Fine needle aspiration cytology diagnosis of lymphoproliferative disease of the breast

OBJECTIVE: To evaluate the role of fine needle aspiration cytology (FNAC) in the diagnosis of lymphoproliferative disease (LPD) of the breast. STUDY DESIGN: Over a period of 20 years (January 1982-December 2001), 13 diagnosed and/or suspected cases of LPD of the breast on FNAC were retrieved and reviewed from the files of the Cytology Laboratory, Department of Pathology, All India Institute of Medical Sciences. For each case, both May-Grünwald-Giemsa- and Papanicolaou-stained smears were reviewed along with hematoxylin and eosin-stained tissue sections and immunohistochemistry, when available. RESULTS: Of the 13 cases, 1 aspirate was from a male breast and the rest were from female. Only 12 cases with documented histology were included in the study. Five of the 12 cases were diagnosed on FNAC as high grade lymphoma, 2 as low grade lymphoma, 2 as poorly differentiated malignant tumor/lymphoma, and 1 each as Hodgkin's lymphoma, acute myeloid leukemia (AML) deposit and immature lymphoid cells, ?leukemia/lymphoma deposit. The tumors manifested mostly as an unilateral mass (10 cases), with 2 cases presenting with bilateral breast lumps. The lymph nodes were involved in 8 cases. Histologically, 2 of the 12 cases were poorly differentiated malignant tumors. Of the remaining 10 cases, 8 were documented as non-Hodgkin's lymphoma and 1 each as Hodgkin's lymphoma, mixed cellularity and AML. CONCLUSION: FNAC is an inexpensive but highly useful diagnostic tool to distinguish between primary lymphoma and carcinoma of the breast. This helps with clinical management in avoiding unnecessary surgical procedures.     

Omnivory and the stability of simple food webs

Traditional ecological theory predicts that the stability of simple food webs will decline with an increasing number of trophic levels and increasing amounts of omnivory. These ideas have been tested using protozoans in laboratory microcosms. However, the results are equivocal, and contrary to expectation, omnivory is common in natural food webs. Two recent developments lead us to re-evaluate these predictions using food webs assembled from protists and bacteria. First, recent modelling work suggests that omnivory is actually stabilizing, providing that interactions are not too strong. Second, it is difficult to evaluate the degree of omnivory of some protozoan species without explicit experimental tests. This study used seven species of ciliated protozoa and a mixed bacterial flora to assemble four food webs with two trophic levels, and four webs with three trophic levels. Protist species were assigned a rank for their degree of omnivory using information in the literature and the results of experiments that tested whether the starvation rate of predators was influenced by the amount of bacteria on which they may have fed and whether cannibalism (a form of omnivory) occurred. Consistent with recent modelling work, both bacterivorous and predatory species with higher degrees of omnivory showed more stable dynamics, measured using time until extinction and the temporal variability of population density. Systems with two protist species were less persistent than systems with one protist species, supporting the prediction that longer food chains will be less stable dynamically. Received: 28 December 1997 / Accepted: 22 June 1998     

Grey Matter Correlates of Three Language Tests in Non-demented Older Adults

Language has been extensively investigated by functional neuroimaging studies. However, only a limited number of structural neuroimaging studies have examined the relationship between language performance and brain structure in healthy adults, and the number is even less in older adults. The present study sought to investigate correlations between grey matter volumes and three standardized language tests in late life. The participants were 344 non-demented, community-dwelling adults aged 70-90 years, who were drawn from the population-based Sydney Memory and Ageing Study. The three language tests included the Controlled Oral Word Association Task (COWAT), Category Fluency (CF), and Boston Naming Test (BNT). Correlation analyses between voxel-wise GM volumes and language tests showed distinctive GM correlation patterns for each language test. The GM correlates were located in the right frontal and left temporal lobes for COWAT, in the left frontal and temporal lobes for CF, and in bilateral temporal lobes for BNT. Our findings largely corresponded to the neural substrates of language tasks revealed in fMRI studies, and we also observed a less hemispheric asymmetry in the GM correlates of the language tests. Furthermore, we divided the participants into two age groups (70-79 and 80-90 years old), and then examined the correlations between structural laterality indices and language performance for each group. A trend toward significant difference in the correlations was found between the two age groups, with stronger correlations in the group of 70-79 years old than those in the group of 80-90 years old. This difference might suggest a further decline of language lateralization in different stages of late life.     

PEST-dependent cytoplasmic retention of v-Rel by I(kappa)B-alpha: evidence that I(kappa)B-alpha regulates cellular localization of c-Rel and v-Rel by distinct mechanisms.

Association of c-Rel with the inhibitor of kappaB-alpha (IkappaB-alpha) protein regulates both cellular localization and DNA binding. The ability of v-Rel, the oncogenic viral counterpart of avian c-Rel, to evade regulation by p40, the avian IkappaB-alpha protein, contributes to v-Rel-mediated oncogenesis. The yeast two-hybrid system was utilized to dissect Rel:IkappaB-alpha interactions in vivo. We find that distinct domains in c-Rel and v-Rel are required for association with p40. Furthermore, while the ankyrin repeat domain of p40 is sufficient for association with c-Rel, both the ankyrin repeat domain and the PEST domain are required for association with v-Rel. Two amino acid differences between c-Rel and v-Rel that are principally responsible for PEST-dependent association of v-Rel with p40 were identified. These same amino acids were principally responsible for PEST-dependent cytoplasmic retention of v-Rel by p40. The presence of mutations in c-Rel that were sufficient to confer PEST-dependent association of the mutant c-Rel protein with p40 did not increase the weak oncogenicity of c-Rel. However, the introduction of these two c-Rel-derived amino acids into v-Rel markedly reduced the oncogenicity of v-Rel. Deletion of the NLS of either c-Rel or v-Rel did not abolish association with p40, but did confer PEST-dependent association of c-Rel with p40. Surprisingly, deletion of the nuclear localization signal in v-Rel did not affect oncogenicity by v-Rel. Analysis of several mutant c-Rel and v-Rel proteins demonstrated that association of Rel proteins with p40 is necessary but not sufficient for cytoplasmic retention. These results are not consistent with the hypothesis that p40 regulates cellular localization of v-Rel and c-Rel by the same mechanism. Rather, these results support the hypothesis that p40 regulates cellular localization of v-Rel and c-Rel by distinct mechanisms.     

Alteration in virulence characteristics of biofilm cells of Pseudomonas aeruginosa in presence of Tamm-Horsfall protein

Summary Tamm-Horsfall glycoprotein is the most abundant protein in human urine. The present investigation was planned to study the effect of Tamm-Horsfall protein (THP) on elaboration of virulence factors by biofilm cells of Pseudomonas aeruginosa. It was observed that with increase in concentration of THP from 10 to 50 μg/ml there was significant enhancement in elaboration of all the virulence factors by biofilm cells of P. aeruginosa. However, with further increase in concentration of THP from 50 to 70 μg/ml, significant decrease in elaboration of all the virulence traits was observed. Implications of these findings in relation to urinary tract infections caused by P. aeruginosa have been discussed.     

Functional genomics of intracellular peptide recognition domains with combinatorial biology methods

Phage-displayed peptide libraries have been used to identify specific ligands for peptide-binding domains that mediate intracellular protein-protein interactions. These studies have provided significant insights into the specificities of particular domains. For PDZ domains that recognize C-terminal sequences, the information has proven useful in identifying natural binding partners from genomic databases. For SH3 domains that recognize internal proline-rich motifs, the results of database searches with phage-derived ligands have been compared with the results of yeast-two-hybrid experiments to produce overlap networks that reliably predict natural protein-protein interactions. In addition, libraries of phage-displayed PDZ and SH3 domains have been used to identify the residues responsible for ligand recognition, and also to engineer domains with altered specificities.     

A specificity map for the PDZ domain family

PDZ domains are protein-protein interaction modules that recognize specific C-terminal sequences to assemble protein complexes in multicellular organisms. By scanning billions of random peptides, we accurately map binding specificity for approximately half of the over 330 PDZ domains in the human and Caenorhabditis elegans proteomes. The domains recognize features of the last seven ligand positions, and we find 16 distinct specificity classes conserved from worm to human, significantly extending the canonical two-class system based on position -2. Thus, most PDZ domains are not promiscuous, but rather are fine-tuned for specific interactions. Specificity profiling of 91 point mutants of a model PDZ domain reveals that the binding site is highly robust, as all mutants were able to recognize C-terminal peptides. However, many mutations altered specificity for ligand positions both close and far from the mutated position, suggesting that binding specificity can evolve rapidly under mutational pressure. Our specificity map enables the prediction and prioritization of natural protein interactions, which can be used to guide PDZ domain cell biology experiments. Using this approach, we predicted and validated several viral ligands for the PDZ domains of the SCRIB polarity protein. These findings indicate that many viruses produce PDZ ligands that disrupt host protein complexes for their own benefit, and that highly pathogenic strains target PDZ domains involved in cell polarity and growth.     

Nuclear import of IkappaBalpha is accomplished by a ran-independent transport pathway

The inhibitor of kappa B alpha (IkappaBalpha) protein is able to shuttle between the cytoplasm and the nucleus. We have utilized a combination of in vivo and in vitro approaches to provide mechanistic insight into nucleocytoplasmic shuttling by IkappaBalpha. IkappaBalpha contains multiple functional domains that contribute to shuttling of IkappaBalpha between the cytoplasm and the nucleus. Nuclear import of IkappaBalpha is mediated by the central ankyrin repeat domain. Similar to previously described nuclear import pathways, nuclear import of IkappaBalpha is temperature and ATP dependent and is blocked by a dominant-negative mutant of importin beta. However, in contrast to classical nuclear import pathways, nuclear import of IkappaBalpha is independent of soluble cytosolic factors and is not blocked by the dominant-negative RanQ69L protein. Nuclear export of IkappaBalpha is mediated by an N-terminal nuclear export sequence. Nuclear export of IkappaBalpha requires the CRM1 nuclear export receptor and is blocked by the dominant-negative RanQ69L protein. Our results are consistent with a model in which nuclear import of IkappaBalpha is mediated through direct interactions with components of the nuclear pore complex, while nuclear export of IkappaBalpha is mediated via a CRM1-dependent pathway.