Primary retroperitoneal mucinous cystadenocarcinoma in a male patient

Primary retroperitoneal mucinous cystadenocarcinomas (PRMCs) are rare. This is the first reported case in the literature in English of PRMC in a man. The 64-year-old man presented with a large retroperitoneal cystic tumour measuring 24 x 20 x 16 cm3, which was removed intact. Areas ranging from a benign mucinous cyst to borderline mucinous tumour to mucinous cystadenocarcinoma were observed on microscopy. Strong patchy staining for cytokeratins 7 and 20 and strong diffuse staining for MUC2 and MUC5AC core peptides, similar to staining patterns in ovarian mucinous tumours, were shown in the benign and atypical epithelium. Staining for CA19.9 and carcinoembryonic antigen was also shown by both components. The theory of its origin from the mucinous metaplasia of peritoneal (mesothelial) inclusion cysts, rather than from ectopic ovarian tissue or ovarian teratomas, is supported by the occurrence of such a tumour in a male patient.     

Rapid detection, serotyping and quantitation of dengue viruses by TaqMan real-time one-step RT-PCR

The use of the polymerase chain reaction (PCR) in molecular diagnosis is now accepted worldwide and has become an essential tool in the research laboratory. In the laboratory, a rapid detection, serotyping and quantitation, one-step real-time RT-PCR assay was developed for dengue virus using TaqMan probes. In this assay, a set of forward and reverse primers were designed targeting the serotype conserved region at the NS5 gene, at the same time flanking a variable region for all four serotypes which were used to design the serotype-specific TaqMan probes. This multiplex one-step RT-PCR assay was evaluated using 376 samples collected during the year 2003. These groups included RNA from prototype dengue virus (1-4), RNA from acute serum from which dengue virus was isolated, RNA from tissue culture supernatants of dengue virus isolated, RNA from seronegative acute samples (which were culture and IgM negative) and RNA from samples of dengue IgM positive sera. The specificity of this assay was also evaluated using a panel of sera which were positive for other common tropical disease agents including herpes simplex virus, cytomegalovirus, measles virus, varicella-zoster virus, rubella virus, mumps virus, WWF, West Nile virus, Japanese encephalitis virus, S. typhi, Legionella, Leptospira, Chlamydia, and Mycoplasma. The sensitivity, specificity and real-time PCR efficiency of this assay were 89.54%, 100% and 91.5%, respectively.     

北京地区汉族人群DNA修复基因XPD单核苷酸多态性与肺癌及食管癌风险的研究

目的：研究核苷酸切除修复基因XPD单核苷酸多态性与北京地区汉族人群肺癌及食管癌风险的关系。方法：采用以医院患者为基础的病例－对照研究方法，包括正常对照383人，肺癌患者351例，食管癌患者325例。以聚合酶链反应－限制性片段长度多态性方法分析了XPD基因Asp312 Asn和Lys751Gln多态性，比较不同基因型与肺癌及食管癌风险的关系，并探讨吸烟与基因多态交互作用对患癌风险的影响。结果：与携带312 Asp/Asp基因型者比较，携带至少1个312Asn等位基因者（即Asp/Asn和Asn/Asn基因型）罹患肺鳞癌的风险增加1．8倍（95％CI1．10－2．93），而与肺腺癌无关（校正的比值比为1．07，95％CI0．55－2．08）。分层分析显示，风险型等位基因312Asn和751Gln与吸烟有明显的交互作用。吸烟剂量≥29包／年且携带312Asn或751Gln者罹患肺鳞癌的风险最高，校正的比值比分别为12．44（95％CI4．97－31．17）和10．74（95％CI4．51－25．57）。XPD基因Asp312Asn和Lys751Gln多态与食管鳞癌风险无关。结论：XPD基因Asp312Asn和Lys751Gln多态是地区汉族人群肺鳞癌遗传易感因素，而与肺腺癌以及食管鳞癌风险无关，可能反映了不同组织学类型肺癌以及肺癌和食管癌之间的病因学差异。     

Acidic amino acid tag enhances response to enzyme replacement in mucopolysaccharidosis type VII mice

We have tested an acidic oligopeptide-based targeting system for delivery of enzymes to tissues, especially bone and brain, in a murine mucopolysaccharidosis type VII (MPS VII) model. This strategy is based upon tagging a short peptide consisting of acidic amino acids (AAA) to N terminus of human beta-glucuronidase (GUS). The pharmacokinetics, biodistribution, and the pathological effect on MPS VII mouse after 12 weekly infusions were determined for recombinant human untagged and tagged GUS. The tagged GUS was taken up by MPS VII fibroblasts in a mannose 6-phosphate receptor-dependent manner. Intravenously injected AAA-tagged enzyme had five times more prolonged blood clearance compared with the untagged enzyme. The tagged enzyme was delivered effectively to bone, bone marrow, and brain in MPS VII mice and was effective in reversing the storage pathology. The storage in osteoblasts was cleared similarly with both enzyme types. However, cartilage showed a little response to any of the enzymes. The tagged enzyme reduced storage in cortical neurons, hippocampus, and glia cells. A highly sensitive method of tandem mass spectrometry on serum indicated that the concentration of serum dermatan sulfate and heparan sulfate in mice treated with the tagged enzyme decreased more than the untagged enzyme. These preclinical studies suggest that this AAA-based targeting system may enhance enzyme-replacement therapy.     

Pulmonary atresia/ventricular septal defect associated with facial port-wine stain and retinal vascular abnormality: a new constellation?

A case with pulmonary atresia/ventricular septal defect associated with port-wine stain and retinal vascular abnormality is reported. Clinical findings were similar to both PHACE syndrome and Sturge-Weber syndrome (SWS). But, the most frequent and well-known features of both syndromes were absent. So, it could not be concluded whether this is a new constellation or an incomplete form of one of the two syndromes. In both situations, presence of a complex congenital heart disease that has not been reported previously makes this case original.     

Engaging participants in a complex intervention trial in Australian General Practice

Background  

The paper examines the key issues experienced in recruiting and retaining practice involvement in a large complex intervention trial in Australian General Practice.     

Germline polymorphisms as modulators of cancer phenotypes

Identifying the complete repertoire of genes and genetic variants that regulate the pathogenesis and progression of human disease is a central goal of post-genomic biomedical research. In cancer, recent studies have shown that genome-wide association studies can be successfully used to identify germline polymorphisms associated with an individual's susceptibility to malignancy. In parallel to these reports, substantial work has also shown that patterns of somatic alterations in human tumors can be successfully employed to predict disease prognosis and treatment response. A paper by Van Ness et al. published this month in BMC Medicine reports the initial results of a multi-institutional consortium for multiple myeloma designed to evaluate the role of germline polymorphisms in influencing multiple myeloma clinical outcome. Applying a custom-designed single nucleotide polymorphism microarray to two separate patient cohorts, the investigators successfully identified specific combinations of germline polymorphisms significantly associated with early clinical relapse. These results raise the exciting possibility that besides somatically acquired alterations, germline genetic background may also exert an important influence on cancer patient prognosis and outcome. Future 'personalized medicine' strategies for cancer may thus require incorporating genomic information from both tumor cells and the non-malignant patient genome.     

Infection with respiratory syncytial virus alters peptidergic innervation in the lower airways of guinea-pigs

To probe the mechanisms by which respiratory syncytial virus (RSV) infection in early life forms an important risk factor for the development of chronic asthma, an airway hyper-responsiveness (AHR) animal model of guinea-pigs with persistent RSV infection was established by intranasal instillation of 2 x 10(5) plaque-forming units RSV. On days 0, 7, 28, 42 and 60 postinoculation, the RSV copy numbers, airway function and peptidergic innervation were measured in the peripheral airways. The results showed that the virus was persistent in the lungs. During persistent infection (days 42 and 60), the lung resistance and the total cells, neutrophils and eosinophils of infected guinea-pigs increased significantly; the airway showed signs of chronic inflammation; and the substance P- and calcitonin gene-related peptide-positive fibres increased, but vasoactive intestinal polypeptide-positive fibres decreased. These results suggest that persistent RSV infection can cause long-term chronic airway inflammation and persistent airway neural network abnormality, which may be related to the occurrence of AHR.     

The genomic profile of HER2-amplified breast cancers: the influence of ER status

Expression profiling studies have suggested that HER2-amplified breast cancers constitute a heterogeneous group that may be subdivided according to their ER status: HER2-amplified ER-positive breast carcinomas that fall into the luminal B cluster; and HER2-amplified ER-negative cancers which form a distinct molecular subgroup, known as the erbB2 or HER2 subgroup. ER-negative breast cancer differs significantly from ER-positive disease in the pattern, type, and complexity of genetic aberrations. Here we have compared the genomic profiles of ER-positive and ER-negative HER2-amplified cancers using tiling path microarray-based comparative genomic hybridization (aCGH). Validation of the differentially amplified regions was performed in an independent series of 70 HER2-amplified breast cancers. Although HER2-amplified cancers had remarkably complex patterns of molecular genetic aberrations, ER-positive and ER-negative HER2-amplified breast carcinomas shared most molecular genetic features as defined by aCGH. Genome-wide Fisher's exact test analysis revealed that less than 1.5% of the genome was significantly differentially gained or lost in ER-positive versus ER-negative HER2-amplified cancers. However, two regions of amplification were significantly associated with ER-positive carcinomas, one of which mapped to 17q21.2 and encompassed GJC1, IGFBP4, TNS4, and TOP2A. Chromogenic in situ hybridization analysis of an independent validation series confirmed the association between ER status and TOP2A amplification. In conclusion, although hormone receptor status does not determine the overall genetic profile of HER2-amplified breast cancers, specific genetic aberrations may be characteristic of subgroups of HER2 breast cancers.     

Silencing preBötzinger complex somatostatin-expressing neurons induces persistent apnea in awake rat

Delineating neurons that underlie complex behaviors is of fundamental interest. Using adeno-associated virus 2, we expressed the Drosophila allatostatin receptor in somatostatin (Sst)-expressing neurons in the preB?tzinger Complex (preB?tC). Rapid silencing of these neurons in awake rats induced a persistent apnea without any respiratory movements to rescue their breathing. We hypothesize that breathing requires preB?tC Sst neurons and that their sudden depression can lead to serious, even fatal, respiratory failure.