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Biomedical subjects

M Herrmann

Publications and source records attributed to M Herrmann.

At least 127 records · Page 7Linked to original sources

Alternatively spliced mRNA molecules of the thrombospondin receptor (CD36) in human PBMC.

We employed reverse transcription polymerase chain reaction (RT-PCR) to detect alternatively spliced CD36 mRNA in human peripheral blood mononuclear cells (PBMC). Sequencing of cloned cDNA revealed alternatively spliced mRNA molecules in 13 out of 39 clones. We observed exon skipping of up to 10 out of 12 coding exons in eight alternative transcripts. Additionally, in five of the transcripts, alternative splice donor or acceptor sites were used during mRNA maturation. Considering the CD36 molecule serves many functions in coagulation, host defence, lipid metabolism, and scavenging, we speculate that the proteins encoded by the alternatively spliced mRNA molecules may be involved in regulation of both CD36 gene expression and function.

Alternative Splicing↗

Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1.

The ability of Staphylococcus aureus to invade mammalian cells may explain its capacity to colonize mucosa and to persist in tissues after bacteraemia. To date, the underlying molecular mechanisms of cellular invasion by S. aureus are unknown, despite its high prevalence and difficulties in treatment. Here, we show cellular invasion as a novel function for an S. aureus adhesin, previously implicated solely in attachment. S. aureus, but not S. epidermidis, invaded epithelial 293 cells in a temperature- and F-actin-dependent manner. Formaldehyde-fixed and live bacteria were equally invasive, suggesting that no active bacterial process was involved. All clinical S. aureus isolates analysed, but only a subset of laboratory strains, were invasive. Fibronectin-binding proteins (FnBPs) acted as S. aureus invasins, because: (i) FnBP deletion mutants of invasive laboratory strains lost invasiveness; (ii) expression of FnBPs in noninvasive strains conferred invasiveness; and (iii) the soluble isolated fibronectin-binding domain of FnBP (D1-D4) completely blocked invasion. Integrin alpha5beta1 served as host cell receptor, which interacted with staphylococcal FnBPs through cellular or soluble fibronectin. FnBP-deficient mutants lost invasiveness for epithelial cells, endothelial cells and fibroblasts. Thus, fibronectin-dependent bridging between S. aureus FnBPs and host cell integrin alpha5beta1 is a conserved mechanism for S. aureus invasion of human cells. This may prove useful in developing new therapeutic and vaccine strategies for S. aureus infections.

Adhesins, Bacterial↗

Transcriptional activation of endogenous retroviral sequences in human epidermal keratinocytes by UVB irradiation.

Ultraviolet radiation is a pathogenic factor in various diseases, e. g., autoimmune disorders such as lupus erythematosus. On the other hand, endogenous retroviruses are discussed as etiologic agents in lupus erythematosus. Therefore, we investigated the influence of ultraviolet irradiation on expression of human endogenous retroviral sequences and human endogenous retroviral sequence promoter-driven transcription of cellular genes using human epidermal keratinocytes as a model system. First, conserved sequences of endogenous retroviral pol genes were amplified from cellular mRNA by reverse transcriptase polymerase chain reaction with degenerate oligonucleotide primers. Polymerase chain reaction products were hybridized in a reverse dot blot hybridization assay to a representative number of distinct cloned human endogenous retroviral pol fragments. Using this method, we could show that irradiation with 30 mJ per cm2 ultraviolet B activates transcription of various endogenous retroviral pol sequences in primary epidermal keratinocytes as well as in a spontaneously immortalized keratinocyte cell line (HaCaT). Interestingly, some of these sequences were found to be closely related to pol sequences of human endogenous retroviral sequences which have been shown to be expressed in autoimmune patients. Analysis of human endogenous retroviral pol expression in vivo using skin biopsies of lupus erythematosus patients revealed similar activation patterns. In a second approach, ultraviolet B- induced chimeric transcripts were isolated which are initiated by human endogenous retroviral promoters and proceed into cellular sequences using a newly established modified differential display polymerase chain reaction technique. The activation of human endogenous retroviral sequence transcription by ultraviolet B may contribute to the pathogenesis of lupus erythematosus, where inappropriate antigenic presentation of ultraviolet B-induced viral and cellular proteins could stimulate autoantibody production.

Base Sequence↗

The emotional impact of aphasia.

In this article we review the negative impact of aphasia on emotional well-being. Depression is the emotional response that has been examined most, and we examine the different causes of depression for people with aphasia. We discuss the relationships between recovery and emotional state and the clinical implications of these relationships, then review briefly issues of drug treatment for depression. We conclude that the emotional impact of aphasia can have a marked negative impact on recovery, response to rehabilitation, and psychosocial adjustment.

Aphasia↗

Perceptions of psychosocial adjustment to aphasia: applications of the Code--Müller Protocols.

We review research that has examined people's perceptions of likely psychosocial adjustment of aphasia. People's perceptions differ depending on whether they have aphasia themselves, are related closely to a person with aphasia, or work with the aphasic person in a professional capacity. In addition, people differ in what they perceive are the most important or relevant factors for psychosocial adjustment, and this too depends on whether they have aphasia themselves, are a relative or "significant other" in the aphasic person's life, or are a health professional working with the person with aphasia. Furthermore, there are marked differences in the way individuals predict likely psychosocial adjustment, and these perceptions can change over time. Most of this research has used the Code-Müller Protocols (CMP) to examine these perceptions. This article describes the development and application of the CMP in aphasia.

Adaptation, Psychological↗

Is there a syndrome of tuberothalamic artery infarction? A case report and critical review.

Short-term post-acute neuropsychological, neurological, and neuroradiological test results and a 16-month follow-up of a 65-year-old patient with a right hemisphere ischemic lesion in the tuberothalamic area of vascular supply are reported. During a 6-week period of examinations the originally left- but trained right-handed patient exhibited fluctuating neuropsychological disorders including aphasia, visuo-perceptive and visuoconstructive disorders, and memory and attention deficits. In the follow-up examination the patient exhibited no aphasia and significant improvements in most neuropsychological tasks. Based on three-dimensional reconstruction of MRI, lesion topography and involvement of thalamic nuclei were established. We discuss the neuropsychological and neurological symptoms of the present case against the background of the 'syndrome of unilateral tuberothalamic artery territory infarction' proposed by Bogousslavsky and coworkers (1986) and the neuropsychological literature on unilateral ischemic anterior/anterolateral thalamic infarction.

Aged↗

In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence.

PURPOSE: Cells undergoing apoptosis contribute to the regulation of activated mononuclear cells (Voll et al. 1997). Low-dose radiotherapy (LD-RT) is known to improve inflammatory symptoms, but the mechanism of action is still unclear. The aim of this study was to investigate the rate of apoptosis of peripheral blood mononuclear cells (PBMC) induced by LD-RT within the therapeutic dose range of anti-inflammatory RT. MATERIALS AND METHODS: PBMC were isolated from venous blood of ten healthy volunteers and were irradiated with single doses between 0.1 and 3.0 Gy. Apoptotic nuclei were detected by flow cytometry after propidium iodide (PI) triton staining, and apoptotic cells were detected by annexin V/PI staining and cell scatter analysis. Since apoptotic cells display increased cytoplasmatic granularity and concomitant reduced cell size, they can be distinguished from viable cells in forward/side scatter (FSC/SSC) histograms. Apoptotic PBMC were further subtyped by double staining with annexin V and directly labelled monoclonal antibodies recognizing the lineage-specific surface markers CD4, CD8, and CD19, respectively. The apoptosis rate of irradiated cells was analysed in a time and dose dependent fashion and was compared to a sham-irradiated control. RESULTS: After irradiation, a dose-dependent increase in apoptosis was observed, with a discontinuity (plateau or peak) between 0.3Gy and 0.7Gy in 9/10 donors (90%) and 59/80 samples (74%). 8/10 donors (80%) and 38/80 samples (47%) showed not only a discontinuous increase with a plateau but a relative maximum of apoptosis peaking within the dose range of 0.3 Gy and up to 0.7 Gy. CONCLUSION: LD-RT induces a relative maximum of apoptosis in PBMC in the does range between 0.3 Gy and 0.7 Gy. This may contribute to its anti-inflammatory effect observed clinically.

Adult↗

A lithium chloride-extracted, broad-spectrum-adhesive 42-kilodalton protein of Staphylococcus epidermidis is ornithine carbamoyltransferase.

To identify novel putative staphylococcal adhesins, lithium chloride extraction (an established method for selective surface molecule solubilization) was employed. N-terminal sequencing and functional assays identified a 42-kDa fibronectin-binding protein from Staphylococcus epidermidis as ornithine carbamoyltransferase (OCTase). However, OCTase was not recognizable extracellularly, and this fact together with the fact that LiCl induced DNA release and a decrease in viability suggests that LiCl extraction may not be the method of choice for selective surface molecule extraction from staphylococci.

Adhesins, Bacterial↗

ELISA-quantitation of phosphorylated tau protein in the Alzheimer's disease brain.

A reliable, sensitive and specific sandwich ELISA for the quantitation of paired helical filament (PHF) tau in human brain was developed using well-defined monoclonal antibodies. We examined rapid-autopsy-derived brain tissue from 21 neuropathologically confirmed Alzheimer's disease (AD) patients and 14 nondemented controls, matched for age, sex and postmortem delay times. We demonstrated significant elevations of phosphorylated tau levels in the frontal and parietal cortex as well as in the hippocampus of AD patients as compared to the nondemented controls. No difference was observed in the cerebellum. Phosphorylated tau levels measured by ELISA were significantly correlated with the presence or absence of neurofibrillary tangles.

Aged↗

Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage.

BACKGROUND AND PURPOSE: The study aimed to investigate the predictive value of neurobiochemical markers of brain damage (protein S-100B and neuron-specific enolase [NSE]) with respect to early neurobehavioral outcome after stroke. METHODS: We investigated 58 patients with completed stroke who were admitted to the stroke unit of the Department of Neurology at Magdeburg University. Serial venous blood samples were taken after admission and during the first 4 days, and protein S-100B and NSE were analyzed by the use of immunoluminometric assays. In all patients, lesion topography and vascular supply were analyzed and volume of infarcted brain areas was calculated. The neurological status was evaluated by a standardized neurological examination and the National Institutes of Health Stroke Scale (NIHSS) on admission, at days 1 and 4 on the stroke unit, at day 10, and at discharge from the hospital. Comprehensive neuropsychological examinations were performed in all patients with first-ever stroke event and supratentorial brain infarctions. Functional outcome was measured with the Barthel score at discharge from the hospital. RESULTS: NSE and protein S-100B concentrations were significantly correlated with both volume of infarcted brain areas and NIHSS scores. Patients with an adverse neurological outcome had a significantly higher and significantly longer release of both markers. Neuropsychological impairment was associated with higher protein S-100B release, but this did not reach statistical significance. CONCLUSIONS: Serum concentrations and kinetics of protein S-100B and NSE have a high predictive value for early neurobehavioral outcome after acute stroke. Protein S-100B concentrations at days 2 to 4 after acute stroke may provide valuable information for both neurological status and functional impairment at discharge from the acute care hospital.

Aged↗

Mechanisms for spatial integration in visual detection: a model based on lateral interactions.

Recent studies of visual detection show a configuration dependent weak improvement of thresholds with the number of targets, which corresponds to a fourth-root power law. We find this result to be inconsistent with probability summation models, and account for it by a model of 'physiological' integration that is based on excitatory lateral interactions in the visual cortex. The model explains several phenomena which are confirmed by the experimental data, such as the absence of spatial and temporal uncertainty effects, temporal summation curves, and facilitation by a pedestal in 2AFC tasks. The summation exponents are dependent on the strength of the lateral interactions, and on the distance and orientation relationship between the elements.

Computer Simulation↗

Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties.

New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.

Acrylates↗

[Perspectives in public health care for refugees in Germany].

Germany in fact became an immigration country during the last 25 years. The German public health service for refugees aims at avoiding epidemic diseases and protecting the local population. In spite of the internationally recognised high capability of the German health system it is open to question whether sufficient health care for refugees who are regarded as highly vulnerable is guaranteed. Relevant investigations are missing. The present article illustrates perspectives of the health situation, health perception, health behaviour and finally also the health resources of refugees. Health as well as the health care of refugees appears to be fragmented. Three possible scenarios of the health care of refugees are discussed: Compartmentalisation of general health care, incorporation of health care through the communities of migrants as well as stronger integration in the German health care system. The article bases on a research of present scientific work about health and illness of refugees as well as on empirical data of a feasibility study in an area in south-west Germany on the health and primary health care for refugees.

Delivery of Health Care↗

The crucial role of frontostriatal circuits for depressive disorders in the postacute stage after stroke.

OBJECTIVE: This study analyzes lesion configuration in patients in the post-acute stage after first single unilateral stroke who suffered from depressive disorders. BACKGROUND: Recent studies indicate a biological origin of poststroke depressive disorders. Due to differences in times of investigation, methods applied, and patient selection, most data are not comparable. Furthermore, only a few studies of poststroke depression report detailed neuropsychologic assessments. METHODS: We investigated 20 consecutive patients who were diagnosed as depressive according to DSM-III-R criteria and exhibited no other severe illness, had no history of neurologic or psychiatric disease, and who were either not aphasic, or only mildly aphasic. A structured clinical interview, self-based and observer-based depression rating scales, a comprehensive neuropsychologic and neurologic examination and ADL-measurement were applied. Neuroradiologic analysis was based on standardized computed tomography scans. RESULTS: Nine of 10 subjects with left hemisphere strokes exhibited a major depression and 7 of 10 subjects with right hemisphere infarcts a minor depression. The most prominent neuropsychologic deficits were found in frontal lobe associated tasks. Type and severity of depression were not related to the severity of neurologic symptoms or impairment in activities of daily living. For both major and minor depression the maximal overlap of lesions was found in subcortical areas, including parts of the caudate nucleus, posterior parts of the putamen, and the deep white matter. CONCLUSIONS: The findings support the theory that poststroke depression is related to the dysfunction of (cortico-) striato-pallido-thalamic-cortical projections that modulate cortico-thalamo-cortical loop systems.

Adult↗

Elongation of the N-acyl side chain of sialic acids in MDCK II cells inhibits influenza A virus infection.

The interaction of influenza A virus with sialyated receptor components is one of the best characterized ligand-receptor interactions. We pretreated MDCK II host cells with three different N-acyl-modified sialic acid precursor analogues, N-propanoyl, N-butanoyl or N-pentanoyl D-mannnosamine. Cellular sialic acid biosynthesis yielded 18-35% of new, modified sialic acids on cell surface glycoconjugates, N-propanoyl, N-butanoyl or N-pentanoyl neuraminic acid, respectively. The elongation of the N-acyl group of sialic acids resulted in an inhibition of influenza A virus (strain X31) binding and subsequent infection of up to 80%. In contrast, the sialic acid-independent infection of vesicular stomatitis virus was unaffected in these cells. Molecular modeling studies based on the crystal structure of the influenza A virus hemagglutinin complexed with sialyllactose suggest a steric hindrance of hemagglutinin binding to aliphatically elongated N-acyl groups. We propose that biosynthetic sialic acid modification in conjunction with molecular modeling is a potent tool to further analyze the influenza A virus-receptor interaction.

Animals↗

[Puerperal sepsis caused by streptococcus group A with a severe form of progression like "toxic shock-like syndrome"].

HISTORY AND CLINICAL FINDINGS: A previously healthy 32-year-old woman was admitted with shock symptoms 5 days after an uneventful home delivery. She developed a fever up to 39.5 degrees C during the days after delivery with sore throat, diarrhoea and muscle aches in all limbs. On physical examination there were swellings of the arms and lower legs as well as macular and vesicular erythrodermia, especially of the trunk. INVESTIGATIONS: Abnormal laboratory findings were thrombocytopenia (20,000/microliters), increased serum concentrations of fibrin breakdown products (102 mg/dl) and of C-reactive protein (> 200 mg/dl), increased creatine kinase (5700 U/l), transaminases (GOT 220 U/l, GPT 52 U/l), creatinine (2.0 mg/dl) and urea (114 mg/dl). Streptococcus pyogenes was grown on blood culture and from vaginal smear. Sonography, echocardiography and radiological examinations failed to demonstrate a septic focus. TREATMENT AND COURSE: Mechanical ventilation was required for 7 days because of respiratory failure and shock symptoms (toxic shock-like syndrome, TSLS). Penicillin G and tobramycin were given after the bacteriological diagnosis. Severe consumption coagulopathy was successfully treated with antithrombin III and platelet concentrates. After extubation she was found to have a flaccid tetraparesis, especially of the right and of the legs, due to soft-tissue necrosis and damage to peripheral nerves. An embolic occlusion of the right brachial artery 4 weeks after onset of the disease required upper-arm amputation. CONCLUSION: One of the decisive factors for the prognosis of TSLS is early antibiotic treatment. The prodromal symptoms in this case underline the necessity of early recognition and treatment to prevent a full-blown picture of the syndrome.

Adult↗

Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus.

OBJECTIVE: To investigate whether the established impaired phagocyte function in systemic lupus erythematosus (SLE) patients also affects apoptotic cell clearance. Accumulation of apoptotic waste as a source for autoantigens that induce and maintain autoimmune responses is discussed. METHODS: Apoptosis was detected by morphology and propidium iodide staining. In vitro phagocytosis of autologous apoptotic cells in cultured peripheral blood mononuclear cells was evaluated microscopically. Cross-feeding experiments were performed to investigate phagocytosis of heterologous apoptotic cells by in vitro-differentiated macrophages. Furthermore, the effect of annexin V on the phagocytosis of apoptotic cells was investigated. RESULTS: Reduced clearance of apoptotic cells in SLE patients was observed. The defective clearance appeared to reflect phagocyte dysfunction and not an abnormal execution of apoptosis. A similar picture was seen when in vitro-differentiated macrophages from control populations were treated with annexin V. CONCLUSION: Noninflammatory engulfment phagocytosis of apoptotic cells is decreased in SLE patients. Persistently circulating apoptotic waste may encounter inflammatory removal pathways and serve as immunogen for the induction of autoreactive lymphocytes and as antigen for immune complex formation.

Annexin A5↗

[Prevention of catheter-related infections, The official American guidelines--from the Centers for Disease Control].

The official German guidelines for prevention of intravascular-device-associated infections were published by the Bundes-gesundheitsamt, now called the Robert-Koch-Institut, 12 years ago. The recently published official "Guidelines for Prevention of Intravascular-Device Associated Infections" of the Centers for Disease Control and Prevention (CDC) are categorized according to scientific evidence. The American guidelines are very detailed and differ in some aspects from the official German guidelines. The purpose of the present paper is to inform the German-speaking anaesthesiologist about the official CDC guidelines and to provide an update on the prevention of intravascular-device-associated infections.

Catheterization↗