Biomedical subjects
Publications and source records attributed to T Schulte.
A large meningioma located in the cerebellopontine angle was an unusual cause for contralateral trigeminal neuralgia. The mass effect displaced the basilar artery affecting the contralateral trigeminal nerve in vicinity of the brain stem. After radical microsurgical removal ot the tumour, the trigeminal neuralgia completely disappeared.
Retrospective analysis of 165 patients (105 males, 60 females) with a mean age of 21.2 years (range 14 to 25 years) of 6933 surgically treated patients from January 1987 to May 1999 focused on age and sex distribution, body mass, familial predisposition, trauma, histology, and clinical course. The incidence of herniated lumbar discs was 2.3% in patients aged up to 25 years. A valid family history was obtained in 121 patients and a positive history was found in 82 of these patients (67.8%). The patients had a higher body mass index compared to a group of individuals with a similar age structure. Radiography demonstrated bony changes in 124 patients (75.2%), primarily attributable to postural deformities such as scoliosis. The condition of the bony structures seems to be more important than the condition of the disc tissue in the occurrence of this disease in young patients.
The Fas (CD95, APO-1) receptor is a membrane-associated polypeptide that can mediate apoptosis in various cell types. Although Fas receptor is expressed in endothelial cells (EC), little is known about its function in these cells. The expression of Fas by liver endothelial cells (LEC) suggests that upon stimulation, apoptosis may occur in these cells. We show that Fas is highly and constitutively expressed in cloned murine liver endothelial cells (LEC-1). In contrast, FasL expression was not detected at the protein and mRNA level in these cells. Our results show that Fas ligation in LEC-1 induces apoptotic cell death, indicating that Fas receptor is functional in these cells. The doses of Fas agonist required to induce LEC-1 apoptosis were higher than those used previously in other cells, including hepatocytes, suggesting that LEC-1 are highly resistant to the Fas apoptotic pathway. TNF treatment of LEC-1 induced up-regulation of Fas receptor on these cells. In contrast, TNF did not induce the expression of FasL on LEC-1. An increased susceptibility to Fas-mediated apoptosis was observed in TNF-treated LEC-1. Enhanced susceptibility to Fas-mediated apoptosis was also observed in LEC-1 pretreated with actinomycin D, suggesting that transcription of message coding for protective proteins is necessary to protect these cells against Fas-mediated apoptosis. Up-regulation of VCAM-1 and ICAM-1 was observed in LEC-1 treated with a dose of Fas agonist that does not induce apoptosis. To our knowledge, this is the first report that Fas mediates apoptosis in LEC, suggesting that apoptosis of these cells may participate in the liver damage observed in animals after receiving anti-Fas mAb or soluble FasL. Our findings also suggest that the Fas/FasL system may transduce activating signals independently of cell death in LEC-1.
Empowering and guiding the team has become crucial to the long-term success of any business. Today, an important measurement for leaders is their ability to facilitate a group of people to work together as a team and successfully accomplish their task. What will separate a good leader from a great leader will be the understanding and development of his or her facilitation skills.
PURPOSE: Brain damage is often accompanied by visual field defects which have been considered to be non-treatable. In recent years, however, new diagnostic methods have revealed hitherto unknown residual vision, which was found, for instance, in transition zones near the blind visual field sectors and in spared islands of vision within the blind regions ("blindsight"). Furthermore, animal studies revealed a high degree of plasticity in the visual system suggesting the possibility that recovery of vision may be induced by systematic visual training. METHODS: Here we summarize a series of studies with patients suffering from visual field defects after brain lesion using some most recently developed computer-based programs for the diagnosis and treatment of visual field defects. Specifically, high-resolution perimetry (HRP) was applied to first diagnose residual function in or near the "blind" sector of the visual field. Thereafter, visual restitution training (VRT, see Kasten et al., Nature med. 4, 1998, p. 1083) was used daily for 6 months to provide systematic stimulation of these areas of residual vision. RESULTS: In a number of studies, we have observed not only residual visual functions within or near the field defect, but we were also able to follow the course of spontaneous recovery of visual functions within weeks or months after visual system damage. Furthermore, even long after spontaneous recovery is complete, computer-based visual restitution training (VRT) in or near the areas of residual vision results in a significant enlargement of intact areas, both after optic nerve damage and postchiasmatic lesions. Using VRT, we found a border shift of about 5 degrees of visual angle which cannot be explained by eye movements or eccentric fixation. We observed a transfer of this training effects to other tasks such as form and color detection, as well as to tests of visual exploration which were not specifically trained. Moreover, 72 % of the patients reported subjective improvements of vision. Training-induced visual field enlargement persisted for at least one year, even in the absence of training beyond 6 months of treatment. CONCLUSIONS: The visual system possesses a remarkable plasticity which becomes apparent in visual field enlargement during spontaneous recovery and specific visual training. Animal studies indicate that a minimum number of residual neurons surviving the lesion, in the order of 10%, provides a sufficient substrate for recovery of vision. Though the precise mechanisms of training-induced visual field enlargement need to be further explored, VRT can be introduced for routine clinical treatment of patients with visual field defects.
Quality inconsistency, whether it exists in products, processes, communication, or services, should serve as a red flag signaling a need to make improvements. More consistency in the workplace can only come through the continual refining of performance. In order for "continual improvement" to become part of the company culture, each person in the organization needs to understand and apply a disciplined step-by-step approach to change. All effective, lasting change comes from the use of problem solving and an effective change process.
The murine interleukin 4 receptor (IL-4R) exists as a transmembrane protein transducing pleiotropic IL-4 functions, or as soluble (s)IL-4-binding molecule with potent immunoregulatory effects. In this study we identified and characterized a murine IL-4R allotype. Sequence analysis of the IL-4R cDNA of BALB/c mice revealed 18 base substitutions leading to three extracellular and five cytoplasmic amino acid changes when compared with the published IL-4R sequence of C57BL/6 mice. Analyses with allotype-specific mAbs revealed that AKR/J and SJL/J mice possess the newly identified BALB/c IL-4R allotype whereas the IL-4Rs of C3H, CBA, DBA-2, and FVB/N mice are identical to that of the C57BL/6 mouse. The extracellular Thr49 to Ile substitution abrogates one N-glycosylation site in the naturally occurring BALB/c IL-4R as well as in the experimentally point mutated C57BL/6-T49I sIL-4R, and both molecules display a nearly threefold reduction in IL-4-neutralizing activity compared to the C57BL/6 sIL-4R. In line with this, a significantly enhanced dissociation rate of IL-4 was detected for the BALB/c IL-4R allotype by surface plasmon resonance and in radioligand binding studies with IL-4R-transfected cell lines. These findings suggest that the altered ligand binding behavior of the newly described IL-4R allotype may influence the IL-4 responsiveness, thus contributing to the diverse phenotypes of inbred mouse strains in IL-4-dependent diseases.
Mutation of the tumor suppressor gene p53 is the most common genetic abnormality detected in human cancers. Wild type p53 is a short-lived protein with very low basal intracellular levels. Most mutated forms of the protein, however, display markedly increased intracellular levels as an essential feature of their positive transforming activity. In this report, we have used selective inhibitors of the 20S proteasome to demonstrate that processing of p53 by ubiquitination and proteasome-mediated degradation is impaired by commonly occuring mutations of the protein. We found that this impairment of p53 turnover can be reversed by treatment of tumor cells with the benzoquinone ansamycin, geldanamycin, leading to a marked reduction in intracellular p53 levels. Finally, using cells which over-express a mutant p53 protein, we were able to demonstrate that restoration of proteasome-mediated degradation by geldanamycin is accompanied by p53 polyubiquitination. Although much remains to be learned about the mechanisms involved, our data demonstrate that selective de-stabilization of mutant transforming proteins such as p53 can be achieved pharmacologically with agents such as geldanamycin which modify the function of molecular chaperone proteins within tumor cells.
Fish--in contrast to mammals--regenerate retinal ganglion cell axons when the optic nerve is severed. Optic nerve injury leads to reexpression of proteins, which typically are first expressed in newly differentiated retinal ganglion cells and axons. Here we identified two new proteins of fish retinal ganglion cells, reggie-1 and reggie-2, with monoclonal antibody M802 and molecular cloning techniques. In normal fish, M802 stained the few retinal axons derived from newborn ganglion cells which in fish are added lifelong to the retinal margin. After optic nerve injury, however, M802 labeled all retinal ganglion cells and retinal axons throughout their path into tectum. Consistent with M802 staining, reggie-1 and reggie-2 mRNAs were present in lesioned retinal ganglion cells, as demonstrated by in situ hybridization, but were not detectable in their normal mature counterparts. In western blots with membrane proteins of the adult goldfish brain, M802 recognizes a 48x10(3) Mr protein band. At the amino acid level, 48x10(3) Mr reggie-1 and reggie-2 are 44% identical, lack transmembrane and membrane anchor domains, but appear membrane associated by ionic interactions. Reggie-1 and reggie-2 are homologous to 35x10(3) Mr ESA (human epidermal surface antigen) but are here identified as neuronal surface proteins, present on newly differentiated ganglion cells at the retinal margin and which are reexpressed in mature ganglion cells upon injury and during axonal regeneration.
c-Raf-1 (Raf-1) is a central component of signal transduction pathways stimulated by various growth factors, protein kinase C, and other protein kinases. Raf-1 activation is thought to be initiated at the plasma membrane after its recruitment by Ras. Raf-1 activation is associated primarily with proliferation and cell survival, but it has also been implicated in apoptosis. Raf-1 has also been shown to form complexes with both R-Ras and Bcl-2, raising the possibility that this component of cellular Raf-1 plays a role in apoptosis. Recently, taxol was reported to induce Bcl-2 phosphorylation and inactivation. We have previously demonstrated Raf-1 activation following taxol in MCF7 cells. We now present evidence that taxol fails to stimulate either apoptosis or phosphorylation of Bel-2 in the absence of Raf-1. Moreover, Raf-1 activation by taxol coincided with Bel-2 phosphorylation, showing similar dose and time dependence. Thus, our data support a role for a distinct subcellular component of Raf-1, which is taxol but not phorbol myristate acetate sensitive, in mediating an apoptotic pathway involving Bc1-2.
In 1990 in Germany for the first time more than 100,000 cases of enteric infections (mostly salmonella enteritidis) were registered. The incidence is still increasing. As only one of ten cases is reported the yearly overall loss to general economy is estimated up to DM 600,000,000. Many hypotheses on causes were suggested but none could be verified (e.g. mass-breeding of animals, modernistic habits of eating and drinking, introduction of microwave-cooking, deterioration of hygiene in kitchens, insufficient cooling of food). This paper reports on the result of retrospective interviews with regard to food- and kitchen-hygiene of persons suffering from salmonellosis during an epidemy in Lübeck in autumn 1990. As no systematic violations of rules of hygiene could be detected we concluded that in future prevention and research should again be concentrated especially on the control of animal feed imports, poultry breeding, cooling and technical processing of eggs and garbage-sanitation. In Sweden consistent elimination of infected poultry stock showed effect. In the Federal Republic of Germany more drastic steps in regard of planed EC-Guidelines on the control of zoonoses are demanded.
Two infants with intussusception were presented with lethargy and vomiting. Initially, the classical abdominal manifestations of the disease were missing. In order to avoid a delay of the correct treatment, intussusception should be considered in infants with altered consciousness and ultrasonography of the abdomen should be included in the diagnostic work up.
We report the case of an infant who developed severe nasal obstruction as an unusual first presentation of cystic fibrosis (CF). Computed tomography (CT) showed homogeneous opacification of the symmetrically enlarged paranasal sinuses that gave the clue for the final diagnosis.
The reliability and predictive value of salivary theophylline levels was investigated in 58 children who were treated with oral sustained-release theophylline preparations for bronchial asthma. Serum and saliva levels were assessed by fluorescence polarization immunoassay (FPIA), and Seralyzer (reagent strip reflectance photometer method). Forty-six paired serum and saliva samples from 28 patients (Group 1) were used to develop a linear regression formula. This formula was tested on 130 paired serum and saliva samples from 32 patients (Group 2). When saliva theophylline levels were assayed using FPIA, 95% of serum levels were predicted within 30% of the measured value. Using Seralyzer, 95% of serum levels were predicted within 45% of the measured value. For patients with three and more paired serum and saliva specimens, individual regression formulas were determined showing considerable variation. This study indicates that salivary theophylline levels provide for an estimation of serum levels if FPIA is used. The Seralyzer technique is only useful for serum theophylline measurements. Using a special device it is now easier to obtain saliva samples than by conventional methods.
A novel amplification system has been developed for the detection of free or antibody-conjugated alkaline phosphatase. The amplification system provides a 100 fold enhancement in the detection of the enzyme, compared to direct detection with chromogenic substrates. The key to the amplification system is the dephosphorylation of a potent phosphorylated inhibitor, and the visualization of this inhibitor using a second, indicator, reaction. This system is shown to provide increased sensitivity for immunoassays detecting either herpes simplex virus or respiratory syncytial virus in clinical samples. In addition, this general concept for amplification may be applicable to a variety of other hydrolytic enzymes, and is demonstrated for the enhanced detection of beta-galactosidase.
The role of sfrB and rfaH genes in the regulation of expression of membrane glycosyltransferases was studied in Escherichia coli and Salmonella typhimurium. The transferase enzymes form part of a multienzyme system involved in biosynthesis of the polysaccharide core of Gram-negative bacterial lipopolysaccharides. Several sfrB mutants of E. coli showed reductions of 90-98% in the activities of two of the glycosyltransferases (UDP-galactose:(glucosyl)lipopolysaccharide 1,6-galactosyltransferase and UDP-glucose: (glucosyl)lipopolysaccharide 1,3-glucosyltransferase). Introduction of a recombinant ColE1 plasmid restored the transferase levels to normal and simultaneously corrected the F-factor defects that also characterize sfrB mutants; recombinant plasmids containing other regions of the E. coli chromosome were ineffective. An amber mutation of the S. typhimurium rfaH gene (thought to be the homologue of the E. coli sfrB gene) resulted in 97% loss of activity of the Salmonella UDP-galactose:(glucosyl)lipopolysaccharide galactosyltransferase. Antibody precipitation studies showed that the loss of enzyme activity in the amber mutant was associated with a corresponding decrease in amount, but not in size, of the transferase protein, indicating that the gene is not the structural gene for the S. typhimurium galactosyltransferase. Taken together, the results indicate that the sfrB(rfaH) gene acts as a positive regulatory element in expression of multiple glycosyltransferases in E. coli and S. typhimurium.
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A case of a rare lethal intoxication with yew leaves (taxus baccata) is reported. The clinical signs were dizziness (onset 1 hr after yew leaves were ingested), nausea, diffuse abdominal pain, unconsciousness, weak breathing, tachycardia, brief ventricular flutter afterwards a slow pulse, and finally death by respiratory arrest and diastolic cardiac standstill. Particular attention was given to the ECG. It showed an atypical bundle branch block with a maximal QRS-duration of 0.24 sec. A striking resemblence to the ECG in the case of hyperkalemia is seen in that P-waves were absent. Therefore, the possibility is noted that an acute hyperkalemia could be partly responsible for the cardiotoxic effect of the leaf.