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Biomedical subjects

H Pfister

Publications and source records attributed to H Pfister.

At least 127 records · Page 7Linked to original sources
PubMed1991

Relation of papillomaviruses to anogenital cancer.

A variety of HPV types infect the anogenital mucosa, giving rise to lesions that differ in clinical appearance, histology, and risk of malignant progression. Human papillomavirus type 16 is distinguished by a strong association with high-grade intraepithelial neoplasia and the greatest prevalence in anogenital malignancy. Most cancers appear to have a multifactorial cause, and HPV infection alone is probably insufficient for malignant transformation. The consistent association between HPV infection and anogenital cancers emphasizes that the papillomaviruses may have a necessary role in carcinogenesis, however. Hence, there is a prospect that vaccination programs may one day allow public health control of HPV infection, thereby eliminating an important risk factor.

Animals↗
PubMed1991

Interferon-gamma treatment impairs Fc receptor type II-mediated phagocytosis of human macrophages by a post-receptor-binding mechanism.

The influence of priming by interferon-gamma (IFN-gamma) on FcR expression and function was investigated with human monocyte-derived macrophages. As a ligand specifically interacting with FcRII, bovine IgG1-coated erythrocytes (Bo1-EA) were used. The uptake of these particles by human monocytes and macrophages could be inhibited with anti-FcRII. Moreover, macrophages representing the phenotype that fails to interact with murine IgG1, as revealed in an anti-CD3 IgG1-driven T-cell proliferation assay, had a low avidity for Bo1-EA, and Bo1-EA-macrophage interaction could not be inhibited by anti-FcRII in these cells. Thus, anti-Leu-4 non-responsiveness in a T-cell stimulation assay is associated with an inability of FcRII to interact with bovine IgG1. An influence of IFN-gamma priming on FcRII expression and function was studied, therefore, in anti-Leu-4 responders (bovine IgG1 high responders in the phagocytosis test, susceptible to anti-FcRII treatment). IFN-gamma-primed macrophages from such donors displayed a markedly reduced phagocytosis of Bo1-EA. This reduction was observed both with adherent and with suspended macrophages This type of modulation was not due to a reduced expression of FcRII, nor due to a reduced avidity of expressed FcR to its ligand, as revealed by flow cytometric and rosetting analysis. Since phagocytosis of latex particles and of tanned erythrocytes is little influenced by IFN-gamma priming, our data suggest that IFN-gamma affects FcRII-mediated phagocytosis by a post-receptor-binding mechanism.

Animals↗
PubMed1990

Cell differentiation-related gene expression of human papillomavirus 33.

The gene expression of human papillomavirus (HPV) 33, which can be detected both in benign and malignant genital tumors, was analyzed in a cervical condyloma acuminatum by in situ hybridization using open reading frame-specific RNA probes. Viral mRNA concentrations increased with the degree of differentiation of the keratinocytes. The probes for reading frames E4 and E5 generated the most intense signals. The patterns of the specific viral mRNAs were very similar to those in condylomas induced by HPV 6 or 11, which are only rarely associated with malignancies. This implies that in tumors of the same degree of morphological differentiation the gene expression program of different HPV types is essentially identical. The pattern observed here most likely corresponds to a productive phase of viral infection.

Autoradiography↗
PubMed1990

The E7 protein of human papillomavirus 8 is a nonphosphorylated protein of 17 kDa and can be generated by two different mechanisms.

The E7 protein of human papillomavirus (HPV) 8 shows no in vitro transforming activity, in contrast to E7 of the genital HPVs, but seems to be involved in the control of viral DNA replication. To determine whether functional differences between the E7 proteins of HPV16 and HPV8 were reflected in differences in their biochemical properties, we characterized the E7 protein of HPV8 expressed from the late simian virus 40 promoter in COS 7 cells. An E7-specific antiserum was obtained by immunizing rabbits with a beta-gal-E7 fusion protein containing all of the E7 polypeptide. This antiserum specifically precipitated from [35S]cysteine but not from 32PO4-labeled transiently transfected COS 7 cells a protein with a low mobility of 17 kDa in SDS-PAGE. The high sedimentation rate in nondenaturing glycerol gradients pointed to an interaction with other proteins or to the existence of E7 oligomers. An association with the retinoblastoma protein could, however, be excluded. The 5' ends of HPV8 transcripts derived from the E6-E7 region in G418 selected rodent cells, which were mapped by nuclease S1 digestion, are located upstream of ORFs E6 and E7, respectively. No evidence for an E6*I-like mRNA was found. In COS 7 cells transfected with a plasmid expressing the E6-E7 region of HPV8 under the control of the late SV40 promoter, however, the E7 protein was translated from a polycistronic mRNA potentially encoding E6 and E7. These data indicate that the E7 protein of HPV8 may be expressed in two ways: (i) through translation of an E7-specific mRNA, as with HPV6 and HPV11, or (ii) through internal initiation of translation at the ATG of E7.

Animals↗
PubMed1990

Human papillomavirus type 8 contains cis-active positive and negative transcriptional control sequences.

Human papillomavirus type 8 (HPV-8) is one aetiological agent of macular and flat wart-like lesions in patients with epidermodysplasia verruciformis and appears to be closely linked to skin carcinogenesis. A 1.2 kb region of the genome, which was previously shown to contain a viral E2-dependent enhancer, was progressively shortened from both ends with Bal 31. The resulting fragments were tested for their ability to stimulate chloramphenicol acetyltransferase (CAT) expression from the simian virus 40 (SV 40) promoter. This analysis showed a complex interaction between cis-active, positive and negative control elements located throughout the non-coding region and the flanking reading frames. Two separate positively acting sequences significantly stimulated expression only in cooperation with a third region, which led to 12-fold, E2-dependent enhancement on its own. A major negative element was not only active in the context of HPV-8 sequences, but also down-regulated SV40 enhancer-promoter-driven CAT expression when cloned downstream of the transcription unit. It acted at the transcriptional levels as shown by RNase protection assays and can therefore be regarded as a cis-acting silencer of transcription.

Base Sequence↗
PubMed1990

Prevalence of antibodies to human papillomavirus type 8 in human sera.

The epidermodysplasia verruciformis-associated human papillomavirus type 8 (HPV-8) poses a high risk for malignant conversion of skin lesions in patients with epidermodysplasia verruciformis. For seroepidemiological studies, the HPV-8 open reading frames for E1, E2, E4, E6, E7, and L1 were bacterially expressed as beta-galactosidase fusion proteins, which were purified by preparative gel electrophoresis. Cleavage with the protease FXa at the engineered recognition site separated the beta-galactosidase polypeptide part from the viral polypeptide. Western blot analysis of 445 serum samples from a randomly selected population with the entire L1 as antigen revealed HPV-8-specific immunoglobulin G antibodies in 20% of the samples. The percentage of positive sera did not significantly differ in different age groups. In some sera, we could also detect immunoglobulin M antibodies. The use of two shortened L1 polypeptides as antigen indicated that there are at least two reactive epitopes in the case of HPV-8 L1. Several sera contained antibodies to the early proteins E1, E2, E4, and E7. E1 and E7 were predominantly detected by sera which were negative for L1. In one case, we found antibodies to E6. Two of four sera of patients with epidermodysplasia verruciformis reacted with HPV-8 L1. The prevalence of anti-HPV-8-L1 antibodies in patients with malignant melanomas was comparable to that in the normal population (27.8%) but was significantly higher in patients with cervical cancer (37.5%), basaliomas (40%), and squamous cell skin carcinomas (72.7%) and in immunocompromised patients with Hodgkin's disease (47.7%).

Antibodies, Viral↗
PubMed1990

[Eruptive viral warts of the burn area].

Eruptive viral warts were observed in a second-to-third degree burn area in a 68-year-old woman; the warts healed spontaneously and completely after approximately 3 weeks. HPV-2-related DNA was demonstrated by Southern blot analysis.

Aged↗
PubMed1990

[Virus-induced papilloma of the conjunctiva. Detection of HPV 6a DNA].

By means of hybridization of nucleic acid, we detected DNA specific for papilloma virus, type 6a, in a caruncle papilloma of a 45-year-old female patient suffering from genital warts. These findings show that papilloma viruses, which are usually responsible for genital warts, may also induce conjunctival papilloma.

Condylomata Acuminata↗
PubMed1989

Inter-laboratory variation as an explanation for varying prevalence estimates of human papillomavirus infection.

Human papillomavirus (HPV) infection has been strongly implicated as a cause of genital neoplasia. Although Southern blot DNA hybridization techniques are regarded as the most accurate means of identifying HPV infection, studies using this technique to measure infection have provided varying estimates of the prevalence of HPV among healthy and diseased groups. This investigation provides a possible explanation for study-to-study differences, by demonstrating inter-laboratory variability in the detection and typing of HPV by Southern blot. Four experienced laboratories tested 40 identical, masked samples of DNA extracted from presumed infected and non-infected tissues. The pairwise percentage agreement between the laboratories in judging samples as HPV-positive or negative ranged from 66 to 97%. Among samples judged to contain HPV, agreement as to type ranged from 77 to 96%. We conclude that inter-laboratory differences are an important consideration in any discussion of HPV prevalence estimates.

Analysis of Variance↗
PubMed1989

Human papillomavirus 16 DNA in cervical cancers and in lymph nodes of cervical cancer patients: a diagnostic marker for early metastases?

Human papillomavirus (HPV) 16 is most prevalent in cervical cancers and also persists in metastases. We examined HPV16-DNA-positive primary cancers and several lymph nodes from each of 14 patients to evaluate the use of HPV16 DNA as a diagnostic marker for the detection of early node involvement. The HPV16 DNA was exclusively integrated in 39% of the primary cancers, predominantly episomal in 36%, and integrated and extrachromosomal to a similar extent in 25%. Thirteen of 16 involved lymph nodes contained HPV16 sequences. Integrated viral DNA showed the same pattern in primary tumors and in metastases. The level of extrachromosomal HPV16 DNA, however, appeared to be considerably reduced in some nodes. HPV16 DNA was also detected in 18 out of 59 histologically negative lymph nodes. This result recommends nucleic acid hybridization as a sensitive method for the detection of HPV-DNA-positive cancer cells. The prognostic significance of viral sequences in histologically negative nodes remains to be established.

Biomarkers, Tumor↗
PubMed1989

Recall and dating of psychiatric symptoms. Test-retest reliability of time-related symptom questions in a standardized psychiatric interview.

The advent of more explicit diagnostic criteria and the growing interest in "lifetime" rates of mental disorders has made imperative an accurate determination of time-related diagnostic criteria. We used data from two independent test-retest studies of the Diagnostic Interview Schedule (DIS) and the Composite International Diagnostic Interview (CIDI) to study the reliability of different time-related questions in these fully standardized diagnostic interviews. With two exceptions (anxiety disorders and alcohol-related questions), the test-retest reliability of most time-related questions in both interviews was judged to be satisfactorily high. Furthermore, the validity of time-related questions in the DIS (age at symptom onset, duration and frequency of illness episodes) was examined by comparing them with detailed "consensus" ratings done independently by different clinicians for 207 former psychiatric inpatients. A surprisingly high concordance was found for former psychotic patients except for those still severely disturbed at the follow-up investigation. Some severe restrictions were also found for nonpsychotic disorders with regard to judgment of the age at onset of phobias, panic attacks, and depression. For a more valid assessment of time-related symptom information, the use of specific memory aids is suggested.

Adult↗
PubMed1989

Duplication of enhancer sequences in human papillomavirus 6 from condylomas of the mamilla.

Human papillomavirus (HPV) 6 usually induces tumors of the genital, oral, or laryngeal mucosa. An HPV 6-related DNA of 8.2 kb was detected in an extrachromosomal state in atypically located condylomas of the mamilla and was molecularly cloned. The identity of the cloned HPV DNA and the viral DNA in the biopsy was confirmed by comparative Pstl cleavage analysis, which showed typical HPV 6 DNA fragment patterns except for 0.2-kb larger B fragments. Sequencing revealed an exact 236-bp duplication encompassing nucleotides 7681 to 7896 of HPV 6b. This tandem repeat is just upstream from the putative early promoter and contains a 20-bp insertion at position 7720, which constitutes an enhancer element described by R. F. Rando, W. D. Lancaster, P. Han, and C. Lopez (Virology 155, 545-556, 1986). A Hinfl-Pstl fragment containing the whole duplication was cloned into an enhancer-dependent CAT expression vector and led to three- to sevenfold increased CAT activity when compared with the monomeric sequence in C127 cells and BPV1 transformed C127 cells. This indicates that the duplication within the HPV 6 isolate from the mamilla may influence early gene expression and possibly tissue tropism.

Adolescent↗