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Biomedical subjects

S Heinemann

Publications and source records attributed to S Heinemann.

At least 19 recordsLinked to original sources

[Quality assurance in echocardiography. Three-level system in formation and qualifying and concept of an external quality review].

Measures of quality assurance in echocardiography can be categorized according to standard principles into measures of reviewing structure, processing, and results. This document contains 1) the description of a three level system for education and qualifying in echocardiographic examinations (quality of structure) and 2) the draft of an external quality assurance process for reviewing the results of one echocardiographic investigator or of one laboratory of echocardiography (quality of results). The document also contains a draft description of a nationwide independent institution for certification, which is needed for both projects.A level 1 investigator should be able to perform and interpret a basic investigation. A basic investigation allows to exclude most of all cardiac diseases that can be diagnosed by echocardiography, and pathological findings should be filtered out. A level 2 investigator is able to perform an extended examination, and a comprehensive echocardiographic diagnosis can be established after her or his examination. Additional specific training and experience is necessary to be certified for TEE and stress echo examinations. A level 3 echocardiographer has done research work in echocardiography and should have performed certified teaching courses in echocardiography. The external quality assurance process should provide the possibility to certify the results and reports of a single investigator or of an echo laboratory, according to standard principles of reviewing the records. The process of certification is exclusively performed on a voluntary basis. The nationwide institution of certification should be part of the academy of education in cardiology of the German Society of Cardiology.

Cardiology↗

Environmental investigations and molecular typing of Aspergillus flavus during an outbreak of postoperative infections.

After an outbreak of sternal surgical-site infections (SSSI) with Aspergillus flavus following cardiac surgery, a mycological survey of air and surfaces (41 and 149 samples, respectively) was performed throughout the surgical ward (SW) and in other areas of the hospital. Results showed massive contamination by A. flavus: more than 100 cfu per contact plate were frequently observed in some areas of the SW. The distribution of the A. flavus spores in the building, and especially in the SW, enabled the location of a possible source within the non-medical part of the SW, but the true source could not be identified. Four other surveys were made to follow up the decontamination process; the contamination level did not fall rapidly, needing repetitive cleaning operations. Strains from patients and from the hospital environment selected all over the SW were typed by random amplification of polymorphic DNA (RAPD), using two different primers (ERIC-1, BG-2). All these strains showed the same genotype, proving the clonal single-source of the environmental contamination and the intra-operative acquisition of A. flavus in the SSSI outbreak.

Air Microbiology↗

Regulation of cell function by methionine oxidation and reduction.

Reactive oxygen species (ROS) are generated during normal cellular activity and may exist in excess in some pathophysiological conditions, such as inflammation or reperfusion injury. These molecules oxidize a variety of cellular constituents, but sulfur-containing amino acid residues are especially susceptible. While reversible cysteine oxidation and reduction is part of well-established signalling systems, the oxidation and the enzymatically catalysed reduction of methionine is just emerging as a novel molecular mechanism for cellular regulation. Here we discuss how the oxidation of methionine to methionine sulfoxide in signalling proteins such as ion channels affects the function of these target proteins. Methionine sulfoxide reductase, which reduces methionine sulfoxide to methionine in a thioredoxin-dependent manner, is therefore not only an enzyme important for the repair of age- or degenerative disease-related protein modifications. It is also a potential missing link in the post-translational modification cycle involved in the specific oxidation and reduction of methionine residues in cellular signalling proteins, which may give rise to activity-dependent plastic changes in cellular excitability.

Animals↗

Ultrastructural colocalization of nidogen-1 and nidogen-2 with laminin-1 in murine kidney basement membranes.

Nidogen-1, a key component of basement membranes, is considered to function as a link between laminin and collagen type IV networks. Recently a new member of the nidogen family, nidogen-2, has been characterized. Preliminary immunohistochemical data indicated that nidogen-1 and nidogen-2 show a similar tissue distribution at the light microscopic level. We have now localized nidogen-1 and nidogen-2, as well as their corresponding mRNAs, at the light and electron microscopic levels in adult mouse kidney, by in situ hybridization and immunogold histochemistry, as well as carrying out double labeling with laminin-1. Both nidogen-1 and nidogen-2 mRNAs are found not only in mesenchymal cells of embryonic tissues, but also in all epithelial and endothelial cells in adult mouse kidney. Both nidogens are ubiquitous basement membrane components in the mouse kidney, being found in glomerular, tubular, and capillary compartments and Bowman's capsule. Furthermore, a substantial fraction of nidogen-1 and nidogen-2 colocalizes with laminin-1. The results indicate that nidogen-1 and nidogen-2 could well substitute for one another in some of their biological activities in kidney, for example, stabilizing basement membrane networks in vivo.

Animals↗

Molecular typing of Aspergillus terreus isolates by random amplification of polymorphic DNA.

Forty three isolates of Aspergillus terreus of environmental or clinical origin were typed by random amplification of polymorphic DNA (RAPD) with two different primers NS3 and NS7 from the fungal ribosomal 18S subunit gene. For the 31 epidemiologically unrelated isolates tested, the primers NS3 and NS7 gave rise to 23 and 24 different genotypes, respectively, and combining the results obtained with the two primers allowed the differentiation of all these isolates. No clustering was found in relation to pathogenicity, clinical signs, or geographic origin of the isolates. Five groups of related isolates of A. terreus were also typed. Analysis of sequential isolates from patients with cystic fibrosis or with invasive aspergillosis showed the clonality of the colonization or infection by A. terreus. Likewise, this straightforward typing method demonstrated the clonal origin of a massive contamination of the environment in a haematology unit. Therefore this RAPD typing method may constitute a valuable tool for the epidemiological follow-up of airway colonization in patients with cystic fibrosis or investigations of links between nosocomial outbreaks of invasive aspergillosis and environmental contamination.

Aspergillosis↗

Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome.

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.

Adolescent↗

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

Adolescent↗

Ultrastructural triple localization of laminin-1, nidogen-1, and collagen type IV helps elucidate basement membrane structure in vivo.

The basement membrane models which have been proposed to date are generally based on biochemical data, mainly binding studies and artificially synthesized polymers in vitro. Basically these have led to models proposing two three-dimensional laminin-1 and collagen type IV networks interconnected by nidogen-1. Whether they reflect the in vivo basement membrane structure is still not clear. We localized laminin-1, nidogen-1, and collagen type IV ultrastructurally in adult and fetal mouse kidney basement membranes with the help of immunogold-histochemistry performing double and triple localization to try to elucidate the molecular organization of basement membranes in vivo. We found laminin-1, nidogen-1, and collagen type IV distributed over the entire basement membranes in adult and fetal kidneys. This contradicts earlier studies ascribing laminin-1 to the lamina lucida and collagen type IV to the lamina densa. In addition, various basement membrane segments exhibited an organized labeling pattern for the BM components. Double-labeling revealed co-localization of laminin-1 and nidogen-1. We conclude that the combination of laminin-1 with collagen type IV as double-network basement membrane partially interconnected by nidogen-1 is found already in the early fetal kidney in vivo. However, our data cannot exclude the possibility of other variants of basement membrane assemblages. This is also indicated by a changing structure even in individual segments of one basement membrane type which renders a more flexible basement membrane architecture plausible.

Age Factors↗

Spatial distribution of kainate receptor subunit mRNA in the mouse basal ganglia and ventral mesencephalon.

In an attempt to gain knowledge of the possible functions of kainate receptors, we have used in situ hybridization to examine the regional and cellular expression patterns of glutamate receptor subunits GluR5-7, KA1 and KA2 in the adult mouse basal ganglia, known to play a pivotal role in the translation of motivation into actions. Kainate receptor subunits were found to be differentially expressed in the circuitry forming the basal ganglia. They differ from each other in expression levels and their spatial localization. GluR6 appeared as the key subunit for the descending gamma-aminobutyric acid (GABA)ergic-glutamatergic pathways, with highest message levels in the caudate putamen, globus pallidus and subthalamic nucleus as well as in the nucleus accumbens and olfactory tubercle. GluR7 exhibited highest expression in the ascending nigrostriatal and mesolimbic dopaminergic neurons. GluR5 had a restricted distribution pattern, with high expression in the ventral pallidum, the islands of Calleja and pars compacta of the substantia nigra. KA2 was usually coexpressed with GluR6, although with a generally lower level of expression. Finally, KA1 mRNA was barely detectable in these neuronal circuits. These data suggest that kainate receptors in general may be involved in the functions associated with the basal ganglia, with a key role in the control of the central dopaminergic transmission. Thus, they might be implicated in the neurodegenerative and psychic disorders associated with an impairment of the basal ganglia.

Animals↗

Cellular distribution in the rat telencephalon of mRNAs encoding for the alpha 3 and alpha 4 subunits of the nicotinic acetylcholine receptor.

Pharmacological and electrophysiological studies provide evidence for the involvement of different nicotinic acetylcholine receptor isoforms in rat neocortical and hippocampal signal transduction. Yet, rather little is known on the cellular localization of these isoforms. With the availability of isoform specific nucleic acid probes and sensitive non-isotopic detection systems, nicotinic receptors can be studied on the mRNA level in individual neurons. In this way, we have paradigmatically studied the distribution of the alpha 3 and alpha 4 isoform mRNAs of the nicotinic receptor in the rat telencephalon. In the cerebral cortex, alpha 3 transcripts were mainly located in pyramidal neurons of layers V and VI and in some non-pyramidal cells in layer IV, while alpha 4 mRNA was detected in different types of neurons located in almost all layers. In the hippocampus, local distribution of both transcripts was comparable. Only very few labeled neurons were observed in the dentate gyrus. In the CA region, the specific mRNAs were detected in pyramidal perikarya and individual neurons in the strata oriens and lacunosum-moleculare. Our data show that the applied method is sufficiently sensitive and isoform-selective in order to study the differential expression of nicotinic receptors on the cellular level in the mammalian brain.

Animals↗

Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family.

Ionotropic glutamate receptors are composed of homomeric or heteromeric configurations of glutamate receptor subunits. We have cloned a member of a novel class of the rat ionotropic glutamate receptor family, termed chi-1. This subunit exhibits an average identity of 27% to NMDA subunits and 23% to non-NMDA subunits. Regional transcript levels of chi-1 are elevated just prior to and during the first postnatal week, with the highest levels present in the spinal cord, brainstem, hypothalamus, thalamus, CA1 field of the hippocampus, and amygdala. The spatial distribution of chi-1 expression is similar from postnatal day 1 (P1) to adulthood. However, transcript levels decline sharply between P7 and P14 and remain attenuated into adulthood. Functional expression studies in Xenopus oocytes injected with in vitro transcribed chi-1 RNA did not demonstrate agonist-activated currents. Pairwise expression of chi-1 with members of the AMPA, KA, or delta class of glutamate recepto subunits either failed to generate agonist-activated currents or failed to alter the underlying current generated by the coexpressed subunit. However, coexpression of chi-1 with subunits forming otherwise functional NMDA receptors resulted in an inhibition of current responses. Since chi-1 did not alter the currents generated by non-NMDA subunits, this suggests that chi-1 may specifically interact with NMDA receptor subunits. Further characterization will be required to establish the precise role of this glutamate receptor subunit in neuronal signaling.

Aging↗

[The effect of nCPAP respiration on hyperreactivity in patients with sleep related respiratory disorder].

Of the 8,973 patients with sleep related breathing disorders examined in our department, about 4% were found to have a hyperreagible bronchial system. Provocation tests were performed before and after a 3-day CPAP therapy in 8 male patients with confirmed bronchial hyperreagibility. Two of these 8 patients revealed a marked increase of the respiratory path resistance and a decrease in FEV1.0 of 30% in the provocation test after 3 days. This did not occur with the other patients. From these findings, it is concluded that CPAP therapy can lead to an increase in the hyperreagibility in some patients with hyperreagible bronchial systems. However, further investigations are needed to identify the underlying causal relationships.

Adult↗

[Occurrence of obstructive sleep related respiratory disorder in conjunction with gastroesophageal reflux].

In 30 patients with suspected or, respectively 27 patients with confirmed, sleep apnea syndrome, 24-h esophagus pH metering was carried out. The patients were divided into two groups (number of apnea per 6 h > or < 100). A pH value of < 4 was defined as a pathological reflux when it occurred in total in at least 4% of the measuring period. Pathological reflux was encountered in 76% of the light SAS group and in 68% of the patients with severe SAS. Positional variations through upright and supine positions were apparent but not significant. Further investigations are therefore necessary to evaluate the relationships between degree of severity, position, and accompanying diseases.

Adult↗

[Effect of n-CPAP therapy on the 24-hour blood pressure profile in severe obstructive sleep apnea syndrome].

We examined circadian blood pressure rhythm before and two days after onset of n-CPAP therapy in 50 patients, suffering from polysomnograhpically ensured severe obstructive sleep-apnea-syndrome. Measurements were performed using a non-invasive blood pressure registration. Patients with normal circadian blood pressure conditions and those with disturbed circadian rhythm could be differentiated. N-CPAP therapy may normalize circadian blood pressure conditions in some patients.

Adult↗

[Theophylline acceptance in long-term therapy of patients with obstructive sleep related respiratory disorder].

In 1,150 patients with sleep apnea syndrome, the apnea number, the morning theophyllin level, the symptom of morning exhaustion were recorded for the first night of theophyllin therapy and in the follow-up period of up to 5 years; in addition, side effects were noted at the end of the observation period. Prior to start of the therapy, the average apnea number was 97 per night; this decreased to 25 per night in the initial therapy. In the observation period of between 3 and 28 months, the number of apnea phases increased slightly on average. The symptoms of morning exhaustion initially decreased to 60% but increased again by about 20% over the next five years. In responders, theophyllin reduces the number of apnea in the long term course; however, frequent therapy controls are needed to determine the optimal dosage. Longitudinally, patients with an apnea index < 20/profited most from this drug therapy.

Adult↗

Gastroesophageal reflux in patients with sleep apnea syndrome.

UNLABELLED: Gastroesophageal reflux (GER) may be associated with pulmonary diseases. The aim of this study was to investigate the role of GER in patients with sleep apnea syndrome (SAS). We evaluated, therefore, in patients with SAS the occurrence of GER during simultaneous apnea monitoring, and whether GER is related to the severity of SAS. METHODS: 17 consecutive patients with proven SAS were divided into two groups according to the severity of SAS: (A) apnea index > or = 5 and < 15, n = 8; (B) apnea index > or = 15, n = 9. All patients underwent 24 hours pH-metry in the proximal and distal esophagus and simultaneous apnea monitoring during the night. RESULTS: There was a high occurrence of GER in patients with SAS, but no significant difference was found between the two groups with respect to reflux times at the distal or at the proximal esophageal site. Reflux episodes and apnea periods were not timely correlated. Most of the patients of both groups were obese. CONCLUSIONS: Patients with SAS often have GER. However, there is neither a relation of GER with the severity of SAS nor a timely association between GER- and SAS-episodes. Thus, it is unlikely that there is a direct link between GER and SAS. However, there may be factors predisposing for both diseases.

Adult↗

Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells.

We report the isolation and functional characterization of a member of the nicotinic acetylcholine receptor subunit gene family, alpha 9. Xenopus oocytes injected with alpha 9 cRNA express a homomeric receptor-channel complex that is activated by acetylcholine. The alpha 9 receptor displays an unusual mixed nicotinic-muscarinic pharmacological profile. The unique properties of the alpha 9 receptor-channel complex closely match those described for the cholinergic receptor present in vertebrate cochlear hair cells. In situ hybridization studies reveal a restricted pattern of alpha 9 gene expression that includes the outer hair cells of the rat cochlea. Our results suggest that the alpha 9 receptor is involved in the cholinergic efferent innervation of cochlear hair cells and thus may modulate the encoding of auditory stimuli.

Amino Acid Sequence↗