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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 1,477 records · Page 82Linked to original sources

Novel non-tumorigenic cell variants showing potentially different susceptibility to v-src-induced metastasis.

Two non-tumorigenic variant cells were isolated from UV-irradiated Balb/c 3T3 cells on the basis of their different responsiveness in phorbol ester-induced morphological change (rounding formation). They showed marked differences of lung metastatic potentials after intravenous injections of their v-src transformants into nude mice; phorbol ester-resistant variant TR4 cells transformed by v-src were hypermetastatic, whereas v-src transformants of phorbol ester-sensitive variant TR5 cells were not metastatic at all. These different metastatic responses were not observed in v-K-ras-induced transformants of the variants. These non-tumorigenic variant cells may pre-acquire the genetic alteration of certain src-specific and metastasis-associated factors. This system may be useful for genetic analysis of the induction of metastasis.

Animals↗

Summation of excitation with a single conditioning stimulus in the canine heart.

A subthreshold stimulus was reported to become effective in producing a propagated ventricular response when preceded by another subthreshold stimulus or stimuli, a phenomenon that is known as summation of excitation but has not been studied systematically. Effect on summation of current intensity and coupling interval of a conditioning stimulus (Sc, protocol #1) and that of stimulation site of Sc (protocol #2) were determined in anesthetized, open-chest dogs. Effective refractory period (ERP) was determined with an extrastimulus (S2) at a ventricular pacing cycle length (S1S1) of 500 msec. Pulse width of S1, S2 and Sc was 2 msec. For pacing protocol #1 (12 dogs), current intensity of S1 and S2 was equal (twice diastolic threshold, 2, 5, or 15 mA), and that of Sc was equal to or lower than that of S1. S1S2 interval was fixed 1 msec shorter than ERP, and Sc was delivered 5 msec prior to S2. The S1Sc interval was shortened in 2 msec steps. Summation was present if Sc plus S2 evoked a propagated response. Prevalence of summation increased along with an increase in current intensity of Sc (P less than 0.01). For pacing protocol #2 (7 dogs), current intensity of S1, S2 and Sc was equal (twice diastolic threshold, 5 or 10 mA). As the distance between site of Sc and that of S2 increased, prevalence of summation decreased (P less than 0.01). Summation did not occur when Sc was delivered at a site only 5 mm away from the site of S2. In conclusion, summation of excitation with a single conditioning stimulus was both time and strength dependent, and limited in development spatially.

Action Potentials↗

Reappraisal of inhibition and summation with a single conditioning stimulus in man.

A noncapturing conditioning stimulus is known to exert inhibitory effect on a subsequent suprathreshold stimulus, while summation occurs rarely in man. The present study was conducted to revaluate whether conditioning stimulus at a relatively low intensity produced inhibition and summation in man. Thirteen patients with various arrhythmias, 47 +/- 19 years old, were studied. Basic ventricular driving stimuli (S1S1 = 600 msec), a conditioning stimulus (Sc), and extrastimulus (S2) were introduced from a catheter electrode. Sc at an intensity of twice the late diastolic threshold inhibited suprathreshold S2 from evoking a response in all 13 patients. The ScS2 interval producing inhibition was from 11 +/- 4 to 38 +/- 26 msec. When Sc preceded S2 by 5 msec, effective refractory period was shortened by 16 +/- 7 msec in 7 of 13 patients, a phenomenon of summation. The present study demonstrates that inhibition and summation are common phenomena with a single conditioning stimulus at relatively low intensities.

Adolescent↗

Glycyrrhetinic acid derivatives: anti-nociceptive activity of deoxoglycyrrhetol dihemiphthalate and the related compounds.

The possible inhibitory effect of deoxoglycyrrhetol dihemiphthalate (I) and the related compounds (18 beta-olean-9(11),12-diene-3 beta,30-diol) (II) and (olean-11,13(18)-diene-3 beta, 30-diol) III derived from glycyrrhetinic acid has been examined on acetic acid-induced writhing in mice. The compounds inhibited writhing dose-dependently. Their ED50 values were 14, 31 and 22 mg kg-1 for I, II, and III, respectively. The compounds like aspirin, also significantly suppressed PGE2 production in peritoneal fluid together with the writhing response. The results suggests that the analgesic effect of deoxyglycyrrhetol dihemiphthalate and the related compounds is partially due to inhibition of PGE2 production.

Analgesics↗

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of surgery].

In a nationwide study conducted in 11 surgical institutions of C-425, a newly developed human native immunoglobulin liquid preparation for intravenous injection, was combined with conventional antibiotic treatment to investigate the efficacy and safety. A total of 47 patients with severe infections which had not symptomatically responded to 3-day or longer treatment with any antibiotics was included. Doctors in charge judged the efficacy of C-425 to be "excellent" in 3 patients, "good" in 13, "fair" in 15, and "poor" in 4. Thus, a total of 16 patients (45.7%) was judged to have responded to C-425 when the "excellent" and "good" responses were combined. The number responding was 31 (88.6%) when the "fair" cases were also included. Excluding 31 patients who did not meet the Committee's criteria, the Committee judged the efficacy of C-425 in a total of 16 patients; the efficacy was "excellent" in 2 patients, "good" in 4, "fair" in 9, and "poor" in 1. The number of responding patients was 6 (37.5%) of the 16 when the "excellent" and "good" cases were combined, and 15 (93.8%) when the "fair" cases were added. Bacteriological assessment was conducted in a total of 9 patients. Causative bacteria were eradicated in 3 patients, decreased in number in 1, replaced in 2, and persisted in 3. Thus, bacteriological efficacy was observed in 6 of the 9 patients (66.7%). Neither adverse reactions nor drug-related laboratory abnormalities were observed in the 47 patients.

Adult↗

Aging effect on oxygen consumption of respiratory muscles in humans.

The first purpose of the present study was to develop a new method to examine oxygen consumption of respiratory muscles (VO2resp) in human subjects. The apparatus consists of an expandable dead space and a respirometer. When the dead space was increased at a constant rate (approximately 100 ml/min), minute ventilation (VE) and VO2resp increased gradually. Because the logarithm of VO2 was found to be approximately linearly related to VE, we characterized this relationship by the slope (logVO2/VE) and the intercept at VE = 0 (VO2met) of the semilog regression line. The second purpose of this study was to examine the relationship between VO2resp and aging. Six anthropometric and spirometric factors (age, height, weight, vital capacity, forced expiratory volume in 1 s, and body surface area) were analyzed in 37 normal subjects by simple and stepwise multiple regression analyses. We found a significant increase in logVO2/VE and a significant decrease in VO2met with age. In conclusion, 1) the present method is convenient to use, and we are able to study VO2resp over a wide range of ventilation without voluntary effort, and 2) age per se is one of the factors accounting for the observed increase in VO2resp with age.

Adult↗

Effect of endogenous tachykinins on neuro-effector transmission of vagal nerve in guinea-pig tracheal tissue.

To elucidate the effect of endogenous tachykinins on neuro-effector transmission of vagal nerves, we performed in vitro experiments using guinea-pig tracheal smooth muscle. The subthreshold dose (the highest dose which did not induce any smooth muscle contraction) of capsaicin (10(-8) to 10(-7) M) increased the amplitudes of contractions evoked by electrical field stimulation (EFS) significantly, but not those by acetylcholine (ACh). The inhibitor of neutral endopeptidase, phosphoramidon (10(-7) to 10(-6) M), increased the contractions evoked by EFS significantly. The inhibitor of cholinesterase, physostigmine (10(-6) to 10(-5) M), induced smooth muscle contractions, but such contractions were inhibited by atropine, suggesting the spontaneous release of ACh from the vagal nerve terminals. The subthreshold dose of substance P or capsaicin increased the contractions evoked by physostigmine. These results indicated that endogenous tachykinins increase the spontaneous ACh release as well as the ACh release in response to vagal stimulation from the nerve terminals. Furthermore, it is suggested that the excitatory effects of the tachykinins on the vagal neuro-effector transmission may be modulated by neutral endopeptidase in the guinea pig.

Acetylcholine↗

Effect of nonadrenergic noncholinergic inhibitory nerve stimulation on the allergic reaction in cat airways.

To examine the effect of nonadrenergic noncholinergic (NANC) inhibitory nerve stimulation on the antigen inhalation with allergic animals, changes in pulmonary resistance (RL) and arterial plasma histamine concentration ([H]) caused by inhalation of Ascaris suum antigen were studied in five control (Group A) and five nerve-stimulated (Group B) cats, which were anesthetized and mechanically ventilated. All animals were actively sensitized with Ascaris antigen before the experiment. After cholinergic and beta-adrenergic blockade with intravenously administered atropine (3 mg/kg) and propranolol (2 mg/kg), inhalation of the antigen (1:100 dilution) was performed for 3 min. For Group B, bilateral cervical vagi were stimulated electrically for 1 min before the antigen inhalation and successively every 30 s until 5 min had passed from the onset of inhalation. RL and [H] were determined before, during, and after antigen inhalation in both groups. Baseline RL and [H] did not differ significantly between groups (16.3 +/- 2.2 (mean +/- SE) cm H2O/L/s and 14.0 +/- 0.7 ng/ml, respectively, for Group A; 14.4 +/- 1.3 and 15.6 +/- 2.7, respectively, for Group B). Increases in RL and [H] of Group B after the antigen inhalation were significantly depressed, compared with Group A (p less than 0.01 and p less than 0.05, respectively, two-way ANOVA). The increase in RL 5 min after antigen inhalation was 113 +/- 19% for Group A and 28 +/- 8% for Group B, and the increase in [H] at the same point was 36.3 +/- 9.1 ng/ml for Group A and 4.4 +/- 1.4 ng/ml for Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Oxygen radicals produce airway constriction and hyperresponsiveness in anesthetized cats.

Using 30 anesthetized cats, we examined whether oxygen radicals produce airway constriction or hyperresponsiveness. In one group, we administered aerosolized xanthine (0.1%) for 3 min followed by aerosolized xanthine oxidase (XO) (1 U/ml) for 5 min in order to generate oxygen radicals enzymatically in the airways. Pulmonary resistance (RL) instantaneously increased from 14.8 +/- 0.9 to 30.8 +/- 1.4 cm H2O/L/s (p less than 0.01). The increase in RL was significantly depressed by prior administration of polyethylene glycol-superoxide dismutase (PEG-SOD) or polyethylene glycolcatalase (PEG-CAT). In a second group, in order to examine changes in airway responsiveness, we studied acetylcholine (ACh) challenge before and 30, 60, and 120 min after inhalations of xanthine and XO. After xanthine-XO, the airways were hyperresponsive to ACh at 30 and at 60 min (p less than 0.05) but not at 120 min. The geometric means of ACh provocative concentrations that caused an increase in RL of 10 cm H2O/L/s above the baseline value before and 30, 60, and 120 min after xanthine-XO were 0.25, 0.045, 0.073, and 0.15%, respectively. The increase in responsiveness to ACh was significantly correlated with the increase in RL after xanthine-XO inhalation (r = 0.88, p less than 0.05). These data support the concept that oxygen radicals generated by xanthine-XO inhalation may induce bronchoconstriction and airway hyperresponsiveness.

Acetylcholine↗

Stimulation of proteoglycan and DNA syntheses in chondrocytes by centrifugation.

So that the effects of biomechanical forces on the proliferation of chondrocytes and their proteoglycan synthesis could be studied, growth-plate and articular chondrocytes were maintained separately as packed masses in centrifuge tubes in the presence of 10% serum. In these conditions, the cells became re-organized into cartilaginous tissue in seven days. After ten days, they were centrifuged at gravities (g) of 1.3-27 for 24 h in a CO2 incubator. Control cells were maintained in the CO2 incubator without centrifugation. Centrifugation of growth-plate chondrocytes at 3 g resulted in a two-fold increase in incorporation of [35S]sulfate into proteoglycans, but had little effect on their [3H]thymidine incorporation into DNA. On the other hand, centrifugation of articular chondrocytes at 3 g for 24 h caused 1.5-fold increases in both [35S]sulfate incorporation into proteoglycans and [3H]thymidine incorporation into DNA. These results suggest that biomechanical forces have different effects on the growth and differentiation of articular and growth-plate chondrocytes.

Animals↗

Synthesis and pharmacological properties of azido derivatives of 1,5-benzothiazepine Ca antagonist.

Since azido derivatives of 1,5-benzothiazepine Ca antagonist available for photoaffinity labeling are required for further studies of voltage-sensitive Ca channels, we synthesized 3-(p-azidobenzoyloxydeacetyl)- and 3-(4-azidobutyryloxydeacetyl)-diltiazem, and studied their pharmacological properties. Both azido compounds showed similar relaxing actions to diltiazem in K(+)-depolarized dog arteries. They also showed a similar increasing action to diltiazem, but less potent, on the coronary and vertebral blood flow in the anesthetized dog. Moreover, their negative inotropic effects in the guinea pig papillary muscle were similar to or slightly more potent than that of diltiazem under physiological conditions, but were less potent when studied in K+ depolarizing solution. A radioligand binding study in rat skeletal muscle microsomes revealed that the azido derivatives had similar properties to diltiazem, but the nonspecific binding of 3-(p-azidobenzoyloxydeacetyl)-diltiazem was too high to allow estimation of its KD and Bmax values. In conclusion, we synthesized azido derivatives of diltiazem which were considered to share a common binding site on the voltage-dependent Ca channel with diltiazem in skeletal muscle microsomes and in vascular smooth muscle.

Animals↗

[Effects of the anti-ulcer agents on the amine contents and regulating enzyme activity of gastric mucosa during the healing process of acetic acid induced gastric ulcer in rats].

In order to elucidate the action of an H2 blocker (cimetidine) and gastric mucosal protection agents (sucralfate and sofalcone) on the relapse and recurrence of gastric ulcer, the effects of cimetidine, sucralfate and sofalcone on the contents of histamine and serotonin and histidine decarboxylase (HDC) activity in the gastric mucosa were examined in the ulcer region and the intact region at the 10th day after the operation to produce acetic acid-induced gastric ulcer in rats. The following results were obtained: 1) HDC activity in the gastric mucosa of rats treated with cimetidine (100 mg/kg twice daily) tended to increase in the intact region, and it was significantly increased in the ulcer region. 2) Increased HDC activity due to cimetidine treatment was observed at the 10th day after interruption of cimetidine administration. 3) The HDC activity in the gastric mucosa was not changed by the treatment with sucralfate (500 mg/kg/day) and sofalcone (200 mg/kg/day). The results suggest that the increased HDC activity in the gastric mucosa might participate in the relapse and recurrence of gastric ulcer after discontinuation of cimetidine administration.

Acetates↗

[Study on ear burn model in mice and its significant application].

The experimental ear burn model in mice was developed in order to research the wound surface on a burn injury biochemically, and the following results were obtained: 1) The ear weight tended to increase up to 3 hr after preparation of the burn and then decreased subsequently. 2) Significant increase in leakage of Evans blue (EB) dye into the ear was observed in the burn group as compared to the non-burnt group. The amount of EB dye leaked per ear became the maximum in 3 hr which was similar to the increase in ear weight. 3) Correlation between the ear weight after burn and the amount of EB dye leaked into the ear on the burned site was observed up to 6 hr after preparation of the burn. 4) Vasopermeability of the ear was depressed with antihistamine treatment, but non-steroidal anti-inflammatory drugs had no effect. The ear weight of glucocorticoid-treated mice tended to be decreased as compared with the weight of the burned ear. 5) The histamine contents in the burned ear did not change, but the bradykinin contents significantly increased after the burn.

Animals↗

Isolation and purification of a low molecular weight protein from bovine urine.

A low molecular weight protein was separated from urine samples obtained from a heifer with spontaneous renal disease and from cows with CaNa2EDTA-induced renal dysfunction. The molecular weight and electrophoretic mobility of the separated protein were examined. The low molecular weight protein collected by gel filtration chromatography was further separated into two fractions by ion exchange chromatography using DEAE-cellulose. One of the two fractions, the lowest molecular weight protein showed a single band in SDS-PAGE, and its molecular weight was approximately 12,000. An antiserum against this protein formed a single precipitin line with the urine from cows with experimentally induced renal dysfunction and a heifer with spontaneous renal disease by the double immunodiffusion technique. However, the antiserum did not form any precipitin line with the concentrated urine of healthy cow and human beta 2-microglobulin. In cellulose acetate membrane electrophoresis, this protein migrated in the same position as that of serum gamma-globulin from healthy cow.

Animals↗

Effects of a thromboxane A2 synthetase inhibitor on ventricular fibrillation threshold during coronary artery occlusion and reperfusion.

The effects of a new thromboxane A2 synthetase inhibitor (DP-1904) on electrical stability of the heart were tested in anesthetized, open chest dogs. The incidence of spontaneous ventricular arrhythmias, ventricular refractory period and ventricular fibrillation threshold (VFT) during ligation of the left anterior descending coronary artery (LAD) for 180 min and after reperfusion were measured as indices of stability. Ventricular fibrillation and ventricular tachycardia occurred spontaneously after ligation of LAD in 56% of 9 control dogs and 29% of 7 dogs which received intravenous DP-1904 (100 mg) before ligation of LAD (n.s.). In the control group, the ventricular refractory period decreased in the ischemic region; consequently, the difference in refractory period duration between the ischemic and non-ischemic regions (i.e., dispersion) increased 30 min after coronary ligation (7 +/- 9 ms vs 32 +/- 17 ms, p less than 0.05). The dispersion at 30 min after coronary ligation, though, was not affected in the DP-1904 treated group (2 +/- 4 ms vs 10 +/- 9 ms, n.s.). The VFT (determined with pulse trains) decreased from 28 +/- 5 mA to 15 +/- 11 mA (p less than 0.05) 30 min after coronary ligation in the control group, but was not affected (30 +/- 0 mA vs 27 +/- 4 mA) in the DP-1904 group. The plasma concentration of thromboxane B2 decreased after DP-1904 administration (baseline vs 30 min after coronary ligation: 475 +/- 165 pg/ml vs 165 +/- 74 pg/ml, n = 3, p less than 0.05), while the concentration of 6-keto-prostaglandin F1 alpha increased gradually. In conclusion, DP-1904 prevents a decline in electrical stability in the ischemic region of the canine heart during coronary occlusion.

6-Ketoprostaglandin F1 alpha↗

Mixed pituitary adenoma and gangliocytoma associated with acromegaly--case report.

A gangliocytoma in the sellar region is very rare. We report a case of an intrasellar gangliocytoma complicated by pituitary adenoma presenting with acromegaly. A 52-year-old female was admitted to our hospital with headache, mild acromegaly, and bitemporal hemianopsia, and endocrinological study found a high serum level of growth hormone (GH). A computed tomographic scan revealed a tumor in the sellar region, which was almost totally removed by trans-sphenoidal surgery. Histological examination of the resected specimen showed diffuse, chromophobe-type pituitary adenoma, partially containing cholesterin clefts. Areas of clusters of dysmorphic neurons, adjacent to or mixed with pituitary adenoma, were diagnosed as gangliocytoma. The immunohistochemical examination showed GH-releasing hormone (GRH)-positive dysmorphic neurons and GH-positive pituitary adenoma. We consider that the trophic effect of GRH secreted by the neurons of GRH-producing intrasellar gangliocytoma probably caused the GH-producing pituitary adenoma.

Acromegaly↗

[Estimation of 3 rate constants of the 3 compartments model in PET measurement by a weighted integral method--simulation of estimation errors].

A simulation study to evaluate the errors in rate constants of the three compartment model using the weighted integral method was performed. Ten combinations of 7 kinds of weight functions, the errors were tested in 18F fluorodeoxyglucose (18FDG) study. The error factors arising in PET measurement were statistical noise, cerebral blood volume, time shift and scanning time of PET measurement. Errors in each rate constant were within the range of 10 percent and those in k1k3/(k2+k3) within 1 percent. The weighted integral method was confirmed to be a faster method than the conventional least squares method within a reasonable error range.

Body Fluid Compartments↗

[A study on the hemodialysis period following cadaveric kidney transplantation--a comparison between two centers sharing cadaver donor kidney pairs].

To study the hemodialysis period following cadaveric renal transplantation, we reviewed 18 consecutive cadaver donor kidney pairs of which one kidney was transplanted at Shiga University of Medical Science (SUMS) while the contralateral kidney was transplanted at Kyoto Prefectural Medical University (KPMU) between January 1983 and September 1988. Of these 18 pairs, graft function was satisfactory and the recipient was free from hemodialysis in 13 pairs. However, the postoperative hemodialysis periods were different between the two centers. To clarify the factors causing this difference, recipient factors, such as age, HLA matching, total ischemic time of the graft (TIT), immunosuppression, onset of diuresis and postoperative complications were studied. There were no significant differences in age, HLA matching, or immunosuppression. TIT of cases at SUMS was significantly longer than that of cases at KPMU. The postoperative hemodialysis period at SUMS was 25.8 days and that at KPMU was 17.8 days, however, the difference was not statistically significant. The results of this study indicate that TIT seems to be a major factor relating to delayed graft function in cadaveric renal transplantation.

Adolescent↗