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Biomedical subjects

A B Jenson

Publications and source records attributed to A B Jenson.

At least 73 records · Page 4Linked to original sources
PubMed1987

Sexually transmitted papillomaviral infections. I. The anatomic distribution and pathologic grade of neoplastic lesions associated with different viral types.

Multiple colposcopic biopsy specimens were collected from 160 women, with sampling of principal cervical and vulvar lesions as well as secondary areas of either minor acetowhitening or normal epithelium. Papillomaviral deoxyribonucleic acid was detected by Southern blot hybridization in 197 (90%) of the 218 principal biopsy specimens and 93 (46%) of 198 secondary biopsy specimens. Although different papillomaviruses were found at different sites in 31 women, only six of 416 specimens contained multiple types within the same sample. Specific viral types were associated with specific disease patterns. Only one of 80 type 6 or 11 infections had a diagnosis greater than cervical intraepithelial neoplasia, grade 2. In contrast, 42 of 48 (90%) biopsy specimens of cervical intraepithelial neoplasia, grade 3, or invasive cancer contained type 16, 18, or 31. Nonetheless, 12 of 124 (10%) cases of condyloma and cervical intraepithelial neoplasia, grade 1, were associated with types 16, 18, and 31 infections. Of 58 women with multicentric disease, 46 had positive hybridizations for both cervical and vulvar lesions (32 showing the same type in both samples and 14 showing different viruses). Differing patterns of papillomavirus-induced disease arise partly from the predilection of specific viral types for certain anatomic sites and partly through variations in host response. Detection of viral deoxyribonucleic acid in 46% of the secondary biopsy specimens suggests that disease expression may represent focal breakdown of host surveillance within a field of latent papillomaviral infection.

Biopsy↗
PubMed1987

Purification of papillomavirus structural polypeptides from papillomas by immunoaffinity chromatography.

A broadly cross-reactive monoclonal antibody directed against papillomavirus, coupled to immunoaffinity columns, was used to isolate bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 1 (HPV-1) structural polypeptides from homogenates of productively infected cells. One of the polypeptides isolated from bovine fibropapillomas appeared to be the BPV-1 major capsid protein since it had a mol. wt. of 54K and was reactive by Western blots with papillomavirus genus- and BPV-1 type-specific rabbit antibodies as well as monoclonal antibodies cross-reactive with BPV-1/BPV-2 and BPV-1/deer PV. A polypeptide from human plantar warts similarly appeared to be the major capsid component since it also had a mass of 54K to 55K and reacted with papillomavirus genus- and HPV type-specific rabbit antibodies. By using this technique structural viral polypeptides from papillomavirus-induced lesions containing readily detectable viral structural antigens but relatively few virus particles, such as seen with mucosotropic HPVs can now be isolated for mapping of virus-specific epitopes.

Animals↗
PubMed1987

Topographical and conformational epitopes of bovine papillomavirus type 1 defined by monoclonal antibodies.

Monoclonal antibodies (MAbs) were generated against sodium dodecyl sulfate-disrupted bovine papillomavirus type 1 (BPV-1). When screened by enzyme-linked immunosorbent assay (ELISA) on intact and disrupted BPV-1, -2, and deer papillomavirus, three patterns of reactivity were defined: reactivity only with intact virus, with both intact and disrupted virus, and only with disrupted virus. On the basis of ELISA results, the topographical location and requirement for conformation for immunoreactivity of epitopes was defined as external conformational, external linear, and internal linear. Cross-reactivity of MAbs with other papillomavirus types was analyzed by immunofluorescence on warts from different species. Type-specific, BPV-1 and/or -2 cross-reactive, broadly cross-reactive, and genus-specific MAbs were identified. MAb reactivity with structural polypeptides of BPV-1 was analyzed by Western blot. MAbs reactive with epitopes defined as conformational by ELISA did not react in Western blot. All MAbs reactive in Western blot reacted with the major capsid protein (MCP) [55 kilodalton (kDa)], demonstrating that the MCP carries both type-specific and cross-reactive epitopes. Most MAbs reactive with the MCP were cross-reactive with structural polypeptides of 48 and 96 kDa, demonstrating the immunologic relatedness of these three polypeptides.

Animals↗
PubMed1987

Oncogenic association of specific human papillomavirus types with cervical neoplasia.

Molecular hybridization analysis of human papillomavirus (HPV) DNA from 190 cervical biopsy specimens from women in the United States, Brazil, and Peru revealed viral sequences in 2 (9%) of 23 biopsy specimens of normal mature squamous epithelium, 7 (44%) of 16 biopsy specimens of metaplastic squamous epithelia, 60 (77%) of 78 cervical intraepithelial neoplasia (CIN), 57 (89%) of 64 invasive squamous carcinomas, and 8 (89%) of 9 endocervical adenocarcinomas. HPV typing by DNA hybridization revealed HPV 6 and HPV 11 sequences in metaplastic squamous epithelia, CIN I, and CIN II, but not in CIN III lesions or invasive carcinomas. HPV 16 was detected in metaplastic epithelium and in nearly half of the invasive squamous carcinomas and adenocarcinomas. It was present in 31% of CIN lesions, increasing in frequency with the severity of CIN from 20% of CIN I to 50% of CIN III. HPV 16 showed a striking difference in geographic distribution, being detected in 36% of the carcinomas from the United States compared to 64% of the carcinomas from Brazil and Peru. HPV 18 was found in metaplastic epithelia and in 17% of carcinomas but in only 1% of CIN lesions. HPV 31 was not found in metaplastic epithelium but was present in 6% of carcinomas and in 18% of CIN lesions. In addition, a group of uncharacterized HPVs, not corresponding to any of the probes used, was found in 5% of normal and metaplastic epithelia and in 18% of CIN and 19% of invasive cancers. These results suggest that individual HPV types that infect the cervix have varying degrees of oncogenic association. HPV 6 and HPV 11 appear to have very little oncogenic association, HPV 31 has low oncogenic association, and HPV 16 and HPV 18 have high oncogenic association.

Biopsy↗
PubMed1987

Tissue effects of and host response to human papillomavirus infection.

Human papillomaviruses are a heterogeneous group of DNA tumor viruses associated with hyperplastic (warts, condylomas), dysplastic (CIN and VIN), and malignant lesions (carcinomas) of squamous epithelium. Each HPV type is preferentially associated with specific clinical lesions and has an anatomic site preference for either cutaneous or mucosal squamous epithelium. Infection appears to begin in the basal cells. Early gene expression is associated with acanthosis, and late gene expression is associated with appearance of structural antigens and virions in nuclei of cells of the granular layer, usually koilocytotic cells. Malignant transformation of warts and papillomas appears to be related to a variety of factors: (1) infection by certain HPV types (HPV-5, HPV-8, HPV-16, HPV-18, HPV-31); (2) decreased cellular immunity to HPV-associated antigens; and (3) interaction with cofactors, such as other microorganisms or sunlight (see also the article by Kashima and Shah). Spontaneous regression or successful treatment of the benign lesions appears to depend on either naturally acquired or iatrogenically related stimulation of HPV type-specific immunity. The humoral antibody response to HPV particles may be important in preventing infection. In contrast, the local events surrounding regression of warts and condylomas are primarily associated with specific cell-mediated immunity. Local cell-mediated immune responses, particularly cell-associated soluble mediators and stationary macrophage-like cells, may be especially important in the host's immune response to mucosal infections.

Epithelium↗
PubMed1987

Human papillomavirus infection and anogenital neoplasia: speculations for the future.

HPV infections of the female genital tract are common. The association of these viruses with anogenital neoplasia has stimulated efforts to devise practical methods of detection and typing of HPV. Although experimental diagnostic tests are available, they are, for the most part, complex and time consuming and are limited to medical centers researching HPV. New methods for preparing probes with higher sensitivities for hybridization tests will allow use of in-situ methods on formalin-fixed tissues and will probably be the method of choice. Antigen detection systems are not available except for antisera directed against the common structural antigens. The most useful immunologic test will be directed toward detection of nonstructural antigens in fixed tissues; such a system could also be useful for virus typing. Therapies based on use of these antigens to stimulate the immune system may be applicable as an alternative to current therapies. Most intriguing are the prospects for a vaccine based on either structural or nonstructural viral antigens. It has been estimated that as many as 20 per cent of female cancer deaths worldwide are associated with HPV. Thus, use of an effective vaccine would relieve considerable human suffering. However, until the host immune response to HPV infection is better defined, much of the effort dedicated to developing a vaccine may be futile.

Female↗
PubMed1986

Human papillomavirus deoxyribonucleic acid in cervical carcinoma from primary and metastatic sites.

Tissue from 13 cervical cancers and pelvic or para-aortic lymph nodes from the same patient were evaluated by deoxyribonucleic acid hybridization with a human papillomavirus type 16 deoxyribonucleic acid probe for the presence of human papillomavirus-related deoxyribonucleic acid sequences. Twelve of the primary malignancies were squamous cancers and one was an adenocarcinoma. Eight of the primary tumors contained human papillomavirus type 16 deoxyribonucleic acid sequences, and five contained viral sequences closely related to human papillomavirus type 16. Histopathologic diagnosis confirmed malignant cells in six of 13 lymph nodes; three of these specimens contained human papillomavirus type 16 sequences while three had human papillomavirus type 16-related sequences. One lymph node that failed to show malignant cells also contained human papillomavirus type 16 deoxyribonucleic acid. The remaining lymph nodes did not contain malignant cells by either histologic examination or deoxyribonucleic acid hybridization. The human papillomavirus deoxyribonucleic acid sequences in the lymph nodes were similar to those in the matched primary cancer in all cases. These data provide further evidence implicating human papillomavirus in the etiology of cervical cancer.

Adenocarcinoma↗
PubMed1986

The role of human papillomaviruses in the pathogenesis and histologic classification of precancerous lesions of the cervix.

It is clear that the relation between HPV infection and cervical neoplasia is more complex than initially realized. Preliminary molecular virologic data suggest preferential distributions of low- and high-risk HPV types in CIN that tend to correlate with the morphologic appearance. Thus, mild and moderate dysplasias (CIN I and II) contain a diverse distribution of HPV types, including a minority that have a high risk of malignant potential. HPV, therefore, appears to play a major role as a promoter. Neoplastic transformation is probably determined by specific HPV types but, in addition, requires initiation by some other carcinogenic stimulus, e.g., HSV II, cigarette smoking. Despite numerous studies, performed during the past 30 years, the long-term behavior of dysplasia remains uncertain. The natural history of HPV-associated lesions is unknown. Until this information is available, it is recommended that the conventional dysplasia--CIS or CIN nomenclature be used. The presence of associated viral changes can be considered and added to the diagnosis, e.g., "moderate dysplasia (CIN II) with evidence of papillomavirus infection." Treatment should be the same for all intraepithelial lesions, regardless of the presence of morphologic evidence of HPV. In the future, it may be necessary to modify the classification of precancerous lesions of the cervix if it is shown that a specific HPV type induces a characteristic morphologic alteration or that the HPV type, in and of itself, has greater prognostic significance. Until then, confusion will be minimized and management optimized if the conventional dysplasia--CIS or CIN nomenclature is employed.

Female↗
PubMed1986

Verrucous carcinoma of the vulva associated with an unusual type 6 human papillomavirus.

An unusually rapid growing vulvar verrucous carcinoma found associated with human papillomavirus type 6 is described. Both human papillomavirus structural antigens and deoxyribonucleic acid (DNA) sequences were detected in the tumor biopsy. The human papillomavirus genome was isolated and compared with the genome of human papillomavirus type 6b, which was cloned from an anogenital wart. The two genomes were extremely homologous in genomic organization and DNA sequence, except for a region on the viral genome containing the virus control elements. A discussion of this observation and how it could relate to the importance of viral subtypes follows.

Adult↗
PubMed1986

Enhancement of respiratory syncytial virus pulmonary pathology in cotton rats by prior intramuscular inoculation of formalin-inactiva ted virus.

Cotton rats previously inoculated with Formalin-inactivated respiratory syncytial virus (RSV) were challenged intranasally with live RSV to induce an enhancement of RSV disease similar to that observed after the administration of Formalin-inactivated RSV vaccine to human infants 20 years ago. Within 24 h after infection with RSV, cotton rats developed pulmonary lesions that reached a maximum by day 4. Histologically, the lesions resembled an experimental pulmonary Arthus reaction. An action of Formalin on RSV appears to be responsible for this effect, because live virus or virus heated in the absence of Formalin did not induce enhanced immunopathology. Selected epitopes on the fusion (F) or attachment (G) or both RSV surface glycoproteins that are involved in inducing neutralizing antibodies were modified to reduce or ablate their antigenicity. However, other epitopes on the F or G or both glycoproteins were not ablated by Formalin, because cotton rats inoculated parenterally with a Formalin-inactivated virus developed a high level of F and G antibodies measurable by an enzyme-linked immunosorbent assay. At this time, the effect of Formalin on RSV cannot be localized to either the F or G glycoprotein of RSV.

Animals↗
PubMed1986

Monoclonal antibodies to genus- and type-specific papillomavirus structural antigens.

Monoclonal antibodies against SDS-disrupted bovine papillomavirus type 1 (BPV1) were obtained from hybridomas prepared by fusing mouse myeloma cell line P3X63Ag8U1 with spleen cells from immunized BALB/c mice. Six hybridoma cell lines were obtained after testing supernatant fluids for positivity by the enzyme-linked immunosorbent assay using the immunogen as antigen and by indirect immunofluorescence (IF) on frozen sections of BPV1-induced bovine fibropapillomas. Monoclonal antibodies (AU1-AU6) from these hybridomas were then tested for reactivity by IF tests on BPV2-induced fibropapillomas and on human plantar warts and vulvar condylomas and by avidin-biotin complex tests on sections of formalin-fixed cervical dysplasias. One monoclonal antibody (AU1) was reactive with all tissues, four (AU3-AU6) were reactive with both BPV1 and BPV2 fibropapillomas, and the remaining antibody (AU2) was only reactive with BPV1-induced fibropapillomas. All monoclonal antibodies reacted with the major capsid protein (mol. wt. 54,000) of BPV1, whereas five (AU1, AU3-AU6) reacted with the major capsid protein of BPV2. These results indicate that papillomavirus genus-specific, cross-reactive, and type-specific antigenic determinants are located on the major capsid protein of BPV1.

Animals↗
PubMed1986

Correlation of cellular atypia and human papillomavirus deoxyribonucleic acid sequences in exfoliated cells of the uterine cervix.

Restriction enzyme digestion and Southern blot hybridization were used to analyze deoxyribonucleic acid (DNA) extracted from exfoliated cervical cells for the presence of human papillomavirus sequences and these results were correlated with cytologic findings on Papanicolaou smears. Specimens (N = 204) were obtained from a nonselected population of women undergoing routine cytologic screening and human papillomavirus DNA sequences were detected in 33 (16%) women. Thirteen smears contained atypical squamous cells, ranging from very mild dysplasia to moderate dysplasia; all showed associated morphologic evidence of human papillomavirus infection characterized by koilocytosis, nuclear enlargement, wrinkling, and hyperchromasia, and human papillomavirus DNA was demonstrable in 12 (92%) smears. Of the remaining 191 samples with normal cytology, 21 (11%) also contained human papillomavirus DNA sequences. Reevaluation of the smears from these women resulted in a revision of the cytologic diagnosis to very mild dysplasia in four cases. These data suggest that human papillomavirus infection occurs more frequently than predicted by cytologic screening.

Base Sequence↗
PubMed1985

Role of papilloma virus in proliferative squamous lesions.

HPVs are associated with a variety of proliferative squamous lesions. 27 different types of HPV have been identified by DNA molecular hybridization studies. Genus- and type-specific HPV structural antigens can be detected in approximately half of benign warts and condylomata by immunocytochemistry; positive lesions are considered infectious. Genus- and type-specific putative HPV DNA sequences replicating as episomes can be recovered from the majority of benign (exophytic and flat condylomata) and malignant squamous lesions of the cervix and anogenital area. The type of HPV determines, in part, the anatomic site, clinical appearance, and natural history (including potential malignant conversion) of the lesion.

Animals↗
PubMed1985

Human papillomavirus in various lesions of the head and neck.

The association of human papillomavirus with benign and malignant epithelial lesions of the head and neck has been studied by a peroxidase-antiperoxidase technique having immunospecificity against genus-specific structural antigens of the papillomaviruses. More than 360 specimen blocks from 144 patients were evaluated. There was evidence of human papillomavirus antigen in three out of eight patients with childhood-onset laryngeal papillomas (37.5%) and in four out of eight patients with adult-onset papillomas (50%). A patient with an unusual flat, wartlike lesion appearing as an oral cavity leukoplakia had detectable papillomavirus antigen in it. None of the 13 cases of inverting papilloma or any of the malignant lesions studied showed evidence for the presence of papillomavirus antigen. There is currently only suggestive evidence for the oncogenic potential of human papillomavirus in the head and neck.

Antigens, Viral↗
PubMed1985

Bovine papillomavirus type 1 monoclonal antibodies.

Bovine papillomavirus type 1 (BPV-1) and type 2 (BPV-2) are the etiologic agents of fibropapillomas in cattle. Polyclonal antisera produced against BPV-1 structural antigens are cross-reactive with BPV-2. In this study BPV-1 type-specific monoclonal antibodies were produced that were not reactive with BPV-2. These monoclonal antibodies could be used for identification of BPV-1 structural antigens in acetone-fixed, frozen sections by immunofluorescence and Formalin-fixed, paraffin-embedded sections by immunoperoxidase techniques. In addition, these antibodies could be used for identification and purification of BPV-1 virions by immune electron microscopy and immunoadsorption techniques, respectively.

Antibodies, Monoclonal↗
PubMed1984

Papillomavirus infection and squamous neoplasia of the cervix.

In the past, the lack of a tissue culture system or an animal model suitable for inducing HPV lesions precluded the study of the role of PV in human disease. The development of a genus-specific cross reacting PV antiserum and molecular hybridization techniques now enables pathologists and molecular virologists to assay tissues for the presence of PV structural antigens and DNA sequences using highly specific and sensitive PV probes. The data that has been generated with these new research tools has far reaching implications. For example, the multifocality of squamous carcinoma of the vulva, vagina and cervix together with their similar histology, epidemiology and relationship to precursor lesions suggests that all of these neoplasms as well as related tumors in males may be caused by HPV. Since the immunoperoxidase technique using the PV antiserum can be performed on formalin-fixed paraffin-embedded tissue, systematic evaluation of these lesions can be done retrospectively. After identifying PV-associated lesions by the immunocytochemical method, prospective studies can be undertaken utilizing molecular hybridization in an effort to detect PV-DNA sequences and thereby to more clearly define the role of HPV in squamous neoplasia of the female genital tract.

Animals↗
PubMed1984

Papillomavirus infection of the cervix. III: Relationship of the presence of viral structural proteins to the expression of involucrin.

Forty-two cervical biopsies with cervical intraepithelial neoplasia were compared with respect to the expression of human papillomavirus (HPV) structural proteins and the expression of the cellular structural protein involucrin, a marker of suprabasal squamous differentiation. HPV structural protein and involucrin expression displayed an inverse correlation with the severity of dysplasia. Both of these proteins were detected in 11 of 28 cases (39%) of mild and moderate dysplasia, but in only two of 14 (14%) cases of severe dysplasia. This difference was statistically significant (p less than 0.001). The presence of HPV was also associated with expression of involucrin in the full thickness of the epithelium, including the basal layer, and an altered staining pattern in the more superficial cells, particularly the koilocytotic cells. These findings support the hypothesis that squamous differentiation is required for the expression of viral structural proteins and that HPV infection begins in the basal epithelium. The study also demonstrates the utility of involucrin staining in differentiating virus-induced cytologic atypia from true neoplasia.

Adult↗