PubMed Health⌕ Search

Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of white wine on esophageal peristalsis and acid clearance.

BACKGROUND: In a previous study it was demonstrated that white wine reduces the lower esophageal sphincter pressure and induces gastroesophageal reflux characterized by reflux episodes of long duration. In the present study, it was evaluated whether wine disturbs esophageal peristalsis and acid clearance. METHODS: Twelve healthy volunteers (7F, 23-37 years) received 300 ml white wine (8% vol/vol; WW), an ethanol solution (8% vol/vol; ET) or tap water (WA) together with a standardized meal in a random order. Acid clearance was tested by instillation of 15 ml 0.1 N HCI into the distal esophagus. The number of swallows (dry swallow every 30 sec) were counted until pH rose again above 5. Five wet swallows (5 ml) were applied to test primary peristalsis and five insufflations of 20 ml of air were performed to test secondary peristalsis. Each test was done immediately after and 60 min after ingestion of the beverages. RESULTS: A significantly higher number of swallows were needed to clear the esophagus immediately after ingestion of wine (P < 0.01; median number: WW 12; ET 8; WA 7) due to an increase in the frequency of failed, simultaneous, and low-amplitude contractions. The frequency of triggered secondary contractions was decreased (P < 0.02; WW 70%; ET 100%; WA 100%) and the latency between air injection and onset of secondary peristalsis was prolonged (P < 0.05; WW 9 sec; ET 7 sec; WA 6 sec) immediately after ingestion of white wine. Wet swallow induced primary peristalsis was not influenced by wine. No significant differences in the measured parameters were seen 60 min after ingestion of the three beverages. CONCLUSION: White wine disturbs temporarily esophageal clearance due to a disturbance of triggering secondary peristalsis and due to an increase in ineffective contractions. The ethanol content alone is not responsible for the effects of white wine on esophageal peristalsis and acid clearance.

Adult↗
PubMed2000

Effects of phorbol ester treatment on dibutyryl cyclic adenosine-5' monophosphate- and carbachol-stimulated aminopyrine accumulation in isolated rat parietal cells.

BACKGROUND: The functional role of the intracellular diacylglycerol/protein kinase C second-messenger pathway in the regulation of gastric acid secretion and the effects on the involved inositotrisphosphate/Ca2+/calmodulin system are not well understood, and contradictory data have been reported. We therefore evaluated the effects of phorbol ester treatment (tetradecanoylphorbol-12,13-acetate (TPA)) on dibutyryl cyclic adenosine-5' monophosphate (dBcAMP)- and carbachol-stimulated aminopyrine (AP) accumulation in comparison with intracellular alterations of the phospholipase C/inostol phosphate signal transduction pathway in isolated rat gastric parietal cells. METHODS: [14C]AP accumulation was determined as an indirect measure of gastric acid secretion. Inositolphosphate second-messenger activation was investigated with [3H]inositolmonophosphate release in [3H]-myoinositol prelabeled rat gastric parietal cells. RESULTS: TPA at a low concentration of 5 nM caused a small (45%) but significant increase in carbachol (0.1 mM)-stimulated AP accumulation, which was dose-dependently inhibited by higher concentrations of TPA with corresponding shifts in the dose-response curve for carbachol-stimulated AP accumulation. AP uptake stimulated by dBcAMP (0.1 mM) and the synergistic stimulatory effect induced by carbachol together with dBcAMP were inhibited by TPA at all concentrations investigated. In the presence of increasing concentrations of the calcium ionophore ionomycin (10(-8)-10(-5) M) TPA at 5 nM increased AP accumulation (AP ratio was 4.02 with 5 nM TPA versus 1.23 in the absence of TPA; P < 0.05), indicating that phorbol ester stimulates AP uptake in rat parietal cells. Simultaneous investigation of [14C]AP accumulation and [3H]inositol monophosphate release showed that inhibitory effects of TPA on carbachol- and carbachol plus dBcAMP-stimulated cells are mediated by an inhibition of the receptor/G-protein/phospholipase C interaction, leading to a reduction of inositolphosphate release. The costimulation of rat parietal cells with dBcAMP, ionomycin, and TPA (5 nM) did not reproduce the synergistic effects of carbachol together with dBcAMP on AP accumulation, suggesting that carbachol-stimulated AP uptake seems to be additionally mediated by a still unknown pathway independent of intracellular calcium release or protein kinase C activation.

Aminopyrine↗
PubMed2000

Effect of estradiol on insulin secreting INS-1 cells overexpressing estrogen receptors.

BACKGROUND: Estrogen has been shown to have profound effects on insulin and glucose metabolism in vivo. Indeed, estrogens were recently shown to modulate ion channel and secretory activities in endocrine cells. DESIGN AND METHODS: To investigate whether estrogenic influences are caused by direct effects on pancreatic beta-cells, we equipped INS-1 insulinoma cells with estrogen receptors and monitored insulin content and Ca(2+) fluxes as well as basal and stimulated insulin secretion upon different stimuli including glucose, the Ca(2+) ionophore ionomycin, the Ca(2+) channel agonist BayK8644, the protein kinase C activator TPA, and the adenylate cyclase activator forskolin. RESULTS AND CONCLUSION: Our data reveal that estradiol has no significant direct effect on proliferation rate, insulin content, basal and stimulated insulin output as well as Ca(2+) fluxes of insulin secreting cells in vitro, indicating that in vivo responses to estrogen on insulin and glucose metabolism result from indirect betacytotropic effects.

Calcium↗
PubMed1999

Anti-proliferative activity of protein kinase C in apical compartments of human colonic crypts: evidence for a less activated protein kinase C in small adenomas.

The protein-kinase-C (PKC) family of iso-enzymes regulates mitogenic signal transduction in colorectal-cell lines. Its function in human colonic mucosal proliferation is controversial. Our study investigated the role of PKC with regard to proliferation and changes of PKC iso-enzyme expression in colonic biopsies compared with small adenomas. In short-term tissue-culture experiments of colonic mucosal biopsies, we found reduced S-phase labeling in the 2 apical compartments of longitudinally sectioned crypts when PKC was activated by 200 nM of the phorbol ester TPA (n = 8). Thus, PKC inhibited growth of differentiated colonocytes which may influence cell homeostasis in colonic crypts. Furthermore, we have determined the expression of PKC alpha, -beta1, -beta2, -delta and -epsilon in colonic adenomas smaller than 1 cm in diameter of 18 patients and found a significant increase of PKC alpha in the cytosolic fraction and decreased membrane levels of PKC beta2 in adenomas compared to normal, neighboring mucosa while protein levels of PKC beta1, -delta and -epsilon were not altered. Moreover PKC delta but not PKC alpha mRNA expression was significantly lowered in adenoma tissue in 7 patients, as determined by ribonuclease-protection analysis. Changes in the regulation patterns of PKC isoforms suggest a decreased activation state of PKC even in small adenomas. This is compatible with an anti-proliferative function of PKC serving to protect mucosa from expanding mutated cells.

Adenoma↗
PubMed1999

Insulin resistance and impaired insulin secretion due to phosphofructo-1-kinase-deficiency in humans.

UNLABELLED: The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is usually explained as a combination of peripheral insulin resistance and impaired beta-cell function. Phosphofructo-1-kinase (PFK1) is a rate limiting enzyme in glycolysis, and its muscle subtype (PFK1-M) deficiency leads to an autosomal recessively inherited disorder known as glycogenosis type VII or Tarui's disease. It was evaluated whether PFK1-M deficiency leads to NIDDM in humans. A core family of four was evaluated for PFK1-M deficiency by DNA- and enzyme-activity-analyses. All members underwent oral and intravenous glucose tolerance test (oGTT/ivgtt), as well as an insulin sensitivity test (IST) using octreotide. RESULTS: Father (46 years, BMI 22.4 kg/m2) and older son (19 years, BMI 17.8 kg/m5) showed homozygous PFK1-M deficiency, while mother (47 years, BMI 28.4 kg/m5) and younger son (13 years, BMI 16.5 kg/m5) were shown to be heterozygously PFK1-M-deficient on enzyme activity levels. DNA analysis revealed an exon 5-missense-mutation at one allele of all four members, and an exon 22-frameshift-mutation at the other allele of the two homozygously affected individuals. By oGTT the father showed impaired glucose tolerance, and the mother clinical diabetes. By ivGTT both parents and the older son had a decreased first phase insulin secretion, and a diminished glucose disappearance rate. The IST showed marked insulin resistance in both parents and the older son, and moderate resistance in the younger son, previously not described. CONCLUSION: PFK1-M-deficiency leads to a metabolic state typical for early NIDDM in homozygously affected humans, especially concerning insulin resistance and loss of first phase beta-cell insulin secretion, and may contribute to the manifestation of NIDDM in a subgroup of patients.

Adult↗
PubMed1999

Dysmotility of the small intestine in achalasia.

During recent years there has been increasing evidence for extraoesophageal dysfunction in achalasia. The aim was to investigate whether motility of the small intestine is abnormal in achalasia. Thirteen patients (eight men, five women) aged 52 (33-85) years were studied. They had all previously undergone treatment with pneumatic balloon dilatation and were free of dysphagia when examined. Ambulatory 24-h motility was recorded in the upper jejunum under standardized caloric intake with a digital datalogger and catheter-mounted pressure transducers located beyond the ligament of Treitz. Visual analysis was performed by two observers and data underwent quantitative analysis of phasic contractile events using a computer program. Normal values were obtained from 50 healthy controls. In the fasting state, a complete loss of cyclic MMC activity (n = 2), an abnormally prolonged phase II (n = 2) and disturbances in the aboral migration of phase III (n = 5) were observed. Postprandial motor response was absent (n = 2) or frequently showed a contraction frequency below the normal range (n = 5). Further abnormalities consisted in hypomotility during phase II (n = 3) and in a reduced frequency of migrating clustered contractions in the fasting (n = 2) or postprandial state (n = 2). In addition, motor events not present in any healthy subject, giant migrating contractions (n = 5), retrograde clustered contractions (n = 6) and repetitive retrograde contractions (n = 3) were identified. Each patient exhibited findings out of the range of normal. Dysmotility of the proximal small intestine is present in achalasia.

Adult↗
PubMed1999

Ca2+/calmodulin-dependent protein kinase II isoenzymes gamma and delta are both present in H+/K+-ATPase-containing rabbit gastric tubulovesicles.

Ca2+/calmodulin-dependent protein kinase II is thought to participate in M3 muscarinic receptor-mediated acid secretion in gastric parietal cells. During acid secretion tubulovesicles carrying H+/K+-ATPase fuse with the apical membrane. We localized Ca2+/calmodulin-dependent protein kinase II from highly purified rabbit gastric tubulovesicles using Ca2+/calmodulin-dependent protein kinase II isoform-specific antibodies, in vitro phosphorylation and pharmacological inhibition of Ca2+/calmodulin-dependent protein kinase II activity by the potent Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62. The presence of Ca2+/calmodulin-dependent protein kinase II in tubulovesicles was shown by immunoblot detection of both Ca2+/calmodulin-dependent protein kinase II-gamma (54 kDa) and Ca2+/calmodulin-dependent protein kinase II-delta (56.5 kDa). The immunoprecipitated Ca2+/calmodulin-dependent protein kinase II from tubulovesicles showed Ca2+/calmodulin-dependent protein kinase activity by phosphorylating autocamtide-II, a specific synthetic Ca2+/calmodulin-dependent protein kinase II substrate. KN-62 inhibited the in vitro autophosphorylation of tubulovesicle-associated Ca2+/calmodulin-dependent protein kinase II (IC50 = 11 nM). During the search for potential Ca2+/calmodulin-dependent protein kinase II substrates we identified different proteins associated with tubulovesicles, such as synaptophysin and beta-tubulin immunoreactivity, which were identified using specific antibodies. These targets are known to participate in intracellular membrane traffic. Ca2+/calmodulin-dependent protein kinase II is thought to play an important role in regulating tubulovesicular motor activity and therefore in acid secretion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Deficient activation and different expression of transforming growth factor-beta isoforms in active proliferative diabetic retinopathy and neovascular eye disease.

An increased expression and secretion of angiogenic growth factors was proposed to occur in proliferative diabetic retinopathy and other neovascularizing retinal diseases. However, a loss of anti-angiogenic factors also might promote retinal neovascularization. Therefore we investigated the active and latent vitreous levels of the subtypes of the endothelial anti-mitogen transforming growth factor-beta in vitreous of 58 patients. Four groups of patients were compared: Controls without retinal hypoxia, patients with quiescent and active proliferative diabetic retinopathy (PDR), and patients with severe retinal hypoxia resulting in rubeosis iridis. Whereas the amount of total TGF-beta in the four groups did not differ significantly, latent TGF-beta isoform expression showed complex alterations in ocular vitreous. Levels of active TGF-beta of patients with active PDR (79.5 +/- 28 pg/ml; n = 8) were decreased to 20% of the control levels (378 +/- 55 pg/ml; n = 12; p = 0.0005) and 25% of the mean concentration in quiescent PDR (346 +/- 64 pg/ml; n = 9; p = 0.0021). Levels in rubeosis (52 +/- 10 pg/ml; n = 10) did not differ significantly from those found in active PDR but were decreased to 15% of those in patients with quiescent PDR (p = 0.0004). Furthermore a highly significant inverse correlation between active TGF-beta and alpha2-antiplasmin, a liver produced inhibitor of the activation of TGF-beta by plasmin was noted (r = -0.59; n = 28; p = 0.001). We conclude that deficient activation of TGF-beta occurs in active proliferative diabetic retinopathy and in hypoxic angiogenesis most likely as a consequence of a blood retina barrier breakdown and influx of alpha2-antiplasmin from serum. The disinhibition of endothelial cell proliferation may be a central component in the process of neovascularization.

Aged↗
PubMed1999

Effect of low and high fat meals on lower esophageal sphincter motility and gastroesophageal reflux in healthy subjects.

OBJECTIVE: The reported effects of fatty meals on lower esophageal sphincter pressure (LESP) and gastroesophageal reflux (GER) are controversial. Therefore, the aim of the present study was to reevaluate the effect of isocaloric and isovolumetric low and high fat meals on LESP and GER. METHODS: Twelve healthy volunteers (six women, six men, 19 to 31 yr) received an isocaloric (842 kcal) solid-liquid (310 ml with 260 kcal) meal with either a low (10% fat, 14% proteins, 76% carbohydrates) or a high fat content (50% fat, 18% proteins, 32% carbohydrates) in a randomized, double-blinded fashion. The nutritional composition was identical for the solid and liquid part of the meals. In the first post-prandial hour LESP was recorded continuously using a Dent sleeve, and esophageal pH measurement was performed for 3 h postprandially with a glass electrode. We calculated the mean LESP, the frequency of transient LES relaxations (TLESR) and of reflux episodes (RE), the percentage of TLESR with GER, and the fraction time pH <4. RESULTS: For all parameters measured no difference was observed between the low and the high fat meal. Mean LESP amounted to a median of 10.7 mm Hg (range, 7.3 to 15.1 mm Hg) after the low fat meal and to 11.1 mm Hg (5.2 to 16.3 mm Hg) after the high fat meal. The frequency of TLESR (n/1 h) rated to 9 (5 to 13) and 8 (4 to 14), and of RE (n/3 h) to 12 (3 to 22) and 11 (1 to 30). The percentage of TLESR with GER were 37% (0 to 100) and 30% (0 to 78). The fraction time pH <4 amounted to 2.3% (0.2 to 23.7) and 1.8% (0.1 to 28.8) after the low and high fat meal, respectively. CONCLUSIONS: In healthy volunteers no difference in post-prandial LESP and GER was seen after a high fat meal compared with an isocaloric and isovolumetric low fat meal. Our results suggest that it is inappropriate to advise GER patients to reduce the fat content of their meals for symptom relief.

Adult↗
PubMed1999

Deficiency of phosphofructo-1-kinase/muscle subtype in humans is associated with impairment of insulin secretory oscillations.

In healthy humans, insulin is secreted in an oscillatory manner. While the underlying mechanisms generating these oscillations are not fully established, increasing evidence suggests a central role for phosphofructo-1-kinase/muscle subtype (PFK1-M), which also serves as the predominantly active PFK1 subtype in the pancreatic beta-cell. The fact that normal oscillatory secretion is impaired in subjects with impaired glucose tolerance and healthy relatives of patients with type 2 diabetes suggests that this defect may be involved in the secretory dysfunction. To evaluate a possible link between inherited PFK1-M deficiency in humans (Tarui's disease or glycogenosis type VII) and altered insulin oscillations, in vivo studies were performed. We determined basal insulin oscillations during 2 h of frequent plasma sampling in two related teen-aged individuals with homozygous and heterozygous PFK1-M deficiency compared with nondeficient, unrelated control subjects. As predicted by the underlying hypothesis, normal oscillations in insulin secretion were completely abolished in the individual with homozygous deficiency of PFK1-M and significantly impaired in the heterozygous individual, as shown by spectral density and autocorrelation analyses. Thus, deficiency of PFK1-M subtype in humans appears to be associated with an impaired oscillatory insulin secretion pattern and may contribute to the commonly observed secretion defects occurring in type 2 diabetes.

Adult↗
PubMed1998

[Continuous blood glucose monitoring: the acute effect of acarbose on blood glucose variations].

BACKGROUND: Acarbose, a pseudo-tetrasaccharid, inhibits intestinal alpha-glucosidases, effects a reduction of postprandial hyperglycemia and is particularly used in the treatment of patients with type-2 diabetes mellitus. The aim of the study is to analyse by a continuous blood glucose measurement the acute effect of acarbose after a carbohydrate loading and during a 12 hours period. PATIENTS AND METHODS: We examined 10 patients with type-2 diabetes mellitus (mean age 59.2 +/- 3.79, HbA1 9.2 +/- 0.26%) treated with sulfonylureas and/or insulin after a carbohydrate meal and 12 hours during daytime, to test whether the first application of acarbose influences the mean blood glucose or the blood glucose amplitudes. Four measurements were enrolled using a portable continuous blood glucose sensor (Glucosensor, unitec Ulm). A measurement after a carbohydrate loading (Fresubin, 500 kcal, 69 g carbohydrate) with 100 mg acarbose (Glucobay) was followed by a 12-hour measurement during daytime with 3 x 100 mg acarbose and standard diet. These measurements were repeated without acarbose. RESULTS: After a carbohydrate loading, the mean blood glucose level (AUC 44,320 +/- 10,660 with acarbose vs. 61,390 +/- 12,590 without acarbose; mean + SD; p = 0.004) decreased by 28%. During daytime blood glucose levels were not significantly decreased (165.7 +/- 50.3 mg/dl vs 183.7 + 67.4 mg/dl; p = 0.1) although the postprandial blood glucose amplitudes after the 3 meals were reduced significantly (85.90 +/- 24.6 mg/dl vs 106.5 +/- 20.5 mg/dl; p = 0.02). CONCLUSIONS: Continuous blood glucose monitoring indicated that acarbose diminished mean blood glucose levels after a carbohydrate loading in patients with type-2 diabetes mellitus, but not during 12 hours of standard diet, although blood glucose amplitudes decreased. Long-term improvements of metabolism by acarbose may therefore be related to the reduction of blood glucose amplitudes which is likely to reduce toxic effects of glucose on islet cell function.

Acarbose↗
PubMed1998

Obesity associated with a mutation in a genetic regulator of adipocyte differentiation.

BACKGROUND: There is increasing evidence of genetic factors leading to obesity, but the exact genes involved have not been defined. Peroxisome-proliferator-activated receptor gamma2 (PPARgamma2) is a transcription factor that has a key role in adipocyte differentiation, and therefore mutations of the gene for this factor might predispose people to obesity. METHODS: We studied 358 unrelated German subjects, including 121 obese subjects (defined as those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of more than 29). We evaluated these subjects for mutations in the gene for PPARgamma2 at or near a site of serine phosphorylation at position 114 that negatively regulates the transcriptional activity of the protein, using a polymerase-chain-reaction-based assay coupled with specific endonuclease digestion. The activity of the mutation identified was analyzed by retroviral transfection and overexpression in murine fibroblasts. RESULTS: Four of the 121 obese subjects had a missense mutation in the gene for PPARgamma2 that resulted in the conversion of proline to glutamine at position 115, as compared with none of the 237 subjects of normal weight (P=0.01). All the subjects with the mutant allele were markedly obese, with body-mass-index values ranging from 37.9 to 47.3, as compared with a mean of 33.6 in the other obese subjects. Overexpression of the mutant gene in murine fibroblasts led to the production of a protein in which the phosphorylation of serine at position 114 was defective, as well as to accelerated differentiation of the cells into adipocytes and greater cellular accumulation of triglyceride than with the wild-type PPARgamma2. These effects were similar to those of an in vitro mutation created directly at the Ser114 phosphorylation site. CONCLUSIONS: A Pro115Gln mutation in PPARgamma2 accelerates the differentiation of adipocytes and may cause obesity.

Adipocytes↗
PubMed1998

Effects of anticonvulsive drugs on pentylenetetrazol kindling and long-term potentiation in freely moving rats.

Drugs with anticonvulsive properties and different mechanisms of action were compared for their influence on long-term potentiation and pentylenetetrazol kindling in freely moving animals. Rats were chronically implanted with a stimulation electrode in the angular bundle and a recording electrode in the dentate gyrus. Field potentials in the dentate gyrus were elicited and long-term potentiation was induced by stimulation of the perforant pathway. The clinically used drugs or the potentially anticonvulsive drugs, diphenylhydantoin (50 mg/kg), diazepam (0.5 mg/kg), pentobarbital (10 mg/kg), dizocilpine (MK 801, 0.2 mg/kg) and CGP 43487 (2-amino-4-methyl-5-phosphono-3-pentenoic acid-carboxyethylester, 10 mg/kg), were injected before tetanization. In behavioural experiments pentylenetetrazol kindling was performed with pretreatment with the substances in dosages indicated above (except MK 801, 0.3 mg/kg). Field potentials recorded in the interval between drug administration and tetanization were influenced only by diphenylhydantoin which enhanced the population spike amplitude to 128% of control values. However, the substances showed different effects on long-term potentiation. MK 801, CGP 43487 and pentobarbital depressed potentiation; diazepam was without effect. Diphenylhydantoin had a minor influence on induction but significantly impaired maintenance of long-term potentiation. Furthermore, MK 801, CGP 43487, diazepam and pentobarbital differentially depressed kindling whereas phenytoin only slightly influenced it. The consequences as to hypothetical common cellular mechanisms for kindling development and long-term potentiation are discussed.

Animals↗
PubMed1998

Purification and characterization of a Ca2+/calmodulin-dependent protein kinase II from hog gastric mucosa using a protein-protein affinity chromatographic technique.

A peripheral member of the Ca2+/calmodulin-dependent protein kinase II (CaMkinase II) group has been purified from hog gastric mucosa with the use of a novel affinity-chromatographic step. For the well known neural isotypes of CaMkinase II, it is proposed that the subunits form holoenzymes through a specific domain at the C-terminus called the 'association domain'. We immobilized a bacterially expressed association domain from CaMkinase II-delta-2 and used it as an affinity column. This matrix was used as the last step in a sequential enzyme purification procedure from hog gastric mucosa and yielded a homogeneous CaMkinase II which showed the typical physical and enzymatic properties of CaMkinase II. The enzyme activity showed a dependence on Ca2+ and calmodulin (apparent K0.5 = 2.7 microM and K0.5 = 0.02 microM, respectively). We found a subunit molecular mass of 61 kDa. An apparent native molecular mass of 310 kDa was calculated. The Stokes radius and the sedimentation coefficient were 6.7 nm and 11.2 S, respectively. Moreover, the isolated CaMkinase II was very well inhibited by the CaMkinase-II-specific inhibitors KN-62 (Ki = 0.52 nM) and KT5926 (Ki = 0.79 nM). The phosphorylation of several substrates revealed its multifunctionality. The purified CaMkinase II had an apparent Km for Mg-ATP of 24.0 microM and for autocamtide-II of 0.62 microM. CaMkinase II is considered as a strong candidate for regulating vesicle released quanta such as acid, neurotransmitters or insulin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Epidermal-growth-factor receptor correlates negatively with cell density in cervical squamous epithelium and is down-regulated in cancers of the human uterus.

The role of the epidermal-growth-factor receptor (EGFR) in cervical cancer is controversial, due to technical difficulties in localizing or in quantifying EGFR by homogenate assays or immunohistochemistry. Our autoradiographic approach, in combination with morphometry, allowed cell-type-specific quantification of EGFR, leading to the following observations: (i) In normal cervical epithelium, EGFR levels per cell were high in non-dividing squamous cells of the upper layers of normal epithelium, where a mitogenic function of these EGFRs can be excluded. (ii) In contrast to earlier findings in tissue homogenates, but consistent with our observation in normal cervical epithelium that cells of the proliferating strata (basal and parabasal cells) express intermediate and comparatively reduced levels of EGFR per cell, cervical cancers displayed a significant reduction both of specific EGF binding and of EGFR levels per cell as compared with normal epithelium. (iii) A significant negative correlation of cell density and EGFR number per cell was obtained. In normal cervical epithelium, cervical intra-epithelial neoplasia and invasive cervical cancer (p = 0.002). This negative correlation was most evident in normal epithelium, where large changes of cell density occur within one slide (p < 0.001). (iv) Specific EGF-binding was also significantly reduced in endometrial cancers when compared with normal endometrium. It is proposed that in uterine tissues low or intermediate levels of EGFR do not exclude their function as mediators of cell proliferation.

Autoradiography↗
PubMed1998

The role of osmolality in the absorption of a nutrient solution.

BACKGROUND: Loss of water during enteral nutrition following massive intestinal resection may be severe. Low osmolality of oral rehydration solutions has recently been shown to mediate an increase in water absorption. AIM: To evaluate the effect of osmolality of a nutrient solution on the intraluminal duodenojejunal water flow, and the net absorption rates of total nitrogen and carbohydrate. METHODS: Eight healthy volunteers with a mean age of 27 (range 25-29) years participated in the study. Enteral nutrition (17% protein, 59% carbohydrate, 24% lipid plus 5 g/L PEG 4000) was infused (5 mL/min 2.64 kcal/min) into the descending duodenum either as a hypotonic (160 mOsmol/kg) or as an isotonic solution in a random order. Intestinal samples were aspirated 20 and 45 cm distally to the infusion point. RESULTS: Intraluminal water flow rates were significantly lower with the hypotonic solution than with the isotonic solution, both in the duodenum (4.9 +/- 0.3 vs. 6.7 +/- 0.5 mL/min; P < 0.02) and the upper jejunum (3.0 +/- 0.1 vs. 3.9 +/- 0.2 mL/min; P < 0.005). The net absorption rates of total nitrogen and carbohydrate were similar with both solutions. CONCLUSION: Low osmolality of a nutrient solution decreases intraluminal water flow rates in the upper intestine without affecting the absorption rates of total nitrogen and carbohydrate. Compared with an isotonic solution, the use of a hypotonic solution might lower the water loss in patients with extensive short bowel intestinal resection.

Adult↗