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Biomedical subjects

I Wolf

Publications and source records attributed to I Wolf.

At least 19 recordsLinked to original sources
PubMed2007

Stereolithographic reproduction of complex cardiac morphology based on high spatial resolution imaging.

BACKGROUND: Precise knowledge of cardiac anatomy is mandatory for diagnosis and treatment of congenital heart disease. Modern imaging techniques allow high resolution three-dimensional (3D) imaging of the heart and great vessels. In this study stereolithography was evaluated for 3D reconstructions of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) data. METHODS: A plastinated heart specimen was scanned with MDCT and after segmentation a stereolithographic (STL) model was produced with laser sinter technique. After scanning the STL model with MDCT these data were compared with those of the original specimen after rigid registration using the iterative closest points algorithm (ICP). The two surfaces of the original specimen and STL model were matched and the symmetric mean distance was calculated. Additionally, the heart and great vessels of patients (age range 41 days-21 years) with congenital heart anomalies were imaged with MDCT (n=2) or free breathing steady, state free-precession MRI (n=3). STL models were produced from these datasets and the cardiac segments were analyzed by two independent observers. RESULTS: All cardiac structures of the heart specimen were reconstructed as a STL model within sub-millimeter resolution (mean surface distance 0.27+/-0.76 mm). Cardiac segments of the STL patient models were correctly analyzed by two independent observers compared to the original 3D datasets, echocardiography (n=5), x-ray angiography (n=5), and surgery (n=4). CONCLUSIONS: High resolution MDCT or MRI 3D datasets can be accurately reconstructed using laser sinter technique. Teaching, research and preoperative planning may be facilitated in the future using this technique.

Adolescent↗
PubMed2006

BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27(Kip1).

We have previously shown that the breast cancer susceptibility gene, BRCA1, can transcriptionally activate the p27(Kip1) promoter. The BRCA1-responsive element was defined as a 35 bp region from position -545 to -511. We next determined that within this region is also a potential binding site for the transcription factor Forkhead box (FOX)A1. RNA and protein analysis as well as immunohistochemistry showed that expression of FOXA1 correlated with the expression of the estrogen receptor in a panel of breast cancer cell lines and tissues. In transient transfection reporter assays, FOXA1 could activate the p27(Kip1) promoter. Cotransfection of BRCA1 and FOXA1 resulted in a synergistic activation of the p27(Kip1) promoter. Mutation of the FOXA1 DNA-binding site in the p27(Kip1) promoter-luciferase construct significantly diminished the activity of FOXA1 alone or in combination with BRCA1. Cotransfection of FOXA1 and BRCA1 resulted in a greater amount of each protein compared to transfection of each expression vector alone. The half-life of FOXA1 was increased when coexpressed with BRCA1. Electrophoretic mobility shift assay analysis demonstrated that FOXA1 could bind to a wild-type oligonucleotide containing the FOXA1 binding site in the p27(Kip1) promoter, but this binding was lost upon mutation of this FOXA1 binding site. The protein-DNA binding complex could be supershifted with an antibody directed against FOXA1. The activity of the p27(Kip1) promoter as well as FOXA1 expression was reduced in cells treated with BRCA1 siRNA, thus silencing the expression of BRCA1 protein. In summary, we identified a FOXA1 binding site within the BRCA1-responsive element of the p27(Kip1) promoter and showed that FOXA1 activated the promoter alone and in conjunction with BRCA1. Furthermore, we identified high expression of FOXA1 in breast cancer cell lines and tissues, discovered a role for BRCA1 in the regulation of p27(Kip1) transcription and a possible interaction with BRCA1.

BRCA1 Protein↗
PubMed2006

Three-dimensional assessment of left ventricular geometry and annular dilatation provides new mechanistic insights into the surgical correction of ischemic mitral regurgitation.

BACKGROUND: The aim of this study was to investigate the relationship between LV geometry, annular shape and the amount of regurgitation in patients with ischemic mitral regurgitation (group 1, n = 30) compared to patients with primary mitral valve lesions (group 2, n = 30). METHODS: LV geometry was assessed by the sphericity index, i.e., LV volume divided by the volume of a sphere with a diameter equal to the longest axis. Annular geometry was evaluated by diameters, areas and their percentual shortening. The degree of mitral regurgitation was assessed as jet volumes by 3D-echocardiography. RESULTS: Group 1 showed significantly larger longitudinal (54.3 +/- 3.1 vs. 40.9 +/- 2.6 mm) and antero-posterior (32.2 +/- 3.3 vs. 27.1 +/- 2.9 mm) annulus diameters and areas (993.3 +/- 66.6 vs. 702.1 +/- 47.9 mm (2)) than group 2. No asymmetric annular enlargement was found in either group. Annular enlargement correlated to the degree of mitral regurgitation in group 1 but not in group 2. Annular area shortening was significantly impaired in group 2 and the sphericity index was larger in group 1 than in group 2. In group 1, the sphericity index was significantly correlated to the degree of mitral regurgitation (r = 0.87; P < 0.001). CONCLUSIONS: These findings suggest that ischemic mitral regurgitation was mostly associated with a global left ventricular enlargement, in which annulus dilatation and its reduced contraction play a significant role.

Echocardiography, Three-Dimensional↗
PubMed2005

CT volumetry of intravertebral cement after kyphoplasty. Comparison of polymethylmethacrylate and calcium phosphate in a 12-month follow-up.

This study was intended to measure the volume of intravertebral cement after balloon kyphoplasty with high resolution computed tomography (CT) and dedicated software. Volume changes of biocompatible calcium phosphate cement (CPC) were detected during a follow-up of 12 months. Measurements were compared with a control group of patients treated with polymethylmethacrylate (PMMA). Twenty-three vertebrae (14 CPC, 9 PMMA) of 12 patients were examined with CT using an identical imaging protocol. Dedicated software was used to quantify intravertebral cement volume in subvoxel resolution by analyzing each cement implant with a density-weighted algorithm. The mean volume reduction of CPC was 0.08 ml after 12 months, which corresponds to an absorption rate of 2 vol%. However, the difference did not reach significance level (P>0.05). The mean error estimate was 0.005 ml, indicating excellent precision of the method. CT volumetry appears a precise tool for measurement of intravertebral cement volume. CT volumetry offers the possibility of in vivo measurement of CPC resorption.

Bone Cements↗
PubMed2005

[Functional imaging of neurocognitive dysfunction in attention deficit hyperactivity disorder].

Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder of early childhood onset. Defining symptoms are chronic impairments of attention, impulse control and motor hyperactivity that frequently persist until adulthood. Miscellaneous causes of the disorder have been discussed. Accumulating evidence from imaging- and molecular genetic studies strengthened the theory of ADHS being a predominantly inherited disorder of neurobiological origin. In the last 15 years, non-invasive brain imaging methods were successfully implemented in pediatric research. Functional magnetic resonance imaging studies gave major insight into the neurobiological correlates of executive malfunction, inhibitory deficits and psychomotoric soft signs. These findings are in good accordance with brain morphometric data indicating a significant volumetric decrease of major components of striato-thalamo-cortical feedback loops, primarily influencing prefrontal executive functioning (e.g. basal ganglia). Empirical evidence points to a broad array of associated behavioral disturbances like deficient visuomotor abilities and oculomotor dysfunctions. This paper reviews the current empirical evidence derived from prior imaging studies. Special emphasis is given to the relevance of oculomotor dysfunctions in clinical and research settings, as well as their assessment in the MR environment.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed2004

Proof of principle for the use of 11C-labelled peptides in tumour diagnosis with PET.

PURPOSE: The future significance of peptide radiopharmaceuticals in diagnostic imaging with PET will be dependent on methodological aspects, as well as other requirements such as availability of the radionuclide and cost-effectiveness of its production. The aim of this study was to evaluate whether recent improvements in the modification of peptide pharmacokinetics by carbohydration may open a niche for the use of 11C-labelled peptide receptor binding tracers. METHODS: A carbohydrated analogue of Tyr3-octreotate was used as a clinically relevant peptide. Oxime-mediated coupling between 4-[11C]methoxy-benzaldehyde and an aminooxy-conjugated peptide precursor provided the 11C-labelled peptide in 21+/-5% decay-corrected yield (n=4) in a synthesis time of about 1 h. RESULTS: In rat pancreas carcinoma xenografted mice, the compound displayed predominant and fast renal clearance combined with high tumour uptake (18.5+/-2.8% ID/g) at 30 min post injection. Corresponding values for kidney, liver and intestine were 18.5+/-2.4% ID/g, 3.2+/-0.5% ID/g and 2.1+/-0.3% ID/g, respectively. In a PET study with xenografted mice, the tumour (0.2-0.3 g) was clearly delineated as early as 20 min after injection. Somatostatin receptor (sstr)-specific uptake was demonstrated by reduction of tumour uptake to 20% of control by co-injection of TOC (0.4 mg/kg; 30 min p.i.). CONCLUSION: A 11C-labelled octreotate derivative has been prepared which shows suitable pharmacokinetics for in vivo imaging of sstr-overexpressing tumours and thus represents the first proof of principle for the potential of 11C-labelled peptides in tumour imaging.

Animals↗
PubMed2001

Involvement of the activation loop of ERK in the detachment from cytosolic anchoring.

The Extracellular signal-regulated kinases (ERKs) are translocated into the nucleus in response to mitogenic stimulation. The mechanism of translocation and the residues in ERKs that govern this process are not clear as yet. Here we studied the involvement of residues in the activation loop of ERK2 in determining its subcellular localization. Substitution of residues in the activation loop to alanines indicated that residues 173-181 do not play a significant role in the phosphorylation and activation of ERK2. However, residues 176-181 are responsible for the detachment of ERK2 from MEK1 upon mitogenic stimulation. This dissociation can be mimicked by substitution of residues 176-178 to alanines and is prevented by deletion of these residues or by substitution of residues 179-181 to alanines. On the other hand, residues 176-181, as well as residues essential for ERK2 dimerization, do not play a role in the shuttle of ERK2 through nuclear pores. Thus, phosphorylation-induced conformational rearrangement of residues in the activation loop of ERK2 plays a major role in the control of subcellular localization of this protein.

Amino Acid Sequence↗
PubMed2001

Needs for mental health care and service provision in single homeless people.

BACKGROUND: Specific problems in sampling methodology, case-finding strategies and a standardised needs assessment in mentally ill homeless people have contributed to their being neglected as a mental health care clientele. METHOD: We assessed a representative sample of homeless people (n=102) in the highly industrialised city of Mannheim (Germany) regarding their prevalence of mental disorders (using the SCID) and their needs for mental health care (using the NCA). RESULTS: We found high prevalences, with 68.6% of all assessed homeless persons having a current mental disorder. Thus, needs for mental health care were very common, with unmet needs predominating in all problem areas, which was supported by a very weak service utilization. Thus, even in a region with a comprehensive community mental health care network, like the study area, mentally ill homeless people are widely under-provided. CONCLUSIONS: Results suggest that the traditional shelter system for homeless people carries most of the mental health care burden for their clientele and must be supported by adequate interventions from community-based mental health care services. A closer connection of both sectors and a better co-ordination of the care offers seems to be a prerequisite for helping to reduce unmet mental health care needs in this specific high-risk group.

Adolescent↗
PubMed2001

[How do mentally ill homeless persons evaluate their quality of life].

Besides pronounced deficiencies in psychiatric research concerning homeless mentally ill in Germany, studies concerned with the quality of life of homeless mentally ill were missing until now. This study reveals in a representative sample of 102 homeless people from the City of Mannheim, Germany that--compared to the homeless without psychiatric disorders of the sample--the mentally ill homeless (prevalence 68.6%) have significantly different subjective views of their quality of life regarding the items "state of health", "physical capabilities" and "support from others". The differences were even stronger if the homeless mentally ill were compared to a group of non-homeless mentally ill schizophrenic patients (n = 104), cared for in the City's well-equipped community care services. Community care patients reported a significantly better quality of life in respect of 11 items. These results were seen as a success of the concept of community-based mental health care. The consequences for improving care strategies for homeless mentally ill are discussed.

Activities of Daily Living↗
PubMed2001

Comparison of sestamibi, tetrofosmin, and Q12 retention in porcine myocardium.

UNLABELLED: Although there are several 99mTc perfusion tracers introduced for clinical use, there are no data available directly comparing these tracers with microsphere-determined flow. The aim of this study was to compare the myocardial retention of sestamibi, tetrofosmin, and Q12 in a porcine model. METHODS: We used a pig model with (n = 6) or without (n = 3) coronary occlusion. Each pig received a simultaneous injection of sestamibi and either tetrofosmin (group 1, n = 5) or Q12 (group 2, n = 4) labeled with either 99mTc or 95mTc (physical half-life, 61 d; photon energy, 204 keV) during pharmacologic vasodilation. Absolute myocardial retention of each tracer was calculated from the myocardial tracer activity and arterial input function. RESULTS: The plot of all three tracers versus flow achieved a plateau at a higher flow range. However, sestamibi showed a higher mean retention than either tetrofosmin (group 1, 0.27 +/- 0.11 vs. 0.16 +/- 0.06 mL/g/min, respectively; P < 0.01) or Q12 (group 2, 0.32 +/- 0.13 vs. 0.09 +/- 0.03 mL/g/min, respectively; P < 0.01). Furthermore, when a linear regression analysis was performed to assess the relationship between retention and microsphere-determined flow, sestamibi showed a greater increment in retention than did tetrofosmin or Q12. CONCLUSION: Although all of the tracers showed a nonlinear increase in retention as flow increased, sestamibi may display more favorable characteristics as a flow tracer in the porcine heart.

Animals↗
PubMed2001

Olanzapine-induced respiratory failure.

Olanzapine is considered a safe drug. However, somnolence appears in up to 39% of the patients treated with 15 mg./day of this drug. The authors describe an elderly patient with chronic lung disease who developed CO2 narcosis and respiratory failure after treatment with olanzapine. The sedative effect of this drug was probably the cause of this life-threatening complication. The authors suggest that elderly patients with chronic lung disease who are treated with olanzapine should be carefully observed, especially during the first weeks of treatment.

Aged↗
PubMed2000

Cloning of the genomic locus of mouse SH2 containing inositol 5-phosphatase (SHIP) and a novel 110-kDa splice isoform, SHIPdelta.

The SH2 domain containing inositol 5'-phosphatase (SHIP) was initially described as a 145-kDa protein phosphorylated on tyrosines upon growth factor and cytokine stimulation. It was shown to be phosphorylated after Fc and B cell receptor activation and plays a role in negative signaling. Different isoforms of the SHIP protein result from alternative mRNA splicing, proteolysis, or a combination of both. The expression of discrete SHIP isoforms changes with the potential developmental-dependent maturation state of myeloid cells, suggesting mechanisms for the regulation of SHIP interactions with other signaling molecules. A p135 (SHIPbeta) spliced isoform is known to be expressed in developing myeloid cells. Now we have identified a new SHIP isoform, SHIPdelta, which is the product of an out-of-frame splice with a deletion of 167 nucleotides in the C-terminal region, resulting in an approximately 110-kDa protein. Biochemically, SHIPdelta differs from SHIPalpha by exhibiting little or no tyrosine phosphorylation or association with the signaling protein Shc after M-CSF activation of FD-Fms cells. In addition, we have characterized the structure of the entire SHIP genomic locus, which provides a basis for understanding the alternative splicing events. SHIP is expressed in hematopoiesis and spermatogenesis, and we also describe the promoter for the SHIP gene, which has potential for explaining the tissue-specific expression pattern.

3T3 Cells↗
PubMed2000

Endovascular irradiation from beta-particle-emitting gold stents results in increased neointima formation in a porcine restenosis model.

BACKGROUND: Recent studies have shown that ionizing radiation reduces neointima formation after balloon angioplasty and stent implantation in experimental models of restenosis and first clinical trials. The objective of this study was to determine the dose distribution of a new beta-particle-emitting radioactive gold stent and to evaluate the dose-dependent vascular response in the coronary overstretch pig model. METHODS AND RESULTS: Sixteen Göttinger minipigs underwent placement of 11 nonradioactive and 36 beta-particle-emitting stents with activity levels of 10.4+/-0.6, 14.9+/-2.4, 22.8+/-1.3, 35.8+/-2. 8, and 55.4+/-5.3 microCi of (198)Au. Three months after implantation, the percent area stenosis, neointimal thickness, neointimal area, and vessel injury were analyzed by quantitative histomorphometry. The lifetime radiation doses at a depth of 1 mm were 3.3+/-0.2, 4.7+/-0.5, 7.2+/-0.4, 11.4+/-0.9, and 17.6+/-1.7 Gy for the different activity groups. No dose-response relationship was observed in the radioactive stents with respect to percent area stenosis (P=0.297), mean neointimal thickness (P=0.82), or mean neointimal area (P=0.65). Significantly lower neointima formation and less luminal narrowing was seen in the control group than in the beta-particle-emitting stents (P<0.001). Multilinear regression analysis revealed that only radioactivity made a significant independent contribution to the degree of percent area stenosis (P<0. 001). CONCLUSIONS: Neointima formation in pigs is markedly increased by beta-particle-emitting stents with (198)Au as the radioisotope. This study provides evidence that dosages of 3 to 18 Gy of low-dose-rate beta-particle irradiation via endovascular stents cause pronounced luminal narrowing in the animal model at 3 months.

Animals↗
PubMed2000

Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11.

20-hydroxyeicosatetraenoic acid (20-HETE), an omega-hydroxylated arachidonic acid (AA) metabolite, elicits specific effects on kidney vascular and tubular function that, in turn, influence blood pressure control. The human kidney's capacity to convert AA to 20-HETE is unclear, however, as is the underlying P450 catalyst. Microsomes from human kidney cortex were found to convert AA to a single major product, namely 20-HETE, but failed to catalyze AA epoxygenation and midchain hydroxylation. Despite the monophasic nature of renal AA omega-hydroxylation kinetics, immunochemical studies revealed participation of two P450s, CYP4F2 and CYP4A11, since antibodies to these enzymes inhibited 20-HETE formation by 65. 9 +/- 17 and 32.5 +/- 14%, respectively. Western blotting confirmed abundant expression of these CYP4 proteins in human kidney and revealed that other AA-oxidizing P450s, including CYP2C8, CYP2C9, and CYP2E1, were not expressed. Immunocytochemistry showed CYP4F2 and CYP4A11 expression in only the S2 and S3 segments of proximal tubules in cortex and outer medulla. Our results demonstrate that CYP4F2 and CYP4A11 underlie conversion of AA to 20-HETE, a natriuretic and vasoactive eicosanoid, in human kidney. Considering their proximal tubular localization, these P450 enzymes may partake in pivotal renal functions, including the regulation of salt and water balance, and arterial blood pressure itself.

Antibodies↗