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M K Jones

Publications and source records attributed to M K Jones.

At least 55 records · Page 3Linked to original sources
PubMed2001

Structure of apolipoprotein B-100 in low density lipoproteins.

There is general consensus that amphipathic alpha-helices and beta sheets represent the major lipid-associating motifs of apolipoprotein (apo)B-100. In this review, we examine the existing experimental and computational evidence for the pentapartite domain structure of apoB. In the pentapartite nomenclature presented in this review (NH(2)-betaalpha(1)-beta(1)-alpha(2)-beta(2)-alpha(3)-COOH), the original alpha(1) globular domain (Segrest, J. P. et al. 1994. Arterioscler. Thromb. 14: 1674;-1685) is expanded to include residues 1;-1,000 and renamed the betaalpha(1) domain. This change reflects the likelihood that the betaalpha(1) domain, like lamprey lipovitellin, is a globular composite of alpha-helical and beta-sheet secondary structures that participates in lipid accumulation in the co-translationally assembled prenascent triglyceride-rich lipoprotein particles. Evidence is presented that the hydrophobic faces of the amphipathic beta sheets of the beta(1) and beta(2) domains of apoB-100 are in direct contact with the neutral lipid core of apoB-containing lipoproteins and play a role in core lipid organization. Evidence is also presented that these beta sheets largely determine LDL particle diameter. Analysis of published data shows that with a reduction in particle size, there is an increase in the number of amphipathic helices of the alpha(2) and alpha(3) domains associated with the surface lipids of the LDL particle; these increases modulate the surface pressure decreases caused by a reduction in radius of curvature. The properties of the LDL receptor-binding region within the overall domain structure of apoB-100 are also discussed. Finally, recent three-dimensional models of LDL obtained by cryoelectron microscopy and X-ray crystallography are discussed. These models show three common features: a semidiscoidal shape, a surface knob with the dimensions of the betaC globular domain of lipovitellin, and planar multilayers in the lipid core that are approximately 35 A apart; the multilayers are thought to represent cholesteryl ester in the smectic phase. These models present a conundrum: are LDL particles circulating at 37 degrees C spheroidal in shape, as generally assumed, or are they semidiscoidal in shape, as suggested by the models? The limited evidence available supports a spheroidal shape.

Animals↗
PubMed2000

Ultrastructure of the digestive tract of Gyliauchen nahaensis (Platyhelminthes, Digenea), an inhabitant of the hindgut of herbivorous fishes.

Digenean parasites of vertebrates usually amplify the surface area of their gut by increasing the size of the absorptive caeca. Some members of the family Gyliauchenidae, however, have relatively small caeca but have a greatly expanded foregut. The morphology of the elongate gut of the digenean Gyliauchen nahaensis, an inhabitant of herbivorous fish of the family Siganidae, was examined by light and transmission electron microscopy. The extensive foregut, consisting of a mouth, pharynx, and esophagus, is lined with a syncytial tegument-like lining, which is connected to nucleated cell bodies sunken in the parenchyma. The apical cytoplasm in the mouth and anterior regions of the pharynx resembles that of the general body tegument, although some regional specialization is present. The lining of posterior regions of the pharynx is armed with large apical projections, which are thought to serve as filtration structures. The lining of the anterior and middle esophagus displays a peculiar form of surface amplification involving the formation of elongate flask-shaped invaginations of the apical cytoplasm. The cell bodies associated with these regions are rich in secretory vesicles and it is proposed that these regions of the esophagus are expanded to promote extracellular digestion. The posterior region of the esophagus lacks the invaginations of other esophageal regions, but displays instead large surface projections. The caeca consists of columnar cells lined by extensive apical microlamellae. The peculiar gut morphology of G. nahaensis, coupled with alterations in the arrangement of suckers, is interpreted to be an adaptation to the predominantly herbivorous diets of the definitive hosts.

Animals↗
PubMed2000

Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation: a key to its antiangiogenic action?

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit angiogenesis in vivo and in vitro, but the mechanism of this action is unclear. Angiogenesis-formation of new capillary vessels-requires endothelial proliferation, migration, and tube formation. It is stimulated by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The cell cycle is regulated positively by cyclins and negatively by cyclin-dependent kinase inhibitors (CKI) and the retinoblastoma protein (pRb). Since the effects of NSAIDs on cell cycle-regulatory proteins in endothelial cells remain unknown, we examined the effect of indomethacin on bFGF-stimulated endothelial cell proliferation and on cell cycle regulatory proteins in rat primary aortic endothelial cells (RAEC). Indomethacin significantly inhibited basal and bFGF-stimulated endothelial cell proliferation. This inhibition correlated significantly with reduced cyclin D1 and increased p21 protein expression. Furthermore, indomethacin reduced pRb phosphorylation. These findings suggest that indomethacin arrests endothelial cell proliferation essential for angiogenesis by modulating cell cycle protein levels.

Animals↗
PubMed2000

Danger expectancies, self-efficacy and insight in spider phobia.

In the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, (1994) Diagnostic and statistical manual of mental disorders (4th ed.) Washington, DC: author) phobic adults and adolescents are said to "recognize that the phobia is excessive or unreasonable" given the actual danger posed by the feared situation. The present study examined perceptions of danger in 15 spider phobic subjects and a matched set of controls before, during and after a spider-avoidance test. When detached from the phobic stimulus, phobic subjects: (1) gave higher estimates of the probability of being bitten than controls did; (2) gave higher estimates of the injuries that would result from being bitten and (3) in line with these first two findings, believed their high levels of anticipated anxiety were more reasonable and appropriate to the demands of the situation than controls did. These findings are inconsistent with the prevailing notion that when detached from the phobic situation patients can accurately evaluate the danger of potential phobic encounters. Instead, the findings suggest that phobic individuals, whether detached or in the presence of the feared object, have relatively limited insight into the irrationality of their fears. In examining the mediation of phobic phenomena, both self-efficacy and danger estimates remained significantly related to the anxiety and avoidance experienced in the spider-avoidance task. Further research designed to experimentally establish the likely causal roles of these two constructs is warranted.

Adolescent↗
PubMed2000

Molecular belt models for the apolipoprotein A-I Paris and Milano mutations.

Models for the binding of the 200-residue carboxy-terminal domain of two mutants of apolipoprotein A-I (apo A-I), apo A-I(R173C)(Milano) and apo A-I(R151C)(Paris), to lipid in discoidal high-density lipoprotein (HDL) particles are presented. In both models, two monomers of the mutant apo A-I molecule bind to lipid in an antiparallel manner, with the long axes of their helical repeats running perpendicular to the normal of the lipid bilayer to form a single disulfide-linked homodimer. The overall structures of the models of these two mutants are very similar, differing only in helix-helix registration. Thus these models are consistent with experimental observations that reconstituted HDL particles containing apo A-I(Milano) and apo A-I(Paris) are very similar in diameter to reconstituted HDL particles containing wild-type apo A-I, and they support the belief that apo A-I binds to lipid in discoidal HDL particles via the belt conformation.

Apolipoprotein A-I↗
PubMed2000

Sequential expression of adrenomedullin and its receptor during gastric ulcer healing in rats.

Adrenomedullin (AM) is a potent vasodilatory peptide. While its growth-regulating action in some cultured cells has been recognized, expression of AM and its receptor during gastric ulcer healing has not been explored. Specimens of gastric walls from control rats or gastric ulcers were obtained at 1, 3, 7, and 14 days after gastric ulcer induction. AM and its receptor mRNAs expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. By RT-PCR, AM mRNA was increased by 167% at three days, while AM receptor mRNA was increased by 234% at seven days (both P < 0.05). By in situ hybridization, AM and AM receptor mRNAs were increased at ulcer margin from three days after ulcer induction. By immunohistochemistry, AM was increased in the ulcer margin at three and seven days. In separate in vitro studies using a rat gastric epithelial (RGM1) cell line, AM treatment significantly increased transforming growth factor-alpha mRNA expression and cell proliferation.

Adrenomedullin↗
PubMed2000

Three new species of Polyclithrum Rogers, 1967 (Gyrodactylidae: Monogenea) from mugilid fishes from Australia and Brazil, with a redescription of P. mugilini Rogers, 1967.

Polyclithrum mugilini Rogers, 1967, a parasite of Mugil cephalus Linnaeus, is redescribed from type-material from Lake Seminole, Georgia, USA. Three new species of Polyclithrum Rogers, 1967 are also described: P. alberti n. sp. from M. cephalus from the Albert River, Queensland, Australia; P. boegeri n. sp. from M. platanus Günther from Rio da Guarda, State of Rio de Janeiro, Brazil; and P. corallense n. sp. from M. cephalus from Heron Island, Great Barrier Reef, Australia. The four species can be distinguished by the size and shape of haptoral sclerites, but in particular by accessory bar number 3, the dorsal bar, the marginal hooks and the hamulus point to shaft angle. The validity of Micropolyclithrum parvum Skinner, 1975, a parasite of M. cephalus in Biscayne Bay, Florida, is discussed, and a key to the species of Polyclithrum is presented.

Animals↗
PubMed2000

Prochristianella spinulifera n. sp. (Cestoda: Trypanorhyncha) from Australian dasyatid and rhinobatid rays.

Prochristianella spinulifera n. sp. (Cestoda: Trypanorhyncha: Eutetrarhynchidae) is described from the spiral valves of the rays Rhinobatos typus (Rhinobatidae) and Himantura fai (Dasyatidae) from Heron Island, Queensland, Australia. The new species is distinguished from all congeners by the deltoid microtriches covering the anterior 80% of the scolex and the presence of a dorsoventrally elongate genital atrium. The species occurred in the anteriormost section of the spiral valve of R. typus. The orientation of the armature of this and other congeners is such that principal rows of hooks begin on the bothridial surface of the tentacle and end on the antibothridial surface.

Animals↗
PubMed2000

Immunogenicity and immunolocalization of the 22.6 kDa antigen of Schistosoma japonicum.

The 22.6 kDa tegumental-associated antigens of Schistosoma mansoni (Sm22.6) and Schistosoma japonicum (Sj22.6) are of recognized interest in schistosomiasis vaccine development, although no direct vaccination/challenge experiments using either Sm22.6 or Sj22.6 had been previously described. We report that Escherichia coli-expressed reSj22.6 failed to protect mice or water buffaloes against subsequent challenge with S. japonicum cercariae. This was despite the fact that specific IgG (buffaloes) and IgG and IgE (CBA mice) antibodies were generated against the 22.6 kDa molecule, observations consistent with some of our earlier findings. We could find no evidence from immunolocalization studies that Sj22.6 is expressed or exposed on the surface of the adult parasite since it appears to be restricted to the apical cytoplasm of the tegument and is not associated with the apical or basal membrane or any membrane-bound structures in the apical cytoplasm. Nevertheless, Sj22.6 must be released to the immune system during the course of infection because specific anti-Sj22.6 IgG antibodies were present in the sera of nonvaccinated but challenged mice. We conclude that it may be necessary to produce reSj22.6 in a more relevant expression system, such as baculovirus, to further establish its vaccine potential and that detailed immunochemical and immunolocalization studies of early developmental stages may be necessary to determine how Sj22.6 is released or shed in S. japonicum infections.

Animals↗
PubMed2000

Ultrastructure of the scolex, rhyncheal system and bothridial pits of Otobothrium mugilis (Cestoda: Trypanorhyncha).

The ultrastructure of the scolex tegument, bothridial pits (=ciliated pits) and rhyncheal system of Otobothrium mugilis Hiscock, 1954 is described from plerocerci collected from the teleosts Arius graeffei Kner et Steindachner and Mugil cephalus Linnaeus. Scanning electron microscopy revealed that filamentous microtriches with shortened caps are abundant across the entire surface of the tegument. Palmate microtriches are dominant on the bothridia and their margins. The surfaces of bothridial pits were covered with large bifid microtriches. The bothridial pits are strongly muscularised invaginations of the tegument. Nervous tissues were not observed within the pits and it is probable that these structures function as accessory attachment structures. The wall of each tentacle sheath consists of one to three bands of fibrils, lined internally by a thin cytoplasmic layer. The tentacular walls are cellular, containing myofilaments. The fibrils of the tentacular walls are arranged into discrete blocks of parallel fibrils and appear to be intracellular. Tentacular walls are lined externally by a modified membrane with an external glycocalyx. Tentacular hooks are solid, bound externally by a membrane. The body of the hook contains numerous longitudinal canaliculi and an electron-opaque medulla lies at the centre of the hook.

Animals↗
PubMed2000

Tetraphyllidean metacestodes of teleosts of the Great Barrier Reef, and the use of in vitro cultivation to identify them.

The tetraphyllidean metacestode diversity of 310 teleost fishes, including 87 species from 31 families, was examined from Heron Island, The Great Barrier Reef, Australia. Eleven metacestode 'types' were identified with the use of light microscopy. Host-specificity varied greatly among metacestode types. Incorporation of in vitro cultivation allowed generic identification for some types. Types 1 and 2 belong to Uncibilocularis Southwell, 1925, and have triloculate bothridia and one pair of forked hooks with unequal prongs; Type 3 has quadriloculate bothridia. Hook development was insufficient to determine in which genus, Acanthobothrium van Beneden, 1849 or Calliobothrium van Beneden, 1850, this type may belong. Type 4 has unilocular bothridia with simple edges and belongs to Anthobothrium van Beneden, 1850. Type 5 has multiloculated bothridia which are invaginated within pouches. This type belongs to the Rhinebothriinae although its generic identity cannot be determined. The bothridia of Type 5 everted within 24 hours of in vitro cultivation and revealed the presence of two forms, one having 48 loculi per bothridium, the other 72 per bothridium. In vitro studies provide additional support for existing theories of onchobothriid scolex development.

Animals↗
PubMed2000

ATP-induced CA2+-signaling enhances rat gastric microvascular endothelial cell migration.

The effects of exogenous ATP on Ca2+ signaling and wound healing were investigated in rat gastric microvascular endothelial cells (RGMEC). ATP (10 microM) triggered a significant rise in intracellular Ca2+ concentration ([Ca2+]i) from 46+/-2 nM at baseline to peak values averaging 283+/-31 nM (n = 5 experiments, 132 cells). Return to the basal [Ca2+]i was delayed by slowly declining plateau phase that persisted for 200+/-30 s. Removal of extracellular Ca2+ did not significantly affect the peak rise in [Ca2+]i, but reduced the plateau. ATP (10 microM) also significantly increased the migration of RGMEC in a wounded monolayer. Addition of the non-subtype selective purinergic receptor antagonist, suramin, abrogated the effects of ATP on [Ca2+]i and migration. We conclude that local elevation of ATP acting through purinergic receptors induce Ca2+ signals in RGMEC and may contribute to endothelial cell migration.

Adenosine Triphosphate↗
PubMed2000

Isolation and characterization of rat gastric microvascular endothelial cells as a model for studying gastric angiogenesis in vitro.

We have previously characterized morphologic features of wounding-induced angiogenesis that occurs in response to acute and chronic gastric mucosal injury. As a means of investigating the molecular mechanisms underlying gastric angiogenesis, microvascular endothelial cells were isolated from stomachs of normal (non-injured) rats. The isolation procedure adapted and combined aspects of previous methods and employed positive selection using magnetic beads coated with monoclonal antibody specific for rat CD31 (PECAM-1), a cell surface marker restricted to platelets, monocytes, T lymphocytes and endothelial cells. The isolated microvascular endothelial cells expressed vascular endothelium-specific antigen and the endothelial-specific receptors, Tie2 and flt-1 (VEGFR1). When plated on growth factor-reduced matrigel, the isolated microvascular endothelial cells formed capillary-like structures reflecting in vitro angiogenesis. These cells were also responsive to vascular endothelial growth factor, VEGF, further verifying their endothelial nature. The rat microvascular endothelial cells isolated by this procedure should be useful in delineating molecular mechanisms and regulation of the angiogenesis that is essential for the healing of acute and chronic gastric injury.

Animals↗
PubMed1999

A detailed molecular belt model for apolipoprotein A-I in discoidal high density lipoprotein.

Apolipoprotein A-I (apoA-I) is the principal protein of high density lipoprotein particles (HDL). ApoA-I contains a globular N-terminal domain (residues 1-43) and a lipid-binding C-terminal domain (residues 44-243). Here we propose a detailed model for the smallest discoidal HDL, consisting of two apoA-I molecules wrapped beltwise around a small patch of bilayer containing 160 lipid molecules. The C-terminal domain of each monomer is ringlike, a curved, planar amphipathic alpha helix with an average of 3.67 residues per turn, and with the hydrophobic surface curved toward the lipids. We have explored all possible geometries for forming the dimer of stacked rings, subject to the hypothesis that the optimal geometry will maximize intermolecular salt bridge interactions. The resulting model is an antiparallel arrangement with an alignment matching that of the (nonplanar) crystal structure of lipid-free apoA-I.

Apolipoprotein A-I↗
PubMed1999

Characterisation of a family of Schistosoma japonicum proteins related to dynein light chains.

Dynein light chains (DLC) are components of dynein, an enzyme complex involved in various aspects of microtubule-based motility. We report here the molecular cloning and sequencing of cDNAs encoding a family of DLC-like polypeptides (SjcDLC1-5) from the human bloodfluke Schistosoma japonicum with open reading frames of 87-104 amino acids and deduced molecular masses ranging from 10.5 to 12.3 kDa. Two-dimensional Western blot analysis confirmed the presence of several S. japonicum DLC isoforms with differing pI values and molecular sizes. We also describe the molecular characterisation, genomic organisation and expression of clone SjcDLC1, and the immunological characterisation and localisation of its encoded protein. Northern blot analysis of adult worm RNA indicated SjcDLC1 is encoded by a single message of approximately 650 bp and Southern analysis suggested one SjcDLC1 gene exists in the S. japonicum genome. Immunolocalisation studies demonstrated that the SjcDLC1 protein is present in the tegument of the adult and cercarial stages of S. japonicum. SjcDLC1 and the other SjcDLC may function in the transport of specialised organelles, comprising membranous and discoid bodies, through the tegument to the schistosome-unique heptalaminate tegumental membrane at the external surface of the adult worm. As a consequence, they may provide novel targets for anti-schistosome vaccine and/or drug development.

Amino Acid Sequence↗
PubMed1999

Gastrointestinal mucosal regeneration: role of growth factors.

Growth factors and their receptors play important roles in cell proliferation, migration, tissue injury repair and ulcer healing. In gastric mucosa, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) by activating their common receptor, control cell proliferation. TGF-alpha predominantly plays this role under normal conditions and after acute injury, while EGF exerts its actions mainly during healing of chronic ulcers. During regeneration of injured gastric mucosa, these growth factors serve predominantly to restore the epithelial component. Other growth factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) serve to promote restoration of the connective tissue and microvessels (angiogenesis) in injured mucosa. During healing of chronic ulcers, a new epithelial lineage secreting EGF and other growth peptides develops and the majority of cells lining the ulcer margin overexpress the EGF receptor. Activation of the EGF receptor induces dramatic increases in MAP (Erk -1 and -2) kinase activity and phosphorylation levels. Inhibition of this signaling pathway dramatically delays ulcer healing. Granulation connective tissue, which grows under the stimulation of bFGF and VEGF is the major source for regeneration of connective tissue lamina propria and microvessels within the ulcer scar. Other growth factors such as insulin - like growth factor, keratinocyte growth factor, hepatocyte growth factor and trefoil peptides have been implicated in gastrointestinal (gastric ulcers, colitis) regeneration following injury. This paper is intended to provide an overview of the role of growth factors in gastrointestinal mucosal regeneration.

Animals↗