Metabotropic glutamate receptor 1 (Grm1) is an oncogene in epithelial cells.

Non-neuronal expression of components of the glutamatergic system has been increasingly observed, and our laboratory previously had demonstrated the etiological role of ectopically expressed metabotropic glutamate receptor 1 (Grm1/mGluR1) in mouse models of melanoma. We hypothesize that inappropriate glutamatergic signaling in other cell types can dysregulate growth leading to transformation and tumorigenesis. As most cancers are carcinomas, we selected an immortalized primary baby mouse kidney (iBMK) cell model to assess whether Grm1 can transform epithelial cells. These iBMK cells, engineered to be immortal yet nontumorigenic and retaining normal epithelial characteristics, were used as recipients for exogenous Grm1 cDNA. Several stable Grm1-expressing clones were isolated and the Grm1-receptors were shown to be functional, as evidenced by the accumulation of second messengers in response to Grm1 agonist. Additionally activated by agonist were mitogen-activated protein kinase (MAPK) and AKT/protein kinase B signaling cascades, the major intracellular pathways shown by many investigators to be critical in melanomagenesis and other neoplasms. These Grm1-iBMK cells exhibited enhanced cell proliferation in in vitro methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays and significant tumorigenicity in in vivo allografts. Persistent Grm1 expression was required for the maintenance of the in vivo tumorigenic phenotype as demonstrated by an inducible Grm1-silencing RNA. These are the first results that indicate that Grm1 can be an oncogene in epithelial cells. In addition, relevance to human disease in the corresponding tumor type of renal cell carcinoma (RCC) may be suggested by observed expression of GRM1/mGluR1 in a number of RCC tumor biopsy samples and cell lines, and the effects of GRM1 modulation on tumorigenicity therein. Moreover, RCC cell lines exhibited elevated levels of extracellular glutamate, and some lines responded to drugs, which modulate the glutamatergic system. These findings imply a possible role for glutamate signaling apparatus in RCC cell growth, and that the glutamatergic system may be a therapeutic target in RCC.

Temporal regulation of gene expression in adipocyte differentiation.

Cells usually become 'committed' to differentiate long before any actual morphological change is apparent. In one model commitment is a decision which corresponds to the expression of a control gene, while differentiation is the ultimate consequence of that decision. We have been studying adipocyte commitment and differentiation at the molecular level. Earlier we showed that the introduction of a specific DNA sequence into 'uncommitted' cells renders those cells committed to differentiate into adipocytes. Here we report temporal regulation of the expression of this DNA sequence; furthermore, we show that this RNA is in the non-polyA+ fraction of total cellular RNA. These data suggest that coordinate regulation of this and other genes is important in promoting differentiation.

Prevalence of microorganisms in dead mink kits from Aleutian-disease-infected and non-infected farms.

Bacterial and fungi were isolated from different tissues (brain, liver, heart) taken from 81 dead newborn mink originating from Aleutian disease (AD) infected and AD-non-infected farms. Of the 123 isolates obtained, 96% were bacterial isolates (predominantly Gram-negative) and 4% were fungi. The prevalence of microorganisms appeared less common in kits from AD-non-infected farms (55%) than from AD-infected farms (73%), although the difference was not significant. The liver was the most highly infected site in both groups and generally was only infected by one microorganism species. Proteus spp (23%), Escherichia coli (16%), Staphylococcus aureus (11%) and Enterobacter cloacae (9%) were the most frequently isolated germs. These findings are similar to those of other studies but the role of these microorganisms as specific pathogens or secondary invaders remains controversial.

Genomic sequences capable of committing mouse and rat fibroblasts to adipogenesis.

The mouse Swiss 3T3-F442A/3T3-C2 cell system is well suited for the isolation of genes involved in commitment to adipogenesis. 3T3-F442A cells convert to adipocytes with high efficiency in response to confluence and insulin. The sister clonal line 3T3-C2 does not respond to these signals, but can convert to adipocytes when transfected with DNA from 3T3-F442A preadipocytes or from human fat. Human fat-tissue biopsy FO46 DNA transfected into 3T3-C2 gave rise to fat foci after two rounds of transfection and selection. A cosmid library of a subclone of secondary transfectant 3T3-C2/FO46-1 was screened for the human repetitive Alu sequence. Five out of eight Alu+ recombinant clones committed 3T3-C2 cells to adipogenesis. The adipose commitment (AC) activity of one cosmid, p18A4, was found to reside in two small, non-identical, subcloned sequences 1.2kb and 2.0kb in length, each separately able to commit 3T3-C2, precrisis mouse and rat fibroblasts and the multipotential C3H10T1/2 cell line to adipogenesis. We conclude that commitment to adipogenesis can be effected in vitro with high efficiency by transfection of specific sequences into a variety of host cells.

A note on diseases of mink.

The paper describes in brief the findings in 5,616 autopsies of adult mink, performed at the Institute of Pathology-CIC, La Plata, during the last five years. Nearly all these carcasses, coming from the most important ranches, were examined bacteriologically and histopathologically. Observations about the incidence of different causes of death, its distribution annually and prophylactic measures were reported. It concludes that Aleutian disease is the most important cause of death and produces severe economic losses.

[Hemorrhagic pneumonia caused by Pseudomonas aeruginosa in mink in Argentina]. / Neumonía hemorrágica por Pseudomonas aeruginosa en visones de la República Argentina.

This work describes the first Haemorrhagic Pneumonia cases in minks not only from Argentina, but from South hemisphere as well. Epidemiology, symptomatology and macro and microscopic lesions found were similar to those described in other countries. The diagnosis was done by isolation of Pseudomonas aeruginosa in large numbers from affected lungs, and serotype no. 6 (Difco system) was the most frequent. Haemorrhagic Pneumonia was experimentally reproduced after infecting intranasally narcotized minks.

Neumonía hemorrágica por Pseudomonas aeruginosa en visones de la República Argentina / Hemorrhagic pneumonia by Pseudomonas aeruginosa in minks of Argentina

Esta es la primera comunicación acerca de la existencia de casos de neumonía hemorrágica en visones en la República Argentina y en el hemisferio sur. La epidemiología de la enfermedad es similar a la descripta en otros países, al igual que la sintomalogía y las lesiones macro y microscópicas. El diagnóstico se efectuó con el aislamiento de Pseudomonas aeruginosa en repetidas ocasiones de los pulmones afectados, siendo el serotipo nro. 6 (Sistema Difco) el más frecuente. Se reprodujo experimentalmente la enfermedad infectando visones por vía intranasal previa narcosis de los mismos

Neumonía hemorrágica por Pseudomonas aeruginosa en visones de la República Argentina. / [Hemorrhagic pneumonia caused by Pseudomonas aeruginosa in mink in Argentina]

This work describes the first Haemorrhagic Pneumonia cases in minks not only from Argentina, but from South hemisphere as well. Epidemiology, symptomatology and macro and microscopic lesions found were similar to those described in other countries. The diagnosis was done by isolation of Pseudomonas aeruginosa in large numbers from affected lungs, and serotype no. 6 (Difco system) was the most frequent. Haemorrhagic Pneumonia was experimentally reproduced after infecting intranasally narcotized minks.

Neumonía hemorrágica por Pseudomonas aeruginosa en visones de la República Argentina / Hemorrhagic pneumonia by Pseudomonas aeruginosa in minks of Argentina

Esta es la primera comunicación acerca de la existencia de casos de neumonía hemorrágica en visones en la República Argentina y en el hemisferio sur. La epidemiología de la enfermedad es similar a la descripta en otros países, al igual que la sintomalogía y las lesiones macro y microscópicas. El diagnóstico se efectuó con el aislamiento de Pseudomonas aeruginosa en repetidas ocasiones de los pulmones afectados, siendo el serotipo nro. 6 (Sistema Difco) el más frecuente. Se reprodujo experimentalmente la enfermedad infectando visones por vía intranasal previa narcosis de los mismos (AU)