Search PubMed⌕ Search

Biomedical subjects

H Ritter

Publications and source records attributed to H Ritter.

At least 19 recordsLinked to original sources
PubMed2001

Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption. Here we carry out mutation analysis of ANKH, revealing six different mutations in eight of nine families. The mutations predict single amino acid substitutions, deletions or insertions. Using a helix prediction program, we propose for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of PPi. The mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. Our results link the PPi channel ANK with bone formation and remodeling.

Amino Acid Sequence↗
PubMed2001

A competitive-layer model for feature binding and sensory segmentation.

We present a recurrent neural network for feature binding and sensory segmentation: the competitive-layer model (CLM). The CLM uses topographically structured competitive and cooperative interactions in a layered network to partition a set of input features into salient groups. The dynamics is formulated within a standard additive recurrent network with linear threshold neurons. Contextual relations among features are coded by pairwise compatibilities, which define an energy function to be minimized by the neural dynamics. Due to the usage of dynamical winner-take-all circuits, the model gains more flexible response properties than spin models of segmentation by exploiting amplitude information in the grouping process. We prove analytic results on the convergence and stable attractors of the CLM, which generalize earlier results on winner-take-all networks, and incorporate deterministic annealing for robustness against local minima. The piecewise linear dynamics of the CLM allows a linear eigensubspace analysis, which we use to analyze the dynamics of binding in conjunction with annealing. For the example of contour detection, we show how the CLM can integrate figure-ground segmentation and grouping into a unified model.

Brain↗
PubMed2001

Dynamical stability conditions for recurrent neural networks with unsaturating piecewise linear transfer functions.

We establish two conditions that ensure the nondivergence of additive recurrent networks with unsaturating piecewise linear transfer functions, also called linear threshold or semilinear transfer functions. As Hahnloser, Sarpeshkar, Mahowald, Douglas, and Seung (2000) showed, networks of this type can be efficiently built in silicon and exhibit the coexistence of digital selection and analog amplification in a single circuit. To obtain this behavior, the network must be multistable and nondivergent, and our conditions allow determining the regimes where this can be achieved with maximal recurrent amplification. The first condition can be applied to nonsymmetric networks and has a simple interpretation of requiring that the strength of local inhibition match the sum over excitatory weights converging onto a neuron. The second condition is restricted to symmetric networks, but can also take into account the stabilizing effect of nonlocal inhibitory interactions. We demonstrate the application of the conditions on a simple example and the orientation-selectivity model of Ben-Yishai, Lev Bar-Or, and Sompolinsky (1995). We show that the conditions can be used to identify in their model regions of maximal orientation-selective amplification and symmetry breaking.

Animals↗
PubMed1998

The short tandem repeat locus D3S1359.

Short tandem repeats (STRs) are used by many laboratories throughout the world performing paternity testing or criminal casework. Nevertheless, many of the established STRs have obvious disadvantages such as low number of common alleles (e.g., hTPO, THO1) or alleles with frequencies of nearly 50% (e.g., hTPO, FES). In this paper the new STR locus D3S1359 is described. In a population study which was carried out on 136 unrelated individuals from southwestern Germany, we have detected 17 different alleles. The most common allele was allele 13 (204 bp) with a frequency of 18.8%. Eight further alleles have frequencies higher than 5%. With a heterozygozity index of 90% and 60 different genotypes, D3S1359 has shown to be a highly polymorphic and informative marker. Sequencing data of this STR locus revealed further variation.

Alleles↗
PubMed1998

D3S1358: sequence analysis and gene frequency in a German population.

Eight alleles of the STR system D3S1358 were observed and sequenced. The alleles ranged in size from 119 bp (13 repeats) to 147 bp (20 repeats) and consist of two diverse tetranucleotides: [AGAT] and [AGAC]. Alleles 16 and 17 show basic repeats which are different in one base. The allele frequency of 499 unrelated persons from SW-Germany yielded no deviation from Hardy-Weinberg equilibrium. A comparison with a Portuguese population showed some small differences, i.e. one allele has not been found in the Portuguese sample until now. The mutation rate was estimated with 0.8% analysing 65 families.

Alleles↗
PubMed1998

Nearby stop codons in exons of the neurofibromatosis type 1 gene are disparate splice effectors.

Stop mutations are known to disrupt gene function in different ways. They both give rise to truncated polypeptides because of the premature-termination codons (PTCs) and frequently affect the metabolism of the corresponding mRNAs. The analysis of neurofibromin transcripts from different neurofibromatosis type 1 (NF1) patients revealed the skipping of exons containing PTCs. The phenomenon of exon skipping induced by nonsense mutations has been described for other disease genes, including the CFTR (cystic fibrosis transmembrance conductance regulator) gene and the fibrillin gene. We characterized several stop mutations localized within a few base pairs in exons 7 and 37 and noticed complete skipping of either exon in some cases. Because skipping of exon 7 and of exon 37 does not lead to a frameshift, PTCs are avoided in that way. Nuclear-scanning mechanisms for PTCs have been postulated to trigger the removal of the affected exons from the transcript. However, other stop mutations that we found in either NF1 exon did not lead to a skip, although they were localized within the same region. Calculations of minimum-free-energy structures of the respective regions suggest that both changes in the secondary structure of the mRNA and creation or disruption of exonic sequences relevant for the splicing process might in fact cause these different splice phenomena observed in the NF1 gene.

Alternative Splicing↗
PubMed1998

[The plasma level of the neurotoxin 1-trichloromethyl-1,2,4,5-tetrahydro-beta-carboline (TaClo) in man after oral administration of chloral hydrate].

Chloral hydrate (CAS 302-17-0) is a widely used hypnotic and sedative agent. It was recently reported in the literature that a neurotoxin, TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline), may be formed in vitro from tryptamine (Ta) and chloral (Clo). Intraperitoneal administration of TaClo led to parkinson-like symptoms in the rat. Hence, the plasma levels of TaClo were determined at various time-points in 18 healthy volunteers in two periods each during a bioavailability study of several chloral hydrate preparations. The limit of quantitation for TaClo was 5 ng/ml. No TaClo could be determined in the plasma of the various volunteers following administration of human therapeutic doses of chloral hydrate. Hence, it is unlikely that TaClo will be formed in man after application of therapeutic doses of chloral hydrate to patients.

Adult↗
PubMed1997

The joint development of orientation and ocular dominance: role of constraints.

Correlation-based learning (CBL) has been suggested as the mechanism that underlies the development of simple-cell receptive fields in the primary visual cortex of cats, including orientation preference (OR) and ocular dominance (OD) (Linsker, 1986; Miller, Keller, & Stryker, 1989). CBL has been applied successfully to the development of OR and OD individually (Miller, Keller, & Stryker, 1989; Miller, 1994; Miyashita & Tanaka, 1991; Erwin, Obermayer, & Schulten, 1995), but the conditions for their joint development have not been studied (but see Erwin & Miller, 1995, for independent work on the same question) in contrast to competitive Hebbian models (Obermayer, Blasdel, & Schulten, 1992). In this article, we provide insight into why this has been the case: OR and OD decouple in symmetric CBL models, and a joint development of OR and OD is possible only in a parameter regime that depends on nonlinear mechanisms.

Animals↗
PubMed1997

Typing of the short tandem repeat D8S347 locus with different fluorescence markers.

The short tandem repeat (STR) locus D8S347 was analyzed by capillary electrophoresis. Sequencing data and a population study of 203 individuals from a southwestern German population are presented. We detected 12 different alleles, 340-388 bp in length, and found 40 different genotypes. The heterozygosity index was 85.7%. Futhermore, we investigated the consequences of different fluorescent dyes, namely 6-FAM, HEX, and ROX, on the ABI-calculated fragment sizes of defined (i.e., sequenced) alleles (348-376 bp in length). 6-FAM-labeled fragments appear to be smaller than the corresponding HEX- or ROX-labeled fragments. On average, 6-FAM-labeled fragments differ by 3.52 bp from the sequencing data, HEX-labeled ones by 2.04 bp, and ROX-labeled ones by 1.42 bp. Generally, small alleles differ less from the expected sequencing data than larger ones.

Chromosome Mapping↗
PubMed1996

Learning and generalization in cascade network architectures.

Incrementally constructed cascade architectures are a promising alternative to networks of predefined size. This paper compares the direct cascade architecture (DCA) proposed in Littmann and Ritter (1992) to the cascade-correlation approach of Fahlman and Lebiere (1990) and to related approaches and discusses the properties on the basis of various benchmark results. One important virtue of DCA is that it allows the cascading of entire subnetworks, even if these admit no error-backpropagation. Exploiting this flexibility and using LLM networks as cascaded elements, we show that the performance of the resulting network cascades can be greatly enhanced compared to the performance of a single network. Our results for the Mackey-Glass time series prediction task indicate that such deeply cascaded network architectures achieve good generalization even on small data sets, when shallow, broad architectures of comparable size suffer from overfitting. We conclude that the DCA approach offers a powerful and flexible alternative to existing schemes such as, e.g., the mixtures of experts approach, for the construction of modular systems from a wide range of subnetwork types.

Generalization, Psychological↗
PubMed1996

Comparison of German population data on the apoB-HVR locus with other Caucasian, Asian and black populations.

A population study of 505 unrelated individuals from Southwestern Germany was carried out on the 3'-apoB hypervariable region (HVR). After amplification via polymerase chain reaction (PCR) and agarose gel electrophoresis, 15 different alleles and 47 genotypes were observed. The most common alleles were hypervariable elements (HVE) 37 and 35 with an allele frequency of 0.374 and 0.244, respectively. The heterozygosity index was calculated to be 78.4%. Allele frequencies of this study are compared with results from other databases obtained from a French, a Spanish, an Asian and an American (Black) population.

Alleles↗
PubMed1996

Disambiguating complex visual information: towards communication of personal views of a scene.

Two experiments on the perception and eye-movement scanning of a set of six overtly ambiguous pictures are reported. In the first experiment it was shown that specific perceptual interpretations of an ambiguous picture usually correlate with parameters of the gaze-position distributions. In the second experiment these distributions were used for an image processing of initial pictures in such a way that in regions which attracted less fixations the brightness of all elements was lowered. The preprocessed pictures were then shown to a group of 150 naïve subjects for an identification. The results of this experiment demonstrated that in four out of six pictures it was possible to influence perception of other persons in the predicted way, ie to shift spontaneous reports of naïve subjects in the direction of interpretations that accompanied gaze-position data used for the preprocessing of initial pictures. Possible reasons for a failure of such a communication of personal views in two cases are also discussed.

Attention↗
PubMed1995

Detection of two hypervariable (ATTTT)n loci in the human genome.

Object of this investigation was the isolation of a single-locus probe from a multi-locus fingerprint. Individual specific multi-locus fingerprints in man were generated by using the oligonucleotide probe (ATTTT)5. An isolated (ATTTT)5-positive DNA fragment was analyzed using polymerase chain reaction (PCR) cycle-sequencing and nonradioactive direct-blotting electrophoresis. A digoxigenated oligonucleotide synthesized according to this sequence was used as a single-locus probe. Two hypervariable loci were detected on Southern blots. Formal genetic investigations for the two loci were performed in order to estimate the allele frequencies. Locus 1 shows an individual-specific banding pattern with an autosomal-codominant inheritance and can be used for forensic investigations. Locus 2 also represents a polymorphic pattern, but the inheritance is not according to the Mendelian rules. Probably we have detected a highly mutagenic locus in the human genome.

Base Sequence↗
PubMed1995

Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group.

PURPOSE: To compare the efficacy and safety of granisetron and ondansetron, serotonin (5-HT3) receptor antagonists shown to be effective in the prevention of chemotherapy-induced emesis. PATIENTS AND METHODS: In a double-blind, randomized, stratified, parallel-group study, the efficacy and safety of granisetron and ondansetron were compared in 987 chemotherapy-naive patients who received cisplatin in doses > or = 60 mg/m2. Granisetron was administered as a single dose of 10 or 40 micrograms/kg before the start of chemotherapy. Ondansetron was administered in doses of 0.15 mg/kg before and 4 and 8 hours after the start of chemotherapy. The three treatment groups were well-matched with respect to demographic characteristics and the dose of cisplatin administered. RESULTS: For all evaluations, single doses of granisetron 10 or 40 micrograms/kg were as effective as three 0.15-mg/kg doses of ondansetron. Total control (no vomiting, no retching, no nausea, and no use of rescue) was attained by 38%, 41%, and 39% of all patients who received granisetron 10 microgram/kg, granisetron 40 micrograms/kg, and ondansetron, respectively. No vomiting or retching and no use of rescue antiemetics were reported in 47%, 48%, and 51% of patients who received granisetron 10 micrograms/kg, granisetron 40 micrograms/kg, and ondansetron, respectively; no nausea and no use of rescue antiemetics were reported in 39%, 42%, and 40% of patients, respectively. CONCLUSION: All three treatment regimens were well-tolerated. The results of this study indicate that a single dose of granisetron 10 or 40 micrograms/kg is as effective as three doses of ondansetron 0.15 mg/kg in the prevention of nausea and vomiting induced by cisplatin chemotherapy.

Adult↗