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Biomedical subjects

W Schubert

Publications and source records attributed to W Schubert.

At least 19 recordsLinked to original sources
PubMed2005

Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates.

AIM: Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino acids levels. METHODS: Infants with a birthweight < or = 1750 g and gestational age < or = 34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid-arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. RESULTS: Twenty-one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8 +/- 5.6 vs formula B 170.1 +/- 2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4 +/- 3.4 vs 20.5 +/- 3.3 g/kg/d; p = 0.045) and lower mean change in Z-scores for weight (-0.18 +/- 0.16 vs 0.00 +/- 0.09; p = 0.009) and for head circumference (-0.06 +/- 0.13 vs 0.06 +/- 0.13; p = 0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B. CONCLUSION: Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis.

Amino Acids, Essential↗
PubMed2001

Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo.

The role of endothelial cell caveolae in the uptake and transport of macromolecules from the blood-space to the tissue-space remains controversial. To address this issue directly, we employed caveolin-1 gene knock-out mice that lack caveolin-1 protein expression and caveolae organelles. Here, we show that endothelial cell caveolae are required for the efficient uptake and transport of a known caveolar ligand, i.e. albumin, in vivo. Caveolin-1-null mice were perfused with 5-nm gold-conjugated albumin, and its uptake was followed by transmission electron microscopy. Our results indicate that gold-conjugated albumin is not endocytosed by Cav-1-deficient lung endothelial cells and remains in the blood vessel lumen; in contrast, gold-conjugated albumin was concentrated and internalized by lung endothelial cell caveolae in wild-type mice, as expected. To quantitate this defect in uptake, we next studied the endocytosis of radioiodinated albumin using aortic ring segments from wild-type and Cav-1-null mice. Interestingly, little or no uptake of radioiodinated albumin was observed in the aortic segments from Cav-1-deficient mice, whereas aortic segments from wild-type mice showed robust uptake that was time- and temperature-dependent and competed by unlabeled albumin. We conclude that endothelial cell caveolae are required for the efficient uptake and transport of albumin from the blood to the interstitium.

Albumins↗
PubMed2001

Identification and characterization of a cell surface marker for embryonic rat spinal accessory motor neurons.

The developing mammalian spinal cord contains distinct populations of motor neurons that can be distinguished by their cell body positions, by the expression of specific combinations of regulatory genes, and by the paths that their axons take to exit the central nervous system (CNS). Subclasses of spinal motor neurons are also thought to express specific cell surface proteins that function as receptors which control the guidance of their axons. We identified monoclonal antibody (mAb) SAC1 in a screen aimed at generating markers for specific subsets of neurons/axons in the developing rat spinal cord. During early embryogenesis, mAb SAC1 selectively labels a small subset of Isl1-positive motor neurons located exclusively within cervical segments of the spinal cord. Strikingly, these neurons extend mAb SAC1-positive axons along a dorsally directed trajectory toward the lateral exit points. Consistent with the finding that mAb SAC1 also labels spinal accessory nerves, these observations identify mAb SAC1 as a specific marker of spinal accessory motor neurons/axons. During later stages of embryogenesis, mAb SAC1 is transiently expressed on both dorsally and ventrally projecting spinal motor neurons/axons. Interestingly, mAb SAC1 also labels the notochord and floor plate during most stages of spinal cord development. The mAb SAC1 antigen is a 100-kD glycoprotein that is likely to be the rat homolog of SC1/BEN/DM-GRASP, a homophilic adhesion molecule that mediates axon outgrowth and fasciculation.

Accessory Nerve↗
PubMed2001

Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities.

Caveolin-1 is the principal structural protein of caveolae membranes in fibroblasts and endothelia. Recently, we have shown that the human CAV-1 gene is localized to a suspected tumor suppressor locus, and mutations in Cav-1 have been implicated in human cancer. Here, we created a caveolin-1 null (CAV-1 -/-) mouse model, using standard homologous recombination techniques, to assess the role of caveolin-1 in caveolae biogenesis, endocytosis, cell proliferation, and endothelial nitric-oxide synthase (eNOS) signaling. Surprisingly, Cav-1 null mice are viable. We show that these mice lack caveolin-1 protein expression and plasmalemmal caveolae. In addition, analysis of cultured fibroblasts from Cav-1 null embryos reveals the following: (i) a loss of caveolin-2 protein expression; (ii) defects in the endocytosis of a known caveolar ligand, i.e. fluorescein isothiocyanate-albumin; and (iii) a hyperproliferative phenotype. Importantly, these phenotypic changes are reversed by recombinant expression of the caveolin-1 cDNA. Furthermore, examination of the lung parenchyma (an endothelial-rich tissue) shows hypercellularity with thickened alveolar septa and an increase in the number of vascular endothelial growth factor receptor (Flk-1)-positive endothelial cells. As predicted, endothelial cells from Cav-1 null mice lack caveolae membranes. Finally, we examined eNOS signaling by measuring the physiological response of aortic rings to various stimuli. Our results indicate that eNOS activity is up-regulated in Cav-1 null animals, and this activity can be blunted by using a specific NOS inhibitor, nitro-l-arginine methyl ester. These findings are in accordance with previous in vitro studies showing that caveolin-1 is an endogenous inhibitor of eNOS. Thus, caveolin-1 expression is required to stabilize the caveolin-2 protein product, to mediate the caveolar endocytosis of specific ligands, to negatively regulate the proliferation of certain cell types, and to provide tonic inhibition of eNOS activity in endothelial cells.

Albumins↗
PubMed2001

A comparison of mutations induced by accelerated iron particles versus those induced by low earth orbit space radiation in the FEM-3 gene of Caenorhabditis elegans.

The fem-3 gene of Caenorhabditis elegans was employed to determine the mutation frequency as well as the nature of mutations induced by low earth orbit space radiation ambient to Space Shuttle flight STS-76. Recovered mutations were compared to those induced by accelerated iron ions generated by the AGS synchrotron accelerator at Brookhaven National Laboratory. For logistical reasons, dauer larvae were prepared at TCU, transported to either Kennedy Space Center or Brookhaven National Laboratory, flown in space or irradiated, returned to TCU and screened for mutants. A total of 25 fem-3 mutants were recovered after the shuttle flight and yielded a mutation frequency of 2.1x10(-5), roughly 3.3-fold higher than the spontaneous rate of 6.3x10(-6). Four of the mutations were homozygous inviable, suggesting that they were large deletions encompassing fem-3 as well as neighboring, essential genes. Southern blot analyses revealed that one of the 25 contained a polymorphism in fem-3, further evidence that space radiation can induce deletions. While no polymorphisms were detected among the iron ion-induced mutations, three of the 15 mutants were homozygous inviable, which is in keeping with previous observations that high LET iron particles generate deficiencies. These data provide evidence, albeit indirect, that an important mutagenic component of ambient space radiation is high LET charged particles such as iron ions.

Animals↗
PubMed2001

Particle size distribution in effluent of trickling filters and in humus tanks.

Particles and aggregates from trickling filters must be eliminated from wastewater. Usually this happens through sedimentation in humus tanks. Investigations to characterize these solids by way of particle size measurements, image analysis and particle charge measurements (zeta potential) are made within the scope of Research Center for Science and Technology "Fundamentals of Aerobic biological wastewater treatment" (SFB 411). The particle size measuring results given within this report were obtained at the Ingolstadt wastewater treatment plant, Germany, which served as an example. They have been confirmed by similar results from other facilities. Particles flushed out from trickling filters will be partially destroyed on their way to the humus tank. A large amount of small particles is to be found there. On average 90% of the particles are smaller than 30 microm. Particle size plays a decisive role in the sedimentation behaviour of solids. Small particles need sedimentation times that cannot be provided in settling tanks. As a result they cause turbidity in the final effluent. Therefore quality of sewage discharge suffers, and there are hardly advantages of the fixed film reactor treatment compared to the activated sludge process regarding sedimentation behaviour.

Environmental Monitoring↗
PubMed2001

Prospective comparison of panoramic tomography (zonography) and helical computed tomography in the diagnosis and operative management of mandibular fractures.

This prospective study compared the sensitivity of panoramic tomography (zonography) and helical computed tomography (CT) in diagnosing 73 mandibular fractures in 42 consecutive patients and correlated the results with known surgical findings. The purpose of the study was to determine the optimal radiologic examination for the diagnosis and operative management of mandibular fractures. The attending surgeons' interpretations of panoramic tomograms and helical CT images in the axial plane were compared with the patients' known surgical findings. A series of questions assessed the relative contribution of these two radiologic examinations in formulating an optimal operative plan for each patient. In the 42 patients studied, the sensitivity of helical CT was 100 percent in diagnosing mandibular fractures; this compared with 86 percent (36 of 42) for panoramic tomography, in which significantly more fractures were missed (p = 0.0412). In the six patients with fractures not visualized, the operative management was altered because of the new fracture visualized on helical CT. Of the seven missed fractures, six were in the posterior portion of the mandible. Comparing fracture detection by region, seven fractures found on helical CT were not visualized on panoramic tomography. Helical CT improved the understanding of the nature of mandibular fractures by providing additional information regarding fracture displacement and comminution and by locating injuries missed using panoramic tomography. This study suggests that helical CT alone may be more diagnostic than panoramic tomography alone in evaluating mandibular fractures. Helical CT sufficiently demonstrated details of fractures in 41 of 42 patients; in one patient, the nature of a dental root fracture was better delineated by panoramic tomography.

Humans↗
PubMed2001

A neural classifier enabling high-throughput topological analysis of lymphocytes in tissue sections.

A neural cell detection system (NCDS) for the automatic quantitation of fluorescent lymphocytes in tissue sections is presented in this paper. The system acquires visual knowledge from a set of training cell-image patches selected by a user. The trained system evaluates an image in 2 min calculating: the number, the positions, and the phenotypes of the fluorescent cells. For validation, the NCDS learning performance was tested by cross validation on digitized images of tissue sections obtained from inherently different types of tissue: diagnostic tissue sections across the human tonsil and across an inflammatory lymphocyte infiltrate of the human skeletal muscle. The NCDS detection results were compared with detection results from biomedical experts and were visually evaluated by our most experienced biomedical expert. Although the micrographs were noisy and the fluorescent cells varied in shape and size, the NCDS detected a minimum of 95% of the cells. In contrast, the cellular counts based on visual cell recognition of the experts were inconsistent and largely unreproducible for approximately 80% of the lymphocytes present in a visual field. The data indicate that the NCDS is rapid and delivers highly reproducible results and, therefore, enables high-throughput topological screening of lymphocytes in many types of tissue, e.g., as obtained by routine diagnostic biopsy procedures. High-throughput screening with the NCDS provides the platform for the quantitative analysis of the interrelationship between tissue environment, cellular phenotype, and cellular topology.

Automation↗
PubMed2000

Incidence of neurapraxia in digital nerve injuries.

Hand surgeons presented with a hand or finger laceration and an abnormal static two-point discrimination (> or =10 mm) must determine which patients require surgical exploration. There appears to be a paucity of data in the literature defining the incidence and nature of neurapraxia in this setting. A study was conducted in a busy urban practice to better understand this problem. To determine the incidence of intact nerves (i.e., neurapraxia) in digital nerve injury patients, the authors reviewed experience with 152 patients who presented with isolated digital nerve injuries over a 33-month period. Preoperative return of sensation and negative exploration cases were combined and referred to as the trauma-induced neurapraxia (TIN) group. There were 18 non-repair cases among the 152 isolated digital nerve injuries, giving a 12 percent incidence of TIN. Sensory recovery among the TIN patients ranged from 12 days to 6 months. In this study, the authors defined a group of patients who did not require surgical repair for isolated digital nerve injury as TIN cases. The TIN group represented 12 percent of the digital nerve trauma patients and required long follow-up for sensory recovery. This information is an important part of patient education and informed consent.

Fingers↗
PubMed2000

Secretion and differential localization of the proteolytic cleavage products Abeta40 and Abeta42 of the Alzheimer amyloid precursor protein in human fetal myogenic cells.

Abeta peptides are major components of the amyloid plaques that characterize Alzheimer's disease. These peptides are proteolytic cleavage products of the amyloid precursor protein (APP) and are generated by beta- and gamma-secretases. Here we show by multiparameter immunofluorescence imaging in muscle cells that localization of the Abeta40 and Abeta42 cleavage products reveals different myocyte types in a three-dimensional culture system. These myocyte types are heterogeneous by selective intracellular concentration of either Abeta40 or Abeta42 in vesicular structures, whilst only the Abeta40 peptide is secreted as indicated by Western blot analysis. This cellular pattern of APP proteolysis and Abeta peptide secretion correlates with lack of L-APP mRNA splice isoforms. Differential secretion and intracellular accumulation of Abeta peptides is characteristic for the early myocyte development and might be related to cell fusion.

Amyloid Precursor Protein Secretases↗
PubMed2000

Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a neurodegenerative disease affecting the anterior horn cells of the spinal cord and cortical motor neurons. Previous findings have suggested a specific impairment of mitochondrial function in skeletal muscle of at least a limited number of patients. Applying flavoprotein/NAD(P)H autofluorescence imaging of mitochondrial function in saponin-permeabilized muscle fibres, we detected a heterogeneous distribution of the respiratory chain defect among individual fibres in muscle biopsies of patients (11 out of 17) with sporadic amyotrophic lateral sclerosis (SALS). These findings correlate with the presence of cytochrome c oxidase (COX)-negative muscle fibres detected histologically. We established the molecular basis for the decreased activities of NADH:CoQ oxidoreductase and COX in SALS muscle. In the skeletal muscle of the investigated patients, diminished levels (13 out of 17) or multiple deletions (one out of 17) of mitochondrial DNA (mtDNA) were observed. These alterations of mtDNA seem to be related to decreased levels of membrane-associated mitochondrial Mn-superoxide dismutase. Our results support the viewpoint that an oxygen radical-induced impairment of mtDNA is of pathophysiological significance in the aetiology of at least a subgroup of patients with SALS.

Adult↗
PubMed2000

Contribution of conventional axial computed tomography (nonhelical), in conjunction with panoramic tomography (zonography), in evaluating mandibular fractures.

Previous studies comparing the sensitivity between different radiological exams have concluded that conventional axial computed tomography (CT; nonhelical) is unsuitable in the assessment of mandibular fractures. Axial CT was shown to have a reduced sensitivity compared with plain radiographs and panoramic tomography because it missed nondisplaced fractures in the posterior portion of the mandible. Because the resolution of CT has improved from the time of these previous studies, the authors were interested in assessing whether axial CT (nonhelical) could now provide additional clinically useful information and enhance our understanding of mandibular fractures, beyond that obtained from panoramic tomography alone. In their study, 5 staff surgeons initially evaluated the panoramic tomograms and then the CT scans of 39 patients with 66 fractures. A series of four questions assessed the relative contribution of these two radiological exams in formulating an optimal operative plan for each patient. The authors found that axial CT provided supplementary information regarding missed fractures, comminution, and the exact size and degree of displacement of fracture fragments. This additional data could have changed the operative plan in a substantial proportion of patients (17 of 39). Axial CT demonstrated two missed parasymphyseal fractures (2 of 39 patients) that were not seen on these patients' panoramic tomograms. Axial CT also revealed undiscovered comminution or demonstrated fracture displacement more precisely in 39% of patients (15 of 39) and 24% of fractures (16 of 66). This study demonstrates that axial CT was clinically useful as an additional investigation to panoramic tomography. Axial CT helped elucidate further the nature of suspected mandibular fractures.

Humans↗
PubMed2000

Latissimus dorsi myocutaneous flap reconstruction of neck and axillary burn contractures.

Neck and axillary burn contractures are both a devastating functional and cosmetic deformity for patients and a challenging problem for reconstructive surgeons. Severe contractures are more commonly seen in the developing world, a result of both the widespread use of open fires and the inadequacy of primary and secondary burn care in these vicinities. When deep burns are allowed to heal spontaneously, patients develop hypertrophic scarring of the neck and axillary areas. The back is typically spared, however, remaining a suitable donor site. We have used nine latissimus dorsi myocutaneous flaps in a total of six patients, finding the flaps effective in resurfacing both the neck and the axillary regions after wide release of burn contractures. Before flap mobilization, surgical neck release is often necessary to ensure safe, effective control of the airway in patients with significant neck contractures. Flap bulkiness in the anterior neck region can eventually be reduced by dividing the thoracodorsal nerve. Anchoring the skin paddle to its recipient site through the placement of tacking sutures will also help achieve a more normal anterior neck contour.

Adult↗
PubMed2000

Characterization and distribution of a new cell surface marker of neuronal precursors.

In a screen for novel cell surface markers of neuronal progenitors, we recently identified mAb 2F7 that recognizes an epitope present on both progenitor cells and postmitotic neurons, in the developing CNS and PNS. In the embryonic rat telencephalon, the mAb 2F7 epitope is expressed by migratory and postmigratory neurons in the developing cerebral cortex, as well as by presumptive neuronal progenitor cells of the ventricular zone. In the neonatal forebrain mAb 2F7 labels postmitotic neurons, including those of the developing cerebral cortex and olfactory bulb, as well as the axons of the corpus callosum. While mAb 2F7 immunoreactivity is present on only a low density of the neuronal progenitor cells situated in the anterior part of the subventricular zone, a progressively higher proportion of cells forming the rostral migratory stream express this epitope. mAb 2F7 labels the surfaces of neurons and neuronal precursors, but not mature oligodendrocytes and astrocytes in primary cultures derived from the rat neural tube. In vivo, migrating neural crest cells, motor neurons, and axonal projections associated with the spinal cord express the mAb 2F7 epitope. Immunoblot analyses reveal that the mAb 2F7 epitope resides on several high-molecular-weight, membrane-associated proteins, and is likely to be composed of N-linked carbohydrate. These findings suggest that mAb 2F7 recognizes a novel epitope that is present on progenitor cells and postmitotic, differentiating neurons in the developing mammalian nervous system.

Animals↗
PubMed1999

The M cell as a portal of entry to the lung for the bacterial pathogen Mycobacterium tuberculosis.

M. tuberculosis accesses the terminal lung and is phagocytosed by alveolar macrophages. Utilizing a mouse intratracheal challenge model, we demonstrate that M. tuberculosis rapidly enters through M cells as well. From there, bacilli are deposited within associated intraepithelial leukocytes and subsequently conveyed to the draining lymph nodes early after infection. Osteopetrotic (Csfm(op)/Csfm(op)) mice, null mutants for macrophage colony-stimulating factor, possess diminished numbers of circulating monocytes and tissue macrophages. Csfm(op)/Csfm(op) mice were highly susceptible to challenge with M. tuberculosis. In contrast to controls, tubercle bacilli were not conveyed to draining lymph nodes early after infection but were instead retained within the mucosa. These results indicate that M cells represent an alternate portal of entry for M. tuberculosis, which may contribute to the rapid development of protective lung immune responses.

Animals↗