Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study.

BACKGROUND: The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection. OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/-5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV. CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.     

Immunohistochemical localization of syndecan-1 in normal and pathological human uterine cervix

Expression of syndecan-1, a cell surface proteoglycan that binds growth factors and extracellular matrix components, was studied in normal and pathological human uterine cervix using immunohistochemical methods. Normal cervical squamous epithelium showed positive staining for syndecan-1 in all cell layers, except the basal cell layer, whereas endocervical columnar epithelium stained weakly. In non-neoplastic reactive lesions, metaplastic squamous cells were positive for syndecan-1, whereas columnar cells showed weak or negative staining. In cervical condylomas, cells showing koilocytotic atypia were positive for syndecan-1. The progression of cervical intraepithelial neoplasia (CIN) grade I to grade III was associated with reduced syndecan-1 expression and localization of syndecan-1 to more superficial cell layers. In squamous cell carcinomas (SCCs), syndecan-1 expression correlated with histological differentiation, being absent from most poorly differentiated tumours. The results suggest that loss of syndecan-1 from atypical cells is an early event during cervical carcinogenesis and show a close association of syndecan-1 expression with preserved epithelial morphology and differentiation.     

B cell precursors in chick embryos surgically bursectomized at 72 h of incubation

To determine the presence of precursor B cells in chick embryos surgically bursectomized at 72 h of incubation (E-Bx) we studied chick chimeras that were produced by establishing parabiotic connections between blood vessels of chorioallantoic membranes of normal and surgically bursectomized chick embryos. Using sex chromosomes and a B cell alloantigen (Bu-1a) as markers we showed that chick embryos bursectomized at 72 h of incubation contain B cell precursors capable of colonizing the bursa of Fabricius and developing into B lymphocytes. The repopulation capacity of 14-day-old embryonic spleen cells from E-Bx recipients was tested by transferring them into age-matched X-irradiated Bu-1-disparate embryos. The results show that B cell precursors are present in 14-day spleen of chick embryos bursectomized at 72 h of incubation. These precursors carry the Bu-1 B cell alloantigen, suggesting that commitment to the B cell lineage can take place in the absence of bursa.     

Immunoglobulin diversification in embryonic chicken bursae and in individual bursal follicles

Previous studies have shown that the same immunoglobulin (Ig) V lambda gene (V lambda 1) is rearranged in all chicken B cells, and that extensive sequence diversification of this gene occurs during B cell development in the bursa of Fabricius. We used two-dimensional gel electrophoresis to compare the heterogeneity of Ig lambda light chains produced by B cells at different stages of bursal development. Somatically diversified light chains were observed in Ig molecules produced by bursal cells as early as 15 days of embryonic incubation. The two principal species of light chain observed probably represent glycosylated and nonglycosylated forms of lambda chain encoded by alleles of a single lambda gene. Extensive diversification was observed during late embryogenesis. We also studied lambda light chain diversity in cyclophosphamide-treated birds repopulated with normal bursal cells. In these birds, individual bursal follicles are repopulated by single B cell precursors. Follicular cells derived from single B cell precursors were able to produce a spectrum of light chains almost as diverse as that of the total bursal cell population. We used two monoclonal anti-idiotype antibodies to study idiotype expression in individual normal or reconstituted follicles. About 30% of follicles contained 0.1% to 5% of lymphocytes which reacted with one or both of the antibodies. The results indicate that within individual bursal follicles bursa stem cells undergo Ig hyperdiversification.     

Testing the reliability of a new measure of life events and experiences in childhood: The Psychosocial Assessment of Childhood Experiences (PACE)

There are few well validated instruments for measuring the impact of life events and experiences in childhood and adolescence. This study examines the reliability of a new instrument, the Psychosocial Assessment of Childhood Experiences of PACE. Fifteen children and parents were interviewed on two cassions ten days apart for the main test-retest reliability study. About half of the events recorded were reported on both occasions (0.45% and 0.55% concordance). When the impact of specific events was examined much higher levels of agreement were found. Inter-rater reliability tests also yielded higher rate (Kappa 0.74 and above). Possible reasons for these important differences are discussed and the inherent methodological difficulties considered.

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Zusammenfassung Es existieren nur wenige gut validierte Meßinstrumente zur Erfassung von Lebensereignissen und Erfahrungen im Kindes- und Jugendalter. Diese Studie untersucht die Reliabilität eines neuen Verfahrens, des Psychosocial Assessment of Childhood Experiences oder PACE. 15 Kinder und Elternteile wurden zweimal im Abstand von 10 Tagen für die Überprüfung der Haupttest-Retest-Reliabilität interviewt. Ca. die Hälfte aller Ereignisse, die beim Interview berichtet wurden, wurdem beim Zweitinterview ebenfalls angegeben (Konkordanzen 0,45 und 0.55). Deutlich höhere Übereinstimmungen fanden sich bei Untersuchung der Auswirkungen spezifischer Ereignisse. Die Inter-Rater-Reliabilitätstests ergaben ebenfalls höhere Werte (Kappa 0.74). Mögliche Ursachen dieser wichtigen Unterschiede werden unter Berücksichtigung der inhärenten methodischen Schwierigkeiten diskutiert.

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Résumé II y a peu d'instruments correctement validés de mesures de l'impact des événements de vie des expériences dans l'enfance et l'adolescence. Cette étude examine la fiabilité d'un nouvel instrument, l'évaluation psycho-sociale des expériences infantiles (Psychosocial Assessment of Childhood Experiences ou PACE). 15 enfants et parents furent interrogés à deux reprises à 10 jours d'intervalle pour evaluer la fiabilité test-retest. Environ la moitié des événements rapportés le furent dans les deux occasions (0.45% et 0.55% de concordance). Quand l'impact des événements déviés spécifiques fut étudié un niveau plus élevé de concordance fut trouvé. La fidélité inter-cotateurs des tests obtinet également des taux plus élevés (kappa 0.74 et audessus). Les raisons possibles de ces différences sont discutées et les difficultés méthodologiques inhérentes prises en compte.

     

The role of Borrelia burgdorferi in interstitial cystitis

BACKGROUND/AIMS: Borrelia burgdorferi spirochete has been found both in bladder biopsies and the urine of patients with Lyme disease (LD) as well as in experimental animals. The urological symptoms in borreliosis resemble those of interstitial cystitis (IC): frequency, urgency and nocturia. The aim of this studies is to find the role of B. burgdorferi in interstitial cystitis. METHODS: We studied antibodies against B. burgdorferi from serum samples of 50 IC patients with two separate EIA tests. Patients with positive serology in both tests underwent cystoscopy and a bladder biopsy was taken. The presence of borrelia DNA was studied with borrelia-specific polymerase chain reaction (PCR), and with universal bacterial PCR. RESULTS: IgM class antibodies to B. burgdorferi were not found, but IgG antibodies were found in four samples (8%). This was higher than in the control material (2%). One patient's sample was strongly positive, whereas three samples were weakly positive. Bladder biopsies taken from the 4 patients were negative for borrelia DNA in both PCR tests. None of the seropositive patients had any symptoms consistent with LD. CONCLUSION: These results indicate that persistent infection of B. burgdorferi has no role in the etiology of IC. On the other hand a connection with a past borrelia infection and IC is not excluded.     

p53Mutations and Presence of HPV DNA Do Not Correlate with Radiosensitivity of Gynecological Cancer Cell Lines

Objective.The correlation betweenp53tumor suppressor gene mutations and the presence of high-risk human papillomavirus (HPV) DNA with thein vitroradiosensitivity of gynecological malignancies was studied in 26 cell lines derived from gynecological cancers of 23 patients.Methods.Comparison of the intrinsic radiosensitivity was performed with mean inactivation dose (D?) determined with the 96-well plate clonogenic assay.p53mutations were investigated with polymerase chain reaction and single-strand conformation polymorphism (PCR–SSCP) analysis and direct DNA sequencing, and the presence of HPV DNA was studied with PCR using HPV consensus primers.Results. p53mutations were found in 6 of 10 vulvar squamous cell carcinoma (SCC) lines. Nine vulvar and 1 vaginal SCC cell lines were HPV DNA negative and 1 vulvar cell line was HPV 16 positive. All 4 cervical SCC lines were HPV positive and possessed the wild-typep53.Three cell lines expressed HPV 16 and 1 HPV 68. Among 10 endometrial cancer cell lines, 2 cell lines with mutantp53and 1 HPV 16 positive cell line were found. No correlation could be demonstrated between inactivation of thep53gene and radiosensitivityin vitro;the cell lines were evaluated as one group or according to their anatomical origin or histology.Conclusion.Our results indicate that inactivation of thep53gene through mutation or binding with HPV DNA does not increase the resistance of gynecological malignancies to ionizing radiationin vitro.     

First trimester combined screening biochemistry in detection of congenital heart defects

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs).

Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down’s syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland.

Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively.

Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.