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Biomedical subjects

W Schmidt

Publications and source records attributed to W Schmidt.

At least 307 records · Page 17Linked to original sources

Distribution patterns of neoglycoprotein-binding sites (endogenous lectins) and lectin-reactive glycoconjugates during cartilage and bone formation in human finger.

The distribution of endogenous lectins, visualized by labelled neoglycoproteins, and of defined oligosaccharide structures, reactive with plant lectins, during fetal development of the fingers was analyzed in sections of human 3- to 8-month-old fetal specimens. Chondrogenesis as well as ossification were correlated with characteristic modulations in the expression of both glycoligand-binding molecules and characteristic carbohydrate structures. Occurrence of xylose-specific receptors was judged to be an early sign of cartilage development. Similarly, alpha-mannosyl residues that had been attached to labelled carrier proteins were strongly bound by the extracellular matrix already during early stages of finger maturation. Staining intensity for heparin gradually increased during chondrogenesis, whereas affinity for mannose showed a stage-related decline. Binding of mannose-6-phosphate was confined to hypertrophied cartilage of primary ossification centers. Accessible binding sites for terminal N-acetylneuraminic acid and N-acetylgalactosamine moieties were detected only in osteoid. In addition to monitoring the sugar-binding capacity, presence and developmental regulation of distinct carbohydrate structures were also assessed. PSA and SBA enabled the demonstration of an abrupt loss of staining affinity in the zone of maturing hypertrophic cartilage. Succinylated WGA proved to be an apparently useful marker of evolving bone tissue. GSL-II binding was restricted to chondroclasts and osteoclasts. The findings of this investigation are consistent with the supposed role of glycoconjugate-lectin interactions in cartilage and bone development.

Binding Sites↗

[Comparison of different methods for determination of proliferative activity of breast carcinomas].

OBJECTIVES: Different methods for evaluation of nuclear atypia and proliferative activity were compared in fifty cases of breast cancer. METHODS: Beneath histopathologic grading, ploidy of the stem cell line and S-phasefraction were measured by flow cytometry. Ki67-index was determined immunohistochemically and by image cytometry on smears grade of malignancy and 2cDI were measured. RESULTS: Only Ki67-index was correlated with histopathological grading. The various proliferative indices (Ki67-index, S-phase-fraction, 2cDI) were not correlated. Between image- and flow-cytometric DNA-analysis significant differences were found. CONCLUSIONS: With the immunohistochemical determination of Ki67-index in conjunction with image-cytometry a morphologic control of the material investigated is possible. So in comparison with flow-cytometry a more differentiated analysis can be performed.

Biomarkers, Tumor↗

[Image fusion of MRI and immunoscintigraphy with MAb-170 in ovarian tumors].

In recent years multimodality imaging achieved growing importance. It is mostly performed by means of quite expensive software and hardware solutions. In the present pilot study a simple and low-cost procedure was developed to achieve image fusion in the pelvis. The image data of immunoscintigraphy (SPECT) and MRI were transferred to a personal computer and combined by standard software for image manipulation. The results in eleven patients with space-occupying lesions in the pelvis showed that adequate anatometabolic slices could be achieved. The results show a tendency to increased specificity and precision of multimodality imaging in comparison with SPECT and MRI alone. In conclusion, the low-cost solution, as developed by us, is feasible in clinical practice. Its results are reliable in clinical decision making.

Adult↗

Demonstration of estrogen and progesterone receptors in breast cancers with monoclonal antibodies. Different results with enzyme-immunoassay and immunohistochemical methods.

Estrogen (ER) and progesterone receptors (PR) were measured in 120 breast cancer biopsies using the same tissue block and the same monoclonal antibody either immunohistochemically on frozen sections or quantitative by means of an enzyme-immunoassay (EIA) on the cytosol-fraction of a tumor homogenate. The immunohistochemical staining was performed by a standard PAP-method and the samples were classified according to the "immuno-reactive score" (IRS). IRS values > = 2 were regarded as receptor-positive; a cut-off-value of 15 fmol/mg protein was chosen for the EIA-test. In 90.8% of cases the findings of immunohistochemical and biochemical methods were concordant when only receptor-positivity or -negativity was regarded. Thus the results were discordant in 9.2%. Immunohistochemically positive and biochemically negative findings were observed more often (8.2% for the ER and 5.8% for the PR) than vice versa (0.8% for the ER and 3.3% for the PR). In all cases of discordant findings the relevant histological and immunohistochemical preparations were reevaluated. In total, there were 5 cases with a positive biochemical result which were classified as receptor-negative by immunohistochemistry. Of these, 3 had borderline findings by EIA together with a massive inflammatory infiltration. The other 2 cases must be interpreted as technical problems with the immunohistochemical staining. In 17 cases with a biochemically negative result receptor-positive cancer cells could be demonstrated by immunohistochemistry. In 13 of these 17 cases only a small fraction of tumor cells showed a positive reaction. Furthermore all these cases were rather acellular and partially necrotic. So the negative results of the enzyme immunoassay can be explained by a low concentration of receptor positive cells in the biopsy specimen or the measurements of necrotic tissue areas. It can be concluded that immunohistochemical receptor analysis is superior to methods using tumor-homogenates. The prognostic and predictive superiority of the immunohistochemical method is in accordance with published data. However, for immunohistochemical staining high internal and external quality standards must be applied as for similar laboratory procedures.

Antibodies, Monoclonal↗

[Prevention of thrombosis with low molecular weight heparin in gynecology].

An observational study on the use of low molecular weight heparin (LMWH) Fraxiparin 0.3 was performed at the Department of Obstetrics and Gynaecology of the University Hospital of the Saarland, Homburg/Saar. The aim of the study was to investigate effectiveness and safety of this LMWH in obstetric and gynaecological surgery for patients with mostly intermediate risk for thromboembolism. We observed 484 women, aged between 14 and 84 years, the majority of whom underwent surgery for benign or malignant gynaecological tumours including breast tumours. 40 patients had obstetrical problems. The patients were given a single daily dose of Fraxiparin 0.3 subcutaneously, beginning on the preoperative day until they were discharged from hospital. In addition, the patients wore antiembolic stockings during the whole period of observation. No thromboembolic events were observed clinically. Normal intraoperative blood loss was observed in 86%, normal postoperative seroma drainage in 74% of cases. During the study period wound haematomas were seen in 7 patients. There was in no case a direct causal link to Fraxiparin treatment. These results are in conformity with previous clinical studies and drug monitorings and emphasize the effectiveness and safety of thromboembolism prophylaxis with low molecular weight heparin also in obstetrics and gynaecology.

Adolescent↗

[Comparison of dinoprostone gel and gemeprost suppositories for induction of abortion in the second and third trimester].

The results of the cervical priming with a Dinoprost-containing gel and a Gemeprost-containing vaginal suppository were compared in 68 patients, who required termination of pregnancy beyond 14 weeks because of a severe maternal disease or a fetal abnormality. The priming consisted of either an intracervical application of Dinoprost (500 micrograms) in a tylose-gel in 6-8 hour intervals or a retrocervical application of Gemeprost (1 mg) as a vaginal suppository in 12 hour intervals. Although no significant parameter variances were found in the selected patient groups, abortion was induced in 75% of cases within 24 hours, in 89% within 36 hours using Gemeprost. Mean induction time for Gemeprost was 19.5 hours. Using Dinoprost only 19% of patients had an abortion within 24 hours (44% within 36 hours, respectively), mean induction time was significantly longer (38.8 hours, p < 0.005). These differences remained unchanged, when patients who had a prior caesarean section were not evaluated. Using Gemeprost the additional systemic administration of Sulprost was necessary in 21% of cases, using Dinoprost, in 50% of cases. Severe complications did not occur and minor side effects such as nausea or vomiting were observed in single cases. These results demonstrate that Gemeprost can be used in cervical priming even after 14 weeks of pregnancy and that the longer application interval of 12 hours results in a reduction of side effects without a decrease in efficacy.

Abortifacient Agents, Nonsteroidal↗

[Uterine reactions to prostaglandins in induced labor--results of a multicenter study].

During a prospective multicentric study concerning labor induction with prostaglandins 1472 prostaglandin-inductions were documented. With a Bishop Score < 5 a gel containing 0.5 mg of PgE2 was applied intracervically, with a Bishop Score > = 5 a tablet containing 3 mg of PgE2 was applied retrocervically inside vagina. In case of lacking success the application was repeated after 6 to 8 hours and after 24 hours according to the actual Bishop-Score. Coordinated labor after application of PG-gel or PG-tablet was observed in 85.2% (83.3% respectively), polycystolia or tetani in 13.9% of cases (9.1% respectively). Differences were not statistically significant. Uterine reactions started in the mean 5-6 hours after the last PG-application, but intervals showed a significant spreading among single cases. In 16.0% of the patients successfully treated with Pg-gel and in 8.3% of the patients successfully treated with a PG-tablet due to a uterine hyperstimulation a tocolytic treatment became necessary. With a ripe cervical score (Bishop-Score > 7 points) a significant shortening of the induction-interval was observed.

Administration, Intravaginal↗

[Role of serum adenosine deaminase as an immune parameter of tuberculosis].

We measured serum levels of adenosine-deaminase (ADA) in 44 tuberculosis patients, 70 patients with lung cancer pre treatment, and 130 normal blood donors. Increased ADA levels were found in 64.4% of the tuberculosis patients, in 95.2% in the case of bacillary tuberculosis, but only in 2.8% in the tumor patients. ADA serum levels were statistically significantly increased in tuberculosis patients when compared to lung cancer patients and controls and did not differ between controls and the tumor group. We conclude that serum ADA is a selective marker of immune stimulation in tuberculosis but not in lung cancer. Serum levels positively correlated to the disease extent in tuberculosis of immunocompetent patients. This marker deserves further investigation with respect to its clinical significance.

Adenosine Deaminase↗

Hemoglobins from Plasmodium-infected rat erythrocytes: functional and molecular characteristics.

Aiming to evaluate the mechanisms responsible for altered O2-transporting properties in blood of Plasmodium-infected animals, stripped (cofactor-free) hemoglobin (Hb) solutions were prepared from infected erythrocytes (IE) and noninfected erythrocytes (NIE) of rats inoculated with Plasmodium berghei bergei for functional and structural characterization. At normal intraerythrocytic pH (+/- 7.2), Hb from IE showed a higher affinity, a larger Bohr effect, and lower sensitivities to 2,3-diphosphoglycerate (DPG) and to temperature than did NIE Hb. Moreover, as judged from electrophoresis, isoelectric focusing, and gel filtration experiments, Hb from IE show changes in charge and molecular assembly. The results indicate that the higher O2 affinity and greater Bohr factors observed in IE compared with those for NIE are attributable to chemical modification of the Hb that increases its intrinsic O2 affinity and decreases its sensitivity to DPG as well as to changes in the intracellular physicochemical milieu, including reduced DPG levels.

Animals↗

Oxygen transport properties in malaria-infected rodents--a comparison between infected and noninfected erythrocytes.

This study was performed to investigate oxygen transport properties in whole blood (WB) of malaria-infected rats as well as in infected erythrocytes (IE) and noninfected erythrocytes (NIE) separated by density centrifugation. One week after inoculation with Plasmodium berghei, mean parasitemia was 26.5% and high correlations were found between parasitemia and hemoglobin concentration ([Hb]; r = -.902), mean cellular Hb concentration (MCHC; r = -.712), MetHb (r = .923), and base excess (r = -.922). Compared with control animals (C), the oxygen affinity was lower in WB under standard (pH 7.40) and simulated "in vivo" (pH 7.00) conditions (difference in P50, 5.7 and 5.1 mm Hg, respectively; 2P < .01, 2P < .05). In IE Hb and 2,3-biphosphoglycerate (2,3-BPG) concentrations were decreased (MCHC: IE 14.6 +/- 1.0, NIE 33.1 +/- 1.7 g/100 mL; [2,3-BPG]: IE 2.0 +/- 0.6, NIE 7.6 +/- 1.8 mmol/L), whereas [MetHb] and [ATP] were increased ([MetHb]: IE 19.0 +/- 3.7, NIE 0.7% +/- 0.8%; [ATP]: IE 33.5 +/- 2.4, NIE 6.2 +/- 1.0 mumol/g Hb). At pH 7.40, half-saturation oxygen tension (P50) was reduced in IE (29.6 +/- 2.6, NIE 39.2 +/- 5.4 mm Hg, 2P < .001), which correlates with lower [2,3-BPG], increased MetHb content, and higher intrinsic Hb-O2 affinity. However, at pH 7.00, the oxygen affinity was lower in IE when compared with NIE, which was most likely due to high [ATP] in IE. The resulting Bohr coefficients (BC) calculated for CO2 and lactic acid were extremely high in IE and low in NIE (at 50% O2-saturation BCCO2: IE -1.04 +/- 0.06, NIE -0.26 +/- 0.10, 2P < .001; BCLac: IE -0.82 +/- 0.16, NIE -0.47 +/- 0.07, 2P < .001), which was caused by different [2,3-BPG] and [ATP] as well as probably by structural changes of the Hb molecule. The O2 capacity was 14.1 mL per 100 mL erythrocytes in IE compared with 44.4 mL/100 mL in NIE. On the basis of the calculated arterio-venous O2 difference under "in vivo" conditions, the infected red blood cell fraction transports 30% of the O2 amount delivered to the tissues by the noninfected cells (IE 8.0, NIE 26.9 mL/100 mL red blood cells). We conclude that the O2 transport in malaria infected blood is not only affected by the degree of anemia but also by the percentage of infected erythrocytes.

Adenosine Triphosphate↗

In vivo production of human factor VII in mice after intrasplenic implantation of primary fibroblasts transfected by receptor-mediated, adenovirus-augmented gene delivery.

Hemophilia A is caused by defects in the factor VIII gene. This results in life-threatening hemorrhages and severe arthropathies. Today, hemophiliacs are treated with human blood-derived factor VIII. In the future, it may be possible to use gene therapy to avoid long-term complications of conventional therapy and to improve the quality of life. However, initial gene therapy models using retroviral vectors and nonviral gene transfer techniques to introduce factor VIII gene constructs have been hampered by low expression levels of factor VIII. We show here that high expression levels of the B-domain-deleted human factor VIII in primary mouse fibroblasts and myoblasts are obtained by using receptor-mediated, adenovirus-augmented gene delivery (transferrinfection). We demonstrate that, presumably owing to the high molecular weight of factor VIII or its metabolic instability, secretion into the blood and attainment of therapeutic in vivo levels of factor VIII is achieved only if transfected autologous primary fibroblasts or myoblasts are delivered to the liver or spleen, but not if myoblasts are implanted into muscle, a strategy known to be successful for factor IX delivery.

Adenoviridae↗