Biomedical subjects

C Horn

Publications and source records attributed to C Horn.

At least 19 recordsLinked to original sources

PubMed2006

Perception-action coupling in children with and without DCD: Frequency locking between task-relevant auditory signals and motor responses in a dual-motor task.

BACKGROUND: The current research examines the relationship between perceptual and motor processes, known as perception-action or sensorimotor coupling, and the potential differences in perception-action coupling among children with and without Developmental Coordination Disorder (DCD) and adults in a gross-motor co-ordination task (clapping while marching) when a task-relevant driving sensory signal is present. METHODS: Ten children with DCD (7.32 + 0.23 years), eight typically developing (TD) children who were age-, gender- and racially/ethnically matched (6.91 + 0.24 years) and 10 college-aged adults were participants in this study. Participants clapped and marched to an auditory beat at four different frequencies: 0.8, 1.2,1.6 and 2.0 Hz. The relative timing measures of mean relative phase (MRP) and variability of relative phase (VRP) were calculated and compared using 3 (group) x 4 (frequency) x 2 (limb) anovas. Qualitatively, participants were assessed for the presence of absolute coupling (100% + 15% MRP). RESULTS: Statistically significant differences in MRP occurred for coupling, frequency and group, and post hoc analysis indicated that the adult group differed from both the DCD and TD groups, who did not differ from each other. In VRP, there were significant main effects for coupling and group, and a significant interaction between group and frequency, with post hoc analysis indicating the DCD group to be different from the TD and adult groups. Qualitatively, both the adult and TD groups increased in the number of participants who adopt absolute coupling as frequency increases. In contrast, the DCD participants adopt this absolute coupling far less frequently overall; in fact, the number of participants adopting this pattern decreases as frequency increases. CONCLUSIONS: These results indicate that children with DCD have difficulties with both the co-ordination and the control of their perception-action coupling for this particular task.

Adolescent↗

PubMed2005

High prevalence of hepatitis B virus infection among tuberculosis patients with and without HIV in Rio de Janeiro, Brazil.

To determine the prevalence and exposure factors associated with hepatitis B infection in tuberculosis patients with and without HIV type 1 coinfection, the presence of hepatitis B virus serological markers was investigated in a retrospective study. The seroprevalence of hepatitis B virus in patients with tuberculosis only was 14.6%, and in tuberculosis patients coinfected with HIV it increased to 35.8%. In patients with HIV and tuberculosis coinfection, homosexuality constituted the principal exposure factor, while in tuberculosis patients without HIV, a gradual increase in hepatitis B virus seroprevalence was noted along with increasing age. The results demonstrate that hepatitis B infection is highly prevalent in tuberculosis patients in Brazil and suggest that a vaccination program for the general population should be considered in order to prevent further hepatitis B infections.

AIDS-Related Opportunistic Infections↗

PubMed2005

The impact of immunological parameters on the development of phantom pain after major amputation.

OBJECTIVES: To investigate the relationship between local and systemic inflammatory markers and phantom limb pain. METHODS: In 39 consecutive patients undergoing major amputations nerve biopsies, serum and clinical data was collected. Patients were followed up for 12 months to report on the incidence and severity of phantom limb pain. RESULTS: After 12 months, 78% of the surviving patients had phantom pain, the symptom usually commencing within 14 days of operation. The severity of macrophage infiltration within the nerve biopsy was negatively correlated to the inception of phantom pain ( P = 0.026). While serum TNF-alpha concentration was positively correlated to mortality ( P = 0.021). CONCLUSIONS: The immune status existing before the amputation and the local immunological milieu influence the onset of phantom pain.

Amputation, Surgical↗

PubMed2004

Quantum control by ultrafast polarization shaping.

We demonstrate that the use of time-dependent light polarization opens a new level of control over quantum systems. With potassium dimer molecules from a supersonic molecular beam, we show that a polarization-shaped laser pulse increases the ionization yield beyond that obtained with an optimally shaped linearly polarized laser pulse. This is due to the different multiphoton ionization pathways in K2 involving dipole transitions which favor different polarization directions of the exciting laser field. This experiment is a qualitative extension of quantum control mechanisms which opens up new directions giving access to the three-dimensional temporal response of molecular systems.

Journal Article↗

PubMed2002

An engineered IN-1 F(ab) fragment with improved affinity for the Nogo-A axonal growth inhibitor permits immunochemical detection and shows enhanced neutralizing activity.

The myelin axonal growth inhibitor NI-220/250 (Nogo-A) has attracted considerable attention in elucidating the mechanisms that account for the lack of plasticity in the adult central nervous system. The cognate monoclonal antibody IN-1, which was obtained prior to the molecular characterization of its Nogo-A antigen, has played a crucial role in this respect. However, this murine IgM/kappa antibody does not only provide an inappropriate format for in vivo studies, its low antigen affinity has also hampered the thorough structure-function analysis of its neutralizing effect toward the Nogo-A inhibitor on a molecular basis. We describe here the affinity maturation of a bacterially produced functional IN-1 F(ab) fragment via protein engineering. A soluble fragment of Nogo-A derived from the central exon 3 of its gene, which was prepared by secretion into the periplasm of Escherichia coli, served as a target in these experiments. After repeated cycles of site-directed random mutagenesis and screening, the mutant II.1.8 of the IN-1 F(ab) fragment was obtained, carrying five side chain substitutions within CDR-L3. Its dissociation constant for the complex with the recombinant Nogo-A fragment was determined in surface plasmon resonance measurements as approximately 1 microM. The affinity of the unmutated IN-1 F(ab) fragment was 8-fold lower. The engineered F(ab) fragment appeared to be well suited for the specific detection of Nogo-A in immunochemical assays and for the histochemical staining of myelin-rich tissue sections. Most importantly, its concentration-dependent neutralizing effect on the Nogo-A inhibitory activity was significantly enhanced in cell culture. This study confirms Nogo-A to be the antigen of the IN-1 antibody and it demonstrates increased potential of the engineered F(ab) fragment as a reagent for promoting axonal regeneration in vivo.

Amino Acid Substitution↗

PubMed2001

Genetic evidence for a microtubule-destabilizing effect of conventional kinesin and analysis of its consequences for the control of nuclear distribution in Aspergillus nidulans.

Conventional kinesin is a microtubule-dependent motor protein believed to be involved in a variety of intracellular transport processes. In filamentous fungi, conventional kinesin has been implicated in different processes, such as vesicle migration, polarized growth, nuclear distribution, mitochondrial movement and vacuole formation. To gain further insights into the functions of this kinesin motor, we identified and characterized the conventional kinesin gene, kinA, of the established model organism Aspergillus nidulans. Disruption of the gene leads to a reduced growth rate and a nuclear positioning defect, resulting in nuclear cluster formation. These clusters are mobile and display a dynamic behaviour. The mutant phenotypes are pronounced at 37 degrees C, but rescued at 25 degrees C. The hyphal growth rate at 25 degrees C was even higher than that of the wild type at the same temperature. In addition, kinesin-deficient strains were less sensitive to the microtubule destabilizing drug benomyl, and disruption of conventional kinesin suppressed the cold sensitivity of an alpha-tubulin mutation (tubA4). These results suggest that conventional kinesin of A. nidulans plays a role in cytoskeletal dynamics, by destabilizing microtubules. This new role of conventional kinesin in microtubule stability could explain the various phenotypes observed in different fungi.

Amino Acid Sequence↗

PubMed2001

Tongue lesions in the pediatric population.

OBJECTIVE: To describe the spectrum of pediatric tongue lesions treated surgically at Columbia-Presbyterian Medical Center from January 1990 to December 1999. STUDY DESIGN AND SETTING: Retrospective case-series at the pediatric hospital of a tertiary care, academic medical center. RESULTS: Seventeen patients were identified. Their ages ranged from 1 to 132 months (median, 7 months). Eight lesions were located anteriorly: mucous cyst (1), polyp (1), chronic inflammatory mass (1), hamartoma (1), squamous papilloma (2), cavernous hemangioma (1), and vascular malformation (1). Four lesions were located posteriorly: teratoma (1), glial choristoma (1), osseous choristoma (1), and benign epithelial cyst (1). Finally, there were 5 diffuse lesions including macroglossia (4) and massively infiltrating congenital lymphatic malformation (1). Symptoms included respiratory distress (3) and dysarthria (3); all other children were asymptomatic. CONCLUSIONS: This series revealed an interesting spectrum of rare solid tumors; compared with other large series, fewer lymphatic and vascular malformations were seen. Presenting symptoms, differential diagnosis, and surgical approach were differentiated according to lesion location.

Child, Preschool↗

PubMed2001

Distinct cortical migrations from the medial and lateral ganglionic eminences.

Recent evidence suggests that projection neurons and interneurons of the cerebral cortex are generally derived from distinct proliferative zones. Cortical projection neurons originate from the cortical ventricular zone (VZ), and then migrate radially into the cortical mantle, whereas most cortical interneurons originate from the basal telencephalon and migrate tangentially into the developing cortex. Previous studies using methods that label both proliferative and postmitotic cells have found that cortical interneurons migrate from two major subdivisions of the developing basal telencephalon: the medial and lateral ganglionic eminences (MGE and LGE). Since these studies labeled cells by methods that do not distinguish between the proliferating cells and those that may have originated elsewhere, we have studied the contribution of the MGE and LGE to cortical interneurons using fate mapping and genetic methods. Transplantation of BrdU-labeled MGE or LGE neuroepithelium into the basal telencephalon of unlabeled telencephalic slices enabled us to follow the fate of neurons derived from each of these primordia. We have determined that early in neurogenesis GABA-expressing cells from the MGE tangentially migrate into the cerebral cortex, primarily via the intermediate zone, whereas cells from the LGE do not. Later in neurogenesis, LGE-derived cells also migrate into the cortex, although this migration occurs primarily through the subventricular zone. Some of these LGE-derived cells invade the cortical plate and express GABA, while others remain within the cortical proliferative zone and appear to become mitotically active late in gestation. In addition, by comparing the phenotypes of mouse mutants with differential effects on MGE and LGE migration, we provide evidence that the MGE and LGE may give rise to different subtypes of cortical interneurons.

Animals↗

PubMed2001

AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon.

PURPOSE: The AKT/PKB kinase controls many of the intracellular processes that are dysregulated in human cancer, including the suppression of apoptosis and anoikis and the induction of cell cycle progression. Three isoforms of AKT have been identified: AKT-1, -2, and -3. Selective up-regulation of AKT-3 RNA expression has been reported in hormone-independent breast and prostate cancer cell lines suggesting that AKT-3 expression may be increased with breast or prostate tumor progression. To determine whether AKT-3 RNA expression is selectively up-regulated in human cancers and whether the patterns of AKT RNA expression may change with tumor development, we examined AKT isoform expression by RT-PCR in human cancer cell lines, primary human cancers, and normal human tissues. EXPERIMENTAL DESIGN: AKT-1, -2, and -3 RNA expression was examined by RT-PCR. Because up-regulated AKT-3 expression has been implicated in human breast and prostate cancer progression, we also examined AKT-3 expression levels by semiquantitative RT-PCR using matched normal/tumor first-strand cDNA pairs from colon, breast, prostate, and lung cancers. RESULTS: Our data reveal that the overwhelming majority of both normal and tumor tissues express all three of the AKT isoforms. Moreover, semiquantitative RT-PCR of matched normal/tumor pairs confirmed similar AKT-3 RNA expression levels in both normal and tumor tissue. CONCLUSIONS: Our data show that both normal and tumor tissues express all three of the AKT isoforms and indicate that tumorigenesis does not involve a dramatic shift in the RNA expression patterns of the three AKT isoforms.

Breast↗

PubMed2000

Crystal supramolecular motifs: columns of embracing Ph3PMe+ or Ph3PCI+ cations controlling formation of.

The crystal structures of (Ph3PCl)2[Cu3Cl8] (1) (triclinic, space group P1, a = 9.480(6) A, b = 10.243(8) A, c = 11.232(6) A, alpha = 86.76(4) degrees, beta = 66.62(5) degrees, gamma = 83.92(4) degrees, Z = 1) and (Ph3PMe)2[Cu3Br8] (2) (triclinic, space group P1, a = 9.795(4) A, b = 10.472(4) A, c = 11.392(4) A, alpha = 86.67(3) degrees, beta = 66.67(3)degrees, gamma = 83.14(3) degrees, Z = 1), reported here, demonstrate a new supramolecular motif for cations of the type Ph3PY+ where Y is CH3 or Cl. The crystals contain columns of cations propagated by alternating 6-fold phenyl embraces (6PE) and pseudo-6PE: the pseudo-6PE described here contains four phenyl rings and two hetero groups (Cl or CH3), and is symbolized as 4P2Y. The zigzag sequence of cations engaged in ...6P...4P2Y...6P...4P2Y... is similar to the zigzag chain of infinite 6-fold phenyl embraces (ZZI6PE) frequently adopted by Ph4P+ cations in crystals. One-dimensionally nonmolecular anion chains with repeat unit [Cu3X8] run parallel to and between the columns of cations. The coordination geometry in the [Cu3X8(2-)]1 to infinity chain has not been observed in crystals with other cations, and it is postulated that the attractive interactions between cations in the pseudo-ZZI6PE crystal supramolecular motif control the geometry of the anions through the requirement for commensurability of cation columns and anion chains.

Journal Article↗

PubMed2000

A versatile vector set for animal transgenesis.

Genetic manipulation of a series of diverged arthropods is a highly desirable goal for a better understanding of developmental and evolutionary processes. A major obstacle so far has been the difficulty in obtaining marker genes that allow easy and reliable identification of transgenic animals. Here, we present a versatile vector set for germline transformation based on the promiscuous transposons mariner, Hermes and piggyBac. Into these vectors, we introduced a potentially universal marker system that is comprised of an artificial promoter containing three Pax-6 homodimer binding sites. This promoter drives strong expression of spectral variants of the enhanced green fluorescent protein (EGFP) in larval, pupal, and adult photoreceptors. Using special filter sets, the yellow (EYFP) and cyan (ECFP) variant are fully distinguishable and therefore represent a separable pair of markers. Furthermore, we adapted a simple plasmid-based transposition assay system to enable quick functional tests of our vectors in different arthropod species before employing them in more laborious germline transformation experiments. Using this system we demonstrate that our vectors transpose in both Drosophila melanogaster and Drosophila virilis.

Animals↗

PubMed2000

Highly sensitive, fluorescent transformation marker for Drosophila transgenesis.

The efficiency of transposon-mediated germline transformation is dependent on the transposon mobility in the host embryo, and on the detectability of the used transformation marker. Therefore, high susceptibility of the transformation marker to position effect suppression is a disadvantage. Here we present data that the eye-specific expression of green fluorescent protein, driven by the 3xP3-EGFP marker, outperforms the commonly used "mini"-white transformation marker in Drosophila germline transformation experiments: 3xP3-EGFP is more sensitive than "mini"-white in identifying transgenic individuals and reacts differently to position effect suppression. Therefore, 3xP3-EGFP offers an ideal marker for applications in functional genomics where as many gene loci as possible should be targeted in the genome of a specific organism, for example, as intended in the Drosophila gene disruption project. Furthermore, we give a detailed description of the embryonic and larval expression mediated by the 3xP3-EGFP marker. These pre-adult expression patterns, and the potentially universal applicability of the transformation marker also offer additional advantages for selecting transgenic individuals in organisms other than Drosophila. This will be of great interest to the field of evolutionary developmental biology and to modern pest management programs.

Animals↗

PubMed2000

Cargo binding and regulatory sites in the tail of fungal conventional kinesin.

Here, using a quantitative in vivo assay, we map three regions in the carboxy terminus of conventional kinesin that are involved in cargo association, folding and regulation, respectively. Using C-terminal and internal deletions, point mutations, localization studies, and an engineered 'minimal' kinesin, we identify five heptads of a coiled-coil domain in the kinesin tail that are necessary and sufficient for cargo association. Mutational analysis and in vitro ATPase assays highlight a conserved motif in the globular tail that is involved in regulation of the motor domain; a region preceding this motif participates in folding. Although these sites are spatially and functionally distinct, they probably cooperate during activation of the motor for cargo transport.

Adenosine Triphosphatases↗

PubMed2000

45/47 kilodalton (APA) antigen capture and antibody detection assays for the diagnosis of tuberculosis.

SETTING: APA complex (45/47 kDa) is an antigen specifically excreted by Mycobacterium tuberculosis and could therefore be a good candidate for diagnosis. OBJECTIVES: To develop three APA immunocapture ELISA assays using monoclonal antibodies (Mabs) and one IgG anti-APA ELISA test, and to determine their usefulness for the diagnosis of tuberculosis in Madagascar. DESIGN: For the Ag assays, 23 negative sputum and serum samples and 64 pairs of sputum and serum from active smear-positive patients (PTM+) were tested. For antibody assay, 116 negative controls, 143 PTM+ and 54 extra-pulmonary tuberculosis patients were tested. RESULTS: The sensitivities of the APA antigen detection assays were low (less than 40%) for a specificity of 95.6%, using either monoclonal antibodies or clinical specimens. The anti-APA serology was more sensitive (76.9% for PTM+ patients) but less specific (73.2%). Due to their poor predictive values, these tests cannot be recommended for the routine diagnosis of tuberculosis in Madagascar.

Antibodies, Bacterial↗

PubMed1999

Decreased capacity of recombinant 45/47-kDa molecules (Apa) of Mycobacterium tuberculosis to stimulate T lymphocyte responses related to changes in their mannosylation pattern.

The Apa molecules secreted by Mycobacterium tuberculosis, Mycobacterium bovis, or BCG have been identified as major immunodominant antigens. Mass spectrometry analysis indicated similar mannosylation, a complete pattern from 1 up to 9 hexose residues/mole of protein, of the native species from the 3 reference strains. The recombinant antigen expressed in M. smegmatis revealed a different mannosylation pattern: species containing 7 to 9 sugar residues/mole of protein were in the highest proportion, whereas species bearing a low number of sugar residues were almost absent. The 45/47-kDa recombinant antigen expressed in E. coli was devoid of sugar residues. The proteins purified from M. tuberculosis, M. bovis, or BCG have a high capacity to elicit in vivo potent delayed-type hypersensitivity (DTH) reactions and to stimulate in vitro sensitized T lymphocytes of guinea pigs immunized with living BCG. The recombinant Apa expressed in Mycobacterium smegmatis was 4-fold less potent in vivo in the DTH assay and 10-fold less active in vitro to stimulate sensitized T lymphocytes than the native proteins. The recombinant protein expressed in Escherichia coli was nearly unable to elicit DTH reactions in vivo or to stimulate T lymphocytes in vitro. Thus the observed biological effects were related to the extent of glycosylation of the antigen.

Amino Acid Sequence↗

PubMed1999

Fast and slow namers: benefits of segmentation and whole word training.

Poor readers in Grade 2 (mean age 7 years 7 months) were categorized into fast and slow namer groups based on their performance on a Rapid Automatized Naming (RAN) task. The fast and slow groups were then trained to read words using 3 different training regimes: one that taught onset/rime segmentation, one that taught phonemic segmentation, and one that used whole word repetition. The main results were that the slow namers acquired the words more slowly across experiences than the fast namers, irrespective of training condition, but they were particularly disadvantaged when trained with word-level units. Unlike beginning nonreaders, poor Grade 2 readers showed poorer retention following onset/rime training compared with phoneme or word level training, even when final level of learning was controlled. Further, they showed the best generalization to reading new words and nonwords following phoneme training and the worst following whole word training, even when final level of acquisition was controlled. The data are related to the P. G. Bowers and M. Wolf (1993, Reading and Writing, 5, 69-85) double-deficit hypothesis and to the specific deficits associated with early reading failure.

Child↗

PubMed1999

Deglycosylation of the 45/47-kilodalton antigen complex of Mycobacterium tuberculosis decreases its capacity to elicit in vivo or in vitro cellular immune responses.

A protection against a challenge with Mycobacterium tuberculosis is induced by previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guérin (BCG). The 45/47-kDa antigen complex (Apa) present in culture filtrates of BCG of M. tuberculosis has been identified and isolated based on its ability to interact mainly with T lymphocytes and/or antibodies induced by immunization with living bacteria. The protein is glycosylated. A large batch of Apa was purified from M. tuberculosis culture filtrate to determine the extent of glycosylation and its role on the expression of the immune responses. Mass spectrometry revealed a spectrum of glycosylated molecules, with the majority of species bearing six, seven, or eight mannose residues (22, 24, and 17%, respectively), while others three, four, or five mannoses (5, 9, and 14%, respectively). Molecules with one, two, or nine mannoses were rare (1.5, 3, and 3%, respectively), as were unglycosylated species (in the range of 1%). To eliminate the mannose residues linked to the protein, the glycosylated Apa molecules were chemically or enzymatically treated. The deglycosylated antigen was 10-fold less active than native molecules in eliciting delayed-type hypersensitivity reactions in guinea pigs immunized with BCG. It was 30-fold less active than native molecules when assayed in vitro for its capacity to stimulate T lymphocytes primed in vivo. The presence of the mannose residues on the Apa protein was essential for the antigenicity of the molecules in T-cell-dependent immune responses in vitro and in vivo.

Animals↗

PubMed1999

In vivo observation of cell division of anaerobic hyperthermophiles by using a high-intensity dark-field microscope.

To study growth and cell division of anaerobic hyperthermophilic archaea in vivo, a cultivation technique using glass capillaries was developed. At temperatures of 90 to 98 degrees C, at least 10 successive cell divisions of Pyrodictium abyssi TAG 11 were documented. Cells divide by binary fission. Visualized under a modified dark-field microscope, the formation of cannulae, which finally connected all cells, was observed. The cannulae elongated at 1.0 to 1.5 micrometers/min and reached final lengths of between 30 and 150 micrometers. A "snapping division"-like mode of cell fission was discovered for Thermoproteus tenax.

Anaerobiosis↗