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Biomedical subjects

G D Luk

Publications and source records attributed to G D Luk.

105 records · Page 6Linked to original sources
PubMed1980

Prophylaxis against acute stress erosions.

Acute gastroduodenal erosions and ulcerations, often with life-threatening gastrointestinal hemorrhage, contribute to high mortality in critically ill patients. Hypersecretion of gastric acid to some degree seems to be necessary. Antacids and recently cimetidine, a histamine H2-receptor antagonist, have been used for prophylaxis against bleeding from these acute "stress" erosions. Review of studies regarding such prophylaxis suggests that either agent may be effective, but massive life-threatening gastrointestinal hemorrhage has not been decreased by this therapy, and, more important, there has not been an increased survival in treated patients. Furthermore, cimetidine is not approved for such use by the FDA. Currently, in critically ill patients there are multiple risk factors for acute "stress" erosions. An intensive antacid regimen may be impractical. Alternatively, cimetidine may be given as an investigational drug. Further studies are needed on the efficacy of antacids and cimetidine in preventing acute "stress" erosion and bleeding, but such studies should be prospective, controlled, double-blind, stratified, and randomized to produce the most useful data.

Animals↗
PubMed1980

Hypothesis: the role of the lung in stomach carcinogenesis.

It is proposed that pulmonary defense mechanisms play an important role in stomach carcinogenesis. Inhaled carcinogens reach the stomach by normal pulmonary clearance and account for the association of stomach cancer with dusty occupations. We postulate that although familial and other factors determine the susceptibility to endothelial cancer (both stomach and lung), those persons whose pulmonary clearance mechanisms are more susceptible to impairment by cigarette smoke retain carcinogens and other particulate matter in the lungs and are at increased risk for lung cancer. Those whose clearance mechanisms are not impaired continue to clear these particles from their lungs, unconsciously swallow the cleared particles, receive more of these substances in the stomach, and are at increased risk for stomach cancer. This accounts for: first, the very striking dose-response relationship between the amount of smoking and lung cancer mortality and the relatively weak relationship between smoking and stomach cancer, and second, for observed reciprocal relationships in time trends of mortality between stomach cancer and lung cancer.

Air Pollutants↗
PubMed1980

Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity.

Diamine oxidase (histaminase) is an enzyme found in high concentrations in the intestinal mucosa of humans and other mammalian species. We investigated whether plasma and mucosal levels of diamine oxidase activity reflect both the maturational status of the mucosa during its development in the newborn rate and the degree of mucosal damage during its injury in the adult rat. Litter mates were reared under identical conditions and killed at different ages from day 0 to day 40 after birth. Diamine oxidase in the small intestine was low at birth, increased gradually with age, reached a peak at 22 d, and then remained at normal adult levels, similar to the developmental patterns of maltase and sucrase. Plasma diamine oxidase rose in parallel with intestinal levels (n = 500, r = 0.84, P less than 0.001), reached a peak at 24 d, and then remained at normal adult levels. Diamine oxidase activity in 15 nonintestinal tissues was less than 5% of ileal mucosal activity, and no nonintestinal activities showed increase with age. Adult rat intestinal loops were perfused with hyperosmolar sodium sulfate solutions to produce selective damage to villus mucosa. With increasing mucosal damage, there was a progressive decrease in the enzyme activities studied; first, lactase levels fell, then maltase and sucrase, and finally mucosal and plasma diamine oxidase activity levels fell. The decrease in plasma diamine oxidase reflected the degree of mucosal damage (n = 29, P less than 0.04). Diamine oxidase activity is thus unique among intestinal mucosal enzymes studied to date in that circulating levels can serve as a marker of mucosal maturation and integrity.

Amine Oxidase (Copper-Containing)↗
PubMed1979

Gastric aspiration in localization of gastrointestinal hemorrhage.

We compared the findings from gastric aspiration for blood with the site of gastrointestinal (GI) hemorrhage ultimately identified by endoscopy or angiography in 1,190 patients whose cases were analyzed retrospectively and prospectively during a six-year period. Gastric aspirates were positive for blood in 837 patients. An upper GI site proximal to Treitz' ligament was identified in 93%, and none had a lower GI site. A negative aspirate was found in 353 patients; a lower GI site was identified in 60%, and 1% (three patients) had an upper GI site. In these three patients, hemorrhage occurred in clinical settings suggesting ulcer disease, and bleeding duodenal ulcers were found in all three. All of the other 180 patients with a bleeding duodenal ulcer had a positive gastric aspirate.

Aged↗
PubMedDate not supplied

Thymosin alpha 1 and thymosin beta 4 modulate human colonic lamina propria lymphocyte function.

Thymosin alpha 1 and thymosin beta 4 are two thymosin fraction 5-derived peptides with the capacity to alter a variety of immune functions in human and animal models. In this study we investigated the effect of both thymosin alpha 1 and thymosin beta 4 on human colonic lamina propria lymphocyte (LPL) proliferation and ornithine decarboxylase (ODC) activity. LPL from eighteen human colon specimens were cultured in the presence or absence of thymosin alpha 1 and thymosin beta 4. We found that both peptides suppressed thymidine incorporation into LPL. However, thymosin alpha 1 and thymosin beta 4 did not alter thymidine incorporation into phorbol ester (PDB) and calcium ionophore (ionomycin)-stimulated LPL. Furthermore, thymosin alpha 1 and thymosin beta 4 also did not alter ODC activity in Con A-stimulated LPL. These results suggest that both peptides alter LPL proliferation, and that the mechanism for this inhibition may not involve the calcium fluxes or the ODC pathway but may involve protein kinase C. We postulate that thymosin alpha 1 and thymosin beta 4 may participate in the modulation of the human mucosal immune system.

Colon↗
PubMedDate not supplied

Inhibition of ornithine decarboxylase activity decreases polyamines and suppresses DNA synthesis in human colonic lamina propria lymphocytes.

Ornithine decarboxylase (ODC) and the polyamines are essential for cell proliferation in a variety of cells including lymphocytes. In this study, we investigated the potential role of ODC and polyamines in human colonic lamina propria lymphocytes (LPL) compared to peripheral blood lymphocytes (PBL). Our results show that con A stimulation of LPL and PBL was associated with marked increases in ODC and polyamines. The specific inhibitor of ODC, alpha-difluoromethylornithine (DFMO), resulted in a complete inhibition of ODC activity and depletion of putrescine, spermidine and spermine levels. DFMO also suppressed DNA synthesis of LPL and PBL by up to 48% and 62% respectively. This antiproliferative effect was reversed by adding back the polyamines putrescine (1 mM), spermidine (10 microM) or spermine (10 microM) to the culture medium. We conclude that ODC and the polyamines are important for human LPL proliferation, and hence may play a role in human mucosal immune function.

Aged↗
PubMedDate not supplied

Gastrointestinal neuropeptides suppress human colonic lamina propria lymphocyte DNA synthesis.

Gastrointestinal neuropeptides have been shown to modulate the circulatory immune system, but their effect on the mucosal immune system is not well defined. We studied the effect of VIP, SOM, S-P and Bomb on thymidine incorporation into human colonic lamina propria lymphocyte (LPL) DNA. Physiologic concentrations of VIP, SOM, S-P and Bomb significantly suppressed thymidine incorporation into Con A-stimulated human LPL. These neuropeptides did not affect DNA synthesis when LPL were induced with phorbol ester (PDB) and calcium ionophore (ionomycin). Our data suggest that a) VIP, SOM, S-P, and Bomb may have a regulatory role in the human mucosal immune system, and b) Bomb should be added to the list of neuropeptides which affect the gut immune system.

Adult↗
PubMedDate not supplied

Congenital diarrhea with intestinal inflammation and epithelial immaturity.

We report an interesting case of congenital inflammatory bowel disease and intestinal epithelial immaturity that presented as secretory diarrhea. No infectious, metabolic, or anatomical basis for these findings was identified. As differentiated from previous reports of neonatal enteropathies, this infant demonstrated involvement of both the small and large intestine with histopathologic findings of acute and chronic inflammation, extensive submucosal fibrosis, and "flat" small intestine mucosa. In addition, this patient had a polyamine deficiency (a primary or secondary phenomenon), which may have contributed to delayed epithelial maturation. These findings suggest that the inflammatory bowel disease and altered epithelial maturation contributed to a fatal intractable diarrhea.

Diarrhea, Infantile↗
PubMedDate not supplied

Inhibition of DNA synthesis in human peripheral and lamina propria lymphocytes by 5-aminosalicylic acid and hydrocortisone.

5-Aminosalicylic acid (5-ASA) and hydrocortisone (HC) have potent antiinflammatory activity, and are commonly used in the treatment of patients with inflammatory bowel disease. Both agents have been reported to modulate immune function in human and animal models. We investigated the effect of 5-ASA and HC on cell proliferation of normal human peripheral blood lymphocytes (PBL) and normal colonic lamina propria lymphocytes (LPL). Both 5-ASA (0.01-4 mM) and HC (0.01-10 microM) significantly inhibited 3H-thymidine incorporation (Thd) into PBL and LPL in a dose dependent manner. Maximal inhibition occurred with the highest concentration tested of both 5-ASA and HC. We found a significantly greater inhibition of DNA synthesis for 5-ASA (4 mM) upon LPL vs. PBL (94 vs. 32%, p less than 0.001). However, DNA synthesis inhibition by HC was similar in PBL and LPL. The profoundly greater inhibitory effect of 5-ASA upon LPL suggests a specific modulation of the mucosal immune system.

Aminosalicylic Acids↗