T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Statistical considerations of isolated maxillofacial fractures in Sao Paulo

Statistical analysis of 550 isolated maxillo-facial fractures is presented. Data obtained illustrated the important number of maxillo-facial fractures in Sao Paulo, the automobilistics accidents were responsible for most maxillo-facial trauma, the jaw and the malar were more predominant than the others structures and the conservative treatment was the most used one.     

Cardiovascular and respiratory changes during acute pulmonary edema produced by nephrotoxic serum in the rat

The intravenous injection of rabbit anti-rat kidney serum in rats produces, with a latency of 30 to 60 seconds, the triad sinus bradycardia (or S-A blockade), systemic hypotension and apnea. Recordings of the intracardiac pressures showed a rise in the right and a simultaneous fall in the left ventricular pressure, 30 to 60 seconds after the serum injection. These initial effects were followed by pulmonary edema and death. Bilateral vagotomy prevented the bradycardia and apnea, but not the intracardiac changes, edema and death. Atropine also prevented the bradycardia, but not the apnea, edema and death. Experiments using alpha and beta adrenergic blocking agents seem to indicate that the edema is not caused by the release of catecholamines. It is suggested that the edema could be explained by a rise in the pulmonary capillary pressure, due to the antigen-antibody reaction. The triad bradycardia, systemic hypotension and apnea seems to be the first sign of the pulmonary edema, is reflex in nature, and is assumed to be due to stimulation of J receptors in the lungs, by a mechanical effect (edema). Phenylbutazone and acetylsalicylic acid give a partial protection against the pulmonary edema. Ultramorphological observations of lungs with edema were described.     

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

p53 immunoreactivity in hepatocellular adenoma, focal nodular hyperplasia, cirrhosis and hepatocellular carcinoma

The prolonged half-life of mutant p53 makes feasible its immunocytochemical detection. In order to assess the pathogenetic role of mutant p53 in regenerative and neoplastc liver disease we studied its immunohistochemical expression in cases of hepatic cirrhosis, hepatocellular carcinoma (HCC), cirrhosis with areas of HCC, hepatocellular adenoma and focal nodular hyperplasia. The study included needle and wedge biopsies of 50 cirrhotic livers, 59 HCCs (36 of them with associated cirrhosis), six adenomas and two focal nodular hyperplasias. Sixty-five HCC fineneedle cytology specimens were also included in the study. There was no immunohistochemical evidence of mutant p53 expression in any of the cases of cirrhotic liver (except for one instance associated with HCC) adenoma or focal nodular hyperplasia. In contrast p53 was detected in 8.5% of HCC cases in the biopsy series and 24% of HCC cases in the fine needle aspiration series. In addition, mutant p53 expression in HCC was positively correlated with tumour grade. According to grade, the distribution of p53 positive immunoreactivity among HCCs was as follows: Grade I-II, 0% of cases in the biopsy series and 9% in the fine needle aspirates; Grade III, 18% in the biopsy series and 55% in the fine needle aspirates; and Grade IV, 40% in the biopsy series. Therefore, mutant p53 expression does not seem to be associated with benign liver lesions but seems to correlate with the progression of HCC through various grades of increasing malignancy.     

电离辐射对放射工作者职业健康的影响

目的 分析放射工作者外周血象、淋巴细胞微核及染色体畸变情况,为放射工作者职业防护和健康监测提供依据。方法 对2015年、2017年和2019年连续3次接受健康检查的127名放射工作者进行淋巴细胞微核、染色体及血象分析,将其设为放射组。另外选取133名无射线接触史的医务人员设为对照组;结果 放射组中淋巴细胞微核率和染色体畸变率高于对照组,白细胞和血小板计数低于对照组,均具有统计学意义（P < 0.05）。127名放射工作者外周血白细胞总数随着接触电离辐射时间的增长逐渐降低,染色体畸变率逐渐增加,均具有统计学意义（P < 0.05）。损害工龄大于20年的放射工作者染色体畸变率高于低工龄组,不同损害工龄之间比较无统计学意义（P > 0.05）。核医学与介入治疗工种染色体畸变率高于其他工种,具有统计学意义（P < 0.05）。结论 长时间接触低剂量电离辐射可使放射工作者白细胞总数降低和淋巴细胞染色体畸变率增加,应加强放射工作者防护措施以备降低电离辐射损伤程度,特别要加强核医学和介入治疗放射工作人员的职业防护。     

Beckwith-Wiedemann syndrome and virilizing cortical adrenal tumor in a child

The authors report a case of a virilizing adrenal tumor that developed in a 2-year-old child with Beckwith-Wiedemann syndrome (BWS). He had a fetal diagnosis of omphalocele and a history of neonatal adrenal cysts. The importance of prenatal diagnosis of BWS and postnatal follow-up of tumors is discussed. The differential diagnosis of adrenal pathologies occurring in BWS also is reviewed.     

Evolução e Estado Atual das Práticas de Implante Transcateter de Válvula Aórtica na América Latina – Estudo WRITTEN LATAM

Background:Transcatheter aortic valve replacement (TAVR) is a worldwide adopted procedure with rapidly evolving practices. Regional and temporal variations are expected to be found.Objective:To compare TAVR practice in Latin America with that around the world and to assess its changes in Latin America from 2015 to 2020.Methods:A survey was applied to global TAVR centers between March and September 2015, and again to Latin-American centers between July 2019 and January 2020. The survey consisted of questions addressing: i) center’s general information; ii) pre-TAVR evaluation; iii) procedural techniques; iv) post-TAVR management; v) follow-up. Answers from the 2015 survey of Latin-American centers (LATAM15) were compared with those of other centers around the world (WORLD15) and with the 2020 updated Latin-American survey (LATAM20). A 5% level of significance was adopted for statistical analysis.Results:250 centers participated in the 2015 survey (LATAM15=29; WORLD15=221) and 46 in the LATAM20. Combined centers experience accounted for 73 707 procedures, with WORLD15 centers performing, on average, 6- and 3-times more procedures than LATAM15 and LATAM20 centers, respectively. LATAM centers performed less minimalistic TAVR than WORLD15 centers, but there was a significant increase in less invasive procedures after 5 years in Latin-American centers. For postprocedural care, a lower period of telemetry and maintenance of temporary pacing wire, along with less utilization of dual antiplatelet therapy was observed in LATAM20 centers.Conclusion:Despite still having a much lower number of procedures, many aspects of TAVR practice in Latin-American centers have evolved in recent years, followingthe trend observed in developed country centers.     

肝脏移植术后移植物抗宿主病的诊断和治疗

【目的】 探讨肝脏移植术后移植物抗宿主病（GVHD）的诊断和治疗。【方法】 分析我院2003年10月至2009年6月完成的772例肝脏移植的临床资料,总结肝脏移植术后GVHD的诊断和治疗经验。【结果】 772例肝脏移植术后5例病人发生GVHD,发病率为0.65%（5/772）,5例患者均在肝脏移植后2～5周出现发热、皮疹、腹泻和全血细胞减少,肝功能均接近正常,经皮肤活检和骨髓穿刺检查证实,并排除巨细胞病毒（CMV）和EB病毒感染。经过调整免疫抑制剂,加用IL-2受体单克隆抗体,积极抗感染和支持对症治疗,2例患者痊愈,3例患者死于严重感染、消化道出血和多器官功能衰竭。【结论】 肝脏移植术后GVHD死亡率高,早期诊断,及时调整免疫抑制剂方案,积极抗感染和营养支持是治疗的关键。