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Biomedical subjects

A Imhof

Publications and source records attributed to A Imhof.

At least 19 recordsLinked to original sources
PubMed2003

Measurement of tidal breathing flow-volume loop indices in horses used for different sporting purposes with and without recurrent airway obstruction.

Tidal breathing flow-volume loop (TBFVL) indices in healthy horses and in horses suffering from mild and moderate to severe recurrent airway obstruction (RAO) were measured. In addition, the ability of these indices to differentiate healthy controls from horses with mild RAO by separating the horses according to their usage was investigated. The horses were assigned to three sporting categories: 1 Leisure horses; 2 Horses competing at events with a duration of more than five minutes (eventing, coaching and endurance); and 3 Horses competing at events with a duration of less than five minutes (dressage and show jumping). Flow-volume curves were recorded with an ultrasonic spirometer and TBFVL indices were calculated with specially dedicated software. The sporting usage of the horses had a significant effect on the differentiating ability of TBFVL indices in diagnosing different degrees of RAO. The index TIF50 differentiated control horses from horses with minor RAO in all sporting categories.

Airway Obstruction↗
PubMed2002

Differences in pulmonary functional indices derived from the single-breath diagram for CO2 (SBD-CO2) in horses related to age, sex and usage.

Although pulmonary function tests have been used to evaluate horses with clinically normal lungs and those with recurrent airway obstruction (RAO), comprehensive studies of equine respiratory function, considering factors such as sex, age and usage are not available. Studies on the influence of these factors on pulmonary function in healthy horses are required for interpretation of measurements made in those with respiratory disease. The study was performed with 63 warmblood horses and the status of their pulmonary health was evaluated by clinical examination. The functional aspect of pulmonary health was assessed by indices derived from the single-breath diagram for CO2 (SBD-CO2). Differences in pulmonary functional indices between the sexes, age groups and usage groups adjusted for pulmonary health were analysed with hierarchical linear models. It was shown that the effects on pulmonary function of age, sex and usage of a horse were significant and have to be considered when establishing the true pulmonary functional status of a horse suffering from RAO. The multivariate statistical model used included the covariates age, sex and sporting discipline of the horses and accounted for the complex, non-linear interactions between the different covariates.

Aging↗
PubMed2002

Validity of pulmonary function indices derived from the volumetric capnogram in horses with recurrent airway obstruction (RAO).

The objective of this study was to determine the accuracy with which pulmonary function indices derived from the volumetric capnogram can diagnose different degrees of recurrent airway obstruction (RAO) in 63 warmblood horses. The sensitivity, specificity, the area under the receiver operating curve (AUC), optimal cut-off values and predictive values of the indices were calculated. The results obtained have shown that there is no single index characterised by specificity and sensitivity to differentiate with an accuracy of >90 per cent between the different degrees of RAO compared to the clinical examination. The indices A(1)/A(2) and VD(alv)/ VT(alv) (AUC=0.55 and 0.53) appeared to have the highest relative sensitivity and specificity to differentiate between healthy horses and horses suffering from subclinical or minor RAO and the indices VD(phys)/ VT and VD(Bohr)/ VT between horses suffering from subclinical or minor RAO and horses with moderate to severe RAO (AUC=0.71 and 0.70). We do not consider it acceptable to use cut off values optimised for both maximal sensitivity and specificity, because a great number of horses would have been inappropriately classified.

Airway Obstruction↗
PubMed2002

Relationship between clinical signs and pulmonary function estimated by the single breath diagram for CO(2) (SBD-CO(2)) in horses with chronic obstructive pulmonary disease.

The pulmonary health of 66 horses was assessed by a clinical examination and simple supplementary diagnostic methods. Single breath diagrams for CO(2) (SBD-CO(2)) and derived lung function indices were used to determine pulmonary function. The clinical signs in different groups were related to the results of the lung function indices derived from the SBD-CO(2). In horses with moderate to severe chronic obstructive pulmonary disease (COPD), a significant relationship was found between the respiratory frequency and the ratio of Bohr's dead space to the tidal volume (VD(Bohr)/VT), and between the physiological dead space/tidal volume ratio (VD(phys)/VT) and the ratio of the alveolar dead space to the alveolar tidal volume (VD(alv)/VT(alv)), but no significant associations were found between the arterial oxygen tension (P(a)O(2)) and lung function indices derived from the SBD-CO(2). The occurrence of cough, the viscosity of tracheobronchial mucus and the amount of polynuclear neutrophils in tracheobronchial aspirates were significantly related to the expiratory tidal volume (VT), the total expired volume of CO(2) (VCO(2)), VD(Bohr)/VT, VD(phys)/VT and VD(alv)/VT(alv). We conclude that abnormal findings in these clinical parameters indicate a measurable ventilation and perfusion (V(A)/Q) mismatch which is reflected by increases in dead space, VD(Bohr)/VT and VD(phys)/VT as well as VD(alv)/VT(alv).

Animals↗
PubMed2002

Effect of inhalation of different mixtures of O(2) and CO(2) on retinal blood flow.

AIM: To determine the effects of various mixtures of O(2) and CO(2) on retinal blood flow in healthy subjects. METHODS: A randomised, double masked, four way crossover trial was carried out in 12 healthy male non-smoking subjects. Gas mixtures (100% O(2), 97.5% O(2) + 2.5% CO(2), 95% O(2) + 5% CO(2), and 92% O(2) + 8% CO(2)) were administered for 10 minutes each. Two non-invasive methods were used: laser Doppler velocimetry (LDV) for measurement of retinal blood velocity and fundus imaging with the Zeiss retinal vessel analyser (RVA) for the assessment of retinal vessel diameters. Arterial pH, pCO(2), and pO(2) were determined with an automatic blood gas analysis system. Retinal blood flow through a major temporal vein was calculated. RESULTS: Retinal blood velocity, retinal vessel diameter, and retinal blood flow decreased during all breathing periods (p <0.001 each). Administration of 92% O(2) + 8% CO(2) significantly increased SBP, MAP, and PR (p <0.001 each, versus baseline), whereas the other gas mixtures had little effect on systemic haemodynamics. Addition of 2.5%, 5%, and 8% CO(2) to oxygen caused a marked decrease in pH and an increase in pCO(2) (p <0.001 versus pure oxygen). CONCLUSIONS: Breathing of pure oxygen and oxygen in combination with carbon dioxide significantly decreases retinal blood flow. Based on these data the authors speculate that hyperoxia induced vasoconstriction is not due to changes in intravascular pH and cannot be counteracted by an intravascular increase in pCO(2).

Adult↗
PubMed2001

Physical and functional association of SU(VAR)3-9 and HDAC1 in Drosophila.

Modification of histones can have a dramatic impact on chromatin structure and function. Acetylation of lysines within the N-terminal tail of the histone octamer marks transcriptionally active regions of the genome whereas deacetylation seems to play a role in transcriptional silencing. Recently, the methylation of the histone tails has also been shown to be important for transcriptional regulation and chromosome structure. Here we show by immunoaffinity purification that two activities important for chromatin-mediated gene silencing, the histone methyltransferase SU(VAR)3-9 and the histone deacetylase HDAC1, associate in vivo. The two activities cooperate to methylate pre-acetylated histones. Both enzymes are modifiers of position effect variegation and interact genetically in flies. We suggest a model in which the concerted histone deacetylation and methylation by a SU(VAR)3-9/HDAC1-containing complex leads to a permanent silencing of transcription in particular areas of the genome.

Animals↗
PubMed2001

Acf1, the largest subunit of CHRAC, regulates ISWI-induced nucleosome remodelling.

The chromatin accessibility complex (CHRAC) was originally defined biochemically as an ATP-dependent 'nucleosome remodelling' activity. Central to its activity is the ATPase ISWI, which catalyses the transfer of histone octamers between DNA segments in cis. In addition to ISWI, four other potential subunits were observed consistently in active CHRAC fractions. We have now identified the p175 subunit of CHRAC as Acf1, a protein known to associate with ISWI in the ACF complex. Interaction of Acf1 with ISWI enhances the efficiency of nucleosome sliding by an order of magnitude. Remarkably, it also modulates the nucleosome remodelling activity of ISWI qualitatively by altering the directionality of nucleosome movements and the histone 'tail' requirements of the reaction. The Acf1-ISWI heteromer tightly interacts with the two recently identified small histone fold proteins CHRAC-14 and CHRAC-16. Whether topoisomerase II is an integral subunit has been controversial. Refined analyses now suggest that topoisomerase II should not be considered a stable subunit of CHRAC. Accordingly, CHRAC can be molecularly defined as a complex consisting of ISWI, Acf1, CHRAC-14 and CHRAC-16.

Adenosine Triphosphatases↗
PubMed2001

Effect of alcohol consumption on systemic markers of inflammation.

BACKGROUND: Epidemiological studies suggest that light to moderate alcohol intake is associated with lower all-cause mortality than abstention or heavy alcohol intake, primarily through reduced risk of coronary heart disease. The underlying mechanisms are incompletely understood. METHODS: We investigated the association between alcohol consumption (assessed by a 7-day food record) and concentrations of C-reactive protein (CRP), alpha1-globulins, alpha2-globulins, albumin, and transferrin, and leucocyte count in a sample of 2006 men and women aged 18-88 years participating in a national health survey carried out in former West Germany in 1987-88. Analyses were based on 781 men and 995 women with complete data. FINDINGS: Among men, alcohol consumption showed a U-shaped association with mean values of CRP (p for linear term 0.65, for quadratic term 0.048), alpha1-globulins (p=0.20, 0.0006), alpha2-globulins (p=0.82, 0.31), and leucocyte count (p=0.51, 0.26) even after adjustment for age, smoking, body-mass index, HDL and LDL cholesterol, history of hypertension, education, and income. There were inverted U-shaped associations between the negative acute-phase reactants albumin (p=0.41, 0.006) and transferrin (p=0.14, 0.28) and alcohol intake. In women, the associations were less strong for CRP (p=0.35, 0.31), leucocyte count (p=0.28, 0.15), and transferrin (p=0.86, 0.83). Concentrations of alpha1-globulins and alpha2-globulins were inversely related to alcohol consumption, and albumin showed a positive association with increasing alcohol intake in women. INTERPRETATION: Non-drinkers and heavy drinkers had higher CRP concentrations than moderate drinkers. In view of the robust association between markers of inflammation, especially CRP, and risk of coronary heart disease, an anti-inflammatory action of alcohol could contribute to the link between moderate consumption and lower cardiovascular mortality.

Acute-Phase Proteins↗
PubMed2001

Reactive hypoglycaemia due to late dumping syndrome: successful treatment with acarbose.

Reactive hypoglycaemia is a rare disease which occurs postprandially in everyday life involving blood glucose levels below 2.5 to 2.8 mmol/l. We report on a 66-year-old patient who developed symptomatic reactive hypoglycaemia due to late dumping syndrome 10 years after oesophagectomy with cervical anastomosis. A 75 g sucrose load revealed a plasma glucose level of 9.4 mmol/l after one hour, followed by symptomatic hypoglycaemia with a plasma glucose level of 1.8 mmol/l after three hours. Concomitantly, high concentrations of insulin (3216 pmol/l at a glucose level of 9.4 mmol/l and 335 pmol/l at a glucose level of 1.8 mmol/l) and glucagon-like peptide 1 (GLP-1) (375 pmol/l at a glucose level of 9.4 mmol/l and 85 pmol/l at a glucose level of 1.8 mmol/l) were measured. While the patient was under treatment with acarbose, another sucrose load did not provoke symptomatic hypoglycaemia (plasma glucose nadir of 4.6 mmol/l after two hours). Insulin and GLP-1 levels increased much less, to peak levels of 375 pmol/l and 75 pmol/l respectively, after one hour when plasma glucose was 6.8 mmol/l. We conclude that in patients with reactive hypoglycaemia due to gastrointestinal surgery, acarbose decreases rapid glucose absorption associated with hyperglycaemia and GLP-1 secretion, and thus diminishes excessive insulin release. Acarbose is therefore a successful treatment modality for reactive hypoglycaemia due to late dumping syndrome.

Acarbose↗
PubMed2001

Exercise and thrombosis.

Long-term moderate or strenuous physical activity is associated with a considerable reduction in cardiovascular morbidity and mortality in primary and secondary prevention. Various mechanisms, including changes in lipids, lifestyle habits, and other positive physiologic effects, have been suggested to mediate these beneficial effects. In addition, the hemostatic and fibrinolytic systems appear to play an important role. Fibrinogen has been convincingly shown to be an independent cardiovascular risk factor. Other hemostatic and fibrinolytic parameters that are predictive of coronary events include factor VII, platelet hyperreactivity, plasminogen-activator inhibitor 1 (PAI-1), and tissue-plasminogen activator. The effects of exercise on fibrinogen have been intensively studied. Several randomized controlled trials, various other intervention studies and a large number of population-based cross-sectional studies all found an inverse relationship between measures of sport activity or leisure activity and plasma fibrinogen. The magnitude of the effect reported might be associated with a sizeable reduction in major coronary events. Relatively few data are available on the effects of endurance exercise on markers of the fibrinolytic system, with inconsistent results. Acute exercise leads to a transient activation of the coagulation system, which is accompanied by an increase in the fibrinolytic capacity in healthy subjects. Patients with ischemic heart disease, who cannot increase their fibrinolytic potential, however, may be at considerable risk for acute ischemic events if they are exposed to unaccustomed strenuous physical exertion.

Blood Coagulation Factors↗
PubMed2001

Modifications of the histone N-terminal domains. Evidence for an "epigenetic code"?

A multicellular organism is made up of a variety of different cell types and tissues. This organization is accomplished by a well-concerted action of different regulatory molecules, which--in a very hierarchical manner--influence the expression of certain cell-specific genes. Many of those regulators are transcription factors, which directly influence the expression of the controlled gene by binding to a specific DNA sequence within its promoter or enhancer region. This binding then leads to an enhancement or a decrease in the rate of transcription of that particular gene and eventually regulates the production of the corresponding polypeptide. One major obstacle to the binding of these transcription factors is the fact that DNA is not readily accessible in the eukaryotic nucleus. It is associated with a class of very basic proteins called histones. This complex of histones and DNA is called chromatin.

Animals↗
PubMed2000

dMi-2 and ISWI chromatin remodelling factors have distinct nucleosome binding and mobilization properties.

Mi-2 and ISWI, two members of the Snf2 superfamily of ATPases, reside in separate ATP-dependent chromatin remodelling complexes. These complexes differ in their biochemical properties and are believed to perform distinct functions in the cell. We have compared the remodelling activity of recombinant Drosophila Mi-2 (dMi-2) with that of recombinant ISWI. Both proteins are nucleosome-stimulated ATPases and promote nucleosome mobilization. However, dMi-2 and ISWI differ in their interaction with nucleosome core particles, in their substrate requirements and in the direction of nucleosome mobilization. We have used antibodies to immobilize a complex containing dMi-2 and the dRPD3 histone deacetylase from Drosophila embryo extracts. This complex shares the nucleosome-stimulated ATPase and nucleosome mobilization properties of recombinant dMi-2, demonstrating that these activities are maintained in a physiological context. Its functional properties distinguish dMi-2 from both SWI2/SNF2 and ISWI, defining a new family of ATP-dependent remodelling machines.

Adenosine Triphosphatases↗
PubMed2000

Association between C-reactive protein and features of the metabolic syndrome: a population-based study.

OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence of diabetes and hypertension were assessed in 747 men and 956 women aged 18-89 years who were participating in the population-based National Health and Nutrition Survey, which was carried out in former West Germany in 1987-1988. RESULTS: There was a statistically significant positive crude correlation between C-reactive protein and TC (R = 0.19), TG (R = 0.29), BMI (R = 0.32), glucose (R = 0.11), and uric acid (R = 0.14) (all P < 0.0001). A negative correlation was found between C-reactive protein and HDL cholesterol (R = 0.13, P < 0.0001). The age-adjusted geometric means of C-reactive protein concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P < 0.0001). CONCLUSIONS: The data suggest that a variety of features of the metabolic syndrome are associated with a systemic inflammatory response.

Adolescent↗
PubMed1999

p300 stimulates transcription instigated by ligand-bound thyroid hormone receptor at a step subsequent to chromatin disruption.

We investigate the role of the transcriptional coactivator p300 in gene activation by thyroid hormone receptor (TR) on addition of ligand. The ligand-bound TR targets chromatin disruption independently of gene activation. Exogenous p300 facilitates transcription from a disrupted chromatin template, but does not itself disrupt chromatin in the presence or absence of ligand-bound receptor. Nevertheless, the acetyltransferase activity of p300 is required to facilitate transcription from a disrupted chromatin template. Expression of E1A prevents aspects of chromatin remodeling and transcriptional activation dependent on TR and p300. E1A selectively inhibits the acetylation of non-histone substrates. E1A does not prevent the assembly of a DNase I-hypersensitive site induced by TR, but does inhibit topological alterations and the loss of canonical nucleosome arrays dependent on the addition of ligand. Mutants of E1A incompetent for interaction with p300 partially inhibit chromatin disruption but still allow nuclear receptors to activate transcription. We conclude that p300 has no essential role in chromatin disruption, but makes use of acetyltransferase activity to stimulate transcription at a subsequent step.

Acetyltransferases↗
PubMed1999

Purification and properties of the Xenopus Hat1 acetyltransferase: association with the 14-3-3 proteins in the oocyte nucleus.

We have purified the Xenopus histone acetyltransferase Hat1 holoenzyme from oocytes. The holoenzyme contains the catalytic subunit Hat1, the retinoblastoma associated protein RbAp48, and members of the phosphoserine binding family of 14-3-3 proteins. We have determined that the Hat1 holoenzyme specifically acetylates free histone H4 but not nucleosomal histones. RbAp48 is a phosphoprotein that contains a consensus recognition motif for the 14-3-3 proteins. The 14-3-3 proteins provide a regulatory function for the activity of many phosphoproteins. We find that the hugely abundant Hat1 holoenzyme is present in 10 000-fold excess over somatic cell levels. The holoenzyme is localized in the oocyte nucleus where acetylated histones are stored. The oocyte form of the Xenopus Hat1 holoenzyme may represent a specialized storage form of histone acetyltransferase. Following oocyte maturation and subsequent embryogenesis, the Hat1 enzyme is redistributed to the cytoplasm, where new histones are synthesized.

14-3-3 Proteins↗
PubMed1999

[A female patient with splenomegaly, interstitial pneumopathy and giant foam cells in bone marrow].

We describe a case of Niemann-Pick disease type B. A 13-year-old female adolescent of Turkish origin suffered from abdominal pain for several months, finally leading to hospitalisation. The investigations revealed splenomegaly and interstitial pneumopathy. The bone marrow contained giant foam cells typical of Niemann-Pick disease. Enzymatic analysis of a fibroblast culture confirmed the diagnosis of Niemann-Pick disease type B, with reduced activity of acid sphingomyelinase. Niemann-Pick disease is an inherited autosomal recessive lysosomal storage disorder of sphingolipids, resulting in an accumulation of sphingomyelin in the cells of the reticulo-histiocytic system due to an enzymatic defect. In Niemann-Pick disease type B the spleen and lung are the main organs affected. At present no treatment exists for this disorder.

Adolescent↗
PubMed1999

Risk factors for type I diabetes mellitus in children in Austria.

UNLABELLED: The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P<0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). CONCLUSION: In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.

Adolescent↗