Biomedical subjects

Thomas Boehm

Publications and source records attributed to Thomas Boehm.

At least 55 records · Page 3Linked to original sources

PubMed2003

Influence of breast lesion size and histologic findings on tumor detection rate of a computer-aided detection system.

PURPOSE: To evaluate associations between histopathologic findings, tumor size, and detection rate of malignant mammographic findings by using a computer-aided detection (CAD) system. MATERIALS AND METHODS: The study included 208 mammographically detected histologically proven malignant breast lesions in 208 women. Findings were 150 masses and 114 microcalcifications; 56 lesions showed both findings; 94 lesions, mass only; and 58 lesions, microcalcification only. CAD was used to evaluate mammograms in two views retrospectively. Also, corresponding histopathologic findings and lesion size were evaluated. CAD marks were considered positive if, on at least one view, they correctly identified the corresponding mammographic lesion location. RESULTS: Ninety percent (135 of 150) of masses and 93.0% (106 of 114) of microcalcifications were marked correctly by the CAD system. Overall tumor detection rate was 93.8% (195 of 208). Size-related detection rate for masses was 83.3% (25 of 30) for lesions up to 10 mm, 100% (45 of 45) for lesions 11-20 mm, 100% (46 of 46) for lesions 21-30 mm, 83.3% (10 of 12) for lesions 31-40 mm, and 52.9% (nine of 17) for lesions larger than 40 mm. Size-related tumor detection rate for microcalcifications was 92.5% (37 of 40) for microcalcifications up to 10 mm, 93.1% (27 of 29) for lesions 11-20 mm, 100% (20 of 20) for lesions 21-30 mm, 87.5% (seven of eight) for lesions 31-40 mm, and 88.2% (15 of 17) for larger microcalcifications. Detection rates for mammographically visible masses (invasive ductal carcinoma, invasive lobular carcinoma, invasive tubular carcinoma, noninvasive cancers, mucinoid cancers, and others) were 92.3% (84 of 91), 89.3% (25 of 28), 75.0% (six of eight), 100% (15 of 15), 33.3% (one of three), and 80.0% (four of five), respectively. Detectability rates for mammographically visible areas suspicious for microcalcifications (invasive ductal carcinoma, invasive lobular carcinoma, invasive tubular carcinoma, and noninvasive cancers) were 92.3% (60 of 65), 100% (eight of eight), 100% (five of five), and 91.9% (31 of 34), respectively. Highest overall detection rates were observed for invasive ductal carcinomas (96.6% [112 of 116]) and noninvasive cancers (92.9% [39 of 42]). CONCLUSION: Highest detection rates were observed for 10-30-mm tumor masses and for invasive ductal carcinomas and noninvasive cancers.

Breast↗

PubMed2003

Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen.

Splenectomized and asplenic patients have a high incidence of infections by encapsulated bacteria and do not respond to polysaccharide vaccines. To understand whether the absence of the spleen is associated with a defined B cell defect, we analyzed B cell subsets in the peripheral blood. We found that a population of B cells known as immunoglobulin (Ig)M memory is lacking in patients without spleen. The absence of IgM memory B cells correlates with an impaired immune response to encapsulated bacteria not only in splenectomized patients, but also in individuals with an intact spleen. We show that the physiological and transient predisposition to pneumococcal infections of young children (0-2 yr) is associated with the lack of circulating IgM memory B cells and of serum antipolysaccharide IgM. We also demonstrate that IgM memory B cells are undetectable in a fraction of patients with common variable immunodeficiency, who have recurrent and invasive infections by encapsulated bacteria. IgM memory B cells, therefore, require the spleen for their generation and/or survival and are responsible for the protection against encapsulated bacteria.

Adult↗

PubMed2003

Attenuation of cell adhesion in lymphocytes is regulated by CYTIP, a protein which mediates signal complex sequestration.

An important theme in molecular cell biology is the regulation of protein recruitment to the plasma membrane. Fundamental biological processes such as proliferation, differentiation or leukocyte functions are initiated and controlled through the reversible binding of signaling proteins to phosphorylated membrane components. This is mediated by specialized interaction modules, such as SH2 and PH domains. Cytohesin-1 is an intracellular guanine nucleotide exchange factor, which regulates leukocyte adhesion. The activity of cytohesin-1 is controlled by phospho inositide-dependent membrane recruitment. An interacting protein was identified, the expression of which is upregulated by cytokines in hematopoietic cells. This molecule, CYTIP, is also recruited to the cell cortex by integrin signaling via its PDZ domain. However, stimulation of Jurkat cells with phorbol ester results in re-localization of CYTIP to the cytoplasm, and membrane detachment of cytohesin-1 strictly requires co-expression of CYTIP. Consequently, stimulated adhesion of Jurkat cells to intracellular adhesion molecule-1 is repressed by CYTIP. These findings outline a novel mechanism of signal chain abrogation through sequestration of a limiting component by specific protein-protein interactions.

Adenosine Triphosphate↗

PubMed2003

Morpholino oligonucleotide-triggered knockdown reveals a role for maternal E-cadherin during early mouse development.

We report that gene silencing via intracytoplasmic microinjections of morpholino-modified antisense oligonucleotides is an effective and reproducible method to study both maternal and zygotic gene functions during early and late stages of mouse preimplantation development. The zygotic expression of the beta-geo transgene in the ROSA26 mouse strain could be inhibited until at least the early blastula stages. Thus morpholino-triggered gene inactivation appears to be a useful method to study the functional role of genes in preimplantation development. Using this approach, we have investigated a potential role of maternal expression of Cdh1, the gene encoding the cell-adhesion molecule E-cadherin. Inhibition of translation of maternal E-cadherin mRNA causes a developmental arrest at the two-cell stage. BrUTP incorporation assays indicated that this developmental defect cannot be explained by a general failure in transcriptional activity. This defect is reversible since E-cadherin mRNA can rescue the affected embryos, suggesting that a functional adhesion complex, present at the junction between blastomeres, is a prerequisite for the normal development of the mouse preimplantation embryo. Our study thus reveals a previously unanticipated role of maternal E-cadherin during early stages of mouse development.

Animals↗

PubMed2003

Susceptibility to anthrax lethal toxin is controlled by three linked quantitative trait loci.

Anthrax lethal toxin (LT) is the principal virulence factor associated with lethal pathologies following infection with Bacillus anthracis. Macrophages are the primary effector cells mediating lethality since macrophage-depleted mice are resistant to LT challenge. Recently, Ltxs1, the gene controlling differential susceptibility of murine macrophages to cytolysis following in vitro exposure to LT, was identified as Kif1c. To directly assess the in vivo role of Kif1c alleles in mortality, we studied a panel of interval-specific recombinant congenic lines carrying various segments of central chromosome 11 derived from LT-resistant DBA/2 mice on the LT-susceptible BALB/c background. The results of this study reveal that mortality is controlled by three linked quantitative trait loci (QTL): Ltxs1/Kif1c (42-43 cM), Ltxs2 (35-37 cM), and Ltxs3 (45-47 cM). The Ltxs3 interval encompasses Nos2, which is an attractive candidate gene for Ltxs3. In this regard, we demonstrate that selective, pharmacologically based inhibition of Nos2 activity in vivo partially overrides genetic resistance to LT and that Nos2 expression as determined by reverse transcription-polymerase chain reaction differs significantly between DBA/2 and BALB/c macrophages. Additionally, to recapitulate dominant resistance to mortality as seen in (BALB/c x DBA/2) F(1) hybrids, DBA/2 alleles are required at all three QTL.

Animals↗

PubMed2003

Genetic dissection of thymus development in mouse and zebrafish.

Lymphoid organs represent a specialized microenvironment for interaction of stromal and lymphoid cells. In primary lymphoid organs, these interactions are required to establish a self-tolerant repertoire of lymphocytes. While detailed information is available about the genes that control lymphocyte differentiation, little is known about the genes that direct the establishment and differentiation of principal components of such microenvironments. Here, we discuss genetic studies addressing the role of thymic epithelial cells (TECs) during thymopoiesis. We have identified an evolutionarily conserved key regulator of TEC differentiation, Foxn1, that is required for the immigration of prothymocytes into the thymic primordium. Because Foxn1 specifies the prospective endodermal domain that gives rise to thymic epithelial cells, it can be used to identify the evolutionary origins of this specialized cell type. In the course of these studies, we have found that early steps of thymus development in zebrafish are very similar to those in mice. Subsequently, we have used chemical mutagenesis to derive zebrafish lines with aberrant thymus development. Strengths and weaknesses of mouse and zebrafish models are largely complementary such that genetic analysis of mouse and zebrafish mutants may lead to a better understanding of thymus development.

Adaptation, Biological↗

PubMed2002

Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease.

Progressive motor neuronopathy (pmn) mutant mice have been widely used as a model for human motoneuron disease. Mice that are homozygous for the pmn gene defect appear healthy at birth but develop progressive motoneuron disease, resulting in severe skeletal muscle weakness and respiratory failure by postnatal week 3. The disease starts at the motor endplates, and then leads to axonal loss and finally to apoptosis of the corresponding cell bodies. We localized the genetic defect in pmn mice to a missense mutation in the tubulin-specific chaperone E (Tbce) gene on mouse chromosome 13. The human orthologue maps to chromosome 1q42.3. The Tbce gene encodes a protein (cofactor E) that is essential for the formation of primary alpha-tubulin and beta-tubulin heterodimeric complexes. Isolated motoneurons from pmn mutant mice exhibit shorter axons and axonal swelling with irregularly structured beta-tubulin and tau immunoreactivity. Thus, the pmn gene mutation provides the first genetic evidence that alterations in tubulin assembly lead to retrograde degeneration of motor axons, ultimately resulting in motoneuron cell death.

Amino Acid Sequence↗

PubMed2002

B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen.

Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.

Animals↗

PubMed2002

Thymopoiesis requires Pax9 function in thymic epithelial cells.

The epithelial thymic anlage develops from the third pharyngeal pouch. Pax9 is expressed in the entire pharyngeal endoderm, and its function is required for normal development of organs derived from pharyngeal pouches. Here, we show that in Pax9 null mice, the thymic anlage develops as an ectopic polyp-like structure in the larynx. It expresses Whn/Foxn1, a marker of thymic epithelium, but fails to perform the normal caudo-ventral movement to the upper mediastinum. The thymic rudiment contains mesenchymal cells, blood vessels and is colonized by T cell progenitors. However, from embryonic day 14.5 onwards, the size of the Pax9 mutant thymus is severely reduced. Whereas expression of TCRbeta chain genes is readily detectable in the mutant thymus, no expression of the TCRgamma chain was detectable. Our results identify a new genetically defined control point of thymopoiesis.

Animals↗

PubMed2002

Differentiation of breast masses using 3-D sonographic and echo-enhancer-based evaluation of the vascular pattern: initial experiences.

To evaluate the potential of combined 3-D B-mode and color Doppler (CD) data sets in the differentiation of breast masses, in 50 patients with histologically proven solid breast lesions, 3-D datasets were acquired. A 3-D display was created and volume calculation of tumors, their periphery and vasculature was performed. Time-intensity curves of enhancement after administration of a contrast agent were analyzed. Volumetry of tumor vasculature yielded no significant differences between malignant and benign tumors regarding vascularization of the center (2.60 vs. 2.88%) and periphery (6.66 vs. 3.78%). Only the mean values for the rise time in the center of the tumor, fibroadenoma (FA): 5.7 s and ductal invasive carcinoma (DIC): 15.8s; p = 0.05, and the time to peak in the periphery, FA: 21.0 s and DIC: 31.6 s; p = 0.03, differed significantly. The 3-D ultrasound (US) technique was of no additional value in differentiating breast masses. The calculation of time-intensity curves after administration of a contrast agent may be helpful in differentiating FA and DIC.

Adolescent↗

PubMed2002

A zebrafish orthologue (whnb) of the mouse nude gene is expressed in the epithelial compartment of the embryonic thymic rudiment.

The cloning and characterization of the zebrafish orthologue of the mouse nude (Whn/Foxn1) gene, whnb are reported. A previously described Whn-like gene from zebrafish, now designated as whna, is shown to be the orthologue of the mouse Foxn4 gene. The whnb gene is specifically expressed in the thymic rudiment of zebrafish embryos at day 3 after fertilization, whereas the whna gene is expressed in eye and brain structures. Whnb expression is maintained in cloche mutants, where endothelial and haematopoietic cell differentiation is defective, but absent in casanova mutants where endoderm formation is impaired. In adult thymi, whnb is expressed throughout cortical and medullary areas, whereas whna expression is observed in rare cell clusters only. Our results provide the first specific marker for the epithelial compartment of the zebrafish thymus.

Amino Acid Sequence↗

PubMed2002

Aortic arch and pharyngeal phenotype in the absence of BMP-dependent neural crest in the mouse.

Neural crest cells are essential for proper development of a variety of tissues and structures, including peripheral and autonomic nervous systems, facial skeleton, aortic arches and pharyngeal glands like the thymus and parathyroids. Previous work has shown that bone morphogenic protein (BMP) signalling is required for the production of migratory neural crest cells that contribute to the neurogenic and skeletogenic lineages. We show here that BMP-dependent neural crest cells are also required for development of the embryonic aortic arches and pharynx-derived glands. Blocking formation or migration of this crest cell population from the caudal hindbrain resulted in strong phenotypes in the cardiac outflow tract and the thymus. Thymic aplasia or hypoplasia occurs despite uncompromised gene induction in the pharyngeal endoderm. In addition, when hypoplastic thymic tissue is found, it is ectopically located, but functional in thymopoiesis. Our data indicate that thymic phenotypes produced by neural crest deficits result from aberrant formation of pharyngeal pouches and impaired migration of thymic primordia because the mesenchymal content in the branchial arches is below a threshold level.

Animals↗

PubMed2002

Radio-frequency tumor ablation: internally cooled electrode versus saline-enhanced technique in an aggressive rabbit tumor model.

PURPOSE: To compare two methods of radio-frequency (RF) ablation, saline enhancement technique and internally cooled electrodes, for the treatment of small breast cancers in an animal model--highly aggressive VX2 rabbit tumors surrounded by adipose tissue. MATERIALS AND METHODS: Twenty-seven tumors were implanted into retroperitoneal fat of 14 New Zealand White rabbits. RF ablation was performed with ultrasonographic (US) guidance after tumors had grown to 15 mm. Fourteen tumors in seven animals were treated with internally cooled electrodes (30-mm-tip single electrode, 60 W, 10 min); 13 tumors in seven animals, with saline enhancement (0.5 mL/min of saline, 25-mm tip, 30 W, 10 min). Autopsy and histopathologic assessment were performed 3 weeks after therapy. RESULTS: Real-time US of RF ablation was not possible with either method because of obscuration by the increasing hyperechogenicity of the tumor and the surrounding adipose tissue. Equivalent efficacy was demonstrated with the two methods. Significantly greater complications were observed with the saline technique: Free retroperitoneal fluid was detected in one of seven animals with internally cooled electrodes and in all seven animals with saline enhancement (P <.01). Damage to remote structures such as the kidney, spine muscle, and skin was observed at autopsy in one of seven animals with internally cooled technique versus five of seven with saline enhancement (P <.01). CONCLUSION: Given a lower complication rate and similar treatment efficacy in an animal tumor model, internally cooled RF electrode may be advantageous to adjuvant saline infusion for the minimally invasive treatment of breast tumors.

Animals↗

PubMed2002

Radio-frequency ablation of VX2 rabbit tumors: assessment of completeness of treatment by using contrast-enhanced harmonic power Doppler US.

PURPOSE: To assess contrast material-enhanced harmonic power Doppler and fundamental color Doppler ultrasonography (US) in the detection of residual viable tumor tissue after radio-frequency (RF) ablation in tumors embedded in fat. MATERIALS AND METHODS: Twenty-eight VX2 tumors were implanted into the retroperitoneum of 14 rabbits. Tumors were examined with contrast-enhanced fundamental color Doppler US and harmonic power Doppler US before and 10 minutes after RF ablation. Saline-enhanced RF ablation (30 mL/h) was performed over 10 minutes with 28-W RF power. Follow-up included repeat US examinations. Necropsies and histopathologic assessment were performed after detection of residual untreated tumor at US or 3 weeks after ablation. RESULTS: VX2 tumors reached a mean size of 21 mm +/- 9 (SD) (size range, 6-43 mm) 25 days after implantation. All tumors larger than 31 mm showed signs of central necrosis at US. Before ablation, intense vascularity was detected in all tumors with both contrast-enhanced US modes. Histopathologic assessment at the end of the follow-up period revealed local relapses due to incomplete ablation in 14 (50%) of 28 cases. Detection of residual tumor was missed in all cases with contrast-enhanced color Doppler US. Contrast-enhanced harmonic power Doppler US depicted residual flow in 12 of the 14 cases (sensitivity, 86%) in which local relapses occurred. There was a significant (P <.005, McNemar test) improvement in detection of residual tumor when the harmonic power Doppler mode was used. CONCLUSION: Contrast-enhanced harmonic power Doppler US has greater sensitivity than contrast-enhanced color Doppler US for detecting residual VX2 tumor following ablation. Therefore, contrast-enhanced harmonic power Doppler US may be a useful additional method for the detection of residual tumors after RF ablation.

Animals↗

PubMed2002

Computerized modeling based on spiral CT data for noninvasive determination of aortic stent-graft length.

PURPOSE: To preprocedurally determine the correct length of a nonbifurcated endovascular prosthesis for abdominal aortic aneurysm (AAA) repair using a computerized model. METHODS: A computer program was implemented to calculate the optimal intraluminal course of nonbifurcated stent-grafts from spiral computed tomographic (CT) images of the aortic lumen reconstructed at 2.5, 5, and 10-mm slice thicknesses. The algorithm was tested using 10 phantoms fabricated from 150-mm-long, 10-mm-diameter copper rods that were bent into shapes mimicking different aortic configurations. Midpoint coordinates and rod diameters were determined from each CT image by 3 independent observers and served as input parameters to the program. The influence of the different CT reconstructions on the calculated lengths and possible observer dependence were assessed using calculated length estimation errors. Spiral CT images from 20 consecutive AAA patients scanned before stent-graft implantation were also processed to evaluate the algorithm under clinical conditions. RESULTS: Length estimation errors of the phantoms depended on the degree of bending as well as on the CT reconstruction slice thickness but were observer independent. Maximum errors were 7% for the 10-mm slices, 3.5% for the 5-mm slices, and 1.2% for a 2.5-mm reconstruction. The mean longitudinal shortening of the aorta due to vessel tortuosity was 9.1% +/- 4.8% among the 20 patients. Based on the results of the phantom study, errors of the calculated stent-graft lengths in patients were estimated to be approximately 1% for a 5-mm CT reconstruction increment and <2% for a 10-mm increment. CONCLUSIONS: The proposed algorithm makes it possible to calculate noninvasively the correct length of straight stent-grafts under clinical conditions with a 1% to 2% error.

Algorithms↗

PubMedDate not supplied

Computational fluid dynamics: hemodynamic changes in abdominal aortic aneurysm after stent-graft implantation.

The aim of this study was to demonstrate quantitatively and qualitatively the hemodynamic changes in abdominal aortic aneurysms (AAA) after stent-graft placement based on multidetector CT angiography (MDCT-A) datasets using the possibilities of computational fluid dynamics (CFD). Eleven patients with AAA and one patient with left-side common iliac aneurysm undergoing MDCT-A before and after stent-graft implantation were included. Based on the CT datasets, three-dimensional grid-based models of AAA were built. The minimal size of tetrahedrons was determined for grid-independence simulation. The CFD program was validated by comparing the calculated flow with an experimentally generated flow in an identical, anatomically correct silicon model of an AAA. Based on the results, pulsatile flow was simulated. A laminar, incompressible flow-based inlet condition, zero traction-force outlet boundary, and a no-slip wall boundary condition was applied. The measured flow volume and visualized flow pattern, wall pressure, and wall shear stress before and after stent-graft implantation were compared. The experimentally and numerically generated streamlines are highly congruent. After stenting, the simulation shows a reduction of wall pressure and wall shear stress and a more equal flow through both external iliac arteries after stenting. The postimplantation flow pattern is characterized by a reduction of turbulences. New areas of high pressure and shear stress appear at the stent bifurcation and docking area. CFD is a versatile and noninvasive tool to demonstrate changes of flow rate and flow pattern caused by stent-graft implantation. The desired effect and possible complications of a stent-graft implantation can be visualized. CFD is a highly promising technique and improves our understanding of the local structural and fluid dynamic conditions for abdominal aortic stent placement.

Aortic Aneurysm, Abdominal↗

PubMedDate not supplied

Accuracy and time efficiency for the detection of thoracic cage fractures: volume rendering compared with transverse computed tomography images.

OBJECTIVE: To compare the accuracy and time efficiency of volume rendering (VR) compared with transverse images of multidetector-row computed tomography data to identify thoracic cage fractures. METHODS: Computed tomography scans of 50 patients with acute blunt chest trauma were retrospectively analyzed by using VR and transverse images. The number, location, and type of rib and sternal fractures revealed by these viewing methods were compared, and the time needed for diagnosis was measured. RESULTS: Thirty of 50 patients had a total of 178 rib fractures. The mean sensitivity, specificity, and accuracy for their detection were similar for transverse (96%, 100%, and 99%) and VR (98%, 100%, and 100%) images. Three sternal fractures were correctly diagnosed with VR, and 1 was missed on transverse images by both readers. The time to read VR images (mean of 105 seconds) was significantly reduced compared with the time needed for transverse image reading (mean of 167 seconds; P < 0.001). CONCLUSION: Volume rendering of computed tomography data depicts thoracic cage fractures with a high accuracy similar to that of transverse images but is considerably faster.

Adolescent↗

PubMedDate not supplied

Nontraumatic emergent abdominal vascular conditions: advantages of multi-detector row CT and three-dimensional imaging.

In the past decade, great strides have been made in the development of helical computed tomography (CT) that have led to shorter scanning time and higher spatial resolution. A wide range of traumatic and nontraumatic emergent conditions may be quickly and accurately diagnosed with multi-detector row CT. Multi-detector row CT angiography is the preferred method for imaging in emergent abdominal vascular conditions because it enables the acquisition of high-spatial-resolution volumetric image data during a single breath hold. Unlike catheter angiography, multi-detector row CT angiography not only depicts the vessels but also allows assessment of perfusion in adjacent organs. To make the most effective diagnostic use of multi-detector row CT angiography and three-dimensional image postprocessing, radiologists must be familiar with the optimal CT angiographic protocols and with the typical CT findings in various emergent vascular conditions. This article describes the protocols used in 11 patients with conditions including ruptured abdominal aortic aneurysm, secondary aortoduodenal fistula, splanchnic segmental arterial mediolysis, and Wegener-type vasculitis with visceral involvement. All of the diagnoses in these 11 cases were made in the emergency department, and the delay between imaging and diagnosis was decreased considerably by avoiding the transfer of patients for catheter angiography.

Abdomen, Acute↗