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Biomedical subjects

A B Jenson

Publications and source records attributed to A B Jenson.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1988

Possible prognostic significance of human papillomavirus type in cervical cancer.

While several different human papillomaviruses (HPV) have been associated with cancer of the cervix, it is yet to be determined if specific HPV types have clinical or prognostic significance. To address this question, 30 cases of invasive carcinoma (squamous carcinoma, adenosquamous carcinoma, and adenocarcinoma) with HPV DNA sequences detectable in the tissue were analyzed. HPV type was determined by Southern blot DNA hybridization. Clinical information was obtained by chart review, and all biopsy and surgical specimens were reviewed microscopically without knowledge of HPV type. HPV 16 was detected in 14 cases, HPV 18 in 6, and HPV 31 in 2. In eight samples there were distinctly different, but as yet uncharacterized, HPV DNAs. Of the factors evaluated, tumor grade was found to have a statistically significant relationship to HPV type. Eighty-three percent of HPV 18-associated tumors were grade 3 tumors (5 of 6) as compared to only 7% of HPV 16-associated tumors (1 of 14) (P = 0.002). Age at diagnosis and nodal status in relation to HPV type exhibited a trend but were not statistically significant. The mean age of the HPV 18 group was 37 years, compared to 49 years for the HPV 16 group. Similarly, among Stage IB cancers, nodal involvement was associated with 60% of HPV 18 cases (3 of 5) as compared with 36% of HPV 16 cases (4 of 11). These observations suggest that HPV 18 may be associated with a more aggressive form of cervical cancer than other HPV types.

Adenocarcinoma↗
PubMed1988

Analysis of individual human papillomavirus types in cervical neoplasia: a possible role for type 18 in rapid progression.

Histologic and molecular analyses of 214 cervical biopsy specimens were performed to test the hypothesis that certain individual human papillomavirus types that are usually grouped together are differentially distributed in various grades of cervical intraepithelial neoplasia and invasive squamous carcinoma. Specifically, types 16 and 18, which are commonly grouped together, were analyzed separately and compared. Biopsies obtained from three different geographic sites in the United States and Brazil were analyzed by Southern blot hybridization and correlated with the histologic diagnosis from the same tissue sample. There was a highly significant correlation between papillomavirus type and histologic grade comparing all grades of cervical intraepithelial neoplasia with invasive cancer (p less than 0.001). Of particular interest was the striking deficit of type 18 in intraepithelial neoplasia (3%) as compared with invasive carcinoma (22%; p less than 0.001). In contrast, there was no significant difference in the distribution of type 16 in intraepithelial neoplasia (37%) as compared with invasive carcinoma (41%). The deficit of type 18 in intraepithelial neoplasia compared with invasive carcinoma could represent a rapid transit time through the precursor stage. Human papillomavirus type 18 may therefore play a role in the development of rapidly progressive cervical cancer.

Brazil↗
PubMed1987

Interferon-alpha therapy of recurrent conjunctival papillomas.

Five patients with multiple, recurrent conjunctival papillomas underwent surgical excision of their tumor and then received interferon alpha-N1, 5 X 10(6) units/m2 (5 Mu/m2), intramuscularly daily for one month. A similar dose was given two to three times per week for the next six months and tapered off or discontinued thereafter. The follow-up period varied from one to four years. Two patients have had no recurrence of tumor. The other three patients have had recurrences of lesser severity upon tapering or discontinuing the interferon, and repeat surgical or laser excision of these lesions has been performed. The presence of koilocytosis and human papillomavirus type 11a DNA sequences was noted in all specimens large enough to examine, whereas papillomavirus structural antigens were detected in only two of five specimens. A regimen of interferon therapy appears to be tumor suppressive, but not curative.

Adult↗
PubMed1987

Natural history of human papillomavirus infection of the anogenital tract.

A number of viruses, most notably herpes virus type 2, have been suggested as etiological agents of cervical neoplasia. Recent studies with human papillomaviruses, however, have demonstrated a remarkable association of a subgroup of these viruses with about 90% of benign, preinvasive and invasive lesions of the cervix and anogenital tract. The oncogenic potential of papillomaviruses has been demonstrated both in laboratory animals and in cultured cells. Furthermore, susceptibility to certain human papillomaviruses has been associated with a recessive genetic defect that results in squamous cell carcinoma of the skin. The human papillomaviruses are difficult to study, however, because of the lack of an animal model, difficulty in developing a tissue culture system permissive for their replication, and a lack of understanding of their biology. Current understanding of the natural history of anogenital neoplasia may provide insights into the mechanisms the host uses to cope with potentially oncogenic human papillomaviruses.

Cell Transformation, Viral↗