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Y Ikegami

Publications and source records attributed to Y Ikegami.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ion-pair reversed-phase high-performance liquid chromatography of adenine nucleotides and nucleoside using triethylamine as a counterion.

An isocratic HPLC method for the simple and selective determination of adenine nucleoside and nucleotides has been developed. The separation is achieved at room temperature by reversed-phase chromatography (Shiseido, Capcell Pak C18). A mixture of 0.1 M triethylamine (TEA) phosphate buffer and methanol (95:5, v/v) is used as a standard eluent. Influence of pH and concentrations of organic modifiers and TEA ion on capacity factors of adenine compounds has been investigated. It has been also found that the TEA ion in the eluent is adsorbed onto the reversed-phase surface. The results clearly demonstrate that ion-pair formation with TEA ion occurs probably both in the mobile phase and on the stationary phase and governs the retention of adenine and nucleotides in the present system. The HPLC system is applied to the analysis of adenine nucleotides formed as intermediates in the synthesis of 3'-phosphoadenosine 5'-phosphosulphate (PAPS) and to the assays of ATPases and 5'-nucleotidase activities in rat liver plasma membrane. This method is a new type of ion-pair reversed-phase HPLC system and is suitable for the separation of highly polar organic anions, especially for adenine nucleotides.

Adenine Nucleotides↗
PubMed1997

A possible immunosuppressant, cycloprodigiosin hydrochloride, obtained from Pseudoalteromonas denitrificans.

Cycloprodigiosin hydrochloride (cPrG.HCl), a member of the prodigiosin family, is a red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. cPrG.HCl markedly suppressed 3H-thymidine incorporation by concanavalin A stimulated murine splenocytes but had little effect on lipopolysaccharide dependent 3H-thymidine incorporation, indicating that cPrG.HCl acts as a selective inhibitor of T cell proliferation in the same way as other members of the prodigiosin family. cPrG.HCl inhibited the proliferation of the PMA stimulated Jurkat cells through an apoptotic process. Intriguingly, cPrG.HCl inhibited the H+ translocation by vacuolar type ATPase in chromaffin granule membranes without any effect on either its ATPase activity nor on the membrane conductance of phospholipid bilayers, suggesting that cPrG.HCl selectively uncouples H+ translocation from the ATPase reaction rather than acting as a non-specific ionophore. Since crystalline cPrG.HCl is highly stable, it raises the possibility of its therapeutic use as an immunosuppressant.

Animals↗
PubMed1997

Cerebral extracellular lactate concentration and blood flow during chemical stimulation of the nucleus tractus solitarii in anesthetized rats.

The extracellular lactate concentration and blood flow in the cerebral cortex of urethane-anesthetized, paralyzed and artificially ventilated rats were monitored continuously and simultaneously using an enzyme electrode and a laser Doppler flowmeter (LDF), respectively, during chemical stimulation of the nucleus tractus solitarii (NTS) by microinjection of L-glutamate (1.7 nmol 50 nl). Chemical stimulation of the NTS significantly decreased the arterial blood pressure (ABP) from 85 +/- 17 to 68 +/- 14 mmHg, heart rate from 418 +/- 13 to 402 +/- 19 beats x min(-1) and cerebral blood flow (CBF) by 17.9 +/- 6.2% (P < 0.001). However, chemical stimulation of the NTS significantly increased the lactate concentration by 58.9 +/- 17.3 microM (P < 0.001). Barostat maneuver, which held systemic ABP constant during chemical stimulation of the NTS attenuated the responses in CBF and lactate concentration by 30 and 27%, respectively. The onset of the increase in lactate concentration was delayed about 19 s after that of the CBF decrease. Circulatory lactate produced no significant change in the cerebral extracellular lactate concentration. These results indicate that chemical stimulation of the NTS induces an increase in extracellular lactate concentration in the cerebral cortex through a decrease in CBF via cerebral vasoconstriction.

Animals↗
PubMed1997

Comparative analysis of the gp120-binding area of murine and human CD4 molecules.

The structural basis for the difference between human and murine CD4 molecules in binding to HIV envelope protein gp120 has been intensively studied. Eighteen mutant human CD4 molecules were produced by segmental replacement of beta strands and loops in the gp120-binding area of the molecule with corresponding murine sequences or by single amino acid substitutions. Examination of these mutant CD4 molecules for gp120 binding indicated that murine CD4 molecule does not bind gp120 for the following three reasons: (a) The loops flanking the C" strand are longer than their human counterparts, causing significant difference in local tertiary structure; (b) valin, rather than phenylalanine, which is the key amino acid for the binding occupies position 43; (c) amino acids at positions 45 and 46 are different, causing further decrease in binding affinity. Furthermore, the present study indicated that the aromatic ring of Phe43 and the negative charge of Arg59 play key roles in gp120 binding.

Amino Acid Sequence↗
PubMed1997

[Functions of the transforming growth factor-beta superfamily in eyes].

One human body is composed of 6 x 10(13) cells, and eyes are also composed of many cells of different functions. The cellular functions and intercellular interaction are regulated by many regulators including cytokines and growth factors to maintain the homeostasis. The transforming growth factor-beta (TGF-beta) superfamily, a large family of multifunctional factors, regulates various cellular functions, including cellular proliferation, migration, differentiation, apoptosis and extracellular matrix production. The TGF-beta superfamily contains about 30 multifunctional factors, and is divided into several families according to the sequence homology. The TGF-beta family, the activin family, and bone morphogenic proteins belong to the TGF-beta superfamily. TGF-beta superfamily members transduce signals through type I and type II serine/threonine type transmembrane receptors. The signals are transduced from receptors through nuclei by Smad family members, which are phosphorylated by the activated type I receptors and translocate from cytoplasm into nuclei. TGF-beta family members and the TGF-beta superfamily receptor family are expressed in ocular tissues including the cornea, ciliary epithelium, lens epithelium, retina, and blood vessels. This observation suggests the importance of the TGF-beta superfamily in eyes. Smad family members (Smad 1, Smad 2, Smad 3 and Smad 4) are expressed in the cultured retinal pigmant epithelial cell line (D407), in which TGF-beta and activin A stimulate the translocation of Smad 2, but not Smad 1 into nuclei, whereas bone morphogenetic protein (BMP) stimulates that of Smad 1, but not Smad 2. TGF-beta superfamily members play important roles in the pathogenesis of retinal neovascularization and in the wound healing process of corneal tissue. TGF-beta inhibits the endothelial functions, but, stimulates angiogenesis in vivo. TGF-beta is involved in the formation of abnormal connective tissue in corneal wound healing. In these processes, many cytokines and growth factors are involved, interacting with each other and forming networks. It is mandatory to clarify the networks to investigate molecular pathogenesis and new therapeutic agents.

Diabetic Retinopathy↗
PubMed1996

Spinal cord lactate concentration during chemical stimulation of the nucleus tractus solitarii in anesthetized rats.

This study was conducted to determine the mechanism of spinal cord blood flow (SCBF) decrease following the nucleus tractus solitarii (NTS) activation. In urethane-anesthetized, paralyzed and artificially ventilated rats, neurons in the NTS were chemically stimulated by microinjection of L-glutamate (1.7 nmol; 50 nl) and the lactate concentration, one of indicators of local neuronal metabolism, in the spinal cord was monitored in real time using an enzyme electrode. Before the chemical stimulation study, the responses of the enzyme electrode and its specificity were tested in vitro and in vivo. The electrode responded to step changes in lactate concentration and a calibration plot and regression line were obtained in vitro. The lactate concentration was significantly (P < 0.01) increased during induced apnea in vivo (n = 8). The lactate concentration in the spinal cord was not significantly changed by chemical stimulation of the NTS when arterial blood pressure (ABP) remained above the lower limit of spinal cord autoregulation (n = 21). When chemical stimulation of the NTS decreased ABP to below the lower limit of autoregulation (n = 18), the lactate concentration in the spinal cord was significantly (P < 0.01) increased. This may only be due to hypotensive effects because the lactate concentration was also significantly (P < 0.01) increased when the ABP was passively decreased below the lower limit of autoregulation by controlled hemorrhage in intact (n = 11) and sinoaortic denervated rats (n = 10). Intravenous lactate injection produced no significant increase in the current from the enzyme electrode in the spinal cord (n = 4). Using the electrode with inactivated enzyme solution, the current from the electrode did not change with the increase in lactate in the spinal cord. These findings indicate that the enzyme electrode can detect rapid changes of lactate, a product of anaerobic metabolism. These results also indicate that the spinal cord vasoconstrictor response elicited by chemical stimulation of the NTS, which was performed above the lower limit of spinal cord autoregulation in our previous study, may be due to neurogenic regulatory mechanism, but not to the secondary effects of changes in metabolism.

Anesthesia↗
PubMed1996

Suppressive effects of Aspergillus fumigatus culture filtrates on human alveolar macrophages and polymorphonuclear leucocytes.

Aspergillus spp., especially A. fumigatus (Af) can colonize the airways and the lungs with localized underlying conditions and further invade the surrounding lung tissues, even in subjects without systemic predisposing factors, presumably by escaping the local host defences. To clarify the mechanisms of colonization and invasion of Af, we investigated the in vitro effects of Af culture filtrates (ACFs) on the functions of human alveolar macrophages (AMs), and polymorphonuclear leucocytes (PMNs). ACFs were obtained by culturing clinically isolated Af in Medium-199 at 37 degrees C for 5 days. In the study of phagocytosis of Af conidia by human AMs, 52% of AMs ingested conidia during a 60 min incubation period in Medium-199. However, the percentage decreased to 24% when incubated with a final concentration of 30% ACF in Medium-199. With respect to the antichemotactic activity on human PMNs, 3% ACF was sufficient for significant suppression, and 30% ACF completely inhibited the migration of PMNs. In addition, phorbol myristate acetate (PMA)-induced O2- release from PMNs was significantly suppressed in Medium-199 which included 12.5% ACF or more. The antichemotactic activity of ACF was partially abolished by trypsin or chicken egg ovomacroglobulin. When ACF was separated into two fractions (molecular weight > 10 and < 10 kDa) by dialysis and centrifugation through CL-LGC filters, both fractions retained the antichemotactic activity. We conclude that Af produce several antiphagocytic factors, which can be responsible for the colonization of Af in the bronchopulmonary tissues and allow this species to invade surrounding lung tissues in pulmonary aspergillosis by suppressing local host defences.

Aspergillus fumigatus↗
PubMed1996

Antitumor effect of CGP41251, a new selective protein kinase C inhibitor, on human non-small cell lung cancer cells.

The antitumor effect of CGP41251 (4'-N-benzoyl staurosporine), a selective protein kinase C (PKC) inhibitor, was examined on two kinds of human non-small cell lung cancer (NSCLC) cell lines (adenocarcinoma: A549 and squamous cell carcinoma: NCI-H520). CGP41251 at 0.5 or 1.0 microM inhibited the proliferation of these tumor cell lines significantly; However, at 0.1 microM, it did not show any significant inhibition. Cell cycle analysis indicated that CGP41251 at 0.5 or 1.0 microM arrested the cell cycle progression at the G2/M phase up to 24 hr, but 0.1 microM did not. It seems that the antiproliferative action of CGP41251 against human NSCLC is related to G2/M accumulation. In NCI-H520, CGP41251 caused DNA re-replication without mitosis. In a nude mice xenograft, CGP41251 at a dose of 200 mg/kg showed antitumor activity against these cell lines. Histopathologically, expansion of central necrosis was observed, although no destruction of tumor nests was seen by CGP41251 administration. In both tumor tissues, the PKC activity of the particulate fraction was significantly decreased by CGP41251 treatment. From these results, it is thought that the antitumor activity of CGP41251 against human NSCLS is accompanied by the decrease of PKC activity in the particulate fraction. Moreover, the G2/M arrest of the cell cycle induced by CGP41251 might be important for the growth inhibitory action of this compound.

Adenocarcinoma↗
PubMed1996

Studies on the effect of the new non-steroidal aromatase inhibitor fadrozole hydrochloride in an endometriosis model in rats.

The therapeutic effect of the new nonsteroidal aromatase inhibitor fadrozole hydrochloride (4-(5,6,7,8-tetrahydro-imidazo[1,5a]pyridin-5-yl)benzonitrile monohydrochloride, fadrozole, CAS 102676-31-3, CGS16949A) was assessed using a surgically induced endometriosis model in rats. In nontreated rats, the endometrial transplants on the abdominal wall developed large cysts with fluid. In the fadrozole treated group, the cystic volume of the transplants decreased in a dose-dependent manner. The weights of the hemi-uteri were markedly reduced by fadrozole treatment. Fadrozole produced a dose-dependent increase in percentage of vaginal diestrous days. In ovariectomized group, the growth of the transplants was also suppressed, and the weights of the hemi-uteri decreased markedly. Histologically, the signs of growth suppression and/or atrophic changes such as minimization of luminal size, cuboidal piknotic epithelium and/or contraction of stroma were observed in ovariectomized or fadrozole treated groups. The right uterine horns also showed marked atrophic changes as with the transplants. The present study strongly indicates that the new selective aromatase inhibitor fadrozole should be useful for the treatment of endometriosis.

Animals↗
PubMed1996

Effects of the new selective protein kinase C inhibitor 4'-N-benzoyl staurosporine on cell cycle distribution and growth inhibition in human small cell lung cancer cells.

CGP 41251 (4'-N-benzoyl staurosporine, CAS 120685-11-2) exerts increased selectivity for Ca(2+)- and phospholipid-dependent protein kinase C inhibition. In this study, the effects of CGP 41251 on cell cycle distribution and growth inhibition were examined in SBC3 human small cell lung cancer (SCLC) cell line. CGP 41251 caused the inhibition of cell proliferation and at 1.0 mumol/l showed almost complete effect. In early S phase synchronized SBC3 cells, CGP 41251 at 1.0 mumol/l did not inhibit an initial progression from early S to G2 phase, but it blocked a process from G2/M to G1 phase completely. After removal of nocodazole block, CGP 41251 at 1.0 mumol/l caused DNA re-replication and induction of polyploidy. In nude mice xenograft, CGP 41251 at a dose of 200 mg/kg showed statistically significant inhibition against this tumor with a T/C value of 21.4%. Histopathologically, expansion of central necrosis was observed by the administration of CGP 41251. These results in SBC3 cells indicated that CGP 41251 showed antitumor activity through the inhibition of cell cycle progression from G2/M to G1 phase, and through induction of cells with higher DNA content.

Animals↗
PubMed1995

canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila.

The canoemisty1 (cnomis1) mutation was isolated by virtue of its severe rough eye phenotype from approximately 500 fly lines, each harboring a single autosomal insertion of a P element (Bm delta w). Excision of the P element generated a lethal, null allele, cnomis10, together with many revertants with normal eye morphology. Ommatidia homozygous for cnomis10, produced in an otherwise wild-type eye by somatic recombination, typically contain a reduced number of outer photoreceptors. Some cnomis1 homozygous adults bear extra macrochaetes on the head, notum, humerus and/or scutellum. cnomis1 hemizygotes often show conspicuous wing phenotypes such as a notched blade and the loss of a cross vein. The sequence of cno cDNA clones isolated from an embryonic cDNA library revealed a long open reading frame that potentially encodes a 1893-amino-acid protein with the GLGF/DHR motif, a conserved sequence in Discs large, Dishevelled, and some other proteins associated with cellular junctions. Flies doubly mutant for cnomis1 and scabrous1 (sca1) and those for cnomis1 and the split (spl) allele of Notch (N) always have rumpled wings curved downward. The spl; cnomis1 double mutant flies also exhibit a "giant socket" phenotype. These phenotypes are rarely observed flies singly mutant for either cnomis1, sca1 or spl. The wing vein gaps caused by Abruptex1, a N allele producing an activated form of N protein, are dominantly suppressed by cnomis1. Heterozygosity for shaggy and myospheroid promotes formation of extra wing veins in cnomis1 homozygotes. The genetic interactions suggest that cno participates with members of the N pathway in regulating adhesive cell-cell interactions for the determination of cell fate.

Amino Acid Sequence↗
PubMed1995

Chemical stimulation of the nucleus tractus solitarii decreases spinal cord blood flow in anesthetized rats.

L-Glutamate was microinjected into the nucleus tractus solitarii (NTS) in anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, and spinal cord blood flow (SCBF) was determined using a combination of labeled microspheres. Unilateral chemical stimulation of the NTS (n = 13) significantly decreased SCBF in the cervical cord from 43 +/- 6 (mean +/- SEM) to 28 +/- 4 (P < 0.05), in the thoracic cord from 35 +/- 3 to 24 +/- 4 (P < 0.01), and in the lumbar cord from 49 +/- 3 to 40 +/- 3 ml min-1 (100 g)-1 (P < 0.05). The decrease in SCBF was not due to the decrease in arterial blood pressure (ABP) because the SCBF during the chemical stimulation of the NTS was significantly smaller (P < 0.05) than the SCBF during controlled hemorrhagic hypotension (n = 11). Chemical stimulation of the NTS did not affect the reactivity of the spinal cord vessels to hypercapnia (n = 5). Microinjection of the vehicle solution into the NTS had no effects on spinal cord circulation (n = 9). These results suggest that the cell bodies within the NTS may play a role in the control of spinal cord circulation.

Animals↗
PubMed1995

[Health appraisal for work adjustment of freshmen employees--information on health checkup just after entering the corporation and condition in the next fiscal year].

In 1990, 365 (males: 197, females: 168) freshmen employees at the headquarters of a large corporation were examined just after being hired in order to observe their health status. We collected (1) data of physical examinations and questionnaires for symptoms as an ordinary health checkup, (2) information on work adjustment, life patterns, and personal characteristics through interviews conducted by ten public health nurses, and (3) personal records, e.g. birth year. Statistical analyses revealed some notable findings as follows: (1) subjects with higher blood pressure had higher scores of extrovert personality among males, (2) female subjects with greater body mass index had higher scores in such manifestations of personal characteristics such as aggression and discontent with superiors, (3) higher scores of personal characteristics were noted among female subjects working in technical sections, (4) positive correlation between the scores of work adjustment and personal characteristics, (5) higher scores of undesirable life patterns among males and of work maladjustment among elder females, (6) unbalanced meal quality of subjects from rural areas, (7) higher mental tension among younger males from rural areas, and (8) higher scores of dependency and lower morale among younger female subjects. Information on health problems was collected over the 1.5 yrs that followed. More problems were detected among females than among males and among younger females than among elder females. Longitudinal analysis was carried out from just after entry into the company for approximately 1.5 yrs. Health problems in females could be predicted by the data on personal characteristics and work adjustment just after entry. Risk of health problems in male freshmen employees with hobbies and unhealthy drinking habits over the 1.5 yrs that followed was higher than in others. It was concluded that a health interview for freshmen employees by public health nurses is valuable for health care, obtaining information regarding work adjustment, life patterns, and personal characteristics.

Adult↗
PubMed1995

Antitumor activity of the new selective protein kinase C inhibitor 4'-N-benzoyl staurosporine on murine and human tumor models.

CGP 41251 (4'-N-benzoyl staurosporine, CAS 120685-11-2) has been shown to exert increased selectivity for the inhibition of protein kinase C (PKC) activity. In the present study the effect of CGP 41251 formulated in gelucire as an antitumor agent was studied in various types of murine and human tumor models. When administered at a dose of 75 mg/kg 3 times daily for 9 days, CGP 41251 prolonged the life span of the mice bearing B16 melanoma (ILS = 36%). CGP 41251, administered orally at doses of 25-225 mg/kg once daily for 9 days, however, did not show distinct efficacy in four kinds of murine tumor models (B16 melanoma, colon 26, colon 38 and M5076). In s.c.inoculated human tumor xenograft models, CGP 41251, administered orally at a dose of 200 mg/kg once daily for 4 weeks showed a broad antitumor spectrum. CGP 41251 inhibited the growth of gastric cancer (H-55), colorectal cancer (H-26), breast cancer (H-31) and lung cancer (H-74 and LC-376) with inhibition rates of 58-80%. In a histopathologic study, increase in central necrosis and condensed nuclei and vacuolar degeneration were observed, but there was no structural destruction by the treatment of CGP 41251. In addition, CGP 41251 decreased the number of PCNA (proliferating cell nuclear antigen) immunoreactive cells in human tumor cells H-55, H-26 and H-74. These results indicate that CGP 41251 shows a broad antitumor spectrum against human tumors, and it is suggested that CGP 41251 is a promising oral antitumor agent which has a novel mechanism of action.

Animals↗
PubMed1994

[Studies on the hormone-binding function of thyroid hormone-binding proteins by heat treatment].

Thyroxine-binding globulin (TBG), a major thyroid hormone-binding protein, is denatured by heat and subsequently loses its binding activity. This study aimed to investigate changes in the function of thyroid hormone-binding proteins utilizing a method of heat treatment. The first aim of this study was to examine how the relationship between thyroid hormones and binding proteins changes with heat treatment at 56 degrees C in serum from normal subjects. When approximately half of the native TBG was denatured by heat, the mean percentage of T4 bound to thyroxine-binding prealbumin (TBPA), measured by a single immunoprecipitation method, was increased from 15.3% to 25.7% and the percentage of T4 bound to albumin was increased from 4.7% to 7.5%. Serum free T4 concentration were increased to 166.0 +/- 17.1% (Mean +/- SD) from the basal value. By heating at 58 degrees C, T4 bound to TBPA was denatured, but T4 bound to albumin showed a significant increase, and serum free T4 concentrations were increased to 396.0 +/- 62.1%. Because T4 binding ratios of TBPA and albumin were increased after TBG denaturation, free hormone concentrations did not increase very greatly. The second aim of this study was to examine the properties of TBG in patients with non familial partial deficiency of TBG (NFPD-TBG). When the serum sample of NFPD-TBG was heated, the half time of NFPD-TBG was 14.1 +/- 5.5 min, which was significantly shorter than that of normal TBG (45.1 +/- 7.0 min, P < 0.001). Isoelectric focusing (IEF) of NFPD-TBG showed that the pIs were not different from those of normal TBG. When serum from NFPD-TBG was mixed with normal serum, the half time was still shorter than the normal serum samples. The data suggest that the molecular structure of NFPD-TBG is not abnormal, but a certain factor which alters the heat stability of TBG exists in the serum from NFPD-TBG.

Adult↗
PubMed1994

Central nervous system arteriovenous malformations with hereditary hemorrhagic telangiectasia: report of a family with three cases.

A family with central nervous system (CNS) arteriovenous malformations (AVMs) and hereditary hemorrhagic telangiectasia (HHT) is reported. A 46-year-old man had an intracerebral hemorrhage. Cerebral angiography showed one AVM and two angiomas. The HHT was diagnosed because of the concomitant existence of cutaneous telangiectasia. The patient's brother had HHT and paraplegia since the age of 21. Magnetic resonance imaging revealed an old spinal cord hemorrhage. The patient's son with HHT had an intracerebral hemorrhage at age 6. Angiograms showed two AVMs and one angioma. Familial CNS AVMs with HHT are extremely rare. The loci for human leukocyte antigen of the affected cases with HHT were evaluated, and the management of CNS AVMs with HHT is discussed.

Adult↗
PubMed1994

Stimulation of calcium sequestration by mezerein, a protein kinase C activator, in saponized rabbit platelets.

1. The saponin-permeabilized platelet was used to examine the effect of mezerein, a moderate activator of protein kinase C (C-kinase), on the sequestration of Ca2+ to its intracellular storage sites. 2. We found that the activation of C-kinase by mezerein causes the potentiation of the Ca2+ sequestration. 3. It was suggested that C-kinase in platelets might function as a negative feedback regulator for the agonist-induced Ca2+ mobilization and might be involved in its oscillation.

Animals↗