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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 487 records · Page 27Linked to original sources
PubMed1996

[Effect of macrolide antibiotics on airway goblet hypersecretion in guinea pigs].

Although macrolide antibiotics have now been widely used in the treatment of chronic airway infections including diffuse panbronchiolitis and chronic bronchitis, the mechanism of the efficacy remains uncertain. Because the increased mucus glycoprotein secretion from airway goblet cells may play a significant role in the development of such diseases, to determine the effects of macrolides on airway goblet cell secretion, we studied guinea pig airways by a semiquantitative morphometric method. The goblet cell secretion was assessed in histological sections of the trachea and main bronchi stained with Alcian blue and PAS by determining mucus score, which is inversely related to the magnitude of mucus discharge. Intravenous IL-8 decreased mucus score in a dose-dependent manner and increased the number of neutrophils present in bronchoalveolar lavage fluid. Oral administration of clarithromycin at a daily dose of 1-10 mg/day for 2 weeks dose-dependently inhibited IL-8 (5 mg/ kg)-induced decrease in mucus score, with the maximal inhibition being 54 +/- 11% (p < 0.001) in the trachea and 48 +/- 8% (p < 0.01) in the main bronchi. This effect was accompanied by the inhibition of neutrophil accumulation into bronchoalveolar lavage fluid. Erythromycin produced similar inhibitory effects on IL-8-induced goblet cell secretion and neutrophil accumulation, whereas amoxicillin and cefaclor had no effect. These results suggest that macrolides protect against goblet cell hypersecretion probably through an inhibition of recruitment of neutrophils into the airway mucosa.

Animals↗
PubMed1996

Temporal shifts in traits of Vibrio cholerae strains isolated from hospitalized patients in Calcutta: a 3-year (1993 to 1995) analysis.

This study presents results of a surveillance on cholera conducted with hospitalized patients admitted to the Infectious Diseases Hospital, Calcutta, India, from January 1993 to December 1995. The O139 serogroup of Vibrio cholerae dominated in 1993 but was replaced by O1 as the dominant serogroup in 1994 and 1995. The isolation rate of V. cholerae non-O1 non-O139 did not exceed 4.9% throughout the study period, while the isolation rate of the O139 serogroup in 1994 and 1995 was below 9%. No temporal clustering of any non-O1 non-O139 serogroup was observed. With the exception of 1 strain, none of the 64 strains belonging to the non-O1 non-O139 serogroup hybridized with ctx, zot, and ace gene probes, while 97.3 and 97.7% of the O139 and O1 strains, respectively, hybridized with all the three probes. Multiplex PCR studies revealed that all the O1 strains belonged to the EIT or biotype. There was a progressive increase in the cytotoxic response on CHO and HeLa cells evoked by culture supernatants of strains of V. cholerae non-O1 non-O139 isolated during 1994 and 1995 compared with the response evoked by those isolated in 1993. Dramatic shifts in patterns of resistance to antibiotics between strains of V. cholerae belonging to different serogroups and within strains of a serogroup isolated during different time periods were observed. There was a discernible increase in the incidence of multidrug-resistant strains of V. cholerae O1 isolated in 1994 and 1995 compared with that in 1993. On the basis of the results of this study, we predict the possibility of newer variants of V. cholerae emerging in the future.

Drug Resistance, Multiple↗
PubMed1996

Nontoxigenic Vibrio cholerae 01 serotype Inaba biotype El Tor associated with a cluster of cases of cholera in southern India.

Thirteen strains of Vibrio cholerae 01 belonging to the Inaba serotype El Tor biotype isolated from patients during an outbreak of cholera in the town of Warangal in southern India were found to be nontoxigenic (NT), since they did not produce cholera toxin or hybridize with DNA probes specific for cholera toxin, Zot, or Ace. The unheated and heated culture supernatants of the NT V. cholerae 01 evoked a rapid cell-rounding effect when introduced on confluent layers of CHO and HeLa cells which could not be inhibited by antiserum against known toxins. Culture supernatants of two representative NT V. cholerae 01 strains caused an increase in short-circuit current in rabbit ileal tissue mounted on an Ussing chamber, and the pattern of increase in short-circuit current was consistent with the presence of a quickly acting toxin like stable toxin. None of the strains of NT V. cholerae 01 hybridized with a DNA probe specific for the heat-stable enterotoxin of V. cholerae non-01, nor did the factor produced by NT V. cholerae 01 resemble the recently described heat-stable enterotoxin produced by enteroaggregative Escherichia coli as determine by a PCR assay. To our knowledge, this is the first report of NT V. cholerae 01 being associated with a cluster of cases of cholera, and it appears that a clone of NT V. cholerae 01 has the potential to cause localized outbreaks of cholera.

Animals↗
PubMed1996

Physiological role of insulin-like-growth-factor-binding protein-4 in human folliculogenesis.

Insulin-like growth factor (IGF)-I and IGF-II, and their binding proteins (IGFBPs) have been demonstrated to play important roles in follicular development as intraovarian regulators. Previous studies have demonstrated that the follicular fluid of atretic follicles contains high levels of IGFBP-2 and IGFBP-4, which are known to inhibit the action of IGFs. In this study, we identified IGFBP-4 protease activity in the follicular fluid of developing but not atretic follicles. To elucidate the regulation mechanism of IGFBP-4 proteolytic activity in the ovary, cultured luteinized granulosa cells (GCs) were incubated with various hormones, and proteolyzed IGFBP-4 in the medium was analyzed. IGFBP-4 proteolytic activity was increased when GCs were incubated with IGFs, estradiol or follicle-stimulating hormone (FSH) but not with testosterone. We also showed that IGFBP-4 inhibited IGF-1-induced estradiol release by GCs while proteolyzed IGFBP-4 did not. These results suggest that human luteinized GCs produce IGFBP-4 protease, and that FSH and IGFs may stimulate folliculogenesis by modulating IGFBP-4 degradation in the ovary.

Cells, Cultured↗
PubMed1996

Persistent bacteriuria caused by uropathogenic Escherichia coli.

The predominant strain of Escherichia coli, the most frequently associated causative agent of urinary tract infections (UTI), in the rectal flora of patients with UTI has been reported to match the strain associated with the etiologic agent of UTI. Since acquisition of UTI may depend on the immediate surrounding flora of the patient, the chromosomal DNAs of strains of E. coli isolated from 3 patients suffering from recurrent cystitis and asymptomatic bacteriuria were examined by multiple polymerase chain reaction using 6 sets of primers for all the known urovirulence factors and by pulsed-filed gel electrophoresis. Genetically identical or similar strains were continuously isolated from these patients and each strain carried the identical urovirulence factors. The findings strongly supported the previous notion that the acquisition of UTI is dependent upon the occurrence of the strain carrying the urovirulence factors in patients or in the environment.

Adult↗
PubMed1996

Endogenous renal 11 beta-hydroxysteroid dehydrogenase inhibitory factors in patients with low-renin essential hypertension.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and is important in blood pressure control. The excretion of renal 11 beta-HSD (ie, NAD(+)-dependent isoform) is thought to protect renal mineralocorticoid receptors from cortisol. To examine whether endogenous renal 11 beta-HSD inhibitory factor(s) may be involved in the pathophysiology of hypertension, we studied the urinary excretion of such inhibitors in 30 patients with low-renin essential hypertension and 20 normotensive control subjects. The effect of sodium restriction on the urinary excretion of the inhibitors wa also evaluated in six normotensive control subjects. Urine was extracted with Sep-Pak cartridges and high-performance liquid chromatography. Endogenous renal 11 beta-HSD inhibitors were measured by the inhibition of 11 beta-HSD bioactivity in microsomes from the human kidney. The urinary excretion of the inhibitors was significantly increased in patients with low-renin essential hypertension (1280 +/- 88 nmol/d, mean +/- SEM) compared with normotensive control subjects (704 +/- 56 nmol/d) (P < .05). Ratios of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone did not differ significantly. Sodium restriction reduced the urinary excretion of the endogenous renal 11 beta-HSD inhibitors but did not affect the ratio of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone. Endogenous renal 11 beta-HSD inhibitory factors may contribute to the pathogenesis of low-renin essential hypertension by modulating the activity of 11 beta-HSD. Sodium intake may directly or indirectly regulate the inhibitory factors.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Prolactin levels and antinuclear antibody profiles in women tested for connective tissue disease.

Hyperprolactinemia has been reported in some patients with active systemic lupus erythematosus (SLE). To determine if there was an association between selected autoantibodies and hyperprolactinemia, we assayed prolactin concentrations in sera from women submitted to a reference antinuclear antibody laboratory. Autoantibody-positive samples were separated into groups that contained antibodies to double-stranded DNA (anti-DNA), antibodies to SSA/Ro (anti-SSA/Ro), or antibodies to both SSA/Ro and SSB/La (anti-SSA/Ro-SSB/La). Results were compared with autoantibody-negative sera from age-matched women, submitted to the same laboratory. We also compared the study groups with a separate cohort of 84 healthy women who were not referred for autoantibody testing. Elevated prolactin levels were clustered in 20% of sera from anti-DNA-positive women < or = 50 years of age. Twenty-one percent of anti-SSA/Ro-SSB/La-positive women < 50 years of age were hyperprolactinemic. Four of the 15 hyperprolactinemic women identified in this survey had no known cause of elevated prolactin. In the other 11 individuals secondary causes such as hypothyroidism, pregnancy, chronic renal failure, and medications may have accounted for high serum prolactin values. We also examined sera by Western blot, to determine if immunoblot patterns were associated with elevated serum prolactin concentrations. The hyperprolactinemic sera yielded novel bands migrating at 70 kd, 32 kd, and 16.5 kd. This study confirmed the reported associations of hyperprolactinemia with SLE and Sjögren's syndrome. Multiple factors appeared to contribute to elevated serum prolactin levels in women with connective tissue diseases, and the presence of hyperprolactinemia was related to unique findings on immunoblot analysis.

Adolescent↗
PubMed1996

Effect of adrenocorticotropin stimulation on the synthesis of 19-noraldosterone in man.

The hormone, 19-noraldosterone, which was recently shown to be synthesized and produced in the human adrenal gland, exhibits potent mineralocorticoid and hypertensinogenic activities. This hormone is controlled in part by the renin-angiotensin system. We studied the effects of ACTH stimulation on the synthesis of 19-noraldosterone in vitro and in six normal men. 19-Noraldosterone was measured by a specific RIA after the urine extract or incubation medium was purified by high performance liquid chromatography. The 24-h urinary excretion of 19-noraldosterone increased approximately 4-fold during the administration of ACTH (40 U, injected im twice daily for 3 days). Virtually identical responses were observed with aldosterone, 18-hydroxycorticosterone, 18,19-dihydroxycorticosterone, and 18-hydroxy-19-norcorticosterone. Glomerulosa cells isolated from human adrenals were incubated with angiotensin II (10(-7), 10(-8), and 10(-9) mol/L) or ACTH (10(-8), 10(-9), and 10(-10) mol/L). Angiotensin II and ACTH increased the production of 19-noraldosterone dose-dependently from isolated glomerulosa cells. The secretion of aldosterone, 18-hydroxycorticosterone, 18,19-dihydroxycorticosterone, and 18-hydroxy-19-norcorticosterone in response to angiotensin II and ACTH was identical to that of 19-noraldosterone. These observations suggest that 19-noraldosterone is stimulated by the renin-angiotensin system as well as ACTH.

18-Hydroxycorticosterone↗
PubMed1996

Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin.

Mineralocorticoids have been suggested to act on blood vessels, leading to increased vasoreactivity and peripheral resistance. Aldosterone is synthesized locally in blood vessels and participates in the hypertrophy of vascular smooth muscle cells. In this study we examined the effects of angiotensin II (ANG II), potassium, and ACTH on the production of aldosterone, the activity of aldosterone synthase, and the expression of CYP11B2 and CYP11B1 messenger ribonucleic acid (mRNA) in cultured human vascular endothelial cells. Human vascular endothelial cells were incubated with ANG II, potassium, or ACTH with or without [14C]deoxycorticosterone ([14C]DOC). Incubation medium was collected, and chromatography was preformed in a reverse phase high performance liquid chromatography system. The concentration of aldosterone in the incubation medium was measured using RIA after separation with the high performance liquid chromatography system. The activity of aldosterone synthase was estimated by the conversion of [14C]DOC to [14C]aldosterone. The levels of CYP11B2 and CYP11B1 mRNA were determined by competitive PCR. ANG II, potassium, and ACTH increased the production levels of aldosterone in a dose-dependent fashion. Both ANG II and potassium increased the conversion of [14C]DOC to [14C]aldosterone, but ACTH did not significantly increase the conversion. Both ANG II and potassium increased the concentration of CYP11B2 mRNA, but not that of CYP11B1 mRNA. Tumor necrosis factor reduced ANG II- and potassium-induced aldosterone synthesis and CYP11B2 mRNA levels. ACTH did not influence the expression of CYP11B2 mRNA. These results suggest that vascular aldosterone synthase is controlled by ANG II and potassium at the transcriptional level.

Adrenocorticotropic Hormone↗
PubMed1996

Cytotoxic components of bardanae fructus (goboshi).

Bardanae Furctus (Goboshi) extract showed potent in vitro cytotoxicity and in vivo antitumor activity against human hepatoma HepG2 cells and mouse sarcoma 180 cells, respectively. In this study, the cytotoxicities of four fractions and three major components (arctiin, arctigenin, and chlorogenic acid) isolated from Goboshi extract were examined. Arctiin and arctigenin, which were contained in the ethylacetate fraction and n-butanol fraction, respectively, showed strong cytotoxicity against HepG2 cells, but little toxicity against Chang liver cells. Chlorogenic acid isolated from the water fraction did not affect the viability of these cells. The cytotoxicity of arctigenin against Chang liver cells was markedly potentiated by treatment with glutathione (GSH) synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). On the other hand, in HepG2 cells, the cytotoxicity of arctigenin was hardly changed by BSO. The cytotoxicity of arctigenin against HepG2 cells increased in an exposure-time dependent manner. These characteristics of arctigenin were similar to those of Goboshi extract, as previously observed. We therefore conclude that the principal cytotoxic components of Goboshi extract are arctiin and its aglycone arctigenin.

Animals↗
PubMed1996

Inhibition of theophylline metabolism by aciclovir.

We report a case of side effects caused by the increase in plasma theophylline concentration after coadministration of aciclovir had been started during theophylline therapy. Interaction between theophylline and aciclovir has not previously been reported. Therefore, a study of the pharmacokinetic and metabolic interactions between theophylline and aciclovir was carried out in five healthy male volunteers. All subjects received a single oral dose of 320 mg theophylline (aminophylline, 400 mg) after they had taken oral aciclovir 800 mg five times daily for two consecutive days. The area under the curve from 0 to infinity of theophylline (AUC0-infinity) after coadministration of aciclovir was increased from 189.9 +/- 18.2 to 274.9 +/- 34.3 micrograms.h/ml (p < 0.01), and total body clearance was decreased from 28.4 +/- 2.9 to 19.8 +/- 2.5 ml/h/kg (p < 0.01). Further, there was a significant increase in urinary theophylline and decreases in urinary 1,3-dimethyluric acid and 1-methyluric acid after coadministration of aciclovir. The decrease in total body clearance is likely to have resulted from inhibition of metabolism via the oxidation pathway. The results indicated that with aciclovir therapy lower doses of theophylline might be necessary and careful monitoring of plasma concentrations was essential.

Acyclovir↗
PubMed1996

Effects of liposome size on penetration of dl-tocopherol acetate into skin.

Liposomes were prepared from hydrogenated lecithin (H-PC) by sonication (S) or injection (I) of H-PC dissolved in ethanol containing dl-tocopherol acetate (VEA). The effects of liposomes on the dermal absorption of VEA were studied. The particle diameter of S-liposomes was smaller than that of I-liposomes. The penetration of liposomal H-PC into the skin was much higher for S-liposomes than for I-liposomes 30 min after application to the arms of healthy human volunteers and also to hairless rat back skin. The penetration of 14C-VEA into hairless rat back skin was higher from the liposomes than from free VEA, and the 14C-VEA penetration was higher from S-liposomes than from I-liposomes. 3H-Dipalmitoylphosphatidylcholine and 14C-VEA, which had been entrapped in liposomes, were not detected in plasma. H-PC inhibited the peroxidation of skin lipids. H-PC enhanced the penetration of VEA into the skin, but the degree of enhancement depended on the size of the liposomes, indicating that this liposomal characteristic was an important factor in dermal absorption and/or penetration.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Antirheumatic agents. I. Novel methotrexate derivatives bearing an indoline moiety.

Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further evaluated using an adjuvant arthritis model in vivo. N-[1-(2,4-Diamino-6-pteridinylmethyl)indoline-5-carbonyl]-L-glutam ic acid 2f showed more potent activities than MTX in vitro and in vivo, and N-[1-(2,4-diamino-6-pteridinylmethyl)-indoline-5-carbonyl]-L-2-ami noadipic acid 2d exhibited fairly good activities in vitro and considerable activity in vivo. Compound 2d was, as expected, not sensitive to folyl-polyglutamate synthetase (FPGS) and did not undergo polyglutamation, a process which may be responsible for a side-effect during MTX therapy.

Animals↗
PubMed1996

Antirheumatic agents. II. Novel methotrexate derivatives bearing an alkyl-substituted benzene ring.

Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted benzene ring were synthesized and initially tested for in vitro anti-proliferative activities using human peripheral blood mononuclear cells (hPBMC) derived from healthy volunteers and synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds with potent activities were further evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a glutamate derivative 3a was more potent as a suppressor of the in vitro cell proliferation and the in vivo experimental arthritis, and a homoglutamate derivative, 3e, exhibited fairly good activities in vitro and considerable activity in vivo in a dose-dependent manner. As expected, 3e did not act as a substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo polyglutamation, which is thought to be responsible for side-effects that occur during MTX therapy.

Antirheumatic Agents↗
PubMed1996

Regulation of insulin-like growth factor-binding protein-4 protease activity by estrogen and parathyroid hormone in SaOS-2 cells: implications for the pathogenesis of postmenopausal osteoporosis.

The cellular mechanisms involved in the accelerated bone loss occurring in association with estrogen deprivation as seen following the menopause are not fully understood. Insulin-like growth factor-I (IGF-I) is the local regulator of osteoblasts and one of its binding proteins, insulin-like growth factor-binding protein-4 (IGFBP-4), binds to IGF-I and suppresses biological activity. Previous studies have shown that the binding activity of IGFBP-4 in the conditioned medium of parathyroid hormone (PTH)-treated SaOS-2 osteoblastic-like cells is enhanced twofold and that this PTH-enhanced IGFBP-4 binding activity is abolished by 17 beta-estradiol. Levels of IGFBP-4 in the conditioned medium have been reported to be regulated not only at the level of production but also at the level of degradation which is catalyzed by a protease that specifically cleaves IGFBP-4. We have, therefore, studied the effects of 17 beta-estradiol and PTH on IGFBP-4 protease activity using SaOS-2 cells. SaOS-2 cells produce a protease that specifically cleaves IGFBP-4 into two fragments of approximately 18 and 14 kilodaltons. IGFBP-4 protease activity in the conditioned medium from PTH-treated cells was suppressed, while this PTH-induced suppression of protease activity was reversed by the addition of 17 beta-estradiol to the cultures. IGFBP-4 proteolytic activity was stimulated by IGF-I or IGF-II added exogenously and was inhibited by EDTA or protease inhibitors. IGFBP-4 proteolyzed in the conditioned medium from cells treated with PTH and 17 beta-estradiol was less effective at inhibiting IGF-I-stimulated [3H]thymidine incorporation into DNA compared with that proteolyzed in the conditioned medium from PTH-treated cells. The simplest explanation is that 17 beta-estradiol suppressed the inhibitory effect of PTH on osteoblastic activity by inhibiting the PTH-induced suppression of IGFBP-4 protease activity.

Cell Line↗
PubMed1996

Stromal bone formation in pleomorphic adenoma of minor salivary gland origin.

We report an unusual case of pleomorphic adenoma with multifocal stromal bone formation, occurring in the upper lip of a 44-year-old Japanese woman. Islands of fibrous bone were in direct contact with stromal fibrocytes and parenchymal epithelial cells. A review of the literature revealed that stromal bone formation in pleomorphic adenoma of minor salivary gland origin is exceedingly rare.

Adenoma, Pleomorphic↗
PubMed1996

Postoperative evaluation of pylorus-preserving gastrectomy for early gastric cancer.

Physical results after pylorus-preserving gastrectomy (PPG) with preservation of the vagus nerve were evaluated. The status of 15 patients with early gastric cancer after PPG was compared with that of 14 patients after distal gastrectomy (DG). The postoperative/preoperative body-weight ratio of the PPG group (0.99) was significantly greater than that of the DG group (0.92). Patients who had PPG had fewer postoperative abdominal symptoms than those who underwent DG. The gastric emptying pattern of patients who had a pylorus-preserving procedure was slower than that of those who had conventional gastrectomy, and more similar to the preoperative pattern. Contraction of the gallbladder after PPG was better than after DG. Gastroscopy revealed that the mucosa of the stomach remnant after PPG was less abnormal than after DG. In conclusion, PPG is a more physiological operation than conventional DG and should be applied in carefully selected cases of early gastric cancer.

Body Weight↗