The relevance of a staging laparotomy for Hodgkin's disease in India.

A retrospective analysis of 328 cases of Hodgkin's Disease (HD) subjected to a staging laparotomy at the Tata Memorial Hospital, Bombay, India, from 1974 to 1986 was undertaken to assess its relevance to our setup. Eighty percent of the patients were from clinical stages (CS) I and II, 38% with lymphocyte predominance (LP), and 41% with mixed cellularity (MC) histologies. Staging laparotomy was positive in 60% cases overall, including 50% from CS IA and IIA, 68% from CS IB and IIB, and 53% and 67%, respectively, from LP and MC histologies. Splenic involvement was seen in 54% cases. Operative complications were encountered in 2% of cases and deaths in two cases only. In view of the high propensity for abdominal spread, only selected CS IA and IIA cases would merit a staging laparotomy within which, nearly 50% cases with a negative yield could be offered radical segmental irradiation alone for cure. The majority of our patients would, however, require combination therapy.     

Constitutional genomic instability, chromosome aberrations in tumor cells and retinoblastoma

Although retinoblastoma (Rb) is initiated as a result of biallelic inactivation of the RB1 gene, additional genetic events (M3) in tumor cells are indicative of their role in the full transformation of retinal cells. We investigated the constitutional genetic instability by fragile site (FS) expression studies and checked its relationship with loci of tumor cytogenetics in a series of 36 retinoblastoma patients (34 nonfamilial and 2 familial cases). Tumor cytogenetics revealed -13/+13, del/t(13)(q14) (50%), +1/del/t(1p/q) (65%), +6/i(6p) (60%), and del(16)(q13)/(q22 approximately q23) (60%). Conventional cytogenetics in leukocytes revealed constitutional del(13q14) in five unilateral Rb (URB) and one trilateral Rb (TRB). Constitutional del(16)(q22) and t(6;12) were also identified in two cases. Constitutional FS analysis showed a significant increase in the cellular fragility, with high prevalence at 13q14, 3p14, 6p23, 16q22 approximately q23, and 13q22 loci in retinoblastoma patients (P<0.05). Patients with constitutional del(13)(q14) demonstrated higher fragility than those with normal constitution. A strong correlation between loci of constitutional FSs and loci of recurrent chromosomal abnormalities in tumors strengthen and support the proposal that FS loci present as inherent genomic instability in retinoblastoma. The chromosomal changes and resultant genetic mutations, along with RB1 mutation events, probably contribute synergistically to the development and progression of Rb malignancy. Implementation of fluorescence in situ hybridization to nonfamilial Rb on a large scale (113 cases) could detect constitutional RB1 deletion in 12.3% of cases, with equally higher incidence in URB (14.7%) and bilateral Rb (13.6%), demonstrating that the true prevalence of patients with predisposition to RB1 mutation in sporadic URB is definitely higher in our populations. Also, higher incidence of constitutional RB1 deletion mosaicism in unilateral than in bilateral Rb indicates that the constitutional genetic mosaicism in URB should be given serious consideration during genetic counseling.     

Complete Nucleotide Sequence Analysis of a Western Pacific Dengue-1 Virus Strain

We have determined the complete nucleotide sequence and the deduced amino acid polypeptide sequence of the genome of a dengue-1 (DEN-1) virus strain isolated from a patient on Nauru in the Western Pacific in 1974 (West Pac 74). The complete genome is 10,735 nucleotides in length and contains a single long open reading frame of 10,176 nucleotides encoding a polyprotein of 3392 amino acids. When compared to DEN-1 Singapore S275/90, the nucleotide and amino acid sequence homology are 94% and 97.8%, respectively. This revised version was published online in July 2006 with corrections to the Cover Date.     

Molecular characterization of scl rearrangements in T-cell all from India and egypt

SCL gene rearrangement is the most common molecular lesion (25%) identified so far in T-cell acute lymphoblastic leukemia (T-ALL). Since the frequency of T-ALL appears to be relatively higher in developing countries, we wished to determine as to what fraction of T-ALL from this population harbor SCL rearrangements. We show in this study that although the overall frequency of SCL/SIL rearrangements in T-ALL is similar to the Western countries this is at the expense of increased type A rearrangements. Whether the paucity of type B rearrangements reflects a difference in disease etiology in this part of the world is to be determined.     

Interphase nucleolar organizer region distribution in the tissues of oral leukoplakia, oral submucous fibrosis and oral cancer

The AgNOR technique, was applied to oral tissue sections of 185 oral cancer, 42 oral leukoplakia, 37 oral submucous fibrosis and 10 normal subjects to investigate whether any correlation held good in these different tissues. Compared to the AgNOR counts in normal oral epithelium, there was a gradation in increase in the mean AgNOR counts from oral leukoplakia to oral submucous fibrosis to oral carcinoma (P<0.01). This suggests that AgNOR count parallels with the degree of neoplastic transformation of oral epithelium. Three oral submucous fibrosis patients who showed very high AgNOR counts as that of oral cancer patients, later developed oral carcinoma. Among the oral cancer tissues, the moderately and poorly differentiated subtypes showed higher AgNOR counts and scattered distribution pattern than the well differentiated subtype which showed a clustered distribution pattern. These results suggest that AgNOR technique can be utilised as a diagnostic and prognostic indicator in premalignant and malignant oral tissues.     

Expression of adhesion molecules in B-cell chronic lymphocytic leukaemia: an analysis in lymphoid compartments--peripheral blood, bone marrow and lymph node

The trafficking or homing of different lymphoid subsets to particular microenvironment is mediated by specific cell adhesion molecules (CAMs) expressed on lymphocytes and endothelial cells. B-cell chronic lymphocytic leukaemia (B-CLL) or Non-Hodgkin's lymphoma of small lymphocytic, B-cell type are monoclonal expansions of mature lymphocytes. The relative distribution of the tumor lymphocytes among various lymphoid compartments vary from patient to patient. Very few studies underlying this issue are available. To this effect, we have analysed the expression of LFA-1; VLA-4, ICAM-1; CD44H and CD44v6 (haematopoietic and variant form respectively) on freshly isolated lymphocytes obtained from bone marrow (BM), peripheral blood (PB) and lymph node (LN) by flow cytometry. Overall, we find strong expression of CD44H, low to moderate expression of LFA-1, negative to low expression of VLA-4 and lack of expression of CD44v6. ICAM-1 expression was observed only in patients with prominent lymphadenopathy. Higher expression of CD44H in PB lymphoid cells relative to that of BM lymphoid cells correlated with higher PB lymphocytosis (p < 0.001). Proliferating cell nuclear antigen expression in LN sections correlated inversely with VLA-4 expression on BM and PB lymphoid cells (p < 0.05). There was no significant correlation between expression of CAMs and bcl-2 protein.     

Analysis of regulation of T-cell responses by soluble inhibitory factors from the sera of patients with Hodgkin's disease.

Soluble inhibitory factors (SIF) have been demonstrated in the sera of cancer patients, which interfere with the T-cell activation process. We have shown that the major contributory factor to the inhibitory effect of sera from patients with Hodgkin's disease (HD) could be the soluble form of Interleukin-2 receptors (sIL-2R). The parameters studied to show the presence of SIF include (i) inhibiton of mitogen-induced proliferation; (ii) status of high- and low-affinity IL-2R; and (iii) internalization of IL-2-IL-2R complex, by lymphocytes from healthy donors activated with mitogen in presence of HD sera. Parameters studied to show the inhibitory role of sIL2R include (i) quantitation of sIL-2R in HD sera; (ii) effect of high-sIL-2R-containing sera on mitogen-induced proliferation and detection of IL-2 in activated lymphocyte culture supernatants; (iii) effect of exogenous IL-2 supplementation; and (iv) abrogation of inhibitory activity of sIL-2R-containing sera after passing them through IL-2 affinity columns. Our results show that 6/23 HD sera tested had high inhibitory activity (greater than 50% inhibition of mitogen-induced proliferation). The SIF did not affect expression of high- and low-affinity IL-2 receptors, or internalization of the complex by activated lymphocytes. Ten of the 15 sera tested showed significantly high levels of sIL-2R. Pooled sera with high sIL-2R content inhibited mitogen-induced proliferation of normal lymphocytes with a concomitant reduction in IL-2 activity in the lymphocyte culture supernatants. When supplemented with exogenous IL-2, there was a partial recovery of the inhibitory effect. When sIL-2R containing serum pool was passed on IL-2 affinity columns, the inhibitory effect was reduced. The eluted "sIL-2R" adsorbed on the IL-2 column showed anti-proliferative effect.