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Mucosa-associated lymphoid tissue (MALT) in Barrett's esophagus: prospective evaluation and association with gastric MALT, MALT lymphoma, and Helicobacter pylori.

OBJECTIVES: Prospective evaluation of the prevalence of mucosa-associated lymphoid tissue (MALT) within Barrett's esophagus and its association with gastric MALT, gastric MALT lymphoma, and H. pylori infection. METHODS: From Barrett's esophagus patients, a minimum of six gastric biopsies were obtained, in addition to Barrett's surveillance biopsies. Additional gastric biopsies were taken from any ulcer(s), nodule(s), polyp(s), or other lesions. Patients with gastroesophageal reflux symptoms without Barrett's esophagus served as controls. RESULTS: One hundred and thirty-nine Barrett's patients were included in the study. One hundred and twenty-two of these patients had gastric biopsies for gastric MALT and H. pylori determination. H. pylori was noted in the stomach of 48 patients and within Barrett's mucosa in 14. Barrett's MALT was noted in seven cases, gastric MALT in 16, and gastric MALT lymphoma in two. None of the 101 control patients had esophageal MALT. Two of the seven patients with Barrett's MALT had gastric MALT. Barrett's MALT was associated with esophageal H. pylori in 57.1% cases and gastric H. pylori in 71.4%. The prevalence of gastric and esophageal H. pylori in patients with Barrett's MALT was significantly higher compared to patients with Barrett's without MALT (p < 0.0001 and p < 0.007, respectively). Barrett's MALT was very focal and its esophageal location variable. CONCLUSIONS: Barrett's MALT was associated with both esophageal and gastric H. pylori colonization. Esophageal MALT was associated with Barrett's esophagus. Gastric biopsy sampling is warranted in any patient with Barrett's MALT to detect gastric MALT and H. pylori, which, if found, should be eradicated.

Adult↗

Comparison of MALT and non-MALT primary large cell lymphoma of the stomach: does histologic evidence of MALT affect chemotherapy response?

BACKGROUND: Although the clinicopathologic features of low grade gastric MALToma (lymphoma of mucosa-associated lymphoid tissue) recently have been well delineated, the significance of identifying histologic evidence of MALT origin in a primary high grade gastric lymphoma is less clear. The authors sought to address this issue and, in particular, to clarify if MALT and non-MALT primary large cell gastric lymphoma might have a different response to systemic chemotherapy. METHODS: The authors reviewed the pathologic specimens of all patients who had a diagnosis of primary large cell lymphoma of the stomach and who had been treated primarily by systemic chemotherapy in our institutions January 1, 1988-December 31, 1998. The patients were divided into two groups by experienced hematopathologists, based on the presence or absence of histologic features suggestive of MALToma, including typical lymphoepithelial lesions and infiltration of characteristic centrocyte-like cells. Disease staging was done according to the AJCC/UICC system with Musshoff modification. The median number of gastric biopsies for each patient was 7 (range, 1-21). RESULTS: Seventeen patients with and 26 patients without histologic evidence of MALToma were identified. Clinical features were similar between the two groups except that a greater proportion of patients without evidence of MALToma had elevated levels of serum lactate dehydrogenase (50% vs. 12%, P = 0.01). The median duration of follow-up for the 43 patients was 46.5 months (range, 17-124 mos). All patients received standard systemic chemotherapy including anthracyclines or anthracenedione. The response rate was 88.2% for patients with evidence of MALToma and 57.7% for those without (P = 0.03). The 5-year overall survival rate was 80.5% for patients with evidence of MALToma and 48.9% for those without (P = 0.02). Multivariate analysis indicated that response to chemotherapy, disease stage (Stage I and II-1 vs. Stage II-2, III, and IV), and the presence of MALToma features were independent prognostic factors for overall survival. CONCLUSION: The results of this relatively small study series suggested that the presence of histologic features of MALToma in patients with primary large cell gastric lymphoma might have been associated with a better response to systemic chemotherapy and a better prognosis. Further studies to consolidate this conclusion are necessary.

Adult↗

Expression of cdc2 and cyclin B1 in Helicobacter pylori-associated gastric MALT and MALT lymphoma : relationship to cell death, proliferation, and transformation.

Mucosa-associated lymphoid tissue (MALT) may accumulate within gastric mucosa as a result of long standing Helicobacter pylori infection, and this acquired MALT may eventually develop into low-grade B-cell MALT lymphoma. To determine the possible association of cell cycle regulatory proteins and apoptotic cell death in the transformation of H. pylori gastritis to MALT lymphoma, the extent of cell proliferation, cell viability, expression of Cdc2/Cdk1 and cyclin B in gastric mucosal from patients with H. pylori-positive chronic gastritis (n = 7), MALT (n = 12), or MALT lymphoma (n = 12) were undertaken. Control tissue was obtained from H. pylori- negative patients (n = 5). Proliferating cell nuclear antigen (PCNA), Cdc2, and cyclin B1 were examined in paraffin embedded tissue by immunohistochemistry, while the apoptotic index (AI) was determined using the TUNEL assay. H&E staining for histology and modified Giemsa staining for the detection of H. pylori was conducted simultaneously. When compared to chronic gastritis tissue, those with MALT or MALT lymphoma had an increase in PCNA labeling index of 3.3- and 2.7-fold, while that for Cdc2/Cdk1 increased 2.3- and 3.1-fold, respectively. cyclin B1 labeling was 1.9 and 3.0 fold, while the AI was 3.4- and 1.4-fold higher in MALT and MALT lymphoma tissue, respectively, in the same comparison. On the other hand, the AI index of MALT lymphoma was 2. 5-fold lower than that for MALT tissues. The labeling scores for Cdc2/Cdk1 and cyclin B1 were significantly higher in the germinal center when compared to the mantle and marginal zones of MALT tissues. Using chi(2) and Pearson/Spearman's rho correlation coefficient with regression analyses, there was an inverse correlation between the AI and Cdc2/Cdk1 or cyclin B1 in MALT and MALT lymphoma tissues. There was no correlation between AI and PCNA labeling in any of the tissues. These results suggest that Cdc2/Cdk1 and cyclin B1 expression may be actively associated in the modulation of cellular death by apoptosis, as well as cellular proliferation and transformation during the evolution of H. pylori-associated gastritis to MALT lymphoma. Subclassification of high labeling score (>/=40) for Cdc2/Cdk1 and cyclin B1 and low labeling index (<0.6) for apoptotic cells in H. pylori-associated MALT may help in identifying a population of patients with an increased risk of developing MALT lymphoma.

Apoptosis↗

Non-random loss of chromosome 3 during transition of Helicobacter pylori-associated gastric MALT to B-cell MALT lymphoma revealed by fluorescence in situ hybridization.

Acquired gastric mucosa-associated lymphoid tissue (MALT) accumulates as a result of long-standing Helicobacter pylori (H. pylori) infection and from this acquired MALT, low-grade B-cell MALT lymphoma may develop. Carcinogenesis is a multistep, multifactorial process involving the progressive accumulation of genetic changes. To determine whether numerical chromosomal alterations are involved in the transition of H. pylori-associated human gastric MALT to low-grade B-cell MALT lymphoma, frozen biopsy specimens prospectively obtained from H. pylori positive gastric MALT and gastric MALT lymphoma patients, as well as normal control patients (normal gastroscopy/gastric mucosal histology/H. pylori negative), were analyzed by fluorescence in situ hybridization (FISH). Fluorescent, directly labeled alpha-satellite DNA probes, specific for the centromeres of chromosomes 1, 3, 4, 11, 17 and Y were used in this study. The non-random loss of chromosome 3 was detected in two MALT patients and in all five MALT lymphoma patients. Trisomy 17 was detected in one MALT patient and one MALT lymphoma patient. Trisomy 1 was detected in a single MALT lymphoma patient as was trisomy 3. None of the MALT patients had trisomy 3 or trisomy 1. Monosomy 17 was noted in one MALT lymphoma patient. Clonal aneusomy was not observed in any patient for chromosomes Y, 4 or 11. These results suggest that the consistent loss of chromosome 3 may be an important genetic alteration in the transformation of H. pylori-associated gastric MALT into low-grade B-cell gastric MALT lymphoma.

Adult↗

Clinicopathological features of gastric mucosa associated lymphoid tissue (MALT) lymphomas: high grade transformation and comparison with diffuse large B cell lymphomas without MALT lymphoma features.

AIMS: To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL). METHODS: Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected. RESULTS: Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL. CONCLUSIONS: The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.

Adult↗

Differentiation of low-grade gastric MALT lymphoma and high-grade gastric MALT lymphoma: the clinical value of Ga-67 citrate scintigraphy--a pilot study.

Ga-67 citrate scintigraphy has been routinely and extensively used to evaluate non-Hodgkin's lymphoma (NHL) for more than 20 years. Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is by far the most common extranodal primary NHL. Gastric MALT lymphoma can be classified as low-grade (LG) or high-grade (HG). Low-grade gastric MALT lymphoma can be cured by eradication of Helicobacter pylori; but radiotherapy and/or chemotherapy and/or surgery are the major methods of treatment for the HG gastric MALT lymphoma. However, it is difficult to differentiate these two groups by clinical parameters and endoscopic findings. The purpose of this study was to determine whether Ga-67 citrate scintigraphy can distinguish the LG gastric MALT lymphoma from the HG gastric MALT lymphoma. Twenty-one patients (11 men and 10 women ranging in age from 38 to 83 years) with histologically confirmed gastric MALT lymphoma were enrolled. Twelve patients had LG and nine patients had HG. All 21 patients underwent Ga-67 citrate scintigraphy before treatment. The results of Ga-67 citrate scintigraphy were classified as positive or negative. In the LG group, nine patients had negative results and three patients had positive results. In the HG group of nine patients, all patients had positive results. Among the three patients who had positive results in the LG group, the uptake of gastric MALT lymphoma was lower than that of the liver. The Ga-67 citrate scintigraphy is of good clinical value for the differentiation of the LG gastric MALT lymphoma and the HG gastric MALT lymphoma. We think that the major value of Ga-67 citrate scintigraphy will be in following the patients with HG gastric MALT lymphoma after treatment to assess response of therapy and to detect possible recurrence and perhaps in determining transformation from the LG to HG gastric MALT lymphoma. However, further investigation is needed to understand the relationship between the uptake of Ga-67 citrate in gastric MALT lymphoma and transformation.

Adult↗

Expression of CD10, CD75 and CD43 in MALT lymphoma and their usefulness in discriminating MALT lymphoma from follicular lymphoma and chronic gastritis.

AIMS: While it may be difficult to discriminate between chronic gastritis, MALT lymphoma and a gastric location of a nodal lymphoma using histology of small endoscopic biopsies alone, additional markers like CD10, CD75 and CD43 and proliferative activity may be of value. We assessed the expression of these antigens in MALT lymphoma and their usefulness in discriminating MALT lymphoma from follicular lymphoma and from gastritis. METHODS AND RESULTS: Tissue samples of 38 patients with gastric MALT lymphoma were immunohistochemically stained for expression of CD10, CD75 and/or CD43. Proliferation index was scored using MIB-1 staining. Ten cases of nodal follicle centre B-cell lymphomas (n = 11) and 18 cases of high-grade MALT lymphoma (n = 22) showed moderate to high CD75 expression (25-100% positive cells). All tested low-grade MALT lymphomas (n = 9) and chronic gastritis (n = 6) were negative (0-25%) for CD75. All MALT lymphomas (n = 25) were negative for CD10. High-grade lymphomas show significantly higher proliferation indices (67% vs. 16%) than low-grade lymphomas. Only four of 26 MALT lymphomas were slightly positive for CD43. All gastritis biopsies (n = 4) were negative for CD43. CONCLUSIONS: These data suggest that combining both CD10 and CD75 may be useful in discriminating between low-grade MALT, high-grade MALT lymphoma and extranodal location of follicular lymphoma. However, CD43 expression cannot in the majority of cases be used to distinguish between low-grade MALT lymphoma and gastritis.

Antigens, CD↗

Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H pylori in gastric MALT lymphoma.

t(11;18)(q21;q21) is a specific chromosomal translocation associated with mucosa-associated lymphoid tissue (MALT) lymphoma. It fuses the amino terminal of the API2 gene to the carboxyl terminal of the MALT1 gene and generates a chimeric fusion product. Although the translocation is frequently detected in gastric and pulmonary MALT lymphoma, its incidence in MALT lymphomas from other sites is largely unknown. It also remains unknown whether the occurrence of the translocation is influenced by the nature of preceding diseases associated with MALT lymphomas. We screened for t(11; 18)(q21;q21) in 417 cases of MALT lymphoma from 8 major sites by reverse transcription-polymerase chain reaction. t(11;18)(q21;q21) was found at highest frequencies in MALT lymphomas from the lung (38%) and stomach (24%), and at moderate frequencies in those from the conjunctiva (19%) and orbit (14%). However, the translocation was found only rarely in MALT lymphomas from the salivary gland (1%) and was absent in those from the thyroid, skin, liver, and other rare sites, and in immunoproliferative small intestinal disease (IPSID). In gastric MALT lymphoma, t(11;18)(q21;q21) was significantly associated with infection by CagA-positive strains of Helicobacter pylori. As CagA-positive strains of H pylori are much more potent in induction of host inflammatory responses, including activation of neutrophils, which release highly genotoxic oxygen reactive species, we therefore examined neutrophil infiltration in recognized precursors of MALT lymphoma including H pylori-associated gastritis, lymphoepithelial sialadenitis, and Hashimoto thyroiditis. Neutrophil infiltration was prominent in H pylori-associated gastritis but not in lymphoepithelial sialadenitis and Hashimoto thyroiditis. Our results demonstrate that t(11;18)(q21; q21) occurs at markedly variable frequencies in MALT lymphoma of different sites and suggest that the occurrence of the translocation is influenced by the nature of premalignant diseases associated with MALT lymphoma. Oxidative damage might play a role in development of t(11;18)(q21; q21).

Adaptor Proteins, Signal Transducing↗

Acquired gastric mucosa-associated lymphoid tissue (MALT): a review with special emphasis on association with extragastric diseases and management problems of gastric MALT.

Mucosa-associated lymphoid tissue is absent physiologically in normal gastric mucosa, but it can develop in some pathologies (dyspepsia, celiac disease, autoimmune diseases) due to certain (Helicobacter pylori, gluten) or uncertain (viruses?) antigenic stimuli. Its importance is related to the consideration that it is the background for the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and its histologic progression to MALT lymphoma may be diagnosed using Isaacson's score. Monoclonal bands can be diagnosed in acquired gastric MALT as well as in gastric MALT lymphoma, but its role is unknown. To prevent development of MALT lymphoma from acquired MALT, currently anti-H. pylori treatment in all H. pylori- and MALT-positive patients is not suggested--only in patients with grade 3 of acquired MALT--due to the high risk of developing MALT lymphoma in these patients. At the same time, the etiology of gastric MALT in autoimmune extragastric diseases is not clear. Additional studies are needed to clarify this relation and its possible causes.

Autoimmune Diseases↗

Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy.

Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases. Furthermore, its exact relation to primary diffuse large B cell lymphoma (DLBCL) of the stomach is not clear. We applied in situ hybridisation (ISH) with centromeric probes on 43 samples of 39 patients with primary gastric lymphoma (13 samples with low-grade MALT lymphoma, 25 with high-grade MALT lymphoma and five with DLBCL) to detect numerical aberrations of 10 chromosomes. ISH was performed immunohistochemically on nuclei isolated from paraffin-embedded resection tissue and on whole paraffin sections using immunofluorescence. In six of 13 low-grade MALT lymphomas trisomy was detected (46%) and mostly involved chromosome 3 (33%). In high-grade MALT lymphomas, trisomies were found in 16 of 25 cases (64%), mainly involving chromosomes 12 and 18. Trisomy 3 was present in only 13% of these cases. Of five DLBCL, only one showed trisomy. Nine of the 16 aberrant high-grade MALT lymphomas (56%) showed trisomy of more than one chromosome per case vs two of six for low-grade cases. In lymphomas with separate low- and high-grade tumour components some trisomies were detected in both components, whereas others occurred only in the high-grade tumour cells. This supports the hypothesis that high-grade MALT lymphomas can develop from a low-grade type and that this progression is accompanied by the acquisition of more genetic aberrations. However, trisomy 3 probably does not play a major role in this progression.

Chromosomes, Human, Pair 3↗

Follicular dendritic cells in extranodal non-Hodgkin lymphomas of MALT and non-MALT type.

Extranodal lymphomas of the thyroid (n = 19), kidney (n = 15) and testis (n = 30) were investigated histologically and immunohistochemically for follicular dendritic cell pattern using the monoclonal antibody Ki-FDClP. This recognizes follicular dendritic cells in paraffin sections. Follicular dendritic cells were most predominant in lymphomas of the thyroid. These thyroid lymphomas showed the morphological features of mucosa-associated lymphoid tissue (MALT) type lymphomas in 18 of 19 cases and were classified as high-grade malignant lymphoma of MALT type with evidence of a low-grade malignant component (n = 18). Ten of these cases contained destroyed reactive follicles of follicular dendritic cells. In 6 of these 10 cases follicular dendritic cells occurred in a pattern of tumour-associated abortive follicle type. The remaining lymphoma of the thyroid was an immunoblastic lymphoma of B-cell type showing no detectable follicular dendritic cells. In extranodal lymphomas of non-MALT type follicular dendritic cells occurred in only two cases where immunocytoma involved the kidney. Malignant lymphomas of the kidney (chronic lymphocytic leukaemia, n = 2; immunocytoma, n = 4; centroblastic lymphoma, n = 9) and of the testis (immunocytoma, n = 2; centroblastic lymphoma, n = 27; immunoblastic lymphoma of B-cell type, n = 1) revealed no characteristics of MALT type lymphoma, cytologically or with respect to follicular dendritic cells. Classical lymphoepithelial lesions formed by centrocyte-like cells, a hallmark of MALT, occurred exclusively in thyroid lymphomas of MALT type. Although occurrence of classical lymphoepithelial lesions formed by centrocyte-like cells was limited to thyroid lymphomas of MALT type, a growth pattern of lymphoid blasts, with formation of lesions mimicking lymphoepithelial lesions superficially, was found in 6 of 27 testicular centroblastic lymphomas. Follicular dendritic cells in non-Hodgkin's lymphomas of MALT type show distinct follicular patterns not found in other extranodal lymphomas such as those found in the kidney and testis.

Dendritic Cells↗

What role does Helicobacter pylori eradication play in gastric MALT and gastric MALT lymphoma?

The concept of mucosa-associated lymphoid tissue (MALT) has been introduced to differentiate biological functions from behavior of nonnodal vs. nodal lymphoid tissues. Lymphomas arising from MALT also behave differently than typical nodal lymphomas. In contrast to other tissues, MALT in the stomach is almost exclusively a result of Helicobacter pylori infection. Thus, MALT is part of the host defense against the pathogen H. pylori. Consequently, lymphomas arising from gastric MALT may be a clonal evolution starting from the infection. In low-grade gastric MALT lymphoma, cure of the infection may induce complete histological remission in the majority of patients. Investigators have recently reported that complete remission rate is between 70% and 80%. In an extended analysis, we have treated 84 patients with low-grade gastric MALT lymphoma in stage El, using a dual regimen to eradicate H. pylori. Complete remission was observed in 68 (80%) patients; a partial remission was found in 4 patients. In contrast, 12 patients showed no change and were referred to alternative treatment. In patients in complete remission, a polymerase chain reaction assay for the rearranged immunoglobulin heavy-chain gene remained positive in many cases. Together with data from the literature, these data suggest that the majority of patients with low-grade gastric MALT lymphomas in stage El respond to eradication of H. pylori. Longer follow-up investigations are necessary to determine if remissions indicate a cure from the disease.

Gastric Mucosa↗

Qualitative and quantitative changes in barley seed protein patterns during the malting process analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with respect to malting quality.

Seeds of two barley cultivars, similar in total protein content and malt extract yield but different in their final attenuation values, were malted. Samples taken at daily intervals during the malting process were extracted sequentially with Tris-HCl buffer, aqueous 2-propanol, aqueous 2-propanol containing 0.5% dithiothreitol, and 4 M urea, containing 0.5% dithiothreitol and 1% Nonidet P-40. The protein composition of these extracts was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and computer densitometry to determine whether differences observed in the rate or extent of protein modification are related to the malting quality character final attenuation. It was found that, common to both cultivars, the albumin and globulin proteins were relatively resistant to proteolysis, whereas the hordeins suffered a dramatic breakdown during malting, with the D hordein being degraded most rapidly, followed by the B and C hordeins. Besides these similarities, differences between both cultivars were observed in the relative rates of D hordein degradation, as this rate was considerably higher in the cultivar with high malting quality. Similar, but much less distinct kinetics were seen with certain B hordeins. Since a possible relationship might exist between the rate of proteolysis of the D hordeins and the character final attenuation, we analyzed a larger number of barley cultivars with different final attenuation values with a simplified technique. For the ten cultivars examined, differences during germination were again seen in the rates of modification of the D hordeins. However, significant correlations between the D hordein breakdown and final attenuation values were not obtained, so that we propose that there exists at best a loose correlation between the relative rate of proteolysis of these proteins and the malting quality character final attenuation.

Edible Grain↗

Regression of gastric MALT lymphoma after eradication of Helicobacter pylori is predicted by endosonographic staging. MALT Lymphoma Study Group.

BACKGROUND & AIMS: Recent studies suggest that eradication of Helicobacter pylori may result in complete regression of low-grade lymphoma of the gastric mucosa-associated lymphoid tissue (MALT). Which patients benefit from this treatment is unknown. The aim of this study was to prospectively study whether staging by echoendoscopy predicts the outcome of treatment of MALT lymphoma by eradication of H. pylori. METHODS: Twenty-two patients positive for H. pylori with low-grade gastric B-cell MALT lymphoma were examined by echoendoscopy at the time of diagnosis. Treatment for H. pylori consisted of a 2-week course of oral omeprazole and amoxicillin. Patients were followed up by endoscopy and biopsy. RESULTS: H. pylori was eradicated in all patients. Complete regression of MALT lymphoma was observed in 12 patients (54%), partial regression in 5 patients (23%), and no response in 5 patients (23%) during follow-up. Twelve of 14 patients with lymphoma restricted to the mucosa or submucosa (stage E-I1) at echoendoscopy, but none of the 10 patients with higher stage (P < 0.01), showed complete regression of MALT lymphoma. In stage E-I1 patients, the probability of complete regression of lymphoma was 60% at 6, 79% at 12, and reached 100% at 14 months, respectively. CONCLUSIONS: Staging of gastric low-grade MALT lymphomas by endoscopic ultrasonography allows prediction of the response to therapy by eradication of H. pylori.

Adult↗

On the puzzling arrangement of the asymmetric MalT-binding sites in the MalT-dependent promoters.

The MalT-dependent promoters of the enterobacteria belong to a small family of positively regulated prokaryotic promoters in which the activator protein recognizes short asymmetric nucleotide sequences present in several locations and orientations. We demonstrate that active MalT-dependent semisynthetic promoters can be constructed by using a synthetic decanucleotide as the MalT site and random nucleotide sequences as connecting sequences, provided that the location and orientation of the sites are the same as in natural MalT-dependent promoters. Strikingly, the induced level of promoter activity and the induction factor of each semisynthetic promoter are identical to those of its natural counterpart, in spite of considerable differences in their nucleotide sequences. The study of these semisynthetic promoters confirms the importance of the structural motif formed by two MalT sites in a direct repeat. This motif is involved in promoter activation either alone or in conjunction with a third MalT site, proximal with respect to the transcription start site. In this latter configuration, the promoters are active irrespective of the orientation of the repeat, and they retain at least some activity when the distance between the repeat and the proximal site is increased, provided that the alignment along the axis of the helix is conserved.

Bacterial Proteins↗

Antigen-dependent progression of mucosa-associated lymphoid tissue (MALT)-type lymphoma in the stomach. Effects of antimicrobial therapy on gastric MALT lymphoma in mice.

In humans, low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach regress when Helicobacter pylori infection is cured by antimicrobial therapy. Using an animal model of human gastric MALT lymphoma, we observed the effects of Helicobacter felis eradication and the relationship between infection and disease progression. Antimicrobial therapy was given to one-half of the BALB/c mice infected with H. felis for 20 months. Groups of antibiotic-treated and untreated mice were killed 2, 3, and 4 months after antimicrobial therapy (ie, 22, 23, and 24 months after infection). The numbers of mice with MALT decreased after H. felis eradication with no lymphoid follicles seen 4 months after treatment. MALT lymphoma was present in a total of 23% (11/48) of antibiotic-treated infected mice compared with 75% (27/36) in untreated infected mice. These lymphomas were further graded into low-, intermediate-, and high-grade lymphoma. In the untreated mice, lymphoma development was more advanced with 36% low-grade (13/36), 39% intermediate-grade (14/36), and 6% high-grade (large B-cell) lymphoma (2/36) whereas in the treated mice the incidence was 21% (10/48), 6% (3/48), and 0% (0/48), respectively. These observations suggest that antigenic stimulation by H. felis sustained growth and progression of low-grade MALT lymphoma and that primary high-grade gastric lymphomas can evolve from the transformation of these tumors. Eradication of the organism caused low-grade tumors to regress, with inhibition or slowing down of lymphoma development toward high-grade lymphoma. The H. felis mouse model of gastric MALT lymphoma presents an opportunity to address the issues arising from antimicrobial treatment of these tumors in humans.

Animals↗

Detection of polypeptides and amylase isoenzyme modifications related to malting quality during malting process of barley by two-dimensional electrophoresis and isoelectric focusing with immobilized pH gradients.

Two cultivars ("Alexis" and "Lenka") of contrasting final attenuation values were malted, and the protein and amylase isoenzyme composition, as well as the change in protein and amylase isoenzyme composition during malting, was investigated by two-dimensional polyacrylamide gel electrophoresis of total proteins, and isoelectric focusing of amylase isoenzymes, respectively. Isoelectric focusing demonstrated that significant differences exist between the amylase isoenzyme patterns of the two cultivars, suggesting a correlation between the presence of certain amylase isoenzyme bands and final attenuation. This finding was confirmed by analysis of 36 barley cultivars with a wide range of quality. It was shown that all cultivars which are of low or, at best, moderate final attenuation values exhibit the amylase band "B" (isoelectric point approximately 6.8), whereas those cultivars which are predominantly of high malting grade do not possess this "B" isoenzyme band, but exhibit the pronounced "A" isoenzyme band (isoelectric point approximately 6.5) instead, suggesting that these isoenzymes (which we suppose to be beta-amylases) can be utilized to predict the final attenuation values of unknown barley samples or new lines. However, "final attenuation" is a complex function. Preliminary results of two-dimensional gel electrophoresis indicate that other factors, such as total amount of amylases, or a 19 kDa A hordein-like polypeptide, which was degraded faster in the low malting grade cultivar "Lenka", may also have a role in determining quality.

Amylases↗

Fecal streptococci on barley and malt kernels and instant malted milk powder.

Among 500 barley kernels, tested singly, 1.8% (9 kernels) were positive for fecal streptococci. Among 800 malt kernels, tested singly by the same procedure, 68% (540 kernels) were positive for fecal streptococci. In unsulfured and sulfured malts, 67 and 68% of the kernels, respectively, were positive for these bacteria. Fecal streptococci were also isolated by an enrichment procedure from two brands of instant malted milk powder sold in supermarkets. Seventy randomly picked isolates from malts were identified to be fecal streptococci, belonging probably to more than one species.

Agar↗