Works of art may serve as a source of evidence of diseases and help to better understand their natural history.
Bernardino da Fossa was a 15th-century Italian Franciscan friar who wrote sermons and ...historical works. He described the events of the Observance Reformation movement since its dawn, but the last chapter is unexplainably interrupted. This has been considered suggestive for an acute and disabling illness. A painting dating back 12 years after his death depicts Bernardino holding a crutch with his left arm. This may represent an important clue to establish a gait disturbance, whereas the permanent interruption in drafting his writing may be ascribed to a serious writing impairment.
The historical detail of the writing suspension and the crutch in this painting represent important hints of the stroke suffered by Bernardino da Fossa.
The church of San Sebastiano in Navelli contains hundreds of mummified bodies dating back to XVI-XIX century and accidentally discovered in 1980. The recovery, started in 2001, yielded the remains of ...206 individuals in different conditions of preservation. The series includes 157 adults (102 males, 42 females, 13 indefinite), with an average age of 51 years, and 49 children. No macroscopic evidence of internal organs was observed in mummified subjects, whereas skin, skeletal muscles and other superficial tissues (eyes, ears, hair) appeared well preserved, suggesting a preminent role of desiccation in mummification process. Limited examples of mummified animals were also recovered, confirming the environment capability in tissue preservation. The initial paleopathologic analysis allowed to identify various pathologic conditions, including degenerative joint disease, periodontal disease, healed bone fractures, occasional tumors and traces of post-mortem examination. A huge amount of information will be available as soon as the recovery will be completed. (The study was partially supported by the “Consorzio Beni Culturali Provincia L’Aquila”)
Cell proliferation requires the orchestrated actions of a myriad of proteins regulating DNA replication, DNA repair and damage tolerance, and cell cycle. Proliferating cell nuclear antigen (PCNA) is ...a master regulator which interacts with multiple proteins functioning in these processes, and this makes PCNA an attractive target in anticancer therapies. Here, we show that a cell-penetrating peptide containing the AlkB homolog 2 PCNA-interacting motif (APIM), ATX-101, has antitumor activity in a panel of human glioblastoma multiforme (GBM) cell lines and patient-derived glioma-initiating cells (GICs). Their sensitivity to ATX-101 was not related to cellular levels of PCNA, or p53, PTEN, or MGMT status. However, ATX-101 reduced Akt/mTOR and DNA-PKcs signaling, and a correlation between high Akt activation and sensitivity for ATX-101 was found. ATX-101 increased the levels of γH2AX, DNA fragmentation, and apoptosis when combined with radiotherapy (RT). In line with the in vitro results, ATX-101 strongly reduced tumor growth in two subcutaneous xenografts and two orthotopic GBM models, both as a single agent and in combination with RT. The ability of ATX-101 to sensitize cells to RT is promising for further development of this compound for use in GBM.
Gaetano Corrado was born in Paglieta (central Italy) in 1858 and, after dealing with ophthalmology, became professor of forensic medicine at the Universities of Cagliari (1894) and Naples (1895). ...Forensic attitudes allowed him to carry out an extremely detailed study of the Cagliari mummy. After careful anthropological analyses he ascribed the mummy to a 50-60 year-old female, disproving the public rumour of a murdered pregnant woman. In analogy with other studies, he pointed out the role of acari in mummification process. By using a conservative anatomic approach, he paid attention to gross and histological identification of organs, as well as microbiologic and chemical analysis. His great talent was also expressed in anatomy, anthropology, rehabilitation of war cripples, public works planning and research for energy production. He died in Naples at the age of 76. We believe that his contributions, although done without a real paleopathological awareness, should not be forgotten.
In about 70% of patients affected by autosomal dominant osteopetrosis type 2 (ADO2), osteoclast activity is reduced by heterozygous mutations of the CLCN7 gene, encoding the ClC-7 chloride/hydrogen ...antiporter. CLCN7G215R-, CLCN7R767W-, and CLCN7R286W-specific siRNAs silenced transfected mutant mRNA/EGFP in HEK293 cells, in RAW264.7 cells and in human osteoclasts, with no change of CLCN7WT mRNA and no effect of scrambled siRNA on the mutant transcripts. Osteoclasts from Clcn7G213R ADO2 mice showed reduced bone resorption, a condition rescued by Clcn7G213R-specific siRNA. Treatment of ADO2 mice with Clcn7G213R-specific siRNA induced increase of bone resorption variables and decrease of trabecular bone mass, leading to an overall improvement of the osteopetrotic bone phenotype. Treatment did not induce overt adverse effects and was effective also with siRNAs specific for other mutants. These results demonstrate that a siRNA-based experimental treatment of ADO2 is feasible, and underscore a translational impact for future strategy to cure this therapeutically neglected form of osteopetrosis.
Celestine V is considered one of the most enigmatic Popes. He has been the subject of much speculation, with legends claiming he was murdered by order of his successor Boniface VIII. Assassination ...rumors first started in medieval times, but they were renewed in 1630 by the discovery of a nail that fitted perfectly into a square opening in his skull. During the latest Canonical Recognition, the morphology of the lesion was examined by visual inspection, showing it could not have been produced during life. The legend that the nail was driven through the Pope’s head may finally be discredited.
Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide ...further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIPmut). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIPmut PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype.
We hypothesized that hormonal therapy favors the development of the hormone-resistant phenotype through epigenetic mechanisms. Human prostate cancer tissues and in vitro and in vivo models were used ...to verify this hypothesis. We demonstrated that tumor cells continuously treated with bicalutamide (BCLT) or cultured in androgen-depleted medium progressively acquire higher DNA methyltransferase (DNMT) activity and expression than cells cultured in standard condition. Increased DNMT expression and activity also paralleled the up-regulation of truncated AR isoforms, which favors the development of the hormone-resistant phenotype. After androgen stimulation with 10−12 m dihydrotestosterone, DNMT activity was significantly reduced in comparison with hormonal therapy. Consistent with these observations, the silencing of DNMT3a and DNMT3b significantly decreased the DNMT activity levels. These findings were also directly correlated with phosphatase and tensin homolog down-regulation and activation of ERK and phosphatidylinositol 3-kinases/AKT8 virus oncogene cellular homolog pathways. The use of a pan-DNMT inhibitor (5-Azacitidine) greatly reduced the development of the hormone-resistant phenotype induced by long-term BCLT treatment, and this finding correlated with low DNMT activity. The regulation of DNMT activity was, in some measure, dependent on the androgen receptor, as small interfering RNA treatment targeting the androgen receptor greatly decreased the modulation of DNMT activity under androgenic and antiandrogenic stimulation. These observations were correlated in vivo in patients, as demonstrated by immunohistochemistry. Patients treated by BCLT before surgery had higher DNMT3a and DNMT3b expression than patients who had not undergone this treatment. Our findings provide evidence of a relationship between the castration-resistant phenotype and DNMT expression and activity in human prostate cancer.
Giacomo Torno was born in 1539 (or 1541) in Naples. At the age of 18 he joined the Clerics Regular Theatines in San Paolo Maggiore and was welcomed on 30 October 1558. He suffered a stroke on 4 ...December 1608 and died 45 days later. Contemporary sources report that he appeared to be tormented by the devil during his illness, tormented by constant spasms in his arm, which caused him great discomfort. During the analysis of his mummified body, a discontinuity of the skin surface at the level of the sacrum was discovered. All morphological features indicate a wound that developed during the subject’s life. Based on historical sources, the fracture of the first coccygeal vertebra, the appearance of the lesion near death, and the shape of the lesion, it appears that this is the first recorded instance of the Kennedy terminal ulcer, identified through both direct and indirect sources
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