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Biomedical subjects

G Willems

Publications and source records attributed to G Willems.

At least 127 records · Page 7Linked to original sources

Histochemical and proliferative changes preceding the onset of spontaneous gastric adenocarcinoma in Mastomys natalensis.

The histochemical and proliferative changes preceding spontaneously developing gastric adenocarcinoma were examined in Mastomys natalensis. The stomachs of 86 inbred animals from the DWZ strain were examined between 1 and 24 months of age. Two thirds of the animals had a small solitary ulcer in the middle of the lesser curvature which was observed by the first month of age. With increasing age, more and more dysplastic glands invading the submucosa were seen around the ulcer and eventually adenocarcinoma was observed after 12 month. Histochemical alterations included increased intracellular peanut lectin and Concanavalin A binding sites in the gastric pits and the development of lectin binding sites and of acid glycoproteins in the surface epithelium. Using 3H thymidine and autoradiography increased labelling and mitotic indices with extension of the progenitor area to the mucosal surface were observed around the ulcer. The coexistence of these histochemical and histokinetic alterations may represent an early sign of malignant potential in the gastric mucosa.

Adenocarcinoma↗

Stopping power and ranges of low-energy protons in tissue-equivalent gas.

Stopping power data for protons in tissue-equivalent gas (64.4% CH4 + 32.4% CO2 + 3.2% N2, partial pressures) were derived from experimentally determined ranges and from differential ionisation distributions using the differential energy required per ion pair formed to convert ionisation to energy loss. The proton energy covered the region from 1 to 100 keV. The results are compared with other data available. In general the present experimental stopping power data tend to higher values than calculated data for energies lower than 20 keV; between 20 and 100 keV they agree well within the stated uncertainties.

Energy Transfer↗

Antral gastrin and somatostatin cell populations in rats after chronic administration of histamine.

Variations in the size of the antral G and D cell populations under the effect of chronic stimulation of acid secretion with histamine were investigated in male Wistar rats. Osmotic minipumps delivering either 0.9% saline or histamine dihydrochloride (4.5 mg/kg/h) were implanted subcutaneously in gastric-fistula rats. Gastric secretion was collected prior to the implantation of the pump, after 7 days and after 14 days. Total antral G and D cell numbers and the G/D ratio were estimated at the end of the experiment. Administration of histamine during 14 days did not induce significant changes in the number of either G or D cells in the antrum despite a 3-fold increase in acid secretion.

Animals↗

Effect of an apple brandy from Normandy and of ethanol on epithelial cell proliferation in the esophagus of rats.

The effects on cell population kinetics in the distal esophagus of an apple brandy from Normandy (Calvados), of ethanol diluted at a similar concentration, and of saline were investigated in rats. Animals were killed at 0, 6, 12, 18 and 24 h after a single intraesophageal instillation, and at 3 weeks after chronic administration of these solutions. In vivo labeling with [3H]-thymidine and autoradiography were carried out to determine the proliferative parameters. Vincristine sulfate was used to increase metaphase figures during the chronic experiment. Instillation of saline did not modify the parameters under study. Single instillations of both apple brandy and 56 degrees ethanol were followed by a significant increase in labeling (p less than 0.01) and mitotic indices (p less than 0.01). Chronic administration of both apple brandy and 56 degrees ethanol increased the labeling index (p less than 0.01) as well as the metaphase index (p less than 0.01). The proliferative responses after the apple brandy and after 56 degrees ethanol were similar in amplitude. These data suggest that ethanol alone may explain the mitogenic effect of Calvados in the esophagus.

Alcoholic Beverages↗

Refeeding of fasting rats stimulates DNA synthesis in implanted colon carcinoma.

Colon carcinoma was implanted into the mesenterium of syngeneic BD IX rats, and 10 weeks later the animals were fasted for 48 h and refed. Control animals were kept fasted for an additional 24-h period. DNA synthesis was measured in mucosal scrapings from the normal colon and in the tumor before and after refeeding. Autoradiography was used to determine the epithelial DNA synthesis index (labeling index) in the progenitor cells from normal colon mucosa, in the adenocarcinoma cells from the tumor, and in the tumor lymphocytes. DNA synthesis increased over control values in the normal mucosa in situ (p less than 0.01), and in the implanted tumor (p less than 0.05) at 16 h after refeeding. The labeling index also increased over control values in the progenitor cells from normal mucosa (p less than 0.01), and in the adenocarcinoma cells from the tumor (p less than 0.01) at 16 h after refeeding. No increase in labeling index was observed in the tumor lymphocytes. These data suggest that cell proliferation in normal colon epithelium as well as in colon adenocarcinoma cells may be stimulated by a common physiological factor released after feeding.

Adenocarcinoma↗

Postprandial stimulation of epithelial cell proliferation in defunctioned colon of rats is not caused by gastrin.

Rats were submitted, at random, to either a diverting colostomy alone or to antrectomy with a colostomy. After a 48-h fasting period, animals from each group were refed, whereas control animals were kept fasting. Animals were killed at 0, 6, 12, 18, and 24 h after the time of refeeding. In vitro labeling of colon mucosa with [3H]thymidine and autoradiography were performed to determine the proliferative parameters in the colonic crypts, and scintillation counts on mucosal scrapings were used for the estimation of mucosal deoxyribonucleic acid synthetic activity. Refeeding increased the labeling index (p less than 0.01), mitotic index (p less than 0.01), and mucosal deoxyribonucleic acid synthesis activity (p less than 0.01) in the proximal colon as well as in the defunctioned distal segment. Despite suppression of the postprandial rise in serum gastrin (p less than 0.01), antrectomy did not abolish the proliferative reaction in any colonic segment. These data confirm the existence of a potent stimulant of colonic cell proliferation that is released systematically after feeding. They indicate that gastrin is not the responsible stimulant and that another, yet unknown, physiological factor is involved.

Animals↗

A biochemical and ultrastructural study on myocardial changes during aorto-coronary bypass surgery: St. Thomas Hospital cardioplegia versus intermittent aortic cross-clamping at 34 and 25 degrees C.

The changes induced by continuous aortic cross-clamping in combination with multidose ice-cold St. Thomas Hospital cardioplegia (myocardial temperature below 16 degrees C), or intermittent aortic cross-clamping at 34 or 25 degrees C were evaluated in a randomized study on 72 patients undergoing extensive aorto-coronary bypass surgery. The cumulative release of heart-specific enzymes was very small and no marked ultrastructural changes in mitochondria of both the subepi- and the subendocardial layer of the left ventricular free wall occurred. No differences between the three operation techniques could be observed on the basis of the above-mentioned parameters. Myocardial ATP and glycogen contents were decreased in post-ischaemic tissue in both the normothermic and hypothermic intermittent aortic cross-clamp groups. This decrease was associated with a release of lactate and inorganic phosphate during the repetitive periods of reperfusion. No change in myocardial ATP and glycogen content could be observed in the cardioplegia-treated hearts. St. Thomas Hospital cardioplegia is obviously most effective in preventing changes in myocardial metabolism such as reduction of ATP and carbohydrate stores during the reversible phase of ischaemic insult.

Adenosine Triphosphate↗

Quantitative study of liver metastases from colon cancer in rats after treatment with cyclosporine A.

Liver metastases were produced in syngeneic BD IX rats by intraportal injection of colon cancer cell aggregates. The cells originated from the DHD/K12 cell line, derived from a 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon adenocarcinoma in BD IX rats. The animals received either cyclosporine A (CSA) or the excipients alone (control) through daily gastric intubation during 6 weeks. Multiple and very large hepatic metastases were observed early in 100% of the CSA-treated rats. The mean tumor volume was approximately 2,000 times higher in the CSA-treated group than in the controls (P less than .01). Survival time in the CSA-treated group was shortened (P less than .01) by generalized metastatic disease. Easy production of metastasis from colon cancer in 100% of the animals and precise estimation of tumor volume may prove useful for future therapeutic studies of secondary hepatic disease.

Adenocarcinoma↗

Hydrochloric acid. A trigger of cell proliferation in the esophagus of dogs.

The effect of a single instillation of acid and pepsin on the cell proliferation in the distal esophageal mucosa was investigated in four dogs. The doses of acid and pepsin used were lower than those provoking acute esophagitis and erosions. Using in vitro labeling with [3H]thymidine and autoradiography, the epithelial mitotic and DNA synthesis indices were determined at 0, 4, 8, 12, 16, 20, and 24 hr after instillation of saline, of, acid alone, or of acid with pepsin. Instillation of acid alone was followed, 16 hr later, by an increase (P less than 0.01) in DNA synthetic activity in the proliferative area. A mitotic peak (P less than 0.01) started from the 20th hour. After instillation of acid with pepsin in the same animals, a similar sequence of kinetic phenomena was observed, suggesting that the concentration of pepsin used did not potentiate the stimulating effect of acid on the cell proliferation in this epithelium. Our data indicate that hydrochloric acid stimulates the proliferative activity in the normal esophageal epithelium.

Animals↗

In vivo metal-ion release from porous titanium-fiber material.

Dense and porous Ti, Ti-alloy, and stainless steel specimens were implanted in canine trabecular bone. After 6 and 12 months the specimens were retrieved together with bone tissue immediately adjacent. The trace metal content in the tissue samples was determined using neutron activation analysis, differential pulse polarography, graphite furnace atomic-absorption spectrophotometry, electron microprobe analysis, and laser microprobe analysis. The results are discussed in view of (i) the release of Ti ions, which is larger for porous than for bulk specimens, (ii) the various artifacts arising in electron microprobe (EMP) and laser microprobe mass analysis (LAMMA) determination of compositional gradients of trace metal-ion content in bone tissue, (iii) the absence of measurable quantities of V in bone tissue, and (iv) the difference in local tissue accumulation between Ti, released from Ti specimens, and Ni, released from stainless steel specimens.

Alloys↗

Administration of caerulein to rats promotes antral epithelial cell renewal.

The growth-promoting effect of caerulein on antral gastric mucosa was explored using Wistar rats. Implanted osmotic minipumps were used to administer submaximal doses of either caerulein or saline to normal rats for up to 4 days. In one group, reflux of bile and pancreatic juice into the stomach was avoided by previous surgical diversion of the distal common bile duct to the jejunum. DNA synthetic and mitotic activity in the antrum epithelium were estimated by 3H-thymidine pulse labelling and autoradiography during the administration of the peptide. The rate of cell migration was determined in animals killed 1, 2 and 3 days after the 3H-thymidine pulse. Administration of caerulein to normal rats provoked significant increases in both labelling and mitotic indices, and a significant acceleration of the upward cell migration in the glandular tubes. In the animals with distal diversion of bile and pancreatic secretions both labelling and mitotic indices were also increased over control values under the effect of the peptide. These data indicate that administration of caerulein stimulates cell proliferation in the antral gastric mucosa. This effect cannot be explained through increased reflux of pancreaticobiliary secretions in the stomach.

Animals↗

The effect of gastrin and CCK-like peptides on epithelial cell proliferation in the stomach.

The growth promoting effect of gastrin on the glandular stem cells and parietal cells of the oxyntic mucosa has been confirmed by several observations. Gastrin has no effect on the antral mucosa. Cholecystokinin, another trophic hormone, stimulates cell proliferation in the exocrine pancreas, duodenum and gallbladder but not in the oxyntic mucosa. More recently, we have observed that caerulein stimulates epithelial cell proliferation in the antrum. The following is seen after acute administration of this cholecystokinin analog: a, after 18 h, there is an increased nuclear 3H-thymidine uptake in the progenitor cells of the antral mucosa and b, after 24 h, there is a mitotic peak. Continuous delivery of caerulein through implanted osmotic minipumps increases not only the mucosal DNA synthesis index and mitotic index, but also the migration rate of the epithelial cells along the glandular tubes.

Animals↗

Refeeding of fasting rats stimulates epithelial cell proliferation in the excluded colon.

The major postprandial factors known to influence epithelial cell proliferation in the colon are intraluminal factors. In this study, a transverse colostomy was created in rats in order to avoid the intraluminal stimulation of the distal colon after feeding. After a 48-h fasting period, the animals were refed whereas controls were kept fasted. Refed animals with their controls were killed at respectively 0, 8, 12, 18, and 24 h after the time of refeeding. Autoradiography of in vitro labeled mucosal samples was used for determining the proliferative parameters in the colonic crypts. The uptake of [3H]thymidine in mucosal scrapings was measured for estimating DNA synthetic activity. Refeeding increased the labeling index of the crypts (p less than 0.01) and the mucosal DNA synthesis (p less than 0.01) not only in the proximal colon but also in the excluded distal colon. The increase in labeling index was followed by a significant mitotic peak in both segments. These data indicate that direct intraluminal stimulation is not the only mechanism involved after feeding. There are other potent physiological stimulants of epithelial cell proliferation in the colon which are released postprandially.

Animals↗

Influence of a diverting colostomy on epithelial cell proliferation in the colon of rats.

The effect of a transverse colostomy was compared to a sham operation and to transsection of the colon with reanastomosis in rats. The autoradiographic study after labeling with tritiated thymidine showed a significant decrease in proliferative activity at 5 days and at 3 weeks in the colonic segment distal to the colostomy. This observation was confirmed by the occurrence of mucosal atrophy and by a significant decrease in the mucosal DNA synthesis activity. It was concluded that the intraluminal presence of fecal bulk is an important factor in the maintenance of cell renewal in the colon of rats. Other factors seem, however, to be involved since a delayed but significant decrease in proliferative parameters was also observed proximal to the colostomy; no mucosal atrophy occurred in the latter segment.

Animals↗

Increase in gastrin and somatostatin cell numbers in the antrum of dogs after small bowel resection.

A proximal 50 p. 100 resection of the small bowel was performed in six dogs while six control animals underwent a simple intestinal transsection and reanastomosis. The pre- and postoperative serum gastrin levels were measured in both groups before and after a standard test meal. The stomach was resected in both groups 6 to 8 weeks after the operation. A morphometric method using specific antigastrin and antisomatostatin antibodies was used to estimate the density and the total number of antral gastrin and somatostatin cells. No variation in basal serum gastrin was found after surgery. A 50 p. 100, though not significant, increase in the postprandial gastrin response was observed after intestinal resection whereas a significant (P less than 0.01) 50 p. 100 increase in the gastrin cell density was found in the antral mucosa of these dogs. At the same time, a remarkable hyperplasia of the antral somatostatin cell population was observed in the animals submitted to small bowel resection.

Animals↗

DNA synthesis index: higher for human gallbladders with cholesterol gallstones than with pigment gallstones.

[3H]dThd uptake by the gallbladder epithelium was estimated in 33 patients with cholesterol stones, in 13 patients with pigment stones, and in 12 gallbladders without stones. Proliferative parameters were estimated by autoradiography after in vitro incubation with [3H]-dThd. Stones were identified by quantitative infrared spectroscopy. The degree of inflammation of the gallbladder wall was estimated by a histologic scoring method. In the gallbladders containing cholesterol stones the DNA synthesis index (1.39 +/- 0.28%) was higher (P less than .01) than in the gallbladders without stones (0.19 +/- 0.04%). No significant increase in proliferative parameters was found in the gallbladders with pigment stones (0.24 +/- 0.06%). No correlation was found between total stone number, weight or volume, and the DNA synthesis index. No evidence was observed that inflammation could influence the epithelial cell proliferation. Something in the bile of patients with cholesterol stones rather than the physical presence of stones may be the cause of the variations observed.

Autoradiography↗

Effect of cholecystokinin-octapeptide, caerulein, and pentagastrin on epithelial cell proliferation in the murine gallbladder.

The growth-promoting effect of cholecystokinin-octapeptide, caerulein, and pentagastrin on gallbladder mucosa was investigated in mice. The acute effects on deoxyribonucleic acid synthesis activity was explored with a [3H]thymidine pulse and autoradiography after subcutaneous injection of the polypeptides. The administration of a supramaximal dose of caerulein or of cholecystokinin-octapeptide induced a significant increase (p less than 0.01) in the nuclear uptake of [3H]thymidine by the gallbladder epithelial cells. The injection of pentagastrin had no effect. Implantation of osmotic minipumps was used for the chronic administration of submaximal doses of caerulein or pentagastrin. Using successive [3H]thymidine pulses and autoradiography, increases in labeling (p less than 0.01) and mitotic indices (p less than 0.05) were observed in the caerulein group, whereas pentagastrin had no effect. In addition, a morphometric method was used to determine the total epithelial cell number in the entire gallbladder after chronic administration of the peptides. A significant (p less than 0.01) epithelial cell hyperplasia was observed to occur after caerulein administration whereas pentagastrin given by the same route had no effect on the epithelial cell population. These data indicate that cholecystokininlike peptides promote epithelial growth in the gallbladder of mice.

Animals↗