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H L Waldum

Publications and source records attributed to H L Waldum.

At least 19 recordsLinked to original sources
PubMed1999

Pre- and postnatal testosterone administration induces proliferative epithelial lesions with neuroendocrine differentiation in the dorsal lobe of the rat prostate.

BACKGROUND: Androgens are implicated in the pathogenesis of prostatic carcinoma. We have elucidated the role of pre- and postnatal testosterone administration in the occurrence of proliferative lesions as well as neuroendocrine (NE) cells in the rat prostatic complex. METHODS: Female rats were given a single dose of 9 mg testosterone enantate i.m. on day 15 of pregnancy; it gave a high testosterone exposure to the fetus in the early organogenetic period of the rat prostatic complex. One group of the male offspring was followed without further testosterone treatment; a second group received testosterone only in the pubertal period; a third group was given testosterone from puberty and throughout life (46 weeks). These groups were compared to parallel groups (1A-1C) of male offspring without a testosterone supplement in pregnancy. RESULTS: The serum testosterone concentrations in the rats receiving testosterone were significantly higher than those of control rats. Histopathologically, the testosterone-induced proliferative lesions, mainly hyperplastic, were almost exclusively located in the dorsal lobe. Chromogranin A-immunoreactive (CgA-IR) cells were rarely found normally, but occurred more often in the proliferative lesions (P < 0.001). CONCLUSIONS: The incidence of proliferative lesions in rats exposed to testosterone only in puberty was comparable to the incidence found in those rats receiving testosterone in puberty and throughout life. This finding may have clinical implications for young athletes, who use testosterone as an anabolic drug. The occurrence of CgA-IR cells increased in proliferative lesions in the dorsal lobe of the rat prostatic complex.

Aging↗
PubMed1999

Vagal stimulation augments maximal (penta) gastrin-stimulated acid secretion in humans.

Since the late sixties, the pentagastrin test has been the standard method to examine maximal gastric acid secretion in humans. However, studies on rats and dogs have shown that maximal pentagastrin-stimulated acid secretion can be augmented by concomitant cholinergic stimulation. The aim of this study was to examine whether the combined stimulation of the vagal nerves and pentagastrin infusion could increase maximal gastric acid secretion compared with pentagastrin alone. Eight healthy medical students (seven males) were included in the study. Gastric acid secretion was determined thrice in each subject. On day one, pentagastrin (6 microg kg(-1) h(-1)) was infused. On day two, insulin-induced hypoglycaemia (plasma glucose approximately 2.3 mM during 30 min) was obtained by applying the glucose clamp technique. On day three, pentagastrin infusion and insulin induced-hypoglycaemia were combined. The combination of insulin-induced hypoglycaemia and pentagastrin infusion increased peak acid output about 20% (P = 0.018) compared with pentagastrin alone. The hypoglycaemia did not cause significant release of gastrin. It is concluded that vagal stimulation of gastric acid secretion may be safely obtained by insulin-induced hypoglycaemia when applying the glucose clamp technique. In addition, maximal pentagastrin-stimulated acid secretion does not represent the maximal acid secretory capacity in humans.

Adult↗
PubMed1998

[Peroxisomes and peroxisome proliferators. Specific environmental poisons and therapeutic agents affecting lipid metabolism and hormone release].

Peroxisomes, also known as microbodies, are the most recently discovered cellular organelles. They are small, with a one-layer membrane, and are associated with several enzymes. Peroxisome proliferators are compounds which induce and increase the quantity of cellular peroxisomes and their enzymes. There are many variations of these compounds, including therapeutic agents, industrial solvents, herbicides, substances added to food to improve taste, and long fatty acids. Experimental exposure to peroxisome proliferators is associated with hepatocellular carcinoma, and peroxisome proliferators are today regarded as complete non-genotoxic carcinogens. In addition, gastric tumours originating from enterochromaffin-like cells have been detected after administrating peroxisome proliferators. Peroxisome proliferators constitute a large group of compounds that may lead to hormone release and tumour development. Peroxisomes and their proliferators are therefore of great importance in the study of hormonal carcinogenesis. This article summarizes peroxisome function and the role of peroxisomes in carcinogenesis and hormone release.

Animals↗
PubMed1998

Neuroendocrine differentiation in human gastric carcinoma.

BACKGROUND: Distinguishing between neuroendocrine carcinoma and adenocarcinoma may be difficult. METHODS: In the current prospective study blood and tumor tissue from patients with gastric carcinoma were collected. The tissue was fixed in different ways to allow examination for neuroendocrine markers by multiple methods such as various histochemical and immunohistochemical methods and electron microscopy. Blood and tumor homogenates were examined by radioimmunoassay for specific hormones and general neuroendocrine markers. RESULTS: Based on examination of general neuroendocrine markers such as chromogranin A (by immunohistochemistry, Northern blot analysis, and tissue concentration), neuron specific enolase (immunohistochemistry) as well as electron microscopy, it was possible to conclude that approximately 10% of the tumors were actually neuroendocrine malignant tumors. Among these tumors, the enterochromaffin-like (ECL) cell was the most preponderant cell of origin (Sevier-Munger positive and serotonin negative immunoreactive tumor cells with secretory granules resembling those observed in normal ECL-cells). As reported previously, tumors of the diffuse type (according to the classification of Laurén) most often were reclassified as neuroendocrine carcinomas. CONCLUSIONS: The current study shows that neuroendocrine and particularly ECL cell-derived tumors are more common in the stomach than previously recognized.

Adenocarcinoma↗
PubMed1998

Carbachol stimulation of gastric acid secretion and its effects on the parietal cell.

1. The acid secretagogue effect of gastrin is mainly mediated by the release of enterochromaffin-like (ECL) cell histamine, but the mechanism of muscarinic stimulation of acid secretion remains unclear. The results of studying aminopyrine uptake in isolated parietal cells, and histamine release in isolated ECL cells suggest that muscarinic agents may act both directly on the parietal cell and indirectly via histamine release from ECL cells. 2. We examined parietal and ECL cell responses to the muscarinic agent carbamylcholine (carbachol) in conscious rats and in rat isolated vascularly perfused stomachs. 3. Intravenous carbachol stimulated acid secretion in conscious gastric fistula rats and increased H+K+ ATPase mRNA abundance, indicating activation of parietal cells. In these experiments there was no increase in portal venous histamine, or in oxyntic mucosal histidine decarboxylase (HDC) enzyme activity and HDC mRNA abundance. 4. In rat isolated stomachs stimulated with carbachol in the dose range 10 nM(-1) mM only the 1 microM concentration increased venous histamine significantly. 5. We concluded that the muscarinic agent carbachol stimulates acid secretion and H+K+ ATPase mRNA in vivo by a direct effect on the parietal cell, that does not depend on the release of ECL cell histamine.

Animals↗
PubMed1998

Potentiating hypergastrinemic effect by the peroxisome proliferator ciprofibrate and omeprazole in the rat.

BACKGROUND: Profound inhibition of gastric acid secretion induces enterochromaffin-like (ECL) cell carcinoids due to hypergastrinemia. Peroxisome proliferators also lead to hypergastrinemia and ECL cell carcinoids but without reducing gastric acidity. Since the peroxisome proliferator ciprofibrate is still in use as lipid-reducing agent, and proton pump inhibitors are among the most commonly used drugs, we found it of interest to evaluate both the effect of a combination of these drugs on serum gastrin and the expression of gastrin and somatostatin mRNA in antral mucosa. METHODS: The drugs were given by gastric gavage once daily for 4 weeks to female rats. Blood was drawn by vein puncture before and at the end of the 4-week period for determination of gastrin by radioimmunoassay. At death the stomachs were removed, the antral mucosa homogenized, and the density of gastrin and somatostatin mRNA determined by Northern blot, using 32P-labelled probes. RESULTS: Omeprazole dosing increased serum gastrin 4-fold, ciprofibrate 5-fold, and the combination 24-fold. Serum gastrin during ciprofibrate dosing increased gradually, reaching significance after 14 days. Antral gastrin mRNA density increased similarly to the increase in serum gastrin, whereas antral somatostatin mRNA tended to be reduced in the omeprazole and increased in the ciprofibrate-dosed rats. CONCLUSION: A potentiating hypergastrinemic effect of the peroxisome proliferator ciprofibrate and the inhibitor of gastric acid secretion omeprazole is shown, indicating different mechanisms of action.

Animals↗
PubMed1998

Treatment with proton pump inhibitors induces tolerance to histamine-2 receptor antagonists in Helicobacter pylori-negative patients.

BACKGROUND: Treatment with H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) induces hypergastrinemia and causes rebound hypersecretion of gastric acid after treatment, and during treatment with H2RAs tolerance develops. In the present study we investigated whether a treatment period with a PPI induced tolerance to an H2RA. METHODS: Thirteen patients with esophagitis were given omeprazole for 90 days. Twenty-four-hour pH monitorings without and with ranitidine were performed before and after treatment with omeprazole. Blood samples and biopsy specimens from the oxyntic mucosa were analyzed for gastrin, histamine, and chromogranin A. RESULTS: An increase in mucosal histamine and a reduction in the effect of ranitidine on gastric pH was found 14 days after discontinuing omeprazole compared with before treatment in Helicobacter pylori-negative but not in H. pylori-positive patients. CONCLUSIONS: Treatment with omeprazole reduces the effect of ranitidine in H. pylori-negative patients. This is caused by an increase in histamine released by the enterochromaffin-like cell secondarily to hypergastrinemia, corresponding to the tolerance towards H2RAs seen in patients with Zollinger-Ellison syndrome.

Adult↗
PubMed1998

NGF-beta, NE-cells and prostatic cancer cell lines. A study of neuroendocrine expression in the human prostatic cancer cell lines DU-145, PC-3, LNCaP, and TSU-pr1 following stimulation of the nerve growth factor-beta.

Neuroendocrine (NE) cells are present in both benign and malignant human prostate. However, their function is poorly understood, mainly due to the lack of suitable experimental models. The nerve growth factor-beta (NGF-beta) promotes the rat pheochromocytoma cell line PC-12 to differentiate into neuronal like cells. We have studied the effect of NGF-beta on four human prostate cancer cell lines, LNCaP, DU-145, PC-3, and TSU-pr1. NGF-beta stimulates the growth rate in all these cell lines, but does not induce a neuronal phenotype. NE tumour markers (chromogranin A [CgA] and chromogranin B[CgB]) could not be demonstrated by immunocytochemistry (CgA and CgB), Northern blotting (CgA), or ELISA techniques (CgA), neither in control nor in NGF-beta stimulated cells. Consequently, other experimental models have to be sought in the study of NE cells in the human prostate.

Blotting, Northern↗
PubMed1998

The effect of the peroxisome proliferator ciprofibrate on the gastric mucosa and particularly the gastrin cell.

The peroxisome proliferator ciprofibrate induces hypergastrinemia without inhibiting acid secretion. The present study was carried out to assess the effect of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of rats and to compare the effect of ciprofibrate with other lipid-reducing agents (lovastatin and simvastatin) which have a different mechanism of action. Serum gastrin was determined by a radioimmunoassay method, G cell density by histomorphometry after immunostaining for G cells, and gastrin, somatostatin and histidine decarboxylase (HDC) mRNA abundance by Northern blot analysis. Ciprofibrate (100 mg/kg/day for three weeks) induced a marked hypergastrinemia (P < 0.01) in male and female Fischer rats as well as in female Wistar rats. Simvastatin and lovastatin did not affect serum gastrin. Antral G cell density increased significantly in female Wistar rats (P < 0.05) and non-significantly in the other rats after ciprofibrate. Both gastrin and somatostatin mRNA abundance in antral mucosa increased markedly and significantly (P < 0.01) after ciprofibrate treatment. The present study shows that the peroxisome proliferator ciprofibrate induces hypergastrinemia secondary to an increased storage and synthesis of antral gastrin. Since somatostatin mRNA abundance also increased, the present study suggests that ciprofibrate and possibly other peroxisome proliferators in sufficient concentrations have a stimulatory effect on endocrine cells.

Animals↗
PubMed1997

[Chromogranin A in blood--a useful tumor marker].

Chromogranin A (CgA) is a protein localized to the secretory granules of neuroendocrine cells. Determination of CgA in blood is a useful marker for neoplasia and hyperplasia of neuroendocrine cells. Chromogranin A in serum should be the first test used for detecting carcinoids. It is also useful for diagnosing other neuroendocrine tumours, such as oat-cell carcinoma of the lung, pheochromocytoma and neuroblastoma.

Biomarkers, Tumor↗
PubMed1997

Neuroendocrine cells in the prostate of the rat, guinea pig, cat, and dog.

BACKGROUND: The neuroendocrine (NE) cells in the human prostate gland probably have a local regulatory role in both prostatic growth and differentiation as well as in the exocrine secretory process. Moreover, NE cells may be involved in the pathogenesis of both prostatic cancer and hyperplasia. To enhance the knowledge of the physiological and pathophysiological role of NE cells in the prostate gland, we wanted to establish an experimental animal model. METHODS: All lobes of the prostatic complex of rats with different serum levels of testosterone, as well as the prostate of the guinea pig, cat, and dog, were studied. Prostatic tissue fixed in different fixatives was studied with regard to NE cells by using cytochemical and immunohistochemical staining techniques, as well as Northern blotting and reverse transcriptase polymerase chain reaction (RT-PCR) for detection of rat chromogranin A (CgA) mRNA. RESULTS: The present study indicates the absence of NE cells in the rat prostatic complex. No expression of CgA RNA was detectable either by Northern blotting or by RT-PCR. Only a few argyrophil cells in the prostatic complex of guinea pig were detected in tissue fixed in Bouin's solution. CONCLUSIONS: Rat, guinea pig, cat, and dog are not suitable animals in physiological studies of NE cells in the prostate gland.

Animals↗