Search PubMed⌕ Search

Biomedical subjects

D Horn

Publications and source records attributed to D Horn.

At least 55 records · Page 3Linked to original sources
PubMed1997

Extreme microcephaly, severe growth and mental retardation, flexion contractures, and ichthyotic skin in two brothers: a new syndrome or mild form of Neu-Laxova syndrome?

Two brothers with congenital microcephaly, growth and mental retardation, flexion contractures, dorsal edema of hands and feet, and ichthyotic skin changes are described. Mild manifestations of Neu-Laxova syndrome have to be considered but long survival and only mild intrauterine growth retardation not described in this syndrome may be evidence of a different condition.

Contracture↗
PubMed1996

Identification of a novel bone/calcium metabolism-regulating factor in porcine pancreas.

We purified from porcine pancreas a hypocalcemic peptide clearly distinguishable from other pancreatic osteotropic factors such as amylin, calcitonin, and glucagon. Porcine pancreas was processed by acetone extraction, anion exchange chromatography, isoelectric focusing, and reverse-phase high performance liquid chromatography. Fractions were assayed for their inhibitory effects on bone resorption in vitro. Amino acid sequence of a homogeneous 28-kDa protein revealed 92% homology to a human elastase IIIB in the N terminus. Recombinant human elastase IIIB (rhEIIIB) inhibited bone resorption in organ culture stimulated by 1,25-dihydroxyvitamin D3 at concentrations as low as 75 ng/ml. Antibodies to rhEIIIB recognized purified pancreatic factor in Western blots and blocked its inhibitory effect on bone resorption. This antiresorptive activity was abolished by phenylmethylsulfonyl fluoride, suggesting the importance of elastase proteolytic activity for inhibition of bone resorption. In vivo, rhEIIIB and purified pancreatic factor significantly decreased recombinant human interleukin-1alpha-induced hypercalcemia. In conclusion, a novel naturally occurring inhibitor of bone resorption and calcium-lowering peptide has been identified in porcine pancreas. Because this pancreatic peptide has systemic effects on bone resorption and blood ionized calcium at low concentrations, it may represent a physiological regulator of normal bone remodeling and calcium homeostasis.

Amino Acid Sequence↗
PubMed1996

Neuronal-based synaptic compensation: a computational study in Alzheimer's disease.

In the framework of an associative memory model, we study the interplay between synaptic deletion and compensation, and memory deterioration, a clinical hallmark of Alzheimer's disease. Our study is motivated by experimental evidence that there are regulatory mechanisms that take part in the homeostasis of neuronal activity and act on the neuronal level. We show that following synaptic deletion, synaptic compensation can be carried out efficiently by a local, dynamic mechanism, where each neuron maintains the profile of its incoming post-synaptic current. Our results open up the possibility that the primary factor in the pathogenesis of cognitive deficiencies in Alzheimer's disease (AD) is the failure of local neuronal regulatory mechanisms. Allowing for neuronal death, we observe two pathological routes in AD, leading to different correlations between the levels of structural damage and functional decline.

Alzheimer Disease↗
PubMed1996

Temporal segmentation in a neural dynamic system.

Oscillatory attractor neural networks can perform temporal segmentation, i.e., separate the joint inputs they receive, through the formation of staggered oscillations. This property, which may be basic to many perceptual functions, is investigated here in the context of a symmetric dynamic system. The fully segmented mode is one type of limit cycle that this system can develop. It can be sustained for only a limited number n of oscillators. This limitation to a small number of segments is a basic phenomenon in such systems. Within our model we can explain it in terms of the limited range of narrow subharmonic solutions of the single nonlinear oscillator. Moreover, this point of view allows us to understand the dominance of three leading amplitudes in solutions of partial segmentation, which are obtained for high n. The latter are also abundant when we replace the common input with a graded one, allowing for different inputs to different oscillators. Switching to an input with fluctuating components, we obtain segmentation dominance for small systems and quite irregular waveforms for large systems.

Electrophysiology↗
PubMed1996

Three novel mutations of the NF1 gene detected by temperature gradient gel electrophoresis of exons 5 and 8.

We screened a total of 100 unrelated patients with neurofibromatosis type 1 (NF1) for mutations on exons 5 and 8 of the NF1 gene using temperature gradient gel electrophoresis (TGGE). Careful interpretation of exon 5 TGGE patterns was necessary due to interference by an exonic polymorphism. Three novel mutations were identified: a stop mutation in exon 5 (Q239X) caused by a C-->T transition at cDNA nucleotide position 715, a transition at the invariant G of the splice acceptor site in the intron 4c (G655-1A), and a transversion at the invariant G of the splice donor site in intron 8 (G1185 + 1T). Analysis of mRNA revealed the predicted abnormal splice products. While skipping of exon 5 causes a shift in the reading frame with a premature stop codon downstream in the middle of exon 6, skipping of exon 8 leads to an in-frame deletion with the predicted protein product being shortened by 41 amino acids.

Electrophoresis, Polyacrylamide Gel↗
PubMed1996

Pathogenesis of schizophrenic delusions and hallucinations: a neural model.

We implement and study a computational model of Stevens' theory of the pathogenesis of schizophrenia. This theory hypothesizes that the onset of schizophrenia is associated with reactive synaptic regeneration in brain regions that receive degenerating temporal lobe projections. Concentrating on one such area, the frontal cortex, we model a frontal module as an associative memory neural network whose input synapses represent incoming temporal projections. Modeling Stevens' hypothesized pathological synaptic changes in this framework results in adverse side effects similar to hallucinations and delusions seen in schizophrenia: spontaneous, stimulus-independent retrieval of stored memories focused on just a few of the stored patterns. These could account for the delusions and hallucinations that occur in schizophrenia without any apparent external trigger and for their tendency to concentrate on a few central cognitive and perceptual themes. The model explains why the positive symptoms of schizophrenia tend to wane as the disease progresses, why delayed therapeutic intervention leads to a much slower response, and why delusions and hallucinations may persist for a long time when they do occur.

Brain↗
PubMed1996

The importance of noise for segmentation and binding in dynamical neural systems.

Segmentation and binding are cognitive operations that underlie the process of perception. They can be understood as taking place in the temporal domain. In models of nonlinear oscillatory neurons and neuronal cell assemblies, we represent binding by phase locking of assemblies in different networks, and segmentation by phase separation of assemblies in the same network, leading to waveforms of staggered oscillations. Both processes can be facilitated if the inputs to the system, representing simultaneously activated memories, possess noisy components. In the binding problem they serve as a tagging device, driving phase locking between assemblies that belong to different networks but carry the same inputs. In the segmentation problem they allow us to overcome an inherent limitation on segmentation that, otherwise, cannot accommodate more than a few commonly excited memories.

Artifacts↗
PubMed1996

Meaning and development in the interpersonal treatment of severe psychopathology.

As a result of increasing empirical evidence for biological etiologies and economic pressures for rapid symptom relief, treatments for patients with severe psychopathology have become more directive, behavioral, and biomedical. Since a more comprehensive understanding of severe mental disorders is gained through both empirical causal explantation and the discovery of meaning (Carpenter, 1987), clinicians are currently under a greater challenge to help patients cultivate more phenomenologically meaningful change experiences. An interpersonal treatment approach based upon narrative, intersubjective, developmental, and relational principles of understanding severe psychopathology that is complementary to behavioral and biomedical intervention is presented. Four universal maturational processes (interpersonal self, boundary formation, symbolization, response differentiation) are then described and used to illustrate how life-story repair, adjustment, and elaboration can create more meaningful treatment experiences.

Combined Modality Therapy↗
PubMed1996

Pupillary dilation and funduscopy with 1.0% hydroxyamphetamine plus 0.25% tropicamide (Paremyd) versus tropicamide (0.5 or 1.0%) as a function of iris and skin pigmentation, and age.

BACKGROUND: This study was designed to evaluate the effect of Paremyd, a combination of 1.0 percent hydroxyamphetamine hydrobromide and 0.25 percent tropicamide, on pupil size during binocular indirect ophthalmoscopy (BIO) upon 164 subjects of various skin pigmentation, iris color, and age. METHODS: Pupillary dilation and ease of performing BIO were measured after 30 minutes following instillation of a single drop of either Paremyd or tropicamide (1.0 or 0.5 percent) to an eye. Subjects were assigned to one of three groups; either Paremyd OU, or Paremyd OS and tropicamide (either 0.5 or 1.0 percent) OD, or Paremyd OD and tropicamide OS. Pupillary dilation was measured during BIO performed at a set illumination using a near point card. RESULTS: Results indicate that Paremyd is a significantly more effective dilator than either concentration of tropicamide alone. BIO was rated good to excellent for all dilating agents. As could be expected (based upon data from previous experiments), there was a small, but significant, negative correlation between dilation and age, skin pigmentation, and iris pigmentation. CONCLUSIONS: Paremyd, because of its superior effect upon dilation without side effects, can be the preferred agent used for routine single-drop dilation in all patients, independent of age, iris color, or skin color.

Adolescent↗
PubMed1995

A developmentally regulated position effect at a telomeric locus in Trypanosoma brucei.

Trypanosoma brucei undergoes antigenic variation in the mammalian host. This can be achieved by activation and inactivation of telomeric variant-specific surface glycoprotein genes (vsg). In procyclic (insect midgut stage) cells, Vsg is not expressed. The mechanisms that regulate transcription of vsg expression sites (ESs) are unknown. Here we demonstrate that transcription from three different promoters was repressed when they were inserted at a transcriptionally silent telomere-proximal locus in bloodstream-form cells. This position effect was stable and heritable. Only transcription from an ES promoter was repressed in procyclic cells. The observed position effect and the promoter-specific developmental regulation suggest that these phenomena reflect the mechanisms that regulate vsg expression.

Animals↗
PubMed1995

Reduced neurofibromin content but normal GAP activity in a patient with neurofibromatosis type 1 caused by a five base pair duplication in exon 12b of the NF1 gene.

We screened a total of 87 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in exons 11, 12a, and 12b of the NF1 gene using temperature gradient gel electrophoresis (TGGE). A novel mutation (1998insCCTCT) was found in exon 12b. The 5-bp duplication comprising nucleotides 1994 to 1998 is predicted to lead to a truncated protein product lacking three quarters of its C-terminal sequence including the entire GTPase-activating protein-(GAP)-related domain. This mutation is associated with a reduction by 50% of the detectable amount of neurofibromin found in this patient. Despite the reduced level of neurofibromin cellular GAP activity was normal, which suggests that defects in other functions of the neurofibromin molecule may be important in the pathogenesis of NF1.

Base Composition↗
PubMed1995

Identification of denatured double-stranded DNA by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

We created double-stranded DNA (dsDNA) by annealing synthetic oligonucleotides and used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to measure the difference in molecular weight of the complementary strands after denaturation. Refined sample preparation and deliberate rectilinear construction at a linear mass spectrometer produced a mass resolution exceeding 1000 for single-stranded DNA. We present methodologies and demonstrate the potential for analysing dsDNA by determining the mass of the complementary strands.

Base Sequence↗