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Biomedical subjects

R Weinberg

Publications and source records attributed to R Weinberg.

At least 19 recordsLinked to original sources
PubMed2001

Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids?

This article gives detailed insight into the kinetics of high-density lipoprotein (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non-human primate HDL with a similar composition. The oxidizability of non-human primate HDL was 1000 times lower than the oxidizability calculated from rate constants derived from liposome oxidation, suggesting that there is a slow step in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for non-human primate HDL were 2-3-fold lower than those for human HDL. Copper-catalyzed oxidation of non-human primate HDL was slower than that of human HDL, but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the kinetics describing the oxidation of HDL were mechanistically similar to those reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL lipids and that HDL will be easily oxidized in vivo when exposed to agents that oxidize LDL.

Amidines↗
PubMed2001

Biochemical and morphological characterization of an intracellular membrane compartment containing AMPA receptors.

AMPA receptors cycle rapidly in and out of the postsynaptic membrane, while NMDA receptors are relatively immobile. Changing the distribution of AMPA receptors between intracellular and surface synaptic pools is an important means of controlling synaptic strength. However, little is known about the intracellular membrane compartments of neurons that contain AMPA receptors. Here we describe biochemical and morphological characteristics of an intracellular pool of AMPA receptors in rat brain. By velocity gradient centrifugation of microsomal light membranes from rat brain, we identified a membrane fraction enriched for AMPA receptor subunits GluR2/3 but lacking NMDA receptors. This membrane compartment sedimented more slowly than synaptosomes but faster than synaptic vesicles and cofractionated with GRIP, PICK-1 and syntaxin-13. Morphological examination of this fraction revealed round and tubular vesicles ranging from approximately 50 to 300 nm in diameter. Immunocytochemistry of cultured hippocampal neurons showed that a significant portion of AMPA receptors colocalized with syntaxin-13 (a SNARE protein associated with tubulovesicular recycling endosomes) and with transferrin receptors. Taken together, these results suggest that a pool of intracellular GluR2/3 resides in a syntaxin 13-positive tubulovesicular membrane compartment, which might serve as a reservoir for the dendritic recycling of AMPA receptors.

Animals↗
PubMed2000

Cyclin D2 is essential for BCR-mediated proliferation and CD5 B cell development.

Progression into G(1) in B lymphocytes is regulated by cyclins D2 and D3, components of the cell cycle machinery currently believed to have overlapping and potentially redundant roles in cell cycle control. To study the specific role of cyclin D2 in B lymphocyte proliferation, we examined B cells from cyclin D2(-/-) mice and demonstrate a specific requirement for cyclin D2 in BCR- but not CD40- or lipopolysaccharide-induced proliferation. Furthermore, conventional B cell development proceeds normally in the mutant mice; however, the CD5 B cell compartment is dramatically reduced, suggesting that cyclin D2 is important in CD5 B cell development as well as antigen-dependent B cell clonal expansion.

Animals↗
PubMed1999

Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo.

The NMDA and AMPA classes of ionotropic glutamate receptors are concentrated at postsynaptic sites in excitatory synapses. NMDA receptors interact via their NR2 subunits with PSD-95/SAP90 family proteins, whereas AMPA receptors bind via their GluR2/3 subunits to glutamate receptor-interacting protein (GRIP), AMPA receptor-binding protein (ABP), and protein interacting with C kinase 1 (PICK1). We report here a novel cDNA (termed ABP-L/GRIP2) that is virtually identical to ABP except for additional GRIP-like sequences at the N-terminal and C-terminal ends. Like GRIP (which we now term GRIP1), ABP-L/GRIP2 contains a seventh PDZ domain at its C terminus. Using antibodies that recognize both these proteins, we examined the subcellular localization of GRIP1 and ABP-L/GRIP2 (collectively termed GRIP) and their biochemical association with AMPA receptors. Immunogold electron microscopy revealed the presence of GRIP at excitatory synapses and also at nonsynaptic membranes and within intracellular compartments. The association of native GRIP and AMPA receptors was confirmed biochemically by coimmunoprecipitation from rat brain extracts. A majority of detergent-extractable GluR2/3 was complexed with GRIP in the brain. However, only approximately half of GRIP was associated with AMPA receptors. Unexpectedly, immunocytochemistry of cultured hippocampal neurons and rat brain at the light microscopic level showed enrichment of GRIP in GABAergic neurons and in GABAergic nerve terminals. Thus GRIP is associated with inhibitory as well as excitatory synapses. Collectively, these findings support a role for GRIP in the synaptic anchoring of AMPA receptors but also suggest that GRIP has additional functions unrelated to the binding of AMPA receptors.

Amino Acid Sequence↗
PubMed1998

Differential regional expression and ultrastructural localization of alpha-actinin-2, a putative NMDA receptor-anchoring protein, in rat brain.

Fast chemical neurotransmission is dependent on ionotropic receptors that are concentrated and immobilized at specific postsynaptic sites. The mechanisms of receptor clustering and anchoring in neuronal synapses are poorly understood but presumably involve molecular linkage of membrane receptor proteins to the postsynaptic cytoskeleton. Recently the actin-binding protein alpha-actinin-2 was shown to bind directly to the NMDA receptor subunits NR1 and NR2B (), suggesting that alpha-actinin-2 may function to attach NMDA receptors to the actin cytoskeleton. Here we show that alpha-actinin-2 is localized specifically in glutamatergic synapses in cultured hippocampal neurons. By immunogold electron microscopy, alpha-actinin-2 is concentrated over the postsynaptic density (PSD) of numerous asymmetric synapses where it colocalizes with NR1 immunoreactivity. Thus alpha-actinin-2 is appropriately positioned at the ultrastructural level to function as a postsynaptic-anchoring protein for NMDA receptors. alpha-Actinin-2 is not, however, exclusively found at the PSD; immunogold labeling was also associated with filaments and the spine apparatus of dendritic spines and with microtubules in dendritic shafts. alpha-Actinin-2 showed marked differential regional expression in rat brain. For instance, the protein is expressed at much higher levels in dentate gyrus than in area CA1 of the hippocampus. This differential regional expression implies that glutamatergic synapses in various parts of the brain differ with respect to their alpha-actinin-2 content and thus, potentially, the extent of possible interaction between alpha-actinin-2 and the NMDA receptor.

Actinin↗
PubMed1998

Bone maintenance 5 to 10 years after sinus grafting.

PURPOSE: This radiographic study determined the amount of bone around hydroxyapatite (HA)-coated dental implants that were placed into bone-grafted maxillary sinuses. PATIENTS AND METHODS: Postoperative complex motion tomograms using the Grossman technique were taken on 16 patients who had 27 maxillary sinus grafts performed using particulate autogenous iliac bone with and without demineralized bone, autogenous iliac corticocancellous block with and without demineralized bone, and autogenous jaw bone with demineralized bone. Bone levels were measured from the new floor of the grafted sinus to the apex of the implant and to the alveolar crest. The resulting bone level measures were compared with the type of graft used. All patients had been restored for 5 to 10 years after simultaneous graft and implant placement. RESULTS: For all patients summed together, the average amount of bone from the top of the graft to the apex of the implant was 3.3 +/- 3.1 mm, and the average amount of bone from the top of the graft to the alveolar crest was 17.6 +/- 3.1 mm. The average level of bone in the sinuses of patients grafted with autogenous iliac bone was greater than the average level of bone in those grafted with autogenous bone combined with demineralized bone. CONCLUSION: The results of this study indicate that autogenous bone grafts are maintained in the maxillary sinus, but the results with autogenous bone alone are better than when demineralized bone is added. However, this difference may not be clinically significant.

Adolescent↗
PubMed1997

Iliac apophyseal cartilage augmentation of the deficient piriform rim and maxilla in alveolar cleft grafting.

This article presents a new approach to cleft lip and cleft palate repair, where the retained bulk of alveolar cleft grafts is augmented by simultaneous cartilage augmentation of the deficient maxilla. Nine patients who provided 10 cleft sites underwent secondary bone grafting of the clefted alveolus by this technique. This study evaluates the following: (1) the postoperative esthetic results, (2) the quantity of bone in the grafted area, and (3) the provision of bone support for unerupted teeth, for teeth adjacent to the cleft, and for orthodontic tooth movement when the secondary bone grafting of the cleft is integrated with the onlay augmentation of the deficient maxilla. Photographic and radiographic investigations were undertaken. The photographic evaluation showed that all patients exhibited improved facial esthetics in the area of the cleft, particularly in the paranasal area of the maxilla; improved alar base support, symmetry of the columella, and less deviation of the tip of the nose were seen. The radiographic evaluation indicated the following: (1) the average percentage of the alveolar bone height of the grafted area was equal to 76% of the normal side; (2) nine canines erupted or were erupting through the grafted area; there were no adequate records to evaluate the fate of the remaining canine; (3) no teeth involved in the cleft area were ankylosed, because of inadequate records, so evaluators could not determine the status of one tooth; (4) all patients had adequate quantity of bone for orthodontic tooth movement through the grafted area; and (5) the periodontal support of the teeth involved in the cleft was adequate.

Alveolar Process↗
PubMed1997

Film-screen systems: sensitometric comparison of Kodak Ektavision system to Kodak T-Mat/RA system.

BACKGROUND: In 1995, Eastman Kodak Company (Rochester, N.Y.) marketed the Ektavision Extraoral Imaging Film and Screen System. It produced high-resolution images by keeping the light emitted by intensifying screens from "punching through" one emulsion layer on the film to another. OBJECTIVES: The objectives of the experiment were (1) to compare the sensitometric properties of the Ektavision system to its predecessor, the T-Mat/RA system and (2) to determine whether films and screens of the Ektavision and the T-Mat/RA systems could be interchanged without clinically changing the sensitometric properties. Ektavision and Lanex Regular intensifying screens were used in combination with Ektavision, T-Mat G/RA, T-Mat L/RA, and T-Mat H/RA films. RESULTS: The results showed that the Ektavision film was slightly slower than the T-Mat G/RA film no matter what type of screen was used. The type of screen used had little effect on inherent contrast or exposure latitude. The Ektavision film had approximately similar inherent contrast as the T-Mat G/RA film but less than that of the T-Mat H/RA film; its latitude was less than that of the T-Mat L/RA film. The manufacturer does not recommend combining T-Mat/RA film with Ektavision screens or Lanex Regular screens with Ektavision film because of a possible reduction in image resolution. But this mismatch did not clinically affect inherent contrast and exposure latitude; however, film speed was slightly affected. CONCLUSIONS: The Ektavision system is the result of advanced technology that produces images of high resolution. The high-resolution Ektavision film is slightly slower than the T-Mat G/RA film but is equivalent to it in its contrast and latitude. Therefore when changing from the combination of T-Mat/RA film plus Lanex Regular screens to that of Ektavision film plus Ektavision screens, a slight increase in x-radiation exposure should be made.

Radiation Dosage↗
PubMed1996

Effects of tomographic motion, slice thickness, and object thickness on film density.

The experiment used the computer-aided CommCat model IS 2000 tomographic machine (Imaging Sciences International, Roebling, N.J.). The objective of the experiment was to study the influence of tomographic tube motion, tomographic slice thickness, and object thickness on film density. The experiment was conducted by x-radiating an aluminum step-wedge placed along the x-axis. Exposures were made for different tube motions and for different slice thicknesses. In linear horizontal and linear vertical motions, an increased slice thickness decreased film density. Slice thickness had a stronger effect on film density when the object to be x-radiated was thinner. In circular, elliptical, spiral, and hypocycloidal motions, changes in slice thickness had no noticeable effect on film density because the manufacturer had programmed the machine to produce approximately similar exposure times by increasing the x-ray tube velocity thickness had a greater effect on film density for circular, elliptical, spiral, and hypocycloidal tube motions than for linear horizontal and linear vertical tube motions. Clinical observation showed that except for the linear vertical motion (motion that was oriented in the same direction as that of the tube travel) all other motions produced a zone of diffusion along the edges of the steps of the step-wedge. An increase in slice thickness had an effect on film density. Slice thickness had a noticeable effect on film density in linear but not in multidirectional tomography. Object thickness had a greater effect on film density in multidirectional than in linear tomography.

Absorptiometry, Photon↗
PubMed1995

Sensitometric comparison of Kodak EKTASPEED Plus, Ektaspeed, and Ultra-speed Dental Films.

In 1994, Eastman Kodak Co. (Rochester, N.Y.) marketed EKTASPEED Plus dental film to combine the advantages of the contrast of Ultra-speed film and the speed of Ektaspeed film. EKTASPEED Plus film uses T-Grain Emulsion technology similar to that used in the manufacture of the light-sensitive indirect exposure Kodak T-Mat film. This study compared the sensitometric properties of Ultra-speed, Ektaspeed, and EKTASEED Plus dental films. EKTASPEED Plus film was faster than Ektaspeed film at all film densities. Ektaspeed film became slower at higher densities and around a density of 1.9 became even slower than the Ultra-speed film. EKTASPEED Plus film had high inherent contrast and narrow exposure latitude similar to that of Ultra-speed film, whereas Ektaspeed film had low inherent contrast and wide exposure latitude. In conclusion, EKTASPEED Plus film had the advantages of the high contrast of Ultra-speed film and the high speed of Ektaspeed film. It maintained its high speed at high densities.

Absorptiometry, Photon↗
PubMed1995

Effects of developer exhaustion on Kodak EKTASPEED Plus, Ektaspeed, and Ultra-speed dental films.

In 1994, Eastman Kodak Co. (Rochester, N.Y.) replaced its Ektaspeed film with the EKTASPEED Plus film. The manufacturer claims that one of the advantages of the new film is that it is not strongly affected by exhausted (depleted plus aged) processing solutions. The objective of the experiment was to test this claim. In exhausted solutions, EKTASPEED Plus film lost its speed more rapidly than Ultra-speed film but less rapidly than Ektaspeed film; that is, Ultra-speed film had the most stable speed. EKTASPEED Plus film lost contrast for 2 weeks before stabilizing, whereas Ultra-speed and Ektaspeed films continued to lose contrast for 3 weeks. Overall, EKTASPEED Plus film held its contrast over the other two films. EKTASPEED Plus film stopped increasing its film latitude after 2 weeks, whereas Ultra-speed and Ektaspeed films continued to increase film latitudes. In conclusion, for the three films studied, EKTASPEED Plus maintained the most constant levels of contrast and latitude in progressively exhausted solutions. All three films lost speed in exhausted solutions; EKTASPEED Plus film was the fastest but Ultra-speed film had the most stable speed.

Absorptiometry, Photon↗
PubMed1994

Information recall of younger and older skilled athletes: the role of display complexity, attentional resources and visual exposure duration.

This study was concerned with the interactive role of experience of athletic skill with other relevant environmental variables (display complexity, attentional resources, exposure time of stimuli) on perception (recall) of structured handball game situations. Nineteen experienced (older) and 19 less experienced (younger) handball players were assigned randomly either to ball-bouncing (diverted attention) or to calm seated (focused attention) conditions. In each of the two conditions, the subjects were exposed to a total of 36 slides containing 2-3, 5-6 and 8-10 players. Eighteen slides were exposed for 0.5 s and 18 for 1.0 s. All the slides contained structured defence and offence situations. Recall scores were subjected to repeated-measures ANOVA using attention condition and age as between-subject factors and task complexity and exposure duration as within-subject factors. The results showed that the recall of less experienced players deteriorated more than the recall of more experienced players following exposure to complex displays (> or = 8 players) while engaging in a secondary task (bouncing). The findings suggest that research paradigms should be applied in the field of sport which share both ecological validity and a potential to discover the cognitive substrates underlying experience and age in skilled motor performance.

Adolescent↗
PubMed1994

Characterization of a cleavage mutant of the measles virus fusion protein defective in syncytium formation.

Membrane fusion caused by measles virus (MV) is a function of the fusion (F) protein. This process is essential for penetration into the host cell and subsequent initiation of the virus replicative cycle. The biological activity of the MV F protein is generated by endoproteolytic cleavage of a precursor protein (F0) into a large F1 subunit and a smaller F2 subunit held together by disulfide bonds. The cleavage site consists of a cluster of five basic amino acids (amino acids 108 to 112) within the predicted primary structure of the F protein. To investigate the role of the arginine residue at the carboxy terminus of the F2 subunit (arginine 112), site-directed mutagenesis was used to construct a cleavage mutant of the MV F protein in which this arginine residue was changed to a leucine residue. The mutated F gene, encoding four out of the five basic amino acids at the cleavage site, was inserted into the genome of vaccinia virus. The resulting recombinant virus was used to study expression of the mutant F protein in infected cells. Analysis of the Leu-112 mutant protein made in infected cells demonstrated that this single-amino-acid substitution resulted in a reduced rate of transport of the mutant protein to the cell surface, despite its efficient cleavage to yield F1 and F2 subunits. However, the electrophoretic mobilities of the Leu-112 polypeptides suggested that the protein was cleaved incorrectly. This aberrant cleavage appears to have abolished the ability of the F protein to cause syncytium formation. The data indicate that the arginine 112 residue is critical for the correct proteolytic cleavage that is required for the membrane fusion activity of the MV F protein.

Amino Acid Sequence↗
PubMed1994

Functional analysis of N-linked glycosylation mutants of the measles virus fusion protein synthesized by recombinant vaccinia virus vectors.

The role of N-linked glycosylation in the biological activity of the measles virus (MV) fusion (F) protein was analyzed by expressing glycosylation mutants with recombinant vaccinia virus vectors. There are three potential N-linked glycosylation sites located on the F2 subunit polypeptide of MV F, at asparagine residues 29, 61, and 67. Each of the three potential glycosylation sites was mutated separately as well as in combination with the other sites. Expression of mutant proteins in mammalian cells showed that all three sites are used for the addition of N-linked oligosaccharides. Cell surface expression of mutant proteins was reduced by 50% relative to the wild-type level when glycosylation at either Asn-29 or Asn-61 was abolished. Despite the similar levels of cell surface expression, the Asn-29 and Asn-61 mutant proteins had different biological activities. While the Asn-61 mutant was capable of inducing syncytium formation, the Asn-29 mutant protein did not exhibit any significant cell fusion activity. Inactivation of the Asn-67 glycosylation site also reduced cell surface transport of mutant protein but had little effect on its ability to cause cell fusion. However, when the Asn-67 mutation was combined with mutations at either of the other two sites, cleavage-dependent activation, cell surface expression, and cell fusion activity were completely abolished. Our data show that the loss of N-linked oligosaccharides markedly impaired the proteolytic cleavage, stability, and biological activity of the MV F protein. The oligosaccharide side chains in MV F are thus essential for optimum conformation of the extracellular F2 subunit that is presumed to bind cellular membranes.

Animals↗