Human papillomaviruses and cervical cancer

In the United States, the Phase I Feasibility Study under IDE G970065 was approved by the Food and Drug Administration on 04/11/97. The approved protocol called for implantation of the bifurcated Talent spring stent-graft system on patients who are high-risk candidates for conventional surgery because of cardio-respiratory, medical, general, or local anatomical reasons which would likely complicate the technical execution of the operation or be accompanied by a high expected mortality rate. Patient enrollment was complete with 16 cases as of September 26, 1997. This was a multicenter experience involving five different sites. This is an ongoing study and patients, of course, will continue to be followed longitudinally. Phase II will likely be approved by the FDA for initiation in January or February of 1998. Standard-risk AAA patients will be entered into the study at this time; comparison with concurrent controls will be used for comparison with conventional surgery.     

Detection of human papillomaviruses in tissue specimens

During the past decade, molecular methods based on the detection of viral DNA have become a key tool for the detection of human papillomaviruses (HPVs) in tissue. The methods can be divided into two groups: those in which tissue destruction is unavoidable for the detection of HPV DNA, and those in which the detection of viral DNA is performed in a way that allows tissue morphology preservation. Polymerase chain reaction is currently the most sensitive method for HPV detection and an excellent research tool. However, because of frequent contamination problems and lack of standardization, it is not readily applicable to diagnostic laboratories. The recent improvements in in situ hybridization have made it possible for this method to become the most appropriate method for routine detection of HPVs in tissue. At present, however, the use of at least two independent HPV DNA detection methods is indispensable for accurate determination of HPVs.     

Distinct manifestations of human papillomaviruses in the vagina

To clarify the pathogenic relationships between human papillomavirus (HPV) and vaginal intraepithelial neoplasia (VAIN), we examined 71 vaginal biopsy specimens by histopathology and immunohistochemistry and analyzed the presence of HPV DNA by blot hybridization at Tm - 40 degrees C using an HPV 58 probe (PBM-58 method). We found 27 cases of VAIN in patients with previous hysterectomy or antecedent or concomitant cervical intraepithelial neoplasia (CIN) and 44 cases of VAIN in patients without any abnormal findings on the cervix and the vulva. Histopathologically, 53 of 71 cases were graded as VAIN I and 15 and 3 cases were VAIN II and III, respectively, while 59 cases showed positivity for HPV capsid antigen by immunohistochemistry. Using the PBM-58 method, all 71 VAIN cases harbored a single HPV type at more than 1,000 viral copies per cell. We identified 15 different types (HPV 16, 18, 30, 31, 35, 40, 42, 43, 51, 52, 53, 54, 56, 58 and 66). Furthermore, we molecularly cloned 7 novel prototypes (HPV 59, 61, 62, 64, 67, 69 and 71) from VAIN I. Our results are strongly indicative that HPVs are etiologic agents of VAIN, like in the case of CIN. The distinct manifestations of HPV infection in the vagina are discussed in comparison with those in the cervix.     

Oncogenic human papillomaviruses and ploidy in cervical lesions

AIM: To compare ploidy measurements obtained on tissue sections of selected low and high grade squamous intraepithelial lesions containing oncogenic HPV (types 16, 18 or 33) detected by in situ hybridisation (ISH) or PCR. METHODS: DNA ploidy was assessed by image cytometry after Feulgen staining of contiguous serial sections of eight lesions exhibiting atypical squamous cells or squamous atypia and 53 low and 63 high grade squamous intraepithelial lesions in which HPV had been detected by ISH or PCR. RESULTS: Aneuploidy was strongly associated with the presence of oncogenic HPV, being detected in 50% of lesions with squamous atypia and 75.5% of the low and 95.2% of the high grade squamous intraepithelial lesions. The multiploid profile was highly associated with high grade lesions and with the pattern of HPV DNA integration. CONCLUSIONS: The presence of aneuploidy is strongly suggestive of the presence of oncogenic HPV types. Combining the detection of HPV by ISH and PCR with DNA image cytometry may provide the pathologist and the physician with important prognostic information about low grade lesions, especially when these lesions have a multiploid DNA profile and contain oncogenic HPV.     

Role of human papillomaviruses in the malignant transformation of keratinocytes

Human papillomaviruses (HPVs) are considered the main etiological agent of cervical cancer and of its precursory lesions (CIN). The HPV transformation potential consists in the presence of two oncogenes, E6 and E7, which inactivate the tumour-suppressor proteins p53 and pRB of the host cell, inducing uncontrolled transformation and proliferation mechanisms. These effects were demonstrated by in vitro experiments.     

Morphology of lesions of the uterine cervix and human papillomaviruses

The question of psychophysiological reactivity of borderline hypertensives is still controversial. METHODS: Young males with borderline blood pressure levels and normotensive controls were recruited during a routine examination. Samples of study I comprised 19 subjects, samples of study II 18 subjects. Two stressors were presented (distressing movie, mental arithmetic), each followed by a recovery phase. Systolic and diastolic blood pressure, heart rate, and electrodermal parameters were assessed repeatedly. RESULTS: Borderline hypertensives showed greater reactions to stressors in systolic blood pressure only. Changes in percentage of baseline levels were essentially the same. Recovery after stress did not differ between groups. CONCLUSION: Only moderate support is given to the hypothesis that borderline hypertensives show increased and slowly recovering psychophysiological responses.     

Human papillomaviruses, tumour suppressor genes and cervical cancer

There is now a considerable body of evidence that links HPV infection with anogenital squamous carcinoma, particularly for specific 'high risk' HPV types (HPV16 and 18) and invasive carcinoma of the cervix. Recent advances in the molecular study of these viruses have elucidated some potential mechanisms by which they may contribute to the development of these diseases. In this review we concentrate on the interactions of 2 of the HPV encoded proteins, E6 and E7, with cellular tumour suppressor gene products. We provide a model of how these interactions may be important in tumourigenesis and draw together current knowledge of this exciting and rapidly evolving field.     

Heterogeneity of intergranular damage

An interface damage function (IDF), which statistically describes the area fraction of interface damage as a function of up to eight parameters defining crystallite interfaces, was determined for commercial-purity copper specimens crept in plane-strain tension. The IDF was determined from stereological parameters measured on plane sections cut through damaged specimens. The eight-dimensional space of the function was investigated by analyzing two-dimensional projections of the complete domain. Certain “special” interfaces were observed to damage preferentially. A low planar density of atoms near crystallite interfaces apparently increased the propensity for the occurrence of damage. Other microstructural mechanisms contributing to the observed heterogeneous distribution of damage are also considered. formerly Graduate Student, Yale University.     

Molecular targets for human papillomaviruses: prospects for antiviral therapy

A substantial medical need exists for the development of antiviral medicines for the treatment of diseases associated with infection by human papillomaviruses (HPVs). HPVs are associated with various benign and malignant lesions including benign genital condyloma, common skin warts, laryngeal papillomas and anogenital cancer. Since treatment options are limited and typically not very satisfactory, the development of safe and effective antiviral drugs for HPV could have substantial clinical impact. In the last few years, exciting advances have been made in our understanding of papillomavirus replication and the effects that the virus has on growth of the host cell. Although still somewhat rudimentary, techniques have been developed for limited virion production in vitro offering the promise of more rapid advances in the dissection and understanding of the virus life cycle. Of the 8-10 HPV gene products that are made during infection, only one encodes enzymatic activities, the E1 helicase. Successful antiviral therapies have traditionally targeted viral enzymes such as polymerases, kinases and proteases. In contrast, macromolecular interactions which mediate the functions of E6, E7 and E2 are thought to be more difficult targets for small molecule therapy.     

Heterogeneity of crystalline antithyroid phytoprecipitin

The crystalline preparation of antithyroid phytoprecipitin has been resolved by chromatography on Whatman CM-32 cellulose on a preparative scale into two components, designed respectively A and B. Each component was further resolved into consisting polypeptide chains alpha (mol. weight 7.000) and beta (mol. weight 17.000) by gel filtration on sephadex G-50 in 1 M acetic acid 6 M urea. Homologous chains were comparatively studied by electrophoresis in acrylamide gel, amino acid analysis and peptide mapping technique. Electrophoresis in acrylamide gel with 6 M urea according to Takayama [8] revealed the identical mobility of beta chains in both components A and B, while alpha chains differed. alphaA chain was more basic, than alphaB, i.e. it had greater positive sharge. The amino acid analysis and peptide mapping showed that alphaA chain had one residue of lysine more than alphaB chain. The comparison of beta chains by peptid mapping confirmed their complete identity.     

Heterogeneity of cardiac glucocorticoid receptors

The work presents the main results obtained in the investigation of properties and distribution of the glucocorticoid cardiac receptors as well as mutual conversions of different forms of the glucocorticoid-receptor complexes. The receptors have been found in hearts of various kinds of animals. The glucocorticoid receptor activity is distributed approximately evenly in the myocardium of the left and right ventricles and auricles. The receptors have been found both in isolated myocytes and in endothelium cells. Methods of chromatography can successfully be used in decomposition of the glucocorticoid-receptor complex to heterogenic components. The role of some factors in the mechanism of the functioning of the receptor system is discussed.     

Heterogeneity of Atlantic salmon troponin-I

Three non-identical, full length troponin-I (Tn-I) clones were isolated from an Atlantic salmon myotomal (trunk) muscle cDNA library. The primary structures, which are predicted to range from 172 to 180 amino acids in length, exhibit similar percent identity scores when compared with fast, slow and cardiac specific Tn-Is from higher vertebrates. When the sequence data are considered along with the results of Western blotting it is evident that Tn-I is more heterogeneous in Atlantic salmon than has been previously shown in higher vertebrates.     

Heterogeneity in exposed uninfected individuals

A case of an autoerotic accident in an extended sense is reported. A heterosexual couple died from strangulation at the same time during common autoerotic practice.     

Detection of human papillomaviruses (HPV-16,18) in cervical smears by in situ hybridization

The rate of human papillomaviruses (HPV) 16 and 18 infections were measured in 109 women with histologically or cytologically determined lesions of the uterine cervix and in 42 healthy women. Cervical swabs were taken as the source of the target viral DNA. In situ hybridization with biotinylated probes was used. HPV-16 was the predominant type in patients and in healthy women. The percentage of positive cases was the highest in cervical cancer patients: 43.3% in squamous cell carcinoma and 33.3% in adenocarcinoma followed by cervical intraepithelial neoplasia (CIN), III, II (21.4%), CIN I (14.3%) and low grade squamous intraepithelial lesions (13.6%). HPV-18 type was detected in a lower percentage in the three groups of patients. In healthy women HPV-16 was determined in 12% and HPV-18 in 4.8%. We believe that the described noninvasive method of obtaining clinical material should be the method of choice for estimating papillomavirus infections in patients and in the general population. Our results are in agreement with suggestions that HPV genotype could be an important prognostic indicator in cervical carcinoma.     

Heterogeneity of variance in clinical data.

Traditional parametric (t, F) and nonparametric (Mann-Whitney-Wilcoxon U, Kruskal-Wallis H) statistics are sensitive to heterogeneity of variance (heteroscedasticity). Moreover, there are theoretical reasons to expect, and empirical results to document, the existence of heteroscedasticity in clinical data. Transformations to reduce heteroscedasticity are problematic. This article reviews the literature on robust methods that are available and that should be widely used to control rate of Type I error and maintain power. No one robust method is ideal for all situations, but such methods are superior to the traditional tests. Specific recommendations are made for application under various conditions of heteroscedasticity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)