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Biomedical subjects

F D Lee

Publications and source records attributed to F D Lee.

At least 19 recordsLinked to original sources
PubMed1992

Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs.

BACKGROUND: Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may lead to inflammation of the small intestine associated with occult blood and protein loss. The aim of this study was to investigate the prevalence and structural correlates of this enteropathy. METHODS: We examined the stomach, duodenum, and small intestine of 713 patients post mortem. Of these patients, 249 had had NSAIDs prescribed during the six months before death and 464 patients had not. All visible small intestinal lesions were removed for histologic examination, and specific etiologic factors were sought. The prevalence of nonspecific small-intestinal ulcers and ulcers of the stomach and duodenum was compared in the two groups of patients. RESULTS: Nonspecific small-intestinal ulceration was found in 21 (8.4 percent) of the users of NSAIDs and 3 (0.6 percent) of the nonusers (difference, 7.8 percent; 95 percent confidence interval, 5.0 to 10.6 percent; P less than 0.001). Three patients who were long-term users of NSAIDs were found to have died of perforated nonspecific small-intestinal ulcers. Ulcers of the stomach or duodenum were found in 54 (21.7 percent) of the patients who used these drugs and 57 (12.3 percent) of those who had not (difference, 9.4 percent; 95 percent confidence interval, 3.9 to 15.1 percent; P less than 0.001). CONCLUSIONS: Patients who take NSAIDs have an increased risk of nonspecific ulceration of the small-intestinal mucosa. These ulcers are less common than ulcers of the stomach or duodenum, but can lead to life-threatening complications.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

The role of interleukin-6 in development.

Interleukin-6 is a member of a class of hormone-like molecules termed cytokines. The actions of IL-6 are highly pleiotropic. In adults IL-6 functions as a major mediator of inflammatory responses as well as inducing the synthesis of acute phase proteins by the liver following infection or injury. Based on in vitro and in vivo studies IL-6 also has important functions in regulating the development of multiple lineages of hemopoietic cells. It may also be an inflammatory mediator in the central nervous system. Although IL-6 has been found in early mouse embryos, its function has not yet been determined. Its expression by placental trophoblasts and maternal decidua suggests that it has some role in fetal-maternal interactions. Finally, the response of fetal hemopoietic progenitor cells to IL-6 suggests that IL-6 may have a broader action on the expansion and maturation of fetal precursors. New approaches such as those involving the disruption of the IL-6 gene in mice will be needed for a more complete understanding of IL-6's role in embryonic development.

Animals↗
PubMed1992

Chemical gastritis and Helicobacter pylori related gastritis in patients receiving non-steroidal anti-inflammatory drugs: comparison and correlation with peptic ulceration.

AIMS: To evaluate the prevalence and significance of chemical gastritis, in comparison with gastritis related to Helicobacter pylori in patients receiving non-steroidal anti inflammatory drugs (NSAIDs). METHODS: Two hundred and eighteen patients were studied, 174 of whom were taking NSAIDs. Chemical gastritis was defined as the presence of foveolar hyperplasia, muscle fibres in the lamina propria, oedema and vasodilation, in the absence of a chronic inflammatory cell infiltrate. RESULTS: Chemical gastritis was found in 46 (26%) patients taking NSAIDs, and three (7%) in subjects not taking these drugs (p less than 0.01). H pylori was detected in 56 (32%) subjects taking NSAIDs compared with 22 (50%) not taking these agents (p less than 0.02). Ulcers were found in 16 out of 72 patients (22%) taking NSAIDs and without H pylori infection or chemical gastritis compared with 27 out of 56 (48%) with H pylori related gastritis (p less than 0.01), and 25 out of 46 (54%) with chemical gastritis (p less than 0.01). CONCLUSIONS: Peptic ulcers associated with the use of NSAIDs seem to occur more commonly in patients with chemical gastritis or H pylori infection. Patients taking NSAIDs also seem to have a greater prevalence of chemical gastritis but a lower prevalence of H pylori than those not taking these drugs.

Adult↗
PubMed1992

Diagnostic tests for Helicobacter pylori: comparison and influence of non-steroidal anti-inflammatory drugs.

AIMS: To evaluate the efficacy of culture, histology, CLO-test, Helico-G and Pyloriset tests in diagnosing Helicobacter pylori in the presence or absence of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Of 134 patients studied, 75 had taken NSAIDs. At endoscopy, biopsy specimens were taken for culture, histology, and CLO-test. Blood was also taken for enzyme linked immunosorbent assay (ELISA) (Helico-G) and latex agglutination (Pyloriset) tests. RESULTS: The sensitivity, specificity, and predictive values of histology and CLO-test, compared with culture, ranged from 90% to 97%, regardless of NSAID intake. In the 59 patients not taking NSAIDs Helico-G had a sensitivity of 75% (p < 0.05) and a specificity of 61%; Pyloriset's sensitivity and specificity were, respectively, 63% (p < 0.05) and 67%. In the 75 patients taking NSAIDs the sensitivity of Helico-G was 81% and its specificity 45% (p < 0.05); Pyloriset had a sensitivity of 61% (p < 0.05) and a specificity of 50% (p < 0.05). CONCLUSION: These findings suggest that H pylori is more reliably diagnosed by culture, histology, and CLO-test than by the serological tests used in this study, especially in patients treated with NSAIDs.

Adult↗
PubMed1991

Inhibition of human gastric cyclic AMP production by Helicobacter pylori protein--possible involvement of mucosal prostaglandin E2.

The effect of Helicobacter pylori protein on cAMP and prostaglandin (PGE2) production was studied in incubates of human gastric fundic mucosa. At 24 hours, specimens incubated in the control fluid had a median cAMP value of 81 pmol/mg protein, compared to 28 pmol/mg (P less than 0.05) when incubated in H. pylori protein, 155 pmol/kg (P less than 0.006) in histamine, and 23 pmol/kg (P less than 0.05) in histamine plus H. pylori protein. A similar trend was observed at 48 hours. Although H. pylori protein had no direct effect on mucosal PGE2, it intensified the inhibitory effect of indomethacin and prevented the stimulatory effect of histamine on both PGE2 and cAMP production. Given the role of cAMP in various physiological responses, these results suggest that H. pylori protein might alter those functional aspects of the human gastric mucosa which rely on cAMP as a second messenger. Assuming that PGE2 is involved in mediating such effect, its role would appear to be either partial or indirect.

Bacterial Proteins↗
PubMed1991

Spiral shaped microorganisms in the human duodenal mucosa.

A new spiral shaped microorganism, Gastrospirillum hominis, distinct from Helicobacter pylori, has recently been described in the gastric mucosa. We report a patient with duodenal erosions who was found to have these organisms in his duodenal mucosa. This bacterium is not necessarily specific to the stomach, and its association with peptic damage needs to be studied further.

Adult↗
PubMed1990

Hypothesis: symmetrical cutaneous lymphoma.

Patients with malignant lymphoma may have cutaneous and subcutaneous involvement that exhibits a striking symmetry about the coronal axis. The symmetry of these lesions may be caused by site-specific migration from the circulation, preferential proliferation by lymphocytes of the neoplastic clones at defined anatomical sites, or both mechanisms. Similar behaviour by benign lymphocytes may explain the symmetry and selective anatomical distribution of lesions in other skin diseases.

Adult↗
PubMed1990

Mechanism for transforming growth factor beta and IL-2 enhancement of IgA expression in lipopolysaccharide-stimulated B cell cultures.

Transforming growth factor beta (TGF-beta), but not IL-2, causes LPS-stimulated surface (s)IgA- cells to express sIgA. Although there is a progression of sIgA- cells to sIgA+ cells and then to IgA-secreting cells, there is not a parallel change in ratio of membrane to secreted form of alpha-mRNA. In fact, the secreted form of alpha-mRNA is always the predominant form even before the expression of sIgA. However, at least some of the secreted alpha-mRNA transcripts are sterile. The increase in sIgA expression and the induction of sterile transcripts indicate that TGF-beta enhances H chain class switching to IgA as opposed to allowing the growth and maturation of cells precommitted to IgA secretion. The addition of IL-2 to cultures with TGF-beta results in a 5- to 10-fold increase in IgA secretion compared to cultures to which only TGF-beta was added. In these cultures IL-2 increases neither the proportion nor the total number of sIgA+ cells suggesting that IL-2 acts to increase IgA secretion. However, IL-2 does not cause a change in the ratio of secreted to membrane form of alpha-mRNA nor does it lead to an increase in the steady state level of alpha-mRNA comparable to the increase in secreted IgA. Thus, it appears that regulation of transcription of IgA as sIgA- cells proliferate and undergo H class switching and maturation does not follow the same sequence as is seen when sIgM+ cells proliferate and mature to Ig-secreting cells. Furthermore, the data suggest that maturation to high level secretion is controlled posttranscriptionally.

Animals↗
PubMed1990

A sensitive method of screening for dominant T cell clones by amplification of T cell gamma gene rearrangements with the polymerase chain reaction.

A sensitive method of screening for dominant T cell clones in small samples of DNA has been developed using the polymerase chain reaction to amplify and identify T cell gamma receptor gene rearrangements. It can detect such rearrangements in nanogram quantities of DNA from cultured T cell clones, even in the presence of 20-100 parts of polyclonal lymph node DNA, and works with DNA extracted from paraffin sections of cloned T cells which have been fixed in formalin. Presumptive clonal reactions have been obtained in preliminary tests on 8 of 10 unfixed T cell lymphomas but in 0 of 10 reactive lymph nodes.

Base Sequence↗
PubMed1990

Molecular characterization of germ-line immunoglobulin A transcripts produced during transforming growth factor type beta-induced isotype switching.

The addition of transforming growth factor type beta to lipopolysaccharide-stimulated murine B-cell cultures enhances isotype switching to IgA and induces the appearance of two sizes of alpha mRNA transcripts. One of these is the same size as mRNA for secreted IgA but the other, which is 300-400 base pairs (bp) shorter, does not correlate in size with any form of productive alpha mRNA. Both sizes of transcript were shown to contain germ-line sequences 5' to the alpha switch region, suggesting that the longer transcripts included both germ-line and productive forms of alpha mRNA, whereas the shorter transcripts were only germ-line alpha mRNA. We isolated cDNA clones corresponding to the shorter, 1.3-kilobase (kb), transcript by using an anchored polymerase chain reaction and a specific primer for the constant region. Analyses of these cDNA clones show that the short transcript consists of a 126-bp exon located approximately 1.5 kb 5' to the alpha switch region spliced to the first exon of the alpha constant region locus. Furthermore, a minor fraction of the longer, approximately 1.7 kb, transcripts also contains this exon. These results demonstrate that transforming growth factor type beta-mediated isotype switching to IgA is preceded by transcriptional activation of the heavy-chain locus.

Animals↗
PubMed1990

The interaction between Helicobacter pylori culture filtrate and indomethacin: effects on the integrity of human gastric antral mucosa and its prostaglandin E2 production in vitro.

Histopathological methods and radioimmunoassay were used to assess the microstructure and prostaglandin E2 production by paired specimens of human gastric antral mucosa; the specimens were studied after 48 h of incubation in base-line tissue culture medium, Helicobacter pylori culture filtrate, H. pylori culture control fluid, indomethacin, and H. pylori culture filtrate plus indomethacin. When applied alone, the filtrate did not affect the structure of the mucosal tissue or its prostaglandin E2 synthesis. In the overall group (n = 21), specimens incubated with the mixture of H. pylori filtrate and indomethacin had a median histological grade of 1 and prostaglandin E2 of 29 pg/mg tissue, compared to 2 pg/mg (P = 0.04) and 60 pg/mg (P = 0.0007) respectively, in specimens incubated with indomethacin alone. These results indicate that an interaction may exist between indomethacin and a factor contained in H. pylori culture filtrate. Such interaction is damaging to the human gastric antral mucosa, and its understanding might have therapeutic implications.

Adult↗
PubMed1990

Observer variability in histopathological reporting of transitional cell carcinoma and epithelial dysplasia in bladders.

Sections from 90 urinary bladder biopsy specimens were examined by 11 consultant histopathologists with varying experience to determine the appropriateness of existing pathology terminology. Analysis with kappa statistics showed fair to good agreement in the grading and staging of transitional cell carcinoma. There was also reasonable agreement in the diagnosis of high grade dysplasia in random biopsy specimens from the urothelium adjacent to the neoplasm, but very poor agreement for lesser degrees of dysplasia. It is concluded that the present classification of bladder carcinomata is reliable and that pathologists can determine stage with a high degree of reproducibility and grade with a fair degree of reproducibility.

Carcinoma, Transitional Cell↗
PubMed1990

Gastric antral vascular ectasia (watermelon stomach)--therapeutic options.

We have encountered five cases of chronic iron deficiency anaemia due to bleeding from gastric antral vascular ectasia (watermelon stomach). Two cases were associated with a lymphoma and in three cases there was evidence of portal hypertension. Two patients were treated conservatively by blood transfusions. The other patients required either surgery or tranexamic acid or endoscopic laser therapy to control the chronic haemorrhage.

Aged↗
PubMed1990

Abrogation of IL-3 dependent growth requires a functional v-src gene product: evidence for an autocrine growth cycle.

We have investigated the ability of the v-src oncogene to abrogate growth factor dependent growth in the interleukin-3 dependent myeloid progenitor cell line 32D c13. Growth factor independent clones were isolated following infection of 32D c13 cells with murine retroviruses containing the v-src oncogene. v-src was demonstrated to be directly responsible for growth factor independence in experiments utilizing temperature-sensitive v-src mutants. The v-src infected cells released a growth factor capable of stimulating the proliferation of normal 32D c13 cells. Analysis of the mRNA from v-src infected 32D c13 did not identify the putative autocrine growth factor as one of the currently identified murine or human hematopoietic growth factors.

Animals↗