Search PubMed⌕ Search

Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 1,297 records · Page 72Linked to original sources
PubMed1992

Studies on antiulcer drugs. IV. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzothiazoles and -benzimidazoles.

A series of 6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzothiazoles (II) and benzimidazole analogues (III) was synthesized and tested for histamine H2-receptor antagonist, gastric antisecretory and anti-stress ulcer activity. A benzimidazole derivative (IIIa) exhibited strong antisecretory activity, whereas the corresponding benzothiazole derivative (IIb) lacked this potency in in vivo test. In contrast to compound IIIa, however, compound IIb demonstrated good inhibition against stress induced ulcer. The structure-activity relationships of these compounds are discussed.

Animals↗
PubMed1992

Studies on antiulcer drugs. V. Synthesis and antiulcer activity of aralkylbenzazoles.

A series of 2-alkylamino-5- or 6-aralkyl-substituted benzazoles were synthesized and tested for histamine H2-receptor antagonist and anti-stress ulcer activities. These new compounds showed little or no histamine H2-receptor antagonist activity in contrast to imidazo[1,2-a]pyridine analogues (I). On antiulcer assay, however, some pyridine derivatives (II) exerted higher activity than the reference compounds, sofalcone, sucralfate and cimetidine. The structure-activity relationships of these compounds are discussed.

Animals↗
PubMed1992

Studies on antiulcer drugs. VI. 4-Furyl-2-guanidinothiazoles and related compounds as potent histamine H2-receptor antagonists.

A series of 4-furyl-2-guanidinothiazole derivatives and related compounds were synthesized and evaluated for histamine H2-receptor antagonist and gastric acid antisecretory activities. Among them, compounds I-17, I-48 and I-49 showed high activities in these tests. In addition, compound I-17 possessed potent inhibitory activities on each of the gastric ulcers induced by stress, ethanol and HCl-aspirin. On the other hand, compound I-48 demonstrated antimicrobial activity against Helicobacter Pylori and the potency was far stronger than that of clinically used H2-antagonists. Some structure-activity relationships are discussed.

Animals↗
PubMed1992

Studies on antiulcer drugs. II. Synthesis and antiulcer activities of imidazo[1,2-alpha]pyridinyl-2-alkylaminobenzoxazoles and 5,6,7,8-tetrahydroimidazo[1,2-alpha]pyridinyl derivatives.

A series of imidazo[1,2-alpha]pyridinylbenzoxazoles (4) and 5,6,7,8-tetrahydroimidazo[1,2-alpha]pyridinylbenzoxazoles (5) were synthesized and tested for anti-stress ulcer activity in rats. Several compounds were found to be more active than the reference compounds, sucralfate, cimetidine and ranitidine. Some of them exhibited potent protective activity against ethanol-induced gastric lesion. The synthesis and structure-activity relationships of these compounds are discussed.

Animals↗
PubMed1992

[Use of water-soluble beta-cyclodextrin derivatives as carriers of anti-inflammatory drug biphenylylacetic acid in rectal delivery].

To improve the rectal delivery of an anti-inflammatory drug, biphenylylacetic acid (BPAA), the use of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) was investigated. Inclusion complex formations of BPAA with both beta-CyDs in a molar ratio of 1:1 in water were ascertained, and their stability constants were determined. The dissolution of BPAA in water and the release of BPAA from an oleaginous suppository (Witepsol H-5) were significantly increased by beta-CyDs, depending on the magnitude of the stability constants of the water-soluble complexes. However, the serum levels of BPAA after rectal administration of the suppositories containing BPAA or its beta-CyDs complexes in rats increased in the order of BPAA alone much less than DM-beta-CyD less than or equal to HP-beta-CyD complex. The in situ recirculation study revealed that the greater the stability constant of the complex, the lesser was the absorption of BPAA from the rectal lumen of rats under the solution state. Both in vivo and in situ studies demonstrated that rather high amount of HP-beta-CyD (about 20% of dose) was absorbable from the rat's rectum, compared with DM-beta-CyD (less than 5% of dose), suggesting the possibility of the permeation of BPAA through the rectal membrane in the form of HP-beta-CyD complex. Furthermore, DM-beta-CyD and HP-beta-CyD significantly reduced the irritation of the rectal mucosa caused by BPAA after the administration of the suppositories to rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Rectal↗
PubMed1992

Vertical Banded Gastroplasty for Sleep Apnea Syndrome Associated with Morbid Obesity.

We report a case of morbid obesity accompanied by obstructive sleep apnea syndrome (SAS) and obesity hypoventilation syndrome (OHS). Satisfactory weight control was obtained without significant surgical complications after vertical banded gastroplasty. With the reduction in weight, the symptoms of SAS and OHS, as well as several other complications caused by the severe obesity, disappeared. Quality of life also improved remarkably, as exhibited by improved activity performance and disappearance of irritability at waking. Thus, it appears that vertical banded gastroplasty is efficacious in the treatment of morbid obesity with sleep apnea and hypoventilation.

Journal Article↗
PubMed1992

Effect of growth factors on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts of Graves' ophthalmopathy in culture.

One of the pathological changes seen in Graves' ophthalmopathy is the deposition of glycosaminoglycans such as hyaluronan and proteoglycan in retroocular connective tissue. We analyzed glycosaminoglycans synthesized by retroocular tissue fibroblasts in culture derived from an individual not suffering from thyroid disease and from three patients with Graves' ophthalmopathy. Retroocular tissue fibroblasts synthesized both hyaluronan and proteoglycan, the latter composed mainly of chondroitin sulfate. This contrasts with the proteoglycan synthesized by adult skin fibroblasts which was composed of dermatan sulfate and heparan sulfate proteoglycan. Chondroitin sulfate proteoglycan secreted by retroocular tissue fibroblasts consisted of large and small chondroitin sulfate proteoglycans (CS-PG), their size being determined by the Sepharose CL-6B column. The effects of IGF-1 and PDGF on hyaluronan and proteoglycan synthesis were studied separately and in combination. Both IGF-1 and PDGF increased the synthesis of hyaluronan and proteoglycan in a dose-dependent manner. IGF-1 predominantly stimulated secretion of small CS-PG, while PDGF increased large CS-PG markedly when studied in retroocular tissue fibroblasts. In contrast, IGF-1 stimulated secretion of small proteoglycan while PDGF had little effect on proteoglycan synthesis in skin fibroblasts. Thus, glycosaminoglycan synthesized by retroocular tissue fibroblasts has a unique composition and each component is regulated independently, at least in part.

Blood↗
PubMed1992

Peritoneal cytology in endometrial carcinoma.

Peritoneal cytology is accepted as part of the evaluation for patients undergoing laparotomy for a suspected or proven gynecologic malignancy. The study subjects were 83 patients with endometrial carcinoma. We investigated the significance of peritoneal cytology in endometrial carcinoma. Cytological positive results were observed in 11 (23%) of the 48 T1 cases, 9 (50%) of the 18 T2 cases and 4 (50%) of the 8 T3 cases. Cytological positive rates by histological differentiations were 14 (28%) for 50 G1 cases, 4 (36%) for 11 G2 cases and 6 (46%) for 13 G3 cases. Cytological positive results were found in 11 (28%) of 39 cases of less than 1/3 of intramuscular infiltration and 13 (37%) of 35 cases of 1/3 or more infiltration. Five (56%) of 9 metastasis cases and 17 (29%) of 59 nonmetastasis cases were found positive cytologically. An analysis of the data indicated that the influence of positive peritoneal cytology on recurrence superceded that of other known risk factors, such as grade, myometrial invasion, extrauterine disease, and lymph node metastasis. The patients with normal cytological findings at laparotomy tend to have a significantly (p less than 0.01) better prognosis than similar patients with abnormal cytological findings.

Adenocarcinoma↗
PubMed1992

Polysaccharide-coated liposomal amphotericin B for the treatment of murine pulmonary candidiasis.

Amylopectin-coated liposomal amphotericin B was investigated in a murine model of pulmonary candidiasis. The LD50 of amylopectin-coated liposomal amphotericin B in normal mice was more than 10.0 mg/kg, and that of conventional amphotericin B was 1.2 mg/kg. Amylopectin-coated liposomes showed twice the concentration in the lungs of conventional liposomes. Candida albicans was inoculated intratracheally into BALB/C mice. Twenty-four hours later, the number of Candida in the lungs of mice treated with amylopectin-coated liposomes was less than in those treated with conventional liposomes, and amylopectin-coated liposomes improved the survival rate of inoculated mice. Coating liposomes with amylopectin aids the targeting of amphotericin B to the lungs.

Amphotericin B↗
PubMed1992

Granulocyte colony-stimulating factor-producing large cell undifferentiated carcinoma of the lung.

We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung cancer. A 38-year-old Japanese woman had a large cell undifferentiated carcinoma of the left lung with severe granulocytosis without any evidence of infection. A specimen was taken from a metastatic cervical lymph node and a tumor cell line was established. The culture supernatant of the line as well as patient's serum exhibited a high level of G-CSF by sandwich enzyme immunoassay. Immunohistochemical analysis demonstrated that tumor cells from transplanted nude mice were stained granularly in the cytoplasma by anti-human G-CSF monoclonal antibody, 4A6.

Adult↗
PubMed1992

Postnatal development of the corticotectal projection from the visual cortex of the mouse.

The postnatal development of the corticotectal projection was investigated by injecting the axon tracer DiI into the visual cortex of mouse pups. It was found that DiI-labeled axons arrive at the ipsilateral superior colliculus and enter the optic nerve layer of this structure on postnatal days 3 and 4 (P3-P4). These corticotectal axons extend into the caudal end of the superior colliculus on P4 and give off small collateral branches that ascend vertically to the superficial gray layer. During the first two postnatal weeks, the collateral branches do not form a demarcated terminal zone, but rather diffusely spread within the superficial gray layer of the superior colliculus. These collateral branches continue to dichotomize and form a bright terminal zone within the superficial gray layer on P11. The terminal zone decreases in size during the second and third postnatal weeks, and appears to be of the same size when compared with the adult counterpart by P19. The terminal zone of the corticotectal axons from the visual cortex is established by P19. In parallel with the maturation of the terminal zone of the corticotectal projection, the distal segment of the corticotectal axons is lost during the second postnatal week. We conclude that the growing tips of the corticotectal axons do not strictly project to their future terminal zone within the superior colliculus, and 'misdirected' axons are eliminated during the early postnatal period.

Animals↗
PubMed1992

Dendritic arbolization of large pyramidal neurons in the motor cortex of normal and reeler mutant mouse.

Reeler, an autosomal recessive mutation in mice, is characterized by abnormal positioning of the neurons in the cerebral cortex. We performed a descriptive analysis on the arborization of dendritic processes of large pyramidal neurons in the motor cortex (hindlimb area) of normal and reeler mice, as seen in the Golgi preparations. In the normal mouse, somata of large pyramidal neurons were located in the layer V, and their apical dendrites ascend vertically to the pial surfaces. Their basal dendrites proceed horizontally or inferiorly. In the reeler mouse, typical large pyramidal neurons with a normal (upright) apical dendrite and a variety of atypical large pyramidal neurons with a disoriented apical dendrite were radially scattered within the motor cortex. Typical large pyramidal neurons occupied the lower half of the motor cortex, whereas atypical large pyramidal neurons were predominantly observed in the upper half of the motor cortex. Atypical large pyramidal neurons were further divided into inverted, tumbled, V-shaped, bipolar and superficial polymorphic cells, as previously reported (Terashima et al., J. Comp. Neurol. 218:314-326, 1983). Superficial polymorphic cells localized in the layer of polymorphic cells and the layer of the large pyramidal cells were characterized by the extremely poor dendritic arborizations and the smooth surface of the dendrites, which suggests development of dendrites of these neurons was deranged by the reeler genetic locus.

Animals↗
PubMed1992

Protective effects of anti-glycoprotein D monoclonal antibodies in murine herpetic keratitis.

The protective effects of passive immunization with two kinds of anti-glycoprotein D (anti-gD) monoclonal antibodies, having different antiviral activities, were investigated in murine herpetic keratitis. One monoclonal antibody, designated M1, had high virus-neutralizing antibody titers, along with undetectable levels of complement-dependent cytolysis (CDC) and antibody-dependent cellular cytotoxicity (ADCC); the other, designated M12, exhibited extremely low titers of virus-neutralization with high level of CDC and ADCC. When systemically administered 24 hours prior to virus inoculation to the cornea, both M1 and M12 almost completely prevented the development of stromal keratitis. The protective efficacy of both was observed to be dose-dependent. Pepsin-treated M1 retained its efficacy in suppressing stromal keratitis, whereas pepsin-treated M12 did not. When the administration of M1 and M12 were delayed, both provided significant (but less complete) protection, up to 24 hours after virus inoculation. These results suggest that both virus neutralization and CDC/ADCC play an important role in preventing virus growth in the corneal stroma during the early stage of corneal infection.

Animals↗
PubMed1992

Failure of c-myc gene expression in B cells of some patients with common variable immunodeficiencies.

Many reports have shown that expression of the c-myc protooncogene represents an early event of lymphocyte activation. Calcium influx and activation of protein kinase C synergistically bypass the early signal transduction of lymphocyte activation. In this study, the c-myc message of B cells or B cell lines stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA), A23187, Staphylococcus aureus Cowan I (SAC), or anti-mu was not expressed or was poorly expressed in common variable immunodeficiency (CVID) patients whose B cells did not differentiate or only poorly differentiated to SAC plus recombinant interleukin 2, whereas the c-myc message of 1 CVID patient's B cells that differentiated well in IgM secretion to SAC plus recombinant interleukin 2 was well expressed when stimulated by TPA, A23187, SAC, or anti-mu. These results suggest that an abnormality exists in the early signal transduction process on some CVID patients' B cells and that it may be in the bypass by calcium influx and direct activation of protein kinase C.

Adult↗
PubMed1992

Two types of septic shock classified by the plasma levels of cytokines and endotoxin.

We investigated plasma levels of cytokines and endotoxin in septic shock to clarify the roles of various cytokines in this type of shock. Endotoxemia was observed in 16 of 22 septic shock patients. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) IL-2, and IL-6 were significantly higher in septic shock than in sepsis without shock. Strong correlations were noted between TNF-alpha and IL-2 levels and between IL-1 beta and IL-6 levels. Patients with high TNF-alpha and IL-2 levels also showed endotoxemia. We defined two types of septic shock from these data, i.e., endotoxin+TNF-alpha + IL-2 shock and IL-beta + IL-6 shock. In the former type, high TNF-alpha and IL-2 levels were present before the onset of shock, and shock itself was associated with endotoxemia. The second type showed simultaneous elevation of IL-1 beta and IL-6 levels at the onset of septic shock, and endotoxin was detected in some of them. These results suggest that endotoxin and extremely high levels of TNF-alpha and IL-2, or the simultaneous elevation of IL-1 beta and IL-6, are related to the onset of septic shock.

Adolescent↗
PubMed1992

Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus.

Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Whole-cell voltage clamp was done on single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus. Depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o (or Ba2+), and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. We conclude that the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, 0.56 on day 14, 0.90 on day 18, and 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na+ channels. The Ca2+ channel current density also was higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and we suggest that the fast Na+ current may be involved in spread of excitation. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 of 12 mM) and nifedipine (K0.5 of 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) (but not IBa) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions cannot be explained by a stimulation of ICa(s).

Animals↗
PubMed1992

Blocking effects of V1 (OPC-21268) and V2 (OPC-31260) antagonists on the negative inotropic response to vasopressin in isolated dog heart preparations.

We investigated the effects of V1 IOPC-21268, 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2( 1H)- quinolinone) and V2 (OPC-31260, 5-dimethylamino-1[4-(2-methylbensoylamino)benzoyl]-2,3,4,5-tetrahy dro-1H- benzazepine) vasopressin receptor antagonists on the negative inotropic response to arginine vasopressin (AVP) in the isolated perfused heart preparations of the dog. AVP (7.5-750 pmol) decreased the atrial and ventricular contractile force when the preparation was perfused with constant pressure or constant flow. AVP induced a small increase in sinus rate. Desmopressin, a selective vasopressin V2 agonist, did not change the sinus rate and atrial or ventricular contractile force. OPC-21268 (0.01-3 mumol) and OPC-31260 (0.01-1 mumol) induced a small negative inotropic effect. Both OPC-21268 and OPC-31260 inhibited the negative inotropic response to AVP in a dose-dependent manner. The doses of 50% inhibition (ID50) for OPC-21268 and OPC-31260 on the inotropic effect were 0.30 +/- 0.16 mumol and 0.084 +/- 0.034 mumol, respectively. Neither OPC-21268 nor OPC-31260 affected the acetylcholine-, adenosine- or norepinephrine-induced inotropic and chronotropic effects. It has been reported that the concentration of OPC-21268 that displaced 50% of specific AVP binding is 0.4 microM for V1 receptors and > 100 microM for V2 receptors and the concentration of OPC-31260 is 0.01 microM for V2 receptors and 1 microM for V1 receptors. We, therefore, suggest that AVP directly causes negative inotropic effects mediated at least in part by V1 receptors in the dog heart.

Animals↗