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Biomedical subjects

M Lehtinen

Publications and source records attributed to M Lehtinen.

At least 91 records · Page 5Linked to original sources
PubMed1992

Pre- and posttreatment serum antibody responses to HPV 16 E2 and HSV 2 ICP8 proteins in women with cervical carcinoma.

Serum antibodies to early proteins of human papillomavirus type 16 (HPV 16 E2 protein) and herpes simplex virus type 2 (HSV 2 ICP8) can be measured by ELISA. In the serum of 122 newly diagnosed cervical carcinoma patients and age-matched controls, enhanced IgA antibody levels to an HPV-16 E2 protein derived peptide no. 245 indicated a 9.5-fold (95% confidence limits 2.8-57.2) relative risk of cervical carcinoma. No significant risk was found with a corresponding HPV 6 E2 peptide or HSV 2 ICP8. To evaluate the HPV 16 E2 peptide as a possible tumor marker for cervical carcinoma serial postoperative serum samples were tested from 27 women with cervical carcinoma. Antibody responses to the HPV 16 E2 peptide depended on the clinical stage. Stage I and II patients showed decreasing posttreatment IgA and/or IgG antipeptide antibody levels. Stage III and IV patients initially showed decreasing antipeptide antibody levels followed by increasing levels. These patients also showed increasing IgG antibody levels to the HSV 2 ICP8. However, increasing antibody levels to the HPV 16 E2 peptide indicated significantly (P less than 0.05) worse 2-year disease free survival (recurring disease) than did stable or decreasing antibody levels. The results suggest that serum antipeptide antibodies to the HPV 16 E2 peptide no. 245 can be used for the monitoring of cervical carcinoma.

Adenocarcinoma↗
PubMed1992

Herpes simplex virus type 2 infection and cervical cancer: a prospective study of 12 years of follow-up in Finland.

This study was initiated to investigate the role of past herpes simplex virus type 2 (HSV-2) infection, as determined by serum antibody analysis, in the etiology of cervical neoplasia. Two Finnish registers, the registry of the Social Insurance Institution's Mobile Clinic Survey and the Finnish Cancer Registry, were linked. About 40,000 blood samples were drawn in 1968-72 and stored by the Social Insurance Institution. According to the Cancer Registry, 32 cases of cervical carcinoma or carcinoma in situ for which serum samples were available were diagnosed in this cohort during a follow-up of 12 years (1968-81). The serum samples of these individuals and age matched controls (2:1) from the cohort were analyzed for HSV-2 antibodies. HSV-2 infection as determined by the best available HSV-2 type-specific antibody assay, glycoprotein gG2-ELISA, was not related to cervical neoplasia, i.e., the risk of cervical neoplasia among the HSV-2 positive women was not higher than that among the negative ones (smoking-adjusted relative risk = 0.5, 95 percent confidence interval = 0.2-1.6). The results do not support the hypothesis that HSV-2 is an etiologic agent for cervical neoplasia.

Adolescent↗
PubMed1992

A T-helper cell epitope overlaps a major B-cell epitope in human papillomavirus type 18 E2 protein.

Cultivated CD4+ T-helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T-cell epitopes, and is located at the beginning of an 11-amino acid-long A-helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T-helper cell epitope and a B-cell epitope) overlap in the HPV 18 E2.

Amino Acid Sequence↗
PubMed1992

Predominance of serum antibodies to synthetic peptide stemming from HPV 18 open reading frame E2 in cervical adenocarcinoma.

AIMS: To determine if there are type specific differences in serum antibody responses to synthetic peptides derived from human papillomavirus (HPV) open reading frame (ORF) E2 in patients with cervical carcinoma. METHODS: Diagnostic phase sera from 88 age-matched women with cervical adenocarcinoma (AC), cervical squamous cell carcinoma (SC), ovarian cancer (OC) or no gynaecological malignancy were available. Serum IgG and IgA antibodies to synthetic peptides corresponding to a residue of HPV 6, 11, 16, and 18 ORF E2 18 amino acids long and a control peptide from mumps virus were determined by ELISA. RESULTS: Both IgA and IgG antibody positivity to the HPV 18 peptide were associated with increased risk (9.0-fold, confidence limits 1.5-199) for AC. IgA positivity to HPV 11, 16, and 18 peptides was associated with an increased risk for SC. However, the association of IgG antibodies to HPV 16 peptide with SC was not significant. IgA or IgG antibodies to HPV 6 or mumps virus peptides were not associated with increased risk for AC, SC, or OC. CONCLUSIONS: These results suggest a specific role for HPV 18 in AC. Differences in antibody responses to HPV peptide in AC and SC suggest immunopathogenetic differences between the two types of cervical carcinoma.

Adenocarcinoma↗
PubMed1992

Determination of antibodies to non-structural and structural adenovirus antigens by ELISA.

We evaluated possibilities to analyze serum antibodies to non-structural (peptides derived from adenovirus E1b protein) and structural (hexon) adenovirus antigens by ELISA. Synthetic dodecapeptides covering a putative A-gliadin cross-reactive antigenic determinant of the E1b protein were used. The aminoterminus of the peptides appeared to be important for antibody binding but the exact sequence of a possible common B-cell epitope within the peptides remained open. Coupling of the peptides to a carrier protein was essential for ELISA analyses of serum antipeptide antibodies. IgA antibodies to both adenovirus derived E1b peptides and hexon antigen could be detected already two weeks after the onset of an acute adenovirus infection, while antipeptide IgG antibodies were seen in a restricted number of patients only.

Adenoviridae Infections↗
PubMed1991

Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix.

Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival.

Adenocarcinoma↗
PubMed1991

Decreased antibody reactivity to Epstein-Barr virus capsid antigen in type 1 (insulin-dependent) diabetes mellitus.

In this study, antibody levels to Epstein-Barr virus (EBV) capsid antigen (VCA) and EBV early antigens (EA) were analysed by enzyme immunoassay in 54 newly diagnosed type 1 diabetic children and in matched controls. The patients had significantly lower EBV VCA IgG-class antibody levels (p less than 0.02). This was true particularly in young patients and in boys (p less than 0.005). VCA IgA-class antibody levels were also decreased in young patients (p less than 0.02). VCA IgM-class antibodies were observed in two of the patients only. IgG- and IgA-class antibodies to EBV EA or rubella virus antigen showed no differences between patients and controls. The results suggest that EBV infections coincide with the onset of clinical diabetes relatively rarely. However, the abnormally low antibody response to EBV VCA in diabetic children suggests abnormalities in the EBV-specific immune response.

Adolescent↗
PubMed1990

Demonstration of evolutionary differences between conserved antigenic epitopes in the minor nucleocapsid protein of human papillomavirus types 6b, 16 and 18.

We studied human papillomavirus (HPV) minor nucleocapsid protein (L2) by epitope scanning. Conserved antigenic epitopes identified by rabbit antiserum to bovine papillomavirus (BPV) were revealed in HPV-6b (amino acids, aa, 196-205); HPV-16 (aa:s 376-85) and HPV-18 (aa:s 221-230). L2 proteins. The first two epitopes were situated in hydrophilic regions of the proteins. Aligning the aa-sequences that corresponded to the epitopes with the total L2 sequences of BPV and HPV1a revealed consensus motifs between BPV, HPV1a and the reactive HPV type. In the non-reactive types amino acid alterations were noted. Mismatch between HPV1a sequences and the corresponding HPV-6b and HPV-16, HPV-6b and HPV-18, and HPV-16 and HPV-18 sequences suggests that the alterations may have evolved to facilitate immune surveillance of the genital HPV types.

Amino Acid Sequence↗
PubMed1990

Deoxyribonucleic acid flow cytometric analysis of cervical adenocarcinoma: prognostic significance of deoxyribonucleic acid ploidy and S-phase fraction.

Paraffin-embedded tumor samples from 125 patients with cervical adenocarcinoma were analyzed by deoxyribonucleic acid flow cytometry. Thirty-one percent of the tumors were aneuploid. Triploid deoxyribonucleic acid content predominated (51.3%) and one third of the deoxyribonucleic acid aneuploid tumors were tetraploid, whereas near-diploid deoxyribonucleic acid aneuploidy was seen infrequently. Deoxyribonucleic acid aneuploidy was associated with tumor size, histologic grade, clinical stage, and high S-phase fraction. Deoxyribonucleic acid ploidy and S-phase fraction value were independent prognostic parameters, together with the presence of lymph node metastases and tumor size. In conclusion, our results indicate that flow cytometric deoxyribonucleic acid analysis helps to predict the prognosis and may thus influence the choice of treatment.

Adenocarcinoma↗
PubMed1989

Lack of serum antibodies to the major HSV-2 specified DNA-binding protein before diagnosis of cervical neoplasia.

We report results based on a prospective case-control study within a cohort obtained by linking the Finnish Social Insurance Institutions Mobile Clinic Survey Registry and the Finnish Cancer Registry. The overall prevalence of herpes virus early antigen (ICSP 11/12) antibodies was similar in controls and in cervical neoplasia cases (consisting of invasive cervical carcinoma, ICC, and cervical intraepithelial neoplasia group III, CIN III cases). However, those CIN III cases, who after a long lag period (average 7 years after the blood sample was drawn) developed cervical neoplasia, had significantly lower antibody levels than did matched controls. Their ICSP 11/12 antibody levels became higher the shorter the lag period. The negative correlation between the ICSP 11/12 antibody levels and the lag period was most pronounced in the HSV-2 seropositive CIN III cases. In an analysis of cross-sectional case-control material from the Clinic of Obstetrics and Gynaecology, Tampere University Central Hospital, the patients with ICC had the highest ICSP 11/12 antibody levels. Statistically significant differences between cases and controls were not found. We conclude that in cervical neoplasia the kinetics of ICSP 11/12 antibody levels are determined by the malignant process itself. The cervical disease may selectively induce early viral antigens, thus giving rise to the antibody response described in this paper.

Antibodies, Viral↗
PubMed1989

Flow cytometric DNA analysis of 199 histologically favourable or unfavourable non-Hodgkin lymphomas.

We have studied the nuclear DNA content of histologically favourable (n = 82) or unfavourable (n = 117) non-Hodgkin lymphomas (NHLs) diagnosed between 1957 and 1978 in the Tampere University Central Hospital. The DNA analysis was done by applying a trypsin digestion method to archival tumour samples. DNA aneuploidy was seen in 40 per cent of the unfavourable cases and in 10 per cent of the favourable cases, but varied considerably between different histological subtypes. The unfavourable cases showed high proliferative activity (S-phase fraction, SPF), while considerable variation in the SPF among the favourable NHLs was noted. Among the unfavourable NHLs, cases with DNA-aneuploid tumours had significantly (P less than 0.01) worse prognosis than stage and treatment matched cases with DNA-diploid tumours. In general, survival of the patients who had high SPF tumours was significantly lower compared with patients with low SPF tumours (P less than 0.01). However, SPF was not related to the prognosis in the unfavourable NHLs. We conclude that the flow cytometric DNA analysis revealed characteristic features in the favourable and unfavourable NHLs and may be useful in predicting the clinical outcome of patients.

Adult↗
PubMed1989

Analysis of DNA synthesis in herpes simplex virus infected cells by dual parameter flow cytometry.

The DNA incorporation of a thymidine analogue bromodeoxyuridine (BrdUrd) in herpes simplex virus type 2 (HSV-2) infected cervical cancer cell lines (CaSki and C-33 A) was studied by dual parameter flow cytometry. HSV-2 infection resulted in an exponential increase in DNA synthesis in the CaSki cells. In the less permissive C-33 A cells the proportion of DNA-synthesizing cells cycled during HSV-2 infection. The inhibition of viral DNA synthesis by phosphonoformate (PFA) was able to inhibit the virus induced changes in the CaSki but not in the C-33 A cells. In the C-33 A cells a part of the virus induced cellular DNA synthesis represents repair replication of cellular DNA.

Bromodeoxyuridine↗
PubMed1989

The relation between serum sex steroid levels and plasma cell infiltrates in endometritis.

We measured serum levels of progesterone and estradiol among 35 patients with endometritis confirmed by endometrial biopsy. The onset of symptoms took place predominantly in the proliferative phase of the cycle. A negative correlation was found between the serum progesterone levels and the histopathologic severity of plasma cell endometritis. Our results suggest that the hormonal status contributes to the immune response and susceptibility to endometrial infection.

Cell Count↗
PubMed1989

Vasopressin levels in CSF of Alzheimer patients: correlations with monoamine metabolites and neuropsychological test performance.

Concentrations of vasopressin (AVP) and monoamine metabolites (HVA, 5-HIAA, MHPG) in cerebrospinal fluid (CSF) were measured and compared with memory functions in patients with dementia of Alzheimer type (DAT) and control subjects. CSF concentrations did not differ between the DAT patients and the controls, or between patients with different degrees of dementia. There were no correlations between concentrations of vasopressin and monoamine metabolites in CSF or between the CSF measures and psychological test scores, except for a correlation between CSF HVA and immediate and delayed story recall. These data suggest that probable damage to the vasopressinergic and monoaminergic systems in DAT is not reflected in the CSF of patients in early stages of the disease, nor is a deficit in these systems or their interaction the primary cause of cognitive impairment in DAT.

Aged↗
PubMed1989

Serum CA 125 in acute pelvic inflammatory disease.

Serum levels of CA 125 and other selected tumour markers were measured in 31 patients with proven pelvic inflammatory disease (PID). Ten (32%) of the patients had elevated CA 125, one (4%) had elevated CEA, and none had elevated CA 15-3, AFP or beta 2-microglobulin. Compared to patients with normal CA 125, patients with elevated CA 125 were older, more often users of intrauterine contraceptive devices, had longer duration of symptoms, higher erythrocyte sedimentation rates, and more often had an adnexal mass on pelvic examination. There was a correlation between CA 125 levels and the severity of adnexal inflammation as defined by laparoscopy. Isolation of specific micro-organisms from the upper genital tract was not associated with elevated CA 125. In most women serum levels of CA 125 decreased during treatment. PID should be considered as a major cause of positive CA 125 findings among young women.

Adult↗
PubMed1989

Class specific antibody response to gonococcal infection.

An enzyme immunoassay was used to determine IgM, IgG, and IgA antibodies to gonococcal pili in 68 patients with uncomplicated gonorrhoea, 35 women with pelvic inflammatory disease, and in 115 normal controls. A clear difference in response rate in all three antibody classes between patients with gonorrhoea and healthy controls was evident. Among women with gonorrhoea, the magnitude of antibody response was higher than among men with gonorrhoea, especially in the IgM class. No major differences were found in the overall distribution of serological findings between women with uncomplicated gonorrhoea and those with gonococcal pelvic inflammatory disease. Among this last group, however, high IgM antibody levels in acute phase sera were significantly associated with the isolation of Neisseria gonorrhoeae in the upper genital tract.

Antibodies, Bacterial↗