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Biomedical subjects

J Meyer

Publications and source records attributed to J Meyer.

At least 91 records · Page 5Linked to original sources

The human dopamine transporter gene: the 5'-flanking region reveals five diallelic polymorphic sites in a Caucasian population sample.

The 5'-flanking region of the human dopamine transporter (hDAT) was systematically screened for variants by single strand conformation analysis (SSCA) between -1586 and +97 basepair (bp) relative to the transcription start site. Five diallelic polymorphisms were found, which were shown to be due to single base substitutions: T-67A, G-660C, C-839T, C-1169G, T-1476G. In a population sample of 119 unrelated Caucasians, allele frequencies of the rarer allele were 47% for -67T, 3% for -660C, 45% for -839T, 50% for -1169G, and 8% for -1476G, respectively. Among 15 observed haplotypes, seven haplotypes collected a frequency of about 96% in our sample. T-67A, C-839T, C-1169G, T-1476G were related to potential transcriptional recognition sites. These findings and the occurrence of distinct haplotypes at the hDAT promoter locus in a Caucasian population sample make this region a promising target in the context of linkage and association studies in certain diseases.

5' Untranslated Regions↗

Angiographic analysis of immediate and long-term results of PTCR vs. PTCA in complex lesions (COBRA study).

We conducted a prospective, randomized trial to compare immediate and long-term effects of percutaneous transluminal coronary angioplasty (PTCA) and high-frequency rotational atherectomy (PTCR) in patients with angiographically predefined complex coronary artery lesions (AHA type B2 and C). The relation of lesion characteristics to procedural results is reported in this angiographic analysis. Patients were randomly assigned to balloon angioplasty (n = 250 patients) or rotational atherectomy (n = 252 patients). Quantitative coronary angiography could be performed in 447 patients to evaluate immediate results and in 293 patients with a 6-month angiographic follow-up. Procedural success was comparable in the PTCR and in the PTCA group (80% vs. 76%, P = 0.260). The need for stent implantation due to a residual stenosis >50% or a bail-out situation was significantly higher in the PTCA group (9.7% vs. 2.0%, P = 0.001). In both treatment groups, diameter stenosis was effectively reduced and MLD increased. The acute gain did not differ between the two groups. At 6-month control, the restenosis rate was comparable in the PTCR and in the PTCA group (37% vs. 35%, P = 0.658), whereas diameter stenosis was significantly more severe in the PTCR group than in the PTCA group (52% vs. 46%, P = 0.039) and, correspondingly, the MLD was significantly smaller in the PTCR group (1.29 mm vs. 1.44 mm, P = 0.031). Late loss was about the same in both groups, however, net gain and net gain index were significantly higher in the PTCA group (0.82 mm vs. 0.64 mm, P = 0.008; and 31% vs. 24%, P = 0.009). Analysis of procedural results for various lesion characteristics revealed no significant difference between treatment groups. In this randomized trial, complex coronary artery lesions were treated with comparable results for angiographic and procedural success and the restenosis rate by both, PTCA and PTCR. Late loss, however, was significantly higher and net gain significantly smaller after PTCR. Stents, although infrequently used, had a relevant impact on immediate PTCA results but not on late results. Cathet Cardiovasc Intervent 2001;53:359-367.

Aged↗

[The role of inflammation and infection in acute coronary syndrome].

UNLABELLED: INFLAMMATORY PROCESS: Within the vessel wall is considered to be crucial for initiation and progression of atherosclerosis. As response to endothelial injury a focal inflammatory response arises which can lead to plaque vulnerability and rupture and a consecutive acute coronary syndrome. Systemic markers of inflammation like C-reactive protein (CRP) or interleukin (IL) 6 are elevated in stable angina and acute coronary syndrome and are associated with future cardiovascular events even in initially healthy people. Alongside classical risk factors infectious agents like cytomegalovirus or Chlamydia pneumoniae are discussed to be involved in the local and systemic inflammatory response. Seroepidemiological studies revealed disparate results of the association between antibody titers against Chlamydia pneumoniae or cytomegalovirus and prevalence of coronary artery disease or future cardiovascular events. In animal models Chlamydia pneumoniae and cytomegalovirus increase accelerated neointimal response, however, molecular mechanisms are not entirely clear. CONCLUSION: Whereas local and systemic inflammatory processes play a crucial role in atherogenesis and prognosis the causal role of infection in atherogenesis remains controversial.

Acute Disease↗

[MR angiography and flow measurement in coronary arteries and coronary bypass grafts].

Better MR image quality of coronary arteries and coronary grafts is the product of increased spatial and temporal resolution. Breathing artifacts could be reduced by implementing breath-holding and navigator techniques. With these developments normal coronary arteries can often be imaged reliably. Several trials have been performed in order to test the reliability of MR angiography to detect coronary artery stenosis. But up to now, sensitivity and specificity have proven to be too low to introduce these techniques in clinical routine. The patency of coronary grafts can be detected reliably using different MR techniques. Coronary flow reserve can be measured using the MR phase contrast technique. This noninvasive approach was tested in diseased coronary arteries and in graft stenoses. A reduced MR coronary flow reserve corresponded to reduced flow reserve measured invasively. Measurement of MR flow reserve in normal and diseased coronary grafts revealed significant differences (3.3 +/- 0.4 vs. 1.3 +/- 0.2).

Blood Flow Velocity↗

Transcriptional repression of the human fibronectin gene in laryngeal squamous cell carcinoma cells.

PURPOSE: The aim of the experiments was to analyze the mRNA expression pattern and verify the repression of FN gene expression in laryngeal squamous cell carcinoma (SCC) cells in comparison with benign mucosal keratinocytes. METHODS: Messenger RNA from SCC cells and benign keratinocytes was reverse transcribed and subjected to PCR following differential display (DD) analysis of the amplicons. Northern hybridization was carried out to confirm the reduction of the FN-mRNA expression in both laryngeal SCC cells and larynx carcinoma biopsies, in contrast to adjacent normal mucosa. Quantitation of protein synthesis was performed with homogenates of fresh tumor biopsies and their normal phenotypes, as well as of benign keratinocytes and laryngeal SCC cell lines, respectively, using ELISA. In the liposome-mediated transient transfection assay, FN promoter activity was analyzed by linking the FN promoter sequence to the chloramphenicol acetyltransferase (CAT) reporter gene. Transfection efficacy was monitored by co-transfection with pGL3 control vector. RESULTS: A 191 bp mRNA fragment revealing a 99% homology with the human FN-mRNA was detected, the expression of which was repressed 20 times as much in SCC cells as compared to benign phenotypes. Northern hybridization confirmed the distinctly reduced expression of FN-mRNA in both laryngeal SCC cells and larynx carcinoma biopsies, in contrast to adjacent normal mucosa. The quantitation experiments showed a correlation between the range of FN synthesis and the expression of FN-mRNA in cell lines and the biopsies which were used. The 1.28 kb FN gene promoter drove expression of the CAT reporter gene, which was similar to the FN-mRNA expression showed by DD and Northern hybridization. CONCLUSIONS: The mechanisms leading to the low level of FN in many tumors have not yet been sufficiently investigated. Our findings suggest that the decrease of FN in laryngeal SCC cells is transcriptionally regulated.

Base Sequence↗

How do urology residents manage personal finances?

OBJECTIVES: To examine personal financial management among residents to answer three research questions: do residents make reasonable financial choices; why do some residents not save; and what steps can be taken to improve residents' personal financial decisions. METHODS: Portions of the Federal Reserve Board's Survey of Consumer Finances were modified and piloted to elicit demographic, expense, saving, and income data. The final questionnaire was completed by 151 urology residents at 20 programs. RESULTS: Comparing residents with the general population in the same age and income categories, the median debt/household income ratio was 2.38 versus 0.64. Residents had greater educational debt, greater noneducational debt, and lower savings. Resident participation in retirement accounts was 100% at institutions with employer-matching 401k or 403b plans, 63% at institutions with nonmatching 401k or 403b plans, and 48% at institutions without retirement plans for residents (P = 0.002). Fifty-nine percent of residents budgeted expenses, 27% had cash balances below $1000, 51% had paid interest charges on credit cards within the previous year, and 12% maintained unpaid credit card balances greater than $10,000. The median resident income was $38,400. CONCLUSIONS: A significant minority of residents appear not to make reasonable financial choices. Some residents save little because of a failure to budget, indebtedness, high projected income growth, or insufficient attention to personal financial management. Residents save more when they are eligible for tax-deferred retirement plans, particularly when their institution matches their contributions. Many residents would benefit from instruction concerning prudent financial management.

Adult↗

Accommodation of couch constraints for coplanar intensity modulated radiation therapy.

PURPOSE: Three treatment couches, henceforth referred to as the standard, the variable standard and the C-arm couch, each based on a different supporting frame system, were investigated for their suitability for the delivery of a high number of coplanar beams (> or =5) as may be required for intensity-modulated radiation therapy treatments. MATERIALS AND METHODS: A number of equispaced beam arrangements (five to nine) were examined in combination with two circular target sizes (Phi6 and Phi10 cm) at different locations within an elliptical body on the investigated couches, resulting in 70 different plans per couch. A rule based advisory system determined possible intersections of the beam paths with the supporting frames of the respective treatment couch and suggested a suitable constellation for the supporting frames. In cases of intersection, a beam-couch collision was eliminated by minimal rotation of the beams from the initial equispaced beam arrangement. To investigate the effect of a rotation of the posterior-oblique beams for five, seven and nine initially equispaced beams by an angle of 10 degrees, a prostate plan was generated and compared with equispaced beam arrangement. RESULTS: Initial beam paths intersected with the standard couch in 63% of the plans, necessitating a rotation of one or two beams. It was necessary to modify the beam angles in 34% of the cases on the variable standard couch to avoid an intersection of the beams with the couch. All the plans would have been delivered satisfactorily on the C-arm couch without a rotation of beams. Simulation studies showed that the dose distribution for a prostate treatment could be affected significantly, but not detrimentally, by the rotation of the two posterior-oblique beam orientations by an angle of 10 degrees.

Equipment and Supplies↗

Functional identification of secondary mutations inducing autonomous growth in synergy with a truncated interleukin-3 receptor: implications for multi-step oncogenesis.

OBJECTIVE: A truncated common beta chain (Deltabeta(C)) of the interleukin-3 (IL-3) receptor complex was previously identified as a key factor in inducing autonomous growth of IL-3-independent mutants. Expression of Deltabeta(C) in IL-3-dependent hematopoietic cells does not result in immediate factor-independent growth, but increases the frequency of obtaining autonomous mutants by three to four orders of magnitude. This study was designed to delineate the mechanisms by which Deltabeta(C) increases the frequency to autonomous growth. DESIGN AND METHODS: Retroviral vectors were used to express Deltabeta(C) into IL-3-dependent myeloid cells, which were then tested for factor-independent growth. To determine if secondary genetic events were required for conversion to autonomous growth, elements of the Cre-loxP recombinant system were used to excise Deltabeta(C) in factor-independent clones. RESULTS: Excision of Deltabeta(C) in factor-independent clones revealed two types of phenotypes: reversion to factor-dependent growth (1/8) or continued IL-3-dependent growth (7/8). Analysis of cells that remained factor independent revealed constitutive activation of STAT5, not observed in factor-dependent revertants. Analysis of revertant cells demonstrated the presence of interacting secondary mutations that synergize with Deltabeta(C)-induced proliferation. A cysteine residue within the truncated extracellular domain of Deltabeta(C) was also found to be required for its oncogenic potential, supporting a model of dimerization for receptor activation. CONCLUSIONS: The high incidence of obtaining factor-independent mutants from cells expressing Deltabeta(C) results from the selection of mutations that either complement Deltabeta(C) expression to promote proliferation or that singly or in synergy with other secondary mutations negate the requirement of Deltabeta(C) expression for proliferation.

Animals↗

Pronounced infracuticular endocytosis in mammalian outer hair cells.

Endocytosis in cochlear hair cells was investigated by staining with the vital fluorescent dye FM 1-43, that partitions reversibly into membranes and is trapped in vesicles during endocytosis. The temporal development and spatial distribution of FM 1-43 induced fluorescence was investigated using confocal laser-scanning microscopy. FM 1-43 rapidly and intensely stained cochlear hair cells, leaving the supporting cells unstained. For short application (0.2-30 s), only the infracuticular region of outer hair cells (OHCs) was labeled, whereas for long application (30-60 s), the OHCs were also labeled in the infranuclear zone and along a central strand extending from the infracuticular zone down to the nucleus, as well as along the entire cell membrane. Except for the cell membrane, the infracuticular zone, directly below the cuticular plate, showed the most rapid and intense staining, and in most cases staining was spherically shaped with a diameter of 3-7 microm. Localization and size of this infracuticular staining coincided with Hensen's body, a specialized variant of the endoplasmic reticulum. In contrast to the OHCs, apical fluorescence of inner hair cells presented a homogeneous distribution. When OHCs were incubated in FM 1-43 for longer than 1 min, many points of contact between the central strand, the infracuticular zone and the lateral cell membrane were observed. Since Hensen's bodies are a specialty of OHCs and the fluorescent staining pattern of these cells was unique, it is proposed that Hensen's body is involved in the turnover of OHC-specific proteins, such as those involved in the molecular machinery of the motor action of the plasma membrane.

Animals↗

US-guided nephrostomy with the aid of a magnetic field-based navigation device in the porcine pelvicaliceal system.

PURPOSE: To assess the technique and feasibility of ultrasound (US)-guided nephrostomy performed with the aid of a magnetic field-based navigation device. MATERIALS AND METHODS: Twelve percutaneous nephrostomy procedures were performed in seven domestic pigs under real-time US guidance employing a navigation system. Two magnetic field sensors registered the actual position of the puncture needle and the US transducer. The actual needle position and the aimed puncture tract were graphically projected into the real-time US images, allowing exact navigation of the needle. After placement of the needle into the renal pelvis, the nephrostomy tube was inserted by means of the Seldinger technique. RESULTS: The puncture procedure was successfully performed in each case. The renal pelvis was punctured in a single attempt in 10 of 12 cases. In two cases, multiple attempts were necessary because bending of the puncture needle led to inaccuracies of the navigation system. With exception of two small perirenal urinomas, no complications were seen. CONCLUSIONS: The magnetic field-based navigation device allows easy and accurate performance of nephrostomy guided solely by US.

Animals↗

Comparison of image compression viability for lossy and lossless JPEG and Wavelet data reduction in coronary angiography.

BACKGROUND: Lossless or lossy compression of coronary angiogram data can reduce the enormous amounts of data generated by coronary angiographic imaging. The recent International Study of Angiographic Data Compression (ISAC) assessed the clinical viability of lossy Joint Photographic Expert Group (JPEG) compression but was unable to resolve two related questions: (A) the performance of lossless modes of compression in coronary angiography and (B) the performance of newer lossy wavelet algorithms. This present study seeks to supply some of this information. METHODS: The performance of several lossless image compression methods was measured in the same set of images as used in the ISAC study. For the assessment of the relative image quality of lossy JPEG and wavelet compression, the observers ranked the perceived image quality of computer-generated coronary angiograms compressed with wavelet compression relative to the same images with JPEG compression. This ranking allowed the matching of compression ratios for wavelet compression with the clinically viable compression ratios for the JPEG method as obtained in the ISAC study. RESULTS: The best lossless compression scheme (LOCO-I) offered a mean compression ratio (CR) of 3.80:1. The quality of images compressed with the lossy wavelet-based method at CR = 10:1 and 20:1 was comparable to JPEG compression at CR = 6:1 and 10:1, respectively. CONCLUSION: The study has shown that lossless compression can exceed the CR of 2:1 usually quoted. For lossy compression, the range of clinically viable compression ratios can probably be extended by 50 to 100% when applying wavelet compression algorithms as compared to JPEG compression. These results can motivate a larger clinical study.

Algorithms↗

The inositol 5-phosphatase SHIP is expressed as 145 and 135 kDa proteins in blood and bone marrow cells in vivo, whereas carboxyl-truncated forms of SHIP are generated by proteolytic cleavage in vitro.

The inositol polyphosphate 5-phosphatase SHIP plays an important role in negative signalling in B cells and mast cells and in the down-regulation of cytokine receptor-mediated signals in myeloid cells. SHIP is expressed as a 145 kDa full-length protein and an isoform of 135 kDa due to alternative splicing. Additional smaller forms of SHIP which are truncated at the carboxy terminus have been described in bone marrow and peripheral blood mononuclear cells (PBMC). Our data demonstrate that human bone marrow cells and PBMC from healthy donors and patients with acute myeloid leukemia express the 145 kDa form of SHIP and low amounts of a 135 kDa form of SHIP in vivo whereas C-terminal-truncated SHIP proteins are generated by a PMSF-sensitive protease during the preparation of cell lysates in vitro. We have further characterized this protease and identified a proteolytic cleavage site in the human SHIP protein C-terminal to tryptophan residue 941. These data support a physiological role for the 145 and 135 kDa forms of SHIP in bone marrow and peripheral blood cells from normal donors and patients with acute myeloid leukemia.

Alternative Splicing↗

A missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree.

Schizophrenia is a common and etiologically heterogeneous disorder. Although inheritance of schizophrenic syndromes is complex with genetic and environmental factors contributing to the clinical phenotype, periodic catatonia, a familial subtype of catatonic schizophrenia, appears to be transmitted in an autosomal dominant manner. We report here that a Leu309Met mutation in WKL1, a positional candidate gene on chromosome 22q13.33 encoding a putative non-selective cation channel expressed exclusively in brain, co-segregates with periodic catatonia in an extended pedigree. Structural analyses revealed that this missense mutation results in conformational changes of the mutant protein. Our results not only underscore the importance of genetic mechanisms in the etiology of schizophrenic syndromes, but also provide a better understanding of the pathogenesis and incapacitating course of catatonic schizophrenia and related disorders.

Amino Acid Sequence↗

C1-esterase-inhibitor treatment at early reperfusion of hemorrhagic shock reduces mesentry leukocyte adhesion and rolling.

OBJECTIVE: Complement activation probably plays a pathogenic role in multiple organ failure in shock. This study evaluates the effects of C1-esterase-inhibitor treatment on leukocyte-endothelial interaction in the mesenteric microcirculation in hemorrhagic shock. METHODS: Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume controlled hemorrhagic shock was provoked by arterial blood withdrawal (2.5 mL/100 g body wt. for 60 minutes) followed by a 4-hour reperfusion period. C1-INH (100 IU/kg body wt. i.v.) or 0.9% NaCl i.v. were administered as a bolus at the beginning of reperfusion. Reperfusion time mimicked a "pre-hospital" phase of 30 minutes followed by a quasi "in-hospital" phase of 3.5 hours. The "in-hospital" phase was initiated by substitution of blood followed by fluid resuscitation with normal saline. RESULTS: Application of C1-INH markedly reduced rolling and adherent leukocytes to numbers approaching baseline values. Vmax and shear rate of the mesenteric microcirculation improved in both groups after reperfusion with a trend to higher values in the C1-INH group (n.s. p = 0.08). CONCLUSION: C1-INH applied in a bolus dose of 100 IU/kg body wt. i.v. abrogated enhanced leukocyte adhesion and rolling in the mesenteric microcirculation after hemorrhagic shock. Single bolus treatment with a complement inhibitor may provide clinical benefit when applied at an early stage of reperfusion during hemorrhagic shock.

Animals↗

Enzyme-linked immunosorbent assays based on peroxidase labels and enzyme-amplified lanthanide luminescence detection.

The enzyme-amplified lanthanide luminescence (EALL) detection is developed and applied for the determination of peroxidase as marker in enzyme-linked immunosorbent assays (ELISA). The detection scheme is based on the peroxidase catalysed dimerization of 4-hydroxyphenylpropionic acid (pHPPA) and the subsequent formation of a ternary complex with Tb(III)EDTA. Quantum yields and fluorescence lifetimes of the luminescent species are presented to give an estimate of the potential of this procedure. Two different ELISA were performed with the EALL detection scheme. For the first, a model ELISA for the determination of goat anti-rabbit IgG, a limit of determination of 3 micrograms dm-3 (2 fmol) of the antibody could be achieved. As second model assay, a commercial ELISA kit was successfully validated for the new detection scheme. Photometric and EALL detection were in good agreement for the determination of human anti-gliadin IgA in serum.

Journal Article↗