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Biomedical subjects

J G Williams

Publications and source records attributed to J G Williams.

At least 163 records · Page 9Linked to original sources
PubMed1991

Resistance to graft-versus-host disease following small bowel transplantation.

Transplantation of a Lewis rat small bowel allograft (SBTx) into Lewis x Brown Norway F1 (LBNF1) hybrid recipients provokes lethal graft-versus-host disease. GVHD in F1 hybrid rats inoculated with large number of parental lymphocytes may be abrogated by prior treatment of F1 hybrids with a sublethal dose (SLD) of the same parental lymphocytes. Therefore, we sought to determine whether this type of immunomodulation would prevent GVHD after SBTx. We examined whether pretreatment of LBNF1 recipients with a SLD of parental lymphocytes, or with a revascularized segment of parental small bowel, might ameliorate GVHD following transplantation of the entire parental small bowel. Nonpretreated LBNF1 recipients died of GVHD after entire Lew SBTx; 95% of LBNF1 recipients pretreated with SLD of Lew lymphocytes and 84% of LBNF1 recipients first transplanted with a segment of Lew small bowel survived GVHD induced by entire Lew SBTx 10 days later. Of LBNF1 recipients pretreated with SLD of Brown Norway lymphocytes or first transplanted with a segment of BN small bowel, none were protected from GVHD induced by entire Lew SBTx 10 days later. We concluded that pretreatment of LBNF1 recipients either with an SLD of parental lymphocytes or with a segment of parental small bowel provides profound protection from the effects of GVHD following transplantation of an entire small bowel of the same parental strain specificity.

Animals↗
PubMed1991

Alkaline reflux oesophagitis.

Duodenal and gastric contents do reflux into the oesophagus and acid alone certainly causes oesophageal damage which will be worsened by pepsin. In the patient who has undergone gastrectomy duodenal secretions may also be harmful. There is evidence that when the two mix there may be a toxic synergism, leading to mucosal disruption and intracellular damage to oesophageal cells which produces the clinical picture of reflux oesophagitis, with or without symptoms. Clear evidence of the toxicity of duodenal refluxate in humans is lacking, but the ability to measure bile and acid reflux continuously, together with a method of detecting oesophageal damage at a cellular level should help to solve this long debated problem.

Animals↗
PubMed1991

An analysis of culmination in Dictyostelium using prestalk and stalk-specific cell autonomous markers.

The ecmA (pDd63) and ecmB (pDd56) genes encode extracellular matrix proteins of the slime sheath and stalk tube of Dictyostelium discoideum. Using fusion genes containing the promoter of one or other gene coupled to an immunologically detectable reporter, we previously identified two classes of prestalk cells in the tip of the migrating slug; a central core of pstB cells, which express the ecmB gene, surrounded by pstA cells, which express the ecmA gene. PstB cells lie at the position where stalk tube formation is initiated at culmination and we show that they act as its founders. As culmination proceeds, pstA cells transform into pstB cells by activating the ecmB gene as they enter the stalk tube. The prespore region of the slug contains a population of cells, termed anterior-like cells (ALC), which have the characteristics of prestalk cells. We show that the ecmA and ecmB genes are expressed at a low level in ALC during slug migration and that their expression in these cells is greatly elevated during culmination. Previous observations have shown that ALC sort to surround the prespore cells during culmination (Sternfeld and David, 1982 Devl Biol. 93, 111-118) and we find just such a distribution for pstB cells. We believe that the ecmB protein plays a structural role in the stalk tube and its presence, as a cradle around the spore head, suggests that it may play a further function, perhaps in ensuring integrity of the spore mass during elevation. If this interpretation is correct, then a primary role of anterior-like cells may be to form these structures at culmination. We previously identified a third class of prestalk cells, pstO cells, which lie behind pstA cells in the slug anterior and which appeared to express neither the ecmA nor the ecmB gene. Using B-galactosidase fusion constructs, which give more sensitive detection of gene expression, we now find that these cells express the ecmA gene but at a much lower level than pstA cells. We also show that expression of the ecmA gene becomes uniformly high throughout the prestalk zone when slugs are allowed to migrate in the light. Overhead light favours culmination and it may be that increased expression of the ecmA gene in the pst 'O' region is a preparatory step in the process.

Cell Movement↗
PubMed1990

DNA polymorphisms amplified by arbitrary primers are useful as genetic markers.

Molecular genetic maps are commonly constructed by analyzing the segregation of restriction fragment length polymorphisms (RFLPs) among the progeny of a sexual cross. Here we describe a new DNA polymorphism assay based on the amplification of random DNA segments with single primers of arbitrary nucleotide sequence. These polymorphisms, simply detected as DNA segments which amplify from one parent but not the other, are inherited in a Mendelian fashion and can be used to construct genetic maps in a variety of species. We suggest that these polymorphisms be called RAPD markers, after Random Amplified Polymorphic DNA.

Base Composition↗
PubMed1990

Paraileostomy hernia: a clinical and radiological study.

Forty-six patients who underwent colectomy with end ileostomy for ulcerative colitis (n = 33) or Crohn's disease (n = 13) have been reviewed for paraileostomy hernia (PIH) formation 1-16 years after surgery. PIH developed in 13 of these patients (28 per cent) and was not related to the original disease or excessive weight gain. Twenty-eight patients underwent limited computed tomography (CT) scanning of the stomal region. Eight of these had a clinically detectable PIH, which was demonstrated on CT. A further two patients had PIH demonstrated on CT which was not detected by clinical examination. The rate of PIH was similar where the stoma emerged lateral to the rectus abdominis muscle (six out of 16 patients, 37 per cent) to where the stoma emerged through the rectus (four out of 12 patients, 33 per cent). Recurrence following operative repair of PIH was common. PIH occurs more frequently than previously supposed. CT can detect PIH and may be useful in evaluating a patient with stoma-related symptoms for occult PIH formation.

Adolescent↗
PubMed1990

Abdominoperineal resection for severe perianal Crohn's disease.

Despite the high incidence of involvement of the perianal region in Crohn's disease, excisional surgery seldom is required for perianal disease alone. Nine patients are presented who had severe perianal Crohn's disease, which eventually required abdominoperineal excision of the anorectum. In all nine patients, it was secondary manifestations of anal Crohn's disease that precipitated proctectomy, such as high fistulas, strictures, and rectovaginal fistulas. These secondary phenomena, especially fistulas caused by cavitating ulceration, become self-perpetuating by the mechanical effect of feces being forced into the tract. During the same period, 17 patients required rectal excision by abdominoperineal resection, where perianal disease was incidental to severe colorectal disease. There is a tendency for excessive delay before advising surgery for severe perianal disease. An attempt should be made to identify patients with a poor prognosis to avoid unnecessarily prolonged morbidity. Assessment of the exact nature of the anal lesion and assessment of Crohn's disease activity are important in making this decision.

Adrenal Cortex Hormones↗
PubMed1990

Cytoplasmic acidification facilitates but does not mediate DIF-induced prestalk gene expression in Dictyostelium discoideum.

Stalk cell differentiation in Dictyostelium can be induced by the differentiation-inducing factor, DIF, or by conditions that decrease intracellular pH (pHi). We have investigated whether cytoplasmic acidification acts directly to induce expression of pDd56 and pDd63, two DIF-regulated genes, specifically expressed in prestalk cells. The weak base methylamine, which increases pHi, inhibits DIF-induced transcription. The weak acid 5,5-dimethyl-2,4-oxazolidinedione (DMO), which decreases pHi, stimulates DIF-induction of the two prestalk genes. After relatively long incubation periods, DMO also induces a low level of prestalk gene expression in the absence of added DIF. However, unlike DIF-mediated induction, the apparent DMO-mediated induction decreases to undetectable levels when the cell density is reduced from 10(7) to 10(5) cells/ml. This indicates that DMO does not itself induce gene expression, but acts to enhance the effects of an autonomously secreted stalk-inducing factor, presumably DIF. These results suggest that the effects of DIF on gene expression are regulated by intracellular pH, but do not support a role for protons as direct intermediates in the DIF signal transduction pathway.

Cyclic AMP↗
PubMed1990

Hepatobiliary cystadenoma: a rare hepatic tumor in a child.

This report describes a 3-year-old child with a hepatobiliary cystadenoma. Cystadenomas are benign, multilocular, cystic neoplasms that usually occur in middle-aged women. The patients may be asymptomatic, but often there are vague abdominal complaints related to extrinsic compression of the stomach, duodenum, or biliary tree. Recurrence following incomplete excision and the presence of carcinoma within otherwise benign cysts has been documented. Complete resection is the therapy of choice, and thorough histopathologic evaluation is imperative.

Child, Preschool↗
PubMed1990

Demonstration of para-ileostomy herniation using computed tomography.

Twenty-eight patients with end ileostomies underwent localised computed tomography (CT) of the ileostomy region. Para-ileostomy herniation was demonstrated in 10 patients. In two of these the hernia was not detectable clinically. This incidence (36%) is higher than that reported previously. Herniation was associated with a larger defect in the anterior abdominal wall at the stomal site and was more common lateral to the stoma. No association was shown between herniation and the underlying disease process, or to the site of the stoma relative to the rectus abdominis muscle. Demonstration of a hernia by clinical examination or CT was important in clinical management decisions. CT is recommended in patients with stoma-related symptoms or unexplained abdominal symptoms following ileostomy formation when a para-stomal hernia is suspected, but clinical examination is negative.

Adult↗
PubMed1990

Effect of intermaxillary fixation on pulmonary function.

A study to measure the pulmonary effects of intermaxillary fixation (IMF) demonstrated that this technique produces a significant degree of airway obstruction. This may be dangerous to patients with limited respiratory reserve due to chronic obstructive airways disease. The impairment of pulmonary function can be assessed pre-operatively and should be estimated in high risk patients. Alternative management of stabilization of jaw fractures that avoid IMF should be considered in such patients.

Airway Obstruction↗
PubMed1990

The evaluation of a gastric bile probe.

The purpose of this study was to validate a new technique for measuring duodenogastric bile reflux in the human subject. A custom built cadmium telluride gamma detector (Radiation Monitoring Devices, Mass), small enough to be passed into the oesophagus and stomach, was developed and tested for sensitivity to 99Tcm and 75Se radioisotopes. When immersed in radiolabelled water, the detector was capable of measuring gamma radiation in quantities as low as 0.1 microCi (0.0037 MBq) per ml. Two patients (A and B) with endoscopically proven bile reflux, and three normal volunteers (C, D and E) underwent oesophageal manometry to map the position of the lower oesophageal sphincter (LOS). The gamma probe was passed via the nose, to a position in the gastric fundus, 5 cm below the LOS. Each subject was placed supine under a gamma camera (Siemens LFOV 37 ZLC head), centred on the epigastrium. A 4 mCi (148 MBq) dose of radiolabelled 99Tcm-HIDA was administered intravenously, and simultaneous internal/external scanning was performed for between 45 and 90 min. Internal gamma probe data was transferred by a screened cable to a Memolog 600 portable recorder, using a 5 s counting interval, and from the gamma camera to a Nodecrest Micas III computer, using a 15 s counting interval. Gamma camera counts from a region of interest over the fundus of the stomach were then correlated with counts from the internal probe using a linear regression analysis program on the Nodecrest. The internal gamma probe functioned well at body temperature in the acidic gastric environment. Radiolabelled bile refluxed into the stomach during HIDA scanning in three out of the five subjects (one patient and two normal volunteers). There was a strong correlation between internal and external gamma counts (A, r = +0.79; C, r = +0.53; E, r = +0.54; P greater than 0.01). In the other two cases, there was no bile reflux, but still a significant correlation between internal and external gamma counts (B, r = +0.89; D, r = +0.75; P greater than 0.01). The mean correlation coefficient for the series of five cases was +0.70. We conclude firstly that the newly developed internal gamma detector is capable of measuring the reflux of radiolabelled bile into the human stomach and, secondly, that bile reflux may occur in normal subjects as well as those with upper gastrointestinal pathology.

Aged↗
PubMed1990

A developmentally regulated trans-acting factor recognizes dissimilar G/C-rich elements controlling a class of cAMP-inducible Dictyostelium genes.

Transcriptional response elements involved in the cAMP-inducible and developmentally regulated expression of the Dictyostelium aggregate-stage gene pst-cath/CP2 have been shown to include a G/C-rich sequence element [G-box regulatory element (GBRE)]. We have recently identified a trans-acting factor, GBF (GBRE binding factor), that specifically interacts with this sequence and have shown that the binding activity of GBF to GBRE is developmentally regulated and inducible by cAMP. Here, we examine further the possible role of GBF in the regulation of pst-cath/CP2 and three other coordinately regulated, cAMP-inducible aggregate-stage genes. We show that GBF itself (or other closely related factors) recognizes dissimilar G/C-rich elements present in the 5'-flanking regions of these genes and that the ability of the individual, distinct G/C-rich elements to confer regulated expression on a promoter deletion mutant of the pst-cath/CP2 gene is correlated with the relative affinity for GBF. G/C-rich elements carrying point mutations that prevent in vitro binding of GBF to two of the G/C-rich elements fail to activate expression in vivo. An analysis of major points of contact between the GBF protein and two distinctly different binding sites suggests that binding of GBF to these sequence elements involves a considerable degree of flexibility in DNA-protein interactions. These results suggest that the regulated expression of a class of aggregate-stage cAMP-inducible genes involves the interaction of GBF or homologous factors with dissimilar G/C-rich sequence elements and that induction of GBF activity or that of homologous factors by cAMP may thus be a limiting step in the induction of this temporally coordinate set of genes during Dictyostelium development.

Base Sequence↗
PubMed1990

Toxic oxygen metabolite production by circulating phagocytic cells in inflammatory bowel disease.

To investigate the possibility that the oxidative capacity of phagocytic cells may be defective in inflammatory bowel disease, toxic oxygen metabolite production by circulating neutrophils and monocytes has been measured by luminol dependent chemiluminescence. Neutrophils from patients with Crohn's disease and ulcerative colitis produced significantly lower chemiluminescent responses after chemotactic stimulation with formylmethionylleucylphenylalanine (fMLP) than neutrophils from control patients, p = 0.018 and 0.043 respectively. Chemiluminescent responses of neutrophils from patients with inflammatory bowel disease, however, were similar to control responses when cells were stimulated with latex beads or phorbol myristate acetate. Monocytes from patients with Crohn's disease produced significantly greater levels of chemiluminescence than control monocytes when stimulated with either fMLP (p less than 0.002), phorbol myristate acetate (p less than 0.0005) or latex beads (p less than 0.002). Monocytes from patients with ulcerative colitis also produced significantly greater levels of chemiluminescence than controls when stimulated with latex beads (p less than 0.5) or phorbol myristate acetate (p less than 0.0005), although there was no difference in the level of chemiluminescence in response to fMLP. These results exclude a generalised defect in phagocytic cell oxidase activity in inflammatory bowel disease and suggest that circulating monocytes are 'activated'.

Adolescent↗
PubMed1990

Phagocytes, toxic oxygen metabolites and inflammatory bowel disease: implications for treatment.

Phagocytic cells are prominent in the inflammatory infiltrate of Crohn's disease and ulcerative colitis. These cells secrete a variety of agents which are thought to be important in the pathogenesis of tissue damage in inflammation. The function of phagocytic cells does not appear to be impaired in inflammatory bowel disease, and certain aspects, including toxic oxygen metabolite production, are enhanced in circulating monocytes and tissue phagocytes isolated from the inflammatory site. 5-Amino-salicylic acid, used in the treatment of inflammatory bowel disease, is a specific scavenger of hypochlorite, a toxic metabolite of oxygen produced by phagocytic cells. These findings suggest that phagocytic cells play an important role in the pathogenesis of tissue damage in inflammatory bowel disease. The future development of pharmacological agents which modify specific aspects of phagocyte function, or act as scavengers of toxic oxygen metabolites produced by these cells, may provide more effective treatment for these conditions.

Aminosalicylic Acids↗
PubMed1990

Enprostil, a prostaglandin E2 analogue, in the treatment of gastric ulcer--a multicentre comparison with pirenzepine.

In a double-blind, multicentre study 77 patients with benign gastric ulcer were randomly allocated to treatment with either enprostil 35 micrograms bd or pirenzepine 50 mg bd. After four weeks of treatment 13/26 (50 per cent) of evaluable enprostil-treated patients and 9/30 (30 per cent) of evaluable pirenzepine-treated patients were healed. Corresponding healing figures after eight weeks were 20/25 (80 per cent) and 25/31 (81 per cent). Both drugs rapidly reduced the severity of ulcer pain and the need for antacid use. No statistically significant differences were detected between the treatments with respect to healing rate or symptom control. Adverse events were reported by eight patients taking enprostil and by 17 patients taking pirenzepine. Two patients withdrew from each treatment group because of adverse events. None of these was serious. In conclusion, enprostil and pirenzepine were equally effective in healing gastric ulcers and no statistically significant differences in safety and efficacy were detected. There was a tendency for earlier healing and fewer side effects in the enprostil-treated patients.

Adolescent↗