First case of postmortem study in a patient vaccinated against SARS-CoV-2.

A previously symptomless 86-year-old man received the first dose of the BNT162b2 mRNA COVID-19 vaccine. He died 4 weeks later from acute renal and respiratory failure. Although he did not present with any COVID-19-specific symptoms, he tested positive for SARS-CoV-2 before he died. Spike protein (S1) antigen-binding showed significant levels for immunoglobulin (Ig) G, while nucleocapsid IgG/IgM was not elicited. Acute bronchopneumonia and tubular failure were assigned as the cause of death at autopsy; however, we did not observe any characteristic morphological features of COVID-19. Postmortem molecular mapping by real-time polymerase chain reaction revealed relevant SARS-CoV-2 cycle threshold values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney and cerebrum) except for the liver and olfactory bulb. These results might suggest that the first vaccination induces immunogenicity but not sterile immunity.

Impact of human papillomaviruses (HPV) on recurrence rate and malignant progression of sinonasal papillomas.

Sinonasal papillomas are characterized by their potential for frequent recurrences and malignant progression. Currently, the role of human papillomavirus (HPV) infection in sinonasal papillomas is unclear. A study was conducted to elucidate the impact of HPV infection on recurrence and malignant progression of sinonasal papillomas. One hundred and seven patients with 151 tumors could be examined. One hundred and one patients suffered from benign papilloma, mostly inverted papillomas (IP); six patients suffered from carcinomas in situ and squamous cell carcinomas (SCC) ex-IP. Recurrent IP were more often HPV-positive than non-recurrent tumors (38.8% vs. 60%-65%). Low-risk (LR) HPV infection (especially HPV 6) increased the risk of tumor recurrences (p = 0.0385 and p = 0.0556, respectively). IP and oncocytic papillomas (both lesions are known for their malignant potential) were more often high-risk (HR) HPV-positive (15.5% and 16.7%) than fungiform papilloma (which usually does not progress to carcinoma). CIS and SCC ex-IP displayed higher HPV rates than benign IP (83.3% vs. 38.8%), especially higher rates of HR-HPV (66.7% vs. 23.8%, p = 0.0415). Data from this study endorse the hypothesis that recurrence of sinonasal papillomas is promoted by LR-HPV infection and that malignant progression of IP is promoted by HR-HPV infection.

Hepatocellular and cholangiolar carcinoma-derived cell lines reveal distinct sets of chromosomal imbalances.

OBJECTIVES: Hepatocellular carcinoma (HCC) and cholangiolar carcinoma (CC) cell lines are used to analyze the basic mechanisms of carcinogenesis and target therapies. However, it is not yet clear which chromosomal aberrations are to be typically expected in such cell lines. It is also not clear whether there are prerequisites for in vitro growth on the genomic and/or expression level. We therefore analyzed HCC and CC cell lines for typical genetic settings. METHODS: The HCC cell lines HLE, HLF, Huh7, HepG2 and Hep3b and the CC cell lines EGI1, MzCha1 and TFK-1 were analyzed using high-density arrays for comparative genomic hybridization (aCGH; 244,000 oligonucleotides). Additional fluorescence in situ hybridization analyses were done to confirm the aCGH results and to add information regarding the aneuploidy of cell lines. RESULTS: The gain of 1q, in particular q21-22, was detected in all HCC cell lines also as a partial loss of 13q. In contrast, a loss of 8p in combination with a relative gain of 8q was seen in all CC but no HCC cell lines. Interestingly, a gain of 17q was seen in all cell lines. These aberrations are also well documented for surgical tumor specimens. Besides these imbalances, the cell lines revealed imbalances for 11p, 12p, 14q, 16p, 16q, 21q and 22q, respectively, only rarely seen in surgical tumor specimens. These aberrations could be of importance for the in vitro cultivation of tumor cells. Structural aberrations were accompanied by aneuploidy in 3 of 5 HCC cell lines and 2 of 3 CC cell lines. Ploidy status was not correlated to any of the imbalances mentioned above. CONCLUSIONS: HCC and CC cell lines revealed characteristic chromosomal imbalances similar to those seen in surgical tumor specimens including chromosomes 1, 8, 13 and 17, respectively. These aberrations are characteristic of the histogenetic origin of the tumor cells. However, the chromosomal imbalances that occurred probably led to the ability of tumor cells to grow in vitro.

Crosstalk and differential response to abiotic and biotic stressors reflected at the transcriptional level of effector genes from secondary metabolism.

Plant secondary metabolism significantly contributes to defensive measures against adverse abiotic and biotic cues. To investigate stress-induced, transcriptional alterations of underlying effector gene families, which encode enzymes acting consecutively in secondary metabolism and defense reactions, a DNA array (MetArray) harboring gene-specific probes was established. It comprised complete sets of genes encoding 109 secondary product glycosyltransferases and 63 glutathione-utilizing enzymes along with 62 cytochrome P450 monooxygenases and 26 ABC transporters. Their transcriptome was monitored in different organs of unstressed plants and in shoots in response to herbicides, UV-B radiation, endogenous stress hormones, and pathogen infection. A principal component analysis based on the transcription of these effector gene families defined distinct responses and crosstalk. Methyl jasmonate and ethylene treatments were separated from a group combining reactions towards two sulfonylurea herbicides, salicylate and an avirulent strain of Pseudomonas syringae pv. tomato . The responses to the herbicide bromoxynil and UV-B radiation were distinct from both groups. In addition, these analyses pinpointed individual effector genes indicating their role in these stress responses. A small group of genes was diagnostic in differentiating the response to two herbicide classes used. Interestingly, a subset of genes induced by P. syringae was not responsive to the applied stress hormones. Small groups of comprehensively induced effector genes indicate common defense strategies. Furthermore, homologous members within branches of these effector gene families displayed differential expression patterns either in both organs or during stress responses arguing for their non-redundant functions.