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Biomedical subjects

M Ogata

Publications and source records attributed to M Ogata.

At least 91 records · Page 5Linked to original sources

Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro.

UNLABELLED: The production of proinflammatory cytokines, such as tumor necrosis factor (TNF) a, interleukin (IL)-6, and IL-8, increases in patients with sepsis; marked production causes organ failure and septic shock. We previously reported that ketamine suppressed lipopolysaccharide (LPS)-induced TNF-alpha production in mice. However, there are no reports on the effect of ketamine on cytokine production in human whole blood. Therefore, in this study, we investigated the efficacy of ketamine on LPS-induced TNF-alpha, IL-6, and IL-8 production and recombinant human (rh) TNF-a-induced IL-6 and IL-8 production in human whole blood. After adding different doses of ketamine to whole blood, the blood was stimulated with LPS or rhTNF. After incubation, the plasma TNF-alpha activity and IL-6 and IL-8 concentrations were measured using the L929 cell cytotoxic assay or an enzyme-linked immunoassay. Ketamine significantly suppressed LPS-induced TNF-alpha production at concentrations >20 microg/mL. At concentrations >100 microg/mL, ketamine also significantly suppressed both LPS-induced and rhTNF-induced IL-6 and IL-8 production. In this study, we demonstrated that ketamine directly inhibits the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-8 in human whole blood. IMPLICATIONS: We found that ketamine suppressed lipopolysaccharide-induced tumor necrosis factor alpha, interleukin (IL)-6, and IL-8 production and recombinant human tumor necrosis factor-induced IL-6 and IL-8 production in human whole blood. Ketamine directly suppresses proinflammatory cytokine production.

Anesthetics, Dissociative↗

Structure determination of rubredoxin from Desulfovibrio vulgaris Miyazaki F in two crystal forms.

The structures of two crystal forms (form I, P3221, a = b = 43.7, c = 50.7 A; form II, P21, a = 27.3, b = 44.9, c = 51.2 A and beta = 90. 6 degrees ) of the rubredoxin from Desulfovibrio vulgaris Miyazaki F have been solved by the molecular-replacement method. Form I has been refined at a resolution of 2.0 A to an R value of 20.8% and includes 32 water molecules. Form II includes 86 water molecules and has been refined at 1.9 A resolution to an R value of 17.5%. In form II, there are three molecules in the asymmetric unit with the molecules related by a non-crystallographic 32 symmetry axis. In both crystal forms, it was found that only a few residues effectively participate in the formation of intermolecular contacts along both the crystallographic (form I) and the non-crystallographic (form II) 32 axes. The crystal structure of the form II crystal is compared with those of other rubredoxin molecules from anaerobic bacteria. From this comparison, a similarity in the core region, which is composed of aromatic residues and includes the active centre, has been revealed.

Amino Acid Sequence↗

Carrageenan primes leukocytes to enhance lipopolysaccharide-induced tumor necrosis factor alpha production.

We have previously reported that pretreatment with carrageenan (CAR) enhances lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production in and lethality for mice. Whole blood cultured in vitro was used to show that CAR pretreatment results in about a 200-fold increase in LPS-induced TNF-alpha production. CAR by itself did not induce TNF-alpha production. However, CAR-treated cultured medium sensitized whole blood to make more LPS-induced TNF than did saline-treated cultured medium in vitro. It was also demonstrated that CAR pretreatment increases TNF-alpha mRNA levels of both blood cells and peritoneal exudate cells, but not of bone marrow cells. Immunoelectron microscopic analysis revealed that polymorphonuclear leukocytes and macrophages are TNF-alpha-producing cells in CAR-treated mice. In CAR-treated mice, TNF-alpha was seen early after LPS injection in leukocytes in hepatic sinusoids and on the surfaces of endothelial cells. TNF-alpha was also detected late after LPS injection in hepatocytes which become edematous. These results suggest that CAR primes leukocytes to produce TNF-alpha in response to LPS and that they play an important role in the pathogenesis of liver injury.

Animals↗

Intravascular lymphomatosis presenting as an ascending cauda equina: conus medullaris syndrome: remission after biweekly CHOP therapy.

A 63 year old man developed dysaesthesia in the legs followed by a subacute ascending flaccid paraparesis with sacral sensory and autonomic involvement. Intravascular lymphomatosis (IVL) was favoured by the presence of low grade fever and raised serum C reactive protein, CSF pleocytosis, raised lymphoma markers (serum LDH, soluble IL-2 receptor), and steroid responsiveness. Only muscle, among several organ biopsies, confirmed IVL. A cytogenetic study of the bone marrow showed chromosome 6 monosomy, as previously reported. The monosomy of chromosome 19, which bears the intercellular cell adhesion molecule-1, newly found in this case, may be related to the unique tumour embolisation of IVL. The CHOP regimen (six courses in 12 weeks) using granulocyte colony stimulating factor (G-CSF) led to gradual resolution of myeloradiculopathy and laboratory supported remission lasting for more than 13 months. The biweekly CHOP with G-CSF support may be a choice of chemotherapy in averting rapidly fatal IVL.

Antineoplastic Combined Chemotherapy Protocols↗

Hypoglycemic coma masquerading thyrotoxic storm.

A 59-year-old woman was hospitalized in hypoglycemic coma. Although hypoglycemia was promptly reversed, she was in a somnolent, restless state with tachycardia, tremor, profuse sweating, and high body temperature. Thyrotoxic storm was highly suspected and vigorous antithyroid regimens gradually brought her up to normal mental and cardiovascular states in several days. However, profound generalized myopathy necessitated the maintenance with a respirator. One month later, an episode of angina pectoris was followed by generalized convulsion, coma, and death in a few days. Neuroimaging study disclosed posterior leukoencephalopathy syndrome. This case is instructive in that hypoglycemic coma may masquerade the major symptomatology of thyrotoxic storm, and that profound myopathy and angiopathic or angiospastic processes of the brain and the heart may interfere with the outcome.

Brain↗

One autopsy case of an elderly traffic accident victim with tetralogy of Fallot.

The case of a 61-year-old male traffic accident victim with Tetralogy of Fallot (TOF) is reported. The autopsy revealed massive hemorrhages in the subcutaneous tissue, muscle, and subarachnoidal space. Furthermore, multiple fractures of ribs, sternum and thoracic vertebrae were observed. Histopathological examination revealed changes characteristic of trauma, such as acute lung congestion, acute renal cortical necrosis, and embolization in the lungs and kidney. These autopsy and histological observations indicated that traumatic shock was cause of his death. Moreover, histologically, we observed changes due to his congenital heart disease, such as right ventricular hypertrophy, heart failure cells in the lungs, sclerosis of the liver, and hyaline degeneration in the kidney. Furthermore, ischemic changes, shrinkage or loss of neurons, were seen in hippocampus, and swelling of astrocytes in both cortex and hippocampus were also observed. These observations lead us to speculate that a hypoxic episode may have caused his accidental death while driving.

Accidents, Traffic↗

[Extracellular matrix influencees proliferation of cultured porcine lens epithelial cells].

PURPOSE: To investigate whether extracellular matrix (ECM) influences the proliferation of cultured lens epithelial cells (LECs). MATERIAL AND METHODS: Porcine LECs were cultured in F-12 nutrient mixture supplemented with 5% fetal bovine serum (FBS) for 24 or 96 hours on the dishes coated with laminin, fibronectin, type I collagen, or type IV collagen. As a control, LECs were cultured on uncoated dishes. Twenty-four or ninety-six hours later, the number of cells was determined. We determined the proliferation ratio of the number of cells 96 hours after plating to the number of cells 24 hours after plating. This ratio was used to assess the cell proliferation. RESULTS: The ratio of the LECs on the uncoated dishes was 2.3. Dish coating with type I or type IV collagen, and fibronectin significantly increased this ratio (4.0, 3.5, and 3.0, respectively), whereas coating with laminin did not affect this ratio (2.5). CONCLUSION: These findings suggest that ECM influences cultured porcine LEC proliferation.

Animals↗

Bonding to caries-affected dentin using self-etching primers.

PURPOSE: To evaluate resin bond strengths to caries-affected versus normal dentin using three self-etching primer adhesive systems. MATERIALS AND METHODS: Carious lesions were excavated and then bonded with one of three self-etching primer adhesive systems (Clearfil Liner Bond 2, Clearfil Liner Bond 2V, A.R.T. Bond). A crown was then built up using a resin composite to a height of 4 mm. Five to six serial slabs approximately 0.7 mm thick were sectioned perpendicular to the bonded surface. The bonded caries-affected or normal dentin areas were isolated to create an hourglass configuration with a cross-sectional area of approximately 1 mm2. The specimens were subjected to tensile stress at a crosshead speed of 1.2 mm/min. The bonded interfaces to caries-affected and normal dentin were examined with an SEM. RESULTS: Clearfil Liner Bond 2 and Clearfil Liner Bond 2V produced high bond strengths to normal dentin, but significantly lower bonds than to caries-affected dentin. (P < 0.05). For A.R.T. Bond, there was no statistically significant difference between types of dentin. All three bonding systems produced thin (+/- 0.5-1.5 microns) hybrid layers in normal dentin. When used on caries-affected dentin, all self-etching primer systems produced hybrid layers that were twice as thick as those produced in normal dentin.

Acid Etching, Dental↗

Physical and functional association between thymic shared antigen-1/stem cell antigen-2 and the T cell receptor complex.

Thymic shared antigen-1 (TSA-1)/stem cell Ag-2 (Sca-2) is a glycosylphosphatidylinositol (GPI)-anchored antigen expressed on lymphocytes. We have previously demonstrated that a signal via TSA-1/Sca-2 inhibits T cell receptor (TCR)-mediated T cell activation and apoptosis. To elucidate a molecular mechanism for TSA-1-mediated modulation of the TCR-signaling pathway, we examined whether TSA-1 is physically coupled to the TCR in the present study. TSA-1 was clearly associated with CD3zeta chains in T cell hybridomas, activated T cells, and COS-7 cells transfected with TSA-1 and CD3zeta cDNA. The physical association was confirmed on the surface of T cells in immunoprecipitation and confocal microscopy. The analysis using stable and transient transfectants expressing a transmembrane form of TSA-1 revealed that the association of CD3zeta did not require the GPI anchor of TSA-1. Finally, tyrosine phosphorylation of CD3zeta chains was induced after stimulation with anti-TSA-1, suggesting that a functional association between these two molecules also exists. These results imply that the physical association to CD3zeta underlies a regulatory role of TSA-1/Sca-2 in the TCR-signaling pathway.

Animals↗

Eosinophilia associated with adult T-cell leukemia: role of interleukin 5 and granulocyte-macrophage colony-stimulating factor.

To clarify the mechanism of eosinophilia in adult T-cell leukemia (ATL), we studied three ATL patients having marked eosinophilia. Eosinophil-predominant colony-stimulating activity was detected in the serum of one patient and in the conditioned media (CM) from cultured ATL cells from two patients. Soluble interleukin 5 (IL-5), but no interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), was detected in sera from all patients. On the other hand, GM-CSF was produced in vitro by ATL cells from all cases, whereas detectable IL-3 and IL-5 was produced by cells from only one, suggesting that in the other two cases, the serum IL-5 was produced by the normal reacting lymphocytes. The fact that no patient showed marked neutrophilia supports the possibility that IL-5 may have a leading role in the development of eosinophilia, with GM-CSF produced by ATL cells playing a complementary role.

Aged↗

Aging and oxidative stress in neurodegeneration.

The effect of oxidative stress on the function of brain synapse, the difference in susceptibility of synapse to hyperoxia with age, and the changes in vitamin E status by stress and aging were investigated. Synaptic membrane permeability to sucrose was increased with age. When rats were subjected to hyperoxia, the membrane permeability on each age increased significantly. The susceptibility of synapse of 25 month old rats exposed to stress was about 2.5 times higher than unexposed old rats. The synaptic plasma membrane fluidity decreased significantly either in response to hyperoxia or during aging. The thiobarbituric acid reactive substances (TBARS) in the synaptic plasma membranes increased with age, and those in the membranes of oxygen-exposed rats were higher than in the unexposed rats. The cholesterol/phospholipids (C/P) ratio of the membranes increased significantly with age, and the values in the membranes of oxygen-exposed rats increased more significantly than in unexposed rats of each age. In a measurement of fatty acid content in the membranes, the content of docosahexaenoic acid (DHA, C22:6) decreased significantly during aging and by hyperoxia. These results suggest that free radicals derived from oxygen may attack nerve terminals and peroxidize the membrane, resulting in the deterioration of function of brain synapse, and that susceptibility of synapse to oxidative stress was significantly increased with age. Vitamin E content in the synaptic plasma membranes decreased with age. When rats were subjected to oxidative stress, the content was lower in each age than in normal rat membranes. An intraperitoneal administration of vitamin E prior to stress reduced these abnormalities. It is obvious that vitamin E contributes to the protection against nerve terminal dysfunction caused by oxidative stress.

Aging↗

Hydrodynamic properties of water in contractile system.

When muscle fragments are compressed, intracellular water leaks out. Unexpectedly, y-intercepts of regression lines in resting and active states become negative, implying "negative compression". It seems that in resting state there is a kind of mechanical equilibrium between proteins and water. This protein-water complex in muscle behaves like a synthesized elastomer under moderate extension, (less than 10%). Employing the data presented by Richie & Wilkie (1958), validity of elastomer model is examined. Compression study also shows that in active state a frictional drag of intracellular water decreases markedly. It leads to the assumption that the negative mechanical resistance may play a role in regenerative activation.

Animals↗

Photodegradation products of methylprednisolone suleptanate in aqueous solution--evidence of a bicyclo[3.1.0]hex-3-en-2-one intermediate.

Two major photodegradation products of methylprednisolone suleptanate (sodium 11 beta, 17 alpha-dihydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxooctyl+ ++]oxy]-pregna-1,4-diene-3,20-dione) in aqueous solution irradiated with white fluorescent light at 2000 lux for 28 days at 25 degrees C were isolated by preparative high-performance liquid chromatography and characterized. Structures of the photodegradation products were determined as sodium 11 beta,17 alpha-dihydroxy-5 alpha, 6 alpha-dimethyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxoocty l]-oxy]-19-norpregna-1(10),3-diene-2,20-dione and sodium 1 beta, 11 beta-epoxy-17 alpha-hydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1, 8-dioxooctyl]oxy]-19 alpha-pregn-4-ene-2.20-dione. Formation of these compounds, especially the 1,11-epoxy analogue, strongly supports the existence of the bicyclo[3.1.0]hex-3-en-2-one intermediate in the photorearrangement of steroidal cross-conjugated dienones. The intermediate can account for all the major ketonic and phenolic products; these products are generated from the intermediate after subsequent transformations and/or further skeletal rearrangements. The 1,11-epoxy analogues were obtained from the prednisolone steroids in high yields by irradiation with a high-pressure mercury lamp.

Drug Stability↗

Stimulation of leukaemic cells from adult T-cell leukaemia patients with bacterial superantigens.

Bacterial superantigens stimulate T cells in a manner that is restricted to the Vbeta of the T-cell receptor. We examined the ability of adult T-cell leukaemia (ATL) cells to respond to these superantigens. Mononuclear cells from 10 patients were cultured with staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin-1 (TSST-1), and their response was determined by MTT assay and 3H-thymidine incorporation assay. Cells from six patients showed a specific response to a single superantigen. In two cases the cells responded to TSST-1 and bore Vbeta2, the known target of TSST-1. In three cases the cells responded to SEA with one bearing Vbeta9, a target of SEA, and one bearing Vbeta16. In one case the cells responded to SEB. Most of the cells which proliferated in response to superantigens were determined genetically to be leukaemic. The response to TSST-1 was inhibited by anti-Vbeta2 antibody. The responding cells showed a strongly enhancement expression of interleukin-2 receptor. These findings indicate that leukaemic cells from a proportion of ATL patients have an ability to respond to T-cell receptor-dependent superantigens. This suggests that bacterial infection in such patients may contribute to the expansion of ATL cells.

Adult↗

Immunoreactive endothelin levels in the vitreous fluid are decreased in diabetic patients with proliferative retinopathy.

Endothelin (ET) plays an important role in the pathogenesis of various cardiovascular lesions. To elucidate the pathophysiologic significance of ET in the development of diabetic retinopathy, we determined immunoreactive ET levels in the vitreous fluid collected during vitrectomy in seven patients with non-insulin dependent diabetes mellitus with proliferative diabetic retinopathy and in 10 nondiabetic subjects as controls. Immunoreactive vitreous ET levels in diabetic patients with proliferative retinopathy (7.5 +/- 3.4 pg/ml, mean +/- SD) were significantly lower than those in the nondiabetic subjects (55.0 +/- 38.1 pg/ml; p < 0.005). The decreased rather than increased immunoreactive ET levels may simply reflect severe endothelial injury to the retinal vessels caused by diabetic microangiopathy rather than an important role in diabetic retinopathy.

Blood Pressure↗

Evolutionary relationships among Japanese pond frogs inferred from mitochondrial DNA sequences of cytochrome b and 12S ribosomal RNA genes.

The evolutionary relationships among Japanese pond frogs (Rana nigromaculata, R.porosa porosa, and R. p. brevipoda) were investigated by analyzing nucleotide sequences of mitochondrial cytochrome b (cyt b) and 12S rRNA genes. The nucleotide sequences of 444-bp segment of the cyt b gene and 410-bp segment of 12S rRNA gene were determined by the PCR-direct sequencing method using 18 frogs from 13 populations of Japanese pond frogs, and phylogenetic trees were constructed by the neighbor-joining and maximum likelihood methods using R. catesbeiana as an outgroup. The sequenced 444-bp segment of cyt b gene provided 69 variables sites, and the sequenced 410-bp segment of 12S rRNA gene provided 21 variables sites. The numbers of nucleotide substitutions per site of the cyt b gene within ingroup were 0.0022-0.0205 at the populational level, 0.0368-0.0462 at the racial or subspecific level, and 0.1038-0.1244 at the specific level, whereas those of the 12S rRNA gene were 0-0.0074 at the populational or subspecific level, and 0.0378-0.0456 at the specific level. Most nucleotide substitutions within ingroup occurred at the third codon position of the cyt b gene and were silent mutations. High frequencies of transitions relative to transversions were shown at cyt b and 12S rRNA genes within ingroup. The phylogenetic trees constructed from the nucleotide sequences of the cyt b gene showed that after outgroup R. catesbeiana separated from ingroup frogs, ingroup Japanese pond frogs diverged into R.nigromaculata and R.porosa, then the latter diverged into R.p. porosa, R.p. brevipoda (the typical Okayama race), and the Nagoya race of R.p.porosa. The phylogenetic trees constructed from the nucleotide sequences of the 12S rRNA gene also showed distinct divergence between two species, but not any divergence within species.

Amino Acid Sequence↗

An electron microscopic study of Helicobacter pylori in the surface mucous gel layer.

This study describes the distribution of spiral and coccoid forms of Helicobacter (H.) pylori within the surface mucous gel layer (SMGL) on human gastric mucosae. Gastric mucosae infected with H. pylori were obtained from surgically removed stomachs of 14 cases of gastric cancer. The glycocalyx of the spiral and coccoid forms of H. pylori was examined for specific lectin labeling. Coccoid forms were identified in 11 of these cases (78.6%). The SMGL, which was from 50 to 100 microns in thickness, contained H. pylori throughout its entire thickness. Variously-sized vacuole-like clear areas were present near H. pylori. The glycocalyx on both the spiral and coccoid forms was similar in its staining with the 8 types of lectins tested. However, the staining pattern of the lectins varied among different samples. The numerous fibrillae-like filaments radiated from the surface of the bacteria and appeared to link the bacteria to the surface mucous cells or the surrounding mucus. These fibrillae-like filaments were not specifically stained by the lectin reactions, suggesting absence of sugar molecules.

Adult↗