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Biomedical subjects

S Müller

Publications and source records attributed to S Müller.

At least 307 records · Page 17Linked to original sources
PubMed1996

Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether.

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. Artemether and chloroquine were highly efficient. Functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen intermediates (ROI) when compared with naive mice. After artemether or chloroquine treatment, the ROI production was significantly enhanced. The interferon-gamma induced production of reactive nitrogen intermediates (RNI) was slightly elevated in mice with cerebral malaria, but markedly elevated in artemether or chloroquine treated mice when compared with naive mice. Moreover, high levels of inducible nitric oxide synthase gene expression could be detected by in-situ hybridization in spleen sections of mice which had been treated with artemether or chloroquine. These findings suggest that increased production of ROI and RNI after chemotherapy may play a protective role for the host during malaria.

Animals↗
PubMed1996

Matrix remodelling in dilated cardiomyopathy entails the occurrence of oncofetal fibronectin molecular variants.

OBJECTIVES: To investigate whether disturbance of the cellular homoeostasis and integrity of cardiomyocytes in dilated cardiomyopathy (DCM) is accompanied by alterations in cell-matrix relations as indicated by changes in the deposition of fibronectin (FN) isoforms. DESIGN: Tissue from a case series of patients with DCM was investigated by immunohistochemistry with antibodies against FN (all variants, clone IST4), ED-A+ FN (clone IST9), ED-B+ FN (clone BC1), and oncofetal glycosylated FN (clone 5C10). The sites of de novo synthesis of FN were demonstrated by means of non-radioactive RNA in situ hybridisation (ISH) with biotinylated FN cDNA fragments as the probe. SETTING: University hospital. PATIENTS: Samples from 10 patients with clinical criteria and histological diagnosis of DCM and from 3 individuals with normal hearts. INTERVENTIONS: Samples were obtained by right ventricular endomyocardial biopsy. MAIN OUTCOME MEASURE: Distribution of oncofetal FN variants in DCM hearts. RESULTS: Immunostaining of FN (IST4, all variants) showed a coarse interstitial network in normal and diseased myocardium. ED-A+ FN was deposited as fine interstitial spots in normal myocardium and in DCM samples. Immunostaining for oncofetal glycosylated FN and ED-B+ FN was not seen in normal adult myocardium, whereas myocardium from DCM patients showed focal and delicate staining in the interstitium. RNA ISH showed that these deposits resulted from local FN synthesis. CONCLUSION: The results accord with de novo expression of oncofetal FN variants in hearts from patients with DCM. The oncofetal FN variants may serve as disease markers in myocardium affected by DCM.

Adult↗
PubMed1996

Detachment of defective septum primum. A potential source of embolism?

Cardiac sources of embolic stroke include various abnormalities of the atrial septum. An atypical detachment of the septum primum was detected in two patients by dynamic three-dimensional echocardiography (DTDE). Between the septum primum and septum secundum a cavity with interatrial communication was detected. Within the cavity a turbulent color Doppler signal and an entry of the contrast agent EchovistR were detected. One of the patients suffered from repeated cerebrovascular events. This unusual defect of the atrial septum may be a potential source of embolism. Transesophageal echocardiography is considered the most sensitive method for the examination of the atrial septum. However, clear anatomic details could only be shown by DTDE.

Adult↗
PubMed1996

Combined CD34 positive plus CD2 negative selection for effective T-cell depletion as GvHD-prophylaxis in HLA-nonidentical blood progenitor cell transplantation.

G-CSF mobilized, T-cell-depleted peripheral blood progenitor cells (PBPC) and T-cell-depleted bone marrow (BM) were given to seven children (6 AL, 1 SCID) to prevent severe graft-versus-host-disease (GvHD) as well as graft rejection after transplantation from HLA-nonidentical parental donors. BM was T-cell-depleted by lectin agglutination and E-rosetting. For T-cell-depletion of the PBPC grafts a combination of CD34+ selection with the Ceprate SC immunoadsorption system and a subsequent depletion of CD2+ cells with immunomagnetic Dynabeads was used. The overall recovery was 0.3 (0.1-1.2)% for nucleated cells, 29 (18-45)% for CD3+ cells, respectively. The purity of CD34+ cells was 87 (68-97)% with a 0.3(0.05-0.7)% residual CD3+ T-cell contamination. In spite of the large T-cell number in the PBPC grafts the combination of CD34 positive and subsequent CD2 negative selection achieved a more than 4 log T-cell depletion and prevents severe GvHD even in HLA-nonidentical transplantation. In addition, if a high dose of progenitor cells ensures stable engraftment, this new approach could increase the possibility of wider use of HLA-mismatched family donors for transplantation.

Adult↗
PubMed1996

Improved lectin agglutination method for T-cell depletion of HLA-mismatched bone marrow grafts in children.

For T-cell depletion in HLA-nonidentical bone marrow transplantation of children with malignant diseases, we improved the original lectin/rosetting method described in 1981 by adding anti-CD2/3 coated donor red blood cells to the combination to achieve lectin agglutination in one step. Further improvements in handling led to a shortened and simplified method and better quality of the graft. Five bone marrow grafts prepared with this modified protocol contained a median number of 6 (0-28) x 10(4) T-cells per kg, corresponding to 0.02 (0-0.08)% CD3+ cells and 6 (3.7-10.5) x 10(6) CD34+ cells per kg at a median body-weight of 7 (5-38)kg. The overall recoveries after T-cell depletion were: NC 17 (10-44)%, CD34+ cells 61 (22-100)%, and CFU-GM 55 (29-212)%.

Agglutination↗
PubMed1996

[Positron emission tomography for primary tumor detection in lymph node metastases with unknown primary tumor].

In a prospective study 16 patients with cervical lymph node metastases from an occult tumor were analyzed by (18F)FDG positron emission tomography (PET). The aim of this study was to locate the primary tumor. In 7 patients a localized increase in activity was seen on PET, with this site of activity histologically proven in 4 patients. No biopsies were taken in 3 patients in areas with a high risk of complications. In a follow-up procedure at 2-22 months after primary radiation therapy in the other 9 patients, no primary tumor has been identified to date.

Biopsy↗
PubMed1996

Interspecies comparison of in vitro plasma degradation of dynorphin A 1-13.

Enzymatic cleavage of peptides might release metabolites with distinct pharmacological profile. Interspecies differences in the metabolism of peptides might represent a potential source of error when animal data are intended to predict the human situation. Therefore, the metabolism of dynorphin (Dyn) A1-13 was investigated in the plasma of various species used in experimental practice (monkey, rabbit, rat, guinea pig) and compared to previously reported human data. The metabolic pathways were evaluated by enzyme inhibition and kinetic analysis, both yielding almost identical results. Rapid metabolism was observed with all dynorphin fragments across all species (half-lives from 0.3 min for Dyn A1-12 in guinea pig plasma to 2.6 min for Dyn A2-12 in monkey plasma). The metabolism of Dyn A1-13 differed mainly with respect to the half-life (from 0.5 min in guinea pig plasma) to 1.1 min in monkey plasma), while the metabolic routes were similar across the species (Dyn A1-12 major metabolite of Dyn A1-13: from 88% in guinea pig plasma to 71% in rabbit plasma). The metabolic fate of Dyn A1-12, the most important metabolite of Dyn A1-13 is much more heterogeneous across the species then the one observed for Dyn A1-13. For a first assessment, the metabolic routes and rates of Dyn A1-13 in plasma of all investigated species, except from guinea pigs, resemble those in human plasma sufficiently.

Animals↗
PubMed1995

[An anticholinergic syndrome with hallucinatory psychosis after diphenhydramine poisoning].

HISTORY AND CLINICAL FINDINGS: A 27-year-old female student was hospitalized as an emergency because of gait and speech disorders which had developed over just a few hours. Conflicts with her partner and frequent alcohol abuse were reported. It was not possible to interview the patient herself. Consciousness was clouded by optical and acoustic hallucination. Body temperature was 38.1 degrees C: the skin was warm and dry, the tongue dry. Heart rate was 120/min, blood pressure 150/100 mm Hg. Neck and limb muscle tone was increased. Hallucinatory psychosis, encephalitis and alcohol withdrawal delirium were considered in the differential diagnosis. TESTS: There was hypokalaemia, slightly increased serum creatinine and metabolic alkalosis. The alcohol level was 0.18%. The ECG was normal except for sinus tachycardia. TREATMENT AND COURSE: In the meantime, two empty packets of 20 tablets each had been found in the patient's flat. They had contained Vivinox and Sediat (total of 1.5 g diphenhydramine), so that a central anticholinergic syndrome due to an overdose with this drug could be assumed. The diphenhydramine level was 2.8 micrograms/ml. After administration of altogether four times 2 mg physostigmine and 5 mg diazepam intravenously and normalization of electrolytes the symptoms regressed within 12 hours. The patient then admitted to having taken the drugs with suicidal intent. She was transferred to the psychiatric department because of the risk of further suicidal attempts.

Adult↗
PubMed1995

Expression, purification, and characterization of the cGMP-dependent protein kinases I beta and II using the baculovirus system.

Detailed studies of differences in distinct cGMP kinase isoforms are highly dependent on expression of large amounts of these enzyme isoforms that are not easily purified by conventional methods. Here cGMP-dependent protein kinases, the type I beta soluble form from human placenta, and the type II membrane-associated form from rat intestine, were each expressed in a baculovirus/Sf9 cell system and purified in milligram amounts by affinity chromatography. The expressed recombinant proteins displayed characteristics like those of their native counterparts. cGK I beta was expressed as a 76 kDa protein predominantly found in the cytosol fraction, whereas cGK II was expressed as an 86 kDa protein predominantly associated with the membrane fraction. The apparent Ka and Vmax of cGMP for activation of cGK I beta were 0.5 microM and 3.4 mumol/min/mg, and for cGK II were 0.04 microM and 1.8 mumol/min/mg.

Animals↗
PubMed1995

Functional significance of symmetrical versus asymmetrical GroEL-GroES chaperonin complexes.

The Escherichia coli chaperonin GroEL and its regulator GroES are thought to mediate adenosine triphosphate-dependent protein folding as an asymmetrical complex, with substrate protein bound within the GroEL cylinder. In contrast, a symmetrical complex formed between one GroEL and two GroES oligomers, with substrate protein binding to the outer surface of GroEL, was recently proposed to be the functional chaperonin unit. Electron microscopic and biochemical analyses have now shown that unphysiologically high magnesium concentrations and increased pH are required to assemble symmetrical complexes, the formation of which precludes the association of unfolded polypeptide. Thus, the functional significance of GroEL:(GroES)2 particles remains to be demonstrated.

Adenosine Triphosphate↗
PubMed1995

Serial triggering of many T-cell receptors by a few peptide-MHC complexes.

T lymphocytes can recognize and be activated by a very small number of complexes of peptide with major histocompatibility complex (MHC) molecules displayed on the surface of antigen-presenting cells (APCs). The interaction between the T-cell receptor (TCR) and its ligand has low affinity and high off-rate. Both findings suggest that an extremely small number of TCRs must be engaged in interaction with APCs and raise the question of how so few receptors can transduce an activation signal. Here we show that a small number of peptide-MHC complexes can achieve a high TCR occupancy, because a single complex can serially engage and trigger up to approximately 200 TCRs. Furthermore, TCR occupancy is proportional to the T cell's biological response. Our findings suggest that the low affinity of the TCR can be instrumental in enabling a small number of antigenic complexes to be detected.

Amino Acid Sequence↗
PubMed1995

Model structure of the Omp alpha rod, a parallel four-stranded coiled coil from the hyperthermophilic eubacterium Thermotoga maritima.

Omp alpha is an outer-membrane protein that spans the periplasmic space of the hyperthermophilic eubacterium Thermotoga maritima. The molecule contains a globular head with an apparent diameter of 8 nm and a rod-shaped tail of 40 nm length. The sequence of the globular domain is homologous to a conserved region of cell wall-bound proteins and probably attaches Omp alpha to the peptidoglycan. The sequence of the rod domain resembles that of coiled coil proteins and ends in a transmembrane segment that anchors Omp alpha to the outer membrane. We have analysed Omp alpha by scanning transmission electron microscopy (STEM) and by statistical sequence analysis methods. The Omp alpha rod is a tetramer with an unusual periodicity of hydrophobic residues close to 3.6 that differs from the 3.5 periodicity of canonical coiled coils. This is due to periodic omissions of three residues in the heptad repeat pattern ("stutters") whose effect is to locally distort the packing of hydrophobic layers in the core of the coiled coil. Residues in position alpha are shifted to occupy a position halfway between positions alpha and d (x layers) and residues in positions d and e are shifted so that both participate in core packing interactions (da layers). Such distorted layers are frequently found in helical bundles and are characteristic of helices that do not undergo supercoiling. The only homo-oligomeric coiled coil of known structure which contains x and da layers is the three-stranded coiled coil of influenza haemagglutinin. Using geometric constraints derived from this structure, we have built a model for the Omp alpha rod in which the helices have a crossing angle of less than 15 degrees and maintain a residual degree of supercoiling with a pitch of approximately 40 nm. Our analysis of distorted layers in the hydrophobic core of coiled coils and helical bundles shows that stutters must not be viewed as discontinuities but rather as a departure from the canonical "knobs-into-holes" packing that allows helices to interact at a low angle without supercoiling. Although stutters have been considered to weaken helical interactions, their occurrence in a rigid, highly thermostable coiled coil indicates that this may not be generally true. Our analysis also indicates that skips and stutters are two different conventions for describing the same underlying structural feature.

Amino Acid Sequence↗
PubMed1995

Laufband therapy based on 'rules of spinal locomotion' is effective in spinal cord injured persons.

Rehabilitation of locomotion in spinal cord (s.c.) injured patients is unsatisfactory. Here we report the effects of a novel 'Laufband (LB; treadmill) therapy' based on 'rules of spinal locomotion' derived from lower vertebrates. Eighty-nine incompletely paralysed (44 chronic and 45 acute) para- and tetraplegics underwent this therapy, then were compared with 64 patients (24 chronic and 40 acute) treated conventionally. The programme consisted of daily upright walking on a motor driven LB initially with body weight support (BWS) provided by a harness and assisted limb movements by the therapists when necessary. Forty-four chronic patients with different degrees of paralysis undertook the programme for 3-20 weeks (median = 10.5), 0.5-18 years after s.c. damage. At the onset of LB therapy 33/44 patients were wheelchair-bound (no standing and/or walking without help by others) whereas at the end of therapy 25 patients (76%) had learned to walk independently, 7 patients with help [corrected]. Only 1 subject did not improve. It was striking that voluntary muscle activity in the resting position was still low in several patients who had gained walking capability. Eleven patients who could already walk before LB therapy improved in speed and endurance. Of the 44 patients, six were capable of staircase walking before LB therapy compared with 34 afterwards. In order to validate the apparent superiority of LB therapy two types of comparisons were performed. In a 'temporal' control 12 spastic paretic patients, still wheelchair-bound after the period of postacute conventional therapy, performed LB immediately thereafter. After completion of LB therapy nine of these patients had learned to walk without help from others.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Plasma concentration of tissue factor and factor VII in patients after abdominal surgery.

Tissue injury following trauma and surgery may induce alterations in blood coagulation and fibrinolysis. Hypercoagulable state after surgery can be associated with the risk of postoperative thromboembolic complications. The contact of coagulation factors with TF after injury of vessel wall and organ tissues may contribute to the development of thrombosis after surgery (1). TF, the cell surface receptor and cofactor of factor VII/VIIa is normally not expressed by cells within the vasculature. Only monocytes and endothelial cells can be stimulated to express TF transiently by a variety of inflammatory and immunological reactions (for review see 2,3). Also surgical treatment was reported to induce TF synthesis in monocytes (4,5,6). TF is present in many extravascular tissues as vascular adventitia, organ capsules, epidermis, colonic mucosal epithelium, liver stroma, pancreas stroma and also on tumor cells (7-12). In this study, we investigated, whether we can detect the release of TF from the traumatized tissues and from activated monocytes into the circulation following abdominal surgery. To test the dependence of the extension of tissue injury during surgery we segregated the patients into group A with major abdominal operations and group B consisting of patients with appendectomy and cholecystectomy. No relationship could be established between changes of TF and postoperative thromboembolic complications.

Abdomen↗
PubMed1995

The thermosome of Thermoplasma acidophilum and its relationship to the eukaryotic chaperonin TRiC.

A high molecular-mass protein complex from the archaebacterium Thermoplasma acidophilum, referred to here as the 'thermosome', is built from two subunits (M(r) 58 and 60). The thermosome has been purified to homogeneity. The molecular mass of the native complex was determined to be 1061 +/- 30 Da by scanning transmission electron microscopy. It shows a weak ATPase activity and is able to bind denatured polypeptides. Averages obtained from electron micrographs of negatively stained molecules in the end-on and side-on orientations, respectively, were compared with those of the t-complex polypeptide 1 ring complex (TRiC), isolated from bovine testes. Both molecules consist of two stacked pseudo eightfold symmetric rings which build up a cylindrical particle with a large cavity in the center. Sequence alignments of peptides generated from both subunits of the thermosome and different subunits of TRiC reveal a high partial similarity to each other and to the archaebacterial chaperonin thermophilic factor 55 from Sulfolobus shibatae as well as to eukaryotic TCP1 proteins. These striking structural similarities confirm the proposition that all these molecules belong to a single protein family which is structurally and functionally related to the GroEL class of molecular chaperones.

Adenosine Triphosphatases↗