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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 73 records · Page 4Linked to original sources
PubMed2001

Membrane relocation but not tight binding of human immunodeficiency virus type 1 Gag particles myristoylated in Escherichia coli.

Expression of human immunodeficiency virus Gag protein and the N-terminal matrix (MA) domain in Escherichia coli yielded spherical structures in the cytoplasm. When human N-myristoyltransferase was coexpressed, both Gag and MA were fully myristoylated and spherical structures were relocated in close proximity to the cytoplasmic membrane. However, neither myristoylated Gag nor MA exhibited tight binding to E. coli membrane, suggesting that myristoylation in E. coli did not confer membrane affinity on Gag despite the relocation. Our data also suggest that the morphogenetic pathway of Gag particles in prokaryotic cells differs from that in eukaryotic cells despite biochemical similarities of in the form of Gag expressed.

Acyltransferases↗
PubMed2001

Induction of choleresis by immunosuppressant FK506 through stimulation of insulin-like growth factor-I production in the liver of rats.

FK506 (Tacrolimus) is an effective immunosuppressant currently used worldwide in organ transplantation. Based on our recent findings that insulin-like growth factor-I (IGF-I) is important for the stimulation of choleresis in vivo, in this study we investigated the effect of FK506 on bile flow and the plasma and hepatic levels of IGF-I in rats. Intravenous treatment of rats with FK506 resulted in a significant increase in bile flow, whereas cyclosporin A induced a significant decrease. A significant increase in plasma levels of IGF-I was observed in rats 30 min after a single intravenous administration of FK506. Oral treatment of rats with FK506 for 1 week also resulted in an increase in both plasma and hepatic levels of IGF-I. Overall, this study showed that FK506 treatment increased bile flow and also induced an increase in the plasma and hepatic levels of IGF-I in rats, suggesting that a stimulation of hepatic IGF-I production by FK506 may contribute to its choleretic profile.

Animals↗
PubMed2001

A pH-sensitive interaction of troponin I with troponin C coupled with strongly binding cross-bridges in cardiac myofilament activation.

Slow skeletal muscle troponin I (ssTnI) expressed predominantly in perinatal heart confers a marked resistance to acidic pH on Ca(2+) regulation of cardiac muscle contraction. To explore the molecular mechanism underlying this phenomenon, we investigated the roles of TnI isoforms (ssTnI and cardiac TnI (cTnI)) in the thin filament activation by strongly binding cross-bridges, by exchanging troponin subunits in cardiac permeabilized muscle fibers. Fetal cardiac muscle showed a marked resistance to acidic pH in activation of the thin filament by strongly binding cross-bridges compared to adult muscle. Exchanging ssTnI into adult fibers altered the pH sensitivity from adult to fetal type, indicating that ssTnI also confers a marked resistance to acidic pH on the cross-bridge-induced thin filament activation. However, the adult fibers containing ssTnI or cTnI but lacking TnC showed no pH sensitivity. These findings provide the first evidence for the coupling between strongly binding cross-bridges and a pH-sensitive interaction of TnI with TnC in cardiac muscle contraction, as a molecular basis of the mechanism conferring the differential pH sensitivity on Ca(2+) regulation.

Actin Cytoskeleton↗
PubMed2001

FK960, a novel potential anti-dementia drug, enhances high K(+)-evoked release of somatostatin from rat hippocampal slices.

We have demonstrated that FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel putative anti-dementia drug of piperazine derivative, ameliorates memory deficits in a variety of animal models of dementia in rats and monkeys, and also augments long-term potentiation (LTP) in the mossy fiber-CA3 pathway in guinea-pig hippocampal slices. Our recent studies have further suggested that somatostatin activation could be a primary mechanism of the pharmacological action of FK960. To clarify the mode of action of FK960 on somatostatinergic neurotransmission, FK960 was examined for its effects on somatostatin release from rat hippocampal slices. FK960 significantly enhanced high K(+)-evoked release, but not basal release, of somatostatin with similar concentration-dependency to its LTP augmenting action. On the other hands, FK960 had no effects on the release of neurotransmitters such as acetylcholine, 5-HT, D-aspartate or GABA from hippocampal slices. Our results provide compelling evidence that FK960 exerts specific and facilitatory actions on neural mechanisms involved in the activity-dependent release of somatostatin from nerve terminals of the hippocampus. These results also strengthen the view that FK960 regulates cognitive functions and augments LTP through an activation of the somatostatinergic nervous system in the hippocampus.

Acetylcholine↗
PubMed2001

A double-functionalized cyclen with carbamoyl and dansyl groups (cyclen = 1,4,7,10-tetraazacyclododecane): a selective fluorescent probe for Y(3+) and La(3+).

A cyclen (=1,4,7,10-tetraazacyclododecane) doubly functionalized with three carbamoylmethyl groups and one dansylaminoethyl (dansyl = 2-(5-(dimethylamino)-1-naphthalenesulfonyl) group (L(2) = 1-(2-(5-(dimethylamino)-1-naphthalenesulfonylamido)ethyl)-4,7,10-tris(carbamoylmethyl)-cyclen) was synthesized and characterized. Potentiometrtic pH titration and UV spectrophotometric titration of L(2) served to determine deprotonation of the pendant dansylamide (L(2) --> H(-1)L(2)) with a pK(a) value of 10.6, while the fluorometric titration disclosed a pK(a) value of 8.8 +/- 0.2, which was assigned to the dansyl deprotonation in the excited state. The 1:1 M(3+)-H(-1)L(2) complexation constants (log K(app) = 6.0 for Y(3+) and 5.2 for La(3+), where K(app)(M-H(-1)L(2)) = [M(3+)-H(-1)L(2)]/[M(3+)](free)[L(2)](free) (M(-1)) at pH 7.4) were determined by potentiometric pH titration and UV and fluorescence spectrophotometric titrations (excitation at 335 nm and emission at 520 nm) in aqueous solution (with I = 0.1 (NaNO(3))) and 25 degrees C. The X-ray structure analysis of the Y(3+)-H(-1)L complex showed nine-coordinated Y(3+) with four nitrogens of cyclen, three carbamoyl oxygens, and the deprotonated nitrogen and a sulfonyl oxygen of the dansylamide. The crystal data are as follow: formula C(28)H(49)N(11)O(13.5)SY (Y(3+)-H(-1)L(2) x 2(NO(3)(-)) x 2.5H(2)O), M(r) = 876.73, monoclinic, space group P2(1)/n (No. 14), a = 18.912(3) A, b = 17.042(3) A, c = 24.318(4) A, beta = 95.99(1) degrees, V = 7794(2) A(3), Z = 8, R1 = 0.099. Upon M(3+)-H(-1)L(2) complexation, the dansyl fluorescence greatly increased (8.6 and 3.8 times for Y(3+) and La(3+), respectively) in aqueous solution at pH 7.4. Other lanthanide ions also yielded Ln(3+)-H(-1)L(2) complexes with similar K(app) values, although all the dansyl fluorescences were weakly quenched. On the other hand, zinc(II) formed only a 1:1 Zn(2+)-L(2) complex at neutral pH with negligible fluorescence change. The X-ray crystal structure of the Zn(2+)-L(2) complex confirmed the pendant dansylamide being noncoordinating. The crystal data are as follow: formula C(28)H(51)N(11)O(14)SZn (Zn(2+)-L(2) x 2(NO(3)(-)) x 3H(2)O), M(r) = 863.22, monoclinic, space group C2/n (No. 15), a = 35.361(1) A, b = 13.7298(5) A, c = 18.5998(6) A, beta = 119.073(2) degrees, V = 7892.3(5) A(3), Z = 8, R1 = 0.084. Other divalent metal ions did not interact with L(2) at all (e.g., Mg(2+) and Ca(2+)) or interacted with L(2) with the dansyl fluorescence quenched (e.g., Cu(2+)).

Journal Article↗
PubMed2001

The effects of zenarestat, an aldose reductase inhibitor, on minimal F-wave latency and nerve blood flow in streptozotocin-induced diabetic rats.

The effects of zenarestat, 3-(4-bromo-2-fluorobenzyl)-7-chloro-3,4-dihydro-2,4-dioxo-1(2H)-quinazolineacetic acid, an aldose reductase inhibitor (ARI), on F-wave conduction abnormalities, nerve blood flow (NBF) reduction and sorbitol accumulation were studied in streptozotocin-induced diabetic rats. Two weeks after the induction of diabetes, zenarestat was given once a day for two weeks. In diabetic control rats, marked accumulation of sorbitol, reduction of NBF and prolongation of minimal F-wave latency (FWL) were observed as compared to normal rats. Zenarestat, at a dose of 32 mg/kg, inhibited sorbitol concentration to nearly the normal rat level and significantly improved not only NBF but also minimal FWL. At a dose of 3.2 mg/kg, sorbitol accumulation was inhibited by approximately 40% and there was a tendency to increase in NBF; however, minimal FWL was not improved at all. These data suggest that a highly inhibition of the nerve sorbitol accumulation is requisite for the treatment of diabetic peripheral neuropathy.

Aldehyde Reductase↗
PubMed2001

Targets of a protease inhibitor, KNI-272, in HIV-1-infected cells.

The targets of a protease inhibitor, KNI-272, in the HIV-1 life cycle were investigated in this study. Neither expression of HIV-1 Gag proteins nor production of virus particles was detected in cells infected acutely with HIV-1 cultured in the presence of KNI-272. Although HIV-1 proviral DNA was detected in the cells by PCR, the inhibitor depressed the amount of the proviral DNA in a concentration dependent manner. These results indicate that one of the targets of KNI-272 occurs in the stage before the expression of viral structural proteins. No direct inhibition of reverse transcription was found with the inhibitor. To confirm the inhibition of viral protease, persistently HIV-1-infected cells were cultured in the presence of the inhibitor and examined by electron microscopy for the morphology of HIV-1 particles. Doughnut-shaped immature particles were observed in the extracellular space of the cells, and disrupted semicircular shaped particles were also seen at the higher concentration of KNI-272. A bioassay for infectivity showed that the virus particles were not infectious, and immunofluorescent assay using anti-p17 antibody, that does not react with the precursor of Gag protein, revealed that Gag precursor p55 protein in the cells was not processed. Thus, KNI-272 blocked the maturation of viral particles. Consequently, KNI-272 has at least two inhibition targets in the stages of the HIV-1 life cycle.

Anti-HIV Agents↗
PubMed2001

Capillary electrophoretic determination of phosphate based on the formation of a Keggin-type [PMo12O40]3- complex.

Based on the formation of a Keggin-type [PMo12O40]3- complex, a sensitive capillary electrophoresis (CE) method was developed for the determination of P(V) with direct UV detection at 220 nm. A mixture of alpha- and beta-Keggin-type [PMo12O40]3- complexes was readily formed in a sample solution consisting of a trace amount of P(V), 2.5 mM Mo(VI), 0.050 M p-C6H3(CH3)-2-SO3H (XSA), and 60% v/v CH3CN. When a 0.05 M HCl and 60% v/v CH3CN solution was used as a migration electrolyte, the Keggin complexes exhibited a sharp and well-defined peak in the electropherogram. The peak area was linearly dependent on the P(V) concentration in the range of 5 x 10(-7)-5 x 10(-5) M; a detection limit of 1 x 10(-7) M was achieved. In comparison with indirect UV detection, the direct UV detection is about ten times more sensitive, because the Keggin complexes possess high molar absorptivities. The developed CE method was applied to the determination of P(V) in river water, and the results were in good agreement with those obtained by ion chromatography (IC) and colorimetry (COL) based on the formation of mixed-valence heteropoly blue species.

Acetonitriles↗
PubMed2001

A novel POZ/zinc finger protein, champignon, interferes with gastrulation movements in Xenopus.

We have cloned a novel krüppel-like transcription factor of Xenopus that encodes POZ/zinc finger protein by expression cloning. Overexpression of mRNA resulted in interference with gastrulation. Because the injected embryo looks like a mushroom in appearance at the neurula stage, we have named this gene champignon (cpg). In cpg-injected embryos, the blastopore appeared normally, but regressed thereafter. The injected embryos then elongated along the primary dorsoventral axis during the tailbud stage. Histologic sections and reverse transcription-polymerase chain reaction analysis showed that cpg had no effect on the cell differentiation. The animal pole region of cpg-injected embryos was thick during the gastrula stage, and mesodermal cells remained in the marginal zone. Furthermore, neither Keller-sandwich explants nor activin-treated animal cap explants excised from cpg-injected embryos elongated. These results suggest that cpg acts as a potent inhibitor of cell migration and cell intercalation during gastrulation.

Animals↗
PubMed2001

Continuity with ganglionic eminence modulates interkinetic nuclear migration in the neocortical pseudostratified ventricular epithelium.

Cells of the pseudostratified ventricular epithelium (PVE) undergo interkinetic nuclear migration whereby position of cell soma with nucleus is systematically dependent upon cell cycle phase. We examined if the interkinetic nuclear migration in the neopallial PVE is influenced by tissue continuity with the ganglionic eminence (GE) of the basal forebrain in explants from embryonic day 13 mice. We found that when continuity between the neopallial wall and the GE is intact, some neopallial PVE cells discontinue interkinetic nuclear migration following S-phase and upon entry into G2-phase. The somata and nuclei of those cells shift outward from the S-phase zone toward the subventricular and the intermediate zones. The outward migration of post-S-phase cells is observed only in the lateral region of the cerebral wall, which is closely adjacent to the GE, but not in the medial region, and only when tissue continuity with GE is maintained. We suggest that the outward moving PVE cells seed the secondary proliferative population (SPP) and that exit of the SPP seeding cells occurs in G2-phase. The phenomenon recapitulates similar migratory behavior of neopallial PVE cells in vivo and appears to represent a "choice" between two opposing options available to post-S-phase cells of the PVE. The choice appears to be imposed by mechanisms dependent upon continuity with the GE. We conclude that GE, and/or other adjacent basal forebrain structures, modulates interkinetic nuclear migration in the neopallial PVE.

Animals↗
PubMed2001

FK506 is superior to methotrexate in therapeutic effects on advanced stage of rat adjuvant-induced arthritis.

OBJECTIVE AND DESIGN: The anti-arthritic properties of FK506 were compared with methotrexate (MTX) in established adjuvant-induced arthritis (AIA) in rats. MATERIAL: Female Lewis rats. TREATMENT: Arthritic rats were orally administered with FK506 (1-5.6 mg/kg) and MTX (0.1-1 mg/kg) from days 15-24. METHODS: Arthritis was induced by injection of Mycobacterium tuberculosis into the right hind footpad on day 0. Efficacy was determined on the basis of paw inflammation measured by paw volume and histological change, hyperalgesia and grip strength. Grip strength measurement was employed as an indication of function of paws in arthritic rats. Peripheral white blood cell (WBC) counts and thymus weights were measured, mainly as indicators of toxic side effects. RESULTS: FK506 suppressed paw inflammation and hyperalgesia without toxic effects on WBC and thymus in established AIA. MTX slightly suppressed paw inflammation and hyperalgesia at the highest dose (1 mg/kg). Toxic effects were observed at lower doses than the effective treatment dose with MTX. Grip strength was found to decrease during development of AIA. FK506, but not MTX, treated rats recovered grip strength loss. CONCLUSIONS: The results show that FK506 is more effective and less toxic than MTX in treating established AIA in rats.

Animals↗
PubMed2001

Serum acid phosphatase as a tumour marker in giant cell tumour of bone.

The serum acid phosphatase value was examined in nine patients with giant cell tumour of bone. Five showed a high level of acid phosphatase, which fell to within normal limits after surgery. Although the remaining four patients showed a normal acid phosphatase level before surgery, the postoperative acid phosphatase level was lower than the preoperative level in each case. Therefore, it is strongly suggested that serum acid phosphatase is a useful tumour marker in diagnosing giant cell tumour of bone as well as in evaluating the efficacy of treatment.

Acid Phosphatase↗
PubMed2001

Soft-tissue haemangioma and periosteal new bone formation on the neighbouring bone.

Deeply situated soft-tissue haemangioma sometimes causes periosteal new bone formation on the neighbouring bone. The purpose of this study was to elucidate the aetiological factors for this phenomenon. We studied 25 patients with soft-tissue haemangioma on whom plain radiographs and computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations were performed. We examined the presence or absence of periosteal new bone formation, haemangioma-bone distance, size of haemangioma and pain. Periosteal new bone formation was seen in 12 of 25 patients. In these 12 patients, the haemangioma was adjacent to the bone in 11 patients, while the haemangioma-bone distance was 4 mm in the other patient. In the remaining 13 patients who had no periosteal new bone formation, the haemangioma-bone distance was 5-27 mm. Pain in the former group was stronger than that in the latter group, the difference being statistically significant. There was no statistically significant difference in size of haemangioma between the two groups. Therefore, the main factor that induces periosteal new bone formation on the neighbouring bone was not the size of haemangioma, but the distance between the haemangioma and the bone.

Adolescent↗
PubMed2001

Expression of cathepsin K mRNA and protein in odontoclasts after experimental tooth movement in the mouse maxilla by in situ hybridization and immunoelectron microscopy.

This study demonstrated the simultaneous expression of cathepsin K (CK) mRNA by in situ hybridization and CK protein by immunoelectron microscopy in odontoclasts in mouse maxillae after experimental tooth movement. On the pressure side (the area under pressure during tooth movement), CK mRNA was detected in odontoclasts in resorption lacunae in the tooth root, in osteoclasts in bone resorption lacuane, and in fibroblasts in the periodontal ligament. Using electron microscopy, CK protein was detected at the apex of odontoclasts, intracellularly in vesicles and granules, and extracellularly in irregularly shaped vacuoles (extracellular spaces), on the plasma membrane of the ruffled border, and on and between typical striated type I collagen fibrils in the lacunae. These vesicles and granules appeared to fuse with irregular vacuoles containing CK-positive fragmented fibril-like structures close to the ruffled border. In the basolateral portion of odontoclasts, small amounts of CK-positive rough endoplasmic reticulum (ER) were found. CK-positive intracellular vacuoles (not extracellular spaces) also appeared to fuse with the vesicles and granules. However, these fused organelles rarely contained fragmented fibril-like structures. They are probably endolysosomes. The distribution of CK in odontoclasts was similar to that previously seen in osteoclasts. Furthermore, CK-positive fibril-like structures were found in the vacuoles of fibroblasts. These results indicated that during tooth movement CK is synthesized in odontoclasts on the pressure side and secreted into the tooth resorption lacunae. Therefore, CK may take part in the degradation of the dentin matrix (type I collagen fibrils and non-collagenous protein) of the tooth root, and in the subsequent intracellular degradation of endocytosed fragmented fibril-like structures in endolysosomes.

Animals↗
PubMed2001

Histological study on local invasiveness of clival chordoma. Case report of autopsy.

BACKGROUND: It is well known that clival chordomas invade bony structures; however, their invasiveness of other structures has rarely been reported. We report an autopsy case of clival chordoma in a 61-year-old woman, who underwent surgery 6 times for a period of 8 years, with special reference to its local invasiveness. METHOD AND FINDINGS: The histological studies showed that the tumour grew in the loose connective tissue in multilayers or multilobular fashion, invading the submucous layer in addition to the bone; however, it did not invade other soft tissue, particularly vital neurovascular structures or the dura itself, even in the advanced stage. INTERPRETATION: The dura may serve as a strong barrier against tumour invasion into the intradural space, which emphasises the importance of not injuring the dura, when the tumour is removed extradurally. For radical removal of clival chordoma, it will be necessary to remove the tumour extensively including normal bone and soft tissues surrounding the tumour, especially the mucous membrane, because the normal mucous membrane is surgically difficult to preserve by dissecting it from the invaded submucous layer.

Autopsy↗
PubMed2001

Intracranial adenoid cystic carcinoma of suprasellar region.

Adenoid cystic carcinoma (ACC) is a relatively common head and neck tumor which grows slowly but locally aggressive and prone to recurrence. ACC most commonly arises in the major and minor salivary glands. Some rare cases of intracranial ACC with an unknown primary site have been reported. The authors present the first case of primary intracranial ACC of the suprasellar region. A 34 year-old female presented with one month's duration of visual disturbance and galactorrhea. Magnetic resonance image (MRI) showed intra- and suprasellar mass mimicking a craniopharyngioma. There was no evidence of invasion from an extracranial site. The operative findings showed the mass existed under the arachnoid membrane and seemed to originate from the pituitary stalk. Pathological diagnosis was ACC. After the first operation, local recurrence and CSF dissemination to the lower clivus occurred within two months. Recurrence repeatedly treated by Gamma knife radiosurgery 10 times and 4 times by surgery during a 3 year follow-up period. But total removal of the tumor at the first operation along with radiosurgery may control the lesion and prevent further recurrence.

Adult↗
PubMed2001

Osteofibrous dysplasia of the ulna.

We experienced two patients with osteofibrous dysplasia of the ulna. Both of them showed typical radiographic findings of osteofibrous dysplasia, except for location. One patient underwent surgery at the age of 15 years to confirm the diagnosis histologically. Although the tumor recurred 5 months after the surgery, expansion of the lesion seemed to cease at the age of 25 years. In the other patient, the natural course was observed. The tumor showed a tendency toward spontaneous regression at the age of 11 years. Therefore, the nature of osteofibrous dysplasia in the ulna seems to be the same as that in the tibia and fibula. Surgery must be delayed for as long as possible in osteofibrous dysplasia of the ulna, as well as that of the tibia and fibula.

Adolescent↗