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PubMed1994

Idiotype identity in a MALT-type lymphoma and B cells in Helicobacter pylori associated chronic gastritis.

BACKGROUND: To investigate the mechanisms triggering MALT-lymphoma development, we examined the occurrence of normal B cells in lymphoid tissue and chronic gastritis with the same idiotype as an IgA-positive MALT lymphoma. EXPERIMENTAL DESIGN: Lymphoma idiotype IgA was produced by monoclonal human antibody technology. Against this idiotype a murine monoclonal antibody 27/165 with anti-idiotypic (alpha Id) specificities was raised, and applied immunohistochemically to identify the non-neoplastic precursor B cells in non-neoplastic human tissues. RESULTS: alpha Id 27/165 reacted exclusively with the IgA expressing MALT lymphoma but not with 20 other MALT-type gastric lymphomas nor with 26 nodal lymphomas and was not reactive with normal and inflamed lymph nodes. alpha Id 27/165 immunoreactivity was also absent from MALT of different mucosal sites but was readily encountered on a substantial number of lymphocytes and plasma cells in 95% cases of chronic gastritis associated with Helicobacter pylori (H.p.). The target antigen of the lymphoma IgA was found to be a common antigen of IgA and IgM plasma cells of MALT but not a constituent of bacteria commonly involved in the pathogenesis of gastritis. CONCLUSIONS: The distinct binding of alpha Id 27/165 to only reactive mucosal B cells is a first direct evidence for the evolution of MALT-type lymphoma from chronic gastritis. Since the target antigen of the lymphoma IgA has been found to be an autoantigen of MALT plasma cells it is suggested that this MALT-type lymphoma may have arisen after triggering by an autoimmune response resulting from H.p.-induced gastritis.

Antibodies, Monoclonal↗
PubMed1999

Are there site-specific differences among the MALT lymphomas--morphologic, clinical?

To qualify as a low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) type, lymphomas at different extranodal sites must conform to specific morphologic features. Lymphoepithelial lesions are typical, and follicular colonization is common. Regardless of site, many MALT lymphomas are associated with a predisposing condition, infectious or autoimmune, leading to the acquisition of extranodal MALT. MALT lymphomas in different regions usually have limited disease and indolent clinical courses in which survival does not substantially differ from healthy controls. There is a tendency for diverse cytologic expressions among different MALT lymphomas, such as small lymphocytes in the lung, monocytoid cells in salivary glands, and plamacytic cells in the thyroid and skin, but the site-specific morphologic differences mainly reflect the unique topographic characteristics of the involved organ, and these topographic features also influence the clinical traits. Some of the unparalleled features of MALT lymphomas in different sites include the association of gastric MALT lymphomas with Helicobacter pylori, the lymphangitic distribution of pulmonary MALT cases, and the relationship between MALT lymphomas of the salivary gland and thyroid with Sjögren's syndrome and Hashimoto's thyroiditis, respectively. The ocular cases and those of the skin, breast, and dura also have characteristic clinical modes of presentation largely owing to the anatomic locale of the lymphoma.

Humans↗
PubMed2002

Initial proteome analysis of mature barley seeds and malt.

Several barley (Hordeum vulgare) cultivars are used in the production of malt for brewing. The malt quality depends on the cultivar, its growth and storage conditions, and the industrial process. To enhance studies on malt quality, we embarked on a proteome analysis approach for barley seeds and malt. The proteome analysis includes two-dimensional (2-D) gel electrophoresis, mass spectrometry, and bioinformatics for identification of selected proteins. This project initially focused on proteins in major spots in the neutral isoelectric point range (pI 4-7) including selected spots that differ between four barley cultivars. The excellent malting barley cultivar Barke was used as reference. Cultivar differences in the 2-D gel spot patterns are observed both at the seed and the malt level. In seed extracts one of the proteins causing variations has been identified as an alpha-amylase/trypsin inhibitor. In malt extracts multiple forms of the alpha-amylase isozyme 2 have been identified in varying cultivar characteristic spot patterns. The present identification of proteins in major spots from 2-D gels includes 27 different proteins from 42 spots from mature seed extract, while only three specific proteins were identified by analysing 13 different spots from the corresponding malt extract. It is suggested that post-translational processing causes the same protein to occur in different spots.

Computational Biology↗
PubMed2006

Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions.

Infectious agents play a critical role in MALT lymphoma development. Studies from Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas and complete or partial regression of the lymphoma after C. psittaci eradication in four of nine cases. However, C. psittaci was not demonstrated in ocular adnexal MALT lymphomas from the USA. This study was thus designed to investigate further the role of C. psittaci, and other infectious agents commonly associated with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1 and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non-marginal zone lymphomas, and 51 ocular adnexal biopsies without a lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci was detected at similar low frequencies in non-LPD and non-marginal zone lymphoma groups from different geographical regions (0-14%). Overall, the prevalence of C. psittaci was significantly higher in MALT lymphomas (22%) than in non-LPD (10%, p=0.042) and non-marginal zone lymphoma cases (9%, p=0.033). However, the prevalence of C. psittaci infection in MALT lymphoma showed marked variation among the six geographical regions examined, being most frequent in Germany (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but relatively low in Italy (13%), the UK (12%), and Southern China (11%). No significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were found between lymphomas and controls from different geographical regions. In conclusion, our results show that C. psittaci, but not C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with ocular adnexal MALT lymphoma and that this association is variable in different geographical areas.

Adenoviridae↗
PubMed2002

Numerical chromosomal abnormality in gastric MALT lymphoma and diffuse large B-cell lymphoma.

BACKGROUND: We investigated numerical chromosomal abnormalities, using the fluorescence in situ hybridization (FISH) method, in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBL). We also compared the histopathological findings, including the presence or absence of Helicobacter pylori infection, with the analytical results. METHODS: Sixteen patients who underwent operation for malignant gastric lymphoma in our department were divided into three groups: patients with low-grade gastric MALT lymphoma (l-MALT; n = 5), those with high-grade gastric MALT lymphoma (h-MALT; n = 8), and those with DLBL (n = 3). Numerical abnormalities of chromosomes 8, 9, 12, and 17 were investigated by the FISH method, and the presence or absence of H. pylori infection was microscopically examined. RESULTS: Numerical abnormality was observed in chromosome 12 in 11 patients (68.8%), in chromosome 8 in 10 (62.5%), and in chromosome 17 in 5 (31.3%), showing a high frequency. H. pylori infection was detected in 80% and 50% of patients with l-MALT and h-MALT, respectively, but no H. pylori infection was observed in patients with DLBL. CONCLUSIONS: A new biological characteristic of gastric MALT lymphoma was obtained, i.e., a high frequency of numerical abnormalities of chromosomes 12, 8, and 17. There was no correlation between the numerical chromosomal abnormalities and the clinicopathological findings.

Adult↗
PubMed2005

Fungi, aflatoxins, fumonisin Bl and zearalenone contaminating sorghum-based traditional malt, wort and beer in Botswana.

Brewing and consumption of traditional beer have social-economic significance in most African countries including Botswana. Traditional sorghum malt, wort, and beer samples were collected from three villages around Gaborone, Botswana. Forty-six malt samples were analyzed for fungi on three different media and developing colonies were subcultured for identification. Rhizopus, Fusarium, Mucor, and Aspergillus were the most common genera isolated. Out of the 46 malt samples, 72% contained Rhizopus stolonifer, 63% Fusarium verticillioides (syn. Fusarium moniliforme), and 37% Aspergillus flavus. Although Aspergillus flavus was isolated from malt samples, aflatoxins (B(1), B(2), G(1), and G(2)) were not detected in any of the samples analyzed. When the malt, wort, and beer samples were analyzed for fumonisin B(l) and zearalenone, fumonisin B(1) was detected in 3 malt samples, with concentrations ranging from 47 to 1316 mug/kg, while zearalenone was detected in 56%, 48% and 48% of the malt, wort and beer samples, respectively. Zearalenone concentration in samples ranged from 102 to 2213 mug/kg in malt, 26 to 285 mug/l in wort and 20 to 201 mug/l, in beer. Zearalenone carry-over from wort to beer ranged from 23 to 403%. Therefore, although aflatoxins and fumonisin B(1) do not appear to be major contaminants, zearalenone is common and could pose a potential problem in traditional beer in Botswana.

Aflatoxins↗
PubMed2003

MALT Lymphomas.

Mucosa-associated lymphoid tissue (MALT) lymphomas occur in a variety of organs, including the orbit, conjunctiva, salivary glands, skin, thyroid gland, lungs, stomach, and intestine. These tumors are often localized and of indolent clinical behavior. Diagnosis is made by pathologic evaluation of a tissue biopsy. Careful staging is mandatory and tailored to the initial presentation. Staging includes a history and physical, chemistries, computed tomography scan, and bone marrow biopsy. This information is supplemented with an ear, nose, and throat consultation, esophagogastro-duodenoscopy, colonoscopy, endoscopic ultrasound of the stomach, and cytogenetic/immunohistochemical analysis of the tumors. Treatment is tailored to organ involvement and stage at presentation. Eradication of Helicobacter pylori using a triple anti-H. pylori regimen approved by the US Food and Drug Administration is standard therapy for all H. pylori-positive gastric MALT lymphomas. Endoscopic ultrasound- and computed tomography-staged gastric MALT stage IE tumors will achieve a complete response with this approach in approximately 60% to 90% of patients (the more superficial the tumor, the better the response). Patients with tumors that are T4 node-positive Musshoff stage IIE1 and IIE2 or tumors with adverse cytogenetics should receive radiotherapy or surgery with or without radiotherapy. Tumors with a significant high-grade component or large cell tumors with a minor low-grade MALT component should receive CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy. Localized MALT lymphomas of the orbit, conjunctiva, salivary glands, and thyroid gland are treated successfully with radiotherapy. Surgery as first-line therapy for gastric MALT lymphomas was replaced by attempts at organ preservation. In the past, margin-free surgical excision or tumor debulking followed by radiation therapy and chemotherapy has been highly effective for gastric MALT lymphomas. Therefore, surgical excision of large cell or bulky tumors of the stomach, thyroid, lung, and salivary gland, followed by adjuvant radiotherapy or chemotherapy, may still be an important consideration in selected patients. Surgery still has a role for patients with relapsed or refractory low-grade disease and life-threatening hemorrhage. Disseminated MALT lymphomas are incurable and are treated primarily with chemotherapy according to symptoms.

Humans↗
PubMed1991

Two MalT binding sites in direct repeat. A structural motif involved in the activation of all the promoters of the maltose regulons in Escherichia coli and Klebsiella pneumoniae.

The maltose regulons of Escherichia coli and Klebsiella pneumoniae are very similar, comprising three operons that code for the proteins required for the utilization of maltodextrins as a carbon source. The maltose regulon of K. pneumoniae contains two additional operons, pulAB and pulC-O, which allow the use of starch as a carbon source. The promoters of all of these operons are strictly controlled by the activator protein MalT. In this paper, we report a detailed study of the structure and the functional role of the MalT binding sites located in the adjacent and divergent pulAp and pulCp promoters. By biochemical and genetic experiments, we show that the 134 base-pair region separating the transcription start sites of pulAp and pulCp contains four MalT binding sites, which leads us to propose a revised consensus for the asymmetrical nucleotide sequence recognized by MalT (5'-GGGGAT/GGAGG). MalT binds co-operatively to these four sites, contacting the major groove of the DNA helix. The genetic dissection of the pulAp-pulCp region shows that the promoters partially overlap: the two central MalT binding sites, which are in direct repeat, are required for the activation of both promoters. We further show that an analogous pair of directly repeated MalT binding sites is also involved in the activation of two other promoters of the regulon, malEp and malKp. This study, which confirms the striking structural diversity of the promoters of the maltose regulon, suggests that the motif formed by two MalT binding sites in direct repeat is a recurrent feature of these promoters and plays a crucial role in their activation.

Bacterial Proteins↗
PubMed2002

Isolation, identification and changes in the composition of lactic acid bacteria during the malting of two different barley cultivars.

Malt has a complex microbial population, which changes as the malting process commences. Little is known about the proliferation of lactic acid bacteria (LAB) in each of the malting phases. In this study, we determined the number of LAB present in the different phases of malting with Clipper and Prisma barley cultivars. The strains were identified to species level by using numerical analysis of total soluble cell protein patterns, RAPD-PCR banding patterns and 16S rRNA sequencing. The number of viable LAB in the barley before steep was higher in Prisma than Clipper (7.6 x 10(4) and 1.2 x 10(3) cfu/g, respectively). Despite this, the number of viable cells recorded in the first steep water was slightly higher for Clipper (9.0 x 10(5) cfu/g) than Prisma (5.5 x 10(5) cfu/g). More or less, the same cell numbers were recorded for the two barley cultivars after the first and second dry stands. Both cultivars displayed more or less the same cell numbers (3.7 x 10(7) for Clipper and 3.2 x 10(7) cfu/g for Prisma) after the third day of germination. However, a higher number of LAB were detected in the kilned Prisma malt (6.9 x 10(4) cfu/g) than the Clipper malt (1.5 x 10(4) cfu/g). Leuconostoc argentinum, Le. lactis and Weissella confusa were the most predominant in both cultivars. A few strains were identified as W. paramesenteroides (four strains), Lactobacillus casei (five strains), Lactococcus lactis (five strains) and Lb. rhamnosus (two strains). Lb. casei and Lb. rhamnosus were not isolated from the Prisma cultivar, while W. paramesenteroides and Lc. lactis were absent in the Clipper cultivar. Kilned malt of the Clipper cultivar contained predominantly Le. argentinum, whereas the Prisma cultivar contained mainly Lc. lactis. To our knowledge. this is the first report of LAB in Clipper and Prisma barley and the various malting phases. The influence of the various groups of lactic acid bacteria on the fermenting ability of brewers' yeast is currently being determined.

Colony Count, Microbial↗
PubMed2002

The effect of mashing on malt endoproteolytic activities.

During malting and mashing, the proteinases of barley (Hordeum vulgare L.) and malt partially hydrolyze their storage proteins. These enzymes are critical because several aspects of the brewing process are affected by the soluble proteins, peptides and/or amino acids that they release. To develop improved malting barleys and/or malting and brewing methods, it is imperative to know whether and when the green malt endoproteinases are inactivated during malting and mashing. These enzyme activities are totally preserved during kilning and, in this study, we have determined when they were inactivated during mashing. Samples were removed from experimental mashes that mirrored those used in commercial breweries and their endoproteolytic activities were analyzed. The malt endoproteinases were stable through the 38 degrees C protein rest phase, but were quickly inactivated when the mash temperature was raised to 72 degrees C for the conversion step. All of the proteinase activities were inactivated at about the same rate. These findings indicate that the soluble protein levels of worts can be varied by adjusting the protein rest phase of mashing, but not by altering the conversion time. The rates of hydrolysis of individual malt proteins probably cannot be changed by altering the mash temperature schedule, since the main enzymes that solubilize these proteins are affected similarly by temperature.

Beer↗
PubMed2004

Multiresidue determination of pesticides in malt beverages by capillary gas chromatography with mass spectrometry and selected ion monitoring.

A method was developed to determine pesticides in malt beverages using solid phase extraction on a polymeric cartridge and sample cleanup with a MgSO4-topped aminopropyl cartridge, followed by capillary gas chromatography with electron impact mass spectrometry in the selected ion monitoring mode [GC-MS(SIM)]. Three GC injections were required to analyze and identify organophosphate, organohalogen, and organonitrogen pesticides. The pesticides were identified by the retention times of peaks of the target ion and qualifier-to-target ion ratios. GC detection limits for most of the pesticides were 5-10 ng/mL, and linearity was determined from 50 to 5000 ng/mL. Fortification studies were performed at 10 ng/mL for three malt beverages that differ in properties such as alcohol content, solids, and appearance. The recoveries from the three malt beverages were greater than 70% for 85 of the 142 pesticides (including isomers) studied. The data showed that the different malt beverage matrixes had no significant effect on the recoveries. This method was then applied to the screening and analysis of malt beverages for pesticides, resulting in the detection of the insectide carbaryl and the fungicide dimethomorph in real samples. The study indicates that pesticide levels in malt beverages are significantly lower than the tolerance levels set by the United States Environmental Protection Agency for malt beverage starting ingredients. The use of the extraction/cleanup procedure and analysis by GC-MS(SIM) proved effective in screening malt beverages for a wide variety of pesticides.

Beer↗
PubMed2005

p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis.

p16/INK4a gene alterations have been associated with tumor progression in lymphoid malignancies. However, their significance in mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. We investigated p16 gene methylation and mutation in a large series of untreated cases of pulmonary MALT lymphoma and diffuse large B-cell lymphoma (DLBL), and correlated p16 gene alterations with a MALT lymphoma-specific API2-MALT1 fusion and the clinicopathologic features of MALT lymphoma. The API2-MALT1 fusion was detected by multiplex reverse transcription polymerase chain reaction in 25/60 (42%) cases of MALT lymphoma, but none of 11 DLBLs. Methylation-sensitive single-strand conformation analysis showed that p16 gene methylation was frequently detected in 36/60 (60%) cases of MALT lymphoma. The gene was similarly methylated in DLBL cases (6/11, 55%). A p16 gene mutation was found in one (p16 gene-methylation) of 44 MALT lymphomas and in none of six diffuse large B-cell lymphomas. Statistical analysis showed that the p16 gene methylation status did not correlate with API2-MALT1 fusion or any of the clinicopathologic factors including serum LDH, clinical stage, and increased large cells. These findings suggest that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis that might be maintained through the progression of the tumor.

Adult↗
PubMed2000

Helicobacter pylori-gastrin link in MALT lymphoma.

BACKGROUND: There is accumulating evidence for the role of Helicobacter pylori in the development of gastric cancer as well as of lymphomas that arise in mucosa-associated lymphoid tissue (MALT). We reported recently that gastric cancer patients show high prevalence of cagA-positive H. pylori and express gastrin and gastrin receptors enabling them to stimulate tumour growth in autocrine fashion. AIMS: Since the H. pylori infection is considered to be more strongly associated with MALT lymphoma than with gastric cancer, we decided to determine the gastrin and its receptors' mRNA expression and gastrin content in this tumour as well as the release of this hormone both into plasma and gastric lumen. Twenty MALT lymphoma patients were compared with 100 age- and gender-matched controls with similar dyspeptic symptoms. RESULTS: The overall H. pylori seropositivity in MALT lymphoma was about 90% and CagA positivity was 70%, compared to 56% and 33%, respectively, in controls. The serum gastrin in MALT lymphoma was about sixfold higher than in controls while gastric luminal gastrin in these patients was over 70 times higher than in controls. Gastrin content in tumour was about 10-fold higher than in antral mucosa. Gastrin and gastrin-receptor (CCKB-receptor) mRNA were detected by reverse transcriptase-polymerase chain reaction in cancer tissue whilst in the fundic and antral mucosa, only enhanced expression of CCKB-receptor mRNA and gastrin mRNA was detected, respectively. Histamine stimulation in MALT lymphoma induced acid secretion that was only about 30% of control value due to atrophic gastritis. This study confirms an important role of CagA-positive H. pylori in the pathogenesis of MALT lymphoma and shows that this lymphoma is capable of synthesizing and releasing potent growth promoting gastrin, possibly due to the action on G-cells of H. pylori-originated Nalpha-methyl histamine and cytokines (tumour necrosis factor alpha and interleukin-8). CONCLUSIONS: Gastric MALT lymphoma is closely linked to CagA-positive H. pylori infection. Gastrin and its receptors may be implicated in the pathogenesis of gastric lymphoma.

Adult↗
PubMed2003

F-18-FDG-PET in a patient with Hashimoto's thyroiditis and MALT lymphoma recurrence of the thyroid.

We report on the case of a 86-year-old male patient with a rapidly growing nodule within the right lobe of the thyroid gland, which after hemithyroidectomy, turned out to be a mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland. In addition, Hashimoto's thyroiditis was reported in the thyroid tissue adjacent to the MALT lymphoma. During follow-up a second nodule emerged within the left lobe and, because of evidence of MALT lymphoma recurrence, F-18-FDG-PET was performed. F-18-FDG-PET imaged a clearly increased accumulation within the whole left lobe and isthmus. Thus, no differences in the degree of hypermetabolism could be imaged between the nodule and the adjacent thyroid tissue. To our knowledge, this is the first report about F-18-FDG-PET in a patient with MALT lymphoma of the thyroid. Literature search revealed only a few cases of MALT lymphomas in locations other than the thyroid gland that were studied with F-18-FDG-PET. In no case was F-18 FDG accumulation seen in the MALT lesions. However, clear F-18 FDG accumulation was reported in some patients with Hashimoto's thyroiditis. It is concluded that the intensive F-18-FDG accumulation within the whole left lobe and isthmus of the presented case was due to the coexisting Hashimoto's thyroiditis. Consequently, F-18-FDG-PET imaging does not seem to be indicated in a patient with MALT lymphoma and known Hashimoto's thyroiditis in order to evaluate the status of the MALT lymphoma.

Aged↗
PubMed1999

Self-association of the Escherichia coli transcription activator MalT in the presence of maltotriose and ATP.

MalT, the transcriptional activator of the Escherichia coli maltose regulon, binds the MalT-dependent promoters and activates transcription initiation only in the presence of maltotriose and ATP (or adenylyl imidodiphosphate (AMP-PNP)). Cooperative binding of MalT to the array of cognate sites present in the MalT-dependent promoters suggests that promoter binding involves MalT oligomerization. Gel filtration and sedimentation experiments were used to analyze the quaternary structure of MalT in solution in the absence or presence of maltotriose and/or AMP-PNP, ATP, or ADP. The protein is monomeric in the absence of ligands and in the presence of ADP. In the presence of maltotriose, AMP-PNP, or ATP only, the protein self-associates, but a large fraction of the protein remains monomeric. In the presence of both maltotriose and AMP-PNP (ATP or ADP), the protein is essentially oligomeric, with the difference being that the oligomerization is less favored in the presence of ADP + maltotriose than in the presence of AMP-PNP + maltotriose. We present evidence that the association pathway comprises the following steps: monomers --> dimers --> (MalT)(n) --> aggregates, where 3 </= n </= 6. From these data, we conclude that the role of maltotriose and ATP as positive effectors is to induce the multimerization of MalT, and hence its cooperative binding to the mal promoters.

Adenosine Diphosphate↗
PubMed2005

Transformation of MALT lymphoma to pure plasma cell histology following treatment with the anti-CD20 antibody rituximab.

Mucosa associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma arising from marginal-zone B-cells which are closely related to plasma cells. As opposed to the large majority of plasma cells, MALT lymphoma cells express CD20, and the anti-CD20 antibody rituximab has been reported as active treatment in patients with MALT lymphoma. We present a patient with MALT lymphoma involving stomach and lung which transformed to a pure plasma cell tumor after therapy with rituximab. This observation again supports the close association between the cell of origin of MALT lymphoma and plasma cells, suggesting that "plasmacytoma of the GI-tract" as anecdotally reported may in fact be a MALT lymphoma with extreme plasmacytic differentiation. In addition, our findings suggest that MALT lymphomas with plasmacytic differentiation might have a different 18F-FDG uptake as compared to classical MALT lymphoma.

Aged, 80 and over↗
PubMed2002

The N terminus of the Escherichia coli transcription activator MalT is the domain of interaction with MalY.

The maltose system of Escherichia coli consists of a number of genes encoding proteins involved in the uptake and metabolism of maltose and maltodextrins. The system is positively regulated by MalT, its transcriptional activator. MalT activity is controlled by two regulatory circuits: a positive one with maltotriose as effector and a negative one involving several proteins. MalK, the ATP-hydrolyzing subunit of the cognate ABC transporter, MalY, an enzyme with the activity of a cystathionase, and Aes, an acetyl esterase, phenotypically act as repressors of MalT activity. By in vivo titration assays, we have shown that the N-terminal 250 amino acids of MalT contain the interaction site for MalY but not for MalK. This was confirmed by gel filtration analysis, where MalY was shown to coelute with the N-terminal MalT structural domain. Mutants in MalT causing elevated mal gene expression in the absence of exogenous maltodextrins were tested in their response to the three repressors. The different MalT mutations exhibited a various degree of sensitivity towards these repressors, but none was resistant to all of them. Some of them became nearly completely resistant to Aes while still being sensitive to MalY. These mutations are located at positions 38, 220, 243, and 359, most likely defining the interaction patch with Aes on the three-dimensional structure of MalT.

ATP-Binding Cassette Transporters↗
PubMed2003

Distinct methylated profiles in Helicobacter pylori dependent and independent gastric MALT lymphomas.

BACKGROUND: Gastric mucosa associated lymphoid tissue (MALT) lymphomas are clinically subdivided into Helicobacter pylori dependent and independent, according to H. pylori infection and the therapeutic course. In previous reports it has been suggested that H. pylori independent cases develop from H. pylori dependent cases, and sometimes transform into high grade diffuse large B cell lymphomas (DLBCLs). METHODS: To better understand the pathogenesis of H. pylori dependent and independent MALT lymphomas, we analysed the methylation profiles of eight independent CpG islands, including p15, p16, p73, hMLH1, death associated protein kinase, MINT1, MINT2, and MINT31 in H. pylori dependent and independent MALT lymphomas, DLBCLs, and H. pylori associated chronic gastritis. RESULTS: We first confirmed that H. pylori independent cases had a high incidence of t(11;18)(q21;q21) (4/8 cases) and aberrant BCL10 expression (7/8 cases) compared with H. pylori dependent cases and gastric DLBCLs. In the methylation pattern study, all 13 H. pylori dependent MALT lymphomas had more than four methylated loci while H. pylori independent cases had less than two. According to the previous criterion, all H. pylori dependent MALT lymphomas (13/13, 100%) and five of 10 (50%) DLBCLs were classified as CpG island methylator phenotype positive (CIMP+). In contrast, all H. pylori independent MALT lymphomas were CIMP-. CONCLUSION: The distinct methylation pattern together with lack of chromosomal translocation in H. pylori dependent MALT lymphomas suggest that H. pylori dependent and independent MALT lymphomas have a different pathogenesis.

Adaptor Proteins, Signal Transducing↗