Biomedical subjects

Y Tani

Publications and source records attributed to Y Tani.

At least 19 recordsLinked to original sources

PubMed1998

Intramedullary fibular graft for supracondylar fracture of the femur following total knee arthroplasty.

We describe a successful treatment, intramedullary fibular grafting, for a patient with a supracondylar fracture of the femur following total knee arthroplasty in which the fracture region was comminuted and a segmental large bone defect was present. Free autogenous fibular was inserted into the medullary cavity from the intercondylar region and fixed to the proximal fragment of the femur with augmented fixation using a small plate and screws. Our procedure makes it easy to perform large segmental bone grafting and internal fixation at the same time for such a condition.

Aged↗

PubMed1997

Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice.

The aim of the present study was to evaluate the effects of nicotinic acetylcholine receptor (nACh-R) agonists such as (-)-nicotine and related compounds on brain monoamine turnover. A single administration of (-)-nicotine (0.04, 0.2, 1.0, and 5.0 mg/kg SC) increased both noradrenaline (NA) and dopamine (DA) turnover in a dose-dependent manner, and the maximum effects were achieved 30 min after treatment with (-)-nicotine (1.0 mg/kg). The effect of (-)-nicotine on serotonin (5-HT) turnover was complicated; 5-HT turnover was increased at a low dose of (-)-nicotine (0.04 mg/kg) but decreased at a high dose (1.0 mg/kg). The (-)-nicotine (1.0 mg/kg)-induced changes in monoamine turnover were blocked by pretreatment with the centrally acting nACh-R channel blocker mecamylamine (2.0 mg/kg i.p.) but not by hexamethonium (2.0 mg/kg i.p.). These findings indicate that systemically administered (-)-nicotine can enhance brain NA and DA turnover and affect 5-HT turnover, both of which are mediated by central nACh-R. The changes in the monoamine turnover induced by (+/-)-anabasine were similar to those induced by (-)-nicotine, while (-)-lobeline and (-)-cytisine had little effect, and 1,1-dimethyl-4-phenyl-piperazinium (DMPP) increased NA and 5-HT turnover but not DA turnover at all doses tested. (S)-3-Methyl-5-(l-methyl-2- pyrrolidinyl)isoxazole (ABT-418), a selective neuronal nACh-R agonist, increased NA, DA and 5-HT turnover, but had a weaker effect on DA turnover than NA and 5-HT turnover. In addition, 9-amino-1,2,3,4-tetrahydroacridine (THA), an acetylcholine esterase inhibitor, also increased monoamine turnover in the brain. Pretreatment with mecamylamine completely blocked the THA-induced increase in NA and 5-HT turnover, but not in DA turnover, suggesting that the nACh-R system is involved in the THA-induced increase in brain NA and 5-HT turnover. On the other hand, (-)-cytisine, a partial agonist for the beta 2 subunit containing nACh-R, completely inhibited the nACh-R agonist- and THA-induced increases in NA turnover, but not in DA turnover, and normalized the changes in 5-HT turnover. In conclusion, the subtypes of nACh-Rs mediating DA turnover may be different from those mediating NA and 5-HT turnover in the CNS.

Alkaloids↗

PubMed1997

Antibodies against bacterial lipopolysaccharides in Japanese patients with ankylosing spondylitis.

We investigated IgG, IgA and IgM class specific antibodies to five bacterial (Klebsiella pneumoniae, Escherichia coli, Salmonella enteritidis, Salmonella typhimurium and Shigella flexneri) lipopolysaccharides (LPS) by enzyme-linked immunosorbent assay in 144 Japanese patients with ankylosing spondylitis (AS). AS patients had significantly elevated IgA antibodies to K. pneumoniae LPS, Salmonella enteritidis LPS and Salmonella typhimurium LPS; however, there was no correlation between antibody level to LPS and acute-phase reactants, erythrocyte sedimentation rate and serum C-reactive protein.

Antibodies, Bacterial↗

PubMed1997

Possible effects of tetrahydrobiopterin treatment in six children with autism--clinical and positron emission tomography data: a pilot study.

Six children, between 3 and 5 years of age, having infantile autism according to DSM-III-R, were treated for 3 months with 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-BH4), a cofactor for tyrosine hydroxylases in the biosynthetic pathway of catecholamines and serotonin. A criterion for inclusion in the study was a relatively low level of R-BH4 in the cerebrospinal fluid. For clinical evaluation, the Parental Satisfaction Survey (PASS) was used every fourth week and the Griffiths Developmental Scales were used before starting and 3 months after completing the treatment. During the treatment period, all parents reported improvements in the child's social functioning-mainly eye contact and desire to interact-and in the number of words or sounds which the child used. Small positive changes were noted on the Griffiths Developmental Scales between the two testing occasions. R-BH4 levels in CSF increased significantly after treatment. The positron emission tomography (PET) study showed that the high value of dopamine D2 receptor binding in the caudate and putamen decreased by about 10% towards the normal level after treatment with R-BH4. The observations in this open study indicate that the drug might be useful for a subgroup of children with autism, but there is a need for a larger double-blind study with a longer treatment period.

Antioxidants↗

PubMed1997

Purification and properties of methyl formate synthase, a mitochondrial alcohol dehydrogenase, participating in formaldehyde oxidation in methylotrophic yeasts.

Methyl formate synthase, which catalyzes methyl formate formation during the growth of methylotrophic yeasts, was purified to homogeneity from methanol-grown Candida boidinii and Pichia methanolica cells. Both purified enzymes were tetrameric, with identical subunits with molecular masses of 42 to 45 kDa, containing two atoms of zinc per subunit. The enzymes catalyze NAD(+)-linked dehydrogenation of the hydroxyl group of the hemiacetal adduct [CH2(OH)OCH3] of methanol and formaldehyde, leading to the formation of a stoichiometric amount of methyl formate. Although neither methanol nor formaldehyde alone acted as a substrate for the enzymes, they showed simple NAD(+)-linked alcohol dehydrogenase activity toward aliphatic long-chain alcohols such as octanol, showing that they belong to the class III alcohol dehydrogenase family. The methyl formate synthase activity of C. boidinii was found in the mitochondrial fraction in subcellular fractionation experiments, suggesting that methyl formate synthase is a homolog of Saccharomyces cerevisiae Adh3p. These results indicate that formaldehyde could be oxidized in a glutathione-independent manner by methyl formate synthase in methylotrophic yeasts. The significance of methyl formate synthase in both formaldehyde resistance and energy metabolism is also discussed.

Alcohol Oxidoreductases↗

PubMed1997

A major human immunodeficiency virus type 1-initiated killing pathway distinct from apoptosis.

We have investigated the relative contribution of apoptosis or programmed cell death (PCD) to cell killing during acute infection with T-cell-tropic, cytopathic human immunodeficiency virus type 1 (HIV-1), by employing diverse strategies to inhibit PCD or to detect its common end-stage sequelae. When Bcl-2-transfected cell lines were infected with HIV-1, their viability was only slightly higher than that of control infections. Although the adenovirus E1B 19-kDa protein has been reported to be a stronger competitor of apoptosis than Bcl-2, it did not inhibit HIV-mediated cell death better than Bcl-2 protein. Competition for Fas ligand or inactivation of the Fas pathway secondary to intracellular mutation (MOLT-4 T cells) also had modest effects on overall cell death during acute HIV infection. In contrast to these observations with HIV infection or with HIV envelope-initiated cell death, Tat-expressing cell lines were much more susceptible (200% enhancement) to Fas-induced apoptosis than controls and Bcl-2 overexpression strongly (75%) inhibited this apoptotic T-cell death. PCD associated with FasR ligation resulted in the cleavage of common interleukin-1beta-converting enzyme (ICE)-protease targets, poly(ADP-ribose) polymerase (PARP) and pro-ICE, whereas cleaved products were not readily detected during HIV infection of peripheral blood mononuclear cells or T-cell lines even during periods of extensive cell death. These results indicate that one important form of HIV-mediated cell killing proceeds by a pathway that lacks the characteristics of T-cell apoptosis. Our observations support the conclusion that at least two HIV genes (env and tat) can kill T cells by distinct pathways and that an envelope-initiated process of T-cell death can be discriminated from apoptosis by many of the properties most closely associated with apoptotic cell death.

Adenovirus E1B Proteins↗

PubMed1997

Extracellular 37-kDa antigenic protein from Actinobacillus actinomycetemcomitans induces TNF-alpha, IL-1 beta, and IL-6 in murine macrophages.

The extracellular antigens of Actinobacillus actinomycetemcomitans Y4 (serotype b) contain a 37-kDa protein which is a major target for IgGs from patients suffering from severe alveolar bone loss. Since the 37-kDa protein has not been studied sufficiently, our investigation focused on its characteristics, e.g., its localization, specificity, and whether it directly stimulates macrophages to produce cytokines. The 37-kDa protein was purified from the culture supernatant of the Y4 strain by means of chromatofocusing and gel filtration. The 37-kDa protein is a unique glycoprotein which forms immune complexes with monoclonal antibodies against rhamnose-fucose polysaccharide. Patients with A. actinomycetemcomitans-associated periodontitis had higher antibody titers to the purified 37-kDa protein than healthy subjects (p < 0.001). Anti-37-kDa protein antibodies recognized a 37-kDa band in the cytosolic, ribosomal, and total membrane fractions from Y4 cells. Extracellular substances from other strains of A. actinomycetemcomitans (serotypes a and c) also reacted in the Western blots, but Haemophilus spp. or several periodontopathic bacteria did not. These results suggested that the 37-kDa protein is a cytosolic protein that is passed through the cell membrane, and its protein portion is specific for A. actinomycetemcomitans but common to serotypes. This protein induced Il-1 beta, Il-6, and TNF-alpha release from murine macrophages. The Il-6-inducing activity of the 37-kDa protein was higher than that of LPS. These findings suggested that the 37-kDa protein which is released from live cells plays a role in A. actinomycetemcomitans-associated periodontitis, as antigen inducing the release of inflammatory cytokines which are associated with alveolar bone loss.

Aggregatibacter actinomycetemcomitans↗

PubMed1997

Amyloid deposits in the gastrointestinal tract of aging dogs.

Pathologic features, immunohistochemical characteristics, and incidence of gastrointestinal amyloid deposition were investigated in 78 canine necropsies, including 43 males and 35 females ranging from 2 months to 20 years of age. In 31 of 78 dogs, amyloid protein was accumulated in or around vessel walls located in submucosal and muscular layers of the alimentary tract and mesenteric tissues. These deposits did not seem to affect the function(s) of the digestive tract histologically. The deposits showed congophilia and green birefringence under polarized microscopy. Transmission electron microscopy revealed randomly arranged amyloid fibrils 6-10 nm in diameter around a blood vessel. Congophilia was retained even after oxidation with potassium permanganate, suggesting that this protein is not the AA form of amyloid. Although immunohistochemical studies were performed using antibodies to canine amyloid apolipoprotein AI and synthetic human beta amyloid peptide, the immunochemical nature of the protein was not determined. The mean ages of both male and female dogs with gastrointestinal amyloid deposition were higher than those of their normal counterparts (P < 0.001), and the incidence of deposition in elderly dogs was higher than that in young dogs (P < 0.005). However, there was no sex predilection with respect to both the mean age of the dogs with deposition and the incidence of occurrence. The mechanism(s) and importance of this form of amyloid deposition remain unclear.

Aging↗

PubMed1997

Ester synthesis by NAD(+)-dependent dehydrogenation of hemiacetal: production of methyl formate by cells of methylotrophic yeasts.

A water-soluble ester, methyl formate, was detected as a metabolite in the culture medium of methylotrophic yeasts. Methyl formate synthase, which catalyses NAD(+)-dependent dehydrogenation of the hemiacetal adduct of methanol and formaldehyde, catalyses the ester synthesis. The enzyme activity was induced on a methanol medium and was increased further by the addition of formaldehyde. In the reaction system using intact cells of Pichia methanolica AKU 4262, 135 mM (8.1 g/liter) methyl formate was produced from 2 M methanol. This is a new biological process for ester synthesis that couples spontaneous formation of hemiacetal and alcohol dehydrogenase.

Esters↗

PubMed1997

Serum IgA1 and IgA2 subclass antibodies against collagens in patients with ankylosing spondylitis.

We measured IgA1 and IgA2 subclass antibody levels against human type I, II, III and IV collagens in patients with ankylosing spondylitis (AS) by enzyme linked immunosorbent assay (ELISA). Significant elevations of IgA1 antibodies against type II collagen (p < 0.01) and IgA2 antibodies against type I (p < 0.001), III (p < 0.001), and IV (p < 0.01) collagens were observed in AS patients compared with those of healthy controls. These findings suggest that serum IgA antibodies against type I, III and IV collagens were mainly produced in secretory lesions in AS patients.

Adult↗

PubMed1997

Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: To determine whether patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) from Japan have antibodies to Klebsiella pneumoniae and Proteus mirabilis and to assess whether such antibodies are activated against peptides sharing sequences with HLA-B27. METHODS: Serum samples from 152 Japanese patients, 52 with AS, 50 with RA, and 50 healthy controls, were tested against 3 bacteria (K. pneumoniae, P. mirabilis, and Escherichia coli) and 3 synthetic peptides (HLA-B27, pullulanase-D, and scrambled pullulanase-D control peptide) by ELISA under coded conditions. Samples were tested for elevations in IgG, IgA, and IgM antibody classes in patients with active AS or RA, in patients with RA with probable disease, and in patients with inactive AS. Disease activity was determined by an elevated serum C-reactive protein (> 10 mg/l) level and elevated erythrocyte sedimentation rate (> 20 mm/h). RESULTS: Patients with active AS showed specific elevations in serum IgA antibody levels against K. pneumoniae compared to patients with RA and controls (p < 0.001). No such elevation was seen in the IgG and IgM antibody classes. Patients with inactive AS showed no elevation in any class of antibody against K. pneumoniae compared to controls or patients with RA. Patients with active or probably active RA showed significant elevations in IgG antibody levels against P. mirabilis compared to AS and controls (p < 0.001). Patients with AS (active or inactive), RA (active or probably active), and controls showed no elevations in any antibody class to E. coli. Both active and inactive AS patients had specific autoantibodies against HLA-B27 peptide compared to patients with RA and controls (active AS: IgG, IgA, IgM, p < 0.001; inactive AS: IgG and IgA, p < 0.001). Patients with active AS had IgG and IgA antibodies against pullulanase-D peptide, which contains a sequence that cross reacts with HLA-B27 compared to controls (p < 0.001). CONCLUSION: These results provide the first evidence of AS and RA patients in Japan having specific elevations of antibody to K. pneumoniae and P. mirabilis, respectively. This suggests that K. pneumoniae in AS and P. mirabilis in RA may play a role in triggering and/or exacerbating these diseases.

Adult↗

PubMed1997

[Optic nerve head and choroidal circulation measured by laser Doppler flowmetry in response to intravenous administration of noradrenaline].

We investigated the change of optic nerve head blood flow (ONHBF) and choroidal blood flow (CBF) in response to noradrenaline (NA) intravenously administered in anesthetized cats. NA (0.03, 0.1, 0.3 micrograms/kg/min) was injected 5 minutes continuously via the femoral vein. The relative blood flow and systemic blood pressure were continuously measured before and after NA administration with fundus camera-based laser Doppler flowmetry. Systemic blood pressure increased by 6%, 42% and 48% according to the dose. The changes in ONHBF after NA administration were -1.4 +/- 3.5% (mean +/- standard deviation) with 0.03 micrograms/kg/min, 2.4 +/- 6.9% with 0.1 micrograms/kg/min, -2.2 +/- 4.4% with 0.3 micrograms/kg/min, respectively. It did not change significantly despite doses of NA. CBF did not change significantly with 0.03 micrograms/kg/min. CBF increased significantly by 62.7 +/- 65.4% with 0.1 micrograms/kg/min, and 80.4 +/- 73.1% with 0.3 micrograms/kg/min. These results suggest that ONHBF is autoregulated despite the change of perfusion pressure by NA administration. This response is different from that of CBF.

Animals↗

PubMed1997

[Prevalence of prolonged APTT and lupus anticoagulant in autoimmune thyroid disease].

We describe prevalences of prolonged activated partial thromboplastin time(APTT) and lupus anticoagulant(LAC) in autoimmune thyroid disease(AITD). Prolonged APTTs were observed in 33(6.2%) blood samples out of 532 AITD cases(327 Graves' diseases and 205 Hashimoto's thyroiditis), but in only 8(2.0%) samples out of 396 non AITD cases(213 thyroid tumors, 14 subacute thyroiditis and 169 normal thyroids). The samples with prolonged APTT showed no abnormality in coagulation factors(factor VIII, IX, XI, XII, von Willebrand factor(vWF), prekallikrein, or high molecular weight kininogen) or factor VIII, IX inhibitor. Among samples with prolonged APTT, LAC evaluated by platelet neutralization procedure(PNP) was positive in 17(51.5%) samples of AITD, and in 2(25.0%) samples of non AITD. In prolonged APTT cases, the frequency of fetal loss in patients with AITD was higher than non AITD patients. But no significant difference was obtained between thyroid autoimmune antibody and the frequency of fatal loss. These indicate unknown biological association of between AITD and LAC.

Abortion, Spontaneous↗

PubMed1996

Primary structures of fungal fructosyl amino acid oxidases and their application to the measurement of glycated proteins.

Fructosyl amino acid oxidase (FAOD), which is active toward model compounds of the glycated proteins in blood, N epsilon-fructosyl N sigma-Z-lysine and N-fructosyl valine, was purified to homogeneity from Aspergillus terreus GP1. Though the enzyme did not use glycated proteins directly as its substrate, it used glycated human serum albumin (HSA) when HSA was treated with a protease. Linear relationships between both the concentration and the increase in absorbance and the glycation rate of glycated HSA and the increase in absorbance were observed. cDNAs coding for FAODs were cloned from cDNA libraries of A. terreus GP1 and Penicillium janthinellum AKU 3413. The coding region for both fungal FAODs consisted of 1314 bp encoding 437 amino acids. The sequence of a dinucleotide-binding motif, GXGXXG, was in the deduced N-terminal region and a similar sequence to that the active site of bacterial sarcosine oxidases was found near the C-terminal region of FAOD. The of C-terminal tripeptides SKL and AKL of FAODs from A. terreus and P. janthinellum, respectively, represent typical peroxisomal-targeting signals. Finally, FAOD protein was produced in Escherichia coli transformants in an active form, and at the same level as in the original fungi.

Amino Acid Oxidoreductases↗

PubMed1996

Activation of JAK-STAT and MAP kinases by leukemia inhibitory factor through gp130 in cardiac myocytes.

BACKGROUND: Interleukin (IL)-6-related cytokines share gp130 as the signal-transducing protein. Downstream of gp130, two signal-transducing pathways have been recognized, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the Ras-mitogen-activated protein kinase (MAPK) pathway. To determine whether these two signaling pathways through gp130 are present in cardiac myocytes, we examined their activation by using leukemia inhibitory factor (LIF), which is a member of the IL-6 cytokine family. METHODS AND RESULTS: Lysates from neonatal rat cardiac myocytes were immunoprecipitated with anti-gp130, anti-JAK1, or anti-STAT3 antibody and blotted with anti-phosphotyrosine antibody. Tyrosine phosphorylation of gp130, JAK1, and STAT3 was observed after LIF stimulation in cardiac myocytes. MAPKs were maximally activated 5 minutes after LIF stimulation. Furthermore, anti-gp130 antibody significantly inhibited the LIF-induced activation of JAK1, STAT3, and MAPKs. To examine whether these signaling pathways were also activated in the adult heart in vivo, LIF was injected intravenously into a 6-week-old mouse, and the heart was examined subsequently. gp130, STAT3, and MAPKs were activated in the heart after LIF treatment. CONCLUSIONS: These results demonstrate for the first time that a JAK-STAT pathway and a MAPK pathway are present down-stream of gp130 in cardiac myocytes and are rapidly activated by LIF both in vitro and in vivo. Activation of gp130 constitutes a novel signaling pathway in cardiac myocytes.

Animals↗

PubMed1996

Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta.

Core binding factor beta (CBF beta) is considered to be a transcriptional coactivator that dimerizes with transcription factors core binding factor alpha 1 (CBFA1), -2, and -3, and enhances DNA binding capacity of these transcription factors. CBF beta and CBFA2, which is also called acute myeloid leukemia 1 gene, are frequently involved in chromosomal translocations in human leukemia. To elucidate the function of CBF beta, mice carrying a mutation in the Cbfb locus were generated. Homozygous mutant embryos died between embryonic days 11.5-13.5 due to hemorrhage in the central nervous system. Mutant embryos had primitive erythropoiesis in yolk sac but lacked definitive hematopoiesis in fetal liver. In the yolk sac of mutant embryos, no erythroid or myeloid progenitors of definitive hematopoietic origin were detected, and the expression of flk-2/flt-3, the marker gene for early precursor cells of definitive hematopoiesis, was absent. These data suggest that Cbfb is essential for definitive hematopoiesis in liver, especially for the commitment to early hematopoietic precursor cells.

Animals↗

PubMed1996

Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels.

Thirty-one patients (27 with acute myeloid leukemia [AML], 2 with acute lymphocytic leukemia [ALL], and 2 with acute mixed lineage leukemia [AMLL]) treated with conventional chemotherapy (CHT) and 23 patients (13 AML, 5 ALL, and 5 with chronic myeloid leukemia [CML]) treated with allogeneic bone marrow transplantation (BMT) were monitored for WT1 expression levels in BM and peripheral blood (PB) by reverse transcriptase-polymerase chain reaction over a long-term period (mean, 29 months for CHT and 24 months for BMT). Sixteen of the patients in the CHT group and 3 in the BMT group who had achieved complete remission suffered clinical relapse. In 10 of these patients, WT1 expression that had returned to normal BM levels (< 10(-3); the WT1 expression level of K562 cells was defined as 1.0) after complete remission (CR) either gradually or rapidly increased again to abnormal levels 1 to 18 months (mean, 7 months) before clinical relapse became apparent. In another 9 patients, WT1 expression never returned to normal BM levels even after CR and the subsequent relapse was accompanied by a rapid increase in WT1 expression to levels higher than 10(-2) (10(-3) levels in PB). On the other hand, the remaining 35 patients (15 CHT and 20 BMT) maintained their CR. In 29 of these patients (11 CHT and 18 BMT), WT1 expression either gradually or rapidly decreased to normal BM levels, whereas in the other 6 (4 CHT and 2 BMT), low or very low levels of WT1 mRNAs (10(-3) to 10(-2) in BM and 10(-5) to 10(-3) in PB) remain detectable, but without any clinical signs of relapse. A clear correlation was found to exist between the minimal residual disease (MRD) detected in the paired BM and PB samples for all types of leukemias (AML, ALL, and CML), with MRD in PB being approximately one-tenth of that in BM. WT1 quantitation of 168 paired BM and PB samples showed that PB samples were superior to BM samples for the detection of MRD. We conclude that monitoring of WT1 expression levels in BM and PB makes it possible to rapidly assess the effectiveness of individual treatment and diagnose clinical relapse in the early stage for all leukemia patients regardless of the presence or absence of tumor-specific DNA markers.

Bone Marrow↗

PubMed1996

Effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin and infusion of L-tyrosine on the in vivo L-[beta-11C] DOPA disposition in the monkey brain.

The effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) and L-tyrosine infusion on [11C]dopamine synthesis was analyzed in the striatum of Rhesus using positron emission tomography (PET). The rate for decarboxylation from L-[beta-11C]DOPA to [11C]dopamine was calculated using a graphical method with cerebellum as a reference region. Although the peripheral administration of 6R-BH4 at low dose (2 mg/kg) did not provide a significant increase in the rate of dopamine biosynthesis, a high dose of 6R-BH4 (20 mg/kg) induced an elevation of the rate. This 6R-BH4-induced elevation of the dopamine synthesis rate was further dose-dependently enhanced by the continuous infusion of L-tyrosine (0.2 and 1.0 mumol/min/kg). L-Tyrosine infusion with a rate of 1.0 mumol/min/kg caused an enhancement of the rate even during low dose administration of 6R-BH4 (2 mg/kg). L-Tyrosine infusion alone did not induce any elevation of the dopamine biosynthesis rate. The analysis of plasma indicated that the metabolic ratios of L-[beta-11C]DOPA to each metabolite were not affected by 6R-BH4 and/or L-tyrosine infusion. The results suggest that the low dose loading of tyrosine facilitates the activity of 6R-BH4 on the presynaptic dopamine biosynthesis, and also that the combined effects can be monitored by PET using L-[beta-11C]DOPA as a biochemical probe.

Animals↗