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Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

At least 19 recordsLinked to original sources

White wine and beer induce gastro-oesophageal reflux in patients with reflux disease.

BACKGROUND: An induction of gastro-oesophageal reflux has been reported after ingestion of alcoholic beverages in healthy volunteers. However, it is unknown whether reflux in gastro-oesophageal reflux disease patients will be enhanced by the ingestion of alcoholic beverages. AIM: To investigate the effects of wine and beer on postprandial reflux in reflux patients. METHODS: Twenty-five patients (reflux oesophagitis 15, non-erosive reflux disease 10; 18 men and seven women) drank 300-mL white wine (n = 17), 500-mL beer (n = 8), or identical amounts of tap water (controls) together with a standardized meal in a randomized order. pH-measurement was carried out during three postprandial hours by pH-metry and the percentage of time pH < 4 was calculated. RESULTS: Both alcoholic beverages increased reflux compared with water [wine 23% (median), water 12%, P < 0.01; beer 25%, water 11%, P < 0.05]. Between wine and beer, no difference in reflux induction was obtained. The reflux induction was seen in patients with (23%, P < 0.01) and without reflux oesophagitis (22%, P < 0.05) and in both sexes (women 23%, men 25%, P < 0.05 each). CONCLUSIONS: Ingestion of commonly consumed alcoholic beverages such as wine and beer induces gastro-oesophageal reflux in gastro-oesophageal reflux disease patients. Therefore, these patients should be advised to avoid the intake of large amounts (> or = 300 mL) of these beverages.

Adult↗

Preliminary evidence of FABP2 A54T polymorphism associated with reduced risk of type 2 diabetes and obesity in women from a German cohort.

The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95 %CI: 0.07 - 0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA (1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study.

Adult↗

Association between functional FABP2 promoter haplotype and type 2 diabetes.

Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb 5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95 % CI = 0.28 - 0.87, p < 0.05) and additional covariates (OR = 0.42, 95 % CI 0.22 - 0.81, p < 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95 % CI 0.06 - 0.49, p < 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11 - 0.94, p < 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA (1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner.

Adult↗

Semihard scattering unraveled from collective dynamics by two-pion azimuthal correlations in 158A GeV/c Pb+Au collisions.

Elliptic flow and two-particle azimuthal correlations of charged hadrons and high-p(T) pions (p(T)>1 GeV/c) have been measured close to midrapidity in 158A GeV/c Pb+Au collisions by the CERES experiment. Elliptic flow (v(2)) rises linearly with p(T) to a value of about 10% at 2 GeV/c. Beyond p(T) approximately 1.5 GeV/c, the slope decreases considerably, possibly indicating a saturation of v(2) at high p(T). Two-pion azimuthal anisotropies for p(T)>1.2 GeV/c exceed the elliptic flow values by about 60% in midcentral collisions. These nonflow contributions are attributed to nearside and back-to-back jetlike correlations, the latter exhibiting centrality dependent broadening.

Journal Article↗

Enhanced production of low-mass electron-positron pairs in 40-AGeV Pb-Au collisions at the CERN SPS.

We report on first measurements of low-mass electron-positron pairs in Pb-Au collisions at the CERN SPS beam energy of 40 AGeV. The observed pair yield integrated over the range of invariant masses 0.2 e(+)e(-) annihilation with a modified rho propagator. They may be linked to chiral symmetry restoration and support the notion that the in-medium modifications of the rho are more driven by baryon density than by temperature.

Journal Article↗

Universal pion freeze-out in heavy-ion collisions.

Based on an evaluation of data on pion interferometry and on particle yields at midrapidity, we propose a universal condition for thermal freeze-out of pions in heavy-ion collisions. We show that freeze-out occurs when the mean free path of pions lambda(f) reaches a value of about 1 fm, which is much smaller than the spatial extent of the system at freeze-out. This critical mean free path is independent of the centrality of the collision and beam energy from the Alternating Gradient Synchrotron to the Relativistic Heavy Ion Collider.

Journal Article↗

Differential ontogeny of GABA(B)-receptor-mediated pre- and postsynaptic modulation of GABA and glycine transmission in respiratory rhythm-generating network in mouse.

Rhythm generation in mature respiratory networks is influenced strongly by synaptic inhibition. In early neonates, GABA(A)-receptor- and glycine-receptor-mediated inhibition is not present, thus the question arises as to whether GABA(B)-receptor-mediated inhibition plays an important role. Using brainstem slices of neonatal mice (postnatal day, P0-P15), we analysed the role of GABA(B)-mediated modulation of GABA and glycine synaptic transmission in the respiratory network. Blockade of GABA uptake by nipecotic acid (0.25-2 mM) reduced the respiratory frequency. This reduction was prevented by the selective GABA(B) receptor antagonist CGP55845A (CGP) alone at P0-P3, but by bicuculline as well as CGP at P7-P15. Blockade of GABA(B) receptors by CGP increased the respiratory frequency at P0-P3, whereas it caused a reduction of frequency in older animals. The effect of CGP on respiratory frequency was diminished in the presence of bicuculline and strychnine in older but not in younger animals. The relative contribution of GABA(B)-receptor-mediated pre- and postsynaptic modulation was examined by analysing the effect of GABA(B) receptors on spontaneous and miniature IPSCs. In younger animals (P0-P3), the GABA(B) receptor agonist baclofen had no detectable effect on IPSC frequency, but caused a significant decrease in the amplitude. In older animals (P7-P15), baclofen decreased both the frequency and amplitude of spontaneous and miniature IPSCs. These results demonstrate that GABA(B)-receptor-mediated postsynaptic modulation plays an important role in the respiratory network from P0 on. GABA(B)-receptor-mediated presynaptic modulation develops with a longer postnatal latency, and becomes predominant within the first postnatal week.

Aging↗

[SSCP (single strand conformation polymorphism) analysis for detection of point mutations. A technique and its limits exemplified by dominantly inherited forms of diabetes (MODY)].

BACKGROUND: Molecular biological techniques of mutation detection become more and more a focus of interest in clinical medicine because the responsible genes are now known for an increasing number of diseases and the detection is essential to enable reliable predictions and to design individual therapies. Therefore the SSCP (Single Strand Conformation Polymorphism) analysis is one of the most commonly applied methods in detection of point mutations. SSCP ANALYSIS: The use of SSCP for detection of the pathogenic mutations of MODY (Maturity Onset Diabetes in the Young) is described as an example. Handling, efficiency and costs are critically analyzed. In a blind test, this method was only partly suitable for reliable analysis. Particularly diseases without a distinct hotspot and with a widespread distribution pattern of mutations throughout the coding sequence require sequencing as the gold standard.

DNA Mutational Analysis↗

[Clinical value of urinary pyridinium crosslinks as osteoporosis markers: evaluation of a population survey of vertebral osteoporosis].

BACKGROUND: The diagnostic value of biochemical parameters of bone turnover for the diagnosis of osteoporosis is open to discussion. We investigated whether the determination of crosslinks, bone type I collagen degradation products, correctly identifies osteoporotic subjects. PATIENTS AND METHOD: In a sample of 370 individuals recruited at random within a population survey of vertebral osteoporosis, urinary concentration of total pyridinoline and desoxypyridinoline were determined by HPLC. Standardized lateral X-rays of the thoracic and lumbar spine were taken and evaluated morphometrically using the method described by Eastell-Melton. RESULTS: Crosslink excretion was significantly higher in female but not in male individuals with vertebral deformities as defined by Eastell. The specificity of these biochemical parameters with regard to radiological osteoporotic alterations was 76-81%, but the sensitivity was 32.4-42.9% only. CONCLUSION: Pyridinoline and desoxypyridinoline reflect the process of bone degradation which leads to vertebral deformity. Crosslinks are specific markers of bone resorption and provide a valid parameter in the diagnosis of osteoporosis. The low sensitivity indicates that the measurement of pyridinoline and desoxypyridinoline is less suitable for screening purposes, but may be useful in confirming presence or extent of osteoporosis.

Aged↗

Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts.

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.

Antigens, CD↗

Effect of caloric density of a meal on lower oesophageal sphincter motility and gastro-oesophageal reflux in healthy subjects.

BACKGROUND: Patients with gastro-oesophageal reflux disease are advised to avoid the ingestion of large meals. In healthy volunteers, a relationship between the amount of postprandial gastro-oesophageal reflux and the volume of a liquid meal has been demonstrated. AIM: To evaluate whether the amount of postprandial gastro-oesophageal reflux is also related to the calorie content of a meal, a second parameter that will be reduced by avoidance of the ingestion of large meals. METHODS: Twelve healthy volunteers (six female, 19-31 years) received two solid-liquid meals with either 842 kcal (solid 582 kcal, liquid 260 kcal) or 582 kcal (31% reduction) in a randomized order. The nutritional components (10% fat, 76% carbohydrates, 14% protein) and the volume of the meals were identical in both meals. The lower oesophageal sphincter pressure was measured continuously in the first postprandial hour with a Dent sleeve, and pH-metry was performed for 3 h postprandially with a glass electrode in the distal oesophagus. Blinded to the type of ingested meal, we calculated the mean lower oesophageal sphincter pressure, the frequency of transient lower oesophageal sphincter relaxations, the number of reflux episodes, and the fraction of time for which pH < 4. RESULTS: A similar decrease in lower oesophageal sphincter pressure was observed after ingestion of the high calorie meal (median 10.9 mmHg, range 4.8-16.7 mmHg) and low calorie meal (median 9.9 mmHg, range 3.9-18.4 mmHg). No difference in the number of transient lower oesophageal sphincter relaxations (high calorie: median 9 per hour, range 5-13 per hour; low calorie: median 7 per hour, range 0-14 per hour) and of reflux episodes (high calorie: median 12 in 3 h, range 3-22 in 3 h; low calorie: median 12 in 3 h, range 3-30 in 3 h) was registered after intake of both types of meal. Additionally, no difference was identified regarding the fraction of time for which pH < 4 between the high calorie (mean 2.3%, 0.2-23.7%) and low calorie meal (3.3%, 0.5-17.8%). CONCLUSION: Reducing the caloric density of a meal neither influences postprandial lower oesophageal sphincter pressure nor decreases gastro-oesophageal reflux in healthy volunteers. Thus, the amount of gastro-oesophageal reflux induced by ingestion of a meal seems to depend on the volume but not on the caloric density of a meal.

Adult↗

Phase III of the migrating motor complex: associated with endogenous xenin plasma peaks and induced by exogenous xenin.

Xenin, a recently discovered peptide produced by specific endocrine cells of the duodenal mucosa, has shown exocrine, endocrine and motility effects in the gastroenteropancreatic system in animal experiments. The aim of the present investigation was to study the role of xenin in the regulation of duodenojejunal motility of humans. Twenty-nine healthy volunteers from the hospital staff gave informed consent to participate in this investigation. In 20 volunteers, we determined plasma concentrations of immunoreactive xenin at 15 min intervals over a mean time period of 8 h fasting and recorded the interdigestive motor activity of the duodenojejunum. In a double-blind randomized crossover study on other nine subjects, synthetic xenin in a dose of 4 pmol kg-1 min-1 or placebo was infused for 10 min intravenously in the interdigestive period and postprandially after a liquid meal. Duodenojejunal motility was recorded simultaneously. Predefined interdigestive xenin plasma peaks were found to be significantly associated with the phases III of the migrating motor complex. In the interdigestive period, xenin induced a premature phase III activity in each volunteer; this was followed by a second phase III in five out of nine subjects. In the postprandial state, xenin significantly increased contraction frequency and the percentage of aborally propagated contractions. These findings suggest a role of the peptide hormone xenin in modulating interdigestive and postprandial duodenojejunal motility in humans.

Adult↗

Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa.

BACKGROUND: Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regulative role of the four other widely expressed epidermal growth factor receptor ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in the gastric mucosa. METHODS: Nineteen patients with Helicobacter pylori-positive gastritis and 32 healthy controls were investigated. Mucosal mRNA expression of EGF receptor ligands was determined by quantitative PCR before and after H. pylori eradication. PCR products were analyzed by soft laser scanning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [125I] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression. RESULTS: Antral and oxyntic biopsies showed strong mRNA expressions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in H. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastritis was associated with decreased antral EGF receptor binding compared to healthy controls, possibly reflecting reduced autoinduction. Immunohistochemical analyses localized TGF-alpha in the cytoplasma of gastric epithelial cells and revealed its increased expression after H. pylori eradication. CONCLUSIONS: The data presented suggest that amphiregulin, heparin binding EGF and TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. pylori infection apparently suppresses their mRNA as well as receptor expression that is reversed by H. pylori eradication. This deficiency of the gastroprotective EGF system may contribute to the gastric pathogenicity of H. pylori infection.

Adult↗

Copurification of two holoenzyme-forming Calcium/Calmodulin-dependent protein kinase II isoforms as holoenzyme from porcine stomach.

Gastric acid secretion is conveyed by different signal transduction pathways, among these being the muscarinic receptor M(3)-mediated acid secretion. There is some evidence that CaMkinase II is involved in the acetylcholine-conveyed acid release. The apparent CaMkinase II-isoenzymes gamma and delta were purified as a holoenzyme from homogenate of pig gastric mucosa to apparent homogeneity. The chromatographical steps comprised cationic exchanger chromatography, calmodulin affinity chromatography, anionic exchanger chromatography, and gel filtration. The CaMkinase II showed an apparent molecular mass of 332 +/- 17.3 kDa composed of 59- and 61-kDa subunits. The latter was characterized by a polyclonal antibody directed against CaMkinase II-delta. The purified CaMkinase II showed autophosphorylation and Ca(2+)/calmodulin-dependent activation (K(0. 5) = 5 nM). Moreover, the enzyme showed inhibition by the potent CaMkinase II inhibitor KN-62 in a dose-dependent manner. Addition of purified CaMkinase II inhibits the endogenous phosphorylation of a 105-kDa protein in the NaCl/Nonidet P-40 soluble fraction of the microsomal fraction of pig gastric mucosa. Our results suggest that CaMkinase II may regulate other protein kinases or phosphoprotein phosphatases, possibly by controlling acid production.

Animals↗

Activation of transforming growth factor-beta1 in diabetic kidney disease.

Recent data have suggested that certain growth factors and cytokines are involved in the development of diabetic nephropathy. The aim of this study was to investigate whether circulating transforming growth factor beta 1 (TGF-beta1) and tumor necrosis factor alpha (TNF-alpha) are associated with diabetic kidney disease. Serum levels of active and total TGF-beta1 and TNF-alpha were measured in type 2 diabetic patients with nephropathy (n = 23) or without (n = 35) and normoglycemic controls (n = 12). Serum levels of circulating active TGF-beta1 were significantly higher in patients with diabetic nephropathy (0.43 +/- 0.06 ng x mL(-1)) compared with diabetic patients without renal involvement (0.23 +/- 0.03 ng x mL(-1), P = .002) and healthy controls (0.24 +/- 0.03 ng x mL(-1), P= .001), whereas the levels of total (active + latent) TGF-beta1 were not different between the subgroups. Active TGF-beta1 concentrations were correlated with urinary albumin excretion (r = .49, P < .003) and serum creatinine (r= .55, P < .01). Sera from patients with type 2 diabetes contained significantly more TNF-alpha than sera from normoglycemic controls (3.07 +/- 0.24 v 1.65 +/- 0.20 pg x mL(-1), P = .001). However, the comparison of serum TNF-alpha concentrations between microalbuminuric and normoalbuminuric diabetic patients showed no significant difference (3.21 +/- 0.28 v 2.97 +/- 0.34 pg x mL(-1), P = .12). In conclusion, type 2 diabetic patients with diabetic nephropathy exhibit increased activation of TGF-beta1, in serum, suggesting an association between circulating TGF-beta1 activity and the development of renal disease.

Aged↗

Spot glucose measurement in epidermal interstitial fluid--an alternative to capillary blood glucose estimation?

Capillary blood glucose estimation is an essential but inconvenient prerequisite in the current management of diabetes mellitus. Spot glucose measurement in epidermal interstitial fluid appears to be a promising alternative to capillary blood glucose estimation, and due to its near non-invasive properties it might be a tool for improving the lives of people with diabetes in the near future. The present status of epidermal interstitial fluid glucose determination, the first clinical results, and some open questions regarding this new technology are reviewed here.

Blood Glucose↗

Association of polycystic ovary syndrome with an interstitial deletion of the long arm of chromosome 11.

Several pathways have been implicated in the etiology of the polycystic ovary syndrome (PCOS). The observation of familial aggregation of PCOS is consistent with a genetic component of this disorder. We report on a 21-year-old woman with menstrual irregularity, hirsutism, elevated serum androgen levels and polycystic ovarian morphology on ultrasonography, meeting the diagnostic criteria of PCOS. A cytogenetic investigation was performed because of a congenital heart defect, craniofacial anomalies in infancy (quadricephaly with protruding forehead, flat nasal bridge, low set ears with attached earlobes, small mouth, high arched palate with submucous palatal cleft, retrognathia), broad neck, motor and speech developmental delay. Chromosomal analysis revealed an unbalanced interstitial deletion of one of the chromosomes 11 [del (11) (q21q23.1)]. Interstitial deletions of the long arm of chromosome 11 have been reported in at least 18 patients. Candidate genes for PCOS have not been suspected at this chromosomal location so far. Follistatin and CYP11A, the genes with the strongest evidence for linkage with PCOS, are located on chromosomes 5 and 15. In the chromosomal region deleted in our patient a progesterone receptor gene is located in band q22. Lowered progesterone receptor concentration is associated with retardation of endometrial development. A disturbance of the hypothalamic-pituitary gonadal axis, due to a reduction of hypothalamic and pituitary progesterone receptors might be a component in the etiology of PCOS.

Adult↗