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Biomedical subjects

T Hartmann

Publications and source records attributed to T Hartmann.

At least 19 recordsLinked to original sources
PubMed2000

Radiation tolerance of complex oxides

The radiation performance of a variety of complex oxides is predicted on the basis of a material's propensity to accommodate lattice point defects. The calculations indicate that a particular class of oxides possessing the fluorite crystal structure should accept radiation-induced defects into their lattices far more readily than a structurally similar class of oxides based on the pyrochlore crystal structure. Preliminary radiation damage experiments substantiate the prediction that fluorites are inherently more radiation resistant than pyrochlores. These results may permit the chemical durability and radiation tolerance of potential hosts for actinides and radioactive wastes to be tailored.

Journal Article↗
PubMed2000

The oesophageal-tracheal Combitube Small Adult.

Airway management during gynaecological laparoscopy is complicated by intraperitoneal carbon dioxide inflation, Trendelenburg tilt, increasing airway pressures and pulmonary aspiration risk. We investigated whether the oesophageal-tracheal Combitube 37 Fr SA is a suitable airway during laparoscopy. One hundred patients were randomly allocated to receive either the Combitube SA (n = 49) or tracheal intubation (n = 51). Oesophageal placement of the Combitube was successful at the first attempt [16 (3) s]. Peak airway pressures were 25 (5) cmH2O. An airtight seal was obtained using air volumes of 55 (13) ml (oropharyngeal balloon) and 10 (1) ml (oesophageal cuff). Significant correlations were observed between patient's height and weight and the balloon volumes necessary to produce a seal. Similar findings were recorded for the control group, with tracheal intubation being difficult in three patients. The Combitube SA provided a patent airway during laparoscopy. Non-traumatic insertion was possible and an airtight seal was provided at airway pressures of up to 30 cmH2O.

Adult↗
PubMed2000

Subacute NO generation induced by Alzheimer's beta-amyloid in the living brain: reversal by inhibition of the inducible NO synthase.

Glial activation contiguous to deposits of amyloid peptide (Abeta) is a characteristic feature in Alzheimer's disease. We performed complementary in vitro and in vivo experiments to study the extent, kinetics, and mechanisms of microglial generation of nitric oxide (NO) induced by challenge with Abeta. We showed that Abeta fibrils dose-dependently induced a marked release of stable metabolites of NO in vivo that was strikingly similar regarding extent and temporal profile to the one in the parallel designed microglial cell culture experiments. However, costimulation with interferon gamma, which was a prerequisite for Abeta-induced NO generation in vitro, was not required in vivo, demonstrating that factors are present in the living brain that activate glial cells synergistically with Abeta. Therefore, in Alzheimer's disease, deposits of Abeta fibrils alone may be sufficient to induce a chronic release of neurotoxic microglial products, explaining the progressive neurodegeneration associated with this disease. Our observation that systemic administration of selective iNOS inhibitors abolishes Abeta-induced NO generation in vivo may have implications for therapy of Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1999

Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase.

Pyrrolizidine alkaloids are preformed plant defense compounds with sporadic phylogenetic distribution. They are thought to have evolved in response to the selective pressure of herbivory. The first pathway-specific intermediate of these alkaloids is the rare polyamine homospermidine, which is synthesized by homospermidine synthase (HSS). The HSS gene from Senecio vernalis was cloned and shown to be derived from the deoxyhypusine synthase (DHS) gene, which is highly conserved among all eukaryotes and archaebacteria. DHS catalyzes the first step in the activation of translation initiation factor 5A (eIF5A), which is essential for eukaryotic cell proliferation and which acts as a cofactor of the HIV-1 Rev regulatory protein. Sequence comparison provides direct evidence for the evolutionary recruitment of an essential gene of primary metabolism (DHS) for the origin of the committing step (HSS) in the biosynthesis of pyrrolizidine alkaloids.

Alkyl and Aryl Transferases↗
PubMed1999

The crystal structure of Tm5Re2O12.

The crystal structure of Tm(5)Re(2)O(12), pentathulium dirhenium dodecaoxide, was determined by synchrotron diffraction on a reticular merohedral twin, revealing space group C2/m with a = 12.3717 (7), b = 5.6744 (3), c = 7.4805 (4) Å, beta = 107.816 (2) degrees and Z = 2. Distorted ReO(6) octahedra form chains with alternating rhenium-rhenium distances of 2.455 (1) and 3.219 (1) Å. Early reports on Ln(2)ReO(5) compounds are critically reviewed in the light of our results for Tm(5)Re(2)O(12).

Journal Article↗
PubMed1999

Deoxyhypusine synthase from tobacco. cDNA isolation, characterization, and bacterial expression of an enzyme with extended substrate specificity.

Deoxyhypusine synthase catalyzes the formation of a deoxyhypusine residue in the translation eukaryotic initiation factor 5A (eIF5A) precursor protein by transferring an aminobutyl moiety from spermidine onto a conserved lysine residue within the eIF5A polypeptide chain. This reaction commences the activation of the initiation factor in fungi and vertebrates. A mechanistically identical reaction is known in the biosynthetic pathway leading to pyrrolizidine alkaloids in plants. Deoxyhypusine synthase from tobacco was cloned and expressed in active form in Escherichia coli. It catalyzes the formation of a deoxyhypusine residue in the tobacco eIF5A substrate as shown by gas chromatography coupled with a mass spectrometer. The enzyme also accepts free putrescine as the aminobutyl acceptor, instead of lysine bound in the eIF5A polypeptide chain, yielding homospermidine. Conversely, it accepts homospermidine instead of spermidine as the aminobutyl donor, whereby the reactions with putrescine and homospermidine proceed at the same rate as those involving the authentic substrates. The conversion of deoxyhypusine synthase-catalyzed eIF5A deoxyhypusinylation pinpoints a function for spermidine in plant metabolism. Furthermore, and quite unexpectedly, the substrate spectrum of deoxyhypusine synthase hints at a biochemical basis behind the sparse and skew occurrence of both homospermidine and its pyrrolizidine derivatives across distantly related plant taxa.

Alkyl and Aryl Transferases↗
PubMed1999

Neural expression profile of alpha-synuclein in developing human cortex.

Alpha-synuclein is a predominantly neuronal presynaptic protein that may play an important role during synaptogenesis and CNS development. In order to elucidate the human developmental expression profile, we used a polyclonal antiserum against the NAC domain of alpha-synuclein. In normal fetal cortex neuroectodermal precursor cells elicited staining in the soma, whereas, in adult cortex, we observed a staining pattern compatible with synaptic function. The same developmental intraneuronal redistribution was found in neurodegenerative disorders, i.e. somatic staining in neuroectodermal precursors in fetal (trisomy 21) and a synaptic pattern in adult (Down's syndrome, Alzheimer's disease) brains. RT-PCR and Western blot analysis revealed expression at all time points studied (4-7.5 months) during human brain development.

Adult↗
PubMed1999

Alpha-synuclein accumulates in Lewy bodies in Parkinson's disease and dementia with Lewy bodies but not in Alzheimer's disease beta-amyloid plaque cores.

A growing body of evidence suggests that the non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP) or alpha-synuclein contributes to the neurodegenerative processes in Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In the present study antisera to the N terminus and the NAC domain of the alpha-synuclein protein were employed to elucidate the expression pattern in brains of patients with AD, PD, DLB and control specimen. Alpha-synuclein exhibited an overall punctuate expression profile compatible with a synaptic function. Interestingly, while Lewy bodies were strongly immunoreactive, none of the alpha-synuclein antisera revealed staining in mature beta-amyloid plaques in AD. These observations suggest that alpha-synuclein does not contribute to late neurodegenerative processes in AD brains.

Alzheimer Disease↗
PubMed1999

Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer's disease and declines with disease progression.

All mutations known to cause familial Alzheimer's disease (AD) act by increasing the levels of soluble beta-amyloid peptide (A beta), especially the longer form, A beta42. However, in vivo elevation of soluble A beta in sporadic AD has so far not been shown. In the present study, we used enzyme-linked immunosorbent assays specific for A beta42 and A beta40 to investigate cerebrospinal fluid from sporadic AD at different stages of disease severity, to clarify the roles of A beta42 and A beta40 during disease progression. We also evaluated three other groups--one group of patients with mild cognitive impairment who were at risk of developing dementia, a cognitively intact, nondemented reference group diagnosed with depression, and a perfectly healthy control group. We found that A beta42 is strongly elevated in early and mid stages of AD, and thereafter it declines with disease progression. On the contrary, A beta40 levels were decreased in early and mid stages of AD. The group of cognitively impaired patients and the depression reference group had significantly higher levels of A beta42 than the healthy control group, implying that A beta42 is increased not only in AD, but in other central nervous system conditions as well. Our data also point out the importance of having thoroughly examined control material. The initial increase and subsequent decrease of A beta42 adds a new biochemical tool to follow the progression of AD and might be important in the monitoring of therapeutics.

Aged↗
PubMed1999

Intracellular biology of Alzheimer's disease amyloid beta peptide.

Strong evidence links excess production of a small peptide and the pathogenesis of Alzheimer's disease (AD). Originally this peptide, beta-amyloid 42 (Abeta42), was assumed to be released by a pathogenic event; it is now well established that Abeta42 is released from cells during normal cellular metabolism of the Alzheimer amyloid precursor protein. Recently, in a series of surprising reports it was discovered that Abeta42 is produced intracellularly, and what might have been regarded first as a strange abnormality of a few selected cell lines has now been recognized as an important cellular pathway for Abeta production. Moreover, the differences between secretory and intracellular Abeta production might hold the clues for brain specificity and cellular mechanisms of AD pathogenesis.

Alzheimer Disease↗
PubMed1999

Occupational exposure to sevoflurane during sedation of adult patients.

OBJECTIVES: In a field study we evaluated the workplace pollution occurring during conscious sedation with sevoflurane in adults. METHODS: Sevoflurane was given in 100% oxygen at a fresh gas flow rate of 3 l/min via a nasal mask. This was conducted in 25 patients scheduled for surgical procedures performed under regional anesthesia. Trace concentrations of sevoflurane were directly measured every minute in the breathing zone by means of a photoacoustic infrared spectrometer in an operating room with an air turnover of 20 changes/h. RESULTS: The mean sedation time was 49.6+/-20.4 min. The average vaporizer setting of the anesthesia machine was 1.63+/-0.6 vol%, resulting in a patient's mean end-tidal sevoflurane concentration of 0.78+/-0.2 vol%. The 8-h time-weighted average was calculated to be 0.58 ppm sevoflurane. CONCLUSIONS: The trace gas concentrations were low and comparable with values obtained under inhalation induction in adults and children. Although no occupational standard for sevoflurane is currently defined, the measured values are clearly under the standards recommended for enflurane (20 ppm) and isoflurane (10 ppm) by the European health authorities. We conclude that the new anesthesiologic method of conscious sedation with sevoflurane in adults using a nasal mask would not result in a violation of occupational standards, provided that the future value set for sevoflurane would be similar to those recommended for isoflurane or enflurane.

Adult↗
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↗