Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 811 records · Page 45Linked to original sources

PubMed1995

Glutathione S-transferases as a cefpiramide binding protein in rat liver.

To clarify the intrahepatical transport mechanism of cefpiramide, we investigated effects of various agents mainly excreted into the bile by several different mechanisms on the biliary excretion of cefpiramide in rats. Sulfobromophthalein, indocyanine green, bilirubin and probenecid, known to be bound to glutathione S-transferases (GST) (EC 2.5.1.18) in liver cytosol, reduced the biliary excretion of cefpiramide, while neither secretory IgA, which is transported via vesicles in the liver, nor colchicine, which inhibits movements of vesicles, had any effect on the excretion of cefpiramide. Propranolol and metoprolol, metabolized by mixed function oxidases, had no effect on the biliary excretion of cefpiramide. In the chromatography of liver cytosol, the amount of sulfobromophthalein or benzylpenicillin bound to the GST fraction decreased in the presence of cefpiramide or probenecid. The study showed that cefpiramide was transported in the liver without relation to mixed function oxidases or vesichle-mediated transporting system, but in relation to GST which binds cefpiramide, sulfobromophthalein, benzylpenicillin and probenecid, indicating an important role of GST in the cefpiramide excretion into the bile.

Animals↗

PubMed1995

Hypertrophy and proliferation of skeletal muscle fibers from aged quail.

The purpose of this study was to determined whether fibers in the anterior latissimus dorsi (ALD) muscle from aged Japanese quail have decreased hypertrophic or proliferative responses to 30 days of stretch overload compared with fibers from adult birds. Two groups of quail were studied, 12-wk-old quail (adult; n = 16) and 90-wk-old quail (aged; n = 16). The left wing of each bird was overloaded with a weight corresponding to 10% of the bird's body weight, and the right wing served as the intra-animal control. Quails were killed after 30 days of stretch overload. Total fiber number was quantified by counting all the fibers in a transverse section from the midbelly of the ALD muscle. ALD muscles in aged quails retained the capacity to increase their muscle mass (145%), total fiber number (49%), and fiber cross-sectional area (54%) in response to stretch overload. The ALD muscle in aged quail had a significantly lower increase in muscle mass (33%) and mass corrected for nonmuscle tissue (36%) compared with the ALD from young adult birds. Age had no effect on fiber type distribution shifts with stretch. These results suggest that although muscles in old birds have a substantial ability to adapt to enlarge, stretch-induced hypertrophy is attenuated in muscles from old quail.

Aging↗

PubMed1995

Hypertrophic Z-line observed in aged one-humped camel (Camelus dromedarius).

The ultrastructure of cardiac muscle from 3 aged one-humped camels (Camelus dromedarius) was examined to see if aged camels also develop hypertrophic Z-lines as observed in the heart of aged humans and other animals. The results proved that the aged camel heart develops hypertrophic Z-lines together with other age-associated alterations, including loss of myofibrils and myofilaments, increase of intermyofibrillar spaces and intercellular spaces, and disruption of mitochondrial cristae and intercalated disc structure. Hypertrophic Z-lines are somewhat smaller than those of other species, but occur both in the atria and ventricles. Although the majority of cardiac muscle samples revealed a normal structure, the finding of hypertrophic Z-lines in camel heart is the first such observation in a ruminant animal. The anomalous camel muscle resembles that of other species in terms of cell alterations commonly associated with aged hearts.

Aging↗

PubMed1995

Proximal paraconal interventricular myocardial bridge in dog: ultrastructural characterization.

The ultrastructure of the dog myocardial bridges (MB), named here the proximal paraconal interventricular-myocardial bridge (PPI-MB), was examined to determine if its structure is identical to that of ordinary cardiac muscle. This study is preparatory to the establishment of PPI-MB as a physical and physiological model system to examine the influence of MB on coronary flow in cardiac function. Five of 46 dog hearts examined possessed PPI-MB, the occurrence of which was independent of sex, age and breed. The dog PPI-MB was localized in a limited area in the proximal third of the paraconal interventricular groove. PPI-MB myocytes and myofibrils were arranged quite straight and smooth, with minimum branching. PPI-MB myocytes formed side-by-side cell junctions through the mediation of mitochondria. Connective tissue elements were involved in terminal cell adhesion to form the myomyous junction beside the intercalated disc. The excitation conductive system of sarcoplasmic reticulum-T tubule often showed a triad. Numerous nerve axons or nerve ending-like structures appeared. Many structural views deviated somewhat from common cardiac muscle structure. This paper represents the first detailed description of PPI-MB muscle.

Animals↗

PubMed1995

Ten-year survey of incidence of infection as a cause of death in hematologic malignancies: study of 90 autopsied cases.

We investigated 90 autopsied cases with hematologic malignancy, including malignant lymphoma (ML), acute leukemia (AL), and adult T-cell leukemia (ATL) peculiar to our district, during the 10-year period 1982-1991 to determine the change in incidence of infection as a cause of death. We divided the cases into two groups representing the first half decade (1982-1986) and the second half decade (1987-1991) and compared the findings made in the two groups. Although infection was the major cause of death in those autopsied cases, the incidence of fatal infections decreased during the latter period. The incidence of fatal bacterial infections decreased, while fungal infections showed a relative increase. Pneumocystis carinii pneumonia and cytomegalovirus (CMV) infection occurred more frequently in patients with ATL than in those with ML or AL. Combined infection by more than three pathogens was observed in 2 cases of ATL. Our study revealed the characteristics of ATL specific to our district, and indicated the need to apply new strategies to prevent and treat fungal and viral infections in patients with hematologic malignancies.

Acute Disease↗

PubMed1995

Inhibition of prostaglandin E2 and interleukin 1-beta production by low-power laser irradiation in stretched human periodontal ligament cells.

It is well-known that orthodontic treatment usually causes some discomfort and pain to the patients. Recently, it has been reported that low-power laser irradiation is effective in reducing the pain accompanying tooth movement. However, the mechanism of such pain relief cannot be elucidated. Since high levels of prostaglandin (PG) E2 and interleukin (IL)-1 beta are found in the periodontal ligament (PDL) during tooth movement, and both factors are involved in the induction of pain, the effects of low-power laser irradiation on PGE2 and IL-1 beta production in stretched human PDL cells were studied in vitro. The PDL cells, derived from healthy premolars extracted for orthodontic treatment, were utilized for experiments. Cells were seeded in flexible-bottomed culture plates, and the bottom of each plate was elongated (18% increase) under vacuum at 6 cycles per min for 1, 3, or 5 days. The stretched cells were irradiated with a Ga-Al-As low-power diode laser (60 mW) once a day for 3, 6, or 10 min (from 10.8 to 36.0 J) for 1, 3, or 5 days. PGE2 and IL-1 beta levels in the medium were measured by radioimmunoassay. In response to mechanical stretching, human PDL cells showed a marked elevation in PGE2 production in a time-dependent manner. IL-1 beta production was also elevated, but this remained constant. The increase in PGE2 production was significantly inhibited by laser irradiation in a dose-dependent manner. The increase in IL-1 beta production was also significantly inhibited by laser irradiation, although the inhibition was only partial.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1995

Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer.

The aim of this study was to investigate whether mouse placenta produces mature mouse GHRF (mGHRF) and whether cytokines regulate placental mGHRF production. Using Sephadex G-50 gel filtration chromatography and reverse phase HPLC, we identified immunoreactive mGHRF in acid-ethanol extract of placental tissues, which had chromatographic characteristics identical to those of hypothalamic mature mGHRF peptide. The major peak of immunoreactive GHRF in the medium from cultured placental cells was resolved by HPLC at a fraction identical to hypothalamic mature mGHRF. Interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin-M, which all use gp130 as a signal transducer, significantly inhibited mGHRF secretion by cultured placental cells. However, IL-1 alpha and tumor necrosis factor-alpha had no effect on mGHRF secretion. Antibodies to IL-6 or IL-6 receptor completely blocked the inhibitory effect of IL-6 on mGHRF secretion. Anti-LIF, and oncostatin-M inhibited the expression of mGHRF messenger RNA. These results suggest that mouse placenta produces and releases the mature mGHRF, which is indistinguishable by chromatographic criteria from that produced by the hypothalamus, and that signals through gp130 lead to the inhibition of mGHRF production and release in the mouse placenta.

Animals↗

PubMed1995

Cyclic adenosine-3',5'-monophosphate stimulates mouse placental lactogen-I (mPL-I) secretion but inhibits mPL-II secretion at midpregnancy.

To determine whether cAMP regulates mouse placental lactogen-I (mPL-I) and mPL-II secretion at midpregnancy in vitro, mouse placental tissue from day 9 of pregnancy was dispersed with collagenase, cells were fractionated on a Percoll gradient, and the purified trophoblast cells were plated in a serum-free medium. The cells were then incubated with various agents that increased the intracellular cAMP level for 5 days. 8-Bromo-cAMP stimulated mPL-I secretion, but inhibited mPL-II secretion in a time- and dose-dependent manner without changing the amount of newly synthesized trichloroacetic acid-precipitable proteins. Cholera toxin and forskolin, which increase intracellular cAMP accumulation, also regulated mPL-I and mPL-II secretion in the same manner. 8-Bromo-cAMP increased the intracellular mPL-I concentration, decreased the intracellular mPL-II concentration, and increased the immunoprecipitable newly synthesized mPL-I concentration in both the medium and cells. 8-Bromo-cAMP increased the expression of mPL-I messenger RNA and decreased the expression of mPL-II messenger RNA. The sequential reverse hemolytic plaque assay and double immunocytochemistry indicated that 8-bromo-cAMP regulates the subpopulation of giant cells containing and releasing mPL. These findings suggest that an increase in intracellular cAMP stimulates mPL-I secretion, but inhibits mPL-II secretion by changing the subpopulation of giant cells containing and releasing mPL.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Cyclic adenosine 3',5'-monophosphate stimulation of placental proliferin and proliferin-related protein secretion.

To identify factors that regulate proliferin (PLF) and PLF-related protein (PRP) secretion by the mouse placenta, placental cells from day 9 of pregnancy were cultured for up to 5 days, and PLF and PRP release into the medium was assessed by RIA. Transforming growth factor-alpha, interleukin-1 alpha, and interleukin-6 did not regulate either PLF or PRP secretion. However, treatment of primary placental cell cultures with 8-bromo-cAMP, cholera toxin, or forskolin resulted in 2- to 3-fold increases in the percentages of PLF- and PRP-producing cells in the population and corresponding increases in both PLF and PRP messenger RNA and secreted protein. The increase in the number of PLF-producing cells was accompanied by an increase in the number of cells expressing both PLF and mouse placental lactogen-I. These data suggest that cAMP levels can regulate trophoblast giant cell differentiation and, consequently, the amount of PLF and PRP secretion.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Estrogen induces epidermal growth factor (EGF) receptor and its ligands in human fallopian tube: involvement of EGF but not transforming growth factor-alpha in estrogen-induced tubal cell growth in vitro.

We studied the estrogen-dependent expression of epidermal growth factor (EGF), transforming growth factor (TGF) alpha, and EGF receptor gene transcripts in human fallopian tubes in vivo and in vitro. Competitive polymerase chain reaction (PCR) was performed on the fallopian tube RNA samples from the postmenopausal women with or without estrogen replacement. Amounts of EGF, TGF alpha, and EGF receptors gene transcripts in the estrogen-treated group (n = 3) were significantly (P < 0.01) more than those in the untreated group (n = 3). Competitive PCR also showed that EGF, TGF alpha, and EGF receptor gene transcripts level in tubal cells were increased by estrogen in vitro: messenger RNA levels of these factors were significantly (P < 0.01, n = 3) increased in cells incubated with 10(-8) M estrogen compared with those in cells without estrogen treatment. We studied whether EGF and/or TGF alpha is involved in the estrogen-induced tubal cell growth in vitro. Estrogen enhanced the [3H]-thymidine incorporation into the cell in dose- and time-dependent manners in culture: estrogen treatment for more than 12 h significantly (P < 0.05) enhanced the [3H]-thymidine incorporation into the cell at 10(-8) M. The estrogen-induced cell growth was observed in association with the increase in EGF, TGF alpha, and EGF receptor messenger RNA levels by estrogen. If the EGF and/or TGF alpha is involved in the cell growth, then the estrogen-induced cell growth should be suppressed by blocking the action of EGF and/or TGF alpha. Therefore, we examined the effects of neutralizing monoclonal antibodies against EGF, TGF alpha, and EGF receptors. Anti-EGF antibody significantly reduced the estrogen-induced increase in [3H]-thymidine incorporation, whereas anti-TGF alpha antibody failed to show the effect. Anti-EGF receptor antibody showed a significant suppressive effect on the estrogen-induced increase in [3H]-thymidine incorporation. Moreover, the growth inhibitory effect by 1 microgram/ml anti-EGF was restored by 10(-8) M EGF but not by TGF alpha even at 10(-6) M. All these data suggest that estrogen induces EGF and TGF alpha/EGF receptors in the human fallopian tube and that EGF but not TGF alpha may be involved in the estrogen-induced human tubal cell growth in vitro.

Antibodies, Monoclonal↗

PubMed1995

Immunohistochemical localization of thromboxane receptor and thromboxane synthase in rat testis.

The cellular localization of thromboxane A2 receptor (TXR) and thromboxane synthase (TXS) in rat testes was examined with an antibody against the carboxyl-terminal tail of rat TXR and anti-porcine lung TXS antibody. By light microscopy immunoreactivity for TXR was shown to be present in spermatids, whereas spermatogonia, spermatocytes, and spermatozoa lacked the immunoreactivity. Immunoelectron microscopic analysis revealed that immunostainable TXR was present in acrosomes of spermatids. In contrast, immunoreactivity for TXS was present in all stages of spermatogenic cells; spermatogonia, spermatocytes, spermatids, and spermatozoa. TX system may possibly contribute to the formation of acrosomes or have some unrecognized functions in an autocrine/paracrine fashion.

Amino Acid Sequence↗

PubMed1995

Distribution of PCNA during postblastoderm cell division cycles in the Drosophila melanogaster embryo: effect of a string- mutation.

We used immunocytochemical methods and a specific antibody to identify proliferating cell nuclear antigen (PCNA) in Drosophila embryos during the postblastoderm cell division cycles. The strong nuclear staining observed during interphase disappeared at prophase, staining remained nil throughout the remaining mitotic (M) phases and reappeared in nuclei at the next interphase. As the embryos with the homozygous string- mutation sustained the strong staining signal in nuclei throughout embryonic development, disappearance of the staining signal probably depends on string function and is coupled with the onset of mitosis. When cells in embryos were arrested at M phase following treatment with TN-16 or Vinblastine, the staining signal with the anti-PCNA antibody was lost. However, Western blots showed that the level of PCNA protein in M phase-arrested embryos did not decrease. Therefore, the disappearance of staining signals is apparently due to reorganization of PCNA protein in the multiprotein complex in nuclei, rendering it inaccessible to the antibody, rather than to the degradation of PCNA protein. In contrast to findings in developing embryos, cultured Drosophila Kc cells stained strongly with the anti-PCNA antibody, during both interphase and the M phase. In genetic crossing experiments of transgenic flies carrying the lacZ gene under the control of the PCNA gene regulatory region (-607 to +137 with respect to the transcription initiation site) with string- mutant files, the PCNA gene promoter seems to function in a manner independent of cell cycle progression or of functions of the string gene.

Animals↗

PubMed1995

Effect of fluoride on the activities of the Na+/glucose cotransporter and Na+/K(+)-ATPase in brush border and basolateral membranes of rat kidney (in vitro and in vivo).

In this study, renal Na+/K(+)-ATPase activity was demonstrated to be strongly suppressed prior to the glucosuria caused by a fluoride dose (NaF 35 mg/kg, i.p.), and the 50% suppression of the enzyme activity was almost at the same dose of NaF, about 30 mg/kg, i.p. to rats. In the rats, renal Na+/glucose cotransporter activity in brush border membranes was not affected by in vivo NaF, whereas the renal Na+/K(+)-ATPase in basolateral membranes showed a dip in activity 3 h after NaF treatment of the whole animal. Moreover, it was suggested from experiments with inhibitors of calphostin C and KT5720 that protein kinase C, but not protein kinase A, may play an important role in the suppression of Na+/K(+)-ATPase following the administration of fluoride to rats. Na+/glucose cotransporter was fairly insensitive to NaF, being competitively inhibited with a Ki of about 100 mM, whereas Na+/K(+)-ATPase was much more sensitive, with a Ki of about 2 mM. From these results, the elevation of urinary glucose excretion after a single dose of fluoride was deduced to be due to suppression of the renal Na+/K(+)-ATPase activity by a direct and/or secondary action of fluoride, rather than of the corresponding Na+/glucose cotransporter activity.

Animals↗

PubMed1995

Synthesis and enantioselectivity of optically active 1- and 3-substituted 4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols and related compounds as norepinephrine potentiators.

Optically active 1,2-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (1R,4R-3a and 1S,4S-3b, 1S,4R-4a, and 1R,4S-4b) and 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolines (4S-5a and 4R-5b) were prepared in order to examine the effects of the 1-, 3-, and 4-substituents of 2-methyl-4-phenyl- 1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1) on the enantioselectivity for norepinephrine (NE) potentiating activity. The conformations and absolute configurations of 3-5 were determined from their 1H-NMR and circular dichroism (CD) spectra and by single-crystal X-ray diffractometric analysis. The NE potentiating activity of the optically active 3-5 and previously prepared 3-methyl derivatives (3R,4R-6a and 3S,4S-6b) of PI-OH were tested. The results show that compounds 3, 4, and 6 had high enantioselectivity for NE potentiation: the 4R series of the enantiomers exhibited activity but not the 4S-enantiomers. The activity of the 4-desoxy compound 5 also resided exclusively in the 4S-enantiomer. These findings suggest the presence of a specific receptor for NE uptake, and the enantiomers 3a, 4a, 5a, and 6a may be antagonistic at this NE uptake receptor.

Adrenergic Uptake Inhibitors↗

PubMed1995

Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. V. Thienopyridazinone derivatives.

Synthesis and pharmacological evaluation of novel thienopyridazinones and related compounds are described. A thiophene ring was found to be able to replace the benzene ring of a phthalazinone without loss of biological activities. This observation supports our hypothesis that the benzene ring plays an important role in both thromboxane A2 (TXA2) synthetase-inhibitory and bronchodilatory activities. Further, it was shown that the carbonyl moiety of a phthalazinone is not necessary for these activities.

Administration, Oral↗

PubMed1995

Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. VI. Indazole derivatives.

Synthesis and pharmacological evaluation of novel indazole derivatives are described. These compounds were found to exhibit both thromboxane A2 (TXA2) synthetase-inhibitory and bronchodilatory activities. This observation supports the idea that the partial structure of the 3-pyridyl and phenyl groups with a methylene insertion is an important component for well-balanced activities.

Administration, Oral↗

PubMed1995

Behavioral involvement of central dopamine D1 and D2 receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys.

To clarify the roles of dopamine D1 and D2 receptors in behavioral symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D1 antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. Both the dopamine D2-receptor agonist quinpirole and the dopamine D1-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose-dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. These results suggest that stimulation of either central dopamine D1 or D2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D1 and D2 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1995

Fine structure of podocytes in the bovine renal corpuscle.

Thick primary processes issued from the hemispherical or plate-like cell bodies of podocytes in bovine renal corpuscles. These processes branched into secondary and tertiary ones, but no fine pedicels were observed on the outer surface of the podocytes by scanning electron microscopy, because each primary process closely interdigitated with those of adjacent cells. Many pedicels, however, were observed under the processes by using the freeze-fractograph and a transmission electron microscope.

Aging↗