[Two cases of acute exacerbation of chronic hepatitis C improved after the administration of an immunosuppressive drug and interferon].
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Antiviral Agents↗
Biomedical subjects
T Kiyono
Publications and source records attributed to T Kiyono.
[Systemic therapy, pain relief and quality of life of breast cancer patients with bone metastasis].
Systemic therapy, pain relief and the quality of life (QOL) of breast cancer patients with bone metastasis were described. QOL was measured using a "QOL questionnaire" developed by the Ministry of Welfare in Japan. It was proved objectively that QOL scores in the cases with bone metastasis were significantly low in terms of activity, physical psychological conditions. Chemoendocrine therapy, endocrine therapy and outpatient therapy showed a high QOL score. The cases with bone pain showed a low QOL scores. In the 45 cases whose first metastatic site was bone only, there were no differences between endocrine therapy and chemoendocrine therapy in the rate and period of response or the total QOL score. MPA showed a higher response rate and a higher pain relief rate than TAM. In the cases with bone metastasis but without severe visceral metastasis, MPA monotherapy showed an excellent response when the tumor was ER or PgR positive, or when there was a long disease-free interval of more than three years, or if there was no previous therapy. MPA monotherapy is a suitable firstline therapy in such cases. Radiation therapy was more effective for bone pain (response rate 96.3%), and it was also effective in cases in which systemic therapy was not.
Antineoplastic Combined Chemotherapy Protocols↗
Correlation between tumorigenicity and expression levels or splicing patterns of transcripts of the human papillomavirus type 16 E6 gene.
For determination of the correlation between tumorigenicity and the expression levels or splicing patterns of E6 mRNAs of the human papillomavirus type 16 in established cells, a vector containing the intact E6 open reading frame which expresses both unspliced and spliced mRNAs, one expressing only unspliced E6 mRNA, and one expressing both unspliced and spliced mRNAs but producing only truncated E6 proteins were constructed. In transformation assays and analyses of E6 mRNAs, a higher expression level of unspliced E6 mRNA was found to be closely associated with tumorigenicity. Furthermore, it was also related with anchorage-independent growth and a decreased serum requirement of the cells.
Alternative Splicing↗
Inhibition of p53-mediated transactivation by E6 of type 1, but not type 5, 8, or 47, human papillomavirus of cutaneous origin.
Transient transfection experiments indicated (i) that E6 protein of non-cancer-associated cutaneous human papillomavirus type 1 (HPV-1) can inhibit p53-mediated transcriptional transactivation in both p53-deficient human cells (H358) and normal rat cells (3Y1), but those of cancer-associated cutaneous HPV-5, -8, and -47 cannot do so in either H358 or 3Y1 cells, and (ii) that E6 proteins of HPV-16 and -18 can inhibit the p53 function in H358 cells but not in 3Y1 cells.
Amino Acid Sequence↗
Diagnosis of thyroid carcinoma by ultrasonic examination: comparison with diagnosis by fine needle aspiration cytology.
Ultrasonic examination was performed on 120 patients who later underwent surgery. Ultrasonically, among the 64 cases of benign nodules and the 56 of carcinomas, 50 and 46 cases respectively were diagnosed correctly. In making the ultrasonic diagnosis, the following findings were considered; shape, margin, boundary, internal echoes, hyperechoic spots, the echo level of the nodule and the cystic pattern. The sensitivity for carcinoma diagnosis was 0.82, specificity was 0.78 and accuracy was 0.80. The diagnostic accuracy for the same patients using a newly devised diagnostic system that utilized a fuzzy inference was almost as high as that of the conventional method. Furthermore, the diagnostic accuracy of both of these methods did not differ significantly from that obtained by fine needle aspiration cytology. Therefore, non invasive ultrasonic examination is considered to be very useful for the detection and diagnosis of thyroid carcinoma.
Biopsy, Needle↗
The incidence of ground glass nuclei in thyroid diseases.
Ground glass nuclei are an important finding in the diagnosis of papillary carcinoma of the thyroid. However, they appear only in specimens in paraffin-embedded histological sections, and not in frozen sections or cytological specimens. This has led to the conclusion that they are an artifact of fixation and/or embedding. However, if this is the case, a question arises as to whether or not such an artifact can be of value as a definitive sign for establishing a diagnosis of papillary carcinoma. This study was undertaken to try to answer that question. 1) To confirm whether or not the author's microscopic observations were correct, we carried out automatic imaging analysis with the Interaktives Bild-Analysen System (IBAS). The author's microscopic observations were consistent with the data obtained by the IBAS. 2) Among 20 cases of papillary carcinoma, clear nuclei were observed in 11 cases (55%), and pseudoclear nuclei were noted in 20 cases (100%). When 1,000 papillary cancer cells were counted in 10 cases, the average incidences of clear nuclei and pseudoclear nuclei were found to be 0.51% and 18.3% respectively. Clear nuclei were seen in papillary carcinomas in all kinds of fixatives except one but were not seen in benign lesions. Even though ground glass nuclei are a type of artifact, we believe that their presence may be considered to be a characteristic feature of papillary carcinomas of the thyroid.
Adenoma↗
Comparative study on E6 and E7 genes of some cutaneous and genital papillomaviruses of human origin for their ability to transform 3Y1 cells.
E6 (or E7) genes of some genital and cutaneous human papillomaviruses (HPVs) were compared for their ability to transform cells of a rat fibroblastic line (3Y1) by using recombinant retroviruses. The E6 gene of genital cancer-associated HPV 16 or 18 was found to induce a characteristic morphological change, i.e., densely packed arrays of elongated cells forming swirl patterns. This change is the same as that induced by the E6 gene of cutaneous cancer-associated HPV 5, 8, or 47, which we described previously. The E6 gene of HPV 1 or 11, associated with benign tumor of cutaneous or genital tissue, respectively, induced no such change. The E6 genes of all these cutaneous and genital HPVs enhanced anchorage-independent growth of the target cells induced by E7 gene of HPV 16 or 18, and this enhancing activity of HPVs 16, 18, and 47 was stronger than that of HPVs 1 and 11. A distinct type of morphological transformation of 3Y1 cells, i.e., rounded miniaturized cells that were densely packed without forming any distinctive arrays, was found to be induced strongly by E7 genes of HPVs 16 and 18, weakly by E7 of HPVs 1 and 11, and not at all by E7 of HPV 47. The results suggest that the intensity of the morphological change induced by E6 genes, rather than E7 genes, is correlated to the risk of malignant conversion of the lesion with which the corresponding HPVs are associated.
Cell Line↗
Surgical strategy for papillary carcinoma of the thyroid in an iodine rich area: decision on the operation table.
In iodine rich areas the incidence of papillary carcinoma of the thyroid is extremely high but its prognosis is favorable. When papillary carcinoma is confined to one lobe, our standard surgical procedure has been total lobectomy with isthmusectomy rather than total thyroidectomy. Our followup study of 185 such patients reveals considerable difference in the outcome between the 85 patients with gross thyroid capsular invasion and the 100 patients without, regardless of the presence of cervical lymph node metastasis. In the latter group, the tumor could be completely resected in all patients; although 4 cases had recurrence and required reoperation, 3 patients are alive and well and one died of other disease. In contrast, 20 patients in the former group had incomplete resection of the tumor, 4 patients developed recurrence and needed to be reoperated and 7 patients eventually died of thyroid cancer. One hundred thirty three patients (71.9%) underwent modified neck dissection at the time of surgery to find lymph node metastasis in 37 of 59 cases (62.7%) without gross thyroid capsular invasion and 64 of 74 cases (86.5%) with such invasion. The difference is statistically significant (P < 0.05). From these results we conclude that for papillary thyroid cancer in iodine rich areas total lobectomy with isthmusectomy is the treatment of choice when gross thyroid capsular invasion is not recognized on the operation table. However, when gross thyroid capsular invasion is recognized, total or near total thyroidectomy has to be performed.
Adult↗
Differences in transforming activity and coded amino acid sequence among E6 genes of several papillomaviruses associated with epidermodysplasia verruciformis.
Using the polymerase chain reaction technique, we cloned and sequenced DNA fragments containing the E6 genes of the epidermodysplasia verruciformis (EV)-associated HPVs 5, 8, 14, 20, 21, 25, and 47, of which only the sequences of HPVs 5, 8, and 47 have previously been reported. Based on the deduced amino acid sequence homology (57.3 to 83.0%), these HPVs could be divided into two clusters: HPVs 5, 8, and 47, and HPVs 14, 20, 21, and 25. The E6 genes of three HPVs from each cluster were examined for transforming activity toward a cultured rat fibroblast cell line, 3Y1, using the retrovirus-mediated gene transfer technique, and all were found to induce morphological transformation. However, the E6 genes of the first cluster were more potent than those of the second. Since HPVs 5 and 8 are the most frequently found HPVs in malignant lesions of EV patients, the observed in vitro transforming activities of the E6 genes may reflect their oncogenic potential in humans.
Amino Acid Sequence↗
Genome organization and taxonomic position of human papillomavirus type 47 inferred from its DNA sequence.
The complete nucleotide sequence of human papillomavirus type 47 (HPV-47) DNA isolated from the lesion of epidermodysplasia verruciformis (EV) was determined. The computer-aided comparison of HPV-47 with other EV-associated viruses using the available sequence data on them revealed that HPV-47 resembles both HPV-5 and HPV-8 as much as HPV-5 and HPV-8 resemble each other, and it led us to regard these three viruses as one cluster and HPV-19 and HPV-25 as another. The conclusion implies that HPV-47 as well as HPV-5 and HPV-8 is associated with the cancer occurrence in EV. Two sets of splicing donor and acceptor sequences in HPV-47, which were previously shown to work in vivo, are also conserved in HPV-5 and HPV-8. One of them allows formation of an ORF predicted to encode an E1/E4 fused protein.
Amino Acid Sequence↗
The primary structure of major viral RNA in a rat cell line transfected with type 47 human papillomavirus DNA and the transforming activity of its cDNA and E6 gene.
A transformed cell line (RC335) showing higher saturation cell density was obtained from 3Y1 cells (a fibroblastic cell line of rat) transfected with DNA of human papillomavirus type 47 (HPV-47), an epidermodysplasia verruciformis-associated virus, which our laboratory reported previously. The cell line was found to produce a major and several minor species of viral RNAs. The primary structure of the major viral RNA in RC335 was extensively studied and found to consist of two exons and contain open reading frames (ORFs) E6, E7, and a fused ORF, E1/E4. The major RNA was indicated to play an important role in the transformation of RC335 by an experiment with the recombinant retrovirus designed to produce the RNA containing these ORFs, i.e., the recombinant virus induced transformation similar to that in RC335 upon infection of 3Y1 cells. Furthermore the experiments with recombinant viruses carrying a nonsense mutation or large deletion in the above ORF(s) indicated that E6 was necessary and sufficient for the transformation.
Animals↗