1.
Wängberg, Bo, 1953, et al.
(författare)
Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.
1996
Ingår i: British journal of cancer. - 0007-0920. ; 73:6, s. 770-5
Tidskriftsartikel (refereegranskat) abstract
After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors.
2.
Andersson, P, et al.
(författare)
Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide.
1996
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:12, s. 2002-6
Tidskriftsartikel (refereegranskat) abstract
Neuroendocrine tumor cells frequently overexpress somatostatin receptors at their cell surfaces. To evaluate the possibility of using the somatostatin analog 111In-DTPA-D-Phe1-octreotide for radiation therapy, we studied the binding and subsequent internalization of 111In into three types of cultured human neuroendocrine tumor cells.
3.
Kölby, Lars, 1963, et al.
(författare)
Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.
1996
Ingår i: Endocrinology. - 0013-7227. ; 137:10, s. 4435-42
Tidskriftsartikel (refereegranskat) abstract
Histamine is an important stimulator of gastric acid secretion. In experimental animals, inhibition of acid secretion by long term histamine2 receptor blockade causes hypergastrinemia, proliferation of enterochromaffin-like (ECL) cells, and formation of histamine-producing gastric carcinoids. The aim of this study was to examine the role of gastrin in histamine synthesis and metabolism of the oxyntic mucosa of normal, hyperplastic, and carcinoid-bearing Mastomys natalensis. Administration of exogenous gastrin to normal animals increased histidine decarboxylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa within 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine2 receptor blockade (loxtidine) for 3-29 days, did not induce tumors, but enhanced the expression of HDC mRNA (2- to 4-fold elevated) and histamine contents (2-fold elevated) in the oxyntic mucosa. Long term histamine2 receptor blockade (7-21 months) resulted in sustained hypergastrinemia and ECL tumor formation. Tumor-bearing animals had a 4-fold increase in HDC mRNA expression and histamine contents of the oxyntic mucosa. Urinary excretion of the histamine metabolite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing animals recovering from histamine2 receptor blockade were normogastrinemic and had normal levels of HDC mRNA and histamine in the oxyntic mucosa as well as normal excretion of methyl-imidazole-acetic acid. The results indicate that ECL cell carcinoids developing during hypergastrinemia are well differentiated tumors that respond to high gastrin levels with increased histamine synthesis and secretion.
4.
Wängberg, Bo, 1953, et al.
(författare)
Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction.
1996
Ingår i: World journal of surgery. - 0364-2313. ; 20:7
Tidskriftsartikel (refereegranskat) abstract
Sixty-four consecutive patients with disseminated midgut carcinoids were treated during an 8-year period according to a single clinical protocol aimed at aggressive tumor reduction by surgery alone or with subsequent hepatic artery embolization. All patients had markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels (581 +/- 79 micromol/24 h) and hormonal symptoms. Fourteen patients (22%) reached anatomic and biochemical cure by surgery alone. At follow-up, the mean 5-HIAA levels were still normal after 69.0 +/- 6. 2 months; two patients had died from unrelated causes. With the introduction of somatostatin receptor scintigraphy, subclinical disease was diagnosed in 7 of these 14 patients. Forty patients with bilobar hepatic disease underwent embolization in combination with octreotide. In this group, 5-HIAA levels were still reduced by 55% after 71 +/- 11 months of follow-up, and the 5-year survival was 56%, estimated from the total death hazard function. After embolization, two subgroups could be identified with marked differences in their long-term response to treatment. Ten patients were not embolized owing to complicating diseases. The 5-year survival for the entire series was 58%. A significantly increased risk of cardiovascular deaths was seen, which underlines the importance of total survival analysis in a disease with multiple hormonal effects. It is concluded that an active surgical approach must be recommended to patients with the midgut carcinoid syndrome. In patients with bilobar hepatic disease, embolization combined with octreotide treatment markedly reduced the 5-HIAA excretion and suggested a prolonged 5-year survival.
5.
Friman, Vanda, 1952, et al.
(författare)
Decreased expression of mannose-specific adhesins by Escherichia coli in the colonic microflora of immunoglobulin A-deficient individuals.
1996
Ingår i: Infection and immunity. - 0019-9567. ; 64:7, s. 2794-8
Tidskriftsartikel (refereegranskat) abstract
Most Escherichia coli isolates can express type 1 fimbriae with mannose-specific adhesins. These adhesins bind to the oligosaccharide chains of secretory immunoglobulin A (IgA). Thus, in addition to specific antibody activity, secretory IgA possesses a broad reactivity with bacteria expressing type 1 fimbriae. The absence of secretory IgA in colonic secretions, as seen in IgA deficiency, might therefore alter the ability of type 1-fimbriated E. coli to colonize the large intestines of these individuals. In the present study, 10 E. coli isolates from each of 17 IgA-deficient and 17 age-matched control individuals were assessed for the carriage of the fim gene cluster by DNA-DNA hybridization and for the expression of type 1 fimbriae by hemagglutination of guinea pig erythrocytes. The contribution of type 1-fimbria-mediated adherence to HT-29 colonic cells was also analyzed. The proportion of fim+ E. coli isolates was lower in IgA-deficient than in control individuals (74 versus 94%, P < 0.05), as was the proportion of isolates expressing type 1 fimbriae in vitro (69% versus 85%, P < 0.05). The median mannose-sensitive adherence to HT-29 cells was lower for isolates from IgA-deficient individuals than from the controls (9 versus 26 bacteria per cell, P < 0.05). Isolates expressing type 1 fimbriae showed lower adherence to HT-29 cells when they were derived from IgA-deficient individuals than when they were derived from control individuals (15 versus 27 bacteria per cell, P < 0.05). The results suggest that the interaction of type 1 fimbriae with secretory IgA contributes to the large intestinal colonization by these bacteria.
6.
Wängberg, Bo, 1953, et al.
(författare)
The effect of vagotomy on enterochromaffin-like cells in Mastomys natalensis.
1996
Ingår i: Journal of the autonomic nervous system. - 0165-1838. ; 59:3, s. 133-9
Tidskriftsartikel (refereegranskat) abstract
The effect of vagotomy on the development of ECL cell tumours was analyzed during drug-induced hypergastrinemia in Mastomys natalensis, a rodent prone to develop ECL cell tumours. Untreated animals were compared with animals receiving the histamine2-receptor blocker loxtidine (LOX) and with animals subjected to unilateral subdiaphragmatic vagotomy prior to loxtidine treatment (VAG+LOX). Loxtidine (2g/l) was administered in drinking water for 48 weeks to allow multiple ECL cell carcinoids to develop. Plasma gastrin levels were increased in LOX animals (94 +/- 31 pmol/l) and in VAG+LOX animals (181 +/- 59 pmol/l) compared to controls (45 +/- 4 pmol/l). Corpus weight and oxyntic mucosal thickness was almost doubled in all loxtidine-treated animals and the density of mucosal endocrine cells was increased by 65% in the LOX group and by 135% in VAG+LOX animals. No significant differences in mucosal thickness and endocrine cell density were seen when denervated and intact parts of the stomach were compared. In the VAG+LOX animals endocrine cell neoplasia was seen in 60% and dysplasia in 40% of animals compared to 40% neoplasia, 45% dysplasia and 15% hyperplasia in LOX animals. The frequency of neoplastic and dysplastic lesions did not differ between denervated and intact parts of the stomach. Untreated animals showed no neoplastic or dysplastic lesions. It is concluded that unilateral vagotomy has no protective effect on the development of ECL-cell tumours in Mastomys during hypergastrinemia, as opposed to previous studies in the rat.
7.
8.
Andersson, K, et al.
(författare)
Depletion of enterochromaffin-like cell histamine increases histidine decarboxylase and chromogranin A mRNA levels in rat stomach by a gastrin-independent mechanism.
1996
Ingår i: Scandinavian Journal of Gastroenterology. - 1502-7708. ; 31:10, s. 65-959
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: Gastrin activates histidine decarboxylase (HDC) and increases HDC and chromogranin A (CGA) mRNA levels in histamine-producing enterochromaffin-like (ECL) cells in the rat stomach. We have studied how histamine depletion by subcutaneous infusion of the HDC inhibitor alpha-fluoromethyl-histidine (alpha-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels. METHODS: In one experiment rats received alpha-FMH for 24 h. In another experiment rats received alpha-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with alpha-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined. RESULTS: alpha-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. alpha-FMH for 10 days increased the serum gastrin concentration twofold. alpha-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after alpha-FMH + omeprazole than after omeprazole alone. alpha-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after alpha-FMH was much lower. In antrectomized rats alpha-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. CONCLUSION: ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.
9.
Andersson, Lena, et al.
(författare)
Pancreatic lipase related protein 2, but not classical lipase hydrolyzes galactolipids
1996
Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002. ; 1302:3, s. 236-240
Tidskriftsartikel (refereegranskat) abstract
The pancreatic lipase family contains three subfamilies, the 'classical' lipases and the pancreatic lipase-related proteins 1 (PLRP1) and 2 (PLRP2). Galactolipids are present in membranes of leaves and vegetables and consist of digalactosyldiacylglycerol (DGalDG) monogalactosyldiacylglycerol (MGalDG) and sulfoquinovosyldiacylglycerol (SQDG). These lipids were incubated with PLRP2 from guinea-pig (GPLRP2) and rat (RPLRP2). In the presence of bile salts DGalDG was efficiently hydrolyzed by GPLRP2 and, although less efficiently, by RPLRP2 to digalactosylmonoacylglycerol (DGalMG), free fatty acids and water-soluble galactose-containing compounds. Also, MGalDG and SQDG were hydrolyzed by GPLRP2 and RPLRP2. These data suggest a possible role of PLRP2 in the digestion of dietary galactolipids
10.
Duan, R D, et al.
(författare)
Distribution of alkaline sphingomyelinase activity in human beings and animals. Tissue and species differences
1996
Ingår i: Digestive Diseases and Sciences. - 1573-2568. ; 41:9, s. 1801-1806
Tidskriftsartikel (refereegranskat) abstract
The alkaline sphingomyelinase (SMase) was first found in rat intestinal brush border. The important roles of this enzyme in digestion of sphingomyelin and in mucosal cell proliferation have been suggested. In the present work, the distribution of the alkaline SMase in the tissues of human beings and animals have been studied. By assaying the enzyme activity in human biopsy samples, we found that the alkaline SMase activity was absent in the stomach, increased in the duodenum, present at high levels in the small intestine, and slightly declined in the colon and rectum. High activities were found similarly in the intestinal contents of the healthy adults and infants. The activities were also found in the intestinal mucosa of rats, normal and germ-free mice, and hamsters with the same distribution pattern as in humans, but not in the intestinal mucosa of guinea pigs. Apart from the intestinal tract, a SMase activity preferring alkaline pH was identified in human and guinea pig bile, but not in the bile of rat, pig, sheep, and cow. No activity was found in either pancreatic tissue or pancreatic juice in all species tested, and none was detected in human urine and milk. In conclusion, alkaline SMase exists predominantly in the digestive system with considerable tissue and species differences.
