Fornaciari Gino
Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie in Medicina Divisione di Paleopatologia, Università di Pisa, I.
Med Secoli. 2006;18(3):843-64.
The paleopathological study of 31 Italian Renaissance mummies from the Basilica of S. Domenico Maggiore in Naples has allowed us to perform about 20 diagnoses, of which 5 concern infectious (smallpox, hepatitis, condyloma, syphilis and pneumonia), 3 metabolic (obesity, atherosclerosis, gallstones), I articular (DISH) and 2 neoplastic (colon adenocarcinoma and skin carcinoma) diseases. The mummy of an anonymous child, dated back to the 16th century (14C: 1569 +/- 60), presented a diffuse vesiculopustular exanthema. Macroscopic aspects and regional distribution suggested smallpox, while EM revealed many egg-shaped, virus-like particles (250 x 50 nm), with a central dense core. Following incubation with anti-smallpox virus antiserum and protein A-gold complex immunostaining, the particles resulted completely covered with protein A-gold. These results clearly show that this Neapolitan child died of a severe form of smallpox some four centuries ago. The mummy of Maria d'Aragona, Marquise of Vasto (1503-1568), revealed on the left arm an oval, cutaneous ulcer (15 x l0 mm) with linen dressing. Indirect immunofluorescence with anti-treponema pallidum antibody identified a large number of filaments with the morphological characteristics of fluorescent treponemes. Electron microscopy evidenced typical spirochetes, with axial fibril. These findings clearly demonstrate a treponemal, probably venereal, infection. Further examination of the mummy showed a large peduncolate arborescent neoformation (2 x 7 mm) of the right inguinal region, which was rehydrated and submitted to histology by hematoxylineosin, Van Gieson and Masson's trichromic staining. Light microscopy evidenced an exophytic, papillary skin lesion, with typical connective axis and pronounced parakeratosis. These macroscopic and histological aspects seemed peculiar of condyloma acuminatum, a papillomavirus-induced squamous lesion also called "venereal wart". Molecular study revealed the presence of HPV 18, a virus with high oncogenic potential. Automated sequencing of several clones revealed 100% similarity sequences of both HPV 18 and JC9813 DNA, a putative novel HPV with low oncogenic potential. This study represents the first molecular diagnosis of HPV in mummies and could pave the way for further research about the secular evolution of these viruses, very important in human oncology. The buccal surfaces of the teeth of Isabella d'Aragona, duchess of Milan ((1470-1524), covered by a black patina with high mercury levels, have been intensively and intentionally abraded. The black patina can be attributed to chronic mercury intoxication, used therapeutically in the treatment of syphilis. The mummy of Ferrante I d'Aragona, King of Naples (1431-1494), revealed an adenocarcinoma extensively infiltrating the muscles of the small pelvis. A molecular study of the neoplastic tissue evidenced a typical mutation of the K-ras gene codon 12: the normal sequence GGT (glycine) was altered into GAT (aspartic acid). At present this genetic change is the most frequent mutation of the K-ras gene in sporadic colorectal cancer. The alimentary "environment" of the Neapolitan court of the XV century, with its abundance of natural alimentary alkylating agents, well explains this acquired mutation. These and other diseases as, for example, a case of cirrhosis, some cases of anthracosis and other peculiar traumatic conditions, such as a mortal stab-wound, can elucidate the pathocenosis of this wealthy classes of the Italian Renaissance.
对那不勒斯圣多梅尼科马焦雷教堂的31具意大利文艺复兴时期木乃伊进行的古病理学研究，使我们能够做出约20种诊断，其中5种涉及感染性疾病（天花、肝炎、湿疣、梅毒和肺炎），3种代谢性疾病（肥胖、动脉粥样硬化、胆结石），1种关节疾病（弥漫性特发性骨肥厚）和2种肿瘤性疾病（结肠腺癌和皮肤癌）。一具可追溯到16世纪（碳-14测定：公元1569年±60年）的无名儿童木乃伊，呈现出弥漫性水疱脓疱疹。宏观特征和区域分布提示为天花，而电子显微镜显示出许多椭圆形、病毒样颗粒（250×50纳米），具有中央致密核心。在用抗天花病毒抗血清孵育并进行蛋白A-金复合物免疫染色后，颗粒完全被蛋白A-金覆盖。这些结果清楚地表明，这个那不勒斯儿童死于大约四个世纪前的一种严重天花。瓦斯托侯爵夫人玛丽亚·德阿拉贡纳（1503 - 1568年）的木乃伊，在左臂上发现一个椭圆形皮肤溃疡（15×10毫米），有亚麻布敷料。用抗梅毒螺旋体抗体进行间接免疫荧光检测，发现大量具有荧光螺旋体形态特征的细丝。电子显微镜证实有典型的螺旋体，带有轴丝。这些发现清楚地证明了一种螺旋体感染，可能是性传播感染。对该木乃伊的进一步检查显示右腹股沟区有一个大的带蒂树状新生物（2×7毫米），将其复水后进行苏木精-伊红、范吉森和马森三色染色的组织学检查。光学显微镜显示为外生性乳头状皮肤病变，有典型的结缔组织轴心和明显的角化不全。这些宏观和组织学特征似乎是尖锐湿疣所特有的，尖锐湿疣是一种由乳头瘤病毒引起的鳞状病变，也称为“性病疣”。分子研究显示存在人乳头瘤病毒18型，这是一种具有高致癌潜力的病毒。对几个克隆进行的自动测序显示，人乳头瘤病毒18型和JC9813 DNA（一种假定的低致癌潜力新型人乳头瘤病毒）的序列相似度为100%。这项研究代表了在木乃伊中对人乳头瘤病毒的首次分子诊断，并可能为进一步研究这些病毒的长期演变铺平道路，这在人类肿瘤学中非常重要。米兰公爵夫人伊莎贝拉·德阿拉贡纳（1470 - 1524年）牙齿的颊面覆盖着高汞含量的黑色铜绿，且有大量有意磨损的痕迹。这种黑色铜绿可归因于慢性汞中毒，汞中毒曾被用于梅毒的治疗。那不勒斯国王费兰特一世·德阿拉贡纳（1431 - 1494年）的木乃伊显示出一个广泛浸润小骨盆肌肉的腺癌。对肿瘤组织的分子研究证实了K-ras基因密码子12的典型突变：正常序列GGT（甘氨酸）被改变为GAT（天冬氨酸）。目前这种基因变化是散发性结直肠癌中K-ras基因最常见的突变。15世纪那不勒斯宫廷丰富的天然食物烷基化剂的饮食“环境”，很好地解释了这种获得性突变。这些以及其他疾病，例如一例肝硬化、一些煤尘肺病例和其他特殊创伤情况，如致命刺伤等，能够阐明意大利文艺复兴时期这些富裕阶层的病理群落情况。
