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Biomedical subjects

N Inoue

Publications and source records attributed to N Inoue.

At least 487 records · Page 27Linked to original sources

Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells.

Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO.

Animals↗

Sub-chronic effects of styrene and styrene oxide on lipid peroxidation and the metabolism of glutathione in rat liver and brain.

Sub-chronic effects of styrene and styrene oxide on lipid peroxidation, glutathione contents and glutathione reductase activities in the liver and brain were examined after intraperitoneal administration to rats 3 times a week for 7 weeks. Styrene (300, 400 and 500 mg/kg) and styrene oxide (200 and 300 mg/kg) increased lipid peroxidation in the liver after 7 weeks of treatment. Hepatic lipid peroxidation in the rats treated with a higher dose of styrene oxide (400 mg/kg) was significantly enhanced even after 2 weeks of treatment. On the other hand, no change in lipid peroxidation was observed in the brain under the above conditions. Neither glutathione contents nor glutathione reductase activities in the liver and brain were altered at 40 h after the last of these sub-chronic treatments. To elucidate the cause of lipid peroxidation, the time courses of glutathione content after treatment with either styrene or styrene oxide (300 mg/kg) were studied in more detail. Significant decreases in both the GSH and GSSG contents were detected shortly after these treatments and the levels recovered to the control values at 40 h in these organs, although the changes were less significant in the brain of rats treated with styrene. These results suggest that enhancement of lipid peroxidation in the liver after treatment with styrene or styrene oxide was a consequence of repeated depletions of glutathione to certain critical levels and delayed recovery of lipid peroxides.

Animals↗

Histochemical profiles of fibers in the rat tibialis anterior muscle during early postnatal development.

The enzyme activities of intra- and extrafusal fibers in the tibialis anterior muscle of rats during postnatal development have been investigated. Muscle fibers 1 day after birth showed a uniform reaction for adenosine triphosphatase (ATPase), succinate dehydrogenase (SDH), and alpha-glycerophosphate dehydrogenase (alpha-GPD) activities. Fast-twitch (F) and slow-twitch (S) fibers with ATPase activity were found at 9 and 11 days. Thereafter, the type shift of muscle fibers from S to F was observed in the deep and middle portions. Fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), and slow-twitch oxidative (SO) fibers with ATPase, SDH, and alpha-GPD activities were found at 15 (the superficial portion) and 17 days (the deep and middle portions). The histochemical differentiation of intrafusal muscle fibers (7 and 9 days) was found earlier than that of extrafusal muscle fibers.

Adenosine Triphosphatases↗

Extracorporeal immunoadsorption with IM-PH or IM-TR column.

In order to selectively remove pathogenic macromolecular reactants, a biological affinity type adsorbent (a DNA colloidin charcoal column or protein A sepharose CL4B = Prosorba) has been developed and used for the treatment of immune disorders, alloimmunization and cancer. However, because physiologically active materials are required in this procedure, it is difficult to ensure an adequate supply of raw materials (and their handling, sterilization and preservation as an immunoadsorbent. To overcome the above-mentioned problems, we developed physicochemical type immunoadsorbents IM-TR and IM-PH, which consist of polyvinyl alcohol gel where tryptophan, in the former, and phenylalanine, in the latter, is used as a ligand. IM-PH has a better selectivity than IM-TR, however, IM-TR is a more efficient adsorbent of anti-acethylcholine receptor antibody than IM-PH. IM-PH plasma perfusion has been successfully used with patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and multiple sclerosis (MS).

Animals↗

Succinate dehydrogenase and synthetic pathways of glucose 6-phosphate are also the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat liver.

In order to find the markers of the toxicity of the autoxidized lipids in the liver, rats were given a lethal amount of secondary autoxidation products of linoleic acid (400 mg/rat/day for 3 days) and then changes in the hepatic metabolic functions were analyzed. A decrease in acetyl-CoA level to half caused by the depletion of CoASH was reported in an associated paper (J. Nutr. Sci. Vitaminol., 35, 11-23, 1989). Citrate, isocitrate, and 2-oxoglutarate also decreased to half the level of those of the control group. Reduction in isocitrate dehydrogenase activity was only 25%, while NADH2 and ATP levels remained unchanged. Thus, the reduction in the citrate cycle activity was due to the decrease in acetyl-CoA. The activity of mitochondrial succinate dehydrogenase was decreased to 1/5. Other appreciable changes were depletion of glucose 6-phosphate and fructose 6-phosphate, accumulation of glucose 1-phosphate, reductions in hexokinase, phosphofructokinase, glucose-6-phosphatase, phosphoglucomutase, and phosphogluconate dehydrogenase activities, and decrease in the NADPH2 level. It was considered that these changes were caused by the depletion of glucose 6-phosphate whose synthetic pathways were abnormal. Therefore, the markers of the hepatotoxicity of secondary products were the changes in the CoASH level and the activities of succinate dehydrogenase and synthetic pathways for glucose 6-phosphate.

Animals↗

Inherited deficiency of functional and free form protein S.

We studied hemostatic function in a family with a history of venous thromboembolic disease. In the propositus, a 36-year-old male, the results of assays for the coagulation, anticoagulation and fibrinolytic factors were almost normal. However, the functional protein S activity in his plasma was less than 5% of normal. Similar laboratory findings were noted in his paternal uncle and two sisters who had recurrent thrombotic episodes and in his asymptomatic father as well. The mean total protein S antigen level in these five patients was 37% (range 19-66%) by conventional Laurell rocket immunoelectrophoresis. However, by crossed immunoelectrophoresis of their plasmas and Laurell rocket immunoelectrophoresis of the polyethyleneglycol 6000-treated plasmas, the free form of protein S was undetectable in their plasmas. The levels of C4b-binding protein in the plasma of three of the five patients were in normal range, and that those in the remaining two were below the normal level. These findings suggest that the recurrent thrombotic disease in this family is due to inherited deficiency of protein S, particularly of the functionally active free form of protein S.

Adult↗

[Thallium-201 myocardial perfusion imaging during transient coronary occlusion at the time of PTCA: comparison with stress imaging].

To evaluate myocardial perfusion during transient coronary arterial occlusion, thallium-201 was administered intravenously during percutaneous transluminal coronary angioplasty (PTCA) in 12 patients with effort angina, and the resulting perfusion images were compared with those of exercise stress obtained before PTCA. Thallium-201 was injected at the last inflation of an angioplastic balloon and occlusion was maintained for 60 to 90 sec. Three projections of planar images were obtained immediately after PTCA, using a portable gamma camera in an angiography room. These perfusion images obtained during PTCA and exercise were visually interpreted and compared. Myocardial perfusion defects due to the responsible vessel occlusion were observed at early imaging after PTCA, and were fully redistributed three hrs post injection. In 10 patients without angiographically imaged collateral vessels, there were no significant differences in perfusion between images during PTCA and during exercise. Two patients whose collaterals were observed during coronary angiography before PTCA had higher perfusion scores during PTCA than during exercise. We concluded that intravenous injection of thallium-201 during PTCA is a useful means for assessing alteration of myocardial perfusion due to transient coronary occlusion without increasing the risk of angioplastic procedures, and that it provides more precise information about the jeopardized myocardium, perfused by antegrade blood flow.

Angioplasty, Balloon↗

[Intrathecal perfusion of ACNU neurotoxicity and intrathecal pharmacokinetics in dogs].

We studied the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma. Intrathecal perfusion was performed in adult dogs by constant drip administration of 1 to 2 mg ACNU dissolved in 10 to 20 ml of lactate Ringer solution into the lateral ventricle and cerebrospinal fluid drainage through the lumbar puncture. The perfusion time was changed from 15 to 71 min. A bolus injection of 2 mg ACNU was also tested in one dog. No neurological symptom was noted during and after perfusion, and histological examination reveal only a minimum denudation of ependyma in a small area. Concentration of ACNU in CSF and serum were measured by HPLC (high-performance liquid chromatography). ACNU was detected in lumbar CSF only by perfusion, not by bolus injection, and the maximum concentrations were 6.26 to 25.76 micrograms/ml. The elimination phase of ACNU in lumbar CSF followed linear kinetics and the half-time was 18 min on average. AUCs (area under the drug concentration-time curve) were 346 to 896 micrograms.min/ml and they were the equivalent of in vitro cell kills in excess of 3 logs for rat 9L gliosarcoma and human glioma 126 cells. Serum concentration was 0.10 micrograms/ml in maximum. These findings suggest the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma and warrant further studies.

Animals↗

[An attempt of thallium-201 myocardial perfusion imaging during transient coronary arterial occlusion by PTCA].

To evaluate the myocardial perfusion during transient coronary occlusion, we attempted to obtain the myocardial scintigraphy during percutaneous transluminal coronary angioplasty (PTCA). Tl-201 was injected at the last inflation of angioplastic balloon and occlusion was kept on for 60 sec. Planar images or SPECT were obtained immediately after PTCA. With this protocol, myocardial perfusion defects were observed during PTCA and fully redistributed 3 hours after Tl injection. Extent of ischemic lesions were almost same as that observed during exercise in two cases without collateral vessels. In a case with well visualized collateral vessels, perfusion defect was smaller in PTCA images than that in exercise stressed images. We conclude that intravenous injection of Tl-201 during PTCA is useful to assess the alteration of myocardial perfusion due to transient coronary occlusion without increasing the risk of angioplastic procedure.

Adult↗

Cinevideodensitometric quantification of relative coronary arterial stenosis: application to evaluating candidates for percutaneous transluminal coronary angioplasty.

As an alternative to visual interpretations of subjects' angiograms, coronary arteries dilated by percutaneous transluminal coronary angioplasty (PTCA) were evaluated using cinevideodensitometry, and the results were compared with those obtained by the edge detection method. Coronary arteriograms were obtained in various projections and suitable frames were selected for analysis. The frames were transformed to digitized images (512 X 512 X 8 bits) with an image analyzer (MIPRON 1), and cinevideodensitometric and edge detection analyses were performed. Phantom models of various shapes were opacified with contrast medium and were used to test our system. The cineangiograms of 58 patients with ischemic heart disease, 28 of whom had underwent PTCA, were analyzed. A highly linear correlation was observed between the cross-sectional areas of the phantoms and the summed gray levels measured using cinevideodensitometry. Percent area stenosis evaluated by the two methods was accurate and reproducible in measuring the symmetrical stenosis models. However, for the model of asymmetrical stenosis, the measurement by the edge detection method differed according to various projections. Similar results were obtained measuring asymmetrical stenosis in the right coronary artery in vivo in various projections. Based on these experimental results, coronary stenoses dilated by PTCA were evaluated. Prior to PTCA, coronary arterial stenosis measured using the two methods closely approximated each other. However, following PTCA, there were discrepancies between the measurements by the two methods in six cases. This can be accounted for by asymmetrical changes in a luminal cross-section, which cannot be accurately assessed using the edge detection method in single plane projection. In conclusion, cinevideodensitometric measurements of relative coronary arterial stenosis were objective, accurate, and reproducible. According to cinevideodensitometric analysis, eccentric lesions can be measured using a single projection, and tracing arterial borders is unnecessary. It is a useful means in measuring quantitatively the degree of dilatation of coronary arterial stenosis accomplished by PTCA.

Angiography↗

[Ultrasonic tissue characterization by spectral analysis of myocardial textural pattern].

Based on the fact that ultrasonic myocardial textural patterns are more irregular in the pathological myocardium than in the normal, evaluation of the myocardial tissue character was attempted in vivo using spectral analysis. Parasternal left ventricular long-axis echocardiograms were obtained from five patients with old myocardial infarction diagnosed by history, electrocardiography and coronary angiography. These echocardiograms were transferred to an image analyzer and digitized (256 x 256 x 8). The waveforms of the gray-scale-changes from the normal myocardium showed periodicity in each 8-pixel cycle, but those from the infarcted myocardium did not. To quantify pattern changes in gray-scale values in the ultrasound beam direction, spectral analysis was performed by the maximum entropy method (MEM). There were four peaks in the MEM spectra both in the normal and infarcted myocardia, but there was a great significance in these patterns: with high, steep peaks in normal MEM spectra, and low, blunt peaks in infarcted ones. By discriminatory analysis of these four peak values, normalized by the whole spatial frequencies as multivariate, the misclassification rate was 4.8-22.7% in anteroseptal infarctions and 5.0-20.0% in posterior infarctions. Thus, spectral analysis of the myocardial textural pattern has advantages for analyzing routine echocardiograms without corrections by any absolute ultrasonic references. Furthermore, the misclassification rate is so low that we are able to characterize myocardial tissue.

Echocardiography↗

[Morphological study on open bite patients].

The purpose of the present study is to investigate the morphological features of open bite patients who have also disharmony of anteroposterior relations between maxilla and mandible. Lateral head films of 40 adult females with open bite were used. The samples were classified into three groups by ANB angle. Three groups were as follows. 1. Type I open bite (12 subjects, 1 degree less than or equal to ANB less than or equal to 4.5 degrees). 2. Type II open bite (13 subjects, ANB less than 4.5 degrees). 3. Type III open bite (15 subjects, ANB less than 1 degree) The normal samples was the longitudinal data of females in our department. Skeletal and dental variables were calculated and compared norm versus type I open bite, type I open bite versus type II open bite and type I open bite versus type III open bite, respectively. The following results were obtained. 1. Disharmony of the vertical dimensions in type I open bite was mainly due to long anterior lower facial height which was accompanied by large gonial angle as compared with norm. 2. There were no difference in anteroposterior position of the maxilla and nasal floor in all three open bite groups. 3. There were no difference in anterior and posterior facial height between type I and type II open bite. However, type II open bite showed the backward rotation of the mandible accompanied by over eruption of upper first molars. 4. Type III open bite showed longer anterior lower facial height which was caused by excessive mandibular growth than type I open bite. 5. Upper incisors showed labial inclination as compared with norm in all three open bite groups. However, lower incisors showed labial inclination in type II open bite and lingual inclination in type III open bite as compared with type I open bite. As a result, the inter-incisal angle was small in type II open bite and large in type III open bite as compared with type I open bite. These results suggested that the dentoalveolar factors were large in type II open bite and the skeletal factors were large in type III open bite as compared with type I open bite.

Cephalometry↗

Effect of oral adsorbent on blood metabolites in hepatic failure dogs.

AST-120 is a specially synthesized carbonaceous adsorbent for oral use. It mainly adsorbs low to middle molecules in the alimentary tract. In the present study, AST-120 was administered to hepatic failure dogs, and blood metabolites were analyzed by high performance liquid chromatography (HPLC). Thirty adult mongrel dogs underwent posta-cavae (P-C) shunts with 40% and 70% hepatectomies. They were divided into two groups, the AST group (n = 19) and control group (n = 11). The AST group received about 0.5 g/kg of the adsorbent intermittently with diet after the operation. The control group was fed the ordinary diet. Body weight, blood ammonia, plasma bile acids were measured, and blood metabolites were analyzed by the multi-column HPLC system. P-C shunt dogs with 70% hepatotectomies died within three months showing about 40-50% body weight loss. HPLC analysis of their plasma showed some specific peaks for middle molecules, about 3000-5000 daltons. After administration of the adsorbent, these peaks were not detected, so it was considered that these substances had been adsorbed.

Administration, Oral↗

[Clinical study on surgical treatment of aortic arch aneurysm using selective cerebral perfusion or hypothermic circulatory arrest].

To improve the surgical results of aneurysms of the transverse aortic arch, it is essential to select the optimal support technique to protect the cerebral ischemia during the aortic arch occlusion. In the four year period between 1983 and 1987, 21 consecutive patients had surgical correction of aneurysms of the transverse aortic arch at our institution. The causes of aneurysms were dissection (type A) in 16 patients and arteriosclerosis in 5 patients. Seven patients had emergency operation for frank or impending rupture. Two method for cerebral protection were employed during the period of arch exclusion. In Group I, 11 patients underwent selective cerebral perfusion both to innominate and left common carotid arteries via one roller pump at a rate of 600 ml/min (25 degrees C). The average cerebral perfusion time was 70.4 +/- 20.5 minutes. In Group II, 10 patients underwent deep hypothermia (15 degrees C to 20 degrees C) and total circulatory arrest to allow repair of the transverse aortic arch. The concomitant AVR was performed in two patients and CABG in one patient. The average cerebral arrest time was 35.2 +/- 3.4 minutes. Two out of 10 patients had additional cerebral perfusion because cerebral ischemic time exceeded over 45 minutes. There were three early deaths (14.3%) in this series. The causes of early death were bleeding in two patients and renal failure in one patient. There were no cerebral complications in both groups. The duration of extracorporeal bypass necessary for cooling and rewarming phase in Group II was longer than that in Group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Diltiazem blood cardioplegia in patients of severe valvular heart disease].

This study was undertaken to analyze the effect of diltiazem blood cardioplegia (D-BCP) in patients of valvular heart disease with severe left ventricular dysfunction (EF = 56.3%, FS = 26.0%, CI = 2.241/min/m3), they were satisfied with NYHA functional class 3 and 4, also cardiothoracic ratio over 65%. By negative choronotropic action of D, the heart rates in D added group tend to be less than those of D free group 4 to 16 hours postoperatively, although that may diminish the incidence of ventricular arrhythmia postoperatively. D-BCP improved better functional recovery (mPAWP-LVSWI relation) during the early postoperative period than those seen in preoperatively. The pulmonary vascular resistance index of D added group showed significantly lower levels than those in the preoperative period, 0 to 16 hours after surgery. Consequently, D-BCP might be safe and provide superior protection for severe valvular heart disease.

Aged↗

[Long-term results of cardiac valve replacement: a 10- to 25-year retrospective study].

A total of 149 patients who underwent cardiac valve replacement between January, 1964 and June, 1979 in our institution have been survived more than 10 years postoperatively. The prosthetic valves primary employed in this series were both mechanical valve such as Starr-Edwards, Smeloff-Cutter, Wada-Cutter, Lillehei-Kaster valves and biological valve such as Hancock valve. Of these, 69 patients (46%) implanted with Starr-Edwards or Wada-Cutter valve were not anticoagulated postoperatively, and 52 (53%) underwent reoperation mainly for valve-related complications or aggravated other valve lesions during the follow-up period. One hundred and thirteen patients were confirmed to be alive at the end of June, 1989, with the follow-up period of 10 to 25 years. Of these, 98 patients (87%) are in the NYHA I or II at the present time. Other twenty-two patients were dead and fourteen were lost to follow-up over 10 years after operation. Although cardiac valve replacement may improve the longevity and the quality of life, available prosthetic valves were not ideal both in material and design. The increased risk of thrombogenesis of mechanical valve and the limited durability of biological valve necessitated re-replacement in the long-term period. Therefore, in addition to selection of the appropriate valve prosthesis, and optimal prevention of valve-related complications, early diagnosis and treatment of these complications are important to improve the long-term results of cardiac valve replacement.

Adolescent↗

[Effects of chronic inhalation of ethylene oxide on the rat testes].

The effects of chronic exposure of ethylene oxide on the testes were investigated. When rats were exposed to 500 ppm, three times a week for 13 weeks, the testes of the exposed group became remarkably atrophic and their DNA content decreased proportionally. However, plasma testosterone concentration did not significantly change. In the testes the activity of glutathione reductase decreased by 45% and glutathione-S-transferase increased by 64%, respectively. These results suggest that ethylene oxide causes a definite toxicity in the testes and the abnormality of glutathione metabolism plays an important role in its toxicity.

Administration, Inhalation↗

Triorthocresyl phosphate poisoning--a review of human cases.

Since the end of the nineteenth century, numerous cases of triorthocresyl phosphate (TOCP) poisoning due to accidental contamination of drink, food or drugs have been reported. Following the ingestion of preparations contaminated by TOCP, gastrointestinal symptoms may occur and after an interval of ten to twenty days, a well-known delayed neurotoxicity gradually develops. In general, the initial symptoms are pain and paresthesia in the lower extremities. In most cases, muscle weakness progresses rapidly developing into a striking paralysis of the lower extremities with or without an involvement of the upper extremities. Severe cases show pyramidal signs. The histopathological findings show axonal degeneration in the peripheral nerves and degenerative changes in the anterior horn cells. Degenerative change also occurs in the lateral and dorsal tracts of the spinal cord. The cardinal therapy is physical rehabilitation.

Axons↗