Intestinal metaplasia of the bladder: implications for management.
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Colon↗
Biomedical subjects
M Falzon
Publications and source records attributed to M Falzon.
Double blind trial of colloidal bismuth subcitrate versus placebo in Helicobacter pylori positive patients with non-ulcer dyspepsia.
We have carried out a double blind placebo controlled trial to assess the effects of treatment with colloidal bismuth subcitrate in Helicobacter pylori associated non-ulcer dyspepsia. Eighty patients with dyspepsia, normal upper gastrointestinal appearances at endoscopy and H pylori associated active chronic gastritis on histology of gastric antral biopsies were included in the trial. The patients were randomised to receive colloidal bismuth subcitrate 240mg twice daily for four weeks or matching placebo and were reassessed four weeks after completing treatment. Twenty-six patients (67%) receiving colloidal bismuth subcitrate had normal histology or improved inflammation compared with five (13%) receiving placebo (p less than 0.001), and symptoms were absent or improved in 32 (82%) and two (5%) respectively (p less than 0.001). Serum IgG level was a marker of infection, and fell with successful treatment. Colloidal bismuth subcitrate is effective treatment for H pylori associated non-ulcer dyspepsia with improved gastric antral histological appearances and has a beneficial effect on symptoms.
Adult↗
The natural history of benign lymphoepithelial lesion of the salivary gland in which there is a monoclonal population of B cells. A report of two cases.
In two patients, a diagnosis of benign lymphoepithelial lesion of the salivary gland was followed by the development of extrasalivary gland lymphoma after 10- and 9-year intervals, respectively. On review, immunohistochemistry revealed immunoglobulin light-chain restriction in the initial biopsy in each case and there was both morphological and immunohistochemical evidence linking the extrasalivary gland lymphoma with the initial lesion. It is argued that in the presence of a monoclonal B-cell population, a diagnosis of benign lymphoepithelial lesion is inappropriate. These patients fulfill the criteria for a diagnosis of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue and should be treated accordingly.
Adult↗
Binding of the transcription factor EBP-80 mediates the methylation response of an intracisternal A-particle long terminal repeat promoter.
Intracisternal A-particle (IAP) expression in mouse cells has been correlated with hypomethylation of HhaI and HpaII sites in proviral long terminal repeats (LTRs). In a previous study, in vitro methylation of three HhaI sites in the U3 region of the LTR from the cloned genomic IAP element, MIA14, was shown to inhibit promoter activity in vivo. In this study, we found by site-directed mutagenesis that the two more downstream HhaI sites within this LTR were responsible for the methylation effects on promoter activity in vivo; methylation of the other (5') HhaI site, which lies within a putative SP1 binding domain, did not affect promoter activity. Methylation of the HhaI sites also inhibited promoter activity of the LTR in a cell-free transcription system. Exonuclease III footprinting demonstrated methylation-induced changes in protein binding over the region encompassing the downstream HhaI site, designated the Enh2 domain. The protein that interacts specifically with this domain, EBP-80, was characterized in a previous study (M. Falzon and E. L. Kuff, J. Biol. Chem. 264:21915-21922, 1989). We show here that the presence of methylcytosine in the HhaI site within the Enh2 domain inhibited binding of EBP-80 in vitro. The methylated MIA14 LTR construct was much less responsive to added EBP-80 in an in vitro transcription system than was the unmethylated construct. These data suggest that CpG methylation within the Enh2 domain may exert its effect on transcription in vivo by altering the interaction between EBP-80 and its cognate DNA sequence.
Base Sequence↗
Extrarenal adult Wilms tumour: presentation, diagnosis and management.
Adult Wilms tumour is an uncommon entity, with fewer than 200 cases reported in the world literature. Strict criteria for the definition of this tumour have been specified, amongst which was the need for it to be a primary renal neoplasm. We present radiological and histological evidence of this tumour occurring at an extrarenal site, and make the case for relaxation of these criteria to include this eventuality.
Adult↗
A variant binding sequence for transcription factor EBP-80 confers increased promoter activity on a retroviral long terminal repeat.
The cloned long terminal repeats (LTRs) of mouse intracisternal A-particle (IAP) proviral elements differ in their promoter activity. In this study, the LTR from a recently transposed IAP element (rc-mos) is shown to be a more effective promoter both in vivo and in vitro than the LTR from a randomly cloned genomic element (MIA14). These LTRs differ in nucleotide sequence in certain previously defined protein-binding domains. In particular, the MIA14 LTR contains two domains, designated Enh1 and Enh2, with sequence homology to the SV40 enhancer core motif, while in rc-mos the Enh2 position is occupied by a variant sequence which lacks core homology. EBP-80 is a general enhancer core-binding protein originally isolated by virtue of its affinity for the MIA14 Enh2 sequence (Falzon, M., and Kuff, E.L. (1989) J. Biol. Chem. 264, 21915-21922). We now find by quantitative binding studies, binding competition, and UV cross-linking that EBP-80 from both human and mouse cells binds to the "Enh2" motif of rc-mos more strongly than to the Enh2 of MIA14. In vitro transcription from both LTRs is strongly enhanced by addition of EBP-80 showing that binding is related to function. The rc-mos LTR remains the more effective promoter in the presence of added EBP-80. Reciprocal substitution of the Enh2 domains in the two LTRs by site-directed mutagenesis shows that the rc-mos variant confers a 3-fold increment in in vivo promotor activity. The rc-mos motif or a closely related sequence is found in the cloned LTRs of many expressed and/or recently transposed IAP elements. EBP-80 is identified as a cellular transcription factor whose heightened levels in certain mouse cells might result in preferential expression of IAP elements containing this sequence motif.
Animals↗
Metabolic activation and biological effects of nitrosamines in the mammalian lung.
Nitrosamines and their precursors are among the most common contaminants of our environment, and many of them are highly carcinogenic. Nitrosamines are believed to require metabolic activation in the host organism, and many of them demonstrate a pronounced organ and cell type specificity. This review summarizes recent in vivo and in vitro experiments which focus on the mechanisms of nitrosamine-induced lung carcinogenesis. Currently available in vivo and in vitro data suggest that nitrosamines may be metabolized by cytochrome P-450, prostaglandin endoperoxide synthetase, or monoamine oxidases. The presence of one or the other of these enzyme systems may be partially responsible for the cell type-specific effects of this class of chemicals. Moreover, evidence in vitro suggests selective uptake of nitrosamines by cell type-specific receptors, a phenomenon which offers a more logical explanation than previously published theories for the selectivity of biological effects exerted by nitrosamines.
Animals↗
Histological classification of the non-Hodgkin's lymphoma.
The non-Hodgkin's lymphomas (NHL) are a diverse group of neoplasms which show subtle histological differences. This has led to difficulties in formulating reproducible classifications of NHL that are both histologically and clinically relevant. In this review we discuss some of the historical aspects of NHL classification leading up to the principal classifications in current use. In comparing these we put forward reasons why we regard the updated Kiel classification as that which is the most soundly based in clinical, histological and biological terms. The Kiel classification, unlike its competitors, lends itself to further updating as new clinicopathological entities become established, without loss of its essentially sound foundations. Thus the classification of T-cell lymphomas can only be regarded as provisional and certain extranodal lymphomas, which are clear clinicopathological entities, await classification. The biological foundation of the Kiel classification should allow further updating to incorporate these entities and the tighter definitions of categories of NHL that will surely result from the application of cytogenetics, molecular biology and studies of lymphocyte homing mechanisms.
B-Lymphocytes↗
Malignant lymphomatous polyposis: diagnosis and response to chemotherapy.
Malignant lymphomatous polyposis is a low-grade lymphoma with aggressive features. It may mimic polyposis coli on a barium enema and colonoscopic examination. An histological diagnosis may be made from a tissue biopsy taken via the colonoscope. We discuss the methods of diagnosis, the clinical behaviour and response to chemotherapy.
Aged↗
Endoscopy in dyspeptic patients: is gastric mucosal biopsy useful?
Should dyspeptic patients coming to endoscopy with "normal" findings also be biopsied? To assess this, we studied the sensitivity and specificity of endoscopic examination compared with histology, microscopic evidence of Helicobacter pylori, CP-TEST, culture, and serum IgG and IgA antibody titers to H. pylori to determine whether endoscopy and antral biopsies really are useful. One hundred seven consecutive dyspeptic patients (mean age 43 yr) were entered. Four antral biopsies were taken routinely for evaluation by histology, microscopy, CP-TEST, and culture. Serum IgG and IgA antibody levels were measured in all patients. Of symptoms, postprandial bloating was statistically more common in H. pylori-positive than in negative patients. Endoscopy had the poorest sensitivity (37.1%) and specificity (53.3%). Patients with normal endoscopic appearances but histologically confirmed gastritis had significantly higher IgG and IgA titers than the patients normal by both endoscopy and histology and without evidence of H. pylori. This study has shown that endoscopy is unhelpful in dyspeptic patients if endoscopic biopsies are not routinely taken.
Adult↗
Isolation and characterization of a protein fraction that binds to enhancer core sequences in intracisternal A-particle long terminal repeats.
The U3 region of mouse intracisternal A-particle (IAP) long terminal repeats (LTRs) contains several nuclear protein-binding domains. Two of these contain sequences with homology to the SV40 enhancer core. We refer to these two domains as Enh1 and Enh2. The Enh2 domain is an important determinant of promoter activity in vivo. We report here the isolation of nuclear fractions from human 293 and mouse MOPC-315 cells which interact with Enh1 and Enh2. Purification was achieved via DNA-affinity chromatography on a multimerized oligonucleotide representing the Enh2 region from the LTR of the mouse genomic IAP element, MIA14. Glycerol gradient sedimentation suggested a native Mr of approximately 80-100 for the binding component(s) in both crude and affinity-purified fractions. UV cross-linking showed that the binding activity involved two polypeptides within this size range. The affinity-isolated fraction from each cell line was highly purified, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in vitro binding analysis. Exonuclease III footprinting showed that the two polypeptides interacted preferentially with the Enh1 and Enh2 domains within a 139-base pair segment from the MIA14 LTR. The polypeptides interacted in a sequence-specific manner with oligonucleotides representing these domains within the IAP LTR and with oligonucleotides containing the enhancer core sequence from SV40 and polyoma virus. Equilibrium binding studies indicated that the apparent dissociation constants for the polypeptides binding to the enhancer core sequence from MIA14, SV40, and polyoma virus were similar. Therefore, this affinity-purified fraction may represent a novel enhancer core-binding component which is distinct from the previously characterized rat CCAAT/enhancer-binding protein, C/EBP.
Animals↗
Technetium-99m pentavalent DMSA imaging detects metastases of poorly differentiated carcinoma of the thyroid.
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Aged↗
Antibody titres to Campylobacter pylori after treatment for gastritis.
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Acute Disease↗
Multiple protein-binding sites in an intracisternal A particle long terminal repeat.
The long terminal repeats (LTRs) of cloned intracisternal A particles (IAPs) can function as effective promoters in heterologous and homologous cell types (K. K. Lueders, J. W. Fewell, E. L. Kuff, and T. Koch, Mol. Cell. Biol. 4:2128-2135, 1984) and respond to transcriptional factors induced by various nuclear oncogene products (S. Luria and M. Horowitz, J. Virol. 57:998-1003, 1986). Using the first 139 base pairs of the U3 region of a cloned mouse IAP LTR as probe, we demonstrated multiple exonuclease III stop sites which appeared specifically in the presence of nuclear extract protein. Various extracts gave similar footprints, but the amount of nuclear protein required varied up to 10-fold. Cell lines transformed with known nuclear oncogenes, such as adenovirus E1a and E1b (293 cells), simian virus 40 large T antigen (COS7 cells), and c-myc (MOPC-315 cells) had more and/or higher-affinity factors for the IAP LTR than extracts from HeLa, CV1, and NIH 3T3 cells did. DNase I footprinting revealed at least five distinct protein-binding domains within the 139-base-pair region. These domains correspond to segments of highly conserved nucleotide sequence among a number of IAP LTRs. Gel retardation studies with oligonucleotides encompassing the DNase I footprint sites showed that the nuclear factors are present in different proportions and different absolute levels in extracts from different cell types. Moreover, the oligonucleotide probes indicate that individual motifs can be occupied independently of one another. Three of the DNase I footprints include a sequence with homology to the simian virus 40 core enhancer and sequence motifs that closely resemble the binding sites for transcription factors SP1 and AP-1. The other two binding sites are not obviously related to previously recognized motifs. The multiple protein-binding sites in close proximity indicate the complex regulatory mechanism for IAP transcription.
Animals↗
Four hour rapid urease test (RUT) for detecting Campylobacter pylori: is it reliable enough to start treatment?
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Bacteriological Techniques↗
Urease tests for Campylobacter pylori: care in interpretation.
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Campylobacter↗
The expression of rat homeobox-containing genes is developmentally regulated and tissue specific.
Seven rat homeobox-containing sequences have been isolated by screening a genomic library with a probe derived from a Drosophila antennapedia cDNA clone. The characterization of two of these homeobox-containing clones has been described (Falzon, M., Sanderson, N.D. and Chung, S. Y. (1987) Gene 54, 23-32). Sequence analysis of the remaining five homeobox regions reveals a 180 bp domain sharing 70-95% identity at the amino acid level with the homeodomain from the Drosophila antennapedia gene and with the homeodomains from other metazoan species. Genomic blot analysis shows that each of the homeobox-containing DNA segments is probably present in a single copy per haploid genome. Northern blot analysis of RNA transcripts indicates that the rat homeobox-containing sequences are expressed during embryogenesis and in newborn and adult tissues in a tissue-specific manner; RNA expression is predominantly detected in spinal cord and kidney. Moreover, the pattern of RNA transcripts observed is distinct for each homeobox sequence, indicating differential regulation. Among the seven rat homeobox-containing sequences, the flanking sequences of five of the clones have no obvious sequence similarity with previously published sequences of homeobox-containing genes from other species. Two of the rat clones have been identified as potential homologues to mouse homeobox-containing sequences. For both pairs, a high degree of amino acid conservation (greater than 95%) is observed within the homeodomain and its immediate flanking regions between the putative homologous genes in mouse and rat. This strengthens the assertion that some of the mammalian homeobox-containing genes encode highly conserved proteins and may serve important biological functions.
Amino Acid Sequence↗
Inhibition of N-diethylnitrosamine metabolism by human lung cancer cell lines with features of well differentiated pulmonary endocrine cells.
Cell lines derived from a human pulmonary carcinoid tumor (NCI-H727) and from a human pulmonary large cell carcinoma (NCI-H460) were investigated by transmission electron microscopy. Both cell lines, at early in vitro passage, demonstrated ultrastructural features of well differentiated pulmonary endocrine cells. Line NCI-H727 had more endoplasmic reticulum than line NCI-H460 and demonstrated L-dopa decarboxylase activity as well as production of calcitonin and bombesin. Because of their ultrastructural resemblance with normal pulmonary endocrine cells, these cell lines were used to test the theory derived from experiments in hamsters that human pulmonary endocrine cells can metabolize N-nitrosodiethylamine (DEN). The cells were incubated in vitro with [14C]DEN. Metabolism was assessed by 14CO2 production. Both cell lines metabolized DEN to a much greater extent than previously investigated human lung cancer cell lines of Clara cell and alveolar type II cell morphology. In keeping with its abundant endoplasmic reticulum, line NCI-H727 yielded 14CO2 in the 300 nM range, whereas NCI-H460 was less active. Metabolism was time dependent. Preincubation with various enzyme inhibitors yielded a highly significant inhibition of DEN metabolism with the two inhibitors of the fatty acid cyclooxygenase component of prostaglandin endoperoxide synthetase, aspirin and indomethacin. Inhibitors of cytochrome P-450 (CO, piperoxylbutoxide) did not inhibit DEN metabolism. Preincubation with sinigrin yielded similar negative results as CO and piperonylbutoxide. Our data are in support of the theory that human pulmonary endocrine cells can metabolize nitrosamines. Moreover, the experiments with enzyme inhibitors suggest that in this cell type such metabolism is largely dependent on prostaglandin endoperoxide synthetase.
Carbon Dioxide↗