Biomedical subjects

H Manabe

Publications and source records attributed to H Manabe.

At least 19 recordsLinked to original sources

PubMed1992

New bronchodilators. 3. Imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones.

In order to develop new oral bronchodilators, a series of novel imidazol[4,5-c][1,8]naphthyridin-4(5H)-ones 5 were designed and synthesized. Some of these new heterocycles exhibited more potent bronchodilator activity in vitro and in vivo than theophylline. With respect to modification at the 5-position, both phenyl and n-butyl substitution produced potent activity. Though bulk tolerance at N-3 is observed with short and small lipophilic groups, any substitution at the other positions and transformations of the parent skeleton eliminated activity. Thus 5-phenyl-1H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (23) (KF17625), which satisfied these conditions, was selected for further studies (antigen inhalation-induced bronchospasm model; minimum effective dose (MED) = 1 mg/kg, po; antigen-induced contraction of trachea (the Schultz-Dale reaction), IC50 = 2.2 microM). Compound 23 inhibited carbachol-, histamine-, or leukotriene D4-induced contraction and relaxed spontaneous tone in guinea pig isolated tracheal preparations with, 4- to 16-fold greater potency than aminophylline. Thus it appeared to relax directly the airway smooth muscle. 23 did not have any influence on adenosine binding at 10 microM, but inhibited canine tracheal phosphodiesterase (PDE) IV (IC50 = 12 microM) and concanavalin-A-induced histamine release from rat mast cells (44% inhibition at 10 microM). Although the detailed mechanisms of these compounds remain to be elucidated, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

Animals↗

PubMed1992

New bronchodilators. 1. 1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel xanthine-based tricyclic heterocycles in 1H-imidazo[4,5-c]quinolin-4(5H)-ones was designed, synthesized, and tested as potential active bronchodilators. Inhibition of the Schulz-Dale (SD) reaction-induced contraction in trachea and inhibition of antigen inhalation-induced bronchospasm in passively sensitized guinea pigs served as primary in vitro and in vivo assays, respectively. Simultaneous measurement of acute lethal toxicity (minimum lethal dose; MLD, po) in mice allowed determination of a safety margin. The bronchodilatory activity of these heterocycles was considerably varied with the nature of substituents at the 5-position. The most active substituents at the 2- and 5-positions and on the aromatic ring were found to be hydrogen, n-butyl, and hydrogen, respectively. There was a bulk tolerance for lipophilic substituents at the 1-position. 5-Butyl-substituted compounds appeared to be less toxic than theophylline on the basis of MLD data. Thus 5-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-4(5H)-one (10) (IC50 value of the SD assay = 0.25 microM, MLD > 300 mg/kg) was selected for further studies. Compound 10 (KF15570) reduced bronchoconstriction produced by antigen (Konzett-Rössler preparation in anesthetized guinea pigs, ED50 = 0.42 mg/kg, iv) more effectively than aminophylline (ethylenediamine salt of theophylline, ED50 = 7.8 mg/kg, iv) but had fewer side effects on the heart and CNS than theophylline. Compound 10 and its derivatives showed weak adenosine antagonism and phosphodiesterase (PDE) inhibition which could not account for their potent bronchodilation. Although their precise mechanism of action remains unclear, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

Airway Resistance↗

PubMed1992

A case-control study on occupational lung cancer risks in an industrialized city of Japan.

A hospital-based case-control study was conducted to evaluate occupational risks of lung cancer in an industrialized city of Japan. The lung cancer cases were obtained from 3 major hospitals in the city. The control group consisted of patients with a variety of diseases hospitalized in the same wards of the same hospitals as the cases. After matching on sex, 5-year age category and hospital, 144 cases and 676 controls comprised the study group. A self-administered questionnaire was used to obtain lifetime job histories and smoking status. The conditional logistic regression model was used to estimate relative risks after controlling for smoking and employment in other jobs. The workers in shipbuilding, ironworks and other plants (mostly chemical plants) showed statistically significant increases in lung cancer risk with relative risks of 6.18, 2.02, and 2.66, respectively. An increase in risk with the duration of employment was also observed in the "other plants" category. Building and road construction workers also showed increased relative risks, 1.95 and 1.79, but they were not significant. When the risk was evaluated on the exposure chemicals, the workers exposed to inorganic acids and bases had significantly increased risk. The workers exposed to asbestos, dust or organic chemicals also showed increased risk but the effects were not significant. The combined effect of smoking and employment in ironworks showed a good fit to an additive model, while that in the "other plants" category was closer to a multiplicative model.

Adenocarcinoma↗

PubMed1992

New bronchodilators. II. 3H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel 3-substituted imidazo[4,5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4,5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen-induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5-position were more tolerant of the activity than those at the 3-position. 5-Ethyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo.

Animals↗

PubMed1992

Treatment of acute profound heart failure by ventricular assist device.

Sixteen patients with acute profound heart failure (HF) have been treated with the left ventricular assist device (LVAD), nine of them were successfully weaned from LVAD, and three of them were discharged and survived longer. Decompression of the left ventricle (LV) at the beginning will prevent overextension of impaired myocardium and accelerate scar formation. Gradual increase of LV work will promote the compensation ability of the residual myocardium. We found that continuous LVAD assistance can give time for the impaired heart to recover while maintaining normal circulation. For patients with profound HF which is beyond the limit of intra-aortic balloon pumping's (IABP) capability, LVAD is a more powerful and effective means. Although the heart recovered, many patients later died of multiple organ failure (MOF) which was probably caused by prolonged ischemia before LVAD application. For completely successful recovery from profound HF, diagnosis and deciding to use LVAD should not be delayed. It should be applied before major organs including the heart itself suffer irreversible damage. We have established a systematic therapeutic concept of treating acute HF patients using assisted circulation including LVAD.

Acute Disease↗

PubMed1992

[Reproductive and developmental toxicity study of suplatast tosilate (IPD-1151T) (3)--Teratological study in rabbits by oral administration].

A teratological study of suplatast tosilate (IPD-1151T), a newly developed anti-allergic agent, was carried out in pregnant NZW rabbits to assess the effects on dams and fetuses. IPD-1151T was administered to dams orally at dose levels of 0, 100, 300, 450 and 700 mg/kg/day from day 6 through day 18 of gestation, and their fetuses were removed for teratological evaluation. The results were as follows: 1. In dams, marked increase in the incidence of abortion, and decrease in body weight gain, food consumption and feces mass were shown in the 700 mg/kg/day group. Slight decrease in body weight gain and food consumption were seen in the 450 mg/kg/day group, but no toxicities were observed in the 300 mg/kg/day or less groups. 2. In fetuses, marked increase in embryo-fetal deaths and decrease in alive fetal body weights and placental weights, but no teratogenicity were shown in the 700 mg/kg/day group. There were no fetal toxicity or teratogenicity in the 450 mg/kg/day or less groups. 3. No effective dose levels were 300 mg/kg/day for maternal general toxicity and 450 mg/kg/day for maternal reproductive toxicity and for fetuses.

Abnormalities, Drug-Induced↗

PubMed1992

[Antigenicity tests of suplatast tosilate (IPD-1151T)].

Antigenicity of suplatast tosilate (IPD-1151T) was investigated in guinea pigs and mice. The results were as follows: 1. Homologous passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA) and Schultz-Dale reaction tests were carried out using guinea pigs which were immunized orally with IPD-1151T alone or subcutaneously with IPD-1151T and Freund's complete adjuvants (CFA). Positive reactions in these tests were not produced by eliciting injection of IPD-1151T or its metabolite, M-1. On the other hand, the sensitization of ovalbumin (OVA) with CFA produced positive reactions in all of PCA, ASA, ACA and Schultz-Dale tests. 2. Heterologous passive cutaneous anaphylaxis (PCA) test using rats was carried out using two strains of mice (C3H/He and BALB/c) which were immunized orally with IPD-1151T alone or intraperitoneally with IPD-1151T and aluminum hydroxide gel (Alum) as an adjuvant. No animals showed positive reaction to both eliciting antigens, IPD-1151T and M-1. On the other hand, a positive reaction in PCA test to eliciting antigen, OVA, was obtained in rats treated with sera of mice sensitized with OVA plus Alum. 3. These findings showed that IPD-1151T had no antigenicity in guinea pigs and mice.

Administration, Oral↗

PubMed1992

[The dura mater adjacent to the attachment of meningiomas: its enhanced MR imaging and histological findings].

The dura mater adjacent to the attachment of meningiomas was enhanced on MR imaging with intravenous Gd-DTPA infusion. It was examined histologically in four patients with intracranial globoid meningiomas. Histological examination revealed that there was no tumor cell invasion within the dura mater enhanced on MR imaging, except at the point of their attachment. A layer of tumor cells was occasionally observed on the surface of the dura mater, but this was limited to within 5 mm of the tumor margin. Our electronmicroscopic observation indicated that enhancement of the dura mater adjacent to the attachment of meningiomas was caused by increased vascular permeability of the dural vessels and extended extravascular space.

Aged↗

PubMed1992

Long-term circulatory maintenance with a left-sided single artificial heart.

The purpose of this study is to examine the feasibility of long-term circulatory maintenance with only a left-sided single artificial heart that is inserted between the left atrium and the aorta to assist a nonfunctioning heart. The basic hemodynamics were determined in short-term experiments in goats (n = 4), and feasibility studies of long-term circulatory maintenance with a single artificial heart during cardiac arrest were performed in long-term experiments (n = 12). When pulmonary vascular resistance was less than 15,000 dynes .sec.cm-5.kg, which was twice the normal value, the circulation was well maintained with the single artificial heart alone, so long as the right atrial pressure was kept at 14 to 16 mm Hg. Under such conditions the flow yielded by the single artificial heart fluctuated between 80 and 140 ml/kg/min depending on the animal's demand, while the mean arterial pressure was kept above 80 mm Hg. The goats behaved normally, although retention of pleural effusion was a serious problem in maintaining normal circulation over a long-term. Maintaining the plasma total protein level above 6.0 gm/dl delayed the onset of retention or even prevented pooling of pleural effusion. The longest survival period to date has been 38 days. We conclude that when the pulmonary vascular resistance is less than twice the normal value and the total protein level is above 6.0 gm/dl, a left-sided single artificial heart alone can maintain normal circulation and provide time for patients with a nonfunctioning heart to undergo a further treatment, such as heart transplantation.

Animals↗

PubMed1991

Clinicopathological study of pulmonary giant cell carcinomas with reference to prognosis of patients.

Giant cell carcinomas of the lung have been notorious in fulminant clinical courses. Thus, this report describes two exceptionally favorable cases among six cases of giant cell carcinoma of the lung. Their histopathological features are a sharply-demarcated tumor of Stage I, absence of vascular permeation of the cancer cells, prominent lymphoid and plasma cell infiltration in the tumor tissue, and lymph follicle formation in the surrounding tissues. Another case with a Stage II tumor showed the same histopathological findings as the above two cases with the exception of lymphatic permeation of the cancer cells. This patient expired about one year after undergoing an operation. As conventional controls, the remaining three cases with Stage III tumors showed an alveolar extension of tumor cells and vascular permeation. There was a fulminant course after the operation. Notwithstanding similar intervals from their clinical onset to operation in the 4 cases other than Cases 4 and 6, their stages showed considerable variations. Hence, each histopathological feature might have substantiated the different clinical courses following the operation. Electron microscopy of three of the cases indicated double-membrane-bound blisters with intermediate junctions in the bizarre giant cells, and cancer cell differentiation toward both glandular and squamous directions.

Aged↗

PubMed1991

The posterior inferior cerebellar artery originating from the internal carotid artery, associated with multiple aneurysms.

We report the rare case of ipsilateral posterior inferior cerebellar artery originating from the carotid artery, and associated with multiple concurrent aneurysms. This is the 23rd reported case of carotid-cerebellar anastomosis and the first case with three concurrent aneurysms reported in the literature. Of the 23 cases, 6 had single aneurysms, 2 had double aneurysms and the present case had triple aneurysms.

Adult↗

PubMed1991

[A case of an intracranially located esthesioneuroepithelioma].

A 1-year-8-month-old boy was admitted to our service on September 30, 1986, complaining of nausea, vomiting and consciousness disturbance lasted for about 2 weeks. In CTs, right frontal cystic mass which was homogeneously enhanced by contrast media was revealed. Neither hypervascularity nor tumor staining were seen angiographically. On October 9, 1986, total removal of the tumor was performed. The tumor was located extracerebrally in the right anterior cranial fossa, but was covered with arachnoid membrane. The tumor showed tight adhesion with falx cerebri, particularly at crista galli where an invasive infiltration was seen. Light microscopic examination demonstrated oval or spherical small cells arranged multilobularly with rosette like formation and numerous mitoses. Ultrastructurally, cilia, microvilli and junctional complexes were observed. No dense-cored secretory granules were found in the tumor cells. Immunohistochemical study on this tumor showed negative NF and GFAP; positive NSE, S-100, vimentin and keratin. From these findings, the tumor was diagnosed as esthesioneuroepithelioma. Postoperatively, irradiation and chemotherapies were also performed, and the patient showed uneventful course. On January 31, 1987, he was discharged on his foot, and no recurrent or metastatic signs could be found until the end of March of 1990.

Brain Neoplasms↗

PubMed1991

[A case of surgically treated simultaneous bilateral squamous cell carcinoma of the lung].

A case of simultaneous, bilateral squamous cell carcinoma of the lung was presented. One located in right basal bronchus had mediastinal lymph node metastasis even though primary lesion was localized within the bronchial wall. So right lower lobectomy with R 2 lymph node dissection was carried out. The left one located in the left basal bronchus was treated using laser preoperatively, which revealed its location and extension. Sequentially S6 segmental sleeve resection was carried out and preserved his residual lung function. Six months later, the third primary lung cancer was found in left B3. We discussed about diagnosis and treatment of the multiple lung cancer and emphasize that bronchoplastic procedures in segmental level is available for treatment of multiple lung cancer.

Aged↗

PubMed1990

Measles associated with coronary arteritis.

A two-year-old girl with measles virus (MV) and chronic Epstein-Barr virus (EBV) infection developed lethal coronary aneurysmal arteritis accompanied by giant cell pneumonia, systemic lymphadenitis and hepatosplenomegaly. In her coronary arteries, lungs and aorta, cells containing intranuclear and intracytoplasmic inclusions, including syncytial giant cells, were detected, the presence of MV in the organs being proved by electron microscopic and immunofluorescent studies. Immunopathology further demonstrated MV to be disseminated in almost all organs other than lymph nodes. Clinical diagnosis of chronic EBV infection was established on the basis of persistent high titers of antibodies against capsid and early antigens of EBV and viral presence was confirmed by Southern blot hybridization in a mesenterial lymph node obtained at autopsy. To the best of our knowledge, this is the first description of MV association with coronary aneurysmal arteritis, raising the possibility that measles infection can cause severe vasculitis under immuno-suppressive states, such as that caused by chronic EBV infection.

Adult↗

PubMed1990

Dipyridamole combined with anticoagulant in prevention of early postoperative thromboembolism after cardiac valve replacement.

The preventive effect of 300 mg/day dipyridamole, plus warfarin, on the development of thromboembolism after cardiac valve replacement was evaluated. Study 1 involved 71 patients receiving dipyridamole, 100 mg t.i.d., plus warfarin and resulted in a 2.8% incidence of thromboembolism. Study 2 involved 179 patients and compared the effectiveness of slow release capsules with tablet form dipyridamole at the same dosage, both plus warfarin. No thromboembolic episodes occurred in either group. No serious side-effects of dipyridamole were seen in either study. The results suggest that both slow release and tablet form dipyridamole in combination with warfarin are useful in the postoperative management of heart valve replacement.

Adolescent↗

PubMed1990

[Experimental study on liquefaction of intracranial hematoma: usefulness of tissue-plasminogen activator (t-PA), a hematolytic agent, and its combination].

In stereotaxic aspiration of intracerebral hematoma and extensive removal, or cisternal drainage for subarachnoid hematoma, rapid and safe liquefaction and removal of clots are important and urgent measures to be taken. We performed a pharmacological experimental study on the efficacy, administration method, and toxicity of various hematolytic agents, especially tissue-Plasminogen Activator (t-PA). The following findings were obtained. 1) The amount, hardness, and histological findings concerning the remaining hematoma differed markedly according to which hematolytic agents were used. 2) The local effects of each hematolytic agent continued for about 4-8 hours but markedly decreased thereafter. 3) The hematolysis rate following single administration (6 hours after the blood collection) was 88.9% with t-PA + Elase (Fibrinolysin + Deoxyribonuclease), 85.4% with t-PA, 84.6% with t-PA + Urokinase, 80.2% with t-PA + Urokinase + Elase, 27.55 with Elase + Urokinase, 24.6% with Elase + Urokinase + Heparin, 17.2% with Heparin + Urokinase, 16.4% with Urokinase, 13.2% with Elase + Heparin, 12.6% with Elase, 9.3% with Heparin, and 10.1% with the control (Saline). Locally administered t-PA had remarkably greater hematolytic effects than Urokinase on the hematoma (p less than 0.001). 4) The hematolysis rate after 24 hours of repeated administration of small doses at 8-hour intervals was 100% with t-PA + Urokinase + Elase, 94.2% with t-PA, 93.8% with t-PA + Urokinase, 50.9% with Elase + Urokinase, 46.6% with Elase + Urokinase + Heparin, 33.7% with Urokinase, and 4.8% with the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Structure of the major O-glycosidic oligosaccharide of monkey erythrocyte glycophorin.

Sialic acids and the major O-glycosidic oligosaccharide of glycophorin MK from monkey (Japanese monkey, Macaca fuscata) erythrocyte membranes were characterized. N-Glycolylneuraminic acid (Neu5Gc) was found as the major sialic acid, which was confirmed by gas-liquid chromatography-mass spectrometry as the trimethylsilyl methyl ester. Three O-glycosidic oligosaccharide units were obtained from a tryptic glycopeptide that contained all of the carbohydrate units in glycophorin MK by mild alkaline borohydride/borotritide treatment. Carbohydrate analyses of the oligosaccharides revealed that they were composed of Neu5Gc, galactose and N-acetylgalactosaminitol in the molar ratios of 1:1:1 (trisaccharide), 2:1:1 (tetrasaccharide) and 3:1:1 (pentasaccharide). The content of oligosaccharide units was estimated to be 1:12:5 for penta-, tetra- and trisaccharide, respectively, based on the yields, the molecular weight, and the number of oligosaccharide attachment sites in the amino-acid sequence. The tetrasaccharide was the major oligosaccharide and its structure was proposed to be Neu5Gc alpha 2-3Gal beta 1-3[Neu5Gc alpha 2-6]GalNAcol.

Animals↗

PubMed1989

Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation.

Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.

Animals↗