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Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

At least 109 records · Page 6Linked to original sources
PubMed1993

Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease. Studies in nondiabetic and diabetic subjects.

Retinal capillary nonperfusion results in neovascularization of the eye, which is restricted to the retina in less severe cases and progresses to the anterior chamber and the iris angle in the most advanced case, called rubeosis. This angioneogenesis may be induced by the release of retinal growth factors into the vitreous. This study compared levels of the IGF-I and IGF-II, and of the IGF binding protein-2 (IGFBP-2) and IGFBP-3 in vitreous from three groups with different degrees of retinal ischemia, as judged by the extent of neovascularization: a control group without new vessel formation, retinal neovascularization in patients with proliferative diabetic retinopathy, and massive ischemia of various causes resulting in rubeosis. IGF-I and IGFBP-3 were increased 10- and 13-fold in rubeosis (P << 0.01) compared with no ischemia (n = 10), while IGF-II and IGFBP-2 were elevated 2.7- and 4.3-fold (P < 0.01). Within the rubeosis group similar changes were observed independently of the cause of ischemia, which was central vein occlusion, ischemic ophthalmopathy, or intraocular tumor in seven cases and diabetic retinopathy in three samples from two patients. Vitreous from patients with proliferative diabetic retinopathy but without rubeosis (n = 16) contained 2.5- and 2.2-fold elevated levels of IGF-I and of IGFBP-2 (P < 0.05), while IGF-II and IGFBP-3 were increased 1.4- and 1.6-fold, which was not significant. We conclude that: (a) ischemia appears to be a strong stimulus for the local production of IGF-I and -II and of IGFBP-2 and -3 in the eye. (b) Changes in IGF-I and IGFBP-2 in proliferative diabetic retinopathy may be secondary to local ischemia rather than being specific for diabetic retinopathy. (c) IGF-I and IGFBP-3 may play a role in mediating angioneogenesis in the eye.

Carrier Proteins↗
PubMed1993

Effect of ethanol on absorption of a nutrient solution in the upper human intestine.

The study compares the duodenal and jejunal absorption of an ethanol-containing nutrient solution (4% wt/vol, 4.06 kcal/min = 17.2 kJ/min, 1190 mosmol/kg) with the corresponding ethanol-free solution (2.64 kcal/min = 11.2 kJ/min, 160 mosmol/kg) and with another ethanol-free solution adapted in caloric load and osmolality (4.06 kcal/min = 17.2 kJ/min, 1160 mosmol/kg) by the addition of NaCl and glucose in eight healthy volunteers, using the intestinal perfusion technique. Ethanol added to a nutrient solution did not exert a significant effect on the net absorption of nutrients in the upper intestine. However, duodenal but not jejunal net water (p < 0.05) and sodium (p < 0.02) movements were significantly modified. Compared with the hyperosmolar ethanol-free solution, perfusion of ethanol induced in the duodenum a significantly lower (p < 0.001) net water and sodium secretion and higher absorption rates of total nitrogen and fatty acids (p < 0.001). The importance of the composition of control solutions in studies investigating the effects of ethanol in the gastrointestinal tract is emphasized.

Adult↗
PubMed1992

Effect of ethanol and commonly ingested alcoholic beverages on gastric emptying and gastrointestinal transit.

Acute ingestion of pure ethanol has been reported to delay gastric emptying and to enhance the propulsive movements of the intestine. The aim of the present study was to investigate the comparative effect of beer (7.0% v/v), white wine (7.5% v/v), ethanol (7.5% v/v), and water on the gastric emptying of a liquid test meal and on the gastrocaecal transit time of lactulose added to the test meal. Gastric liquid emptying was assessed by means of a nasogastric intubation technique using polyethylene glycol 4000 as the non-absorbable marker. The gastrocaecal transit time was evaluated by a hydrogen breath test. Beer (P less than 0.001) and white wine (P less than 0.05) significantly accelerated gastric emptying in comparison with ethanol of the same concentration. The gastrocaecal transit time was significantly shorter when the liquid meal was administered with beer compared with ethanol (P less than 0.005) and water (P less than 0.01). The constituents in beer and white wine responsible for our observations remain to be found.

Adult↗
PubMed1992

Effects of loperamide on the human hypothalamo-pituitary-adrenal axis in vivo and in vitro.

Loperamide, an opiate agonist of high specificity for mu-receptors, was recently reported to suppress ACTH and cortisol levels in normal subjects, but not in patients with proven ACTH-dependent Cushing's disease. However, there is little information on the site of action of loperamide in the hypothalamo-pituitary-adrenal axis of man. We investigated the effect of loperamide on pituitary hormone secretion in vivo and in vitro. In seven normal subjects, basal ACTH plasma levels were significantly suppressed 3 h after loperamide administration (16 mg, orally) from 5 +/- 1 to 2 +/- 0 pmol/L (P less than 0.0001). After the combined pituitary stimulation test (100 micrograms human CRH, 100 micrograms GnRH, 100 micrograms GH-releasing hormone, and 200 micrograms TRH), the ACTH peak (maximum increase at 30 min) was significantly blunted by loperamide from 9 +/- 1 to 4 +/- 1 pmol/L (P less than 0.001) and the area under the curve of ACTH from 0-120 min was reduced from 35 +/- 5 to 23 +/- 4 pmol/L.2 h (P less than 0.05). In the insulin-hypoglycemia test (0.15 IU/kg BW), neither the ACTH peak nor the area under the curve of ACTH was affected by loperamide. In six patients with Cushing's disease and one patient with secondary adrenal insufficiency due to hypothalamic failure, neither basal ACTH and cortisol levels nor CRH-stimulated levels were influenced by loperamide. In four cultured human corticotropic adenomas, loperamide was not able to reduce basal and CRH-induced ACTH secretion. In summary, loperamide is able to reduce basal and CRH-induced ACTH and cortisol levels in normal subjects, but not in patients with Cushing's disease or secondary adrenal failure of hypothalamic origin. Loperamide has no significant effect on insulin-hypoglycemia-induced ACTH and cortisol levels and, therefore, no effect on stress-induced elevation of cortisol levels. Loperamide might act at a suprapituitary site in man in vivo, but, nevertheless, a pituitary site cannot be excluded.

Adenoma↗
PubMed1992

Absorption of a nutrient solution in chronic alcoholics without nutrient deficiencies and liver cirrhosis.

Duodenal and jejunal absorption of a nutrient solution at two different caloric loads (1.32 and 3.96 kcal/min = 5.6 and 16.8 kJ/min) was compared in chronic alcoholics without malnutrition, liver cirrhosis, obvious small-bowel dysfunction, and exocrine pancreatic insufficiency and in an age-matched control group, by means of the intestinal perfusion technique. In chronic alcoholics duodenal net absorption of water (p < 0.025), sodium (p < 0.02), potassium (p < 0.005), total nitrogen (p < 0.02), carbohydrates (p < 0.05), and lipids (p < 0.05) was lower than in controls when both caloric loads were administered, but jejunal absorption rates were not decreased. Biliopancreatic secretion did not differ between alcoholics and controls. Higher serum protein leakage in alcoholics was indicated by an increased (p < 0.01) duodenal alpha 1-antitrypsin clearance under low caloric load infusion. It is concluded that the absorptive function of the duodenum is impaired in alcoholics, whereas the upper jejunum is not affected.

Adult↗
PubMed1992

123I-iomazenil: a quantitative study of the central benzodiazepine receptor distribution.

Fourteen patients with temporal lobe epilepsy, 9 patients after amygdalohippocampectomy and 3 healthy volunteers were examined with the new benzodiazepine receptor marker 123I-Iomazenil and SPECT. For comparison perfusion SPECT studies with 99mTc-HMPAO were done and a quantitative ROI analysis of the data performed. This quantitative analysis consisted of calculation of right-to-left ratios for 123I-Iomazenil SPECTs, whereby values of 1 were obtained with narrow standard deviations. ROI measurements of the medial occipital, frontal and parietal cortex, the cerebellum and white matter showed a pattern of benzodiazepine receptor concentration in concordance with that previously found in PET and autoradiographic studies, if 123I-Iomazenil ROIs were normalized to the corresponding 99mTc-HMPAO ROIs. The abnormal distribution in the temporal lobes will not be discussed in this paper.

Adult↗
PubMed1992

Gastric emptying, esophageal 24-hour pH and gastric potential difference measurements in non-ulcer dyspepsia.

Pathological gastroesophageal reflux, prolonged gastric emptying and abnormal gastric potential difference have been claimed to be functional disorders often detectable in non-ulcer dyspspsia (NUD). The role of Helicobacter pylori in NUD is still unclear. The aim of the present study was to evaluate the prevalence of these factors in 47 patients with NUD. According to DeMeester's criteria, 60 percent of NUD patients had abnormal gastroesophageal reflux, while 38 percent had prolonged gastric emptying of a liquid meal. Seventy-nine percent showed abnormal gastric potential difference which was unrelated to Helicobacter pylori colonization, detected in 46 percent of NUD patients. When esophageal pHmetry, gastric emptying evaluation and measurement of gastric potential difference were performed, 89 percent of NUD patients presented at least one abnormal finding.

Adult↗
PubMed1991

Altered protein kinase C activity in biopsies of human colonic adenomas and carcinomas.

Protein kinase C (PK-C) seems to be involved in the regulation of growth and differentiation of normal epithelial cells. Colonic adenomas and carcinomas show increased proliferation and decreased differentiation. We investigated the activity and subcellular distribution of PK-C in biopsies of normal, neoplastic, and malignant colonic epithelium to evaluate alterations in enzyme activity. In the control group (n = 7), the activity of PK-C was highest in the distal ileum (597 pmol/min/mg protein) and declined to the lowest amounts in rectal mucosa (225 pmol/min/mg protein). In patients with colonic adenomas (n = 16), total PK-C activity was significantly reduced as compared to adjacent mucosa (146 versus 336 pmol/min/mg protein, P less than 0.05) and to values determined in the control group (372 pmol/min/mg protein, P less than 0.01). The reduction of total PK-C activity in the adenoma group was even more evident in intraindividual comparison to paired adjacent mucosa (41.8% of adjacent mucosa, P less than 0.001). Specific activity of membrane-associated PK-C was equally decreased in colonic adenomas (36.3 pmol/min/mg protein) when compared to adjacent mucosa (102 pmol/min/mg protein, P less than 0.05) or to the control group (107 pmol/min/mg protein). In patients with colonic carcinomas (n = 10), the amount of total PK-C activity was also decreased (198 pmol/min/mg protein) when compared to adjacent mucosa or to the control group (P less than 0.05). In addition, the amount of membrane-associated PK-C activity (89.1 pmol/min/mg protein) was significantly reduced in carcinoma when compared to adjacent mucosa (P less than 0.05). The ratio of membrane-associated/total PK-C was not altered in adenomas, while in patients bearing carcinomas the relative fraction of membrane-associated PK-C activity was increased in samples from carcinomas and equally from adjacent colonic mucosa (45.0 and 44.6 versus 28.9%, P less than 0.05) when compared to controls. These results indicate that alterations within the protein kinase C pathway occur as early events in the adenoma-carcinoma sequence of intestinal mucosa, suggesting an important role of PK-C in epithelial differentiation and growth.

Adenoma↗
PubMed1991

Perioperative myocardial perfusion scintigraphy at rest with technetium 99m methoxyisobutylisonitrile before and after coronary bypass operations.

Eighteen patients were examined at rest by technetium 99m methoxyisobutylisonitrile (99mTc-MIBI) myocardial scintigraphy 1 day before and 1 week after aorto-coronary bypass operation with planar and single photon emission tomography (SPET) imaging. One day postoperatively, a planar scintigraph in the intensive care unit (ICU) was done. Inter-observer variability was 3.8% for all examinations and for SPET alone, 3.9%. The quality of the planar images taken under emergency conditions in the ICU was quite comparable with those taken under routine conditions. The postoperative myocardial infarction in a patient who died 6 days later could clearly be demonstrated. In 16.2% of all segments which were hypoperfused at rest on preoperative scintigraphy, an amelioration of perfusion could be shown in the 1st week after the bypass operation. 99mTc-MIBI proved to be a useful agent to assess perioperative perfusion, in the ICU as well as under standard conditions.

Adult↗
PubMed1991

Inositol phosphate formation and [Ca2+]i in secretagogue-stimulated rabbit gastric mucous cells.

The formation of inositol phosphates and the changes in free intracellular Ca2+ ([Ca2+]i) in isolated rabbit gastric mucous cells during cholinergic stimulation were examined and the potential role of inositol phosphate turnover and [Ca2+]i in gastric mucus secretion evaluated. Rabbit chief and parietal cells were studied for comparison. The formation of [3H]inositol phosphates in mucous, chief, and parietal cells was stimulated in a time- and concentration-dependent fashion by acetylcholine (ACh). The ACh-induced initial [Ca2+]i peak was maximally (10(-4) M ACh) 199 +/- 8% of basal in mucous cells, 427 +/- 20% in chief, and 455 +/- 31% in parietal cells and was followed by a lower-level plateau in mucous and parietal cells but by a more rapid decline in chief cells. As in parietal and chief cells, the initial [Ca2+]i peak occurred in mucous cells in the absence of external Ca2+. ACh stimulated a mucous cell membrane Ca2(+)-entry mechanism in addition to release of Ca2+ from intracellular stores. The concentration-response relationships for the production of [3H]-inositol phosphates, the initial rise in [Ca2+]i, and the stimulation of glycoprotein secretion by ACh were virtually identical. Suppression of the [Ca2+]i rise by the intracellular Ca2(+)-chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) abolished the secretory response. As with many other secretory cells, gastric mucous cells possess cholinergic receptors that upon stimulation mediate the hydrolysis of phosphoinositides, a release of Ca2+ from intracellular stores, and a stimulation of Ca2+ influx through the plasma membrane.

Acetylcholine↗
PubMed1991

[Fetal movement and acceleration behavior in hypertension in pregnancy].

Under standardized conditions, 26 pregnant women with pregnancy-related hypertension of different degrees were submitted to cardiogram-synchronous recording of fetal body and respiratory movements. The gestational age was between the completed 34th and 38th weeks. Of the 26 fetuses of the risk group, 20 were normotrophic and 6 hypotrophic. 40 normotrophic unimpaired fetuses of the same gestational age served as a control group. The average duration of the examination period was 70 minutes. The fetal movement and acceleration behaviours did not differ between the normotrophic fetuses of the risk group and those of the control group. The hypotrophic fetuses from the risk group, however, had significantly lower fetal body and respiratory activities than the normotrophic fetuses from this group. The same holds true for the degrees of heart rate activity. It can be concluded that pregnancy-related hypertension as the only pregnancy complication does not have a measurable influence on fetal movement and acceleration behaviours. This is true for both treated and untreated pregnancy-related hypertensions. The severity of pregnancy-related hypertension is not primarily reflected in changes of fetal movement and acceleration behaviours, either. This means that the parameters presented are not suited to prognosticate the effects of pregnancy-related hypertension on the fetus a priori. The situation becomes quite different if in addition to pregnancy-related hypertension some intrauterine fetal growth retardation develops. In this case, the fetus indicates its impairment by increasingly impaired movement and heart rate activities as a consequence of chronic oxygen deficiency.

Female↗
PubMed1991

Radioimmuno positron emission tomography with monoclonal antibodies: a new approach to quantifying in vivo tumour concentration and biodistribution for radioimmunotherapy.

Radioimmunodetection of tumours with monoclonal antibodies is becoming an established procedure. Positron emission tomography (PET) shows better resolution than normal gamma camera single photon emission tomography and can provide more precise quantitative data. Thus, in the present study, these powerful methods have been combined to perform radioimmuno PET (RI-PET). Monoclonal antibodies directed against carcinoembryonic antigen (CEA) an IgG, its F(ab')2 and a mouse-human chimeric IgG derived from it were labelled with 124I, a positron-emitting radionuclide with a convenient physical half-life of four days. Mice, xenografted with a CEA-producing human colon carcinoma, were injected with the 124I-MAb and the tumours were visualized using PET. The concentrations of 124I in tumour and normal tissue were determined by both PET and direct radioactivity counting of the dissected animals, with very good agreement. To allow PET quantification, a procedure was established to account for the presence of radioactivity during the absorption correction measurement (transmission scan). Comparison of PET and tissue counting indicates that this novel combination of radioimmunolocalization and PET (RI-PET) will provide, in addition to more precise diagnosis, more accurate radiation dosimetry for radioimmunotherapy.

Animals↗
PubMed1990

Suramin alters phosphoinositide synthesis and inhibits growth factor receptor binding in HT-29 cells.

Initiation of cell growth frequently involves activation of growth factor receptor-coupled tyrosine kinases and stimulation of the phosphoinositide second messenger system. The antitrypanosomal and antifiliarial drug suramin has been shown to exert antiproliferative activities by inhibition of growth factor receptor binding. We therefore investigated the effect of suramin on epidermal growth factor receptor-binding characteristics and, additionally, searched for effects on basal or cholinergically stimulated phospholipid metabolism in HT-29 cells. Suramin caused a dose-dependent and noncompetitive inhibition of 125I-epidermal growth factor binding (concentration producing 50% inhibition, 44.2 micrograms/ml) but did not alter muscarinic receptor binding. Suramin did not affect the basal 32P incorporation into phosphoinositides at concentrations of less than 200 micrograms/ml suramin. In contrast, the carbachol-stimulated enhancement of 32P incorporation into phosphatidic acid, phosphatidylinositol, and polyphosphoinositides was reduced by 48-95% in the presence of 100 micrograms/ml suramin. Thus, phosphoinositide and diacylglycerol kinases involved in basal and receptor-stimulated phosphoinositide metabolism may be localized in different subcellular compartments, which can be dissociated by the use of suramin. Direct measurements of phosphatidylinositol kinase and diacylglycerol kinase activities showed a potent inhibition when treated with suramin. Suramin did not affect the stimulation of phospholipase C by carbachol, determined by release of [3H]inositol phosphates in [3H]myoinositol-prelabeled cells. Our data indicate that suramin potently inhibits phosphoinositide resynthesis under stimulated conditions. Additionally, we confirm the inhibitory effects of suramin on epidermal growth factor receptor binding in a human intestinal cell line. The inhibitory effects of suramin on phospholipid metabolism may play a role in the antiproliferative actions of this drug.

1-Phosphatidylinositol 4-Kinase↗
PubMed1990

Agonist-induced desensitization of cholinergically stimulated phosphoinositide breakdown is independent of endogenously activated protein kinase C in HT-29 human colon carcinoma cells.

Activation of M3 muscarinic receptors in HT-29 cells by carbachol rapidly increases polyphosphoinositide breakdown. Pretreatment of these cells with carbachol (0.1 mM) for 5 h completely inhibits the subsequent ability of carbachol to increase [3H]inositol monophosphate ([3H]InsP) accumulation, paralleled by a total loss of muscarinic binding sites. In contrast, protein kinase C (PK-C)-mediated desensitization by incubation with phorbol esters [PMA (phorbol 12-myristate 13-acetate)], leading to a time- and dose-dependent inhibition of cholinergically stimulated InsP release (95% inhibition after 4 h with 0.1 microM-PMA), is accompanied by only a 40% decrease in muscarinic receptor binding, which suggests an additional mechanism of negative-feedback control. Neither carbachol nor PMA pretreatment had any effect on receptor affinity. Incubation with carbachol for 15 min caused a small increase of membrane-associated PK-C activity (15% increase, P less than 0.05) as compared with the potency of phorbol esters (PMA) (3-4-fold increase, P less than 0.01). Long-term incubation (4-24 h) with PMA resulted in a complete down-regulation of cytosolic and particulate PK-C activity. Stimulation of InsP release by NaF (20 mM) was not affected after a pretreatment with phorbol esters or carbachol, demonstrating an intact function of G-protein and phospholipase-C (PL-C) at the effector side. Determination of PL-C activity in a liposomal system with [3H]PtdInsP2 as substrate, showed no change in PL-C activity after carbachol (13 h) and short-term PMA (2.5 h) pretreatment, whereas long-term preincubation with phorbol esters (13 h) caused a small but significant decrease in PL-C activity (19%, P less than 0.05). Our results indicate that agonist-induced desensitization of phosphoinositide turnover occurs predominantly at the receptor level, with a rapid loss of muscarinic receptors. Exogenous activation of PK-C by phorbol esters seems to dissociate the interaction between receptor and G-protein/PL-C, without major effects on total cellular PL-C activity.

Carbachol↗