Search PubMed⌕ Search

Biomedical subjects

Y Sakuma

Publications and source records attributed to Y Sakuma.

At least 163 records · Page 9Linked to original sources

[Preliminary studies on phagocytosis of cultured mouse peritoneal macrophage exposed to anti-inflammatory agents].

The effect of anti-inflammatory agents, indomethacin, acetylsalicylic acid, and dexamethasone on phagocytosis of cultured mouse peritoneal macrophages was studied. Peritoneal macrophages, obtained from CBA/N mice were cultivated on plastic dishes (35mm in diameter) with Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum. Phagocytosis, as determined by uptake of Latex particles into the macrophages were suppressed by treatment with indomethacin, acetylsalicylic acid or dexamethasone. The level of suppression by dexamethasone was greater than by indomethacine or acetylsalicylic acid. The similar inhibition of phagocytosis by these agents was observed with elicited macrophages, obtained from the mice treated with 3% thioglycollate medium.

Animals↗

[Local immunotherapy with streptococcal preparation, OK-432 in superficial bladder tumors, and common antigens between OK-432 and the tumor].

In 38 patients with superficial bladder, local immunotherapy with streptococcal preparation OK-432 has been performed. We investigated whether OK-432 was an effective biological response modifier (BRM) against bladder tumors or not, and the relationship between the common antigens which OK-432 shared with the tumors, and antitumor effects of OK-432. In six out of 28 patients treated by intravesical instillation, and three out of 10 cases treated by intratumor injection, tumors were eliminated endoscopically. In the other patients, the tumors did not change. The PAP study using an anti-OK-432 antibody, showed a positive reaction in 66.7% of the instillation cases and in 40.0% in the injection cases. In 66.7% of the patients with the common antigens treated by the instillation and in 75.0% of patients with the antigens treated by the injection, tumors were eliminated. However, the PAP study showed a positive reaction in 9.1% of the no-change cases treated by the instillation and in 14.3% out of the no-change cases treated by the injection. We concluded that OK-432 was a favorable BRM for topical immunotherapy against bladder tumor and the presence of the common antigens between OK-432 and tumor may enhance the immune response of patients and promote tumor regression.

Administration, Intravesical↗

Neural inputs from the uterus to the paraventricular magnocellular neurons in the rat.

Extracellular action potentials were recorded from antidromically identified, tonically firing cells in the hypothalamic paraventricular nucleus (PVN) of ovariectomized, estrogen-treated female rats under urethane anesthesia. Genital or somatic sensory stimuli, or electrical stimulation of the nerves innervating the pelvis were applied. Uterine horn or vaginal distension each excited 33% of the neurons tested. Probing of the cervix had no effect. Hindpaw pinch produced excitation in 39% and inhibition in 11% of the neurons tested. Non-noxious somatic stimuli had no effect. Stimulation of the uterine afferent nerves, the hypogastric and pelvic nerves, excited 55% and 30% of the neurons tested, respectively. Stimulation of a somatic nerve of the hindleg, the sciatic nerve, activated 80% of the neurons tested. These results indicate that specific sensory afferents arrive at the PVN from the uterus; in addition, somatic afferents converge in this hypothalamic nucleus.

Afferent Pathways↗

Generation of leukotrienes in guinea-pigs in vivo during antigen-induced bronchospasm.

Anaphylactic bronchoconstriction in passively sensitized guinea-pigs was induced by intravenous injection of antigen (ovalbumin). Five min after injection of the antigen, when the increase in airways resistance to overflow (bronchospasm) was maximum, the plasma levels of leukotrienes LTC4 and LTD4 had increased from undetectable levels of 0.280 and 1.423 ng/ml, respectively. Administration of 5-lipoxygenase inhibitors clearly suppressed the increase in the leukotriene levels concomitant with the suppression of bronchospasm.

Animals↗

Ascending fiber projections from the midbrain central gray to the ventromedial hypothalamus in the rat.

In 18 urethane-anesthetized ovariectomized female rats, 54 neurons in and around the hypothalamic ventromedial nucleus were transynaptically activated by electrical stimulation of the mesencephalic central gray matter. Ventromedial nucleus afferents from either the dorsal longitudinal fascicle (N = 10) or the medial forebrain bundle (N = 8) were disrupted by a small knife cut. In animals which lacked inputs from the dorsal longitudinal fascicle by a cut posterior to the ventromedial nucleus, transynaptic activation followed central gray stimulation in 20 cells; 26 cells were driven from the central gray in animals deprived of afferents through the medial forebrain bundle by a cut placed laterally to the ventromedial nucleus. Two patterns of synaptic activation followed electrical stimulation at 0.5 Hz: one type of response occurred during a latency range of 4 to 20 ms with fluctuation of each response less than 5 ms, the other type was characterized by diffuse activation for 50 ms following central gray stimulation. It was noted that the former time-locked response occurred in 19 among 20 cells in the posterior-cut animals, and the latter diffuse response was seen in 20 of 26 cells in the lateral-cut animals. Electrical stimulation of the ventromedial nucleus in another group of seven animals with the posterior cut caused antidromic activation of 19 central gray cells at latencies of 4.8 to 21.0 ms. Thus, central gray axons in the medial forebrain bundle were shown to have direct access to the ventromedial nucleus and multisynaptic pathways intervened for those in the dorsal longitudinal fascicle.

Action Potentials↗

Nerve growth factor-mediated sexual differentiation of the rat hypothalamus.

Injection of antibody to nerve growth factor into the cerebral lateral ventricle blocked testosterone-induced behavioral defeminization of neonatal female rats. When tested as adults following ovariectomy and combined estrogen-progesterone treatment, the injected animals showed a significantly higher lordosis quotient than the testosterone-treated, normal rabbit serum-infused controls. Failure of vaginal opening and clitoral enlargement manifested the well-documented masculinizing effect of testosterone on the genitalia in the experimental as well as the control animals. Estrogen sensitivity of hypothalamic neurons which are responsible for the induction of lordosis was retained in the experimental animals. Recordings of the antidromic action potentials from neurons in the ventromedial nucleus of the hypothalamus following stimulation of the midbrain central gray revealed that estrogen decreased the antidromic activation threshold and shortened the absolute refractory period of the hypothalamic efferents along with the estrogen-induced behavioral activation in the experimental animals. In the control group, the estrogen-induced neuronal activation was lost altogether with the behavioral activation.

Action Potentials↗

Effect of the hydroxyl group of the p-hydroxyphenyl moiety of aspoxicillin, a semisynthetic penicillin, on its pharmacokinetic property.

The serum concentrations, urinary and biliary excretions of six penicillin derivatives including aspoxicillin (ASPC) were studied in rats and the correlation between the values of pharmacokinetic parameters thus obtained and the Rm values measured by means of reversed phase TLC were analyzed. Among the penicillins studied, the hydrophilicity of amoxicillin was the highest (the lowest Rm value), which was followed by those of ASPC, ampicillin, p-hydroxypiperacillin, dehydroxyaspoxicillin and piperacillin in descending order. These Rm values were then correlated with the AUC values at 20 mg/kg of dosing, giving the results that more hydrophilic penicillins having a hydroxyl group show higher serum concentrations as well as greater AUC values. The studies of correlation between the Rm values and the urinary or biliary excretion revealed that hydrophilic penicillins were almost excreted into urine, but more hydrophobic ones were mainly eliminated into bile. From the above results, a hydroxyl group introduced to the phenyl group of ASPC was considered to have a role that increases the hydrophilicity of ASPC, giving higher and longer persistency of the serum levels and increasing the excretion of drugs into urine.

Amoxicillin↗

Leumorphin, a novel opioid peptide, promotes lordosis in female rats.

The actions of leumorphin, a recently characterized endogenous opioid peptide, oppose of most opioid peptides in facilitating lordosis reflex, a major component of female sexual behavior in the rat. Maximal lordosis appeared promptly after infusion of 1 nmol leumorphin into the ventromedial hypothalamus of ovariectomized estrogen-primed rats. This facilitation lasted for as long as 5 h, unless interrupted by midbrain infusion of an antiserum to prolactin. The result is a discovery of a novel substance of remarkable strength in facilitating lordosis, an effect presumably mediated by midbrain release of prolactin.

Animals↗

Cell size, projection path, and localization of estrogen-sensitive neurons in the rat ventromedial hypothalamus.

Antidromic action potentials were recorded in and around the ventromedial nucleus of the hypothalamus (VMN) of the ovariectomized female rat following stimulation of the central gray matter of the mesencephalon (CG). The animals had either the lateral or caudal trajectory of the VMN efferent disrupted by a small knife cut. Changes in the polarity, peak-to-peak amplitude, and the duration of the initial positive deflection of the antidromic action potentials were recorded for each response as the recording electrode was advanced at 10-micron intervals from the point of detection of the potential until its deterioration. Seventy-four recordings in which potentials exceeded 2 mV at the maxima were subjected to further analysis. The mean spatial spread of the extracellular antidromic action potentials, which was measured by moving the recording electrode at 10-micron intervals, was significantly larger in responses in 17 animals bearing the posterior knife cut (n = 41) than those in 15 animals with the lateral knife cut (n = 33). Mean peak-to-peak amplitude was also significantly greater in responses from the posterior-cut animals than in those from the lateral-cut ones. In the former, action potentials were completed with a shorter time lapse than the latter. In the posterior-cut animals, estrogen treatment of the ovariectomized rats significantly lowered antidromic activation thresholds and shortened absolute refractory periods for CG stimulation. Estrogen had no detectable effect on the excitability of cells that survived the lateral cut. Histological analyses located antidromically driven cells in the posterior-cut animals in the rostral extremity of the VMN and the adjacent retrochiasmatic area; those in the lateral-cut animals were scattered in and around the VMN, caudad to the former. These results suggest that rostral VMN neurons with large soma and laterally projecting axons are responsible for estrogen-dependent autonomic, neuroendocrine, and behavioral functions, such as reproduction and feeding.

Action Potentials↗

Effect of azelastine on the release and action of leukotriene C4 and D4.

The effect of azelastine on the release of leukotriene C4 and D4 (LTC4 and LTD4), and the antagonistic action of the drug against the leukotrienes were determined by using in vitro tests and compared with those of ketotifen and chlorpheniramine. Azelastine inhibited LTC4 and LTD4 release from guinea pig lung fragments passively sensitized with homologous anti-ovalbumin IgGl-b antibody. The 50% inhibitory concentration (IC50) of azelastine was 6.4 X 10(-5) M for a 15-min preincubation or 4.7 X 10(-5) M for a 30-min preincubation. Ketotifen and chlorpheniramine were inhibitory only at the highest concentration tested (3 X 10(-4) M), giving inhibitions of 35.6 and 21.3%, respectively. Azelastine also inhibited calcium ionophore A23187-induced release of leukotrienes from human polymorphonuclear leukocytes; the IC50 values were 3.6 X 10(-5) M for 15 min and 2.3 X 10(-6) M for 30 min of preincubation. Ketotifen and chlorpheniramine were inhibitory only after a 30-min preincubation, with IC50 values of 2.1 X 10(-5) and 5.9 X 10(-5) M, respectively. The potent inhibition by azelastine might be partly a result of the inhibition of 5-lipoxygenase, since 5-hydroxyeicosatetraenoic acid formation in rat basophilic leukemia cell homogenate was inhibited by azelastine. Pretreatment of guinea pig ileum with azelastine antagonized LTC4- and LTD4-induced contraction of the ileum with IC50 values of 7.0 X 10(-6) and 1.1 X 10(-5) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of the novel non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-one on in vitro generation of some inflammatory mediators.

A newly synthesized compound, the non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne (E-5110) was investigated. E-5110 inhibited prostaglandin E2 (PGE2) generation by cultured rat synovial cells upon stimulation with interleukin-1-like factor of rat polymorphonuclear leucocytes (PMN). The IC50 values (mumol/l) for PGE2 generation were 0.026 for E-5110, 0.008 for indometacin, 0.112 for piroxicam and 0.667 for the compound B (3-amino-1-(M-trifluoromethyl-phenyl-2-pyrazoline). Calcium ionophore A23187-stimulated leukotriene B4 generation by human PMN was inhibited by E-5110 with an IC50 value of 0.20 mumol/l; E-5110 was as inhibitory as nordihydroguaiaretic acid and was more potent than the compound B (IC50 of 2.58 mumol/l). E-5110 suppressed superoxide generation by human PMN stimulated with opsonized zymosan, f-Met-Leu-Phe and phorbol myristate acetate. E-5110 also inhibited the generation of leucocytic pyrogen and leucocyte factor(s) which stimulated collagenase production by cultured synovial cells.

Animals↗