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Actinic keratoses and cutaneous squamous cell carcinomas are associated with infections with human papillomavirus of genus beta (betaHPV) in immunosuppressed patients. To date, targeted therapy against betaHPV-associated skin cancer does not exist because of the large number of betaHPV without defined high-risk types. In this study, we hypothesized that the activation of innate antiviral immunity in the skin, asymptomatically infected with betaHPV, induces an antitumor response by in situ autovaccination and prevents the formation of betaHPV-associated skin cancer. To test this, we used the preclinical keratin-14–HPV8 transgenic mouse model, which develops skin tumors after mechanical wounding. Remarkably, treatment with the antiviral immune response activating polyinosinic-polycytidylic acid (poly[I:C]) completely prevented cutaneous tumor growth. The induction of the IFN-induced genes Cxcl10and Ifit1by poly(I:C) depended on MDA5 activation. Increased numbers of total and activated CD4 and CD8 T cells were detected in poly(I:C)-treated skin. T cells were found in the skin of poly(I:C)-treated mice but not in the skin tumors of untreated mice. T-cell depletion showed a predominant role of CD4 T cells in poly(I:C)-mediated tumor prevention. Our findings identify the MDA5 ligand poly(I:C) as a promising candidate for in situ autovaccination approaches, which might serve as a treatment strategy against betaHPV-related skin diseases.

Organ transplant recipients (OTRs) have a 100-fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003-2006 (n = 274) and cohort 2 was transplanted in 1986-2002 (n = 352). Participants were followed until death or cessation of follow-up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1-2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2-2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.

β-Human papillomaviruses (HPVs) cause near ubiquitous latent skin infection within long-lived hair follicle (HF) keratinocyte stem cells. In patients with epidermodysplasia verruciformis, β-HPV viral replication is associated with skin keratosis and cutaneous squamous cell carcinoma. To determine the role of HF keratinocyte stem cells in β-HPV-induced skin carcinogenesis, we utilized a transgenic mouse model in which the keratin 14 promoter drives expression of the entire HPV8 early region (HPV8tg). HPV8tg mice developed thicker skin in comparison with wild-type littermates consistent with a hyperproliferative epidermis. HF keratinocyte proliferation was evident within the Lrig1+ keratinocyte stem cell population (69 vs. 55%, P< 0.01, n = 7), and not in the CD34+, LGR5+, and LGR6+ keratinocyte stem cell populations. This was associated with a 2.8-fold expansion in Lrig1+ keratinocytes and 3.8-fold increased colony-forming efficiency. Consistent with this, we observed nuclear p63 expression throughout this population and the HF infundibulum and adjoining interfollicular epidermis, associated with a switch from p63 transcriptional activation isoforms to ΔNp63 isoforms in HPV8tg skin. Epidermodysplasia verruciformis keratosis and in some cases actinic keratoses demonstrated similar histology associated with β-HPV reactivation and nuclear p63 expression within the HF infundibulum and perifollicular epidermis. These findings would suggest that β-HPV field cancerization arises from the HF junctional zone and predispose to squamous cell carcinoma.

IMPORTANCE: Human papillomavirus (HPV)-induced anogenital lesions are very frequent in men who have sex with men (MSM) who are HIV-positive (HIV+). Anogenital warts (AGWs) are considered benign lesions caused by low-risk HPV-types, whereas anogenital dysplasias are potential cancer precursors associated with high-risk HPV-types. Both types of lesions can usually be distinguished clinically. OBJECTIVE: To describe a case series of HIV+ MSM with typical AGW that harbored different grades of dysplasia. DESIGN, SETTING, AND PARTICIPANTS: For this retrospective virological analysis, we recruited 25 HIV+ MSM with AGWs (n = 38) harboring areas of dysplasia and 22 patients who were HIV-negative (HIV−) with AGWs seen between February 2013 and March 2015 at a tertiary dermatological referral center for anal cancer screening. Dysplasia-containing AGW tissue of HIV+ MSM were compared with randomly selected AGWs of patients who were HIV−. MAIN OUTCOMES AND MEASURES: Histopathological analysis, immunohistochemical staining for p16INK4a and Ki67, HPV-typing, and viral load determination in AGWs of HIV+ compared with patients who were HIV−. RESULTS: Overall, 25 HIV+ MSM with AGWs (mean [SD] age, 47.3 [11.1] years) harboring areas of dysplasia and 22 patients who were HIV− (5 women, 17 men; mean [SD] age, 35.5 [12.8] years) with AGWs were included in this study. The 38 dysplasia-containing AGWs of HIV+ MSM harbored low-grade dysplasia in 6 cases (16%), high-grade dysplasia in 31 cases (81%), and areas of invasive anal carcinoma in 1 (3%) case. With the exception of 1 biopsy, all low-grade lesions were p16INK4a-negative, whereas 25 of 31 (81%) AGWs with high-grade lesions or an anal carcinoma were p16INK4a-positive. Only low-risk HPV-types were present in 11 samples (29%; 2 low-grade lesions and 9 high-grade lesions), low-risk and high-risk types were found in 19 samples (50%; 1 low-grade lesion and 18 high-grade lesions), and only high-risk HPV-types were present in 8 samples (21%; 3 low-grade lesions, 4 high-grade lesion, and 1 cancer-containing lesion). High low-risk HPV DNA loads were found in low-grade and high-grade lesions, while high high-risk HPV DNA loads were only found in AGWs harboring high-grade lesions. The 22 AGWs of patients who were HIV− showed no signs of dysplasia, and p16INK4a-staining was always negative. All of these samples carried low-risk HPV types, and in 2 cases high-risk HPV-types were detected additionally. CONCLUSIONS AND RELEVANCE: In contrast to immunocompetent patients, AGWs of HIV+ MSM may harbor high-grade dysplasia or even invasive squamous cell carcinoma. A substantial proportion of theses lesions may only contain low-risk HPV-types. Anogenital warts in patients who are HIV+ should be evaluated histopathologically to exclude cancer precursors.

In Europe and beyond, several advisory bodies have been monitoring the developments in the field of Synthetic Biology. Reports have been sent to national governments for information on the developments and possible regulatory and risk assessment questions raised by this field. To put the issues in a broader perspective, four national biosafety advisory bodies (the French High Council for Biotechnology, the German Central Committee on Biological Safety, the Netherlands Commission on Genetic Modification and the Belgian Scientific Institute of Public Health (Biosafety and Biotechnology Unit)) decided to join forces and organize an international scientific workshop to review some of the latest scientific insights and look into possible challenges in the risk assessment of Synthetic Biology. The SynBio Workshop (Paris 2012) – Risk assessment challenges of Synthetic Biologytook place on the 12th of December 2012 and gathered scientists from biosafety advisory bodies from fifteen European countries, from the European Food Safety Authority as well as representatives of the European Commission, together with research scientists selected for their excellence in the field. The workshop was divided into two sessions: the first session gave an overview of four major fields in Synthetic Biology. The second session was set up for discussion with a scientific panel and the audience to identify and address relevant questions for risk assessment raised by recent and future developments of Synthetic Biology. An overview of the workshop and the discussion points put forward during the day are discussed in this document.

OBJECTIVE To evaluate Merkel cell polyomavirus (MCPyV) DNA prevalence and load among men with human immunodeficiency virus (HIV) (hereafter referred to as HIV-positive men) and among healthy male control subjects. DESIGN Prospective study from February 4, 2009, through April 24, 2010. SETTING Dermatology department of a university hospital. PATIENTS A total of 449 male adults were prospectively recruited, including 210 HIV-positive men who have sex with men and 239 healthy controls. Cutaneous swabs were obtained once from the surface of the forehead in all participants. MAIN OUTCOME MEASURES Swabs were evaluated for the presence of MCPyV DNA using single-round and nested polymerase chain reaction. The MCPyV DNA load (the number of MCPyV DNA copies per β-globin gene copy) was determined in MCPyV-positive samples using quantitative real-time polymerase chain reaction. RESULTS Among 449 forehead swabs analyzed, MCPyV DNA was detected in 242 (53.9%). Compared with healthy controls, HIV-positive men more frequently had MCPyV DNA on nested polymerase chain reaction (49.4% vs 59.0%, P = .046) and on single-round polymerase chain reaction (15.9% vs 28.1%, P = .002). The MCPyV DNA loads in HIV-positive men were similar to those in HIV-negative men, but HIV-positive men with poorly controlled HIV infection had significantly higher MCPyV DNA loads than those who had well-controlled HIV infection (median and mean MCPyV DNA loads, 2.48 and 273.04 vs 0.48 and 11.84; P = .046). CONCLUSIONS Cutaneous MCPyV prevalence is increased among HIV-positive men who have sex with men. Furthermore, MCPyV DNA loads are significantly higher in HIV-positive men with poorly controlled HIV infection compared with those who have well-controlled HIV infection. This could explain the increased risk of MCPyV-associated Merkel cell carcinoma observed among HIV-positive individuals.Arch Dermatol. 2011;147(4):401-406--

Background Mutations in the genome of HIV conferring drug resistance are a major reason for the failure of antiretroviral therapy, but they often compromise viral fitness. Protease (PR) cleavage site (CS) mutations could compensate for impaired replication capacity of drug-resistant viruses.Patients and methods We analysed the cleavage sites p1/p7 and p1/p6-gag of 500 HIV-1 subtype B infected patients. The collective consists of 275 therapy-naive and 225 therapy-experienced patients with at least one primary PR mutation, from whom eight underwent therapy-interruption in different clinical settings.Results Multiple mutations within the CS p7/p1 and p1/p6-gag accumulated in therapy-experienced isolates (p7/p1: A431V-K436R-I437Vand p1/p6-gag: L449F/V-P452S-P453L/A).Further rare CS mutations were totally absent in therapy-naive viruses. Sixty percent of all therapy-experienced viruses exhibited at least one therapy-associated CS mutation, but so did 10% of therapy-naive viruses. The analysis of CS and PR mutations in therapy-experienced viruses revealed several positive correlations - A431Vwith L24I-M46I/L-I54V-V82A; I437Vwith I54V-V82F/T/S; L449Vwith I54M/L/S/T/A; and L449F/R452S/P453L:with D30N-I84V - whereas P453Land V82A were negatively correlated. Mutagenetic trees constructed form this cross-sectional data showed an ordered accumulation of the most prominent CS mutations along two pathways - L90M-I84V-P453Land I54-V82–A431Vfollowed by either M46L or L24I. Furthermore, eight viruses with at least one therapy-associated mutation at each CS displayed an outstanding maintenance of major PR mutations during therapy interruption.Conclusions These findings emphasize the relevance of CS mutations in the evolution of HIV resistance to PR inhibitors. Therefore, therapy-associated CS mutations should be considered in HIV resistance tests to estimate viral fitness in different clinical settings.

A high prevalence of human papillomavirus (HPV) DNA, particularly in squamous cell skin carcinoma of immunosuppressed but also of immunocompetent patients, has renewed great interest in a possible etiologic role of HPV in nonmelanoma skin cancer. It is difficult, however, to interpret these findings against a background of low-level infections with multiple HPV types from supergroup B (HPV4-related and epidermodysplasia verruciformis [EV] HPV), probably acquired by everyone early in and throughout life. Thus far, no high-risk HPV types have been identified. Because of the low copy numbers of HPV DNA in skin cancers, probably not every tumor cell contains a viral genome, which is compatible with cutaneous HPV being possibly important for tumor initiation and progression, but not for maintenance of the malignant phenotype. The question with regard to high-risk types should, therefore, be readdressed in case–control studies on the basis of serology, which can reveal viral activities over years. The viruses lingering in all people are apparently activated by sunlight (UV) exposure, by immunosuppression, and by hyperproliferation of the epithelium (psoriasis) and/or in the specific genetic background of the host (EV). It is intriguing that most of these factors are established risk factors in skin carcinogenesis. The weak transforming activity of cutaneous HPV in vitro compared with the transforming activity of genital HPV may explain the need for activators and synergistic factors. The antiapoptotic activities of E6 proteins of cutaneous HPV could be relevant to oncogenesis in the interplay with UV exposure. Prospective studies should determine the kinetics of HPV activation relative to tumor development.

Recent analyses of head and neck squamous cell carcinomas revealed frequent infections by oncogenic human papillomavirus (HPV) type 16 in tonsillar carcinomas. Concerning involvement of risk factors, clinical course of the disease, and prognosis there are strong indications arguing that the HPV-positive tonsillar carcinomas may represent a separate tumor entity. Looking for a surrogate marker, which in further epidemiological studies could replace the laborious and expensive HPV detection and typing we analyzed p16 protein expression in 34 tonsillar carcinoma for correlation to HPV status and load of viral DNA. p16 has been shown to be of diagnostic value for clinical evaluation of cervical dysplasia. We found 53% of the tested tonsillar carcinomas to be HPV-positive. Fifty-six percent of all tumors tested were immunohistochemically positive for the p16 protein. In 16 of 18 of the HPV-positive carcinomas diffuse p16 expression was observed. In contrast, only one of the HPV-negative carcinomas showed focal p16 staining (P< 0.001). As determined by laser-assisted microdissection and quantitative real-time polymerase chain reaction, p16 expression correlated with the presence of HPV-DNA in the individual tumor specimens. Clinical outcome analysis revealed significant correlation of p16 expression with increased disease-free survival (P= 0.02). These data indicate that p16 is a technically simple immunohistological marker, applicable for routine pathological histology, and its prognostic value for survival is fully equivalent to HPV-DNA detection.

Matrix-metalloproteinases (MMPs) are essentially required for tumor cell invasion and metastasis. Production of precursor enzymes is regulated on transcriptional level, while activation of the pro-enzymes is tightly controlled by posttranscriptional mechanisms. The enzyme activity can be blocked by specific tissue inhibitors of MMPs (TIMPs). In cervical carcinomas strong up-regulation of the type IV collagenase MMP-9 had been demonstrated. We show that activation of CD40, a receptor highly expressed on cervical carcinomas, induces MMP-9 in cervical carcinoma cells, whereas TIMP-1 production inhibiting MMP-9 activity was not affected. This gene induction pattern corresponded to the differential activation of the transcription factor nuclear factor κB (NF-κB) regulating MMP-9, but not signal transducer and activator of transcription 3 (STAT3), which is involved in TIMP-1 gene regulation. Transient expression of the CD40-inducible NF-κB subunit p65 was sufficient for MMP-9 induction. Agents that suppressed CD40-mediated NF-κB activation also reduced MMP-9 induction, further supporting an important role of NF-κB in CD40-mediated MMP-9 induction. Our data suggest that CD40 expression in carcinoma cells might convert a CD40L-dependent immunological defense signal into a tumor-promoting signal. Selective CD40-mediated signaling through NF-κB but not STAT3 correlates to a shift of the balance between MMP-9 and TIMP-1 toward the protease.

The mathematical problem of the existence of solutions for Newtonian dust stars is formulated, and proofs for the non-existence of such stars as isolated objects are given. It is however shown that such stars can be stabilized by reasonable exterior (strained) matter. Comments are made on the problem of Einsteinian rotating dust stars.

Dilated cardiomyopathy (DCM) is a major cause of heart failure in younger individuals. Its prognosis is poor with 40–50% of patients dying within 2 years after diagnosis. Although the etiology of DCM is poorly understood, there is increasing evidence that DCM may represent an autoimmune disease in a significant subset of patients. In order to identify candidate antigens in DCM, we applied a molecular strategy which combines recombinant expression cloning and autoimmunological screening procedures. A left ventricle from a male DCM patient was explanted at heart transplantation and a human DCM left ventricular cDNA-expression library was constructed. 2 × 106 clones were immunologically screened with serum collected from the same patient prior transplantation. Subsequent rounds of screening and purification allowed isolation of a positive clone which was sequenced and identified as Recombination Signal Binding Protein-jκ (RBP-jκ). RBP-jκ is an already identified transcription factor, e.g., involved in Epstein-Barr-virus-induced immortalization processes. Radioactively labeled RBP-jκ protein was synthesized via in vitro translation using the isolated RBP-jκ cDNA. This RBP-jκ protein was used for immunoprecipitation reactions to screen sera of healthy controls and patients suffering of DCM for the presence of RBP-jκ autoantibodies. Analysis revealed that only 31% (n = 16) of healthy but 70.6% of DCM patients (n = 17) carry an autoantibody against RBP-jκ. Patients suffering from ischemic cardiomyopathy showed a prevalence of 22% of RBP-jκ autoantibodies. Western analysis with an monoclonal antibody raised against RBP-jκ showed that RBP-jκ was overexpressed to 488 ± 140% in DCM hearts compared to non-failing controls (n = 8). Autologous immunological screening of a cDNA expression library is a powerful and novel technology to gain insights into the etiology of human idiopathic DCM. Human DCM displays an autoimmune response against RBP-jκ and an overexpression of RBP-jκ. Since RBP-jκ is involved in cellular immortalization and exerts antiapoptotic effects, the increased RBP-jκ autoantibody level during DCM may inhibit this growth-regulating feature of RBP-jκ. In this setting, enhanced myocardial RBP-jκ expression could represent a compensatory but ineffective response to counteract the increased rate of apoptosis in DCM. Furthermore, RBP-jκ may be a useful diagnostic marker for DCM.

Human papillomavirus 8 (HPV8) is one of the oncogenic HPV types specifically associated with skin cancers of epidermodysplasia verruciformis patients. The early gene products of this virus exert functions in transformation (E2, E6, E7), replication (E1, E2) and in the control of viral transcription (E2, E7). Many viral and cellular transactivators of transcription have been shown to interact selectively and directly with a number of TATA-box-binding protein (TBP)-associated factors (TAFIIs), which then play a role as coactivators. Using glutathione-S-transferase (GST) pull-down experiments, we tested in vitro interactions between GST-HPV8-E1, -E2, -E6 and -E7 and 7 in-vitro-translated TAFIIs in the human (h) system (hTAFII18, hTAFII20, hTAFII28, hTAFII30, hTAFII55, hTAFII100, hTAFIIΔN135) or TBP. We could show that GST-HPV8-E2 interacts directly at least with hTAFII55 and TBP. Deletion analysis indicated that a domain overlapping with the C-terminal moiety of HPV8-E2 is required for binding to TBP, whereas determinants for interactions with hTAFII55 are in the central and C-terminal part of the E2 protein. In similar binding studies, GST-HPV8-E6 interacted with hTAFII28, hTAFIIΔN135 and TBP, and more weakly with hTAFII20, whereas GST- HPV8-E7 bound to hTAFII20, hTAFII28, hTAFII55, hTAFIIΔN135 and TBP. Deletion analysis revealed that the C-terminal part of HPV8-E7 is required for the interaction with these hTAFIIs. In contrast, no interactions were observed between GST-HPV8-E1 and in-vitro-translated hTAFIIs.

Human papillomavirus (HPV) 8 belongs to the HPV types frequently associated with skin cancers of Epidermodysplasis verruciformis (EV)-patients. There are 33 nucleotides (M33 motif) in the 5'-part of the non-coding regulatory region of HPV8, which appear highly conserved among EV-specific HPVs and are consistently followed by an AP1 binding site. These sequences were shown to constitute an essential activator of transcription driven by the HPV8 late promoter P₇₅₃₅. The M33/AP1 element displayed properties of a constitutive enhancer, being also able to stimulate the activity of the heterologous thymidine kinase promoter in a position-independent manner. No protein binding could be detected within the 5'-part of the M33/AP1 region, which contributed significantly to the overall activity of the HPV8 enhancer. As shown by DNasel-footprinting, the central and the 3'-part of the enhancer region were involved in interactions with nuclear proteins. Three specific complexes could be observed in gel retardation tests with nuclear extracts from epithelial cells. One of these interactions involved the AP1 protein. Analysis of deletion and point mutations revealed binding of the AP1 protein to be essential for transcriptional activation, but DNA-protein interactions within M33 were important for maximal stimulation. The response to the phorbol ester TPA also required a cooperation of M33 and AP1. Copyright 1993, 1999 Academic Press

Bacterial strain 16-12 was isolated from the root nodules of lupines and was found to be mitomycin C-inducible for the production of a bacteriophage (“16-12-1”) with a long noncontractile tail. The phage was found to attach with a fork-like terminal tail structure to the pili of strain 16-12. In addition, it was also found adsorbed to the bacterial cell poles. It is suggested that phage 16-12-1 may be pilus dependent.

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.

Two different characteristic patterns of human papilloma virus (HPV) type 16 DNA were found by Southern blot hybridization in four pelvic and paraaortic lymph node metastases in a patient with FIGO stage IIIb cervical cancer. Both patterns added up to give the HPV 16 DNA pattern of the primary tumor. This strongly suggests that the tumor was composed of two distinct compartments, each spawning its own lymph node metastases. A second patient presented with a vaginal tumor 4 years after stage IIb cervical cancer had been treated with hysterectomy only. The vaginal tumor was removed and pelvic lymphadenectomy performed. Integrated HPV 16 DNA was found in the vaginal tumor whereas one involved and one free lymph node contained episomal HPV 16 DNA with a characteristic deletion. The apparent heterogeneity of the cancer cell population may indicate that the metastasis is not related to the vaginal tumor but that it is a late sequel of the cervical cancer. Alternatively the metastasis could have originated from an unsampled portion of the vaginal tumor. Copyright 1993, 1999 Academic Press

This study describes sequence variation in both the enhancer and promoter segments of the upstream regulatory region (URR) of 28 human papillomavirus (HPV) type 18 isolates from cervical cancers, 25 from women treated at an Australian center and three from overseas included for comparison. No large-scale changes were found in either region. Fourteen substitutions were identified in the enhancer region with the number in individual isolates ranging from one to eight. Four substitutions impacted cellular transcription factor binding sites but there were no obvious associations with clinicopathological variables. The promoter segment was found to be more highly conserved than the enhancer, but four of the five point mutations identified involved cellular transcription factor binding motifs including a substitution of C for T at nt 104 which affected 21 samples. This change was found to impact upon a previously unrecognized Yin Yang (YY1) binding site. Electrophoretic mobility shift assays (EMSA) showed that this substitution significantly reduced protein–DNA binding and evidence was sought for its possible clinical implications. Of the 24 women with less than Stage III disease and known clinical outcome, tumor recurrence was observed in all of the 6 women whose isolates had the “prototype” T at nt 104, whereas only 8 of the 18 cancers with the mutation at this YY1 site recurred. This is the first report on URR variation in HPV 18 isolates from the South Pacific region. The study also provides initial data on diversity in the promoter region and preliminary evidence suggesting that a specific point mutation in this region may be clinically significant.

A variety of HPV types infect the anogenital mucosa, giving rise to lesions that differ in clinical appearance, histology, and their risk of malignant progression. HPV-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 etiology, and HPV infection alone is probably insufficient for malignant transformation. However, the consistent association between HPV infection and anogenital cancers emphasizes that the sexually transmitted papillomaviruses may have a necessary role in carcinogenesis. Hence, there is a prospect that vaccination programs may one day allow public health control of HPV infection, thereby eliminating an important risk factor.

The serological characterization of virus isolates from verrucae vulgares and plantar warts revealed that HPV 1 and HPV 4 are present in about 50% of these warts with HPV 1 being more prevalent, especially in plantar warts. Parallel to the high incidence of HPV 1 infections, about 50% of non-selected young adults contained antibodies against HPV 1. Only HPV 4 particles, however, reacted with serum from a patient with epidermodysplasia verruciformis when tested by immuno-electron microscopy.

This article describes the HPV type-specific characteristics of papil!omavirus- induced lesions of the anogenital region and the association of defined HPV types with malignant tumors. The possible role of papillomaviruses in malignant conversion is discussed, with consideration of synergistic effects of carcinogens and other infections. Prospects of vaccination are analyzed.

The article presents information on print collection the Mead Art Museum at Amherst College in Massachusetts. The collection of mid-nineteenth-century prints at the museum was augmented by a gift from Edward C. Crossett. The commitment to American art was also established by George D. Pratt, who firmly believed in encouraging American artists. Some of the popular examples from the American print collection in the museum include George Bellow's lithograph "The Cigarette," prints by Picasso, and a series of etchings and aquatints of Edgar Chahine.

The article offers step-by-step instructions for sharpening knives using a homemade "oilstone."

Within a dynamic theory of fusion the three-particle-system is examined. Under suitable boundary conditions a method of integra ion is developed, which yields the exact solution of the relativistic three-particle-equation. This solution describes an elementary particle with internal structure. A thorough discussion of the collective motion supplies the massM and spin 1/2 for the new particle and the proper Diracequation, so that an identification of the three-particle-system with the electron is possible.

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At least 45 different human papillomavirus (HPV) types are presently known, which induce epithelial tumors of the skin or mucosa.1 The majority of the warts, papillomas, leukoplakias, or hyperplasias are benign, but some lesions, particularly dysplasias of the cervix uteri, macules of patients with epidermodysplasia verruciformis (EV), and laryngeal papillomas in adults, may progress to squamous cell carcinomas. Infection by HPV elicits humoral and cellular immune mechanisms against virus particles and tumor tissue,2,3 which trigger tumor regression and leave the host immune to reinfection.The incidence of some HPV types appears rather unaffected by the immune status of the patient, while susceptibility to other types depends more or less on an impaired immune system. Infections by HPV 2, 3, 4, and 10, for example, are considerably favored by a compromised immune system, which is reflected by the frequent occurrence in immunosuppressed allograft recipients.4-6

The efficacy of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is influenced by factors such as potency of applied drugs, adherence of the patient, and resistance-associated mutations. Up to now, there is insufficient data on the impact of the therapeutic setting.

The regulatory regions of the human papillomaviruses (HPVs) 9, 17, 20, and 36 were mapped, sequenced, and aligned. They revealed an arrangement of putative protein binding sites specific for the epidermodysplasia verruciformis associated HPVs. Three subgroups could be differentiated.

We followed with interest the discussion in several articles that appeared in the Archives on the controversy about the significance of human papillomaviruses (HPVs) for nonmelanoma skin cancers (NMSCs).1-3 Despite several reports on the recovery of HPVs from NMSCs, it is still unclear if HPVs are in fact involved in the genesis of these tumors.1 Also, the types of HPVs that are possibly implicated are a matter of controversy: chiefly mucosal HPVs (types 6, 11, 16, and 18) are reported by Goldberg and Griego,2 Moy and Eliezri,3 Euvrard et al,4 and Soler et al.5 In sharp contrast, only HPV types of the epidermodysplasia verruciformis group were detected in NMSCs by Berkhout et al6 and De Jong-Tieben et al,7 whereas mucosal HPVs, as described by others, were ruled out. The primers used for this study are suitable for the amplification of both the