RESUMO
Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to redshifts of z approximately 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 +/- 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe.
RESUMO
Cell surface proteins encoded by members of the immunoglobulin supergene family are sequentially expressed during T cell ontogeny. The molecular mechanisms responsible for the regulation of these surface molecules are not well understood. To investigate this issue, we used a series of well characterized T lymphoma cell clones with phenotypes characteristic of distinct stages of early thymocyte maturation. Somatic cell hybrids formed from these cell lines were employed to detect the presence of negative regulatory molecules. The expression of CD4 and CD8 was strongly repressed in hybrids formed between a CD4+ CD8+ lymphoma clone and "immature" CD4- CD8- lymphoma clones. Individual subunits of the T cell receptor (TCR)/CD3 complex displayed independent regulation in unique patterns in hybrid cells. Hybrids formed by fusing CD3+ and CD3- cells completely repressed CD3-delta mRNA expression while CD3-gamma, -epsilon, and -zeta transcripts were moderately inhibited or codominantly regulated. Similar to CD3-delta, interleukin 2R-alpha(IL-2R-alpha), and TCR-beta mRNA accumulation was trans-negatively regulated. Transcription rate measurements demonstrated that the inhibition of CD4, CD8, CD3-gamma, CD3-epsilon, TCR-beta, and IL-2R-alpha mRNA accumulation in hybrid cells was exerted, at least in part, at the transcriptional level. To test whether repressional regulation is a general feature of T cells, we examined the regulation of six novel genes which were selected solely on the basis of their differential expression between two of the cell lines used in this study. Five of the six novel gene transcripts were repressed in the somatic cell hybrids. Thus, inhibitor factors appear to play a general role in controlling T cell gene expression. The model system presented here may be useful for the identification and characterization of repressor molecules responsible for the regulation of genes expressed during T cell ontogeny.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Antígenos CD4/genética , Linfoma de Células T/imunologia , Linfócitos T/imunologia , Transcrição Gênica , Animais , Antígenos de Superfície/genética , Northern Blotting , Antígenos CD8 , Linhagem Celular , Núcleo Celular/fisiologia , Células Clonais , Sondas de DNA , Citometria de Fluxo , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Células Híbridas , Linfoma de Células T/genética , Camundongos , RNA Mensageiro/genética , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Receptores de Interleucina-2/genéticaRESUMO
The XLR gene family consists of approximately 10 X-linked genes, the expression of which is regulated in lymphocyte development. Certain members of the gene family are closely linked to the murine xid immune deficiency mutation. Sequence analysis of a cDNA clone pM1 derived from the plasmacytoma MOPC167 showed an open reading frame capable of coding for a protein of 208 amino acids and mol wt 24,000. The lack of a signal peptide or transmembrane region indicates a probable cytoplasmic or nuclear localization for the predicted pM1 protein. The predicted protein shares significant homology with lamins A and C and other members of the intermediate filament family of proteins, and shares features important for the coiled-coil structure proposed for these proteins. Analysis of cDNA clones derived from a presecretory lymphoma and from adult thymus indicates that B and T lymphocytes transcribe a common major mRNA identical to pM1, while other rare transcripts were also identified by these studies. A series of clonal T lymphoma lines representing distinct stages of thymic differentiation showed that, as with B lymphoid tumors, XLR expression is correlated with the maturation of the thymomas.
Assuntos
Síndromes de Imunodeficiência/genética , Linfócitos/fisiologia , Família Multigênica , Cromossomo X , Sequência de Aminoácidos , Animais , Sequência de Bases , Diferenciação Celular , Clonagem Molecular , DNA/genética , Regulação da Expressão Gênica , Proteínas de Filamentos Intermediários/genética , Laminas , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares/genéticaRESUMO
Cisplatin (DDP) is the most effective drug for the treatment of human ovarian cancer, but the mechanisms that determine sensitivity to the cytotoxic action of DDP are not well understood. Treatment of two human ovarian carcinoma cell lines with epidermal growth factor (EGF) simultaneously increased sensitivity to DDP and caused a persistent change in morphology in the absence of any mitogenic effect. Sensitization to DDP was shown to be dependent on both EGF concentration and EGF receptor number in C127 mouse fibroblasts expressing the human EGF receptor after transfection with a pBPV plasmid construct containing the human EGF receptor gene under control of the transferrin receptor 3'-inducible regulator. Sensitization of human ovarian carcinoma cells to DDP was not blocked by inhibition of protein synthesis. EGF did not enhance sensitivity to DDP or alter morphology in DDP-resistant human ovarian carcinoma cells despite the presence of functional EGF receptors on these cells. These results showed that elements of the signal transduction pathway activated by EGF determined cellular sensitivity to DDP, and that a DDP-resistant phenotype is associated with a defect in this signal transduction pathway.
Assuntos
Cisplatino/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Neoplasias Ovarianas/metabolismo , Animais , Linhagem Celular , Receptores ErbB/metabolismo , Feminino , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Transdução de Sinais , Fatores de Tempo , Células Tumorais CultivadasRESUMO
A novel cDNA clone (20.5) which is differentially expressed between two closely related T-lymphoma cell clones was isolated by subtraction-enriched differential screening. SL12.4 cells, from which the cDNA was isolated, have characteristics of thymocytes at an intermediate stage in development. A sister cell clone derived from the same tumor, SL12.3, does not express this mRNA, has a distinct phenotype, and expresses fewer genes required for mature T-cell function. The cDNA sequence predicts a highly hydrophobic protein (approximately 49.5 kilodaltons) which contains seven putative membrane spanning domains. The gene was expressed on concanavalin A-activated T lymphocytes and was designated Tea (T-cell early activation gene). The Tea gene mapped to chromosome 8 and appeared to be conserved among mammalian and avian species. The Tea gene is distinct from, but bears extensive amino acid and DNA sequence similarity with, the murine ecotropic retroviral receptor which is encoded by the Rec-1 gene. Neither gene product displayed significant homology with other known transmembrane-spanning proteins. Thus, the Tea and Rec-1 genes establish a new family encoding multiple membrane-spanning proteins.
Assuntos
Cromossomos Humanos Par 8 , Genes , Ativação Linfocitária , Receptores Virais/genética , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Células Cultivadas , DNA/genética , DNA/isolamento & purificação , Biblioteca Gênica , Humanos , Camundongos , Dados de Sequência Molecular , Fenótipo , Conformação Proteica , RNA/genética , RNA/isolamento & purificação , Homologia de Sequência do Ácido NucleicoRESUMO
It has been observed that subclones from the spontaneous murine AKR/J T-lymphoma cell line SL12 with similar in vitro growth characteristics exhibit stable differences in tumorigenicity. The cell line is composed of at least three distinct cloned cell types that are highly, moderately, or poorly tumorigenic in syngeneic host animals. When healthy, young, syngeneic host animals were given iv injections with the same number of viable growth phase cells, each cloned cell type had a different tumor incidence, latent period, and pattern of tumor spread. The unusual stability of the cloned cell lines is shown by a similar incidence, latency, and spread of the tumors when studied after more than 1 year of continuous in vitro culture. The SL12 clones also differ in several phenotypic characteristics commonly used to classify thymocyte maturation, e.g., a) the expression of three of seven surface antigens examined, b) the cellular response to glucocorticoid hormone, and c) the expression of terminal deoxynucleotidyl transferase.
Assuntos
Linfoma/patologia , Animais , Antígenos de Superfície/análise , Divisão Celular/efeitos dos fármacos , Células Clonais , DNA/análise , DNA Nucleotidilexotransferase/análise , Dexametasona/farmacologia , Linfoma/secundário , Linfoma/ultraestrutura , Camundongos , Camundongos Endogâmicos AKR , Transplante de Neoplasias , Células Neoplásicas Circulantes , Fenótipo , Linfócitos T/classificação , Linfócitos T/ultraestrutura , Timoma/patologiaRESUMO
Several well characterized murine T-lymphoma cell lines were used in somatic cell hybridization experiments to study the genetic regulation of glucocorticoid-induced lysis. Cell fusions were carried out among the SL12-derived cloned lines and between the W7 and SAK8 lines all of which have functional hormone receptors. These cell lines differ in their sensitivity to glucocorticoid-induced lysis. The resultant hybrids were characterized by their growth response to 1 microM dexamethasone, their hormone receptor content, their chromosome number, and the expression of surface antigens. Fusion of the hormone-sensitive W7 parent to a number of glucocorticoid-resistant cell lines resulted in hybrids which were of the sensitive phenotype. In contrast the fusion of another hormone-sensitive clone, SL12.4, with glucocorticoid-resistant SL12 clones or with SAK8 always resulted in hybrids resistant to glucocorticoid lysis. These results reveal a complex genetic regulation of the hormone response or the requirement for multiple gene activity in the mechanism for glucocorticoid-induced cell lysis.
Assuntos
Glucocorticoides/farmacologia , Linfoma/patologia , Animais , Linhagem Celular , DNA/análise , Dexametasona/farmacologia , Regulação da Expressão Gênica , Células Híbridas , Camundongos , Camundongos Endogâmicos AKR , Receptores de Glucocorticoides/análise , Linfócitos TRESUMO
We have established and characterized a continuous T-cell line derived from the bone marrow of an AKR mouse with disseminated lymphoma. The original tumor cell line is heterogeneous with respect to several markers of thymocyte differentiation. Clones from the line differ in the expression of ThB, Pgp-1, and H-2Kk surface antigens. These clones also differ in their sensitivity to glucocorticoid-induced cell lysis. The quantity, affinity, and nuclear translocation properties of the glucocorticoid receptor are similar in the hormone-sensitive and -resistant clones. Furthermore, dexamethasone-resistant T-cells can be selected in vitro from freshly cloned cells sensitive to hormone-induced lysis at high frequency and without mutagenesis. Of several randomly sampled, spontaneously arising, independently derived dexamethasone resistant clones, all show a coordinate reduction in cell surface Thy-1 and ThB expression with no detectable changes in glucocorticoid receptor properties. Following treatment with the DNA-demethylating agent 5-azacytidine, the original dexamethasone-resistant T-cell line as well as the dexamethasone-resistant derivatives obtained in vitro regain sensitivity to lysis. These results collectively suggest a role of DNA methylation in hormone resistance and are consistent with a model of thymocyte differentiation in which a glucocorticoid-sensitive cell is the progenitor of hormone-resistant T-cells.
Assuntos
Timoma/fisiopatologia , Neoplasias do Timo/fisiopatologia , Animais , Antígenos de Superfície/análise , Azacitidina/toxicidade , Sobrevivência Celular/efeitos dos fármacos , DNA de Neoplasias/análise , Dexametasona/metabolismo , Dexametasona/toxicidade , Feminino , Cinética , Camundongos , Camundongos Endogâmicos AKR , Receptores de Glucocorticoides/metabolismo , Timoma/imunologia , Neoplasias do Timo/imunologiaRESUMO
To test the relationship between the concentration of epidermal growth factor (EGF) receptors and tumor growth in vivo, we measured the rate of growth of several independently isolated A431 cell lines in athymic mice. This series of A431 clonal variants with differing extents of EGF receptor gene amplification and protein expression were implanted into athymic mice and the time to solid tumor formation and rate of growth were measured. Results of these experiments indicate that the degree of gene amplification and concentration of EGF receptors are directly correlated with the growth of these cells as solid tumors in host animals. Complementary DNA hybridization analysis revealed no change in the extent of gene amplification and expression in implanted cells versus excised tumors nor any evidence of further gene rearrangement in vivo. A high concentration of EGF receptors appears to facilitate the growth of tumor cells in vivo and in vitro.
Assuntos
Fator de Crescimento Epidérmico/fisiologia , Neoplasias Experimentais/patologia , Receptores de Superfície Celular/fisiologia , Animais , Receptores ErbB , Amplificação de Genes , Regulação da Expressão Gênica , Camundongos , Camundongos Nus , RNA Mensageiro/genética , Receptores de Superfície Celular/genéticaRESUMO
Mice transgenic for the Polyomavirus middle T (PyV-mT) gene have been widely used to study mammary tumorigenesis and metastasis. Although numerous molecular insights were gained from the analysis of these transgenic malignant tumors, the early events leading to malignant transformation have not been systematically investigated nor has the biological potential of hyperplastic lesions been documented. This paper presents the first comprehensive histopathological characterization of transgenic PyV-mT hyperplasias together with classical transplantation experiments designed to test the growth potential of these lesions. Moreover, stable hyperplastic outgrowth lines were established as a tool to study premalignant PyV-mT-induced hyperplasias in detail. Each line has a different tumor latency, indicating that PyV-mT-induced hyperplasias, like early proliferative lesions seen in the human breast, are heterogeneous with respect to their malignant potential. Our results settle a controversy; they establish that PyV-mT gene expression alone is insufficient to induce tumors and that additional events are required for tumorigenesis and metastasis. These results support the use of PyV-mT transgenic mice as a model for investigating the multistep progression of malignant mammary tumorigenesis and metastasis.
Assuntos
Antígenos Transformantes de Poliomavirus/genética , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Animais , Antígenos Transformantes de Poliomavirus/biossíntese , Divisão Celular/fisiologia , Modelos Animais de Doenças , Feminino , Expressão Gênica , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/metabolismo , Vírus do Tumor Mamário do Camundongo/genética , Camundongos , Camundongos Transgênicos , Transplante de Neoplasias , Lesões Pré-Cancerosas/irrigação sanguínea , Lesões Pré-Cancerosas/metabolismo , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Proteína Supressora de Tumor p53/biossínteseRESUMO
In vitro studies have shown that loss of DNA mismatch repair due to lack of either hMSH2 or hMLH1 activity results in low-level resistance to cisplatin but not to oxaliplatin, an analogue that produces a different type of DNA adduct. No information is currently available on whether this low-level resistance is sufficient to result in enrichment of mismatch repair-deficient cells during drug exposure in vitro or to account for clinical failure of treatment in vivo. Mixed populations of cells containing a minority of DNA mismatch repair-deficient cells constitutively expressing green fluorescence protein were exposed repeatedly in vitro to cisplatin and oxaliplatin. Treatment with cisplatin resulted in a gradual enrichment for DNA mismatch repair-deficient cells, whereas treatment with oxaliplatin did not. MSH2-/- and MSH2+/+ embryonic stem cells were established as xenografts in athymic nude mice. Animals were treated 48 h after tumor implantation with a single LD10 dose of either cisplatin or oxaliplatin. MSH2-/- tumors were significantly less responsive to cisplatin than MSH2+/+ tumors, whereas there was no difference in sensitivity to oxaliplatin. These results demonstrate that the degree of cisplatin resistance conferred by loss of DNA mismatch repair is sufficient to produce both enrichment of mismatch repair-deficient cells during treatment in vitro and a large difference in clinical responsiveness in vivo. The results identify loss of DNA mismatch repair as a mechanism of resistance to cisplatin but not oxaliplatin.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Reparo do DNA , Adenocarcinoma/metabolismo , Animais , Neoplasias Colorretais/metabolismo , DNA de Neoplasias/metabolismo , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Expression of putative amino acid transport proteins is usually assumed to be associated with expression of a single component of transport. It is shown in this report, however, that murine cationic amino acid transporter (mCAT) expression in Xenopus oocytes is associated in important instances with expression of more than one kinetically distinguishable transport process. Accurate knowledge of the kinetics of transport continues, therefore, to be needed to understand how transport proteins function.
Assuntos
Proteínas de Transporte/metabolismo , Glicoproteínas de Membrana , Proteínas de Membrana/metabolismo , Fenitoína/análogos & derivados , Receptores Virais , Animais , Arginina/metabolismo , Técnicas In Vitro , Cinética , Camundongos , Microinjeções , Oócitos , Fenitoína/metabolismo , Xenopus laevisRESUMO
The amino acid l-arginine plays a central role in several adaptive metabolic pathways and we postulate that regulated L-arginine transport contributes to important physiological responses. The majority of L-arginine flux is mediated by transport system y+ that is encoded by at least three genes, Cat1, Cat2 and Cat3. Cat2 encodes two distinct protein isoforms (CAT2/CAT2a) that differ by 10-fold in their apparent substrate affinity. Cat2 transcription is controlled by four widely spaced promoters. The expression of CAT2/2a transcripts was tested in skeletal muscle and macrophages following specific stresses or activators. Unexpectedly, CAT2a transcripts accumulated in skeletal muscle in response to surgical trauma (hepatectomy and splenectomy) as well as food deprivation, although neither high affinity CAT2 nor CAT1 were detectably altered. Activated macrophages decreased CAT1 levels, but accumulated CAT2 and iNOS mRNA and protein with parallel kinetics suggesting that CAT2 mediated L-arginine transport might regulate the L-arginine:nitric oxide pathway. In macrophages, liver and skeletal muscle, the most distal CAT2 promoter was predominant. No change in promoter usage was apparent under any stress conditions tested nor was alternate splicing of the CAT2 transcript dictated by promoter usage. The differential regulation of the Cat genes indicates their encoded transporter proteins meet different requirements for cationic amino acids in the intact animal.
Assuntos
Proteínas de Transporte/biossíntese , Regulação da Expressão Gênica , Macrófagos/metabolismo , Proteínas de Membrana/biossíntese , Músculo Esquelético/metabolismo , Sistemas de Transporte de Aminoácidos Básicos , Animais , Arginina/metabolismo , Proteínas de Transporte/genética , Linhagem Celular , Privação de Alimentos , Hepatectomia , Fatores Imunológicos , Fígado/metabolismo , Ativação de Macrófagos , Proteínas de Membrana/genética , Camundongos , Músculo Liso/metabolismo , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The oncofetal gene, Pem, is expressed in a stage specific manner during murine ontogeny. The carboxy terminal portion of the predicted Pem protein has significant similarity to homeodomains of the Drosophila prd family. The Pem gene is expressed in undifferentiated embryonal stem (ES) and embryonal carcinoma (EC) cell lines. Pem mRNA is induced 35-fold in ES cells differentiated in the absence of retinoic acid. Pem mRNA is increased in EC cells differentiated towards parietal or visceral endoderm, consistent with the abundant Pem expression in embryonic yolk sac. In 10T mesenchymal stem cells committed to muscle cell differentiation, Pem mRNA expression is dramatically increased. The elevation in Pem expression preceded the induction of the muscle master regulatory gene, myoD. We conclude that the Pem gene encodes a candidate transcription factor which is developmentally regulated.
Assuntos
Regulação da Expressão Gênica , Genes Homeobox/genética , Genes Reguladores/genética , Músculos/embriologia , Células-Tronco/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Sequência de Bases , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Células Cultivadas , Regulação Neoplásica da Expressão Gênica , Mesoderma/citologia , Mesoderma/metabolismo , Camundongos , Dados de Sequência Molecular , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculos/citologia , Músculos/metabolismo , Proteína MyoD , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Transcrição Gênica/genética , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologiaRESUMO
The cell cycle progression and viability of stimulated and intact lymphocytes from 20 subjects with acquired immune deficiency syndrome (AIDS) was determined by flow cytometry. As compared to controls, 62% less AIDS lymphocytes, cultured for 72 hr in the presence of lectins (Con-A, PHA, PWM), had entered the proliferative phases of the cell cycle, while the respective value for periodic-acid (H5IO6)-stimulated cells was 34%. The helper-suppressor ratios and natural kill cell percentages of the unstimulated and PHA-activated AIDS lymphocytes increased approximately 3-fold after 72 hr in culture. The natural killer (NK) cell fraction of the PHA-stimulated and unstimulated AIDS cultures comprised approximately 20% as compared to 10% in controls. However, no changes in the percentages of T-lymphocytes were detected in the AIDS cell cultures. Throughout the culture period, viability of the unstimulated AIDS lymphocytes exceeded 90%, whereas in stimulated cultures it fluctuated within the 65-90% range. It is concluded that the liability of AIDS lymphocytes to mitogens is probably a direct consequence of the human immunodeficiency virus (HIV) infection.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Antígenos de Superfície/análise , Ativação Linfocitária , Linfócitos T/imunologia , Ciclo Celular/efeitos dos fármacos , Humanos , Interleucina-2/biossíntese , Masculino , Fenótipo , Fito-Hemaglutininas/farmacologia , Linfócitos T/classificaçãoRESUMO
The T-cell surface proteins CD4 (L3T4) and CD8 (Lyt2) are first expressed on thymocytes as they undergo maturation in the thymus. Two immature T-lymphoma cell clones SL12.4 and RS4.2 which constitutively express low or undetectable levels of CD4 and CD8 were used to investigate the activation of CD4 and CD8 gene expression. The protein synthesis inhibitors cycloheximide (CHX) and pactamycin rapidly and reversibly increased CD4 and CD8 mRNA in the cloned cell lines, suggesting that a labile inhibitor protein(s) may regulate the expression of these transcripts. Cell surface CD4 and CD8 proteins were transiently detectable following a pulse of CHX. Thymic epithelial cell lines also induced CD4 and CD8 mRNA and cell surface protein, as well as TCR-alpha mRNA when co-cultivated with SL12.4 T lymphoma cells. The increase in CD4 and CD8 was modest, but stable for at least 22 cell generations after the thymic epithelial inducer cells were removed. Epithelial cells of non-thymic origin did not cause induction of these T-cell differentiation markers in SL12.4 T-lymphoma cells. Since the induction elicited by thymic epithelial cells and protein synthesis inhibitors differed dramatically in kinetics and reversibility, it is likely that these inducers act, at least in part, via different mechanisms. This lymphoma model system may be useful for analysis of molecular events which occur in immature thymocytes undergoing differentiation.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Linfoma de Células T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Subpopulações de Linfócitos T/citologia , Timo/citologia , Animais , Antígenos de Superfície/genética , Northern Blotting , Antígenos CD4/genética , Linfócitos T CD4-Positivos/citologia , Antígenos CD8 , Diferenciação Celular , Membrana Celular/imunologia , Células Cultivadas , Cicloeximida/farmacologia , Células Epiteliais , Citometria de Fluxo , Expressão Gênica , Linfoma de Células T/patologia , Camundongos , RNA Mensageiro/genética , Receptores de Antígenos de Linfócitos T alfa-beta , Subpopulações de Linfócitos T/imunologia , Antígenos Thy-1 , Transcrição Gênica/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
We demonstrate that three integral membrane receptors of mammals--the ecotropic retroviral leukemia receptor (ERR), the human retroviral receptor (HRR), and the T-cell early activator (Tea)--are homologous to a family of transporters specific for amino acids, polyamines, and choline (APC), which catalyze solute uniport, solute:cation symport, or solute:solute antiport in yeast, fungi, and eubacteria. Interestingly, the ERR membrane protein was recently shown to function as a cation:amino acid cotransporter. A binary sequence similarity matrix and an evolutionary tree of the 14 members of this family, illustrating their sequence similarities and divergences, were constructed. Other proteins, including the developmentally controlled GerAII spore germination protein of Bacillus subtilis and the acetylcholine receptor of Drosophila melanogaster gave sequence comparison scores of a sufficiently large magnitude to suggest (but not to establish) a common evolutionary origin with members of the APC family. We report an extended and corrected Tea cDNA sequence and show that the mammalian Tea and ERR encoding genes are differentially expressed in tissues and cell lines. Furthermore, the two mammalian cDNA sequences hybridize with other vertebrate and yeast genomic DNAs under stringent conditions. These observations support the notion that cell surface receptor proteins in mammals are transport proteins that share a common origin with transport proteins of single-celled organisms. Thus, permeases of essential metabolites may function pathologically as viral receptors.
Assuntos
Proteínas de Membrana/genética , Receptores de Superfície Celular/genética , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/genética , Sequência de Bases , Proteínas de Transporte/genética , DNA/genética , Proteínas Fúngicas/genética , Humanos , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de Aminoácidos , Especificidade da EspécieRESUMO
Ten patients were identified at Jackson Memorial hospital/University of Miami Hospitals and Clinics with enteric coccidial infection due to Cryptosporidium spp. or Isospora belli. All had the acquired immunodeficiency syndrome as manifested by Kaposi's sarcoma or multiple opportunistic infections, or both. They presented with profuse diarrhea associated with weakness, anorexia, and weight loss. Routine examinations of stools for eggs and parasites as performed by the hospital laboratory were negative in all patients. Sugar flotation and modified acid fast techniques were used in the Tropical Disease Laboratory to identify oocysts of Cryptosporidium spp. in stools of seven patients. Malabsorption, characterized by a low 5-hour D-xylose and positive fecal fat, was observed in 6/6 of these patients. In three other patients Isospora belli oocysts were identified in stool specimens or via a duodenal string test. Spiramycin was the only drug found to be effective in treating patients with cryptosporidiosis. Patients with Isospora belli responded to a prolonged course of trimethoprim-sulfamethoxazole.
Assuntos
Síndrome da Imunodeficiência Adquirida/parasitologia , Coccidiose/complicações , Enteropatias Parasitárias/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Animais , Coccidiose/diagnóstico , Coccidiose/tratamento farmacológico , Criptosporidiose/complicações , Cryptosporidium , Diarreia/parasitologia , Combinação de Medicamentos/uso terapêutico , Feminino , Furazolidona/uso terapêutico , Humanos , Isospora , Leucomicinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Sulfametoxazol/uso terapêutico , Trimetoprima/uso terapêutico , Combinação Trimetoprima e SulfametoxazolRESUMO
The pregnant traveler should seek current and specific advice from experts even if she is traveling to a nearby wilderness area. This advice will make a significant contribution to the safety and health of the pregnant woman and her future newborn. There are many situations, for example, travel to Kenya, the Andes, or the Amazon basin in Peru, where the pregnant traveler is best advised to stay at home, or to defer the trip.
Assuntos
Gravidez , Viagem , Feminino , Humanos , ImunizaçãoRESUMO
Recent changes in the UK's coastal defence strategy have resulted in the introduction of Managed Realignment (MR), a technique which attempts to establish salt marshes on low-lying coastal farmland. This work investigates the impact of MR, in particular on the interactions between sediment movement, changes in heavy metal concentrations and salt marsh development. Pre- and post-inundation samples were collected and analysed between 1995 and 1997. Sediment transport patterns (1996) demonstrated that sediment particles were distributed by tides around the site, resulting in a change in the spatial distribution of the metals which was related to the sediment particle size distribution. Despite the presence of some metal contaminants found within the MR site, vegetated salt marsh has developed since 1997. However, heavy metals such as Cu, Mn, Ni, Pb and Zn exhibited relative depletion in the sediment developing with salt marsh in 1997, which is in agreement with data indicating that concentrations of metals within sediments is related to frequency of tidal inundation. During initial development of the site, sediment transport was the main factor controlling metal distribution, however, subsequently the frequency of tidal inundation became the most significant factor. Further work may allow for prediction of how future MR sites will develop with respect to redistribution of sediments and subsequent transport of contaminants in the dissolved phase.