RESUMEN
Helicobacter infection is associated with gastric cell growth alterations, plausibly predisposing to ulcer disease and gastric adenocarcinoma. Previous investigations from our laboratory have implicated the involvement of the Fas pathway in Helicobacter-induced apoptotic signaling in vitro. In this report we use C57BL/6J00064 mice to examine the direct role of Fas signaling in Helicobacter-mediated growth alterations in vivo. Helicobacter infection up-regulated gastric cell Fas antigen (Fas Ag) mRNA and increased surface receptor expression, along with concomitant altered apoptotic and proliferative response, measured by terminal deoxytransferase-deoxyuridine 5'-triphosphate nick end labeling and 5-bromo-2'-deoxuridine immunohistochemistry, respectively. In addition, histopathological alterations, including parietal cell loss and gastric atrophy, were noted. In contrast, infection in B6. MRL-FAS(lpr), a Fas Ag knockout mouse in the C57BL/6 background, did not result in increased apoptosis, proliferation, or histological alterations, a finding that argues strongly for the role of Fas-signaling pathway in orchestrating diverse growth responses to Helicobacter infection.
Asunto(s)
Infecciones por Helicobacter/patología , Estómago/patología , Receptor fas/fisiología , Animales , Apoptosis , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Infecciones por Helicobacter/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Ratones Noqueados , ARN Mensajero/metabolismo , Transducción de Señal , Receptor fas/genéticaRESUMEN
Chromosome 3p is consistently deleted in lung cancer, oral squamous cell carcinoma, and renal cell carcinoma, and is believed to contain several tumor suppressor genes. We have shown a role for chromosome 3 in tumor suppression by microcell-mediated chromosome transfer experiments. We have isolated a gene that is located at 3p21.3 within the smallest region of deletion overlap in lung tumors and is the human homolog of the ribosomal protein L14 gene (RPL14). The RPL14 sequence contains a highly polymorphic trinucleotide repeat array which encodes a variable-length polyalanine tract. Genotype analysis of RPL14 shows that this locus is 68% heterozygous in the normal population, compared with 25% in non-small cell lung cancer (NSCLC) cell lines (p = 0.008). Cell cultures derived from normal bronchial epithelium show a 65% level of heterozygosity, reflecting that of the normal population. Squamous cell carcinoma of the head and neck (SCCHN), which has the same risk factors as lung cancer and is hypothesized to have a similar etiology, demonstrates 54% loss of heterozygosity at the RNA level, suggesting that transcriptional loss may be a primary mechanism of RPL14 alteration in SCCHN. In addition, RPL14 shows significant differences in allele frequency distribution in ethnically-defined populations, making this sequence a useful marker for the study of ethnicity-adjusted lung cancer risk.
Asunto(s)
Cromosomas Humanos Par 3 , Pérdida de Heterocigocidad , Neoplasias Pulmonares/genética , Neoplasias de la Boca/genética , Proteínas Ribosómicas/genética , Repeticiones de Trinucleótidos , Biopsia , Carcinoma de Células Renales/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Mapeo Cromosómico , Clonación Molecular , Marcadores Genéticos , Variación Genética , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Neoplasias Pulmonares/patología , Proteínas Recombinantes/biosíntesisRESUMEN
The role of human immunodeficiency virus type 1 (HIV-1) accessory genes in pathogenesis has remained unclear because of the lack of a suitable in vivo model. The most controversial of these genes is nef. We investigated the requirement for Nef for in vivo replication and pathogenicity of two isolates of HIV-1 (HIV-1JR-CSF and HIV-1NL4-3) in human fetal thymus and liver implants in severe combined immunodeficient mice. HIV-1JR-CSF and HIV-1NL4-3 differ in their in vitro phenotypes in that HIV-1JR-CSF does not induce syncytia and is relatively noncytopathic, while HIV-1NL4-3 is highly cytopathic and readily induces syncytia. The nef mutants of both isolates grew with kinetics similar to those of parental virus strains in stimulated peripheral blood lymphocytes but demonstrated attenuated growth properties in vivo. HIV-1NL4-3 induced severe depletion of human thymocytes within 6 weeks of infection, whereas its nef mutant did not. Thus, HIV-1 Nef is required for efficient in vivo viral replication and pathogenicity.
Asunto(s)
Genes nef , VIH-1/genética , Animales , Secuencia de Bases , Efecto Citopatogénico Viral/genética , ADN Viral/genética , Infecciones por VIH/inmunología , Infecciones por VIH/microbiología , VIH-1/patogenicidad , VIH-1/fisiología , Humanos , Ratones , Ratones SCID , Datos de Secuencia Molecular , Mutación , Subgrupos de Linfocitos T/inmunología , Replicación Viral/genéticaRESUMEN
Testes of 15-day-old rats preincubated and incubated during different times with various doses of FSH (0.2; 2.0 and 20.0 mU/ml) in Krebs-Ringer bicarbonate (KRb) buffer increase the uptake of [14C] methylaminoisobutyric acid and [14C] aminoisobutyric acid. The basal and FSH stimulated amino acid transport occurs at absolute lower levels when the protein or glycoprotein synthesis is inhibited by cycloheximide (350 mumol/l) or tunicamycin (12 mumol/l) or when the microtubules are depolymerized with colchicine (1.2 mumol/l). However, the proportional increase of amino acid transport produced by FSH was maintained. The blockage of the voltage-dependent Ca++ channels with verapamil or the competitive inhibition of the bivalent ion channels by Co++ or Ni++ nullified the stimulatory action of FSH on the amino acid transport. Also quinine, that blocks the ATP dependent K+ channels, abolished the FSH action. It was concluded that in immature rat testes FSH stimulates amino acid transport through a mechanism involving voltage-dependent Ca++ channels and ATP-sensitive K+ channel.
Asunto(s)
Aminoácidos/metabolismo , Hormona Folículo Estimulante/fisiología , Testículo/metabolismo , Análisis de Varianza , Animales , Transporte Biológico Activo/fisiología , Canales de Calcio/metabolismo , Técnicas In Vitro , Masculino , Microtúbulos/metabolismo , Canales de Potasio/metabolismo , Inhibidores de la Síntesis de la Proteína/farmacología , Ratas , Ratas EndogámicasRESUMEN
A method of fascicular nerve repair utilizing silicone rubber tubes has been developed and tested in the dog whose nerves, like those of man, have a thick epineurial sheath. The closely fitting tubes provide a noncompressive enclosure which minimizes axonal escape and facilitates axon regeneration in at least two ways: First, they provide an impermeable conduit for endoneurial fluid whose constituents create an environment favoring the regeneration of axons and Schwann cells. Second, the biocompatible tube induces rapid development of a highly organized capsule which isolates the repair site, prevents adhesions, and strengthens the discontinuity. Enclosure of coapted fascicles also improves alignment of endoneurial components while providing space for the resolution of edema. The inert, noncompressive enclosures appear to minimize unregulated axonal growth at the site of injury by providing a qualitatively distinct environment from that in loose or open tubes.