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Biomedical subjects

J Seidel

Publications and source records attributed to J Seidel.

At least 19 recordsLinked to original sources
PubMed2000

Formation of unexpected substitution patterns in sulfonylbutylation of cyclomaltoheptaose promoted by host-guest interaction.

The distribution of substituents in sulfonylbutylethers of cyclomaltoheptaose (beta-cyclodextrin) formed in aqueous medium has been determined by gas chromatography after hydrolysis and formation of the permethylated sulfonylfluoride derivatives. In contrast to other etherification reactions of beta-cyclodextrin, preferred substitution in position 3 of the glucose units has been detected. From 1H NMR and microcalorimetric experiments, the formation of host-guest complexes by beta-cyclodextrin and the reagent 1,4-butane sultone in water became evident. This spatial preorganization presumably favors the reaction with the O-3. In contrast, in methyl sulfoxide preferred 2-O-alkylation was obtained, indicating that host-guest interaction does not influence regioselectivity in this solvent.

Alkanesulfonates↗
PubMed2000

Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome.

More than 150 point mutations have now been identified in the ATP7A gene. Most of these mutations lead to the classic form of Menkes disease (MD), and a few lead to the milder occipital horn syndrome (OHS). To get a better understanding of molecular changes leading to classic MD and OHS, we took advantage of the unique finding of three patients with similar mutations but different phenotypes. Although all three patients had mutations located in the splice-donor site of intron 6, only two of the patients had the MD phenotype; the third had the OHS phenotype. Fibroblast cultures from the three patients were analyzed by reverse transcriptase (RT)-PCR to try to find an explanation of the different phenotypes. In all three patients, exon 6 was deleted in the majority of the ATP7A transcripts. However, by RT-PCR amplification with an exon 6-specific primer, we were able to amplify exon 6-containing mRNA products from all three patients, even though they were in low abundance. Sequencing of these products indicated that only the patient with OHS had correctly spliced exon 6-containing transcripts. We used two different methods of quantitative RT-PCR analysis and found that the level of correctly spliced mRNA in this patient was 2%-5% of the level found in unaffected individuals. These findings indicate that the presence of barely detectable amounts of correctly spliced ATP7A transcript is sufficient to permit the development of the milder OHS phenotype, as opposed to classic MD.

Adenosine Triphosphatases↗
PubMed2000

Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations.

Phenylketonuria (PKU) is an important error of amino acid metabolism which results in most patients from phenylalanine hydroxylase (PAH) deficiency. PKU displays a marked genotypic heterogeneity both within and between different populations. The aim of this study was to establish the genotypic spectrum of PKU in eastern Germany, and to compare this to the distribution of mutations in western Germany. The study population included 302 patients in 290 families who were followed at treatment centers in Berlin, Leipzig and Jena. The study showed marked genotypic variability with a total of 75 mutations, including 15 that have so far not been described (eleven missense mutations, one splicing mutation, and three small deletions). One of these novel mutations, E183Q, occurred in cis to a R408W mutation. In the non-immigrant eastern German population, the frequency of R408W accounted for 40.1% of the PKU alleles. In the immigrant Turkish population of the former West Berlin, the most prevalent mutation was IVS10-11G>A (57%). There was a marked difference of the genotypic spectrum between the population studied here and the data reported from the western part of the country.

Amino Acid Substitution↗
PubMed2000

Spatial distribution of in-patient service use of psychiatric patients: somatic departments versus psychiatric units.

BACKGROUND: It has long been recognized that a high proportion of psychiatric patients are admitted to emergency, medical and surgical wards. However, until now no assessment has been made of which urban general hospitals would be most appropriate for the establishment of specific psychiatric facilities. METHOD: Our study concerned Germany's second largest city, Hamburg (population 1.7 million), and involved an evaluation of psychiatric principal diagnoses in general and psychiatric hospitals. The research was based on data collected between 1988 and 1994 embracing approximately 77% of all psychiatric patients (n = 64,000) in 41 hospitals. The evaluation was carried out using the statistics programs SPSS and DismapWin. RESULTS: We established that the proportion of male patients discharged from somatic wards, mainly internal medicine, with alcohol and drug abuse as well as with neuroses and personality disorders or illegal drug abuse was surprisingly high (70%, 34% and 24% respectively). For female patients the figures were 67%, 40% and 35% respectively. A geographical analysis of spatial heterogeneity of hospitalization risks showed that general hospitals admit a disproportionately high number of patients from areas of lower social status - both male and female from the above-mentioned diagnostic categories. A rank correlation between the classification of areas based on the heterogeneity model and the social status of the areas supports this hypothesis, at least for males. CONCLUSION: Our findings lead us to the conclusion that the establishment of new psychiatric services should focus on internal wards in hospitals located in areas of low social status.

Adult↗
PubMed2000

Phenotypic variation and genetic heterogeneity in Léri-Weill syndrome.

Léri-Weill syndrome (LWS) or dyschondrosteosis represents a short stature syndrome characterised by the mesomelic shortening of the forearms and lower legs and by bilateral Madelung deformity of the wrists. Recently, mutations in the pseudoautosomal homeobox gene SHOX have been shown to be causative for this disorder. This gene has previously been described as the short stature gene implicated in Turner syndrome (TS). We studied 32 Léri-Weill patients from 18 different German and Dutch families and present clinical, radiological and molecular data. Phenotypic inter- and intrafamilial heterogeneity is a frequent finding in LWS, and phenotypic manifestations are generally more severe in females. In males, muscular hypertrophy is a frequent finding. To test for SHOX mutations we used FISH, Southern blot and SSCP analysis as well as long-range PCR and sequencing. We identified (sub)microscopic deletions encompassing the SHOX gene region in 10 out of 18 families investigated. Deletion sizes varied between 100 kb and 9 Mb and did not correlate with the severity of the phenotype. We did not detect SHOX mutations in almost half (41%) the LWS families studied, which suggests different genetic etiologies.

Adolescent↗
PubMed2000

Interior-point methodology for 3-D PET reconstruction.

Interior-point methods have been successfully applied to a wide variety of linear and nonlinear programming applications. This paper presents a class of algorithms, based on path-following interior-point methodology, for performing regularized maximum-likelihood (ML) reconstructions on three-dimensional (3-D) emission tomography data. The algorithms solve a sequence of subproblems that converge to the regularized maximum likelihood solution from the interior of the feasible region (the nonnegative orthant). We propose two methods, a primal method which updates only the primal image variables and a primal-dual method which simultaneously updates the primal variables and the Lagrange multipliers. A parallel implementation permits the interior-point methods to scale to very large reconstruction problems. Termination is based on well-defined convergence measures, namely, the Karush-Kuhn-Tucker first-order necessary conditions for optimality. We demonstrate the rapid convergence of the path-following interior-point methods using both data from a small animal scanner and Monte Carlo simulated data. The proposed methods can readily be applied to solve the regularized, weighted least squares reconstruction problem.

Algorithms↗
PubMed2000

Performance characteristics of the 3-D OSEM algorithm in the reconstruction of small animal PET images. Ordered-subsets expectation-maximixation.

Rat brain images acquired with a small animal positron emission tomography (PET) camera and reconstructed with the three-dimensional (3-D) ordered-subsets expectation-maximization (OSEM) algorithm with resolution recovery have better quality when the brain is imaged by itself than when inside the head with surrounding background activity. The purpose of this study was to characterize the dependence of this effect on the level of background activity, attenuation, and scatter. Monte Carlo simulations of the imaging system were performed. The coefficient of variation from replicate images, full-width at half-maximum (FWHM) from point sources and image profile fitting, and image contrast and uniformity were used to evaluate algorithm performance. A rat head with the typical levels of five and ten times the brain activity in the surrounding background requires additional iterations to achieve the same resolution as the brain-only case at a cost of 24% and 64% additional noise, respectively. For the same phantoms, object scatter reduced contrast by 3%-5%. However, attenuation degraded resolution by 0.2 mm and was responsible for up to 12% nonuniformity in the brain images suggesting that attenuation correction is useful. Given the effects of emission and attenuation distribution on both resolution and noise, simulations or phantom studies should be used for each imaging situation to select the appropriate number of OSEM iterations to achieve the desired resolution-noise levels.

Algorithms↗
PubMed2000

Molecular cytogenetic characterisation of partial trisomy 9q in a case with pyloric stenosis and a review.

Partial trisomy 9q represents a rare and heterogeneous group of chromosomal aberrations characterised by various clinical features including pyloric stenosis. Here, we describe the case of a 1 year old female patient with different dysmorphic features including pyloric stenosis and prenatally detected partial trisomy 9q. This partial trisomy 9q has been analysed in detail to determine the size of the duplication and to characterise the chromosomal breakpoints. According to the data gained by different molecular cytogenetic techniques, such as fluorescence in situ hybridisation (FISH) with whole and partial chromosome painting probes, yeast artificial chromosome (YAC) probes, and comparative genomic hybridisation (CGH), the derivative chromosome 9 can be described as dup(9)(pter-->q22. 1::q31.1-->q22.1::q31.1--> q22.1::q31.1-->qter). Four breakpoint spanning YACs have been identified (y806f02, y906g6, y945f5, and y747b3) for the proximal breakpoint. According to this new case and previously published data, the recently postulated putative critical region for pyloric stenosis can be narrowed down to the subbands 9q22.1-q31.1 and is the result of either partial trisomy of gene(s) located in this region or a gene disrupted in 9q31.

Chromosome Banding↗
PubMed2000

Inequity in the hospital care of patients with alcoholism and medication addiction.

In a psychiatric/ecological study, the authors investigated which aspects of a town district would provide an explanation to the fact that alcoholics are treated above average in addiction-psychiatric wards in a given city district, while in other districts treatment is carried out in internal medical wards. The research was based on data collected between 1988 and 1994 from approximately 77% of all patients suffering from alcohol and legal drug abuse (n = 15,473) in 41 hospitals in Hamburg. It was established that in somatic departments, mainly internal medicine, 70% of male and 67% of female patients were admitted for alcohol and legal drug abuse. The results of a geographical analysis of hospitalization risks showed that the addiction-psychiatric facilities of psychiatric wards are mainly utilized by inhabitants from nearby districts. Risks of above-average hospitalization for alcoholics and legal drug abusers in internal wards, as well as insufficient addiction-psychiatric care, are to be expected in town districts where a shortage of psychiatrists exists, and where the unemployment rate is high. In these crucial areas, addiction-specific facilities, such as qualified programs for detoxication or techniques for short intervention, should be established within the framework of an addiction-specific liaison service in general hospitals.

Alcoholism↗
PubMed2000

Microdeletion 4p16.3 in three unrelated patients with Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) is a multiple malformation syndrome caused by partial monosomy of 4p16.3. Pitt-Rogers-Danks syndrome, first thought to be a distinct entity, is a similar condition associated with a microdeletion overlapping the WHS critical region. In this paper we evaluate three WHS patients showing a microdeletion of 4p and remarkable development with respect to the clinical spectrum of WHS.

Abnormalities, Multiple↗
PubMed2000

Insulin-like growth factor serum concentrations reflect insufficient growth in a hypoplastic infant with partial trisomy 9q in the 12th week of life.

This report presents changes of IGFs and IGFBPs in a female infant with partial trisomy 9q in the 12th week of life. Studying deficient growth in this hypoplastic infant (birth weight 1405 g, birth length 36 cm) with dysmorphic features, the following changes in IGFs and IGFBPs were detected (microg/l): IGF-I: 26.5 vs 48.1 in healthy infants; IGF-II: 420 vs 728; IGFBP-2: 931 vs 524; IGFBP-3: 800 vs 1070. This demonstrates that IGFs and IGFBPs may reflect individual insufficient growth even at this early age.

Adult↗
PubMed1999

Mosaicism for a full mutation and a normal size allele in two fragile X males.

Confirmation of the clinical diagnosis of fragile X syndrome by molecular tests is based on both the presence of a full mutation and methylation of the promotor region of the FMR1 gene. The mechanism leading to mosaic alleles of repeat number and the role of methylation in this process is still under discussion. We report two cases of males who show mosaic patterns for both number of CGG repeats and methylation status. In the first patient, a mosaic pattern of a normal allele of 34+/-1 CGGs, a borderline premutation/full mutation, and a full mutation was observed. The mother exhibited alleles of 30+/-1 and approximately 100 CGGs. The second patient was mosaic for a normal allele of 47+/-1 CGGs and a full mutation. His mother carried alleles of 40+/-1 and approximately 100 CGGs. Chromosomal analysis in the patients showed normal male karyotypes with no evidence that they had inherited both maternal X chromosomes. Furthermore, haplotyping excluded disomy of the repeat flanking region in these patients. So far, it is not clear whether the normal alleles in the patients, leukocytes of 34 and 47 CGGs, respectively, may be caused by the contraction of the maternal premutations of 100 CGGs or be caused by the deletion from the full mutation alleles.

Blotting, Southern↗
PubMed1999

Vascular complications (splenic and hepatic artery aneurysms) in the occipital horn syndrome: report of a patient and review of the literature.

We report an 18-year-old boy with occipital horn syndrome who developed aneurysms of the splenic and hepatic arteries. Occipital horn syndrome, also called X-linked cutis laxa or Ehlers-Danlos syndrome (EDS) type IX, is characterised by a skeletal dysplasia which includes occipital horns, broad clavicles, deformed radii, ulnae and humeri, narrow rib cage, undercalcified long bones and coxa valga. Distinctive features common to all patients are unusual facial appearance, hypermobility of finger joints, limitation of extension of elbows, chronic diarrhoea and genitourinary abnormalities. In this case report we describe the difficulties encountered in the diagnostic management of patients with EDS-related vascular lesions.

Adolescent↗
PubMed1999

Geographical analysis of the risk of psychiatric hospitalization in Hamburg from 1988 - 1994.

The analysis of the geographical distribution of hospital cases is obviously important for the purpose of planning hospital services, but it is of even greater significance in the planning of psychiatric services. This concern motivated our seven-year-long study, which examined hospitalization risks among various categories of psychiatric disorders in the major German city of Hamburg. Our database encompassed 77% (n = 64,000) of all psychiatric admissions in a total of 41 hospitals, most of which are general hospitals. In order to carry out the geographical analysis we employed a new statistical method based on a mixture distribution model. According to our findings, the strongest indications of an increased frequency were among male cases of schizophrenia, drug abuse and organic psychoses, and female cases of neurotic disorders, personality disorders, drug abuse and schizophrenia. We found that some areas are exposed to a risk of hospitalization for these diagnostic categories which is more than 50% above the reference. Contrary to other authors we did not identify an increased frequency of admission concentrated in the inner-city area for any of the diagnostic groups. The risk of hospitalization for schizophrenics was almost entirely associated with the close proximity of psychiatric units, while the risks for neuroses and personality disorders, as well as alcohol and drug abuse, appeared to be concentrated in areas of low social status. However, a statistically relevant correlation between an increased risk of hospitalization and low social status could be determined only for drug abuse and alcoholism. In the end, we did identify two areas in which there was an increased risk of hospitalization for several diagnostic groups, and this information will undoubtedly facilitate the planning of hospital and psychiatric services. The fact that our findings deviate to some extent from other authors - especially with respect to neuroses and personality disorders, but also to addiction - can be attributed to the inclusion of psychiatric cases from general hospitals in our geographic analysis.

Adolescent↗
PubMed1999

Evaluation of 99mTc-mercaptoacetyltriglycine-biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin.

We evaluated 99mTc-labeled mercaptoacetyltriglycine (99mTc-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (rmax) and half clearance time (HCT) with those of 99mTc-labeled diisopropyl-iminodiacetic acid (99mTc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent (99mTc-MAG3-biocytin or 99mTc-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma-camera equipped with a pinhole collimator. Dynamic images showed rapid hepatic uptake of 99mTc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas 99mTc-disofenin coinjected with bilirubin showed a higher blood background than 99mTc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, rmax and HCT. The rmax was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. 99mTc-MAG3-biocytin without bilirubin coinjection showed an rmax of 8.9+/-1.3 and an HCT of 399+/-36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for 99mTc-disofenin with bilirubin were significantly (p < 0.01) affected by 14 mg/kg of bilirubin coinjection: rmax was decreased from 7.9+/-2.5 to 1.4+/-0.2 and HCT was increased from 292+/-32 s to 782+/-133 s. 99mTc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels.

Animals↗
PubMed1999

How good is the match between the plane of the text and the plane of focus during reading?

Because results from animal models demonstrate that retinal image defocus is a crucial factor in the visual control of eye growth, we have measured the precision of accommodation during reading at 1 m and at 30 cm distance. A newly developed photorefractor was used to sample both the refraction in the vertical meridian and direction of gaze at 25 Hz. Using these two parameters, a three-dimensional "refraction map" of the visual field was plotted. It showed the optic disc as an area with more myopic refractions and the course of refractions across a visual field of about +/- 25 deg. A special calibration scheme was employed to ensure that the precision of the refractions was 0.2 dpt or better (as estimated from the standard deviations of repeated measurements and the noise in the calibration curve). Twelve young adults (students from the lab) served as subjects. We found considerable inter-individual variability in the off-axis refractions but little variability among repeated measurements in the same subjects. Inter-individual variability reached a minimum in the foveal region. Both myopes wearing their spectacle corrections (n = 6) and emmetropes (n = 6) under-accommodated by about 0.3 D during reading at 30 cm distance but, at 1 m distance, only the emmetropes under-accommodated. Since both refraction groups under-accommodated similarly during reading at close distance, it remains unclear whether the small amount of defocus is critical for their future myopia development. Either accommodation errors differ at earlier times when myopia first appears (as suggested by the literature), or the subjects' eye growth was differently sensitive to defocus, or our simple protocol did not pick up existent differences in accommodation among the two groups.

Accommodation, Ocular↗
PubMed1999

Molecular analysis of SALL1 mutations in Townes-Brocks syndrome.

Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal, limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations. In 9 of these families mutations were identified. None of the mutations has previously been described. Two of these mutations are nonsense mutations, one of which occurred in three unrelated families. Five of the mutations are short deletions. All of the mutations are located 5' of the first double zinc finger (DZF) encoding region and are therefore predicted to result in putative prematurely terminated proteins lacking all DZF domains. This suggests that only SALL1 mutations that remove the DZF domains result in TBS. We also present evidence that in rare cases SALL1 mutations can lead to phenotypes similar to Goldenhar syndrome. However, phenotypic differences in TBS do not seem to depend on the site of mutation.

Abnormalities, Multiple↗