Rauno Mäntyjärvi

Prognostic factors in cervical human papillomavirus infections

A prospective follow-up study, without further treatment, of a series of 528 women with cervical human papillomavirus (HPV) infections was conducted from 1981 to the present, with a mean follow-up time of 60.3 months (standard deviation 25.1 months). The women visited the Outpatient Department of Gynecology, Kuopio University Hospital, Kuopio, Finland at six-month intervals. At each visit, a thorough gynecologic examination, PAP-smear, and colposcopy with or without punch biopsy were performed. Epidemiologic data were collected by questionnaire, and complete follow-up data were available for 480 of the 528 women. Of these 480 cases of HPV infection, 58.3% regressed spontaneously, and clinical progression was detected in 14.8%. To establish the prognostic factors associated with the clinical course of cervical HPV infections, the Cox proportional hazards regression model was applied. In the analysis, five variables were included: age, PAP-smear class, grade of cervical intraepithelial neoplasia (CIN), HPV type, and colposcopic appearance at the first visit. In general, patient age at the time of diagnosis was inversely related to the probability of spontaneous regression (P less than 0.01). CIN II, CIN III and HPV type 16 were the most significant independent prognostic factors for progression of cervical HPV infections (P less than 0.001, P less than 0.0001, and P less than 0.001, respectively). We conclude that whenever HPV 16 DNA is found in the cervical biopsy with any grade of CIN, the lesion should be treated. Similarly, the presence of CIN II and CIN III indicates treatment whether HPV DNA are detected or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical course of cervical human papillomavirus lesions in relation to coexistent cervical infections.

A prospective follow-up of 530 women with cervical human papillomavirus (HPV) infection was conducted from 1981 to the present (mean 62.9 months). The patients were examined by PAP smears and colposcopy with or without biopsies every sixth month. Endocervical swabs were taken for culture of cytomegalovirus (CMV), herpes simplex virus (HSV), and Chlamydia trachomatis at each visit. During the follow-up period, 179 of the 530 patients (33.8%) had cervical infection and 351 (66.2%) had no coexistent cervicitis. On average, the patients with coexistent cervicitis were younger than those without cervicitis (32 +/- 7.2 years and 37.1 +/- 11.4 years, respectively; P less than 0.0001). C. Trachomatis was isolated from 95 of the 530 women (17.9%), and 19 of the patients had chlamydial cervicitis twice. Cytomegalovirus was isolated from 27 (5.1%) women, 2 of whom also had HSV, and 12 patients had a chlamydial infection. Herpes simplex virus was isolated from 11 (2.1%) women, including 2 patients with coexistent CMV infection. A total of 60 (1.3%) women had nonspecific cervicitis. Of the HPV lesions without coexistent cervical infection, 56.7% regressed, 24.5% persisted, 16.5% progressed, and recurrence was found in 2.3%. The corresponding figures for HPV lesions with coexistent cervicitis were as follows: 66.5%, 22.9%, 9.5%, and 1.1%, respectively. Coexistent active cervical infections had no influence on the clinical course of HPV lesions.

Circulating immune complexes in sera from patients with Alzheimer's disease, multi-infarct dementia and Down's syndrome.

Recent data suggest that immunological mechanisms may be implicated in the pathogenesis of Alzheimers disease (AD). We tested the presence of circulating immune complexes (CIC) in the sera from dementia and Downs syndrome (DS) patients and age-matched controls using two methods: Clq-binding Elisa (ClqB-Elisa) and conglutinin-binding Elisa (KgB-Elisa). The probable AD and multi-infarct dementia (MID) patients had more frequently CIC in their sera as compared to elderly non-demented subjects (Chi-square; P < 0.05). The highest frequency of positive findings was detected for 10 DS patients (8 KgB-Elisa and 7 ClqB-Elisa positive) whereas only 1 of 10 young controls showed ClqB-positivity. In the AD patients the cognitive decline as assessed by the Mini-Mental Status test correlated significantly with CIC values. The study supports the view that systemic autoimmune mechanisms may be involved, at least partly, in dementing processes.

Generation of cell-mediated cytotoxicity against bovine-papilloma-virus-transformed primary mouse cell lines

SummaryThe immunogenicity and immunosensitivity of primary mouse cell lines transformed by bovine papilloma virus 1 (BPV1) DNA were studied in a syngeneic mouse model by determining cell-mediated cytotoxicity in the spleens of mice immunized with the transformed cells. One of the cell lines induced the generation of cell-line-specific Thy1.2-positive cytotoxic effector cells. However, most of the cell lines tested induced the generation of Thy1.2-positive effector cells, which in addition to BPV1-transformed cells were able to lyse a syngeneic cell line transformed by methylcholanthrene. The lysis of BPV1- and methylcholanthrene-transformed cell lines was mediated by recognition of the same antigenic determinants expressed on these cells, and all the BPV1-transformed cell lines were sensitive to lysis by these nonspecific effector cells of the lymphokine-activated killer (LAK) type.

Tumorigenicity and H-2 expression of papillomavirus-transformed mouse cell lines

SummaryTumorigenicity in immunocompetent syngeneic mice and H-2 class I antigen expression of BPV1-transformed mouse cell lines had no correlation. H-2 expression was examined using monoclonal anti-(H-2Kb) and anti-(H-2Db) antibodies in immunofluorescence staining for flow cytometry analysis and by determining the sensitivity of the cells to cytolysis by allostimulated spleen cells. Nontumorigenic cell lines were as resistant as tumorigenic cell lines to natural killer activity. The results indicate that in our model defence by natural killer cells is not a decisive factor. The results also show that instead of or in addition to H-2 class I antigens other factors (e. g. the presence or absence of virus-specific antigens) are important in determining the tumorigenicity of BPV1-transformed cell lines.

Prevalence of antibodies to a human papova virus (BK virus) in subacute sclerosing panencephalitis and multiple sclerosis patients

SummarySera and cerebrospinal fluids (CSF) from 10 patients with subacute sclerosing panencephalitis (SSPE) were tested for antibodies to the BK virus, a new tentative member of the papovavirus group, in an effort to determine any relationships between BK virus and SSPE and the papova-like virus seen in glial cells of SSPE patients. Serum specimens from a group of 50 multiple sclerosis (MS) patients and from corresponding control groups were also included in the tests. All the CSF samples were antibody negative. The prevalence of antibodies in the SSPE and the MS groups, 70% and 60% respectively, and the distributions of individual titers were similar to those in the corresponding control groups. These results suggest that BK virus probably has no connection with SSPE. Further studies of the etiological role of the BK virus in human diseases and the role of the papova-like virus seen in SSPE patients brains are needed.ZusammenfassungSerum- und Liquorproben von 10 Patienten mit subakuter sklerosierenden Panencephalitis (SSPE) wurden auf Antikörper gegen das BK-Virus, ein neues Glied der Papovavirusgruppe, untersucht, um die mögliche Verbindung des BK-Virus zu der SSPE und zu dem papovaähnlichen Virus, das in Gliazellen der SSPE-Patienten gesehen worden ist, zu finden. Eine Gruppe von 50 Patienten mit Multipler Sklerose (MS) und ihre Kontrollen wurden auch in die Untersuchungen einbezogen. Keine Antikörper waren in den Liquorproben nachweisbar. In den Seren war es möglich, in 70% in der SSPE-Gruppe und in 60% in der MS-Gruppe beziehungsweise in 70 und 46% in den Kontrollgruppen Antikörper gegen das BK-Virus zu finden. Auch die Verteilung von individuellen Titern in den verschiedenen Gruppen war sehr ähnlich. Diese Untersuchungsergebnisse zeigen, daß das BK-Virus kaum eine Verbindung zu der SSPE hat. Weitere Untersuchungen über die ätiologische Rolle des BK-Virus in menschlichen Krankheiten und über die Rolle des papovaähnlichen Virus, das im Gehirn der Patienten mit SSPE gesehen worden ist, werden diskutiert.

Local immune reaction in syngeneic mice against tumorigenic and nontumorigenic BPV-transformed mouse cell lines

The role of cytotoxic T cells in immune response to Bovine Papillomavirus type 1 (BPVl)‐transformed mouse cell lines was assessed. The chromium release assay was used to follow the induction of cytotoxicity in local lymph nodes of syngeneic C57BL/6J (B6) mice after injection of BPV1‐transformed cell lines tumorigenic in nude mice but tumorigenic or nontumorigenic in B6 mice. The nontumorigenic cell line B6B31. C‐NuT.A induced cell line‐specific cytotoxicity with a maximal activity on day 7 after subcutaneous inoculation of one million B6B31.C‐NuT.A cells. After injection of nontumorigenic B6B31.J or tumorigenic B6B31 J‐NuT. A or B6B31. A cell lines, only low levels of nonspecific cytotoxicity were observed. These results suggest a role for cytotoxic T cells only in rejection of B6B31. C‐NuT. A cells. One reason for the poor immunogenicity could be the lack of transformation‐induced/virus‐specific antigens on most of the present BPV1‐transformed cell lines. However, in a transplantation rejection experiment, protection was induced in B6 mice against a challenge of the highly tumorigenic B6B31.A‐B6T. 1 line by repeated injections of BPV1 ‐transformed cells. These results suggest the expression of common transplantation rejection antigens on the three BPV 1‐transformed cell lines used in the immunization experiments.

Effect of interferon γ on the sensitivity of bovine-papilloma-virus(BPV1)-transformed cell lines to cell-mediated cytotoxicity

SummaryThe effect of interferon γ (IFNγ) on the immunogenicity and immunosensitivity of mouse cell lines transformed by bovine papillomavirus type 1 (BPV1) DNA was examined in a syngeneic mouse model. The overnight incubation of BPV1-transformed cell lines with 100 IU/ml IFNγ did not affect their ability to induce the generation of cytotoxic effector cells but it clearly increased their sensitivity to lysis by interleukin-2-induced lymphokine-activated killer (LAK) cells and by nonspecific LAK-type effector cells induced by BPV-1-transformed cell lines. The treatment of two allogeneic lymphoid tumour cell lines, P815X2 and YAC-1, with IFNγ either decreased or had no effect on their sensitivity to LAK-cell-mediated lysis.