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Biomedical subjects

G Luk

Publications and source records attributed to G Luk.

12 recordsLinked to original sources
PubMed1999

Monoclonal antibody Adnab-9 defines a preneoplastic marker in epithelium at risk for adenocarcinoma of the small intestine.

Unlike colorectal cancer, risk markers for adenocarcinoma of the small intestine (ASI) have not been identified. Because the demographic and pathological features of both of these diseases are similar, immunohistochemistry was performed using monoclonal antibodies for three colonic premalignant markers, Adnab-9 (recognizes a colonic adenoma epitope), CaCo3/61, and FBB2/29 (small intestine proteoglycans expressed ectopically in colonic neoplasms), in normal and neoplastic small intestinal epithelium, and the results were compared with normal controls. Adnab-9 was also examined in 20 familial adenomatous polyposis (FAP) patients, a population known to be at an increased risk for ASI. Immunohistochemistry in normal and neoplastic tissue (adenoma, adenocarcinoma) from 18 patients with primary adenocarcinoma of the small intestine was compared with normal small intestine from 10 nonneoplastic controls. Four of 10 (40%) cases of normal small intestinal epithelium from controls were mildly positive in less than 10% of crypts, versus strong staining (>50% of crypts) in 16 of 18 (89%) patients with adenocarcinoma, and in 17 of 20 (85%) patients with FAP (P<.05). Adnab-9 predominantly stained Paneth cells as well as rare crypt and basal villous goblet cells. Adenomatous epithelium from the adenocarcinoma cases and adenomas from the FAP patients showed staining of Adnab-9 in 63% and 78% of cases, respectively. Only 17% of adenocarcinomas were positive for Adnab-9. In contrast, neither CaCo3/61 nor FBB2/29 showed any significant differences in the degree of staining in normal small intestinal epithelium in patients with adenocarcinoma compared with controls. Enhanced Adnab-9 staining in normal small intestinal epithelium from patients who harbor adenocarcinoma, and in FAP patients, supports its role as a risk marker of small intestinal neoplasia.

Adenocarcinoma↗
PubMed1996

Comparison of results of stent implantation in small (<20 kg) children versus larger children with pulmonary artery stenoses.

We compared the results of stent implantation for pulmonary artery stenoses in patients weighing <20 kg (group 1, 17 patients, 21 stents) versus those weighing > or = 20 kg (group 2, 11 patients, 13 stents). There was no significant difference in the mean percent increase in diameter or mean percent gradient reduction acutely and at short-term follow-up between group 1 and 2 patients.

Adolescent↗
PubMed1995

Omeprazole inhibits growth of cancer cell line of colonic origin.

The direct effects of omeprazole on colonic cells has not been evaluated. Controversy exists regarding the potential adverse effects of omeprazole on cell proliferation. In order to mimic the in vivo situation in the patient treated with omeprazole, proliferation cell culture experiments were performed, monitoring directly the effects of gastrin and omeprazole both alone and in combination. Three colonic cancer cell lines were used, two with neuroendocrine features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In these in vitro proliferation experiments, only the NCI-H716 colorectal cancer cell line responded to omeprazole by decreased proliferation (P < 0.05). The effect was concentration dependent shown for all doses of omeprazole used. Gastrin had a statistically significant effect on increasing proliferation in the NCS-H716 cell line alone but only at the highest concentration (10(-6) M). Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines but the mechanism for this effect of omeprazole and its potential role in treatment awaits elucidation.

Cell Division↗
PubMed1994

Acute and follow-up intravascular ultrasound findings after balloon dilation of coarctation of the aorta.

BACKGROUND: The study objective was to examine the vascular wall changes caused by balloon dilation of coarctation of the aorta (CoA) acutely and at short-term follow-up using intravascular ultrasound imaging. Intravascular ultrasound has been valuable in assessing the vessel wall changes in coronary and peripheral arteries after balloon dilation, often with more detail than angiography. METHODS AND RESULTS: Intravascular ultrasound imaging, using 4.8F, 20-MHz or 6.2F, 12.5-MHz catheters on either Diasonics or HP scanners, was performed in 17 patients during balloon angioplasty for native (n = 12) and recurrent (n = 5) CoAs. Nine patients were also studied at the time of follow-up cardiac catheterization 28.1 +/- 18.0 months after angioplasty. Immediately after dilation, the mean pressure gradient across the CoA decreased from 42.9 +/- 16.4 to 9.0 +/- 5.4 mm Hg (P < .001) and the mean diameter of the coarcted segment increased from 4.4 +/- 1.9 to 7.9 +/- 2.4 mm (P < .001). An intimal tear or flap was noted by ultrasound in 12 of the 12 native CoAs and 4 of the 5 recoarctations. In contrast, only 6 of the native CoAs and 2 of the recoarctations had an intimal flap or dissection detected by angiography. At follow-up, the residual pressure gradient did not significantly change from that measured immediately after dilation, but the CoA diameter increased from 7.8 +/- 1.5 to 9.9 +/- 2.3 mm (P < .01). No aneurysms were detected. Four of the 9 patients showed ultrasonic and angiographic evidence of healing and remodeling with diminution in size or disappearance of the intimal tears. CONCLUSIONS: There is a high incidence of intimal tears and dissections immediately after balloon angioplasty for native and recurrent CoAs. Intravascular ultrasound is more sensitive than angiography in detecting the vascular wall changes. Even significant intimal tears are not necessarily associated with aneurysm formation, and many decrease in size or disappear at short-term follow-up.

Adolescent↗
PubMed1993

Contralateral femoral vein removal of a circumferentially ruptured balloon-catheter following pulmonary artery angioplasty.

While attempting to remove a circumferentially ruptured balloon following branch pulmonary artery angioplasty, the shaft of the catheter broke, leaving the distal portion of the balloon and catheter in the femoral vein but still on the exchange wire. We describe a method to retrieve the broken balloon catheter via the contralateral femoral vein.

Angioplasty, Balloon↗
PubMed1992

Adenoma-derived antibody, Adnab-9 recognizes a membrane-bound glycoprotein in colonic tissue and effluent material from patients with colorectal neoplasia.

The binding in pre-colonoscopic effluent of Adnab-9, a monoclonal antibody raised against colonic adenomas, was evaluated for specificity in the diagnosis of colorectal cancer. A heterogeneous group of 58 patients was evaluated by ELISA. Effluent samples and tissue extracts were subjected to Western blotting or ELISA to confirm specificity. Immunohistochemistry was performed on the cancer tissue sections. The proportion of positive effluent binding was higher in the cancer when compared to the normal group (P = 0.036). A dominant 87 M(r) band was found in adenoma extracts and some effluent samples. Adnab-9 binding in effluent samples predominated in membrane-bound fractions. Immunohistochemistry showed no specific staining in the cancer cells. The antigen recognised is a glycoprotein shown by effects of N-glycanase digestion and not cross-reactive with carcinoembryonic antigen. Non-gastro-intestinal tissue extracts did not bind Adnab-9. The major 87 M(r) adenoma-derived antigen may be found in effluent material, particularly in the membrane-bound fraction.

Adenoma↗
PubMed1988

Role of polyamines in the growth of hormone-responsive experimental breast cancer in vivo.

We have provided evidence for a critical role of polyamines in the growth of the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor in vitro. The present experiments were designed to test whether polyamines are involved in the growth of this experimental tumor in vivo. To test this hypothesis, groups of rats bearing NMU-induced mammary cancers were randomly allocated to receive no treatment or escalating doses of the polyamine biosynthesis inhibitor alpha-difluoromethyl-ornithine (DFMO) (0.5%, 1%, 2%, 3% in drinking water). DFMO inhibited tumor growth in a dose-dependent fashion and consistently reduced tumor putrescine level. To evaluate the time dependency of this effect, additional groups of rats received either no treatment or 2% DFMO for 3, 7, 14, and 21 days. At all times DFMO suppressed tumor putrescine level as well as spermidine to spermine ratio. Finally, exogenous administration of putrescine (200 mg/kg/i.p./day x 21 days) given concomitantly with DFMO restored tumor growth, partially repleted tumor putrescine level, and raised the spermidine to spermine ratio to control levels. Putrescine, given alone, had no significant effect on either tumor polyamine levels or tumor growth. Except for modest weight loss, no major toxicity was encountered. These results indicate that polyamines play an important role in the growth of the NMU rat mammary tumor in vivo. The interaction between polyamines and hormones in supporting NMU mammary tumor growth in vivo remains to be elucidated.

Animals↗
PubMed1987

Role of polyamines in the synthesis of prolactin-regulated growth factors by experimental breast cancer in culture.

The present experiments were designed to test whether polyamines play an essential role in the synthesis of growth factors induced by ovine prolactin (oPRL), using the N-nitrosomethylurea (NMU)-induced rat mammary tumor cultured in the soft agar clonogenic assay. Conditioned media (CM) obtained from tumors treated with oPRL and the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) (1 mM) no longer exerted the colony-stimulating effect which was observed with oPRL-CM. Such growth-promoting activity was restored with conditioned media obtained from tumors treated with oPRL, DFMO, and increasing concentrations of spermidine from 1 to 500 microM. The colony-stimulating effect of the CM employed could not be accounted for by the contaminating presence in the media of oPRL, DFMO, and polyamines. These results indicate that in our system polyamines play an important role in the synthesis of oPRL-regulated growth factors.

Animals↗
PubMed1987

Total parenteral nutrition and intestinal development: a neonatal model.

Total parenteral nutrition (TPN) is widely used in premature and/or surgical neonates, but there is little information available about its effects on intestinal growth and development. Adult TPN models have demonstrated mucosal atrophy, and a young piglet model showed similar but increased intestinal hypotrophy. We have investigated these effects in the neonatal piglet model. Five three-day old piglets received a glucose (40 g/kg/d), amino acid (8 g/kg/d), and fat (4 g/kg/d) solution intravenously for 3 weeks. Matched littermates were fed an artificial sow-milk formula enterally at an equivalent caloric rate (215 kcal/kg/d). A third littermate was sow breast fed for the same study period. No differences were seen in the TPN or formula-fed piglets in weight gain (31 to 34 g/kg/d), hematocrit (25% to 27%), BUN (12 to 13 mg/dL), total serum protein (4.1 to 4.4 g/dL), or total bilirubin (0.4 to 0.6 mg/dL); however, the TPN animals were mildly hyperglycemic (167 mg/dL). The sow-fed control group had greater weight gain (51 g/kg/d) but were without caloric restriction. There were significant decreases in weight and length of the gastrointestinal tract, particularly in the proximal small bowel of the TPN piglets. Compared with formula piglets or sow-fed controls, the TPN proximal small bowel weight was reduced by 67% and 72%, respectively. Similar but less marked differences were seen in the TPN distal small bowel. There were no significant differences in the proximal or distal small bowel measurements between the formula and sow-fed piglets, despite their differences in overall weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Polyamines and hormonal regulation of N-nitrosomethylurea-induced rat mammary tumor growth in vivo.

We have observed that polyamines play an essential role in the expression of hormonal action on the growth of the N-nitrosomethylurea-induced mammary tumor cultured in soft agar. Since polyamine levels cannot be measured in this system, we could not determine whether tumor polyamine pools are under endocrine control. To test this hypothesis, the following experiments were conducted in N-nitrosomethylurea tumor-bearing rats in vivo. Both tamoxifen administration (200 micrograms/day) and ovariectomy produced dramatic reductions in tumor growth but neither treatment significantly altered tumor polyamine levels after either 7 or 21 days of treatment. Some decrease in tumor level of putrescine, spermidine, and spermine was observed 21 days after ovariectomy but it was not statistically significant. Exogenous administration of putrescine (300 mg/kg/day) reversed the antitumor effect of tamoxifen but did not prevent tumor regression induced by ovariectomy. This effect of putrescine was, however, variable in magnitude from experiment to experiment. To test whether the reversal of tamoxifen effect by putrescine might simply be due to interference with tamoxifen uptake by the tumor cells, we measured estrogen and progesterone receptors in the tumors of rats chronically treated with tamoxifen and tamoxifen plus putrescine. In both groups estrogen receptors are virtually undetectable, thus suggesting that putrescine had not inhibited tamoxifen entry into the cells and binding to estrogen receptors. Progesterone receptor levels were similarly high in both groups and not significantly different from control. These results indicate that at least under these experimental conditions N-nitrosomethylurea mammary tumor polyamine pools are not under ovarian hormone control. The mechanism by which putrescine reverses tamoxifen's effect remains unclear.

Animals↗