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Biomedical subjects

S Weis

Publications and source records attributed to S Weis.

At least 19 recordsLinked to original sources
PubMed2003

Intrasubject reproducibility of presurgical language lateralization and mapping using fMRI.

BACKGROUND: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored. OBJECTIVE: To evaluate within-test and test-retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery. METHODS: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test-retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca's area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values). RESULTS: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%. CONCLUSION: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

Adolescent↗
PubMed2002

Uterine leiomyosarcoma metastatic to the brain stem.

A patient with a history of an uterine leiomyosarcoma presented with diplopia, gait disturbances, and hypesthesia of the right face. MRI of the head showed a lesion located in the pons and causing obstructive hydrocephalus. Open biopsy revealed a metastatic tumor with histological features of leiomyosarcoma. Despite whole-brain irradiation, the patient died due to respiratory arrest. This case illustrates that brain stem metastasis may occur as a rare complication in uterine leiomyosarcoma.

Brain Neoplasms↗
PubMed2002

Comparison between mitochondrial DNA sequences in low grade astrocytomas and corresponding blood samples.

BACKGROUND/AIMS: To identify somatic mutations in the mitochondrial DNA of glioblastomas, in a previous study the displacement loops of 17 glioblastomas and corresponding blood samples were sequenced and instabilities in repeats or transitions were detected in seven tumours. This study was extended by sequencing 10 DNA samples of diffuse astrocytomas (World Health Organisation grade II) and corresponding blood samples. METHODS: The 10 DNA samples of diffuse astrocytomas and corresponding blood samples were amplified and sequenced using fluorescent nucleotides. RESULTS: No sequence differences were detected, with the exception of a quantitative shift between two genotypes heteroplasmic within the hypervariable region 2, which can be interpreted as mitotic drift. In the glioblastoma series, any particular somatic mutation was usually found in only one tumour. The only frequent alteration was coupled to a mitochondrial germline polymorphism under-represented in the low grade astrocytoma group. Moreover, a single mutation in two patients with secondary glioblastomas had already been detected in diffuse astrocytomas of these individuals. CONCLUSIONS: A lower percentage of mitochondrial DNA mutations in low grade tumours cannot be deduced from these data.

Astrocytoma↗
PubMed2001

Expression of GABA(B1) and GABA(B2) mRNA in the human brain.

GABA(B) receptors are widely expressed in the CNS. The distribution of the recently cloned GABA(B1) receptor is highly concordant with GABA(B) ligand binding sites, but experiments with transfected cell lines indicate that GABA(B1) has to heterodimerize with GABA(B2) to gain the functionality of a native GABA(B) receptor. Using in situ hybridization we investigated the expression of GABA(B1) and GABA(B2) mRNAs in the human brain. Both transcripts were detectable in prefrontal cortex, hippocampus and cerebellum with no apparent mismatch. A distinct expression of GABA(B1) was detected in putative Bergmann glia. In the human striatum GABA(B1) mRNA was expressed in moderate amounts, whereas the GABA(B2) mRNA signal was not clearly above background. According to our data, the current concept on GABA(B) receptor composition needs re-evaluation, at least for certain brain structures.

Aged↗
PubMed2001

High frequency of mitochondrial DNA mutations in glioblastoma multiforme identified by direct sequence comparison to blood samples.

In an earlier study, we showed that heteroplasmy in the mitochondrial genome of gliomas sometimes occurs in a D-loop polycytosine tract. We extended this study by pairwise comparisons between glioma samples and adjacent brain tissue of 55 patients (50 glioblastomas, 1 astrocytoma WHO grade III, 4 astrocytomas WHO grade II). We used a combination of laser microdissection and PCR to detect and quantify variations in the polycytosine tract. New length variants undetectable in the adjacent brain tissue were observed in 5 glioblastomas (9%). In 2 of these cases, samples from a lower tumor stage (WHO grade II) could be analyzed and revealed the early occurrence of these mutations in both cases. Since the mitochondrial D-loop contains additional repeats and highly polymorphic non-coding sequences, we compared 17 glioblastomas with the corresponding blood samples of the same patients by direct sequencing of the complete D-loop. In 6 of these tumors (35%), instability was detected in 1 or 2 of 3 repeat regions; in 1 of these repeats, the instability was linked to a germline T-to-C transition. Furthermore, of 2 tumors (12%) 1 carried 1 and the other 9 additional transitions. In the latter patient, 6.7 kb of the protein coding mtDNA sequence were analyzed. Six silent transitions and 2 missense mutations (transitions) were found. All base substitutions appeared to be homoplasmic upon sequencing, and 89% occurred at known polymorphic sites in humans. Our data suggest that the same mechanisms that generate inherited mtDNA polymorphisms are strongly enhanced in gliomas and produce somatic mutations.

Adult↗
PubMed2001

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin.

This study presents the long-term safety data from AFCAPS/TexCAPS, the first primary prevention trial to demonstrate that men and women with average levels of low-density lipoprotein cholesterol (LDL-C) and below average levels of high-density lipoprotein cholesterol (HDL-C) can significantly benefit from long-term treatment to lower LDL-C; lovastatin 20 to 40 mg/day reduced the risk of a first acute major coronary event (fatal or nonfatal myocardial infarction, unstable angina, or sudden death) by 37% (p = 0.00008). This double-blind randomized, placebo-controlled trial, in 6,605 generally healthy middle-aged and older men and women, had prespecified end point and cancer analyses. All analyses were intention-to-treat. Safety monitoring included history, physical examination, and laboratory studies (including hepatic transaminases and creatine phosphokinase [CPK]). All participants, even those who discontinued treatment, were contacted annually for vital status, cardiovascular events, and cancer history. After an average of 5.2 years of follow-up, there were 157 deaths (80 receiving lovastatin and 77 receiving placebo; relative risk [RR] 1.04; 95% confidence interval [CI] 0.76 to 1.42; p = 0.82); of which 115 were noncardiovascular (RR 1.21; CI 0.84 to 1.74; p = 0.31), and of these, 82 were due to cancer (RR 1.41; CI 0.91 to 2.19; p = 0.13). There were no significant differences between treatment groups in overall cancer rates, discontinuations for noncardiovascular adverse experiences, or clinically important elevations of hepatic transaminases or CPK. Among those who used cytochrome P450 isoform (CYP3A4) inhibitors, there were no treatment group differences in the frequency of clinically important muscle-related adverse events. Treatment with lovastatin 20 to 40 mg daily for primary prevention of coronary heart disease was well tolerated and reduced the risk of first acute coronary events without increasing the risk of either noncardiovascular mortality or cancer.

Aged↗
PubMed2001

Streptolysin O: the C-terminal, tryptophan-rich domain carries functional sites for both membrane binding and self-interaction but not for stable oligomerization.

Streptolysin O belongs to the class of thiol-activated toxins, which are single chain, four-domain proteins that bind to membranes containing cholesterol and then assemble to form large oligomeric pores. Membrane binding involves a conserved tryptophan-rich sequence motif located within the C-terminally located domain 4. In contrast, sites involved in oligomerization and pore formation have been assigned to domains 1 and 3, respectively. We here examined the functional properties of domain 4, which was recombinantly expressed with an N-terminal histidine tag for purification and an additional cysteine residue for covalent labeling. The fluorescently labeled fragment readily bound to membranes, but it did not form oligomers nor lyse cell membranes. Moreover, the labeled fragment did not detectably become incorporated into hybrid oligomers when combined with lytically active full-length toxin. However, when present in large excess over the active toxin, the domain 4 fragment effected reduction of hemolytic activity and of functional pore size, which indicates interference with oligomerization of the lytically active species. Our findings support the notion that domain 4 of the streptolysin O molecule may fold autonomously, is essential for membrane binding and is capable not of irreversible but of reversible association with the entire toxin molecule.

Bacterial Proteins↗
PubMed2001

Coupling of cholesterol and cone-shaped lipids in bilayers augments membrane permeabilization by the cholesterol-specific toxins streptolysin O and Vibrio cholerae cytolysin.

Vibrio cholerae cytolysin (VCC) forms oligomeric pores in lipid bilayers containing cholesterol. Membrane permeabilization is inefficient if the sterol is embedded within bilayers prepared from phosphatidylcholine only but is greatly enhanced if the target membrane also contains ceramide. Although the enhancement of VCC action is stereospecific with respect to cholesterol, we show here that no such specificity applies to the two stereocenters in ceramide; all four stereoisomers of ceramide enhanced VCC activity in cholesterol-containing bilayers. A wide variety of ceramide analogs were as effective as D-erythro-ceramide, as was diacylglycerol, suggesting that the effect of ceramide exemplifies a general trend of lipids with a small headgroup to augment the activity of VCC. Incorporation of these cone-shaped lipids into cholesterol-containing bilayers also gave similar effects with streptolysin O, another cholesterol-specific but structurally unrelated cytolysin. In contrast, the activity of staphylococcal alpha-hemolysin, which does not share with the other toxins the requirement for cholesterol, was far less affected by the presence of lipids with a conical shape. The collective data indicate that sphingolipids and glycerolipids do not interact with the cytolysins specifically. Instead, lipids that have a conical molecular shape appear to effect a change in the energetic state of membrane cholesterol that in turn augments the interaction of the sterol with the cholesterol-specific cytolysins.

Bacterial Proteins↗
PubMed2001

Apoptosis in the basal ganglia of the developing human nervous system.

Programmed cell death (PCD) plays a crucial role in the development of the central nervous system through controlling neuronal numbers and adequate synaptic connections. PCD has been considered to occur in the form of apoptosis. To examine how apoptosis occurs in the developing human brain, we performed a morphometric TUNEL study, using a commercially available kit (ApopTag Kit, Oncor Inc.). We examined apoptotic cells in the basal ganglia of 47 fetuses and newborns without macroscopical and microscopical evident congenital anomalies. Gestational age ranged from 12 to 40 weeks. The numerical density as well as the labeling index of TUNEL-positively labeled nuclei were evaluated. In the caudate nucleus and putamen, TUNEL-labeled cells were observed around the 12th week of gestation. The numerical density of total cells was significantly decreased, whereas the labeling index of apoptotic cells was significantly increased with advanced gestational age. In the globus pallidus, the numerical density of total cells decreased with advancing gestational age, while the labeling index of apoptotic cells increased between the 20th and 28th week, followed by a decrease until the 40th week. The analysis of TUNEL-positive cells revealed a different reaction pattern for the various basal ganglia with regard to the timing and degree of the apoptotic process in regulating cell numbers.

Age Factors↗
PubMed2001

Progressive idiopathic bilateral striato-pallido-dentate calcinosis (Fahr's disease) in a person with anabolic steroid abuse.

A 33-year-old male black student suddenly died during a basketball game. His previous medical history, including his neurological status, was unremarkable, but he was known to take anabolic steroids for several years. At autopsy, the cause of death was due to a fresh myocardial infarction. On neuropathological examination, there was extensive bilateral symmetrical calcification involving the basal ganglia as well as the dentate nuclei and the white matter of the cerebellum (Fahr's disease). A possible correlation between anabolic steroid-induced hypercalcemia and brain calcification is discussed.

Journal Article↗
PubMed2001

The diagnostic relevance of cerebral amyloid angiopathy in the setting of forensic pathology - a report of two cases and review of the literature.

The neuropathological features seen in two cases with cerebral amyloid angiopathy (CAA) are presented. An 85-year-old woman was found comatose at home and died on the way to the hospital. The cause of death was an intracerebral hemorrhage (ICH) in the right parietal lobe. A 93-year-old woman with a history of traumatic subarachnoid hemorrhage was operated on for a chronic subdural hematoma. Intraoperatively, she developed severe ICH and died. The cause of death was an ICH in the parieto-occipital lobe. The morphology of the vessels was studied on differently stained sections and the neuropathological findings of the surrounding brain tissue were investigated. The affected vessels showed the characteristic alterations seen in CAA and included vascular amyloid deposition, fibrinoid necrosis, double-barrel lumen, splitting of the internal elastic lamina, defects of the vessel wall, and microaneurysms. Visualization of beta-amyloid protein was performed by histological and immunohistochemical methods. The immunohistochemistry for beta-amyloid was more sensitive and yielded better results compared with Congo red. In cases of ICH, CAA has to be considered in the differential diagnosis. Besides the use of Congo red stain, the application of beta-amyloid immunohistochemistry is requested to reliably make the diagnosis of CAA. Additional staining with a modified silver impregnation technique (AgNOR) is useful to detect associated neurodegenerative changes.

Journal Article↗
PubMed2001

Primary meningeal sarcomas in two children.

Primary meningeal sarcomas are rare but highly aggressive tumors predominantly affecting children. The clinical course, imaging characteristics and histopathological features of meningeal sarcomas in two pediatric patients are presented. Furthermore, we critically discuss the new WHO classification of these entities comparing them to older descriptions. In a 6-year-old girl, a cranial computed tomography (CT) scan was performed, after a mild head trauma, showing a parieto-occipital hemorrhage. One month later, a circumscribed mass adhering to the meninges and with central areas of hemorrhage was evident on magnetic resonance imaging (MRI) scans. Brain biopsy revealed a polymorphocellular sarcoma originating from the leptomeninges and infiltrating the brain. In an 8-year-old girl, who presented with headaches and vomiting, several MRI-examinations were inconspicuous for nearly one year until the latest MR-scan revealed a diffuse contrast enhancement of the leptomeninges of the whole brain and spinal canal. After open biopsy, primary leptomeningeal sarcomatosis was diagnosed. Although CT and MRI did not allow a specific diagnosis in both cases the exact visualization of the extent of the tumor and/or meningeal involvement was possible. Since there are no specific imaging criteria to differentiate meningeal sarcoma from other solid brain tumors or from other tumoral or inflammatory meningioses brain biopsy is indispensable. In order to avoid misinterpretations and delays of therapy, early open brain biopsy or surgical resection of the lesion is necessary in cases of unclear brain masses, especially of unclear meningeal processes. Due to the low number of cases published so far, the biological behavior and clinical management of this tumor entity still awaits further investigation.

Child↗
PubMed2001

Gliomatosis cerebri: post-mortem molecular and immunohistochemical analyses in a case treated with thalidomide.

Gliomatosis cerebri (GC) is a rare tumor of the central nervous system (CNS) characterized by widespread diffuse infiltration of the brain and spinal cord by neoplastic glial cells. We report the case of a 17-year-old boy with a bioptically diagnosed fibrillary astrocytoma. The administration of thalidomide, which was suggested to be beneficial in the treatment of human cancers, had no substantial clinical effect on our patient. Autopsy studies revealed a diffuse infiltration of the frontal and temporal lobes of the right hemisphere, brainstem, and the leptomeninges covering the whole spinal cord by an astrocytic tumor, which showed features both of low-grade astrocytoma and glioblastoma multiforme. No mutations in the p53 and PTEN tumor suppressor genes were found; immunoreactivities for p53, PTEN, and EGFR could not be detected.

Adolescent↗
PubMed2001

Etomidate and thiopental inhibit platelet function in patients undergoing infrainguinal vascular surgery.

BACKGROUND: Postoperative platelet hyperaggregability following general anesthesia has been reported in patients undergoing major vascular surgery. In contrast, since anesthetic agents inhibited platelet function both in vitro and in vivo, an increased risk for postoperative bleedings due to prolonged platelet dysfunction has been discussed. Nevertheless, data describing platelet-affecting properties of induction agents such as etomidate and thiopental in patients undergoing major vascular surgery are lacking. METHODS: Platelet function was determined at 0, 2, 20, and 200 microg/ml thiopental and at 0, 0.2, 2, 20 microg/ml etomidate in vitro in blood samples drawn from 16 patients suffering from severe occlusive arterial disease. In addition, 30 patients undergoing vascular surgery were investigated before (PRE) and after anesthesia induction (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14), and 2 h after the beginning of surgery (T2). Platelet function was determined according to platelet aggregation, in vitro bleeding time, and flow cytometric measurements. RESULTS: In vitro, P-selectin expression was inhibited by etomidate at 2 and 20 microg/ml (-28% and -38%, respectively) and also by thiopental at 200 microg/ml (-27%). In patients undergoing vascular surgery, anesthesia induction in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and an inhibition of ADP- and collagen-induced platelet aggregation (-30% and -17%, respectively) and of P-selectin expression (-25%) at T0. In the THIO group, only ADP-induced platelet aggregation was affected (-16%). At T2, all parameters had reached PRE level again in both groups. Furthermore, in comparison with the THIO group, operation time was significantly prolonged and transfusion volume was significantly increased in the ETO group. In addition, platelet count and hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1, fibrinogen and antithrombin III and partial thromboplastin time remained unchanged in both groups during the study period. CONCLUSIONS: In the present study, etomidate and, to a minor extent, thiopental offered significant platelet inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher transfusion rates and prolonged operation times. Therefore, anesthetic-related platelet inhibitory properties should be considered when searching for the anesthetic agent of choice, especially in patients with compromised hemostasis and co-existing bleeding disorders.

Aged↗
PubMed2001

Sonography and neuropathology of a congenital brain tumor: report of a rare incident.

A rare case of a congenital brain tumor was diagnosed by sonography in a fetus at 33 weeks' gestation. The ultrasound examination showed a large area of both increased echogenicity and echolucency in one hemisphere suggestive of brain tumor or hemorrhage. The neuropathological examination revealed an undifferentiated glial tumor with large areas of necrosis.

Adult↗
PubMed2001

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): efficacy and tolerability of long-term treatment with lovastatin in women.

The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first coronary heart disease (CHD) primary prevention trial of the cholesterol-reducing agents called "statins" to include women. For 5608 men and 997 postmenopausal women without clinical evidence of cardiovascular disease (CVD) who had average low-density lipoprotein cholesterol (LDL-C) and below average high-density lipoprotein cholesterol (HDL-C), 20-40 mg/day lovastatin reduced first acute major coronary events (AMCEs) 37% (for those receiving placebo and lovastatin, respectively, 183 and 116 first AMCEs defined as fatal or nonfatal myocardial infarction [MI], unstable angina, or sudden cardiac death; relative risk [RR] 0.63; 95% confidence interval [95% CI] 0.50, 0.79; p < 0.001). Statistically significant reductions in prespecified secondary end points (coronary revascularizations, unstable angina, MI, cardiovascular end point events, and coronary end point events) were also associated with lovastatin treatment in the overall cohort. This paper provides results in women, a prespecified subgroup. Among women, 20-40 mg/day lovastatin reduced LDL-C 25% and increased HDLC 9% (p < 0.001). A prespecified analysis revealed consistency with the overall results regardless of gender (i.e., there were no statistical differences between men and women in risk reduction for first AMCEs with lovastatin). However, the number of women who had an AMCE was small, and there was insufficient power to detect a treatment group difference among women (7 of 499 vs. 13 of 498 first AMCEs in those receiving lovastatin and placebo, respectively; RR 0.54; 95% CI 0.22, 1.35; p = 0.183). Numerical reductions in all prespecified secondary end points were observed for women treated with lovastatin, but again, the numbers of events were small and the differences were not statistically significant. Chronic long-term treatment with lovastatin was well tolerated, with no treatment group differences in the frequency of cancer, muscle symptoms, and clinically important liver enzyme elevations. In AFCAPS/TexCAPS, a consistent pattern of numerical reductions in all prespecified primary and secondary cardiovascular end points was observed in women treated with lovastatin for primary prevention of CHD. However, because of the small number of events, there was insufficient power to detect significant treatment group differences. Lovastatin treatment was associated with statistically significant decreases in LDL-C and increases in HDL-C, and chronic long-term treatment with 20-40 mg/day lovastatin was well tolerated in women.

Aged↗
PubMed2001

Defective mitochondrial oxidative phosphorylation in myopathies with tubular aggregates originating from sarcoplasmic reticulum.

Abnormalities of the sarcotubular system presenting as tubular aggregates (TAs) have been described in a variety of neuromuscular disorders. Here, we report on immunohistochemical and biochemical findings in 7 patients (2 familial and 5 sporadic cases) suffering from myopathies with TAs. In muscle biopsy specimens from 5 of the 7 patients, TAs were immunopositive for the ryanodine receptor (RYR 1) of the sarcoplasmic reticulum (SR), the SR Ca2+ pump (SERCA2-ATPase), and the intraluminal SR Ca2+ binding protein calsequestrin, indicating an SR origin of these aggregates. Furthermore, these 5 cases showed decreased respiratory chain enzyme activities (NADH:CoQ oxidoreductase. complex I and cytochrome c oxidase [COX], complex IV), while the remaining 2 patients exhibited normal values. Our findings indicate a functional link between mitochondrial dysfunction and the presence of TAs originating from the sarcoplasmic reticulum.

Adult↗