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Biomedical subjects

H Inaba

Publications and source records attributed to H Inaba.

At least 91 records · Page 5Linked to original sources
PubMed1997

Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene.

Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A8TA2 sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient's plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) "ribosomal frameshifting" resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A10 instead of A8TA2, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype.

DNA Replication↗
PubMed1997

[An operative case of bilateral peripheral pulmonary arterial aneurysms].

An operative case of bilateral peripheral pulmonary arterial aneurysms is described. Nine cases of bilateral peripheral pulmonary arterial aneurysms reported in Japan are reviewed. The patient was a 26-year-old woman complaining of massive hemoptysis. Her chest X-ray showed coin lesions in the bilateral hilus region. After admission, body CT and pulmonary arteriography revealed saccular dilatation of the bilateral peripheral pulmonary artery. We diagnosed as bilateral peripheral pulmonary arterial aneurysms. Bronchoscopic examination revealed bleeding from the left lower lobe bronchus. She underwent left lower lobectomy. Histological examination of the resected specimen demonstrated a marked destruction of the wall of the aneurysm. This patient died of recurrence of hemoptysis from bilateral lung on the 42nd postoperative day.

Adult↗
PubMed1997

[A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy].

The premortem diagnosis of cytomegalovirus (CMV) pneumonia is usually difficult, and mortality of it is high. A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy is reported. The patient was a 76-year-old man. Under diagnosis as lung cancer, the right lower lobectomy was performed. After operation, pneumonia occurred on the nonoperated side and in a few days reticular shadows rapidly spread to the whole lung. Although pulse steroid therapy was performed, the interstitial pneumonitis improved only a little. Then intranuclear inclusion body-bearing giant cells were found in sputum obtained by bronchoscopy. So we diagnosed the interstitial pneumonitis as CMV pneumonia and ganciclovir was administrated. CMV pneumonia had improved for two weeks and the patient has no recurrence. When interstitial pneumonitis develop in patients after operation or steroid therapy, the differential diagnosis should include the possibility of CMV pneumonia.

Aged↗
PubMed1996

Design of a suitable formulation of FK613, a novel antiallergic agent, based on its pharmacokinetic and pharmacodynamic properties in healthy subjects.

The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and >89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80-250 ng center dot ml-1 was recommended to ensure the suppression of histamine-induced wheal by >50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.

Adult↗
PubMed1996

High-dose fentanyl does not suppress interleukin-1 beta-induced increases in plasma ACTH and corticosterone in rats.

BACKGROUND: High-dose fentanyl anesthesia is reported to attenuate the metabolic and endocrinal responses to surgery. Interleukin-1 (IL-1) is one of the key mediators in the immunoneuroendocrine system, and may be involved in the stress responses to surgery. We studied whether high-dose fentanyl may influence the IL-1 beta-induced alterations in plasma ACTH and corticosterone in rats. METHODS: Plasma ACTH, corticosterone, blood pressure, heart rate and acid-base status were determined in either awake or fentanyl-anesthetized animals immediately before and after either phosphate buffered saline or IL-1 beta administration. Fentanyl anesthesia was induced by bolus intravenous injections of fentanyl at 50 micrograms/kg and pancuronium bromide at 0.2 mg/kg, and maintained by continuous administrations of fentanyl at 100 or 200 micrograms.kg-1.h-1 and pancuronium bromide at 0.4 microgram.kg-1.h-1. RESULTS: In awake rats, IL-1 beta at incremental doses of 0.25, 0.5 and 1 microgram/kg increased plasma ACTH in a dose-dependent manner, but heat-inactivated IL-1 beta at 4 micrograms/kg did not influence plasma ACTH. A noxious stimulus with tail clamping for 30 min did not significantly alter plasma ACTH in fentanyl-anesthetized rats. Fentanyl reduced the basal plasma corticosterone, but it did not modulate the increases in plasma ACTH and corticosterone after the administration of IL-1 beta at 1 microgram/kg. Fentanyl moderately increased the basal blood pressure and heart rate, but it moderately attenuated the IL-1 beta-induced elevations of blood pressure and heart rate. IL-1 beta moderately decreased PCO2 in awake animals. CONCLUSIONS: Fentanyl anesthesia, which is able to suppress the endocrine responses to noxious stimuli, does not attenuate the IL-1 beta-mediated activation of the pituitary-adrenal axis in rats.

Adrenocorticotropic Hormone↗
PubMed1996

Effects of halothane, isoflurane and sevoflurane on ischemia-reperfusion injury in the perfused liver of fasted rats.

BACKGROUND: Although intraoperative ischemia-reperfusion of the liver generally occurs under general anesthesia, little is known about the direct effect of anesthetic agents on hepatic injury due to this phenomenon. The effect of volatile anesthetics on ischemia-reperfusion injury was studied using isolated liver perfusion. METHODS: The liver was isolated from 24-h-fasted male Sprague-Dawley rats and perfused through the portal vein with a modified Krebs-Ringer bicarbonate solution in a recirculating perfusion-aeration system. Ischemia was induced by reducing the baseline perfusion pressure from 1.2 to 0.2 kPa followed by reperfusion to baseline level. The ischemia-reperfusion injury was assessed by LDH release from the perfused liver. We studied the effect of halothane, isoflurane and sevoflurane on the ischemia-reperfusion injury during 20 min of control conditions, exposure of the liver to 60 min of ischemia and reperfusion for 90 min. RESULTS: Ischemia was evident by reduced portal vein flow and oxygen consumption, and caused an increase in lactate production. Reperfusion caused a transient reduction in lactate production and a significant increase in LDH release. All anesthetics reduced hepatic oxygen consumption and increased the net lactate production during control conditions. Volatile anesthetics also significantly attenuated LDH release during reperfusion. The suppression of LDH release was observed even when isoflurane was administered during the reperfusion period, but not when it was administered only during ischemia. CONCLUSION: These results indicate that volatile anesthetics may protect the fasted liver from early, neutrophil-independent, ischemia-reperfusion injury by acting during the reperfusion phase.

Anesthetics, Inhalation↗
PubMed1996

[Major findings from the second public opinion survey on population issues in Japan, 1995].

"The Institute of Population Problems carried out the second public opinion survey on population issues in Japan on 15 June, 1995....[It] aimed at grasping current public opinions on population issues, and it also intended to derive [the] most recent reproduction indices in Japan, for the purpose of contributing to the population projections and the effective planning and management of the administration." Information is included on marriage intentions and timing, fertility decline, population size, urbanization, and attitudes toward the provision of foreign aid for population control. (SUMMARY IN ENG)

Asia↗
PubMed1996

[Mutation detection enhancement (MDE) gel electrophoresis method for analysis of the von Willebrand factor gene].

We conducted electrophoresis using Mutation Detection Enhancement (MDETM) gel (AT Biochem) on the von Willebrand factor (vWF) gene from three unrelated patients with type 2A von Willebrand disease and one type 3 patient whose point mutations we had identified earlier. The mutations were located on the 3'region of exon 28 in the vWF gene in which three known polymorphisms were included. To eliminate any influence of the polymorphisms, 671bp including two AluI sites amplified by polymerase chain reaction (PCR) from the region of the vWF gene was digested with the restriction enzyme AluI and three fragments (283, 148, and 240bp) were obtained. Three polymorphisms were contained in the 283bp fragment and four mutations were found in the remaining fragments. Following MDETM gel electrophoresis, three of the four cases showed heteroduplex formations. One mutation was not detected, although the mutation was found to be heterozygous by the restriction analysis of MspI. Failure to detect this mutation may be attributed to the fact that it was located on the extreme end of the 148bp fragment of the 5' region. The results of this study suggest the MDETM gel electrophoresis method is useful in detecting gene mutations or polymorphisms in heterozygous subjects. Furthermore, this technique is more convenient than other methods for a base mismatch detection since specific apparatus or radioisotopes are not required.

Electrophoresis↗
PubMed1996

[Limited operation and simple lobectomy for primary lung cancer in poor risk patients].

During the years 1990 to 1994, 54 poor risk patients were performed relative noncurative operation for primary lung cancer, such as limited operation or lobectomy without mediastinal lymphnodal dissection. The indication for lesser resection were mainly cardiopulmonary diseases and the elderly over 75 years old. 3 were bilobectomies, 32 were lobectomies, 1 was lobectomy and segmentectomy, 10 were segmentectomies, 8 were wedge resections. The number of cases with stage I were 41 (75.9%). Postoperative complications occurred in 13 patients (24.1%). The overall 5-year survival rate was 63.5%. The 5-year survial rate of p 0 approximately p 1, pN 0 cases was 73.9%. Relative noncurative cases undergoing lesser resection showed relatively good result compared to standard lobectomy. It was considered that lesser resection for such poor risk patients with stage I can be a beneficial therapeutic modality.

Adenocarcinoma↗
PubMed1996

[Use of the inferior epigastric artery for coronary artery bypass grafting: preoperative digital subtraction angiography].

Between September 1994 and January 1995, the inferior epigastric artery (IEA) was used as a free graft for direct coronary artery bypass grafting in 4 patients. The IEA is excised from its origin from the external iliac artery as a pedicle with an "oval cuff" of 3 mm in diameter to facilitate the direct anastomosis with the aorta. The 4-week postoperative angiographic study showed that the IEA grafts were patent in all patients. We found that the IEA varies in length, diameter, and the pattern of branching between patients and between the right and left sides in the same patient. The preoperative digital subtraction angiography was useful for evaluating the suitability of IEA.

Anastomosis, Surgical↗
PubMed1996

A novel mutation Gly 1672-->Arg in type 2A and a homozygous mutation in type 2B von Willebrand disease.

Genetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEII.

Arginine↗
PubMed1996

[Cardiomyoplasty effectiveness: review of the mechanism].

The effectiveness of cardiomyoplasty on cardiac function is discussed, and the four mechanisms proposed to explain cardiomyoplasty effectiveness are reviewed. The first such mechanism, termed the squeezing effect, suggests that skeletal muscle wrapped around the heart squeezes the heart in the same way as cardiac massage, resulting in direct improvement in cardiac function. Hemodynamic improvement is rarely detectable, but significant subjective improvement is commonly seen clinically. The second mechanism, termed the sparing effect, suggests that even if cardiac performance remains unchanged after cardiomyoplasty, contraction of the wrapped lattisimus dorsi muscle causes an increase in the slope of the end-systolic pressure-volume relationship, and a reduction in left ventricular wall stress. Myocardial oxygen consumption is thereby reduced. The third mechanism, called the girdling effect, suggests that cardiomyoplasty may act like an elastic girdle around the heart to prevent enlargement of the failing heart. The fourth mechanism, called the collateral effect, suggests that, when applied to the ischemic heart, cardiomyoplasty increases collateral blood flow to the myocardium, thereby benefiting cardiac function. However, the existence of unknown mechanisms is suggested by two phenomena that cannot be explained by these four mechanisms alone. Cardiomyoplasty was introduced as a method of direct cardiac assistance. However, it now appears that the relatively passive role of cardiomyoplasty in oxygen consumption saving and ventricular enlargement prevention may be of great importance.

Assisted Circulation↗
PubMed1996

Thromboxane rather than platelet activating factor mediates pulmonary vasoconstriction after antigen challenge in rabbits.

To investigate whether thromboxane and/or platelet activating factor (PAF) mediate the pulmonary vasoconstrictive response to antigen in vivo, we intra-arterially injected human erythrocytes as antigen into sensitized rabbits after administration of putative inhibitors: a cyclooxygenase synthetase inhibitor (indomethacin, 5 mg.kg-1), a thromboxane synthetase inhibitor (OKY 046, 10 mg.kg-1 + 100 micrograms.kg-1.min-1), and a PAF blocker (CV6209, .1 mg.kg-1). Pulmonary artery and airway pressures significantly increased after the antigen challenge in sensitized rabbits, but did not in nonsensitized rabbits. Both indomethacin and OKY046 significantly inhibited the increase in pulmonary artery pressure after the antigen challenge, while CV6209 did not. CV6209 significantly attenuated the decrease in femoral artery pressure after the antigen challenge, while neither indomethacin nor OKY046 did. There were no significant differences in the increase in airway pressure among the groups. We conclude that thromboxane rather than PAF mediates the pulmonary vasoconstriction after the antigen challenge and that mediators other than thromboxane and PAF mediate bronchoconstriction after the antigen challenge in sensitized rabbits.

Anesthesia↗