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P Lance

Publications and source records attributed to P Lance.

At least 19 recordsLinked to original sources
PubMed1995

Determinants of differential liver-colonizing potential of variants of the MCA-38 murine colon cancer cell line.

We investigated factors that might contribute to the differing liver tumor colonizing potentials of MCA-38 colonic cancer cell line variants injected into the ileocolic veins of C57Bl/6J mice. Non-colonizing (MCA-38 CD) cells were sensitive to lysis by hepatic natural killer (NK) cells in vitro (51Cr-release assay) and cells with high liver-colonizing potential (MCA-38 LD) were resistant. Following abrogation of NK activity by treatment with anti-asialoGM1, liver-colonizing ability to LD cells but not CD cells was enhanced. MCA-38 CD cells were, however, capable of initial liver colonization after ileocolic vein injection. Differing patterns of membrane sialylation may have contributed to the contrasting hepatic tumorigenicities of LD and CD cells; beta-galactoside alpha 2,6-sialyltransferase mRNA levels and activity were approximately four-fold higher in LD than CD cells and qualitative and quantitative differences existed between their ganglioside profiles. In the MCA-38 model outlined, tumor cell susceptibility or resistance to NK lysis was a relatively unimportant determinant of liver-colonizing potential.

Animals↗
PubMed1995

n-Butyrate mediation of ganglioside expression of human and murine cancer cells demonstrates relative cell specificity.

1. n-Butyrate, a short chain fatty acid produced by colonic fermentation, induces differentiation in human neoplastic cell lines, and reduces expression in vitro of a sialyltransferase that glycosylates N-linked glycoproteins in hepatoblastoma cells. Gangliosides are amphipathic, sialylated glycosphingolipids that undergo profound changes in many transformed cells and may protect neoplastic cells from host immune surveillance. Colonic mucosal cells are exposed to luminal short-chain fatty acid concentrations of up to 80 mmol/l, and there is some evidence that short-chain fatty acids may alter ganglioside expression in colon cancer cells. 2. Because of the importance of gangliosides in cancer pathogenesis, we investigated the effects of n-butyrate on ganglioside expression of colonic (human and murine) and non-colonic cancer cells. 3. Three separate colon cancer cell lines (LS174T, T84 and MCA-38), when butyrate treated, demonstrated striking amplification of specific individual gangliosides. However, the total lipid-bound sialic acid content of gangliosides of butyrate-treated LS174T cells diminished. In contrast to earlier reports, n-butyrate did not mediate expression of all gangliosides and specifically did not mediate expression of GM3. This effect persisted even after removal of butyrate. 4. In contrast, exposure of extracolonic cells to butyrate, including cervical cancer (HeLa) and laryngeal cancer (HEp-2) cell lines in this study and hepatoblastoma cells (Hep G2) in our previous work, caused no detectable changes in ganglioside expression. 5. In conclusion, our results indicate a relative tissue specificity of butyrate-mediated alterations in ganglioside expression that is not universal but is limited to specific gangliosides.

Animals↗
PubMed1995

Expression and regulation of glycosyltransferases for N-glycosyl oligosaccharides in fresh human surgical and murine tissues and cultured cell lines.

1. Mammalian membrane and serum proteins are glycosylated by the addition of heterogeneous N-linked oligosaccharides. It has been widely speculated that oligosaccharide diversity is achieved by corresponding heterogeneity of expression of the glycosyltransferases that are responsible for oligosaccharide synthesis. 2. We surveyed mRNA levels of three sequentially acting glycosyltransferases, N-acetylglucosaminyl-transferase I, beta 1,4-galactosyltransferase and alpha 2,6-sialyltransferase, in 11 human tissues and confirmed the expected variations. 3. The size heterogeneity of alpha 2,6-sialytransferase transcripts reported in rat tissues was evident neither in the human tissue survey nor in a panel of murine RNAs. Tissue distributions of alternative terminal sialyltransferases, alpha 2,6-sialyltransferase and alpha 2,3-sialyltransferase, were distinct. 4. Relative glycosyltransferase mRNA levels in four transformed human cell lines cultured in vitro did not fully reflect levels in the corresponding human tissues. 5. Expression of alpha 2,6-sialyltransferase mRNA was approximately 2.6-fold greater in adenocarcinomatous than in normal human colon, and beta 1,4-galactosyltransferase expression was approximately 1.8-fold greater in normal than in adenocarcinomatous colon. 6. n-Butyrate (0.003-0.005 mol/l), a short-chain fatty acid that is produced by colonic bacterial fermentation, caused approximately 80% inhibition of alpha 2,6-sialyltransferase, approximately 2.5-fold induction of beta 1,4-galactosyltransferase and approximately 6-fold induction of N-acetylglucosaminyltransferase mRNAs in T84 (colonic) cells. The effects on alpha 2,6-sialyltransferase and beta 1,4-galactosyltransferase were near maximal by 6h, but induction of N-acetylglucosaminyltransferase was fully apparent only after exposure for 24 h.

Adenocarcinoma↗
PubMed1992

n-butyrate reduces the expression of beta-galactoside alpha 2,6-sialyltransferase in Hep G2 cells.

n-Butyrate, a short chain fatty acid that is produced by colonic bacterial fermentation, is detectable in portal blood and induces differentiation in various human neoplastic cell lines. Earlier reports indicated approximately 20-fold induction in vitro by n-butyrate of the sialyltransferase that catalyzes terminal glycosylation of GM3 ganglioside in HeLa and colon cancer cells. We previously isolated a 1.3-kilobase cDNA for a human beta-galactoside alpha 2,6-sialyltransferase, for which N-linked glycoproteins are the acceptors. We report here that treatment of Hep G2 cells with 5 mM n-butyrate for 24 h reduced beta-galactoside alpha 2,6-sialyltransferase mRNA levels by approximately 90%. Reductions in mRNA level were followed by approximately 75 and approximately 90% reductions, respectively, in specific beta-galactoside alpha 2,6-sialyltransferase enzyme activity after treatment for 24 and 36 h with 5 mM n-butyrate. However, in contrast with earlier reports of enhanced ganglioside synthesis in response to n-butyrate treatment, incubation of Hep G2 cells with n-butyrate did not alter the ganglioside pattern as assessed by thin layer chromatography of lipids extracted from treated cells. Nuclear run-on reactions indicated that the rate of transcription of beta-galactoside, alpha 2,6-sialyltransferase was not altered by treatment with 5 mM n-butyrate for 24 h, but the effects of this treatment on cytoplasmic levels of beta-galactoside alpha 2,6-sialyltransferase mRNA were largely negated by co-treatment with actinomycin D or cycloheximide. Therefore, our results show that n-butyrate reduces expression of mature beta-galactoside alpha 2,6-sialyltransferase mRNA by post-transcriptional mechanisms.

Antigens, CD↗
PubMed1992

Interferon-alpha prevents endotoxin-induced mortality in mice.

Endotoxins, the lipopolysaccharide (LPS) moieties on the bacterial cell wall, cause many of the pathological features of Gram-negative septicemia. Tumor necrosis factor (TNF), primarily a product of monocyte/macrophages, has been shown to mediate many of the pathophysiological effects of endotoxin. Kupffer cells, the largest macrophage population in the body, release TNF when stimulated by LPS in vitro. A recombinant human hybrid interferon-alpha A/D (rIFN-alpha) markedly inhibited this LPS-elicited TNF production by Kupffer cells. The effects of rIFN-alpha were further tested in C57BL/6 mice receiving a lethal dose (400 micrograms/mouse) of LPS. All LPS-treated mice died within 2 days. Pretreatment with rIFN-alpha 1 h before LPS challenge improved the survival at 3 days to 22% (5/23, p < 0.04). In contrast, rIFN-alpha was more effective when administered 20 min after LPS injection, increasing the survival rate to 81% (13/16, p < 0.0001). TNF mRNA expression in the liver and spleen 50 min after LPS challenge, and plasma TNF 1.5 h after LPS were also reduced by either pretreatment or post-treatment with rIFN-alpha. Subsequently, experiments were carried out to test the efficacy of delayed rIFN-alpha treatment. A significant protective effect was still apparent when rIFN-alpha was administered 6, 10 and even 14 h (81%, 62% and 28% survival, respectively) after LPS challenge when serum TNF levels had already returned to near baseline. These experimental results suggest that rIFN-alpha might have a therapeutic potential for the prevention and treatment of the deleterious effects associated with endotoxemia besides mechanisms initially blocking TNF production.

Animals↗
PubMed1991

Colonic oligosaccharide structures deduced from lectin-binding studies before and after desialylation.

Dolichos biflorus agglutinin (DBA) binds N-acetylgalactosamine (GalNAc), and peanut agglutinin (PNA) binds Gal beta(1-3)GalNAc residues (Gal = galactose). We used these lectins with neuraminidase to probe colonic oligosaccharides. Tissues included normal epithelium, adenocarcinomas (T) with contiguous transitional (TM) and normal mucosae (RM), and adenomatous polyps. Except for DBA binding in carcinomas, neuraminidase digestion increased DBA and PNA binding in all epithelia. In untreated specimens, reciprocal gradients for binding by DBA (T less than TM and TM less than RM) and PNA (T greater than TM and T greater than RM) were seen. After neuraminidase, all gradients were abolished except for T less than TM and T less than RM with DBA. We conclude that (1) qualitative as well as quantitative differences may exist between the mucins of benign and neoplastic colonic epithelium, (2) the NeuAc-GalNAc dimer is a widely prevalent terminal oligosaccharide in benign epithelium at all stages of differentiation (NeuAc = sialic acid), and (3) in contrast with evidence from recent biochemical studies, the Gal beta(1-3)GalNAc dimer is a common masked oligosaccharide in benign epithelium.

Adenocarcinoma↗
PubMed1991

Palatability of colonic lavage solution is improved by the addition of artificially sweetened flavored drink mixes.

A frequent complaint of patients asked to drink polyethylene glycol (PEG) colonic lavage solution is the salty flavor. This often results in failure to ingest the entire 4 liters of the solution and compromises bowel cleansing. The purpose of this study was to determine systematically whether the addition of a flavored drink mix sweetened with aspartame to the PEG lavage solution would improve palatability without significantly altering the osmolality of the solution. Eighty-seven (87) staff volunteers participated in a taste test of PEG lavage solutions containing varying amounts of commercially available drink mixes. The solution containing two packages of lemon-flavored KoolAid drink mix sweetened with aspartame was significantly more palatable than the others (p less than 0.005), while osmolality remained within the range specified by the manufacturer of Colyte.

Colon↗
PubMed1991

Long-term enteral feeding: a retrospective comparison of delivery via percutaneous endoscopic gastrostomy and nasoenteric tubes.

The use of percutaneous endoscopic gastrostomy (PEG) tubes for enteral feeding is widespread, although their superiority to other feeding devices, such as nasoenteric tubes (NET), has not been substantiated. We retrospectively compared clinical outcomes in patients who received enteral feeding via PEG (n = 80) or NET (n = 29) from 1984 to 1988. Mean follow-up was 192 days in the PEG group and 141 days in the NET group. Changes in nutritional and performance status were similar in both groups. Aspiration pneumonia occurred within 14 days of tube placement in 6% and 24% (p = 0.01) of the PEG and NET patients, respectively. With the exception of tube replacement, cumulative rates of minor and major complications (including aspiration pneumonia) were similar in both groups during follow-up. None of the clinical variables that were assessed correlated with the development of aspiration pneumonia. Mortality was similar in both groups. These results suggest that, for long-term enteral feeding, PEG offers no substantial advantages over NET with respect to patient nutrition, performance, or survival. The reasons for the observed difference in short-term aspiration pneumonia rates are unknown, and must be investigated prospectively.

Aged↗
PubMed1990

Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes.

Murine lymphokine-activated-killer cell activity was readily induced by culturing spleen cells with 10 U/ml of interleukin-2 for 4 days. In contrast, very little activity was generated under the same culture conditions when nonparenchymal liver cells were used as the responding cells. It was concluded that Kupffer cells produced prostaglandin and interferon alpha/beta, which suppressed lymphokine-activated-killer induction because (a) induction of lymphokine-activated-killer activity from nonparenchymal liver cells was observed in the presence of indomethacin and anti-interferon alpha/beta antibody; (b) when adherent nonparenchymal liver cells, primarily Kupffer cells, were removed, lymphokine-activated-killer activity could be obtained with interleukin-2 alone; (c) coculture of Kupffer cells with nonadherent nonparenchymal liver cells in a two-chambered system inhibited lymphokine-activated killer cell induction in a dose-dependent manner; (d) exogenous prostaglandin E2 and interferon alpha/beta added at the start of culture inhibited interleukin-2-induced cytotoxicity and proliferation, whereas the other major prostaglandin species in the liver, prostaglandin D2, had little effect. These findings are distinctive with Kupffer cells because splenic macrophages did not exert such inhibition in parallel experiments. Moreover, the supernatant collected from the 24-hr culture of nonparenchymal liver cells contained greater than 20-fold more prostaglandin E2 and interferon alpha/beta than that from culture of spleen cells. In subsequent in vivo experiments, when interleukin-2 was given intraperitoneally to mice, the combination of indomethacin and anti-interferon alpha/beta antibody significantly enhanced lymphokine-activated-killer activity recovered from the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Isolation and characterization of a partial cDNA for a human sialyltransferase.

A probe generated from the coding sequence of the rat hepatic beta-galactoside alpha 2,6-sialyltransferase was used to screen a human cDNA library constructed of human submaxillary gland mRNA lambda gt-11. We report the isolation and characterization of a human cDNA, HSM-ST1, that is putatively the human homolog of the beta-galactoside alpha 2,6-sialyltransferase. The largest human clone contains a 1.3 kb cDNA insert and is predicted to encompass 75% of the coding sequence as well as a small portion of the 3' untranslated region. Comparative analysis of this insert with the rat hepatic alpha 2,6-sialyltransferase sequence indicates 79% nucleotide similarity between the two sequences in the predicted coding region. On the amino acid level, the degree of conservation is 86%. Substantial sequence similarity is observed in the 3'-untranslated region between the rat and human sequences as well. S1 nuclease analysis was performed to demonstrate the expression of HSM-ST1 transcripts in the human hepatoma cell line, HepG2, and in the human colonic adenocarcinoma cell lines, LS174T.

Amino Acid Sequence↗
PubMed1986

A controlled trial of cimetidine for the treatment of nonulcer dyspepsia.

Sixty patients with nonulcer dyspepsia took cimetidine 1 g daily or a placebo for 5 weeks in a double-blind trial. Thirty-four men and 26 women with normal double-contrast barium meals were included. Five percent had the endoscopic appearances of duodenitis. Symptoms improved during treatment in 62% of those taking cimetidine and in 54% of the placebo group (NS, p = 0.5). We suggest that significant duodenitis is uncommon in the absence of active or quiescent duodenal ulcer disease. From this study there is no evidence that cimetidine benefits those patients with normal double-contrast barium meals and no duodenitis endoscopically who nonetheless have symptoms similar to those of peptic ulcer disease.

Adult↗
PubMed1985

Histochemical and morphologic studies of mucosa bordering rectosigmoid carcinomas: comparisons with normal, diseased, and malignant colonic epithelium.

Surgically obtained rectosigmoid mucosa ("transitional" mucosa, TM) adjacent to eight primary carcinomas was compared with diseased mucosa (DM) from eight patients without primary carcinoma and mucosa from two normal control subjects by mucin histochemical and morphologic techniques. No differences were found between TM and DM that might have suggested premalignant changes unique to TM. An excess of sialidase-susceptible sialomucins was found in both TM and DM, as was loss of the sulfomucin-sialomucin gradient usually found between normal crypts and surface cells. Increased sialic acid in TM and DM may represent a nonspecific response to injury or inflammation and has been found in other epithelia under similar circumstances. Sialidase also induced substantial reduction of periodic acid-Schiff (PAS) staining, probably due to loss of sialic acid since no other sugars were released during sialidase digestion, as determined by thin-layer chromatography analysis of post-digestion supernatants. Carcinomas generally showed more staining with PAS than with basic dyes; PAS staining was minimally reduced by diastase and sialidase but markedly reduced by phenylhydrazine interposition, suggesting that some type of neutral glycoprotein was responsible. Finally, it was found that overreliance on the high-iron diamine-Alcian blue technique as a single procedure is unwise; this procedure should be accompanied by the use of singly applied dyes, especially high-iron diamine, together with other enzymatic and staining procedures.

Adenocarcinoma↗
PubMed1985

Chronic dyspepsia pain in general practice--its causes and diagnosis.

One hundred consecutive patients who had consulted their general practitioner because of upper abdominal pain related to eating, were investigated after initial interviews by the general practitioner, a medical registrar and the same consultant physician. Thirty seven had active upper gastrointestinal or biliary tract diseases, including 29 with peptic ulcers. The general practitioner and consultant correctly distinguished between organic and non-organic dyspepsia (NOD) in 51 and 65 cases respectively. Although the sensitivity of the general practitioner diagnosis of organic disease was high (95%), the specificity (23%) and predictive value (42%) were low. There were fewer organic diagnoses amongst the patients under the age of 30 (P less than 0.05) and those with symptoms for less than 3 months (P less than 0.01). No patient under 30 with symptoms for less than 3 months had organic dyspepsia. We suggest that if dyspeptic patients over the age of 30 and those under 30 with symptoms for longer than 3 months are investigated, about one-third will be found to have organic diseases.

Adult↗
PubMed1985

[A few reflections on the practice of urban medical angiology. Activity, role, future].

The author attempts to evaluate the practice of private medical angiologists. He presents the results of a survey conducted amongst his colleagues in the South of France and the Pyrenees and analyses the principal reasons for consultation from 6,900 cases seen in angiology practices. It seems that although vascular functional investigations take an increasingly large place in angiology practice, phlebology remains the predominant activity and the clinician is still very involved in therapy. Although the angiologist has defined his specificity, it is essential that he works within a team, in cooperation with the vascular radiologist and the vascular surgeon.

France↗
PubMed1984

Abnormal goblet cell glycoconjugates in rectal biopsies associated with an increased risk of neoplasia in patients with ulcerative colitis: early results of a prospective study.

A group of 18 patients with stable ulcerative colitis involving the entire colon for at least eight years was subjected to a biopsy of normal appearing rectal mucosa and followed prospectively over four years for the development of either dysplasia or cancer. Goblet cell glycoconjugate structure was examined in the rectal biopsies using fluorescein conjugated lectins. At the beginning of the study, 13 of the 18 patients had abnormalities of goblet cell mucin or cytoplasmic glycoconjugates in the rectal biopsies. Dysplasia subsequently developed in six and carcinoma in one of these patients. Among the five patients with normal lectin binding studies in the initial rectal biopsies, colonic dysplasia has subsequently developed in one. The abnormalities seen in the rectal goblet cells resembled in part those previously seen in immature and neoplastic colonic cells. The dysplastic tissues all contained the form of mucin which has been found in other neoplastic colonic tissues. This preliminary report after four years of prospective study suggests that abnormalities of glycoconjugate structure may be associated with, and may precede, neoplastic events in the setting of chronic ulcerative colitis.

Colitis, Ulcerative↗