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Biomedical subjects

A B Jenson

Publications and source records attributed to A B Jenson.

At least 19 recordsLinked to original sources
PubMed1992

HPV-1 L1 protein expressed in cos cells displays conformational epitopes found on intact virions.

Seven polyclonal and monoclonal antibodies were characterized for their ability to react specifically with either conformational or nonconformational epitopes of the HPV-1 virion. Using these antibodies, it was shown that the HPV-1 L1 protein (when expressed by an SV40 vector in cos cells) displayed conformational epitopes characteristic of intact viral particles. In addition, the L1 capsid protein was translocated normally into cell nuclei, was of appropriate size (57 kDa), and could be isolated in native form by immunoprecipitation techniques. Most importantly, the screening of expressed papillomavirus capsid proteins for reactivity with conformation-dependent antibodies represents a new, general methodology for ensuring that such proteins will be suitable for use in vaccine development or in the serologic detection/typing of human papillomavirus infections.

Animals↗
PubMed1992

Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types.

During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.

Blotting, Southern↗
PubMed1991

Comparison of neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts.

BPV-1 induces focus formation in murine C127 cells and fibropapillomas in bovine fetal skin xenografts. In this study, we compared the specificity of neutralization of BPV-1 in both assay systems, using sera and monoclonal antibodies (MAbs) selected to define neutralizing epitopes. Sera from rabbits and cattle, inoculated with intact BPV-1 or PBV-2 virions, neutralize BPV-1 infectivity in both C127 cells and xenografts. Selected human sera and murine MAbs that react with intact BPV-1 particles, serum of a rabbit immunized with denatured BPV-1 particles, and sera from calves vaccinated with a recombinant LI fusion protein did not neutralize BPV-1 infection in either system. It was concluded that neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts by hyperimmune sera is specific and concordant for both assay systems, and involves conformational BPV-1 capsid epitopes.

Animals↗
PubMed1991

Should cervical cytologic testing be augmented by cervicography or human papillomavirus deoxyribonucleic acid detection?

Criticism of the Papanicolaou smear in the lay press and recent federal legislation regulating cytology laboratories indicate a need to reappraise cervical cancer screening programs. This study directly compares three potential screening tests, used alone or in combination. A total of 1012 women aged 18 to 35 years were screened by cytologic testing, cervicography, and hybridization for human papillomavirus deoxyribonucleic acid, with discrepancies being referred by the last two authors. After findings from the entire lower genital tract were combined, 116 women (11.5%) showed definite clinical abnormalities (either exophytic vulvovaginal condylomas or cervical squamous intraepithelial lesions). Another 72 (7.2%) had positive Southern blot hybridizations without accompanying viral expression, yielding a cumulative frequency for established disease or latent infection of 18.6%. When associated vulvovaginal condylomas are disregarded, final groupings with regard to cervical pathologic classification were: 23 high-grade and 71 low-grade squamous intraepithelial lesions, 164 cases of equivocal atypia (34 of which had detectable human papillomavirus deoxyribonucleic acid), and 754 cases with negative results (38 of which had detectable human papillomavirus deoxyribonucleic acid). Cervical screening tests were compared principally by plotting increasingly liberal recall criteria onto receiver operating characteristic curves (i.e., graphs of true-positive results on the Y axis versus false-positive results on the X axis). Used individually, each screening test was valid, but none was substantially better than the others. No matter how liberal the recall criteria, no single test was able to detect all of the 23 definite precursors in this sample. Applying conventional recall criteria (i.e., high- or low-grade lesion suspected), cytologic testing alone detected 12 high-grade squamous intraepithelial lesions (52.2%), at a cost of having to perform colposcopy in 8.7% of the sample. Combining all three tests and setting the end point as just a high-positive result by at least one test, 19 high-grade squamous intraepithelial lesions (83%) were detected, with a recall of 7%. Optimal test performance (96% sensitivity, 4% recall) would have been attained by recalling all patients with high-grade cytologic results or positive cervicography results, plus any patients with low-grade morphologic atypia in which hybridization detected an oncogenic human papillomavirus type. Our conclusions are as follows: (1) Cytologic detection rates are markedly improved by a second or third test; (2) increased screening costs could be offset by not recalling patients with minor lesions with no apparent potential for progression.

Adolescent↗
PubMed1991

Identification of linear epitopes of the BPV-1 L1 protein recognized by sera of infected or immunized animals.

Sera from cattle that had been inoculated with BPV-1 virions or with recombinant L1 proteins and serum from a rabbit that had been immunized with SDS-denatured virions were evaluated for their reactivity with 466 overlapping synthetic peptides corresponding to 95% of the BPV-1 L1 protein. The late serological response of cattle to both intact virions and recombinant L1 proteins exhibited a similar profile of reactivity with approximately 70% (7 of 10) of L1 antigenic sites. However, the L1 serological response of the rabbit to SDS-denatured virions exhibited a significant difference from bovine serum antibodies in the profile of epitopes recognized, including a relative lack of response to major bovine epitopes located between L1 amino acids (AAs) 300-400. Importantly, only the sera from animals inoculated/immunized with intact virions was capable of neutralizing BPV-1 infectivity of murine C127 cells, suggesting that nonlinear epitopes are important for papillomavirus neutralization.

Amino Acids↗
PubMed1991

Tissue effects of and host response to human papillomavirus infection.

Human papillomaviruses are a heterogeneous group of DNA tumor viruses associated with hyperplastic (warts, condylomata), 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. 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 condylomata 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.

Cervix Uteri↗
PubMed1991

Human papillomavirus infection and neoplasia. Speculations for the future.

Human papillomavirus infections of the skin and anogenital tract are common. The association of these viruses with neoplasia, particularly of the anogenital tract, 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% of cancer deaths in women worldwide are associated with HPV. Thus, use of an effective vaccine would relieve considerable human suffering. Until the host immune response to HPV infection is better defined, however, much of the effort dedicated to developing a vaccine may be futile.

Antibodies, Viral↗
PubMed1990

The use of in situ hybridization to show human papillomavirus deoxyribonucleic acid in metastatic cancer cells within lymph nodes.

Southern blot hybridization has been used to identify human papillomavirus types in both primary tumors and lymph node metastases. However, this technique requires fresh-frozen tissue and is incapable of localizing deoxyribonucleic acid sequences to specific cell types in the tumor sample. In contrast, in situ hybridization precisely locates viral sequences within tumor cells while preserving cellular architecture. Further, in situ hybridization requires only small samples of formalin-fixed, paraffin-embedded tissues. Five lymph nodes (from four patients) containing metastatic cervical squamous tumor cells (identified with hematoxylin and eosinophil staining) were analyzed with in situ hybridization techniques with human papillomavirus type 16 deoxyribonucleic acid probes labeled with sulfur 35. The primary cervical cancer from all four patients had been shown to contain human papillomavirus type 16 sequences by Southern blot. Three specimens from two patients clearly showed the presence of human papillomavirus type 16 sequences within the nuclei of metastatic tumor cells, whereas two specimens were nondiagnostic most likely as a result of the small volume of cancer relative to the size of the lymph node. This information indicates that it is the tumor cells themselves that contain viral deoxyribonucleic acid and provides additional evidence linking human papillomavirus with cervical carcinogenesis.

Autoradiography↗
PubMed1990

Rapid dysplastic transformation of human genital cells by human papillomavirus type 18.

This study delineates differences in biologic activity between human papillomavirus (HPV) types 16 and 18. Human cervical and foreskin epithelial cells were cultured and transfected with recombinant HPV-16 and -18 DNA, resulting in immortalized cell lines. Normal epithelial cells as well as HPV-16 and -18 immortalized cells of both early passages (less than 40 population doublings) and late passages (greater than 180 population doublings) were transplanted in athymic mice. Normal squamous cells formed well-stratified epithelium, while HPV immortalized cells developed either normal-appearing epithelium or typical dysplastic changes. Dysplastic changes were seen in none of the 13 grafts with early-passage HPV-16 cell lines, while 9 of 14 grafts with early-passage HPV-18 cell lines developed dysplasias (P less than 0.0004). These results support previous clinical observations suggesting that HPV-18 may be associated with a more aggressive and rapidly progressive form of cervical neoplasia.

Cell Transformation, Viral↗
PubMed1990

Distribution and specific identification of papillomavirus major capsid protein epitopes by immunocytochemistry and epitope scanning of synthetic peptides.

Monoclonal (MAbs) and polyclonal antibodies were produced against the major capsid protein of detergent-disrupted, purified bovine papillomavirus type 1 (BPV-1). The precise locations of the corresponding epitopes were identified by the reactivity of MAbs and selected polyclonal antibodies with synthetic, overlapping, hexameric peptides corresponding with 95% of the BPV-1 major capsid protein. The topography of these epitopes was determined by reactivity of antibodies with intact (conformational and nonconformational surface epitopes) and disrupted (external or internal nonconformational epitopes) BPV-1 virions. The distribution of epitopes in various papillomaviruses of 13 different species was determined by reactivity of the MAbs and polyclonal sera with productively infected, formalin-fixed papillomas, fibropapillomas, and fibromas. Epitope scanning, using MAbs and polyclonal antisera, resulted in the precise location of BPV-1 hexameric epitopes that could be correlated with their topography on the capsid and distribution in papillomatous lesions of various species.

Animals↗
PubMed1990

Bovine serological response to a recombinant BPV-1 major capsid protein vaccine.

Four of five groups of Holestine by Angus calves (5 calves/group) were immunized with different formulations of a recombinant BPV-1 DNA vaccine using a BPV-1 major capsid:B-galactosidase fusion protein as the immunogen. Group 5 was not vaccinated. Vaccinated calves received the vaccine on days 0 and 21 of the trial, and calves from all five groups were challenged intradermally with 10(10) BPV-1 particles at each of two different sites on day 56. All calves were bled on days 3, 24, 55, 77, and 104 of the trial, and the sera were tested for reactivity with intact and disrupted BPV-1 particles by ELISA. At the time of challenge with BPV-1 virions (day 56), 19 of 20 vaccinated calves were seropositive for disrupted BPV-1 particles; sera from 3 of 20 calves reacted with intact BPV-1 virions. By day 77, 11 of 19 vaccinated calves had developed antibody titers to intact BPV-1 virions; only 1 calf in group 5 developed antibodies (transiently) against BPV-1 capsid epitopes. After challenge, 24 of 25 calves from the five groups developed intradermal fibromas, the biological end point of this study. Fibromas appeared to increase in size in group 5 (unvaccinated, inoculated controls), whereas most tumors from the four vaccinated groups (1-4) stabilized or decreased in size. Although the calves developed fibromas, 90% of calves (in groups 1-4) developed antibodies against disrupted BPV-1 capsid proteins whereas 58% developed antibodies that reacted with intact virions. The immunologic response of vaccinated calves to intact and disrupted BPV-1 particles appeared to be determined in large part by the various formulations of the vaccine, particularly the adjuvant.

Animals↗
PubMed1989

Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease.

A formalin-inactivated respiratory syncytial virus (RSV) vaccine tested 22 years ago failed to protect infant vaccinees against RSV infection or disease. Instead, lower respiratory tract disease was enhanced during subsequent infection by RSV. Enhancement of pulmonary pathology is also observed when cotton rats are immunized with formalin-inactivated RSV and subsequently infected with this virus. A major question that must be addressed for each new paramyxovirus vaccine is whether the immunogen possesses the capacity to potentiate disease. In the present study, we evaluated a newly developed purified F and G glycoprotein vaccine over a wide dosage range for immunogenicity, efficacy and capacity to potentiate pulmonary pathology in cotton rats. In addition, a formalin-inactivated RSV vaccine, which served as a positive control for enhancement of pulmonary pathology, was evaluated simultaneously. The results of these comparisons indicate that the purified F and G glycoprotein vaccine was highly immunogenic and was efficacious even in animals that developed low levels of serum-neutralizing antibodies. Furthermore, the F and G vaccine did not induce potentiation of pulmonary pathology. In contrast, formalin-inactivated RSV potentiated RSV pulmonary histopathology, but there was a sparing of potentiation at high and low doses. Both the formalin-inactivated RSV and purified F and G preparations induced a high level of serum antibodies capable of binding to purified F and G glycoproteins but both sets of antibodies had significantly reduced neutralizing activity. These results are encouraging because they suggest that purified paramyxovirus glycoproteins might be used safely as a vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Human papillomavirus typing of penile condyloma.

Infection with human papillomavirus has been identified as a significant risk factor for the development of cervical neoplasia. Knowledge of the characteristics of infecting human papillomavirus in male patients is lacking. We studied 37 men who presented with genital condyloma to identify the clinical appearance of the lesion, histological features and human papillomavirus type as determined by deoxyribonucleic acid molecular hybridization analysis. Of the patients 32 had penile shaft condyloma: 23 noticed the lesion themselves and 9 presented because the partner had condyloma. An adequate amount of deoxyribonucleic acid was available for analysis in 26 men. Lesions were caused by human papillomavirus types 6, 11 and 31, and uncharacterized types. Five patients had penile shaft and urethral condyloma. In 4 patients infection was caused by more than 1 type or subtype. Neither clinical nor histological features could reliably predict the infecting human papillomavirus type.

Adult↗
PubMed1989

Correlation of the histologic appearance of intraepithelial neoplasia of the cervix with human papillomavirus types. Emphasis on low grade lesions including so-called flat condyloma.

Cervical condylomas and intraepithelial neoplasia (CIN) were correlated with human papillomavirus (HPV) types and analyzed for the presence of abnormal mitotic figures. Colposcopically directed cervical biopsies were divided in half and processed for routine microscopy and Southern blot hybridization. Of 83 specimens from 71 patients, 70 (84%) contained HPV-DNA sequences. The HPV distribution was as follows: HPV 16 in 6/25 flat condylomas (FC), 2/8 CIN I, 8/18 CIN II, 12/14 CIN III; HPV 18 in 1/25 FC; HPV 31 in 3/25 FC, 3/18 CIN II, and 1/14 CIN III; HPV 6/11 in 12/18 exophytic condylomas (EC), 5/25 FC, 2/8 CIN I, and 3/18 CIN II. Uncharacterized HPVs were identified in 4/18 EC, 5/25 FC, 2/8 CIN I, and 1/18 CIN II. A similar heterogeneous distribution of HPV types was found in flat condylomas and CIN I. A more homogeneous distribution was noted in the exophytic condylomas and high grade CIN lesions, with HPV 6/11 found in the former and predominantly HPV 16 in the latter. Abnormal mitotic figures were predominantly seen in the high grade CIN lesions. Based on our findings, we would recommend that the term flat condyloma be abandoned and that low grade flat lesions of the cervix be graded according to CIN criteria.

Blotting, Southern↗
PubMed1989

Identification of L2 open reading frame gene products of bovine papillomavirus type 1 using monoclonal antibodies.

Four hybridoma cell lines producing monoclonal antibodies (MAbs) to bovine papillomavirus type 1 (BPV-1) L2 open reading frame (ORF) gene products have been established from mice immunized with a BPV-1 L2-beta-galactosidase fusion protein. Hybridomas were selected and cloned (from over 700 hybridomas) on the basis of specific reactivity of supernatant fluids with BPV-1 L2 epitopes on disrupted BPV-1 particles and L2-beta-galactosidase fusion proteins by ELISA and Western blotting, and with acetone-fixed frozen sections of BPV-1-induced fibropapillomas by immunofluorescence. These MAbs were not reactive with intact BPV-1 particles or BPV-1 L1-beta-galactosidase fusion proteins by ELISA or with beta-galactosidase by ELISA and Western blotting. The four MAbs detected viral structural proteins of Mr 76K, 68K and possibly 55K in purified BPV-1 preparations by Western blotting. Two of the four MAbs were cross-reactive with BPV-2-induced fibropapillomas. These findings suggest that (i) the BPV-1 L2 ORF encodes the minor capsid protein(s), (ii) the gene products of the BPV-1 L2 ORF have Mr values of 76K, 68K and possibly 55K, (iii) minor capsid epitopes are internal to the BPV-1 particle, and (iv) MAbs reactive with genetically engineered truncated BPV-1 L2 ORF gene products can distinguish between BPV-1 and BPV-2 productive infections.

Animals↗
PubMed1989

Comparison of human papillomavirus type 1 serotyping by monoclonal antibodies with genotyping by in situ hybridization of plantar warts.

Thirty plantar warts were analyzed for the presence of HPV-1 type-specific and PV genus-specific capsid antigens by immunofluorescence (IF) using monoclonal and polyclonal antibodies and type-specific HPV-1 DNA employing in situ hybridization methods. Fifteen of 30 plantar warts were positive by IF for PV genus-specific structural viral antigens. Thirteen of the 15 productively infected plantar warts expressed intranuclear HPV-1 type-specific capsid antigens and viral DNA, which were detected in the same distribution in each individual wart. The 2 productively infected plantar warts that did not react with HPV-1 type-specific MoAbs did not react with HPV-1 type-specific DNA by in situ hybridization. Thus, serotyping of HPV-1 capsid antigens by monoclonal antibodies is concordant with genotyping of HPV-1 viral DNA by in situ hybridization in productively infected plantar warts.

Antibodies, Monoclonal↗
PubMed1988

Identification of the bovine papillomavirus L1 gene product using monoclonal antibodies.

Monoclonal antibodies (MoAbs) produced against SDS-disrupted bovine papillomavirus type 1 (BPV-1) were used to identify the product of the L1 open reading frame (ORF) of BPV-1. MoAbs were tested in ELISA with purified BPV-1 major capsid protein, fusion proteins from two constructions of the BPV-1 L1 ORF, and one construction of the L2 ORF. All MoAbs were reactive with purified MCP and both L1 fusion proteins. No MoAbs were identified that were reactive with the L2 fusion protein. Polyclonal antisera raised against SDS-disrupted BPV-1 were immunoreactive with both L1 and the L2 fusion proteins. These data show that the L1 ORF of BPV-1 encodes, at least in part, the MCP of BPV-1. Further, it has been shown that the L1 encodes the papillomavirus (PV) genus-specific epitope, PV broadly cross-reactive epitope, BPV minimally cross-reactive epitope, and a BPV-1 type-specific epitope.

Antibodies, Monoclonal↗