Recommended guidelines for studies of human subjects with spinal cord injury.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
S Whittemore
Publications and source records attributed to S Whittemore.
Analysis of NMDA receptors in the human spinal cord.
NMDA receptors in postmortem human spinal cord were analyzed using [3H]MK-801 ligand binding and immunoblotting with NMDA receptor subunit-specific antibodies. The average KD for [3H]MK-801 binding was 1.77 nM with a Bmax of 0.103 pmol/mg. The EC50 for stimulation of -3H-MK-801 binding with L-glutamate was 0.34 microM. None of these parameters were affected by postmortem intervals up to 72 h. Immunoblotting of native NMDA receptors showed that NR1, NR2A, NR2C, and NR2D subunits could all be found in the human spinal cord of which NR1 was preferentially located to the dorsal half. Immunoprecipitation of solubilized receptors revealed that NR1, NR2C, and NR2D subunits coprecipitated with the NR2A subunit, indicating that native human spinal cord NMDA receptors are heteroligimeric receptors assembled by at least three different receptor subunits. These results provide a basis for the development of drugs selectively aimed at spinal cord NMDA receptors for the future treatment of spinal cord disorders.
Cadaver↗
No protective effect of the NMDA antagonist memantine in experimental spinal cord injuries.
We have investigated the effect of memantine, a clinically used NMDA receptor antagonist, in two experimental animals models of spinal cord injury. The lesions were laser-induced photothrombosis to induce focal spinal cord ischemia and clip compression to mimic traumatic spinal cord injury. Pre- or posttreatment of rats with a dose of memantine (20 mg/kg ip) previously shown to be neuroprotective in cerebral ischemia, failed to affect both the neurological and morphological outcome of ischemic spinal cord injury. Likewise, memantine had no effects on neurological and morphological outcome after experimental traumatic injury. In view of the regional heterogeneity of NMDA receptors, the affinity of memantine for spinal cord NMDA receptors was also determined by studying displacement of [3H] (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cyclohepten-5-10-imine (MK-801) to rat and human spinal cord homogenates. We found that memantine had an affinity for NMDA receptors in the spinal cord (Ki = 0.58 microM) that was significantly lower compared to that of the cerebral cortex (Ki = 0.23 microM) and that the affinity for NMDA receptors in human spinal cord was even lower. We conclude that in view of available data, memantine should not be chosen for clinical studies on neuroprotection in spinal cord injuries and that the lack of protective effect is most likely due to insufficient affinity of memantine for spinal cord NMDA receptors.
Adult↗
Recent development in the treatment and prevention of disseminated Mycobacterium avium complex (MAC).
Explore the source record for details and available documents.
AIDS-Related Opportunistic Infections↗
Cellular uptake of 3,5,3'-triiodothyronine and thyroxine by red blood and thymus cells.
During recent studies of receptor binding of T3 and T4 in tadpole red blood cells (RBCs), it was found that the fractional uptake of T3 was 3-5 times greater than that of T4. The present studies were performed to determine if this difference was due to facilitated uptake of T3. All studies were performed in cells incubated at 22 C in phosphate-buffered amphibian or mammalian Ringer solution containing 10(-11) M [125I]T3 or [125I]T4, with or without nonradioactive L-T3, D-T3, or L-T4 in concentrations ranging from 10(-10) to 2 X 10(-7) M. In tadpole, frog, rat, and human RBCs and in rat thymus cells, the rate of uptake of [125I]T3 and its appearance in the cytosol (extranuclear) fraction of the cell was greatly retarded in the presence of 10(-7) M T3. This effect was not due to saturation of the T3-binding proteins in cytosol, since the presence of 10(-7) M T3 did not influence the percentage of [125I]T3 in cytosol at equilibrium. These data suggest the presence of a saturable system for the cellular uptake of T3. T4 (10(-7) M) had relatively little effect, and D-T3 (10(-7) M) had no effect on this system. No saturable system for T4 uptake could be demonstrated, and at low concentrations of hormone, T4 uptake was only 10-30% of T3 uptake, although the binding activities of cytosol and cellular uptake via nonsaturable systems were quantitatively similar for both hormones. From kinetic studies of [125I]T3 uptake, it was found that at low concentrations of T3 (10(-11)-10(-9) M), the saturable system accounted for more than 60% of the total uptake of [125I]T3. The apparent Km values of the saturable system in RBCs of tadpole, frog, and rat were 4.5 +/- 0.09 (+/- SE), 5.7 +/- 1.10, and 4.6 +/- 0.73 X 10(-8) M T3, respectively. Corresponding values for maximum velocity were 5.92 +/- 1.02, 2.86 +/- 0.70, and 2.08 +/- 0.34 pmol/min X 10(7) cells. In rat thymus cells, the Km was 16.9 +/- 0.93 X 10(-8) M, and the maximum velocity was 9.10 +/- 0.5 pmol/min X 10(7) cells. The saturable uptake system was not influenced by ouabain, dinitrophenol, sodium fluoride, oligomycin, or sodium cyanide. These findings suggest that the uptake of T3, but not T4, into some tissues is facilitated by a specific carrier-mediated system that is not dependent on metabolic energy.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗