Immunocytoma: a retrospective analysis from St Bartholomew's Hospital-1972 to 1996.

PURPOSE: To analyze the presentation features and outcome for patients with immunocytoma (IMC) managed at St Bartholomew's Hospital (SBH), London, United Kingdom, between 1972 and 1996. Outcome was compared with that of patients with small lymphocytic lymphoma (SLL)/B-cell chronic lymphocytic leukemia (B-CLL) treated at SBH during the same period. PATIENTS AND METHODS: One hundred twenty-six patients with newly diagnosed IMC were identified. Patients were subclassified (using the Kiel classification) as having lymphoplasmacytoid (n =92), lymphoplasmacytic (n = 24), polymorphous (n = 9), or undetermined (n = 1) IMC. Six patients (5%) had stage I to IIE disease; the rest had advanced disease. Treatment was given according to disease stage. Seven patients were managed expectantly. RESULTS: Eighty-two (69%) of 119 patients responded to treatment, but complete remission was seen in only 15 (13%) of 119. Treatment failed in 29 (24%) of 119 patients. There were three treatment-related deaths; five patients were not assessable for response. When survival of patients with IMC was compared with that of patients with B-CLL/SLL, a significant difference was found (P <. 01); this difference was maintained when only patients in whom the diagnosis was based on lymph node biopsy were considered (P =.01). A comparison of the three IMC subgroups showed that there was a trend (P =.06) toward a difference between B-CLL/SLL and the lymphoplasmacytoid subtype. CONCLUSION: Patients diagnosed with IMC are generally older and present with advanced disease. Conventional therapies usually result in incomplete responses of short duration. Overall, these results support the proposed World Health Organization reclassification of IMC to include lymphoplasmacytoid lymphoma (Kiel classification) as a variant of B-CLL/SLL.     

Characterisation of Two Metallothionein cDNAs from the Shore Crab for use as Biomarkers of Heavy Metal Pollution

Molecular biological procedures open up possibilities for the development of new biomarker assays for use in environmental monitoring studies. Metallothionein (MT) is a useful biomarker for monitoring pollution by heavy metals and since very little information is available on the genes for MT in marine invertebrates, studies have been initiated in order to develop probes for use in biomarker assays for MT in the shore crab (Carcinus maenas). RNA isolated from the gills of shore crabs was used to produce complementary DNA (cDNA) from which two incomplete and two complete MT cDNAs have been isolated and characterised. The first complete cDNA (cDNA-4) encodes for a protein of 58 amino acids with a predicted molecular mass of 6151 Da; the predicted amino acid sequence of this protein is identical to that determined earlier for MT-Ib isolated from cadmium-exposed crabs. The second complete cDNA (cDNA-3) encodes a protein of 41 amino acids with a predicted molecular mass of 4484 Da; only the 5 C-terminal residues of this truncated MT differ from those at the corresponding positions of MT-Ib and this may correspond to a 4100 Da MT also reported previously. The implications of these findings and the use of these cDNAs as biomarkers in ecotoxicological studies are discussed.     

HLA Class II Alleles and the Presence of Circulating Epstein-Barr Virus DNA in Greek Patients with Nasopharyngeal Carcinoma

BACKGROUND AND PURPOSE: Nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. PATIENTS AND METHODS: A total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. RESULTS: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p = 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. CONCLUSION: Circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection.     

A mathematical model of mortality dynamics across the lifespan combining heterogeneity and stochastic effects

The mortality patterns in human populations reflect biological, social and medical factors affecting our lives, and mathematical modelling is an important tool for the analysis of these patterns. It is known that the mortality rate in all human populations increases with age after sexual maturity. This increase is predominantly exponential and satisfies the Gompertz equation. Although the exponential growth of mortality rates is observed over a wide range of ages, it excludes early- and late-life intervals. In this work we accept the fact that the mortality rate is an exponential function of age and analyse possible mechanisms underlying the deviations from the exponential law across the human lifespan. We consider the effect of heterogeneity as well as stochastic factors in altering the exponential law and compare our results to publicly available age-dependent mortality data for Swedish and US populations. In a model of heterogeneous populations we study how differences in parameters of the Gompertz equation describing different subpopulations account for mortality dynamics at different ages. Particularly, we show that the mortality data on Swedish populations can be reproduced fairly well by a model comprising four subpopulations. We then analyse the influence of stochastic effects on the mortality dynamics to show that they play a role only at early and late ages, when only a few individuals contribute to mortality. We conclude that the deviations from exponential law at young ages can be explained by heterogeneity, namely by the presence of a subpopulation with high initial mortality rate presumably due to congenital defects, while those for old ages can be viewed as fluctuations and explained by stochastic effects.     

Propagation and characterization of lymphocytes infiltrating livers of patients with primary biliary cirrhosis and autoimmune hepatitis

Lymphocytes were propagated with interleukin 2 from liver tissue removed at transplantation from patients with primary biliary cirrhosis or autoimmune chronic active hepatitis. Phenotypic analysis of the cultured lymphocytes as well as the infiltrating cells in situ indicated that the culture technique did not select for a particular phenotype. Eight cultures were tested for cell-mediated lympholysis activity against a bile duct tumor line as well as a hepatocellular carcinoma line, but no specific killing was seen. In addition, no natural killer activity was detected. However, the lymphocyte cultures were able to kill the targets in a lectin-dependent cytotoxicity assay, indicating their cytolytic effector activity. Preliminary studies have demonstrated that lymphocytes extracted from hepatic tissue and hilar lymph nodes from a patient with primary biliary cirrhosis proliferated in response to autologous biliary epithelial cells. These methods might be useful in studying the pathogenesis of primary biliary cirrhosis and other liver diseases with autoimmune features.     

Banff Schema for Grading Pancreas Allograft Rejection: Working Proposal by a Multi-Disciplinary International Consensus Panel

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined.
The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.