The direct effect of FK506 and rapamycin on interleukin 1(beta) and immunoglobulin production in vitro.
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Cell Line↗
Biomedical subjects
T Oka
Publications and source records attributed to T Oka.
Condon modulation spectroscopy of solid hydrogen and measurement of the temperature dependence of the Q1(0) transition.
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Journal Article↗
A simple method for detecting single base substitutions and its application to HLA-DPB1 typing.
We have developed a simple and reliable method, PCR-PHFA (polymerase chain reaction dependent preferential homoduplex formation assay), for detection of single base substitutions within PCR amplicons. This technique is based upon strand competition during hybridization between a double labeled amplicon, prepared from biotin and DNP labeled primers, and an unlabeled amplicon. Under the precisely controlled temperature gradient, the preferential formation of a homoduplex over a heteroduplex occurs. After annealing, the identical sequence of the double labeled and unlabeled amplicon resulted in a low population of regenerated double labeled dsDNA due to strand exchange between them. Even when the two differed by only a single base substitution, double labeled molecule was regenerated efficiently because of preferential homoduplex formation. The regenerated double labeled molecule was captured onto a streptavidin coated microtiter plate and quantified enzymatically with a chromogenic substrate. The technique has been successfully applied in HLA-DPB1 typing. Furthermore, we detected a mutated gene even in the presence of a large excess of the corresponding normal gene.
Base Sequence↗
Effect of vitamin B6 deficiency on the expression of glycogen phosphorylase mRNA in rat liver and skeletal muscle.
The effect of vitamin B6 deficiency on the expression of glycogen phosphorylase mRNA in rat liver and skeletal muscle was investigated. The level of phosphorylase mRNA in the muscle of vitamin B6-deficient rats was reduced to 40% of that in the control rats. By contrast, the phosphorylase mRNA level was increased 5-fold in the liver of the deficient animals. It was also found that the expression of the beta-actin gene, generally regarded as a 'housekeeping' gene, was unaffected by B6 deficiency in the muscle but was enhanced in the liver of the deficient animals. These observations suggest that vitamin B6 may modulate the transcriptional activation of the phosphorylase gene in a tissue-specific manner.
Actins↗
Feasibility of agarose microbeads with xenogeneic islets as a bioartificial pancreas.
A bioartificial pancreas, that is, transplantation of islets of Langerhans (islets) which are enclosed in a semipermeable membrane, has been proposed as a treatment for type I diabetes. The islets are immuno-isolated from the host by the semipermeable membrane preventing rejection while maintaining control of glucose metabolism for an extended period. The purpose of the current research is to evaluate the feasibility of preparing agarose microbeads with xenogeneic hamster islets as a bioartificial pancreas in streptozotocin induced diabetic mice. In the recipients with a low level of anti-hamster antibodies, the combination of encapsulation of hamster islets in 5% agarose microbeads and in vitro culture of them prolonged xenograft survivals. Four of 6 recipients were still normoglycemic at 100 days after implantation. However, the same procedure was not effective in the recipients which were sensitized in advance by transplantation of free hamster islets and thus had high levels of anti-hamster antibodies. The average normoglycemic period was 32 days. Antibodies permeated through the microbeads and activated complement on the cell surfaces. The network of agarose microbeads was rendered dense by increasing the concentration of agarose to restrict the diffusion of antibodies. Graft survivals were prolonged with increasing concentrations of agarose. As an analysis using diffusion equations predicted, the survivals were inversely proportional to the diffusion coefficient of IgG in each agarose gel. Islet xenotransplantation was enabled by the combination of the microbeads with a concentration of agarose higher than 7.5% and in vitro culture even in recipients having a high level of preformed antibodies.
Animals↗
Strategy for developing microbeads applicable to islet xenotransplantation into a spontaneous diabetic NOD mouse.
A bioartificial pancreas (BAP) created through the encapsulation of islets of Langerhans (islets) in a semipermeable membrane has been proposed as a promising approach to treating insulin-dependent diabetes patients. A nonobese diabetic (NOD) mouse, which shares many features of human insulin-dependent diabetes mellitus, is an ideal model for evaluating the function of BAP. However, the functions of BAPs that have been developed have been limited in NOD mice. We propose novel microbeads that can realize long-term BAP function in NOD mice. The novel microbeads were composed of agarose and poly(styrene sulfonic acid) (PSSa) mixed gel. A polyion complex layer between PSSa and polycationic polybrene was formed on and just inside the microbead, and the microbead surfaces were further covered by polyanions to produce anionic surface charges. The islets in the novel microbeads were intraperitoneally implanted. Graft-functioning periods were dependent on both PSSa concentration and the kinds of polyanion. Islets in the microbeads composed of 5% agarose and 5% PSSa, which had an outermost surface covered by carboxymethyl cellulose, produced normoglycemic periods of more than 60 days in all five recipients. Control mice receiving either transplants of unenclosed islets or islets in agarose microbeads showed normoglycemic periods of less than 12 days. We believe that agarose/PSSa microbeads are promising for producing semipermeable membranes that enable xenotransplantation of islets in spontaneous diabetes mellitus.
Animals↗
Effects of preoperative chemotherapy on DNA ploidy patterns, cell cycle, and histological findings in gastric and colonic cancer patients.
The effects of preoperative chemotherapy on gastric and colonic cancers have yet to be evaluated fully. In this study, its effects were assessed by studying DNA ploidy patterns, cell cycles, and histological findings in such patients. Thirty-nine patients with gastric or colonic cancer were given preoperative chemotherapy with UFT (an admixture of tegafur and uracil). Biopsy specimens for analysis were obtained before chemotherapy through a gastroscope or colonoscope and after chemotherapy from resected tumors. The DNA ploidy patterns and cell cycles were evaluated using a flow cytometer and the tissues were examined histologically. The DNA ploidy pattern was diploid (D) in 12 gastric and 13 colonic cancer patients and aneuploid (A) in 10 and 4 patients, respectively. After chemotherapy, the pattern changed in nine gastric (A-->D: 7, D-->A: 2) and six colonic cancer patients (A-->D: 3, D-->A: 3) and was unchanged in the remaining patients. Cell cyclic analysis showed decreased G1- and increased S-phase fractions in 10 of 12 patients with gastric and 6 of 10 patients with colonic cancer. Histologically, decreased tumor cellularity, increased fibrosis, and/or cytological changes were observed in both cancers after chemotherapy. Gastric and colonic cancers in which the DNA ploidy pattern changed from aneuploid to diploid, G1- decreased and S-phase increased, and/or histological changes were observed, were considered to have responded to preoperative UFT administration.
Adult↗
The increase in the intracellular Ca2+ concentration induced by mechanical stimulation is propagated via release of pyrophosphorylated nucleotides in mammary epithelial cells.
Mechanical stimulation of one mammary tumor cell in culture induced an increase in its intracellular calcium concentration which spread to surrounding cells. The increase in calcium can also be induced by addition of a solution in which cultured mammary tumor cells were stimulated by repeated pipetting (solution after pipetting cells, SAPC). The activity of the SAPC was completely abolished by treatment with snake venom phosphodiesterase or pyrophosphatase. Uridine triphosphate (UTP), uridine diphosphate (UDP) and ATP (1 microM each) were detected in the SAPC, whereas 5'-UMP and 5'-AMP were produced by phosphodiesterase digestion. A mixture of UTP, UDP and ATP (1 microM each) elicited a calcium response which was comparable to that induced by SAPC, while UTP, UDP or ATP alone at 1 microM elicited a small increase in calcium concentration in mammary tumor cells. Suramin, a competitive antagonist of P2 purinoceptors, diminished the spreading of the calcium wave induced by mechanical stimulation. It also blocked the responses to SAPC, UTP, UDP and ATP. These findings suggest that the mechanical stimulation results in the release of UTP, UDP and ATP into the extracellular space which mediates induction of the spreading calcium response via P2U-type purinoceptors.
Adenosine Triphosphate↗
Marked clinical improvement in patients with hepatocellular carcinoma by surgical removal of extended tumor mass in right atrium and pulmonary arteries.
Two patients with advanced hepatocellular carcinoma presented severe exertional dyspnea because of extension of a tumor into the right side of the heart. Removable of the tumor thrombus by open-heart surgery ameliorated the symptoms in each case, but their subsequent courses differed considerably. One patient survived for as long as 8 months thanks to successive multi-disciplinary treatments, whereas the other patient died suddenly 1 month after the surgery. The first patient's hepatocellular carcinoma was more differentiated, and the dyspnea was caused by a low cardiac output due to the intracardiac tumor mass, not by pulmonary embolism as in the second patient's case. We conclude that successive multidisciplinary treatments to control the growth of hepatocellular carcinoma is the most important approach and is indispensable for improving the prognosis.
Adult↗
A comparative histological and immunohistochemical study of thymomas with and without myasthenia gravis.
Because myasthenia gravis (MG) is frequently associated with thymoma, in this study the histological patterns of thymomas from 11 patients with MG (group A) were compared with those from 8 patients without MG (group B). An immunohistochemical examination was also conducted to determine whether the thymoma associated with MG is the site where autoantibodies are produced or secreted. Lymphoid follicles (LFs) and medullary differentiation (MD) were histologically evident only in group A in 4 and 5 patients, respectively, but were completely absent in group B. Moreover, an elevated serum antiacetylcholine receptor antibody titer was found in group A. Typical LFs were histologically and phenotypically similar to the lymph follicles seen in reactive lymph nodes. The number of cells expressing the B-cell antigen differed between groups A and B in terms of IgM- or IgD-bearing cells in the mantle zones and LN1-positive cells in the germinal centers of LFs. Thus, it is thought that LFs consist of B cells under stimulatory conditions and that these B cells may have the potential to produce autoantibodies in MG; however, since the differentiation of these Ig-bearing cells to plasma cells was hardly evident, the thymoma itself is possibly not the site of autoantibody production or secretion in patients with MG.
Adult↗
Idiopathic portal hypertension in renal transplant recipients: report of two cases.
We present herein the cases of two patients who developed idiopathic portal hypertension (IPH) following renal transplantation. Both patients had been treated with azathioprine and prednisolone for 6 years and 4 months and for 4 years and 7 months, respectively, and presented with splenomegaly and thrombocytopenia suggesting hypersplenism. Celiac angiography showed a dilated splenic artery and vein in both patients. When the splenic artery was obliterated with a balloon catheter in case 1, the portal venous pressure decreased from 51 cmH2O to 36 cmH2O, and the direction of the superiomesenteric venous blood flow became hepatopetal rather than hepatofugal. These results suggested that the spleen might have played an important role in the development of IPH in these two patients. A splenectomy was therefore performed, immediately following which the portal venous pressure decreased remarkably, and the esophageal varices disappeared during the postoperative follow-up period. Microscopic examination of liver biopsies taken at the operation revealed lymphoplasmacytic infiltration with bile duct hyperplasia but no evidence of periportal fibrosis, and electron microscopy demonstrated very mild perisinusoidal fibrosis. Thus, the histological changes seen in the livers of these patients seemed not to have caused the portal hypertension. In conclusion, although few patients develop IPH after renal transplantation, we should be aware of its possibility and consider splenectomy as the treatment of choice.
Adult↗
Pseudomyxoma peritonei due to adenocarcinoma of the lung: case report.
A rare case of pseudomyxoma peritonei whose primary site was presumed to be the lung is reported. A 76-year-old woman was admitted to Hospital presenting with progressive abdominal distention. She had been admitted twice, 2 and 1 year previously for the evaluation of high plasma carcinoembryonic antigen (CEA) level, of 11.6 ng/ml. Chest computed tomography (CT) scan and chest X-ray film on the third admission revealed a nodular lesion in the left lower lung field, and transbronchial lung biopsy (TBLB) revealed mucus-producing tall columnar epithelial carcinoma. Paracentesis revealed gelatinous ascitic fluid. At laparotomy, appendix and ovary were normal, and there were many small cystic tumors on the peritoneal surface and omentum. The patient died 2 years later, after repeated episodes of dynamic ileus. The lung and abdominal tumors gradually increased in size during the 2-year period, but she developed no respiratory symptoms. Based on both the clinical and pathophysiological findings, the final diagnosis made was pseudomyxoma peritonei whose origin was a lung adenocarcinoma.
Adenocarcinoma↗
Hemodilution reduces early reperfusion injury in an ex vivo rabbit lung preservation model.
We sought to reduce early ischemia-reperfusion injury after lung preservation by an initial brief period of hemodilute reperfusion. Left lungs of New Zealand White rabbits were ventilated with room air and reperfused in an ex vivo ventilation-perfusion apparatus after 18 hours of storage at 10 degrees C. Lungs were randomly assigned to one of three groups (n = 6) according to the composition of initial reperfusate. In group 1 (control), preserved lungs were reperfused with whole blood for 20 minutes (hematocrit, 38%). In the experimental groups, blood was diluted to a hematocrit of 10% with Ringer's lactate (group 2) or low-potassium-dextran solution (group 3) for the first 10 minutes of reperfusion, followed immediately by whole blood for 10 minutes. Oxygen tension of left ventricular effluent at the end of the 20-minute assessment period was significantly higher in both hemodiluted groups (mean +/- standard error of the mean: group 2, 81.3 +/- 6.6 mmHg; group 3, 77.0 +/- 9.5 mmHg, versus Group 1, 46.3 +/- 7.4 mmHg; p < 0.006). Similarly, mean tracheal airway pressure was reduced in the hemodiluted groups, suggesting improved compliance (group 2; 3.1 +/- 0.3 mmHg; group 3, 2.8 +/- 0.6 mmHg; versus group 1, 6.5 +/- 1.4 mm Hg; p < 0.05). An initial 10-minute period of hemodilute reperfusion appears to reduce early pulmonary ischemia-reperfusion injury in this 18-hour ex vivo rabbit lung preservation model.
Airway Resistance↗
Enhancing effects of pertussis toxin B oligomer on the immunogenicity of influenza vaccine administered intranasally.
Influenza vaccines together with pertussis toxin B oligomer (PTB) purified from a culture supernatant of Bordetella pertussis were administered intranasally into mice to test for an adjuvant effect of the PTB. An inactivated virus vaccine and an ether-treated HA vaccine prepared from influenza virus A/Yamagata/120/86 (H1N1) and formulated with PTB, stimulated production of serum haemagglutinin inhibition (HI) antibody and pulmonary and endotracheal secretory IgA antibody to high titres. In addition, mice immunized with the influenza vaccines formulated with PTB were protected against exposure with a challenge virus. These results demonstrate that PTB can enhance the immunogenicity of influenza vaccines administered intranasally.
Adjuvants, Immunologic↗
Influence of Korean pine (Pinus koraiensis)-seed oil containing cis-5,cis-9,cis-12-octadecatrienoic acid on polyunsaturated fatty acid metabolism, eicosanoid production and blood pressure of rats.
The effects of dietary Korean pine (Pinus koraiensis)-seed oil containing a peculiar trienoic acid (cis-5,cis-9,cis-12-18:3, pinolenic acid, approximately 18%) on various lipid variables were compared in rats with those of flaxseed (Linum usitatissimum L.) oil, safflower (Carthamus tinctorius L.) oil and evening primrose (Oenothera biennis L.) oil under experimental conditions where the effects of different polyunsaturated fatty acids could be estimated. In Sprague-Dawley rats fed on diets containing 100 g fat and 5 g cholesterol/kg, the hypocholesterolaemic activity of pinolenic acid was intermediate between alpha-linolenic and linoleic acids. Analysis of the fatty acid composition of liver phosphatidylcholine indicated that, in contrast to alpha-linolenic acid, pinolenic acid does not interfere with the desaturation of linoleic acid to arachidonic acid. However, the effects on ADP-induced platelet aggregation and aortic prostacyclin production were comparable. When spontaneously hypertensive rats were fed on diets containing 100 g fat/kg but free of cholesterol, gamma-linolenic and pinolenic acids, as compared with linoleic acid, increased prostacyclin production and tended to reduce platelet aggregation. In addition, pinolenic acid attenuated the elevation of blood pressure after 5 weeks of feeding. Thus, the results of the present studies indicate the beneficial effects of pinolenic acid on various lipid variables.
Animals↗
Inhibition of GTP hydrolysis by Sar1p causes accumulation of vesicles that are a functional intermediate of the ER-to-Golgi transport in yeast.
The SAR1 gene product (Sar1p), a 21-kD GTPase, is a key component of the ER-to-Golgi transport in the budding yeast. We previously reported that the in vitro reconstitution of protein transport from the ER to the Golgi was dependent on Sar1p and Sec12p (Oka, T., S. Nishikawa, and A. Nakano. 1991. J. Cell Biol. 114:671-679). Sec12p is an integral membrane protein in the ER and is essential for the Sar1 function. In this paper, we show that Sar1p can remedy the temperature-sensitive defect of the sec12 mutant membranes, which is in the formation of ER-to-Golgi transport vesicles. The addition of Sar1p promotes vesicle formation from the ER irrespective of the GTP- or GTP gamma S-bound form, indicating that the active form of Sar1p but not the hydrolysis of GTP is required for this process. The inhibition of GTP hydrolysis blocks transport of vesicles to the Golgi and thus causes their accumulation. The accumulating vesicles, which carry Sar1p on them, can be separated from other membranes, and, after an appropriate wash that removes Sar1p, are capable of delivering the content to the Golgi when added back to fresh membranes. Thus we have established a new method for isolation of functional intermediate vesicles in the ER-to-Golgi transport. The sec23 mutant is defective in activation of Sar1 GTPase (Yoshihisa, T., C. Barlowe, and R. Schekman. 1993. Science (Wash. DC). 259:1466-1468). The membranes and cytosol from the sec23 mutant show only a partial defect in vesicle formation and this defect is also suppressed by the increase of Sar1p. Again GTP hydrolysis is not needed for the suppression of the defect in vesicle formation. Based on these results, we propose a model in which Sar1p in the GTP-bound form is required for the formation of transport vesicles from the ER and the GTP hydrolysis by Sar1p is essential for entering the next step of vesicular transport to the Golgi apparatus.
Biological Transport↗
Mutational analysis of the Sar1 protein, a small GTPase which is essential for vesicular transport from the endoplasmic reticulum.
SAR1 encodes a 21-kDa GTPase, which is required for vesicle formation from the endoplasmic reticulum in yeast. Although it belongs to the expanding small GTPase superfamily, there are interesting structural features that are unique to the Sar1 protein. We performed a site-directed mutational study to identify the amino acid residues that are essential for the Sar1p function. Among seven mutants we constructed, four are functionless by themselves, while two confer temperature sensitivity to cells. When the mutant proteins are overproduced in wild-type cells, all of these six show a dominant negative effect on cell growth. The replacement by serine of the only cysteine residue present in Sar1p caused no significant change in the growth phenotype. These findings are not only important for analyzing the mechanism of the Sar1p action in yeast, but will also be very useful for studying the function of Sar1p counterparts in higher eukaryotes.
Amino Acid Sequence↗
Benchmark test of neutron transport calculations: indium, nickel, gold, europium, and cobalt activation with and without energy moderated fission neutrons by iron simulating the Hiroshima atomic bomb casing.
A benchmark test of the Monte Carlo neutron and photon transport code system (MCNP) was performed using a bare- and energy-moderated 252Cf fission neutron source which was obtained by transmission through 10-cm-thick iron. An iron plate was used to simulate the effect of the Hiroshima atomic bomb casing. This test includes the activation of indium and nickel for fast neutrons and gold, europium, and cobalt for thermal and epithermal neutrons, which were inserted in the moderators. The latter two activations are also to validate 152Eu and 60Co activity data obtained from the atomic bomb-exposed specimens collected at Hiroshima and Nagasaki, Japan. The neutron moderators used were Lucite and Nylon 6 and the total thickness of each moderator was 60 cm or 65 cm. Measured activity data (reaction yield) of the neutron-irradiated detectors in these moderators decreased to about 1/1,000th or 1/10,000th, which corresponds to about 1,500 m ground distance from the hypocenter in Hiroshima. For all of the indium, nickel, and gold activity data, the measured and calculated values agreed within 25%, and the corresponding values for europium and cobalt were within 40%. From this study, the MCNP code was found to be accurate enough for the bare- and energy-moderated 252Cf neutron activation calculations of these elements using moderators containing hydrogen, carbon, nitrogen, and oxygen.
Cobalt↗