Prostaglandins as mediators of lower esophageal sphincter dysfunction in esophagitis.
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Biomedical subjects
Publications and source records attributed to J G Williams.
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The relationships among age, gender, involvement in family activities, involvement in peer activities, and teenage alcohol and other drug use were examined. Data from a random sample of South Carolina public school 7th through 12th graders were analyzed. Consistent with previous research, it was found that older subjects reported greater substance use than younger subjects, whites reported greater use of alcohol and other drugs than blacks, boys reported greater use than girls, and less involvement in family activities and greater involvement in peer activities was associated with greater reported alcohol and other drug use. Interactions among these variables also were examined. Multiple regressions indicated that 74% of the variance in alcohol use, 80% of the variance in marijuana use, and 85% of the variance in use of other drugs were predicted by these variables.
OBJECTIVE: This study was performed to (1) correlate and sphincter defects, identified by endoanal ultrasound with operative findings, and (2) define the appearance of such sphincter defects as seen at operation. SUMMARY BACKGROUND DATA: Endoanal ultrasonography is a minimally invasive method of imaging the anal sphincter complex and enables identification of anal sphincter defects. Little is known about the accuracy and limitations of endoanal ultrasound in identifying such defects. Furthermore, there are no data about the appearances of these endosonic sphincter defects as seen at operation. METHODS: Forty-four patients (40 women; age range, 26 to 80 years; mean age, 56 years) with fecal incontinence, undergoing pelvic floor repair, were investigated by endoanal ultrasound before operation. Endosonic findings were correlated with the appearances of external anal sphincter, internal anal sphincter, and intersphincteric space, at operation. Diagnosis of the site and type of defect was made by macroscopic appearances. Uncertainty about the type of sphincter defect was resolved by obtaining muscle biopsies for histology. RESULTS: All external sphincter defects seen by endoanal ultrasound (n = 23) were confirmed at operation. Twenty-one of 22 internal sphincter defects identified by endosonography also were confirmed at operation. In ten patients with a neuropathic anal sphincter complex, the morphology was normal on endosonography, and this was confirmed at operation. (Sensitivity and specificity of 100% for external anal sphincter; 100% and 95.5%, respectively, for internal and sphincter) CONCLUSIONS: These data show that endoanal ultrasound is an accurate method of identifying anal sphincter defects.
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Forty six patients (median age 61 years; 42 women) with faecal incontinence and 16 age and sex matched controls undergoing a restorative proctocolectomy were assessed by clinical examination, anorectal physiology, and anal endosonography. Forty patients (87%) with faecal incontinence had a sphincter defect demonstrated on anal endosonography (31 external and 21 internal anal sphincter defects). The commonest cause of faecal incontinence was obstetric trauma. This occurred in 35 women, 30 of whom exhibited a morphological defect in the anorectal sphincter complex. In 22 of these patients with a history of a perineal tear or episiotomy, 21 (95%) had a sphincter defect. Sphincter defects were commonly located at the level of the midanal canal.
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Two cases of mucosa associated lymphoma (pseudolymphoma) of the lung are described which highlight the varied clinical and radiological features of this rare pulmonary condition. Following chemotherapy with prednisolone and chlorambucil, both patients are disease free three years later.
The ecmA gene of Dictyostelium encodes an extracellular matrix protein and is selectively expressed in prestalk cells. We show that its promoter contains discrete elements that direct expression in different subpopulations of prestalk cells. Prestalk(pst)A cells occupy the front half of the prestalk region. Expression in pstA cells requires DNA sequences close to the cap site of the gene and a separate, upstream region that acts in combination with the gene proximal sequences. PstO cells are situated in the rear half of the prestalk region and at least two separate and redundant promoter regions direct expression within them. All constructs that are expressed in pstO cells are also expressed in anterior-like cells (ALCs); cells that resemble prestalk cells but which are scattered throughout the prespore region. This observation suggests that pstO cells and ALCs may be very similar in their properties. If development occurs under conditions in which a migratory slug is not formed, there is an ordered movement of cells into the stalk tube. PstA cells enter the stalk tube first, followed by a proportion of the pstO cells. The remainder of the pstO cells contribute to the upper cup, an ALC-derived subpopulation of prestalk cells which is located at the apex of the spore head. After prolonged slug migration, a discrete pstO zone appears not to be maintained and, at culmination, pstO cells are found scattered throughout the stalk.
The ecmA and ecmB genes of Dictyostelium encode related extracellular matrix proteins and both are induced by DIF, the stalk cell-specific morphogen. The ecmA gene is expressed throughout the prestalk region of the migrating slug but only later, at culmination, do the prestalk cells express the ecmB gene. Expression of the ecmB gene is induced at the entrance to the stalk tube and we have identified two, apparently redundant, promoter elements that control this process. They act as repressors, preventing transcription in the tip of the migrating slug and the apical papilla of the culminant. They have a semi-palindromic consensus sequence TTGnCAA, where n is in one case 2 and in the other 4 bp. Either element alone is able to repress ecmB promoter activity in prestalk cells. Introduction of a single repressor element into the promoter of the ecmA gene changes its expression pattern to resemble that of the ecmB gene. Mutant elements, where n is altered, cause repression during the slug stage but allow premature ecmB expression during culmination; suggesting that the effective strength of the inductive signal may increase during culmination. Inhibition of cAMP-dependent protein kinase (PKA) in prestalk cells blocks both stalk cell maturation and ecmB gene expression. We show that the block to gene expression correlates precisely with the presence of a functional repressor element and this is consistent with the notion that expression of the ecmB gene is controlled by a PKA-dependent release from transcriptional repression.
Expression of the catalytic (C) subunit of the cAMP-dependent protein kinase (PKA) of Dictyostelium under the control of heterologous, cell-type-specific promoters causes ectopic terminal differentiation. When expressed under the control of a prespore-specific promoter, development is accelerated, to yield highly aberrant fruiting bodies that contain a basal mass of spore cells surrounding a central stalk-like structure. When expressed under the control of a prestalk-specific promoter, development arrests much earlier, at the tight mound stage. Prestalk cells move to the apices of these mounds, apparently normally, but no tip is formed. Most of the prestalk cells remain arrested in their development but there are a few isolated stalk cells scattered within such mounds. We show that extracellular cAMP represses stalk cell-specific gene expression in cells where the kinase is constitutively active, suggesting that inhibition of stalk cell differentiation by cAMP in normal cells (Berks and Kay, 1988) occurs because of an effect of extracellular cAMP on an intracellular signalling pathway independent of PKA. We propose a scheme whereby two separate events, a rise in intracellular cAMP levels and a fall in extracellular cAMP concentration, are required to induce stalk cell differentiation.
Achillodynia (Achilles tendon pain) is a significant source of disability to many people taking part in sports. Papers in the English language published since 1986 are reviewed here, grouped into specific subject areas including biomechanics, pathology, general clinical presentations, experimental treatments, steroids, podiatry and surgery. While there has been no dramatic breakthrough in the field, there have been various interesting advances with particular reference to imaging and conservative management, which will hopefully stimulate further studies. Many problems of Achilles tendon lesions in athletes remain unsolved, however, and much is yet to be done to provide adequate and generally effective methods of prevention and conservative treatment.
This study investigated empirical clusters of MMPI scale T scores for 186 men and 112 women involuntarily committed to a chemical dependency unit of a state psychiatric hospital. Ward's method of cluster analysis produced six clusters which were similar to those reported in other cluster-analytic studies of alcoholics but with a prominent increase in Scale 6 elevations. Average profiles for the six clusters were Spike 6, 6-2-8-4, within normal limits (Clusters 3 and 4), and 2-6-8-3-4-1-9. Results are discussed in terms of treatment planning for this population.
BACKGROUND: Multiple organ failure syndrome (MOFS) and adult respiratory distress syndrome (ARDS) continue to be significant clinical problems. Microvascular thrombosis and intraalveolar fibrin deposition play an integral role in the pathogenesis of MOFS and ARDS. The macrophage participates in these processes by expressing procoagulant activity (PCA) after exposure to endotoxin. One potential method to ameliorate organ dysfunction in ARDS and MOFS is to prevent macrophage activation of the coagulation cascade. Because inhibitors of arachidonic acid metabolism attenuate inflammatory lung injury, we investigated the role of eicosanoids in endotoxin-induced alveolar macrophage PCA. METHODS: Rabbit alveolar macrophages were incubated with selective inhibitors of arachidonic acid metabolism. PCA was determined in cell lysates. PCA was also assessed in cultures treated with cyclooxygenase inhibitor that had exogenous prostaglandin E2 (PGE2) added. Intracellular cyclic adenosine monophosphate (cAMP) was examined after treatment with lipopolysaccharide, ibuprofen, PGE2, and forskolin. RESULTS: Ibuprofen significantly reduces lipopolysaccharide-stimulated PCA by alveolar macrophages. 5-Lipoxygenase and thromboxane synthetase inhibitors had no effect on PCA. Inhibition of PCA by ibuprofen is reversed by adding exogenous PGE2. Decreased intracellular cAMP is associated with attenuated lipopolysaccharide-stimulated PCA elaboration. CONCLUSIONS: Endotoxin-stimulated alveolar macrophage PCA is prostanoid dependent, with cAMP acting as a second messenger. Although expression of PCA is prostanoid-cAMP dependent, neither prostanoids nor agents that directly increase cAMP are sufficient to elicit PCA in the absence of lipopolysaccharide.
Dictyostelium transformants that overproduce the extracellular form of cyclic nucleotide phosphodiesterase and so accumulate a reduced amount of cAMP are blocked in development after aggregation in the form of a tight mound, prior to formation of the apical tip. In such mounds, prespore cell differentiation is repressed, and the apical accumulation of prestalk cells is greatly retarded. When a source of cAMP is placed below the arrested mounds, prestalk cells that would normally migrate in an apical direction instead sort downwards to the substratum. Thus, by acting as the chemoattractant that draws prestalk cells to the apex, cAMP signaling directs the formation of a patterned structure.