Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 1,279 records · Page 71Linked to original sources

PubMed1989

Stimulation of gastric alkaline secretion by histamine in rats: possible involvement of histamine H2-receptors and endogenous prostaglandins.

The mechanism of stimulatory action of histamine on gastric alkaline secretion was investigated in anesthetized rats. Intravenous infusion of histamine (2-8 mg/kg/hr) dose-dependently stimulated acid secretion and in the presence of omeprazole (60 mg/kg), an H+/K+-adenosine triphosphatase inhibitor, produced an increase of gastric but not duodenal alkaline secretion; the degree of gastric alkalinization was also dependent on the dose of histamine, reaching the maximal values of approximately 1.0 microEq/10 min. Cimetidine (100 mg/kg s.c.) significantly inhibited both acid and alkaline secretory responses caused by histamine, whereas indomethacin (5 mg/kg s.c.) significantly prevented the increased alkaline secretion caused by histamine as well as mucosal acidification (100 mM HCl for 10 min). Tripelennamine (10 mg/kg s.c.) had no effect on either acid or alkaline secretion. Histamine (8 mg/kg/hr) reduced the arterial blood pressure (25.3%) and increased the mucosal vascular permeability in the stomach as determined by Evans blue (160%), but these vascular responses were significantly prevented only by tripelennamine, excluding the possible contribution of the vascular effects to the increased gastric alkaline secretion. These results suggest that histamine may stimulate gastric alkaline secretion as well as acid secretion, and the mechanism of histamine-induced alkaline secretion may involve both endogenous prostaglandins and stimulation of H2-receptors.

Animals↗

PubMed1989

Role of sulfhydryls in mucosal injury caused by ethanol: relation to microvascular permeability, gastric motility and cytoprotection.

The relationship between gastric mucosal glutathione (GSH) levels, vascular permeability, gastric motility and mucosal injury caused by ethanol was investigated in rats. Oral administration of 50% ethanol (1 ml) produced elongated reddish bands of lesions in the mucosa with a significant reduction of GSH levels and increase of microvascular permeability. These lesions were significantly inhibited by pretreatment with s.c. administered diethylmaleate (DEM: 1 ml/kg), cysteamine (100 mg/kg) and 16, 16-dimethyl prostaglandin E2 (dmPGE2, 10 micrograms/kg) but worsened markedly by N-ethylmaleimide (NEM: 10 mg/kg). Irrespective of whether the animals were treated with 50% ethanol or not, the mucosal GSH levels were significantly decreased or increased, respectively, by DEM or cysteamine, and were not affected by both NEM and dmPGE2. NEM significantly enhanced the vascular permeability in the absence or presence of ethanol (greater than 10%), whereas other agents significantly inhibited only the increased vascular permeability caused by ethanol. On the other hand, gastric motility was potently and persistently inhibited by either DEM, cysteamine or dmPGE2 at the doses which prevented ethanol-induced mucosal injury, whereas NEM had no effect on the motility. These results suggest that 1) the mucosal GSH levels do not relate directly to either development or prevention of ethanol-induced gastric injury, 2) potentiation by NEM of the mucosal injury may be accounted for by its enhancement of the vascular permeability and 3) inhibition of gastric motility may be associated with prevention of mucosal lesions.

16,16-Dimethylprostaglandin E2↗

PubMed1989

[Mitral valve replacement following myomectomy for idiopathic hypertrophic subaortic stenosis].

A patient is reported with IHSS where mitral valve replacement was performed 3 years following myomectomy because of a residual pressure gradient of left ventricular outflow tract. After mitral valve replacement, the left ventricular outflow tract obstruction was almost completely relieved not only at rest but also at provocation by isoproterenol. The patient successfully returned to work with no symptoms.

Adult↗

PubMed1988

Degradation of aspartate aminotransferase in rat liver lysosomes.

Highly purified lysosomes from the normal and leupeptin-treated rat livers were subjected to immunoblot analysis using antibodies against cytosolic and mitochondrial isozymes of aspartate aminotransferase (cAspAT and mAspAT). In the case of cAspAT (subunit M.W. = 46K), the leupeptin-treated lysosomes showed a major band of 46K and a minor band of 36K while normal lysosomes showed a major band of 36K and a minor band of 41K. In the case of mAspAT (subunit M.W. = 44K), the leupeptin-treated lysosomes showed a 44K band and the normal lysosomes showed a 40K band. These observations suggest that both cAspAT and mAspAT are sequestered into lysosomes with the original subunit molecular weights and are degraded in the lysosomes by way of sequential formation of relatively stable intermediates with distinct molecular weights.

Animals↗

PubMed1988

IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells.

rIL-6/B cell stimulatory factor 2 was found to augment CTL generation from mature as well as immature human T cells stimulated with UV-treated allogeneic cells. rIL-6 also acted on peanut agglutinin-positive murine thymocytes and Lyt-2-positive splenic T cells to give rise to CTL. rIL-6 alone could not induce CTL generation, the presence of IL-2 during the early phase of culture period was found to be essential for the IL-6 activity in the induction of CTL. The effect of rIL-6 was not mediated by the induction of IL-2 inasmuch as rIL-6 did not augment IL-2 production in MLC and anti-IL-2 antibody could not neutralize IL-6 activity. rIL-6 augmented CTL generation even when added 72 h after the initiation of cultures. The enhancing activity of rIL-6 could be neutralized with anti-IL-6 antibodies even when added 72 h after the initiation of cultures. The present data indicate that IL-6 acts in the late phase of CTL generation.

Adjuvants, Immunologic↗

PubMed1988

Identification of a novel protein tyrosine kinase that phosphorylates pp60c-src and regulates its activity in neonatal rat brain.

A novel protein tyrosine kinase not related to pp60c-src, designated as N-PTK, has recently been found in neonatal rat brain. In the present study, the enzyme was purified further by heparin-Sepharose column chromatography, and identified as a monomer protein with a Mr of 47 K and a pI of 7.0 by two-dimensional gel electrophoresis. The enzyme was found to phosphorylate purified pp60c-src at a tyrosine residue(s). The major phosphorylation site was shown by alpha-chymotryptic peptide mapping to be in the carboxy terminal V8 protease fragment (V2), but to be different from the autophosphorylation site, Tyr-416. The phosphorylation significantly suppressed pp60c-src activity with enolase as a substrate. These findings strongly suggest that N-PTK is a specific kinase that phosphorylates pp60c-src and regulates its function in the cell.

Animals↗

PubMed1988

Combined effects of L-ascorbic acid, citric acid or their sodium salts on tumor induction by N-butyl-N-(4-hydroxybutyl)nitrosamine or N-ethyl-N-(4-hydroxybutyl)nitrosamine in the rat urinary bladder.

L-Ascorbic acid, citric acid or their sodium salts (at levels equivalent to 5% sodium L-ascorbate) were fed in the diet simultaneously with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) (0.025% BBN or 0.021% EHBN) in the drinking water to male F344 rats for 20 weeks to determine whether urinary pH changes affect the carcinogenicity of BBN or EHBN. In the urine, pH was decreased in rats fed the acidic chemicals and increased in rats fed their corresponding sodium salts. Histopathologically, the incidences and numbers of preneoplastic and neoplastic lesions in groups treated with each test chemical were not different from those in control groups except for sodium citrate-treated groups in which induction of carcinomas was higher, resulting from increased intake of either carcinogen and also from increased urinary excretion of main carcinogenic metabolites. These results show that the test chemicals do not affect the carcinogenicity of BBN or EHBN on the rat urinary bladder when simultaneously administered despite significant differences in urinary pH.

Animals↗

PubMed1988

IL-2 receptor(p55)/Tac-inducing factor. Purification and characterization of adult T cell leukemia-derived factor.

Many human T cell lymphotropic virus-I (HTLV-I) transformed T cells from adult T cell leukemia (ATL) patients continuously produce a humoral factor called ATL-derived factor (ADF) which induces IL-2R/Tac expression on T and NK cells. Using gel filtration, procion red Sepharose, DEAE, and reverse phase chromatography, we have purified ADF protein to homogeneity from 15 liters of serum-free culture supernatant of an HTLV-I(+) T cell line ATL-2. Purified ADF protein had the m.w. of 14,000 by SDS-PAGE and gel filtration, and its isoelectric point is around 5.0. ADF did not react with heteroantibodies against IL-1 alpha and IL-1 beta, which have also IL-2R/Tac-inducing activity on suitable target cells. Partial N-terminal amino acid sequence of ADF is different from other cytokines such as, IFN, BSF-2, and various IL whose cDNA has been cloned. Western blot analysis using rabbit antibodies against N-terminal 10mer synthetic peptide of ADF showed that IL-1 alpha and ADF are different proteins. ADF had its IL-2R/Tac-inducing activity not only on human NK-like cell line YT, but also on HTLV-I(+) T cells, such as ED. In contrast, macrophage-derived IL-1 lacked IL-2R/Tac-inducing activity on ED cells despite their IL-2R/Tac induction on YT, indicating that ADF and IL-1 have their effect via different receptors.

Adolescent↗

PubMed1988

Interaction of tissue-type plasminogen activator and plasminogen activator inhibitor 1 on the surface of endothelial cells.

The site of the reaction between plasminogen activators and plasminogen activator inhibitor 1 (PAI-1) was investigated in cultures of human umbilical vein endothelial cells. In conditioned medium from endothelial cells, two forms of a plasminogen activator-specific inhibitor can be demonstrated: an active form that readily binds to and inhibits plasminogen activators and an immunologically related quiescent form which has no anti-activator activity but which can be activated by denaturation. In conditioned medium, only a few percent of PAI-1 is the active form. However, the addition of increasing concentrations of tissue-type plasminogen activator (t-PA) or urokinase to confluent endothelial cells produced a saturable (3.0 pmol/5 x 10(5) cells), dose-dependent increase of the activator-PAI-1 complex in the conditioned medium even in the presence of actinomycin D or cycloheximide. This resulted also in a dose-dependent decrease of the residual PAI activity measured by reverse fibrin autography both in the conditioned medium and cell extracts. Short-time exposure of endothelial cells to a large amount of t-PA caused almost complete depletion of all cell-associated PAI activity. Although there was no detectable PAI activity even after activation of PAI by denaturants or antigen in the culture medium at 4 degrees C without the addition of t-PA, the addition of t-PA at 4 degrees C not only resulted in the formation of 70% of the amount of the t-PA.PAI complex in conditioned medium at 37 degrees C, but also induced PAI-1 antigen in a time and dose-dependent manner in the conditioned medium. Moreover, 125I-labeled t-PA immobilized on Sepharose added directly to endothelial cells formed a complex with PAI-1 in a dose-dependent manner. On the other hand, no detectable complex was formed with PAI-1 when Sepharose-immobilized 125I-labeled t-PA was added to endothelial cells under conditions in which the added t-PA could not contact the cells directly but other proteins could pass freely by the use of a Transwell. All these results suggest that a "storage pool" on the surface of endothelial cells or the extracellular matrix produced by endothelial cells contains almost all the active PAI-1, and reaction between PA and PAI-1 mainly occurs on the endothelial cell membranes, resulting in a decrease of the conversion of active PAI-1 to the quiescent form.

Dose-Response Relationship, Drug↗

PubMed1988

CT findings of cerebral paragonimiasis in the chronic state.

The CT findings in 5 patients with cerebral paragonimiasis in the chronic state are presented. The findings were: 1) multiple, densely calcified areas with a variety of round or nodular shapes in the brain, 2) a large low density area surrounding or connecting with the calcified areas, and 3) cortical atrophy and ventricular dilatation. The relation between the CT findings and the previously reported plain skull X-ray findings or neuropathological findings are discussed.

Adult↗

PubMed1988

Involvement of fibronectin in in vitro regeneration of retinal pigment epithelium.

Argon laser photocoagulation was placed on the confluent monolayer of cultured chick retinal pigment epithelial cells as a model of the regeneration process of retinal pigment epithelium after laser burn. The intense fibrillar net immunofluorescent pattern of fibronectin appeared on the burnt area from 2 h after the laser application, before the beginning of tissue reconstruction. Fibronectin was observed for several days, then became undetectable before the complete regeneration of retinal pigment epithelial cells. This indicates that fibronectin is involved in the early regeneration process of retinal pigment epithelium.

Animals↗

PubMed1988

Simultaneous determination of noradrenaline and 3-methoxy-4-hydroxyphenylglycol in plasma with high-performance liquid chromatography using electrochemical detection.

We herein report the simultaneous determination of the levels of noradrenaline (NA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of NA. The sample was subjected to a Sep Pak C18 cartridge prior to the NA and MHPG assay by high-performance liquid chromatography with an electrochemical detector. The results correlated well with the established methods. The average percentage of recovery was 91.2 and 98.7% for NA and MHPG, respectively. The intraassay coefficients of variation were 3.7 and 4.6% for NA and MHPG. The interassay coefficients of variation were 3.5 and 7.5% for NA and MHPG, respectively.

Chromatography, High Pressure Liquid↗

PubMed1988

Prolog-based system for nursing staff scheduling implemented on a personal computer.

An approach to the problem of nursing staff scheduling in a hospital is presented. For scheduling nurses, a variety of requirements with varied levels of significance has to be taken into account simultaneously. Because of the nature of the problem, where it is difficult to define what is the optimal solution in a strict sense, we aimed at automating scheduling by following the manual method in a faithful manner. A system for nurse scheduling has been implemented on a personal computer using Prolog. It determines favorable shift assignments on a day-to-day basis, referring to the information accumulated in the data base. In Prolog, various requirements can be expressed with relative ease, and the process of the manual method can be incorporated into the system in a natural way. The computer simulation has been conducted to test the system performance, and the obtained results demonstrated the validity of the approach.

Management Information Systems↗

PubMed1988

Puff induction in permeabilized Drosophila salivary glands in a chemically defined medium.

We showed previously that digitonin-permeabilized salivary glands form prominent puffs in response to ecdysterone only when the incubation medium is supplemented with a homogenate of intact glands. To develop a chemically defined medium that supports puff formation in permeabilized salivary glands, we examined the requirement of ribonucleoside triphosphates (NTPs), precursors of RNA synthesis, for puff formation in permeabilized salivary glands. We found that prominent ecdysone puffs were induced in permeabilized salivary glands when the concentration of each NTP in the medium was higher than 0.5 mM. The puff size was significantly reduced if the volume of the medium were more than 2.0 microliter per gland. This suggests the existence of a factor(s), in addition to NTPs, which is required for puff formation and is diffusible from permeabilized glands.

Animals↗

PubMed1988

Digitonin treatment activates specific genes including the heat-shock genes in salivary glands of Drosophila melanogaster.

A large number of chromosomal sites were found to form puffs in Drosophila salivary glands after treatment with the mild detergent digitonin and incubation in a defined medium for 2 hr. The cytological locations of these puffs were determined, and the puff size was measured at 43 loci in both digitonin-treated salivary glands and intact glands. On the basis of comparisons of puffing between digitonin-treated and intact salivary glands, the puffs were classified into three categories: (1) digitonin-unaffected preexisting puffs (8 sites), (2) digitonin-activated preexisting puffs (6 sites), and (3) digitonin-induced new puffs ("digitonin puffs", 29 sites). The digitonin puffs included some of the developmentally regulated puffs and all the heat-shock puffs known in Drosophila melanogaster. The activation of the specific loci by digitonin treatment suggests that gene expression at these loci is suppressed in salivary glands by a mechanism(s) sensitive to digitonin.

Animals↗

PubMed1988

Molecular analysis of a cytoplasmic factor essential for pole cell formation in Drosophila embryos.

This article reviews recent analytical studies of cytoplasmic factors involved in a mechanism underlying pole cell formation in Drosophila embryogenesis. Polar plasm, or germ plasm, includes sources of two independent functions in the germ-line segregation from the somatic line: pole cell formation and commitment of pole cells to germ cells. The UV-caused inability of pole cell formation in embryos was restored by poly(A)+ RNA, of which cDNA was cloned. The nucleotide sequence of the cDNA was highly homologous with mitochondrial large rRNA.

Animals↗

PubMed1988

Abnormal molecules of mitochondrial aspartate aminotransferase in the liver of vitamin B-6--deficient rats may be produced in the mitochondrial matrix.

The distribution of mitochondrial aspartate aminotransferase (AspATm) in liver cells was studied in rats fed pyridoxine-deficient and control diets. Mitochondrial aminotransferase activity was found mainly in the matrix fraction, with smaller amounts in the outer membranes, intermembrane space and cytosol. The precursor of the enzyme was detected in the liver cytosol of both vitamin B-6--deficient and control rats, and its amount was similar in the two groups. When pyridoxal phosphate was added to the assay system, the ratio of enzyme activity to antigenic activity (E/A) of mitochondrial aspartate aminotransferase in the cytosol of both vitamin B-6--deficient and control rats was about 70% of that in the matrix of control rats. On the other hand, the E/A of the matrix enzyme in deficient rats was 53% of that of controls. From these results we concluded that pyridoxal phosphate is not necessary for translocation of mitochondrial aspartate aminotransferase into mitochondrial matrix and that abnormal molecules of the enzyme may be formed in the matrix of vitamin B-6--deficient rat liver.

Animals↗

PubMed1988

Protein tyrosine kinase in rat brain: neonatal rat brain expresses two types of pp60c-src and a novel protein tyrosine kinase.

Using angiotensin I as a substrate, the activity of protein tyrosine kinase was determined in various rat tissues, and its developmental change in rat brain was investigated. The specific activity was shown to be the highest in the brain among the tissues examined in neonatal rats, while it was the highest in the spleen in adult rats. In the brain, the activity varied during development and was the highest in the first postnatal week. To identify the protein tyrosine kinase and examine its relationship with pp60c-src, which is known to be highly expressed in neuronal cells, we attempted to characterize the enzyme from neonatal and adult rat brain, using poly(Glu,Tyr) as a substrate. Neonatal brain was found to express two types of pp60c-src and a novel protein tyrosine kinase to almost the same level, while adult brain expressed pp60c-src predominantly. The neonatal type of pp60c-src and the novel enzyme were designated as pp60nc-src and N-PTK in the present study, respectively. pp60c-src, pp60nc-src, and N-PTK were purified about 660-. 370-, and 260-fold from crude homogenate of neonatal brain, respectively, by procedures including sequential column chromatography on DEAE cellulose, hydroxylapatite, Ultrogel AcA44, and poly(Glu,Tyr) Sepharose. N-PTK behaved as a molecule with apparent Mr = 50,000 on Ultrogel AcA44 gel filtration chromatography. It was not immunoprecipitated by anti-pp60c-src antiserum and did not phosphorylate IgG heavy chain of anti-pp60c-src antibody. It required mainly Mn2+ for activity and phosphorylated tyrosine-containing polyamino acids and synthetic peptides such as angiotensin II and RR-SRC peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗