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Biomedical subjects

M Walter

Publications and source records attributed to M Walter.

At least 55 records · Page 3Linked to original sources
PubMed2001

Immunohistochemical detection of scrapie prion proteins in clinically normal sheep in Pennsylvania.

Following diagnosis of scrapie in a clinically suspect Suffolk sheep, 7 clinically normal flockmates were purchased by the Pennsylvania Department of Agriculture to determine their scrapie status using an immunohistochemical procedure. Two of the 7 euthanized healthy sheep had positive immunohistochemical staining of the prion protein of scrapie (PrP-Sc) in their brains, nictitating membranes, and tonsils. The PrP-Sc was localized in the areas of the brain where, histopathologically, there was neurodegeneration and astrocytosis. The PrP-Sc occurred within germinal centers of the affected nictitating membranes and tonsils and was located in the cytoplasm of the dendrite-like cells, lymphoid cells, and macrophages. These results confirm that immunohistochemical examination of the nictitating membrane can be used as a screen for the presence of scrapie infection in clinically normal sheep at a capable veterinary diagnostic laboratory. In sheep with a PrP-Sc-positive nictitating membrane, the diagnosis of scrapie should be confirmed by histopathology and immunohistochemical examination of the brain following necropsy. Following full validation, immunohistochemistry assays for detection of PrP-Sc in nictitating membrane lymphoid tissues can improve the effectiveness of the scrapie control and eradication program by allowing diagnosis of the disease in sheep before the appearance of clinical signs.

Animals↗
PubMed2001

High density lipoproteins induce cell cycle entry in vascular smooth muscle cells via mitogen activated protein kinase-dependent pathway.

In this study we found that HDL acts as a potent and specific mitogen in vascular smooth muscle cells (VSMC) by stimulating entry into S-phase and DNA synthesis in a time- and concentration-dependent manner, induction of cyclins D1, E, and A, as well as activation of cyclin D-dependent kinases as inferred from phosphorylation of the retinoblastoma protein (pRb). Moreover, HDL induced activation of the mitogen-activated protein kinase pathway including Raf-, MEK-1, and ERK1/2, as well as the expression of proto-oncogen c-fos, which is controlled by ERK1/2. PD98059, an inhibitor of MEK-1 blocked the mitogenic activity of HDL and cyclin D1 expression. HDL-induced VSMC proliferation, cell cycle progression, cyclin D1 expression, and activation of the Raf-1/MEK-1/ERK1/2 cascade were blocked by preincubation of cells with pertussis toxin indicating involvement of trimeric G-protein. By contrast, none of these responses was inhibited by the protein kinase C inhibitor, GF109203X. The mitogenic effects of native HDL were not mimicked by apo A-I, reconstituted HDL containing apo A-I, or cholesterol-containing liposomes. In conclusion, HDL possesses an intrinsic property to induce G-protein- and MAP-kinase-dependent proliferation and cell cycle progression in VSMC. The strong and specific mitogenic effect of HDL should be taken into account, when therapeutic strategies to elevate the plasma level of these lipoproteins are developed.

Animals↗
PubMed2000

Activation of phosphatidylinositol-specific phospholipase C by HDL-associated lysosphingolipid. Involvement in mitogenesis but not in cholesterol efflux.

Our earlier studies demonstrated that high-density lipoproteins (HDLs) stimulate multiple signaling pathways, including activation of phosphatidylcholine-specific phospholipases C and D (PC-PLs) and phosphatidylinositol-specific phospholipase C (PI-PLC). However, only activation of PC-PLs was linked to the HDL-induced cholesterol efflux. In the study presented here, the role of HDL-induced PI-PLC activation was studied. In human skin fibroblasts, HDL potently induced PI-PLC as inferred from enhanced phosphatidylinositol bisphosphate (PtdInsP(2)) turnover and Ca(2+) mobilization. The major protein component of HDL, apo A-I, did not induce PtdInsP(2) turnover or Ca(2+) mobilization in these cells. Both HDL and apo A-I promoted cellular cholesterol efflux, whereas only HDL induced fibroblast proliferation. Inhibition of PI-PLC with U73122 or blocking intracellular Ca(2+) elevation with Ni(2+) or EGTA markedly reduced the extent of HDL-induced cell proliferation but had no effect on cholesterol efflux. In fibroblasts from patients with Tangier disease which are characterized by defective cholesterol efflux, neither HDL-induced PtdInsP(2) breakdown and Ca(2+) mobilization nor cell proliferation was impaired. HDL-induced fibroblast proliferation, PtdInsP(2) turnover, and Ca(2+) mobilization were fully mimicked by the lipid fraction isolated from HDL. Analysis of this fraction with high-performance liquid chromatography (HPLC) and time-of-flight secondary ion mass spectroscopy (TOF-SIMS) revealed that the PI-PLC-inducing activity is identical with two bioactive lysosphingolipids, namely, lysosulfatide (LSF) and sphingosylphosphorylcholine (SPC). Like native HDL, LSF and SPC induced PtdInsP(2) turnover, Ca(2+) mobilization, and fibroblast proliferation. However, both compounds did not promote cholesterol efflux. In conclusion, two agonist activities are carried by HDL. Apo A-I stimulates phosphatidylcholine breakdown and thereby facilitates cholesterol efflux, whereas LSF and SPC trigger PI-PLC activation and thereby stimulate cell proliferation.

Apolipoprotein A-I↗
PubMed2000

A placebo-controlled crossover trial of creatine in mitochondrial diseases.

To test the efficacy and safety of creatine (Cr) monohydrate in mitochondrial diseases, 16 patients with chronic progressive external ophthalmoplegia or mitochondrial myopathy were randomized in a crossover design to receive double-blind placebo or 20 g Cr/day for 4 weeks. Cr was well tolerated, but there were no significant effects with regard to exercise performance, eye movements, or activities of daily life. The power of this pilot study was limited and future multicenter trials are needed.

Adult↗
PubMed2000

Involvement of phospholipase D in store-operated calcium influx in vascular smooth muscle cells.

In non-excitable cells, sustained intracellular Ca2+ increase critically depends on influx of extracellular Ca2+. Such Ca2+ influx is thought to occur by a 'store-operated' mechanism, i.e. the signal for Ca2+ entry is believed to result from the initial release of Ca2+ from inositol 1,4,5-trisphosphate-sensitive intracellular stores. Here we show that the depletion of cellular Ca2+ stores by thapsigargin or bradykinin is functionally linked to a phosphoinositide-specific phospholipase D (PLD) activity in cultured vascular smooth muscle cells (VSMC), and that phosphatidic acid formed via PLD enhances sustained calcium entry in this cell type. These results suggest a regulatory role for PLD in store-operated Ca2+ entry in VSMC.

Animals↗
PubMed2000

Phospholipase A(2) is involved in thapsigargin-induced sodium influx in human lymphocytes.

Previously, we reported that emptying of intracellular Ca(2+) pools with endoplasmatic Ca(2+)-ATP-ase inhibitor thapsigargin leads to the Na(+) influx in human lymphocytes (M. Tepel et al., 1994, J. Biol. Chem. 269, 26239-26242). In the present study we examined the mechanism underlying the thapsigargin-induced Na(+) entry. We found that the thapsigargin-induced increase in Na(+) concentration was effectively inhibited by three structurally unrelated phospholipase A(2) (PLA(2)) inhibitors, p-bromophenacyl bromide, 3-(4-octadecyl)-benzoylacrylic acid (OBAA), and bromoenol lactone (BEL). The thapsigargin-induced Na(+) influx could be mimicked by PLA(2) exogenously added to the lymphocyte suspension. In addition, thapsigargin stimulated formation of arachidonic acid (AA), the physiological PLA(2) product. AA induced Na(+) entry in a time- and concentration-dependent fashion. Both, thapsigargin-induced Na(+) influx and AA liberation were completely inhibited in the presence of tyrosine kinase inhibitor genistein but not in the absence of extracellular Ca(2+). Collectively, these data show that thapsigargin-induced Na(+) entry is associated with tyrosine kinase-dependent stimulation of PLA(2).

Acetophenones↗
PubMed2000

[Significance of hydrostatic valves in therapy of chronic hydrocephalus].

Earlier design changes in hydrocephalus valves focusing on reducing overdrainage failed. Since the middle of the 1990s, hydrostatic valve constructions have been available which are claimed to solve this problem. The objective of this study was to evaluate the efficiency of these constructions. Clinical status and ventricular size were evaluated in 45 patients with chronic hydrocephalus before and 1, 6, and 26 weeks after operation. In 35 of these, a Miethke dual-switch valve was implanted (treatment group 1), and the others received a combination of a programmable Codman-Hakim valve and a Miethke shunt assistant as the hydrostatic element of the configuration (treatment group 2). A third group (n = 6) had already been shunted but suffered from overdrainage symptoms which could not be overcome by conservative measures. In these cases, the only operative treatment was the implantation of a Miethke shunt assistant adjunctively to the existing valve. In groups 1 and 2, there was a significant permanent improvement in the clinical state in nearly 80% of cases and a moderate permanent improvement in about 10%. Mild clinical and radiological signs of overdrainage occurred in three patients during the first postoperative week but resolved without further operative measures within the next 5 weeks. Typically, the ventricular width was not or only marginally reduced in these 45 patients. In the patients treated for symptoms of overdrainage (group 3), complaints resolved within the first week after implantation of the shunt assistant. The study indicates that gravitational shunts may be very effective in preventing overdrainage in chronic hydrocephalus, and therefore these constructions could represent the gold standard in the treatment of chronic hydrocephalus.

Adult↗
PubMed2000

Pulmonary function after thoracoscopic thymectomy versus median sternotomy for myasthenia gravis.

BACKGROUND: Impaired pulmonary function due to myasthenia gravis (MG) is further compromised by thymectomy, which is necessary in most cases. Thoracoscopic thymectomy (tThx) can achieve the same resection and functional improvement of MG as median sternotomy (sThx). The possible advantage of tThx in maintaining better perioperative lung function was quantified. METHODS: In a prospective trial, 20 patients with MG were randomly allocated to undergo tThx (n = 10) by three-trocar left-sided approach or sThx (n = 10) performed as an extended procedure. Complete pulmonary function was measured at 12-hour intervals, beginning 6 hours postoperatively. Effective postoperative pain control in both groups was achieved by patient-controlled analgesia with morphine sulfate assessed by a visual analogue scale. Statistical analysis for comparison of tThx and sThx was performed using the Mann-Whitney U test. RESULTS: Postoperative vital capacity, forced vital capacity, forced expiratory volume per second, and peak expiratory flow, measured as a percentage of the individual preoperative capacity, were significantly better with tThx compared with sThx. Immediate postoperative lung function was reduced to 35% and 65% after tThx and sThx, respectively. By the third postoperative day, recovery of pulmonary function was complete after tThx but only 55% after sThx. CONCLUSIONS: Less pronounced impairment and faster recovery of pulmonary function after tThx characterize this new approach for thymectomy as minimally invasive. These results could make tThx the preferred surgical treatment of MG, which was improved to the same extent as after sThx.

Adolescent↗
PubMed2000

Case matching and relative clause attachment.

Two accounts of relative clause attachment will be discussed, the case-matching hypothesis proposed by Sauerland and Gibson (1998) and the attachment-binding dualism (Hemforth et al., in press a, b). While the case-matching hypothesis predicts that relative clauses are preferentially attached to NPs whose case matches that of the relative pronoun, attachment binding predicts that NPs are preferentially attached to the most salient host, that is NP1 in constructions with two NPs. We conducted two off-line studies, one sentence completion task and one magnitude estimation experiment using subject (nominative pronoun) and object (accusative pronoun) relative clauses that can be attached to either of the two nouns in a complex subject (NP1 = nominative, NP2 = genitive) or object NP (NP1 = accusative, NP2 = genitive). While attachment binding predicts an across-the-board NP1 preference, the case-matching hypothesis predicts an NP1 prefence only in the case of subject (object) NPs followed by subject (object) relative clauses. The results of both experiments provide evidence for attachment binding and against case matching.

Humans↗
PubMed2000

Prospective study on titanium bar-retained overdentures: 2-year results.

Within a monometallic concept 29 patients received titanium bar-retained mandibular overdentures on 2 IMZ implants. The study had a prospective design with 3 months recall intervals. One of 58 implants failed after 11 months. There were no significant differences of the mean plaque scores (Silness, Löe) and the mean sulcus bleeding scores (Mühlemann, Son) at the abutments between baseline, 12 months and 24 months. Less than 40% of the subjects showed plaque score zero at 24 months. However, 89% exhibited sulcus bleeding score zero indicating health of the peri-implant soft tissues in most cases. Plaque at the basal site of the bar was scored separately at additional measuring points located at the central area and the contact areas between bar and abutments. Bar plaque scores nearly doubled between baseline and 12 months and remained high at 24 months. Median maximal vertical bone loss around the implants was 1.7 mm after 2 years. Bone loss did not exceed one quarter of the implant length in 79%. The monometallic concept in bar-retained overdentures on 2 implants proved its clinical suitability except for the applicability of pure titanium for bar clips. Plaque formation beneath the bar seems to be one of the major clinical problems.

Adult↗
PubMed2000

The use of an in situ curing hydroxyapatite cement as an alternative to bone graft following removal of enchondroma of the hand.

Following curettage of enchondromata of the phalanges we filled the resultant bone cavity with hydroxyapatite cement in eight patients to avoid cancellous bone grafting. This material differs significantly from the ceramic hydroxyapatite commonly used in clinical practice. It is produced by the combination of two calcium phosphates which, in the presence of water, form a paste that cures to a solid implant with a microporous structure. Like ceramic hydroxyapatite, this cement is highly biocompatible and does not provoke a foreign body giant cell reaction, a sustained inflammatory response or a toxic reaction. We performed a prospective study with X-rays and clinical assessment up to 1 year after the operation. There were no complications, and all patients regained full function of the hand.

Adult↗
PubMed2000

Stopping power of ions in a magnetized two-temperature plasma.

Using the dielectric theory for a weakly coupled plasma, we investigate the stopping power of an ion in an anisotropic two-temperature electron plasma in the presence of a magnetic field. The analysis is based on the assumption that the energy variation of the ion is much less than its kinetic energy. A general expression for the stopping power is analyzed for weak and strong magnetic fields (i.e., for the electron cyclotron frequency less than and greater than the plasma frequency), and for low and high ion velocities. It is found that the usually velocity independent friction coefficient contains an anomalous term which diverges logarithmically as the projectile velocity approaches zero. The physical origin of this anomalous term is the coupling between the cyclotron motion of the electrons and the long-wavelength, low-frequency fluctuations produced by the projectile ion.

Journal Article↗
PubMed2000

Circadian variation and onset mechanisms of ventricular tachyarrhythmias in patients with coronary disease versus idiopathic dilated cardiomyopathy.

To determine the circadian variations and the onset mechanisms of ventricular tachyarrhythmias (VT) in patients with implantable cardioverter defibrillators, stored electrograms of 364 VT episodes occurring in 40 patients with coronary artery disease (CAD) and in 29 patients with idiopathic dilated cardiomyopathy (DCM) were analyzed. A similar circadian distribution of VT episodes was observed in both groups, with a morning peak and less pronounced evening peak. After exclusion of patients with atrial fibrillation, VT onset was classified as (1) sudden if preceded by > or = 8 regular cycles without ventricular premature beats, (2) onset with a short-long-short interval, and (3) a more complex onset with variable patterns of ventricular premature beats before initiation of VT. Sudden onset was found in 26% and 21% of VTs in CAD and DCM respectively. A short-long-short interval preceded 29% of VTs in CAD compared to 14% of VTs in DCM (P < 0.05). A more complex onset was observed in the remaining 45% of VTs in CAD and 65% of VTs in DCM (P < 0.05). In conclusion, patients with DCM and CAD had similar circadian distributions of VT episodes. The majority of episodes were preceded by complex occurrence of ventricular premature beats rather than by the classic short-long-short sequence. These findings have important implications for the development of preventive pacing methods.

Cardiomyopathy, Dilated↗
PubMed2000

Immunohistochemical study of constitutive neuronal and inducible nitric oxide synthase in the central nervous system of goat with natural listeriosis.

The expression of both constitutive and inducible forms of nitric oxide synthase (NOS) was investigated by immunohistochemical staining of formalin-fixed paraffin-embedded sections in normal and Listeria monocytogenes-infected brains of goats. In normal control goats, a small number of neurons showed immunoreactivity of both iNOS and nNOS, and the number of iNOS-positive neurons was higher than the number of nNOS-positive neurons. In natural listeriosis, listeria antigens were easily immunostained in the inflammatory cells of microabscesses. In this lesion, the immunoreactivity of iNOS in neurons was more intense than the control, but nNOS was not. In microabscesses, nNOS was weakly visualized in macrophages and neutrophils, while iNOS was expressed in macrophages, but not in neutrophils. These findings suggest that normal caprine brain cells, including neurons, constitutively express iNOS and nNOS, and the expressions of these molecules is increased in Listeria monocytogenes infections. Furthermore, inflammatory cells, including macrophages, expressing both nNOS and iNOS may play important roles in the pathogenesis of bacterial meningoencephalitis in goat.

Animals↗