Recombinant protein-based assays for detection of antibodies to severe acute respiratory syndrome coronavirus spike and nucleocapsid proteins

Recombinant severe acute respiratory syndrome (SARS) nucleocapsid and spike protein-based immunoglobulin G immunoassays were developed and evaluated. Our assays demonstrated high sensitivity and specificity to the SARS coronavirus in sera collected from patients as late as 2 years postonset of symptoms. These assays will be useful not only for routine SARS coronavirus diagnostics but also for epidemiological and antibody kinetic studies.     

Basaloid carcinoma of the pancreas

A case of basaloid carcinoma of the pancreas in a 26-year-old woman is reported. The tumour was constituted by solid nests of relatively uniform neoplastic cells with hyperchromatic nuclei and scant cytoplasm, showing distinct peripheral palisading. There were necrotic areas and deposition of hyaline material, suggesting a basement membrane-like substance. Small foci of clear-cut squamous differentiation were present. Tumour cells were positive for cytokeratin 14 and P63 and negative for neuroendocrine and acinic cell markers. Ultrastructurally, the tumour was constituted by polygonal cells with round nuclei containing clumped chromatin. Occasional tight junctions and keratin filaments were present. Basaloid carcinomas may arise in several sites of the body, the most frequent being the anus and oesophagus, and have poor clinical outcome. The present case appears to be, to the best of our knowledge, the first documented example in the literature of basaloid carcinoma of the pancreas.     

Pigmented mucoepidermoid carcinoma of the oral cavity: a case report

Melanocytes are normally present in the oral mucosa, but unlike the skin, melanocytic colonization and pigmentation of nonmelanocytic tumors rarely occur. A case of pigmented mucoepidermoid carcinoma (MEC) in a 36-year-old woman is reported. On H&E-stained sections, brownish granules were seen in intermediate and epidermoid neoplastic elements and in elongated or dendritic cells showing histologic and immunohistochemical features of melanocytes. Ultrastructurally numerous epithelial cells contained large aggregates of melanin granules, a feature suggestive of phagocytosis. In addition small individual melanin granules were observed at the external border of the epithelial cell membrane. These features suggest that melanocytes colonized the MEC and that neoplastic cells may phagocytose the granules, similarly to what occurs with epidermal melanocytes. The phenomenon of melanocyte colonization of nonmelanocytic tumors should be taken into consideration in dealing with pigmented lesions of the oral cavity.     

Trisomy 1q generating translocations in Wilms tumor

Unbalanced translocations generating trisomy of 1q are common in Wilms tumor (WT). We present eight unbalanced 1q translocations from seven tumors and a review of the literature. An unbalanced translocation that results in a der(16)t(1q;16q) chromosome represents more than half of the published +1q generating translocations in WT. This translocation is also common to many other tumor types. Four of the tumors presented here contained this chromosome and,in two cases, it was the primary acquired cytogenetic abnormality within the tumor. The other four translocations involved 9q31, 9q34, 17p1?, and 21p11 as the partner to 1q. The chromosome 17 and 21 translocations occurred within the same tumor as apparently independent events. In contrast with the 16q translocations, these other translocations were secondary cytogenetic events, thereby indicating a role in tumor progression rather than initiation. Probes mapping to 1q12 and 1q21 were employed for fluorescence in situ hybridization and it was demonstrated that different 1q breakpoints are possible. In this series, the majority of breakpoints either mapped to 1q12 or were centromeric to this region.     

Case Report: Congenital Radioulnar Synostosis and Its Embryological Correlation and Functional Assessment

Congenital radioulnar synostosis(CRS) is a rare anomaly and approximately 400 cases were reported worldwide so far. CRS is the failure of the longitudinal segmentation and the persistence of the cartilaginous anlage between the radius and ulna during the seventh week of development that results in a persistent bridge of tissue. Here we are discussing on a case of 25yrs old, male patient with bilateral congenital synostosis. On the left hand the pronation and supination movements are restricted completely where as on right side 10 degree of supination and 20 degree of pronation is possible. Radiologically in our patient synostosis is classified as type II variety by Wilkie(1914)1 classification and type IV by the Cleary and Omer classification(1985). The position of forearm was not found to be related to subjective functional limitation, or employment status. Main line of treatment is surgical mainly rotational osteotomy but is rarely indicated. Our patient is not able to rotate his forearm especially on the left side still he has no functional limitation so he has refused for the operative treatment. No study has objectively compared the preoperative functional limitation of the patients with their postoperative functional improvement in order to justify surgical intervention In the authors opinion the only major factor that is to be taken into consideration of operative treatment is functional limitation to the patient.     

Living in a house of cards: re-evaluating CD8+ T-cell immune correlates against HIV

The Merck STEP and the Thai RV144 human immunodeficiency virus (HIV) vaccine trials confirmed that we still have a long way to go before developing a prophylactic HIV vaccine. The main issue at hand is that we have yet to identify an immunological correlate of protection against HIV. While many question the T-cell-based approach towards vaccine development, it is likely that T cells will be a necessary part of any vaccine strategy. CD8(+) T cells remain an attractive option because of their ability to specifically recognize and eliminate virally infected host cells. In this review, we recapitulate the evidence for CD8(+) T cells as an immunological correlate against HIV, but more importantly, we assess the means by which we evaluate their antiviral capacity. To achieve a breakthrough in the domain of T-cell-based HIV vaccine development, it has become abundantly clear that we must overhaul our system of immune monitoring and come up with a 'rational' tactic to evaluate the efficacy of HIV-specific CD8(+) T cells.     

Peripheral cytokine responses to Trichuris muris reflect those occurring locally at the site of infection

The study of human cellular immune responses to parasite infection under field conditions is very complex. Often, the only practical site from which to sample the cellular responses is the peripheral blood. Sampling peripheral blood lymphocytes (PBL) relies on the assumption that these peripheral responses accurately reflect the immune responses acting locally at the site of infection. This is a particularly important point for the human intestinal helminth Trichuris trichiura, which solely inhabits the cecum and large intestine and so will stimulate a localized immune response. Using the well-defined model of T. trichiura, T. muris in the mouse, we have demonstrated that the dominant cytokine responses of the mesenteric lymph nodes (MLN) can be detected by sampling PBL. Resistant mice which mount a type 2 cytokine response in their MLN had PBL producing interleukin-4 (IL-4), IL-5, and IL-9, with negligible levels of gamma interferon (IFN-gamma). Conversely, susceptible mice which mount a type 1 cytokine response in their MLN had PBL producing IFN-gamma and negligible levels of type 2 cytokines. We have also shown that the PBL are capable of mounting a functional immune response against T. muris. PBL from immune mice were capable of transferring immunity to T. muris-infected severe combined immunodeficient (C.B-17 scid/scid) mice. Sampling PBL responses is therefore a viable option for monitoring human intestinal immune responses during T. trichiura infection in the field.     

FGFR2, HER2 and cMet in gastric adenocarcinoma: detection,prognostic significance and assessment of downstream pathway activation

Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2 amplification was identified in 2 % of cases and associated with worse survival (P?=?0.005). HER2 overexpression was observed in 10 % of cases and associated with increased survival (P?=?0.041). cMet overexpression was observed in 4 % of cases and associated with worse survival (P?<?0.001). On multivariate analysis, only cMet retained significance (P?=?0.006). pS6 and pERK expression were observed in 73 % and 30 % of tumours, respectively, with no association with survival. HER2 (P?=?0.004) and pERK (P?=?0.001) expression differed between tumour regions with HER2 expression increased in the LS compared with the TB and IE. These findings confirm subpopulations in gastric adenocarcinoma with poor outcome that may benefit from specific therapeutic strategies. However, we found heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for their use as predictive biomarkers in gastric biopsies. The potential downstream pharmacodynamic markers pS6 and pERK were expressed across tumour regions, providing evidence that resections and biopsies would yield comparative results in clinical trials.