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Biomedical subjects

R Pounder

Publications and source records attributed to R Pounder.

13 recordsLinked to original sources

Effect of gastrin and anti-gastrin antibodies on proliferation of hepatocyte cell lines.

Gastrin (G-17) and its precursor glycine-extended gastrin (G-17-gly) have been shown to be trophic to some gastrointestinal tumors. This in vitro study assessed the effect of G-17, G-17-gly, anti-gastrin antibodies (anti-G-17), and the CCK-B receptor antagonist PD135,158 on three hepatoma cell lines (PLC/PRF/5, HepG2 and MCA-RH7777) and an embryonic liver cell line (WRL68). The pancreatic adenocarcinoma cell line AR42J was used as a positive control. G-17 and G-17-gly caused significant proliferation of AR42J and WRL68 cell lines. G-17-gly but not G-17 induced significant proliferation of the PLC/PRF/5 cell line. Anti-G-17 and PD135,158 significantly inhibited unstimulated AR42J and WRL68 cell lines. Anti-G-17 also inhibited the proliferative effects of G-17 and G-17-gly on AR42J, WRL68, and PLC/PRF/5 cell lines, whereas PD135,158 inhibited the proliferative effect of G-17 only. G-17 and G-17-gly as well as anti-G-17 and PD135,158 had no effect on HepG2 and MCA-RH77777 cell lines. It is concluded that G-17-stimulated proliferation is mediated via the CCK-B receptor and G-17-gly via a separate, as yet uncharacterized, receptor. There may therefore be a role for gastrin in embryonic hepatocellular proliferation and perhaps also in the proliferation of some hepatocellular tumors.

Animals↗

Expression and processing of gastrin in hepatocellular carcinoma, fibrolamellar carcinoma and cholangiocarcinoma.

BACKGROUND/AIMS: Gastrin is a trophic factor within the normal gastrointestinal tract and is also a mitogen for a number of gastrointestinal and non-gastrointestinal tumours. Precursor forms of gastrin including progastrin (proG) and glycine-extended gastrin (G-gly) as well as the fully processed amidated gastrin (G-NH2) are expressed by tumours. There has been little study of the role of gastrin in either normal liver or liver tumours. The aim of this study was to identify the expression of CCK-B/gastrin receptor (CCK-BR), proG, G-gly and G-NH2 in normal liver and liver tumours. METHODS: Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-BR and gastrin isoforms. RESULTS: Most liver tumours express CCK-BR and are able to process gastrin as far as proG and G-gly, although not as far as the amidated form. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver. CONCLUSIONS: Liver tumours express the CCK-BR and precursor forms of gastrin. This expression may be associated with tumour proliferation.

Bile Duct Neoplasms↗

A sensitive and robust method for measles RNA detection.

The aim of this study was to compare measles RNA amplification methods and to develop and select the most rapid, sensitive and robust procedure. The use of hybrid capture for measles RNA isolation was evaluated, and three RNA amplification detection techniques were compared. These were: (a) reverse transcription followed by nested polymerase chain reaction (RT-PCR) with MMLV reverse transcriptase and Taq polymerase; (b) a combined RT-PCR reaction using rTth polymerase; and (c) NASBA. An internal positive control was also developed. The sensitivities of the detection methods were quantified by using a dilution series of a known amount of total RNA from measles-infected Vero cells or by calculation of the number of transcript molecules (produced from a recombinant plasmid containing an insert measles nucleoprotein DNA) present in each amplification reaction, respectively. The results indicated that hybrid capture followed by combined RT-PCR with rTth polymerase was the most reproducibly robust and sensitive protocol and could detect as few as 10(4) synthetic measles RNA transcripts added to tissue homogenates. However, NASBA proved to be the most sensitive method for measles RNA detection in water.

Animals↗

Fulminant ulcerative colitis in pregnancy.

Most pregnant women with a history of ulcerative colitis will have a normal pregnancy and deliver a healthy child. Medical therapy can usually control the disease in those patients who experience an exacerbation, and only a minority of women progress to severe colitis necessitating surgery in pregnancy. We describe a woman who developed colitis in the first weeks of pregnancy that initially responded to steroid enemas. She then relapsed and progressed to severe colitis requiring a sub-total colectomy in the 26th wk of pregnancy. This was complicated by intra-abdominal sepsis and an abscess that required drainage. She successfully completed pregnancy, to be delivered of a healthy daughter in the 32nd wk of pregnancy.

Adult↗

Immunohistochemical study of tissue factor expression in normal intestine and idiopathic inflammatory bowel disease.

AIMS: To investigate the localisation of tissue factor expression in normal and inflamed intestine. METHODS: Serial cryostat sections of tissue taken from patients with Crohn's disease (n = 8), ulcerative colitis (n = 5), and from controls (n = 5) were stained with haematoxylin and eosin and immunostained for tissue factor, collagen type IV, fibrinogen and platelet glycoprotein IIIa. RESULTS: In control tissues tissue factor was present as a continuous layer along the epithelial basal lamina: sections from controls did not immunostain for fibrinogen or platelets. In non-ulcerated inflamed mucosa, tissue factor staining intensified in cases of Crohn's disease and was associated with fibrin deposition. Staining for tissue factor was either patchy or absent in cases of ulcerative colitis and there was no fibrin deposition. This change accompanied the early destruction of the epithelial basal lamina in ulcerative colitis that was not seen in Crohn's disease. In both diseases tissue factor expression in severely inflamed and ulcerated mucosa was present on lamina propria macrophages and vascular endothelium and was associated with fibrin or platelet thrombi. In three of eight cases of Crohn's disease tissue factor expression and thrombi were evident in areas of submucosal vasculitis. These were not seen in adjacent normal vessels. CONCLUSIONS: These observations are consistent with a tissue factor haemostatic barrier in the intestine: this barrier seems to be incomplete or defective in ulcerative colitis. Tissue factor expression by macrophages and endothelial cells may be important, particularly in the microvascular thrombosis and induration which are characteristic of Crohn's disease.

Adult↗

Drug-induced changes of plasma gastrin concentration.

There is a significant inverse relationship between intragastric acidity and plasma gastrin concentration. All generally available gastric acid antisecretory drugs induce a release of gastrin into the circulation. The more potent the gastric antisecretory dosage regimen or drug, the greater the rise of plasma gastrin concentration. The drug-induced rise of plasma gastrin concentration is of no direct clinical concern, although it may be partly responsible for the phenomenon of tolerance to H2-blockade. Drug-induced hypergastrinemia could stimulate the proliferation of certain cell lines associated with the gastrointestinal tract, for example, the gastric epithelium, ECL cells, or colonic neoplasms.

Adenocarcinoma↗

Silent peptic ulceration: deadly silence or golden silence?

Peptic ulcer hemorrhage or perforation occur commonly in patients with hitherto silent ulceration, particularly in the elderly or in those taking nonsteroidal antiinflammatory drugs. The majority of patients dying from peptic ulceration have no symptoms of ulcer disease until the presentation of their final, fatal illness. There is a need for more studies investigating the early symptoms of the fatal ulcer disease, the effects of therapies that may prevent fatalities, and the management of potentially lethal ulcer disease upon clinical presentation. Silent ulceration also occurs in patients after successful healing with medical treatment, and the apparent point prevalence of silent ulceration (in the framework of a clinical trial) is critically dependent on the frequency of repeat endoscopic examination and the treatment modality. Maintenance treatment with H2-receptor antagonists appears to some extent to decrease the frequency of asymptomatic ulcers, but more interestingly to halt the progression of asymptomatic ulcers toward symptomatic or complicated ulceration, although more careful studies in comparison with other modalities are needed.

Acute Disease↗

Histamine H2-receptor antagonists.

The first histamine H2-receptor antagonists were developed in the early 1970s, and they have a dominant role in today's management of peptic ulceration. The original regimens using either cimetidine or ranitidine attempted to control acidity across the 24 hours, but more 'modern' regimens use a large single dose of the H2-blocker in the evening, which produces a pulse of decreased intragastric acidity during the night with a normal acidity in the daytime. High-dose regimens using a new generation of extremely potent histamine H2-receptor antagonists may improve ulcer healing rates at 4 weeks, and may be particularly useful for the management of either severe oesophagitis or intractable duodenal ulceration.

Animals↗

Is pseudomembranous colitis infectious?

A cluster of eight patients in two adjacent hospital wards acquired acute diarrhoea within a period of 11 days. All their stool samples contained Clostridium difficile toxin and C. difficile was isolated in every case. Three patients had rectal biopsy findings compatible with pseudomembranous colitis (PMC). All the patients responded to treatment with oral vancomycin. Until the possibility of PMC being acquired by cross-infection is clarified such patients should be nursed in isolation with strict enteric precautions.

Adult↗

Abnormal intestinal permeability to sugars in villous atrophy.

Intestinal permeability to a monosaccharide and a disaccharide was compared by simultaneous measurement of the urinary excretion of L-rhamnose and lactulose after oral ingestion of an hypertonic solution containing both sugars. Urine samples were analysed for sugar content by quantitative thin-layer or paper chromatography. Results in thirteen patients with untreated villous atrophy were compared with those in twelve healthy volunteers. Urinary L-rhamnose excretion was significantly decreased (-40%, p less than 0.02) in patients with villous atrophy, whereas lactulose excretion was paradoxically and significantly increased (+345%, p less than 0.01). The median value of the lactulose/L-rhamnose urinary excretion ratio was sevenfold higher in the patients with villous atrophy; there was no overlap of values for patients and volunteers (p less than 0.01). It is postulated that reduced L-rhamnose urinary excretion in untreated villous atrophy is due to a decreased absorptive area in the small bowel, whereas increased lactulose excretion indicates leakiness of the abnormal mucosa to larger polar molecules.

Adult↗