Parvovirus b19 persistence in abnormal thyroid tissue of a mature cystic ovarian teratoma: a case report.

Ovarian teratomas represent the most common neoplasm derived from germ cells and can contain mature ectodermal, mesodermal, and endodermal tissues. In rare cases, these teratomas can be composed predominantly or solely of thyroid tissue. These thyroid cells often function similarly to normal thyroid tissues. This laboratory and others have previously shown that parvovirus B19 (B19V) persists in primary and metastatic thyroid tissues. No reports exist on possible B19V persistence in thyroid tissues that may arise de novo outside the thyroid gland proper. In this case report, the detection of B19V (genotype 1) in the thyroid epithelial cells of a mature teratoma is reported. Nested PCR and immunohistochemistry were used to detect viral nucleic acids and proteins, respectively. Viral genomes were amplified in lesion DNA, confirming persistence of B19V. Positive immunohistochemical staining was seen for B19V capsid proteins in the thyroid epithelial cells within the mature teratoma, but not in surrounding ovarian tissue or in the non-thyroidal elements of the mature teratoma. These results demonstrate for the first time that thyroid epithelial cells, derived from non-thyroid tissue, are capable of supporting B19V infection and persistence.

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. CASE PRESENTATION: A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. CONCLUSIONS: Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis.

Mouse embryonic stem cells are not susceptible to cytomegalovirus but acquire susceptibility during differentiation.

BACKGROUND: Cytomegalovirus (CMV) is the most significant infectious cause of congenital anomalies of the central nervous system caused by intrauterine infection in humans. The timing of infection and the susceptibility of cells in early gestational stages are not well understood. In this study we investigated the susceptibility of embryonic stem (ES) cells to CMV infection during differentiation. METHODS: ES cell lines were established from transgenic mice integrated with the murine CMV (MCMV) immediate-early (IE) promoter connected with a reporter lacZ gene. The susceptibility of the ES cells was analyzed in terms of viral gene expression and viral replication after induction of differentiation. RESULTS: ES cells were nonpermissive to MCMV infection in the undifferentiated state. Upon differentiation, permissive cells appeared approximately 2 weeks after the leukemia inhibitory factor was removed. Upon neural differentiation by retinoic acid (RA), glial cells showed specific susceptibility in terms of expression of the viral antigen. The MCMV IE promoter was not activated in ES cells from the transgenic mice. Activation of the IE promoter was detected approximately 2 weeks after induction of differentiation and observed predominantly in glial cells. Upon MCMV infection of the ES cells, viral infection was correlated with the activation of the IE promoter. CONCLUSIONS: ES cells are nonpermissive to MCMV infection and acquire permissiveness about 2 weeks after induction of differentiation, especially in glial cells. Acquisition of permissiveness in differentiated ES cells may be associated with activation of the IE promoter.

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus.

BACKGROUND: p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. METHODS: p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. RESULTS: p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. CONCLUSION: Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein.

Alleviation of murine leukemia virus repression in embryonic carcinoma cells by genetically engineered primer binding sites and artificial tRNA primers.

The primer binding site (PBS) plays pivotal roles during reverse transcription of retroviruses and also is the target of a cellular host defense impeding the transcription of murine leukemia virus (MLV) harboring a proline (pro) PBS in embryonic cells. Both the PBS and the tRNA primer are copied during reverse transcription and anneal as complementary DNA sequences creating the PBS of the integrated provirus. The pro PBS of MLV can be exchanged by PBS sequences matching endogenous or engineered tRNAs to allow replication of Akv MLV-derived vectors in fibroblasts. Here we use the PBS escape mutant B2 to demonstrate the capacity of the synthetic tRNA(B2) to function in reverse transcription in competition with endogenous tRNAs in fibroblasts and embryonic carcinoma (EC) cells. We further show symmetry between PBS and the primer by the ability of the synthetic tRNA(B2) to confer escape from EC repression of a PBS-Pro vector. Of a panel of vectors with the repressed pro PBS substituted for other natural or artificial PBS sequences, all except one efficiently expressed the neo marker gene when transferred to NIH/3T3 and EC cells, hence avoiding PBS-mediated silencing in EC cells. A non-natural PBS matching an artificially designed tRNA molecule conferred no further relief from repression than that attained with the B2 escape mutant or the natural alternative PBSs. Interestingly, a vector harboring a PBS matching tRNA(Lys1.2) suffered repression similar to the wild-type PBS-Pro but was partially rescued by a single point mutation of the PBS.

A cervical teratoma with invasive squamous cell carcinoma in an HIV-infected patient: a case report.

HIV infection among women is increasing in the United States. Since January 1993, cervical cancer has been considered an AIDS-defining illness. We report a rare case of squamous cell carcinoma arising in a teratoma of the uterine cervix in an HIV-infected patient. This patient was treated with a radical hysterectomy, para-aortic and pelvic lymphadenectomy. She is currently 1 year from treatment and is without evidence of recurrence.

p53 mutation in carcinomas arising in ovarian cystic teratomas.

Carcinomas arising in mature cystic teratomas of the ovaries from nine women were examined for the presence of p53 mutations. The nine tumors comprised six squamous cell carcinomas, one squamous cell carcinoma in situ, one undifferentiated small cell carcinoma, and one mucoepidermoid carcinoma. Abnormal nuclear accumulation of the p53 protein was observed in four of the tumors. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue blocks and subjected to polymerase chain reaction (PCR) for specific amplification of the p53 gene exons 5-8, followed by direct chemiluminescence sequencing analysis. A frameshift mutation in exon 8 (codon 278, CCT > del T; stop at codon 344) was detected in one poorly differentiated squamous cell carcinoma. The samples were also evaluated for the possible association of 'benign' and 'malignant' types of human papillomavirus (HPV) by PCR using universal primer sets. None of the samples contained detectable HPV genome. These data suggest that p53 mutations are relatively uncommon in secondary carcinomas developing in ovarian dermoid cysts, although the number of samples studied was admittedly small.