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1.

001-es BibID:BIBFORM035823
Első szerző:Kónya József (szakorvos, klinikai mikrobiológus)
Cím:Identification of a cytotoxic T-lymphocyte epitope in the human papillomavirus type 16 E2 protein / Kónya J., Eklund C., af Geijersstam V., Yuan F., Stuber G., Dillner J.
Dátum:1997
ISSN:0022-1317
Megjegyzések:Persistent infection with oncogenic types of human papillomaviruses (HPV) is the major cause of cervical cancer precursor lesions. Cellular immune responses are considered important in the elimination of HPV infection, but the targets are not well defined. HPV E1 and E2 proteins form a replicative complex necessary for viral genome maintenance. To investigate whether epitopes in the E1 or E2 proteins can serve as targets for cytotoxic T-lymphocyte (CTL)-mediated killing, we identified peptides containing the human leukocyte antigen (HLA)-A*0201 binding motif in the deduced amino acid sequences of the HPV-16 E1 and E2 genes. Binding affinity of the peptides was measured by HLA-A*0201 up-regulation on T2 cells. Peptides with high binding-affinity were tested for their ability to elicit peptide-specific CTLs from healthy blood donors. We found one peptide from the E1 and one from the E2 protein sequence that were capable of eliciting peptide-specific CTLs. The E2-specific CTLs lysed an HPV-16-transfected cervical carcinoma cell line, but not the untransfected HPV-negative parental cell line, indicating that the identified E2 epitope can be presented to CTLs in HPV-positive epithelial cells. These findings might have potentially important implications for studies of the natural history of HPV infection in relation to cervical carcinogenesis.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of General Virology. - 78 : Pt10 (1997), p. 2615-2620. -
További szerzők:Eklund, Carina af Geijersstam, Veronika Yuan, Fang Stuber György Dillner, Joakim
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2.

001-es BibID:BIBFORM035822
Első szerző:Kónya József (szakorvos, klinikai mikrobiológus)
Cím:Primary induction of human cytotoxic lymphocytes against a synthetic peptide of the human immunodeficiency virus type 1 protease / Kónya J., Stuber G., Björndal A., Fenyö E. M., Dillner J.
Dátum:1997
ISSN:0022-1317
Megjegyzések:Identification of in vitro immunogenic T-cell epitopes is important for the design of immunotherapeutics targeted to specific antigenic sites. To identify candidate cytotoxic T-lymphocyte (CTL) epitopes in the protease of human immunodeficiency virus type 1 (HIV-1) strain MN, we synthesized 9-mer and 10-mer peptides containing the HLA-A*0201 binding motif. Binding affinity of the peptides was measured by HLA-A*0201 up-regulation on T2 cells. Peptides with high binding-affinity were tested for their ability to stimulate primary CTLs from healthy HIV-negative blood donors. Peptide-specific CTLs were obtained from five out of six donors by stimulation with a 9-mer (LVGPTPVNI) or a 10-mer (VLVGPTPVNI) peptide derived from a highly conserved amino acid stretch in the C-terminal region of the protease. Addition of peptide-specific CTLs to acutely HIV-infected lymphocytes resulted in inhibition of p24gag production. In conclusion, a highly conserved HIV protease peptide regularly elicits peptide-specific CTLs. Targeting immune responses against defined epitopes in non-variable regions may be a feasible way to minimize the risk of virus escape from immune surveillance.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of General Virology. - 78 : Pt9 (1997), p. 2217-2224. -
További szerzők:Stuber György Björndal A. Fenyö E. M. Dillner, Joakim
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3.

001-es BibID:BIBFORM035817
Első szerző:Kónya József (szakorvos, klinikai mikrobiológus)
Cím:Immunity to oncogenic human papillomaviruses / Kónya J., Dillner J.
Dátum:2001
ISSN:0065-230X
Megjegyzések:The establishment of human papillomavirus (HPV) infection as a major cause of several human cancer forms, notably cervical cancer, has spurred development of prophylactic and/or therapeutic HPV vaccines for prevention of cervical neoplasia. Knowledge of the immunity to HPV forms the basis for such endeavors. METHOD: A literature review of humoral and cellular immunity to HPV. The overview on human leukocyte antigen (HLA) and cervical cancer was expanded to a formal metaanalysis, where relevant articles were located by Medline search and citation analysis and graded by preassigned quality criteria on study design. RESULTS: The antibody response to the HPV particle is dominated by a neutralizing antibody response to a typespecific, conformationally dependent immunodominant epitope. Vaccines based on viral particles lacking the viral genome (virus-like particles, VLPs) have been highly successful in preventing and treating HPV infection in several animal model systems. In humans, the serum antibody response to VLPs is stable over time, also after the HPV infection has been cleared, resulting in HPV serology being used as a marker of cumulative HPV exposure in spite of the fact that a significant proportion of HPV-exposed subjects fail to seroconvert. More than 90% of HPV infections will clear spontaneously. The factors that determine whether an HPV infection is cleared or persists and increases the risk for cancer are not known, but cellular immunity is implicated. Several HLA class II haplotypes are associated with cervical cancer: DQw3 increases and DR13 decreases the risk for cervical cancer in general (odds ratios (OR) and 95% confidence intervals (CI): 1.25(1.15-1.37) and 0.69 (0.56-0.85), respectively); DR15 increases the risk for HPV16-carrying cancer (OR: 1.47; CI: 1.20-1.81); and DR7 may be either protective or increase the risk. Most cervical cancers have downregulated the expression of at least one HLA class I antigen, whereas class II expression is increased in infected epithelium. A Th2 cytokine profile is associated with progression to cervical cancer. HPV-antigen-specific proliferative responses have been detected in many studies, although it is not entirely clear whether these responses are HPV type specific or may be cross-reactive between HPV types. Specific cytotoxic T lymphocyte (CTL) responses were originally reported in only a minority of infected subjects, typically cancer patients, but with advancing technology, specific CTLs can be stimulated from about half of the women with HPV-carrying disease. In animal model systems, CTL responses can mediate clearance. CONCLUSION: The antibody response to HPV is a mediator of type-specific protective immunity, which forms the basis for prophylactic vaccine candidates. The cellular immunity to HPV is implicated as an important factor in cervical carcinogenesis, but the main targets and types of responses that mediate HPV clearance are not established.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Advances In Cancer Research. - 82 (2001), p. 205-238. -
További szerzők:Dillner, Joakim
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4.

001-es BibID:BIBFORM014060
Első szerző:Szőke Krisztina
Cím:Moderate variation of the oncogenic potential among high-risk human papillomavirus types in gynecologic patients with cervical abnormalities / Szőke Krisztina, Sápy Tamás, Krasznai Zoárd, Hernádi Zoltán, Szládek Györgyi, Veress György, Dillner Joakim, Gergely Lajos, Kónya József
Dátum:2003
ISSN:0146-6615
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of Medical Virology. - 71 : 4 (2003), p. 585-592. -
További szerzők:Sápy Tamás Krasznai Zoárd Tibor (1973-) (szülész-nőgyógyász, gyermeknőgyógyász) Hernádi Zoltán (1948-) (szülész-nőgyógyász, klinikai onkológus) Szládek Györgyi Veress György (1966-) (biológus, mikrobiológus) Dillner, Joakim Gergely Lajos (1940-) (szakorvos, klinikai mikrobiológus) Kónya József (1964-) (szakorvos, klinikai mikrobiológus)
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5.

001-es BibID:BIBFORM035819
Első szerző:Wang, Zhaohui
Cím:Human papillomavirus antibody responses among patients with incident cervical carcinoma / Wang Zhaohui, Konya Jozsef, Avall-Lundkvist Elisabeth, Sapp Martin, Dillner Joakim, Dillner Lena
Dátum:1997
ISSN:0146-6615
Megjegyzések:The human papillomavirus (HPV) is recognized as a major cause of cervical cancer precursor lesions. HPV serology is a key method in the continuing elucidation of the importance of HPV exposure for cancer development and in predicting HPV-associated diseases. To extend previous HPV serological studies on cervical cancer, serum samples from a consecutive series of 216 women with incident untreated cervical carcinoma and 243 age- and sex-matched healthy blood donors were evaluated for the presence of antibodies against HPV capsids, a marker of past or present HPV exposure, as well as against several cervical cancer-associated defined HPV epitopes. Among the capsid antibody responses, HPV type 16 seropositivity had the strongest association with cervical cancer (OR 2.7, 95% CI 1.8-4.2), but HPV 18 and HPV 33 seropositivities were also significantly associated with cervical cancer (OR 1.6, 95% CI 1.1-2.5; and OR 1.5, 95% CI 1.0-2.2, respectively). The antibody responses against the defined HPV epitopes were confirmed to be associated with cervical cancer, at ORs ranging from 1.4 to 2.0. In conclusion, the study confirms that antibodies against defined HPV epitopes are associated with cervical cancer and provides evidence that seropositivities for HPV types 16, 18, and 33 are associated with cervical cancer risk.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of Medical Virology. - 52 : 4 (1997), p. 436-440. -
További szerzők:Kónya József (1964-) (szakorvos, klinikai mikrobiológus) Avall-Lundkvist, Elisabeth Sapp, Martin Dillner, Joakim Dillner, Lena
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