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T Hartmann

Publications and source records attributed to T Hartmann.

At least 73 records · Page 4Linked to original sources
PubMed1997

Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides.

The Alzheimer amyloid precursor protein (APP) is cleaved by several proteases, the most studied, but still unidentified ones, are those involved in the release of a fragment of APP, the amyloidogenic beta-protein A beta. Proteolysis by gamma-secretase is the last processing step resulting in release of A beta. Cleavage occurs after residue 40 of A beta [A beta(1-40)], occasionally after residue 42 [A beta(1-42)]. Even slightly increased amounts of this A beta(1-42) might be sufficient to cause Alzheimer's disease (AD) (reviewed in ref. 1, 2). It is thus generally believed that inhibition of this enzyme could aid in prevention of AD. Unexpectedly we have identified in neurons the endoplasmic reticulum (ER) as the site for generation of A beta(1-42) and the trans-Golgi network (TGN) as the site for A beta(1-40) generation. It is interesting that intracellular generation of A beta seemed to be unique to neurons, because we found that nonneuronal cells produced significant amounts of A beta(1-40) and A beta(1-42) only at the cell surface. The specific production of the critical A beta isoform in the ER of neurons links this compartment with the generation of A beta and explains why primarily ER localized (mutant) proteins such as the presenilins could induce AD. We suggest that the earliest event taking place in AD might be the generation of A beta(1-42) in the ER.

Alzheimer Disease↗
PubMed1997

A rare presentation of thoracic aortic dissection as detected by transoesophageal echocardiography.

A case of atypical movement of the intimal flap (tear) during aortic aneurysm dissection is reported. Aortic dissection is caused by the sudden development of a tear in the aortic intima, opening the way for a column of blood driven by the force of the arterial pressure to enter the aortic wall, destroying the media and stripping the intima from the adventitia for variable distance along the length of the aorta. Echocardiographically, aortic dissection is characterized by separation of the normal single dominant echo from the aortic wall in the region of the dissection into two discrete echoes. The inner echo arises from the tunica intima, whereas the outer echo arises from the medial and adventitial structures external to the tear and it is possible to identify two lumens separated by an intimal flap within the aorta. The two echoes generally move in unison with one another, i.e. movement of the flap away from the true lumen during systole and recoil during diastole as the blood flows from true to false lumen. The dissection flap can also move inward during systole owing to the suction caused by high-velocity flow (Venturi effect), as shown in this case report. In any instances, motion of the intimal flap during the cardiac cycle is strong evidence of dissecting aneurysm.

Aged↗
PubMed1997

Biplane transoesophageal echocardiographic detection of myocardial ischaemia in patients with coronary artery disease undergoing non-cardiac surgery: segmental wall motion vs. electrocardiography and haemodynamic performance.

Intra-operative segmental wall motion abnormalities (SWMA) detected by transoesophageal echocardiography (TOE) have been shown to be a sensitive indicator of myocardial ischaemia. To determine the incidence and characteristics of segmental wall motion abnormalities and to relate these changes to perioperative myocardial ischaemia, biplane TEE, electrocardiogram (ECG) (II+V5) and pulmonary capillary wedge pressure (PCWP) were continuously monitored in 62 consecutive patients with ischaemic heart disease undergoing non-cardiac surgery. Short-axis view at mid-papillary level in transverse scan (T-scan) and long-axis in longitudinal (L-scan) two-chamber view were used for wall motion analysis. New segmental wall motion abnormalities were detected in 16 of 64 patients (25%) using biplane transoesophageal echocardiography. Monoplane transoesophageal echocardiography showed a sensitivity of 75% and a specificity of 100%, electrocardiogram two lead showed a sensitivity of 56% and a specificity of 98%, whereas pulmonary capillary wedge pressure had a sensitivity of 25%, and a specificity of 93% and pressure rate quotient (PRQ) < 1 demonstrated sensitivity of 19% and a specificity of 92% in the detection of myocardial ischaemia. It is concluded that the long-axis view of the left ventricle provides additional information for the detection of segmental wall motion abnormalities. Neither changes in haemodynamic performance nor in electrocardiography leads II and V5 match those of transoesophageal echocardiography for the identification of myocardial ischaemia.

Adult↗
PubMed1997

Validity of acoustic quantification colour kinesis for detection of left ventricular regional wall motion abnormalities: a transoesophageal echocardiographic study.

Transoesophageal echocardiography is a sensitive monitor for intraoperative myocardial ischaemia. Colour kinesis is a new technology for echocardiographic assessment of regional wall motion based on acoustic quantification. We have examined the feasibility and accuracy of quantitative segmental analysis of colour kinesis images to provide objective evaluation of systolic regional wall motion during the perioperative period using transoesophageal echocardiography (TOE). Two-dimensional echocardiograms were obtained in the transgastric short-axis and long-axis views in 60 patients with coronary artery disease undergoing noncardiac surgery. End-systolic colour overlays superimposed on the grey scale images were obtained with colour kinesis to colour encode left ventricular endocardial motion throughout systole. These colour-encoded images were divided into segments and compared with corresponding conventional two-dimensional images. Six hundred of a potential 720 left ventricular wall segments were of sufficient resolution for grading by experts; they diagnosed wall motion abnormalities in 61 of these segments by a conventional method. In comparing the conventional TOE method with colour kinesis, there were 60 true positives, 482 true negatives, 57 false positives and 1 false negative result. This yielded a sensitivity of 98%, specificity of 89%, positive predictive value of 51% and negative predictive value of 100%. Translational and rotational movement of the heart and papillary muscle interference were common problems accounting for false positive diagnoses. We conclude that colour kinesis provides a basis for objective and on-line evaluation of left ventricular regional wall motion which is a sensitive but non-specific method. It may be a useful aid for the less experienced because it can potentially direct the anaesthetist's attention towards specific segments.

Adult↗
PubMed1997

The HELLP syndrome.

Explore the source record for details and available documents.

Analgesia, Obstetrical↗
PubMed1997

Sedation and anaesthesia outside the OR.

The sedation of paediatric patients is associated with serious risks such as hypoventilation, apnoea, airway obstruction, and cardiopulmonary impairment; these risks should be avoided or accurately and rapidly diagnosed and appropriately treated. Appropriate management may include ventilation by mask and cardiopulmonary resuscitation, which require special training and skills.

Airway Obstruction↗
PubMed1996

The beta-amyloid domain is essential for axonal sorting of amyloid precursor protein.

We have analysed the axonal sorting signals of amyloid precursor protein (APP). Wild-type and mutant versions of human APP were expressed in hippocampal neurons using the Semliki forest virus system. We show that wild-type APP and mutations implicated in Alzheimer's disease and another brain beta-amyloidosis are sorted to the axon. By analysis of deletion mutants we found that the membrane-inserted APP ectodomain but not the cytoplasmic tail is required for axonal sorting. Systematic deletions of the APP ectodomain identified two regions required for axonal delivery: one encoded by exons 11-15 in the carbohydrate domain, the other encoded by exons 16-17 in the juxtamembraneous beta-amyloid domain. Treatment of the cells with the N-glycosylation inhibitor tunicamycin induced missorting of wild-type APP, supporting the importance of glycosylation in axonal sorting of APP. The data revealed a hierarchy of sorting signals on APP: the beta-amyloid-dependent membrane proximal signal was the major contributor to axonal sorting, while N-glycosylation had a weaker effect. Furthermore, recessive somatodendritic signals, most likely in the cytoplasmic tail, directed the protein to the dendrites when the ectodomain was deleted. Analysis of detergent solubility of APP and another axonally delivered protein, hemagglutinin, demonstrated that only hemagglutinin formed CHAPS-insoluble complexes, suggesting distinct mechanisms of axonal sorting for these two proteins. This study is the first delineation of sorting requirements of an axonally targeted protein in polarized neurons and indicates that the beta-amyloid domain plays a major role in axonal delivery of APP.

Alzheimer Disease↗
PubMed1996

Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay.

The betaA4 peptide, a major component of senile plaques in Alzheimer's disease (AD) brain, has been found in cerebrospinal fluid (CSF) and blood of both AD patients and normal subjects. Although betaA4 1-40 is the major form produced by cell metabolism and found in CSF, recent observations suggest that the long-tailed betaA4 1-42 plays a more crucial role in AD pathogenesis. Here, we established new monoclonal antibodies against the C-terminal end of betaA4 1-40 and 1-42, and used them for the specific Western blot detection. After optimizing the assay conditions, these antibodies detected low picogram amount of betaA4, and both betaA4 1-40 and 1-42 levels in CSF could be determined by direct loading of the samples. Blood levels of betaA4 1-40 and 1-42 were also determined by specific immunoprecipitation followed by Western blot detection. We found that CSF betaA4 1-42 level is lower in AD patients compared with non-demented controls, although there was a significant overlap between the groups. The level of betaA4 1-40 in CSF, and of betaA4 1-40 as well as betaA4 1-42 in plasma, were not different between AD patients and controls. Besides the 4-kDa full-length betaA4 band, we could also detect several N-terminal variants of betaA4 in CSF and plasma of both AD patients and controls. Two N-terminally truncated betaA4 species migrating at the position of 3.3 and 3.7 kDa were found in CSF, while 3.7- and 5-kDa forms were found in plasma. The relative abundance of these various species were considerably different in the CSF and plasma, suggesting that the cellular source and/or clearance of betaA4 is different in these two compartments.

Aged↗
PubMed1996

Purification, molecular cloning and expression in Escherichia coli of homospermidine synthase from Rhodopseudomonas viridis.

Homospermidine synthase (HSS) catalyzes the synthesis of the polyamine homospermidine from 2 mol putrescine in an NAD(+)-dependent reaction. In this study, the enzyme was purified from anaerobically grown cultures of the photosynthetic bacterium Rhodopseudomonas viridis to electrophoretic homogeneity using a three-step procedure. The enzyme was shown to be a homodimer of 52-kDa subunits. Six endopeptidase LysC fragments were sequenced from the purified protein. With the aid of degenerate primers designed against these peptides, specific PCR products from R. viridis DNA were obtained that were used as hybridization probes to isolate the hss gene from a library constructed in lambda EMBL4. The hss gene and flanking regions were sequenced and were shown to exist as a single copy in the R. viridis genome. HSS is translated from a monocistronic mRNA and possesses no detectable similarity to previously sequenced gene products. Escherichia coli, which lacks HSS activity, was transformed with an expression plasmid containing the hss coding region under the control of a bacteriophage T7 promoter. Upon induction, transformed F. coli cells accumulate enzymatically active and highly stable R. viridis HSS at levels corresponding to 40-50% of the soluble protein in crude extracts.

Alkyl and Aryl Transferases↗
PubMed1996

Alzheimer's disease betaA4 protein release and amyloid precursor protein sorting are regulated by alternative splicing.

We show here that alternative splicing influences the polarized secretion of amyloid precursor protein (APP) as well as the release of its proteolytic 3-4-kDa fragments betaA4 and p3. In Madin-Darby canine kidney II cells stably transfected with various APP isoforms and APP mutants, APPsec was consistently secreted basolaterally. In contrast, Madin-Darby canine kidney II cells transfected with L-APP677, which occurs naturally by alternative splicing of exon 15, secreted this isoform both apically and basolaterally, while maintaining the basolateral sorting of endogenous APPsec. This suggests that the alternative splicing of APP exon 15 modulates the polarized sorting of secretory APP. The same alternative splicing event also decreased the production of betaA4 relative to p3. This is the first example of alternative splicing regulating polarized trafficking of a secretory protein.

Alternative Splicing↗
PubMed1996

Lay beliefs about diarrhoeal diseases: their role in health education in a developing country.

This study examines the beliefs and understandings concerning diarrhoea among 2 groups of Zimbabwean women. Mothers with formal education are compared to those with less formal education. Differences and commonalities of beliefs are examined. The findings show that traditional explanations of an illness such as diarrhoea can inhibit health education campaigns against this disease which kills many children every year.

Adult↗