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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 397 records · Page 22Linked to original sources

Differential effects of the immunosuppressants cyclosporin A, FK506 and KM2210 on cytokine gene expression.

Cyclosporin A (CsA) inhibited interleukin 2 (IL-2), IL-3, interferon gamma (IFN gamma), GM-CSF and tumor necrosis factor alpha (TNF alpha) mRNA expression in spleen cells stimulated with concavalin A (Con A) when determined by the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. FK506 which has a similar immunosuppressive mechanism to that of CsA also showed the same inhibitory effects except for decreased IL-5 and IL-6 mRNA expression. In contrast, both CsA and FK506 enhanced transforming growth factor beta (TGF beta) and IL-1 beta mRNA expression. Another immunosuppressant KM2210 did not show any inhibitory effects on cytokine gene expression but rather enhanced IL-10, IL-6, TGF beta and IL-1 mRNA expression, thus suggesting that KM2210 has a completely different immunosuppressive mechanism from that of CsA and FK506. Anti-TFG beta 1 antibody abrogated the suppression by KM2210 of BALB/c anti-3H/He mixed lymphocyte reaction (MLR) whereas this antibody did not abrogate the suppression by CsA and FK506 of BALB/c anti-C3H/He MLR. These results indicate that TGF beta is one of the major cytokines in KM2210 immunosuppression, in addition to IL-10, but not in immunosuppression by CsA and FK506.

Animals↗

Laparoscopic retrieval of disconnected ventriculoperitoneal shunt catheters: report of two cases.

Two patients previously treated with ventriculoperitoneal shunt for hydrocephalus had the distal catheters disconnected, and they migrated to the free peritoneal cavity. The signs and symptoms of increased intracranial pressure occurred as a result of mechanical failure of the shunt system. Both patients successfully underwent a laparoscopic retrieval of the catheters using endoscopic grasping forceps, and revision of the ventriculoperitoneal shunt by inserting the new catheters into the peritoneal cavity was performed through a small entrance for the laparoscope. Recently, conventional laparotomy has been often replaced by laparoscopic surgery, and general surgeons are well familiar with the laparoscopic procedures. The significant advantage of this procedure is the ability to explore the entire peritoneal cavity for both diagnosis and treatment, and it is by far a less invasive approach than conventional laparotomy. The present report describes the laparoscopic procedure for removal of the migrated catheters and discusses its advantages over conventional laparotomy.

Adult↗

[Left thoracotomy approach for coronary reoperation].

We experienced reoperative coronary revascularization through a left thoracotomy in 12 patients between June 1992 and June 1994. All patients underwent grafting to the left coronary system except one, who underwent bypass procedure to the atrioventricular branch of the right coronary artery in addition to grafting to the left anterior descending artery, using the pedicled left internal thoracic artery, the gastroepiploic artery as a free graft, or a reversed saphenous vein graft. In one patient, revascularization was accomplished during temporary occlusion of the coronary artery without cardiopulmonary bypass. On the other hand, in 11 patients, cardiopulmonary bypass was used. Coronary bypass procedure was employed under the ventricular fibrillation with hypothermia in those but one, who underwent revascularization under the beating heart with cardiopulmonary support. All patients were hemodynamically stable in postoperative stage, and artificial ventilation time was not prolonged, with a mean time of 15.7 hours. Postoperative morbidity included reexploration for hemorrhage in one patient, convulsion in one, worsening of hemianopsia in one, ventricular arrhythmia in one, and wound complication in one, however, there were no hospital deaths. All patients underwent repeat coronary angiography, which revealed that all grafts were widely patient except one, which had inadequate flow due to diffuse narrowing. Based on these clinical results, we conclude that a left thoracotomy is a useful approach for reoperative coronary bypass procedures to reduce the surgical risk associated with a sternal reentry in properly selected patients.

Adult↗

Comparison of peripheral blood stem cells mobilized with granulocyte colony-stimulating factor with or without prior standard-dose chemotherapy in patients with malignancy.

We studied the effect of granulocyte colony-stimulating factor on the magnitude of peripheral blood stem cell mobilization in patients with malignancy. The leukapheresis products mobilized with granulocyte colony-stimulating factor alone at a steady state (a period of full hematopoietic recovery) (group 1) were compared with those obtained after cytotoxic chemotherapy using granulocyte colony-stimulating factor (group 2). In group 1, six patients underwent six courses of stem cell collection with a median of 20 l leukapheresis. In group 2, 10 patients underwent 12 courses of stem cell collection with a median of 10 l leukapheresis. Median yields of group 1 vs. group 2 were mononuclear cells (x 10(9)), 21.9 vs. 11.6; CD34+ cells (x 10(6)/l), 14.5 vs. 17.1; colony-forming unit for granulocyte-macrophage (/ml), 223 vs. 1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-forming unit for erythroid (/ml), 42 vs. 29; colony-forming unit for megakaryocyte (/ml), 26 vs. 59. While there were no statistically significant differences in the number of CD34+ cells between the two groups, granulocyte-macrophage-committed progenitor cells were more enriched in the apheresis products of group 2. The correlation between CD34+ cells and colony-forming unit for granulocyte-macrophage was poor. Our results demonstrate that granulocyte colony-stimulating factor can mobilize a sufficient number of progenitor cells into the peripheral blood for stem cell transplantation with or without prior chemotherapy.

Adolescent↗

[Treatment with bolus methylprednisolone for pure red cell aplasia after ABO incompatible bone marrow transplantation in a patient with chronic myelocytic leukemia].

Pure red cell aplasia (PRCA) was found in a male patient with chronic myelocytic leukemia after major ABO incompatible bone marrow transplantation (BMT). He had blood group O, and received BMT from an HLA identical sibling (blood group A). Erythrocyte-depleted marrow was transplanted. Methotrexate for short time and cyclosporine (CyA) were used for graft versus host disease (GVHD) prophylaxis. Engraftment of neutrophils and platelets were observed on day 14 and 22, respectively. The Ph1 chromosome disappeared on day 133. However engraftment of erythrocytes was not observed on day + 280. Bone marrow puncture revealed depletion of erythrocyte precursors. Anti-A isoagglutinin was persisted. There was no evidence of acute or chronic GVHD. Administration of prednisolone, discontinuance of CyA and subcutaneous infusion of recombinant human erythropoietin failed to improve PRCA. Bolus methylprednisolone (m-PSL) therapy started on day 284 resulted in rapid increase in reticulocyte counts within 6 days, which was followed by normal hemoglobin concentrations. We conclude that bolus m-PSL may be one treatment for PRCA after BMT.

ABO Blood-Group System↗

CCK activates excitatory ventral tegmental pathways to the posterior nucleus accumbens.

In urethane-anaesthetized male rats, electrical stimulation of the ventral tegmental area (VTA) produced either excitation (n = 26) or inhibition (n = 5) in the activity of neurones in the posterior nucleus accumbens (PNAc). Local administration of sulfatedcholecystokinin octapeptide (CCK8, 0.03 microgram) into the stimulation site enhanced the neuronal excitability in 10 out of 21 PNAc neurones that demonstrated the excitation to VTA stimulation, but did not affect the remaining 11 neurones. Similar administration, on the other hand, was without effect in any of PNAc neurones (n = 5) that displayed the inhibition to VTA stimulation. These results suggest that CCK8 may act at the VTA to elicit an activation of the excitatory pathways from the VTA to the PNAc.

Animals↗

Mitogenic effects of platelet-derived growth factor, fibroblast growth factor, transforming growth factor-beta, and heparin-binding serum factor for adult mouse Schwann cells.

Mitogenic effects of fetal calf serum (FCS), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF-beta), and forskolin to adult mouse Schwann cells were examined by bromodeoxyuridine (BrdU) incorporation and double immunofluorescence for S100 and BrdU. PDGF-BB, basic FGF, and TGF-beta 1 and beta 2 were all mitogenic for Schwann cells in media containing FCS. Forskolin suppressed the mitogenic activity of these factors. In serum-free media, PDGF-BB and bFGF were also mitogenic, but TGF-beta 1 and beta 2 were not. Heparin-binding fractions of FCS obtained by heparin-Sepharose chromatography synergized with TGF-beta 1 and beta 2 to produce a mitogenic response. Since PDGF-BB, acidic FGF, and basic FGF were not detected in these fractions by immunoabsorption and immunoblot assays, the presence of unidentified heparin-binding molecules in FCS bioactive for adult mouse Schwann cells is suggested.

Animals↗

A variant of Gerstmann-Sträussler-Scheinker disease carrying codon 105 mutation with codon 129 polymorphism of the prion protein gene: a clinicopathological study.

A case was reported of variant Gerstmann-Sträussler-Scheinker disease (GSS) carrying codon 105 mutation (Pro to Leu) with codon 129 polymorphism (Met/Val) of the prion protein (PrP) gene. The male patient had developed clumsiness of the right hand at age 42, and subsequently exhibited slowly progressive spastic paraparesis, ataxia, dysarthria, memory disturbance and apraxia. Myoclonus or periodic synchronous discharge was not observed. He died at age 53. The cerebral cortex and white matter showed atrophy, which was prominent in the frontal regions. There were numerous amyloid plaques throughout the cerebral cortex, which were reactive with the antibody to PrP, but not to beta/A 4 peptide. PrP immunostaining also revealed many amorphous deposits in the deep cortical layers, where neuronal loss and glial proliferation was evident. The cerebellum was almost intact, except a few amyloid plaques in the white matter. This variant GSS with codon 105 mutation has been found in four pedigrees, only in Japan up to the present, and the clinicopathological phenotype is summarized as follows: (1) onset at age 38-48, with a duration of 7-11 years, (2) prominent spastic paraparesis, associated with dementia and ataxia, (3) numerous amyloid plaques in the cerebral cortex, (4) amorphous PrP deposits with neuronal loss in the deep cortical layers, and (5) minor change of cerebellum.

Adult↗

Effects of 15-deoxyspergualin in vitro and in vivo on cytokine gene expression.

Reverse transcriptase-polymerase chain reaction showed that interleukin 3, IL-4, IL-5, IL-6, interferon-gamma and stem cell factor mRNA expression were higher in 15-deoxyspergualin-treated spleen cells than in control spleen cells. Increased IL-2 and IFN-gamma mRNA expression were observed in 15-deoxyspergualin-treated bone marrow cells. On the other hand, increased platelet counts in BALB/c-->C3H/He bone marrow chimeras were observed from days 20 to 33 in our previous work, when they were treated with 15-deoxyspergualin from days 14 to 25. In contrast, marked leukocytopenia and anemia were simultaneously observed, although a marked leukocytosis and a rapid recovery of anemia were observed on day 33 and thereafter. To analyze effects of 15-deoxyspergualin on hematopoiesis and the immune system, we examined mRNA expression in bone marrow and spleen cells from BALB/c-->C3H/He bone marrow chimeras treated with 15-deoxyspergualin from days 14 to 25. Reverse transcriptase-polymerase chain reaction showed that IL-3, IL-4, IL-6, stem cell factor, granulocyte colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor mRNA expression were higher in 15-deoxyspergualin-treated chimeras than in control chimeras, indicating that these cytokines are responsible for an enhancement of hematopoiesis. It was conceivable that IL-6 supported thrombopoiesis in concert with other cytokines. On the contrary, increased IFN-gamma, IL-2, IL-3, IL-4, and IL-10 mRNA expression may play an immunosuppressive role in vivo.

Actins↗

Systemic administration of CCK-8S, but not CCK-4, enhances dopamine turnover in the posterior nucleus accumbens: a microdialysis study in freely moving rats.

The present study was carried out to examine the effects of peripheral administration of sulfatedcholecystokinin octapeptide (CCK-8S) on dopamine (DA) turnover in the posterior nucleus accumbens (PNAc) and the caudate-putamen (CP) in awake rats. Microdialysis was used to quantify the extracellular concentrations of DA and its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Intraperitoneal injections of CCK-8S (0.3 mg/kg b.wt.) caused a significant increase in DOPAC and HVA concentrations in the PNAc, but did not affect the DA level. Such increases in the metabolite contents were not found in the CP. Similar injections of vehicle (1% NaHCO3 solution, 1 ml/kg b.wt.) did not have an effect in either brain region. In an attempt to determine the type of receptor involved in the CCK-8S-induced changes, CCK tetrapeptide (CCK-4, 0.3 mg/kg b.wt.) known to have high affinity for CCKB subtype or vehicle (10% DMSO-saline, 1 ml/kg b.wt.) was administered intraperitoneally. Neither CCK-4 nor vehicle caused significant changes in any of extracellular DA, DOPAC and HVA contents in the PNAc. These results suggest that peripherally administered CCK-8S has stimulatory effects on the dopaminergic system in the PNAc, and raise the possibility that the effect appears to be mediated via CCKA receptors.

3,4-Dihydroxyphenylacetic Acid↗

In vivo effects of the immunosuppressant 15-deoxyspergualin on hematopoiesis in murine allogeneic bone marrow chimeras. Its thrombopoietic activity and reversal of adverse effects with granulocyte colony-stimulating factor and/or erythropoietin.

When 15-deoxyspergualin (DSG), a potent immunosuppressant, was administered into [BALB/c-->C3H/He] bone marrow chimeras from day 14 to day 25, increased thrombopoiesis was induced on day 20 to day 33, accompanied by marked leukocytopenia and anemia. The mean platelet counts in DSG-treated and control [BALB/c-->C3H/He] bone marrow chimeras on day 25 were (114.1 +/- 0.5) x 10(4)/microliter versus (58.6 +/- 2.6) x 10(4)/microliter (1.9-fold increase). Colony-forming units-megakaryocyte (CFU-Meg) were not significantly increased in DSG-treated bone marrow chimeras. Colony-forming units-granulocyte/macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E) were decreased during DSG-treatment whereas CFU-Mix colony formations were rather increased, and more primitive hematopoietic progenitor cells (highly proliferative potential colony-forming units [CFU-HPP]) were not decreased in the same time period. Since CFU-GM and BFU-E colony formations were increased immediately after the cessation of DSG treatment, followed by the rebound of leukocyte counts and the recovery of hemoglobin (Hb) levels, the leukocytopenia and anemia appeared to be induced by a cytostatic effect of DSG. The adverse effect of DSG was partly reversed by the simultaneous administration of granulocyte colony-stimulating factor (G-CSF) and/or erythropoietin (EPO), suggesting the need for the administration of these cytokines in the case of bone marrow transplants treated with DSG. Furthermore, it was of note that DSG modulated hematopoiesis and stimulated the production of thrombopoietin (TPO)-like cytokine(s) as well as interleukin-3 (IL-3).

Anemia↗

Phosphorylation of neurofilament H subunit as related to arrangement of neurofilaments.

To find out what causes differences in phosphorylation states in neurofilaments (NF), we selected two types of dendrite, one provided with very few NFs (Purkinje cell) and the other with relatively many (anterior horn cell). We examined these with four monoclonal antibodies selected by the Western blot analysis, two (NE14 and SMI31) recognizing only phosphorylated, SMI32 recognizing only nonphosphorylated, and N52 recognizing phosphorylation-independent epitopes of NF-H. The immunoperoxidase labeling of dendrites, and also of perikarya, in both neurons was detectable with all four antibodies. After the tissue was treated with Triton X-100, the labeling was still detectable with SMI32 or N52, but undetectable with NE14 and SMI31. The brain homogenate Triton-extracted supernatant after centrifugation at 100,000g for 1 hr showed the staining of NE14, SMI31, and N52 but not that of SMI32. In Purkinje cell dendrite and perikaryon, NFs always appeared singly. In the immunogold labeling, they were labeled only with SMI32 or N52. Labeling by NE14 or SMI31 was distributed throughout the cytoplasm and hardly associated with NFs. In the anterior horn cell dendrite and perikaryon, NFs appeared both singly and in bundles. They were predominantly labeled with SMI32 or N52 when they were single, and with NE14, SMI31, or N52 when they were bundled. Even in one NF, portions that appeared single were labeled mostly with SMI32 or N52, while the remainder, to which other NFs approached closely, were labeled mostly with NE14, SMI31, or N52. Thus, when NFs appear singly, NF-H in their projections or cross-bridges with other organelles is not phosphorylated, while when NFs are bundled, NF-H is phosphorylated in crossbridges between NF core filaments. These data may explain why the NF-H is heavily phosphorylated in axons, where NFs are abundant, and not in dendrites and perikarya, where NFs are sparse.

Animals↗

Cloning and expression of the gene encoding alpha-acetolactate decarboxylase from Acetobacter aceti ssp. xylinum in brewer's yeast.

Acetobacter aceti ssp. xylinum genomic library was constructed using cosmid pJB8 in Escherichia coli. The gene encoding alpha-acetolactate decarboxylase (ALDC) was isolated from the library by direct measurement of ALDC activity. The ALDC gene was expressed by its own promoter in E. coli. The nucleotide sequence was determined, and an open reading frame which may encode a protein composed of 304 amino acids with a molecular weight of 33,747 was found. A brewer's yeast was transformed with the YEp-type plasmid containing the ALDC gene placed under the control of the glyceraldehyde-3-phosphate dehydrogenase promoter. The laboratory-scale growth test confirmed that the total diacetyl concentration was considerably reduced by the transformant. The analysis of the wort indicates that the Acetobacter ALDC reduces the concentration of diacetyl more effectively than that of 2,3-pentanedione.

Amino Acid Sequence↗

Construction of a brewer's yeast having alpha-acetolactate decarboxylase gene from Acetobacter aceti ssp. xylinum integrated in the genome.

alpha-Acetolactate decarboxylase (ALDC) gene from Acetobacter aceti ssp. xylinum has several possible initiation codons in the N-terminus. To determine the initiation codon of the ALDC giving the highest expression levels, glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter was linked just upstream of each possible initiation codon. The ALDC whose translation starts 130 bp downstream from the first ATG codon had the highest activity in yeast cells. When expression levels of the ALDC gene were compared using three strong yeast promoters of glycolytic genes, alcohol dehydrogenase I (ADC1), phosphoglycerate kinase (PGK) and GPD, the GPD promoter was the strongest. The ALDC gene was integrated in a ribosomal RNA gene of a brewer's yeast by co-transformation with an expression plasmid of G418-resistance gene. The laboratory-scale growth test confirmed that the total diacetyl concentration was reduced in wort.

Base Sequence↗