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Biomedical subjects

M K Jones

Publications and source records attributed to M K Jones.

At least 37 records · Page 2Linked to original sources
PubMed2001

MAPK (ERK2) kinase--a key target for NSAIDs-induced inhibition of gastric cancer cell proliferation and growth.

UNLABELLED: Limited clinical and experimental studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit gastric cancer growth. However, the mechanisms involved are not completely understood and cannot be explained by COX-2 inhibition alone. MAPK signaling pathway is essential for cell proliferation, but the effect of NSAIDs on MAPK activity and phosphorylation in gastric cancer has never been studied. Since increased and unregulated cell proliferation and reduced cell apoptosis are important features of cancer growth, we studied whether NS-398, a selective COX-2 inhibitor and/ or indomethacin (IND), a non-selective NSAID: 1) inhibit gastric cancer cell proliferation, 2) whether this inhibition is mediated via MAPK (ERK2), and 3) whether NSAIDs enhance apoptosis in gastric cancer cells. Human gastric epithelial cells (MKN28) derived from gastric tubular adenocarcinoma were cultured and treated with either vehicle, IND (0.25-0.5mM) or NS-398 (50-100 microM) for 6, 16, 24 and 48h. STUDIES: 1) Cellular proliferation was determined by 3H-thymidine uptake. 2) MAPK activity was measured by incorporation of radiolabeled phosphate into myelin basic protein. 3) Apoptosis was evaluated using TUNEL assay. IND and NS-398 significantly inhibited the proliferation of MKN28 cells at 24h by 3.5 - 5 fold (p<0.002) and at 48h by 2.5 - 10 fold (p<0.02). Both NSAIDs also significantly inhibited ERK2 activity: IND >53% inhibition, NS-398, 100 microM >72% inhibition; all p<0.05. Both IND and NS-398 significantly increased apoptotic index. In conclusion, IND and NS-398 significantly inhibit proliferation and growth of human gastric cancer cell line MKN28. This effect is mediated by NSAID-induced inhibition of MAPK (ERK2) kinase signaling pathway, essential for cell proliferation. NSAIDs also increase apoptosis in MKN28 cells. In addition to inhibiting cyclooxygenase, NSAIDs inhibit phosphorylating enzymes--kinases essential for signaling cell proliferation.

Adenocarcinoma↗
PubMed2001

Giardia trophozoites in dog hookworm, Ancylostoma caninum: accident or hyperparasitism?

During the course of transmission electron microscopic studies of adult Ancylostoma caninum removed from a dog, several Giardia trophozoites were found in sections of the buccal cavity, oesophagus and intestine of several hookworms. Although the protozoa appeared viable, this unusual finding probably represents accidental uptake by, rather than an established infection of, the hookworm. It is feasible, however, that the trophozoites might have survived and even multiplied in this aberrant site.

Ancylostoma↗
PubMed2001

Dynamics of the 16O(e, e'p) reaction at high missing energies.

We measured the cross section and response functions for the quasielastic 16O(e,e'p) reaction for missing energies 25< or =E(m)< or =120 MeV at missing momenta P(m)< or =340 MeV/c. For 25<E(m)<50 MeV and P(m) approximately 60 MeV/c, the reaction is dominated by a single 1s(1/2) proton knockout. At larger P(m), the single-particle aspects are increasingly masked by more complicated processes. Calculations which include pion exchange currents, isobar currents, and short-range correlations account for the shape and the transversity, but for only half of the magnitude of the measured cross section.

Journal Article↗
PubMed2001

Polarization measurements in high-energy deuteron photodisintegration.

We present measurements of the recoil proton polarization for the d(gamma-->,p-->)n reaction at straight theta(c.m.) = 90 degrees for photon energies up to 2.4 GeV. These are the first data in this reaction for polarization transfer with circularly polarized photons. The induced polarization p(y) vanishes above 1 GeV, contrary to meson-baryon model expectations, in which resonances lead to large polarizations. However, the polarization transfer Cx does not vanish above 1 GeV, inconsistent with hadron helicity conservation. Thus, we show that the scaling behavior observed in the d(gamma,p)n cross sections is not a result of perturbative QCD. These data should provide important tests of new nonperturbative calculations in the intermediate energy regime.

Journal Article↗
PubMed2001

Measurement of the charged pion electromagnetic form factor.

Separated longitudinal and transverse structure functions for the reaction 1H(e,e(')pi(+))n were measured in the momentum transfer region Q2 = 0.6--1.6 (GeV/c)(2) at a value of the invariant mass W = 1.95 GeV. New values for the pion charge form factor were extracted from the longitudinal cross section by using a recently developed Regge model. The results indicate that the pion form factor in this region is larger than previously assumed and is consistent with a monopole parametrization fitted to very low Q2 elastic data.

Journal Article↗
PubMed2001

Portal hypertensive gastric mucosa has reduced activation of MAP kinase (ERK2) in response to alcohol injury: a key to impaired healing?

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Because our previous study showed that ulcer-induced activation of mitogen-activated protein (MAP) kinase (ERK) plays a pivotal role in gastric mucosal healing, we investigated whether ERK activation is altered in PHT gastric mucosa following alcohol injury. We studied ERK2 phosphorylation and activity and expression of MAP kinase phosphatase-1 (MKP-1) in gastric mucosa of PHT and sham-operated (SO) normal rats both at baseline and following alcohol injury. In SO gastric mucosa, ERK2 phosphorylation and activity were significantly increased time-dependently following alcohol injury: by 221% and 137%, respectively at 24 h vs. baseline. In contrast, in PHT gastric mucosa following alcohol injury, neither ERK2 phosphorylation nor activity was increased versus baseline. In PHT gastric mucosa, MKP-1 mRNA and protein expression were increased at baseline versus SO rats and were increased further following alcohol injury with values higher by 20%-40% at each study time versus SO rats. Because ERK2 is crucial for mucosal healing, reduced ERK2 activation resulting from the overexpression of MKP-1 might be the basis for the impaired mucosal healing in PHT gastric mucosa.

Alcohols↗
PubMed2001

Danger Ideation Reduction Therapy (DIRT) for treatment-resistant compulsive washing.

Five intractable cases of obsessive-compulsive disorder were treated with the Danger Ideation Reduction Therapy (DIRT) program. All five cases: (1) had displayed excessive washing/cleaning behaviour for at least 10 years; (2) had failed to respond to a minimum of two separate, 12-week drug trials with serotonergic agents; (3) failed to respond to at least 15 sessions of exposure and response prevention at the beginning of the present trial, and; (4) satisfied the DSM-IV criteria for OCD with Poor Insight. DIRT was conducted in 14, weekly, individual sessions or until, in the judgement of the treating clinician: (1) clinically significant gains were apparent with minimal symptomatology remaining, and (2) clients displayed a sound grasp of the cognitive model underpinning DIRT procedures. At post-treatment, substantial reductions in scores on the Padua Inventory (PI), Maudsley Obsessional-Compulsive Inventory (MOCI), Beck Depression Inventory-II (BDI-II) and two global rating scales were apparent for four of the five subjects. These improvements were maintained at 4-to-6 month follow-up, with four of the five cases meeting Jacobson and Truax's (1991) criteria for 'recovery' on the MOCI and the PI by this assessment stage. While one subject remained non-responsive, the present findings suggest that DIRT may be a viable option for treatment-resistant cases of compulsive washing. The theoretical implications of the findings are discussed.

Adult↗
PubMed2001

Solution NMR structure of a model class A (apolipoprotein) amphipathic alpha helical peptide.

To better understand the structural determinants of the physical-chemical and the biological properties of Ac-18A-NH(2) (acetyl-AspTrpLeuLysAlaPheTyrAspLysValAlaGluLysLeuLysGluAlaPhe-amide), we have determined its structure in 50% (v/v) trifluroethanol (TFE-d(3))/water mixture (5 mM potassium phosphate, pH 5.5, 310K) using two-dimensional proton NMR spectroscopy. Stereospecific assignments have been made for C(beta)H protons (all the residues except Ala and Val) and gammaCH(3) (Val) groups. Nuclear Overhauser effects are observed between the nonpolar side chains spaced at (i) and (i + 4) position in the primary sequence, e.g., Trp2 and Phe6, and Phe6 and Val10. This suggests that in addition to N-terminal acetyl and C-terminal amide groups, the amphipathic alpha helical structure of Ac-18A-NH(2) is further stabilized by interactions between the hydrophobic residues on the nonpolar face of the helix.

Amino Acid Sequence↗
PubMed2001

Immunolocalization of the 38.3 kDa calponin-like protein in stratified muscles of the tail of Schistosoma japonicum cercariae.

Calponins are proteins present in vertebrate smooth musculature where they occur in association with thin myofilaments. Calponins are not present in vertebrate or invertebrate striated muscles. The blood fluke Schistosoma japonicum expresses a 38.3-kDa protein that bears substantial homology with vertebrate calponin and occurs entirely within smooth musculature of adults. Calponin-like immunoreactivity has been demonstrated in smooth muscles of many invertebrate phyla. The Schistosoma japonicum calponin has been localised in smooth myofibrils of adults where it is associated with myofilaments and sarcoplasmic reticulum. In this study, the ultrastructural localisation of the protein in muscles of S. japonicum cercariae is described. The protein is present in smooth muscles of the forebody and the stratified muscle of the tail. Within the stratified layer, the protein occurs predominantly in transverse arrays of sarcoplasmic reticulum. The localisation data suggest that the calponin-like protein of S. japonicum is involved in contraction of the stratified tail muscle. Furthermore, the presence of a calponin system in the stratified muscle suggests that this muscle is simply a superior form of muscle, closely related to smooth muscles that use a caldesmin-calponin system in contraction.

Actin Cytoskeleton↗
PubMed2001

Echinobothrium chisholmae n. sp. (Cestoda, Diphyllidea) from the giant shovel-nose ray Rhinobatos typus from Australia, with observations on the ultrastructure of its scolex musculature and peduncular spines.

Echinobothrium chisholmae n. sp. is described from Rhinobatos typus Bennett (Rhinobatidae), collected from Heron Island, Great Barrier Reef, Australia. E. chisholmae differs from all congeners in possessing 11 hooks in each dorsal and ventral group on the rostellum and groups of 3-6 hooklets on either side of the hooks. A single metacestode of E. chisholmae was collected from the decapod crustacean Penaeus longistylus Kubo. Yellow pigmentation of the cephalic peduncle in immature adults is caused by the accumulation of large vesicles in the distal cytoplasm of the tegument. The vesicles probably provide materials for spine formation. Ultrastructural examination of the rostellar musculature revealed that the muscles are stratified (striated-like), consisting of a periodic repetition of sarcomeres separated by perforated Z-like lines that are oblique to the long axes of the myofilaments.

Animals↗
PubMed2001

Cancrum oris in a Caucasian male with Type 2 diabetes mellitus.

We describe a patient with Type 2 diabetes mellitus who developed cancrum oris requiring extensive oro-facial reconstructive surgery. There are no previous published reports of cancrum oris occurring in a Caucasian subject with no risk factors other than Type 2 diabetes.

Aged↗
PubMed2001

Gene therapy for gastric ulcers with single local injection of naked DNA encoding VEGF and angiopoietin-1.

BACKGROUND & AIMS: Angiogenesis, formation of new capillary blood vessels, is crucial for gastroduodenal ulcer healing because it enables delivery of oxygen and nutrients to the healing site. Because angiogenesis is stimulated by vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), we studied whether local gene therapy with nonviral DNA encoding VEGF and/or Ang1 into the ulcer base could accelerate ulcer healing through enhanced angiogenesis. METHODS: Gastric ulcers were induced in rats by acetic acid applied to the serosal surface of the stomach, and the site around the ulcer was injected with nonviral plasmid-encoding full-length complementary DNA (cDNA) of human recombinant (rh) VEGF165, rhAng1, or their combination. For some studies, neutralizing anti-VEGF antibody was administered. RESULTS: Single local injection of plasmids encoding VEGF165 and Ang1 significantly increased neovascularization and accelerated ulcer healing. A neutralizing anti-VEGF antibody significantly reduced the acceleration of ulcer healing resulting from the treatment. Coinjection of both plasmids encoding rhVEGF165 and rhAng1 resulted in formation of more mature vessels and to more complete restoration of gastric glandular structures within the ulcer scar. However, this did not result in further reduction of ulcer size. CONCLUSIONS: VEGF and Ang1 gene therapy, with limited duration of target gene expression, significantly accelerates gastric ulcer healing. Coinjection of both plasmids leads to more complete structural restoration. Inhibition of accelerated healing by a neutralizing anti-VEGF antibody indicates an essential role for VEGF and enhanced angiogenesis in ulcer healing.

Angiopoietin-1↗
PubMed2001

Lymph nodes in the human female breast: a review of their detection and significance.

Our experience led us to test the hypothesis that lymph nodes are not uncommon within the substance of the human female breast mound. The following specimen types and sources were used to survey the presence of intramammary lymph nodes in the human female breast mound: (1) cadaver breasts; (2) community hospital breast specimens; and (3) university and VA hospital specimens. We found true lymph nodes within and associated with breast specific tissue (ie, tissue that includes duct and gland structures), thereby validating the hypothesis posed. We discuss the significance of these findings in terms of our dominant patient care paradigm (the Triple Test-physical examination, imaging, and fine-needle aspiration [FNA]) and the choice of patient care management options. We conclude the following: lymph nodes occur in any quadrant of the breast mound; recognizing the possibility of intramammary lymph nodes is important when choosing between patient management options; intramammary lymph nodes can be sampled by FNA; intramammary lymph nodes can contain various disease processes; and in the Oregon Health Sciences University Multidisciplinary Breast Clinic, these intramammary lymph nodes are commonly identified by imaging methods and are more likely to be sampled by FNA than either by core or excisional biopsy.

Adult↗
PubMed2001

Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications.

Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against cellular stress and induces cell proliferation, we postulated that oxidative stress-induced ERK2 activation is defective in PHT gastric mucosa. Here we show that in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired. This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1. Furthermore, we found that supplementing vitamin E, a free radical scavenger, reduces the oxidative state in PHT gastric mucosa, normalizes MKP-1 expression, and thereby reverses impairment of oxidative stress-induced ERK2 activation. Finally, we show that orally administered vitamin E completely reverses the increased susceptibility of PHT gastric mucosa to alcohol injury. Our findings point to a new molecular and mechanistic basis for PHT gastropathy and provide a new therapeutic modality for protection of PHT gastric mucosa.

Animals↗
PubMed2001

Multifocal fibrosclerosis: a case of thyroiditis and bilateral lacrimal gland involvement.

A patient with invasive fibrous thyroiditis (Riedel's thyroiditis), dysphagia, and bilateral lacrimal gland involvement is described. Resolution of the thyroid mass and orbital swellings followed corticosteroid therapy. The unusual ocular features of this case are briefly discussed and the use of corticosteroid and other immunosuppressant therapy in multifocal fibrosclerosis is reviewed.

Adrenal Cortex Hormones↗
PubMed2001

Receptor for Fc on the surfaces of schistosomes.

Schistosoma mansoni masks its surface with adsorbed host proteins including erythrocyte antigens, immunoglobulins, major histocompatibility complex class I, and beta(2)-microglobulin (beta(2)m), presumably as a means of avoiding host immune responses. How this is accomplished has not been explained. To identify surface receptors for host proteins, we biotinylated the tegument of live S. mansoni adults and mechanically transformed schistosomula and then removed the parasite surface with detergent. Incubation of biotinylated schistosome surface extracts with human immunoglobulin G (IgG) Fc-Sepharose resulted in purification of a 97-kDa protein that was subsequently identified as paramyosin (Pmy), using antiserum specific for recombinant Pmy. Fc also bound recombinant S. mansoni Pmy and native S. japonicum Pmy. Antiserum to Pmy decreased the binding of Pmy to Fc-Sepharose, and no proteins bound after removal of Pmy from extracts. Fluoresceinated human Fc bound to the surface, vestigial penetration glands, and nascent oral cavity of mechanically transformed schistosomula, and rabbit anti-Pmy Fab fragments ablated the binding of Fc to the schistosome surface. Pmy coprecipitated with host IgG from parasite surface extracts, indicating that complexes formed on the parasite surface as well as in vitro. Binding of Pmy to Fc was not inhibited by soluble protein A, suggesting that Pmy does not bind to the region between the CH2 and CH3 domains used by many other Fc-binding proteins. beta(2)m did not bind to the schistosome Fc receptor (Pmy), a finding that contradicts reports from earlier workers but did bind to a heteromultimer of labeled schistosomula surface proteins. This is the first report of the molecular identity of a schistosome Fc receptor; moreover it demonstrates an additional aspect of the unusual and multifunctional properties of Pmy from schistosomes and other parasitic flatworms.

Animals↗