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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 559 records · Page 31Linked to original sources

Human hepatocellular cancers show decreased prostaglandin E1 binding capacity.

Specific binding of 3H-PGE1 to plasma membranes prepared from normal human hepatic tissue in the presence of Mg2+ reached saturation at concentrations greater than 50 nM, and could be displaced in the rank-order PGE1 greater than PGE2 greater than PGI2 greater than PGD2 greater than PGF2 alpha at 4 degrees C. Plasma membranes prepared from normal human hepatic tissue showed a high-affinity 3H-PGE1-binding capacity of 51.3 +/- 19.2 fmol mg-1 plasma membrane protein with an equilibrium dissociation constant of 3.8 +/- 1.9 nM, and a low-affinity 3H-PGE1-binding capacity of 104.2 +/- 17.3 fmol mg-1 protein with an equilibrium dissociation constant of 13.9 +/- 2.7 nM. Plasma membranes prepared from hepatocellular cancer tissue revealed a single class of binding sites with an apparent binding capacity of 38.4 +/- 17.3 fmol mg-1 plasma membrane protein (P less than 0.05) and an equilibrium dissociation constant of 12.1 +/- 2.8 nM. Competition studies on plasma membranes prepared from hepatocellular cancer tissue indicated no significant difference in the affinity of various prostaglandins to the receptor proteins as compared to normal hepatic tissue. It is assumed that the decreased 3H-PGE1-binding capacity found in human hepatocellular cancer tissue may reflect an alteration of the receptor protein content of the hepatocytes during carcinogenesis.

Adult↗

Optimisation of density and contrast yielded by multiformat photographic imagers used for scintigraphy.

The maximum optical density (MOD) and contrast (characterised by an effective gamma, gamma eff) yielded by multiformat photographic imagers used for scintigraphy, was determined by densitometry of a computer image, which consisted of a pattern of uniform squares containing known counts. A series of clinical scintigrams were photographed using various MOD and gamma eff values, and were graded by three experienced clinicians. It was found that a MOD of 1.6 and a gamma eff of 2.9 yielded optimal images for general use if bone scintigrams are also to be photographed. Lesion detectability in phantom images using extreme MOD and gamma eff values that were still clinically acceptable was determined. At very low false-positive rates (less than or equal to 1%) the higher gamma eff yielded a significantly greater lesion detectability (p = 0.02) at an information density of 2200 counts cm-2 in accordance with White-head's theory. It is concluded that quantification and optimisation of density and contrast factors are important and that the technique described enables quality control of multiformat imagers with respect to these factors.

ROC Curve↗

Molecularly cloned simian immunodeficiency virus SIVagm3 is highly divergent from other SIVagm isolates and is biologically active in vitro and in vivo.

Simian immunodeficiency viruses have been isolated from African green monkeys originating from Ethiopia. A molecular clone, termed SIVagm3, was found to be highly divergent from SIVagmTYO-1 in terms of its restriction map and partial nucleotide sequence. A premature stop codon present in the transmembrane protein of SIVagm TYO-1 was absent in SIVagm3. SIVagm3 was biologically active in vitro and in vivo and displayed characteristics reminiscent of the wild-type virus. Biological activity was demonstrated by seroconversion of juvenile African green monkeys and Macaca nemestrina after inoculation. In contrast to antibody reactivity mainly directed against env proteins in naturally infected African green monkeys. African green monkeys and M. nemestrina infected with the cloned virus showed antibody reactivity directed against all major proteins as demonstrated by immunoblot analysis. The availability of a biologically fully competent molecular clone of SIVagm allows us now to address various pertinent questions in an animal model system which should help to understand features of human immunodeficiency virus infection in human beings.

Amino Acid Sequence↗

Interleukin-1 production in acute viral hepatitis.

The in vitro production of interleukin-1 in 15 children with acute hepatitis A and five children with acute hepatitis B was determined by measuring lymphocyte activating factor secreted by peripheral blood monocytes in a thymocyte proliferation assay. Aluminium hydroxide induced production of lymphocyte activating factor was significantly lower in patients with acute hepatitis A as well as patients with hepatitis B as compared with healthy control subjects. In both forms of acute viral hepatitis production of lymphocyte activating factor was severely depressed during the first week, increased gradually during the further course of the illness, but did not reach normal concentrations within the first three weeks after onset of the acute symptoms of the disease. No correlation could be found between in vitro production of lymphocyte activating factor and the severity of liver disease as estimated by the rise of serum concentrations of transaminases, bilirubin, or several parameters of acute phase reaction (alpha 1 antitrypsin, C reactive protein, erythrocyte sedimentation rate). The reduced production of interleukin-1, as assessed by determination of lymphocyte activating factor, could explain the only moderate acute phase reaction seen during acute viral hepatitis.

Acute Disease↗

Diffuse cerebrospinal gliomatosis presenting as motor neuron disease for two years.

A patient with symptoms and signs of motor neuron disease for 2 years finally developed sensory disturbances and increased intracranial pressure. MRI and CT showed enlargement of the right side of the cerebellum, the brainstem and parts of the cerebral hemisphere with focal hyperperfusion demonstrated by SPECT. Necropsy revealed a diffuse cerebrospinal gliomatosis with loss of spinal motor neurons in tumour infiltration of the anterior horns. This type of spinal cord involvement is considered responsible for the unusual clinical presentation of the neoplasm.

Adult↗

Immunohistology of genital warts in different stages of regression after therapy with interferon gamma.

Twenty patients with papillomavirus-induced genital warts received pulsatory treatment with interferon gamma by subcutaneous injections in the abdominal skin. The condylomata regressed completely in 11 of the 20 patients analyzed. Sequential biopsies taken from genital warts and nonlesional skin were investigated by immunohistological techniques with the use of monoclonal antibodies against differentiation and HLA antigens to evaluate immunological effector mechanisms of condylomata regression. In all responders regression was shown to be associated with increasing dermal and epidermal infiltrates of activated CD4 and CD8 T lymphocytes, as well as with aberrant expression of HLA-DR and/or DY antigens on keratinocytes. Thus alteration of HLA class II antigen expression on keratinocytes in the presence of T lymphocytes is an important criterium for regression of genital warts.

Condylomata Acuminata↗

Quantification of regional cerebral blood flow with IMP-SPECT. Reproducibility and clinical relevance of flow values.

Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine (IMP-SPECT) was performed in 14 normal volunteers (seven men and seven women aged 25.1 +/- 5.3 years) and 29 patients with cerebrovascular disease (18 men and 11 women aged 54.1 +/- 13.7 years). The fluid microsphere model was used to estimate cerebral blood flow (CBF). Normal subjects were scanned twice, 1 week apart, to determine the reproducibility of the CBF estimates. Hemispheric blood flow (hCBF) was calculated as the mean of regional cerebral blood flow (rCBF) values in 16 gray matter regions per hemisphere. In normal subjects mean hCBF was 68 ml/100 g/min. The highest rCBF was found in the occipital cortex, followed by the frontal, temporal, and parietal cortexes. CBF values were reproducible (p less than 0.001 except the right thalamic region, where p less than 0.01). Intraindividual variation ranged between 0.3% and 15%. Women exhibited significantly higher (16%, p less than 0.02) CBF than men. Patients were subdivided into groups with reversible (n = 19) and persistent (n = 10) symptoms. Significant hCBF differences between the affected and the contralateral hemispheres were recorded only in the group with reversible symptoms (p less than 0.005), whereas the group with persistent symptoms showed a significant bilateral decrease of hCBF compared with normal subjects and patients with reversible symptoms. Focal CBF was significantly lower in patients with completed stroke than in patients with transient symptoms (p less than 0.001). Our results indicate that IMP-SPECT can be used for the routine estimation of CBF in normal and pathologic states.

Aged↗

Pressure-controlled reperfusion improves postischemic recovery of LV-hypertrophied rat hearts.

The influence of pressure-controlled postischemic reperfusion (Rp) on functional and metabolic parameters in hearts of sham-operated rats and hypertrophied hearts of rats with aortic constriction were studied. Hypertrophied hearts are considered to be more susceptible to ischemia. The hearts were perfused in the Langendorff-technique for thirty minutes at 35 degrees C with Krebs-Henseleit bicarbonate buffer at a perfusion pressure (PP) of 75 mmHg and for five minutes at 15 degrees C with St. Thomas' Hospital cardioplegic solution at a PP of 60 mmHg. After a period of global ischemia of forty minutes' duration at 15 degrees C, reperfusion was started either abruptly (aRp: PP 75 mmHg immediately) or gently (gRp: PP 75 mmHg within thirty minutes); it lasted for forty-five minutes. Intraventricular peak systolic pressure (ISP) was monitored and energy-rich compounds (ATP, ADP, AMP, CrP, free Cr) were analyzed. In normal hearts, metabolic recovery was not affected by the mode of reperfusion, but functional recovery (ISP) averaged 88% of the preischemic control value after gRp as compared with 73% after aRp. In hypertrophied hearts, gentle reperfusion ameliorated both metabolic and functional recovery. At forty-five minute recovery, CrP averaged 5.1 mumol/g ww after aRp and 6.6 mumol/g ww after gRp (p less than 0.01), and ISP amounted to 73% of the preischemic control after aRp and to 85% after gRp.

Adenine Nucleotides↗

Developmental changes in the glycosylation and binding properties of human fibronectins. Characterization of the glycan structures and ligand binding of human fibronectins from adult plasma, cord blood and amniotic fluid.

Fibronectins from human adult plasma, fetal plasma and from amniotic fluid obtained during early and late gestation were compared with respect to (i) their reactivity with lectins, (ii) their binding to the physiological ligands gelatin and heparin, and (iii) the role of the carbohydrate residues in the binding to these two ligands. The two fibronectin isoforms displayed distinct developmental differences in both glycosylation and binding properties: (i) Proportions of tri/tetraantennary complex glycans compared to the fraction of biantennary structures, as inferred from the reactivity with concanavalin A, were highest in amniotic fluid fibronectin from late pregnancy, lower in amniotic fluid fibronectin from early gestation, and even lower in fetal and adult plasma fibronectins. Likewise, fucose (alpha 1-6) linked to the innermost N-acetylglucosamine of the chitobiosyl core, defined by reactivity with Lens culinaris agglutinin (LCA), was present primarily in amniotic fluid fibronectin, and decreased in content during gestation from the 2nd. to the 3rd. trimenon. Both fetal and adult plasma fibronectins were only weakly reactive with LCA, indicating a low content of (alpha 1-6) linked fucose residues. After prior treatment with sialidase, both plasma and amniotic fluid fibronectins strongly reacted with erythrocyte phytohaemagglutinin (E-PHA), indicating that both fibronectin isoforms contain bisecting (beta 1-4) N-acetylglucosamine residues. Amniotic fluid fibronectins showed much greater reactivity than adult and fetal plasma fibronectins with wheat germ agglutinin; binding of this lectin to amnion fluid fibronectins was not decreased by desialylation indicating the presence of poly(N-acetyllactosamine) units. Whereas amniotic fluid fibronectins were strongly reactive with peanut agglutinin, neither adult nor fetal plasma fibronectins did bind to this lectin unless after prior desialylation. Hence, both fibronectin isoforms contain O-glycan residues that are fully sialylated in fetal and adult plasma fibronectins, but only partly sialylated in amniotic fluid fibronectins. According to these differences, glycosylation of plasma and amniotic fluid fibronectins is under developmental regulation. (ii) Amniotic fluid fibronectins had a significantly lower binding activity for both heparin and gelatin than plasma fibronectins. Moreover, amnion fibronectin from late gestation displayed a significantly lower binding to these two ligands than amnion fibronectin from early gestation. Fetal plasma fibronectins had a lower binding activity for gelatin than adult plasma fibronectin. (iii) Treatment of fibronectins with sialidase, fucosidase and removal of N-glycans with endoglycosidases H and F did not affect binding to gelatin and heparin, indicating that the interaction of plasma and amnion fibronectin with these two ligands is not influenced by their oligosaccharide moieties.

Adult↗

[Real-time analysis of orofacial movements using electromagnetic articulography].

A real-time version of electromagnetic articulography is presented, which permits the recording of five positions of the articulators in the oro-facial system. Movements can be shown online on PC screen. Owing to its biological safety and ease of handling, the system is especially suitable for clinical applications.

Electromagnetic Phenomena↗

Gastric ulcer is accompanied by a decrease of epidermal growth factor in gastric juice and saliva.

Numerous studies have indicated a role of epidermal growth factor in the maintenance of the gastrointestinal mucosa. In the present study epidermal growth factor concentrations in saliva and gastric juice of patients with gastric or duodenal ulcer or gastritis are compared with those of healthy controls. For this purpose a novel ELISA system has been developed and shown to be sensitive and specific. It is demonstrated that gastric juice and saliva of patients with gastric ulcer contain less epidermal growth factor than the samples of healthy controls (p less than 0.01). Epidermal growth factor concentrations and outputs (product of epidermal growth factor concentration and the volume secreted in 15 min) in the gastric juice of patients with duodenal ulcer do not differ from those of healthy controls.

Duodenal Ulcer↗

Effects of cyclosporin A upon humoral and cellular immune parameters in insulin-dependent diabetes mellitus type I: a long-term follow-up study.

Patients who had been included in a randomized double-blind placebo-controlled trial on the efficacy of cyclosporin A (CyA) in producing remissions in insulin-dependent diabetes mellitus (IDDM) type I were investigated for humoral and cellular immunologic parameters. Whereas metabolic derangement before the initiation of insulin treatment led to small but significant decreases in the percentage of CD4-positive lymphocytes as well as of the activity of natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC), the administration of CyA did not influence any of the immunologic parameters tested, which included proliferative lymphocyte responses to mitogens and alloantigens and serum concentrations of immunoglobulins G, A and M. Thus NK cell activity, ADCC as well as the percentage of CD4-positive lymphocytes returned to normal levels in parallel with the normalization of glycosylated haemoglobin (HbAlc), but were not further influenced in their course by the administration of CyA, as compared with patients receiving placebo. Interferon-induced augmentation of NK cell activity did not differ between patients with IDDM on placebo and those under CyA therapy. All other investigated parameters also remained unchanged during the time of CyA therapy. We conclude that metabolic derangement leads to a reversible disturbance of certain cellular immune functions, but their normalization achieved by insulin treatment and their further course remains uninfluenced by the administration of CyA.

Adolescent↗

Allogeneic grafts for bone tumor. 21 cases of osteoarticular and segmental grafts.

We treated 21 aggressive and malignant bone tumors by wide resection and replacement with deep-frozen osteoarticular and segmental (intercalary and block) allografts. Radiologic and histologic studies showed a gradual accretion of new bone on the graft trabeculae, sometimes with total creeping substitution. Substantial resorption of grafted condylar bone occurred in 3 of 14 cases. One of them ended with arthrodesis; in the other 2 the result after augmentation autografts was fair. Radiographically, a gradual joint surface destruction was observed in all the osteoarticular grafts after 5 years, not correlating with joint function, however. Biopsies showed some cartilage regeneration. Each patient underwent, on an average, two operations. Function after osteoarticular grafts at 3-16 years was excellent in 1 case, good in 4, fair in 6, and poor in 1 case; 2 cases were too recent for evaluation. Function 3-12 years after segmental grafts was excellent in 3 cases and poor in 3 cases (1 amputation due to nonunion, 1 amputation due to recurrence, and 1 prosthetic replacement due to recurrence); 1 case was too recent for evaluation. We conclude that an allograft is an acceptable alternative in the reconstruction of large tumor defects. However, it still presents unsolved immunologic and preservation problems, which make the prognosis guarded.

Adolescent↗

In vivo tracing of indium-111 oxine-labeled human peripheral blood mononuclear cells in patients with lymphatic malignancies.

The in vivo migration of [111In]oxine-labeled peripheral mononuclear cells (PMNC) was studied in 20 patients with various lymphatic malignancies and palpable enlarged lymph nodes. The maximal labeling dose of 10 microCi (0.37 MBq) [111In]oxine/10(8) PMNC was found not to adversely influence either cell viability or lymphocyte proliferation in vitro. For in vivo studies, 1.5 X 10(9) PMNC were gained by lymphapheresis and reinjected intravenously after radioactive labeling, 150 microCi (5.55 MBq). The labeling of enlarged palpable lymph nodes was achieved in three out of three patients with Hodgkin's disease and in five out of five with high-malignant lymphoma, whereas three out of seven patients with low malignant lymphoma and no patient with chronic lymphatic leukemia had positive lymph node imaging. We thus conclude that PMNC retain their ability to migrate after [111In]oxine labeling and that these cells traffic to involved lymph nodes of some, but not all hematologic malignancies.

Adult↗

Isolated pericardial relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia.

A 34-year-old male patient developed an isolated pericardial relapse of an acute myelogenous leukemia (M3) 11 months after marrow grafting from his HLA-identical brother. Alloenzyme pattern analysis revealed recipient type of the myeloblasts obtained from the pericardial effusion. Recurrence of the original leukemia was preceded by a reactivation of latent cytomegalovirus (CMV) infection which, in spite of a systemic humoral immune response to the virus, persisted in the pericardium as shown by dot-blot hybridization using CMV-specific DNA fragments. Activated T cells propagated with IL-2 from the pericardial effusion did not reveal any cytotoxic or restimulation capacity on the original or relapse myeloblasts, nor on other donor, recipient or NK target cells. Local coincidence of virus persistence and leukemic relapse suggested CMV-mediated modulation of the immune response in the pericardium with consequent induction of a proliferation of the original malignant cell clone. After local chemotherapy and one course of systemic treatment the patient is still in complete remission--longer than after the marrow grafting.

Adult↗

[Animal experiment studies of the effect of the hazardous substance carbon tetrachloride on peripheral nerves].

The deleterious effects of Carbon Tetrachloride, widely used industrially, on the peripheral nervous system was investigated by experimentation on rabbits. Long-term infusion simulated various conditions of exposure to obtain pharmacological and electroneurographic data. Tetrachlorethen is shown to induce reversible dysfunctions of the peripheral nervous system depending on the degree of concentration. The mode of molecular action remains open. Our results are compared with references in existing literature.

Animals↗