[Endocytosis of lipoproteins by the liver and their intracellular transport in comparison with other ligands].
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Animals↗
Biomedical subjects
H Greten
Publications and source records attributed to H Greten.
[In whom, when and how should increased cholesterol values be treated?].
High cholesterol values enhance the development of coronary heart disease. Therefore they must be normalized within the framework of a primary and secondary prevention. Apart from the risk factor cholesterol, other influencable and non-influencencable risk factors play a decisive role for the patient concerned. The simultaneous presence of these factors also finally determines the intensity of the lipid-lowering therapy. For a successful therapy, besides dietary measures, modern therapeutic drugs are available, and their use--as a rule--helps to normalize moderate and strongly increased cholesterol values. Despite all help in decision-making it always will remain the decision of a responsible doctor, which measures he will take to reduce the individual coronary risk of a particular patient entrusted to him.
Coronary Disease↗
Influence of the acyl-coenzyme A:cholesterol--acyltransferase inhibitor octimibate on cholesterol transport in rat mesenteric lymph.
The effect of the new inhibitor of acyl-coenzyme A:cholesterol-acyltransferase, octimibate (sodium 8-[1,4,5-triphenyl-1H-imidazole-2yl)-oxy)octanoate), on the cholesterol transport in rat mesenteric lymph was evaluated. During intraduodenal infusion of a triglyceride-phospholipid emulsion, volume and triglyceride concentration of lymph collected from a mesenteric lymph fistula remained constant in control and treated rats. After addition of 3.75 mg 3H-cholesterol/h to the intraduodenal infusion, cholesterol content of lymph increased to about double the basic concentration in control rats. Yet there was no significant change of lymph cholesterol in treated animals, which had received 40 mg octimibate followed by ca. 120 mg/24 h x kg body weight octimibate added to the intraduodenal infusion. Up to 35% of the infused dose of 3H-cholesterol were recovered in lymph of control rats, in contrast to only 23% in lymph of treated rats. It is concluded that the inhibition of the intestinal acyl-coenzyme A:cholesterol-acyltransferase by octimibate may prevent the increase of cholesterol in mesenteric lymph induced by dietary cholesterol.
Animals↗
Assessment of in vivo activated T cells in patients with Crohn's disease.
Besides clinical indices, acute phase reactants and measurement of permeability of the gut immunological parameters have been proposed for assessment of clinical activity in Crohn's disease (CD). The latter refers in particular to the number of activated peripheral T cells (APT) which are found to be increased in patients with CD and ulcerative colitis. Further analysis of the subset of APT revealed that in CD their number is correlated to the histopathological ratings and the number of activated T cells of the affected mucosa. A major subset of APTs in CD and ulcerative colitis expresses receptors for IgA (Fc-alpha-R). This T cell subset seems to be characteristic of patients with inflammatory bowel diseases, exhibiting a specificity of 88% and a sensitivity of 92% for CD as compared with non-inflammatory bowel diseases. Methodological complexity turned out to be the major disadvantage of assessment of APT and their subsets.
Adolescent↗
[Comparative measurement of oxygen uptake and cardiac output at rest and during stress--evaluation of a new monitor for continuous determination of oxygen uptake and carbon dioxide release].
A new device for the continuous monitoring of oxygen uptake and carbon dioxide delivery is presented, which is based on a continuous expired gas analysis using a paramagnetic oxygen and an infrared-absorption carbon dioxide sensor. To validate the results, data of measured oxygen uptake and cardiac output calculated by the Fick principle were compared to synchronous thermodilution measurements at rest and during exercise. Measurements were performed at rest on 18 patients, additionally 13 of the patients were exercised with either 25 W or 50 W workload. The results indicate, for both measurement series, a significant correlation (r greater than 0.95, p less than 0.001) and exemplify that the measurement of oxygen uptake by expired gas analysis permits a precise analysis of the cardiovascular transport function during exercise.
Adult↗
Effects of neuropeptides on gastric acid and duodenal bicarbonate secretions in freely moving rats.
The central nervous system effects of neuropeptides on gastric acid and duodenal bicarbonate secretions were examined. In freely moving rats, i.c.v. administration of thyrotropin-releasing hormone (TRH), human gastrin-17 (hG-17) and the somatostatin analogue, desAA 1,2,4,5,12,13 [D-Trp8]somatostatin (ODT8-SS), significantly increased gastric acid secretion, while vasoactive intestinal peptide (VIP) had no effect. In the order of potency and efficacy, the following peptides decreased acid secretion: bombesin (BOM) greater than calcitonin gene-related peptide (CGRP) greater than calcitonin (CT) greater than corticotropin-releasing factor (CRF) greater than beta-endorphin (beta-END) greater than neurotensin (NT). In anesthetized rats, none of these peptides significantly altered proximal duodenal bicarbonate secretion. In awake, freely moving rats, cerebroventricular administration of CGRP significantly decreased while ODT8-SS, TRH and CRF significantly increased duodenal bicarbonate secretion. beta-Endorphin, VIP, CT, BOM, NT and hG-17 given i.c.v. did not significantly alter the bicarbonate response. These results indicate that neuropeptides administered into the central nervous system modulate gastric acid as well as duodenal bicarbonate secretions in awake, freely moving rats in a differentiated fashion. CGRP inhibits both acid and bicarbonate secretions, a somatostatin analogue and TRH both stimulate acid and bicarbonate secretions and CRF inhibits gastric acid but stimulates duodenal bicarbonate secretions.
Animals↗
Pathways mediating CRF-induced inhibition of gastric acid secretion in rats.
The pathways involved in mediating the central nervous system actions of corticotropin-releasing factor (CRF) on gastric acid secretion were examined in conscious rats. CRF (0.1-2.0 nmol) given cerebroventricularly inhibited gastric acid secretion stimulated by pentagastrin (P less than 0.01). This effect was abolished by cerebroventricular but not intravenous administration of a specific CRF receptor antagonist, alpha-helical CRF-(9-41). Ganglionic blockade with chlorisondamine chloride, noradrenergic blockade with bretylium, or adrenalectomy abolished the gastric inhibitory action of CRF whereas truncal vagotomy or opiate blockade with naloxone did not. A vasopressin receptor antagonist significantly inhibited but did not abolish the gastric inhibitory action of CRF. An intravenous infusion of epinephrine that mimicked the epinephrine plasma concentrations which were observed after cerebroventricular administration of CRF did not alter pentagastrin-stimulated gastric acid secretion. These results indicate that CRF acts within the central nervous system to inhibit gastric acid secretion by a specific receptor-mediated event. Inhibition of gastric acid secretion by CRF in conscious rats is mediated by efferent fibers of the sympathetic nervous system and in part by a vasopressin-dependent pathway but not by the parasympathetic nervous system, adrenal epinephrine release, or opiate-sensitive pathways.
Adrenalectomy↗
[The clinical picture of a giant elongated basilar artery].
Lack of volition and immobilizing dizziness were the cardinal presenting symptoms of a 67-year-old man. On account of nonspecific inflammatory signs and weight loss of 18 kg, broad diagnostic tests were undertaken to exclude inflammatory or malignant disease. All were negative, but discrete neurological deficits pointed to cranial nerve or cerebral lesions which had brought about dizziness and dysphagia with vomiting and recurrent aspirations. The cause was found to be a giant aneurysmic dilation and lengthening of the basilar artery. Anticoagulant treatment may be used to reduce the risk of embolism, but complications caused by pressure on cerebral structures or by rupture cannot be avoided.
Aged↗
Binding of rat chylomicrons and their remnants to the hepatic low-density-lipoprotein receptor and its role in remnant removal.
Binding and uptake of rat chylomicrons of different metabolic stages by the hepatic low-density-lipoprotein (LDL) receptor were studied. Pure chylomicrons, characterized by apolipoprotein B-48 devoid of contaminating B-100, were labelled in their cholesteryl esters. Lymph chylomicrons and serum chylomicrons, enriched in apolipoprotein E and the C-apolipoproteins, bound poorly to rat hepatic membranes. In contrast, chylomicron remnants, containing the apolipoproteins B-48 and E, bound with high affinity. Specific binding of remnants was virtually completely competed for by LDL free of apolipoprotein E. In addition, in ligand blots both remnants and LDL associated with the same protein with an Mr characteristic of the LDL receptor. Uptake of remnants during a single pass through isolated perfused rat livers was decreased to about 50% by an excess of LDL. It is concluded that rat chylomicron remnants are a ligand of the hepatic LDL receptor. The much higher affinity as compared with LDL is mediated by apolipoprotein E but not B-48, and is inhibited by the C-apolipoproteins. This explains why serum chylomicrons are not taken up by the liver, whereas remnants are rapidly removed from the circulation. Results from experiments in vivo suggest that the LDL receptor makes an important contribution to the hepatic uptake of remnants and may be the principal binding site of the liver responsible for remnant removal.
Animals↗
[Can and should we manipulate our LDL receptors?].
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Cholesterol↗
Activated Fc alpha T cells in Crohn's disease are involved in regulation of IgA.
Activated peripheral T cells (APT) of patients with Crohn's disease (CD) have been analysed for the expression of IgA-Fc receptors and for competence of IgA regulation. It was found that within the subset of APT an increased number of cells express binding sites for IgA (IgA-Fc), that was not found in other diseases with elevated numbers of APT. Moreover the number of IgA-Fc receptor expressing T cells was found to be increased in the inflamed mucosa too. Cocultures with autologous B cells revealed that isolated IgA-Fc receptor bearing T cells of patients with CD suppress IgA secretion. These data support the hypothesis that APT are involved in the immunopathogenesis of CD.
Antibodies, Monoclonal↗
Evidence for contrasuppression in patients with Crohn's disease.
Patients with Crohn's disease (CD) have elevated numbers of Vicia villosa agglutinin (VVA) binding cells in the peripheral blood. These cells represent a major subset of activated peripheral T cells. VVA binding T lymphocytes express either the T8 or the T4 determinant on their cell surface. In contrast in normal controls only a minor subset of peripheral T cell expresses binding sites for VVA. The majority of these cells coexpress T8. VVA binding T cells display no helper activity. Only in a subfraction of patients with CD and not in normal controls these cells mediate contrasuppressor activity for Ig and in particular for IgA. This subgroup of patients is characterized by the lack of extramucosal manifestations. It has now been shown that VVA binding T cells in their majority do not possess phenotypic features of helper inducer cells. This further supports the hypothesis of their involvement in contrasuppression. Moreover it was shown that IgA produced in the presence of VVA binding T cells is IgA1 and IgA2 (ratio 2:1) which are both modulated by VVA binding T cells.
Antigens, Differentiation, T-Lymphocyte↗
Regulation of sterol synthesis by histamine in human mononuclear leukocytes: roles of H1- and H2-receptors.
The effect of histamine on sterol synthesis has been investigated in freshly isolated human mononuclear leukocytes from healthy subjects. Incubation of cells for 6 h in a medium containing lipid depleted serum led to a threefold increase in the incorporation of (14C)-acetate or tritiated water into sterols. Histamine 0.3 microM added to the incubation medium at zero time inhibited this induction by 35% with a sigmoidal log dose-effect curve. The receptors mediating this action were characterised pharmacologically by using selective H1- and H2-agonists and -antagonists. The H2-agonists impromidine and 4-methylhistamine mimicked the effect of histamine on sterol synthesis, the suppression being 42% and 31%, respectively, at a concentration of 1 microM. In contrast, the H1-agonist 2-pyridylethylamine did not affect the pathway. The H2-antagonist cimetidine (10 microM) but not the H1-antagonist mepyramine (10 microM) totally reversed the inhibition of sterol synthesis by histamine. The results provide evidence that sterol synthesis in human mononuclear leukocytes is regulated by histamine, which appears to act predominantly via H2-receptors.
Cimetidine↗
Lipase deficiencies.
Two enzymes, lipoprotein lipase and hepatic triglyceride lipase, are involved in the hydrolysis of triglycerides from chylomicrons and very low density lipoprotein (VLDL). Lipoprotein lipase has an absolute requirement for apolipoprotein CII for activity. Three inborn errors of metabolism which give rise to hypertriglyceridaemia have been described. The biochemical and clinical aspects of these disorders, lipoprotein lipase deficiency (familial type I hyperlipoproteinaemia), hepatic triglyceride lipase deficiency and apo-CII deficiency are discussed.
Humans↗
Central nervous system effects of corticotropin-releasing factor on gastrointestinal transit in the rat.
Corticotropin-releasing factor (CRF) administered into the lateral cerebral ventricle significantly inhibited gastric emptying and small bowel transit, but most markedly increased large bowel transit in a dose-related fashion in freely moving rats. Inhibition of gastric emptying induced by central administration of CRF was completely abolished by pretreatment of the animals with either the ganglionic blocking agent chlorisondamine or the opioid antagonist naloxone, or by noradrenergic blockade with bretylium, but not by truncal vagotomy. Either chlorisondamine, naloxone, or vagotomy--but not bretylium--reversed the inhibitory effect of central CRF on small bowel transit. Chlorisondamine or vagotomy, but neither bretylium nor naloxone, abolished the stimulatory effect of central CRF on large bowel transit. Neither hypophysectomy nor adrenalectomy altered the gastrointestinal motor responses induced by central administration of CRF. Intraperitoneal administration of CRF also significantly inhibited gastric emptying and stimulated large bowel transit but did not alter small bowel transit. These peripheral effects of CRF were not prevented by blockade of autonomic efferents with bretylium or chlorisondamine. It is concluded that (a) CRF acts within the central nervous system to delay gastric emptying, to inhibit small bowel transit, and to increase large bowel transit in freely moving rats and (b) CRF exerts these biological actions by modulation of the autonomic nervous system and, in part, by opioid pathways.
Animals↗
Interactions of aromatic amino acids with gastric secretagogues in humans.
To determine the interactions of phenylalanine and tryptophan with gastric secretagogues, acid secretory studies were performed in 10 healthy subjects. Phenylalanine and tryptophan potentiated the gastric secretory responses following low doses of pentagastrin, whereas their effects on acid secretion stimulated by low doses of histamine or the cholinergic bethanecol were additive. Phenylalanine and tryptophan did not increase maximal acid output stimulated by pentagastrin, histamine, or bethanecol. Doses of the H2-receptor antagonist ranitidine, the prostaglandin E1 analogue misoprostol, atropine, and somatostatin that produced approximately 50% inhibition of pentagastrin-stimulated acid secretion significantly inhibited phenylalanine- and tryptophan-stimulated acid secretion. After the combination of either phenylalanine or tryptophan with pentagastrin, the H2-receptor antagonist significantly inhibited gastric acid secretion, whereas somatostatin, atropine, and the prostaglandin E1 analogue were not effective. These results indicate that both phenylalanine and tryptophan potentiate gastric acid secretion stimulated by a submaximal dose of pentagastrin, whereas their effects on histamine- and bethanecol-stimulated secretion are additive. The potentiating effects of phenylalanine and tryptophan on pentagastrin-stimulated acid secretion depend, at least in part, on intact histamine pathways.
Adult↗
Stress-induced gastrointestinal secretory and motor responses in rats are mediated by endogenous corticotropin-releasing factor.
Corticotropin-releasing factor (CRF) has been implicated as a central nervous system mediator of stress. This study examined the effects of CRF and stress on gastric secretory and gastrointestinal motor functions in rats. Partial body restraint as a stress-producing stimulus significantly decreased gastric acid secretion, gastric emptying, and small bowel transit but markedly increased large bowel transit. Corticotropin-releasing factor given cerebroventricularly mimicked the gastrointestinal secretory and motor responses induced by partial body restraint. Cerebroventricular administration of a specific CRF receptor antagonist, alpha-helical CRF-(9-41), but not of the CRF fragment CRF-(1-20), prevented the gastrointestinal secretory and motor responses elicited either by partial body restraint or by exogenous administration of CRF in a dose-dependent fashion. These results suggest that the gastrointestinal secretory and motor responses in rats produced by stress (partial body restraint) are mediated by the endogenous release of CRF. They also indicate that CRF exerts its central nervous system actions on the gastrointestinal tract by a receptor-mediated event.
Animals↗
Antiproliferative effects exerted by recombinant human tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human pancreatic tumor cell lines.
Modulation of the growth of human pancreatic cancer cell lines in vitro by recombinant human tumor necrosis factor-alpha (TNF-alpha) and recombinant human interferon-gamma (IFN-gamma) was investigated. TNF-alpha exerted antiproliferative effects on three of nine pancreatic cancer cell lines and WiDR colorectal cancer cells. When administered together with IFN-gamma TNF-alpha showed enhanced antiproliferative effects on a subset of the pancreatic cancer cell lines tested, including those found to be insensitive to treatment with TNF-alpha alone. Thus the antiproliferative effect achieved by a combined treatment with TNF-alpha and IFN-gamma exceeded that observed with either drug alone in seven of nine pancreatic cancer cell lines.
Cell Division↗