Epidermal growth factor and leukemia inhibitory factor levels in follicular fluid. Association with in vitro fertilization outcome.

OBJECTIVE: To determine the levels of epidermal growth factor (EGF) and leukemia inhibitory factor (LIF) in follicular fluid, if any, and to assess the association of these cytokines with the outcome of in vitro fertilization (IVF). STUDY DESIGN: EGF and LIF levels determined by enzyme-linked immunosorbent assay in 60 preovulatory follicular fluids were compared with 25 IVF outcomes. RESULTS: Immunoreactive EGF and LIF could be detected in human follicular fluid. Levels of these cytokines were similar in FF obtained from follicles that resulted in fertilized oocytes and those that did not. EGF levels were significantly lower in patients establishing a pregnancy as compared to patients achieving no pregnancy (P < .007). LIF levels were similar in both groups of patients. CONCLUSION: EGF appears to be associated with IVF outcome.

[Diagnostic and therapeutic concepts of HPV infection in HIV-positive women]. / Diagnostische und therapeutische Konzepte bei HPV-Infektion HIV-positiver Frauen.

Among HIV-seropositive women there is a high prevalence of anogenital human papillomavirus (HPV) infection. HPV-DNA is more frequent detected in cervicovaginal-lavage specimens from HIV-seropositive women as in those from HIV-seronegative women. We and others suggest that HIV-infection increases the risk to have HPV-associated lesions of the lower female genital tract, especially the risk for developing a squamous intraepithelial lesion of the cervix. In this report we describe the current diagnostic and therapeutic strategies in HIV-seropositive women with HPV-infection. The gynecological examination should be performed at six to twelve month intervals, including the colposcopy and the Pap smear test. We hope to improve the quality of our screening program by doing an additional HPV-test. At last we investigate the CD4+ T-lymphocyte counts because it is observed that women with low CD4+ cell counts (< 200/microliter) were more likely to have persistent HPV-infection as those with higher counts (> 500/microliter). The treatment method is dependent on the development of the HPV-associated lesion and the clinical status of the HIV infected women. In cases with external warts local application of Condylox should be the first line treatment. Probably in about few months we could use other drugs like Wartec or Aldara in Germany. But the effectiveness of these drugs in HIV-positive women has to be proven yet. In the cause of persistence of external warts or recurrence of the disease the systemical application of Intron A or Roferon A is possible. The CO2-lasertreatment is performed under colposcopic guidance, especially in cases with multicentric condylomatous lesions. The treatment of cervical intraepithelial neoplasia (CIN) by CO2-laservaporisation or Loop Electrosurgical Excision Procedure (LEEP) is based on the clear colposcopic visualisation of the upper limit of the lesion. If CIN reaches the endocervix, being out of colposcopic view, and the squamocolumnar junction is localised in the endocervical canal conisation by laser or cold knife has to be performed. Before performing the treatment of CIN one should exclude multicentric cervical, vaginal and vulval intraepithelial neoplasia by colposcopy, because multicentric intraepithelial neoplasia of the lower female genital tract is more frequently than in HIV-seronegative women. Multicentric disease seems to be one cause of the high recurrence of HIV-seropositive women. However, higher levels of immunosuppression (CD4+ T-lymphocyte counts < 200/microliter) are also important determinants of recurrence of the disease. Therefore, an accurate short-term follow-up with colposcopy, Pap test and HPV test should be carried out after the treatment of HIV-seropositive women with low CD4+ counts.

Regulation of CD95 (Apo-1/Fas) ligand and receptor expression in squamous-cell carcinoma by interferon-gamma and cisplatin.

CD95 (Apo-1/Fas) ligand (CD95L) expression has been observed in various malignancies. In human primary cell lines from a squamous cell carcinoma (SCC) of the vulva, the effect of cisplatin (CDDP) and IFNgamma on the expression of CD95L and its 2 receptor isoforms, CD95 transmembrane (CD95tm) and CD95 soluble receptor, was studied at the mRNA and protein levels. Addition of CDDP and IFNgamma increased CD95L mRNA levels in the primary cell line 6-fold and 1.7-fold, respectively. In comparison, CD95tm mRNA levels were diminished by CDDP but increased 8-fold upon IFNgamma challenge. CD95L expressed by SCC cells was functionally relevant since these cells were able to induce CD95-specific apoptosis in autologous lymphocytes from the SCC-bearing patient. Thus, CD95L expression in SCC may contribute to tumor-associated immunosuppression, which may be modulated by CDDP and IFNgamma. In tumor samples of the primary SCC, CD95L expression was enhanced in the area of the border between invasive tumor tissue and surrounding stroma cells. The locally restricted over-expression of CD95L was congruent with the arrangement of apoptotic stroma cells in the direct vicinity of invading tumor tongues, suggesting a role as invasion factor for CD95L.

[Pattern of various cytokeratins of normal vulva, vulvar intraepithelial neoplasia (VIN) and vulvar carcinoma]. / Muster verschiedener Zytokeratine der normalen Vulva, der vulvären intraepithelialen Neoplasia (VIN) und des Vulvakarzinoms.

The presence of specific keratins can be of diagnostic value for studying normal and neoplastic epithelium of the vulva. The aim of the present study was to investigate normal, preneoplastic and neoplastic epithelium of the vulva. Keratins 5, 6 and 18, identified by a polyspecific anti-human CK antibody (clone LP 34, DAKO), and the keratin subtypes 7, 10, 14, 18, 19 and 20 of normal, dysplastic and malignant vulval epithelium (paraffin-embedded sections) were detected by immunohistochemical APAAP staining. Keratins 5, 6, and 18 (clone LP 34) and keratin subtype 10 are expressed in the upper third of the normal vulval epithelium. In mild and moderate intraepithelial neoplasia only a few cells express these keratins. In patients with severe intraepithelial neoplasia (VIN III) the expression of these keratins seems to be associated with recurrence of the disease. In biopsy specimens of patients without recurrence we find positive results for keratins 5, 6 and 18 (clone LP 34) and keratin 10. If patients have a recurrence of the disease, expression of these keratins is only diffuse or is absent. The expression of these keratin subtypes in vulval carcinomas is mostly seen in differentiated cells. There was no association between recurrence and keratin pattern. We have not found any other expression of the tested keratin subtypes in VIN and in vulval carcinoma.

Products of the Major Histocompatibility Complex and CD4/CD8 Cell Infiltration in Cervical Intraepithelial Neoplasia and in Cervical Carcinoma.

OBJECTIVES: Major histocompatibility complex (MHC) products and the CD4/CD8 cell ratio in the lymphocyte infiltrate in cervical preneoplastic and neoplastic lesions are investigated to determine the correlation between the infiltration of lymphocytes in subepithelial stromal tissue and the expression of MHC class I and MHC class II antigens on epithelial cells. MATERIALS AND METHODS: The expression of MHC products and the lymphocyte infiltration were studied by an indirect immunohistochemical staining (alkaline phosphataseanti-alkaline phosphatase) in 6 biopsies of normal cervical squamous epithelium, in 22 biopsies of cervical intraepithelial neoplasia (CIN), and in 9 biopsies of cervical carcinoma. Immunohistochemically positive lymphocytes were counted in highpower fields. The density of MHC expression in CIN and cervical carcinoma was described semiquantitatively in the histological slides. RESULTS: We have seen a number of differences in the expression of MHC products between normal cervical squamous epithelium and CIN or cervical carcinoma. Our results also show that the CD4/CD8 cell ratio in normal, in dysplastic, and in malignant cervical tissues differs from peripheral blood. We found statistically significant differences (Mann Whitney U test, p < .05) between the CD4/CD8 ratio of the normal epithelium when compared to the preneoplastic and neoplastic cervical lesions. In the histological sections tested, CD8 cells exceeded the number of CD4 cells in CIN and cervical carcinoma. Expression of MHC products is independent of the infiltration of CD4 and CD8 cells in the tissue of low-grade and high-grade cervical squamous intraepithelial lesions (SILs) and in cervical carcinoma. CONCLUSIONS: We found a significant decrease of the CD4/CD8 cell ratio in low-grade SILs, high-grade SILs, and squamous cell carcinoma compared to normal cervical epithelium. The loss of MHC class I antigen expression in poorly differentiated tumor cells does not correlate with the amount of lymphocyte infiltration.

Interferon-gamma production by the human preimplantation embryo.

PROBLEM: This study demonstrated that the human embryo produces interferon-gamma (IFNgamma). It is important to know whether IFNgamma can be produced before implantation. Therefore the aim of this study was to evaluate the profile of IFNgamma production between days 2 and 5 after in vitro fertilization. METHOD: Twenty embryos were cultured from day 2 to 5 after fertilization. The embryo stages were checked each day and the media refreshed. IFNgamma levels were estimated by an enzyme-linked immunosorbent assay. RESULTS: All embryos produced measurable IFNgamma at least for 1 day. Yields of IFNgamma were: 0.46 +/- 0.45 (n = 4) on day 2, 0.69 +/- 0.52 (n = 19) on day 3, 0.73 +/- 0.52 (n = 15) on day 4, 0.55 +/- 0.32 (n = 11) IU/ml on day 5, respectively. There was no significant difference in the IFNgamma production between in vitro culture days or between the developmental stages of embryos. CONCLUSION: IFNgamma is produced by all the embryos and seems to peak between days 3 and 4, which is just before implantation.

Interactions between autologous CD4+ and CD8+ T lymphocytes and human squamous cell carcinoma of the head and neck.

The autotumor (AuTu)-specific cytolytic T lymphocyte (CTL) line established from the peripheral blood of a patient with oral squamous cell carcinoma (Cancer Res. 53, 1461, 1993) contained >95% of CD8+ and <5% of CD4+ T cells. This CTL line was infected with Herpesvirus saimiri to increase its life span in culture. Two transformed T cell sublines were obtained: the monoclonal CD4+ line (TCR Vbeta2+ V alpha15+) and the oligoclonal CD8+ line (TCR Vbeta6+, Vbeta7+ and Vbeta9+) both of which were maintained in culture for >6 months without AuTu restimulation and which did not produce any virus. The virus-transformed and untransformed T cell lines were compared for phenotypic and functional characteristics, including the ability to kill AuTu, induce expression of the major histocompatibility complex (MHC) antigens on AuTu, and respond to AuTu by cytokine production and/or proliferation. The H. saimiri-transformed CD4+ T cells expressed higher levels of surface adhesion molecules and CD45RO than untransformed cells and lysed AuTu by inducing DNA fragmentation as well as necrosis. This lysis was inhibited by antibodies to CD4 but not to class I or II MHC molecules. The CD4+ T cells produced IL2, TNF-alpha, and GM-CSF and proliferated in response to AuTu. They induced and sustained proliferation of CD8+ T cells in cocultures with AuTu. Supernatants obtained from cocultures of the CD4+ T cells with AuTu also induced proliferation of the CD8+ T cell line. In contrast, the H. saimiri-transformed CD8+ T cells did not kill AuTu or release cytokines in response to AuTu. However, upon pretreatment of AuTu with IFN-gamma to increase expression of MHC antigens, these T cells regained the ability to recognize and kill AuTu targets. Coincubation of AuTu with the CD4+ or CD8+ T cells significantly augmented expression of class I and II MHC antigens on AuTu. These data indicate that H. saimiri-transformed tumor-reactive T cell lines provide a useful model of interactions between immune effector cells and AuTu, and that CD4+ T cells play a critical role in the regulation of immune responses to squamous cell carcinoma of the head and neck.

Comparison of europium and chromium release assays: cytotoxicity in healthy individuals and patients with cervical carcinoma.

Natural killer (NK) and lymphokine-activated killer (LAK) cell activities were measured in peripheral blood obtained from healthy women to compare a standard 51Cr release assay with a nonradioactive europium (Eu3+) release assay based on time-resolved fluorescence. The two types of cytotoxicity assays were first compared in paired determinations performed on 28 samples of peripheral blood mononuclear cells obtained from healthy women who had normal pap smears or no biopsy evidence of cervical squamous intraepithelial lesions (SIL). Target cells (NK-sensitive K562 and NK-resistant Raji cell lines) were labeled with Eu3+ only, 51Cr only, or both labels and compared in cytotoxicity assays using fresh or interleukin 2 (IL-2)-activated effector cells. Spontaneous release in the Eu3+ release assay was comparable to that observed in the 51Cr release assay, but maximum Eu3+ release always exceeded that of 51Cr. In 4-h assays, specific release of Eu3+ from target cells was more rapid than that of 51Cr, consistently resulting in 30 to 40% higher levels of activity. However, a significant linear correlation (P < 0.001) was observed between cytotoxicity levels based on measurements of Eu3+ and 51Cr release in 4-h assays. The Eu3+ release assay was then used to measure NK and LAK activities in the peripheral blood of women with cervical SIL or cervical squamous cell carcinoma (SCC). Mean NK activity of women with advanced SIL (121 lytic units [LU]) or SCC (93 LU) was found to be similar to that of controls (101 LU) or patients with normal cervical biopsies (90 LU), as was the ability to generate IL-2-stimulated NK activity. However, LAK activity during 18 h of incubation in the presence of IL-2 was reduced in patients with cervical SCC (P < 0.05) compared with that in normal controls. Results of 51Cr assays performed in parallel with patient samples gave comparable results. Advantages of EU3+ release assays for routine evaluation of cytotoxicity are discussed.

The effect of antigamete antibodies on the success of assisted reproduction.

The aim of the study was to investigate the presence of antigamente antibodies in unexplained infertility patients and to prove the efficiency of IUI and IVF-ET treatments for these patients. The study includes 46 unexplained infertility patients and as controls, a group of 21 tubal infertility patients. Serum, follicular fluid and cervical mucus samples were collected from each patient and antibodies were measured with commercial ELISA kits. Twenty-two of the 46 unexplained infertility patients produced at least one of the antibodies against sperm or ovary. Fertilization rates were lower in immunological and unexplained infertility patients than in tubal infertility patients, being statistically significant. Pregnancy rates were lower in immunological and unexplained infertility patients than in tubal infertility patients after IVF-ET, but this was not statistically significant. Pregnancy rates after IUI treatment were equal in both immunological and unexplained infertility groups. AGA (antigamete antibodies) were found in 45% of unexplained infertility patients and therefore may be a possible cause of infertility. IUI and IVF-ET are successful choices for treatment of these patients.

Immunological investigations in vaginal mycoses.

In 42 women with chronically recurrent and 20 women with acute Candida albicans vulvovaginitis, as well as 14 women with Candida glabrata vaginitis, the following investigations were carried out: determination of protein content and secretory immunoglobulin A (sIgA) in the cervicovaginal secretion by a self-modified ELISA technique; determination of immunocells and cellbound IgA in the cervicovaginal secretion by immunofluorescence and nephelometric analysis of IgA in the serum. The results were compared with those of 77 pre-menopausal non-pregnant women with or without intake of anti-ovulants, 17 healthy pregnant women and four hysterectomised pre-menopausal women. Due to inflammation, women with acute and chronically recurrent Candida albicans vulvovaginitis had a higher protein content in the cervicovaginal secretion than healthy women. However, the content of secretory IgA was not increased but even slightly decreased in chronic cases. The number of macrophages and granulocytes in the vaginal content was not increased compared with healthy patients. In only a few cases was IgA detected on yeast cells and in the cervicovaginal secretion by fluorescence microscopy. In chronically-relapsing vaginal candidosis, the frequency of the serotype B of C. albicans was strikingly high. Women with Candida glabrata vaginitis showed lower values of secretory sIgA in the vaginal secretion compared with healthy patients as well as women with vaginitis caused by C. albicans. However, like healthy women, they had normal protein values in the cervicovaginal secretion and also lower values of IgA in the serum compared with women of C. albicans vulvovaginitis patients. Macrophages and granulocytes were demonstrable in the cervicovaginal secretion just as in healthy persons. Women with C. glabrata vaginitis showed a more conspicuous, although not a significantly more frequent, binding of IgA to budding cells demonstrated by fluorescence microscopy than women with C. albicans.

Investigations by cell-mediated immunologic tests and therapeutic trials with thymopentin in vaginal mycoses.

OBJECTIVE: According to unsatisfactory therapeutic results in patients with chronically recurrent vaginal candidosis, we investigated if immunologic patient factors could be found and treated. METHODS: In 42 women with chronically recurrent and 20 women with acute Candida albicans vulvovaginitis, as well as 14 women with C. glabrata vaginitis, the following investigations were carried out: identification of yeast species; quantification of T lymphocytes and their subpopulations in sera; proliferation tests of T lymphocytes in vitro; treatment of 18 patients with chronically recurrent vaginal candidosis with the synthetic T-lymphocyte- stimulator thymopentin; and, finally, control of the above-mentioned parameters in the clinical course. RESULTS: Women with C. albicans vulvovaginitis showed fewer T lymphocytes and subpopulations in the peripheral blood than healthy women. Only the number of non-specific killer (NK) cells, however, was significantly lower in cases of acute C. albicans vulvovaginitis. In women with C. glabrata vaginitis, the number of T lymphocytes in the blood was within the normal range. In vitro proliferation tests using mitogens, bacterial antigens, and commercially available candida antigens with and without addition of thymopentin were carried out on the T lymphocytes of women with chronically recurrent C. albicans vulvovaginitis. These tests revealed no significant differences compared with the other patients with C. albicans infections. The patients were treated with thymopentin. Those women who revealed an increase of initially low numbers of T-helper cells recovered from vaginal candidosis after thymopentin treatment. CONCLUSIONS: The peripheral T lymphocytes may be diminished in patients with chronically recurrent C. albicans vaginitis, and immunologic treatment can reduce the relapse rate.

Interferon gamma and interleukin 10 levels in preimplantation embryo culture media.

PURPOSE: The aim of our study is to elucidate whether human oocytes/embryos secrete IFN gamma and/or IL-10 and whether the fertilization process depends on the balance between these cytokines. METHODS: A total of 142 embryo culture media from 24 patients were collected and the cytokine levels were tested with ELISA. RESULTS: IFN gamma and IL-10 were detectable in 40.1% and 29.6% of culture media respectively. The difference of IFN gamma and IL-10 levels in media from fertilized oocytes between day 1 and day 2 are significant (0.46 vs. 1.47 and 34.2 vs. 12.7, respectively). However there was no significant difference between the IFN gamma levels of the media from fertilized and nonfertilized oocytes 0.46 vs. 0.85 at day 1 and 1.47 vs 1.49 at day 2, as well as IL-10 levels 34.2 vs. 30.9 at day 1 and 12.7 vs. 9.58 at day 2 respectively. CONCLUSIONS: Human preimplantation embryos secrete the cytokines IFN gamma and IL-10. No effect of these cytokines on fertilization process could be shown.

[Treatment and after-care of HIV patients with cervix dysplasia]. / Behandlung und Nachsorge von HIV-Patientinnen mit einer Zervixdysplasie.

We have been observing an increased prevalence of cervical intraepithelial neoplasia in HIV-infected women in our department of obstetrics and gynaecology. 10 HIV-infected patients with cervical intraepithelial neoplasia were treated by CO2-laser - 6 were subjected to laser excision conisation, and 4 patients to laser vaporisation. After laser vaporisation and laser excision conisation, no postoperative complications were observed. Intraoperative bleeding was rarely seen. The preoperative examination of the CD4-cell count had no influence on the choice of the applied method of laser treatment, laser vaporisation or laser excision conisation. But all the 4 patients with a CD4-cell count < or = 200/microliters experienced recurrence of disease shortly after the first laser treatment. Only one out of five patients with CD4-cell counts between 200-499/microliters had a recurrence of disease after laser treatment. All in all, a recurrence of disease was seen in five out of ten HIV-infected patients with cervical intraepithelial neoplasia. The recurrence rate is possibly increased because HIV-infected women have multifocal cervical, vulval and vaginal dysplasia more frequently than HIV-negative patients. In our study, we observed multifocal cervical, vulval and vaginal dysplasia in four HIV-infected patients. Therefore, an accurate short-term follow-up with colposcopy and cytological smears should be carried out after the treatment of HIV-infected patients with cervical intraepithelial neoplasia.

Monoclonal antibody 2B5 defines a truncated O-glycan, GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-6 (GalNAc), on mucins from deep gastric and duodenal glands as well as metaplasia and neoplasia of gastric differentiation.

Monoclonal antibody (MAb) 2B5 previously generated in BALB/c mice using gastric mucosa of the corpus as immunogen was characterized with regard to its binding epitope. Binding assays on structurally defined neoglycolipids from mucin glycans revealed that MAb 2B5 recognizes a carbohydrate epitope on a neutral O-glycan sequence from gastric mucins. This oligosaccharide chain has been characterized by mass spectrometry and methylation analysis and sequential exoglycosidase treatment of the derived neoglycolipid as GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-6OY (where 6OY corresponds to the GalNAc-ol fragment--O--(CH2)2 conjugated to dipalmitoylphosphatidylethanolamine). The selective binding of MAb 2B5 to mucus from deep gastric and duodenal glands, to gastric metaplasia or neoplasia with gastric differentiation may imply that mucin glycosylation in the respective cells is incomplete resulting in the accumulation of truncated blood group precursor chains. MAb 2B5 is the first monoclonal antibody which defines an epitope on M2-type antigens and may substitute, accordingly, for the inconvenient "paradoxical concanavalin A-horseradish peroxidase method" in histochemistry.

Human papillomavirus type 18 E6 and E7 antibodies in human sera: increased anti-E7 prevalence in cervical cancer patients.

Antibody-reactive regions on the human papillomavirus type 18 (HPV-18) E6 and E7 proteins were identified with rabbit polyclonal anti-fusion protein sera by screening of an fd phage expression library containing subgenomic HPV-18 DNA fragments and by testing of overlapping decapeptides representing the E6 and E7 open reading frames. Peptides comprising the delineated regions (designated E6/1 to E6/4 and E7/1) were synthesized and used in an enzyme-linked immunosorbent assay (ELISA) to detect anti-HPV-18 antibodies in human sera. A total of 232 human serum samples (identical numbers of cervical cancer patients and age-matched controls) collected in Tanzania were tested. Similar prevalences (between 0.8 and 4.3%) of antibodies recognizing the different E6 peptides were found in the sera from tumor patients and controls. With a synthetic 28-mer peptide (designated pepE701) comprising the E7/1 region, a significant difference was found: 10 of 116 tumor serum samples but 0 of 116 control serum samples showed a specific reaction (P less than 0.001). This observation confirms earlier results with HPV-16 E7 fusion proteins (I. Jochmus-Kudielka, A. Schneider, R. Braun, R. Kimmig, U. Koldovsky, K. E. Schneweis, K. Seedorf, and L. Gissmann, J. Natl. Cancer Inst. 81:1698-1704, 1989). A lower prevalence of anti-HPV-18 E7 antibodies was observed when 188 human serum samples collected in Germany from tumor patients and controls were tested (3 of 94 positive in the cancer group; 0 of 94 positive in the control group). The type specificity of anti-HPV-18 E7 antibodies was demonstrated when the HPV type found by Southern hybridization in the cervical cancer biopsies was compared with seroreactivity: 4 of 8 serum samples obtained from HPV-18 DNA-positive but 0 of 16 serum samples from HPV-18 DNA-negative tumor patients reacted in the HPV-18 E7 ELISA. In addition, HPV-18-positive sera failed to react in a peptide ELISA with the homologous HPV-16 E7 region (M. Müller, H. Gausepohl, G. de Martinoff, R. Frank, R. Brasseur, and L. Gissmann, J. Gen. Virol. 71:2709-2717, 1990) and vice versa.

[Cultural and serologic Chlamydia detection in diagnosis of sterility and increased risk of infection]. / Kultureller und serologischer Chlamydien-Nachweis in der Sterilitätsdiagnostik und bei erhöhtem Infektionsrisiko.

364 women were studied for the possible role of chlamydia trachomatis infection as a factor related to infertility. C. trachomatis was isolated from the cervix in 20% of our high-risk STD patients and in a much lower proportion in patients with tubal (5%) or unexplained (4%) infertility. IgG-antibodies to C. trachomatis were found in 75% of patients with tubal infertility, in 44% of women without gynaecological diseases and in 87% of the high-risk STD patients. By contrast, the difference was significant in the IgA-antibody tests. 67% of the women with tubal infertility and only 25% of the women with nontubal infertility were positive. From these data it appears, that antecedent infections with C. trachomatis, as measured by antibody prevalence, are an important factor in infertility of tubal origin.

Antibodies against the human papillomavirus type 16 early proteins in human sera: correlation of anti-E7 reactivity with cervical cancer.

By Western blot technique, 519 samples of human sera were tested for the presence of antibodies to the human papillomavirus (HPV) type 16 proteins E4 and E7 that had been expressed in Escherichia coli as fusion proteins. Sera were obtained from patients attending the University hospitals for reasons unrelated to HPV infections (controls), from patients with HPV-associated lesions, as well as from patients suffering from cervical cancer. Within the control population, 18.1% of them had antibodies that reacted with the E4 protein, and 3.9% of them had antibodies that reacted with the E7 protein. No sex-specific difference in the antibody prevalence was observed. The highest proportion of anti-E4 antibody-positive individuals (40.7%) was observed in the age group between 11 and 20 years. The frequency of anti-E4-positive sera was threefold higher in patients with HPV-associated genital lesions than that in age-matched controls. Antibodies against the HPV16 E7 protein were found 14 times more frequently in patients with cervical cancer, compared with age- and sex-matched controls (P less than .00001). From these data, we concluded that anti-E4 antibodies may be correlated with virus replication and that anti-E7 antibodies may represent a marker for cervical cancer development.

Immunological findings in patients with chronically recurrent vaginal candidosis and new therapeutic approaches.

Eighteen patients with chronically recurrent vaginal candidosis showed low T-lymphocyte counts twice as frequent as a control group of 55 women. The patients were treated with azoles locally and lymphocyte stimulating pentapeptide thymopentin. The prolongation of disease-free intervals and a cure was mainly seen in the patients with low T-cell values before therapy. In vitro-proliferation assays upon stimulation with Candida albicans bore no correlation with the course of the disease. We suspect a failure in the co-operation of the immune cells, caused by differing strong responses to the Candida albicans stimulation.