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Biomedical subjects

S Walter

Publications and source records attributed to S Walter.

At least 37 records · Page 2Linked to original sources

[Anemia, eosinophilia and generalized weakness in a 20-year old African].

CASE HISTORY AND DIAGNOSIS: A 20-year-old African man was admitted to hospital with anemia, eosinophilia, raised liver enzymes and hepatosplenomegaly. Previously, on arrival in Germany, he had undergone a routine medical check-up where simple microscopy of a feces sample as well as serology for lues, AIDS and hepatitis B had all been negative. In our hospital a stool specimen was examined for ova and parasites and revealed ova of Schistosoma mansoni and confirmed the diagnosis of bilharziosis. For the detection of helmintic ova repeated stool examinations with use of concentration techniques are required. Staging by endoscopies, ultrasonography revealed colon pseudopolyposis and periportal fibrosis complicated by portal hypertension and esophageal varices. TREATMENT AND COURSE: Chemotherapy with Praziquantel was effective in eliminating the parasites but in advanced stages chronic fibrotic changes are usually irreversible. Further monitoring will therefore be necessary in our patient. CONCLUSION: Due to increasing migration and international travel, also doctors working in industrialized countries should be aware of tropical diseases.

Adult↗

[Leading symptoms of chest pain in the emergency room. Using cardiac markers for risk stratification].

BACKGROUND AND OBJECTIVE: The acute coronary syndrome (ACS)--acute infarction or unstable angina pectoris--requires special monitoring and differentiated treatment. A prospective trial was undertaken to determine (1) clinical characteristics of patients with chest pain; (2) value of cardiac markers troponin T, myoglobin and CK-MB mass in differentiating cardiac and noncardiac chest pain; (3) the proportion of patients with ACS in whom these markers provided helpful additional information on admission and afterwards. PATIENTS AND METHODS: 233 consecutive patients (134 men, 99 women; aged 18-98 years), presenting in 1998 with nontraumatic chest pain at the emergency unit of the Lippe-Detmold Hospital were prospectively enrolled in the study. Levels of troponin T, myoglobin, CK-MB mass and activity and creatine kinase were measured on admission and after 2, 4 and 12-24 hours. RESULTS: ACS was ultimately diagnosed in 73 patients (31%). These were significantly older (p = 0.0015) and more often male (p = 0.046). 91% of patients with ACS but only 68% of those without described the chest pain as a sense of pressure or stabbing (p = 0.0002). Measurement of troponin T and myoglobin on admission was helpful in 39% of those with ACS, compared with 15% of those without. When the admission ECG was normal or nonspecific in patients with ACS, troponin T was elevated in 16%, CK-MB mass in 24%. In patients with unstable angina no single marker was associated with an increased risk (high rate of special supervision and intervention). CONCLUSION: In the assessment of patients with acute chest pain clinical judgement plays the predominant role. In the mostly elderly and male patients with ACS (31% of the cohort) feeling of pressure or stabbing chest pain were most prominent (91%). Cardiac markers troponin T, CK-MB mass and myoglobin were helpful in the differential diagnosis of chest pain, even when the ECG was unremarkable or nonspecific. At the time of admission myoglobin was the most significant marker for acute myocardial infarction or unstable angina.

Adolescent↗

Stability, folding, dimerization, and assembly properties of the yeast prion Ure2p.

The [URE3] factor of Saccharomyces cerevisiae propagates by a prion-like mechanism and corresponds to the loss of the function of the cellular protein Ure2. The molecular basis of the propagation of this phenotype is unknown. We recently expressed Ure2p in Escherichia coli and demonstrated that the N-terminal region of the protein is flexible and unstructured, while its C-terminal region is compactly folded. Ure2p oligomerizes in solution to form mainly dimers that assemble into fibrils [Thual et al. (1999) J. Biol. Chem. 274, 13666-13674]. To determine the role played by each domain of Ure2p in the overall properties of the protein, specifically, its stability, conformation, and capacity to assemble into fibrils, we have further analyzed the properties of Ure2p N- and C-terminal regions. We show here that Ure2p dimerizes through its C-terminal region. We also show that the N-terminal region is essential for directing the assembly of the protein into a particular pathway that yields amyloid fibrils. A full-length Ure2p variant that possesses an additional tryptophan residue in its N-terminal moiety was generated to follow conformational changes affecting this domain. Comparison of the overall conformation, folding, and unfolding properties, and the behavior upon proteolytic treatments of full-length Ure2p, Ure2pW37 variant, and Ure2p C-terminal fragment reveals that Ure2p N-terminal domain confers no additional stability to the protein. This study reveals the existence of a stable unfolding intermediate of Ure2p under conditions where the protein assembles into amyloid fibrils. Our results contradict the intramolecular interaction between the N- and C-terminal moieties of Ure2p and the single unfolding transitions reported in a number of previous studies.

Amyloid↗

The gene encoding p202, an interferon-inducible negative regulator of the p53 tumor suppressor, is a target of p53-mediated transcriptional repression.

The p53 tumor suppressor protein regulates the transcription of regulatory genes involved in cell cycle arrest and apoptosis. We reported previously that overexpression of p202, an interferon-inducible negative regulator of cell growth, negatively regulates the transcriptional activity of p53. Now we identify the gene encoding p202 as one whose mRNA and protein expression decrease in cells following the expression of wild-type, but not mutant, p53. Furthermore, the levels of p202 also decrease after exposure of cells to ultra violet light, which correlate with increase in the levels of p53. We report that the sequence-specific DNA binding of p53 to the 5'-regulatory region of the 202 gene contributes to the transcriptional repression of the 202 gene. Interestingly, overexpression of p202 in cells induced to undergo p53-dependent apoptosis significantly delays this process, indicating that the negative regulation of the 202 gene by wild-type p53 is important to potentiate apoptosis.

Animals↗

Latency of compound muscle action potentials of the anal sphincter after magnetic sacral stimulation.

The aim of this study was to present the failure rate and normal values for motor latency of the anal sphincter after magnetic sacral stimulation (LMSS) using a modified recording technique. A bipolar sponge electrode was placed in the anal canal for recording. A ground electrode was placed in the rectum to reduce stimulus artifact. Magnetic stimulation was induced through a twin coil energized by a Maglite-r25 generator. Two groups were examined: 14 healthy volunteers and 14 patients with a spinal cord injury (SCI) above the conus. Nine of 56 studies (16%) failed. There were no significant differences in latency between right- and left-sided stimulation or between the healthy group and the SCI patients. As described, LMSS measurements are minimally invasive and have a low failure rate. They may be used to test the integrity of the distal motor pathway in patients with bladder or bowel dysfunction who may benefit from continuous electrical sacral root stimulation.

Action Potentials↗

Evaluation of the sacroanal motor pathway by magnetic and electric stimulation in patients with fecal incontinence.

PURPOSE: The aim of this controlled study was to examine whether it was feasible to use magnetic stimulation as a new diagnostic tool to evaluate the motor function of the sacral roots and the pudendal nerves in patients with fecal incontinence. PATIENTS AND METHODS: Nineteen consecutive patients (17 females) with a median age of 67 (range, 36-78) years referred for fecal incontinence and 14 healthy volunteers (six females) with a median age of 42 (range, 23-69) years were examined. Latency times of the motor response of the external anal sphincter were measured after electric transrectal stimulation of the pudendal nerve and magnetic stimulation of the sacral roots. RESULTS: The success rates of pudendal nerve terminal motor latency and sacral root terminal motor latency measurements were 100 and 85 percent, respectively, in the control group and 94 and 81 percent, respectively, in the fecal incontinence group. Median left pudendal nerve terminal motor latency was 1.88 (range, 1.4-2.9) milliseconds in the control group and 2.3 (range, 1.8-4) milliseconds in the fecal incontinence group (P < 0.006). Median right pudendal nerve terminal motor latency was 1.7 (range, 1.3-3.4) milliseconds in the control group and 2.5 (range, 1.7-6) milliseconds in the fecal incontinence group (P < 0.003). Median left sacral root terminal motor latency was 3.3 (range, 2.1-6) milliseconds in the control group and 3.7 (range, 2.8-4.8) milliseconds in the fecal incontinence group (P < 0.03). Median right sacral root terminal motor latency was 3 (range, 2.6-5.8) milliseconds in the control group and 3.9 (range, 2.5-7.2) milliseconds in the fecal incontinence group (P = 0.15). CONCLUSIONS: Combined pudendal nerve terminal motor latency and sacral root terminal motor latency measurements may allow us to study both proximal and distal pudendal nerve motor function in patients with fecal incontinence. Values of sacral root terminal motor latency have to be interpreted cautiously because of the uncertainty about the exact site of magnetic stimulation and the limited magnetic field strength.

Adult↗

Effects of magnetic sacral root stimulation on anorectal pressure and volume.

PURPOSE: Electrical sacral root stimulation induces defecation in spinal cord injury patients and is currently under examination as a new therapy for fecal incontinence. In contrast to electrical stimulation, magnetic stimulation is noninvasive. To gain more insight into the mechanism of action of sacral root stimulation, we studied the effects of magnetic sacral root stimulation on anorectal pressure and volume in both fecal incontinence and spinal cord injury patients. METHODS: Three groups were examined: 14 healthy volunteers, 18 fecal incontinence patients, and 14 spinal cord injury patients. Repetitive magnetic sacral root stimulation was performed bilaterally using bursts of five seconds at 5 Hz. Anal and rectal pressure changes and rectal volume changes were measured. RESULTS: An increase in anal pressure was seen in 100 percent of the control subjects, in 86 percent of the spinal cord injury patients, and in 73 percent of the fecal incontinence patients (P = 0.03). The overall median pressure rise after right-sided and left-sided stimulation was 12 (interquartile range, 8-18.5) and 13 (interquartile range, 6-18) mmHg at the mid anal level. A decrease in rectal volume was provoked in 72 percent of the control subjects, in 79 percent of the spinal cord injury patients, and in 50 percent of the fecal incontinence patients. Overall median volume changes after right-sided and left-sided stimulation were 10 (range, 5-22) and 9 (range, 5-21) percent from baseline volume. An increase in rectal pressure could be measured in 56 percent of the control subjects, 77 percent of the fecal incontinence patients, and 43 percent of the spinal cord injury patients. Median pressure rises after right-sided and left-sided stimulation were 5 (range, 3-12) and 5 (range, 3-5) mmHg. CONCLUSIONS: Magnetic sacral root stimulation produces an increase in anal and rectal pressure and a decrease in rectal volume in healthy subjects and patients with fecal incontinence or a spinal cord injury.

Adult↗

[Intraoperative radiotherapy--progress with a CT-assisted navigation system].

INTRODUCTION: The fact that conventional intraoperative radiotherapy (IORT) does not give the opportunity for exact documentation of the applied radiation volume and dose distribution has been criticised. We would like to introduce a system for surgical navigation and documentation of the flab positioning for intraoperative brachytherapy in afterloading flab technique. METHODS: Our system consists of an electromagnetic 3D digitizer and a PC workstation. Preoperatively taken spiral CT scans of the tumour region are used for navigation and documentation of the flab positioning, analogous to the procedure in neuronavigation. Registration is done via an external reference system attached to the iliac bone of the patient. RESULTS: The mean accuracy of digitalization of the 100 spheres in a pelvis model is about 2.6 +/- 0.5-3.7 +/- 0.9 mm. Mean navigation accuracy is 2.4 +/- 0.8-3.3 +/- 0.8 mm. These figures correspond to the clinical experience of our surgeons. CONCLUSIONS: The optimization of the flab positioning by CT-guided navigation and the more accurate documentation of the dose volume and distribution in the patient is an important step towards improving the quality of individual radiotherapy. We are of the opinion that surgical navigation in the pelvic region should be subject to additional investigation in order to optimize the procedure.

Brachytherapy↗

[TFF peptides. New mucus-associated secretory products of the conjunctiva].

The molecular architecture of the human ocular mucus is not yet completely understood. Recently, TFF peptides (formerly known as trefoil factors or P-domain peptides) could be identified as new constituents of this delicate mucus. Members of the TFF-peptide family are typical secretory products of mucous epithelia and three are known in humans and designated as TFF1, TFF2 and TFF3. They enhance cell migratory processes (motogenic effect), they show anti-apoptotic effects and are inflammatory modulators Both TFF1 and TFF3 expression could be monitored by the reverse transcription-polymerase chain reaction (RT-PCR) in the human conjunctiva; in contrast, TFF2 transcripts were not detectable. Using immunohistochemistry, TFF1 and TFF3 peptides were found in varying concentrations solely in secretory vesicles of conjunctival goblet cells. This localisation matches precisely that of the secretory mucin MUC5AC. Thus, conjunctival TFF1 and TFF3 have to be considered as typical mucin-associated peptides probably modulating the rheological properties of the ocular mucus and the tear fluid. Future investigations are in progress to elucidate the role of TFF-peptides during pathological conditions of the eye as well as their diagnostic and therapeutic potential.

Conjunctiva↗

Steroid-mediated inhibition of radiation-induced apoptosis in C4-1 cervical carcinoma cells is p53-dependent.

In human papillomavirus (HPV) infected cervical epithelial cells the synthetic steroid dexamethasone inhibits radiation-induced apoptosis and increases the transcription of HPV E6/E7, enhancing p53 degradation. The aim of this study was to determine if suppression of apoptosis was mechanistically linked to changes in p53. HPV 16 E6 or E6/E7 expression vectors were transiently transfected into C4-1 HPV 18-positive cervical carcinoma cells to mimic the enhanced transcription following steroid treatment. After irradiation, apoptosis was suppressed in these cells comparable to the effect observed after steroid treatment alone. To confirm whether loss of p53 was responsible for the inhibition of apoptosis, residual p53 in C4-1 cells was targeted by stable transfection with a dominant-negative p53 mutant. While radiation-induced apoptosis increased after mutant transfection, inhibition of programmed cell death by steroid treatment was either eliminated or substantially reduced. Steroid-dependent inhibition of radiation-induced apoptosis in carcinoma of the cervix involves E6 modulation of p53 expression and may adversely affect treatment.

Anti-Inflammatory Agents↗

Folding of malate dehydrogenase inside the GroEL-GroES cavity.

The chaperonin GroEL binds nonnative substrate protein in the hydrophobic central cavity of an open ring. ATP and GroES binding to the same ring converts this cavity into an encapsulated, hydrophilic chamber that mediates productive folding. A 'rack' mechanism of initial protein unfolding proposes that, upon GroES and ATP binding, the polypeptide is stretched between the binding sites on the twisting apical domains of GroEL before complete release into the chamber. Here, the structure of malate dehydrogenase (MDH) subunit during folding is monitored by deuterium exchange, peptic fragment production and mass spectrometry. When bound to GroEL, MDH exhibits a core of partially protected secondary structure that is only modestly deprotected upon ATP and GroES binding. Moreover, deprotection is broadly distributed throughout MDH, suggesting that it results from breaking hydrogen bonds between MDH and the cavity wall or global destabilization, as opposed to forced mechanical unfolding.

Adenosine Triphosphate↗