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Biomedical subjects

T Otake

Publications and source records attributed to T Otake.

At least 37 records · Page 2Linked to original sources

Pitch accent in spoken-word recognition in Japanese.

Three experiments addressed the question of whether pitch-accent information may be exploited in the process of recognizing spoken words in Tokyo Japanese. In a two-choice classification task, listeners judged from which of two words, differing in accentual structure, isolated syllables had been extracted (e.g., ka from baka HL or gaka LH); most judgments were correct, and listeners' decisions were correlated with the fundamental frequency characteristics of the syllables. In a gating experiment, listeners heard initial fragments of words and guessed what the words were; their guesses overwhelmingly had the same initial accent structure as the gated word even when only the beginning CV of the stimulus (e.g., na- from nagasa HLL or nagashi LHH) was presented. In addition, listeners were more confident in guesses with the same initial accent structure as the stimulus than in guesses with different accent. In a lexical decision experiment, responses to spoken words (e.g., ame HL) were speeded by previous presentation of the same word (e.g., ame HL) but not by previous presentation of a word differing only in accent (e.g., ame LH). Together these findings provide strong evidence that accentual information constrains the activation and selection of candidates for spoken-word recognition.

Humans↗

Characterization of human immunodeficiency virus type 1 resistant to modified cyclodextrin sulphate (mCDS71) in vitro.

Drug resistance of human immunodeficiency virus type 1 (HIV) to modified cyclodextrin sulphate (mCDS71) has been analysed with respect to both the in vitro appearance of resistance to the compound and the mechanism of the acquisition of resistance. Resistant strains could be obtained in all three strains (NL432, KK-1 and A018) tested after serial passages in MT-4 cells with a gradual increase of the concentration of mCDS71. Cross-resistance both to mCDS71 and dextran sulphate 8000 was observed. As a result of sequencing analysis of the gp120 V3-C5 region of resistant strains, the mechanism of resistance can be explained in several ways: (i) substitution of sugar chain-binding amino acids, N and S; (ii) three to five amino acid deletion in V4 loop; and (iii) several mutations in V3 and V4 regions. The real cause of the resistance may be a combination of these three mechanisms. The results suggest that the target of mCDS71 is relatively widely distributed on the viral surface glycoprotein.

Amino Acid Sequence↗

12-O-acetylphorbol-13-decanoate potently inhibits cytopathic effects of human immunodeficiency virus type 1 (HIV-1), without activation of protein kinase C.

Through bioactivity-guided fractionation, eight phorbol diesters, including five new ones (1-5), were isolated from the seeds of Croton tiglium collected in Egypt. 12-O-Acetylphorbol-13-decanoate (6) and 12-O-decanoylphorbol-13-(2-methylbutyrate) (4) potently inhibited the HIV-1-induced cytopathic effect on MT-4 cells (IC100 values of 7.6 ng/ml and 7.81 micrograms/ml, and CC0 values of 62.5 micrograms/ml and 31.3 micrograms/ml, respectively) without activating protein kinase C.

Anti-HIV Agents↗

HIV-1 protease inhibition and anti-HIV effect of natural and synthetic water-soluble lignin-like substances.

Water-soluble lignin extracted from natural sources and dehydrogenated polymers of p-coumaric acid and ferulic acid inhibited HIV-1 protease activity. The dehydrogenated polymers, which are thought to be model compounds for lignin, were synthesized and fractionated into four ranges of molecular mass by ultra-filtration: i.e., over 30 kDa, 30-10 kDa, 10-1 kDa and 1 kDa-500 Da. All of these fractions had HIV-1 protease inhibitory activity. The anti-HIV-1 effect of the smallest mass fractions of the dehydrogenated polymers (1 kDa-500 Da) was also tested, and it was found that these fractions inhibited the replication of HIV-1 in MT-4 cells.

Cell Line↗

Bone atrophy in complex regional pain syndrome patients measured by microdensitometry.

PURPOSE: To determine the usefulness of quantitative measurement of bone atrophy in the diagnosis and the long-term follow-up of patients with complex regional pain syndrome (CRPS). The bone-sparing effect of a 5-hydroxytriptamine (5-HT2) antagonist was also studied. METHODS: Bone mass was measured by computerized micro-densitometry at the middle position of the second metacarpal. The effect of repeated stellate ganglion blocks (SGBs) three times per week with mepivacaine (n = 11), administration of a 5-HT2 antagonist (sarpogrelate hydrochloride, 300 mg a day po) (n = 12), and combined therapy (n = 10) were compared by micro-densitometry and conventional visual analogue scale (VAS) for analgesia after three months of treatment. RESULTS: In CRPS patients, metacarpal index (cortical bone thickness), maximum bone density (cortical bone density), minimum bone density (trabecular bone density), and average bone density were reduced on the affected side (14.1%, 12.1%, 25.0% and 19.3% respectively). The rate of reduction in bone mass correlated with the duration of the disease (P < 0.05). Therapy with the 5-HT2 receptor antagonist (with or without repeated SGBs) decreased pain intensity (from 6.10 to 3.81 with SGB, from 6.30 to 2.91 without SGB, respectively; P < 0.01) and bone atrophy evaluated by micro-densitometry (P < 0.05). In contrast, repeated SGBs alone reduced pain intensity (from 6.30 to 2.91; P < 0.01) but did not ameliorate bone atrophy. CONCLUSION: Bone micro-densitometry is useful in the assessment and follow-up of CRPS and for evaluation of treatment. The 5-HT2 antagonist, sarpogrelate hydrochloride, is a promising treatment for CRPS patients.

Administration, Oral↗

Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum.

A new highly oxygenated triterpene named ganoderic acid alpha has been isolated from a methanol extract of the fruiting bodies of Ganoderma lucidum together with twelve known compounds. The structures of the isolated compounds were determined by spectroscopic means including 2D-NMR. Ganoderiol F and ganodermanontriol were found to be active as anti-HIV-1 agents with an inhibitory concentration of 7.8 micrograms ml-1 for both, and ganoderic acid B, ganoderiol B, ganoderic acid C1, 3 beta-5 alpha-dihydroxy-6 beta-methoxyergosta-7,22-diene, ganoderic acid alpha, ganoderic acid H and ganoderiol A were moderately active inhibitors against HIV-1 PR with a 50% inhibitory concentration of 0.17-0.23 mM.

Anti-HIV Agents↗

[Studies for dynamics of reverse transcriptase inhibiting antibody in sera from HIV-1 infected individuals].

Antibodies inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcriptase activity (RTI-antibody), Binding inhibition antibody (BI-antibody) and polymerization inhibition antibody (PI-antibody) were investigated for their ability to inhibiting RT activity in 248 HIV-1 infected individuals and 99 healthy individuals. In BI-antibody, high titer samples were determined more in than in RTI- and PI-antibodies. No significance was indicated between AC, ARC and AIDS is any antibody, however, progression from AC to AIDS was poled to high titer and low titer in RTI- and BI-antibodies. Moreover, time course of each antibody levels in the same infected individuals were resulted in no change, going up or down through all the experimental term, though all samples were collected in AC. These results were suggested that the determination factor of each stage in HIV progression would be multiple, and that the various dynamics of RTI-, BI- and PI-antibodies in the same infected individuals might be caused in the term from HIV infection to AIDS progression, prognosis or appearing of the drug resistant strain but stages of the disease.

Acquired Immunodeficiency Syndrome↗

Anti-HIV-1 activity of herbs in Labiatae.

The anti-HIV-1 activity of aromatic herbs in Labiatae was evaluated in vitro. Forty five extract from among 51 samples obtained from 46 herb species showed significant inhibitory effects against HIV-1 induced cytopathogenicity in MT-4 cells. In particular, the aqueous extracts of Melissa officinalis, a family of Mentha x piperita "grapefruit mint," Mentha x piperita var. crispa, Ocimum basilicum cv "cinnamon," Perilla frutescens var. crispa f. viridis, Prunella vulgaris subsp. asiatica and Satureja montana showed potent anti-HIV-1 activity (with an ED of 16 microg/ml). The active components in the extract samples were found to be water-soluble polar substances, not nonpolar compounds such as essential oils. In addition, these aqueous extracts inhibited giant cell formation in co-culture of Molt-4 cells with and without HIV-1 infection and showed inhibitory activity against HIV-1 reverse transcriptase.

Anti-HIV Agents↗

Design and racemic synthesis of conformationally restricted carbocyclic pyrimidine nucleoside analogs based on the structure of the L-nucleoside residue in heterochiral DNA.

Carbocyclic pyrimidine nucleoside analogs which have restricted glycosidic conformation at chi approximately 180 degrees were designed, based on the conformational features of the L-nucleotide residue in heterochiral DNA, and synthesized. The synthesis of (+/-)-carbocyclic 6,6'-O-cyclo-2'-deoxyuridine was achieved via bromination and subsequent intramolecular cyclization of carbocyclic 6'beta-hydroxy-2'-deoxyuridine. (+/-)-Carbocyclic 6,6'-O-cyclo-2'-deoxycytidine was synthesized from protected carbocyclic 6,6'-O-cyclo-2'-deoxyuridine via the 4-triazole intermediate.

Anti-HIV Agents↗

[Use of 99mTc-labeled myocardial perfusion agents in the Kanto-Koshinetsu area].

We sent out a questionnaire to investigate how the 99mTc-labeled myocardial perfusion agents are used in the Kanto-Koshinetsu area. Answers were obtained from 83 laboratories. Examinations using 99mTc-labeled agents were performed more frequently than those using 201T1 only in 10 of 83 laboratories. Main reasons for not using 99mTc-labeled agents were as follows: two injections required in the stress study, superiority of thallium-201 in the assessment of myocardial viability, a large amount of clinical data cumulated in thallium-201 imaging, and problems caused by abdominal uptake of 99mTc-labeled agents. Comparing purposes of the examinations using 201T1 and 99mTc-labeled agents, evaluation of myocardial viability was more common in 201Tl imaging, meanwhile, detection of myocardial ischemia was more common in imaging with 99mTc-labeled agents. It was pointed out that dual isotope imaging using 201Tl and 99mTc-labeled agents and simultaneous evaluation of myocardial perfusion and cardiac function are clinically feasible as new diagnostic procedures.

Heart↗

Inhibition of octapeptide N-myristoylation by acyl amino acids and acyl alkanolamines.

Several acyl amino acids and acyl alkanolamines were prepared and screened for their inhibition of octapeptide N-myristoylation and HIV-1 replication in MT-4 cells. Of the 62 acyl derivatives tested, N-myristoyl-O-caproyl-L-serine, N-myristoyl-O-caproyl-D-serine and N-decanoyl-O-myristoyl-L-serine were found to be uncompetitive inhibitors of N-myristoylation, but did not prevent HIV-induced cytopathicity in MT-4 cells. However, other acyl derivatives such as N-3-hydroxymyristoyl ethanolamine, N-3-hydroxymyristoyl-D-serine and N-myristoyl-L-cysteine, which did not inhibit N-myristoylation, suppressed the cytopathicity in the infected cells. The acyl derivatives described here may serve as lead compounds for antiviral agents.

Acylation↗

[MR spectroscopy in acute brain infarction: differentiation of infarcted and non-infarcted areas].

Two cases of brain infarction were studied using multivoxel proton MR spectroscopy (MRS). MRS of both cases clearly demonstrated an increased level of lactate and decreased N-acetylaspartate (NAA), resulting in a high lactate/NAA ratio (LNR). Case 1 without thrombolysis therapy revealed that the area where LNR was less than 1.0 did not develop to infarction. This was also confirmed by MRS of case 2, who received an interventional reperfusion 4 hours after onset. In acute stags of brain infarction, on LNR greater than 1.0 on H-MRS may predict the margin of the infarcted region. Elevation of lactate in the non-infarcted cerebral hemisphere has not been reported before, and farther evaluation is necessary.

Aspartic Acid↗

Human antibodies responsible for binding inhibition and polymerization inhibition of human immunodeficiency virus type 1 reverse transcriptase.

Using a solid-phase non-radioisotopic (non-RI) reverse transcriptase (RT) assay, antibodies inhibiting human immunodeficiency virus type 1 (HIV-1) RT activity (RTI antibody) were investigated for their ability to inhibit binding of RT to a template-primer and DNA polymerization. The RTI antibody inhibited the binding of RT to the template-primer (BI antibody), and directly reacted with the RT-template-primer complex and inhibited enzymatic activity (PI antibody). The RTI antibody interfered with formation of the RT-template-primer complex suggesting that it recognized the antigenic site involved in template-primer binding of RT molecules. Since deoxynucleotide triphosphates (dNTPs) blocked inhibition of the RT activity by the PI antibody, the antigenic site recognized by the PI antibody may be closely related to the dNTP binding site. The seropositivities of the BI and PI antibodies were 84.6% and 91.2%, respectively, in HIV-1-infected individuals; healthy individuals, HTLV-I-positive individuals, autoimmune disease patients and leukemia patients were all seronegative. No significant correlation of residual RT activities was observed when BI and PI antibodies were compared (r = 0.688). It is possible that the epitopes recognized by the BI antibody differs from those recognized by the PI antibody. The assays described are able to detect BI and PI antibodies in the sera of HIV-1-infected individuals.

Animals↗

[Follow-up of HIV carriers by a laboratory method. I: Virus isolation is useful for prognostication of the onset of symptoms].

We followed 54 HIV-1 carriers (44 asymptomatic carriers and 10 AIDS patients) by virus isolation and immunological examination and evaluated their usefulness for prognostication of the onset of symptoms. From 37 carriers (27 asymptomatic carriers and 10 symptomatic), 132 HIV-1 strains were isolated; the virus isolation rate was 60% in the asymptomatic carriers (AC) but 100% in the symptomatic. In the AC, the isolation rate was 54.5% in the group showing stable in the CD4+ level but 95.5% in the group showing a decrease in the CD4+ level. With progression of the disease, the culture time required for virus isolation was shortened, and the percentage of isolates showing infectivity to the T-cell line (MT-4 cells) increased. These findings suggest that the virus in the body is changed with progression of the disease to that showing rapid replication, T-cell tropic, and high pathogenicity. Indeed, progression of the disease was observed in all carriers in whom a highly pathogenic virus was detected; some developed the disease within 1 year, some showed temporary recovery in the CD4+ level after AZT administration followed by progression to ARC, and others showed a rapid decrease in the CD4+ level. In contrast, in carriers with only slightly pathogenic virus, the CD4+ level was maintained for a long period. These results suggest that the detection of a highly pathogenic virus is one of the most reliable marker for the prognostication of the onset of the disease. The detection of HIV-1 antigen in the plasma and a decrease in the gag antibody were also associated with the progression of the disease. However, the reliability of these markers seems to be lower than that of virus isolation.

Acquired Immunodeficiency Syndrome↗

[Prognosis and evaluation of drug therapy by V3 and RT gene analysis of HIV-1].

We have reported on the investigation of 54 HIV-1 patients concerning the isolation and clinical marker in the preceding paper. We have attempted the analysis of the V3 and RT genes. HIV-1 from a patient who had rapidly taken a turn for the worse had basic amino acid at position 11 (Arg) and lost an acidic amino acid at position 25 (Gln) of V3. This sequence pattern was a distinguished feature of a virus with a rapid-high, syncytium inducing (SI) and T-cell-line tropic phenotype. In contrast, patients with no or mild clinical symptoms had sequences characterized as slow-low, non-synsytium inducing (NSI) and macrophage tropic. We then investigated the appearance of resistant to AZT and ddI. It was shown that the virulent virus obtained drug resistant variants faster than the wild type by analysis of the RT gene. We consider that these data concerning virus isolation and gene analysis are useful for prognosis and strategy for clinical therapy.

Acquired Immunodeficiency Syndrome↗