N-cadherin/FGFR promotes metastasis through epithelial-to-mesenchymal transition and stem/progenitor cell-like properties.

N-cadherin and HER2/neu were found to be co-expressed in invasive breast carcinomas. To test the contribution of N-cadherin and HER2 in mammary tumor metastasis, we targeted N-cadherin expression in the mammary epithelium of the MMTV-Neu mouse. In the context of ErbB2/Neu, N-cadherin stimulated carcinoma cell invasion, proliferation and metastasis. N-cadherin caused fibroblast growth factor receptor (FGFR) upmodulation, resulting in epithelial-to-mesenchymal transition (EMT) and stem/progenitor like properties, involving Snail and Slug upregulation, mammosphere formation and aldehyde dehydrogenase activity. N-cadherin potentiation of the FGFR stimulated extracellular signal regulated kinase (ERK) and protein kinase B (AKT) phosphorylation resulting in differential effects on metastasis. Although ERK inhibition suppressed cyclin D1 expression, cell proliferation and stem/progenitor cell properties, it did not affect invasion or EMT. Conversely, AKT inhibition suppressed invasion through Akt 2 attenuation, and EMT through Snail inhibition, but had no effect on cyclin D1 expression, cell proliferation or mammosphere formation. These findings suggest N-cadherin/FGFR has a pivotal role in promoting metastasis through differential regulation of ERK and AKT, and underscore the potential for targeting the FGFR in advanced ErbB2-amplified breast tumors.

Isolation of Coxiella burnetii from human sources.

A total of 153 human milk samples were subjected to Capillary Agglutination Test (CAT) for determination of C. burnetii antibodies using phase-I CAT antigen and 22 (14.37%) samples were found to be positive. Twenty two CAT positive milk samples were further processed for the isolation of C. burnetii. Of seven samples positive in first screening, only four revealed presence of C. burnetii by giving specific seroconversion in guineapigs. Similarly, 16 aborted placentas were processed for C. burnetii and three yielded morphological evidence for rickettsial bodies on first screening. However, only one of three samples positive in first screening showed presence of C. burnetii in aborted placentas by specific seroconversion in guineapigs. Isolation of C. burnetii from aborted human placenta is the first report from India.

Cellular and humoral immune responses in sheep experimentally injected with killed and live Corynebacterium pseudotuberculosis.

Both humoral and cellular immune responses have been found to be operative in sheep experimentally injected with killed and live Corynebacterium pseudotuberculosis. However, immunity to sonicated C. pseudotuberculosis cells was primarily of humoral nature though cellular response was also noted. In contrast, live C. pseudotuberculosis cells evoked primarily a cellular response and the encountered humoral response was of lesser intensity. Challenge experiment revealed that humoral response alone was insufficient to protect, and the use of live cells to induce cellular response enhanced the immune status of sheep. It was also observed that nonvaccinated sheep in a herd can acquire immunity from their vaccinated counterparts suggesting a certain importance of 'herd immunity' in C. pseudotuberculosis vaccination.

Enterotoxigenicity and invasiveness of Salmonella species.

A large number of enterotoxigenic strain was encountered in a group 56 Salmonella cultures belonging to 8 species viz., S. alachua, S. anatum, S. dublin, S. Enteritidis, S. hindmarsh, S. newport, S. typhimurium, S. weltevreden, and 5 serotypes of S. arizona (16:z4:--; 48:1,v:z56; 53:z52:z53; 60:r:z; 60:i:z53). These cultures were isolated mainly from humans and animals suffering from gasteroenteritis. The enterotoxigenic (diarrhoeagenic) Salmonella cultures possess capacities for both skin permeation and epithelial penetration (invasiveness). Preliminary characterization revealed that Salmonella enterotoxin is a heat-labile protein of high molecular weight. It is suggested that enterotoxigenic and invasive properties play a vital role in the pathogenesis of Salmonella diarrhoea.

Isolation and characterization of Mycoplasma and Acholeplasma from apparently healthy and diseased (infectious sinusitis) turkeys.

Investigation of 136 turkeys (24 manifesting infra-orbital sinusitis, 112 apparently healthy) resulted in isolation of 79 strains of Mycoplasma and 4 of Acholeplasma. By the disc growth inhibition test with 16 reference antisera of avian serogroups, 55 strains were identified serologically and 28 remained unidentified. Thirteen strains of Mycoplasma gallisepticum, 1 of M. meleagridis, and 2 of Acholeplasma laidlawii were isolated from turkey sinusitis whereas serogroups C (2), D (19), F (8), M. meleagridis (4), M. anatis (4), A. laidlawii (2), and 28 unidentified strains were isolated from apparently healthy turkeys. Three patterns were recognized on the basis of glucose, maltose, and sucrose, fermentation. The most frequent, pattern I, included 13 M. gallisepticum strains whereas 5 M. meleagridis strains belonged to fermentation pattern III. Isolates were also studied for reduction of tetrazolium, methylene blue, potassium tellurite, resistance to methylene blue and sodium taurocholate, and production of arginine deiminase and "film and sports." Inoculation of selected isolates into developing chick embryos revealed that 2 A. laidlawii strains were nonpathogenic and 13 M. gallisepticum, 1 serogroup D and 2 serogroup F strains were pathogenic, causing 50--100% mortality. In vitro antibiotic disc sensitivity tests indicated that rovamycin (solubilized spiramycin) may be recommended for turkey mycoplasmosis. Isolation of 2 A. laidlawii strains from turkey sinusitis and 4 M. anatis strains from apparently healthy turkeys appears interesting.