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Biomedical subjects

O Schmidt

Publications and source records attributed to O Schmidt.

At least 55 records · Page 3Linked to original sources

Induction of a graft-versus-leukemia reaction by cyclosporin A withdrawal as immunotherapy for leukemia relapsing after allogeneic bone marrow transplantation.

We studied the immunomodulating effect of withdrawal of immunosuppression with cyclosporin A (CsA) in 42 patients with leukemic relapse of chronic myelogenous leukemia (CML) (n = 24), acute myeloid leukemia (AML) (n = 13) and acute lymphoblastic leukemia (ALL) (n = 5) after allogeneic unmanipulated bone marrow (BMT) or peripheral blood stem cell transplantation (PBSCT). Response to CsA withdrawal was monitored molecularly by the polymerase chain reaction for elimination of CML cells containing the bcr-abl messenger RNA (mRNA) transcript (n = 24), or mll-af4 mRNA transcript characteristic of leukemic cells with a 11q23 chromosomal abnormality (n = 1). Rapid tapering of CsA resulted in subsequent achievement of cytogenetic remission in 11 of 14 CML patients (79%) who relapsed in early disease phase (n = 9 cytogenetic relapse, n = 2 hematological relapse) after a median of 57 days. Three of 13 AML patients and one of five ALL patients achieved complete remission. CsA withdrawal was accompanied by the development of acute graft-versus-host disease (GVHD) grade II in most of the 24 patients with CML. Two patients who achieved remission of AML or ALL died from severe GVHD grade III-IV. We calculated a probability of 84% for achieving and remaining in remission with early relapse of CML 4 years after relapse post BMT, whereas patients with AML have only a probability of about 10% of achieving and remaining in remission after 3 years. Patients with advanced CML and ALL had no chance of achieving and remaining in remission in the same time period.

Adolescent↗

Molecular genetic analysis as a tool for evaluating stereotactic biopsies of glioma specimens.

Over the last years, distinct genetic lesions have been associated with individual tumor entities. Stereotactic biopsy has become an essential diagnostic tool in surgical neuro-oncology. In order to evaluate the potential of molecular analyses in stereotactic biopsies, we examined a series of 156 human brain tumors from patients undergoing stereotactic biopsy for molecular alterations typically seen in astrocytic gliomas and compared those results with a control group of 268 astrocytic tumors obtained at open surgery. Stereotactic biopsies of astrocytomas with borderline histopathological features between the WHO grades II and III showed a higher rate of allelic losses on chromosome 10 than those of the WHO grade II from open surgery (p = 0.011). Stereotactic biopsies of astrocytomas with borderline histopathological features between the WHO grades III and IV showed a higher rate of allelic losses on chromosome 10 than those of the WHO grade III from open surgery (p = 0.013). This indicates that stereotactic biopsies with features intermediate between grades are likely to correspond to the higher malignancy grade. Our data demonstrate that molecular genetic approaches can be successfully applied to stereotactic glioma biopsies. The difference in the distribution of malignancy associated genetic alterations between a stereotactic and openly resected group of gliomas indicates that histopathology may underestimate the malignant potential in some stereotactic specimens. We propose to further evaluate the molecular analysis of stereotactic glioma biopsies as a useful adjunct to standard histopathological procedures.

Biopsy↗

Comparison between the physiological response to roller skiing and in-line skating in biathletes.

PURPOSE: Roller skiing is frequently used in Nordic disciplines during the off-season periods. Recently, in-line skating has become a potential alternative. In the present study, the responses of heart rate, oxygen uptake, respiratory exchange ratio, and lactic acid concentration to roller skiing and in-line skating were compared in competitive biathletes. METHODS: Eight male subjects performed three tests with both devices on a hilly outdoor track. They were requested to adjust their speed in such a way that the following criteria were met: intensity 1, lactate concentration about 2 mmol x L(-1); intensity 2, lactate concentration about 4 mmol x L(-1); AND intensity 3, maximal speed. RESULTS: Though the subjects were not experienced in-line skaters, all managed to adjust the required intensities. This was achieved through increased velocities during in-line skating. Independent of the exercise intensity the differences in speed ranged between 1.0 and 1.4 m x s(-1). The relationships between lactic acid concentration, oxygen uptake, respiratory exchange ratio, and heart rate were not influenced by the test device. The respiratory exchange ratio amounted to 0.88, 0.95, and 1.02 for intensities 1 to 3, respectively. CONCLUSIONS: These results show that in-line skating can be regarded as an alternative to roller skiing for off-seasonal training in Nordic disciplines. A potential advantage of in-line skating is that aerobic training intensities can be obtained at competitive velocities.

Adult↗

The visby lenses.

PURPOSE: In this study, 10 lens-shaped rock crystals, manufactured not later than the early Middle Ages, have been examined with respect to their image-forming qualities. METHODS: The spherical aberration of the lenses served as a scale for comparison. Measurements have been taken with a specially designed light section method. Some of the examined lenses have a silver mounting and have been used as pendants, whereas others are unmounted and show no signs of use as jewelry. RESULTS: The two largest unmounted lenses have very interesting surface curvatures, rendering a very small spherical aberration of the lens. The combination of top and bottom surfaces of the lens causes an imaging quality comparable to the modern aspheric lenses used, e.g., in today's projectors. CONCLUSION: According to the results of this study, the knowledge and comprehension of optical design was much further developed in the Middle Ages than we assume today.

History, Medieval↗

[Heparin-induced thrombocytopenia type II. Intra- and postoperative lepirudin treatment in acute ischemia of the extremities].

HISTORY AND ADMISSION FINDINGS: A 60-year-old woman was admitted because of acute ischemia of the right leg. The patient had been immobilized during diagnostic procedures for a thoracic paraspinal space-occupying lesion and over 5 days had received unfractionated sodium heparin by subcutaneous injection. The pedal pulses were no longer palpable. INVESTIGATIONS, DIAGNOSIS AND TREATMENT: The thrombocyte count had fallen from 207,000/microliter to 45,000/microliter. Angiography revealed occlusion of the common femoral artery. Heparin-induced platelet aggregation (HIPA) test demonstrated type II heparin-induced thrombocytopenia. Thrombectomy was performed and intraoperatively an i.v. bolus of the recombinant hirudin, lepirudin (Refludan), was given (0.2 mg/kg body weight), continual lepirudin infusion being continued postoperatively. Normal blood flow was re-established in the limb and the pedal pulse was palpable. There were no complications. CONCLUSION: Recombinant hirudin is the only alternative licensed in Germany to heparin and seem to be suitable also for the intraoperative bolus administration in heparin-induced thromboembolic vascular occlusions.

Angiography, Digital Subtraction↗

31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected death in adolescents and young adults. Alterations in myocardial metabolism are considered to be causes for contractile dysfunction. We examined the question of whether metabolic abnormalities antedate the manifestation of symptoms in patients with HCM. METHODS AND RESULTS: Proton-decoupled 31P NMR spectroscopy of the anterior left ventricular wall of the heart of 14 young, asymptomatic patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the phosphate metabolites were compared with those of normal control subjects. The patients exhibited a significantly reduced (P<0.02) ratio of phosphocreatine (PCr) to ATP of 1.98+/-0.37 (mean+/-SD), compared with 2.46+/-0.53 obtained in 11 normal control subjects. In addition, the group of patients with severe hypertrophy of the interventricular septum (n=8) showed a significantly increased (P<0.05) Pi-to-PCr ratio, with a Pi x 100/PCr of 20.0+/-8.3 versus 9.7+/-7.2 in control subjects. Both abnormalities are similar to those found in ischemic myocardium. This view is also supported by a significantly increased (P<0.01) phosphomonoester (PME)-to-PCr ratio, with a PME x 100/PCr of 20.7+/-11.2 compared with 8.4+/-6.7 in control subjects, indicating altered glucose metabolism. CONCLUSIONS: 31P NMR spectroscopy detects alterations of myocardial metabolism in asymptomatic patients with HCM. These alterations may contribute to the understanding of the pathophysiology and natural history of the disease.

Adolescent↗

A protein with protective properties against the cellular defense reactions in insects.

The molecular mechanism of how insects recognize intruding microorganisms and parasites and distinguish them from own body structures is not well known. We explored evolutionary adaptations in an insect parasitoid host interaction to identify components that interfere with the recognition of foreign objects and cellular encapsulation. Because some parasitoids provide protection for the developing wasp in the absence of an overt suppression of the insect host defense, we analyzed the surface of eggs and symbiotic viruses for protective properties. Here we report on the molecular cloning of a 32-kDa protein (Crp32) that is one of the major protective components. It is produced in the calyx cells of the female wasp ovaries and attached to the surface of the egg and other particles including polydnaviruses. The recombinant protein confers protection to coated objects in a cellular encapsulation assay suggesting that a layer of Crp32 may prevent cellular encapsulation reactions by a local inactivation of the host defense system.

Amino Acid Sequence↗

Detection of phosphomonoester signals in proton-decoupled 31P NMR spectra of the myocardium of patients with myocardial hypertrophy.

Proton-decoupled 31P NMR spectroscopy at 1.5 T of the anterior left ventricular myocardium was used to monitor myocardial phosphate metabolism in asymptomatic patients with hypertrophic cardiomyopathy (HCM, n = 14) and aortic stenosis (AS, n = 12). In addition to the well-known phosphorus signals a phosphomonoester (PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This signal was not observed in the spectra of normal controls (n = 11). We suggest that in spectra of patients with myocardial hypertrophy the presence of a PME signal reflects alterations in myocardial glucose metabolism.

2,3-Diphosphoglycerate↗

[Reconstruction of incisional hernias with defined tensiometrically controlled tension--a possibility for anatomically correct reconstruction of the abdominal wall].

The repair of incisional hernias of the abdominal wall is characterized by high rates of recurrence if arbitrary tension is applied. A rationale for selecting the appropriate reconstruction technique as defined by intraoperative tension measurements has proven effective and successful. Here, the inlay/onlay technique tolerates up to 3.5 kilopounds (kp). Our results show that using this technique, complete reconstruction is possible in 65% of cases with a recurrence rate of 2.3%.

Cicatrix↗

[Malignant melanoma of the skin: is there a curative surgical approach in locoregional metastasis?].

Between 1969 and 1993 at the Surgical University Hospital of Erlangen, 273 patients with synchronous or metachronous locoregional metastases were operated on with curative intent; patients with distant metastases at the time of primary operation or first recurrency were excluded. In 216 patients (79.1%) a curative operation was performed and we achieved a statistically significant improvement of the 5-year-survival rate compared with those patients treated only palliatively (39.3% vs. 21.1%, p < 0.01). If regional lymph node metastases occur, the prognosis becomes significantly worse (5-year survival rate 45.2% vs. 25.2%, p < 0.01); hyperthermic isolated limb perfusion shows a high importance in the treatment of locoregional metastases and the 5-year survival rate of patients treated with hyperthermic limb perfusion is significantly higher (39.0 vs. 64.2%, p < 0.05).

Adolescent↗

Proton-decoupled myocardial 31P NMR spectroscopy reveals decreased PCr/Pi in patients with severe hypertrophic cardiomyopathy.

Disturbed myocardial energy metabolism may occur in patients with primary hypertrophic cardiomyopathy (HCM). A noninvasive way to gain insight into cardiac energy metabolism is provided by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectroscopy with proton decoupling was performed in 13 patients aged 13-36 years with HCM on a 1.5 T Magnetom with a double resonant surface coil. A 2D chemical shift imaging (CSI) sequence in combination with slice selective excitation was used to acquire spectra of the anteroseptal region of the left ventricle (volume element: 38 mL). The chemical shifts of the phosphorus metabolites, intracellular pHi, and coupling constants J(alphabeta) and J(gammabeta) were calculated. Peak areas of 2,3-diphosphoglycerate (DPG), Pi, and adenosine triphosphate (ATP) were determined and corrected for blood contamination, saturation, and differences in nuclear Overhauser enhancements (NOE). The maximum thickness of the interventricular septum (IVSmax) was determined from tomographic long-axis images and expressed as number of standard deviations above the mean of the normal population (Z score). The patients were then divided into 2 groups: 6 patients with moderate HCM (HCMm, Z score < or = 5) and 7 patients with severe HCM (HCMs, Z score > 5). No differences between both groups and a control group of healthy volunteers (n = 16) were found with respect to phosphocreatine (PCr)/gamma-ATP ratio, pHi, or the coupling constants. Only the PCr/Pi ratio differed significantly from the control group (HCM(all), alpha < 0.05, HCMs, alpha < 0.02, 2-sided U test). The decrease of the PCr/Pi ratio in patients with HCM is probably caused by ischemically decreased oxygen supply in the severely hypertrophied myocardium.

Adenosine Triphosphate↗

Helix pomatia lectin and annexin V, two molecular probes for insect microparticles: possible involvement in hemolymph coagulation.

Insect hemolymph coagulation involves a complex reaction with contributions from hemocytes and soluble factors. Here we present evidence for the presence of microparticles in the coagulation reaction. These particles are formed by hemocytes in a calcium-dependent process. Both the particles and the remaining cells are labelled by annexin V indicating the presence of phosphatidylserine on the outer membrane. Microparticles are enriched in hemomucin, a surface protein of Drosophila hemocytes that is specifically recognised by a snail (Helix pomatia) lectin. Hemomucin is shown to bind to lipophorin, a multifunctional hemolymph molecule previously implied in coagulation. Our findings suggest similarities at a biochemical and cellular level between vertebrate blood and insect hemolymph coagulation.

Journal Article↗

A polydnavirus-encoded protein of an endoparasitoid wasp is an immune suppressor.

The molecular mechanism by which polydnaviruses of endoparasitoid wasps disrupt cell-mediated encapsulation reactions of host insects is largely unknown. Here we show that a polydnavirus-encoded protein, produced from baculovirus and plasmid expression vectors, prevents cell surface exposure of lectin-binding sites and microparticle formation during immune stimulation of haemocytes. The inactivation of immune-related cellular processes by this protein was analysed using a specific lectin and annexin V and shown to be virtually identical to polydnavirus-mediated effects on haemocytes. Cytochalasin D application has similar effects on haemocytes, suggesting that the immune suppression by the polydnavirus protein is caused by the destabilization of actin filaments. Since the exposure of cell surface glycoproteins and the formation of microparticles are part of an immune response to foreign objects or microorganisms and a prerequisite for cell-mediated encapsulation of microorganisms and parasites, the virus-encoded protein may become an important tool for the inactivation of cellular immune reactions in insects and an essential component in understanding immune suppression in parasitized host insects.

Animals↗

[Experiences with a new vacuum-accelerated microwave histoprocessor].

Methods of microwave and vacuum accelerated fixation, dehydration and paraffin embedding are described. They can be carried out in a new type of vacuum and temperature stabilizable microwave histoprocessor: MFX-800. The whole histoprocessing lasts 3.5-5.5 hours depending on the thickness of the tissue blocks. Preserved structural detail, intensive staining and good antigen preservation were achieved with various tissues. This new histoprocessing facility can be highly recommended for pathology laboratories interested in speeding up the processing procedure, as well as in immunohistochemistry.

Equipment Design↗

Helix pomatia lectin, an inducer of Drosophila immune response, binds to hemomucin, a novel surface mucin.

We describe the isolation and initial characterization of hemomucin, a novel Drosophila surface mucin that is likely to be involved in the induction of antibacterial effector molecules after binding a snail lectin (Helix pomatia A hemagglutinin). Two proteins of 100 and 220 kDa were purified from the membrane fraction of a Drosophila blood cell line using lectin columns. The two proteins are products of the same gene, as demonstrated by peptide sequencing. The corresponding cDNAs code for a product that contains an amino-terminal putative transmembrane domain, a domain related to the plant enzyme strictosidine synthase, and a mucin-like domain in the carboxyl-terminal part of the protein. The gene is expressed throughout development. In adult flies, high expression is found in hemocytes, in specialized regions of the gut, and in the ovary, where the protein is deposited onto the egg surface. In the gut, the mucin co-localizes with the peritrophic membrane. The cytogenetic location of the gene is on the third chromosome in the region 97F-98A.

Amino Acid Sequence↗