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PubMed2003

Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18) (q21;q21) MALT lymphoma.

t(11; 18) (q21; q21) is a chromosomal aberration specific to low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and generates the chimeric product apoptosis inhibitor 2 (API2)-MALT1, which has been suggested to play an important role in MALT lymphomagenesis. However, little is known about the characteristics of API2, MALT1, and API2-MALT1 proteins. We therefore investigated the subcellular localization and stability of these products. API2 was localized in the nucleus and the cytoplasm, and MALT1 and API2-MALT1 in the cytoplasm only. Western blot analysis showed that the products of API2 and MALT1 were unstable, while the API2-MALT1 product was stable. The API2 deletion mutants at the end of the C-terminal and the MALT1 deletion mutants at the end of the N-terminal were stable compared with the full-length products. These results indicate that the domains responsible for protein instability are located in the end of the C-terminal of API2 and in that of the N-terminal of MALT1, and also that API2-MALT1 became stable because it lacks these domains. It has been suggested that NF-kappaB activation plays an important role in the tumorigenesis of MALT lymphoma. Our findings further suggest that the stabilized expression of API2-MALT1 products may continuously stimulate the NF-kappaB activating pathway, thus leading to MALT lymphomagenesis.

Animals↗
PubMed1996

Additional neoplasms and HCV infection in low-grade lymphoma of MALT type.

Several chronic inflammatory conditions and genetic alterations are likely to be involved in the pathogenesis of low-grade lymphoma of MALT type. In a well-characterized series of 27 patients with low-grade lymphoma of MALT type, we studied: (1) the incidence of other neoplasms, which might be indicative of genetic instability, apparently a characteristic of this disease; (2) the prevalence of serologic and molecular markers of HCV infection, which has been found in association with other lymphoproliferative disorders. Three patients had one or more additional cancers; a total of eight tumours, five of which occurred in the same patient, suggests the presence of some genetic instability in at least some cases of the disease. Rather unexpectedly, anti-HCV antibodies and HCV RNA sequences were documented in 50% of the patients examined, without elevation of serum transaminases. Of interest, the two patients with parotid and conjunctival MALT lymphomas, respectively, with a previous history of Sjögren's syndrome, were HCV positive. We suggest, for the first time, that HCV may be considered, in addition to Helicobacter pylori, as another potential infectious co-factor in the multistep pathogenesis of low-grade lymphomas of MALT type.

Adult↗
PubMed1997

Immunoglobulin heavy chain diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process.

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement. DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences. Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen. The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.

Amino Acid Sequence↗
PubMed2001

An analysis of bacteriocins produced by lactic acid bacteria isolated from malted barley.

AIMS: The aim of this study was to perform a detailed characterization of bacteriocins produced by lactic acid bacteria (LAB) isolated from malted barley. METHODS AND RESULTS: Bacteriocin activities produced by eight LAB, isolated from various types of malted barley, were purified to homogeneity by ammonium sulphate precipitation, cation exchange, hydrophobic interaction and reverse-phase liquid chromatography. Molecular mass analysis and N-terminal amino acid sequencing of the purified bacteriocins showed that four non-identical Lactobacillus sakei strains produced sakacin P, while four Leuconostoc mesenteroides strains were shown to produce bacteriocins highly similar or identical to leucocin A, leucocin C or mesenterocin Y105. Two of these bacteriocin-producing strains, Lb. sakei 5 and Leuc. mesenteroides 6, were shown to produce more than one bacteriocin. Lactobacillus sakei 5 produced sakacin P as well as two novel bacteriocins, which were termed sakacin 5X and sakacin 5T. The inhibitory spectrum of each purified bacteriocin was analysed and demonstrated that sakacin 5X was capable of inhibiting the widest range of beer spoilage organisms. CONCLUSION: All bacteriocins purified in this study were class II bacteriocins. Two of the bacteriocins have not been described previously in the literature while the remaining purified bacteriocins have been isolated from environments other than malted barley. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents a thorough analysis of bacteriocin-producing LAB from malt and demonstrates, for the first time, the variety of previously identified and novel inhibitory peptides produced by isolates from this environment. It also highlights the potential of these LAB cultures to be used as biological controlling agents in the brewing industry.

Amino Acid Sequence↗
PubMed1998

Negative transcriptional regulation of a positive regulator: the expression of malT, encoding the transcriptional activator of the maltose regulon of Escherichia coli, is negatively controlled by Mlc.

The maltose regulon consists of 10 genes encoding a multicomponent and binding protein-dependent ABC transporter for maltose and maltodextrins as well as enzymes necessary for the degradation of these sugars. MalT, the transcriptional activator of the system, is necessary for the transcription of all mal genes. MalK, the energy-transducing subunit of the transport system, acts phenotypically as repressor, particularly when overproduced. We isolated an insertion mutation that strongly reduced the repressing effect of overproduced MalK. The affected gene was sequenced and identified as mlc, a known gene encoding a protein of unknown function with homology to the Escherichia coli NagC protein. The loss of Mlc function led to a threefold increase in malT expression, and the presence of mlc on a multicopy plasmid reduced malT expression. By DNasel protection assay, we found that Mlc protected a DNA region comprising positions +1 to +23 of the malT transcriptional start point. Using a mlc-lacZ fusion in a mlc and mlc+ background, we found that Mlc represses its own expression. As Mlc also regulates another operon (manXYZ, see pages 369-379 of this issue), it may very well constitute a new global regulator of carbohydrate utilization.

ATP-Binding Cassette Transporters↗
PubMed1999

Glycerol-3-phosphate-mediated repression of malT in Escherichia coli does not require metabolism, depends on enzyme IIAGlc and is mediated by cAMP levels.

malT encodes the central activator of the maltose system in Escherichia coli, a gene that is typically under positive control of the cAMP/CAP catabolite repression system. When cells were grown in tryptone broth, the addition of glycerol reduced malT expression two- to threefold. Phosphorylation of glycerol to glycerol-3-phosphate (G3P) was necessary for this repression, but further metabolism to dihydroxyacetone phosphate was not. Mutants lacking adenylate cyclase and harbouring a crp* mutation (synthesizing a cAMP receptor protein that is independent of cAMP) no longer repressed a transcriptional malT-lacZ fusion but still repressed a translational malT-lacZ fusion. Similar results were obtained with a mutant lacking enzyme IIAGlc. For the translational fusion (in a cya crp* genetic background) to be repressed by glycerol, a drop to pH 5 of the growth medium was necessary. Thus, while transcriptional repression by glycerol requires enzyme IIAGlc, cAMP and CAP, pH-mediated translational repression is cAMP independent. Other sugars that are not transported by the phosphotransferase system, most notably D-xylose, showed the same effect as glycerol.

Artificial Gene Fusion↗
PubMed2000

Low grade gastric MALT Lymphoma: radiographic findings.

AIMS: Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is now recognized as a distinct entity within extranodal non-Hodgkin's lymphoma. The purpose of this study was to describe the radiographic findings in low grade gastric MALT lymphoma. MATERIALS AND METHODS: We retrospectively reviewed the radiographic findings in 22 cases of low-grade gastric MALT lymphoma. The study group consisted of 15 men and seven women (median age 68 years, range 41-91 years). Lesions were designated as infiltrative or polypoid by consensus of two radiologists. Polypoid lesions were categorized by number and size. Anatomical site within the stomach and presence of transpyloric or oesophagogastric extension was determined for each case. The presence of abdominal lymphadenopathy was categorized as regional or distant. The presence of Helicobacter pylori was determined from endoscopic and surgical biopsies. RESULTS: Computed tomography (CT) revealed abnormalities of the stomach in 19 cases of the 21 in which it was performed. There were 14 infiltrative lesions and five polypoid lesions. Of the 14 infiltrative lesions, the mean gastric wall thickness was 2.2 cm (range 0.8-6.0 cm). There were three single and two multiple polypoid lesions (mean size 2.2 cm, range 1. 5-2.7 cm). Transpyloric extension was observed in two cases and oesophagogastric extension in one. Abdominal lymphadenopathy was observed in 10 of 21 patients. Helicobacter pylori was found in 19 of 22 cases (86%). CONCLUSION: Low grade B cell gastric MALT lymphomas present with an infiltrative form on CT in about three-quarters of cases and a polypoid pattern in the remainder. Abdominal lymphadenopathy is seen in approximately one-half of cases. There is a high association with Helicobacter pylori.

Adult↗
PubMed2000

[Eyelid tumor as a recurrence of a gastric MALT-lymphoma].

BACKGROUND: MALT Lymphoma of the conjunctiva, eyelid and orbit represents a primary manifestation of the disease in most of the cases. CASE REPORT: A 58-year-old male presented with a tumor in the left inferior eyelid. A full-thickness incisional biopsy was performed. Histopathologically, a lymphoid infiltrate involved the eyelid in its full width, with reactive follicles surrounded by small cells with irregular nucleus. Follicular colonization and lymphoepithelial lesions were detected. The tumor was CD20 positive. The molecular genetic analysis disclosed a monoclonal B-cell proliferation. The patient had a history of gastric MALT lymphoma treated 9 years ago and he had been otherwise in good health. The histopathologic features of the gastric tumor were identical to those of the eyelid lesion. Since the eyelid tumor represented a recurrence of the disease, treatment consisted of systemic chemotherapy. Complete tumor eradication was obtained. CONCLUSION: Ocular adnexal MALT-lymphomas may represent a recurrence of a distant primary MALT-lymphoma after a long disease-free period and, therefore, be an indication for systemic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

[Orbital MALT lymphomas: clinicopathological correlation].

BACKGROUND: Extranodal MALT lymphomas are slow growing tumors of B-cell origin which may be found in the orbit. They are associated with mucosa and epithelial structures. PATIENTS AND METHODS: We present eight patients with biopsy confirmed orbital MALT Lymphomas. The diagnostic imaging techniques are described. Histopathological and immunohistological analysis showed typical findings of MALT lymphomas. RESULTS: After staging six patients had radiation therapy. Two patients refused treatment due to lack of discomfort. CONCLUSIONS: MALT lymphomas should be considered in the differential diagnosis of orbital tumors. While ultrasonography and MRI are needed to determine the extension of these tumors, their identification requires excision or biopsy with histological/immunohistochemical analysis, especially in view of new treatment options.

Adult↗
PubMed1991

C-terminal processing of barley alpha-amylase 1 in malt, aleurone protoplasts, and yeast.

C-terminal processing of low pI barley alpha-amylase (AMY1) results in multiple forms in malt, aleurone protoplasts, and transformed yeast. Expression of an AMY1 cDNA in yeast thus leads to four secreted forms with distinct pI values between 4.7 and 5.1 and essentially identical Mr. AMY1-1 and AMY1-2 lacking the C-terminal Arg-Ser are generated by carboxypeptidase in vitro from AMY1-3 and AMY1-4, respectively. In vivo processing is due to the KEX1-encoded yeast carboxypeptidase. AMY1-2 and AMY1-4 are fully active, whereas AMY+-1 and AMY1-3 retain 3-4% activity toward p-nitrophenyl maltoheptaoside and have one fewer SH group, due to reaction with glutathione. AMY1-1-AMY1-4 are indistinguishable from malt AMY1 with respect to Ca(2+)-, substrate-, and beta-cyclodextrin-binding as well as recognition by three monoclonal antibodies and limited proteolysis by proteinase K. Transient AMY1 precursors present in barley aleurone protoplasts were trapped by addition of serine carboxypeptidase inhibitors, indicating that endogenous carboxypeptidase participates in the maturation of AMY1 during germination. Three pairs of precursor/mature AMY1 forms are recognized, presumably corresponding to the three genes encoding AMY1. Malt carboxypeptidase II can convert in vitro the precursors isolated from protoplasts into processed enzyme, and AMY1 from malt accordingly lacks the C-terminal heptapeptide. This report thus demonstrates posttranslational protein modification by carboxypeptidase in higher plants.

Amino Acid Sequence↗
PubMed2001

A complex signaling module governs the activity of MalT, the prototype of an emerging transactivator family.

MalT, the specific activator of the maltose regulon, is the prototype of a family of high-molecular-mass ATP-binding bacterial transcription activators. On binding of its two positive effectors, the inducer maltotriose and ATP, MalT oligomerizes to an active state competent for promoter binding and transcription activation. In addition to its previously known DNA-binding domain, limited proteolysis showed that MalT contains three other domains, the boundaries of which were accurately delimited by N-terminal microsequencing. The N-terminal domain alone binds ATP. Maltotriose binding involves an extended region corresponding to domains 2 and 3, although weak binding to domain 3 alone was also observed. Moreover, maltotriose binding induces a conformational shift involving a movement of both domains 1 and 3 with respect to domain 2, leading to the active form of the protein. Sequence examination of the MalT homologues suggests that these three domains might constitute a signaling module.

Adenosine Diphosphate↗
PubMed2004

MALT-type lymphoma and Warthin's tumour presenting in the same parotid gland.

Non-disseminated malignant lymphomas of salivary glands occurring in association with Warthin's tumour have rarely been reported. We describe the first case of association of an extranodal mucosa-associated lymphoid tissue (MALT)-type non-Hodgkin's lymphoma with Warthin's tumour of the parotid gland. Total parotidectomy with preservation of the facial nerve was performed. Surgical and pathological evidence confirmed that the parotid MALT lymphoma did not arise in the lymphoid stroma of the Warthin's tumour. Immunostaining of the MALT lymphoma cells proved negative for Epstein-Barr virus and Helicobacter pylori antibodies and polymerase chain reaction assays did not identify human herpesvirus 8. The patient has been followed up for 11 months, without evidence of recurrent disease. It cannot be ruled out that long-term immunological stimulation by the Warthin's tumour may have caused lymphoid accumulation, chronic stimulation of B cells and extranodal parotid MALT lymphomagenesis.

Adenolymphoma↗
PubMedDate not supplied

International N-nitroso compounds check sample programme: report on the performance in the second study dedicated to their determination in beer and malt.

The second check sample survey for the determination of N-nitrosamines in beer and malt has been initiated. Each laboratory received four samples: two beer, from the same batch, spiked respectively with 0.5 microgram/l N-nitrosodimethylamine (NDMA) and 4 micrograms/l NDMA plus 30 micrograms/l N-nitrosoproline (NPRO) and two naturally contaminated malts. Sixteen laboratories sent their results and two apologized in view of analytical problems. Results from this have been statistically evaluated. Comparison to those from the previous study demonstrated a distinct improvement in the results from the analysis of NDMA in beer and malt. Little has been achieved for the other two common contaminants of beer and malt, N-nitrosopyrrolidine (NPYR) and NPRO. For this latter compound in beer, however, some hope came from the data produced by the method of Sen et al. (1983), but the number of results is insufficient to allow firm conclusions to be drawn.

Beer↗
PubMed2006

18F-FDG PET in mucosa-associated lymphoid tissue (MALT) lymphoma.

To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 - 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma.

Adult↗
PubMed2006

'Blind' antibiotic treatment targeting Chlamydia is not effective in patients with MALT lymphoma of the ocular adnexa.

BACKGROUND: Recent results have implicated Chlamydia, especially Chlamydia psittaci, in the development of ocular adnexal lymphoma in the large majority of patients. We present our experience with ex-juvantibus antibiotic treatment in patients diagnosed with MALT lymphoma of the ocular adnexa. PATIENTS AND METHODS: A retrospective analysis identified a total of 11 patients (six female, five male) with MALT-lymphoma of the ocular adnexa who were given doxycyclin 200 mg p.o. daily over 3 weeks. Patients were tested also for autoimmune conditions, Helicobacter status and hepatitis along with assessment of MALT-lymphoma specific genetic changes. RESULTS: After a median follow-up of 9 months, none of the patients responded to 'blind' antibiotic treatment with doxycyclin. Only one patient with bilateral conjunctival lymphoma related a short lasting subjective improvement, but was referred to alternative therapy due to progression and worsening symptoms after 6 months. CONCLUSIONS: In this uncontrolled series, no effect of 'blind' antibiotic treatment with doxycyclin could be found in our patients with MALT lymphoma of the ocular adnexa. These results are in contrast to other series and suggest a potential geographic difference in the role of Chlamydia in ocular adnexal lymphoma. Thus, antibiotic therapy without prior testing for Chlamydia should be discouraged.

Adult↗
PubMed2006

Clinical implications of hepatitis C virus infection in MALT-type lymphoma of the ocular adnexa.

BACKGROUND: A pathogenic link between hepatitis C virus (HCV) and MALT-type lymphomas has been suggested. However, studies assessing the role of HCV infection separately in different forms of MALT lymphomas are not available. PATIENTS AND METHODS: The prevalence and clinical implications of HCV seropositivity were analyzed in 55 patients with ocular adnexa lymphoma (OAL) of MALT-type. RESULTS: HCV seropositivity was detected in seven (13%) patients. At presentation, HCV infection was significantly associated with concomitant extra-orbital disease, lymph node dissemination and involvement of additional extranodal organs. HCV seropositivity was associated also with a higher relapse rate and worse progression-free survival. In fact, 16 patients experienced relapse after first-line treatment: five (71%) were HCV-seropositive and 11 (23%) were HCV-seronegative, with a median TTP of 31 and 50+ months (P = 0.01), and a 5-year progression-free survival of 43 +/- 18% and 77 +/- 7% (P = 0.005), respectively. HCV-seropositive patients experienced frequent relapses despite further lines of therapy; relapses were systemic in all cases but one; multiple subcutaneous nodules were common at relapse. CONCLUSIONS: HCV seropositivity is present in 13% of OAL of MALT-type. Concomitant HCV infection is associated with more disseminated disease and aggressive behavior in OAL, with a consequent potential negative impact in patients managed with radiotherapy alone.

Adult↗
PubMed2000

Synergistic transcription activation: a dual role for CRP in the activation of an Escherichia coli promoter depending on MalT and CRP.

Activation of the Escherichia coli malEp promoter relies on the formation of a higher order structure involving cooperative binding of MalT to promoter-proximal and promoter-distal sites as well as CRP binding to three sites located in between. MalT is the primary activator and one function of CRP is to facilitate cooperative binding of MalT to its cognate sites by bending the intervening DNA. It is shown here that CRP also participates directly in malEp activation. This function is carried out by the molecule of CRP bound to the CRP site centered at -139.5 (CRP site 3). This molecule of CRP recruits RNA polymerase by promoting the binding of the RNA polymerase alpha subunit C-terminal domain (alphaCTD) to DNA immediately downstream from CRP site 3, via a contact between alphaCTD and activating region I of CRP. The action of MalT and CRP at malEp hence provides the example of a novel and complex mechanism for transcriptional synergy in prokaryotes whereby one activator both helps the primary activator to form a productive complex with promoter DNA and interacts directly with RNA polymerase holoenzyme.

ATP-Binding Cassette Transporters↗
PubMed1985

The mac promoters: functional hybrid promoters activated by the malT product and repressed by the lacI product.

Using in vitro techniques we have fused upstream sequences from the malPp promoter (normally activated by the MalT protein) to downstream sequences from the lacZp promoter (normally repressed by the LacI protein). Several hybrid promoters were thus obtained, which were controlled by the MalT protein, but were poorly active. More efficient promoters were then isolated using in vivo selection. Three main conclusions could be derived from the analysis of all of these hybrid promoters. Firstly, the MalT protein seems able to force RNA polymerase to start transcription at any DNA sequence, albeit with a low efficiency. Secondly, the strength of the hybrid promoters is considerably increased if a Pribnow Box is positioned at a precise location with respect to the MalT binding site. Thirdly, the presence of the lac operator, even when properly positioned with respect to the transcription startpoint, does not suffice to permit full repression by the lacI product.

Base Sequence↗