Search PubMed⌕ Search

Biomedical subjects

Y Nagata

Publications and source records attributed to Y Nagata.

At least 235 records · Page 13Linked to original sources

Prevention of onset in an insulin-dependent diabetes mellitus model, NOD mice, by oral feeding of Lactobacillus casei.

The effect of Lactobacillus casei (LC) on the onset of diabetes in an insulin-dependent diabetes mellitus model, nonobese diabetic (NOD) mice, were examined. From the age of 4 weeks, female NOD mice were fed a diet of either standard laboratory chow (n = 12) or the same chow containing 0.05% weight heat-killed cells of LC (n = 12), and the onset of diabetes was thereafter recorded. The incidence of diabetes in the control group (10/12) was significantly higher than that in the LC-treated group (3/12) (p < 0.01). Pathological analysis in the LC-treated group revealed strong inhibition of the disappearance of insulin-secreting beta cells in Langerhans islets caused by autoimmune disease. The proportion of CD45R+ B-cells in the spleen was increased and that of CD8+ T-cells in spleen cells was decreased in the LC-treated group. Analysis of cytokine production revealed lower interferon-gamma production in the LC-treated group compared to the control group, while the interleukin (IL)-2 production was higher. The levels of IL-4, IL-5, IL-6 and IL-10 in the LC-treated group were somewhat higher than in the control group. Taken together, these findings clearly demonstrated that oral feeding of LC to NOD mice effectively inhibited the occurrence of diabetes and regulated the host immune response.

Animals↗

Purification and characterization of a haloalkane dehalogenase of a new substrate class from a gamma-hexachlorocyclohexane-degrading bacterium, Sphingomonas paucimobilis UT26.

The linB gene product (LinB), 1,3,4,6-tetrachloro-1,4-cyclohexadiene halidohydrolase, which is involved in the degradation of gamma-hexachlorocyclohexane in Sphingomonas paucimobilis UT26 (Y. Nagata, T. Nariya, R. Ohtomo, M. Fukuda, K. Yano, and M. Takagi, J. Bacteriol. 175:6403-6410, 1993), was overproduced in E. coli and purified to homogeneity. The molecular mass of LinB was deduced to be 30 kDa by gel filtration chromatography and 32 kDa by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel, indicating that LiuB is a monomeric enzyme. The optimal pH for activity was 8.2. Not only monochloroalkanes (C3 to C10) but also dichloroalkanes, bromoalkanes, and chlorinated allphatic alcohols were good substrates for LinB, suggesting that LinB shares properties with another haloalkane dehalogenase, DhlA (S. Keuning, D.B. Janssen, and B. Witholt, J. Bacteriol. 163:635-639, 1985), which shows significant similarity to LinB in primary structure (D. B. Janssen, F. Pries, J. van der Ploeg, B. Kazemier, P. Terpstra, and B. Witholt, J. Bacteriol. 171:6791-6799, 1989) but not in substrate specificity. Principal component analysis of substrate activities of various haloalkane dehalogenases suggested that LinB probably constitutes a new substrate specificity class within this group of enzymes.

Biodegradation, Environmental↗

Synthesis of nitric oxide from the two equivalent guanidino nitrogens of L-arginine by Lactobacillus fermentum.

Ten strains of Lactobacillus fermentum that differed in origin converted metmyoglobin to nitrosylmyoglobin [a pentacoordinate nitric oxide (NO) complex of Fe(II) myoglobin] in MRS broth at pH 4.3. Of the 10 strains, L. fermentum IFO 3956 possessed the strongest capacity to convert metmyoglobin to nitrosylmyoglobin. This strain synthesizes NO enzymatically from the two equivalent guanidino nitrogens of L-arginine. To our knowledge, this demonstrates for the first time the production of NO synthesized from the guanidino nitrogens of L-arginine by lactic acid bacteria. IFO 3956 may possess a bacterial NO synthase.

Arginine↗

Water-soluble prodrug of vitamin E for parenteral use and its effect on endotoxin-induced liver toxicity.

The acid salts of aminoalkanecarboxylic acid esters of d-alpha-tocopherol were in a previous in vitro study identified as prodrug candidates for a parenteral form of d-alpha-tocopherol. The disposition of d-alpha-tocopheryl N,N-dimethylaminoacetate hydrochloride (TDMA), the most potential candidate for the prodrug, after a single intravenous administration was investigated and compared with that of the d-alpha-tocopheryl acetate (TA) and dl-alpha-tocopherol, solubilized with HCO-60, in order to establish the utility as a prodrug for i.v. administration. The preventive effect of the prodrug against endotoxin (lipopolysaccharide (LPS))-induced liver lipid peroxidation was also investigated in mice. The plasma and liver levels of alpha-tocopherol (Toc) were increased rapidly after i.v. administration of the prodrug. The distribution of Toc and TDMA in the plasma and the liver at 1 h was as follows; 2.1 +/- 0.2 (plasma, Toc), 2.0 +/- 0.2 (plasma, TDMA), 32.8 +/- 2.9 (liver, Toc), and 35.3 +/- 6.5% of dose (liver, TDMA). The rapid and liver-selective uptake and liver-esterase specific regeneration characteristics of the prodrug enhance the delivery of Toc to liver. The liver availability of Toc after i.v. administration of TDMA, TA and Toc were 116, 50 and 100%, respectively. The elevation of liver lipid peroxide induced with LPS was significantly suppressed to a normal range by a single i.v. postadministration of TDMA (over 10 mg/kg equivalent for Toc). These results indicated that the water-soluble and liver-esterase hydrolyzable derivative of Toc was a potential candidate for a parenteral prodrug which can thus achieve the systemic liver-specific delivery of Toc. Such effective and selective delivery of Toc into the liver can therefore lead to enhanced pharmacological efficacy against liver oxidative injury associated with free radicals.

Animals↗

CD8+ T lymphocyte counts as an adjunctive predictor of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

We encountered a case of cytomegalovirus (CMV) retinitis with spontaneous regression in association with an increased number of CD8+ but not CD4+ T lymphocytes in a patient with acquired immunodeficiency syndrome (AIDS). Thus, we examined the number of CD4 and CD8 counts at the diagnosis of CMV retinitis and compared with those of Pneumocystis carinii pneumonia (PCP). All 21 patients with a confirmed diagnosis of PCP (22 episodes) and 14 CMV retinitis patients were included in this study. Although PCP occurred after depletion of CD4 count to below 200/microl, CD8 count at that time varied widely and remained normal in some patients (median: 276.5/microl, range: 133-900/microl). In contrast, as CMV retinitis occurred after further depletion of CD4 count to below 50/microl, CD8 count decreased to below 500/microl (median: 238/microl, range: 43-448/microl) (p<0.05; PCP vs CMV retinitis). The values of the sensitivity and specificity for CMV retinitis obtained at the cutoff point of either 400/microl in CD8 count and 50/microl in CD4 count were similar. When these two cutoff points were combined, the positive predictive value was 46%. Monitoring of CD8 count may prove valuable as an additional predictor of CMV retinitis in patients with AIDS after CD4 depletion.

AIDS-Related Opportunistic Infections↗

[Two cases of tracheobronchial disruption due to blunt trauma].

Tracheobronchial disruption by blunt trauma is relative rate, but clinical course is various and sometimes fatal. A 22-year-old man (case 1) was admitted with traffic accident. Chest CT demonstrated pneumomediastinum and left pneumothorax. Bronchoscopy showed tracheal tear, but conservative therapy was selected because the peritracheal sheath remained intact. The second case was 27-year-old man, who was admitted with traffic accident. Pneumomediastinum and left tension pneumothorax were diagnosed, but bronchoscopy could not confirm the tracheobronchial disruption. As bronchial injury, lacerations and contusions of the lingular division were found in the thoracotomy, segmentectomy was carried out. When pneumomediastinum or pneumothorax is recognized in the patient of the blunt trauma, more careful examination of bronchoscopy is necessary to confirm the tracheobronchial disruption.

Adult↗

A new surgical technique for the treatment of life-threatening congenital arteriovenous malformation--intraluminal graft implantation.

A new surgical intraluminal graft implantation technique was undertaken in a 27-year-old man with a massive, life-threatening, high-flow congenital arteriovenous malformation (AVM) involving the left lower extremity, which was resistant to such challenges as transarterial embolizations or partial resections. For occlusion of the feeder branches, a composite graft composed of two grafts with different diameters, which matched to the arterial lumen, was surgically inserted into the superficial femoral artery. The implanted graft occluded 2 weeks after the insertion. Although amputation distal to the knee was necessary because of the foot necrosis, the graft was useful in reducing the cardiac output (from 14.3 l/min to 9.8 l/min) and obviating hip joint amputation. A further clinical study is necessary to examine whether or not it is an acceptable treatment modality.

Adult↗

Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis.

Thrombopoietin (Tpo) regulates platelet production, but the mechanisms regulating the serum Tpo level and platelet count in circulation have been a subject of debate. Tpo was reported to be expressed mainly in liver and kidney, but we found that Tpo is expressed in all tissues examined: abundantly in liver, kidney, muscle, colon, brain and intestine, and moderately in bone marrow, spleen, lung, stomach, heart, thymus, ovary, and endothelial and leukemic cell lines. The levels of Tpo transcripts in major Tpo producing organs, liver and kidney, and in the platelet production sites bone marrow and spleen, were constant during acute thrombocytopenia induced by anti-platelet monoclonal antibody administration in mice, and during thrombocytosis induced by Tpo injection. Furthermore, we noticed that platelet count is not exactly inversely proportional to serum Tpo level. During acute thrombocytopenia, serum Tpo level transiently increased a few hours after antibody injection, and returned to the basal level just when matured megakaryocytes accumulated in bone marrow and spleen but the platelet count was still low. Matured megakaryocytes in bone marrow and spleen increased when the serum Tpo level decreased, and decreased when platelet count rebounded. Taken together with other observations, we propose here a modified version of Kuter and Rosenberg's theory, that is, Tpo is constitutively expressed in a variety of organs throughout the body, even in acute thrombocytopenia and thrombocytosis, and that the serum Tpo level is not regulated by Tpo gene expression nor only by platelet counts in circulation, but by the total counts of both megakaryocytes in bone marrow and spleen and of platelets in circulation.

Animals↗

Regulation of megakaryocytopoiesis by thrombopoietin and stromal cells.

Thrombopoietin (Tpo) is a cytokine which stimulates megakaryocyte maturation. We found that Tpo is constitutively and ubiquitously expressed in all tissues examined, including bone marrow stromal cells, even in thrombocytopenia, thrombosis and steady-state condition in mice. Thus, platelet level in circulation is not regulated by Tpo gene expression. Furthermore, when the purified megakaryocytes were cocultured with the stromal cells, most of the megakaryocytes adhered to the stromal cells and remained unchanged, while free megakaryocytes induced proplatelet formation. Thus the stromal cells in bone marrow secrete Tpo and stimulate megakaryocytopoiesis, but the interaction of megakaryocytes with the stromal cells may suppress platelet formation. Study on signal transduction through Mp1 revealed that Tpo induces activation of JAK2 and Tyk2, which in turn activate STAT1, STAT3 and STAT5. Further, Tpo stimulates transcription factors GATA-1 and NF-E2, which induce differentiation markers, GPIIb/IIIa and Pm-1. In addition, Shc, Vav, Ras, Raf-1, MAPKK, MAPK and Pim-1 are also activated. Thus, Tpo activates a lineage-specific cascade as well as a specific JAK-STAT cascade and a common signaling cascade.

Animals↗

[A new handpiece attachment for Nd:YAG laser ablation of emphysematous bullae].

Recently, attention has been drawn to lung volume reduction for bullous emphysema by wedge excision or laser ablation. We used a neodymium: yttrium-aluminum garnet (Nd:YAG) laser with a free-beam mode to ablate peripheral emphysematous areas of lung tissue. To aid us in this procedure, we developed an attachment consisting of a stainless steel rod 3 cm in effective length, with a 1.8-cm diameter ring attached to its tip, and installed it on the tip of the laser handpiece used for free-beam laser ablation. This device has the following distinct advantages: 1) the distance between the tip of the laser and the pleura can easily be held constant, 2) the angle of irradiation can easily be maintained at 90 degrees. These result in 3) a constant area of irradiation (one square centimeter), and 4) an irradiated area that is clearly distinguished by the ring. In addition, the attachment is 5) simple and easy to construct. Three patients with bullous emphysema underwent unilateral laser ablation of the visceral pleura with the new device. All patients recovered completely. We found this rod-and-ring attachment to be useful for free-beam laser ablation.

Aged↗

Effect of oral administration of Lactobacillus casei on alloxan-induced diabetes in mice.

The effect of Lactobacillus casei (LC) on the onset of alloxan (AXN)-induced diabetes in 7-week-old BALB/c mice were examined. It was observed that the mice given a diet containing 0.1% or 0.05% LC or orally administered LC showed significantly decreased incidence of diabetes induced by intravenous injection of AXN and that the plasma glucose level was slightly lower than that in the control group. The body weight in the LC-treated groups was higher than that in the control group, although the food intake weights were almost the same. Pathological analysis revealed that the AXN-induced disappearance of insulin-secreting beta-cells in the islets of Langerhans was strongly inhibited in the LC-treated groups. It was also shown that the serum nitric oxide level was maintained at a normal level in LC-treated mice, whereas the level in the control group was increased by AXN administration. Taken together, these findings suggest that oral administration of LC to AXN-treated BALB/c mice contributed to the reduction of diabetes and the increase in plasma glucose level.

Alloxan↗

[A case of thymic cyst and thymoma with myasthenia gravis].

A case of 53-year-old male with thymic cyst was reported. We established diagnosis for myasthenia gravis. The chest CT and MRI demonstrated a cystic and mass lesion on the anterosuperior mediastinum. This finding suggested a thymic cyst and tumor with myasthenia gravis. The extended thymectomy was performed. Histological examination demonstrated the clear separation of the mixed type thymoma and the thymic cyst. The few reported cases of thymic cyst and thymoma with myasthenia gravis were reviewed.

Humans↗

A phase I and II clinical trial of a newly developed ultrasound hyperthermia system with an improved planar transducer.

PURPOSE: The clinical usefulness of a newly developed ultrasound hyperthermia system was evaluated. METHODS AND MATERIALS: The hyperthermia system uses a modified planer transducer operated at frequencies of 0.5, 1.0, and 1.5 MHz. The transducer has a nonvibrating part at the center to reduce the central hot spot. Frequency sweeping technique is also used to eliminate the annular hot spot around the center. Thirty-eight tumors in 29 patients were examined in this study. In 35 tumors, hyperthermia was given in conjunction with irradiation and/or chemotherapy, and in the remaining 3 tumors, hyperthermia alone was given. In all, a total of 153 hyperthermia sessions were performed. RESULTS: The number of hyperthermia sessions per tumor ranged from 1 to 7 (mean, 4.0 +/- 1.3). The number of intratumor thermometry points per session ranged from 1 to 8 (mean, 4.3 +/- 1.5). The average intratumor temperature for tumors with a maximum depth of <3 cm, 3-6 cm, and >6 cm was 42.1 +/- 1.2, 41.7 +/- 1.4, and 39.9 +/- 2.0 degrees C, respectively. The percentage of monitored intratumor points with temperature exceeding 42 degrees C was 56 +/- 31%, 43 +/- 34%, and 21 +/- 24%, respectively. Of the 30 evaluable tumors treated with combined irradiation, 12 showed complete response, 14 partial response, and 4 no change. Observed complications included pain at the treatment site in 13 of the 153 treatment sessions and vesicle formation in 3 of the 38 treatment sites. No serious complication was seen. CONCLUSIONS: These results indicate that the newly developed ultrasound hyperthermia system is clinically useful for the treatment of localized superficial and subsurface tumors with a maximum tumor depth of no more than 6 cm.

Adult↗

Decreased cytochrome c oxidase activity but unchanged superoxide dismutase and glutathione peroxidase activities in the spinal cords of patients with amyotrophic lateral sclerosis.

The cause of selective degeneration of motor neurons in the ventral horn of the spinal cord associated with amyotrophic lateral sclerosis (ALS) has still not been elucidated. Recently, so-called oxidative stress has been suggested to be a significant factor in the pathogenesis of this disease. We measured the antioxidant actions of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and cytochrome c oxidase (CO) of the human spinal cord in patients with ALS in comparison with those in control patients. Total SOD activity in spinal cord transections from patients with sporadic ALS was not significantly different from the controls in ventral, lateral, or dorsal regions, although enzymic activity was relatively higher in the ventral compared with the dorsal region. GSH-Px activity in the spinal cord of ALS patients was not very different from that in the control tissue. In contrast, CO activity was significantly reduced in all three regions of the spinal cord in patients with ALS, although the reduction was more marked in the ventral region. These results suggest that reactive oxygen species may attack the mitochondrial respiratory chain, leading eventually to the degeneration of vulnerable motor neurons in the spinal cord, even though no obvious changes in the activity of antioxidant enzymes are detectable.

Adult↗

Reaction of phosphatidylcholine hydroperoxide in human plasma: the role of peroxidase and lecithin:cholesterol acyltransferase.

In order to elucidate the reason why phosphatidylcholine hydroperoxide is unstable in human plasma, 1-palmitoyl-2-linoleoylphosphatidylcholine hydroperoxide (PLPC-OOH) was incubated aerobically in human plasma at 37 degrees C, and its decomposition products were measured. The major product was the corresponding alcohol (PLPC-OH) and this reduction probably occurred by an enzymatic process since no acceleration in ascorbate depletion and no significant decrease in other plasma antioxidants were observed upon addition of PLPC-OOH. Cholesteryl linoleate hydroperoxide and its alcohol (Ch18:2-OH) were also detected as minor products. Similarly, 1-stearoyl-2-arachidonoylphosphatidylcholine hydroperoxide gave its alcohol (SAPC-OH) as a major product and cholesteryl arachidonate hydroperoxide and its hydroxide (Ch20:4=OH) as minor products. These oxidized cholesteryl esters are likely to be produced by the action of lecithin:cholesterol acyltransferase (LCAT) present in high-density lipoprotein (HDL) since (a) incubation of PLPC-OH and SAPC-OH in human plasma gave Ch18:2-OH and Ch20:4-OH, respectively, (b) isolated human HDL converted PLPC-OH to Ch18:2 OH and SAPC-OH to Ch20:4-OH while isolated human low-density lipoprotein was inactive for this conversion, and (c) formation of oxidized cholesteryl esters in plasma and HDL was inhibited by the LCAT inhibitor 5,5'-dithiobis(2-nitrobenzoic acid). A possible beneficial role of LCAT for converting phosphatdylcholine hydroperoxide to cholesteryl ester hydroperoxide is also discussed.

Adult↗

Interleukin 3 activates not only JAK2 and STAT5, but also Tyk2, STAT1, and STAT3.

It has been described that interleukin 3 (IL3) activates JAK2, which in turn stimulates STAT5 activation. We found, however, that IL3 induces tyrosine-phosphorylation of Tyk2 as well as JAK2 in IL3-dependent mouse cell lines, FDC-P2 and Ba/F3. Furthermore, we found that IL3 induces activation of not only STAT5 but also STAT1 and STAT3. Taken together with other observations, these results indicate that IL3, erythropoietin and thrombopoietin share a common JAK-STAT signaling pathway.

Animals↗

Development of an integrated radiotherapy network system.

PURPOSE: To introduce the process of developing an integrated radiotherapy network. METHODS AND MATERIALS: We developed a new radiotherapy treatment-planning system in 1987 that we named the Computer Tomography (CT) simulator. CT images were immediately transported to multiimage monitors and to a planning computer, and treatment planning could be performed with the patient lying on the CT couch. The results of planning were used to guide a laser projector, and radiation fields were projected onto the skin of the patient. Since 1991, an integrated radiotherapy network system has been developed, which consists of a picture archiving and communicating system (PACS), a radiotherapy information database, a CT simulator, and a linear accelerator with a multileaf collimator. RESULTS: Clinical experience has been accumulated in more than 1,000 patients. Based on our 7 years of experience, we have modified several components of our original CT simulator and have developed a second generation CT simulator. A standard protocol has been developed for communication between the CT scanner, treatment planning computer, and radiotherapy apparatus using the Ethernet network. As a result, treatment planning data can be transported to the linear accelerator within 1 min after completion of treatment planning. CONCLUSION: This system enables us to make optimal use of CT information and to devise accurate three-dimensional (3D) treatment-planning programs. Our network also allows for the performance of fully computer-controlled dynamic arc conformal therapy.

Computer Communication Networks↗