Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 199 records · Page 11Linked to original sources

PubMed1998

[Primary varices of the colon. A rare cause of gastrointestinal bleeding].

HISTORY: A 34-year-old patient presented with a two-day history of passing bright-red blood with his stools. There was no contributory past or family history and he had no accompanying symptoms. INVESTIGATIONS: Colonoscopy revealed many varices in the colon and terminal ileum without an active source of bleeding. Angiography failed to demonstrate any bleeding or vascular anomaly in the splanchnic region. Abdominal ultrasound and gastroscopy as well as biochemical tests did not indicate portal hypertension or liver cirrhosis. TREATMENT AND COURSE: On the night of admission there was a renewed fall in haemoglobin concentration. Emergency colonoscopy again failed to discover a source of bleeding. After transfusion of four units of erythrocyte concentrate the further course was uneventful. 8 months and 3 years later there were further episodes of marked bleeding per rectum. At the latest admission no source for the bleeding was found but there was some blood oozing in the sigmoid colon. Biochemical tests were unremarkable. The large varices were again seen in the colon and terminal ileum. Gastroscopy, Doppler sonography of the liver and repeat abdominal sonography again failed to demonstrate portal vein thrombosis, liver cirrhosis or portal hypertension. CONCLUSION: In case of colonic varices the differential diagnosis should include portal hypertension with chronic liver disease, portal vein thrombosis, vascular anomalies or postoperative complications. The treatment of primary varices, which are rare, is conservative.

Adult↗

PubMed1998

Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients.

The Sry-related protein Sox10 is selectively expressed in neural crest cells during early stages of development and in glial cells of the peripheral and central nervous systems during late development and in the adult. Mutation of the Sox10 gene leads to neural crest defects in the Dominant megacolon mouse mutant and to combined Waardenburg-Hirschsprung syndrome in humans. Here, we have studied the four Sox10 mutations found to date in Waardenburg-Hirschsprung patients both in the context of the rat and the human cDNA. Unlike the rat Sox10 protein, which failed to show transcriptional activity on its own, human Sox10 displayed a weak, but reproducible, activity as a transcriptional activator. All mutant Sox10 proteins, including the one that only lacked the 106 last amino acids were deficient in this capacity, indicating that the carboxyl terminus of human Sox10 carries a transactivation domain. Whereas all four mutants failed to transactivate, only two failed to synergistically enhance the activity of other transcription factors. Synergy required both the ability to bind to DNA and a region in the amino-terminal part of Sox10. Those mutants that failed to synergize were unable to bind to DNA. Analysis of the naturally occurring Sox10 mutations not only helps to dissect Sox10 structure, but also allows limited predictions on the severity of the disease.

Animals↗

PubMed1998

Increased IL-12 P40 homodimer secretion by spleen cells during in vivo growth of the BW-19 T cell hybridoma accompanies suppression of natural immunity.

The high capacity of the T cell hybridoma BW-19 to metastasize to the spleen, despite its high and moderate sensitivity to lysis by macrophages and natural killer (NK) cells, respectively, appears to be linked to its capacity to suppress local resident NK cell and macrophage activity. Such suppression of splenic NK cell and macrophage activity is accompanied by an increased production of the p40 subunit of interleukin-12 (IL-12) by spleen cells. Closer examination revealed that most of the p40 subunit is present under the form of the homodimer (p40)2, whereas the heterodimeric form of IL-12 is present only in small amounts. Since (p40)2 is known to be a strong antagonist of IL-12-mediated effects, i.e., NK cell activation and interferon-gamma (IFN-gamma) secretion, the increased production of (p40)2 after BW-19 cell inoculation may contribute to the suppression of NK cell and macrophage activity. In addition, we found that the high production of (p40)2 in our tumor model was accompanied by a drastic decrease in IL-2 and IFN-gamma production by spleen cells, further favoring the possibility that (p40)2 plays a role in the suppression of NK cell and macrophage cytotoxicity. Our results show that normal spleen cells can produce (p40)2 in response to cancer cell growth in vivo and are highly suggestive of a role for (p40)2 in the suppression of natural immunity.

Animals↗

PubMed1998

Biochemical engineering of neural cell surfaces by the synthetic N-propanoyl-substituted neuraminic acid precursor.

Sialylation of glycoproteins and glycolipids plays an important role during development, regeneration, and pathogenesis of diseases. During times of intense plasticity within the nervous system, such as development and regeneration, sialylation of neural cells is distinct from the time of its maintenance. In this study, a synthetic precursor of neuraminic acid, N-propanoylmannosamine (N-propanoyl neuraminic acid precursor (P-NAP)), is applied to the culture medium of oligodendrocyte progenitor cells, microglia, astrocytes, and neurons from neonatal rat brains to alter sialylation of glycoconjugates within these cells. P-NAP is metabolized and incorporated as N-propanoyl neuraminic acid into glycoproteins of the cell membrane. P-NAP stimulates the proliferation of astrocytes and microglia but not of oligodendrocyte progenitor in vitro. However, P-NAP increases the number of oligodendrocyte progenitor cells expressing the early oligodendroglial surface marker A2B5 epitope. In the presence of P-NAP, cerebellar neurons (but not astrocytes) in microexplant cultures start to express the oligodendroglial progenitor marker A2B5 epitope, which is normally undetectable on these cells. The controls, which were performed in the absence of any additive or in the presence of the physiological precursor of neuraminic acid, N-acetylmannosamine, did not show any increase in A2B5 expression.

Animals↗

PubMed1998

T-cell and monocyte subsets, inflammatory molecules, rejection, and hemodynamics early after cardiac transplantation.

BACKGROUND: In the early period after cardiac transplantation, differential diagnosis of graft failure due to rejection, infection, and other causes is important but difficult. METHODS: In 22 consecutive patients undergoing heart transplantation, we prospectively determined levels of interleukin-6 as well as T-cell and monocyte subsets at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first 3 months after transplantation. RESULTS: Worse hemodynamic parameters, as characterized by dichotomization according to median values (pulmonary capillary wedge pressure >10 mmHg, mean pulmonary arterial pressure > 18 mmHg, pulmonary vascular resistance > 115 dyn x sec x cm(-5), right atrial pressure > 5 mmHg, cardiac index <3 L/min/m2, early mitral deceleration time < 135 msec, and isovolumic relaxation time <80 msec), were associated with higher levels of interleukin-6, C-reactive protein, polymorphonuclear cells, CD71+/CD14+ monocytes, and IgM levels and, in contrast, with lower levels of immunocompetence markers such as CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+/CD25+ T cells, CD4+/ CD45RO+ T cells, NK cells, and lower biopsy scores. CONCLUSION: Early after cardiac transplantation, elevated levels of inflammatory cells and soluble inflammatory molecules and lower levels of immunocompetence markers are associated with impaired allograft function in the absence of cellular rejection.

Adult↗

PubMed1998

Mechanical stressing of integrin receptors induces enhanced tyrosine phosphorylation of cytoskeletally anchored proteins.

Physical forces play a fundamental role in the regulation of cell function in many tissues, but little is known about how cells are able to sense mechanical loads and realize signal transduction. Adhesion receptors like integrins are candidates for mechanotransducers. We used a magnetic drag force device to apply forces on integrin receptors in an osteoblastic cell line and studied the effect on tyrosine phosphorylation as a biochemical event in signal transduction. Mechanical stressing of both the beta1 and the alpha2 integrin subunit induced an enhanced tyrosine phosphorylation of proteins compared with integrin clustering. Application of cyclic forces with a frequency of 1 Hz was more effective than a continuous stress. Using Triton X-100 for cell extraction, we found that tyrosine-phosphorylated proteins became physically anchored to the cytoskeleton due to mechanical integrin loading. This cytoskeletal linkage was dependent on intracellular calcium. To see if mechanical integrin stressing induced further downstream signaling, we analyzed the activation of mitogen-activated protein (MAP) kinases and found an increased phosphorylation of MAP kinases due to mechanical stress. We conclude that integrins sense physical forces that control gene expression by activation of the MAP kinase pathway. The cytoskeleton may play a key role in the physical anchorage of activated signaling molecules, which enables the switch of physical forces to biochemical signaling events.

Antigens, CD↗

PubMed1998

Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1.

Recent evidence points to a role of cytokines like tumor necrosis factor-alpha (TNF) in the generation of hyperalgesia not only in inflammatory, but also in neuropathic pain. We used the model of chronic constrictive injury (CCI) of one sciatic nerve in the mouse to investigate which of the two known TNF receptors is involved in the process that leads to hyperalgesia after nerve injury. Neutralizing antibodies to TNF, to the TNF receptor 1 (TNFR1), and to the TNF receptor 2 (TNFR2) were administered by epineurial injection once daily to mice with CCI. Testing of the animals' hind paws with thermal and innocuous mechanical stimuli revealed a reduction in thermal hyperalgesia and mechanical allodynia in mice treated with neutralizing antibodies to TNF and to TNFR1. Neutralizing antibodies to TNFR2 had no effect. We conclude that TNFR1, but not TNFR2, is mediating thermal hyperalgesia and mechanical allodynia after nerve injury.

Animals↗

PubMed1998

Faraday Laser Magnetic Resonance Spectroscopy of Vibrationally Excited C2D.

We studied the gas phase spectrum of the deuterated ethynyl radical C2D in the region between 3196 and 3243 cm-1 using a Faraday LMR spectrometer in combination with a CO overtone laser. The C2D radicals were generated in a dc glow discharge containing helium, deuterium, and acetylene. We observed a hot band between two vibronic 2Pi states with an origin at 3225 cm-1. The lower level is assigned to the first excited bending level of the electronic X ground state. The upper level corresponds to the first excited electronic state A at 3513 cm-1, which was observed previously [J. Mol. Struct. 190, 41-60 (1988)]. This region is subject to strong vibronic interaction, caused by mixing of the electronic X ground state with the A state at 3513 cm-1. From the analysis of the spectra we could determine the orbital g factor of the upper level, which gave important information about the mixing ratios. In addition we were able to derive a precise term value for the first excited bending level of the electronic X ground state. The experimentally derived molecular parameters are compared with theoretically calculated values, obtained by ab initio calculations. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

[Artificial bradycardias due to tape-running problems of old long-term ECG records].

Artificial bradycardias due to tape-running alterations of old long-term ECG recorders were observed with increasing frequency in the last 2 years at our hospital. To document the extent of this problem, 115 consecutive 24-hour long-term ECG recordings of 10 still used tape recorders with an age of 12 +/- 4 years were examined. Analysis of the tapes with a new analysis system revealed artificial bradycardias with rates of 10 to 40/min in 22 of 115 long-term ECG recordings (19%). These artificial bradycardias were observed in 4 out of 10 examined tape recorders (40%). Three of 4 concerned recorders were 14 years old at the time of examination, and one recorder was only 5 years old. Artificial bradycardias were caused by extensive alterations of tape-running speed in all cases. Diagnostic proof of artificial bradycardias due to tape running alterations on long-term ECG are simultaneous with prolonged RR-intervals occurring increases in all ECG times including P-width. PQ-time, QRS-width and QT-duration with otherwise unchanged ECG morphology. To avoid prolonged hospital stays or therapeutic mistakes like unnecessary pacemaker implantation, especially older long-term ECG-tape recorders should be checked regularly and, if necessary, be replaced by new devices.

Artifacts↗

PubMed1998

Changes at the extracellular matrix during acute and chronic rejection in human liver transplantation.

We have previously observed changes at the extracellular matrix (ECM) which significantly correlated with the extent of preservation and reperfusion injury. In the present study, we attempted to investigate whether the ECM may be also involved in the pathophysiological sequelae of acute and chronic rejection. Of 81 patients monitored for the ECM parameters laminin, hyaluronic acid, fibronectin receptor, and transforming growth factor (TGF)-beta, 28 patients developed acute rejection (< 1 month), in 14 patients (17.4%) acute rejection was steroid resistant, 4 patients (4.5%) developed early chronic rejection following acute steroid-resistant rejection. Acute and chronic rejection were confirmed by established clinical and histological criteria. Laminin levels were significantly increased in patients experiencing acute steroid-resistant rejection (4204 +/- 133 ng/ml; P < or = 0.01) compared with patients with steroid-sensitive rejection (1059 +/- 27.3 ng/ ml) and with an uneventful postoperative course (1214 +/- 17.4 ng/ml). No increase in laminin was observed in those four patients who developed early chronic rejection (1099 +/- 58.7 ng/ml). Hyaluronic acid, fibronectin receptor, and TGF-beta levels also increased in patients with acute steroid-resistant rejection; hyaluronic acid: 290 +/- 10.8 micrograms/l vs 154 +/- 13.6 micrograms/l and 131 +/- 11.7 micrograms/l in patients with steroid-sensitive and no rejection, respectively; fibronectin receptor: 1003 +/- 23.5 ng/ml vs 573 +/- 24.8 ng/ml and 428 +/- 13.6 ng/ ml in patients with steroid-sensitive and no rejection, respectively; and TGF-beta: 393 +/- 14.9 pg/ml versus 315 +/- 10.7 pg/ml and 233 +/- 8.9 pg/ml in patients with steroid-sensitive and no rejection, respectively. A further increase in hyaluronic acid levels was observed in patients who developed early chronic rejection, while fibronectin receptor and TGF-beta levels remained low, similarly to laminin levels. The increase in laminin, hyaluronic acid, fibronectin receptor, and TGF-beta during acute steroid-resistant rejection may be stimulated by the rejection-related release of cytokines and adhesion molecules which paralleled the increase in ECM parameters. The lack of increase in laminin and fibronectin receptor levels in those patients who developed early chronic rejection may reflect an inability to recover from acute rejection.

Acute Disease↗

PubMed1998

Segmentation of the vertebrate body.

The segmental character of the vertebrate body wall is reflected by metamerically arranged tissues that are patterned during embryonic life as a consequence of somite formation, compartmentalization and differentiation. The somites bud off the paraxial mesoderm in a cranio-caudal sequence and are compartmentalized by local signals from adjacent structures. These signals may be mediated by diffusible substances such as Sonic hedgehog (Shh), Wnts and Bone morphogenetic protein (BMPs) or by cell-cell interactions via membrane-bound receptors and ligands such as Delta and Notch. Compartmentalization of the somites and their derivatives is reflected by the differential expression of developmental regulatory genes such as Pax-1, 3, 7 and 9, MyoD, paraxis, twist and others. Secondary segmentation is imposed upon other tissues, such as blood vessels and nerves, by the rearrangement and regionalization of the somitic derivatives, especially the sclerotome. Early cranio-caudal identity is determined by the expression of different Hox genes. Finally, fusion of segmental anlagen occurs to form segment-overbridging skeletal elements and muscles. The expression of homologous genes indicates that the process of segmentation in vertebrates and invertebrates is homologous, derived by descent from a common ancestor.

Animals↗

PubMed1998

Comparison between a twin-screw extruder and a rotary ring die press. Part II: influence of process variables.

The influence of different processing steps on pellet quality was investigated: granulation/extrusion and spheronization. Pellets were produced at two levels of water content on two different types of extruders: a twin screw extruder and a rotary ring die press. In order to control the spheronization process each extrudate was rounded in two spheronizers using two radial velocities, respectively. Pellet shape and size were selected to describe the pellet quality. Under constant spheronization conditions the extrudates behaved dissimilar on the two spheronizers. This could be attributed to the geometry of the friction plates. The spheronizer with the rougher surface applied more mechanical energy to the extrudate and wet pellets which reduced the water content necessary for the formation of good pellets. Eliminating the influence of the spheronization process, high differences were observed in the quality of the extrudates produced by the two extruders. This confirmed the results from the first part of this study. Due to the crystallite-gel-model the different extruder types apply different mechanical stress on the extrudate which affect the network structure of the microcrystalline cellulose gel. The twin-screw extruder produced a more delicate network with a lower water movement. This led to a shift of the optimal moisture content towards higher values. Compared with spheronization, process changes in the granulation/extrusion process were more critical.

Chemistry, Pharmaceutical↗

PubMed1998

Plasma levels of glutathione, alpha-tocopherol and lipid peroxides in polytraumatized patients; evidence for a stimulating effect of TNF alpha on glutathione synthesis.

Prognosis and outcome of polytraumatized patients are determined by the possible development of multiple organ failure (MOF). Among the direct traumatic organ damage, it is caused by a systemic inflammatory reaction. This might be triggered by an activation of the inflammatory mediator cascade following hemorrhagic-traumatic shock as well as by oxygen-derived free radicals (ROS). The aim of our present study was to answer the following questions: 1. Is the "oxidative stress" measurable during the development of MOF after polytraumatic injury? 2. Is there a relation between the activation of the inflammatory mediator cascade and changes of the organism's antioxidative system? The study group included 26 patients (15 survivors, 11 non-survivors) suffering from severe polytraumatic injury (Hannover Polytrauma Score 12-63 points). Plasma levels of reduced (GSH) and oxidized (GSSG) glutathione alpha-tocopherol (TOC), lipid peroxides (expressed in terms of thiobarbituric acid reagible substances = TBARS), and tumor necrosis factor alpha (TNF) were measured each day from the point of admission on the ICU until the discharge or death of the patients. The following results were obtained: Independent from the outcome, we observed a continuous loss of plasma sulfhydryl groups and TOC. In the patients developing a MOF score > 5 on 10th day after injury (n = 6), a significant increase in plasma GSSG level was measurable. Additionally, a total loss of plasma GSH was seen in some of these patients indicating the collapse of the GSH-dependent antioxidative system. Similar changes were never observed in patients with MOF score < or = 5 on 10th day after injury (n = 15). In this group, a significant correlation between plasma TNF peaks and short time GSH boosts was obtained as a possible indicative for a stimulating effect of TNF on GSH synthesis. It can be concluded that processes of oxidative stress in connection with a consumption of endogenic antioxidants might be able to promote the development of MOF after polytraumatic injury.

Adolescent↗

PubMed1998

Accurate sequencing by hybridization for DNA diagnostics and individual genomics.

Medical DNA diagnostics will increasingly rely on an accurate and inexpensive identification of mutations that affect the function of a gene. To validate diagnostic sequencing by hybridization (SBH), a number of p53 samples were analyzed with the complete set of 8192 noncomplementary 7-mer oligonucleotides. In four repeated, blind experiments we accurately sequenced 1.1 kb per each of 12 homozygote and heterozygote samples possessing base substitutions, insertions, and deletions. This SBH variant offers a high throughput platform to inexpensively sequence individual gene or pathogen genome samples within the clinical laboratory setting.

DNA↗

PubMed1998

Parasitological detection of Trypanosoma brucei gambiense in serologically negative sleeping-sickness suspects from north-western Uganda.

Forty-five parasitologically confirmed cases of sleeping sickness were diagnosed in north-western Uganda using a combination of two or three techniques. Forty of the cases were positive by the card agglutination test for trypanosomiasis (CATT), four were negative and one was not screened by the CATT. Trypanosomes isolated from the four CATT-negative but parasitologically positive cases were propagated for detailed biochemical genetic analysis. The aim was to demonstrate whether these four stocks lacked the LiTat 1.3 gene which encodes the antigen on which the CATT is based. All the DNA extracts isolated from these CATT-negative stocks and from six CATT-positive stocks of Trypanosoma brucei gambiense were targeted for amplification by the three variable-surface-glycoprotein genes thought to be ubiquitous in T. b. gambiense. The LiTat 1.3 gene was shown to be present in all 10 stocks. Trypanosome carriers may be CATT-negative because the CATT is not sensitive enough, because their parasites lack the LiTat 1.3 gene, or because their parasites have this gene but do not express it. The four sleeping-sickness cases who gave negative CATT results in the present study have very important implications in the diagnosis of T. b. gambiense infections using the CATT. Following treatment of the CATT-positive cases, the CATT-negative carriers of the trypanosomes remain as human reservoir hosts for continuous infection of the population. Because CATT-negative individuals are rarely examined further, the general prevalence of parasitologically positive but CATT-negative cases is unclear. This study demonstrates the value of co-ordinated use of serological and parasitological techniques in the diagnosis of Gambian sleeping sickness.

Agglutination Tests↗

PubMed1998

Usefulness of short-term urine collection in the nutritional monitoring of low birthweight infants.

To establish adequacy of urine collection times shorter than 24h in the metabolic monitoring of low birthweight infants, we collected urine for 24 h in 39 LBW infants during the third and fourth week of life. All urine voidings over the 24-h period were separately collected, the volume of each sampling and the time of voiding were recorded, and 20% of the volume was removed for pooling. All individual and pooled samples were analysed for total nitrogen, urea and ammonia, alpha-amino nitrogen, creatinine, sodium, potassium, calcium and phosphorus, and for each compound the ratio to 1 mol creatinine was established. Individual sample results were "pooled" to obtain 3-, 6- and 12-h period excretion and than related to the 24-h excretion as measured in the pooled 24-h sample. As the volume of urine obtained in any 6-h collecting period depended on the time of sampling (06:00-12:00 h, 17.5+/-3.1% of total; 12:00-18:00 h, 31.6+/-5.1% of total; 18:00-24:00 h, 25.6+/-3.1% of total; and 0:00-06:00h, 25.3+/-2.9% of total), calculations were based on samples obtained from 18:00 to 06:00 h. The correlation between results of 3- and 24 h-collection periods was weakest, while results of the 6-h collection correlated highly with the total daily excretion (r = between 0.82 and 0.93 for the different compounds) and the correlation was only slightly better when the 12-h collection period was considered. The correlation between the mean molar substrate/creatinine ratio of all individual samples of a 24-h collecting period and the and total daily excretion of the respective substrate was weaker (r = between 0.46 and 0.76 for the different compounds) than the correlation between the results of a 6-h collecting period and the daily excretion is not as stable than in later life. The data indicate that 6-h urine sampling may be sufficient for metabolic monitoring of LBW infants. By contrast, urinary substrate/creatinine ratios are not good markers of the daily excretions of the respective substrate during the first weeks of life.

Ammonia↗

PubMed1998

Critical illness polyneuropathy following cardiac surgery.

Critical illness polyneuropathy (CIP), a neurologic complication which may occur secondary to surgery, trauma and coma, is associated with sepsis or multiple organ failure (MOF). CIP is characterized by an axonal distal degeneration of sensory and motor fibres. The patients will often become neurologically conspicuous when weaning from mechanical ventilation is unexpectedly difficult. In such cases electrophysiologic examinations must be performed. CIP following cardiac surgery is widely unrecognized. The most important aspect of CIP therapy is treatment of the underlying disease, because no specific treatment for CIP exists. We report on a 64-year old patient who developed sepsis and CIP following cardiovascular surgery. The neurological complication was initially misinterpreted as hypoxic brain damage.

Anti-Bacterial Agents↗

PubMed1998

Kinetics of the antibody response against human cytomegalovirus-specific proteins in allogeneic bone marrow transplant recipients.

The humoral immune response against human cytomegalovirus (CMV) was retrospectively investigated in >800 serum samples from 31 recipients of allogeneic bone marrow transplants. To this end, an ELISA was performed that allowed the individual analysis of IgG antibodies against known antigenic domains of CMV-derived phospho- and glycoproteins and nonstructural polypeptides. Twenty-nine patients developed active CMV infection after transplantation, as determined by repeatedly positive samples in polymerase chain reaction (PCR) assays. Seventeen patients responded serologically to viral replication by producing CMV-specific antibodies against a variety of antigens. The response was detectable concomitantly with PCR positivity and was seen as early as 20 days after transplantation. High titers of glycoprotein-specific neutralizing antibodies were correlated with the absence of viral DNA in blood (P<.002). Nineteen patients developed CMV disease. Survival was associated with the production of high titers of CMV glycoprotein-specific antibodies in response to viral replication.

Antibodies, Viral↗