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Biomedical subjects

Y Ohkuma

Publications and source records attributed to Y Ohkuma.

At least 55 records · Page 3Linked to original sources

[Parameter in fulminant hepatitis].

Serum complement hemolytic activities (CH 50) and plasma prothrombin time (PTT) of patients with fulminant hepatitis (FH, 11 cases of acute type and 11 cases of subacute type), severe acute hepatitis (AH-S, 9 cases) and typical acute hepatitis (AH-T, 20 cases) were examined. AH-S was diagnosed as AH patients with PTT under 40% and without hepatic coma. Survival rates were 100% in AH-S, 45.5% (5/11) in acute type of FH and 9.1% (1/11) in subacute type of FH. The mean levels of CH 50 on their admission were 42.6 U/ml in AH-T, 28.8 U/ml in AH-S and 13.1 U/ml in FH. CH50 levels in acute hepatitis decreased in parallel to the severity of the disease and correlated with PTT (r = 0.809). In many cases of FH and almost all cases of AH-S, CH50 levels changed more slowly than those of PTT. The patients with AH-S and subacute type of FH showed a prolonged PTT and the normal levels of CH 50 in their acute phase. These results indicate that CH50 and PTT could be useful markers differentiating subacute type from acute type of fulminant hepatitis.

Acute Disease↗

Analysis of structure-function relationships of yeast TATA box binding factor TFIID.

A systematic series of N-terminal, C-terminal, and internal deletion mutants of S. cerevisiae TFIID were expressed in vitro and tested for TATA box binding and basal level transcription activities using, respectively, DNA mobility shift and in vitro transcription assays. The domains responsible for these activities were colocalized to a surprisingly large region containing C-terminal residues 63-240. This region was noted previously to contain potentially interesting structural motifs (central basic core, direct repeats, and sigma factor homology) and, more recently, to be highly conserved among TFIID from different species. Deletion mutant cotranslation studies revealed that TFIID binds DNA as a monomer. The implications of these results for TFIID structure and function are discussed.

Base Sequence↗

[The clinical significance of serum sialyl SSEA-1 antigen in obstetrical and gynecological patients].

To evaluate the clinical significance of serum SSEA-1 level, the antigen level was measured in sera of obstetric and gynecologic patients. A positive rate was low in patients with endometriosis (9.1%), myoma uteri (0%), benign ovarian tumor (15%), cervical squamous cell carcinoma (14%) and endometrial carcinoma (18%). In this series of study, interest was that positive cases in benign ovarian tumor group were all patients with dermoid cyst. On the other hand, a high positive rate was observed among the patients with cervical adenocarcinoma (50%), primary ovarian malignancies (55%) and secondary ovarian malignancies (50%). Among the patients with ovarian malignancies, serum sialyl SSEA-1 level significantly increased according to clinical stage. In patients with positive serum sialyl SSEA-1, rising or falling of the serum level of this antigen correlated well with progression or regression of the disease. Measurement of serum CA125 was also performed in patients with ovarian malignancies, which showed a significantly higher positive rate (96%) and revealed that this antigen has no correlation with sialyl SSEA-1. A low positive rate of serum sialyl SSEA-1 level (9.1%) was observed in gravidas, while a higher positive rate (43%) in puerperas, especially within three days after parturition. This evidence should be considered when serum sialyl SSEA-1 antigen is measured as tumor marker. All these observations suggest that the measurement of serum sialyl SSEA-1 level is useful not only in the diagnosis of ovarian malignancies but for the judgment of the effect of treatment and the search for their recurrences.

Antigens, Neoplasm↗

Binding site-dependent direct activation and repression of in vitro transcription by Drosophila homeodomain proteins.

Fushi tarazu and engrailed are two of the genes required for proper segmentation of the Drosophila embryo. Their protein products Fushi tarazu and Engrailed (Ftz and En) each contain a homeodomain and have been shown to act as transcriptional regulators in transient expression experiments in a Drosophila cell culture system. We used an in vitro transcription system to test whether the effects of Ftz and En on transcription were direct or indirect. Purified Ftz directly activates in vitro transcription by binding to homeodomain binding sites inserted upstream of the TATA box of the Drosophila hsp70 promoter. Equimolar amounts of purified En repress this activation by competition with Ftz for binding to these sites. These results indicate that Ftz and En act directly as transcription factors and suggest that such homeodomain proteins regulate development by combinatorial transcriptional control.

Animals↗

Factors involved in specific transcription by mammalian RNA polymerase II: identification of general transcription factor TFIIG.

We have identified and partially characterized another human general transcription factor, TFIIG. Using a reconstituted in vitro system comprised of purified RNA polymerase II, TFIIB, TFIID, TFIIE, and TFIIF, we found that TFIIG was essential for specific initiation from all class II genes tested. In this system TFIIA could partially replace TFIIG; however, even at saturating concentrations of TFIIA, addition of TFIIG further stimulated transcription. Since the chromatographic properties of TFIIG differed significantly from those of TFIIA, we concluded that TFIIA and TFIIG are distinct but functionally related transcription factors. Heparin challenge assays showed that TFIIG is required for the assembly of a functional preinitiation complex. However, it must act after template commitment by TFIID, since this step did not require, and was unaffected by, either TFIIG or TFIIA.

Cell Nucleus↗

Factors involved in specific transcription by mammalian RNA polymerase II: purification and characterization of general transcription factor TFIIE.

Human transcription factor TFIIE, a ubiquitous factor required for transcription initiation by RNA polymerase II, was purified to homogeneity by a combination of conventional and HPLC steps. The purified TFIIE contained equimolar amounts of 57-kDa (TFIIE-alpha) and 34-kDa (TFIIE-beta) polypeptides that were judged to be functional subunits on the basis of their copurification with transcriptional activity and the recovery of activity following renaturation of polypeptides separated by reverse-phase HPLC. TFIIE-alpha had an independent TFIIE activity whereas TFIIE-beta had no activity alone but enhanced the activity of TFIIE-alpha. In conjunction with gel filtration studies, which indicated a molecular mass of approximately 180 kDa for the native protein, these results suggested that TFIIE is a heterotetramer containing two alpha and two beta polypeptides. Functional studies with the purified TFIIE demonstrated that it is a general initiation factor, required for all of the genes tested, but it failed to show any DNA-dependent ATPase activity.

Cell Nucleus↗

Engrailed, a homeodomain protein, can repress in vitro transcription by competition with the TATA box-binding protein transcription factor IID.

Engrailed (En) is a homeodomain protein that binds to a consensus sequence (NP) and plays an important role during Drosophila development. Purified En, which is produced in Escherichia coli, binds not only to this consensus sequence but also to the TATA box of the Drosophila Hsp70 promoter and of other eukaryotic promoters. Interestingly, En represses transcription of these promoters in an in vitro-reconstituted mammalian transcription system and footprint analyses show that En competes with the TATA box-binding protein transcription factor IID for binding to the TATA box. In contrast, a stable template-committed complex formed by preincubation of transcription factor IID with the promoter is not disrupted by addition of En, and in this case transcription is not repressed. These in vitro studies suggest a transcriptional repression mechanism, involving competition between En and transcription factor IID for TATA box binding, that may be involved in En-mediated repression in vivo.

Animals↗

[Clinical evaluation of the treatment of early cervical neoplasia by carbon dioxide laser conization].

One hundred twenty patients with cervical neoplasia were treated by conization, 78 with a carbon dioxide laser and 42 with a cold knife. Bleeding during the conization was 82.5 +/- 91.4 ml with the laser and 117.3 +/- 82.6 ml with the cold knife. The time required for the operation was 55.0 +/- 16.7 min and 37.7 +/- 10.2 min, respectively. With the aid of a local injection of epinephrine, peroperative bleeding was much less pronounced in the laser group (25.4 +/- 39.5 ml) and the time required for the operation was further shortened to 36.4 +/- 15.0 min. Six patients treated with the cold knife (14.3%) suffered postoperative hemorrhage requiring hemostasis, but only one in the laser series (1.3%). Forty-nine patients of 78 treated with the laser and 15 of 42 treated with the cold knife were subjected to conservative therapy. All of them were followed up by cytology, colposcopy and histology, and there was no failure or recurrence at either 8 weeks and 1 year after the operation. Unsatisfactory colposcopic findings developed in 9 patients (18.4%) in the laser group compared with 11 patients (73.3%) in the cold knife group. Specimens obtained after laser conization were satisfactory for use in histopathological evaluation. Conization with a carbon dioxide laser appears to be an acceptable procedure as a diagnostic method and conservative therapy for cervical neoplasia.

Adult↗

Identification and characterization of Sarcophaga lectin receptor on the surface of murine macrophages by use of monoclonal antibodies.

The structure of Sarcophaga lectin receptor on the surface of murine macrophages was analyzed using monoclonal antibodies. This receptor was found by gel filtration to have a molecular weight of 460 kDa. SDS-polyacrylamide gel electrophoresis showed that this receptor consists of two subunits of 170 kDa and 110 kDa. The results indicated that it is probably a heterotetramer of two molecules of each subunit. Two monoclonal antibodies recognized epitopes in the 110 kDa subunit, and one of them specifically inhibited the binding of Sarcophaga lectin to macrophages and the cytotoxic reaction mediated by this lectin in the presence of macrophages. Therefore, it is likely that the 110 kDa protein in the receptor plays a role in activation of macrophages by this lectin.

Animals↗

Antitumor activities of human recombinant interferon-gamma against cervical tumor transplanted into nude mice.

This study examines the antitumor effects of recombinant interferon-gamma (ReIFN-gamma), by comparing various routes for its administration in nude mice transplanted with human cervical tumor cells. Daily intratumoral injection of ReIFN-gamma showed the best inhibitory effect, although intramuscular daily administration of this IFN also showed a significant antitumor effect. Furthermore, the earlier treatment was initiated after tumor inoculation, the better was the antitumor effect of the IFN. Histologic examination of the transplanted tumors after treatment with ReIFN-gamma showed a sparse or reticular arrangement of the tumor cells, and very large multinucleated giant cells. Unlike the original tumor, 'pearl' formation and isolated cell keratinization were frequently observed in the transplanted tumors obtained from IFN-treated groups.

Animals↗

Participation of common surface receptor(s) in the activation of murine macrophages by Sarcophaga lectin and wheat germ agglutinin.

Mouse peritoneal macrophage surface proteins which bind Sarcophaga lectin were studied. Two major binding proteins with molecular masses of 170 and 110 kDa were identified. Sarcophaga lectin and wheat germ agglutinin were found to share common binding proteins for activating macrophages, although their hapten sugars are different. Antibody raised against the Sarcophaga lectin-binding proteins inhibited both the production of tumor-specific cytotoxic protein by the macrophage-like cell line J774.1 cells and the lectin-dependent macrophage-mediated cytotoxic reaction induced by Sarcophaga lectin or wheat germ agglutinin. Thus the 170-kDa and/or 110-kDa protein is important in activation of macrophages.

Animals↗

[Clinical evaluation of specificity of serum CA125 as a tumor marker of ovarian carcinoma].

To evaluate whether elevated serum CA125 levels have specificity to ovarian malignancies, CA125 levels were measured in sera of 48 malignancies, 56 benign diseases and 40 healthy women. Furthermore serum CA125 levels were serially followed up in all the patients with positive serum CA125 levels (35 U/ml less than or equal to) to evaluate the correlation between serum CA125 levels and the response to treatment. Results obtained were as follows. A significantly higher positive rate (91%) of serum CA125 levels was observed in patients with ovarian malignancies than that (30%) in patients with other malignancies. Positive serum CA125 levels were also observed in patients with endometriosis, benign ovarian tumor, hydrosalpinx, uterine myoma and peritoneal tuberculosis. Serum CA125 levels in patients with malignancies depend on the volume of the solid part of the tumor irrespective of the tumor type. In patients with positive serum CA125 levels, rising or falling of the serum levels of this antigen correlated well with progression or regression of all kinds of diseases. These results suggested that a high positive rate of this antigen in patients with ovarian malignancies was not merely derived from the tumor specificity of this marker but partly from the fact that tumor sizes of ovarian malignancies were generally larger than those of other malignancies.

Adenocarcinoma↗

[The effects of intention and mental imagery on the learning of peripheral skin temperature control].

This study aimed to examine the effects of intention to raise the skin temperature and the use of warm imagery as a strategy for the control of skin temperature without biofeedback. Thirty-two adult female subjects were assigned to either one of following four groups: intention-imagery (It-Im), intention-no imagery (It-NIm), no intention-imagery (NIt-Im), and no intention-no imagery (NIt-NIm) groups. The finger-tip skin temperature was measured during following sessions: first trial, first rest, second trial, and second rest sessions. Results were as follows: the It-Im group was able to raise its skin temperature in the first and the second trial sessions, the It-NIm and NIt-Im groups were not able to raise their skin temperature in any sessions, and the skin temperature of the NIt-NIm group was raised during the first trial session, but it was stopped at the second trial session. These results suggest that both intention and strategy are necessary for the control of skin temperature without biofeedback.

Adolescent↗

Identification of target proteins participating in a lectin-dependent macrophage-mediated cytotoxic reaction.

Membrane proteins of mouse macrophages and mammary tumor cells having affinity to Sarcophaga lectin were isolated by affinity chromatography. The electrophoretic profiles and antigenicities of lectin-binding proteins from macrophages and tumor cells were different. Antibody raised against tumor cell lectin-binding proteins inhibited both the binding of the lectin to tumor cells and the lectin-dependent macrophage-mediated cytotoxic reaction. However, it did not inhibit the binding of the lectin to macrophages. It was suggested that the same lectin molecule transmitted different stimuli to macrophages and tumor cells via different receptor proteins.

Animals↗

Comparison of binding proteins on the surface of murine tumor cells for two lectins active in the lectin-dependent macrophage-mediated cytotoxic reaction.

The binding proteins for Sarcophaga lectin and wheat germ agglutinin on the surface of Ehrlich ascites tumor cells were compared. Studies with antibody against the binding protein for Sarcophaga lectin showed that these two binding proteins are different. Since these two lectins are both active in the lectin-dependent macrophage-mediated cytotoxic reaction with Ehrlich ascites tumor cells as target cells, there must be multiple proteins on the surface of target cells that can trigger cytolytic reaction in response to different lectins in the presence of macrophages.

Animals↗