor (NKR) molecules (CD94, NKG2A, p58.2, p58.1, p140, p70, p50.

A method for constructing the C44-C51 side chain of altohyrtin C.

[formula: see text] A method to construct the C44-C51 side chain of altohyrtin C has been developed and applied to a model aldehyde derived from D-glucose. The approach relies on a Wittig reaction to couple the side chain to an aldehyde and utilizes an allylic diazene rearrangement to place the C45 double bond in the correct position.

Novel anionic microparticles are a potent adjuvant for the induction of cytotoxic T lymphocytes against recombinant p55 gag from HIV-1.

Microparticles with entrapped antigens have recently been shown to possess significant potential as vaccine delivery systems and adjuvants. However, the potential of microparticles as adjuvants has been seriously limited by the common problem of degradation and denaturation of antigens following encapsulation and release. To overcome these problems, we have developed a novel way to use microparticles as adjuvants, by the adsorption of proteins onto their surface.

Genetic imbalances in primary gastric diffuse large B-cell lymphomas: comparison of comparative genomic hybridization, microsatellite, and cytogenetic analysis.

Extranodal malignant non-Hodgkin's lymphomas account for about 40% of lymphoid neoplasms, but few data are available concerning the genetic background of primary gastric diffuse large B-cell lymphoma (DLBCL). A study was performed of 27 primary gastric DLBCLs and 5 gastric DLBCLs with a concomitant low grade component of mucosa-associated lymphoid tissue-type lymphoma using comparative genomic hybridization (CGH), microsatellite studies, classic cytogenetics, and fluorescence in situ hybridization (FISH) to search for specific genetic aberrations. The most frequent aberrations were losses of material on chromosome 6q and gains of parts of chromosome 3.

[MALT-type non-Hodgkin's lymphoma: advances in biopsy diagnosis and pathogenesis].

Malignant Non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue display unique morphological and biological features. Unlike the situation in nodal lymphomas, they almost invariably arise from defined and recognisable precursor lesions, such as chronic infections or autoimmune diseases. From the diagnostic point of view, efforts have been undertaken to define (1) the minimal requirements for the unequivocal diagnosis of MALT-type lymphoma, (2) the regression stages after Helicobacter pylori eradication, and (3) to establish a grading system for the respective lesions.

The ATM gene in the pathogenesis of mantle-cell lymphoma.

Background: Mantle-cell lymphoma (MCL) is genetically characterized by the translocation t(11;14)(q13;q32) leading to an overexpression of cyclin-D1, but additional chromosomal abnormalities appear to be required for MCL pathogenesis.

Patients And Methods: Deletions involving chromosome 11q, which were recently found as recurrent aberrations in MCL, were analyzed at the molecular level in a series of 81 MCL by fluorescence in situ hybridization (FISH) with probes from a contiguous set of yeast artificial chromosomes (YACs) spanning bands 11q14-q24.

Results And Conclusions: Loss of chromosome 11 material was observed in 37 of the 81 MCL cases (46%).

Microparticles in MF59, a potent adjuvant combination for a recombinant protein vaccine against HIV-1.

Novel adjuvant formulations involving PLG microparticles with entrapped recombinant protein antigens (env gp120 and p24 gag) from human immunodeficiency virus type-1 (HIV-1), dispersed in the emulsion adjuvant MF59 were evaluated as potential HIV-1 vaccine candidates in mice and baboons. In mice, the adjuvant combination induced significantly enhanced antibody responses in comparison to either adjuvant used alone. In addition, the polylactide co-glycolide polymer (PLG) microparticles and MF59 combination induced CTL activity against HIV-1 p24 gag.