A 7.5-year prospective study of longer than 18 months type-specific human papillomavirus persistence in a routine cytology-based cervical screening population of about 31,000 women in West Germany.

The objective of this study was to analyse the prevalence, infection pattern, duration and outcome of long-term, type-specific, persistent human papillomavirus (HPV) infections in a routine cytology-based cervical screening population of West German women followed up for 7.5 years. From a screening population of 31,000 women, a strictly selected cohort of 100 patients with > or =18-month persistent, type-specific HPV infection were prospectively followed up for a mean of 35.

Prevalence and genotype distribution of multiple human papillomavirus infection in the uterine cervix: a 7.5-year longitudinal study in a routine cytology-based screening population in West Germany.

The availability of vaccines against certain HPV types and the development of broad spectrum genotyping methods have increased interest in co-infections with different HPV types. In the present study, the prevalence and type-specific composition of multiple HPV infections were investigated in a routine cervical screening population in West Germany both at a cross-sectional level and longitudinally. Four hundred eighty-nine out of 8,090 women were diagnosed with multiple HPV infections once or repeatedly.

Predictive testing of early cervical pre-cancer by detecting human papillomavirus E6/E7 mRNA in cervical cytologies up to high-grade squamous intraepithelial lesions: diagnostic and prognostic implications.

The type-specific persistence of oncogenic human papillomavirus (HPV) is considered to be the true precursor of cervical cancer at which the transcription of the viral oncogenes E6 and E7 is necessary for the malignant transformation and maintenance of the neoplastic state. In the present pilot study, a cohort of 66 women was investigated from a routine office-based screening population who had an index cytological result from normal to high-grade squamous intraepithelial lesions and who were also HPV-DNA positive for at least one of the following high-risk HPV types: HPV 16, 18, 31, 33 and 45 detected by MY09/MY11 consensus and GP5+/6+ general primers, followed by sequencing. The expression of E6/E7 transcripts from the same HPV types was detected by the PreTect HPV-Proofer.

Inter-laboratory validation of PCR-based HPV detection in pathology specimens.

The detection and typing of human papilloma virus (HPV) in pathology specimens is gaining increasingly in importance. In the context of the initiative for quality assurance in pathology (QuIP) of the German Society of Pathology and the Professional Association of German Pathologists, four panel laboratories with experience and expertise in polymerase chain reaction (PCR)-based HPV detection were selected to establish an inter-laboratory trial. In a first step, these laboratories performed an internal testing of their own methodologies, which comprised DNA sequencing, multiplex nested PCR and hybridization techniques.

Predicting treatment outcome in cervical diseases using liquid-based cytology, dynamic HPV genotyping and DNA cytometry.

Background: In this study, our prospective experience with a multimodal follow-up protocol is summarized, with special emphasis on predicting the treatment outcome of cervical diseases.

Materials And Methods: Liquid-based cytology samples (ThinPrep) from 209 women exhibiting the whole spectrum of human papilloma virus (HPV)-related cervical diseases were investigated by cytology, PCR-based HPV genotyping and DNA cytometry pre-surgery. The first control cytology and type-specific HPV tests were performed at 3 months post-surgery.

HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN). Impact of HPV analysis of anal lesions on diagnosis and prognosis.

Background And Aims: Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN). This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN. Results were clinically correlated.

Can we detect cervical human papillomavirus (HPV) infection by cytomorphology alone? Diagnostic value of non-classic cytological signs of HPV effect in minimally abnormal Pap tests.

Objective: Our aim was to assess the validity of non-classical cytological signs in minimally abnormal cervical smears for the prediction of HPV infection.

Methods: 164 ThinPrep monolayers were re-screened for mild nuclear changes, disorders of keratinisation, abortive koilocytes and 'measles cells', as well as degenerative changes. HPV DNA was detected by GP5+/6+ and MY09/MY11 consensus primer PCR assays.

Validity of combined cytology and human papillomavirus (HPV) genotyping with adjuvant DNA-cytometry in routine cervical screening: results from 31031 women from the Bonn-region in West Germany.

Our aim was to improve the accuracy of routine cervical screening by a risk-adapted multimodal protocol with special focus on possible reduction and prognostic assessment of false positive results. A cohort of 31031 women from the Bonn-region in West Germany, median age 36 years, were screened by cytology (conventional or liquid-based), followed by PCR-based HVP detection with genotyping and adjuvant DNA image cytometry, if indicated, in a sequential manner. The true prevalence of high-grade cervical intraepithelial neoplasia and carcinoma (>/=CIN2) was 0.

Aberrant, highly hyperdiploid cells in human papillomavirus-positive, abnormal cytologic samples are associated with progressive lesions of the uterine cervix.

Background: Infection with oncogenic-type human papillomavirus (HPV) and consecutive cytologic abnormalities of the uterine cervix precede the evolution of carcinoma. However, the specificity of both changes is too low to predict the true malignant potential of the change in a given time point, because the majority of the HPV infections revert to normal with time. In preliminary studies, the authors demonstrated that, among many dysregulatory phenomena at the cytologic level, the occurrence of significant DNA content aberrations were in good correlation with progressive cervical changes; and, as a marker for this, the significance of cells with nuclear DNA content > 9c (9c cells) was investigated using slide-based cytometry.

Chromosomal aberrations accumulate in polyploid cells of high-grade squamous intraepithelial lesions (HSIL).

Persistant infection with human papillomavirus (HPV) of the uterine cervix is related with cytological atypia (SIL), the oncogenic potential of which is unclear in a given time point of monitoring. HPV-induced genetic instability result in polyploidization as well as in low frequency random chromosome aberrations in squamous cells. In the present work we analyzed whether highly polyploid/aneuploid cells reflect genomic changes at the chromosomal level.

Human papillomavirus (HPV) study of 2916 cytological samples by PCR and DNA sequencing: genotype spectrum of patients from the west German area.

Human papillomaviruses (HPVs) are aetiological agents for cervical cancer. More than 70 different HPV types that infect genital mucosa have been found. In order to develop a sensitive and specific detection and typing assay, a PCR/direct sequencing approach was used.

Measuring telomerase activity in various human tumors in routine histology and cytology.

The aim of this study was to investigate telomerase reactivation, to quantitatively measure the human telomerase reverse transcriptase (hTERT) content and telomerase activity level (TA) in routine histological and cytological samples, and to examine the relationship between these values and morphological factors. We analyzed 86 (35 cytological and 51 histological) lesions which were divided into four main groups: renal tumors, soft tissue tumors, bladder-urine and thyroid gland lesions. The relative expression of mRNA of hTERT was examined by real-time polymerase chain reaction (RT-PCR).

Determination of features indicating progression in atypical squamous cells with undetermined significance: human papillomavirus typing and DNA ploidy analysis from liquid-based cytologic samples.

Background: The Bethesda System of cervical cytologic findings introduced the term ASCUS (atypical squamous cells of undetermined significance) to cover the broad zone separating normal cytomorphology from definitive squamous intraepithelial lesions (SILs). The management of patients with ASCUS is particularly problematic as approximately 10% of ASCUS patients develop SIL and 1 per 1000 develop cervical carcinoma.

Methods: Our aim was to demonstrate the combined use of polymerase chain reaction for human papillomavirus (HPV) typing and laser scanning cytometry for DNA content measurements in the subcategorization of ASCUS cases according to the risk for progression toward cancer.

Human papillomavirus typing and DNA ploidy determination of squamous intraepithelial lesions in liquid-based cytologic samples.

Background: Infection by high-risk human papillomavirus (HPV) plays a role in the evolution of cervical carcinoma. Cellular atypia and consecutive DNA content alterations in cytologic samples are consequences of a preexisting viral infection.

Methods: We analyzed the frequency and association of HPV types and the presence of rare cells with abnormally high DNA content.

A dissimilatory sirohaem-sulfite-reductase-type protein from the hyperthermophilic archaeon Pyrobaculum islandicum.

A sulfite-reductase-type protein was purified from the hyperthermophilic crenarchaeote Pyrobaculum islandicum grown chemoorganoheterotrophically with thiosulfate as terminal electron acceptor. In common with dissimilatory sulfite reductases the protein has an alpha 2 beta 2 structure and contains high-spin sirohaem, non-haem iron and acid-labile sulfide. The oxidized protein exhibits absorption maxima at 280, 392, 578 and 710 nm with shoulders at 430 and 610 nm.

Six new polymorphic microsatellite markers used for the integration of genetic and physical maps of human chromosome 7.

We report the isolation and characterization of six new polymorphic dinucleotide repeat microsatellite markers (D7S1491, D7S1492, D7S1493, D7S1494, D7S1495, and D7S1496), their integration into the genetic map of human chromosome 7 by analysis of 40 CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees, and their use for integration of physical and genetic maps of this chromosome.

Proximal myotonic myopathy. Clinical features of a multisystem disorder similar to myotonic dystrophy.

Background: Previous investigations in three families have shown that proximal myotonic myopathy (PROMM) is not linked to the gene loci for myotonic dystrophy (DM) or to the loci of the genes of the muscle sodium and chloride channels associated with other myotonic disorders. It is important to extend our clinical knowledge of this interesting new disorder by studying other families.

Patients: Thirty-five patients in 14 new families; 27 patients were examined.

Regional localization of 725 human chromosome 7-specific yeast artificial chromosome clones.

Toward the construction of a complete physical map of human chromosome 7, we have localized 725 YAC clones to cytogenetically defined regions using fluorescence in situ hybridization (FISH) and by screening with DNA markers of known chromosomal locations. These chromosome 7-specific YAC clones are part of a library constructed with DNA isolated from monochromosomal 7 human-hamster somatic cell hybrid lines. The FISH mapping for 575 clones was accomplished by using "Alu-PCR" amplified YAC DNA against metaphase chromosome spreads made from a monochromosomal 7 human-mouse somatic cell hybrid line.

Adenylylsulphate reductase from the sulphate-reducing archaeon Archaeoglobus fulgidus: cloning and characterization of the genes and comparison of the enzyme with other iron-sulphur flavoproteins.

Adenylylsulphate (adenosine-5'-phosphosulphate, APS) reductase from the extremely thermophilic sulphate-reducing archaeon Archaeoglobus fulgidus is an iron-sulphur flavoprotein containing one non-covalently bound flavin group, eight non-haem iron and six labile sulphide atoms per molecule. Reevaluation of the enzyme structure revealed the presence of two different subunits with molecular masses of 80 and 18.5 kDa.

Spectroscopic studies on APS reductase isolated from the hyperthermophilic sulfate-reducing archaebacterium Archaeglobus fulgidus.

Adenylyl sulfate (APS) reductase, the key enzyme of the dissimilatory sulfate respiration, catalyzes the reduction of APS (the activated form of sulfate) to sulfite with release of AMP. A spectroscopic study was carried out with the APS reductase purified from the extremely thermophilic sulfate-reducing archaebacterium Archaeoglobus fulgidus DSM 4304. Combined ultraviolet/visible spectroscopy and low temperature electron paramagnetic resonance (EPR) studies were used in order to characterize the active centers and the reactivity towards AMP and sulfite of this enzyme.