Multiple viruses in diabetes mellitus.
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Animals↗
Biomedical subjects
A B Jenson
Publications and source records attributed to A B Jenson.
Morphological effects of inorganic salts, chloramine-T, and citric acid on subgingival plaque bacteria.
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Bacteria↗
Detection of human papillomavirus DNA sequences in conjunctival papilloma.
Two histologically proven conjunctival papillomas (one from a 33-month-old boy and the other from a 28-year-old woman) were examined for the presence of papillomavirus by DNA molecular hybridization. The first case, a recurrent tumor known to be positive for papillomavirus structural antigen, demonstrated human papillomavirus DNA sequences that cross-hybridized to a human papillomavirus type 11 DNA probe. The second case, an initial tumor, which was negative for papillomavirus structural antigen, demonstrated no viral DNA sequences by hybridization.
Adult↗
Papillomavirus in human conjunctival papillomas.
Forty-one human conjunctival papillomas were histopathologically examined for koilocytosis and papillomavirus common antigen with a peroxidase-antiperoxidase technique immunospecific for genus-specific papillomavirus antigen. Koilocytotic cells, typically found in other papillomavirus-induced tumors, were present in 24 of the 41 specimens. Two of the 41 specimens were positive for viral antigen. The positive reactions were intranuclear within the superficial layers of the epithelium.
Antigens, Viral↗
Papillomavirus structural antigens in condyloma acuminatum of the male urethra.
Current developments in the technology of viral identification have rekindled interest in the relationship of human papillomaviruses, condylomata acuminata and neoplasia. Although important observations are being reported in the female genital system the association of human papillomavirus and mucosal condylomata in male patients has not been well documented. Using the horseradish peroxidase technique and antisera to papillomaviruses, viral antigens were identified in 62 per cent of male patients with urethral condylomata acuminata. The implications of this relationship are discussed briefly.
Adult↗
Human papillomavirus structural antigens in squamous papillomas of the male urethra.
Twenty-five squamous papillomas of the male urethra were examined for the presence of human papillomavirus (HPV) whole (structural) virion antigens by a peroxidase-antiperoxidase technique having immunospecificity against genus-specific (common) antigens of the papillomavirus genus. Eleven of 25 (44 per cent) lesions were positive for HPV. The positive reaction was invariably intranuclear in the superficial epithelium. Evidence suggests that these papillomas arise by HPV infection of metaplastic squamous epithelium and not transitional epithelium. This study shows that at least some squamous papillomas of the male urethra are associated with HPV infections and suggest that this lesion may play an important role in venereally transmitted diseases such as cervical dysplasia and condylomas of the vulva and anus.
Adolescent↗
Human papillomavirus: detection of viral DNA sequences and evidence for molecular heterogeneity in metaplasias and dysplasias of the uterine cervix.
Colposcopic-directed biopsies of the uterine cervix from 22 patients were analyzed for the presence of human papillomavirus (HPV) DNA and structural antigens. 11 of the biopsies were classified microscopically as mild dysplasia, 3 as moderate dysplasia, 1 as severe dysplasia, and 7 as squamous metaplasia. Nonstringent hybridization with a bovine papillomavirus type 1 DNA probe and immunocytochemical analysis with an antiserum against papillomavirus genus-specific structural antigens were performed on all specimens. Of the 11 mild dysplasias, both HPV DNA and structural antigens were detected in 5, only HPV antigens in 3, only HPV DNA in 1, and neither DNA nor structural antigens in 2. Both HPV DNA and structural antigens were present in the 3 cases of moderate dysplasia. Only HPV DNA sequences were detected in the single case of severe dysplasia. HPV DNA was detected in 2 cases of squamous metaplasia. The 5 remaining cervical biopsies showing squamous metaplasia, tissue from 3 placentas, and 6 cervical carcinomas were negative for HPV DNA and structural antigens. Restriction enzyme cleavage patterns of HPV DNA in the dysplasias suggested that there are multiple virus types or subtypes associated with cervical dysplasia. Stringent hybridization with a HPV type 11 (HPV-11) probe revealed that only 1 of 10 dysplasias contained sequences with homology to the probe. Of the remaining 9 dysplasias, 5 contained HPV sequences detected under nonstringent hybridization. 2 of 4 squamous metaplasias contained viral sequences which hybridized to the HPV-11 probe as well as 1 of 6 cervical carcinomas.
Adolescent↗
Papillomavirus infection of the cervix. II. Relationship to intraepithelial neoplasia based on the presence of specific viral structural proteins.
Three hundred twenty-two cases of cervical dysplasia (mild, moderate, and severe) and carcinoma in situ (CIS) were examined for the presence of papillomavirus structural antigens with a peroxidase-antiperoxidase method on formalin-fixed, paraffin-embedded tissue. The primary antiserum, prepared from purified, detergent-disrupted bovine papillomavirus type 1 virions, is broadly reactive against the genus-specific (common) antigen(s) of the papillomaviruses. Using the peroxidase-antiperoxidase technique on cervical tissue obtained from biopsy, conization and hysterectomy specimens, papillomavirus structural proteins were identified in association with mild dysplasia in 65 of 152 (43%) cases, with moderate dysplasia in 12 of 82 (15%) cases, with severe dysplasia in eight of 47 (17%) cases, and with CIS in four of 41 (10%) cases. Papillomavirus antigens were found directly within the lesion in all the cases of mild and moderate dysplasia but in only two instances of severe dysplasia and in none of the examples of CIS. In the remaining 10 cases of severe dysplasia and CIS associated with the presence of papillomavirus antigens, cells containing papillomavirus structural proteins were present in areas of moderate dysplasia immediately adjacent to the high-grade lesions in seven instances and in areas of mild or moderate dysplasia not directly in contact with the high-grade lesions in three. Among the 12 high-grade lesions associated with the presence of papillomavirus antigens, a morphologic transition from areas of moderate dysplasia containing papillomavirus antigens to the areas of severe dysplasia and CIS was present in five instances. The results of this study, therefore, provide direct evidence demonstrating the relationship of papillomavirus to intraepithelial cervical neoplasia ranging from mild dysplasia to severe dysplasia and CIS.
Animals↗
Papillomavirus infection of the cervix I. Correlation of histology with viral structural antigens and DNA sequences.
Eight cervical biopsies showing mild dysplasia and one showing squamous metaplasia were studied for the presence of papillomavirus (PV) antigens using an immunoperoxidase method having immunospecificity against the genus-specific (common) structural antigen(s) and for PV-specific DNA sequences by molecular hybridization under nonstrigent conditions. Of the eight cases showing mild dysplasia, both PV antigens and PV DNA sequences were detected in five, PV antigens only in one, and PV DNA sequences only in one; viral antigens and DNA sequences were not detected in the remaining lesion. A characteristic cellular atypia (PV-induced atypia) was present in the superficial and intermediate layers of the epithelium in the six cases positive for viral antigens, and a proliferation of basal and parabasal cells (PV-induced hyperplasia) occurred in five of these. PV structural antigens were localized within nuclei of some of the cells displaying atypia but not in the proliferating cells. The PV-specific DNA sequences in all six cases had the properties of unintegrated PV-DNA. In view of the demonstration of both PV antigens and DNA sequences in this distinctive lesion (PV-induced atypia and/or hyperplasia), traditionally regarded as a form of dysplasia, it is proposed that this lesion be referred to as "papillomavirus infection of the cervix."
Animals↗
Frequency and distribution of papillomavirus structural antigens in verrucae, multiple papillomas, and condylomata of the oral cavity.
Sixty-seven proliferous squamous epithelial lesions of the oral cavity were examined for the presence of human papillomavirus whole (structural) virion antigens by a peroxidase-antiperoxidase technique having immunospecificity against genus-specific (common) antigens of the papillomaviruses. A positive reaction for papillomavirus genus specific antigens was found in 18 of 29 verrucae, 2 of 5 multiple papillomas, and 3 of 5 condylomata; common antigens were not detected in 28 keratoacanthomas. The positive reaction was invariably intranuclear in cells having a focal or diffuse distribution in the superficial epithelium. This study shows that a variety of squamous epithelial lesions of the mucosa are associated with human papillomaviruses and suggests that these viruses may play an important role in the etiology of some cases of squamous hyperplasia of the oral cavity.
Adolescent↗
Human papillomavirus. Frequency and distribution in plantar and common warts.
Fifty-nine (24 plantar, 35 common) warts surgically excised from 44 patients (15 female, 29 male), 18 to 32 years old, were examined by electron microscopy (EM) for papillomavirus particles and by fluorescent antibody (FA) and peroxidase-antiperoxidase (PAP) tests for human papillomavirus type 1 (HPV-1)-specific antigens and papillomavirus genus-specific (common) antigens. Fifty per cent of plantar warts and 52 per cent of common warts were positive for HPV by EM. When examined by FA and PAP for genus-specific antigens, 58 per cent of plantar warts and 68 per cent of common warts were positive. Fifty per cent of plantar warts and 11 per cent of common warts were caused by HPV-1 as determined by reactivity with HPV-1 type-specific antiserum. All warts positive by EM were positive by FA and PAP. Sampling error accounted for warts positive by FA and PAP but not by EM. Forty-two per cent of plantar warts and 31 per cent of common warts were negative by both EM and FA and PAP. The warts caused by HPV-1 contained more virus and were more clinically aggressive than warts caused by other HPV. This study shows that the results obtained by the PAP technique using papillomavirus genus- and type-specific antisera on formalin-fixed, paraffin-embedded tissue available to the diagnostic pathologist are concordant with the results obtained by methodology usually available only to the experimental pathologist.
Adolescent↗
Etiopathology of diabetes mellitus.
Available evidence suggests a multifactorial etiology (especially genetic, immunologic and environmental) for IDDM. Genetic factors appear to be related to certain HLA types, which in turn might be associated with abnormal immunologic responses directed against pancreatic beta cells. Environmental agents, particularly diabetogenic chemicals or viruses, or both, might actually trigger an autoimmune response leading to cumulative damage to beta cells and development of diabetes mellitus in genetically predisposed persons. Much attention is being directed toward the elucidation of the immunologic and environmental factors in IDDM. Islet cell antibodies (either against the cytoplasmic components (ICA) or surface determinants (ICSA)) are found in 90% of IDDM and inflammation of the islets (insulitis) consistent with either a viral infection and/or autoimmune response can be found at autopsy, particularly in children. Virus-induced diabetes has been accepted as one of the animal models for the study of IDDM in humans. Moreover, viruses diabetogenic for the animal model have been recovered from persons with IDDM. It has also been observed that viruses may damage beta cells during fatal infections. The identification of possible environmental triggers such as viruses that damage human beta cells in vivo and the elucidation of the events that follow the infection may represent one of the first steps toward eventual prevention (e.g., vaccination) or therapeutic intervention (e.g., immunosuppression) of IDDM.
Animals↗
Immunoperoxidase localization of papillomavirus antigens in cervical dysplasia and vulvar condylomas.
Biopsies of 50 cases of cervical dysplasia (46 mild and 4 moderate) and 40 cases of vulvar condyloma acuminata (genital warts) were screened for the presence of papillomavirus antigens by means of a peroxidase-antiperoxidase method having immunospecificity against the genus-specific (common) antigen(s) of the papillomaviruses. With the use of this technique, on formalin-fixed, paraffin-embedded tissue, papillomavirus antigens were detected in cells with cytologic and histologic features of wart virus infection (so-called koilocytotic atypia). Cells showing a positive reaction for papillomavirus antigens were identified in 24 of 50 (48%) cases of cervical dysplasia and in 20 of 40 (50%) cases of vulvar condyloma. The results of this study provide specific confirmation of the presence of papillomavirus antigens in cervical dysplasia and suggest that the papillomavirus may be an important factor in the etiology of this disease.
Antigens, Viral↗
Virus-induced diabetes mellitus. XX. Polyendocrinopathy and autoimmunity.
Mice infected with reovirus type 1 developed transient diabetes and a runting syndrome. The diabetes was characterized by hyperglycemia, abnormal glucose tolerance tests, and hypoinsulinemia. Inflammatory cells and viral antigens were found in the islets of Langerhans, and virus particles were seen in alpha, beta, and delta cells. The runting syndrome consisted of retarded growth, oily hair, alopecia, and steatorrhea. Inflammatory cells and viral antigens were found in the anterior, but not posterior pituitary. Electron microscopy revealed virus particles in growth hormone (GH)-producing cells and radioimmunoassay showed that the concentration of GH in the blood was decreased. Examination of sera from infected mice revealed autoantibodies that, by immunofluorescence, reacted with cytoplasmic antigens in the islets of Langerhans, anterior pituitary, and gastric mucosa of uninfected mice. Absorption studies and enzyme-linked immunosorbent assays designed to identify the reactive antigens showed that some of the autoantibodies were directed against insulin and others against GH. Reovirus type 3, in contrast to reovirus type 1, did not induce autoantibodies to GH. By use of recombinant viruses, the segment of the reovirus genome responsible for the induction of autoantibodies to GH was identified. Virus containing the S1 gene segment from reovirus type 1, which codes for the sigma 1 polypeptide (i.e., hemagglutinin), infected cells in the anterior pituitary and induced autoantibodies to GH, whereas virus containing the S1 gene segment from reovirus type 3 failed to infect cells in the anterior pituitary and did not induce autoantibodies to GH. We conclude that reovirus type 1 infection can lead to polyendocrinopathy and autoimmunity and that the S1 gene segment is required for the induction of autoantibodies to GH.
Animals↗
Congenital rubella, insulitis, and diabetes mellitus in an infant.
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Diabetes Mellitus, Type 1↗
Infection of cultured human pancreatic B cells with reovirus type 3.
The capacity of reovirus type 3 to infect insulin-producing B cells was studied in human pancreatic cell cultures. Antibody to reovirus was labelled with fluorescein isothiocyanate and antibody to insulin was labelled with tetramethyl rhodamine isothiocyanate. By using a double-labelled immunofluorescent antibody technique, it was shown that only about 6% of the insulin-containing human B cells in culture became infected when inoculated with unpassaged reovirus type 3. However, by repeated passage of the virus in human pancreatic B cell cultures, the percentage of infected B cells increased to 27%, and the virus titre in cultures rose from 8.0 X 19(4) pfu/ml in the first passage, to 4.9 X 10(6) pfu/ml in the 5th passage. As measured by radioimmunoassay, the intracellular immunoreactive insulin began to decrease at 24 h after infection. This decrease roughly paralleled the increase in virus titre. In contrast, there was relatively little change in immunoreactive insulin in cultures inoculated with unpassaged reovirus type 3. These studies show that the ability of reovirus type 3 to infect human B cells is enhanced by serial passage in human pancreatic cell cultures and that the infection resulted in the destruction of B cells and release of insulin.
Cells, Cultured↗
Evidence for papillomavirus genus-specific antigens and DNA in laryngeal papilloma.
Four juvenile laryngeal papillomas (JLPs) were examined for papillomavirus genus-specific structural antigens and polynucleotide sequences employing reagents derived from bovine papillomavirus type 1 (BPV-1). Three of four JLPs contained intranuclear antigens in the granular layer of differentiating epithelial cells of formalin-fixed, paraffin-embedded papillomas assayed by the peroxidase-antiperoxidase reaction using an antiserum prepared against purified detergent-disrupted BPV-1. Examination of these JLPs for viral sequences indicated two tumor DNA preparations contained polynucleotide sequences which hybridized to an in vitro labeled BPV-1 DNA probe under nonstringent conditions. These sequences were detectable after gel electrophoresis and immobilization of restriction-endonuclease-digested JLP DNAs onto nitrocellulose membranes. Specific hybridization of probe to digested JLP DNA was visualized as bands in autoradiograms coincidental with open circular and linearized papillomavirus DNA. Hybridization was extensively reduced when JLP DNA preparations were prehybridized to an unlabeled papillomavirus DNA heterologous to the probe. These results provide direct evidence for the association of a papillomavirus in JLP.
Antigens, Viral↗
Squamous cell carcinoma arising in a linear epidermal nevus.
An isolated, pruritic lesion developed in the right breast of a 17-year-old girl during a period of four months. The lesion was well circumscribed, erythematous, indurated, and markedly hyperkeratotic in the center. The histologic diagnosis was well-differentiated squamous cell carcinoma arising in a linear epidermal nevus. The development of squamous cell carcinoma in a linear epidermal nevus is a rare event, previously reported only in long-standing, extensive lesions of middle-aged to elderly patients. This case seems to be unique in regard to the patient's young age, the short duration of the nevus, and the lack of identifiable predisposing factors.
Adolescent↗