PubMed Health⌕ Search

Biomedical subjects

P Neumann

Publications and source records attributed to P Neumann.

At least 55 records · Page 3Linked to original sources

Molecular and cytogenetic analysis of repetitive DNA in pea (pisum sativum L.).

A set of pea DNA sequences representing the most abundant genomic repeats was obtained by combining several approaches. Dispersed repeats were isolated by screening a short-insert genomic library using genomic DNA as a probe. Thirty-two clones ranging from 149 to 2961 bp in size and from 1,000 to 39,000/lC in their copy number were sequenced and further characterized. Fourteen clones were identified as retrotransposon-like sequences, based on their homologies to known elements. Fluorescence in situ hybridization using clones of reverse transcriptase and integrase coding sequences as probes revealed that corresponding retroelements were scattered along all pea chromosomes. Two novel families of tandem repeats, named PisTR-A and PisTR-B, were isolated by screening a genomic DNA library with Cot-1 DNA and by employing genomic self-priming PCR, respectively. PisTR-A repeats are 211-212 bp long, their abundance is 2 x 10(4) copies/lC, and they are partially clustered in a secondary constriction of one chromosome pair with the rest of their copies dispersed on all chromosomes. PisTR-B sequences are of similar abundance (10(4) copies/lC) but differ from the "A" family in their monomer length (50 bp), high A/T content, and chromosomal localization in a limited number of discrete bands. These bands are located mainly in (sub)telomeric and pericentromeric regions. and their patterns, together with chromosome morphology, allow discrimination of all chromosome types within the pea karyotype. Whereas both tandem repeat families are mostly specific to the genus Pisum, many of the dispersed repeats were detected in other legume species, mainly those in the genus Vicia.

Base Sequence↗

Structural basis of negative cooperativity in transthyretin.

A comparison of the AC and BD binding sites of transthyretin (TTR) was made in terms of the interatomic distances between the Ca atoms of equivalent amino acids, measured across the tetramer channel in each binding site. The comparison of the channel diameter for apo TTR from different sources revealed that in the unliganded transthyretin tetramers the distances between the A, D and H beta-strands are consistently larger, while the distances between the G beta-strands are smaller in one site than in the other. These differences might be described to have a 'wave' character. An analogous analysis performed for transthyretin complexes reveals that the shape of the plot is similar, although the amplitudes of the changes are smaller. The analysis leads us to a model of the changes in the binding sites caused by ligand binding. The sequence of events includes ligand binding in the first site, followed by a slight collapse of this site and concomitant opening of the second site, binding of the second molecule and collapse of the second site. The following opening of the first, already occupied site upon ligand binding in the second site is smaller because of the bridging interactions already formed by the first ligand. This explains the negative cooperativity (NC) effect observed for many ligands in transthyretin.

Animals↗

Two new families of tandem repeats isolated from genus Vicia using genomic self-priming PCR.

A modified genomic self-priming technique was used for rapid isolation of tandem repeats from several Vicia species. Based on homologies of their nucleotide sequences the newly isolated clones were assigned to two repeat families named VicTR-A and VicTR-B. Both families are rich in AT (74%) and are organized as long blocks of tandemly repeated units. The VicTR-A repeats are characterized by a monomer size of 69 bp, whereas the VicTR-B repeat monomer is about 38 bp long, and the two families do not share significant sequence homology. VicTR sequences show different degrees of amplification (up to 10(6)-10(7) copies/haploid genome) in individual Vicia species and are not amplified in other legumes. The abundances of these repeats do not correlate with genome sizes but are similar in species that belong to the same taxonomic section within the genus Vicia. Primed in situ (PRINS) labeling of metaphase chromosomes of V. pannonica revealed that VicTR-A sequences are located predominantly in the telomeric regions of the short arms of all chromosomes. In contrast, labeling of VicTR-B repeats in V. sativa resulted in mainly intercalary bands of various intensities and only weak telomeric signals.

Base Composition↗

Protein kinase C-alpha mediates endothelial barrier dysfunction induced by TNF-alpha.

We tested the hypothesis that protein kinase C-alpha (PKC-alpha) mediates tumor necrosis factor-alpha (TNF-alpha)-induced alterations in permeability of pulmonary microvessel endothelial monolayers (PEM). The permeability of PEM was assessed by the clearance rate of Evans blue-labeled albumin. PEM lysates were analyzed for PKC-alpha mRNA (Northern cDNA blot), protein (Western immunoblot), and activity (translocation and phosphorylation of myristoylated arginine-rich C kinase substrate). Incubation of PEM with TNF-alpha (1,000 U/ml) for 4 h resulted in increases in 1) PKC-alpha protein, 2) cytoskeletal-associated PKC-alpha, 3) PKC-alpha activity, and 4) permeability to albumin. The TNF-alpha-induced increase in PKC-alpha protein, PKC-alpha activity, and permeability was prevented by a 4-h pretreatment with PKC-alpha antisense oligonucleotide but not by the scrambled nonsense oligonucleotide. The TNF-alpha-induced increase in permeability to albumin was prevented by myristoylated protein kinase C inhibitor (an inhibitor of PKC-alpha/beta, 100 microM) and calphostin (an inhibitor of the classic and novel PKC isotypes, 200 nM). The treatment with calphostin from 0.5 to 3.0 h after TNF-alpha still prevented barrier dysfunction induced by 4 h of TNF-alpha treatment. The data indicate that prolonged activation of PKC-alpha, maintained by a translation-dependent pool of PKC-alpha protein, mediates TNF-alpha-induced increases in endothelial permeability in PEM.

Animals↗

Effects of inverse ratio ventilation and positive end-expiratory pressure in oleic acid-induced lung injury.

Continuous as well as cyclic (with each expiration) lung collapse in acute respiratory failure can be reduced by positive end-expiratory pressure (PEEP) or short expiration times, as in inverse ratio ventilation (IRV). In 20 pigs with oleic acid-induced lung edema, we compared the effects of a PEEP of 20 cm H(2)O with IRV, using an inspiratory-to-expiratory ratio of 3:1 without external PEEP. During IRV, expiration times of 0.5 or 1.0 s were obtained with respiratory rates of 30 breaths/min or 15 breaths/min, respectively. In 15 animals, ventilation-perfusion relationships were studied through the multiple inert gas elimination technique, and lung morphology was studied with computed tomography. In another five pigs, blood flow distribution was studied with perfusion scintigraphy. All three ventilatory modes had similar effects on mean arterial blood pressure, cardiac output, oxygen delivery, and mean airway pressure. PEEP reduced shunt and improved oxygenation to a greater extent than the two modes of IRV, although there was a large variation within each group. The improvement, irrespective of which ventilatory mode was superior in a particular pig, was caused by greater and more even aeration of the lung, whereas the perfusion distribution with PEEP was the same as with IRV. Thus, the strategy of stabilizing the lungs through short expiration times, as in IRV, did not offer any advantages in our lung injury model.

Animals↗

Tumor necrosis factor-alpha-induced activating protein-1 activity is modulated by nitric oxide-mediated protein kinase G activation.

We tested the hypothesis that protein kinase (PK)G activation in response to nitric oxide ((*)NO) mediates tumor necrosis factor (TNF)-alpha-induced activation of the transcription factor activating protein-1 (AP-1) in pulmonary microvessel endothelial monolayers (PEM). The DNA-binding activity of AP-1 was assessed using the electrophoretic mobility shift assay. TNF treatment (1,000 U/ml) for 4 h induced a significant increase in DNA binding of AP-1. The effects of TNF were prevented by the superoxide radical scavenger superoxide dismutase (SOD) (100 U/ml), the (*)NO synthase inhibitor aminoguanidine (100 microM), the guanylate cyclase inhibitor ODQ (100 microM), and the PKG inhibitors KT5823 (1 microM) and 8-bromo-cyclic guanosine monophosphate (cGMP)-thioate (100 microM). Spermine-NO (1 microM) and L-arginine (400 microM) prevented the aminoguanidine-induced ablation of AP-1 activation in response to TNF. Phosphorylation of H-Arg-Lys-Ile-Ser-Ala-Ser-Glu-Phe-Asp-Arg-Pro-Leu-Arg-OH (BPDEtide), a specific substrate for PKG, measured the activity of cGMP-dependent protein kinase (PKG). TNF for 0.5 h induced an increase in PKG activity that was prevented by aminoguanidine, ODQ, KT5823, and 8-bromo-cGMP-thioate; however, SOD had no effect. The PKG agonist 8-bromo-cGMP (100 microM), when given alone, increased PKG activity but induced significant DNA-binding activity of AP-1 only when given in the ODQ + TNF Group. SIN-1 (1 mM, a peroxynitrite agonist) increased DNA-binding activity of AP-1. SOD prevented SIN-1-induced AP-1 activation, a response similar to that of the SOD + TNF Group. PEM were transfected with the chloramphenicol acetyltransferase (CAT) reporter plasmid pBLCAT2, which contains a regulation sequence responsive to AP-1. The pharmacologic profile of TNF-induced CAT activity was identical to TNF-induced DNA binding by AP-1. Thus, TNF-induced AP-1-dependent gene transcription is modulated by (*)NO-dependent mediated activation of PKG.

Animals↗

Extravascular lung water and intrathoracic blood volume: double versus single indicator dilution technique.

OBJECTIVE: The accuracy of single thermodilution was assessed in measuring extravascular lung water (EVLW) and intrathoracic blood volume (ITBV). DESIGN: Single thermodilution (ST) was prospectively compared with thermo-dye dilution (TD) in 13 mechanically ventilated pigs using the Pulsion Cold Z-021 monitor. INTERVENTIONS: Lung injury was induced with oleic acid injection. RESULTS: EVLWI(TD) increased from 4.3 +/- 1.4 to 11.3 +/- 4.5 ml/kg (p = 0.0014) and ITBV(TD) decreased from 581 +/- 66 to 540 +/- 85 ml (p = 0.039) after induction of lung injury. EVLW(ST) was systematically overestimated (0.5-1 ml/kg) and ITBV(ST) was slightly underestimated (15-20 ml) when calculated automatically by the Pulsion Cold Z-021 monitor. This bias could be removed by adjusting two coefficients needed for the computation of ITBV(ST) and EVLW(ST) so that the following regression equations were obtained: EVLWI(ST) = 0.98 EVLWI(TD) + 0.27 (r = 0.94, p < 10(-6)) and ITBV(ST) = 1.0 x ITBV(TD) + 0 (r = 0.87, p < 10(-6)). CONCLUSIONS: Single thermodilution allows estimation of ITBV and EVLW values with reasonable accuracy and therefore provides useful information about the cardiac preload and the severity of lung injury. However, automatic calculation of EVLWI(ST) and ITBV(ST) using the Pulsion Cold Z-021 might be biased. Therefore, researchers and clinicians should validate single thermodilution for the given settings, before employing this method to estimate EVLW and ITBV.

Animals↗

Determination of inter-spinous process distance in the lumbar spine. Evaluation of reference population to facilitate detection of severe trauma.

Fracture of a spinal segment with minimal or no compression of the vertebral body can be highly unstable. Screening for such an injury in the lumbar spine is often obstructed in a multi-injured patient, because of difficulty in obtaining adequate sagittal radiographs. The position of the spinous processes in relation to each other is the key for proper evaluation of the status of the posterior stabilising structures. The amount of separation or axial rotation of the posterior part of the vertebra that can occur before failure of the posterior structures has not been unambiguously defined. Despite this, it can be assumed that severe separation of the spinous processes indicates a more or less pronounced loss of mechanical support. An analysis of how the posterior spinous processes relate to each other on an anteroposterior (AP) radiograph could obviate this problem. A new, simple and reproducible radiographic tool is presented for screening of an eventual rupture of posterior structures of the lumbar spine. This method is based on measurements of the variation in interspinal process distance between adjacent levels in lumbar spine in a normal population. Two hundred normal AP radiographs of non-injured thoracolumbar spine were studied. The interspinal process distance was measured as the distance between the cranial ends of the adjacent projections of spinous processes on AP radiographs. The mean values and 99% confidence limits for changes in the interspinal process distances between adjacent spinal levels were determined and analysed in relation to age, gender and spinal segment level. An upper limit of a normal difference in distance between the spinous processes at two adjacent levels was determined to be 7-10 mm, depending on age and location in the lumbar spine. A difference in interspinal process distance exceeding 7 mm between two adjacent lumbar levels should alert a surgeon to severe and unstable injury.

Adult↗

Positive end-expiratory pressure prevents atelectasis during general anaesthesia even in the presence of a high inspired oxygen concentration.

BACKGROUND: General anaesthesia impairs the gas exchange in the lungs, and moderate desaturation (SaO2 86-90%) occurred in 50% of anaesthetised patients in a blinded pulse oximetry study. A high FiO2 might reduce the risk of hypoxaemia, but can also promote atelectasis. We hypothesised that a moderate positive end-expiratory pressure (PEEP) level of 10 cmH2O can prevent atelectasis during ventilation with an FiO2 = 1.0. METHODS: Atelectasis was evaluated by computed tomography (CT) in 13 ASA I-II patients undergoing elective surgery. CT scans were obtained before and 15 min after induction of anaesthesia. Then, recruitment of collapsed lung tissue was performed as a "vital capacity manoeuvre" (VCM, inspiration with Paw = 40 cmH2O for 15 s), and a CT scan was obtained at the end of the VCM. Thereafter, PEEP = 0 cmH2O was applied in group 1, and PEEP = 10 cmH2O in group 2. Additional CT scans were obtained after the VCM. Oxygenation was measured before and after the VCM. RESULTS: Atelectasis (> 1 cm2) was present in 12 of the 13 patients after induction of anaesthesia. At 5 and 10 min after the VCM, atelectasis was significantly smaller in group 2 than group 1 (P < 0.005). A significant inverse correlation was found between PaO2 and atelectasis. CONCLUSIONS: PEEP = 10 cmH2O reduced atelectasis formation after a VCM, when FiO2 = 1.0 was used. Thus, a VCM followed by PEEP = 10 cmH2O should be considered when patients are ventilated with a high FiO2 and gas exchange is impaired.

Adult↗

Dynamics of re-expansion of atelectasis during general anaesthesia.

A major cause of impaired gas exchange during general anaesthesia is atelectasis, causing pulmonary shunt. A 'vital capacity' (VC) manoeuvre (i.e. inflation of the lungs up to 40 cm H2O, maintained for 15 s) may re-expand atelectasis and improve oxygenation. However, such a manoeuvre may cause adverse cardiovascular effects. Reducing the time of maximal inflation may improve the margin of safety. The aim of this study was to analyse the change over time in the amount of atelectasis during a VC manoeuvre in 12 anaesthetized adults with healthy lungs. I.v. anaesthesia with controlled mechanical ventilation (VT 9 (SD 1) ml kg-1) was used. For the VC manoeuvre, the lungs were inflated up to an airway pressure (Paw) of 40 cm H2O. This pressure was maintained for 26 s. Atelectasis was assessed by analysis of computed x-ray tomography. The amount of atelectasis, measured at the base of the lungs, was 4.0 (SD 2.7) cm2 after induction of anaesthesia. The decrease in the amount of atelectasis over time during the VC manoeuvre was described by a negative exponential function with a time constant of 2.6 s. At an inspired oxygen concentration of 40%, PaO2 increased from 17.2 (4.0) kPa before to 22.2 (6.0) kPa (P = 0.013) after the VC manoeuvre. Thus in anaesthetized adults undergoing mechanical ventilation with healthy lungs, inflation of the lungs to a Paw of 40 cm H2O, maintained for 7-8 s only, may re-expand all previously collapsed lung tissue, as detected by lung computed tomography, and improve oxygenation. We conclude that the previously proposed time for a VC manoeuvre may be halved in such subjects.

Adult↗

Gas exchange in acute respiratory failure.

Acute respiratory failure is accompanied by a severe gas exchange impairment that is signified by a large shunt and no or only little of additional ventilation-perfusion mismatch. The shunt is caused by perfusion of collapsed and consolidated lung tissue that is mainly located in the lower, dependent lung region. The ventilation, on the other hand, is redistributed towards upper, non-dependent regions. By applying external PEEP, or producing an intrinsic PEEP by shortening the expiratory period, not only recruitment of collapsed or consolidated lung tissue may be achieved, but also a redistribution of inspired gas towards more dependent regions. Spontaneous breathing seems to improve gas exchange, and in proportion to its share of total ventilation, when added to mechanical ventilation. A shift from total mechanical ventilation to partial or fully spontaneous breathing may be the road of the future and should be tested further.

Humans↗

[Effect of infrared rays on the eye in progressive myopia].

In the submitted paper the authors pay attention to infrared radiation close to visible light is intensely absorbed by haemoglobin, melanin and xanthophyll whereby part of the radiation energy is transformed into heat. The authors present three series of experiments where they investigated by different methods changes in the vitreous body after exposure to light, infrared radiation or raised temperature. They assume that on the defocused eye with a myopic conus which developed as a result of an inborn inadequate closure of the optic cup the light can cause a rise of temperature in the vitreous body. This leads to metabolic changes characterized by increased activity of lysosomal enzymes causing loss of the spatial structure of hyaluronic acid and collagen biomolecules. Penetration of the altered vitreous fluid thought the conus can lead to degradation of the interstitial substances of the sclera. Suitable absorption glasses filtering infrared light close to visible light could reduce the hyperthermia of the vitreous body.

Humans↗

The economic cost of Alzheimer's disease and related dementias to the California Medicaid program ("Medi-Cal") in 1995.

Although state Medicaid programs may bear a large portion of the costs of Alzheimer's disease (AD), current information on spending is not available. Using a health insurance claims database for a 10% random sample of California Medicaid ("Medi-Cal") recipients 60+ years of age, the authors estimated the excess cost of AD to Medi-Cal in 1995 as the difference in expenditures between an AD cohort (those with AD or related dementias) and an age- and sex-matched cohort without AD. Among 62,450 recipients, 2,575 (4.1%) were found to have AD or related dementias, and their average payments were approximately $7,700 higher (P<0.01) than those for the comparison group. These estimates suggest that Medi-Cal spends about $200 million on AD and related dementias annually, a burden that represents nearly 10% of state spending on elderly patients.

Aged↗

Virtual 3D cutting for bone segment extraction in maxillofacial surgery planning.

An important step toward our main goal of a completely computer-based maxillofacial surgical planning system is the availability of tools for the surgeon to define bone segments from skull and jaw bones. We have developed an easy-to-handle user interface that employs visual and force-feedback devices to define subvolumes of a patient's volume dataset. This interface is a main component of our maxillofacial surgical planning tool MeVisTo-Jaw [1]. The defined subvolumes together with their spatial arrangements lead to an operation plan.

Humans↗

Determination of functional residual capacity (FRC) by multibreath nitrogen washout in a lung model and in mechanically ventilated patients. Accuracy depends on continuous dynamic compensation for changes of gas sampling delay time.

OBJECTIVE: Validation of an open-circuit multibreath nitrogen washout technique (MBNW) for measurement of functional residual capacity (FRC). The accuracy of FRC measurement with and without continuous viscosity correction of mass spectrometer delay time (TD) relative to gas flow signal and the influence of baseline FIO2 was investigated. DESIGN: Laboratory study and measurements in mechanically ventilated patients. SETTING: Experimental laboratory and anesthesiological intensive care unit of a university hospital. PATIENTS: 16 postoperative patients with normal pulmonary function (NORM), 8 patients with acute lung injury (ALI) and 6 patients with chronic obstructive pulmonary disease (COPD) were included. INTERVENTIONS: Change of FIO2 from baseline to 1.0. MEASUREMENTS AND MAIN RESULTS: FRC was determined by MBNW using continuous viscosity correction of TD(TDdyn), a constant TD based on the viscosity of a calibration gas mixture (TD0) and a constant TD referring to the mean viscosity between onset and end of MBNW (TDmean). Using TDdyn, the mean deviation between 15 measurements of three different lung model FRCs (FRCmeasured) and absolute volumes (FRCmodel) was 0.2%. For baseline FIO2 ranging from 0.21 to 0.8, the mean deviation between FRCmeasured and FRCmodel was -0.8%. However, depending on baseline FIO2, the calculation of FRC using TDmean and TD0 increased the mean deviation between FRCmeasured and FRCmodel to 2-4% and 8-12%, respectively. In patients (n = 30) the average repeatability coefficient was 6.0%. FRC determinations with TDmean and TD0 were 0.8-13.3% and 4.2-23.9% (median 2.7% and 8.7%) smaller than those calculated with TDdyn. CONCLUSION: A dynamic viscosity correction of TD improves the accuracy of FRC determinations by MBNW considerably, when gas concentrations are measured in a sidestream. If dynamic TD correction cannot be performed, the use of constant TDmean might be suitable. However, in patient measurements this can cause an FRC underestimation of up to 13%.

Adult↗