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Biomedical subjects

E Sperber

Publications and source records attributed to E Sperber.

12 recordsLinked to original sources

Center for Synchrotron Biosciences' U2B beamline: an international resource for biological infrared spectroscopy.

A synchrotron infrared (IR) beamline, U2B, dedicated to the biomedical and biological sciences has been constructed and is in operation at the National Synchrotron Light Source (NSLS) of Brookhaven National Laboratory. The facility is operated by the Center for Synchrotron Biosciences of the Albert Einstein College of Medicine in cooperation with the NSLS. Owing to the broadband nature of the synchrotron beam with brightness 1000 times that of conventional sources, Fourier transform IR spectroscopy experiments are feasible on diffraction-limited sample areas at high signal-to-noise ratios and with relatively short data-acquisition times. A number of synchrotron IR microscopy experiments that have been performed in the mid-IR spectral range (500-5000 cm(-1)) are summarized, including time-resolved protein-folding studies in the microsecond time regime, IR imaging of neurons, bone and other biological tissues, as well as imaging of samples of interest in the chemical and environmental sciences. Owing to the high flux output of this beamline in the far-IR region (50-500 cm(-1)), investigations of hydrogen bonding and dynamic molecular motions of biomolecules have been carried out from 10 to 300 K using a custom-made cryostat and an evacuated box. This facility is intended as an international resource for biological IR spectroscopy fully available to outside users based on competitive proposal.

Bone and Bones↗

Safety and immunogenicity of live attenuated quadrivalent human-bovine (UK) reassortant rotavirus vaccine administered with childhood vaccines to infants.

The safety and immunogenicity of an orally administered, live rotavirus vaccine comprised of four strains, each with a titer of 10(5.3) or 10(5.8) pfu, and each having 10 genes from the UK bovine strain and the VP7 gene from human rotavirus serotype 1, 2, 3, or 4, were evaluated in adults, young children and infants in randomized, double-blind phase 1 trials. Three doses of rotavirus vaccine or placebo given with childhood immunizations to infants at 2, 4, and 6 months of age were well tolerated and did not inhibit antibody responses to childhood vaccines which included DTP, Hib, hepatitis B and OPV. Serum rotavirus antibody responses were detected in 12 of 20 infants after 1 dose, and in 19/19 of the vaccinees after three doses. Neutralizing antibody responses were detected more often against the bovine rotavirus UK strain (95%) than to human rotavirus VP7 serotypes 1 (37%), 2 (32%), 3 (32%) or 4 (32%). The efficacy of this quadrivalent rotavirus vaccine needs to be evaluated further.

Adolescent↗

Safety and immunogenicity of live attenuated human-bovine (UK) reassortant rotavirus vaccines with VP7-specificity for serotypes 1, 2, 3 or 4 in adults, children and infants.

Live rotavirus vaccine candidates representing VP7 serotypes 1, 2, 3 or 4 derived by reassortment between bovine UK rotavirus and human rotavirus strains D, DS-1, P or ST3 were evaluated for safety and immunogenicity in adults, children and infants. Infection was defined by evidence of rotavirus shed in stools or a 4-fold or greater increase in serum rotavirus-specific IgA or IgG ELISA or plaque reduction neutralization antibody. A single oral dose (10(5.3) or 10(5.8) pfu) of reassortant virus was well tolerated and infected most infants: 10/20 (50%) by D x UK; 9/11 (82%) by DS-1 x UK; 8/10 (80%) by P x UK and 13/14 (93%) by ST3 x UK. All 14 infants given two doses of D x UK were infected. These findings demonstrating satisfactory levels of attenuation, safety, infectivity and immunogenicity of each reassortant in infants warrant additional studies of a candidate vaccine containing these four strains.

Adolescent↗

The density of GABAB binding sites in the substantia nigra is greater in rat pups than in adults.

Baclofen-displaced [3H]GABA (gamma-aminobutyric acid) binding to GABAB sites was assayed in brain regions obtained from adult and 14- to 17-day-old rats. The substantia nigra of rat pups exhibited a 3- to 5-fold higher density (Bmax) of GABAB binding sites than the nigra of adult rats. In contrast, the density of GABAB sites was lower in hippocampal and cerebellar tissue from pups, both approximately two-thirds the density in corresponding adult structures. This anatomically selective overproduction of GABAB receptors in immature substantia nigra is consistent with the increased anticonvulsant efficacy of the GABAB agonist baclofen observed in rat pups.

Age Factors↗

Potentiation of cold-water swim analgesia and hypothermia by clonidine.

The analgesia induced by acute exposure to cold-water swims (CWS) covaries with levels of brain norepinephrine and is reduced by lesions placed in the locus coeruleus. In assessing whether alpha-noradrenergic receptor mechanisms mediated CWS analgesia, the first experiment found that clonidine pretreatment (500, 1000 micrograms/kg) elevated jump thresholds 60 min following injection. While clonidine (1000 micrograms/kg) paired with a 2 degrees C CWS potentiated CWS analgesia in a synergistic manner, additivity of analgesic effects was observed following pairing of clonidine (500 micrograms/kg) with a 2 degrees C CWS and pairing of clonidine (500 and 1000 micrograms/kg) with a 15 degrees C CWS. The second experiment showed that clonidine (500 micrograms/kg) paired with a 2 degrees C CWS enhanced CWS enhanced CWS analgesia on the tail-flick test. The third experiment indicated that while clonidine (500 and 1000 micrograms/kg) or CWS (2 degrees C) each produced hypothermia, pairing of these clonidine doses with CWS enhanced CWS hypothermia. These data are discussed in terms of the possible modulatory role that norepinephrine, and particularly its alpha-noradrenergic receptor subclass, plays in the full expression of CWS analgesia and hypothermia.

Analgesics↗

Communicating hydrocephalus. Cisternographic and neuropathologic studies.

Chronic communicating hydrocephalus was produced in adult dogs by injection of silastic into the subarachnoid space. Electron microscopy was used to verify the sequence of pathologic changes in the ventricular wall. The pathologic findings were correlated with cisternographic images and measurements of cerebrospinal fluid (CSF) pressure. Early in hydrocephalus, the CSF pressure was increased and cisternograms showed ventricular entry and clearing; the ependyma was stretched and fluid accumulated in subependymal regions. In animals with chronic hydrocephalus, the CSF pressure was normal and cisternograms disclosed radioactivity persisting in the ventricles. At this time the ependyma was severely damaged, the subependymal white matter showed enlargement of the extracellular space, and degenerative changes were present in axons and myelin sheaths.

Animals↗