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Query: UNIPROT:P06889 (Mol)
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Multigene families are a ubiquitous feature of eukaryotes; however, their presence in Saccharomyces is more limited. The MAL multigene family is comprised of five unlinked loci, MAL1, MAL2, MAL3, MAL4 and MAL6, any one of which is sufficient for yeast to metabolize maltose. A cloned MAL6 locus was used as a probe to facilitate the cloning of the other four functional loci as well as two partially active alleles of MAL1. Each locus could be characterized as a cluster of three genes, MALR (regulatory), MALT (maltose transport or permease) and MALS (structural or maltase), encoded by a total of about 7 kb of DNA; however, homologous sequences at each locus extend beyond the coding regions. Our results indicate that there is extensive homology among the MAL loci, especially within their maltase genes. The greatest sequence diversity occurs in their regulatory gene regions. Southern cross analyses of the cloned MAL loci indicate a single duplication of the MAL6R-homologous sequences upstream of the MAL6R gene as well as an extensive duplication of more than 10 kb at the MAL3 locus. The large repeat at the MAL3 locus results in the presence of four copies of MAL3R-homologous sequences and two copies of MAL3T-homologous sequences at that locus. Two naturally occurring inactive alleles of MAL1 show a deletion or divergence of their MALR sequences. The significance of these repeats in the evolution of the MAL multigene family is discussed.
Mol Gen Genet 1989 May
PMID:Structure of the multigene family of MAL loci in Saccharomyces. 254 70

Both the MAL1 and MAL6 loci in Saccharomyces strains have been shown by functional and structural studies to comprise a cluster of at least three genes necessary for maltose utilization. They include regulatory, maltose transport and maltase genes designated MALR, MALT and MALS, respectively. Subclones of each gene derived from the MAL6 locus were inserted into the multicopy shuttle plasmid YEp13, introduced into MAL1 and mal1 strains and the effects of altered gene dosage of each gene, or a combination of them, on MAL gene expression investigated. MAL1 strains transformed with a plasmid carrying the MAL6S gene showed coordinate four to five fold increases in both maltase enzyme activity and its mRNA, whereas no increase in maltose transport activity or of MALT mRNA was observed when MAL6T was present on multicopy plasmids. The presence of the MAL6R gene on a multicopy plasmid led to greatly increased transcription of both inducible and constitutive mRNAs with homology to the regulatory gene; it also gave rise to two fold increases in both induced maltase mRNA levels and enzyme activity, but only in the presence of maltose. However, it had no apparent effect on the accumulation of MALT mRNA. Finally, the induction kinetics of plasmid-borne and chromosomal MALS and MALT gene expression were examined under conditions of altered gene dosage of the MAL6 regulatory and structural genes. The results of these experiments indicate that MALR encodes a trans-acting positive activator that requires maltose for induction of MALS and MALT transcription even when the regulatory gene is present on a multicopy plasmid. Maltose transport can be a rate-limiting factor in MAL gene expression, at least in the early stages of induction. The regulation of the MALS and MALT genes, whose activities are coordinately induced in MAL1 strains by maltose, may in fact exhibit some important differences.
Mol Gen Genet 1987 Oct
PMID:Regulation of MAL gene expression in yeast: gene dosage effects. 332 27

Maltose utilization in yeast requires the presence of any one of the five unlinked, homologous MAL loci. Transcription of the two structural genes MALT (permease) and MALS (maltase) is induced by maltose and catabolite-repressed by glucose. MAL6T and MAL6S share a common 5' intergenic sequence; deletion studies within this sequence revealed a bi-directionally functioning upstream activation sequence (UASM) consisting of four 11 bp homologous sites. Activation of these sites by the MALR protein results in the coordinate expression of MAL6T and MAL6S. The basal promoter activates MALS expression to a greater extent than MALT and is located in a region that overlaps UASM. Deletion of several subsites within the UASM has an asymmetric effect on MAL gene expression, having a greater affect on MALT than on MALS. Catabolite repression of MAL6T and MAL6S by glucose is controlled at several levels. Using disruption mutants, the positively acting MAL1R protein was also found to play a role in catabolite repression of MAL6T and MAL6S.
Mol Gen Genet 1994 Jun 15
PMID:Shared control of maltose induction and catabolite repression of the MAL structural genes in Saccharomyces. 802 78

Twenty-one cases of mucosa-associated lymphoid tissue (MALT) lesions have been analyzed by Southern blot for immunoglobulin heavy chain (IgH) and T-cell receptor beta chain (TcR beta) gene rearrangements (GR). The sites included colon, stomach, liver, nasopharynx, salivary and lacrimal gland, conjunctiva, tonsil, breast, and lung. Two of the lesions (parotid and conjunctiva) were malignant lymphomas and one case showed lymphoproliferative disorder. In the cases of malignant lymphomas, IgH GR were detected, and in the case of lymphoproliferative disorder, both IgH and TcR beta genes were rearranged. Among the remaining 18 cases, 9 showed inflammatory infiltrate, 3 lymphoid hyperplasia, 3 atypical lymphoid hyperplasia, 1 carcinoma of the tonsil, 1 breast carcinoma, and one was a sample of normal Peyer's patches. Among these 18 cases, 3 showed TcR beta GR, 6 showed double IgH and TcR beta GR, and 4 IgH GR. Often multiple rearranged bands were observed, composing 10-30% of the total DNA analyzed. The control tissue (Peyer's patches) showed no GR. Because IgH and TcR beta GR are used to determine monoclonal proliferations of T and B lymphocytes, which occur in malignant lymphomas, it is vital to determine the specificity of such a test. This report stresses the fact that in MALT lesions false-positive results are not uncommon and therefore the results of IgH and TcR beta GR studies have to be interpreted with caution. The presence of multiple GR in the inflammatory lesions indicates proliferation of minor monoclonal populations that can be detected with the use of Southern blot technology.
Diagn Mol Pathol 1993 Dec
PMID:Immunoglobulin and T-cell receptor gene rearrangements in lesions of mucosa-associated lymphoid tissue. 811

Recently, the association of Epstein-Barr virus (EBV) with undifferentiated lymphoepithelioma-like carcinoma and adenocarcinoma of the stomach has been described. In this study of 55 primary gastric lymphomas, most of them belonging to the group of MALT lymphomas, the question of possible EBV involvement has been addressed using in-situ hybridization (ISH) and blot techniques. EBV DNA and/or DNA sequences were found in only two of 24 centroblastic and B-immunoblastic lymphomas and in one anaplastic large cell lymphoma of null cell phenotype. In a further centroblastic lymphoma, a few positive nontumorous (bystander) cells were identified by ISH. By means of ISH, no positive signals could be detected in the preserved overlying mucosa nor in regenerating epithelium adjacent to lymphoma-induced ulcerations.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Primary gastric lymphoma is rarely associated with Epstein-Barr virus. 828 24

Local stimulation by Helicobacter pylori (HP), autoantigen, and a concurrent T-cell-mediated stimulation of B cells are believed to play an important role in gastric mucosa-associated lymphoid tissue (MALT) type B cell lymphomagenesis. Many autoimmune diseases have shown to lead to a skewed T-cell repertoire with autoantigen specific expansions and deletions. Characterization of lymphoma and gastritis areas of seven gastrectomy specimens using a T-cell receptor beta variable chain (TCR betaV) family-specific reverse transcriptase (RT)-polymerase chain reaction (PCR) assay and fluorescence-activated cell sorter (FACS) analysis revealed a local chronic and acute activation of T cells in lymphoma and an oligoclonal T-cell repertoire in gastritis and in lymphoma, partially sharing the same clones. Local activation and a partial identity suggest that an antigenic challenge caused by a common local pathogen may still continue to take place in MALT type lymphoma as in gastritis, consistent with the view that gastritis may be a precursor lesion of MALT type lymphoma. Expansions that were found only in one of the compartments suggest that also an immune hyperstimulation may contribute to the T-cell repertoire, possibly because of certain tissue antigens. Deletions of TCR betaV families found only in gastritis underline the view that autoantigen may play an important role in its pathogenesis.
Diagn Mol Pathol 1999 Sep
PMID:Oligoclonal expansions of T-cell repertoire in gastric mucosa associated lymphoid tissue type B-cell lymphoma and adjacent gastritis. 1056 85

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. In three cases, a total of six high level DNA amplifications were detected, with five of them involving chromosomal regions not having been reported before in gastric DLBCL. A high overall concordance of 91.4% between microsatellite analysis and CGH was observed using DNA extracted from the same tissue block. The concordance achieved using DNA from different tissue blocks of the same patient was 85%. Microsatellite studies, CGH, FISH, and classic cytogenetics represent complementary techniques that facilitate a comprehensive view of genetic alterations in malignancies such as primary gastric DLBCL.
Diagn Mol Pathol 2000 Mar
PMID:Genetic imbalances in primary gastric diffuse large B-cell lymphomas: comparison of comparative genomic hybridization, microsatellite, and cytogenetic analysis. 1071 14

Mantle cell lymphoma (MCL) has a worse prognosis than MALT lymphoma (MALTL). Distinction between MCL and MALTL on purely morphologic grounds can be difficult. Cyclin D1 (PRAD1/bcl1) is overexpressed in MCL as a result of a t(11:14) gene rearrangement, which leads to overexpression of cyclin D1 mRNA and protein. The immunohistochemical detection of cyclin D1 in MCL has been reported by several authors to be highly specific with sensitivity ranging from 70%-100%, but diagnostic laboratories have reported difficulty in finding a reliable method for cyclin D1 immunostaining. The aim of this study was to evaluate and optimize a method for detection of cyclin D1 by paraffin section immunoperoxidase staining. Sections of routinely processed tissue from five MCL and one splenic marginal zone lymphoma (MZL) were immunostained using a mixture of two primary monoclonal antibodies and a standard avidin-streptavidin method. Antigen retrieval was performed using 1) steam heat in citrate buffer, 2) as in "1" followed by sonication for one minute, and 3) as in "2" followed by enzymatic digestion. All the above were repeated, with the additional use of catalyzed signal amplification (CSA). Later, sections of the same cases, plus three MALTL were immunostained as in "2". Steam heat antigen retrieval alone produced the best results. All MCL showed positive nuclear staining while the MZL and all MALTL were negative. Sonication did not enhance staining noticeably, whereas enzymatic digestion produced cytoplasmic staining. CSA increased background staining with no significant gain in nuclear stain intensity. We conclude that cyclin D1 immunostaining of formalin-fixed, paraffin-embedded tissue can be reliably achieved by heat induces antigen retrieval and a cocktail of two monoclonal antibodies.
Appl Immunohistochem Mol Morphol 2000 Mar
PMID:Optimized cyclin D1 immunoperoxidase staining in mantle cell lymphoma. 1093 50

Clonal expansion of the germinal center B cells of human reactive lymph nodes was analyzed. By micromanipulation, 28 germinal centers were microdissected from three nonneoplastic lymph nodes that had been fixed with formalin. Immunoglobulin heavy chain variable (V) region gene rearrangement was examined by seminested polymerase chain reaction (PCR) using two sets of primers (FR2-J and FR3A-J). An oligoclonal development (one to five clones) was found in each germinal center. Depending on the primer used, four or five (16%) of the germinal centers showed a single rearrangement band. The average number of B-cell clones in each germinal center was approximately 2.5. Next, the authors analyzed 50 endoscopic biopsy specimens from 6 patients with non-mucosa-associated lymphoid tissue (MALT) type gastric lymphoma, 25 patients with chronic gastritis, and 19 patients with nonspecific colitis. In addition to the samples from the 6 patients with malignant lymphoma, 8 of 44 biopsy samples (18.2%) from patients diagnosed as having chronic gastritis or nonspecific colitis showed one or two amplified bands. These results indicate that PCR analysis of immunoglobulin heavy chain V region gene rearrangement in small biopsy specimens could be misleading, causing overdiagnosis of reactive lymphoid tissue as B-cell clonal proliferation.
Diagn Mol Pathol 2000 Sep
PMID:Clonal proliferation of B lymphocytes in the germinal centers of human reactive lymph nodes: possibility of overdiagnosis of B cell clonal proliferation. 1097 19

Gastric infections by Helicobacter pylori are characteristically associated with an intense inflammation and infiltration of mainly polymorphonuclear lymphocytes (PMNs) and monocytes. The inflammatory response by infiltrated immune cells appears to be a primary cause of the damage to surface epithelial layers and may eventually result in gastritis, peptic ulcer, gastric cancer and/or MALT-associated gastric lymphoma. Our analysis of the interaction between H. pylori and PMNs and monocytes revealed that H. pylori inhibits its own uptake by these professional phagocytes. To some degree, this effect resembles antiphagocytosis by Yersinia enterocolitica. Increasing numbers of bacteria associated per cell are more efficient at blocking their own engulfment. In H. pylori, bacterial protein synthesis is necessary to block phagocytic uptake, as shown by the time and concentration dependence of the bacteriostatic protein synthesis inhibitor chloramphenicol. Furthermore, H. pylori appears broadly to inhibit the phagocytic function of monocytes and PMNs, as infection with H. pylori abrogates the phagocytes' ability to engulf latex beads or adherent Neisseria gonorrhoeae cells. This antiphagocytic phenotype depends on distinct virulence (vir) genes, such as virB7 and virB11, encoding core components of a putative type IV secretion apparatus. Our data indicate that H. pylori exhibits an antiphagocytic activity that may play an essential role in the immune escape of this persistent pathogen.
Mol Microbiol 2000 Sep
PMID:Helicobacter pylori inhibits phagocytosis by professional phagocytes involving type IV secretion components. 1099 71


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