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PubMed1995

Duffy and receptors for P. vivax and chemotactic peptides.

The Duffy blood group system consists of two principal antigens, Fya and Fyb produced by FY*A and FY*B co-dominant alleles. Antisera, anti-Fya and anti-Fyb, define four phenotypes: Fy(a+b-), Fy(a-b+), Fy(a+b+) and Fy(a-b-). Neither antiserum agglutinates Fy(a-b-) cells, the predominant phenotype in Blacks. Outside the Black population, Fy(a-b-) phenotype is very rare. Duffy antigens appear to be multimeric erythrocyte-membrane proteins composed of different subunits. A glycoprotein of 35-45 kDa, gp-Fy, is the major subunit of the complex and has antigenic determinants defined by Duffy antibodies. The protein consists of 337 amino acid residues with a M(r) of 35,733, the same as deglycosylated gp-Fy. The hydropathy map predicts an exocellular N-terminal domain of 64 residues, nine transmembrane alpha-helices, three short protruding hydrophilic loops and an endocellular C-terminal domain of 23 residues. Duffy specific transcript, a approximately 1.3 kb mRNA, is produced by the bone marrow of Duffy-positive individuals, but it is not produced by the bone marrow of Duffy-negative individuals. The same size mRNA is produced in many tissues of Duffy-positive individuals. The same tissues of Duffy-negative individuals also synthesize the same size mRNA and the same gp-Fy as that of Duffy-positive individuals. There is not, therefore, Duffy null phenotype in the Black population. The difference between FY*A and FY*B alleles is a single nucleotide change at position 306; guanine is in FY*A, and adenine is in FY*B.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Measuring effectiveness in health visiting.

While resources for health remain limited, all managers must be able to demonstrate the cost-effectiveness of the services provided. Computer technology now provides the data with which to measure efficiency. Health visitors (together with other community-based professions) need to recognise the opportunities that information technology (IT) offers to help improve the planning and management of services. This article outlines the use of information to understand better the present delivery of health visitor services, to set objectives for the future and to measure actual performance against intended; in the near future to match better the supply of services to demand by developing neighbourhood or GP-practice profiles using mapping and graphics techniques; and in the longer term to refine measures of need or 'dependency' and 'outcome' to target resources and improve effectiveness.

Community Health Nursing↗
PubMed1999

The concept mapping method. An alternative to focus group inquiry in general practice.

BACKGROUND: The concept mapping rationale and process are explained step by step. The concept mapping method produces a two dimensional conceptual map of ideas produced by the group which can be analysed at the level of individual statements, clusters of statements, and groups of similar clusters. An example of concept mapping conducted with four general practitioner (GP) groups from different practice types and demographic locations is provided. A total of 51 participating GPs were asked to complete an 'evaluation questionnaire' at the end of each group session. The majority of GP participants (68%) rated the method as highly useful. OBJECTIVE: To describe the concept mapping method and its interpretation for use in general practice research. To report on its perceived usefulness and acceptability by general practitioners. DISCUSSION: Concept mapping is a very useful method combining benefits from qualitative and quantitative approaches for exploring the breadth of a topic in its entirety, especially for abstract concepts. GPs found the concept mapping method to be efficient for group inquiry, rating it high on utility. There is scope to refine the method, reducing time spent in some stages of the session, and substituting more time on final analysis.

Australia↗
PubMed1996

The human PECAM1 gene maps to 17q23.

We have determined the chromosomal and regional location of the gene encoding PECAM-1 (termed PECAM1 by GBD nomenclature) using a polymerase chain reaction (PCR)-based analysis of somatic cell hybrids. Analysis of a somatic cell hybrid chromosome panel established that the PECAM1 gene is on chromosome 17. Interestingly, several adhesion molecules expressed on platelets and endothelium also localize to chromosome 17: the GP1BA locus (glycoprotein (GP) Ibalpha) has been provisionally mapped to the region 17p12-pter, the ITGA2B (GPIIb) and the ITGB3 (GPIIIa) loci have been confirmed to the region 17q21.32; and the ICAM2 locus has been provisionally mapped to the region 17q23-q25. To determine if the PECAM1 locus colocalizes with any of the loci for these adhesion molecules, PCR-based analysis of a regional mapping panel for human chromosome 17 was conducted. We found that the PECAM1 locus is on the long arm of chromosome 17, in the region q23-qter. To confirm this observation and obtain a more precise localization of the PECAM1 locus, fluorescence in situ hybridization was conducted. Together our data allowed assignment of the PECAM1 locus to the region 17q23.

Animals↗
PubMedDate not supplied

CoMFA and docking studies on glycogen phosphorylase a inhibitors as antidiabetic agents.

Glycogen phosphorylase (GP(a)) is a specific target for the design of inhibitors and may prevent glycogenolysis under high glucose conditions in type II diabetes. The carboxamides first reported by Hoover D. J. et al. (J. Med. Chem. 1998, 41, 2934-2938) are one of the major classes of GP(a) inhibitors other than glucose derivatives. The recent, X-ray crystallographic analyses (Oikonomakos et al. Biochim. Biophys. Acta 2003, 1647, 325-332) have revealed a distinct mechanism of action for these inhibitors, which bind at a new allosteric site away from the inhibitory and catalytic sites. To elucidate the essential structural and physicochemical requirements responsible for binding to the GP(a) enzyme and to develop predictive models, CoMFA and docking studies have been carried out on a series of indole-2-carboxamide derivates. The CoMFA model developed using pharmacophoric alignments and hydrogen-bonding fields demonstrated high predictive ability against the training (r2 = 0.98, q2 = 0.68) and the test set (r2pred = 0.85). Further the superimposition of PLS coefficient contour maps from CoMFA with the GP(a) active site (PDB: 1lwo) has shown a high level of compatibility.

Binding Sites↗
PubMed1998

Activation of phosphatidylinositol 3-kinase through glycoprotein 130 induces protein kinase B and p70 S6 kinase phosphorylation in cardiac myocytes.

Phosphatidylinositol (PI) 3-kinase is known to be activated by cytokine stimulation through different types of receptors to transduce intracellular responses. We have previously reported that leukemia inhibitory factor (LIF) induces the activation of Janus kinase signal transducer and activator of transcription (JAK-STAT) and mitogen-activated protein (MAP) kinase pathways through glycoprotein (gp) 130 in cardiac myocytes. However, whether PI 3-kinase is involved in regulation of gp130 signaling and the activation mechanisms by which it associates with other tyrosine-phosphorylated proteins remain unknown. We found that LIF induced the activation of PI 3-kinase in cardiac myocytes. Moreover, JAK1 binds to PI 3-kinase, and LIF stimulation increases the PI 3-kinase activity in JAK1 immunoprecipitates. Activation of MAP kinase and protein kinase B by LIF was attenuated by wortmannin. LIF-induced p70 S6 kinase activation, protein synthesis, and c-fos mRNA expression were inhibited by wortmannin and rapamycin. Both inhibitors failed to appreciably affect the phosphorylation of STAT3. In conclusion, PI 3-kinase is activated with LIF in cardiac myocytes, and JAK1 is found to associate with this enzyme. PI 3-kinase provides a crucial link between gp130, MAP kinase, protein kinase B, and p70 S6 kinase in cardiac myocytes.

Androstadienes↗
PubMed2002

Ischemic brain tissue salvaged from infarction by the GP IIb/IIIa platelet antagonist tirofiban.

In an open pilot study, the authors tested whether the nonpeptide glycoprotein (GP) IIb/IIIa antagonist tirofiban, a highly effective and selective blocker of platelet aggregation, prevents the transition of ischemic brain tissue into the infarct proper as defined by MRI (perfusion-weighted/T2-weighted) in patients with acute ischemic stroke. The infarct volume (T2 lesion after 1 week) was smaller in treated patients (n = 10) compared with matched control subjects (n = 10; p = 0.029) with similar initial perfusion deficit (TTP-maps). The authors conclude that GP IIb/IIIa antagonists have therapeutic potential in acute stroke therapy.

Adult↗
PubMed2005

Comparison of axial and tangential topographic algorithms for contact lens fitting after LASIK.

PURPOSE: Computerized videokeratography (CVK) has become the standard method for measuring the corneal curvature after refractive surgery. However, few resources exist on the use of CVK data for postoperative contact lens fitting, and no recommendations exist on the selection of the best topographic algorithm relevant to gas-permeable (GP) lens fitting. This study assessed the optimal use of topographic data to fit spherical GP contact lenses on patients who have undergone laser in situ keratomileusis. METHODS: A retrospective analysis of CVK maps from eight post-LASIK eyes fitted with spherical GP lenses was performed in the Contact Lens Service of the Department of Ophthalmology at Case Western Reserve University and University Hospitals of Cleveland. Axial and tangential maps from the Dicon CT 200 (version 3.50) or Humphrey Atlas (version A8) topographer were analyzed. Averaged dioptric curvatures from different locations (inferior, superior, and temporal) at various distances (2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, and 4.0 mm) from the vertex normal of each eye were compared with the base curves of the prescribed GP contact lenses. RESULTS: One-way analysis of variance, Pearson correlation analysis, and paired t tests showed that the best topographic predictors of a successful GP base curve were the average curvatures at the 4.0 mm distance on the axial maps (r=0.8078, P=0.05) and at the 2.0 mm distance on the tangential maps (r=0.9738, P=0.0002). The mean dioptric powers of the GP base curve, axial map 4.0 mm curvature, and tangential map 2.0 mm curvature were 41.50 diopters (D), 42.65 D, and 42.67 D, respectively. CONCLUSION: To simplify and guide GP fitting after LASIK, the average dioptric curvature 4.0 mm from the vertex normal on axial maps or 2.0 mm from the vertex normal on tangential maps are the best predictors of accurate GP base curve selection.

Algorithms↗
PubMed1994

Cerebellothalamocortical and pallidothalamocortical projections to the primary and supplementary motor cortical areas: a multiple tracing study in macaque monkeys.

The goal of the present study was to clarify whether the primary motor cortex (M1) and the supplementary motor cortex (SMA) both receive, via the motor thalamus, input from cerebellar and basal ganglia output nuclei. This is the first investigation that explores the problem by direct comparison, in the same animal, of thalamic zones that 1) project to M1 and SMA and 2) receive cerebellar-nuclear (CN) and pallidal (GP) afferents. These four zones were mapped in two monkeys by means of two retrograde tracers for M1 and SMA injections and of two anterograde tracers for CN and GP injections. All injections were performed under electrophysiological control (microstimulation and multiunit recordings). Injections in cortical areas were restricted to the hand/arm representation; in the SMA, the tracer deposit was within the "SMA-proper" (or "area F3") and did not include its rostral extension ("pre-SMA" or "area F6"). It was found that zones of all four types formed a number of highly complex patches of labeling that were usually not confined to one cytoarchitectonically defined thalamic nucleus. The overlap of clusters of labeled terminals and perikarya was evaluated morphometrically (area measurements) on a number of coronal sections along the anteroposterior extent of the motor thalamus. In line with previous studies, the thalamic territories innervated by CN and GP afferents rarely overlapped. However, zones projecting to M1 and/or to SMA included thalamic regions receiving CN as well as GP projections, providing the first evidence of such overlap from individual animals. The present observations support the previous conclusion from this laboratory (based on transsynaptic labeling) that the SMA receives, apart from its strong pallidal transthalamic input, a CN transthalamic input. These present findings that both M1 and SMA are recipients of transthalamic inputs from GP and CN thus support the concept that a mixed subcortical input consisting of weighted contributions from cerebellum, basal ganglia, substantia nigra, and spinothalamic tract is directed to each functional component of the sensorimotor cortex.

Animals↗
PubMed1991

Role of arachidonic acid metabolites in oleic acid induced pulmonary injury in a canine model. Effect of ketoconazole (thromboxane synthetase inhibitor).

This study was designed to investigate the effects of ketoconazole, a thromboxane synthetase inhibitor, on pulmonary and systemic hemodynamics and pulmonary function in experimental respiratory distress syndrome. Pulmonary artery infusion of oleic acid (PAIOA), 0.1 ml/kg, was used to cause lung injury. Ten dogs were randomized into two groups (Gps): Gp I (n = 5) acted as control, whereas Gp II (n = 5) were treated with IV ketoconazole (2.5 mg/kg bolus then 10 mg/kg/hour for 2.5 hours). Hemodynamics, extravascular lung water (EVLW), serum levels of PGE2, and TxB2 were obtained at baseline (BL) and at 30-minute intervals for 2.5 hours (T30-T150). After 30 minutes of PAIOA the mean arterial pressure (MAP) decreased significantly in both Gps (131 +/- 17 vs. 88 +/- 9 mmHg Gp 1, 119 +/- 9 vs. 79 +/- 8 mmHg Gp II, P less than 0.05); however, while MAP returned to BL values in Gp II, it remained significantly lower throughout the experimental interval in Gp I. Mean pulmonary artery pressure (MAP) was not significantly affected by PAIOA in either Gp, while pulmonary vascular resistance increased significantly from BL at T120 in Gp II. Pulmonary function measured by partial pressure of arterial O2 (PaO2) and extravascular lung water (EVLW) were significantly affected by PAIOA. There was a significant decrease in PaO2 (66 +/- 6 vs. 96 +/- 8 mmHg, Gp I and 60 +/- 7 vs. 100 +/- 6 mmHg, Gp II) as well as an increase in EVLW (604 +/- 61 vs. 135 +/- 9 ml, Gp I and 641 +/- 110 vs. 117 +/- 18 ml, Gp II) in both Gps.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Pea rms6 mutants exhibit increased basal branching.

Our studies on two branching mutants of pea (Pisum sativum L.) have identified a further Ramosus locus, Rms6, with two recessive or partially recessive mutant alleles: rms6-1 (type line S2-271) and rms6-2 (type line K586). Mutants rms6-1 and rms6-2 were derived from dwarf and tall cultivars, Solara and Torsdag, respectively. The rms6 mutants are characterized by increased branching from basal nodes. In contrast, mutants rms1 through rms5 have increased branching from both basal and aerial (upper stem) nodes. Buds at the cotyledonary node of wild-type (WT) plants remain dormant but in rms6 plants these buds were usually released from dormancy. Their growth was either subsequently inhibited, sometimes even prior to emergence above ground, or they grew into secondary stems. The mutant phenotype was strongest for rms6-1 on the dwarf background. Although rms6-2 had a weak single-mutant phenotype, the rms3-1 rms6-2 double mutant showed clear transgression and an additive branching phenotype, with a total lateral length almost 2-fold greater than rms3-1 and nearly 5-fold greater than rms6-2. Grafting studies between WT and rms6-1 plants demonstrated the primary action of Rms6 may be confined to the shoot. Young WT and rms6-1 shoots had similar auxin levels, and decapitated plants had a similar magnitude of response to applied auxin. Abscisic acid levels were elevated 2-fold at node 2 of young rms6-1 plants. The Rms6 locus mapped to the R to Gp segment of linkage group V (chromosome 3). The rms6 mutants will be useful for basic research and also have possible agronomical value.

Journal Article↗
PubMed2001

Fast EM-like methods for maximum "a posteriori" estimates in emission tomography.

The maximum-likelihood (ML) approach in emission tomography provides images with superior noise characteristics compared to conventional filtered backprojection (FBP) algorithms. The expectation-maximization (EM) algorithm is an iterative algorithm for maximizing the Poisson likelihood in emission computed tomography that became very popular for solving the ML problem because of its attractive theoretical and practical properties. Recently, (Browne and DePierro, 1996 and Hudson and Larkin, 1994) block sequential versions of the EM algorithm that take advantage of the scanner's geometry have been proposed in order to accelerate its convergence. In Hudson and Larkin, 1994, the ordered subsets EM (OS-EM) method was applied to the ML problem and a modification (OS-GP) to the maximum a posteriori (MAP) regularized approach without showing convergence. In Browne and DePierro, 1996, we presented a relaxed version of OS-EM (RAMLA) that converges to an ML solution. In this paper, we present an extension of RAMLA for MAP reconstruction. We show that, if the sequence generated by this method converges, then it must converge to the true MAP solution. Experimental evidence of this convergence is also shown. To illustrate this behavior we apply the algorithm to positron emission tomography simulated data comparing its performance to OS-GP.

Algorithms↗
PubMed1994

Effect of nonprotective vaccination on antibody response to subsequent human immunodeficiency virus infection.

We have investigated the systemic anti-HIV antibody response in chimpanzees who were immunized with live vaccinia containing either the HIV envelope glycoprotein (gp160IIIB) or a control antigen (herpes simplex virus glycoprotein D) and then challenged with either a high dose (300,000 TCID50) or low dose (100 TCID50) of HIVIIIB. HIV was subsequently isolated from all animals, indicating failure of the vaccination to protect against HIV infection. Serum antibody responses were evaluated before immunization, at the time of challenge with HIV, and at multiple time points in the 9 mo after challenge. Immunization resulted in a more rapid rise of antibody to gp160 in both high and low dose animals. Antibodies to the V3 loop induced upon infection were unaffected by immunization. In low dose animals, neutralizing antibody rose more rapidly and to higher levels in the immunized animals as compared with the control. There was no difference in neutralizing antibodies between immunized and control chimpanzees in the high dose group. Epitope mapping of the anti-gp 160 response indicated that immunization with gp160 vaccinia induced a postinfection antibody response to a region of gp41 (amino acids 718-743) that was not immunogenic in control-vaccinated animals. These data indicate that failed vaccination with the HIV envelope can alter both the timing and epitope specificity of the subsequent anti-HIV antibody response. These studies also define the evolution and fine specificity of the antibody response during the critical period immediately postinfection.

AIDS Vaccines↗
PubMed1984

Integration and expression of MCF-13 provirus in MCF-13-induced lymphomas.

Polytropic viruses were isolated from 11 MCF-13-induced lymphomas using multiple infectious cycles on the mink lung and SC1 cell lines. The viruses were characterized by host range infectious properties and by biochemical properties using Cleveland's polypeptide mapping of the p30 and gp 70 viral proteins demonstrating identity in their biological properties with the MCF-13 lymphoma-inducing virus. Restriction enzyme analysis of the high molecular weight tumoral DNAs confirmed the presence of proviral sequences homologous to the inducing provirus in the lymphoma genomes indicating that MCF-13 MuLV has integrated in the cellular genome of the induced lymphomas.

Animals↗
PubMed2002

A potential endogenous ligand of annexin IV in the exocrine pancreas. Carbohydrate structure of GP-2, a glycosylphosphatidylinositol-anchored glycoprotein of zymogen granule membranes.

We demonstrated previously that annexins IV, V, and VI, proteins of the calcium/phospholipid-binding annexin family, have glycosaminoglycan binding properties (Ishitsuka, R., Kojima, K., Utsumi, H., Ogawa, H., and Matsumoto, I. (1998) J. Biol. Chem. 273, 9935-9941). In this study, we investigated the endogenous ligands of annexin IV in the exocrine pancreas. Immunohistochemical study of bovine pancreas showed that annexin IV localized in the apical cytoplasmic region of pancreatic acinar cells where zymogen granules are concentrated. Because it is the major component of the zymogen granule membrane, the glycosylphosphatidylinositol-anchored glycoprotein GP-2 was suggested to play a role in apical sorting and secretion of zymogens. We isolated GP-2 from porcine pancreas extract and determined the structure of its N-linked oligosaccharides by two-dimensional mapping. The major carbohydrate structures of porcine GP-2 were trisialo-triantennary and tetrasialo-tetra-antennary complex-type oligosaccharides. Dot-blot assay showed that annexin IV interacts with GP-2 in the presence of calcium and that it recognizes the terminal sialic acid residues linked through alpha2-3 linkages to the carbohydrate of GP-2. Lectin blot assay showed that Maackia amurensis mitogen, a plant lectin specific for the trisaccharide sequence Sia(alpha)2-3Galbeta1-4GlcNAc of N-linked oligosaccharides, has strong affinity for GP-2. Thus, M. amurensis mitogen was used as a specific probe for GP-2 in the histochemical staining of the bovine pancreas. GP-2 was found to localize exclusively in the same apical cytoplasmic region of pancreatic acinar cells as annexin IV does. These results suggest that GP-2 is an endogenous ligand of annexin IV in the exocrine pancreas.

Animals↗
PubMed2003

The major envelope protein, GP5, of a European porcine reproductive and respiratory syndrome virus contains a neutralization epitope in its N-terminal ectodomain.

A set of neutralizing monoclonal antibodies (mAbs) directed against the GP(5) protein of European type porcine reproductive and respiratory syndrome virus (PRRSV) has been produced previously (Weiland et al., 1999). This set reacted with a plaque-purified virus (PPV) subpopulation of Dutch isolate Intervet-10 (I-10), but not with the European prototype PRRSV LV. In order to map the neutralization epitope in the GP(5) protein of the PPV strain, the ORF5 nucleotide sequence of PPV was determined. When the amino acid sequence derived from this nucleotide sequence was compared with that of PRRSV LV, four amino acid differences were found. Using site-directed mutagenesis, we showed that a proline residue at position 24 of the GP(5) sequence of the PPV strain enabled recognition by the neutralizing mAbs. Pepscan analysis demonstrated that the epitope recognized by the neutralizing mAbs stretched from residues 29 to 35. Surprisingly, the reactivity of the mAbs in the Pepscan system was independent of the presence of a proline in position 24. Moreover, residue 24 is located within the predicted signal peptide, implying that either the signal peptide is not cleaved or is cleaved due to the presence of Pro(24) such that the epitope remains intact. Our results demonstrate the presence of a neutralization epitope in the N-terminal ectodomain of the GP(5) protein of PRRSV and imply a role for the ectodomain of GP(5) in the infection of PRRSV.

Amino Acid Sequence↗
PubMed2005

Expression profile of genes related to osteoclastogenesis in mouse growth plate and articular cartilage.

Based on developmental fate and function, cartilage tissue is broadly classified into transient cartilage (e.g. growth plate, GP) and permanent cartilage (e.g. articular cartilage, AC). The former eventually disappears and is replaced by bone during the endochondral ossification process, whereas the latter retains its permanency. Osteo(chondro)clasts, multinucleated giant cells of the monocyte/macrophage lineage, are selectively induced in the GP during endochondral ossification and play central roles in the resorption of cartilagenous matrices. The aim of this study was to investigate the factors determining the GP-specific recruitment of osteo(chondro)clasts. We especially focused on the expression pattern of the receptor activator of NF-kappaB ligand (RANKL), an essential factor for osteo(chondro)clast differentiation, and on that of epigenetic and transcriptional factors affecting RANKL gene expression. Knee joints of male BALB/c mice aged 8 weeks were dissected and subjected to immunohistochemical analysis using anti-RANKL, Runx2, Dlx5 and Msx2 antibodies. The methylation status of the mouse RANKL gene promoter in both the GP and the AC was analyzed by sodium bisulfite mapping using microdissected mouse tissue. The expression of BMP-2, -3, -4, -6 and type X collagen mRNA was examined by in situ hybridization (ISH). At the boundary between the calcifying cartilage and the hypertrophic chondrocytes of the GP, RANKL-expressing chondrocytes overlapped those expressing Runx2, Dlx5 and Msx2, near numerous osteo(chondro)clasts. Although similar BMP-2 and -4 expression was observed in chondrocytes in both the GP and the AC as well as in maturing osteoblasts, a rather restricted BMP-6 expression pattern was observed in resting and proliferating chondrocytes in the GP. On the other hand, sodium bisulfite mapping showed that mostly non-CpG methylation was similarly scattered in a non-specific manner in chondrocytes in the GP and the AC. Taken together with the fact that putative Runx2 binding elements are located in the RANKL promoter, our data suggest that Runx2, an essential transcription factor for skeletal development, is also a key regulator of RANKL expression in chondrocytes in the GP. Furthermore, a selective and sequential expression of a subset of BMP and of transcription factors may define the expression pattern of RANKL through Runx2.

Animals↗
PubMed1984

Evidence that a cerebellum-enriched, synaptic junction glycoprotein is related to fodrin and resists extraction with triton in a calcium-dependent manner.

Subcellular fractions from rat cerebellum and other tissues were examined for the presence of a 240K glycoprotein, designated GP-A. Previous results have shown that GP-A is enriched in cerebellum synaptic junction (SJ) fractions when compared to parent synaptic plasma membrane (SPM) fractions and is not detected in forebrain SPM or SJ fractions. In the present studies, GP-A was not detected in myelin, mitochondria, purified nuclei, or cytosolic fractions from cerebellum, but was present in microsomal fractions. GP-A is partially soluble in the non-ionic detergent Triton X-100 and is completely soluble when cerebellum SPMs are treated with the ionic detergent N-lauryl sarcosinate. The solubilization of GP-A from cerebellum membranes was shown to be a function of bound calcium ions, e.g., pretreating SPMs with 100 microM-1mM Ca2+ decreased the solubility of GP-A in Triton by approximately threefold. GP-A is a major concanavalin A (Con A)-binding glycoprotein in cerebellum SJ fractions and migrates on sodium dodecyl sulfate (SDS) gels with a slower relative mobility than the 235K/230K fodrin doublet. Comparisons between purified fodrin and the 235K/230K doublet in cerebellum and forebrain synaptic fractions by two-dimensional peptide mapping indicated that they were identical. The Con A-binding property of GP-A was exploited to purify it by affinity chromatography with agarose-Con A. Peptide mapping comparisons between affinity-purified GP-A and GP-A in SPM and SJ fractions indicated that GP-A in synaptic fractions is apparently homogeneous. Peptide map comparisons between GP-A and 235K fodrin poly-peptide indicated that these two synaptic components are highly related (50% of their respective peptides are shared). The 235K fodrin polypeptide in SJs reacted with anti-fodrin antisera on Western blots; however, GP-A failed to cross-react. These observations, together with results from previous studies, indicate that GP-A is highly enriched in cerebellum compared to other neuronal and nonneural tissues. Moreover, GP-A is enriched in SJs relative to SPM fractions, is related to fodrin, and is most likely a cell-surface glycoprotein at asymmetric synapses in cerebellum. GP-A may be involved in neuronal recognition or synaptic transmission in the cerebellum. The important role of calcium in synaptic transmission, together with the decreased solubility of GP-A in Triton that results from micromolar concentrations of calcium, suggest that GP-A may play a role in stabilizing cerebellar synaptic junctions.

Animals↗