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Biomedical subjects

A Hakura

Publications and source records attributed to A Hakura.

At least 91 records · Page 5Linked to original sources
PubMed1990

A novel monoclonal antibody against squamous cell carcinoma.

The monoclonal antibody, INS-2, was raised against rat fibroblasts transformed by open reading frames E6 and E7 of human papillomavirus (HPV) DNA. In immunoperoxidase testing of frozen sections, the INS-2 antibody was reactive with all squamous cell carcinomas of the uterine cervix and esophagus tested. In contrast, no antibody binding was detected with adenocarcinomas of various origins. Similarly, normal tissues, lymphoid cells and erythrocytes from multiple donors were negative, except that binding localized at basal cells in normal squamous epithelium was observed. Interestingly, strong staining was observed in dysplastic cells of cervical intraepithelial neoplasia and at the growing edge of squamous cell carcinomas. The antigen for the INS-2 antibody is a non-sialyl glycoprotein with Mw. 40,000 and appears to be a squamous cell-specific cell differentiation marker, although it is not related to HPV-DNA-derived protein.

Animals↗
PubMed1990

[Transforming genes of human papillomaviruses and cancer].

The human papillomaviruses (HPVs) are epitheliotropic viruses that induce epithelial hyperproliferation including cutaneous warts and condylomas in cervical and vaginal epithelia. Certain types of HPVs, such as HPV 16, 18 are closely associated with cervical cancer, penile cancer and skin cancer of EV (epidermodysplasia verruciformis) patient. Experimental studies in cultured cell lines provide strong support for the idea that HPV 16 and 18 have transforming genes and are involved in the development of above cancers. However, their transforming genes are unable to induce malignant transformation of primary cultured cells originated from rodent, human for skin and cervical epithelial cells. For the carcinogenesis by HPVs, alteration of some additional factor(s) is thought to be necessary. It is the aim of this review to summarize recent knowledge about transforming genes of HPVs and their additional factors associated with carcinogenesis focused on cervical cancer.

Cell Transformation, Viral↗
PubMed1989

A rat mutant cell clone showing temperature-dependent transformed phenotypes with functional expression of the src gene product.

The cellular mutant B814 isolated from a Fischer rat cell line shows temperature-sensitivity of focus formation on infection with Moloney murine sarcoma virus (Mo-MSV) and Rous sarcoma virus (RSV). An RSV-transformed clone (S814-2) isolated from B814 cells shows temperature-sensitive transformed phenotypes for morphology, growth in soft agar, and glucose uptake. The expression, phosphorylation, and tyrosine kinase activity of pp60v-src in S814-2 were not affected at the nonpermissive temperature, and virus rescued from this clone had wild-type transforming ability, suggesting that a cellular factor altered in S814-2 is responsible for the cellular steps of transformation after the function of pp60v-src. In addition, the cellular 36K protein, a possible candidate as a target of pp60v-src, was phosphorylated at the nonpermissive temperature in S814-2, indicating that phosphorylation of the 36K protein is not correlated with transformed phenotypes.

Animals↗
PubMed1989

Isolation and characterization of temperature-sensitive mutants of Abelson murine leukaemia virus that exhibit dissociation among morphological transformation, soft agar colony-forming ability and tyrosine kinase activity.

Seven temperature-sensitive (ts) mutants of Abelson murine leukaemia virus (A-MuLV) were isolated on the basis of the temperature dependence of their soft agar colony-forming ability. These seven ts mutants exhibited similar characteristics and were not ts for morphological transformation and autophosphorylation of P120gag-abl protein. The dissociation of the properties of morphology, soft agar colony formation and tyrosine kinase activity might suggest that the v-abl product has more than one primary intracellular target.

Abelson murine leukemia virus↗
PubMed1989

Types of human papillomavirus isolated from Japanese patients with epidermodysplasia verruciformis.

Virological studies were performed on 12 patients with epidermodysplasia verruciformis (EV). Three types of lesions were observed: red plaques, pityriasis versicolor (PV)-like macules and plane warts. Human papillomavirus (HPV) 14, 20 and 21 were isolated from the plaques, HPV 3, 14 and 38 from flat warts and HPV 5, 12, 17, 20 and 38 from PV-like lesions. No clear relationship could be established between the different lesions and the types of HPV. Types 17 and 20 have been isolated most frequently from Japanese EV patients and HPV 5, frequently detected in other countries, is less common, whereas HPV 8 has not been isolated. Skin cancers occurred in six of the cases (50%) and all had benign lesions that were PV-like. At least one type of HPV 5, 17 or 20 could be isolated from these benign lesions and HPV 17 or 20 detected in the cancers. These three types of HPV in EV patients appear to be involved in the malignant transformation.

Adult↗
PubMed1989

A cell mutant that exhibits temperature-dependent sensitivity to transformation by various oncogenes.

We previously isolated a Fisher rat fibroblast mutant, B812, that has the unique property of temperature-dependent transformation by various oncogenic retroviruses. At the permissive temperature (35 degrees C), this mutant was sensitive to oncogenic transformation and formed foci on a dish at the same frequency as did the parental fibroblast cell line. When Kirsten murine sarcoma virus (Ki-MSV) was applied to the cells, the frequency of focus formation decreased more than 25-fold at the nonpermissive temperature (39 degrees C), whereas the cells expressed nearly the same level of the ras transcript as well as the ras protein. The temperature-restricted focus formation was fully reversible and was completely suppressed upon fusion with the wild-type parent cell. In addition to ras, the mos, fos, src, and erbB-2 oncogenes transformed this mutant with the same temperature dependence as described above; polyomavirus middle T antigen, adenovirus type 12, and human papillomavirus 16-E67 also transformed, but without temperature dependence. These results suggest that ras, fos, mos, src, and erbB-2 use a common cellular pathway for transforming cells.

Animals↗
PubMed1989

[Oncogene of human papillomavirus].

Although certain types of human papillomavirus (HPV) have been supposed to be associated with carcinogenesis of cervix, a definitive conclusion has not yet been reported. To show that HPV is a causative agent of cervical cancer, we performed several lines of experiments and obtained the results described below. 1) In attempting to identify an activated oncogene(s), we showed that cellular DNAs from 8 cervical carcinomas induced transformation of NIH 3 T 3 cells and, in all cases, HPV sequences were retained in the secondary transformants. 2) Using a retrovirus vector system, we showed that HPV-16 had transforming activity for mouse or rat established cells. The transforming genes are located in the E6 and E7 ORF: the former governs tumorigenicity in nude mice and the latter influences cell growth properties such as saturation density, colony formation in soft ager and immortalization. These results strongly suggest that specific types of HPV are involved in carcinogenesis of the cervix. However, HPV only may not be sufficient to induce carcinomas, because even the E6 and E7 ORFs of HPV-16 could not transform rat primary cells immediately after infection, but could do so after a long latency. Evaluation of the change during the latency is very important to clarify the mechanism of cervical carcinogenesis.

Animals↗
PubMed1988

Functional dissociation of transforming genes of human papillomavirus type 16.

Human papillomavirus (HPV) type 16 is thought to be responsible for development of cervical carcinomas, but the mechanism of its carcinogenic action is unknown. To determine which viral genes are involved in cellular transformation, we constructed recombinant murine retrovirus DNAs containing various subgenomic fragments of the HPV 16 early region and examined their transforming activities. The results show that the E6 and E7 ORFs are the transforming genes of HPV 16; the former governs the tumorigenicity in nude mice and the latter influences cell growth properties such as saturation density and colony formation in soft agar. There may also be a tumor-suppressing gene in the E1-E2 ORF region, because the tumorigenic activity of recombinant DNA containing the E1 ORF and the 5' portion of the E2 ORF in addition to the E6 and E7 ORFs was much lower than that of recombinant DNA containing only the E6 and E7 ORFs.

Animals↗
PubMed1988

Temperature-sensitive cellular mutant for expression of mRNA from murine retrovirus.

The cellular mutant B812 isolated from a Fisher rat cell line shows temperature sensitivity of focus formation induced by various retroviruses such as recombinant murine retrovirus containing the middle T gene of polyomavirus (PyMLV), Kirsten murine sarcoma virus, Moloney murine sarcoma virus, and recombinant murine retrovirus containing the src gene of Rous sarcoma virus. B812 cells, however, show normal ability to proliferate and synthesize protein at the nonpermissive temperature, suggesting that their mutation is in a gene specifically concerned with the process of transformation by retroviruses. In this work, experiments with hybrids of mutant and wild-type cells showed that the temperature-dependent defect of this mutant was complemented by wild-type cells. To determine the step of transformation that is restricted at the nonpermissive temperature in B812, we examined the expressions of the oncogene (middle T antigen) in no. 7 (wild-type cells) and B812 cultures infected with PyMLV (the chimeric retrovirus containing the middle T gene of polyomavirus) at the permissive and nonpermissive temperatures. Middle T-associated protein kinase activity, the expression of middle T antigen, and PyMLV-specific mRNA were reduced at the nonpermissive temperature in B812 cultures infected with PyMLV. However, integration of PyMLV into the chromosomal DNA of the mutant was not affected at the nonpermissive temperature. These results suggest that B812 cells have a mutation affecting the expression of viral mRNAs from integrated proviral DNA at the nonpermissive temperature.

Animals↗
PubMed1988

[Papillomavirus and cancer].

Papillomaviruses are causative agents of benign tumor (papilloma) and are widely distributed in most of animals. The papillomaviruses are small DNA viruses grouped in the papovavirus family. The genomes of all papillomaviruses pce double stranded circular DNA of approximately 8 K. base pairs. Classification of the viruses is presently based on the host range and relatedness of the nucleic acids. In the case of human papillomavirus (HPV), more than 50 types have been isolated. The amount of information about the HPV has grown considerably in the last few years, and at present it has been considered that the specific types of HPV are involved in the development of human genital cancer and the skin cancer developed in the patients with EV (epidermodysplasia verruciformis). The reasons are; i) Epidemiological evidence distinctly indicates that cervical carcinoma and other high-grade lesions of female and male genital tracts derive from a sexually transmitted disease. ii) Many cervical carcinomas, most cell lines derived from the carcinoma and almost all skin tumors of EV patient contain specific types of HPV DNA (genital tumors; HPV-16, 18, 31, 33 and 25, skin tumor of EV patient; HPV-5, 8, 17 and 20). Moreover, genetic information of the viruses can be detected in the cancer cells. iii) Follow-up studies of HPV carriers suggested that HPV-16, 18 have high oncogenic potential. iv) Oncogenic functions (transformation and immortalization) can be detected in the early genetic region of HPV-16 DNA. v) Cottontail rabbit papillomavirus (CRPV) induces tumor in rabbit (and that almost all of these tumors contain CRPV DNA. When rabbits are infected with CRPV, benign papillomas are induced in 100% of the rabbits and the lesion are progressed to skin cancer at the frequency of 40-60%). In human cases, however, the presence of specific types of HPV does not seem to be sufficient to assure the development of benign tumors into carcinomas, since only a part of all such cases progress after latent period of several to several ten years. This emphasizes that other etiological agents or cofactors must be involved.

Animals↗
PubMed1987

Formation of 8-hydroxyguanine residues in DNA treated with 4-hydroxyaminoquinoline 1-oxide and its related compounds in the presence of seryl-AMP.

The mechanism whereby treatment of DNA with 4-hydroxyaminoquinoline 1-oxide (4HAQO) in the presence of seryl-AMP leads to the formation of 8-hydroxyguanine (8-OH-Gua) residues in DNA (Kohda et al., this journal, 139, 626, 1986) has been studied. In the survey of other N-arylhydroxylamines, only 4HAQO analogues which could bind to DNA produced 8-OH-Gua. The amount of 8-OH-Gua varied depending on the structure of 4HAQO analogues and that of DNA. The formation of 8-OH-Gua was not inhibited by active oxygen scavengers. Possible mechanisms are discussed.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1987

Purification and properties of a non-histone chromatin protein with a molecular weight of 38,000 daltons specific for transformed rat cells.

Non-histone chromatin proteins prepared from a normal rat cell line (No. 7) and the cells transformed with Rous sarcoma virus (RSV) (s7-1) were compared by means of reverse-phase high performance liquid chromatography (reverse-phase HPLC), followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The results revealed that several proteins were specifically present in the transformed cell chromatin. A specific non-histone chromatin protein with a molecular weight of 38,000 daltons, 38K protein, was purified as a single species from s7-1 cells. This 38K protein was only detected in the transformed state of the cells transformed with a temperature-sensitive (ts) mutant of the src gene and the mutant cells which showed temperature sensitivity as to the transformation with wild type RSV.

Animals↗
PubMed1987

Human papillomavirus type 17 transcripts expressed in skin carcinoma tissue of a patient with epidermodysplasia verruciformis.

Certain types of human papillomavirus (HPV) are involved in skin carcinogenesis in epidermodysplasia verruciformis. However, no gene or gene product of HPV associated with skin carcinogenesis has yet been identified. Here, we report HPV-17 transcripts expressed in skin carcinoma tissue of an epidermodysplasia verruciformis patient infected with HPV-17. Further, we show that one of these transcripts was localized to a portion of the genome which contains the 3' open reading frames of the early region (E2, E3, E4 and E5). The analogous region in bovine papillomavirus type I has been shown to contain a transforming gene (Nakabayashi et al., 1983; Sarver et al., 1984; Yang et al., 1985a).

Bovine papillomavirus 1↗
PubMed1987

Inhibitory effect of heavy water on mutability of chemically injured Escherichia coli cells.

After E. coli cells (WP2 and WP2uvrA) were treated with chemical mutagens (methyl methanesulfonate, MMS; N-methyl-N-nitrosourea, MNU; 4-nitroquinoline 1-oxide, 4NQO) in 1/15 M phosphate buffer, the mutability of the treated cells plated on a D2O-agar plate was compared with that plated on an ordinary H2O-agar plate. The mutation frequency decreased more or less on the D2O-agar plate. The D2O-substitution effects, as termed by the relative mutation frequencies (MFD2O/MFH2O), are 0.92 for MMS, 0.29 for MNU, and 0.42 for 4NQO in WP2, and 0.68 for MMS, 0.49 for MNU, and 0.16 for 4NQO in WP2uvrA. The D2O effect seemed to be partly related to the function of the uvrA gene-associated products. The pH dependence of mutability was discussed in connection with the D2O-substitution effect.

4-Nitroquinoline-1-oxide↗
PubMed1987

IgA multiple myeloma coexistent with atypical adult T-cell leukemia.

We report a 65-yr-old male with adult T-cell leukemia (ATL) who developed multiple myeloma (MM) concomitantly. Skin lesions and peripheral leukocytosis were noted during the 5-yr observation period. There was abnormal lymphocytosis with indented or lobulated nuclei in the peripheral blood and in the bone marrow. The neoplastic cells reacted with monoclonal antibodies, OKT3, OKT4, OKIa1 and anti-Tac. His serum was positive for the antibodies to ATL-associated antigens. Human T-cell leukemia virus (HTLV) proviral DNA was detected in the leukemic cells. Thus, a diagnosis of ATL was made. There was IgA (k) paraprotein in his serum, and Bence-Jones protein (k) in urine samples. Fine needle aspiration revealed pathologic flaming plasma cells. Multiple osteolytic lesions appeared on his skull 5 yr after the initial examination. Thus, a diagnosis of MM concomitant with ATL was made.

Aged↗
PubMed1987

New human papillomavirus sequences in female genital tumors from Japanese patients.

Tissues from 52 cervical carcinomas, 15 cervical intraepithelial neoplasias III (CINs III), and 3 vulvar carcinomas were examined for the presence of human papillomavirus (HPV) sequences by Southern blot hybridization with HPV 16 or 18 DNA as the probe. HPV 16 or 18 DNA was detected in only 17 cervical carcinomas (33%), 5 CINs III (33%), and 1 vulvar carcinoma (33%). These frequencies are lower than those reported by others. However, new, as yet unidentified, HPVs were also detected at rather high frequency under less stringent conditions of hybridization using HPV 16 and 18 DNAs as probes. These HPVs did not hybridize with HPV 6, 11, 16, or 18 under stringent conditions, and were different from two other known types of genital tumor-associated HPVs, HPV 31 and HPV 33, judging from the patterns of their restriction enzyme digests. The total frequencies of HPV sequences were 48% (25/52) for cervical carcinomas, 53% (8/15) for CINs III, and 67% (2/3) for vulvar carcinomas.

Carcinoma↗