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Biomedical subjects

D Hayden

Publications and source records attributed to D Hayden.

28 records · Page 2Linked to original sources
PubMed1990

An evaluation of the biological response to Fraxiparine, (a low molecular weight heparin) in the healthy individual.

The tolerance of a low molecular weight heparin (Fraxiparine, Choay, Paris, France) in normal individuals was determined using a two part investigation. Study 1 consisted of administering escalating doses of Fraxiparine in a single blinded, placebo controlled, rising dose tolerance evaluation. The daily doses tested were 3750 U AXA IC, 7500 U AXa IC, 11250 U AXa IC, 15000 U AXa IC, and 22500 U AXa IC Fraxiparine subcutaneously for 5 consecutive days. In study 2, we compared the tolerance of unfractionated heparin (UH) administered as 5000 IU every 8 hours, to that of 7500 U AXa IC/day or 15000 U AXa IC/day of Fraxiparine administered once daily. Our results indicated very good tolerance to this low molecular weight heparin (LMWH) at doses up to and including 22500 U AXa IC/day. We observed significantly elevated increases in transaminases following LMWH administration. In our second study we observed that the increase in serum transaminases seen after 15000 U AXa IC/day Fraxiparine was without significant difference from that observed following UH (5000 IU every 8 hours). AXa examination revealed an accumulation of AXa effect after 5 days of administration at doses greater than 15000 U AXa IC, and there was good correlation between AXa and APTT at Fraxiparine doses greater than 15000 U AXa IC/day. No thrombocytopenia was associated with Fraxiparine. We conclude that Fraxiparine is relatively well tolerated and shows accumulation after daily dosing with greater than 15000 U AXa IC.

Adult↗
PubMed1989

Fibroblasts transfected with Torpedo acetylcholine receptor beta-, gamma-, and delta-subunit cDNAs express functional receptors when infected with a retroviral alpha recombinant.

Torpedo californica acetylcholine receptor (AChR) alpha-, beta-, gamma-, and delta-subunit cDNAs were each stably introduced into muscle and/or fibroblast cell lines using recombinant retroviral vectors and viral infection, or using SV-40 vectors and DNA-mediated cotransfection. The expressed proteins were characterized in terms of their molecular mass, antigenicity, posttranslational processing, cell surface expression, stability in fibroblasts, stability in differentiated and undifferentiated muscle cells, and ability (of alpha) to bind alpha-bungarotoxin (BuTx). We demonstrated that the alpha, beta, gamma, and delta polypeptides acquired one, one, two, and three units of oligosaccharide, respectively. If all four subunits were expressed in the same cell, fully functional cell surface AChRs were produced which had a Kd for BuTx of 7.8 X 10(-11) M. In contrast, subunits expressed individually were not detected on the surface of fibroblasts and the Kd for BuTx binding to individual alpha polypeptides was only approximately 4 X 10(-7) M. The half-lives of the alpha, gamma, and delta subunits at 37 degrees C were all found to be quite short (approximately 43 min), while the half-life of the beta subunit was found to be even shorter (approximately 12 min). The unique half-life of the beta subunit suggests that it might perform a key regulatory role in the process of AChR subunit assembly. One stable fibroblast cell line was established by transfection that expressed beta, gamma, and delta subunits simultaneously. When this cell line was infected with a retroviral alpha recombinant, fully functional cell surface AChRs were produced. The successful expression of this pentameric protein complex combining transfection and infection techniques demonstrates one strategy for stably introducing the genes of a heterologous multisubunit protein complex into cells.

Animals↗
PubMed1988

Limb and oral praxic abilities of children with verbal sequencing deficits.

This study was concerned with children with impaired articulation, with a specific deficit in verbal sequences of consonant-vowel syllables; i.e. verbal sequenced motion rate (SMR). Speech-disordered children with and without this SMR disorder were compared with a group of control children on their performance of single limb and oral gestures and sequences of limb and oral gestures. Performances of an action requiring four different responses and of one requiring the same repeated response were also examined. The children with verbal SMR disorder had greater difficulty in performing both single and sequences of limb and oral gestures compared with the other two groups, as they also had in the task requiring four different responses. There were no differences between the groups in the task requiring the same repeated response. These findings suggest that children with verbal SMR disorder may have a generalized motor disorder which affects performance of both single gestures and sequences of gestures.

Apraxias↗
PubMed1987

Genetic reconstitution of functional acetylcholine receptor channels in mouse fibroblasts.

Foreign genes can be stably integrated into the genome of a cell by means of DNA-mediated gene transfer techniques, and large quantities of homogenous cells that continuously express these gene products can then be isolated. Such an expression system can be used to study the functional consequences of introducing specific mutations into genes and to study the expressed protein in the absence of cellular components with which it is normally in contact. All four Torpedo acetylcholine receptor (AChR) subunit complementary DNA's were introduced into the genome of a mouse fibroblast cell by DNA-mediated gene transfer. A clonal cell line that stably produced high concentrations of correctly assembled cell surface AChR's and formed proper ligand-gated ion channels was isolated. With this new expression system, recombinant DNA, biochemical, pharmacological, and electrophysiological techniques were combined to study Torpedo AChR's in a single intact system. The physiological and pharmacological profiles of Torpedo AChR's expressed in mouse fibroblast cells differ in some details from those described earlier, and may provide a more accurate reflection of the properties of this receptor in its natural environment.

Animals↗
PubMed1986

Effects of cyclosporine in spontaneous, posterior uveitis.

Cyclosporin A (CsA) was administered to chicks of the Smyth delayed-amelanotic (SDA) line from day of hatch to 4, 8 or 12 weeks of age. Animals were evaluated at 8, 12, 16 or 20 weeks with regard to major features of the SDA-line disorder, including extent of feather and choroidal amelanosis, choroidal inflammation, and histopathology of the retinal pigment epithelium and outer retina. A suppression and delay in the onset of both amelanosis and ocular histopathology occurred during CsA administration. However, a rebound enhancement of symptoms occurred 4-8 weeks after withdrawal of CsA that was closely associated with the duration of CsA treatment. These results indicate that CSA may yield therapeutic effects during the period of treatment, but its withdrawal may lead to more severe symptoms that would have occurred without treatment.

Animals↗
PubMed1985

The accessory optic system and temporal correlates of visuomotor orientation.

Surgical transection of the basal optic root in Rana pipiens leads to substantial increases in prey-orientation latencies for stimuli presented in the contralateral visual field. In general, the greater the reduction in retinal innervation of nBOR, the greater the postoperative increase in prey-orientation latencies. The results support Herrick's earlier suggestion that the accessory optic system may be substantially involved in early activation and temporal modulation of visuomotor behaviors mediated via mesencephalic circuits.

Animals↗
PubMedDate not supplied

Cell-specific induction of hsp72-mediated protection by glutamine against oxidant injury in IEC18 cells.

Glutamine is a major metabolic fuel and trophic agent for intestinal epithelial cells that can enhance intestinal epithelial cell survival against oxidant and thermal stress, possibly through the induction of heat shock protein 72 (hsp72). In this study, we examined the possibility of a direct causal relationship and tissue specificity of glutamine-induced hsp72. Glutamine treatment of intestinal (epithelial) IEC18 cells, but not HeLa (epidermoid) cells, induces the production of hsp72 in a concentration-dependent fashion, without affecting the expression of the constitutively expressed heat shock protein, hsc73. To determine the specific role that hsp72 induction by glutamine plays in resistance of IEC18 cells to oxidant injury, stable transfected cells expressing an hsp72 antisense construct were established. Although thermal induction of hsp72 was blocked only partially by the antisense construct, glutamine induction of hsp72 was completely inhibited. This was associated with a loss of the protective effects of glutamine against oxidant-induced stress. Thus, glutamine specifically induces hsp72 in intestinal epithelial cells, which mediates cell protection against inflammation-induced stress such as oxidants.

Animals↗