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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 361 records · Page 20Linked to original sources

Role of prostaglandin E2 in cholinergic-mediated glycoprotein synthesis in canine antrum.

We studied the mechanism of cholinergic stimulation of mucin synthesis in canine antral explants, including the role of PGE2 as an intermediate messenger. Isolated antral mucosa was incubated with 10(-5) M carbachol (Cb), 10(-5) M indomethacin (IND), 10(-5) M pirenzepine (PZ), 10(-5) M Cb + 10(-5) M PZ, 10(-5) M Cb + 10(-5) M IND, and 10(-5) M IND + PGE2 (10(-8), 10(-7) and 10(-6) M) in the presence or absence of [3H]glucosamine. After 24 hr, total glycoprotein synthesis was quantitated by Sepharose-4B chromatography and by 10% TCA/1% PTA precipitation with lipid extraction. PGE2 released into the media was measured by radioimmunoassay (RIA). Cb significantly increased total glycoprotein synthesis and produced a significant increase in PGE2 release. The increase in glycoprotein synthesis and the release of PGE2 was blocked by the addition of muscarinic antagonist PZ. The addition of IND significantly inhibited glycoprotein synthesis and almost entirely suppressed PGE2 secretion. IND also inhibited the effect of Cb on glycoprotein synthesis and PGE2 release. Moreover, PGE2 (10(-6) and 10(-7) M) significantly increased the glycoprotein synthesis in the canine stomach. This suggests the coordinate participation of PGE2-releasing cell population in modulation of glycoprotein synthesis in gastric mucosa.

Animals↗

Effect of sucralfate on components of mucosal barrier produced by cultured canine epithelial cells in vitro.

The mucous gel maintains a neutral microclimate at the epithelial cell surface, which may play a role in both the prevention of gastroduodenal injury and the provision of an environment essential for epithelial restitution and regeneration after injury. Enhancement of the components of the mucous barrier by sucralfate may explain its therapeutic efficacy for upper gastrointestinal tract protection, repair, and healing. We studied the effect of sucralfate and its major soluble component, sucrose octasulfate (SOS), on the synthesis and release of gastric mucin and surface active phospholipid, utilizing an isolated canine gastric mucous cells in culture. We correlated these results with the effect of the agents on mucin synthesis and secretion utilizing explants of canine fundus in vitro. Sucralfate and SOS significantly stimulated phospholipid secretion by isolated canine mucous cells in culture (123% and 112% of control, respectively). Indomethacin pretreatment significantly inhibited the effect of sucralfate, but not SOS, on the stimulation of phospholipid release. Administration of either sucralfate or SOS to the isolated canine mucous cells had no effect upon mucin synthesis or secretion using a sensitive immunoassay. Sucralfate and SOS did not stimulate mucin release in the canine explants; sucralfate significantly stimulated the synthesis of mucin, but only to 108% of that observed in untreated explants. No increase in PGE2 release was observed after sucralfate or SOS exposure to the isolated canine mucous cells. Our results suggest sucralfate affects the mucous barrier largely in a qualitative manner. No increase in mucin secretion or major effect on synthesis was noted, although a significant increase in surface active phospholipid release was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The phase of sperm flagellar beating is not conserved over a brief imposed interruption.

We have studied the phase component of flagellar beating by holding the head of a sea urchin sperm in the tip of a sinusoidally vibrating micropipet and then abruptly displacing the pipet laterally at a speed of 2.5 microns/ms for various durations. This rapid displacement of the pipet delayed the initiation of the next bend for as long as the displacement continued, up to a duration of 1 beat cycle, corresponding to a delay of 0.5 beat cycle. At the end of this displacement, the movement of the pipet was stopped completely without resumption of the initial vibration. Analysis of the flagellar waveform showed that immediately when the pipet was stopped, the flagellum started to beat by spontaneously initiating the bend that had been delayed. The flagellum then continued steady-state beating, with normal waveform and a new phase that was independent of the original phase of beating. These data suggest that the information on the phase of beating is located only at the basal end of the flagellum, and not in oscillators distributed along the axoneme. After this information has been lost, the flagellum can resume beating at any arbitrary phase relative to its original phase.

Animals↗

Millardia meltada, a new host for Acanthocheilonema viteae and a simple technique for separation of microfilariae from peripheral blood.

Millardia meltada were infected with Acanthocheilonema viteae and examined for their susceptibility. The morbidity of infected M. meltada was low compared with that of jirds. On day 47 post-infection (p.i.), 13 of 14 M. meltada developed microfilaremia. Male M. meltada then showed gradually increasing microfilaremia with a peak level of 7000 per 30 microliters blood at week 20 p.i., which was much higher than that (3000) of male jirds. In contrast, microfilarial densities of female M. meltada were markedly low with a peak level of 200 during weeks 10-12 p.i. A simple centrifugation technique with Lympholyte-M was devised for microfilarial separation from the peripheral blood of infected M. meltada and yielded approximately 17 x 10(5) viable microfilariae from 1 ml of blood. This method also makes it possible to collect microfilariae from the same individuals repeatedly. M. meltada, coupled with this microfilarial separation technique, serves as a useful animal model for microfilarial studies of A. viteae.

Animals↗

The influence of Mesocestoides corti on subsequent Angiostrongylus cantonensis infections in mice.

The influence of Mesocestoides corti on subsequent Angiostrongylus cantonensis infection in mice (C57BL/6 and BALB/c) was assessed. Both strains of mice infected with M. corti demonstrated a peak blood eosinophilia at around 3 weeks post-infection (p.i.). C57BL/6 and BALB/c mice primarily infected with M. corti were given A. cantonensis infection 18 days later, but pre-existing M. corti infection did not affect the recovery of intracranial worms of A. cantonensis at day 21 p.i. BALB/c mice with mixed parasite infections showed low morbidity and mortality as compared with mice singly infected with A. cantonensis and some mice demonstrated a pulmonary migration of intracranial worms. In C57BL/6 mice, intracranial worms were killed and thus all mice survived. C57BL/6 mice with mixed parasite infections failed to resist A. cantonensis reinfection. The blastogenic responses of spleen cells against A. cantonensis antigen were lower in BALB/c than in C57BL/6 mice and mixed parasite infections also resulted in less blastogenic responses against both concanavalin A and A. cantonensis antigen than monoinfection. The recovery of M. corti biomass was significantly higher in mice with mixed parasite infections than mice with monoinfection with M. corti. These data suggest a distinct difference in response to A. cantonensis infection between C57BL/6 and BALB/c mice, and the induction of immunosuppression in both mouse strains following M. corti infection. Blood eosinophilia provoked by M. corti infection is not directly associated with the killing of worms in subsequent A. cantonensis infection.

Angiostrongylus cantonensis↗

Restoration of the defective natural defence of beige mice against tissue-migrating larvae of Strongyloides ratti by transfer with normal peritoneal cells.

The effects of cell transfer on the defective natural defences of beige (bgj/bgj) mice against Strongyloides ratti were studied by assessing recovery of tissue-migrating larvae from head and lung. Transfer of peritoneal resident cells from normal bgj/+ mice restored the defective natural defence of beige mice. The non-adherent population of normal peritoneal cells did not have the restorative capacity. Macrophages may be important to the natural defence against S. ratti.

Animals↗

Effects of polyoxyethylene (20) sorbitan monooleate on the acute toxicity of linear alkylbenzenesulfonate (C12LAS) to fish.

Effects of polyoxyethylene (20) sorbitan monooleate (SMOE20) on the acute toxicity of linear alkylbenzenesulfonate (C12LAS) to fish were investigated in red killifish (Orizias latipes) and carp (Cyprinus carpio). By adding polyoxyethylene sorbitan ester to C12LAS solution, the acute toxicity of C12LAS decreased. As a decreasing toxic effect of these nonionic surfactants, the depression of gill damage was histopathologically observed. No significant hematological and blood biochemical differences were observed between two tests using a single C12LAS solution and a mixed solution of C12LAS/SMOE20. The addition of SMOE20 to C12LAS decreased the incorporation of C12LAS into blood and each organ except spleen and gall bladder as well as the adsorption of C12LAS to the gill. The farther inward the phenyl position in the alkyl side chain, the lower the adsorption of C12LAS to gill. Since the acute toxicity of LAS phenyl isomers to fish was known to decrease according to the order of adsorption, these results suggest that the decreasing toxic effect of SMOE20 on the acute toxicity of C12LAS is due to depression of more toxic C12LAS adsorption on the gill.

Adsorption↗

Postsurgical inflammation after phacoemulsification and extracapsular extraction with soft or conventional intraocular lens implantation.

A one-year prospective study was conducted in 120 patients to assess the time course of changes in intraocular inflammation after three cataract surgery procedures: planned extracapsular extraction with poly(methyl methacrylate) (PMMA) intraocular lens (IOL) implantation (11 mm incision group), phacoemulsification with PMMA IOL implantation (7 mm incision group), and phacoemulsification with foldable silicone single-piece IOL implantation (4 mm incision group). Each group was carefully matched for patients' ophthalmologic and systemic backgrounds. Patients with hard nuclei were excluded. The degree of inflammation was evaluated by quantitating aqueous flare intensity and cell count with the laser flare-cell meter. In the early postoperative period, both aqueous flare intensity and cell count were highest in the 11 mm incision group followed, in decreasing order, by the 7 mm and 4 mm incision groups. Significant between-group differences were observed at one, two, and seven postoperative days for flare and one day through one week for cells. Both parameters in each group decreased to a similar level one month after surgery, but flare intensity in all groups remained significantly higher than that of age-matched normal controls up to six months postoperatively.

Aged↗

Protease resistant interleukin-3 stimulating components in excretory and secretory products from adult worms of Strongyloides ratti.

Excretory and secretory (ES) products collected from adult worms of Strongyloides ratti stimulated interleukin-3 (IL-3) production with mesenteric lymph node cells from infected C57BL/6 mice, but not with normal mesenteric lymph node cells. The IL-3 stimulating components were not major IgG binding antigens. Activity of the IL-3 stimulating components was stable by treatment with protease, although reduced by heating in boiling water.

Animals↗

A case of adult T cell leukemia with bullae in the palmoplantar regions followed by a crisis.

A 48-year-old Japanese female who had had chronic ATL for 4 years suddenly developed vesicles on the palms and soles. Histologically, these bullae were specific lesions of ATL. After a tendency toward improvement, a crisis appeared with increases in the following: peripheral white blood cells, atypical lymphocytes, CD25 positive cells, serum LDH, and soluble IL-2R. Palmoplantar bullae, a rather rare finding, may be indicative of a following crisis.

Female↗

Clostridium botulinum type C in healthy swine in Japan.

Healthy cattle and swine bred in a district of Japan were examined for the presence of Clostridium botulinum in their liver. Liver specimens were cultivated in chopped meat-glucose medium and the cultures were examined for botulinum toxin. In cattle, none of the cultures of 100 liver specimens yielded the toxin. In swine, however, C1 or C2 toxin was demonstrated in 8 of 100 liver specimens from 36 farms. One of the five farms where the carrier-state swine were present was surveyed for about 2 years to determine whether the carrier-state was transient or resident. C. botulinum type C was found in swine livers and feces, and environmental specimens at extremely high rates during the surveillances, with 76% of specimens yielding botulinum toxin following the culture. These data suggest that it is not uncommon for healthy swine to carry C. botulinum type C in the liver and that there is a close relationship between C. botulinum carrier-state in swine and the presence of this organism in their raising environments. In 20 cattle and 20 swine suffering from parturient paresis of unknown etiology no evidence for involvement of C. botulinum type C was obtained.

Animals↗

HTLV-I uveitis: a distinct clinical entity caused by HTLV-I.

Seroepidemiological, clinical and virological studies were carried out in an HTLV-I endemic area to find out if HTLV-I caused an intraocular inflammatory disorder, uveitis. The seroprevalence in patients with uveitis without defined etiologies (62/175, 35.4%) was significantly higher than that in patients with non-uveitic ocular diseases (42/261, 16.1%) or in patients with uveitis with defined etiologies (8/78, 10.3%). Moreover, the seroprevalence in young adults (20-49 years) with uveitis without defined etiologies was 30/67 (44.8%), whereas it was only 10/107 (9.3%) in the other two groups. The uveitis in HTLV-I carriers was characterized clinically by a moderate inflammation of the vitreous body accompanied by a mild iritis and retinal vasculitis. The proviral DNA of HTLV-I was detected by polymerase chain reaction from the inflammatory cells in the anterior chamber in 9 out of 9 seropositive patients with the uveitis, but not in any of the tested patients with other types of uveitis. These data, thus, indicate that HTLV-I causes a specific type of intraocular inflammation, uveitis.

Adult↗

Characterization of monoclonal antibodies against eosinophil chemotactic factors from young adult worms of Angiostrongylus cantonensis.

Two kinds of IgG1 monoclonal antibodies against eosinophil chemotactic factors (ECFs) derived from Angiostrongylus cantonensis young adult worms (YA) were established. Western blot analyses demonstrated that one monoclonal antibody recognized a 16.1 kD component of YA-whole worm extract, and the other an 85 kD component. These antibodies did not show any cross reactions against several helminth antigens, as assessed by ELISA. The chemotactic activity of YA-whole worm extract for guinea-pig-eosinophils was significantly inhibited by previous incubation of the extract with these monoclonal antibodies; the monoclonal antibody recognizing the 16.1 kD component inhibited 56-61% of the ECF activity whilst the antibody recognizing the 85 kD component inhibited 20-34% of the activity. The combination of both monoclonal antibodies showed a stronger inhibitory effect (71-81%) than either antibody alone. Similar magnitudes of inhibition were noted when the chemotactic activity for human eosinophils was measured using YA-whole worm extract preincubated with these monoclonal antibodies. Neither monoclonal antibodies inhibited the chemotactic activity of whole worm extracts of A. cantonensis first stage larvae, Metastrongylus apri adult worms, Spirometra erinacei plerocercoids and Fasciola sp. adult worms. These data suggest that the two monoclonal antibodies will be useful for the isolation and purification of ECF-YA as well as for elucidating the possible in vivo role of ECF-YA.

Angiostrongylus cantonensis↗

Down-regulation of cystic fibrosis transmembrane conductance regulator gene expression by agents that modulate intracellular divalent cations.

In cystic fibrosis (CF), epithelial cells are unable to normally up-regulate apical membrane Cl- secretion in response to agents which increase cyclic AMP, but they do increase Cl- secretion in response to increases in intracellular Ca2+. Since intracellular divalent cations regulate the expression of many genes, we hypothesized that mobilization of intracellular Ca2+ and/or other divalent cations might modulate not only Ca(2+)-dependent Cl- channels but also cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. To evaluate this concept, HT-29 human colon carcinoma cells were cultured under various conditions designed to manipulate intracellular divalent cation concentrations and CFTR gene expression was quantified at the levels of transcription, mRNA accumulation, mRNA half-life, and protein. Exposure to the divalent cation ionophores A23187 and ionomycin (agents which increase intracellular divalent cation concentrations) caused dose- and time-dependent reductions of CFTR mRNA levels, which could be blocked by the use of Ca(2+)- and Mg(2+)-free media. Ionophore-induced CFTR gene modulation was also observed with T84 human colon carcinoma cells and freshly isolated normal human bronchial epithelial cells. Incubation of HT-29 cells with thapsigargin, an agent that releases Ca2+ from intracellular stores, or in medium containing increased extracellular concentrations of Ca2+ or Mg2+ also caused down-regulation of CFTR mRNA levels. Transcription run-on analysis showed that, parallel with the decrease in CFTR mRNA levels, A23187 reduced the rate of transcription of the CFTR gene, while CFTR mRNA transcript half-life was unaffected. Consistent with the down-regulation of CFTR gene expression, CFTR protein levels also decreased after exposure to A23187. Thus, despite the independence of Ca(2+)-dependent Cl- channels and cyclic AMP-dependent CFTR-related Cl- channels in epithelial cells, increases in intracellular divalent cation concentrations down-regulate the expression of the CFTR gene at the transcriptional level, with consequent decreases in CFTR mRNA and protein.

Calcimycin↗

Ontogeny of neonatal pulmonary vascular pressure-flow relationships.

Previously we reported that pulmonary vascular pressure gradients determined by vascular occlusion varied as a function of neonatal age. The purpose of this study was to evaluate the effect of blood flow on pressure gradients during normoxia (inspired O2 28%) and hypoxia (inspired O2 4.2%) in isolated, indomethacin-treated lungs obtained from lambs at less than 1, 2-4, 12-14, and 30-32 days of age (n = 6 at each age). The total pulmonary pressure gradient was partitioned into pressure gradients across relatively indistensible arteries and veins and relatively compliant vessels in the middle region (delta Pm) by inflow and outflow occlusions at flows of 25, 50, 75, and 100 ml.kg-1.min-1. During normoxia, lungs from lambs less than 1 day of age had significantly greater pressures at each flow than lungs from older lambs, due primarily to a significantly greater delta Pm in this age group. During hypoxia, the greatest vasoconstriction occurred in the youngest group, also due mostly to an increased delta Pm. This enhanced response to hypoxia in the younger age groups was due to inhibition of prostaglandin synthesis; without indomethacin treatment, the older age groups had a greater hypoxic pressor response than the younger groups. The arterial vascular resistance at all ages was relatively constant as a function of blood flow during both normoxia and hypoxia, whereas the total and middle vascular resistances generally decreased as a function of flow. The venous resistance initially decreased and then was constant. These results suggest that the neonatal pulmonary circulation h as a fixed arterial resistance, a slightly distensible venous region at low flows, and a more distensible middle region.

Aging↗

Dibutyryl cyclic AMP attenuates lung responses induced by endotoxin in conscious sheep.

Dibutyryl cyclic AMP (DBcAMP) could inhibit the production of prostanoids and modulate the pulmonary vascular responses induced by endotoxin. Diffuse lung injury after endotoxemia in sheep is accompanied by the production of prostanoids and an increase in endothelial permeability. To determine whether exogenous DBcAMP could prevent the endotoxin responses, we measured pulmonary hemodynamics, gas exchange, and lung lymph responses to an intravenous infusion of Escherichia coli endotoxin (1.0 micrograms/kg over 30 min) in unanesthetized sheep in the presence and absence of DBcAMP (30 micrograms/kg/min) infused intravenously for 6 h beginning 1 h before endotoxin infusion or for 4.5 h after 30 min of treatment with endotoxin infusion. We also measured circulating leukocytes and lung lymph and plasma concentrations of thromboxane B2 (TXB2) and prostacyclin (6-keto-PGF1 alpha) metabolites by radioimmunoassay. DBcAMP infusion before endotoxin infusion decreased endotoxin-induced pulmonary hypertension and hypoxemia and markedly attenuated the increased lung lymph flow and lymph protein clearance. DBcAMP after endotoxin only attenuated the increased lung lymph flow and lymph protein clearance. DBcAMP treatment both before and after endotoxin infusion blocked endotoxin-induced increases in lung lymph and plasma TXB2 and 6-keto-PGF1 alpha. DBcAMP did not affect the number of circulating leukocytes. Although DBcAMP alone did not affect the pulmonary and systemic hemodynamics and lung lymph balance, the potential that DBcAMP directly modulates the pulmonary vascular responses to endotoxin as a vasodilator could be expected. We conclude that DBcAMP infusion attenuates lung dysfunction caused by endotoxemia, possibly by preventing prostanoid release and modulating the pulmonary vascular responses.

6-Ketoprostaglandin F1 alpha↗

Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line.

The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by epithelial cells, thus recruiting neutrophils to the airways. BET-1A human bronchial epithelial cells at rest or incubated with normal ELF showed little IL-8 gene expression, but after incubation with CF ELF, a marked increase in IL-8 transcript levels was observed. CF ELF contained high levels of neutrophil elastase (NE) and various serine protease inhibitors prevented CF ELF from inducing IL-8 gene expression in BET-1A cells, suggesting that NE was the dominant inducer for IL-8 production in CF ELF. The addition of purified NE caused BET-1A cells to increase IL-8 gene transcription with accumulation of mRNA transcripts and to release IL-8-like neutrophil chemotactic activity. These observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced the bronchial epithelium to secrete IL-8, which in turn recruits additional neutrophils to the bronchial surface.

Base Sequence↗