Search PubMed⌕ Search

Biomedical subjects

T Hartmann

Publications and source records attributed to T Hartmann.

At least 55 records · Page 3Linked to original sources
PubMed1999

Non-Abeta component of Alzheimer's disease amyloid (NAC) revisited. NAC and alpha-synuclein are not associated with Abeta amyloid.

alpha-Synuclein (alphaSN), also termed the precursor of the non-Abeta component of Alzheimer's disease (AD) amyloid (NACP), is a major component of Lewy bodies and Lewy neurites pathognomonic of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). A fragment of alphaSN termed the non-Abeta component of AD amyloid (NAC) had previously been identified as a constituent of AD amyloid plaques. To clarify the relationship of NAC and alphaSN with Abeta plaques, antibodies were raised to three domains of alphaSN. All antibodies produced punctate labeling of human cortex and strong labeling of Lewy bodies. Using antibodies to alphaSN(75-91) to label cortical and hippocampal sections of pathologically proven AD cases, we found no evidence for NAC in Abeta amyloid plaques. Double labeling of tissue sections in mixed DLB/AD cases revealed alphaSN in dystrophic neuritic processes, some of which were in close association with Abeta plaques restricted to the CA1 hippocampal region. In brain homogenates alphaSN was predominantly recovered in the cytosolic fraction as a 16-kd protein on Western analysis; however, significant amounts of aggregated and alphaSN fragments were also found in urea extracts of SDS-insoluble material from DLB and PD cases. NAC antibodies identified an endogenous fragment of 6 kd in the cytosolic and urea-soluble brain fractions. This fragment may be produced as a consequence of alphaSN aggregation or alternatively may accelerate aggregation of the full-length alphaSN.

Alzheimer Disease↗
PubMed1999

Alzheimer's disease: correlation of the suppression of beta-amyloid peptide secretion from cultured cells with inhibition of the chymotrypsin-like activity of the proteasome.

Peptide aldehyde inhibitors of the chymotrypsin-like activity of the proteasome (CLIP) such as N-acetyl-Leu-Leu-Nle-H (or ALLN) have been shown previously to inhibit the secretion of beta-amyloid peptide (A beta) from cells. To evaluate more fully the role of the proteasome in this process, we have tested the effects on A beta formation of a much wider range of peptide-based inhibitors of CLIP than published previously. The inhibitors tested included several peptide boronates, some of which proved to be the most potent peptide-based inhibitors of beta-amyloid production reported so far. We found that the ability of the peptide aldehyde and boronate inhibitors to suppress A beta formation from cells correlated extremely well with their potency as CLIP inhibitors. Thus, we conclude that the proteasome may be involved either directly or indirectly in A beta formation.

Aldehydes↗
PubMed1999

TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs.

The appearance of inflammatory markers associated with amyloid plaques indicates a state of chronic inflammation in Alzheimer's disease (AD). Multiple epidemiological studies also suggest that patients taking anti-inflammatory drugs have a decreased risk of developing AD. Here we present evidence that inflammatory cytokines can alter the metabolism of the beta-amyloid precursor protein (betaAPP). We show that the combination of tumor necrosis factor alpha and interferon gamma triggers the production of beta-amyloid peptides and inhibits the secretion of soluble APPs by human neuronal and extraneuronal cells. The results demonstrate a new mechanism by which inflammatory components can exacerbate the fundamental pathology in AD.

Alzheimer Disease↗
PubMed1999

A new noninvasive method to measure blood pressure: results of a multicenter trial.

BACKGROUND: Blood pressure (BP) monitoring with arterial waveform display requires an arterial cannula. We evaluated a new noninvasive device, Vasotrac (Medwave, Arden Hills, MN) that provides BP measurements approximately every 12-15 beats and displays pulse rate and a calibrated arterial waveform for each BP measurement. METHODS: Surgical and critically ill patients (n = 80) served as subjects for the study. BPs, pulse waveforms, and pulse rates measured via a radial artery catheter were compared with those obtained by the Vasotrac from the opposite radial artery. Data were analyzed to determine agreement between the two systems of measurement. RESULTS: Blood pressure measured noninvasively by the Vasotrac demonstrated excellent correlation (P<0.01) with BP measured via a radial arterial catheter (systolic r2 = 0.93; diastolic r2 = 0.89; mean r2 = 0.95). Differences in BP measured by the Vasotrac versus the radial arterial catheter were small. The mean+/-SD bias and precision were as follows: systolic BP 0.02+/-5.4 mm Hg and 3.9+/-3.7 mm Hg; diastolic BP -0.39+/-3.9 mm Hg and 2.7+/-2.8 mm Hg; mean BP -0.21+/-3.0 mm Hg and 2.1+/-2.2 mm Hg compared with radial artery measurements. The Vasotrac pulse rates were almost identical to those measured directly (r2 = 0.95). The Vasotrac BP waveform resembled those directly obtained radial artery pulsatile waveforms. CONCLUSIONS: In surgical and critically ill patients, the Vasotrac measured BP, pulse rate, and displayed radial artery waveform, which was similar to direct radial arterial measurements. It should be a suitable device to measure BP frequently in a noninvasive fashion.

Adult↗
PubMed1998

Autoclaving impairs the connector-tube bond of the laryngeal mask airway but not its airtightness.

The general-purpose laryngeal mask airway (LMA) is re-usable when undamaged, and cleaned and autoclaved correctly. We had found weakening of the silicone adhesive that bonds the connector of the LMA to the tube. We report that repeated autoclaving damaged the adhesive such that the connector could be rotated in the tube after the 12th autoclave cycle in almost all of the LMA tested. The damage to the adhesive did not affect the airtightness of the junction, which appears to be maintained by the material properties of the connector and tube and by the shape of the join.

Adhesives↗
PubMed1998

Subcellular localization of the Alzheimer's disease amyloid precursor protein and derived polypeptides expressed in a recombinant yeast system.

Different isoforms and derived polypeptides of the Alzheimer's disease amyloid protein precursor (A beta PP) have been expressed in the yeast Pichia pastoris. The expression characteristics of the different A beta PP polypeptides were studied by post-embedding immunogold electron microscopy with various A beta PP antibodies. The site of intracellular expression could be readily identified with specific antibodies. Full length A beta PP was expressed in association with the nuclear membrane and the endoplasmic reticulum. Secretory derivatives of A beta PP were localized in membrane-bound secretory vesicles. A construct encoding two copies of beta A4[1-42] linked head-to-tail (beta A4duplex) accumulated as irregular dense cytoplasmic and intranuclear inclusions which reacted with all beta A4 antibodies tested. A beta A4-C-terminal construct accumulated into membranous structures in the cytoplasm and nucleus and reacted with most antibodies to beta A4 and the cytoplasmic domain of A beta PP. The two shorter constructs containing the beta A4 sequence formed similar intranuclear aggregates to those reported for intranuclear inclusions of polyglutamine peptides from huntingtin (in Huntington's disease) and ataxin protein fragments (in spinocerebellar ataxia). This is of interest because intracellular aggregation of the polyglutamine and beta A4 peptides may affect cells by similar toxic mechanisms. These studies demonstrate clear differences in the expression properties of different A beta PP polypeptides.

Alzheimer Disease↗
PubMed1997

The two facies of pyrrolizidine alkaloids: the role of the tertiary amine and its N-oxide in chemical defense of insects with acquired plant alkaloids.

Larvae of Creatonotos transiens (Lepidoptera, Arctiidae) and Zonocerus variegatus (Orthoptera, Pyrgomorphidae) ingest 14C-labeled senecionine and its N-oxide with the same efficiency but sequester the two tracers exclusively as N-oxide. Larvae of the non-sequestering Spodoptera littoralis eliminate efficiently the ingested alkaloids. During feeding on the two alkaloidal forms transient levels of senecionine (but not of the N-oxide) are built up in the haemolymph of S. littoralis larvae. Based on these results, senecionine [18O]N-oxide was fed to C. transiens larvae and Z. variegatus adults. The senecionine N-oxide recovered from the haemolymph of the two insects shows an almost complete loss of 18O label, indicating reduction of the orally fed N-oxide in the guts, uptake of the tertiary alkaloid and its re-N-oxidation in the haemolymph. The enzyme responsible for N-oxidation is a soluble mixed function monooxygenase. It was isolated from the haemolymph of the sequestering arctiid Tyria jacobaeae and purified to electrophoretic homogeneity. The enzyme is a flavoprotein with a native Mr of 200000 and a subunit Mr of 51000. It shows a pH optimum at 7.0, has its maximal activity at a temperature of 40-45 degrees C and an isoelectric point at pH 4.9. The reaction is strictly NADPH-dependent (Km 1.3 microM). From 20 pyrrolizidine alkaloids so far tested as substrates, the enyzme N-oxidizes only alkaloids with structural elements which are essential for hepatotoxic and genotoxic pyrrolizidine alkaloids (i.e. 1,2-double bond, esterification of the allylic hydroxyl group, presence of a second free or esterified hydroxyl group at carbon 7). A great variety of related alkaloids and xenobiotics were tested as substrate, none was accepted. The Km values of senecionine, monocrotaline and heliotrine, representing the three main types of pyrrolizidine alkaloids, are 1.3 microM, 12.5 microM and 290 microM, respectively. The novel enzyme was named senecionine N-oxygenase (SNO). The enzyme was partially purified from two other arctiids. The three SNOs show the same general substrate specificity but differ in their affinities towards the main structural types of pyrrolizidine alkaloids. The enzymes from the two generalists (Creatonotos transiens and Arctia caja) display a broader substrate affinity than the enzyme from the specialist (Tyria jacobaeae). The two molecular forms of pyrrolizidine alkaloids, the lipophilic protoxic tertiary amine and its hydrophilic nontoxic N-oxide are discussed in respect to their bioactivation and detoxification in mammals and their role as defensive chemicals in specialized insects. Pyrrolizidine-alkaloid-sequestering insects store the alkaloids as nontoxic N-oxides which are reduced in the guts of any potential insectivore. The lipophilic tertiary alkaloid is absorbed passively and then bioactivated by cytochrome P-450 oxidase.

Amines↗
PubMed1997

A phenomenological variant of ecological systems theory (PVEST): a self-organization perspective in context.

A framework that emphasizes and integrates individuals' intersubjective experiences with Bronfenbrenner's ecological systems theory (PVEST) is introduced and compared with self-organizational perspectives. Similarities, differences and advantages of each framework are described. In a demonstration of PVEST's utility, a subset of data from the 3rd year of a longitudinal study (14- to 16-year-old middle adolescent African-Americans) is used for examining an achievement variable: negative learning attitude. Explored separately by gender, a regression model that contained risk, stress, and a reactive coping variable for the prediction of negative learning attitudes was investigated. For boys, stress was an independent stressor across steps independent of the other variables entered; social support variable, perceived unpopularity with peers, that was a significant predictor of girls' negative learning attitude. Particularly for boys, the findings suggest critically important roles for teachers and peers in the negative learning attitude of midadolescent economically disadvantaged African-American students.

Adolescent↗
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↗