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Biomedical subjects

J Meyer

Publications and source records attributed to J Meyer.

At least 37 records · Page 2Linked to original sources

[Hartmann's procedure indication in colorectal carcinoma].

Based on data obtained in a prospective, multicenter trial investigating the surgical treatment of colorectal carcinomas, the aim of this study was to investigate the value and relevance of Hartmann's procedure compared with alternative surgical approaches in elective interventions and emergency situations in carcinoma of the rectum (n=10,355) and the left hemicolon (n=8,825). Only in 3.4% (n=353) of patients with rectal carcinoma was the Hartmann's procedure executed with curative intention, indicating that this approach is recommendable only in (1) rare emergency situations (1.66%, n=172), (2) selected cases with elective intervention such as high-risk patients or subjects with poor prognosis, and (3) individuals with rectal carcinoma of the lower third who require deep resection (2+3, 1.75%, n=181). However, Hartmann's procedure resulted in the lowest mortality (7.5%) of the various procedures aiming for radical resection in the case of luminal obstruction or perforation at the left hemicolon. With palliative intention, 4.3% of patients with rectal carcinoma (n=449) received primary colostomies. At the left hemicolon, palliative segmental colon resection with primary anastomosis maintaining intestinal passage showed the lowest mortality (6.1%) and perioperative morbidity (33.9%) under elective circumstances, whereas Hartmann's procedure was preferred in emergency situations.

Adenocarcinoma↗

MEG response to median nerve stimulation correlates with recovery of sensory and motor function after stroke.

OBJECTIVE: Hemiparesis due to damage by stroke in primary motor cortex (MI) or its underlying projections presents a problem for functional neuroimaging technologies that attempt to evaluate the neurophysiological basis for restoration of motor function. Traditional assessments of MI function require patients to move their fingers, hands, or limbs, which can be either impossible or markedly compromised after stroke. We recently demonstrated in normal subjects that magnetoencephalography (MEG), a non-invasive neuromagnetic functional imaging technique, detects neuronal response elicited by electrical median nerve stimulation in MI, as well as primary somatosensory cortex (SI). In the present study, we used the MEG response from median nerve stimulation to investigate the recovery of primary motor and somatosensory in acute ischemic stroke patients. METHODS: Twelve patients with unilateral ischemic strokes that affected sensorimotor functions of their hand were studied in the acute stage (4.4+/-1.2 days, mean+/-SD) and during a 1-month follow-up (38.6+/-5.6 days, except for one patient's follow-up done 6 month after stroke). RESULTS: Among the multiple cortical sources localized after median nerve stimulation, one source localized to SI and another localized to the vicinity of MI. Changes in the source strengths of the first component post-stimulus of MI and SI correlated with the extent of recovery of sensorimotor functions as determined by neurological exams. CONCLUSIONS: This study provides a novel way of indirectly assessing MI function using MEG during the acute stroke phase, when many patients often cannot perform motor tasks due to paralysis.

Adult↗

Efficient expansion and gene transduction of mouse neural stem/progenitor cells on recombinant fibronectin.

Neural stem/progenitor cells (NSCs) are commonly grown as floating neurospheres in medium containing basic fibroblast growth factor and epidermal growth factor. Under these conditions, about 1% of the cells retain multipotentiality. We developed a protocol based on culture of NSCs in adherence on recombinant fibronectin (rFN) to transduce up to 90% NSCs at a multiplicity of infection of 2 with no need for viral concentration or production of serum-free retroviral supernatants. NSCs grew faster on rFN than as neurospheres on tissue culture plastic and did not lose their stem cell nature or multipotentiality. Furthermore, retroviral-mediated transgene expression was sustained with time in culture and upon differentiation into neurons and astrocytes. These experimental conditions may be utilized to study the function of various genes in NSCs, and to manipulate NSCs for gene and cell therapy of several neurological diseases.

Animals↗

Self-inactivating retroviral vectors with improved RNA processing.

Three RNA features have been identified that elevate retroviral transgene expression: an intron in the 5' untranslated region (5'UTR), the absence of aberrant translational start codons and the presence of the post-transcriptional regulatory element (PRE) of the woodchuck hepatitis virus in the 3'UTR. To include such elements into self-inactivating (SIN) vectors with potentially improved safety, we excised the strong retroviral promoter from the U3 region of the 3' long terminal repeat (LTR) and inserted it either downstream or upstream of the retroviral RNA packaging signal (Psi). The latter concept is new and allows the use of an intron in the 5'UTR, taking advantage of retroviral splice sites surrounding Psi. Three LTR and four SIN vectors were compared to address the impact of RNA elements on titer, splice regulation and transgene expression. Although titers of SIN vectors were about 20-fold lower than those of their LTR counterparts, inclusion of the PRE allowed production of more than 10(6) infectious units per ml without further vector optimizations. In comparison with state-of-the-art LTR vectors, the intron-containing SIN vectors showed greatly improved splicing. With regard to transgene expression, the intron-containing SIN vectors largely matched or even exceeded the LTR counterparts in all cell types investigated (embryonic carcinoma cells, fibroblasts, primary T cells and hematopoietic progenitor cells).

Animals↗

Replication of 1q42 linkage in Finnish schizophrenia pedigrees.

Chromosome 1q has been implicated in the etiology of schizophrenia in several independent studies. However, the peak linkage findings have been dispersed over a large chromosomal region, with negative findings in this region also being reported. Our group has previously observed linkage on chromosome 1q42, maximizing within the DISC1 gene, which has also been implied in the etiology of schizophrenia based on functional studies. In the study presented here, we genotyped 300 polymorphic markers on chromosome 1 using a study sample of 70 families with multiple individuals affected with schizophrenia or related conditions, independent of the study samples in our previous reports. We again found evidence for linkage on 1q42 maximizing within the DISC1 gene (rs1000731, lod=2.70). Further, a haplotype containing the most strongly linked markers showed some evidence of association with the disease. This replicates the previous linkage finding in the same region and constitutes supportive evidence for a susceptibility gene in this region.

Chromosome Mapping↗

[Primary adenocarcinoma of the left atrium mimicking benign myxoma].

Primary tumors of the heart are rare, whereas cardiac metastases, most frequently from adenocarcinomas, occur in up to 20% of malignant tumors. We report about a 61-year-old female patient who was admitted with recurrent stress-induced dizziness, intermittent tachycardia and a fall due to a pre-syncope. Echocardiography showed a left atrial tumor with the typical features of a pediculated myxoma, leading to open heart surgery. However, histopathology revealed a 2.2 x 1.5 cm adenocarcinoma. The subsequent search for a primary tumor, including tumor markers and (18)F-FDG-PET, was unsuccessful, as was a second thorough diagnostic workup half a year later. The tumor was therefore classified as a primary cardiac adenocarcinoma.

Adenocarcinoma↗

The genomic organization of the murine Mlc1 (Wkl1, KIAA0027) gene.

The human MLC1( WKL1, KIAA0027) gene encodes a putative transmembrane protein expressed exclusively in brain. Recessive mutations within this gene cause megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM 604004, 605908). Furthermore, a missense mutation in this gene is suggestively linked with hereditary catatonic schizophrenia in a large pedigree. The murine gene Mlc1is composed of 12 exons spanning approximately 20 kb, and all exon-intron boundaries conform to the GT/AG consensus. The single copy transcript after splicing is approximately 2.8 kb in length, it contains 496 bp of 5' untranslated region (5'-UTR) and 1143 bp of 3'-UTR, and encodes a protein of 382 amino acids. Potential binding sites for transcription factors including CCAAT-boxes are present in the 5'-flanking region. Fluorescent in situ hybridization localizes the gene to mouse chromosome 15E-F, a region syntenic to human chromosome 22q13. The characterization of the genomic structure of the murine gene will facilitate studies of gene function and physiological properties of the encoded protein in transgenic mouse models.

Amino Acid Sequence↗

A Hammondia-like parasite from the European fox (Vulpes vulpes) forms biologically viable tissue cysts in cell culture.

Tissue cysts of parasites of the genus Hammondia are rarely described in naturally or experimentally infected intermediate hosts. However, ultrastructural examinations on tissue cyst stages of Hammondia sp. are needed, e.g. to compare these stages with those of Neospora caninum and other related parasites. We describe a cell culture system employed to examine the in vitro development of tissue cysts of a Hammondia sp.-like parasite (isolate FOX 2000/1) which uses the European fox as a definitive host. Cells of a diploid finite cell line from embryonal bovine heart (KH-R; CCLV, RIE 090) were infected by inoculation of sporozoites und cultivated for up to 3 months. Transmission electron microscopic examination of 17 day old cell culture material revealed the presence of cyst walls. Infected cell cultures cultivated for 2 months were used to feed a fox. Six to 13 days post infection the fox shed large numbers (n=1.2 x 10(7)) of Hammondia-sp. like oocysts which could not be distinguished from those used to infect the cell culture as determined by DNA sequencing of the internal transcribed spacer 1 and the D2/D3 domain of the large subunit ribosomal DNA. To find out the proportion of parasitophorous vacuoles that had developed into tissue cysts, the expression of bradyzoite markers was examined by probing infected cell cultures with mouse polyclonal antibodies against Toxoplasma gondii bradyzoite antigen 1 (anti-BAG1) and rat monoclonal antibodies against a cyst wall protein (mAbCC2). Nineteen and 90 days post infection all parasitophorous vacuoles in the cell cultures were positive with anti-BAG1 and mAbCC2. This shows that biologically viable (i.e. infectious) tissue cysts of a fox-derived Hammondia sp. isolate (FOX 2000/1) can be efficiently produced in this cell culture system. Since in vitro cystogenesis of dog-derived Hammondia heydorni has not been observed yet, in vitro cyst formation might be one trait to separate fox-derived Hammondia sp. from H. heydorni on a species level.

Animals↗

SELPLG gene polymorphisms in relation to plasma SELPLG levels and coronary artery disease.

P-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD risk.

Adult↗

Diagnostic value of onset-recordings and marker annotations in dual chamber pacemaker stored electrograms.

AIMS: Stored electrograms (EGM) have recently been introduced into pacemaker therapy. New generation devices offer the possibility to store the onset of the EGM (several seconds preceding storage trigger) and marker annotations. The aim of the study was to evaluate whether the diagnostic capabilities of EGMs are improved by these new features. METHODS: We studied 65 patients (age 68+/-12 years, 41 male) implanted with a DDDR-system (PulsarMax II 1280; Guidant). During a 1-month period 319 EGMs have been recorded. EGM triggers were: Ventricular Tachycardia (VT), Non-Sustained VT (NSVT), Atrial Tachycardia Response (ATR), Pacemaker Mediated Tachycardia (PMT) and Sudden Bradycardia Response (SBR). First, each EGM was analysed with onset and markers blinded. EGMs were classified with respect to their trigger as confirmed, not-confirmed or false-positive. Analysis was then repeated with markers visible but without onset, and thereafter vice versa. Finally, EGMs were analysed with both features. It was noted whether the presence of marker annotations and/or onset-recording changed the initial classification of the stored EGMs. RESULTS: 169 EGMs were triggered by SBR, which can only be confirmed with onset recording. False positive EGMs (atrial undersensing) occurred in 12%. The remaining 150 EGMs were triggered by ATR (80%), NSVT (11%), VT (6%) and by PMT (3%). Without onset/markers 37 of these 150 EGMs (25%) could not be confirmed. With markers and onset 33/37 (89%) of these EGMs could now be classified as confirmed or false positive. These EGMs became diagnostic with onset alone in 24%, with markers alone in 24%, and with the combination of both in 41%. In 4 EGMs no definite diagnosis could be established. CONCLUSION: Stored electrograms provide direct insights into device function, thereby providing a validation of diagnostic data. The expanded recording of onset and markers results in markedly improved diagnostic capabilities - compared with conventional EGMs. These new features were necessary to interpret correctly 61% of all stored electrograms, without which a diagnosis would not have been possible. Both onset-recording and marker annotation are necessary for optimal analysis.

Aged↗

[The cadherin hypothesis of schizophrenia].

Disturbance of prenatal brain development and/or postnatal brain maturation in the context of the etiology and pathophysiology of schizophrenic psychoses is increasingly recognized as the developmental hypothesis of schizophrenia. This hypothesis is based on findings in neuroimaging and neuroanatomical findings in schizophrenic disorders. Cell adhesion molecules, such as the cadherins, are of critical importance for morphogenesis in the CNS during embryonic development. Recent investigations of the genomic organization and chromosomal localization of cadherins show a remarkable association with linkage results in affected multiplex pedigrees. Taken together, these findings should lead to an investigation of the role of cadherins in complex psychiatric disorders.

Brain↗

[A novel hirudin coating of vascular endoprostheses: experimental results].

PURPOSE: Does hirudin coating improve the patency of iliac artery endoprostheses in comparison to non-hirudin-coated endoprostheses? MATERIALS AND METHODS: Nitinol stents and stentgrafts covered with polytetrafluoroethylene (PTFE) were coated with the polymer polyamino-p-xylylene-co-poly-p-xylylene using chemical vapor deposition (CVD) technique. Hirudin was covalently bound to the surface of the endoprostheses via the amino-group. External factors (mounting of the prosthesis, sterilization, storage time and temperature, release) affecting the hirudin activity were evaluated in vitro. Five types of prostheses were compared in vivo: (1) plain and (2) CVD- and hirudin-coated stents; (3) plain, (4) CVD-coated, and (5) CVD- and hirudin-coated PTFE-stentgrafts. In 20 sheep, 16 protheses of each type were inserted in arteries pretreated with a Fogarty maneuver. The animals were followed for either 1 (n = 10) or 6 (n = 10) months. Immediately after implantation and after 1, 3, and 6 months, intravascular ultrasound (IVUS) and angiography were performed. The vascular specimens were analyzed histologically. RESULTS: Within 10 weeks, the hirudin activity of coated stents dropped 60 % due to external factors; the activity of coated PTFE stentgrafts dropped 20 %. After 1, 3, and 6 months, IVUS and histology revealed a significantly reduced patency of the hirudin-coated stentgrafts compared to the other prostheses. Only IVUS showed a significantly reduced patency of hirudin coated stents after 1 and 3 months compared to plain and CVD-coated PTFE-stentgrafts. The reduced patency was caused by neointimal hyperplasia. CONCLUSIONS: In an experimental setting, hirudin coating did not improve the patency of vascular endoprostheses.

Angiography↗