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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 109 records · Page 6Linked to original sources
PubMed2002

Femoral revision using the Wagner stem: results at 2-9 years.

We followed 39 patients with 40 revision hip arthroplasties using the Wagner stem. Mean follow-up was 65 (29-108) months. There were 12 intraoperative proximal femoral fractures, which all united, five postoperative dislocations not related to subsidence, and two loose stems that were revised. Clinical improvement was best for pain. Once the stem was osteointegrated the clinical and radiological result remained stable for up to 9 years.

Adult↗
PubMed2002

Formation of cartilage matrix proteins by BMP-transfected murine mesenchymal stem cells encapsulated in a novel class of alginates.

Proliferation and differentiation of wild-type, BMP-2 and BMP-4 transfected cells of C3H10T1/2, a mouse mesenchymal stem cell line that can differentiate into chondrocytes, were studied under monolayer (2D-) and encapsulation (3D-) conditions. Cells were encapsulated in a novel class of alginate. The alginate was of clinical grade (CG) because of complete removal of mitogenic and cytotoxic contaminants by chemical means. Compared to commercial alginates used so far for encapsulation it was characterized by ultra-high viscosity (UHV; viscosity of a 0.1% w/v solution of about 20 cP). In contrast to monolayer cultures, proliferation of cells was prevented when the cells were encapsulated in UHV/CG alginate at the same suspension density. As revealed by immunohistochemistry and quantitative RT-PCR, transfected and wild-type monolayer cells showed synthesis of type I collagen after transfer into differentiation medium, while culture in an alginate scaffold resulted in an upregulation of type II collagen and other hyaline cartilage proteins. BMP-4 transfected cells produced considerably more type II collagen than BMP-2 transfected and wild-type cells. BMP-4 transfected cells were also characterized by type I collagen production up to Day 10 and exhibited transient alkaline phosphatase activity levels that were much higher than the peak values observed for the other two cell lines. The coincidence of the ALP peak values with downregulation of type I collagen in BMP-4 transfected cells suggested that C3H10T1/2 cells differentiate into chondrocytes via a chondroprogenitor-like cell.

Alginates↗
PubMed2002

In vitro sensitivity of Mycobacterium xenopi to five antibiotics.

We tested 20 strains of Mycobacterium xenopi (M. xenopi) in order to evaluate their in vitro sensitivity to amikacine, clarithromycine, ethambutol, ofloxacine and rifampicin, by establishing minimal inhibitory concentration (MIC) on agar medium. MICs of amikacine, clarithromycine and ofloxacine are low, so that these antibiotics can be used in the treatment of M. xenopi infections. MICs of ethambutol are higher than seric concentrations. Though, its therapeutic use is due to its in vivo ability to enhance penetration of other antibiotics in mycobacteria. Strain sensitivity to rifampicin seems heterogeneous but the small number of tested strains does not entitle the exclusion of rifampicin from the treatment of M. xenopi infections.

Amikacin↗
PubMed2002

Change of pneumococcal resistance to antibiotics in adults between 1995 and 1997: a study in eight French counties.

The main object of this study was to describe the evolution of antibiotic resistance in pneumococci from adults, in eight French counties of France between 1995 and 1997. Despite the high and increasing prevalence (23-35%) of pneumococci with diminished susceptibility to penicillin G (PSDP), resistance to amoxycillin (0.8-0.5%) and to cefotaxime (0-0.3%) was rare in both 1995 and 1997 respectively. The percentage of pneumococci resistant to penicillin G (PRP, minimum inhibitory concentration >1 mg/l) remained stable between the two periods. PSDP showed increased resistance to macrolides (30-41%), to cotrimoxazole (28-34%) and to tetracycline (19-25%). These figures are lower than those obtained over the same periods and the same regions in children. The distribution of PSDP serotypes isolated in adults was the same as that seen in children: by descending order serotypes 23, 14, 9 and 6. This study by the Regional Pneumococcal Observatories confirms the high prevalence and the main characteristics of antibiotic resistance among pneumococci with variations in levels of resistance with the age of patients, with the site of sampling and from one Observatory to another.

Adolescent↗
PubMed2002

Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts.

NF-kappaB/Rel transcription factors are modulators of immune and inflammatory processes and are also involved in malignancy. Phosphorylation of the IkappaB inhibitors by the IkappaB kinase (IKK) complex leads to their proteasomal degradation, resulting in activated NF-kappaB. Here, we investigated the activation status of NF-kappaB and the IKK complex in acute myeloid leukemia (AML). Gelshift assays revealed an increased level of activated nuclear NF-kappaB in myeloid blasts. Both bone marrow and peripheral blood blasts from AML patients showed enhanced IKK activity relative to controls, whereas the IKK protein concentrations were comparable. In addition, an increased level of IkappaB-alpha was detected in AML blast cells, although this appeared to be insufficient to block nuclear translocation of NF-kappaB, also confirmed by immunofluorescence. In subtype M4 and M5 AML cells a more extensive NF-kappaB activation and higher IKK activity was found than in M1/M2 specimens. Isolated AML blasts cultured ex vivo responded to external stimulation (TNF, LPS) by further IKK activation, IkappaB degradation and NF-kappaB activation. Preincubation with the proteasome inhibitor PSI inhibited the NF-kappaB system in isolated AML blasts. This study established for the first time a dysregulation of IKK signaling in AML leading to increased NF-kappaB activity suggesting potential therapeutic avenues.

Acute Disease↗
PubMed2002

[Influence of general practitioners' personal knowledge on migraine in medical attitudes towards their patients suffering from migraine].

The subjective aspects of the doctor-patient relationship may impact disease management methods applied to migraine patients. This prospective study compared the medical attitudes of doctors towards migraine headache in relationship to their personal sensitivity to this disease. The study concerned data on the health care management of migraine headache by 711 general practitioners, 325 of whom suffer from migraine headache themselves, 227 who do not suffer from migraines, but who have a close family member that does, and 159 who neither suffer from migraine headache, nor have anyone close who does. Each doctor filled out a medical practice questionnaire concerning this pathology and included one migraine patient in the survey. Each patient answered a specific quality of life questionnaire. It was shown that doctors suffering from migraine headache themselves declared having more migraine patients in their practices than the other doctors. Nonetheless, the doctor's sensitivity to migraine headache does not seem to have an impact on the diagnosis and therapeutic care of patients; diagnosis criteria are the same within the three groups and correspond to international headache society criteria. Furthermore, the therapeutic means applied, whether acute first or second intention treatment, or long-term treatment, do not differ amongst the three groups. Quality of life and patients' feelings about medical support were significantly related to the doctor's level of sensitivity towards the disease: they were highest amongst patients treated by doctors suffering from migraines themselves, and lowest amongst patients treated by doctors with no close family members suffering from migraines. Although therapeutical attitudes do not vary, the quality of life perceived by patients is better when the doctors themselves are concerned by the disease.

Adult↗
PubMed2002

Aqueous ethanolic extract of St. John's wort (Hypericum perforatum L.) induces growth inhibition and apoptosis in human malignant cells in vitro.

Extracts of Hypericum perforatum (St. John's wort) are widely and effectively used in the treatment of mild to moderate depression. In addition, hypericin, a component of Hypericum p. extracts, exhibits light-dependent phototoxic properties and can be used in phototherapy. We therefore investigated the cytotoxic activity of two total Hypericum p. extracts, namely from fresh and dried plants in the dark and after exposure to 7.5 J/cm2 white light illumination and compared it with the effect of hypericin on K562, U937, LN229 glioblastoma cell lines and normal human astrocytes. The chemical toxicity of non-illuminated Hypericum p. extracts in the cells tested is low as expressed by a LC50 between 1.9-4.1 mg/ml, which corresponds to 10.3-17.3 microM hypericin and 114.4-190.7 microM hyperforin after 48 h treatment. Hypericum p. extracts induced dose-dependent growth arrest of human malignant cells in the absence of illumination with GI50 values between 0.43-1.77 mg/ml (2.3-9.7 microM hypericin, 26.1-106.7 microM hyperforin) for the fresh plant extract and 0.59-3.03 mg/ml (2.5-12.8 microM hypericin, 24.2-124.7 microM hyperforin) for the dried extract. The growth inhibitory effect of fresh Hypericum p. extract was more pronounced in leukemia cell lines K562 and U937, the GI50 concentrations being about 7-fold lower than the corresponding LC50 for the cell lines K562 and U937, but almost the same as the LC50 for LN229 and NHA cells. GI50 (microgram/ml) for tumor cell lines K562 and U937 (432 and 799) established after 48 h differed significantly (p < 0.05) from those of LN229 and normal human astrocytes (1767 and 2900). The light-exposed extracts were more toxic, their LC50 and GI50 values were reduced to values corresponding to LC50 concentration of 3.7-7.4 microM and a GI50 of 1.3-3.5 microM for phototoxic hypericin. After exposure to light, there was a significant difference (p = 0.006) between the GI50 of glioblastoma LN229 cells (582 micrograms/ml) and normal human astrocytes (1050 micrograms/ml). Morphological examination by light microscopy and phosphaditylserine exposure on the outer plasma membrane investigated by Annexin V-binding with flow cytometry after 24 h confirmed that Hypericum p. extracts caused apoptosis of treated cells without exposure to light. Hypericum p. extracts derived from fresh herbs and from dried herbs which differ in their levels of phloroglucinols (hyperforin and adhyperforin) were compared. The hyperforin content of fresh St. John's wort extract exceeded that of dried plant extract by 47% and the GI50 values of fresh plant extract were 73%, 77% and 58% of those established for dried extract in the three malignant cell lines K562, U937 and LN229 in the dark (p < 0.05). Under white light (7.5 J/cm2), both extracts exerted comparable growth inhibitory and apoptosis inducing effects due to the phototoxicity of hypericin, the corresponding concentrations of which were in the range of 1.3-3.5 microM. The data reported in this study suggest that illumination is not essential for the growth inhibitory and apoptotic effects of Hypericum p. extracts, but light activation potentiates them. Furthermore, the constituent hyperforin is at least partly responsible for these effects in the dark.

Annexin A5↗
PubMed2001

The important role of neuropeptides in complex regional pain syndrome.

OBJECTIVE: To test the contribution of neurogenic inflammation and neuropeptide release to the pathophysiology of complex regional pain syndrome (CRPS). BACKGROUND: CRPS is characterized by edema and increased skin temperature, sympathetic dysfunction and pain, or hyperalgesia. This investigation was prompted by a recent study by the authors that suggested a facilitated neurogenic inflammation in CRPS. METHODS: In addition to physical examination, calcitonin gene-related peptide (CGRP) serum concentrations were measured using a radioimmunoassay (RIA) for human CGRP in 19 patients with acute CRPS, on the affected and unaffected sides (n = 13), before and 9 months after therapy (n = 9). In addition, an age- and sex-matched group of 16 healthy controls was investigated. RESULTS: In blood from the cubital vein, CGRP levels in patients with CRPS (122.2 +/- 14.6 pmol/L) were increased (controls 83.8 +/- 6.7 pmol/L, p < 0.03). There was no difference between the affected and unaffected sides. There was, however, a reduction of serum CGRP after therapy (acute disease: 141.2 +/- 18.5 pmol/L, after therapy 106.7 +/- 11.3 pmol/L, p < 0.005); absolute CGRP levels then no longer differed from controls. Increased serum CGRP was correlated to the incidence of nerve lesions (p < 0.02) and hyperhidrosis (p < 0.04). There was no correlation to other clinical symptoms, duration of CRPS, or pain. However, normalization of CGRP after therapy was accompanied by clinical improvement of local inflammatory signs, but not by pain reduction. CONCLUSIONS: Increased systemic CGRP levels in patients with acute CRPS suggest neurogenic inflammation as a pathophysiologic mechanism contributing to vasodilation, edema, and increased sweating. However, pain and hyperalgesia, in particular in chronic stages, were independent of increased neuropeptide concentration.

Adult↗
PubMed2001

Improvement of the long-term adhesive strength between metal stem and polymethylmethacrylate bone cement by a silica/silane interlayer system.

A loss of adhesive strength between metal stem and bone cement is clinically found to be a serious problem in total hip arthroplasty and causes many operative revisions. The objective of this study was to improve the long-term adhesive strength at this interface. A new silica/silane interlayer coating system is introduced. The layers are designed to bond the metal stem surface to the polymethylmethacrylate bone cement marginally leakage free. In vitro tensile tests were performed on specimens of TiAl6V4 and CoCrMo that were cemented by pairs with different bone cements with and without the new coating system. The specimens were stored in isotonic saline solution up to 150 days. The adhesive strength decreased about 75% within 30 days of storage on specimens of both metal alloys that were conventionally cemented without the new interlayer system. With the new coating, the high initial adhesive strength (40-50 MPa) could be stabilized for TiAl6V4 over 150 days. For the same 150-day storage period, the adhesive strength of the coated CoCrMo alloy still decreased but the decrease was only half that experienced by the uncoated CoCrMo. The loss of adhesive strength on CoCrMo specimens could be reduced if the metal surface was activated by a plasma treatment. The new coating interface system could help to considerably reduce revision operations caused by debonding effects at the interface metal/polymethylmethacrylate bone cement.

Adhesiveness↗
PubMed2001

The effect of peroxynitrite on the catalytic activity of soluble guanylyl cyclase.

Soluble guanylyl cyclase (sGC) is a key enzyme of the *NO/cGMP pathway. Many cardiovascular disorders are associated with reduced *NO-mediated effects, while vascular superoxide (O(2)*(-)) production is increased. Both radicals rapidly react to peroxynitrite. We investigated whether peroxynitrite affects the activity and protein expression of sGC in intact vascular preparations. Catalytic sGC activity and expression of the sGC-beta(1) subunit was measured by conversion of radiolabeled GTP and western blot, respectively, using cytosolic extracts from rat aorta that had been incubated for 4 h with *NO/O(2)*(-) systems (devoid of free *NO) generating either 0.13 microM or 7.5 microM peroxynitrite/min. Incubation of rat aorta with 0.13 microM peroxynitrite/min had no effect. In striking contrast, incubation with 7.5 microM peroxynitrite/min resulted in a shift of the concentration-response curve obtained with a *NO donor (p =.0004) and a reduction of maximal specific activity from 3579 +/- 495 to 2422 +/- 265 pmol cGMP/mg/min (p =.036). The expression of the sGC-beta(1) subunit was unchanged. Exposure of aorta to the O(2)*(-) component had no effect, while exposure to the *NO-component reduced sGC expression to 58.8 +/- 7% (p <.001) and maximal sGC activity from 4041 +/- 992 to 1429 +/- 491 pmol cGMP/mg/min (p =.031). These data suggest that continuous generation of extracellular peroxynitrite might interfere with the *NO/cGMP signaling in vascular cells.

Animals↗
PubMed2001

Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence, recurrence, and long-term survival rates of ischemic stroke subtypes by a mechanism-based classification scheme (Trial of ORG 10172 in Acute Stroke Treatment, or TOAST). METHODS: We identified all 583 residents of the city of Erlangen, Bavaria, Germany, with a first ischemic stroke between 1994 and 1998. Multiple overlapping sources of information were used to ensure completeness of case ascertainment. The cause of ischemic stroke was classified according to the TOAST criteria. Patients were followed up at 3 months and 1 and 2 years after stroke onset. RESULTS: The age-standardized incidence rates for the European population (per 100 000) regarding ischemic stroke subtypes were as follows: cardioembolism, 30.2 (95% CI 25.6 to 35.7); small-artery occlusion, 25.8 (95% CI 21.5 to 30.9); and large-artery atherosclerosis, 15.3 (95% CI 12 to 19.3). When age-adjusted to the European population, the incidence rate for large-artery atherosclerosis was more than twice as high for men than for women (23.6/100 000 versus 9.2/100 000). Two years after onset, patients in the small-artery occlusion subgroup were 3 times more likely to be alive than those with cardioembolism. Ischemic stroke subtype according to the TOAST criteria was a significant predictor for long-term survival, whereas subtype was not a significant predictor of long-term recurrence up to 2 years, both before and after adjustment for age and sex. CONCLUSIONS: Epidemiological observational studies that possess wide access to appropriate diagnostic technologies and apply standardized etiologic classifications provide a much better understanding of underlying risk factors for initial stroke, recurrence, and mortality.

Age Distribution↗
PubMed2001

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Electromyography of respiratory muscles in amyotrophic lateral sclerosis.

We reviewed the records of 52 amyotrophic lateral sclerosis (ALS) patients examined between 1995 and 2000 who had needle electromyography (EMG) of their respiratory muscles, including the diaphragm, at or near the time of their diagnosis. With respiratory function testing, patients with abnormal diaphragmatic EMG at diagnosis (Group 1, n=23) had significantly lower forced vital capacity (FVC), lower daytime arterial PO(2) and higher PCO(2) measurements (p<0.05) than patients with normal diaphragmatic EMG (Group 2, n=29). Twenty-eight percent of the patients without symptoms or signs of respiratory insufficiency at the time they were examined had an abnormal diaphragm EMG. Mean survival of Groups 1 and 2 were similar. However, sub-analysis of patients within each group, comparing those treated with non-invasive positive pressure ventilation (NIPPV) with those not treated, showed that treated patients in Group 1 (abnormal diaphragm EMG) survived significantly longer (p<0.05) than untreated patients. They also started NIPPV earlier than treated patients in Group 2. We conclude that respiratory muscle EMG was simply and safely performed on ALS patients at or around the time of diagnosis. The procedure can detect sub-clinical respiratory muscle dysfunction. The technique used for EMG of the respiratory muscles, its pitfalls and contraindications are also reviewed.

Aged↗
PubMed2001

Plant adenosine 5'-phosphosulfate reductase is a novel iron-sulfur protein.

Adenosine 5'-phosphosulfate reductase (APR) catalyzes the two-electron reduction of adenosine 5'-phosphosulfate to sulfite and AMP, which represents the key step of sulfate assimilation in higher plants. Recombinant APRs from both Lemna minor and Arabidopsis thaliana were overexpressed in Escherichia coli and isolated as yellow-brown proteins. UV-visible spectra of these recombinant proteins indicated the presence of iron-sulfur centers, whereas flavin was absent. This result was confirmed by quantitative analysis of iron and acid-labile sulfide, suggesting a [4Fe-4S] cluster as the cofactor. EPR spectroscopy of freshly purified enzyme showed, however, only a minor signal at g = 2.01. Therefore, Mössbauer spectra of (57)Fe-enriched APR were obtained at 4.2 K in magnetic fields of up to 7 tesla, which were assigned to a diamagnetic [4Fe-4S](2+) cluster. This cluster was unusual because only three of the iron sites exhibited the same Mössbauer parameters. The fourth iron site gave, because of the bistability of the fit, a significantly smaller isomer shift or larger quadrupole splitting than the other three sites. Thus, plant assimilatory APR represents a novel type of adenosine 5'-phosphosulfate reductase with a [4Fe-4S] center as the sole cofactor, which is clearly different from the dissimilatory adenosine 5'-phosphosulfate reductases found in sulfate reducing bacteria.

Amino Acid Sequence↗
PubMed2001

Regulation of mesangial cell function by vasodilatory signaling molecules.

Proliferation of mesangial cells and expansion of mesangial matrix is a hallmark of glomerular disease leading to end-stage renal failure and requiring renal replacement therapy. Independently from the type of injury, e.g. in glomerulonephritis or diabetic nephropathy, the response to injury is remarkably uniform. Chronic glomerular disease is frequently associated with increases in systemic blood pressure and altered intraglomerular hemodynamics. Furthermore, reduction of systemic blood pressure and inhibition of the vasoconstrictor peptide angiotensin II have been shown to delay end-stage renal failure in various types of human kidney disease. Since vasoconstrictors of mesangial cells and efferent glomerular arterioli, such as angiotensin II, are thought to be detrimental for the progression of chronic glomerular disease, we propose that vasodilatory factors which antagonize the effects of angiotensin II, might have beneficial effects during the course of progressive kidney disease. To support this concept we will summarize currently available data on the role of vasodilatory signaling molecules such as natriuretic peptides (ANP, BNP and CNP), nitric oxide (NO), the prostaglandines PGE2 and prostacycline, and the purine mediator adenosine in the regulation of mesangial function.

Adenosine↗
PubMed2001

Upregulation of vascular NAD(P)H oxidase subunit gp91phox and impairment of the nitric oxide signal transduction pathway in hypertension.

In this study we analyzed the role of vascular NAD(P)H oxidase in the generation of O(2)(-) and the endothelial impairment of NO signal transduction pathway in hypertension. In aortic rings of 15-month-old stroke-prone spontaneously hypertensive rats (SHR15) we found a 10-fold increased expression of NAD(P)H oxidase subunit gp91phox mRNA associated with a 3-fold increased production of O(2)(-) compared to age-matched Wistar rats (WIS15). Vasorelaxation studies in aortas of SHR15 showed a strongly diminished response to acetylcholine, NO-donor S-nitroso-N-acetyl-d,l-penicillamine, and organic nitrate glyceryl trinitrate compared to WIS15. Soluble guanylate cyclase (sGC) activity and sGC beta(1)-subunit protein expression was downregulated in aortas and lungs of SHR15. These data suggest an upregulation of vascular NAD(P)H oxidase and an impairment of the NO signal transduction pathway in hypertension.

Animals↗