Search PubMed⌕ Search

Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 469 records · Page 26Linked to original sources

[A case report of thymolipoma with high titer of serum anti-acetylcholine receptor antibodies--thymolipoma, a review of 49 reports in Japan].

A 22-year-old man was diagnosed as thymolipoma by chest CT scan & MRI. In spite of high titer of serum anti-acetylcholine receptor antibodies, he showed no symptom of myasthenia gravis. An extended thymectomy was done successfully. Tumor was 21 x 15 cm in size and 620 g in weight. Histopathologically the tumor was diagnosed as thymolipoma. The titer of serum anti-acetylcholine receptor antibodies was decreased within normal limit and postoperative course was uneventful. To our knowledge, the 49 case reports in Japan were reviewed.

Adult↗

Accuracy of computed tomography in determining pancreatic cancer tumor size.

We compared tumor sizes determined by computed tomography (CT) with those of the resected specimens in 26 patients with pancreatic cancer in order to clarify whether or not the size of a pancreatic tumor can be accurately determined by CT. From the precontrast, postcontrast and arterial dominant phases of dynamic CT, the arterial dominant phase was found to yield the highest correlation between CT measured tumor size and that of the resected specimens (P < 0.01). The correlation coefficient was, however, not high (r = 0.67). CT alone may therefore be insufficient to determine tumor size in pancreatic cancer accurately.

Adenocarcinoma↗

Novel inhibitors of poly(ADP-ribose) glycohydrolase.

The inhibitory effects on poly(ADP-ribose) glycohydrolase purified from human placenta of three classes of chemically defined tannins; gallotannins, ellagitannins and condensed tannins, were examined in vitro. Oligomeric ellagitannins were found to be most potent inhibitors of poly(ADP-ribose) glycohydrolase, their potencies increasing with increasing number of monomeric residues (dimer < trimer < tetramer). Monomeric ellagitannins and gallotannins were less inhibitory. Condensed tannins, which consist of an epicatechin gallate oligomer without a glucose core, were not appreciably inhibitory. A structure-activity study showed that higher-order conformations of the conjugates with glucose of hexahydroxydiphenoyl and valoneoyl groups, which are unique components of ellagitannins, cooperatively potentiated the inhibitory activity.

Enzyme Inhibitors↗

Specific IgG autoantibodies are potent inhibitors of autoreactive T cell response to phytohemagglutinin-activated T cells.

PHA-activated human T cells express MHC class II molecules and have been shown to stimulate autoreactive T cells in autologous mixed lymphocyte reaction (T-T AMLR). We now demonstrate that normal human serum can dramatically suppress the proliferative response in T-T AMLR. The inhibitory factor was detected in the IgG fraction, and the activity was found to be mediated through the F(ab')2 portion of the IgG molecule, implying that the inhibitor could be specific. All homologous as well as autologous sera tested contained the inhibitory activity. Human serum was also found to suppress allogenic MLR stimulated by PHA-activated T lymphocytes but not allogenic MLR stimulated by nonactivated PBMC, indicating that the mechanism of inhibition is related to PHA activation of the stimulator cells. Moreover, pretreatment of the PHA-activated T lymphocytes with human serum resulted in a significant inhibition of T-T AMLR, as opposed to pretreatment of nonactivated PBMC, indicating that PHA-activated stimulators are functionally involved in the inhibition. Cytofluorometric analysis revealed that autologous IgG specifically binds to PHA-activated T lymphocytes and not to nonactivated CD3+ T cells. Furthermore, serum absorbed by PHA-activated T lymphocytes substantially lost its inhibitory activity whereas serum absorbed by nonactivated PBMC did not, suggesting that a surface molecule(s) expressed during activation of the stimulator cells is involved in the inhibition. The addition of human serum later in the culture period (> 3 days) resulted in a marked decrease in inhibition, implying that the presence of IgG in the early recognition phase of T-T AMLR is essential for maximum inhibitory effect. These results raise the possibility that natural autoantibodies present in normal human IgG may play an important role in regulating immune response mediated by autoreactive T cells.

Autoantibodies↗

Preferential degradation of protein-bound (ADP-ribose)n by nuclear poly(ADP-ribose) glycohydrolase from human placenta.

Poly(ADP-ribose) glycohydrolase, extensively purified to homogeneity from nuclei of human placenta, is composed of a single polypeptide with a molecular mass of 71,000 daltons on sodium dodecyl sulfate-polyacrylamide gel. Judging from its physico-chemical and catalytic properties, the enzyme is similar to the nuclear glycohydrolase (glycohydrolase I), but not to the cytoplasmic glycohydrolase (glycohydrolase II) that has been purified from guinea pig liver (Tanuma, S., Kawashima, K., and Endo, H. (1986) J. Biol. Chem. 261, 965-969; Maruta, H., Inageda, K., Aoki, T., Nishina, H., and Tanuma, S. (1991) Biochemistry 30, 5907-5912). The rates of hydrolysis of (ADP-ribose)n bound to various proteins by the purified nuclear glycohydrolase were higher than those of the corresponding free polymers. Kinetic analyses revealed that the enzyme had more activity toward poly(ADP-ribose) bound to histone H1 or to poly(ADP-ribose) polymerase than toward oligo(ADP-ribose) bound to cytoplasmic proteins from mitochondria or mRNA ribonucleoprotein although the Km and Vmax values were dependent on the chain length (n). In contrast, cytoplasmic glycohydrolase purified from human erythrocytes was more active toward oligo(ADP-ribose) (n = 2.6 or 4.2) bound to the cytoplasmic proteins than to poly(ADP-ribose) (n = 14.6) bound to histone H1, and their kinetic parameters of glycohydrolase II were rather dependent on the acceptor molecules for (ADP-ribose)n. These results suggest that poly(ADP-ribose) glycohydrolase I may play an important role in regulation of poly(ADP-ribosyl)ation levels on chromosomal proteins in nuclei.

Amino Acids↗

The UDP-galactose translocator gene is mapped to band Xp11.23-p11.22 containing the Wiskott-Aldrich syndrome locus.

We have cloned a segment of the human gene encoding UDP-galactose translocator by genetic complementation of its defective mutant in mouse FM3A cells. Chromosome mapping using fluorescent in situ hybridization revealed that the cloned gene hybridized to the Xp11.23-11.23 region of the X chromosome. This region is shared by the locus of Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency disorder, characterized by defective sugar chains on cell surface components. Genetic and phenotypic similarities suggest a possible link between UDP-galactose translocator and the Wiskott-Aldrich syndrome (WAS).

Animals↗

Clinical evaluation of immunotherapy in early pregnancy with x-irradiated paternal mononuclear cells for primary recurrent aborters.

OBJECTIVE: The purpose of this study was to evaluate the beneficial effect of immunotherapy for the treatment of recurrent abortion. STUDY DESIGN: We immunized 106 primary recurrent aborters, twice at around 5 and 7 weeks of gestation, with intradermal injection of approximately 100 to 200 million x-irradiated (50 Gy) paternal mononuclear cells. We injected another 38 primary recurrent aborters in the same manner with only 1 million such paternal cells, to examine the relationship between the paternal cell dose used for immunization and pregnancy outcome. RESULTS: The pregnancy success rate (83.0%) in patients immunized with a large number of cells was significantly higher than that (55.3%) in those immunized with a small number of cells (p < 0.001). Furthermore, the frequency of twins in the former group was high (5.7%, five of 88). CONCLUSION: This positive relationship between the paternal cell dose used for immunization in early pregnancy and the pregnancy outcome reflects the efficacy of this mode of immunotherapy for recurrent aborters.

Abortion, Habitual↗

Interaction of pine cone extract fraction VI with mutagens.

Pine cone extract fraction VI (PC-VI) inhibited the mutagenicity of the promutagens tested: the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) dose-dependently, and the aromatic amines 2-aminoanthracene (AA) and 2-acetylaminofluorene (AAF) at high concentrations. PC-VI had no effect on the mutagenicity of the direct-acting mutagens 2-(2-furyl)-3-(5-nitrofuryl)acrylamide (AF-2) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but inhibited the mutagenicity of the direct-acting mutagen N-hydroxy 2-acetylaminofluorene (N-OH AAF, proximate mutagen of AAF). The addition of PC-VI to rat hepatic microsomes resulted in a decrease of their enzyme activities, especially NADPH-cytochrome c reductase. By gas-chromatographic analysis of B[a]P or AA contents after incubation of B[a]P or AA and PC-VI and S9 mix, the inhibition of hepatic metabolizing enzymes and the interaction between AA and PC-VI were confirmed. On the other hand, PC-VI had no effect on the DNA repair systems for B[a]P- or AA-induced mutagenesis. We conclude that PC-VI shows indirect antimutagenicity by interfering with cytochrome P-450-dependent bioactivation and by direct interaction with AA and the proximate mutagenic product of AAF.

2-Acetylaminofluorene↗

Age dependence of O6-methylguanine-DNA methyltransferase activity and its depletion after carcinogen treatment in the teleost medaka (Oryzias latipes).

O6-Methylguanine-DNA methyltransferase (O6-MT) is considered to play an important role in the repair of DNA lesions induced by alkylating carcinogens in a wide range of animals. The activity of O6-MT was compared in liver extracts from the teleost medaka (Oryzias latipes) at various ages (3-5 years old) reared under natural conditions. O6-MT activity decreased significantly with advancing age. When medaka were exposed continuously to the alkylating agent methylazoxymethanol (MAM) acetate at levels of 0.1, 0.15 and 0.3 ppm in water, O6-MT activity was markedly reduced from days 1 to 7, with a slight increase thereafter. Furthermore, when fish were exposed to MAM acetate at levels of 1-2 ppm for 1 h and then maintained in normal tap water, O6-MT activity remained suppressed for 2 weeks, followed by a partial recovery.

Aging↗

Prognostic significance of selected lifestyle factors in urinary bladder cancer.

To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.

Adult↗

Specific antiphospholipid antibodies as a predictive variable in patients with recurrent pregnancy loss.

PROBLEM: Antiphospholipid antibodies (APLs) consist of very heterogenous autoantibodies. It has not been fully explored what kind of specificities are most relevant to recurrent pregnancy loss. Thus, we investigated the effects of specific APLs on recurrent aborters. METHOD: IgG and IgM antibodies against PE (treated with 1% acetic acid) and five negatively-charged phospholipids were measured by ELISA among 334 recurrent aborters without autoimmune disease. The relationships between APL specificities and subsequent pregnancy outcome were prospectively investigated in 38 recurrent aborters with positive APL who did not receive treatment with prednisolone and aspirin. Antibody levels exceeding the 99th percentile of 280 healthy women were considered positive. RESULTS: Positive IgG and/or IgM APLs were detected in 14%, IgG APLs in 12%, and IgG antibodies against PA, PG, PI, PS, CL and PE, respectively, in 9%, 7%, 7%, 7%, 8%, and 8%. In a prospective study of the 38 untreated patients, fetal loss recurred in 82% of the 33 IgG APL-positive patients, but in 40% of the five patients positive for only IgM APLs. The incidence of fetal loss in the next pregnancy of patients with IgG specific APL-positive against PE, PI, PS, or Cl was even higher at 90% and over, and fetal loss recurred in all of 21 patients with two or more IgG APL-positive against PE, PI, PS, or CL. CONCLUSION: These results suggest the possibility that two or more IgG APL-positive value against treated PE, PI, PS, or CL, may be more accurate as a predictive variable than that of only one IgG APL-positive in patients with recurrent pregnancy loss.

Abortion, Habitual↗

[Seroepidemiological study on hepatitis C virus infection in an endemic area of hepatitis C virus].

To clarify the prevalence of hepatitis C virus infection in a rural area with high incidence of chronic liver disease in Japan, sera from 412 inhabitants, aged 20-89 years, collected in 1989-1990 and sera from 483 inhabitants in the same area, collected in 1982 were tested for anti-HCV (antibody to C100-3) with the first-generation enzyme-linked-immunosorbent-assay (ELISA). In addition, sera from 118 inhabitants, aged 20-49 years, collected in 1989-1990 were tested for HCV-RNA with the polymerase chain reaction technique, with use of primers from the 5'-untranslated region of the HCV genome. Anti-HCV was positive in 175 out of 412 sera collected in 1989-1990 (42.5%): prevalence was higher in male (54.0%) than in female (34.9%). The prevalence rates in the 20-29, 30-39, 40-49, 50-59, 60-69, and 70-89 year-old group were 0%, 14.3%, 51.9%, 41.7%, 49.1%, and 53.1%, respectively. On the other hand, in sera collected in 1982, the overall prevalence of anti-HCV was 42.5% (175 of 412). The prevalence rates in the 20-29, 30-39, 40-49, 50-59, 60-69, and 70-89 year-old group were 12.5%, 43.3%, 51.5%, 50.3%, 60.7%, and 68.9%, respectively. The prevalence rate of young adults less than 40 years old in 1982 were higher than that in 1989-1990. In short, the prevalence of hepatitis C virus infection in this area had altered a great deal. HCV-RAN was detected in 42 of 118 (35.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A phase 2 study of cisplatin in patients with hepatocellular carcinoma.

A phase 2 study of cisplatin was performed in 28 previously untreated patients with unresectable hepatocellular carcinoma. The drug was given intravenously at a dose of 80 mg/m2/day every 4 weeks. Of 26 patients evaluated, 4 (15.4%) showed partial responses lasting for > 3 months, while no patient achieved a complete response. Of 22 patients whose serum level of alpha-fetoprotein (AFP) was high (> 400 ng/ml) before treatment, 6 (27.3%) showed a > 50% reduction in serum AFP levels after treatment. The current study indicates that cisplatin is an anticancer agent worthy of further testing in patients with this disease.

Adult↗

[Inhibitory effects of palonidipine hydrochloride (TC-81) on contractions induced by various vasoconstrictors in rat aorta].

Inhibitions by palonidipine hydrochloride (TC-81), a new Ca entry blocker, of the contractile responses to norepinephrine (NE), serotonin (5-HT), prostaglandin F2 alpha (PGF2 alpha) and U-46619, a thromboxane A2 analog, were investigated in isolated rat aorta strips and compared with the inhibition of the high K+ response. TC-81 and nicardipine inhibited the contractile responses to NE, 5-HT, PGF2 alpha, and U-46619 in a concentration-dependent manner, but their relative inhibitions were less than 50% at 10(-8) M. In a Ca(2+)-free medium, 2-hr pretreatment with TC-81 or nicardipine did not inhibit the contractile responses to various vasoconstrictors, but it inhibited the responses to the addition of Ca. Their inhibitory potencies were less than the inhibition with high K+. Also, the treatment with TC-81 or nicardipine at 10(-7) M did not affect the tissue level of cyclic AMP. These results suggest that in isolated rat aorta, the inhibition by TC-81 of the contractile responses to NE, 5-HT, PGF2 alpha and U-46619 is not due to inhibition of intracellular Ca2+ release or an increase in cyclic AMP; rather, it is due to inhibition of the Ca2+ influx. This inhibitory effect was less than that seen on the high K+ response.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

[Effect of palonidipine hydrochloride (TC-81), a novel calcium antagonist, on the canine coronary artery].

The effects of palonidipine hydrochloride [TC-81: (+/-)-3-benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride], a new calcium antagonist, on the coronary artery were studied in dogs. In the isolated canine coronary artery, TC-81 inhibited high K+ (60 mM)-induced contraction in a concentration-dependent manner. The relaxant activity of TC-81 was equal to that of nicardipine and more potent than those of nifedipine and diltiazem. TC-81 increased coronary blood flow in a dose-dependent manner after i.v.-administration in anesthetized open-chest dogs. The activity of TC-81 was equal to that of nifedipine or nicardipine, but the duration of its effect was longer than that of nifedipine or nicardipine. By oral administration in conscious dogs, TC-81 increased coronary blood flow at 0.1 mg/kg or more, and its activity was 10 times more potent than that of nifedipine. These results suggest that TC-81 increases coronary blood flow and is capable of improving the oxygen supply-demand relationship during angina pectoris.

Animals↗