Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 325 records · Page 18Linked to original sources

PubMed1997

Effects of PTH-rP(107-111) and PTH-rP(7-34) on adult cardiomyocytes.

We investigated whether parathyroid hormone-related peptide (PTH-rP), recently found expressed in the heart, exerts growth and contractile effects on adult cardiomyocytes from rat hearts. Synthetic PTH-rP peptides were used covering either a protein kinase C (PKC)-activating domain [PTH-rP(107-111)], or an adenylate cyclase activating domain [PTH-rP(1-34) and PTH-rP(7-34)]. PTH-rP(107-111) (1 micro M) increased creatine kinase BB activity (CK-BB), a CK isoform re-expressed during cardiac hypertrophy, within 24 h by 62+/-12%. This induction was abolished in the presence of the mitogen-activated-protein (MAP)-kinase-kinase inhibitor PD 98059. PTH-rP(107-111) activated p42-MAP-kinase within 15 min, increased protein synthesis (19+/- 4%), total protein mass (19+/-5%), cell volume (45+/-7%), and cross-sectional area (38+/-9%) of cardiomyocytes. Activation of p42-MAP-kinase and increase in protein synthesis were abolished in presence of bisindolylmaleimide, a PKC inhibitor. PTH- rP(107-111) did not directly influence contractile activity but reduced the contractile response to isoprenaline. In contrast, PTH-rP(1-34) and PTH-rP(7-34) induced spontaneous contractile activity in 3-day-old cultures. This induction was abolished in presence of Rp-cAMPS, a protein kinase A inhibitor, indicating an involvement of cAMP in this response. PTH-rP(1-34) also increased the cellular accumulation of cAMP. It is concluded that PTH-rP exert direct effects on adult cardiomyocytes by activating either PKC via a functional domain covered by amino acids 107-111 or by activation of cAMP-dependent protein kinase via a functional domain covered by amino acids 7-34. Since these parts of PTH-rP have either no homology [PTH-rP(107-111)] or only a limited structural similarity [PTH-rP(7-34)] to parathyroid hormone, these activities of PTH-rP have to be clearly distinguished from those described for parathyroid hormone.

Animals↗

PubMed1997

Adenoviral transfection of isolated pancreatic islets: a study of programmed cell death (apoptosis) and islet function.

Gene therapy provides a potential technique to modify immunity in vitro and therefore may prolong graft survival in vivo. However, viral infection and gene transfer may damage target cells and interfere with biologic function. Viruses, including adenovirus, are known to be capable of modulating apoptosis and initiating cell death by either inducing or suppressing specific processes, depending on the virus and cell system studied. The effect of adenovirus on islet cell viability and function has not been examined in detail. In this study, the dose-dependent effect of an adenoviral vector on islet cell death and glucose-stimulated insulin secretion (GSIS) was investigated to establish a therapeutic window for the dose of viral vector administered. Isolated pancreatic rat islets were incubated with an adenovirus expressing a beta-galactosidase gene (AdHCMVsp1LacZ) at different viral concentrations [multiplicity of infection (MOI) 1:10, 1:100, and 1:1000]. Transfection rate, in vitro and in vivo islet viability, and occurrence of programmed cell death were determined 1, 3, and 7 days after transfection. Islets, transfected at MOI 1:10 and 1:100, demonstrated apoptosis not significantly different from nontransfected controls. Islets, transfected at MOI 1:1000, demonstrated a significant increase in apoptosis at 24 hr, which decreased over 7 days of culture. The increase in apoptosis was not reflected by a significant decrease in in vitro GSIS of surviving islet cells, as assessed by stimulation index following in vitro perifusion. SCID or nude mice transplanted with AdlacZ-transfected islets (MOI 1:100 and 1:1000) remained normoglycemic for > or = 30 days. These results demonstrate that transfection of islets using adenoviral vectors can be manipulated such that efficient expression of the gene product encoded by the transfected gene (beta-galactosidase) can be achieved at lower transfecting concentrations of the adenoviral vector (MOI 1:10, 20.2%; MOI 1:100, 30.7%) while preserving islet function. This efficiency of transfection may allow pretransplant manipulation of isolated islet cells without vector-specific alteration of islet function. In cases where high virus concentrations are required for efficient gene transfer (adequate expression of the transgene product), a deleterious effect of the vector on islet cell function, with increased cell loss due to increased apoptotic events, is predicted. Using the AdlacZ vector, cell loss by apoptotic mechanisms appears limited to the first days following coculture with high viral concentrations, and does not appear to influence in vitro or in vivo cell function of the surviving islet cells.

Adenoviridae↗

PubMed1997

Do "whiplash injuries" occur in low-speed rear impacts?

A study was conducted to find out whether in a rear-impact motor vehicle accident, velocity changes in the impact vehicle of between 10 and 15 km/h can cause so-called "whiplash injuries". An assessment of the actual injury mechanism of such whiplash injuries and comparison of vehicle rear-end collisions with amusement park bumper car collisions was also carried out. The study was based on experimental biochemical, kinematic, and clinical analysis with volunteers. In Europe between DM 10 and 20 billion each year is paid out by insurance companies alone for whiplash injuries, although various studies show that the biodynamic stresses arising in the case of slight to moderate vehicle damage may not be high enough to cause such injuries. Most of these experimental studies with cadavers, dummies, and some with volunteers were performed with velocity changes below 10 km/h. About 65% of the insurance claims, however, take place in cases with velocity changes of up to 15 km/h. Fourteen made volunteers (aged 28-47 years; average 33.2 years) and five female volunteers (aged 26-37 years; average 32.8 years) participated in 17 vehicle rear-end collisions and 3 bumper car collisions. All cars were fitted with normal European bumper systems. Before, 1 day after and 4-5 weeks after each vehicle crash test and in two of the three bumper car crash tests a clinical examination, a computerized motion analysis, and an MRI examination with Gd-DTPA of the cervical spine of the test persons were performed. During each crash test, in which the test persons were completely screened-off visually and acoustically, the muscle tension of various neck muscles was recorded by surface electromyography (EMG). The kinematic responses of the test persons and the forces occurring were measured by accelerometers. The kinematic analyses were performed with movement markers and a screening frequency of 700 Hz. To record the acceleration effects of the target vehicle and the bullet vehicle, vehicle accident data recorders were installed in both. The contact phase of the vehicle structures and the kinematics of the test persons were also recorded using high-speed cameras. The results showed that the range of velocity change (vehicle collisions) was 8.7-14.2 km/h (average 11.4 km/h) and the range of mean acceleration of the target vehicle was 2.1-3.6 g (average 2.7 g). The range of velocity change (bumper car collisions) was 8.3- 10.6 km/h (average 9.9 km/h) and the range of mean acceleration of the target bumper car was 1.8-2.6 g (average 2.2 g). No injury signs were found at the physical examinations, computerized motion analyses, or at the MRI examinations. Only one of the male volunteers suffered a reduction of rotation of the cervical spine to the left of 10 degrees for 10 weeks. The kinematic analysis very clearly showed that the whiplash mechanism consists of translation/extension (high energy) of the cervical spine with consecutive flexion (low energy) of the cervical spine: hyperextension of the cervical spine during the vehicle crashes was not observed. All the tests showed that the EMG signal of the neck muscles starts before the head movement takes place. The stresses recorded in the vehicle collisions were in the same range as those recorded in the bumper car crashes. From the extent of the damage to the vehicles after a collision it is possible to determine the level of the velocity change. The study concluded that, the "limit of harmlessness" for stresses arising from rear-end impacts with regard to the velocity changes lies between 10 and 15 km/h. For everyday practice, photographs of the damage to cars involved in a rear-end impact are essential to determine this velocity change. The stress occurring in vehicle rear-end collisions can be compared to the stress in bumper car collisions.

Accidents, Traffic↗

PubMed1997

[Acute thoracic aortic dissection with occlusion of the left coronary artery].

Aortic dissection is the most common fatal condition that involves the aorta. Occasionally, symptoms mimic acute myocardial infarction leading to thrombolytic treatment. Accurate diagnosis in patients with chest pain is therefore essential. We describe a case of acute aortic dissection which resulted in myocardial infarction due to obstruction of the left coronary ostium. A 65-year-old female patient with no previous cardiac history was admitted to a local hospital because of severe chest pain of acute onset. Physical examination was normal except for a low blood pressure (90/50 mm Hg), heart rate 45 beats/min and parasthesia in both hands. The ECG showed sinus bradycardia with negative T-wave in VI and with 1 mm ST-segment elevation in V3. A chest X-ray was normal. Five hours later, the patient experienced once more severe chest pain followed by non-sustained polymorphic ventricular tachycardia (Figure 1). Another ECG showed bifascicular bundle branch block (right bundle branch block and left anterior fascicular block). The ECG was interpreted as showing acute myocardial infarction and treatment with intravenous streptokinase started. Since the patient remained severely hypotensive despite infusion of dobutamine, she was intubated, ventilated and transferred to our hospital. Cardiac catheterization showed acute dissection of the ascending aorta with an aortic intimal flap and an occlusion of the left coronary artery (Figures 2a and b). During catheterization, she suffered a cardiac arrest from which she could not be resuscitated. A postmortem examination confirmed the acute aortic dissection which reached to the ostium of the left coronary artery (Figures 3a and b, 4a and b) and an anterior myocardial infarction probably due to intermitted diastolic obstruction of the ostium of the left coronary artery by an aortic intimal flap.

Aged↗

PubMed1997

Is endotoxin and cytokine release related to a decrease in gastric intramucosal pH after hemorrhagic shock?

OBJECTIVES: (a) To investigate the relationship between gut ischemia parameters (gastric intramucosal pH [pHi], mucosal-arterial carbon dioxide difference [PCO2-gap]), and endotoxin or cytokine release during hemorrhagic shock; (b) to compare the predictive value of pHi, PCO2-gap and arterial lactate concentrations. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 multiple trauma patients with severe hemorrhagic shock. INTERVENTIONS: Intramucosal measurements and blood samples were obtained on admission to the emergency room and repeatedly over 48 h. MEASUREMENTS AND RESULTS: Endotoxin was measured using a chromogenic limulus amoebocyte assay. Cytokine [tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6)] values were evaluated by immunoradiometric assays. Only 3 patients had positive blood cultures but endotoxins were detected at least once in all patients. Endotoxin levels were similar in survivors and non-survivors over the study period and were not related to pHi or PCO2-gap. Initially, high levels of IL-6 were observed in both nonsurvivors and survivors [median 1778 pg/ml (range 435-44,540) vs 2068 pg/ml (range 996-92,300)]. IL-6 levels progressively decreased in the survivors but not significantly. On admission, TNF alpha concentrations were similar in nonsurvivors and survivors (42 +/- 35 vs 46 +/- 27 pg/ml). From the 24th h, TNF alpha values were higher in the nonsurvivors than in the survivors (24 h: 72 +/- 38 vs 34 +/- 17 pg/ml, p < 0.05). The greatest IL-6 levels were found for a pHi < 7.20 (28.5 +/- 36.5 vs 1.8 +/- 1.3 ng/ml, p < 0.05) or a PCO2-gap > 7.5 mmHg (1 kPa) (32.5 +/- 37.5 vs 1.7 +/- 1.3 ng/ml, p < 0.01). With the same pHi threshold, no difference was found in endotoxin levels. The lactate concentrations were predictive for outcome from the 12th h (9.5 +/- 5.9 vs 3.6 +/- 2.3 mmol/l, p < 0.05). CONCLUSIONS: During severe hemorrhagic shock, endotoxin translocation from the gut was a common phenomenon that seemed independent of both pHi values and outcome. It could not explain IL-6 and TNF alpha release. In severe hemorrhagic shock, neither pHi nor PCO2-gap provides additional information to the lactate measurements.

Adult↗

PubMed1997

[Results of testing defibrillator function of implanted cardioverter/defibrillators].

Postoperative tests of implantable cardioverter defibrillators (ICDs) are routinely performed to ensure appropriate defibrillation by the device. However, efficacy and complications of this procedure are unknown. To scrutinize the currently accepted indications to test the defibrillation function of the ICD we retrospectively analyzed 844 ICD-tests in 439 ICD-systems and 409 patients. 755 ICD-tests (89.4%) were routinely performed (57% before discharge and 43% during follow-up); 58 tests (6.9%) were performed after a change of the antiarrhythmic drug regimen, 24 tests (2.9%) after a revision of a part of the ICD-system, and seven tests (0.8%) because of a suspected dysfunction of the ICD. During routine-tests six ICD-systems (0.8%) failed to defibrillate the patient. However, in all but one test abnormalities of the ICD-system had been observed before the test. After addition of antiarrhythmic drugs, three of 58 ICD-systems (5.2%) failed to defibrillate the patient during the test (amiodarone: n = 2, flecainide: n = 1). Four of seven ICD-systems (57%) tested due to a suspected dysfunction failed to defibrillate the patient. After revisions of parts of the ICD-systems, ICD-tests never revealed a failure of defibrillation. During 16 ICD-tests (1.9%) complications occurred. The most frequent complications was inappropriate shocks (n = 10; 1.2%), the most severe one (transient) neurologic symptoms (n = 4; 0.48%). Our experience demonstrates that postoperative tests of the defibrillation function of ICDs rarely reveal ICD-dysfunction. As testing is unpleasant for the patient and not free of complications, tests might be restricted to those patients in whom an ICD-dysfunction is suspected (based on clinical presentation, results of chest-x-ray, testing of sensing signal and stimulation threshold) or class I or class III antiarrhythmic drugs have been added to the antiarrhythmic drug regimen.

Adolescent↗

PubMed1997