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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 379 records · Page 21Linked to original sources

In vitro and in vivo antibacterial activities of S-1090, a new oral cephalosporin.

S-1090, a new oral cephalosporin, was active against selected gram-negative bacteria and methicillin-susceptible clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus warneri, against which it had excellent activity. S-1090 was the most active compound against Streptococcus pyogenes and Streptococcus agalactiae among the agents compared. The in vivo efficacy of S-1090 against systemic and urinary and respiratory tract infections caused by gram-positive and -negative bacteria was superior to that expected from the in vitro and in vivo activities of the agents against which it was compared.

Animals↗

In vitro and in vivo antibacterial activities of BO-2727, a new carbapenem.

BO-2727, a new injectable carbapenem, was evaluated for its in vitro and in vivo antibacterial activities in comparison with those of biapenem, meropenem, imipenem, cefpirome, and ceftazidime. BO-2727 had activity comparable to that of imipenem against methicillin-susceptible staphylococci and streptococci, with MICs at which 90% of strains tested (MIC90s) are inhibited being equal to 0.5 microgram/ml or less. Against methicillin-resistant staphylococci, BO-2727 was the most active among the antibiotics tested, with MIC90s ranging from 4 to 8 micrograms/ml. BO-2727 was highly active against members of the family Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with MIC90s ranging from 0.006 to 2 micrograms/ml. BO-2727 was also highly active against Pseudomonas aeruginosa (imipenem-susceptible strains), for which the MIC90 was 2 micrograms/ml, which was lower than those of imipenem, cefpirome, and ceftazidime and comparable to those of biapenem and meropenem. Differences in activity between BO-2727 and the other carbapenems against imipenem-resistant P. aeruginosa were particularly striking (MIC90, 8 micrograms/ml). Furthermore, BO-2727 displayed a high degree of activity against many of the ceftazidime-, ciprofloxacin-, and/or gentamicin-resistant isolates of P. aeruginosa. The in vivo efficacy of BO-2727 against experimental septicemia caused by gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus and imipenem-resistant P. aeruginosa, reflected its potent in vitro activity and high levels in plasma.

Animals↗

Int-6, a highly conserved, widely expressed gene, is mutated by mouse mammary tumor virus in mammary preneoplasia.

With a unique mouse mammary tumor model system in which mouse mammary tumor virus (MMTV) insertional mutations can be detected during progression from preneoplasia to frank malignancy, including metastasis, we have discovered a new common integration site (designated Int-6) for MMTV in mouse mammary tumors. MMTV was integrated into Int-6 in a mammary hyperplastic outgrowth line, its tumors and metastases, and two independent mammary tumors arising in unrelated mice. The Int-6 gene is ubiquitously expressed as a 1.4-kb RNA species in adult tissues and is detected beginning at day 8 of embryonic development. The nucleotide sequence of Int-6 is unrelated to any of the known genes in the GenBank database. MMTV integrates within introns of the gene in the opposite transcriptional orientation. In each tumor tested, this results in the expression of a truncated Int-6/long terminal repeat (LTR) chimeric RNA species which is terminated at a cryptic termination signal in the MMTV LTR. Since the nonrearranged Int-6 alleles in these tumors contain no mutations, we favor the conclusion that truncation of the Int-6 gene product either biologically activates its function or represents a dominant-negative mutation.

Amino Acid Sequence↗

Inhibition of leukotriene production by FK506 in rat basophilic leukemia-1 cells.

We investigated the inhibitory action of FK506 (0.0005-5 micrograms/ml) on the metabolism of arachidonate 5-lipoxygenase in rat basophilic leukemia-1 cells. Cells were stimulated with A23187 (10(-5) mol/l) for 15 min in the absence or presence of various concentrations of FK506. Arachidonate 5-lipoxygenase metabolites, peptide leukotrienes (LTs), leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) were measured by high-performance liquid chromatography. FK506 inhibited A23187-stimulated production of peptide LTs, LTB4 and 5-HETE in intact cells by up to 77, 73 and 60%, respectively. Phospholipase A2 activity, measured by the release of 3H-arachidonic acid (AA), was not significantly inhibited by FK506. The synthesis of peptide LTs and LTB4 was not inhibited by FK506 when leukotriene A4-free acid was added to the culture medium. The synthesis of peptide LTs, LTB4 and 5-HETE was not affected by FK506 in a cell lysate study using AA as the substrate. These results indicate that FK506 inhibits the production of peptide LTs, LTB4 and 5-HETE by inhibiting 5-lipoxygenase activity in intact cells. The inhibition is not a direct action on 5-lipoxygenase but results from the activating processes of this enzyme.

Animals↗

Production and expression of granulocyte- and macrophage-colony-stimulating factors in newborns: their roles in leukocytosis at birth.

We analyzed the production and expression of three colony-stimulating factors (CSFs) in neonates to clarify the mechanism of leukocytosis at birth. Serial blood samples (n = 23) were collected from mothers, cord blood, and from newborn infants on days 1, 5, and 30 after birth. The serum levels of granulocyte-CSF (G-CSF), granulocyte/macrophage/CSF (GM-CSF) and macrophage-CSF (M-CSF) were measured by ELISA. The G-CSF levels on day 1 after birth were significantly higher than those thereafter, and they were also higher in the mothers than those on days 5 and 30 after birth. The GM-CSF levels did not change significantly during the neonatal period. The serum M-CSF levels were higher on postnatal day 1 than at other times, and gradually decreased thereafter. To confirm the production sites of G-CSF and M-CSF, the mRNA for these CSFs in peripheral mononuclear cells (MNCs) from healthy adults, mothers, and cord blood were analyzed by PCR. The expression of G-CSF and GM-CSF mRNA was undetectable in MNCs from adults, mothers, and cord blood, while these cells expressed low levels of M-CSF mRNA. After stimulation with lipopolysaccharide or phorbol myristate acetate, the MNCs expressed high levels of G-CSF and GM-CSF mRNA. The levels of G-CSF PCR products in cord MNCs were lower than those in adult and maternal MNCs. The expression of M-CSF mRNA was virtually unchanged by stimulation. To detect the localization of G-CSF and M-CSF in the placenta and umbilical cord, these tissues were immunocytochemically stained with anti-G-CSF and anti-M-CSF antibodies, G-CSF and M-CSF were expressed in trophoblasts and decidual stromal cells, whereas the umbilical cord did not express these CSFs. Moreover, large amounts of G-CSF and M-CSF were detected in the supernatant of cultured trophoblasts and decidual stromal cells. The expression of G-CSF and M-CSF in these cells was confirmed by PCR. These findings suggested that G-CSF and M-CSF produced in the placenta (trophoblasts and decidual stromal cells) are the major factors that induce leukocytosis in newborn infants at birth.

Base Sequence↗

Identification of macrophage colony-stimulating factor in human milk and mammary gland epithelial cells.

Human milk contains cellular and soluble host-protective components. Macrophages in human milk constitute a major cellular component in contrast to those in the peripheral blood. We have investigated a mechanism of local expansion of macrophages in human milk. First, biologically active macrophage colony-stimulating factor (M-CSF) was identified in human milk. The maximal concentrations of M-CSF in human milk were 10- to 100-fold higher than those in the serum. The concentrations of M-CSF in the milk had no correlation with those in the serum. M-CSF was immunohistochemically detected in the epithelial cells of the ducts and alveoli of the mammary gland. In situ hybridization study confirmed the local synthesis of M-CSF in the mammary gland epithelial cells. A possible role of female sex steroids was discussed in the regulation of M-CSF production by mammary gland epithelial cells.

Adult↗

Thermally gelling poloxamine Synperonic T908 solution as a vehicle for rectal drug delivery.

Thermally reversible gels of the block copolymer, Synperonic T908, have been evaluated as vehicles for the rectal administration of indomethacin. Prolonged plasma levels of indomethacin following rectal administration in such gels was observed with the 40% w/w Synperonic T908 gels when compared with commercial suppositories. The release rate decreased with an increase in gel concentration over the range 30% to 40% w/w. Histological observation showed no damage to the rectal mucosal membrane in animals at 6 h after the administration of a 40% w/w gel.

Animals↗

Transport mechanisms of enoxacin in rat brush-border membrane of renal cortex: interaction with organic cation transport system and ionic diffusion potential dependent uptake.

The mechanism of the renal transport of enoxacin (ENX) has been investigated using brush-border membrane vesicles (BBMVs) isolated from the rat renal cortex. The initial rate and time-course of ENX uptake were quite dependent upon the medium pH (pH 5.5 > pH 7.5). The pH dependence was in accordance with the degree of cationic form. Carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) affected the transient uphill transport of ENX across the renal brush-border membrane in the presence of an outward-directed H(+)-gradient. The initial uptake was saturable, and transport kinetic parameters were given for a Km and Vmax of 0.59mM and 1.37nmol/(mg protein)/30s, respectively. On the other hand, an outward H(+)-gradient (pHin = 5.5, out = 7.5) dependent uptake of ENX was partially decreased by the voltage-clamped BBMVs. Furthermore, a valinomycin-induced K(+)-diffusion potential (interior negative) was found to increase the uptake of ENX at pH 5.5, which is cationic form-rich. These results suggest that ENX uptake participates in not only the H+/organic cation antiport system for organic cation secretion but also the ionic diffusion potential (interior negative) dependent permeation through the membrane.

Animals↗

[The uptake of nalidixic acid and enoxacin by rat renal cortical slices in rat].

The mechanisms involved in the renal excretion of quinolone and new quinolone antibacterial drugs are still incompletely understood. The purpose of this study was to examine the renal handling of nalidixic acid (NA) and enoxacin (ENX), using the renal cortical slices uptake techniques in rats. It was demonstrated that both NA and ENX were taken against a concentration gradient by a saturable processes resulting from the ratio of slice to medium (ratio of S/M) being dependent on the time and the concentration. It was indicated that the inhibition of uptake by 2,4-dinitrophenol, ouabain and sodium cyanate was shown to be an energy dependence. Probenecid and cimetidine exhibited that they might inhibit NA uptake slightly. ENX uptake was inhibited by probenecid, cimetidine, guanidine and disopyramide, suggesting that ENX might possess an affinity for both anionic and cationic transport mechanisms.

Animals↗

Serum cardiac troponin T in patients with acute myocardial infarction. Detection of coronary reperfusion and prediction of cardiac function.

Serum troponin T, a myocardial contractile protein, has been reported to be a sensitive marker for the diagnosis of acute myocardial infarction. However, there have been few reports on its ability to detect coronary reperfusion and to predict left ventricular function in the chronic stage. Twenty two patients (20 males and 2 females, 61 +/- 10 y.o.) with acute myocardial infarction were enrolled in this study. They were divided into 2 groups, one with successful reperfusion (group A: n = 13) and one without reperfusion (Group B: n = 9) and the serial changes of their serum troponin T levels were evaluated. Serum myosin light chain was measured in another group of patients with acute myocardial infarction without history of old myocardial infarction (group C: n = 8). The slope of the logarithm of serum troponin T on a time-value curve was calculated from the time of admission to the first peak within 24 hours of the onset of acute myocardial infarction. The correlation coefficient between the late peak of serum troponin T and the left ventricular ejection fraction in 11 patients with first Q wave acute myocardial infarction was compared with that between the serum myosin light chain peak and the left ventricular ejection fraction in group C. 1) The slope of the logarithm of serum troponin T on the time-value curve in group A was greater than that in group B (0.57 +/- 0.45 vs. 0.22 +/- 0.16) (p < 0.05). 2) There was a good correlation between the late peak level of serum troponin T (78 +/- 10 hours after the onset) and the left ventricular ejection fraction in 11 patients with first Q wave acute myocardial infarction (r = -0.84, p < 0.01), which was similar to that of the serum myosin light chain peak and the left ventricular ejection fraction (r = -0.72, p < 0.05). On the other hand, there was no correlation between the peak level of serum creatine phosphokinase and the left ventricular ejection fraction (r = -0.55, NS). The serum troponin T levels 24, 36, 48 and 60 hours after the onset also correlated well with the left ventricular ejection fraction (r = -0.65, -0.7, -0.65 and -0.89, respectively). We conclude that the serial measurement of serum troponin T in patients with acute myocardial infarction is useful in the evaluation of left ventricular function in the chronic stage and that it is a potential non-invasive predictor of coronary reperfusion.

Aged↗

Adult T cell leukemia clinically manifested with ascites and pleural effusion.

A 62-year-old man with adult T cell leukemia (ATL) presented with complaints of anorexia and abdominal fullness. Evaluation revealed ascites and pleural effusion, but no lymph node swelling, hepatosplenomegaly, or skin involvement. The diagnosis of ATL was made by the detection of specific surface markers for T lymphocytes in pleural effusion and ascitic fluid, and by determination of human T cell leukemia virus type I (HTLV-I) proviral DNA integration in mononuclear cells of pleural effusion. This case was considered a rare type of ATL with infiltration of the pleura and peritoneum.

Ascites↗

Comparison of the therapeutic efficacy of continuous and intermittent injection of isosorbide dinitrate: a randomized study on unstable angina.

Therapeutic efficacy of intermittent and continuous injection of isosorbide dinitrate (ISDN) was compared in 22 patients (mean age 64 +/- 10, 18 males and 4 females) with unstable angina at rest. They were randomized into 2 groups that received either continuous (10 mg/h, group A) or intermittent (10 mg/10 min every 2 hours, group B) injection of ISDN for 3 days (phase 1). Each injection protocol was switched (phase 2) and subsequently switched back to the initial protocol (phase 3) in a cross-over fashion. The serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-ISMN were measured serially during both intermittent and continuous injection protocols. In addition, the incidence and duration of angina and changes in systolic blood pressure were analyzed. There were 3 treatment-failure cases during the intermittent injection period and 1 during the continuous injection period. Three of these treatment-failure cases developed small acute myocardial infarcts despite emergent coronary arteriography followed by intra-coronary thrombolysis and percutaneous balloon angioplasty. There was no difference in therapeutic efficacy between continuous and intermittent ISDN in terms of the incidence, duration of angina attacks and the number of patients whose angina was suppressed. After bolus injection of ISDN (10 mg/10 min), the serum concentration of ISDN increased rapidly and returned to the control level at 60 minutes after the injection. The serum 5-ISMN and 2-ISMN concentrations also increased immediately after injection and then decreased gradually reaching statistically insignificant level to the control values at 60 minutes after injection. With continuous injection, ISDN and its metabolites increased gradually and reached similar but slightly lower serum concentrations to the peak levels during intermittent injection. We conclude that the therapeutic efficacy of intermittent and continuous injection of ISDN is similar in patients with unstable angina.

Adult↗

[A case of systemic lupus erythematosus associated with cerebral infarction and cerebral hemorrhage].

This is a report of cerebral infarction and cerebral hemorrhage derived from systemic lupus erythematosus. A 49-year-old male was admitted to our hospital due to dysarthria and supranuclear facial palsy. He had been suffering from SLE and medicated incompletely since 9 years prior to admission. A CT scan showed a small infarction in the left parietal area. An angiography revealed a tapering stenosis of the left carotid siphon and an occlusion of the left vertebral artery at the cisternal portion. On the 13 days after the admission, he complained of a high fever and right hemiparesis. The CT scan disclosed newly multiple small infarctions in the left parietal area. The angiography showed the progressing of the tapering stenosis at the left carotid siphon, and demonstrated the narrowing of the left superior temporal artery and ophthalmic artery in addition to the disappearance of a left posterior communicating artery. High dose of steroid was given to him, but cerebral hemorrhage and huge left cerebral infarction were complicated. On the 26 days after the admission, his general condition was worsened and died. It was considered that the cerebral infarction and hemorrhage might be derived from the vasculitis of SLE.

Cerebral Angiography↗

The effects of anxiolytics and anxiogenics on evaluation of learning and memory in an elevated plus-maze test in mice.

We examined the effects of anxiolytics and anxiogenics on evaluation of learning and memory in the elevated plus-maze test in mice. Transfer latency (TL), the time mice took to move from the open arm to the enclosed arm, was used as an index of learning and memory. The TL on day 2 was shorter than that on day 1 with the maze at a height of 40 cm, and was not affected by anxiolytics and anxiogenics such as 8-OH-DPAT (0.4 mg/kg), picrotoxin (2 mg/kg), and FG-7142 (20 mg/kg), but was affected by diazepam (8 mg/kg). On the other hand, the TL on day 2 was prolonged by changing the experimental room between day 1 and day 2. TL on day 1 and day 2. TL on day 2 was prolonged by treatment with scopolamine before the trial on day 1 compared with vehicle-treated groups. This scopolamine-induced prolongation of TL was reversed by pretreatment with physostigmine and piracetam. The TL on day 2 was also prolonged by treatment with cycloheximide or normobaric hypoxia initiated immediately after the trial on day 1. The cycloheximide- and hypoxia-induced prolongation of TL were reversed by pretreatment with piracetam. These results indicate that disruption of learning and memory and its amelioration, induced by the treatments described above, can be detected using the plus-maze test, suggesting that the elevated plus-maze test could be used for evaluation of learning and memory without influence of anxiolytics and anxiogenics.

Animals↗

[Extramedullary relapse in childhood acute lymphoblastic leukemia: experience at the Kyushu Yamaguchi Children's Cancer Study Group].

Since October 1984, children with acute lymphoblastic leukemia (ALL) were treated with six protocols of the Kyushu-Yamaguchi Children's Cancer Study Group (KYCCSG). We reviewed cases in whom the first relapse sites of ALL were CNS, testis and ovary. Between October 1984 and July 1993, 302 children with ALL were registered. Ten children (3.3%) developed CNS-L. After treatment for CNS-L, four cases were alive, however one of them has had several episodes of CNS-L. Testicular relapse occurred in 8 boys and three of them are alive. One girl developed ovarian and uterine involvement 7 months after completion of treatment and she survived after intensive chemotherapy for an additional 3 years. Before September 1990, children with ALL received 18Gy cranial irradiation in standard risk group and 24Gy in high risk group. Since October 1990, children with ALL received no cranial irradiation in low risk group, 15Gy in intermediate risk group and 18Gy in high risk group. Incidence of CNS-L has not increased in children treated with protocols, in which cranial irradiation was reduced.

Adolescent↗