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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 307 records · Page 17Linked to original sources
PubMed1994

A study on lipid peroxide-induced lens damage in vitro.

The effects of linolenic acid hydroperoxide (LAPO) on isolated rat lenses were investigated, because they are believed to be cataractogenic in vivo. They were also compared with the effect of linolenic acid (LA), source of LAPO. Rat lenses, which were exposed for 5 hr to either 210 microM or 420 microM LAPO, became cloudy and this change was associated with increases in the level of malondialdehyde (MDA), a breakdown product of lipid peroxide, and decreases in non-protein thiol (NP-SH) content. Concomitantly, there were changes in cation contents: Na+ and Ca2+ were increased whereas K+ and Mg2+ were decreased. The changes in the levels of the above parameters, correlated with the concentration and the treatment time of LAPO to which the lenses were exposed. The increase of MDA was 2-4-fold over normal level and was consistent with those in cataractous lenses of the human and experimental animal models. On the other hand, if the lenses were exposed to LA, the only change observed was a small alteration of cationic content. If the lenses were cultured for an additional 24 hr in the absence of either LA or LAPO, the cation content continued to change only in those lenses which were previously exposed to LAPO. These results show that at concentrations of lipid peroxides, which are associated with the development of cataract in the human and animal models, there are changes in vitro in cation content, MDA and NP-SH levels, which accompany the development of a lens opacity.

Animals↗
PubMed1994

Specific immunotherapy reduces the antigen-dependent production of eosinophil chemotactic activity from mononuclear cells in patients with atopic asthma.

BACKGROUND: The efficacy of specific immunotherapy has been verified. There is accumulating evidence focusing on the T lymphocyte-eosinophil interaction in the pathogenesis of asthma. The aim of this study was to clarify whether immunotherapy affects the production of eosinophil chemotactic activity (ECA) from peripheral blood mononuclear cells (PBMC). METHODS: PBMC obtained from persons with bronchial asthma who were sensitive to Dermatophagoides farinae (Df) or from healthy volunteers were cultured for 96 hours in the presence or absence of Df. ECA in culture supernatants was assayed by means of the modified Boyden's chamber method. RESULTS: There was no significant difference in the baseline levels of ECA between asthmatic persons treated with immunotherapy and those without immunotherapy. The addition of Df (10 to 10(4) ng/ml) enhanced the ECA production in a dose-dependent fashion in asthmatic persons without immunotherapy, and there was a statistically significant correlation between the concentrations of Df and the levels of ECA (rk = 0.34; p < 0.05). In contrast, Df-dependent ECA production was suppressed in asthmatic persons with immunotherapy, and the suppressive effect was observed from 4 weeks after rush immunotherapy. CONCLUSIONS: These results indicate that immunotherapy induces the suppression of antigen-dependent production of ECA from PBMC. This may contribute to the attenuation of eosinophil infiltration into the airways in asthma patients.

Adolescent↗
PubMed1994

An organic acid-induced sigmoidal release system for oral controlled-release preparations.

To achieve time-controlled or site-specific drug delivery in the gastrointestinal tract, a sigmoidal release system (SRS) was developed, which achieved a prolonged lag time, followed by rapid release. The theophylline beads with a thick Eudragit RS film coating showed very low drug release in water, whereas the release rate increased considerably in organic acid solutions. A hydration study of Eudragit RS films suggested that the increase in drug release was attributable to structural changes of the film induced by polymer-acid interactions. When succinic acid was incorporated into the core of Eudragit RS-coated theophylline beads, the drug release profile showed a typical sigmoidal pattern. SRS beads containing acetaminophen were also prepared by the same technique. Again, a sigmoidal release pattern was observed in which the lag time was prolonged with an increase in the coating level, whereas the drug release rate thereafter was almost constant irrespective of the coating level. Acetaminophen-containing SRS beads with different coating thickness were orally administered to beagle dogs. The drug plasma concentration curves showed lag periods similar to the in vitro lag time.

Acetaminophen↗
PubMed1994

Effect of ascorbic acid 2-O-alpha-glucoside on hydrocortisone-induced cataract formation in developing chick embryos: II. Influence on glutathione and lipid peroxide contents in the lens.

In developing chick embryos, hydrocortisone induces cataract formation following a decrease in lens glutathione content but an increase in lipid peroxide content in lens, blood and liver. The preventive effects of ascorbic acid 2-O-alpha-glucoside (AA-2G) on these parameters were compared on cataract formation with those of ascorbic acid (AsA) and ascorbic acid 2-O-phosphate (AA-2P). In these tissues, AA-2G inhibited a decrease in glutathione content and an increase in lipid peroxide content more effectively than either AsA or AA-2P. Various tissues including lens and liver have alpha-glucosidase activity, strongly suggesting that AsA is enzymatically liberated from AA-2G in these tissues. In summary, these results suggest that AA-2G exerts a potent anti-cataract activity via a reduction in oxidative damage through AsA release.

Animals↗
PubMed1994

Artificial fiber complexes composed of cellulose and guar gum or psyllium may be better sources of soluble fiber for rats than comparable fiber mixtures.

Three fiber complexes composed of cellulose and the same weight of guar gum, cornstarch or psyllium were constructed as three-dimensional networks of cellulose fiber filled with the soluble components. Physiological properties of these fiber complexes were examined in comparison with a mixture of powdered cellulose and the corresponding polysaccharides at a ratio of 1:1 in rats. Another group of rats was fed a fiber-free diet. Body weight gain in the guar gum-cellulose mixture group, but not in guar gum-cellulose complex group, was lower than that of the fiber-free group. The cecal walls in the groups fed the guar gum-cellulose and psyllium-cellulose mixture diets were heavier than those in the corresponding fiber complex-fed groups. Weights of the small intestinal wall and ileal mucosa were also greater in the guar gum-cellulose mixture-fed group than in the guar gum-cellulose complex-fed and the fiber-free diet-fed groups. Fermentable energy in dietary fiber estimated from fecal energy excretion, short-chain fatty acid contents and in vitro short-chain fatty acid production rates in the cecum of the complex-fed groups were similar to those in the fiber mixture-fed groups. However, butyric acid content and production rate in the group fed the guar gum-cellulose complex were markedly higher than in the other groups. The lowering effects of guar gum-cellulose and psyllium-cellulose mixtures on plasma cholesterol concentration tended to be greater than those of guar gum-cellulose and psyllium-cellulose complexes. These findings demonstrate that the artificial fiber complexes supply soluble fibers without increasing mechanical stress to the intestines and decreasing cecal fermentation.

Animals↗
PubMed1994

Chemotherapy targeting regional lymph nodes by gastric submucosal injection of liposomal adriamycin in patients with gastric carcinoma.

We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in another 18 patients. Prior to radical gastrectomy, Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 ml of Lipo-ADR was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of F-ADR. The ADR levels (micrograms/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4); and 11.9 +/- 4.80 on day 4 (n = 6). Those after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4); and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (P < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Such preoperative adjuvant chemotherapy targeting the regional lymph nodes may be useful for preventing the lymph node recurrence of gastric carcinoma.

Adult↗
PubMed1994

Inhibition of analgesic-induced asthma by leukotriene receptor antagonist ONO-1078.

We evaluated the effect of ONO-1078, a selective leukotriene-C4, -D4, and -E4-receptor antagonist, on bronchoconstriction intensity during inhalation challenge with dipyrone (a pyrazolone derivative) in six aspirin-sensitive asthmatics. A double-blind, randomized, crossover design was used. After ingestion of 225 mg ONO-1078 or matching placebo, subjects underwent bronchial provocation with dipyrone on two occasions, separated by 4 wk. Aerosol inhalation of dipyrone was performed increasing the concentration stepwise from 0.08 to 10% (wt/vol). FEV1 was measured every 10 min up to 30 min after inhalation of each concentration. Threshold concentrations causing a fall in FEV1 > or = 20% of baseline value were 0.4% in four subjects and 2% in the other two on the placebo day. After pretreatment with ONO-1078, threshold concentration was 10% in two subjects, and no fall in FEV1 was observed in the other four, even after inhalation of 10% dipyrone. Values of PD20 were 21.9 +/- 8.2 units (mean +/- SEM) after placebo and 311.6 +/- 40.3 units after ONO-1078, respectively, and a statistically significant difference occurred (p < 0.001). Provocation of bronchoconstriction was completely inhibited in subjects whose plasma ONO-1078 levels were more than 0.5 microgram/ml. These results support the hypothesis that sulfidopeptide leukotriene-induced bronchoconstriction is one important component in the pathophysiology of aspirin-induced asthma.

Adult↗
PubMed1994

Urinary excretion levels of hydroxylysine glycosides in osteoporotic patients.

The urinary excretion levels of hydroxylysine glycosides [Hyl-Gs; O-beta-D-Galactopyranosylhydroxylysine (GH) and 2-O-alpha-D-glucopyranosyl-O-beta-D-galactopyranosylhydroxylysine (GGH)], provide a new index of collagen metabolism. The determination of urinary hydroxylysine glycoside excretion levels was applied to 20 osteoporotic patients and 208 healthy control subjects (69 females and 139 males) in order to evaluate the conditions of bone collagen metabolism. Urinary Hyl-Gs were analyzed by the method of pre-column fluorescent derivatized HPLC. Compared to the age and sex-adjusted control, the urinary excretion levels of hydroxylysine glycosides, especially GH, in osteoporotic patients were significantly higher than in the age and sex-adjusted control, and the urinary GGH/GH ratio was lower. Sixteen of the 20 patients whose Hyl-Gs levels we followed exhibited significantly lower values after 200 d compared to the initial levels. These results suggest that clinical therapeutics affected the bone resorption and, therefore, demonstrated the usefulness of determining urinary excretion levels of Hyl-Gs for evaluating the conditions of bone metabolism.

Adult↗
PubMed1994

Urinary excretion level of hydroxylysylpyridinoline as an index of bone resorption.

Hydroxylysylpyridinoline (HP), an intermolecular cross-linking amino acid, is present only in bone and cartilage collagen. We examined urinary HP levels in order to assess bone collagen metabolism using HPLC. Urinary HP excretion levels (nmol/mmol creatinine) of healthy control groups gradually increased with aging. Urinary HP excretion levels of females were higher than those of age-adjusted males. On the other hand, the urinary excretion levels of HP in osteoporotic patients were significantly higher than those of age and sex-adjusted controls. It is suggested that the determination of urinary HP excretion levels is useful in the clinical evaluation of metabolic bone diseases, especially osteoporosis.

Adult↗
PubMed1994

[Fine structural studies on the cytoplasmic membrane morphology of transitional cell carcinoma in men].

Transitional cell carcinomas (TCC) in the human urinary bladder were observed on the fine morphological behaviour of the plasma membrane, with special references to the morphological differences in various grades of TCC utilizing thin sections and freeze fracture replica electron microscopically. The purpose of this study is to clarify the characteristic differences between various grades of human TCC as a indicator suggestive of the TCC malignancy using electron microscopic techniques. (1) The asymmetric unit membrane seen on the luminal membrane of the superficial cells was unique in all of TCC G1 and some TCC G2 cases. In other TCC G2 and TCC G3, there observed the symmetric unit membrane. Fusiform vesicles directly beneath the luminal plasma membrane were recognized only in TCC G1. (2) Microvilli (MV) seen on the luminal plasma membrane in TCC G1 were found to have the same appearance and distribution as on the normal bladder epithelium. As the grades increased in severity, there were less MV being shorter and club-like-forms. Even deformed with bleb formation microvilli were more apparent in TCC G3 cases than in TCC G2. (3) There was no difference observed between the junctional complex of the superficial cells of the all TCC grades and normal cells. As the cellular malignancies develop, however, the interdigitation structures and desmosomal appearances situated between neighboring intermediate cells tended to decrease. (4) Intracytoplasmic tonofilaments proliferation was obvious in TCC G2, but not in G3. (5) With increasing severity of TCC grades, intramembranous particles showed significant decrease in number as seen on freeze-fracture replica. In conclusion, these results suggest that fine structural observation may prove to be a useful parameter to know the grades of TCC in human bladder tumors.

Carcinoma, Transitional Cell↗
PubMed1994

Time-course of lens opacity and morphological changes in rabbit lens epithelial cells after intravitreal silicone oil injection.

The clinical course of lens opacity and the morphological changes in lens epithelial cells after intravitreal silicone oil injection were observed for 3 months in 21 normal adult albino rabbits. After the simple vitrectomy in both eyes of each rabbit, silicone oil was injected into the vitreous in one eye and the other eye was kept as the control. By photoslit-lamp microscopy, 8 of the 14 examined eyes showed early posterior subcapsular lens opacity one month after silicone oil injection. By transmission electron microscopy, intracellular vesicles near the interdigitation of the lens epithelial cells were observed in all of the 7 eyes examined histologically 2 weeks after the procedure. These changes were not observed in the 7 fellow control eyes. As a result, it is surmised that cataract formation after intravitreal silicone oil injection may be associated with morphological changes in the lens epithelial cells.

Animals↗
PubMed1994

[Thrombotic thrombocytopenic purpura (TTP) with a low level of apolipoprotein A-I (Apo A-I) which responded to combination of vincristine and beraprost].

A 51-year-old man was admitted to the psychiatric ward because of increasing confusion and irrational behavior. He was later transferred to our department due to anemia and thrombocytopenia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made based on the presence of thrombocytopenic purpura, microangiopathic hemolytic anemia, neurological symptoms and fever. Corticosteroids, plasma exchange (PE), dextrans, dipyridamole and vincristine (VCR) were given without satisfactory response. Beraprost sodium was prescribed followed by a dramatic improvement and complete remission. A number of reports indicated that prostacyclin metabolism was involved in the pathogenesis of TTP. Recently Apo A-I was identified to be a prostacyclin-stabilizing factor, which was initially low in this patient. If patients do not respond to either PE or VCR, consideration should be given to treatment with beraprost, especially when the level of Apo A-I is low.

Apolipoprotein A-I↗
PubMed1994

[Multicenter prospective study of retinopathy of prematurity--II. Optimum timing of the first examination].

We reviewed the records of 360 cases of retinopathy of prematurity (ROP) in 12 institutions in Japan, and investigated the optimum timing of the first examination. On the basis of the onset of ROP and the timing of the first treatment, the first ophthalmological examination should be performed 3 weeks after birth or 29 weeks of postconceptional age at the latest. Regarding the visibility of the fundus, there was little hazy media after 29 weeks of postconceptional age. Under the basic policy that the severe progressive "plus" disease should be properly treated, we concluded that the first ophthalmological examination should be performed 3 weeks after birth at the latest. When the gestational age at birth is less than 26 weeks, funduscopy at the post conceptional age of 29 weeks is advisable.

Humans↗
PubMed1994

[Multicenter prospective study of retinopathy of prematurity--III. Timing of the coagulation therapy and the course of retinopathy of prematurity after coagulation].

We reviewed the records of 360 cases of retinopathy of prematurity (ROP) in 12 institutions in Japan, and investigated the timing of the coagulation therapy and the course of ROP after coagulation. The first coagulation therapy was performed at 9.6 weeks after birth and 35.9 weeks of postconceptional age on the average. The severity index in individual infants also showed that the disease became worse during the period from 32 to 36 weeks of postconceptional age. However, the fundus was clearly visible and there was no primary hazy media during this period. On the basis of the results of the timing of the first treatment, the visibility of the fundus, and the severity index in individual infants, we concluded that an ophthalmological examination with special care should be performed during the period from 32 to 36 weeks of postconceptional age.

Humans↗
PubMed1994

[Multicenter prospective study of retinopathy of prematurity--IV. Comparison with the data from University of Miami].

We investigated the records of 360 cases of retinopathy of prematurity (ROP) in 12 institutions in Japan (we treated the severe progressive "plus" disease by coagulation therapy), and compared them with data from University of Miami (Ophthalmology 94: 620-629, 1987), as representative of the natural course of ROP without coagulation therapy in those days. The timing of the first examination and the first positive diagnosis were later at University of Miami than in Japan. The time of maximal severity of the disease and occurrence of regression were also later the University of Miami than in Japan. In Japan, the first examination was performed at 29 weeks of postconceptional age or at 3 weeks after birth. At the University of Miami, the first examination was performed at 32 weeks of postconceptional age. If the severe progressive "plus" disease is to be properly treated by photo-coagulation or cryotherapy, it is essential to commence fundus examination earlier.

Florida↗
PubMed1994

[Mechanism and prevention of postoperative hemolysis in the corrective surgery of subarterial ventricular septal defects].

Intravascular hemolysis following the repair of subarterial ventricular septal defects (VSD) was studied in 34 patients. The VSD was closed through a main pulmonary arteriotomy with a Dacron double-velour patch (Meadox, Oakland, NJ) in 17 cases (Group B) and with a Dacron single-velour patch covered by autologous pericardium facing toward the right ventricular outflow tract (RVOT) in 17 cases (Group A). No significant intergroup difference in age, weight, Qp/Qs, Pp/Ps, and Rp/Rs was found. There were no significant differences in the preoperative values of serum LDH, total bilirubin, and flow velocity at the RVOT (Group A: 1.7 +/- 0.4 m/sec vs Group B 1.8 +/- 1.0 m/sec). The severity of hemolysis was evaluated by serum LDH levels, total bilirubin levels, and hemoglobinuria on the morning of the first operative day. Postoperative LDH levels were significantly lower in the Group A (812 +/- 205 IU/L) than in the Group B (1098 +/- 427 IU/L) (p < 0.05). Hemoglobinuria developed in 2 patients in Group B (12%) and none in Group A. These data suggest that the pericardium apparently protects against postoperative hemolysis. The intensity of the turbulence at the RVOT was graded as follows using color-doppler echocardiography (0: none; Grade 1: turbulence was detected near the patch only; Grade 2: turbulence was detected halfway to the RVOT; Grade 3: turbulence extended to the anterior wall of the RVOT). The relationship between the presence of hemolysis and the degree of turbulence was examined. Turbulence at the RVOT appeared in 73% of those in Group A and in 82% of those in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Experience with atrioventricular valve replacement in infants and children].

From 1980 to 1989, nine infants and children underwent valve replacement. These replacements consisted of seven mitral valve replacement (MVR), one left atrioventricular valve replacement, and one aortic valve (AVR) replacement. We excluded AVR from this report. Follow-up period of 8 cases were 68 months in an average. During this period, 2 cases were not thought to be satisfactory as antithrombotic therapy, in which one revealed malfunctioning prosthesis, and secondary MVR implantation was performed. Another one is free from any complications. We experienced the difficulty of antithrombotic therapy following valve replacement in infants and children. It is supposed that combined use of anticoagulant therapy agent and antiplatelet agent may be necessary as antithrombotic therapy, especially in childhood.

Adolescent↗