Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H- RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.     

Rheologic predictors of the severity of the painful sickle cell crisis

Deformable sickle erythrocytes have been reported by Mohandas and Evans to be more adherent to vascular endothelium than rigid irreversibly sickled cells (ISC). To define the clinical implications of this finding we have determined genetic, hematological, clinical, and rheological characteristics of sickle erythrocytes obtained from 65 patients with sickle cell anemia and fetal hemoglobin (Hb F) levels less than 15%. The alpha-globin gene number had a significant effect on the hematological parameters, the percentage of dense cells, ISC number, and HB A2 levels. The presence or absence of alpha thalassemia, however, had no effect on the frequency and severity of the sickle cell painful crisis (r = 0.06, P greater than .05). RBC deformability, determined by an ektacytometer, showed great heterogeneity among patients with three or four alpha-globin genes. Linear regression analyses of the data showed significant positive correlation of the frequency and severity of the painful crisis with RBC deformability (r = 0.49, P less than .001), and negative correlations with the percentage of dense cells (r = -0.37, P = .002), and the percentage of ISC (r = -0.46, P less than .001). We propose that the more deformable the sickle RBC are, the greater their adherence to vascular endothelium, and the more they cause vaso-occlusive crises, RBC deformability and the percentage of dense cells (or ISC) seem to have a predictive value of the frequency and severity of painful crises in sickle cell anemia.     

Continent-wide evolutionary trends of emerging SARS-CoV-2 variants: dynamic profiles from Alpha to Omicron

The ongoing SARS-CoV-2 evolution process has generated several variants due to its continuous mutations, making pandemics more critical. The present study illustrates SARS-CoV-2 evolution and its emerging mutations in five directions. First, the significant mutations in the genome and S-glycoprotein were analyzed in different variants. Three linear models were developed with the regression line to depict the mutational load for S-glycoprotein, total genome excluding S-glycoprotein, and whole genome. Second, the continent-wide evolution of SARS-CoV-2 and its variants with their clades and divergence were evaluated. It showed the region-wise evolution of the SARS-CoV-2 variants and their clustering event. The major clades for each variant were identified. One example is clade 21K, a major clade of the Omicron variant. Third, lineage dynamics and comparison between SARS-CoV-2 lineages across different countries are also illustrated, demonstrating dominant variants in various countries over time. Fourth, gene-wise mutation patterns and genetic variability of SARS-CoV-2 variants across various countries are illustrated. High mutation patterns were found in the ORF10, ORF6, S, and low mutation pattern E genes. Finally, emerging AA point mutations (T478K, L452R, N501Y, S477N, E484A, Q498R, and Y505H), their frequencies, and country-wise occurrence were identified, and the highest event of two mutations (T478K and L452R) was observed.

     

A community-based, comparative evaluation of direct agglutination and rK39 strip tests in the early detection of subclinical Leishmania donovani infection

In the Indian state of Bihar, the sensitivities and specificities of direct agglutination tests (DAT) and rK39 test strips for the detection of Leishmania donovani infection in humans were explored and found to be generally good (92%-100%). When 172 asymptomatic individuals [16 'case-contacts' who lived in the same households as past or current, confirmed cases of visceral leishmaniasis (VL) and 156 other subjects from neighbouring households] were tested, the same 36 (21%) individuals, including all 16 'case-contacts', were found seropositive using each type of test. When followed-up after 3 months, 18 of the individuals who had been found seropositive in the baseline survey remained seropositive, and eight (44%) of these had developed symptomatic VL, with amastigotes in their splenic aspirates. Seven (44%) of the 16 'case-contacts' but only one (5%) of the other 20 subjects found seropositive at baseline went on to develop VL within 3 months. Although the strip test appeared slightly better than DAT for predicting the development of VL in the 172 subjects, either type of test may be very useful for the early detection of asymptomatic L. donovani infection and thus the identification of those at relatively high risk of developing VL.     

Detection and characterization of HIV type 2 in Calcutta, India

Since the first report of HIV/AIDS in India in 1986, continuous serosurveillance has been undertaken in all Indian states. Recently, five cases of HIV-2 infection have been detected in Calcutta, situated in the eastern part of India. The full-length envelope gene (2.5 kb) of one of the strains was amplified, cloned, and sequenced. Phylogenetic analysis of the Calcutta HIV-2 envelope revealed a close relatedness to the HIV-2 Rod sequence isolated in offshore Senegal. This strain, however, showed a genetic diversity of 13.5% to other Indian HIV-2 isolates.     

Clinical, haematological and histomorphological profile of adult myelodysplastic syndrome. Study of 96 cases in a single institute

Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders characterised by ineffective and dyspoietic haematopoiesis. The natural history of these disorders is variable and ranges from a chronic to a rapid course towards leukaemic progression. Certain shortcomings have been encountered in the French-American-British (FAB) classification over the years, and therefore there is a need for an alternative method of classification. In 1999, the WHO published a revised classification of MDS. In the present study, we have analysed the clinical, haematological and histomorphological features in 96 cases of primary MDS seen in the department of haematology at the All India Institute of Medical Sciences (AIIMS) over a 6-yr period (1996-2001). Both FAB and WHO classifications have been incorporated and the Bournemouth scoring system applied in each case at presentation. The Bournemouth scoring system, in the absence of a cytogenetic study, offers a good prognostication and long-term survival estimate.