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M Lehtinen

Publications and source records attributed to M Lehtinen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Serological evidence of an association between chlamydial infections and malignant lymphomas.

Chronic infections may predispose to malignant growth. Recently, serological markers of chronic Chlamydia pneumoniae infection have been associated with lung cancer. Our aim was to study the possible association between chronic chlamydial infections and malignant lymphomas. The present case-control study involved 72 patients with lymphoma (31 females and 41 males) and matched controls. 53 patients had non-Hodgkin's lymphoma (NHL) and 19 had Hodgkin's disease. The sera, collected at the time of diagnosis, were tested for IgG antibodies and immune complexes to C. pneumoniae and C. trachomatis by a microimmunofluorescence method and ELISA and for IgG antibodies and immune complexes to Helicobacter pylori by ELISA. The serological markers suggesting chronic chlamydial infection were associated with malignant lymphoma. The association was most evident for the presence of C. pneumoniae-specific immune complexes in NHL (OR = 7.3, 95% CI 2.2-25) and appeared to be limited to men. No association between H. pylori antibodies or immune complexes and malignant lymphomas could be demonstrated. Our study provides seroepidemiological evidence of an association between chronic chlamydial infections and lymphomas.

Adult↗
PubMed1998

Stability over time of serum antibody levels to human papillomavirus type 16.

The stability over time of serum IgG antibody levels to human papillomavirus type 16 (HPV-16) was determined by comparing the HPV-16 capsid antibody levels in serial serum samples of an age-stratified random subsample of 1656 primiparous mothers resident in Helsinki who were followed until their second pregnancy, on average 29.5 months later. The correlation between the first and second pregnancy HPV-16 serum antibody levels of the same woman was high, even when >4 years had elapsed between pregnancies (r = .822). Between negativity, indeterminate results, or quartiles of positivity, the predictive values for being classified in the same category on both occasions ranged between 42% and 91%. Correlation coefficients, predictive values, and kappa coefficients between serial samples all were comparable with those of repeat analyses of the same sample, indicating that HPV capsid antibody levels are generally stable during several years of follow-up.

Adolescent↗
PubMed1998

Common and emerging infectious causes of hematological malignancies in the young.

Comparative epidemiological studies have for a long time suggested a link (or links) between infectious agents and hematological malignancies in the young. Identification of Epstein-Barr virus (EBV) as the major cause of specific subtypes of Burkitt's lymphoma and Hodgkin's disease 20 and 10 years ago, respectively, and the recent involvement of human T-cell leukemia virus in non-Hodgkin's lymphomas of the T-cell lineage in young adults in Jamaica have given further credit to early presumptions that these diseases have an infectious etiology. The spectrum of possibly involved viruses: old, EBV, and new, herpesviruses 6, 7 and 8, and unknown retroviruses - as well as the list of partially or totally unresolved disease entities: Hodgkin's disease in adolescents, non-Hodgkin's lymphomas in the immunocompromised, and acute lymphocytic leukemia - is rapidly expanding. Both direct and indirect transforming effects of the above-mentioned viruses are being rapidly disclosed. However, the complex interaction between the different viruses and other causes of hematological malignancies in the young guarantees that many things remain to be discovered also in the future.

Adolescent↗
PubMed1998

Comparison of performances of two commercially available tests, a PCR assay and a ligase chain reaction test, in detection of urogenital Chlamydia trachomatis infection.

The diagnostic performance of a PCR test (Roche Cobas Amplicor CT/NG Test) and that of a ligase chain reaction (LCR) test (Abbott LCx Chlamydia trachomatis assay) were compared by using endocervical and urethral swab specimen culture as a reference test. First-void urine (FVU) and endocervical and urethral swab specimens were collected from 1,015 unselected patients attending a sexually transmitted disease clinic and a clinic for adolescents in Helsinki, Finland. Chlamydia trachomatis was cultured from samples from the endocervix or urethra. PCR was performed with fresh and frozen urine and the culture transport medium. LCR was performed with fresh and frozen urine and LCx swab transport medium. Diagnostic consistency and diagnostic accuracy were statistically tested. The test results were identical for 984 patients (97%). Discrepant results were observed for 31 patients. Overall, LCR and PCR showed excellent kappa coefficients of consistency for both swab and FVU specimens (0.93 and 0.95, respectively). Sixty-one patients (6%) were culture positive. Testing of FVU by LCR or PCR increased the overall positivity rates to 7.0 and 7.7%, respectively. While PCR of FVU detected the greatest number of C. trachomatis infections (sensitivity, 96.1%), for some PCR-positive FVU specimens the results could not be confirmed (specificity, 99.6%). PCR and LCR were more sensitive than culture (sensitivities, 92 and 93% versus 79% for culture) in the diagnosis of genital C. trachomatis infection. In conclusion, both tests can be recommended for use in the clinical laboratory and for the screening of asymptomatic C. trachomatis infections.

Cervix Uteri↗
PubMed1997

A prospective, seroepidemiological study of the role of human papillomavirus in esophageal cancer in Norway.

Infection with the human papillomavirus (HPV), notably HPV type 16, has been associated with esophageal cancer in seroepidemiological studies. To evaluate the consistency of the association, we performed a nested case-control study of HPV seropositivity and risk of esophageal cancer within a prospectively followed cohort of 300,000 Norwegian men and women who had donated blood samples to a serum bank. The data file of the serum bank was linked with the nationwide Cancer Registry of Norway to identify esophageal cancers diagnosed after donation of the serum sample. Fifty-seven cases and 171 matched controls were analyzed for antibodies to specific microorganisms, and odds ratios for developing esophageal cancer were calculated. There was an increased risk of developing esophageal cancer among HPV 16-seropositive subjects (odds ratio = 6.6; 95% confidence interval, 1.1-71) but not among Chlamydia trachomatis-seropositive subjects. Adjustment for the presence of serum cotinine, a marker of smoking habits, did not affect the estimates substantially. The seroepidemiological association between HPV 16 and esophageal cancer seems to be consistent in different countries.

Adult↗
PubMed1997

Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers.

OBJECTIVE: To evaluate the association between infection with the major oncogenic types of human papillomavirus and the risk of developing non-cervical anogenital cancers in a cohort followed up prospectively. DESIGN: Data from two large serum banks to which about 700,000 people had donated serum samples were followed up for a mean of 8 years. People who developed non-cervical anogenital cancers during follow up were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Within this cohort a nested case-control study was conducted based on the serological diagnosis of infection with human papillomavirus types 16, 18, and 33. SUBJECTS: 81 cases and 240 controls matched for sex, age, and storage time of serum samples. MAIN OUTCOME MEASURES: Odds ratios of developing non-cervical anogenital cancers in presence of IgG antibodies to specific micro-organisms. RESULTS: Subjects seropositive for human papillomavirus type 16 had an increased risk of developing non-cervical anogenital cancers (odds ratio 3.1 (95% confidence interval 1.4 to 6.9)). Subjects seropositive for type 33 also had an increased risk (odds ratio 2.8 (1.0 to 8.3)) but not significantly after adjustment for infection with type 16. Seropositivity for human papillomavirus type 16 was associated with an increased risk of developing vulvar and vaginal cancers (odds ratio 4.5 (1.1 to 22)) and a strongly increased risk of developing preinvasive vulvar and vaginal lesions (odds ratio infinity (3.8 to infinity)). Seropositivity for human papillomavirus type 18 increased the risk of developing preinvasive lesions (odds ratio 12 (1.2 to 590)). High, but non-significant odds ratios for types 16 and 33 were seen for penile cancers. CONCLUSIONS: This study provides prospective seroepidemiological evidence that infection with human papillomavirus type 16 confers an increased risk of developing non-cervical genital cancers, particularly vulvar and vaginal cancers.

Adult↗
PubMed1997

Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer.

BACKGROUND: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. METHODS: A nested case-control study within a joint cohort of 700,000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were estimated by use of conditional logistic regression. RESULTS: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7). HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C. trachomatis, the HPV16-associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis, no excess risk was found. CONCLUSION: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.

Adenocarcinoma↗
PubMed1997

Human papillomavirus in squamous cell carcinoma of the vulva by polymerase chain reaction.

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) DNA in squamous cell carcinoma of the vulva by polymerase chain reaction (PCR). METHODS: Archival diagnostic phase biopsies from 74 patients with squamous cell carcinoma of the vulva were investigated for HPV DNA by PCR. We used both consensus primers located in the open reading frame L1 and type-specific primers for HPV 6 (open reading frame E5), HPV 11 (open reading frame L1), HPV 16, HPV 18, and HPV 33 (open reading frame E6). RESULTS: HPV DNA was detected in 27 (36%) of the 74 patients, of whom 19 had HPV 16, nine had HPV 18, one had HPV 33, and one had unclassified HPV DNA. No case of HPV type 6 or 11 was detected. Two squamous cell carcinomas were positive for both HPV 16 and 18, and one was positive for both HPV types 16 and 33. Three squamous cell carcinomas positive for E6 gene using type-specific primers were negative using L1 consensus primers. CONCLUSION: Our PCR methods using both consensus open reading frame L1-derived primers and type-specific open reading frame E6-derived primers of HPV types 16, 18, and 33 seemed to be an appropriate combination for the detection of HPV DNA in archival tissues of vulvar carcinoma. Both HPV types 16 and 18 were associated with squamous cell carcinoma of the vulva, although the prevalence of HPV 16 was considerably lower than in cervical carcinoma. It appears that vulvar and cervical carcinomas are not identical etiologically and that factors other than HPV are important in vulvar carcinogenesis.

Adult↗
PubMed1997

Genetic aberrations in pediatric acute lymphoblastic leukemia by comparative genomic hybridization.

Classical cytogenetic analysis plays an important role in the diagnosis and classification of childhood acute lymphoblastic leukemia (ALL). However, poor in vitro growth of the malignant cells and suboptimal quality of metaphase spreads may sometimes cause false-negative findings (normal karyotype). We used comparative genomic hybridization (CGH) to study whether this new method is able to detect and characterize genetic aberrations not detected by karyotyping. CGH showed clonal genetic aberrations in 8 of 13 cases, most of which showed gains of several chromosomes, indicating hyperdiploidy. The sensitivity of CGH was sufficient to detect a small interstitial deletion of 6q. One karyotypically complex case was resolved by CGH showing a high-level amplification of DNA sequences originating from the 12p12-13. Interphase fluorescence in situ hybridization (FISH) analyses confirmed the CGH findings in 2 cases, validating the accuracy of CGH. In conclusion, CGH experiments established the known fact that hyperdiploidy is the most common finding in pediatric ALLs and that CGH may detect aberrations that are not seen in the G-banded karyotype. CGH was also able to further characterize genetic aberrations such as gene amplification, which is occasionally involved in pediatric ALL as well as in other leukemias.

Child↗
PubMed1997

Diagnostic phase antibody response to the human papillomavirus type 16 E2 protein is associated with successful treatment of genital HPV lesions with systemic interferon alpha-2b.

BACKGROUND AND OBJECTIVE: Systemic interferon alpha-2b treatment reduces relapses of genital human papillomavirus (HPV) lesions in some but not all females. The aim of the present study was to investigate possible predictive pretreatment factors for the outcome of therapy. MATERIAL AND METHODS: HPV DNA status and HPV antibody response were evaluated in 100 randomized patients treated with laser ablation and systemic interferon alpha-2b or placebo, and followed up to 6 months. RESULTS: Overall, adjuvant therapy with systemic interferon-alpha did not differ from placebo. However, detectable diagnostic phase levels of serum antibodies to e.g. HPV16 open reading frame (ORF) E2 derived peptide 141EEASVTVVEGQVDYY155 predicted 10-fold difference in the risk of recurrence of HPV infection following adjuvant interferon alpha-2b therapy as compared with placebo (odds ratio, OR, 0.5, 95% confidence interval (CI), 0.1-2.3; OR, 4.6, 95% CI 0.5-41, respectively). This trend was statistically significant in the whole study population (2P < 0.05), and in patients with high viral load (2P < 0.01). CONCLUSIONS: Evaluation of the E2 antibody responses may help to identify women with genital HPV lesions who respond to systemic interferon alpha-2b treatment.

Adolescent↗
PubMed1997

Type 1 cytokine response and treatment outcome of genital HPV lesions.

OBJECTIVES: To determine the role of type 1 cytokines as predictors of response to treatment of genital HPV lesions with laser ablation with or without adjuvant systemic interferon alpha 2b (IFN-alpha). METHODS: Measurement of serum interleukin 2 (IL-2), IL-2 soluble receptor alpha (sIL-2 alpha), interferon gamma, and human papilloma virus (HPV) DNA in patients undergoing treatment of genital HPV lesions with carbon dioxide laser and systemic IFN-alpha. A randomised, placebo controlled study of 92 cases with 6 months of follow up. RESULTS: High IL-2/sIL-2 alpha was associated with 60% to 70% protection against recurrences both in the IFN-alpha and placebo groups (OR = 0.4, 90%, CI 0.1-2.5; OR = 0.3, 90% CI 0.0-1.8, respectively). Diagnostic phase serum IL-2 predicted favourable outcome (OR = 0.2, 90% CI 0.0-1.0) in women with high load of HPV DNA or HPV 16/18 DNA regardless of the adjuvant therapy. CONCLUSIONS: Serum IL-2 determinations may identify women with good prognosis following laser ablation of genital HPV lesions.

Adjuvants, Immunologic↗
PubMed1996

Human papillomavirus DNA in uterine cervix squamous cell carcinoma and adenocarcinoma detected by polymerase chain reaction.

BACKGROUND: Substantial clinical, epidemiologic, and experimental evidence has reinforced the role of high risk human papillomavirus (HPV) types in the development of cervical carcinoma. The authors investigated HPV in the uterine cervix squamous cell carcinomas and adenocarcinomas of Finnish patients. METHODS: Specimens from 352 patients with uterine cervix squamous cell carcinomas and 108 with adenocarcinoma were examined for HPV DNA by polymerase chain reaction. The authors used consensus primers located in the L1 region, as well as HPV16, 18, and 33 type-specific primers located in the E6 region. RESULTS: HPV DNA was detected in 324 of 352 squamous cell carcinomas (92%), and 81 of 108 adenocarcinomas (75%). Two-hundred seventy-four of 352 squamous cell carcinomas (78%) and 18 of 108 adenocarcinomas (17%) contained HPV16 DNA, whereas 55 of 352 squamous cell carcinomas (16%) and 60 of 108 adenocarcinomas (56%) contained HPV18 DNA. Eight squamous cell carcinomas and 4 adenocarcinomas were positive for HPV33. Twenty-eight squamous cell carcinomas and 5 adenocarcinomas were positive for either HPV16 and HPV18 or HPV16 and HPV33. Unclassified HPV DNA was detected in 17 squamous cell carcinomas and 4 adenocarcinomas. Twenty-eight squamous cell carcinomas and 9 adenocarcinomas, which were positive for E6 DNA using type-specific primers, were negative for the L1 gene. All 460 cervical specimens were tested twice with identical results. CONCLUSIONS: HPV DNA was highly prevalent in both uterine cervix squamous cell carcinoma and adenocarcinoma. HPV16 was detected more often in squamous cell carcinoma and HPV18 was detected more often in adenocarcinoma. Both consensus structural L1 gene-derived primers and type-specific viral E6 oncogene-derived primers were necessary to detect HPV DNA in cervical carcinoma.

Adenocarcinoma↗
PubMed1996

Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study.

OBJECTIVE: To study human papillomavirus type 16 in the aetiology of cervical carcinoma. DESIGN: Within a cohort of 18814 Finnish women followed up to 23 years a nested case-control study was conducted based on serological diagnosis of past infection with human papillomavirus type 16. SUBJECTS: 72 women (27 with invasive carcinoma and 45 with in situ carcinoma) and 143 matched controls were identified during the follow up. MAIN OUTCOME MEASURE: Relative risk of cervical carcinoma in presence of IgG antibodies to human papillomavirus type 16. RESULTS: After adjustment for smoking and for antibodies to various other agents of sexually transmitted disease, such as herpes simplex virus type 2 and Chlamydia trachomatis, the only significant association was with infection with human papillomavirus type 16 (odds ratio 12.5; 95% confidence interval 2.7 to 57, 2P<0.001). CONCLUSION: This prospective study provides epidemiological evidence that infection with human papillomavirus type 16 confers an excess risk for subsequent development of cervical carcinoma.

Adolescent↗
PubMed1996

Serum p53 accumulation and altered antibody responses to Epstein-Barr virus proteins precede diagnosis of haemopoietic malignancies of lymphoid origin.

We analysed antibodies to Epstein-Barr virus nuclear antigens (EBNAs 1, 2, 5 and 6) and the presence of serum p53 in 100 individuals, 37 of whom has developed a haemopoietic malignancy during a 12-year follow-up of 39,000 Finnish adults. Serum p53 was detectable in six of the 63 (10%) matched controls and in 13/31 (42%) patients who developed a malignancy of lymphoid origin approximately 7 years after serum withdrawal. Six patients who developed a malignancy of myeloid origin were negative for p53. The presence of p53 alone was associated with a highly significant increased risk of lymphoid malignancies (relative risk (RR)p53 = 6.7, 95% confidence limits (CL) 1.9, 24) whereas high levels of antibody to EBNA2 seemed to be inversely related to the risk (RREBNA2 = 0.1, CL 0.0, 1.1). Among lymphoid malignancies, a combination of serum p53 and high EBNA1 antibody levels gave a greater than expected risk (RRp53 and EBNA1 = 14, CL 1.4, 130; RRexpected = 4.4), whereas interaction with high levels of EBNA5 antibody gave an expected risk (RRp53 and EBNA5 = 19, CL 1.7, 220; RRexpected = 17). Thus detectable levels of p53 appear early in the development of lymphoid malignancies, and high EBNA1 antibody levels, and accumulated p53 may both be synergistic risk indicators for lymphoid malignancies, whereas high EBNA5 antibody levels and accumulation of p53 seem to raise the RR independently of each other.

Adult↗
PubMed1996

Definition of three minimal T helper cell epitopes of rubella virus E1 glycoprotein.

To characterize T cell-recognized epitopes on rubella virus (RV) E1 glycoprotein, IL-2-dependent RV-specific T cell lines were established from 14 rubella-seropositive healthy donors. The responses of these lines were studied by using a panel of 94 partially overlapping synthetic peptides of 15 amino acids (aa) length covering the known nucleotide sequence of RVE1 glycoprotein. Two to seven peptide-defined epitopes were recognized by the T cell lines, but a large interindividual variation was found. T cell reactivity was most often localized to the regions between aa 276 and 290, aa 381 and 395 and aa 410 and 420. Analysis of overlapping, truncated peptides revealed three minimal T helper cell epitopes VIGSQARK, KFVTAALLN and RVIDPAAQ in aa positions 280-287, 385-393 and 412-419, respectively.

Animals↗
PubMed1996

Seropositivities to human papillomavirus types 16, 18, or 33 capsids and to Chlamydia trachomatis are markers of sexual behavior.

The association of seropositivity to human papillomavirus (HPV) capsids of types 11, 16, 18, or 33 with sexual behavior was investigated. Among 1002 women visiting family planning or youth clinics in Sweden, an age-matched subsample of 274 women stratified according to lifetime number of sex partners was analyzed. The proportion of HPV-16-seropositive subjects increased linearly at approximately 4% per partner (P < .001), from 4% among those with 1 lifetime partner to 35% among those with >5 lifetime partners. Also, HPV-33 and HPV-18 seroprevalences were linearly dependent on the number of partners (P < .001, increase with 4% per partner, and P = .008, increase with approximately 3% per partner, respectively), providing serologic confirmation that the important mode of transmission of HPV-16, -18, or -33 infection in women is sexual. HPV serology appears to be suitable as a marker of sexual behavior in populations.

Adolescent↗
PubMed1996

Serological responses to human papillomavirus type 6 and 16 virus-like particles in patients with cervical neoplastic lesions.

Serum samples from 36 cervical carcinoma patients, 33 patients with high-grade squamous intraepithelial lesions, and 31 cytologically normal women were tested by enzyme-linked immunosorbent assay (ELISA) using human papilloma virus type 6 (HPV 6) and HPV 16 virus-like particles as antigens. Forty serum specimens from 1-year-old children were used to assign cutoff points. When serum samples from the subjects infected with HPV 16 were tested in an HPV 16 ELISA detecting immunoglobulin A (IgA), IgG, and IgM binding, 61% showed IgA, 44% showed IgG, and 39% showed IgM reactivity. Of HPV 6- or 11- or HPV 18-infected subjects. fewer than 17% showed IgA or IgG responses and 33% showed IgM reactivity. In contrast, 13% showed IgA, 10% showed IgG, and 16% showed IgM reactivity in the HPV DNA-negative controls. The results suggest that the IgA and IgG responses are HPV 16 specific and the IgM response is cross-reactive to different HPV types. On the other hand, the serological responses to HPV 6 did not differ in the patient and control groups. The percentages of patients positive for both IgA and IgG antibodies were significantly higher in the groups with high-grade squamous intraepithelial lesions (12% [4 of 33]; P = 0.04) and cancer (17% [6 of 36]; P = 0.02) than in the healty women (0% [0 of 31]), and the percentages for either IgA or IgG were higher for the cancer group (47% [17 of 36]; P = 0.01) than in the normal group (19% [6 of 31]). Most sera positive for IgA and IgG in the patient groups showed higher titers than those in the normal group. All these results suggest that high IgA and IgG responses are good indicators for estimating HPV 16 infection.

Adult↗