Search PubMed⌕ Search

Biomedical subjects

K Ohkura

Publications and source records attributed to K Ohkura.

At least 19 recordsLinked to original sources

[Selections of aortic reconstruction procedures and brain protection methods during aortic arch repairs; including mid-term survival and freedom from cerebral infarction].

Aortic reconstruction procedures and brain protection methods are very important among operative factors that have direct influence on surgical results. We nowadays use hypothermic circulatory arrest (HCA) with or without retrograde cerebral perfusion (RCP) as brain protection methods during hemiarch replacement (HAR) and selective cerebral perfusion (SCP) during total arch replacement (TAR) using 4-branched arch graft. The purpose of this study was to verify the appropriateness of this strategy. From April 1997 to August 2001, we performed 120 TAR assisted by SCP and 30 HAR assisted by HCA with or without RCP. Incidences of in-hospital death and postoperative neurological dysfunction were compared between the 2 groups. In-hospital deaths were 4 (3.3%) and 1 (3.3%), permanent neurological dysfunction were 3 (2.5%) and 1 (3.3%), temporary neurological dysfunction were 4 (3.3%) and 1 (3.3%), 3-year survival were 92 +/- 3% and 97 +/- 3% and cerebral infarctions after discharge were 2 and 0 in TAR and HAR, respectively. Appropriate selections of aortic reconstruction procedures and brain protection methods lead to good operative results in aortic arch repairs.

Aged↗

Modification of cell response to insulin by membrane-acting agents in rat white adipocytes: analysis of structural features by computational simulation.

The effect of membrane-acting agents, biscoclaurine alkaloids (cepharanthine, tetrandrine, isotetrandrine), carbobenzoxy-D-Phe-L-Phe-Gly (z-FFG), and tyrphostin AG17, on the insulin-involved fatty acid synthesis by an beta-agonist (e.g., isoproterenol) in adipocytes was examined. The alkaloids dose-dependently enhanced the insulin-involved fatty acid synthesis in rat white adipocytes, stabilized the C(6)-NBD-PC (1-acyl-2-[6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-caproyl]-sn-glycero-3-phosphatidylcholine) model membrane, and suppressed the phospholipase A(2)-induced phospholipid degradation. In contrast, z-FFG had no effect on the fatty acid synthesis or the membrane stability. Tyrphostin AG17 suppressed insulin action, but promoted the model membrane stabilization. In the same culture conditions as for the fatty acid synthesis assay, cepharanthine, z-FFG and tyrphostin AG17 had no effect on the transcript levels of glucose transporter isoforms (GLUT 1, 4) and hexokinase isozymes (HK I, II) in rat white adipocytes. Thus, these membrane-acting agents modify the insulin action via a change in the cell membrane condition, and do not directly act on the insulin-involved glucose metabolism. Then we analyzed the structural conformation of these membrane-acting agents by computational simulations. The alkaloids had an elliptic macrocyclic structure, and the order of ellipticity (cepharanthine>tetrandrine>isotetrandrine) agreed with that of the modifying ability for insulin action. The distribution of electrostatic potential fields of these alkaloids was essentially equal by turn in surrounding with the dipole moments. Both in z-FFG and tyrphostin AG17, the distribution pattern of electrostatic potential fields was different from that of the alkaloids. Judging from these results, we concluded that the electrostatic potential field is a good index of the modification of insulin action, and the elliptic structure in these alkaloids is regarded with the modification of insulin action.

Adipocytes↗

Dietary gamma-linolenic acid dose-dependently modifies fatty acid composition and immune parameters in rats.

gamma-linolenic acid (GLA) has been reported to improve several inflammatory disorders through regulation of eicosanoid production. However, since GLA is a precursor of arachidonic acid, it may bring about increasing tissue arachidonic acid levels with subsequent pro-inflammatory events. To explore this possibility, we examined the effect of high-dose GLA acid on the fatty acid profile of immune cells, leukotriene B4 production by peritoneal exudate cells and immunoglobulin productivity of mesenteric lymph node lymphocytes of Sprague-Dawley rats. Male rats were fed 10% fat diets containing graded levels, 0, 20, 40 and 60% of GLA for 3 weeks. The results showed the distinction in activity of metabolizing GLA between immune cells and liver. Thus, in immune cells such as mesenteric lymph node and spleen lymphocytes and peritoneal exudate cells, more dihomo-gamma-linolenic acid was found than in the liver. Leukotriene B4 production by peritoneal exudate cells was significantly suppressed when fed the highest level of GLA suggesting a lower risk of allergic reaction. Moreover, immunoglobulin productivity in mesenteric lymph node lymphocytes was promoted by dietary GLA. The present study indicates that a high dose of GLA may exert anti-inflammatory effects through suppression of leukotriene B4 release and strengthening of gut immune system, thus ameliorating allergic reaction.

Animals↗

Changes in bite force and occlusal contact area after orthognathic surgery for correction of mandibular prognathism.

OBJECTIVE: This study examined the long-term changes of bite force and occlusal contact area in patients with prognathous after orthognathic surgery with a newly developed pressure-sensitive sheet (Dental-Prescale; Fuji Photo Film Co). STUDY DESIGN: Fifty-seven patients with prognathous were examined. Bite force and occlusal contact area were measured just before operation and at 2 weeks, 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years after operation. Forty control subjects with normal occlusion were also measured. RESULTS: The bite force and occlusal contact area of the patients were significantly greater than the preoperative level at 1 year, 2 years, and 3 years after operation. However, they were still significantly lower than the control subject level even at 3 years after operation. CONCLUSIONS: This study suggests that orthognathic surgery improves the bite force and occlusal contact area of patients with prognathous. However, at 3 years from the time of operation, patients had not reached control subject levels.

Adolescent↗

Acid-catalyzed photoreaction of 6-chloro-1,3-dimethyluracil and mesitylene: formation of photocycloadducts and their characterization.

In contrast to the previously reported short time required (1 h) for photolysis of 6-chloro-1,3-dimethyluracil (6-CIDMU) and mesitylene, in the presence of TFA, resulting in two major products: 1,3,6,8,10-pentamethylcyclooctapyrimidine derivative (1d), and diazapentacyclo[6.4.0.0(1,3).0(2,5).0(4,8)]dodecane (2c), prolonged irradiation (18h) of this same mixture yields novel pentalenopyrimidine derivatives, including diazapentacyclo[6.4.0.0(1,3).0(2,6).0(4,8)]dodecane (3c).

Acids↗

Electrocyclic rearrangement of pentamethylcyclooctapyrimidine-2,4-diones: reaction pathway into a 9,11-diazapentacyclo-[6.4.0.0(1,3).0(2,5).0(4,8)]dodecane system and a 9,11-diazapentacyclo [6.4.0.0(1,3).0(2,6).0(4,8)]dodecane system.

Photolysis of 6-chloro-1,3-dimethyluracil and mesitylene in the presence of trifluoroacetic acid (TFA) at low temperature gave 1,3,5,7,9- and 1,3,6,8,10-pentamethylcyclooctapyrimidine-2,4-diones (1b, 1c). Sequential photoreaction of the former (1b) resulted in the formation of 9,11-diazapentacyclo[6.4.0.0(1,3).0(2,5).0(4,8)]dodecane-2,4-dione (2b) by way of 9-exo-methylene derivative (7b) and cyclobutaquinazoline (8b). On the other hand, UV-irradiation of 1c led to the bond shift isomer (5c) whose photolysis in the presence of TFA gave rise to the formation of the [6.4.0.0(1,3).0(2,6).0(4,8)]dodecane isomer (3c).

Journal Article↗

[Clinicopathological studies on localized cemento-osseous dysplasia of the jaws].

The aim of this study was to clarify the entity of localized cemento-osseous dysplasia (COD), which occurs mainly in the posterior mandible. The clinical, radiographical, and histopathological features of 51 patients with COD were retrospectively studied. Radiographic features of the COD were classified into four types, according to the appearance of calcified bodies with related teeth and without related teeth. Pathological features of the COD were classified into four grades, based on the maturation of cemental masses. The results are summarized as follows: 1. Forty-four (86%) of the 51 patients were women. The mean age of the total group was 52.5 years, and 98% of COD lesions occurred in the posterior mandible. Clinical symptoms of COD were significantly more frequent in cases without related teeth (87%) than in cases with related teeth (55%). 2. The radiolographical calcification of COD was not related to the mean age, but it was related to the grade of histopathological maturation. 3. The four progressive stages of COD were recognizable both radiographically and histopathologically. The early stage is the osteolytic process, the intermediary stage is the cementoblastic process, the mature stage is the cementosclerotic process, and the end stage is necrotization of the cemental mass. These results suggested that localized COD in the posterior mandible had progressive stages both radiographically and histopathologically. The entity of localized cemento-osseous dysplasia was identified with focal cemento-osseous dysplasia, which was reported by Summerlin and Tomich.

Adult↗

Interactions of dietary fats and proteins on fatty acid composition of immune cells and LTB4 production by peritoneal exudate cells of rats.

The interaction of dietary fats and proteins on lipid parameters of rats was studied using safflower oil (linoleic acid-rich), borage oil (gamma-linolenic acid-rich) or perilla oil (alpha-linolenic acid-rich) in combination with casein or soybean protein. The experiment was focused on the fatty acid composition of immune cells and the leukotriene B4 production by peritoneal exudate cells. Serum total cholesterol, triglyceride, and phospholipid levels were low in perilla oil-fed or soybean protein-fed rats. Fatty acid compositions of serum and liver phospholipids reflected those of dietary fats. However, feeding borage oil resulted in a marked increase in the proportion of dihomo-gamma-linolenic acid in phospholipids of peritoneal exudate cells, spleen lymphocytes, and mesenteric lymph node lymphocytes in relation to those of liver and serum. It is suggested that activities of metabolic n-6 polyunsaturated fatty acids are different between immune and other tissues. In addition, the magnitude of the reduction of the proportion of linoleic acid of perilla oil in immune cells was considerably more moderate than serum and liver, indicating a different degree of interference of alpha-linolenic acid with linoleic acid metabolism. Leukotriene release from peritoneal exudate cells was in the order of safflower oil > borage oil > perilla oil groups as reflecting the proportion of arachidonic acid, and tended to be lower in soybean protein-fed groups. These suggest an anti-inflammatory property of gamma-linolenic acid as well as alpha-linolenic acid tended to be strengthened when they were combined with soybean protein than with casein.

Animals↗

Three-dimensional magnetic resonance imaging of lung and liver tumors in mice by use of transversal multislice magnetic resonance images.

PURPOSE: To diagnose lung and liver tumors experimentally induced in mice in three-dimensional magnetic resonance (MR) images constructed by superimposing transversal multislice MR images of thoracic and abdominal regions taken under a high magnetic field of 7.05 tesla (T). METHODS: Lung and liver tumors were induced by administration of urethane to A/J mice and implantation of transplantable colon-26 cells into BALB/c mice, respectively. Two-dimensional (2-D) multislice MR images from the thoracic to abdominal regions were taken under the proton density-weighted conditions. Each organ in the 2-D MR images was pseudocolored, and a three-dimensional (3-D) image was constructed by superimposing them on a UNIX computer, using volume-rendering software. RESULTS: In the normal mouse, each organ in the thoracic and abdominal regions was three-dimensionally imaged and was clearly distinguished from the others. In mice with tumors in the lung or liver, the pathologic changes in the tissue could be visualized in 3-D images. CONCLUSIONS: The MR images three-dimensionally constructed by use of a method combining MR imaging under a high magnetic field of 7.05 T and a computer technique using volume-rendering software was useful for diagnosis of lung and liver tumors experimentally induced in mice.

Abdomen↗

Measure of bite force and occlusal contact area before and after bilateral sagittal split ramus osteotomy of the mandible using a new pressure-sensitive device: a preliminary report.

PURPOSE: This study examined bite force and occlusal contact area in prognathic patients before and after bilateral sagittal split ramus osteotomy of the mandible using a newly developed pressure-sensitive sheet (Dental-Prescale, Fuji Photo Film Co, Tokyo, Japan). PATIENTS AND METHODS: Twenty-five prognathic patients were examined. Bite force and occlusal contact area were measured preoperatively, at 2, 4, and 8 weeks, and at 3 and 6 months after surgery. The bite force and occlusal contact area of 20 healthy subjects were also measured. RESULTS: Both bite force and occlusal contact area of the patients were the lowest 2 weeks after surgery and recovered to the preoperative level between 8 weeks and 3 months. Subsequently, they increased slowly and exceeded the preoperative level at 6 months after surgery. However, even at 6 months, both the bite force and the occlusal contact area of the patients were still only about half or less than that of healthy subjects. CONCLUSION: This pressure-sensitive device can be used as a simple indicator of postoperative recovery and occlusal improvement in patients following orthognathic surgery.

Adolescent↗

Evaluation of the cytotoxic effects of bis-quaternary ammonium antimicrobial reagents on human cells.

The cytotoxic effects of newly synthesized bis-quaternary ammonium compounds (bis-QACs) and benzalkonium chloride were investigated on skin and blood cells, namely normal human epidermal keratinocytes of neonatal foreskin, a normal human skin fibroblast cell line NB1RGB, erythrocytes and a lymphoma cell line JM. The bis-QACs tested were 4, 4'-(1,6-hexamethylenedithio)bis(1-octylpyridinium iodide) (4DTBP-6, 8), N,N'-tetramethylenebis(1-dodecyl-4-carbamoylpyridinium iodide) (4BCAP-4,12), N,N'-hexamethylenebis(1-decyl-4-carbamoylpyridinium iodide) (4BCAP-6,10), 4,4'-(1,4-tetramethylenedicarbonyldiamine) bis (1-decylpyridinium iodide) (4DCABP-4,10), 4,4'-(1, 4-tetramethylenedicarbonyldiamine) bis (1-dodecylpyridinium iodide) (4DCABP-4,12), 4,4'-(1, 4-phenyldicarbonyldiamine)bis(1-dodecylpyridinium iodide) (4DCABP-P, 12), and 4,4'-(1, 6-hexamethylenedioxydicarbonyl)bis(1-dodecylpyridinium iodide) (4DOCBP-6,12). All bis-QACs consisted of two identical alkylpyridinium rings and bridge structure linking rings to each other have a methylene bridge but only 4DCABP-P,12 has a phenyl ring as a bridge. Most of the LD(50) values in acute cytotoxic assays of these bis-QACs tended to be lower than those of benzalkonium chloride. However, the comparison of the antibacterial activity against cytotoxic effects on several human cells revealed that bis-QACs, especially 4DTBP-6,8, have wide concentration ranges showing sufficient antibacterial activity and lower cytotoxic effect on human cells (except for 4DOCBP-6,12), although benzalkonium chloride caused significant human cell damage at the concentrations necessary for antibacterial activity. Moreover, judging from the LD(50) value of 4DTBP-6,8 [67 microM, a 6.7-fold higher concentration than the upper value of MIC] obtained in an artificial human skin model TESTSKIN, 4DTBP-6,8 is thought to be a more effective and safer antiseptic reagent for application to the skin surface than benzalkonium chloride. Taken together, bis-QACs are expected to be a promising new generation of antimicrobial QACs.

Anti-Bacterial Agents↗

Analyses of insulin-potentiating fragments of human growth hormone by computative simulation; essential unit for insulin-involved biological responses.

We analyzed the structural features of insulin-potentiating fragments of human growth hormone by computative simulations. The peptides were designated from the N-terminus sequences of the hormone positions at 1-15 (hGH(1-15); H2N-Phe1-Pro2-Thr3-Ile4-Pro5-Leu6-Ser7-Arg8-L eu9-Phe10-Asp11-Asn12-Ala13-Met14-Leu15 -COOH), 6-13 (hGH(6-13)), 7-13 (hGH(7-13)) and 8-13 (hGH(8-13)), which enhanced insulin-producing hypoglycemia. In these peptide molecules, ionic bonds were predicted to form between 8th-arginyl residue and 11th-aspartic residue, and this intramolecular interaction caused the formation of a macrocyclic structure containing a tetrapeptide Arg8-Leu9-Phe10-Asp11. The peptide positions at 6-10 (hGH(6-10)), 9-13 (hGH(9-13)) and 10-13 (hGH(10-13)) did not lead to a macrocyclic formation in the molecules, and had no effect on the insulin action. Although beta-Ala13hGH(1-15), in which the 13th-alanine was replaced by a beta-alanyl residue, had no effect on insulin-producing hypoglycemia, the macrocyclic region (Arg8-Leu9-Phe10-Asp11) was observed by the computative simulation. An isothermal vibration analysis of both of beta-Ala13hGH(1-15) and hGH(1-15) peptide suggested that beta-Ala13hGH(1-15) is molecule was more flexible than hGH(1-15); C-terminal carboxyl group of Leu15 easily accessed to Arg8 and inhibited the ionic bond formation between Arg8 and Asp11 in beta-Ala13hGH(1-15). The peptide of hGH(8-13) dose-dependently enhanced the insulin-involved fatty acid synthesis in rat white adipocytes, and stabilized the C6-NBD-PC (1-acyl-2-[6-[(7-nitro-2,1,3benzoxadiazol-4-yl)amino]-caproyl]-sn- glycero-3-phosphatidylcholine) model membranes. In contrast, hGH(9-13) had no effect both on the fatty acid synthesis and the membrane stability. In the same culture conditions as the fatty acid synthesis assay, hGH(8-13) had no effect on the transcript levels of glucose transporter isoforms (GLUT 1, 4) and hexokinase isozymes (HK I, II) in rat white adipocytes. Judging from these results we considered that the macrocyclic structure in human growth hormonal peptides is regarded with the modification of insulin action, and hGH(8-13) is an essential sequence for the modification of insulin action. This hGH(8-13) peptide modifies the insulin action via stabilizing the cell membrane, and does not directly act on the insulin-involved glucose metabolism.

Adipocytes↗

Elucidation of strict structural requirements of brefeldin A as an inducer of differentiation and apoptosis.

Brefeldin A (BFA) can induce a wide variety of human cancer cells to differentiation and apoptosis and is in development as an anticancer agent. To elucidate structural requirements for cytotoxicity and induction of differentiation and apoptosis, BFA was structurally modified into various derivatives including 4-epi-BFA in this study. Their inducing activities of apoptosis were evaluated with their cytotoxicities, DNA fragmentation and morphological changes in human colon cancer cell HCT 116. The cytotoxicity of 4-epi-BFA (TX-1923) (IC50 = 60 microM) was 300 times lower than that of BFA (IC50 = 0.2 microM). Furthermore, 4-epi-BFA induced DNA fragmentation and apoptotic morphological changes at much higher concentrations (70 and 50 microM, respectively) than BFA (0.11 and 0.36 microM, respectively). These results indicated that the configuration of 4-hydroxyl group of brefeldin A plays a key role in the cytotoxicity and induction of apoptosis. On the other hand, 7-O-acetyl-BFA, 4-O-acetyl-BFA, and 4,7-di-O-acetyl-BFA exhibited potential activities in cytotoxicity and inducibility of apoptosis. We suggested that the structural determinants for BFA include the moiety of the Michael acceptor, the conformational rigidity of the 13-membered ring, and the configuration of 4-hydroxyl group.

Apoptosis↗

Dietary effects of eicosapentaenoic and docosahexaenoic acid esters on lipid metabolism and immune parameters in Sprague-Dawley rats.

Sprague-Dawley rats were fed eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) ethyl esters at the 2% level for 3 weeks to clarify their effects on immune functions. In the rats fed EPA or DHA, serum cholesterol, triglyceride, and phospholipid (PL) levels were significantly lower than those in the rats fed safflower oil. In PL fractions of serum, liver, lung, splenocytes, and peritoneal exudate cells (PEC), increases in linoleic and dihomo-gamma-linolenic acid contents and a decrease in arachidonic acid (AA) content were observed in the rats fed EPA or DHA. In addition, the EPA content increased in the rats fed EPA and DHA. In the rats fed EPA or DHA, a decrease of LTB4 productivity and an increase of LTBs productivity were observed in the PEC, in response to the treatment with 5 microM calcium ionophore A23187 for 20 min. The changes in leukotriene production were more marked in EPA-fed rats than in DHA-fed rats. These results suggest that dietary EPA affects lipid metabolism and leukotriene synthesis more strongly than DHA.

Animals↗

Analysis of structure-permeability correlation of nitrophenol analogues in newborn rat abdominal skin using semiempirical molecular orbital calculation.

Theoretical analysis of the permeation process in percutaneous absorption is important for the molecular design of bioavailable transdermal drugs. In the present study, we examined the difference in permeability of nitrophenols across newborn rat abdominal skin and analyzed the structure-permeability correlation by molecular orbital calculation. The permeable rate of o-, n-, p-nitrophenol and 2,4-, 2,5-, 2,6-dinitrophenols was 0.291, 0.212, 0.085 and 0.042, 0.109, 0.027 micromol/cm2/h, respectively. The permeability of the nitrophenols correlated with their pKa values, indicating the ionizing process related to the permeation through the skin. The pKa values better correlated with the ionization potential (IP) energies than lowest unoccupied molecular orbital (LUMO) energies. Solvation free energies (dGW) of molecular form nitrophenols correlated better with permeabilities (pA) than partition coefficients (log P). In analyzing the dGW values with the permeability at pH 7.4, o-nitrophenol outlay from the theoretical line by ortho-effect. We conclude solvation free energy is a practical parameter and very useful for the molecular design of transdermal drugs.

Abdomen↗

Dietary effect of EPA-rich and DHA-rich fish oils on the immune function of Sprague-Dawley rats.

The dietary effect of fish oils (FOs) rich in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on the immune function of Sprague-Dawley rats was compared with that of safflower oil. After 3 weeks of feeding at the 10% level of a dietary fat, the IgG and IgM production by splenocytes and IgG production by mesenteric lymph node (MLN) lymphocytes were significantly higher in the FO-fed rats, while no significant difference was found in IgA or IgE productivity by both the spleen and MLN lymphocytes. In the FO-fed rats, peritoneal exudate cells released a lower amount of LTB4, reflecting their lower arachidonic acid level, and a higher amount of LTB5, reflecting their higher EPA level in phospholipids. On these EPA-rich FO exerted a stronger effect than DHA-rich FO immune functions.

Adjuvants, Immunologic↗

Dietary effect of guar gum and its partially hydrolyzed product on the lipid metabolism and immune function of Sprague-Dawley rats.

The dietary effect of the water-soluble dietary fibers (WSDF), guar gum, partially hydrolyzed guar gum (PHGG), glucomannan, highly methoxylated (HM) pectin, on the serum lipid level and immunoglobulin (Ig) production of Sprague-Dawley rats was compared with that of water-insoluble cellulose. Although serum total cholesterol and triglyceride levels were significantly lower in the rats fed with WSDF than in those fed with cellulose, a decrease in the level of phospholipids was only observed in the rats that had been fed on guar gum or glucomannan. In addition, all WSDF feeding enhanced IgA productivity in the spleen and mesenteric lymph node lymphocytes, although the increase in serum IgA level was only observed in the rats fed on WSDF, and not on PHGG. When mesenteric lymph node lymphocytes were cultured in the presence of various concentrations of guar gum or glucomannan, no significant increase in Ig production was apparent. These data suggest that WSDF indirectly enhanced the Ig production of lymphocytes, and that serum lipid reduction and IgA production-enhancing activities of WSDF were dependent on their molecular sizes.

Animals↗