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Biomedical subjects

M Okuno

Publications and source records attributed to M Okuno.

At least 163 records · Page 9Linked to original sources

Purification and partial characterization of rat epididymal retinoic acid-binding protein, and its immunohistochemical localization.

Two types of retinoic acid-binding proteins, designated as epididymal retinoic acid-binding protein (ERABP) types A and B, have been purified to homogeneity from rat genital organs. ERABP types A and B had molecular weights of 19,000 and 18,500 and isoelectric points of 5.72 and 5.90, respectively. The absorption spectrum of ERABP complex with retinoic acid had two peaks at 277 and 354 nm, and showed similar uncorrected fluorescence spectra to that of cellular retinoic acid-binding protein (CRABP). These ERABPs were identified as major androgen-dependent epididymal proteins by amino acid sequences analyses. Furthermore, immunohistochemical examinations revealed that the ERABPs exist in the epithelium of the proximal portion of the epididymis and in the lumen of epididymal canal and seminal tract leading from the epididymis. The existence of ERABP strongly suggests that retinoic acid might be involved in the maturation of spermatozoa.

Amino Acid Sequence↗

[Usefulness and limitations of stress 201-thallium myocardial imaging in patients with Kawasaki disease].

Thallium-201 myocardial imaging was performed in 150 patients with a history of Kawasaki disease, aged 6 months to 16 years old. Forty-five patients were studied with ergometer exercise and 105 patients had dipyridamole administration. The findings of thallium imaging were compared with those of coronary angiography. Seventy-two cases with severe coronary stenosis (over 75%) were classified in 3 groups; 13 with the left anterior descending artery lesion, 31 with only the right coronary artery lesion and 28 with multi-vessel involvement. In 72 cases with severe coronary stenosis, the sensitivity of thallium imaging for detecting coronary stenotic lesions was 85%, 74% and 67% in the 3 groups, respectively. In 78 cases without severe coronary stenosis, 5 cases (6%) had persistent perfusion defects on thallium imaging, 3 of which were associated with dyskinesis of the left ventricle documented by cineangiography. They were considered to have damaged myocardium probably due to peripheral myocardial infarction or myocarditic problems. Thallium-201 myocardial imaging was proved to be a useful method to detect coronary stenosis, however its sensitivity for detecting lesions of the right coronary artery or multi-vessels was relatively low. This may be attributable to a significantly higher incidence of segmental stenosis (recanalization) with sufficient coronary flow and multiple coronary collateral vessels in patients with such lesions.

Adolescent↗

Phosphorothioate analogs of ATP as the substrates of dynein and ciliary or flagellar movement.

The phosphorothioate analog of ATP has a sulfur atom replacing a non-bridging oxygen atom of the triphosphate moiety of ATP. Due to the tetrahedral nature of the phosphorus atom, stereoisomers are known to exist, designated as the Sp and Rp isomers. We have reported [Shimizu & Furusawa (1986) Biochemistry 25, 5787] on the hydrolytic activity of the 22S dynein from Tetrahymena cilia towards the phosphorothioate analogs of ATP. In this paper, we extend our study and report on the microtubule-dynein dissociation by these analogs and on their ability to support sea urchin flagellar dynein enzymatic activity as well as ciliary or flagellar motility. It has been shown that the microtubule--22S-dynein complex is dissociated by the binding of ATP to the dynein enzymatic sites [Porter & Johnson (1983) J. Biol. Chem. 258, 6575]. We studied the dissociation by adenosine 5'-[alpha-thio]triphosphate (ATP[alpha S]), Sp or Rp, by light-scattering stopped-flow methods. The dissociation by (Sp)ATP[alpha S] was rapid and the rate of the light-scattering change by (Sp)ATP[alpha S] was a hyperbolic function of the nucleotide concentration, indicating that dissociation was a two-step process. On the other hand, (Rp)ATP[alpha S] up to 2 mM induced only slow and partial dissociation of the complex, while, in the presence of vanadate, it induced complete dissociation with a slightly higher rate (0.5 s-1). The adenosine 5'-[beta-thio]triphosphate (ATP[beta S]) isomers did not induce dissociation. The hydrolytic activity of the outer arm dynein from sea urchin sperm flagella towards these analogs was similar to that of 22S dynein. The ratios of Vmax (nmol.mg protein-1.min-1)/apparent Km (microM) of this dynein were 400-720, 53, 9.7, 0.62 and 0.028 for ATP, ATP[alpha S] (Sp or Rp), ATP[beta S] (Sp or Rp), respectively, in the presence of Mg2+ as the supporting cation. This dynein exhibited the same stereospecificity at beta phosphate as the 22S dynein or myosin. The detergent models of Tetrahymena or sea urchin spermatozoa were reactivated only by ATP or (Sp)ATP[alpha S] while other analogs were ineffective. The maximal beat frequency of the cilia or flagella reactivated by (Sp)ATP[alpha S] was one-quarter to one-half of that produced by ATP reactivation.

Adenosine Triphosphatases↗

Purification and partial characterization of a novel cellular retinol-binding protein, type three, from the piscine eyes.

A novel cellular retinol-binding protein, termed type three (CRBP III), was isolated from eyes of the bigeye of tuna. CRBP III showed a molecular weight of 15,400, an isoelectric point of 4.80, alpha 1-mobility in electrophoresis, and a lambda max of 350 nm. All-trans-retinol, the endogenous ligand, could be competitively displaced by retinoic acid but not by retinal. CRBP III was differentiated from purified piscine and rat cellular retinol-binding proteins (CRBP) and cellular retinoic acid-binding proteins (CRABP) by its amino-acid composition, electrophoretic mobility, fluorescence spectra and ligand-binding specificity.

Amino Acids↗

Plasma retinol transport system and taste acuity in patients with obstructive jaundice.

A study was conducted to elucidate the correlation between the plasma retinol transport system and taste acuity in patients with obstructive jaundice (OJ). Plasma levels of retinol, retinol-binding protein (RBP), transthyretin (TTR) and holo-RBP (retinol-RBP complex unbound to TTR), as well as the threshold of taste acuity, were determined in 8 cases with OJ (6 cases with common bile duct cancer and 2 cases with pancreas head cancer) and in 20 apparently healthy volunteers. These parameters were also measured serially in patients with OJ before and after percutaneous transhepatic biliary drainage (PTBD). Plasma levels of retinol, RBP and TTR were significantly decreased in every patients with OJ as compared with healthy controls, whereas changes in holo-RBP levels were not consistent. Taste acuity was found to be reduced in patients with decreased holo-RBP levels, while the acuity was preserved well in patients whose holo-RBP levels remained normal. Impaired taste acuity was rapidly improved in every patients after treatment with PTBD, significantly correlating with the recovery of plasma RBP and holo-RBP levels, and with the reduction of plasma total bilirubin levels. These results suggest that taste acuity is affected by the plasma retinol transport system, including serum levels of holo-RBP, from which retinol is delivered, presumably through a receptor-mediated manner, to the taste buds.

Adult↗

Inhibitory effect of acyclic retinoid (polyprenoic acid) on hepatic fibrosis in CCl4-treated rats.

A study was conducted to examine the inhibitory effect of acyclic retinoid (polyprenoic acid) on the development of hepatic fibrosis induced by CCl4 in rats. Oral administration of the compound brought about a significant reduction in both serum and tissue levels of immunoreactive prolyl hydroxylase, a key enzyme of collagen formation. The result indicated that the rate of collagen synthesis in the liver was decreased which was consistent with histological findings. Acyclic retinoid also decreased both AST and ALT activities in serum, demonstrating the reduction in hepatic parenchymal damage. This cytoprotective effect on parenchymal cells may be related, at least in part, to inhibition of hepatic fibrosis. No significant side effects were observed, despite a long-term administration of the acyclic retinoid. The present findings suggest the potential scope of therapy of hepatic fibrosis by retinoid.

Alanine Transaminase↗

Reduction of serum lipoprotein(a) levels in hyperlipidaemic patients with alpha-tocopheryl nicotinate.

The effect of low dose (600 mg/day) alpha-tocopheryl nicotinate on serum lipoprotein(a) (Lp(a] concentration was studied in 28 hyperlipidaemic patients. Serum lipids, lipoproteins and apolipoproteins, except for Lp(a), tended to increase after treatment. In particular, the changes in HDL-cholesterol and apo C-II levels were statistically significant. On the other hand, serum Lp(a) levels in all patients decreased significantly after 2 months of treatment. Furthermore, no difference between before and after treatment was observed in the group with initial Lp(a) levels less than 18 mg/dl, whereas Lp(a) concentrations decreased significantly after treatment in the group with levels greater than or equal to 18 mg/dl. The effects of probucol and alpha-tocopheryl nicotinate on serum Lp(a), total cholesterol and HDL-cholesterol were entirely different. Possible mechanisms of alpha-tocopheryl nicotinate on serum Lp(a) and lipoprotein metabolism are discussed.

Adult↗

Aortocoronary bypass surgery for coronary arterial lesions resulting from Kawasaki disease.

To establish the indications for aortocoronary bypass surgery on coronary artery lesions caused by Kawasaki disease, we analyzed surgical outcome in 26 patients. Ages at operation ranged from 1 to 17 years. All patients were followed up with selective coronary arteriography, thallium myocardial imaging, electrocardiography at rest, and the Master "two-step" and treadmill exercise tests for coronary insufficiency. Surgical outcome was analyzed by comparing results of patient examinations made preoperatively with those both at 1 month and 1 year postoperatively. One month after the operation, 25 (93%) of 27 internal mammary artery grafts and 6 (86%) of 7 saphenous vein grafts were patent; 1 year after the operation, 19 (86%) of 22 internal mammary artery grafts and 6 (67%) of 9 saphenous vein grafts were patent. By comparing the preoperative findings of myocardial imaging with those obtained 1 month after surgery, we found that 17 (68%) of 25 showed improvement and 3 (12%) of 25 were worse. At 1 year, 6 (29%) of 21 showed further improvement than at 1 month, suggesting increased development of the coronary bed after internal mammary artery graft anastomosis. Thus an internal mammary artery graft has proved to be satisfactory in the management of children with coronary artery obstruction caused by Kawasaki disease; it appears that both the quality of life and the life expectancy of those patients can be improved by the surgery.

Adolescent↗

Inhibitory effects of acyclic retinoid (polyprenoic acid) and its hydroxy derivative on cell growth and on secretion of alpha-fetoprotein in human hepatoma-derived cell line (PLC/PRF/5).

Acyclic retinoid (polyprenoic acid) has a slightly different structure from retinoic acid. However, acyclic retinoid acts similarly to retinoic acid, because both bind to cellular retinoic acid-binding protein and cellular retinoid-binding protein. F-type, with the same strong binding affinity. We studied the effects of acyclic retinoid, the 7-hydroxy derivative of acyclic retinoid (7OH-acyclic retinoid) and retinoic acid on a human hepatoma-derived cell line PLC/PRF/5 (Alexander cells). Acyclic retinoid inhibited cell growth with an ID50 value of 14 microM, and reduced cell viability with an LD50 value of 86 microM. The ratios of LD50 value to ID50 value were 6.1 for acyclic retinoid, 2.4 for 7OH-acyclic retinoid and 1.4 for all-trans-retinoic acid. Taking this ratio as a parameter of relative cytotoxicity, we concluded that acyclic retinoid is the least toxic compound. Growth inhibition of cells by acyclic retinoid was associated with the incorporation of 3H-thymidine in the logarithmic phase. Acyclic retinoid reduced secretion of alpha-fetoprotein (AFP) and reciprocally increased secretion of albumin in the culture media, suggesting that acyclic retinoid influences gene expression of these proteins. Thus, acyclic retinoid, one of the less toxic retinoids, inhibits cell growth of human cancer cell line PLC/PRF/5 and appears to alter gene expression of AFP and albumin toward a "normal" direction.

Acrylates↗

Inhibitory effect of acyclic retinoid (polyprenoic acid) on the secretion of alpha-fetoprotein in CCl4-treated rats.

A study was conducted to examine the inhibitory effect of acyclic retinoid (polyprenoic acid) on the secretion of alpha-fetoprotein (AFP) in rats with chronic liver damage induced by CCl4. Oral administration of the compound brought about a significant reduction of serum AFP levels at the time when liver cirrhosis was formed. Acyclic retinoid also decreased the activities of serum aminotransferases and ornithine carbamyl transferase, while it increased serum albumin levels, demonstrating the reduction of hepatic parenchymal damage. Significant negative correlation was observed between serum AFP and albumin levels. This cytoprotective effect of the retinoid on the parenchymal cell may well be related to the inhibition of the synthesis and/or secretion of AFP. No significant side effect was observed, despite a long-term administration of the compound. The present finding will provide a potential scope for the future use of acyclic retinoid for the treatment of chronic liver damage.

Animals↗

[Subsets of peripheral blood lymphocytes and tumor infiltrating lymphocytes in cancer patients received chemotherapy].

Forty-three patients with advanced cancer were evaluated for the changes of absolute counts of peripheral blood lymphocytes and lymphocyte subsets during chemotherapy or chemoimmunotherapy. In 27 patients who did not respond to the therapy, whole lymphocytes, T cells, helper/inducer T cells and NK cells decreased significantly in number. In contrast, they showed little decrease in 16 cases responded to the therapy. In situ immunohistochemical analysis of the tumor infiltrating lymphocytes was performed on the carcinoma tissues obtained from 25 gastric cancer patients. T cell infiltration, in which helper/inducer T cells were predominant over suppressor/cytotoxic T cells, and NK cell infiltration were found in most of the tissues comprised various carcinoma types of histology. Furthermore, an analysis of a gastric cancer patient treated with systemic administration of 3 BRMs and intratumoral injection of OK-432 indicated that infiltration of cytotoxic T cells and NK cells augmented by cytokines such as IFN-gamma produced from activated helper/inducer T cells and NK cells. Therefore, it is suggested that movements of helper/inducer T cells and NK cells relate to the response to chemotherapy and participate in prognosis of advanced cancer patients.

Adult↗

[An early cancer of the descending colon, histologically showing a poorly differentiated adenocarcinoma].

Reported is the case of a 71 year-old male with a poorly differentiated adenocarcinoma of the colon that had invaded the submucosal layer. A barium enema had revealed a polyp, 1.5 cm in diameter, in the descending colon, and an endoscopic polypectomy was performed. The resected specimen mainly consisted of an adenoma and a partial, poorly differentiated adenocarcinoma that had massively infiltrated into the submucosal layer. A left hemicolectomy was carried out, and no carcinoma was identified in the resected colon and/or the regional lymph nodes.

Adenocarcinoma↗

Anthraniloyl ATP, a fluorescent analog of ATP, as a substrate for dynein ATPase and flagellar motility.

We synthesized an anthraniloyl ATP (ant-ATP), which has a fluorescent anthraniloyl moiety at the OH group of ribose, to elucidate the mechanism of flagellar bend formation and its propagation in relation to the mechanochemical cycle of dynein ATPase. This fluorescent analog of ATP was efficiently hydrolyzed by 21 S dynein from sea urchin sperm flagella with Km = 7.6 microM, whereas the Km was 12 microM when ATP was used as the substrate. Similar Vmax values were obtained with both ATP and ant-ATP. Inhibition of the hydrolysis of ant-ATP by vanadate was a little smaller than that with ATP. Photosensitized cleavage of 21 S dynein heavy chains in the presence of ant-ATP and vanadate was also a little less efficient than that in the presence of ATP and vanadate. Ant-ATP also induced the disintegration of the trypsin-treated axoneme and the motility of demembranated sperm in a manner similar to ATP. When ATP was used as a substrate for the demembranated sperm, the apparent Michaelis constant for beat frequency (Km f) was 0.22 mM and the maximum frequency (fmax) was 36 Hz, whereas Km f) was 0.14 mM and fmax was 20 Hz for ant-ATP. Thus ant-ATP could be an efficient fluorescent analog of ATP for studying dynein ATPase and the mechanisms of flagellar motility.

Adenosine Triphosphatases↗

Fat emulsion in surgical patients with liver disorders.

Total parenteral nutrition (TPN) with fat emulsion was evaluated in 68 patients with liver disorders who were admitted to the First Department of Surgery, Osaka City University Medical School. All patients received transabdominal direct operation for esophageal varices. Immediately after their operations, 28 received TPN with carbohydrate and fat emulsion as an energy source (FAT group), and 40 received TPN with only carbohydrate as an energy source (non-FAT group). Liver function tests, blood glucose levels, intravenous fat tolerance tests, serum lipid levels, fatty acid composition of serum total lipids, and nitrogen balance of the two groups were compared during postoperative TPN. The administration of fat emulsion during postoperative TPN in patients with liver disorders did not worsen the results of liver function tests and the relatively low levels of blood glucose were retained, thereby correcting the abnormalities in the fatty acid composition of serum total lipids. Rates of clearance of fat emulsion during postoperative TPN were significantly higher than in the preoperative period, and changes in serum lipid levels revealed no tendency toward retention of fat emulsion administered intravenously. Nitrogen balance and change in body weight during postoperative TPN were similar in both groups. These results suggest that for patients with liver disorders, the administration of fat emulsion is useful during postoperative TPN.

Esophageal and Gastric Varices↗

Posterior extensive simultaneous multisegment decompression with posterolateral fusion for cervical myelopathy with cervical instability and kyphotic and/or S-shaped deformities.

From June 1978 to May 1988, posterior decompression with posterolateral fusion was performed at Tenri Hospital on 63 cases of cervical myelopathy with instability and/or malalignment including kyphotic and/or S-shaped deformities. Among 46 cases followed up for more than 1 year, 41 cases (89.1%) improved; 21 cases (45.7%) were rated excellent, six (13%), good; 14 (30.4%), fair; one (2.2%), unchanged; and four (8.7%), poor. On x-ray examination, bone consolidation at the bone implanted area was satisfactory in 30 cases (65.2%). Cervical instability disappeared at 55 cervical interspaces of 40 cases (78.6%). Displacement at unstable interspace disappeared or improved at 49 of 61 cervical interspaces (80.3%). Although cervical kyphosis or S-shaped deformity could not be improved, accelerated progression of these deformities appeared to be prevented.

Adult↗

[Sequential changes in plasma lipoprotein(a) as acute phase protein after myocardial infarction and surgery group].

The plasma lipoprotein(a), apo AI, apo B, and acute phase proteins, were studied in 21 patients with myocardial infarction and in 11 patients after surgery. In the both groups, C-reactive protein showed a rapid increase, and alpha 1 acid glycoprotein, alpha 1 antitrypsin and lipoprotein(a) followed by a moderate increase and restored to normal values after one month. Lipoprotein(a) increased to a maximum on day 11 in the myocardial infarction group, and on day 8 in the surgery group. Only slight changes in apolipoprotein AI and B were noted. We speculate that lipoprotein(a) is an acute phase protein that plays an important roles in recovery from trauma. Recently it was reported that the amino acid sequence of apolipoprotein(a) is partly identical to that of plasminogen. This sequence suggests that lipoprotein(a) and plasminogen are related immunochemically. We examined by immunoblotting technique whether our antibody for lipoprotein(a) is influenced by a plasminogen in plasma. By enzyme-linked immunosorbent assay, it was found that the purity of plasminogen does not influence determination of lipoprotein(a).

Acute-Phase Proteins↗