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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 55 records · Page 3Linked to original sources

An integrated taxonomic study of Fusarium langsethiae, Fusarium poae and Fusarium sporotrichioides based on the use of composite datasets.

An integrated systematic study was carried out to clarify the taxonomical position and relationship of Fusarium langsethiae to other taxa within the Fusarium section Sporotrichiella. Strains of this species were compared with strains of the closely related species Fusarium poae and Fusarium sporotrichioides using a composite dataset. This set consisted of DNA sequences derived from the ribosomal internal transcribed spacer (ITS) regions, partial sequences of the ribosomal intergenic spacer (IGS) region, the beta-tubulin and translation elongation factor-1 alpha (EF-1alpha) genes, AFLP fingerprints, chromatographic data on secondary metabolites and morphological data and growth characteristics. From these combined data, a consensus matrix was calculated by taking the mean of all pairwise distances between single isolates over all separate datasets. The consensus matrix was used as the basis for the construction of a UPGMA dendrogram and a multidimensional scaling, both of which revealed a clear separation of the three taxa. Partial IGS, EF-1alpha and beta-tubulin sequence-as well as chromatography-and AFLP-derived similarities turned out to be comparably consistent, while ITS sequence- and morphology-derived similarity matrices were rather divergent.

Base Sequence↗

[Interventional catheter closure of persistent foramen ovale (PFO) in a patient with paradoxical embolism and Brugada's syndrome].

HISTORY AND ADMISSION FINDINGS: A 41-year-man was admitted because of acute bluish-grey skin discoloration in cold sensation in the right hand. His brother had suffered sudden cardiac death, aged 42 years. INVESTIGATIONS: Angiography demonstrated embolic occlusion of the digital artery of the right thumb. Transesophageal echocardiography showed a persistent foramen ovale (PFO) with an aneurysm of the atrial septum (ASA) with marked right-to-left shunt of contrast medium during a Valsalva maneuvre as well as two smaller septal fenestrations. There was no evidence of any other source of embolism. The resting electrocardiogram showed an incomplete right bundle branch block with ST elevations in V (1)-V (3), changes like those described in Brugada's syndrome. TREATMENT AND COURSE: Paradoxical embolism having been demonstrated, the PFO with ASA were closed with a percutaneously introduced Helex septum occluder. Later an implantable cardioverter-defibrillator (ICD) was introduced. CONCLUSIONS: A PFO, particularly if associated with an atrial aneurysm, is an important site of paradoxical embolism. In symptomatic patients percutaneous transcatheter septal occlusion should be considered preceding any ICD insertion thought necessary for concurrent Brugada's syndrome.

Adult↗

[Multifocal nodular fatty infiltration of the liver associated with porphyria and haemochromatosis].

HISTORY AND CLINICAL FINDINGS: A 64-year-old woman suffered from severe fatigue. She was admitted to our outpatient unit for a diagnostic evaluation of multiple liver lesions as well as an adrenal gland tumor. Diabetes mellitus was diagnosed 22 years ago. Clinical evaluation revealed a mild obesity and a facial hypertrichosis. INVESTIGATIONS: Apart from elevated liver enzymes, serum ferritin and transferrin saturation were increased. Suspected haemochromatosis was verified by genetic analyses. Analyses of a 24 hours urine sample revealed typical constellation of a chronic hepatic porphyria. The liver lesions were diagnosed as multifocal fatty infiltrations using computer tomography. The patient refused a liver biopsy. The tumor of the adrenal gland represented an adenoma without endocrine activity. TREATMENT AND COURSE: Repeated phlebotomies were performed for the treatment of haemochromatosis. In the following serum ferritin returned to normal and liver enzymes as well as hyperporphyriuria decreased markedly. Diabetes was better controlled due to decrease of insulin requirements, too. CONCLUSION: This case report highlights the association of hereditary haemochromatosis and chronic hepatic porphyria, which presumably cause multifocal nodal fatty infiltration of the liver. Iron overload is likely the underlying cause, which represents the target for treatment options.

Adenoma↗

CSF lactate dehydrogenase activity in patients with Creutzfeldt-Jakob disease exceeds that in other dementias.

The diagnosis of Creutzfeldt-Jakob disease (CJD) is still made by exclusion of other dementias. We now evaluated lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) as a possible additional diagnostic tool. CSF LDH levels of patients with CJD (n = 26) were compared with those in other dementias (n = 28). LDH isoenzymes were determined in a subset (n = 9). Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients. We conclude that in addition to established CSF parameters, LDH and its isoenzymes might serve as a further help to discriminate between CJD and other dementias.

Aged↗

Inhibition of lung carcinoma cell growth by high density lipoprotein-associated alpha-tocopheryl-succinate.

Alpha-tocopheryl-succinate (alphaTS) is a synthetic, anti-neoplastic derivative of alpha-tocopherol. Here we studied the effects of free and high-density lipoprotein subclass 3 (HDL3)-associated alphaTS on the growth of human (A549) and mouse Lewis (LL2) lung carcinoma cells. Both free and HDL3-associated alphaTS inhibited A549 growth in a time- and concentration-dependent manner. Treatment of A549 cells with alphaTS-enriched HDL3 led to DNA fragmentation and a time-dependent decrease in immunoreactivity of poly(ADP-ribose)polymerase. Uptake experiments revealed a high capacity for selective alphaTS uptake in excess of holoparticle endocytosis. Overexpression of scavenger receptor class B, type I (SR-BI), the prime receptor mediating selective lipid uptake, in A549 cells resulted in significantly increased selective alphaTS uptake, a finding associated with complete cellular growth arrest. The present in vitro findings were verified in an in vivo model: tumor inoculation in C57BL6 was performed with either wild-type, beta-galactosidase- or SR-BI-overexpressing LL2 cells. After tumor inoculation, the animals received six consecutive intravenous injections of alphaTS. This experimental setup resulted in significantly reduced tumor burden in animals that were inoculated with SR-BI-overexpressing LL2 cells but not in animals inoculated with wild-type or beta-galactocidase-transfected cells. Based on our in vitro and in vivo findings, we propose that SR-BI could provide a novel route for HDL3-mediated drug delivery of anti-neoplastic drugs.

Adenoviridae↗

Keratin 8 Y54H and G62C mutations are not associated with inflammatory bowel disease.

BACKGROUND: Keratin 8 is a major component of intermediate filaments in single-layered epithelia of the gastrointestinal tract. Keratin 8 deficient mice display signs of colitis and diarrhoea characteristic for inflammatory bowel disease. Very recently, two keratin 8 mutations, Y54H and G62C, were identified. AIMS: We investigated if these keratin 8 missense mutations were associated with inflammatory bowel disease. PATIENTS: In total, 217 German patients with Crohn' s disease, 131 German patients with ulcerative colitis, and 560 German control subjects were enrolled in this study. METHODS: Samples were analysed by PCR amplification and subsequent melting curve analysis using fluorescence resonance energy transfer probes. RESULTS: The G62C mutation was detected in five (2.3%) patients presenting with Crohn's disease and in three (2.3%) with ulcerative colitis. In comparison, 9 (1.6%) out of 560 controls were heterozygous for this mutation. No patient or control was homozygous for this mutation. Patients carrying one mutant allele did not show any noticeable characteristics in their corresponding phenotype. In contrast, the Y54H mutation was observed in neither any of the 348 patients with inflammatory bowel disease nor in any control subject. CONCLUSIONS: Our data indicate that both keratin 8 mutations, G62C and Y54H, do not play a relevant pathogenic role in inflammatory bowel disease.

Adolescent↗

Alu insertion polymorphisms in the Balkans and the origins of the Aromuns.

We have analysed 11 human-specific Alu insertion polymorphisms in the Balkans to elucidate the origins of the Aromuns, a linguistic isolate inhabiting scattered areas in the Balkan Peninsula. Four Aromun samples (two from the Republic of Macedonia, one from Albania, and one from Romania) and five neighbouring populations (Macedonians, Albanians, Romanians, Greeks, and Turks) were analysed by means of genetic distances, principal components and analyses of the molecular variance (AMOVA). Three hypotheses were tested: Aromuns are Romanophonic Greeks; the result of a Romanian southward migration; or local descendants of the Thracians. The analyses show that the Aromuns do not constitute a homogeneous group separated from the rest of the Balkan populations. Grouping by language or geography does not explain the genetic differences observed in the region, suggesting a lack of genetic structure in the area. Aromuns do not seem to be particularly related to Greeks, Romanians, or to other Romance speakers. The Aromuns might have their origin to the south of the Danube river, with extensive gene flow with the neighbouring populations. The present results suggest a common ancestry of all Balkan populations, including Aromuns, with a lack of correlation between genetic differentiation and language or ethnicity, stressing that no major migration barriers have existed in the making of the complex Balkan human puzzle.

Alu Elements↗

Linear systems approach to analysis of complex dynamic behaviours in biochemical networks.

Central functions in the cell are often linked to complex dynamic behaviours, such as sustained oscillations and multistability, in a biochemical reaction network. Determination of the specific mechanisms underlying such behaviours is important, e.g. to determine sensitivity, robustness, and modelling requirements of given cell functions. In this work we adopt a systems approach to the analysis of complex behaviours in intracellular reaction networks, described by ordinary differential equations with known kinetic parameters. We propose to decompose the overall system into a number of low complexity subsystems, and consider the importance of interactions between these in generating specific behaviours. Rather than analysing the network in a state corresponding to the complex non-linear behaviour, we move the system to the underlying unstable steady state, and focus on the mechanisms causing destabilisation of this steady state. This is motivated by the fact that all complex behaviours in unforced systems can be traced to destabilisation (bifurcation) of some steady state, and hence enables us to use tools from linear system theory to qualitatively analyse the sources of given network behaviours. One important objective of the present study is to see how far one can come with a relatively simple approach to the analysis of highly complex biochemical networks. The proposed method is demonstrated by application to a model of mitotic control in Xenopus frog eggs, and to a model of circadian oscillations in Drosophila. In both examples we are able to identify the subsystems, and the related interactions, which are instrumental in generating the observed complex non-linear behaviours.

Animals↗

[Reference values of MRI flow measurements of the pulmonary outflow tract in healthy children].

PURPOSE: To provide reference values for MRI-based flow measurements in the main pulmonary artery in healthy children. MATERIALS AND METHODS: In 98 healthy children (age: 3 - 17 years, median: 11 years), the main pulmonary artery was examined using MRI-based flow measurements with high temporal resolution (9.6 ms per cardiac phase). RESULTS: The acceleration time revealed a distinct age dependency and varied between 90 and 155 ms (mean: 124 ms +/- 14). The relative acceleration time (related to the RR-interval) varied between 12.7 and 27 % (mean: 18 % +/- 2.6). The mean values and the standard deviations for the determined values were as follows: cardiac output (5.4 l/min +/- 1.4), cardiac output normalized to the body surface area (4.2 [l/min]/m(2) +/- 0.8), average systolic flow velocity (66 cm/s +/- 12), maximum systolic flow (309 ml/s +/- 79), mean flow (110 ml/s +/- 30), distensibility of the wall of the main pulmonary artery (79 % +/- 26), peak velocity (96 cm/s +/- 15), pressure gradient along the pulmonary valve (3.8 mm Hg +/- 1.2), stroke volume (63.2 ml +/- 17.9), acceleration volume (23.7 ml +/- 8.7), maximum acceleration of flow (4924 ml/s(2) +/- 1431), and reverse volume (0.2 ml +/- 0.3). CONCLUSIONS: The acquired values of reference are applicable to all pediatric patients and serve as a framework for the communication between the radiologist and the pediatric cardiologists. High temporal resolution of the measurement sequence is mandatory. Noticeable deviations of these values should induce additional (probably invasive) evaluation.

Adolescent↗

[Imaging characteristics of childhood lipoblastoma].

PURPOSE: Lipoblastoma and lipoblastomatosis are very rare benign neoplasms, which almost exclusively occur in infants and young children. Despite their potential to local invasion and rapid growth, these tumors have an excellent prognosis, particularly if resected completely. Usually, the diagnosis is not taken into consideration preoperatively, and depends on histopathological evaluation. This study was done to determine imaging characteristics of lipoblastoma. MATERIALS AND METHODS: Eight cases of histopathologically proven lipoblastoma treated from 1988 to 2003 were reviewed, comprising four girls and four boys ranging in age from 17 months to nine years. The localization was chest wall (four times), abdominal wall (once), gluteal region (once), lower leg (once) and forearm (once). Ultrasound, MRI and CT scans were evaluated and correlated to clinical data of the patients. RESULTS: Ultrasound showed lipomatous echogenicity and echotexture. The tumors appeared signal intensive on T1-weighted MR images and had a mean intensive signal on T2-weighted MR images with fat suppression. They were markedly hypodense on CT. The growth pattern was invasive in all imaging methods, with extension into preformed spaces, such as intercostal spaces and neural foramina, but without infiltration into surrounding structures or metastases. CONCLUSION: Ultrasound and MRI are the methods of choice to diagnose lipoblastoma by revealing structures and local growth pattern that appear specific of this rare tumor entity. The imaging characteristics of the lipoblastoma have to be correlated with the age of patients to exclude other conditions in the differential diagnosis.

Child↗

[Benefits and effectiveness of recording somatosensory evoked potentials in surgery on the carotid artery].

BACKGROUND: Operative treatment of high-grade carotid stenosis is an established procedure. The question whether a temporary - either selective or routine - shunt is needed, is a matter of controversy, and the decision is based on a number of available monitoring procedures. Within the framework of quality assurance based on the regular collection of our own patient data, carotid thromboendarterectomy (TEA) with recording of somatosensory evoked potentials (SEP) was analysed for its effectiveness. PATIENTS AND METHODS: Two non-randomised groups of patients were analysed retrospectively: Group I: 99 carotid TEAs with no recording of SEP (1.1.99-31.12.99); Group II: 139 carotid TEAs with SEP recording (1.1.01-31.12.01). These two groups were unselected in terms of procedure, as also with regard to age, sex, stage or degree of carotid stenosis or surgeon, and were homogeneously distributed. A comparison was made of anaesthesia and operating times, shunt rate and the outcome of the two groups. Additionally, the two subgroups surgery with no shunt, and surgery with shunt, and the subgroups thromboendarterectomy with patchplasty (TEA) and eversion endarterectomy (EEA), were analysed. RESULTS: A temporary shunt was employed in 41 (41.4 %) of the patients in Group I (no SEP recording) and in 16 (11.5 %) of those in Group II (SEP recording). The average operating time in Group II was 11.4 min shorter (p < 0.001) than in Group I. The average carotid clamping time in Group II was significantly reduced (by 4.2 min; p < 0.001), while the duration of anaesthesia prior to skin incision was increased by an average of 18.3 min (p < 0.001), and the overall duration of anaesthesia by an average of 15.8 min (p < 0.001). A comparison of the subgroups surgery with no shunt and surgery with shunt revealed - both in Group I and Group II - a significant prolongation of the anaesthesia time and operating time (p < 0.001). In both Groups I and II, the subgroup TEA revealed a significant prolongation of both the anaesthesia and operating times vis-à-vis EEA. The major stroke rate was 2.0 % in Group I and 1.4 % in Group II, and the minor stroke rate 3.0 in Group I and 3.6 % in Group II; no deaths were observed. CONCLUSIONS: A reduction in the shunt rate to 11 % (by means of SEP) significantly decreased the average operating time (incision - suture) and the clamping time, with identical outcome in Groups I and II. Despite a reduction in the average incision-suture time in Group II (with SEP recording), the average overall operating time (anaesthesia time) was significantly increased due to the greater technical effort required. Carotid TEA with a selective shunt as determined by SEP is a high-cost procedure with no demonstrable benefit. At a stroke rate < 5 % and a need for stratification into several groups in accordance with the AHA classification, it is not possible to achieve adequate patient recruitment for a randomised analysis of outcome of the individual monitoring procedures. Alternative procedures are the routine use of a shunt and operation under regional anaesthesia.

Adult↗

FH clinical phenotype in Greek patients with LDL-R defective vs. negative mutations.

BACKGROUND: Familial hypercholesterolaemia (FH) is caused by mutations in the low-density lipoprotein receptor gene and the gene encoding apolipoprotein B-100, affecting one in 500 individuals. METHODS: One hundred and eighty-three Greek FH patients were screened for mutations on the LDLR and ApoB genes. RESULTS: We identified mutations in 67 probands and 11 relatives. Sixteen mutations located in eight different exons and the promoter of the LDLR were discovered. Among them 10 were missense mutations (C6W, S265R, A370T, Q363P, D365E, V408M, A410T, A517T, G528D, G571E), two were nonsense mutations (Q363X and C660X), three were splice defects (2140 + 5G-->A and 2140 + 9C-->T, 1706 - 10G-->A), and one was a nucleotide substitution (- 45delT) on the promoter. None of the subjects carried any apoB mutation. The detection rate of mutations in this study was 43%. From the above mutations, A410T, A519T and the splice site defects 2140 + 9C-->T were detected for the first time in the Greek population. Among them V408M, G528D, C6W and S265R account for 73% of heterozygous FH probands. V408M mutation is more common in Central West, while C6W is more common in Central East. Separating the patients into two groups (receptor defective and receptor negative) we found that the receptor negative group had higher levels of total cholesterol, low-density lipoprotein cholesterol and higher prevalence of tendon xanthomas compared with the receptor-defective group. DISCUSSION: The homogenous molecular basis of familial hypercholesterolaemia in Greece facilitates the application of a DNA diagnostic strategy based on the origin of the patient. The early mutation analysis would add valuable information on the severity of the disease.

Apolipoprotein B-100↗

Utilization of AFLP markers for PCR-based identification of Aspergillus carbonarius and indication of its presence in green coffee samples.

AIMS: The objective of this work was to test whether ochratoxin A (OTA) production of Aspergillus niger and A. carbonarius is linked to a certain genotype and to identify marker sequences with diagnostic value aiding identification of A. carbonarius, a fungus of major concern regarding OTA production in food and food raw materials. METHODS AND RESULTS: Aspergillus niger and A. carbonarius were isolated mainly from Brazilian coffee sources. The ability of isolates to produce OTA was tested by thin layer chromatography (TLC). Strains were genetically characterized by AFLP fingerprinting and compared with each other and with reference strains. Cluster analysis of fingerprints showed clear separation of A. niger from A. carbonarius strains. To obtain marker sequences, AFLP fragments were isolated from silver stained polyacrylamide gels, cloned and sequenced. Sequences obtained were used to develop species- specific PCR primers for the identification of A. carbonarius in pure culture and in artificially and naturally infected samples of green coffee. CONCLUSIONS: No clear correlation between genetic similarity of the strains studied and their potential to produce OTA was found. The PCR assays designed are a useful and specific tool for identification and highly sensitive detection of A. carbonarius. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed PCR assays allow specific and sensitive detection and identification of A. carbonarius, a fungus considered to be one of the major causative agents for OTA in coffee and grape-derived products. Assays may provide powerful tools to improve quality control and consumer safety in the food processing industry.

Aspergillus↗

Detection and quantification of Aspergillus ochraceus in green coffee by PCR.

AIMS: The aim of this study was to detect and quantify DNA of the ochratoxinogenic fungus Aspergillus ochraceus in green coffee and to compare the results with the ochratoxin A content of naturally contaminated samples. METHODS AND RESULTS: A DNA extraction protocol based on a combination of ultrasonification and a commercial kit was tested for the recovery of fungal DNA. PCR and real-time PCR protocols were established for the detection of A. ochraceus. Sensitivity of the PCR was checked by the addition of inoculated green coffee and pure fungal DNA to uncontaminated green coffee samples. The A. ochraceus DNA content of 30 naturally contaminated green coffee samples was determined and compared with the ochratoxin A concentrations. CONCLUSIONS: Aspergillus ochraceus can be rapidly and specifically detected in green coffee by PCR. A positive correlation between the ochratoxin A content and the DNA quantity was established. SIGNIFICANCE AND IMPACT OF THE STUDY: This work offers a quick alternative to the conventional mycological detection and quantification of A. ochraceus in green coffee.

Aspergillus ochraceus↗

Standard reference values for musculoskeletal ultrasonography.

OBJECTIVES: To determine standard reference values for musculoskeletal ultrasonography in healthy adults. METHODS: Ultrasonography was performed on 204 shoulders, elbows, hands, hips, knees, and feet of 102 healthy volunteers (mean age 38.4 years; range 20-60; 54 women) with a linear probe (10-5 MHz; Esaote Technos MP). Diameters of tendons, bursae, cartilage, erosions, hypoechoic rims around tendons and at joints were measured with regard to established standard scans. Mean, minimum, and maximum values, as well as two standard deviations (2 SD) were determined. Mean values +/-2 SD were defined as standard reference values. RESULTS: Hypoechoic rims were normally present in joints and tendon sheaths owing to physiological synovial fluid and/or cartilage. Similarly, fluid was found in the subdeltoid bursa in 173/204 (85%), at the long biceps tendon in 56 (27%), in the suprapatellar recess in 158 (77%), in the popliteal bursae in 32 (16%), and in the retrocalcaneal bursa in 49 (24%). Erosions of >1 mm were seen at the humeral head in 47 (23%). Values for important intervals were determined. The correlation between two investigators was 0.96 (0.78-0.99). The reliability of follow up investigations was 0.83 (0.52-0.99). CONCLUSIONS: Fluid in bursae as well as hypoechoic rims within joints and around tendons are common findings in healthy people. This study defines standard reference values for musculoskeletal ultrasonography to prevent misinterpretation of normal fluid as an anatomical abnormality.

Adult↗

Cationic silica nanoparticles as gene carriers: synthesis, characterization and transfection efficiency in vitro and in vivo.

The potential of cationic SiO2 nanoparticles was investigated for in vivo gene transfer in this study. Cationic SiO2 nanoparticles with surface modification were generated using amino-hexyl-amino-propyltri-methoxysilane (AHAPS). The zeta potential of the nanoparticles at pH = 7.4 varied from -31.4 mV (unmodified particles; 10 nm) to +9.6 mV (modified by AHAPS). Complete immobilization of DNA at the nanoparticle surface was achieved at a particle ratio of 80 (w/w nanoparticle/DNA ratio). The surface modified nanoparticle had a size of 42 nm with a distribution from 10-100 nm. The ability of these particles to transfect pCMVbeta reporter gene was tested in Cos-1 cells, and optimum results were obtained in the presence of FCS and chloroquine at a particle ratio of 80. These nanoparticles were tested for their ability to transfer genes in vivo in the mouse lung, and a two-times increase in the expression levels was found with silica particles in comparison to EGFP alone. Very low or no cell toxicity was observed, suggesting silica nanoparticles as potential alternatives for gene transfection.

Animals↗

Expression of alternatively and aberrantly spliced transcripts of the MDM2 mRNA is not tumor-specific.

The MDM2 proto-oncogene encodes a 90-kDa protein that binds to and inactivates the tumor suppressor p53. Several reports describe the presence of different alternatively, as well as, aberrantly spliced transcripts of the MDM2 mRNA in a variety of human cancers that have lost the ability to bind p53. Due to the transforming ability of at least some of the isoforms it has been suggested that they might contribute to tumorigenesis. Here we show that shorter MDM2 transcripts are also widely expressed in normal tissues, including lung and renal tissue, and in lymphocytes. Alteration in MDM2 RNA transcripts were found in the majority of the samples. Although we cannot exclude that alterations in MDM2 preferentially occur during cancer development, our data rather indicate that in this context the commonly observed transcript variants may also possess a normal physiological function.

Alternative Splicing↗

[HDMX amplification and high levels of HDMX-S splice variant are correlated with a poor prognosis in soft tissue sarcomas].

The aim of this study was to determine the amplification status of the HDMX gene and the expression of the HDMX mRNA particularly that of the HDMX-S splice variant in soft tissue sarcomas (STS). We show that the HDMX gene is amplified in 27% of STSs, which was associated with a worse prognosis (RR = 2.8, p = 0.03). We have also found that the transcript of the HDMX-S variant was predominant in a subset of (14%) of tumor samples, which was correlated with a significantly decreased overall survival time (15 vs. 53 months, p < 0.0001, log-Rank-test) and with a 9-fold-increased risk of tumor-related death (p < 0.0001). There was no correlation between the HMDX gene amplification and the HDMX-S splice variant overexpression. In summary, our data indicate that both the overexpression of the HDMX-S transcript, as well as, the HDMX gene amplification are important prognostic markers for STS.

Alternative Splicing↗