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R A Boulton

Publications and source records attributed to R A Boulton.

8 recordsLinked to original sources
PubMed1998

Augmentation of the early phase of liver regeneration after 70% partial hepatectomy in rats following selective Kupffer cell depletion.

BACKGROUND/AIMS: Kupffer cells are located in the liver sinusoids adjacent to hepatocytes and elaborate a range of growth regulatory molecules involved in regulating hepatocyte proliferation. In vitro observations imply the potential for Kupffer cells to exert both stimulatory and inhibitory influences on hepatocyte DNA synthesis. We aimed to determine the overall effect of Kupffer cell activity during the early regenerative processes after partial hepatectomy. METHODS: We investigated hepatocyte DNA synthesis, induced by partial hepatectomy in rats, following selective elimination of Kupffer cells by liposome encapsulated dichlormethylene bisphosphonate (Cl2MBP). RESULTS: We demonstrate that the early phase of liver regeneration was enhanced following Kupffer depletion, as indicated by a greater proportion of hepatocytes undergoing DNA synthesis, and a higher mitotic index. This was associated with an alteration in the balance of growth factors in the liver; HGF and TGFbeta mRNA were reduced in Kupffer cell-depleted animals, and IL-1beta mRNA was absent. In addition, in the absence of partial hepatectomy, the selective depletion of Kupffer cells leads to an increase in the proliferation of hepatocytes in resting liver undergoing DNA synthesis. CONCLUSION: The overall effect of depleting the liver of Kupffer cells is to enhance the proliferation rate of hepatocytes, both after partial hepatectomy and in the resting state.

Animals↗
PubMed1998

Alterations in classical cadherins associated with progression in ulcerative and Crohn's colitis.

Human colitis is a condition associated with a spectrum of altered morphologic changes and cellular adhesion. The role of cadherins, which are powerful morphoregulatory cell adhesion molecules, in colitis is provocative and as yet unknown. Herein, we present results that suggest a strong correlation between the deregulation of two cadherin molecules, E- and P-cadherins, and the progression of human colitis. We examined the expression and structural integrity of E- and P-cadherins in inflamed, dysplastic, or neoplastic human ulcerative colitis (UC) (n=58), human Crohn's colitis (n = 30), and normal tissue (n = 20) to assess cadherin function in normal and abnormal epithelium. E-cadherin is strongly expressed in normal colorectal epithelium, whereas in left-sided UC it is either down-regulated or has a single-base pair mutation in exon 4 resulting in an amino acid alteration (6 of 58 UC cases). By contrast, P-cadherin is dramatically up-regulated in both Crohn's disease and ulcerative colitis and especially in dysplastic ulcerative tissue. In vitro transfected SW-480 colorectal cells containing E-cadherin mutations identical to those in vivo were associated with increased spontaneous disaggregation compared with cells transfected with wild-type E-cadherin. Based on this evidence, we hypothesize that a small subset of colorectal cells expressing mutant E-cadherin are associated with widespread ulceration, whereas those expressing P-cadherin are associated with a rapidly dividing immature phenotype that includes dysplasia. The differential expression of mutated and wild-type cadherins examined herein are associated with a broad spectrum of abnormal epithelial phenotypes, lymphocyte integrin binding, and resistance to denudation, as is seen in the colitis adenocarcinoma sequence.

Adult↗
PubMed1995

Human spasmolytic polypeptide is a cytoprotective agent that stimulates cell migration.

BACKGROUND/AIMS: Gastric epithelium is attacked by acid, pepsin, and ingested agents. When a mucosal lesion occurs, the defect is rapidly closed by cell migration. Because spasmolytic polypeptide is rapidly produced at sites of injury, we postulated that human spasmolytic polypeptide (hSP) was important in mucosal repair. Recombinant hSP was used to test this hypothesis. METHODS: The ulcer healing effect of various doses of hSP administered orally and subcutaneously was examined using an indomethacin (20 mg/kg) restraint rat model of gastric damage. Stability of hSP in gastrointestinal juice was determined using size-exclusion chromatography. The effect of hSP on migration of human colonic carcinoma cell lines HT29 and SW480 was determined using collagen gel invasion and wounded monolayer assays. Proliferation was assessed using [3H]thymidine incorporation and toluidine blue staining. RESULTS: Infusions of hSP at 25 and 50 micrograms.kg-1.h-1 subcutaneously decreased gastric damage by about 50% (P < 0.01) without changing acid secretion. Oral hSP was ineffective. hSP was stable in gastrointestinal juice. hSP stimulated migration of HT29 cells but did not affect proliferation and had no effect on SW480 cells. CONCLUSIONS: hSP may play a key role in the early stages of mucosal repair by stimulating the initial re-epithelialization by cell migration.

Animals↗
PubMed1985

Quantitative relationship between T3 and the T-cell antigen receptor on a human leukaemic line.

The T-cell antigen receptor complex consists of an idiotypic molecule, Ti, and T3. We have investigated the relationship between Ti and T3 on a leukaemic line HPB-ALL. This has shown that the two molecules are expressed on the cell surface in equal numbers, and that a similar stoichiometric relationship is seen on sublines of HPB-ALL selected for diminished expression of Ti. Furthermore, the degrees of modulation and rates of resynthesis of Ti and T3 following modulation were very similar, regardless of whether anti-Ti or anti-T3 was used to produce the modulation. This work strongly suggests that the expression of Ti and T3 are under common control.

Antibodies, Monoclonal↗