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Biomedical subjects

K V Shah

Publications and source records attributed to K V Shah.

At least 145 records · Page 8Linked to original sources

Immunohistochemical and ultrastructural evidence of papilloma virus infection associated with in situ and microinvasive squamous cell carcinoma of the vulva.

Of 21 patients with predominantly intraepithelial carcinoma of the vulva, 14 had coexisting papilloma virus (PV)-related cytopathic changes in the neoplastic and non-neoplastic epithelial cells. A PV species-nonspecific internal capsid antigen (PV-Ag) was detected in 64% of the cases in a variable number of nuclei by avidin-biotin complex-immunoperoxidase tests. Intranuclear viral particles were identified in 44% of specimens by electron microscopy. The main clinicopathologic features were the gross appearance of multiple papillary growths or, less often, of giant condyloma, the young age of the patients (75% of whom were less than 40 years old), the association in 57% of the cases with simultaneous intraepithelial neoplasia of the cervix or perineal skin, and an incidence of recurrences in 28%. PV infection of the genital area recurred in 14% of the cases. Nodal metastases of squamous cell carcinoma were observed in two cases. The histopathologic features and the main characteristics in terms of natural history of this PV-associated neoplasia are very similar to so-called bowenoid carcinoma and different from those of verrucous carcinoma of the vulva, six cases of which were investigated for comparison. In the latter, the search for PV-Ag was consistently negative, the patients were much older, and metastatic nodal involvement was absent.

Adult↗

Histologic, nuclear DNA, and human papillomavirus studies of cervical condylomas.

Fifty-four cervical condylomatous lesions, with and without nuclear atypia, from 42 women, were studied with the Feulgen microspectrophotometric technique for nuclear DNA quantitation and an immunoperoxidase technique for human papillomavirus (HPV) antigen. All ordinary cervical condylomas (without atypia/dysplasia) had a diploid or polyploid nuclear DNA distribution; 61% had detectable HPV antigen. Among the cervical condylomas with atypia/dysplasia, 55% (17/31) had diploid or polyploid nuclear DNA pattern, and, of these, 59% (10/17) had demonstrable papillomavirus antigen. Fourteen (45%) were aneuploid lesions, 2 of which had a small number of cells with papillomavirus antigen (14%). These findings suggest that the majority of cervical condylomas are related to papillomavirus infection. That lesions with dysplasia, including high degrees of dysplasia, may also exhibit coexistence of papillomavirus infection suggests the possibility of an infectious etiology in the genesis of cervical squamous neoplasia.

Adolescent↗

Immunoperoxidase localization of papillomavirus antigen in cutaneous warts and bowenoid papulosis.

Using the immunoperoxidase technique and a broadly cross-reactive antiserum which detects infection with any papillomavirus, papillomavirus capsid antigen was demonstrated in 25 of 48 cutaneous papillomas and in two of 38 cutaneous dysplasias. Both positive dysplastic lesions were diagnosed on histopathologic examination as bowenoid papulosis. Antigen-positive cutaneous warts were scattered in all age categories and at all body sites. In addition, there was little variation in antigen expression by morphologic type of wart. Antigen was localized in the nucleus of superficial epithelial cells. The amount of staining was variable, with some warts showing large numbers of stained nuclei. In other warts only isolated cells stained. In both cases of bowenoid papulosis, small foci of positively stained cells were observed. The finding of papillomavirus antigen in two of 21 cases of bowenoid papulosis is suggestive of an etiologic relationship between this lesion and a papillomavirus. An examination of antigen-negative cases of bowenoid papulosis for a papillomavirus genome will be necessary to confirm these results.

Adolescent↗

Distribution of human papillomavirus antigen in cervicovaginal smears and cervical tissues.

An immunoperoxidase study, using the avidin-biotin complex method and a cross-reactive, antihuman papillomavirus (HPV) antiserum, was carried out on paired Papanicolaou-stained cervicovaginal smears and tissue sections from 45 cases of histologically diagnosed genital condyloma. There was a close correlation between the results of smears and cervical tissue sections. The smears were positive for intranuclear HPV antigen(s) in 67% of the cases and the tissues in 62% of the cases. Both cervical smears and tissues were positive in 53% of the cases. The combined detection rate (smears or tissues) was 76%. Only a small proportion of condylomatous cells in the smears displayed the HPV antigen. The antigen-positive cells were cytologically indistinguishable from antigen-negative cells. Antigen positivity correlated with increasing depth of condylomatous change in the tissues, with increasing numbers of condylomatous cells in the smears, and with decreasing severity of epithelial atypia. Immunologic staining of Papanicolaou-stained cervicovaginal smears for HPV provides a noninvasive technique for detection and long-term follow-up of genital papillomavirus infections without altering the biology of the lesion. This technique can be effectively utilized for both prospective and retrospective investigations.

Adult↗

Colposcopy in the diagnosis of papillomavirus infection of the uterine cervix.

Morphological criteria are described for the diagnosis of papillomavirus lesions at colposcopy. Using these criteria, evidence of cervical papillomavirus infection was found in 58 (29.0%) of 200 women referred for colposcopy because of an abnormal cytology report. Directed biopsies were obtained from 152 of these patients and histological changes suggestive of papillomavirus infection were found in 47 (30.9%); additional biopsy material from 139 was studied using an immunohistochemical technique and human papillomavirus antigen was demonstrated in 28 (20.1%). Comparison between the colposcopic results and those obtained by histology suggests that whereas it is not possible to make a distinction at colposcopy between lesions due to papillomavirus and those of cervical intraepithelial neoplasia, it is possible to identify those epithelial abnormalities that are most likely to be associated with a papillomavirus infection.

Animals↗

Pathogenesis of K papovavirus infection in athymic nude mice.

The fatal outcome of K virus infection in infant mice and cytoxan-treated adult mice is related to their inability to mount a prompt antibody response to the virus. Athymic nude mice infected with K virus exhibited no clinical illness and no detectable virus-specific immunoglobulin G (IgG) response, but they did exhibit a low level of virus-specific immunoglobulin M response. Transfer of spleen cells from K virus-primed nude mice to infected infant mice conferred complete protection against K virus-induced mortality. This protection was diminished by the depletion of B cells but not by the depletion of adherent cells from the primed spleen cells. B cell response is therefore important in the recovery of nude mice from K virus infection.

Animals↗

Serologic studies of papovavirus infections in pregnant women and renal transplant recipients.

Serologic studies were performed to determine if BKV and JCV are transmitted congenitally and to assess if the virus present in donor kidney contributes to virus activity in renal transplant recipients. Fourteen of 100 normal women showed antibody rise to BKV or JCV during pregnancy; in all instances, these were reactivation infections occurring in initially seropositive women. BKV-and JCV-specific antibodies of the IgM class were not detected in over 300 umbilical cord sera. Thus, there was no evidence of congenital transmission of BKV or JCV. BKV-seronegative renal transplant recipients who received kidneys from BKV-seropositive donors had a frequency of BKV infection which was about four times greater than that in BKV-seronegative recipients receiving kidneys from BKV-seronegative donors. These data suggest that BKV in donor kidney contributes to primary BKV infections in renal transplant recipients.

Animals↗

Detection of human papovaviruses BKV and JCV in urines by ELISA.

A double-antibody indirect ELISA using a chromogenic substrate and a single-antibody sandwich direct ELISA using chromogenic and fluorogenic substrates were developed for the detection of the human papovaviruses BKV and JCV. All three assays were comparable in their sensitivity. BKV was detected in urine from 12 of 63 (19%) highly immunocompromised patients and JCV in urine from 4 of 31 (12.9%) patients by the indirect method.

Antigens, Viral↗

Propagation and primary isolation of JCV and BKV in urinary epithelial cell cultures.

Human papovavirus JC, previously passaged in amnion cells, produced a cytopathic effect in urine-derived epithelial cells, and virus-specific antigens were demonstrable by indirect immunofluorescence. The hemagglutinating titer of JCV purified from infected cell cultures was generally 100- to 1000-fold higher than the amount of viral hemagglutinin used to initiate infection. Amnion-passaged JCV was readily adapted to growth in urine-derived epithelial cells. The prototype strain of human papovavirus BK, adapted to growth in human embryonic lung cells, also productively infected urine-derived epithelial cells. Primary human fetal glial cells and urine-derived cells were used in parallel experiments for primary isolation of JCV from diseased brain tissue. For this purpose, primary human fetal glial cells were more sensitive than urine-derived epithelial cells. Primary isolations of JCV and BKV from urine sediments of transplant patients and a normal male were made in urine-derived cells. Two renal transplant patients were identified as simultaneously excreting JCV and BKV. Both JCV and BKV genomes were molecularly cloned from one urine specimen of a double excretor. Although direct comparisons between primary human fetal glial and urine-derived epithelial cells were not made, it appears that the latter may be more suitable for primary isolation of JCV from urine.

BK Virus↗

Papovavirus antigens in paraffin sections of PML brains.

Brain tissue of 36 patients with definite PML (showing histologically the pathognomonic "PML cells") and of 12 cases with possible PML (showing patchy demyelination without PML cells) were studied for the presence of papovavirus antigens. A cross-reactive genus-specific serum and a serum raised against JCV were used in the peroxidase-antiperoxidase technique on formalin-fixed paraffin sections of autopsy brain. There was some variability in intensity of staining between the cases and between the sera. Papovavirus antigen-containing cells--mainly PML cells--were found in 35 definite and in one possible PML case. Twenty-nine of these brains reacted with anti-JCV serum. In five brains, antigen deposits were prominent in cytoplasm and processes of astrocytes in some areas of PML lesions. Giant astrocytes demonstrated viral antigens in six cases, indicating that these cells are indeed infected in PML. There was no staining of nerve cells or endothelial cells.

Adolescent↗

Vulvar intraepithelial neoplasia: correlation of nuclear DNA content and the presence of a human papilloma virus (HPV) structural antigen.

Immunoperoxidase localization of a human papilloma virus structural antigen (HPV) was attempted in 68 intraepithelial lesions of the vulva, 39 of which were analyzed for nuclear DNA content by microspectrophotometry. Overall, 5.9% (4/68) stained positive for HPV. Ninety percent (35/39) of the cases tested were aneuploid, and, of these, 2.8% (1/35) stained positive for HPV. In contrast, 50% (2/4) of the polyploid lesions were positive. Hence DNA microspectrophotometry and immunoperoxidase localization of HPV are useful coparameters for distinguishing wart virus infection (condylomata) from vulvar intraepithelial neoplasia. HPV is detected infrequently within aneuploid lesions, in keeping with the concept that epithelial maturation is required for virion assembly. Whether the HPV genome exists in a nonreplicative state within the aneuploid cell population is unknown.

Antigens, Viral↗

Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx.

Juvenile- and adult-onset laryngeal papillomas were examined for the presence of a human papillomavirus (HPV) genome and capsid antigens. DNA was isolated from a portion of tissue removed for therapeutic purposes, and the presence of a papillomavirus genome was detected by Southern transfer analysis. The viral DNA found in the 12 juvenile-onset and the 8 adult-onset laryngeal papillomas examined was identified as HPV-6 on the basis of size, restriction endonuclease digestion patterns, and homology detected under stringent conditions. Restriction endonuclease analysis of the viral genomes revealed at least four different subtypes, designated HPV-6c through HPV-6f. The most common subtype, HPV-6c, was detected in over half of the papillomas studied, including both juvenile and adult types. The remaining tissue was fixed and processed for immunocytochemistry. The immunoperoxidase technique was used with an antiserum that reacts with capsid antigen(s) common to all HPV serotypes. HPV antigen was found in two of the juvenile-onset papillomas and two of the adult-onset papillomas. The antigen was localized to the nucleus and was distributed in the superficial layers of the epithelium. HPV capsid antigen had not previously been detected in cases of adult-onset papilloma, and the HPV genome in both juvenile- and adult-onset laryngeal papillomas had not been characterized. Despite the absence of detectable viral antigen in most of the specimens examined, the presence of the HPV genome provides strong evidence for the papillomavirus etiology of these tumors.

Adolescent↗

BK papovavirus infections in renal transplant recipients: contribution of donor kidneys.

Infections due to BK papovavirus frequently occur in renal transplant recipients [2] and may be involved in a variety of syndromes, including ureteral obstruction, deterioration of graft function, and pancreatic disease. The source of the BK papovavirus in these cases is not clear. Because the renal allograft has been implicated as a source of primary cytomegalovirus infections in renal transplant recipients [3], we investigated the possibility that donor kidneys may also contribute to the transmission of BK papovavirus. A fourfold or greater increase in titers of HAI antibodies to BK papovavirus was observed in 55 (24%) of 230 renal transplant recipients. Seronegative recipients who received kidneys from seropositive donors were 3.5 times more likely to develop an infection due to BK papovavirus than were seronegative recipients of kidneys from seronegative donors. The antibody status of the donor did not affect the likelihood of an increase in titers of antibody to BK papovavirus in seropositive recipients. These results suggest that BK papovavirus may be transmitted with transplanted kidneys and that transplant recipients who are at risk for primary infection by this route are more than twice as likely to have increased titers of antibody to BK papovavirus as those who are at risk for the reactivation of an infection. Further studies should be performed to define the relative role of cadaver vs. living, related kidney donors in the transmission of BK papovavirus and the clinical syndromes that are related to primary and reactivated infections.

Humans↗

Propagation and primary isolation of papovavirus JC in epithelial cells derived from human urine.

Human papovavirus JC, previously passaged in amnion cells or in primary human fetal glial cells, replicated efficiently in urine-derived epithelial cells. Primary isolation of the virus from brain extracts was possible in urine-derived cells, but these cells were not as sensitive as primary human fetal glial cells for this purpose. Primary isolations of human papovavirus JC from urine sediments of renal transplant patients were made in urine-derived cells.

Cells, Cultured↗

Human papillomavirus (HPV) in condylomatous lesions of cervix.

Ninety-seven cervical condylomata classified histologically as flat condyloma (planum), papillary condyloma (acuminatum), and endophytic condyloma were studied by transmission electron microscopy (TEM) and by immunoperoxidase technique (IPT) for the presence of human papillomavirus (HPV) particles and antigen, respectively. Both techniques localized HPV chiefly in nuclei of koilocytotic cells. HPV particles were found in 25% of the cases by TEM and HPV antigen was detected in 48% of the cases by IPT. All cases positive by TEM were also positive by IPT, thus confirming the specificity of the immunological staining. The viral antigen was detected in 56% of 68 flat condylomata, 35% of 26 papillary condylomata, and in none of 3 cases of endophytic condylomata. However, when histiotypes of virus-positive condylomata were controlled for the intraepithelial extent of koilcytotic cells, the prevalence of HPV correlated with the extent of koilocytosis rather than with the histiotype. The immunologic technique will be of value for the further characterization of cervical condylomata and of the relationship between HPV infection and cervical intraepithelial neoplasia.

Adolescent↗