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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 127 records · Page 7Linked to original sources

Detection of brain-specific autoantibodies to myelin oligodendrocyte glycoprotein, S100beta and myelin basic protein in patients with Devic's neuromyelitis optica.

Neuromyelitis optica (NMO) is a rare syndrome characterized by the combination of acute optic neuritis and transverse myelitis, usually not seen in Multiple Sclerosis (MS) and other demyelinating syndromes of the central nervous system (CNS). A high prevalence of various autoantibodies has been described in patients with NMO suggesting a polyclonal activation of the humoral immune system. We examined autoantibody responses to myelin (MBP, MOG with isotypes and epitopes) and astroglial (S100beta) antigens in four patients with NMO by ELISA and Immunoblot. All patients showed a positive anti-MOG response, with one showing reaction to the MOG epitope corresponding to amino acid sequence 63-87. MBP-autoantibodies were only detected in two and S100beta-autoantibodies in one patient. Despite the limited number of samples, these findings suggest a predominant anti-MOG rather than anti-MBP or anti-S100beta autoantibody response in NMO, though no NMO-specific antibody pattern was found, which is in keeping with a widespread acute immune activation, including a strong B-cell response.

Adult↗

Patients with Multiple Sclerosis and concomitant uveitis/periphlebitis retinae are not distinct from those without intraocular inflammation.

Recent models of experimental autoimmune encephalomyelitis (EAE) have indicated that antigens co-expressed in the retina and uvea might be of pathogenetic relevance in Multiple Sclerosis (MS). We investigated the clinical spectrum and magnetic resonance imaging of 11 MS patients with concomitant uveitis, and determined the frequency of clinically silent intraocular inflammation in a prospective series of 50 patients. Two of the 11 patients had panuveitis, seven had anterior, and the remaining two had intermediate uveitis. The onset of uveitis preceded that of neurological symptoms by a mean of 8.5 years (range 1-20). None of the 50 MS patients studied prospectively by using slit lamp examinations and dilated funduscopy showed any evidence of uveitis but six patients had signs of retinal inflammation ("periphlebitis retinae"). Cranial MRI did not reveal "atypical" lesional distribution in MS patients with uveitis or periphlebitis retinae. No correlation between the type of MS and uveitis, or between the degree of neurological disability and the type of uveitis was found.

Adult↗

Soft acoustic modes in the two-dimensional spin system SrCu2(BO3)(2).

SrCu2(BO3)(2) is a two-dimensional dimerized quantum spin system which is close to a quantum critical point. The sound velocity for the longitudinal and transverse acoustic modes shows strong spin-lattice effects. The shear c(66) mode exhibits a pronounced softening of 4.5% as a function of temperature and softens more than 25% in fields up to 50 T. This huge effect occurs in the vicinity of the magnetization plateaus m/m(0) = 1/4 and 1/3. We can analyze quantitatively the temperature dependence of all measured elastic modes c(11), c(44), and c(66) with an exchange striction mechanism. The soft c(66) mode with B(2g) symmetry enables us to predict the possible symmetry of the condensed triplets in some plateaus.

Journal Article↗

Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate proton magnetic resonance spectroscopy for detection and monitoring of upper motoneuron degeneration in patients with amyotrophic lateral sclerosis. METHODS: Seventy patients with amyotrophic lateral sclerosis according to the El Escorial criteria were compared with 48 healthy control subjects. Single-volume proton magnetic resonance spectroscopy (echo time, 272 milliseconds; repetition time, 2000 milliseconds) was performed in both motor cortices for detection of N-acetylaspartate (NAA), phosphocreatine + creatine ([P]Cr), and choline-containing compounds (Cho) to calculate the metabolite ratios NAA/Cho, NAA/(P)Cr, and Cho/(P)Cr. In addition, absolute metabolite concentrations of NAA, (P)Cr, and Cho were obtained in 30 patients and 15 controls with the unsuppressed water signal used as an internal reference. RESULTS: Absolute concentrations of NAA (P<.001) and (P)Cr (P<.05) were reduced in motor cortices of patients, whereas Cho concentrations remained unchanged. The NAA/Cho and NAA/(P)Cr ratios were reduced in all El Escorial subgroups (P<.001). The Cho/(P)Cr ratio was elevated in patients with definite amyotrophic lateral sclerosis (P<.05). Metabolite ratio changes corresponded to the lateralization of clinical symptoms and were weakly correlated with disease duration and disease severity. In follow-up observations of 16 patients during a mean (+/-SD) of 12.1 +/- 8.7 months, NAA/Cho dropped by 9.1% (P<.01), and Cho/(P)Cr increased by 7.0% (P<.01). Changes of metabolite ratios were significantly correlated with progression of disease severity. CONCLUSIONS: Measurement of NAA concentrations and NAA/Cho ratios appear to be most suitable for detection of motor cortex degeneration by single-volume proton magnetic resonance spectroscopy. Reduced NAA/Cho ratios correspond to aspects of the clinical presentation and reflect disease progression in follow-up measurements.

Adult↗

Life after the screen: making sense of many P-values.

A multiple analytic approach may be useful for analyzing complex traits since different methods extract both similar and distinct, but complementary pieces of information from genome screen data on extended pedigrees. We examined the usefulness of combining p-values both across methods and across adjacent markers, taking into account the observed correlation structure among these p-values. To this end, we employed the recently proposed truncated product method [Zaykin et al., Genet Epidemiol, in press]. It appears that this approach is helpful for visualizing priority regions for follow-up analysis and reducing the number of false-positive linkage signals.

Chromosome Mapping↗

Reduced perisomatic inhibition, increased excitatory transmission, and impaired long-term potentiation in mice deficient for the extracellular matrix glycoprotein tenascin-R.

The role of the extracellular matrix molecule tenascin-R (TN-R) in regulation of synaptic transmission and plasticity in the CA1 region of the hippocampus was studied using mice deficient in expression of this molecule. The mutant mice showed normal NMDA-receptor-mediated currents but an impaired NMDA-receptor-dependent form of long-term potentiation (LTP) as compared to wild-type littermates. Reduced LTP in mutants was accompanied by increased basal excitatory synaptic transmission in synapses formed on CA1 pyramidal neurons. A possible mechanism for increased excitatory synaptic transmission in mutants could involve modulation of inhibition, since TN-R and its associated carbohydrate HNK-1 decorate perisomatic interneurons. Indeed, the amplitudes of unitary perisomatic inhibitory currents were smaller in mutants compared to wild-type mice. Thus, our data show that a deficit in TN-R results in reduction of perisomatic inhibition and, as a consequence, in an increase of excitatory synaptic transmission in CA1 to the levels close to saturation, impeding further expression of LTP.

Animals↗

Preliminary phylogeny of Encarsia Förster (Hymenoptera: Aphelinidae) based on morphology and 28S rDNA.

Species of Encarsia Förster (Hymenoptera: Aphelinidae, Coccophaginae) are economically important for the biological control of whitefly and armored scale pests (Hemiptera: Aleyrodidae, Diaspididae). Whereas some regional keys for identification of Encarsia species are now available, few studies have addressed relationships within this diverse and cosmopolitan genus because of unreliable morphological data. Nuclear sequences of the D2 expansion region of 28S rDNA were determined from 67 strains of 24 species representing 10 species groups of Encarsia, 2 strains of Encarsiella noyesi Hayat, and 1 strain of Coccophagoides fuscipennis Girault. Analysis of molecular data alone and combined with morphological data resolves many nodes not resolved by morphology alone and offer insights into which morphological characters are useful for supporting group relationships. All analyses that include molecular data reveal Encarsia to be paraphyletic with respect to Encarsiella. If monophyly of Encarsia is constrained, the relationships are the same but with a different root within Encarsia, and these trees are presented as an alternate hypothesis. The luteola and strenua species groups are shown by both morphological and molecular data to be monophyletic, whereas the inaron group, the E. nigricephala + luteola group, and the E. quericola + strenua group are supported only by molecular data. The aurantii and parvella species groups are not supported in any of the analyses. The utility of morphological characters for defining species group relationships is discussed.

Animals↗

[Hairdex: a tool for evaluation of disease-specific quality of life in patients with hair diseases].

Because of a strong reduction of life quality in patients with hair loss, a special questionnaire was developed following the general Skindex questionnaire for dermatoses. The Hairdex was evaluated in 75 female hair patients. The aim of the study was to prove the questionnaire's statistical values, reliability, validity, general acceptance and accuracy. The clinical manifestation of hair loss was categorized as "not visible", slightly visible" and "obviously visible". The hair loss lead to great differences in the life quality of both the patients with obvious hair loss and in patients with non-visible hair loss, especially in the categories "emotions", "self-confidence" and "stigmatization". The convergent and discriminant validity of the questionnaire was satisfactory. The acceptance of the questionnaire was very good with 90%. The hairdex-questionnaire represents a reliable and patient-oriented instrument for evaluation of life quality in hair diseases. The reliability of the questionnaire concerning longitudinal therapeutic effects will need to be investigated in further studies.

Adult↗

Brain involvement in haemolytic-uraemic syndrome: MRI features of coagulative necrosis.

We describe radiological demonstration of brain involvement in haemolytic-uraemic syndrome (HUS) in two siblings with a very different clinical course. While the brother presented with a mild, reversible encephalopathy, his sister developed high-signal lesions in the cortex, putamen and caudate nucleus on T1-weighted images, seen as dense areas on CT. Biopsy revealed coagulative necrosis due to microthrombosis without haemorrhage, calcification or infection. These findings suggest a possible prognostic role for MRI in cases of encephalopathy due to HUS.

Blood Coagulation Disorders↗

[Effect of prostaglandin F2 alpha on proliferation of corneal endothelial cells in vitro].

INTRODUCTION: Prostaglandins, especially PG-F2 alpha, have recently been introduced as a new local glaucoma medication. The modulation of cell proliferation and collagen synthesis in various tissues are the major effects of these agents. However, it is unknown whether PG-F2 alpha also modulates the proliferation of the corneal endothelium. METHODS: Bovine corneal endothelial cells (BCEC) were cultured according to established protocols. Experiments were performed after the 1st passage under serum-reduced conditions. A total of 10(4) cells/well were seeded and the cells were then incubated with different (5 x 10(-6) bis 5 x 10(-4) mg/ml) concentrations of PG-F2 (Sigma). The number of cells was determined every 24 h until day 5. Toxicity tests were performed by means of the trypan blue exclusion assay. RESULTS: PG-F2 alpha induced a significant stimulation of BCEC proliferation with all concentrations tested. At the highest concentration of PG-F2 alpha, a 2-fold increase in cell number was found after 5 days only compared to unsupplemented control cultures. No signs of cellular toxicity or morphological alterations could be detected in PG-F2 alpha-supplemented cells. DISCUSSION: For the first time, the present study demonstrates a stimulatory effect of PG-F2 alpha on the corneal endothelium. It appears that this effect is also induced by the PG-F2 alpha concentration determined in the aqueous humour of patients after topical latanoprost application. However, due to the strong contact inhibition of endothelial cells in situ, these results cannot be directly extrapolated to the situation in patients with topical latanoprost treatment.

Animals↗

Frequency discrimination threshold at search call frequencies in the echolocating bat, Eptesicus fuscus.

While searching for prey in open spaces, Epteisicus fuscus emits long-duration, downward frequency-modulated calls which cover a frequency band of about 28-22 kHz. In the ascending auditory pathways of E. fuscus, neurons tuned to these search call frequencies are characterised by a remarkably high frequency selectivity and very sensitive absolute thresholds. We investigated whether this narrow tuning is reflected in an exceptional psychoacoustic frequency discrimination ability. The average frequency difference limen of E. fuscus at search call frequencies determined in a two-alternative, forced-choice experiment amounted to about 420 Hz, corresponding to a Weber ratio of 0.017. This value is similar to those found in non-echolocating mammals, and an order of magnitude larger than the frequency difference limens of bats emitting constant-frequency call components. We discuss these differences in frequency difference limen, and relate them to different echolocation strategies.

Acoustics↗

Photoradiation of perfused placental tissue--a suitable in vitro model for photodynamic therapy?

Our aim was to evaluate the isolated placental lobule as a model to study the cytotoxic effects of photodynamic therapy (PDT) in vitro. Ten human placental lobules were dually perfused with a modified medium 199 for a 4-hour period. Photosan III was added to the fetal perfusate at a dose of 5 mg/kg tissue, and laser light (630 nm wavelength) provided by an argon-pumped dye laser was applied at 50 J/cm2 in the experimental group (n=5). Potassium and lactate dehydrogenase (LDH) release into the perfusate as well as the transplacental creatinine passage from PDT-treated placentas and control placentas (n=5) were compared, and light microscopic examinations of the placental tissue were performed after the experiments. Potassium release into the fetal perfusate was higher in the PDT-treated placental lobules (p<0.05), and weight gain during the artificial perfusion suggests the development of edema only in the photoradiated lobules (p<0.01). The release of the bigger molecules of the LDH however was comparable in the two experimental groups, and transplacental creatinine passage was not affected by photoradiation. Light microscopic examinations demonstrated lesions at the cytotrophoblast, the syncytiotrophoblast and the endothelium of the fetal vessels of the photoradiated placentas, although they were not specific and could also be found in the control tissue. We conclude that the isolated placenta may be used to study cytotoxic effects of photoradiation in vitro, but better specifity and sensitivity might be achieved if a. The perfusion time is prolonged to make the difference between the experimental and the control group clearer and b. Electron microscopic investigations are made to demonstrate intracellular lesions of the mitochondria and the endoplasmic reticulum.

Cell Nucleolus↗

Phenotype assignment in symptomatic female carriers of X-linked adrenoleukodystrophy.

However, only very few studies have systematically investigated the extent and distribution of nervous and endocrine system involvement in female carriers of X-ALD. To define the phenotype in symptomatic female carriers of X-ALD we performed a prospective study including eight symptomatic women who were followed for a mean period of 3.4+/-1.8 years (range 1-6) using standardized clinical examination protocols, magnetic resonance imaging and spectroscopy, evoked potential studies including visual, brainstem auditory, somatosensory and magnetic evoked potentials, neurographic recordings and endocrine studies. Spastic paraparesis and decreased vibration sense in the lower extremities were the most frequent clinical findings. Slightly hyperintense symmetric parieto-occipital white matter lesions on magnetic resonance imaging were detectable in two of seven cases, and the N-acetylaspartate/choline ratios on magnetic resonance spectroscopy were decreased in three of seven patients. P40 latencies were abnormal in all patients, and central motor conduction times to the lower extremities in seven of eight patients. Prolonged latencies of brainstem auditory evoked potential waves III-V or interpeak latencies of waves I-III, I-V and III-V were detectable in all patients. The degree of walking impairment was positively correlated with the duration of clinical disease (r=0.58, P < 0.05) and inversely correlated with the N-acetylaspartate/choline ratios (r=0.85; P < 0.05). Neurographic recordings revealed only subtle abnormalities, suggesting that nervous system involvement in symptomatic female carriers of X-ALD is confined mainly to the central nervous system. No evidence of adrenal insufficiency was detected in any of the patients.

Adrenal Insufficiency↗

Prostate-specific antigen in female urine: a prospective study involving 217 women.

OBJECTIVES: Histomorphologic studies have provided evidence of prostate-specific antigen (PSA)-producing tissue in the female urethra. Some urine samples from women in a small series were positive for PSA, but no systematic investigation of this subject has been done to date. METHODS: In a prospective study, we analyzed whether PSA occurs in the urine of women and what factors induce detectable PSA levels. The urine samples of 217 women were analyzed (Hybritech-Tandem E-PSA) under standardized conditions. The impact of urine pH and volume was investigated, and the results were correlated with clinical data (age, residual urine, urinary tract infection and prior sexual intercourse within 48 hours). RESULTS: A positive PSA level greater than the detection limit of 0.1 ng/mL was found in 11% of the analyzed samples; their mean value was 0.29 ng/mL. pH correction did not result in a significant difference. The voiding volume had no influence on the PSA level. Among the cases of detectable PSA, women younger than 50 years of age (n = 14) had a mean PSA of 0.34 ng/mL and those older than 50 years (n = 9) a mean of 0.23 ng/mL. One of 9 women with and 22 of 208 women without residual urine volume had a detectable PSA level, as did 0 of 20 with and 23 of 197 women without urinary tract infection, and 3 of 7 with and 20 of 210 women without prior sexual intercourse within the previous 48 hours. None of the differences were significant. CONCLUSIONS: A urine PSA level was detected in 11% of all women studied, with PSA values apparently age dependent. Any urine portion is suitable for analysis. No influence was determined for residual urine volume or urinary tract infection. Sexual intercourse may cause detectable PSA values, but the data of this study did not provide sufficient evidence for this hypothesis.

Adult↗

Medical target prediction from genome sequence: combining different sequence analysis algorithms with expert knowledge and input from artificial intelligence approaches.

By exploiting the rapid increase in available sequence data, the definition of medically relevant protein targets has been improved by a combination of: (i) differential genome analysis (target list): and (ii) analysis of individual proteins (target analysis). Fast sequence comparisons, data mining, and genetic algorithms further promote these procedures. Mycobacterium tuberculosis proteins were chosen as applied examples.

Algorithms↗

Simultaneous determination of total and free drug plasma concentrations combined with batch-wise pH-adjustment for the free concentration determinations.

Batch-wise pH-adjustment of plasma samples for free concentration determinations can be performed directly in the ultrafiltration devices using a CO(2) incubator. The pH of the samples could be adjusted to within a sufficiently narrow interval though the initial differences in pH were large. The possibilities for simultaneous determination of free and total concentrations were studied using NAD-299 as a model compound. By adding a known concentration of a (13)C-labelled isotope of the studied drug to the sample prior to ultrafiltration it was possible to calculate the total concentration from the ratio of the drug peak area to the isotope peak area while the free concentration was calculated from the drug peak area. Initial experiments showed good precision and accuracy as well as a good correlation with concentration data acquired in the conventional way.

Chromatography, Liquid↗

Quality of life in breast cancer patients: a cluster analytic approach. Empirically derived subgroups of the EORTC-QLQ BR 23--a clinically oriented assessment.

Quality of life (QOL) questionnaires are integrated into clinical trials in order to evaluate different treatments, and rarely used in a diagnostic sense. The aim of this study was to identify clinically meaningful subgroups by means of established QOL tools. Since January 1995, a field study funded by the German Ministry of Health was conducted to evaluate quality of care of breast cancer patients in eastern Thuringia. During the follow-up period, the European Organization of Research and Treatment of Cancer (EORTC), Quality of Life C30 and the breast specific module BR23 were mailed. One-hundred-fifty-eight women answered both questionnaires. A cluster analysis was performed to distinguish subgroups on the basis of QOL-BR23 scores. According to the QOL outcomes, four subgroups could be described. There was a strong relation to operative treatment (p < 0.05), while no association with the adjuvant treatment strategy was observed. The subsets identified on the basis of BR23 scores were significantly related to all C30 domains. It was possible to demonstrate the clinical validity in terms of clinical and sociodemographic data. No association was found with the marital status or the highest level of education, while a worsening of the financial situation was associated. It could be shown that a distinction of patient subgroups based on clinically meaningful BR23 data is possible. Subgroups with specific profiles could be identified. In the future, the characterisation of subgroups could provide a possibility to generate indications for specific supportive interventions.

Aged↗

Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH)-Re-evaluation of chromosome aberration rates in early spontaneous abortions.

Comparative genomic hybridisation (CGH) represents an alternative molecular-cytogenetic technique capable of detecting chromosomal imbalances by reverse fluorescence in situ hybridisation. As the technique uses genomic DNA for assessment it does not rely on metaphase chromosomes in the test material and thus circumvents technical problems associated with tissue culturing. In the present study, we applied CGH to identify chromosome anomalies in 60 spontaneous abortions of the first trimester, that had failed to grow in culture. In 57 out of 60 cases CGH analyses were successful. The overall aneuploidy rate detected was 72%. Trisomy was the predominant chromosome anomaly accounting for 68.0% of abnormal abortions, followed by triploidy (17.1%) and monosomy X (9.8%). An unbalanced structural rearrangement was found in one (2.4%) abortion. Most frequently involved in trisomies were chromosomes 16 (32.1%), 7 and 22 (10.7% each), 4, 13, 15, and 21 (7.2 % each). Three triploid cases and one complete mole were detected by microsatellite analysis as supplementary method. CGH data on culture failures were compared with data derived from 4693 successfully karyotyped first trimester spontaneous abortions, resulting in a chromosome aberration rate of 64.8%. The distribution of the different chromosome anomalies was similar with the exception of a higher rate of trisomies 7 and of XYY-triploidies in the culture failures. Based on our data we suggest that the genetic contribution to pregnancy loss is still underestimated. Investigating abortion tissues hitherto unassessed by conventional methods, we suggest that the contribution of chromosome aberrations to first trimester pregnancy loss is nearly 70%.

Abortion, Spontaneous↗