An autopsy of a patient in Japan with coronavirus disease indicated pneumonia lung pathology, manifested as diffuse alveolar damage. We detected severe acute respiratory syndrome coronavirus 2 antigen in alveolar epithelial cells and macrophages. Coronavirus disease is essentially a lower respiratory tract disease characterized by direct viral injury of alveolar epithelial cells.

We investigated the possibility of using a pharmacologic agent to modulate viral gene expression in order to target radiotherapy to tumor tissue. In a murine xenograft model, we had previously shown targeting of [125I]2'-fluoro-2'-deoxy-beta-D-5-iodouracilarabinofuranoside ([125I]FIAU) to tumors engineered to express the Epstein-Barr virus (EBV)-thymidine kinase (TK). Here we extend those results to targeting of a therapeutic radiopharmaceutical [131I]FIAU to slow or stop tumor growth or to achieve tumor regression. These outcomes were achieved in xenografts with tumors that constitutively expressed the EBV-TK, as well as with naturally-infected EBV tumor cell lines. Burkitt's lymphoma and gastric carcinoma required activation of viral gene expression by pretreatment with bortezomib. Marked changes in tumor growth could also be achieved in naturally-infected Kaposi's sarcoma herpesvirus (KSHV) tumors following bortezomib activation. Bortezomib-induced enzyme-targeted radiation (BETR) therapy illustrates the possibility of pharmacologically modulating tumor gene expression to effect targeted radiotherapy.

Purpose: EBV and other herpesviruses are associated with a variety of malignancies. The EBV thymidine kinase (TK) is either not expressed or is expressed at very low levels in EBV-associated tumors. However, EBV-TK expression can be induced in vitro with several chemotherapeutic agents that promote viral lytic induction. The goal of this study is to image EBV-associated tumors by induction of viral TK expression with radiolabeled 2 ¶-fluoro-2 ¶-deoxy-h-D-5-iodouracil-arabinofuranoside (FIAU). Experimental Design: Immunoblot, luciferase reporter assay, and in vitro assay with [

The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective.

Context Adrenocortical zonation is associated with a markedly complex developmental process, and the pathogenesis and/or etiology of many disorders of adrenocortical zonal development have remained unknown. Cells from the three adrenocortical zones are morphologically and functionally differentiated, and the mature stage of cell development or senescence has been recently reported to be correlated with telomere length. However, the telomere length of each adrenocortical zonal cell has not yet been studied in human adrenal glands. Objective We aimed to study the telomere lengths of adrenocortical parenchymal cells from three different zones of the adrenal glands present during childhood, adolescence, and adulthood. Methods Adrenal glands of 30 autopsied subjects, aged between 0 and 68 years, were retrieved from pathology files. The normalized telomere to centromere ratio (NTCR), an index of telomere length, was determined in the parenchymal cells of the zona glomerulosa, zona fasciculata, and zona reticularis (ZR), using quantitative fluorescence in situ hybridization. Results NTCR of ZR cells was the longest, followed in decreasing order by that of zona glomerulosa and zona fasciculata cells in subjects aged 20 to 68 years, but no substantial differences in NTCR were detected among these three zones in the group <20 years of age. NTCR of ZR increased with age in subjects aged 20 to 68 years, whereas no important age-dependent changes in NTCR were detected in the group <20 years of age. Conclusion The telomere lengths for three zones in adrenal cortex were correlated with their differentiation in adulthood but not in childhood and adolescence.