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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 73 records · Page 4Linked to original sources

Reappraisal of the coupling interval of ventricular extrasystoles as an index of ectopic mechanisms.

OBJECTIVE: A mathematical model of modulated ventricular parasystole based on the relation between the coupling interval and the preceding RR interval was developed in an attempt to distinguish between parasystolic automaticity and other mechanisms. MATHEMATICAL MODEL: The relation between the coupling interval and the preceding RR interval was examined by plotting the coupling interval of each extrasystole against the preceding RR interval (coupling interval/RR diagram). The coupling interval/RR diagrams obtained from simulations with various modulation modes suggested that the parasystolic mechanism was likely when the dots representing extrasystoles appeared as discrete clusters. In contrast, a linear horizontal accumulation of dots indicated a non-parasystolic mechanism. CLINICAL OBSERVATION: To verify the validity of the simulations, 24 hour electrocardiographic recordings from 60 patients with frequent ventricular extrasystoles (> 1000/day) were analysed to determine whether the extrasystoles showed intrinsic periodicity. Intrinsic periodicity indicative of a parasystolic mechanism was seen in 14 (93%) of 15 patients in whom the coupling interval/RR diagram was characteristic of a parasystolic mechanism. When the coupling interval did not change (variability < 200 ms) over a wide range of RR intervals (> 700 ms) intrinsic periodicity was never identified (0/17). Parasystolic automaticity was the likely mechanism in 11 of the remaining 28 patients (39.3%) in whom coupling interval/RR diagrams were not definitive. CONCLUSION: These data indicate that definite patterns of coupling interval/RR diagrams can be used to distinguish between parasystolic and non-parasystolic mechanisms.

Adolescent

Measurement of biventricular septal-to-free wall diameters using sonomicrocrystals.

An ultrasonic system for the measurement of biventricular septal-to-free wall internal diameters in the dog was described. The ventricular endocardial ultrasonic microcrystals were implanted via the left and right atrial appendages and arranged in a straight line, with minimal invasion of the myocardium and pericardium. Reliable signals were obtained during right ventricular pressure overload and septal myocardial ischemia.

Animals

Dysfunction of nonadrenergic noncholinergic inhibitory system after antigen inhalation in actively sensitized cat airways.

We have investigated whether proteases released during antigen inhalation cause dysfunction of the nonadrenergic noncholinergic inhibitory nervous system (NANCIS). Frequency-response (F-R) studies of NANCIS were performed before and after Ascaris antigen (ASC) inhalation using actively sensitized cats. NANC dilatatory effects were obtained by stimulating bilateral cervical vagi under cholinergic and beta-adrenergic blockade and serotonin-induced bronchoconstriction, and assessed by maximal percent relaxation (rmax) and the frequency causing 50% of maximal relaxation (EF50). ASC inhalation caused a transient increase in pulmonary resistance in all animals. One hour after ASC inhalation, pulmonary resistance returned to the baseline value, but ASC inhalation significantly attenuated NANC inhibitory activities: rmax decreased from 82.2 +/- 4.7 (mean +/- SE) to 64.3 +/- 11.2% (p less than 0.05), and the geometric mean of EF50 increased from 1.7 to 4.3 Hz (p less than 0.05). Dilatatory effects of infused VIP, a possible neurotransmitter of NANCIS, was also attenuated after ASC inhalation. Pretreatment with leupeptin (3 mg/kg) abolished ASC-induced impairment of NANC inhibitory activities. By contrast, dilatatory effects of adrenergic nerve stimulation were not affected by ASC inhalation. These results suggest that NANC inhibitory activities can be impaired after ASC inhalation, and that this impairment of NANCIS may be due to effects of proteases released during allergic reaction.

Administration, Inhalation

Bradykinin causes airway hyperresponsiveness and enhances maximal airway narrowing. Role of microvascular leakage and airway edema.

The relationship between bronchial edema and airway responsiveness was studied in cats in situ. Five cats were exsanguinated, and the bronchial arteries were perfused. We monitored pulmonary resistance (RL), and the provocative dose of acetylcholine (ACh) required to produce a 300% increase in RL (PD300) was determined. Bronchial vascular permeability was measured by quantifying extravasation of Evans blue (EB) dye. Bradykinin (BK) and ACh were administered via the bronchial arteries to increase leakage and bronchoconstriction, respectively. BK preperfusion (for 30 min) significantly increased bronchial vascular permeability to four times the control values (p < 0.05). BK preperfusion did not alter baseline RL but caused hyperresponsiveness to ACh, with log [PD300 (mole)] of -6.53 +/- 0.42 (mean +/- SD) and -6.90 +/- 0.30, before and after BK, respectively (p < 0.01). Furthermore, the maximal airway narrowing after BK was 58% higher than before BK (p < 0.01). Histologic study showed peribronchial edema after BK. The enhancement of maximal airway narrowing was significantly correlated with the degree of EB dye extravasation. These results suggest that BK causes airway hyperresponsiveness to ACh and increases maximal airway narrowing, possibly because of airway edema.

Acetylcholine

Excitatory role of axon reflex in bradykinin-induced contraction of guinea pig tracheal smooth muscle.

To elucidate the role of the axon reflex in the airways, we studied the effects of atropine (10(-6) M) and tetrodotoxin (10(-7) M) on the bradykinin-induced contraction of guinea pig tracheal smooth muscle, with or without pretreatment of the animals with capsaicin. The concentration-response curves to bradykinin (10(-9) to 10(-5) M) were measured in the presence of both indomethacin and propranolol. In the guinea pigs not given capsaicin pretreatment, baseline tension values did not differ before versus after the application of atropine or tetrodotoxin. Tetrodotoxin reduced the bradykinin-induced contraction significantly, but atropine did not change the contraction induced by bradykinin. These observations indicate that bradykinin-induced contraction is potentiated by a neurally mediated action, but that is not mediated by acetylcholine released from the efferent vagal nerve terminals. The contractile response to bradykinin was significantly reduced in the animals treated with capsaicin as compared with those administered vehicle only. Furthermore, in the animals treated with capsaicin, tetrodotoxin did not affect the response to bradykinin. These observations indicate that bradykinin-induced airway smooth muscle contraction is mediated in part by tachykinins released from C-fiber endings, presumably via an axon reflex.

Animals

Effects of sialagogues on ornithine decarboxylase induction and proto-oncogene expression in murine parotid gland.

The mechanism of a sialagogue-induced increase in ornithine decarboxylase (ODC) activity and the expressions of proto-oncogenes in murine parotid gland were investigated by use of isoproterenol (IPR), carbachol (CC), and methoxamine (MTX). The results were as follows: (1) The three sialagogues had similar effects on the parotid in vivo (mouse parotid after a single injection of IPR) and/or in vitro (rat parotid explants cultured on siliconized lens paper floating on 199 medium containing IPR, CC, or MTX), the order of their effectiveness being IPR > CC > MTX. (2) Northern/dot and Western blot analyses revealed that the sialagogues elevated the steady-state levels of ODC mRNA and ODC protein to maxima at two h and six h, respectively, after stimulation. The increases were roughly proportional to those in ODC activity, suggesting that sialagogue-dependent enzyme induction is regulated at the transcriptional level. (3) The mRNAs of four of nine proto-oncogenes examined showed sialagogue-dependent increases to maxima at 30 min (c-fos) or 60 min (c-jun, c-myc, and c-src) after the beginning of stimulation. These increases were all transient, with the levels returning to the control values (without sialagogue) within 60 min. (4) The IPR-dependent elevations of ODC activity and the mRNAs of ODC, c-fos, and c-jun were inhibited by monensin, but not by polymyxin B. On the other hand, the CC-dependent increases in these parameters were inhibited by polymyxin B but not by monensin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amanitins

Immortalization of fetal mouse brain glial cells by human papillomavirus type 16 E7 genes.

Fetal mouse brain glial cells in primary cultures were immortalized by recombinant retroviruses containing human papillomavirus type 16 E7 genes, and named VR-2g cells. The presence and expression of E7 genes in VR-2g cells were demonstrated by the Southern and the Northern blot analyses. VR-2g cells did not form colonies in soft agar culture, indicating that VR-2g cells have no transforming phenotypes. By the karyotype analysis, VR-2g cells consisted of two cell populations, the pseudo-diploid and the pseudo-tetraploid. VR-2g cells were positive in immunostaining with mono- and polyclonal antibodies against glial fibrillary acidic proteins (glial-specific intermediate filaments). In addition, VR-2g cells secreted neurotrophic factors as assayed with primary cultures of fetal rat striatum neurons, although molecular characterization of the factor(s) was not yet determined. These results indicate that the present method for cell immortalization will be useful for establishing untransformed cell lines from primary cultures of fetal brain cells.

Animals

Synthesis of N-substituted C-normorphinans and their pharmacological properties.

Several N-substituted C-normorphinans (VIII and IX) were synthesized and tested for their analgetic and narcotic antagonist activities and physical dependence capacity. Treatment of N-formyl- octahydro-2-pyrindine (IIIc) with polyphosphoric acid readily gave N-formyl-C-normorphinan (IV). The N-nor bases (V and VII) obtained from IV were converted to VIII and IX. The N-methyl derivative (I), which was previously reported to be inactive by Haffner's method, exhibited potent analgetic activity by the hot plate method and the AcOH-induced writhing test. Compounds VIII and IX showed pharmacological properties similar to those of N-substituted morphinans and exhibited agonist (analgetic) and/or narcotic antagonist activities. The C-nor analogue (IXa) of cyclorphan (IIc) exhibited potent analgetic and antagonist activities with no physical dependence capacity in the single-dose suppression tests both in rats and monkeys.

Analgesics

Synthesis of the optically active trans-isomers of diltiazem and their cardiovascular effects and Ca-antagonistic activity.

Optically active trans-isomers of diltiazem were synthesized and their cardiovascular effects were evaluated in anesthetized dogs and in isolated guinea pig hearts. Both (+)-2 (2R,3S) and (-)-2 (2S,3R) were much less active than diltiazem (1, 2S,3S) with short duration of action. No substantial enantiomeric difference in activity was seen between them. Their Ca-antagonistic activities on Ca(2+)-induced contractions in K(+)-depolarized canine basilar arteries were also examined. Absolute stereochemistry of (+)-2 was determined to be 2R,3S by X-ray crystallographic analysis.

Animals

In vitro replication study of modified bases in ras sequences.

DNA templates containing a modified base (O6-methylguanine, 8-hydroxyguanine, xanthine or hypoxanthine) which was located in nucleotide sequences corresponding to the 12th or 61st codon of a ras gene were synthesized and deoxynucleotide incorporation opposite the lesions was investigated. The templates were replicated by Taq DNA polymerase, recombinant rat DNA polymerase beta and mouse DNA polymerase alpha-primase complex. Sequence analysis of the replicated products indicated selective incorporation of nucleotide(s) opposite a modified base, depending on the kind of base and of DNA polymerase. This system is very useful to obtain results of in vitro replication of modified bases in ras sequences.

Animals

[Study on the kinetics of bradykinin level in the wound produced by thermal injury in the ear burn model in mice].

The kinetics of bradykinin derived from localized thermal injury on vascular-permeability were investigated in mice with experimental ear burn. The leakage of plasma into the ear tissue by accelerated vascular-permeability reached the maximum at 3 hr and decreased gradually until 6 hr after the thermal injury. The contents of bradykinin increased by the thermal injury and the increment continued up to 24 hr. Although the bradykinin contents in the burned ear decreased by using a protease inhibitor, the hyperpermeability of injured ear vessels was unchanged by protease inhibitors. These results suggest that bradykinin is concerned with the pain reaction rather than vascular-permeability.

Animals

Characterization of insulin receptors in the bovine adrenal cortex and medulla.

In order to identify insulin receptors in the bovine adrenal cortex and medulla, we have studied 125I-porcine insulin binding to the membrane preparations from the bovine adrenal cortex and medulla. 125I-porcine insulin bound not only to the bovine adrenal cortex but to the medulla in time-, temperature-, and pH-dependent manners. The maximum levels of 125I-porcine insulin binding in the two tissues were observed at 4 degrees C for 24 h of incubation, and its optimum pH ranged from 7.6 to 8.0. Under these conditions, at tracer concentration of porcine insulin (200 pg/ml), 10.4% and 6.6% of 125I-porcine insulin added to each reaction tube bound specifically to 10(5) x g-pellet fractions (microsomal membrane) from the cortical tissue (0.3 mg of protein) and from the medullary tissue (2 mg of protein), respectively. 125I-porcine insulin binding was observed predominantly in the microsomal membrane from the bovine adrenal cortex, and in a 15,000 x g- pellet fraction (synaptosomal membrane) from the bovine adrenal medulla. Scatchard analysis of binding data yielded curvilinear plots in each tissue. Analysis of curvilinear plots based on two sites model revealed similar affinity constant between the cortex and medulla. Receptor concentration of the cortex was several times higher than that of the medulla. In the two bovine adrenal tissues, human proinsulin and insulin-like growth factor I (IGF-I) had about 1/100 potency compared to porcine insulin in displacing 125I-porcine insulin binding. Porcine glucagon added with concentration up to 10(-6) M did not inhibit 125I-porcine insulin binding to both the cortex and the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex

Clinical study of malignant tumors originating in the pelvic region.

We evaluated the surgical problems encountered during treatment of 14 patients with malignant tumors originating in the pelvic region at our department. The tumor involved the iliac bone in 6 patients, the ischial bone in 2, the pubic bone in 2, and the gluteal region in 4. Invasion to the sacrum was observed in 7 patients. Twelve patients underwent surgical procedures consisting of intralesional resection in 6, marginal resection in 3, and wide margin resection in 3. Six of the 7 patients with sacral invasion developed local recurrence. Two patients with chondrosarcoma and one with parosteal osteosarcoma survived for 4 or more years, but the mean survival period in those with high grade malignant tumors was 11 months. These findings indicate the difficulties encountered in the treatment of malignant pelvic tumors.

Adolescent

Gadolinium-DTPA enhanced magnetic resonance imaging of bone and soft tissue sarcomas in comparison with pathological findings.

We compared gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced T1-weighted images (T1-Gd) with the histopathological findings in 13 patients with bone or soft tissue sarcomas. Signal intensity of the viable tumor tissue was increased in T1-Gd in 92% of the patients. The necrotic or cystic areas in the tumor were not enhanced, rendering them distinctly. The degree of enhancement of the edematous area around the tumor was similar to or more marked than that of the tumor in 54% of the patients. Area showing inflammatory cells infiltration and edematous areas in the tumor tissue were also enhanced. Thus, the effect of preoperative chemotherapy in tumor tissues other than necrotic and cystic areas tended to be underestimated in T1-Gd. Its effect should be comprehensively evaluated based on not only T1-Gd but also T2-weighted images and findings of other imaging techniques.

Antineoplastic Agents

Radiological long-term follow-up of grafted xenogeneic bone in patients with bone tumors.

Radiological findings on the fate of grafted Kiel bone implants for the treatment of bone tumors were evaluated in 25 lesions. The mean follow-up period was 14.8 years, ranging from 5 to 21.8 years. We classified the radiological findings into 4 grades; Excellent (4 lesions), Good (14 lesions), Fair (2 lesions), and Poor (5 lesions). All cases of the Poor grade were polyostotic fibrous dysplasia. The younger the patient at the time of the operation, the more rapidly Kiel bone grafts tended to be incorporated. The grafted bone can become enmeshed in the structure of the recipient bed (Good or Excellent grades) within 10 years in most cases, except in polyostotic fibrous dysplasia.

Adolescent

Bilateral Bochdalek hernias in an elderly patient diagnosed by magnetic resonance imaging.

An elderly patient with asymptomatic bilateral Bochdalek hernias is reported. The chest roentgenogram showed dome-shaped supradiaphragmatic masses about 6 cm in diameter in the posteromedial regions of both sides of the lungs. Computed tomography showed a discontinuity of the lines of diaphragmatic musculature in the left thorax, and a mass with a homogenous low density area indicative of fatty tissues in the right thorax. The magnetic resonance imaging, coronal and sagittal T1-weighted images revealed interruptions of the diaphragmatic musculature adjacent to the masses and protrusion of retroperitoneal fat into the thoracic cavity. The lesions were therefore diagnosed as bilateral Bochdalek hernias of the diaphragm.

Adipose Tissue

Tolbutamide inhibits cAMP-dependent phosphorylation of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

The activity of a bifunctional enzyme, liver 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (F-2,6-Pase), which regulates the level of liver fructose-2,6-bisphosphate (F-2,6-P2), the most potent activator of PFK, is modulated by its phosphorylation rate mainly catalyzed by cAMP-dependent protein kinase A (PKA). To elucidate the action mechanism of sulfonylurea on liver F-2,6-P2 production, effects of tolbutamide on PKA-dependent phosphorylation of purified liver PFK-2/F-2,6-Phase protein and on kinase and phosphatase activities of the purified enzyme were examined in vitro. The purified enzyme was phosphorylated in the presence of the catalytic subunit of PKA, and tolbutamide inhibited the enzyme phosphorylation catalyzed by PKA in a dose-dependent manner. By adding the same dosages of tolbutamide used in the phosphorylation experiment, reduced activity of PFK-2 and increased activity of F-2,6-Pase in the presence of PKA were restored to the levels observed in the absence of PKA. On the other hand, carboxytolbutamide, an inactive metabolite of tolbutamide, had little effect on enzyme phosphorylation and activity. Our results indicate that tolbutamide inhibits a phosphorylation of the liver PFK-2/F-2,6-Pase catalyzed by PKA along with an activation of PFK-2 and an inactivation of F-2,6-Pase, leading to liver F-2,6-P2 production.

Animals