Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 37 records · Page 2Linked to original sources

PubMed2003

The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary bypass.

OBJECTIVE: Neuropsychologic disorders are common after coronary artery bypass operations. Air microbubbles are identified as a contributing factor. A dynamic bubble trap might reduce the number of gaseous microemboli. METHODS: A total of 50 patients undergoing coronary artery bypass operation were recruited for this study. In 26 patients a dynamic bubble trap was placed between the arterial filter and the aortic cannula (group 1), and in 24 patients a placebo dynamic bubble trap was used (group 2). The number of high-intensity transient signals within the proximal middle cerebral artery was continuously measured on both sides during bypass, which was separated into 4 periods: phase 1, start of bypass until aortic clamping; phase 2, aortic clamping until rewarming; phase 3, rewarming until clamp removal; and phase 4, clamp removal until end of bypass. S100 beta values were measured before, immediately after, and 6 and 48 hours after the operation and before hospital discharge. RESULTS: The bubble elimination rate during bypass was 77% in group 1 and 28% in group 2 (P <.0001). The number of high-intensity signals was lower in group 1 during phase 1 (5.8 +/- 7.3 vs 16 +/- 15.4, P <.05 vs group 2) and phase 2 (6.9 +/- 7.3 vs 24.2 +/- 27.3, P <.05 vs group 2) but not during phases 3 and 4. Serum S100 beta values were equally increased in both groups immediately after the operation. Group 2 patients had higher S100 beta values 6 hours after the operation and significantly higher S100 beta values 48 hours after the operation (0.06 +/- 0.14 vs 0.18 +/- 0.24, P =.0133 vs group 2). Age and S100 beta values were correlated in group 2 but not in group 1. CONCLUSION: Gaseous microemboli can be removed with a dynamic bubble trap. Subclinical cerebral injury detectable by increases of S100 beta disappears earlier after surgical intervention.

Aged↗

PubMed2003

[Outpatient primary stent-angioplasty in symptomatic internal carotid artery stenoses].

In 81 patients, average age 69.3 (57-79) years with symptomatic ICA stenosis stent implantation was performed under outpatient conditions. An interdisciplinary consensus ascertained that the patients were suitable for outpatient therapy. In accordance with the NASCET criteria all patients belonged to the high-risk group. Within 120 days before the intervention, the following clinical events had occurred: 32 minor strokes, 43 TIA, 20 amaurosis fugax. 61/81 patients revealed a bulbar, 20/81 a postbulbar ICA stenosis, the average degree of stenosis was 88.6 % (75-97). Stent application, using 3 different stent models, and subsequent PTA were always performed under protection. The transfemoral route was always treated with an endovascular closure system. All patients were given follow-up examinations by means of colour duplex sonography (CDS) of the neck vessels on days 1, 30, 180 and 360, and contrast-medium intensified MRT on day 5 post-intervention. The technical success rate with regard to stenting and PTA was 100 %. One case of hypotonic dysregulation occurred during the intervention. Atheromatous particles and plaque fragments were found in the protection system in 3/81 (3.7%) of the patients. A plaque embolism was excluded clinically and in the contrast-medium intensified MRT 5 days after the intervention in 79/81 (97.5%) of the patients, while two patients were found to sustain an asymptomatic cortical barrier impairment. After 180 days, no restenosis or stent dislocation were found in the CDS, all ECAs were perfused. After 360 days, one asymptomatic occlusion and four restenoses > 70% were found (5/81 = 6.2% restenosis rate after 1 year), which were successfully treated by angioplasty. The method presented bears a low complication rate and shows a high success rate. If patient recruitment is adequate, this intervention can safely be performed on an outpatient basis.

Aged↗

PubMed2003

Leukocyte-depleted secondary blood cardioplegia attenuates reperfusion injury after myocardial ischemia.

BACKGROUND: Activated neutrophils have been implicated in reperfusion injury of the myocardium; leukocyte depletion at the time of reperfusion may contribute to better myocardial protection after cardiac surgery. In the present study, we examined whether leukocyte depletion as an adjunct to terminal blood cardioplegia attenuates reperfusion injury. METHODS: Porcine hearts that had undergone 60 minutes of normothermic ischemia with cardioplegia and 60 minutes of reperfusion under cardiopulmonary bypass were divided into four groups according to the methods of 15 min of controlled initial reperfusion: whole blood reperfusion (n = 6), leukocyte-depleted reperfusion (n = 6), secondary blood cardioplegia (n = 6) and leukocyte-depleted secondary blood cardioplegia (n = 6). At 60 min of reperfusion, hemodynamic recovery, release of malondialdehyde (MDA) as a marker for free oxygen radicals, CK-MB-isoenzyme from the coronary sinus, recovery of adenosine triphosphate, and myocardial water content were evaluated. RESULTS: The group with leukocyte-depleted secondary blood cardioplegia showed the best hemodynamic recovery (Emax and total dp/dt), lowest levels of MDA, CK-MB and myocardial water content, and highest adenosine triphosphate recovery. CONCLUSIONS: These results suggest that controlled reperfusion with leukocyte-depleted secondary blood cardioplegia attenuated severe damage of the myocardium as compared to whole blood reperfusion.

Animals↗

PubMed2002

Toxicity and pathological effects of orally and intraperitoneally administered ivermectin on sea bass Dicentrarchus labrax.

The toxicity and histopathology of ivermectin was studied in 3 and 35 g sea bass Dicentrarchus labrax L. following in-feed, oral intubation and injection administration at dose rates ranging from 0.5 to 3.5 mg kg(-1). Estimated LD50 values for 3 g fish were 0.335 and 0.106 mg kg(-1) following oral intubation and injection administration respectively, for fish reared at 11 degrees C; and 0.839 and 1.023 mg kg(-1) following oral intubation and injection administration, respectively for fish reared at 20 degrees C. For 35 g fish reared at 11 degrees C, the estimated LD50 was 0.523 and 0.361 mg kg(-1) following oral intubation and injection administration respectively. No signs of toxicity were observed when the compound was administered via the feed at 0.5 and 0.7 mg kg(-1). However, toxicity (> 10%) was observed at dose rates of 0.2 mg kg(-1) and higher when the compound was administered via oral intubation and at 0.5 mg kg(-1) when administered via injection. The compound was significantly more toxic to fish reared at 11 degrees C than at 20 degrees C. Further, ivermectin was more toxic to 3 g than to 35 g sea bass when administered via injection. Histopathological examination of the major organs revealed pathology was largely restricted to gills and intestinal tissue. In 3 g sea bass, lesions were also found in the kidneys.

Animals↗

PubMed2002

MeV ion jets from short-pulse-laser interaction with thin foils.

Collimated jets of carbon and fluorine ions up to 5 MeV/nucleon ( approximately 100 MeV) are observed from the rear surface of thin foils irradiated with laser intensities of up to 5 x 10 (19)W/cm(2). The normally dominant proton acceleration could be surpressed by removing the hydrocarbon contaminants by resistive heating. This inhibits screening effects and permits effective energy transfer and acceleration of other ion species. The acceleration dynamics and the spatiotemporal distributions of the accelerating E fields at the rear surface of the target are inferred from the detailed spectra.

Journal Article↗

PubMed2002

Diagnosis of the hypothenar hammer syndrome by high-resolution contrast-enhanced MR angiography.

Our objective was to describe the imaging features of hypothenar hammer syndrome using minimally invasive contrast-enhanced MR angiography in comparison with oscillography study. In five patients with hypothenar hammer syndrome Gd-BOPTA-enhanced elliptically reordered 3D pulse sequence MR was compared with oscillography findings and clinical symptoms focusing on angiographic appearance of vessel injury, distribution pattern of hand vasculature and joining branches between the radial and ulnar artery supply. All patients showed segmental occlusion at the site of trauma impact with varying involvement of the superficial palmar arch, common volar digital arteries. Embolic disease was present in 50% of patients and could be clearly identified with MRA. Good correspondence was found between angiographic appearance including the presence of collaterals, clinical symptoms and oscillography. Bilateral comparison was helpful in distinguishing between vessel variants and pathology. Bilateral Gd-BOPTA-enhanced MR angiography is a minimally invasive method to depict clearly the localization and extent of vessel injury in hypothenar hammer syndrome providing valuable information about distribution pattern of hand vasculature and presence of collaterals; however, no flow data can be obtained.

Adult↗

PubMed2002

FIP: a highly automated beamline for multiwavelength anomalous diffraction experiments.

FIP is a French Collaborating Research Group (CRG) beamline at the European Synchrotron Radiation Facility (ESRF) dedicated exclusively to crystallography of biological macromolecules, with a special emphasis on multiwavelength anomalous diffraction data collection in the 0.7-1.81 A wavelength range. The optics, consisting of long cylindrical grazing-angle mirrors associated with a cryocooled double-crystal monochromator, delivers an optimal beam in the corresponding energy range. The high level of automation, which includes automated crystal centring, automated data-collection management and data processing, makes the use of this beamline very easy. This is illustrated by the large number of challenging structures that have been solved since 1999.

Automation↗

PubMed2002

Contrast-echocardiography: confirmation of patency of laser channels after transmyocardial laser revascularization.

AIMS: Apart from casuistic autopsy results there is no long-term evidence for channel perfusion after transmyocardial laser revascularization in humans. METHODS AND RESULTS: Fifteen consecutive patients aged 63+/-17 years were investigated 71+/-15 days after coronary artery bypass surgery and/or transmyocardial revascularization with 13-37 (20+/-5) channels (CO(2) laser, 40 J/pulse). Echocardiography was performed after injection of 6 ml echo contrast medium into left ventricular cavity and after injection of 3 ml contrast medium into the left main coronary artery. In five patients with additional bypass surgery to the same region, we also injected 3 ml contrast medium into bypass graft. We could prove in 10 of 15 patients (67%) one or two laser channels in the apical left ventricular myocardium. Channels were perfused exclusively during systole. During following heart cycles myocardium was opacified up to a mean width of 1.4+/-0.4 cm, a mean depth of 0.71+/-0.1cm, and a mean area of 1.0+/-0.6 cm(2). Contrast medium was washed out via coronary venous system in 9+/-8 systoles. CONCLUSION: This is the first clinical evidence of long-term laser-channel patency in humans showing perfused myocardium via left ventricular cavity.

Contrast Media↗

PubMed2001

Persistent infection of B lymphocytes by bovine respiratory syncytial virus.

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in young cattle. Here we demonstrate BRSV persistence at low levels in tracheobronchial and mediastinal lymph nodes up to 71 days after the experimental infection of calves. Positive results were obtained on viral genomic RNA and messenger RNA coding for the nucleoprotein, glycoprotein (G), and fusion protein (F). G and F proteins were also detected in the pulmonary lymph nodes by immunohistochemistry. Double-staining experiments revealed that viral antigen was present in B-lymphocytes. Coculture experiments with the lymph node cells showed that the virus was still able to infect permissive target cells, even though no cytopathic effect was recorded. In vitro studies indicate that BRSV was still able to replicate in bovine B-lymphocyte cell lines 6 months after infection. These results may also be relevant to the understanding not only of the epidemiology and the peculiarities of the immune response of BRSV infections but also of human respiratory syncytial virus infections.

Animals↗

PubMed2001

Mechanisms of airway remodeling. Airway smooth muscle.

The airway smooth muscle cell can contract; relax; participate in allergic and inflammatory responses by expressing adhesion molecules, releasing cytokines, and producing matrix proteins and proteases; and, as has been reported, undergo migration. These properties enable the muscle cell to be a key component in the airway wall remodeling that accompanies persistent asthma. Evidence is emerging that identifies the pivotal steps in the signal transduction pathways that lead to the excessive proliferation of the muscle observed in vitro in airway smooth muscle cells from subjects with asthma. The contractile, biochemical, and growth characteristics of muscle from allergic subjects are different from those of nonallergic subjects. In addition, the allergic response impacts on the extracellular matrix in which the muscle is embedded, by altering the profile of matrix proteins released. Once the relationships between allergy and inflammation of the smooth muscle and its extracellular matrix are better defined, opportunities to prevent or reverse airway remodeling will become available.

Allergens↗

PubMed2001

How does a DNA interacting enzyme change its specificity during molecular evolution? A site-directed mutagenesis study at the DNA binding site of the DNA-(adenine-N6)-methyltransferase EcoRV.

The EcoRV DNA-(adenine-N6)-methyltransferase (MTase) recognizes GATATC sequences and modifies the first adenine residue within this site. Parts of its DNA interface show high sequence homology to DNA MTases of the dam family which recognize and modify GATC sequences. A phylogenetic analysis of M.EcoRV and dam-MTases suggests that EcoRV arose in evolution from a primordial dam-MTase in agreement to the finding that M.EcoRV also methylates GATC sites albeit at a strongly reduced rate. GATCTC sites that deviate in only one position from the EcoRV sequence are preferred over general dam sites. We have investigated by site-directed mutagenesis the function of 17 conserved and nonconserved residues within three loops flanking the DNA binding cleft of M.EcoRV. M.EcoRV contacts the GATATC sequence with two highly cooperative recognition modules. The contacts to the GAT-part of the recognition sequence are formed by residues conserved between dam MTases and M.EcoRV. Mutations at these positions lead to an increase in the discrimination between GATATC and GATC substrates. Our data show that the change in sequence specificity from dam (GATC) to EcoRV (GATATC) was accompanied by the generation of a second recognition module that contacts the second half of the target sequence. The new DNA contacts are formed by residues from all three loops that are not conserved between M.EcoRV and dam MTases. Mutagenesis at important residues within this module leads to variants that show a decreased ability to recognize the TC-part of the GATATC sequence.

Amino Acid Sequence↗

PubMed2001

Changing the target base specificity of the EcoRV DNA methyltransferase by rational de novo protein-design.

The EcoRV DNA-(adenine-N(6))-methyltransferase (M.EcoRV) specifically modifies the first adenine residue within GATATC sequences. During catalysis, the enzyme flips its target base out of the DNA helix and binds it into a target base binding pocket which is formed in part by Lys16 and Tyr196. A cytosine residue is accepted by wild-type M.EcoRV as a substrate at a 31-fold reduced efficiency with respect to the k(cat)/K(M) values if it is located in a CT mismatch substrate (GCTATC/GATATC). Cytosine residues positioned in a CG base pair (GCTATC/GATAGC) are modified at much more reduced rates, because flipping out the target base is much more difficult in this case. We intended to change the target base specificity of M.EcoRV from adenine-N(6) to cytosine-N(4). To this end we generated, purified and characterized 15 variants of the enzyme, containing single, double and triple amino acid exchanges following different design approaches. One concept was to reduce the size of the target base binding pocket by site-directed mutagenesis. The K16R variant showed an altered specificity, with a 22-fold preference for cytosine as the target base in a mismatch substrate. This corresponds to a 680-fold change in specificity, which was accompanied by only a small loss in catalytic activity with the cytosine substrate. The K16R/Y196W variant no longer methylated adenine residues at all and its activity towards cytosine was reduced only 17-fold. Therefore, we have changed the target base specificity of M.EcoRV from adenine to cytosine by rational protein design. Because there are no natural paragons for the variants described here, a change of the target base specificity of a DNA interacting enzyme was possible by rational de novo design of its active site.

Adenine↗

PubMed2001

Airway smooth muscle cell proliferation is increased in asthma.

UNLABELLED: Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be the result of increased muscle proliferation. We have for the first time been able to culture ASM cells from asthmatic patients and to compare their proliferation rate with that of nonasthmatic patients. Asthmatic ASM cell cultures (n = 12) were established from explanted lungs and endobronchial biopsies. Nonasthmatic ASM cells (n = 10) were obtained from explanted tissue from patients with no airway disease, emphysema, carcinoma, and fibrosing alveolitis. Cell counts, tritiated thymidine incorporation, and cell cycle analysis were conducted over 7 d. Asthmatic ASM cell numbers at Days 3, 5, and 7 were significantly higher than corresponding values for nonasthmatic cells (p < 0.05). Tritiated thymidine incorporation was increased 3.2-fold in asthmatic cells compared with nonasthmatic cells within the first 24 h (p = 0.026). Flow cytometric analysis of DNA content on Days 1 and 2 revealed that a significantly greater percentage of asthmatic ASM cells were in the G2 + M phase (p < 0.05). This study shows for the first time that proliferation of ASM cells is increased in patients with asthma and provides evidence for an intrinsic abnormality in the ASM cell in this disease. KEYWORDS: asthma; human airway smooth muscle; cell culture; cell proliferation; hyperplasia

Adolescent↗

PubMed2001

Distinct endobronchial expression of matrix-metalloproteinases (MMP) and their endogenous inhibitors in lung cancer.

BACKGROUND: Degradation of extracellular matrix (ECM) and basement membranes is required for tumour cell invasion and metastasis. The ECM is degraded by matrix metalloproteinases (MMP) which are counteracted by tissue inhibitors of metalloproteinases (TIMP). In aggressive tumours the balance of proteolysis and antiproteolysis is disrupted, resulting in fast tumour progression and invasiveness. We examined MMP and TIMP expression patterns in bronchial washings of 58 consecutive lung tumour patients and 10 controls. Pathohistological investigations revealed squamous cell carcinoma (n = 23), adenocarcinoma (n = 18), small cell lung carcinoma (n = 9), and pulmonary metastases of extrapulmonary tumours (n = 8). MMP/TIMP expression was correlated to histology, location, or staging of tumours. METHODS: Expression and activity of MMP was identified by zymography and Western blotting. Expression of TIMP-1 and TIMP-2 was analysed by Western blotting and enzyme-linked immunosorbent assays. RESULTS: We identified MMP-1, MMP-2 and MMP-9, but not MMP-3 or MMP-8 in bronchial washings. All MMPs were expressed in the tumour-affected and the tumour-free parts of the lung. While MMP-1 and MMP-9 were present in all samples, the inactive precursor of MMP-2 was specifically expressed in adenocarcinoma or lung metastases of extrapulmonary tumours. No MMP-2 was found in controls. While TIMP-1 was expressed in all samples, TIMP-2 was not detectable. CONCLUSION: The tumour type-specific expression of the MMP-2 precursor in adenocarcinoma and lung metastases suggests that MMP-2 in the absence of TIMP-2 correlates with aggressive tumour progression and may serve as an indicator for poor prognosis.

Adenocarcinoma↗

PubMed2001

Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor.

Transforming growth factor-beta (TGF-beta) signals through membrane-bound serine/threonine kinase receptors, which upon stimulation phosphorylate Smad proteins and thereby trigger their nuclear translocation and transcriptional activity. Although the three mammalian isoforms of TGF-beta are highly homologous at the level of sequence, analysis of their in vivo function by gene knockouts revealed striking differences, suggesting no significant functional redundancy between TGF-beta1, -2 and -3. While signal transduction by TGF-beta1 has been well characterized, receptor binding and activation by the TGF-beta2 isoform is less well understood. Here, we show that TbetaRII-B, an alternatively spliced variant of the TGF-beta type II receptor, is a TGF-beta2 binding receptor, which mediates signalling via the Smad pathway in the absence of any TGF-beta type III receptor (TbetaRIII). L6 cells lacking endogenous TbetaRIII as well as TbetaRII-B do not respond to TGF-beta2. Transfection of these cells with TbetaRII-B restores TGF-beta2 sensitivity. The expression of TbetaRII-B is restricted to cells originating from tissues such as bone where the isoform TGF-beta2 has a predominant role. This reflects the importance of this receptor in TGF-beta isoform-specific signalling.

Activin Receptors, Type I↗

PubMed2001

Primary fibroblast cell cultures from transbronchial biopsies of lung transplant recipients.

BACKGROUND: Survival after lung transplantation is limited by the development of bronchiolitis obliterans (BO) that is a fibroproliferative process and regarded as the histological marker of chronic rejection. To study further the pathogenesis of BO we attempted to establish primary fibroblast cell cultures from transbronchial lung biopsies (TBBs)of lung transplant recipients. METHODS: One to two TBB samples from each patient were collected in sterile phosphate-buffered saline. Biopsies were cut into small pieces and placed onto 25-cm2 culture flasks for cell culture and kept under standard cell culture conditions (21% O2, 5% CO2, 37 degrees C). Culture medium consisted of RPMI 1640, 10% fetal calf serum, L-glutamine, HEPES, and antibiotics. After reaching confluence, fibroblasts were passaged into 75-cm2 flasks. RESULTS: The success rate of establishing fibroblast cultures from transbronchial lung biopsies was 54% (27/50). Cell growth was independent of patient age, transplant type, underlying lung disease, indication for transbronchial lung biopsies, grade, or type of re jection and infection. CONCLUSIONS: We have established a novel method of culturing fibroblasts from lung transplant recipients. We consider this method as an unique human in vitro model to study the pathogenetic mechanisms leading to BO.

Adult↗

PubMed2001

Fast ignition by intense laser-accelerated proton beams.

The concept of fast ignition with inertial confinement fusion (ICF) is a way to reduce the energy required for ignition and burn and to maximize the gain produced by a single implosion. Based on recent experimental findings at the PETAWATT laser at Lawrence Livermore National Laboratory, an intense proton beam to achieve fast ignition is proposed. It is produced by direct laser acceleration and focused onto the pellet from the rear side of an irradiated target and can be integrated into a hohlraum for indirect drive ICF.

Journal Article↗

PubMed2001

The validity of informant report for grading the severity of Alzheimer's dementia.

The validity of informant-based techniques has been established for the detection of dementia cases by non-pathological individuals, but is still controversial for the assessment of the severity of dementia. This study aimed at ascertaining whether informant-based evaluation (the so-called informant report) of the cognitive and behavioral impairment of a patient is valid for grading the severity of dementia, and consistent with objective assessment of the patient's cognitive and behavioral functioning. We enrolled 96 community-dwelling outpatients and 56 controls assessed at the Geriatric Evaluation Unit of the University of Modena, Italy. All patients scored lower than 27 on the MMSE, and met DSM-IV inclusion criteria for Alzheimer's dementia. Patients and controls were administered the CAMDEX interview, containing a section which collects participant (patient or control) and informant evaluations on dementia-related cognitive and behavioral deficits. The informant report resulted effective at MANOVA for grading the severity of dementia in 4 of its 5 measures (namely, memory, everyday activities, general mental functioning and depressed mood), and was correlated with the scores of several scales of the CAMDEX cognitive section (i.e., CAMCOG). Instead, the participant's (patient or control) report showed a lower capacity for grading dementia, and was poorly correlated with the psychometric outcomes of cognitive functioning. On the whole, the results corroborated the validity of the informant report in the diagnostic work-up for grading dementia, given its sensitivity to the severity of dementia, and its consistency with cognitive psychometric outcomes.

Aged↗