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INTRODUCTION: In Senegal, marital infertility is a real problem for society. We undertook the study of this subject to make an analysis of the spermatic parameters of the infertile Senegalese man and to better understand the impact of testicular morphological anomalies on male fertility. PATIENTS AND METHODS: We conducted a cross-sectional, descriptive, retrospective study of 100 infertile patients followed at the Histology-Embryology-Cytogenetics laboratory of UCAD in Dakar, during the year 2020. Sperm parameters, presence of varicocele, and testicular volume were evaluated in our patients. RESULTS/DISCUSSION: The mean age of the patients was 35.17±8.7 years. A history of sexually transmitted infections was found in 57% of patients. The mean duration of infertility was 5.67±3.2 years. The mean sperm count was 14,871,230/ml±4,950,000. Necrospermia was the most frequent abnormality found (60%), followed by asthenospermia (51%). The high rate of necrospermia could be explained by the high frequency of sexually transmitted infections. Other abnormalities were oligospermia (48%, including 09% cryptospermia), azoospermia (19%), teratospermia (19%), and hypospermia (13%). The predominance of azoospermia and oligospermia should prompt a search for a genetic predisposition in these subjects. The mean testicular volume was 10.3±4.9 cc on the right and 9.5±4.8 cc on the left. A single or bilateral varicocele was found in 43% of subjects. Patients with azoospermia and teratospermia were associated with testicular hypotrophy with a significant value (p=0.04). CONCLUSION: Overall, the senegalese man consulting for infertility is a young adult, married for an average of 5 years. Necrospermia is the most frequently found anomaly. The severity of both qualitative and quantitative abnormalities should lead to a systematic search for a genetic origin. The etiological research of infertile patients must be done within a multidisciplinary framework to propose better management of these patients.
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Azoospermia , Infertilidad Masculina , Oligospermia , Teratozoospermia , Varicocele , Adulto Joven , Humanos , Masculino , Adulto , Oligospermia/complicaciones , Oligospermia/patología , Azoospermia/genética , Azoospermia/complicaciones , Azoospermia/patología , Varicocele/complicaciones , Varicocele/genética , Varicocele/patología , Estudios Retrospectivos , Teratozoospermia/complicaciones , Teratozoospermia/patología , Estudios Transversales , Estudios de Seguimiento , Universidades , Semen , Senegal , Infertilidad Masculina/genética , Testículo/patología , Espermatozoides , Análisis CitogenéticoRESUMEN
BACKGROUND: Urban malaria is an increasing concern in most of the sub-Saharan Africa countries. In Dakar, the capital city of Senegal, the malaria epidemiology has been complicated by recurrent flooding since 2005. The main vector control measure for malaria prevention in Dakar is the community use of long-lasting insecticide-treated nets. However, the increase of insecticide resistance reported in this area needs to be better understood for suitable resistance management. This study reports the situation of insecticide resistance and underlying mechanisms in Anopheles arabiensis populations from Dakar and its suburbs. RESULTS: All the populations tested showed resistance to almost all insecticides except organophosphates families, which remain the only lethal molecules. Piperonil butoxide (PBO) and ethacrinic acid (EA) the two synergists used, have respectively and significantly restored the susceptibility to DDT and permethrin of Anopheles population. Molecular identification of specimens revealed the presence of An. arabiensis only. Kdr genotyping showed the presence of the L1014F mutation (kdr-West) as well as L1014S (kdr-East). This L1014S mutation was found at very high frequencies (89.53%) in almost all districts surveyed, and in association with the L1014F (10.24%). CONCLUSION: Results showed the contribution of both target-site and metabolic mechanisms in conferring pyrethroid resistance to An. arabiensis from the flooded areas of Dakar suburbs. These data, although preliminary, stress the need for close monitoring of the urban An. arabiensis populations for a suitable insecticide resistance management system to preserve core insecticide-based vector control tools in this flooded area.
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Anopheles/efectos de los fármacos , Resistencia a los Insecticidas , Insecticidas/farmacología , Piretrinas/farmacología , Animales , Ciudades , Larva/efectos de los fármacos , Pupa/efectos de los fármacos , Estaciones del Año , SenegalRESUMEN
CONTEXT: Sleep restriction alters responses to food. However, the underlying neural mechanisms for this effect are not well understood. OBJECTIVE: The purpose of this study was to determine whether there is a neural system that is preferentially activated in response to unhealthy compared with healthy foods. PARTICIPANTS: Twenty-five normal-weight individuals, who normally slept 7-9 h per night, completed both phases of this randomized controlled study. INTERVENTION: Each participant was tested after a period of five nights of either 4 or 9 h in bed. Functional magnetic resonance imaging (fMRI) was performed in the fasted state, presenting healthy and unhealthy food stimuli and objects in a block design. Neuronal responses to unhealthy, relative to healthy food stimuli after each sleep period were assessed and compared. RESULTS: After a period of restricted sleep, viewing unhealthy foods led to greater activation in the superior and middle temporal gyri, middle and superior frontal gyri, left inferior parietal lobule, orbitofrontal cortex, and right insula compared with healthy foods. These same stimuli presented after a period of habitual sleep did not produce marked activity patterns specific to unhealthy foods. Further, food intake during restricted sleep increased in association with a relative decrease in brain oxygenation level-dependent (BOLD) activity observed in the right insula. CONCLUSION: This inverse relationship between insula activity and food intake and enhanced activation in brain reward and food-sensitive centers in response to unhealthy foods provides a model of neuronal mechanisms relating short sleep duration to obesity.
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Apetito/fisiología , Encéfalo/fisiología , Ingestión de Alimentos/fisiología , Alimentos , Hambre/fisiología , Imagen por Resonancia Magnética , Privación de Sueño/fisiopatología , Adulto , Mapeo Encefálico , Señales (Psicología) , Ayuno , Femenino , Humanos , Masculino , Estimulación Luminosa , RecompensaRESUMEN
Acidovorax citrulli causes bacterial fruit blotch of cucurbits, a serious economic threat to watermelon (Citrullus lanatus) and melon (Cucumis melo) production worldwide. Based on genetic and biochemical traits, A. citrulli strains have been divided into two distinct groups: group I strains have been mainly isolated from various non-watermelon hosts, while group II strains have been generally isolated from and are highly virulent on watermelon. The pathogen depends on a functional type III secretion system for pathogenicity. Annotation of the genome of the group II strain AAC00-1 revealed 11 genes encoding putative type III secreted (T3S) effectors. Due to the crucial role of type III secretion for A. citrulli pathogenicity, we hypothesized that group I and II strains differ in their T3S effector repertoire. Comparative analysis of the 11 effector genes from a collection of 22 A. citrulli strains confirmed this hypothesis. Moreover, this analysis led to the identification of a third A. citrulli group, which was supported by DNA:DNA hybridization, DNA fingerprinting, multilocus sequence analysis of conserved genes, and virulence assays. The effector genes assessed in this study are homologous to effectors from other plant-pathogenic bacteria, mainly belonging to Xanthomonas spp. and Ralstonia solanacearum. Analyses of the effective number of codons and gas chromatography content of effector genes relative to a representative set of housekeeping genes support the idea that these effector genes were acquired by lateral gene transfer. Further investigation is required to identify new T3S effectors of A. citrulli and to determine their contribution to virulence and host preferential association.
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Citrullus/microbiología , Comamonadaceae/genética , Cucumis melo/microbiología , Enfermedades de las Plantas/microbiología , Polimorfismo de Nucleótido Simple , Sistemas de Secreción Tipo III/genética , Secuencia de Bases , Comamonadaceae/metabolismo , Comamonadaceae/patogenicidad , Frutas/microbiología , Datos de Secuencia Molecular , Fenotipo , Filogenia , Plantones/microbiología , Análisis de Secuencia de ADN , Sistemas de Secreción Tipo III/metabolismo , VirulenciaRESUMEN
BACKGROUND: Frailty is associated with mortality in older adults hospitalized with COVID-19, yet few studies have quantified healthcare utilization and spending following COVID-19 hospitalization. OBJECTIVE: To evaluate whether survival and follow-up healthcare utilization and expenditures varied as a function of claims-based frailty status for older adults hospitalized with COVID-19. DESIGN: Retrospective cohort study. PARTICIPANTS: 136 patients aged 65 and older enrolled in an Accountable Care Organization (ACO) risk contract at an academic medical center and hospitalized for COVID-19 between March 11, 2020 - June 3, 2020. MEASUREMENTS: We linked a COVID-19 Registry with administrative claims data to quantify a frailty index and its relationship to mortality, healthcare utilization, and expenditures over 6 months following hospital discharge. Kaplan Meier curves and Cox Proportional Hazards models were used to evaluate survival by frailty. Kruskal-Wallis tests were used to compare utilization. A generalized linear model with a gamma distribution was used to evaluate differences in monthly Medicare expenditures. RESULTS: Much of the cohort was classified as moderate to severely frail (65.4%), 24.3% mildly frail, and 10.3% robust or pre-frail. Overall, 27.2% (n=37) of the cohort died (n=26 during hospitalization, n=11 after discharge) and survival did not significantly differ by frailty. Among survivors, inpatient hospitalizations during the 6-month follow-up period varied significantly by frailty (p=0.02). Mean cost over follow-up was $856.37 for the mild and $4914.16 for the moderate to severe frailty group, and monthly expenditures increased with higher frailty classification (p <.001). CONCLUSIONS: In this cohort, claims-based frailty was not significantly associated with survival but was associated with follow-up hospitalizations and Medicare expenditures.
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COVID-19 , Fragilidad , Anciano , Humanos , Estados Unidos/epidemiología , Gastos en Salud , Medicare , Anciano Frágil , Estudios Retrospectivos , Atención a la Salud , Centros Médicos AcadémicosRESUMEN
Climate change is significantly impacting agricultural production worldwide. Peanuts provide food and nutritional security to millions of people across the globe because of its high nutritive values. Drought and heat stress alone or in combination cause substantial yield losses to peanut production. The stress, in addition, adversely impact nutritional quality. Peanuts exposed to drought stress at reproductive stage are prone to aflatoxin contamination, which imposes a restriction on use of peanuts as health food and also adversely impact peanut trade. A comprehensive understanding of the impact of drought and heat stress at physiological and molecular levels may accelerate the development of stress tolerant productive peanut cultivars adapted to a given production system. Significant progress has been achieved towards the characterization of germplasm for drought and heat stress tolerance, unlocking the physiological and molecular basis of stress tolerance, identifying significant marker-trait associations as well major QTLs and candidate genes associated with drought tolerance, which after validation may be deployed to initiate marker-assisted breeding for abiotic stress adaptation in peanut. The proof of concept about the use of transgenic technology to add value to peanuts has been demonstrated. Advances in phenomics and artificial intelligence to accelerate the timely and cost-effective collection of phenotyping data in large germplasm/breeding populations have also been discussed. Greater focus is needed to accelerate research on heat stress tolerance in peanut. A suits of technological innovations are now available in the breeders toolbox to enhance productivity and nutritional quality of peanuts in harsh environments. A holistic breeding approach that considers drought and heat-tolerant traits to simultaneously address both stresses could be a successful strategy to produce climate-resilient peanut genotypes with improved nutritional quality.
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Peanut (Arachis hypogaea L.) seed is a rich source of edible oil, comprised primarily of monounsaturated oleic acid and polyunsaturated linoleic acid, accounting for 80% of its fatty acid repertoire. The conversion of oleic acid to linoleic acid, catalyzed by Fatty Acid Desaturase 2 (FAD2) enzymes, is an important regulatory point linked to improved abiotic stress responses while the ratio of these components is a significant determinant of commercial oil quality. Specifically, oleic acid has better oxidative stability leading to longer shelf life and better taste qualities while also providing nutritional based health benefits. Naturally occurring FAD2 gene knockouts that lead to high oleic acid levels improve oil quality at the potential expense of plant health though. We undertook a CRISPR/Cas9 based site-specific genome modification approach designed to downregulate the expression of two homeologous FAD2 genes in seed while maintaining regulation in other plant tissues. Two cis-regulatory elements the RY repeat motif and 2S seed protein motif in the 5'UTR and associated intron of FAD2 genes are potentially important for regulating seed-specific gene expression. Using hairy root and stable germ line transformation, differential editing efficiencies were observed at both CREs when targeted by single gRNAs using two different gRNA scaffolds. The editing efficiencies also differed when two gRNAs were expressed simultaneously. Additionally, stably transformed seed exhibited an increase in oleic acid levels relative to wild type. Taken together, the results demonstrate the immense potential of CRISPR/Cas9 based approaches to achieve high frequency targeted edits in regulatory sequences for the generation of novel transcriptional alleles, which may lead to fine tuning of gene expression and functional genomic studies in peanut.
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Peanut (Arachis hypogaea L.), an allotetraploid legume of the Fabaceae family, is able to thrive in tropical and subtropical regions and is considered as a promising oil seed crop worldwide. Increasing the content of oleic acid has become one of the major goals in peanut breeding because of health benefits such as reduced blood cholesterol level, antioxidant properties and industrial benefits such as longer shelf life. Genomic sequencing of peanut has provided evidence of homeologous AhFAD2A and AhFAD2B genes encoding Fatty Acid Desaturase2 (FAD2), which are responsible for catalyzing the conversion of monounsaturated oleic acid into polyunsaturated linoleic acid. Research studies demonstrate that mutations resulting in a frameshift or stop codon in an FAD2 gene leads to higher oleic acid content in oil. In this study, two expression vectors, pDW3873 and pDW3876, were constructed using Cas9 fused to different deaminases, which were tested as tools to induce point mutations in the promoter and the coding sequences of peanut AhFAD2 genes. Both constructs harbor the single nuclease null variant, nCas9 D10A, to which the PmCDA1 cytosine deaminase was fused to the C-terminal (pDW3873) while rAPOBEC1 deaminase and an uracil glycosylase inhibitor (UGI) were fused to the N-terminal and the C-terminal respectively (pDW3876). Three gRNAs were cloned independently into both constructs and the functionality and efficiency were tested at three target sites in the AhFAD2 genes. Both constructs displayed base editing activity in which cytosine was replaced by thymine or other bases in the targeted editing window. pDW3873 showed higher efficiency compared to pDW3876 suggesting that the former is a better base editor in peanut. This is an important step forward considering introgression of existing mutations into elite varieties can take up to 15 years making this tool a benefit for peanut breeders, farmers, industry and ultimately for consumers.
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Peanuts are an economically important crop cultivated worldwide. However, several limitations restrained its productivity, including biotic/abiotic stresses. CRISPR/Cas9-based gene-editing technology holds a promising approach to developing new crops with improved agronomic and nutritional traits. Its application has been successful in many important crops. However, the application of this technology in peanut research is limited, probably due to the lack of suitable constructs and protocols. In this study, two different constructs were generated to induce insertion/deletion mutations in the targeted gene for a loss of function study. The first construct harbors the regular gRNA scaffold, while the second construct has the extended scaffold plus terminator. The designed gRNA targeting the coding sequence of the FAD2 genes was cloned into both constructs, and their functionality and efficiency were validated using the hairy root transformation system. Both constructs displayed insertions and deletions as the types of edits. The construct harboring the extended plus gRNA terminator showed a higher editing efficiency than the regular scaffold for monoallelic and biallelic mutations. These two constructs can be used for gene editing in peanuts and could provide tools for improving peanut lines for the benefit of peanut breeders, farmers, and industry.
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The lymphoid system is known to be involved in the propagation and spread of scrapie. However, the identity of the cell type responsible for scrapie replication remains controversial. A new study provides evidence that the follicular dendritic cells in the spleen are the targets of this infectious form of prion (pages 1308-1312).
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Células Dendríticas/inmunología , Priones/fisiología , Scrapie/inmunología , Animales , Ratones , Scrapie/transmisiónRESUMEN
AIMS: The object of this work is the study of especially ancient clinical forms of the effusion of Morel-Lavallée, to discuss the place of deep fascial fenestration by Ronceray and to propose criteria of therapeutic indication. PATIENTS AND METHOD: Our study concerns a continuous retrospective series over 20 years from 1989 till 2009. Eleven men and eight women, 36.7 year-old on average were treated for an effusion of Morel-Lavallée. The dominant etiology was represented by the accidents of the public highway. The collection was discovered after 41.4 days on average (extremes of 1-180 days). The volume of the collection was on average of 1237cm(3) (extremes 60cm(3)-12L). RESULTS: The conservative treatment concerned all patients who had a recent collection lower than three weeks and three others who had an ancient collection. The surgical treatment was established after all 10 times among which four in first intention and six times after failure of the previous treatment. The cure was obtained in 91% of the patients who had a recent collection by the only conservative method and among four patients by the method of Ronceray. To the three others, it was obtained after iterative unbridlings and talcage treatment. CONCLUSION: The authors insist on certain rare forms met in Africa in particular the "virtual form", the ancient forms and the too plentiful forms (12L). They plead for use deep fascial fenestrations by Ronceray for these last ones.
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Piel/lesiones , Tejido Subcutáneo/lesiones , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos , Estudios Retrospectivos , Heridas y Lesiones/terapia , Adulto JovenRESUMEN
Genome-wide association studies (GWAS) have been utilized to detect genetic variations related to several agronomic traits and disease resistance in common bean. However, its application in the powdery mildew (PM) disease to identify candidate genes and their location in the common bean genome has not been fully addressed. Single-nucleotide polymorphism (SNP) genotyping with a BeadChip containing 5398 SNPs was used to detect genetic variations related to PM disease resistance in a panel of 211 genotypes grown under two field conditions for two consecutive years. Significant SNPs identified on chromosomes Pv04 and Pv10 were repeatable, ensuring the phenotypic data's reliability and the causal relationship. A cluster of resistance genes was revealed on the Pv04 of the common bean genome, coiled-coil-nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR, CNL), and Toll/interleukin-1 receptor-nucleotide-binding site-leucine-rich repeat type (TIR-NBS-LRR, TNL)-like resistance genes were identified. Furthermore, two resistance genes, Phavu_010G1320001g and Phavu_010G136800g, were also identified on Pv10. Further sequence analysis showed that these genes were homologs to the disease-resistance protein (RLM1A-like) and the putative disease-resistance protein (At4g11170.1) in Arabidopsis. Significant SNPs related to two LRR receptor-like kinases (RLK) were only identified on Pv11 in 2018. Many genes encoding the auxin-responsive protein, TIFY10A protein, growth-regulating factor five-like, ubiquitin-like protein, and cell wall RBR3-like protein related to PM disease resistance were identified nearby significant SNPs. These results suggested that the resistance to PM pathogen involves a network of many genes constitutively co-expressed.
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In the transmembrane domain and cytoplasmic domain of human CD44 protein there are two cysteine residues. These two cysteines are conserved in all known mammalian CD44 proteins. The functions of these cysteine residues are not known. Site-specific mutagenesis was used to create CD44 mutant proteins lacking either one or both of these cysteine residues. Wild-type CD44 and mutant CD44 genes were transfected into CD44- Jurkat cells to establish stable transfectants. These transfectants were used to study whether these two cysteine residues are important in the binding of CD44(H) to fluorescein-conjugated hyaluronic acid (F-HA). Jurkat transfectant bearing wild-type CD44 did not bind F-HA, unless they were stimulated in vitro with immobilized anti-CD3 monoclonal antibody. Anti-CD3 antibody also stimulated the binding of F-HA in Jurkat CD44.C295A transfectant in which the cytoplasmic cysteine residue has been replaced with alanine. In contrast, anti-CD3 antibody failed to stimulate the binding of F-HA in Jurkat transfectant (CD44.C286A), in which the transmembrane domain cysteine 286 has been replaced with an alanine, and in Jurkat transfectant CD44.2C2A, in which both of the cysteine residues have been altered. Binding can also be induced with a monoclonal anti-CD44 antibody (F-44-10-2) in Jurkat wild-type CD44 and Jurkat CD44.C295A transfectants but not in CD44. C286A transfectant. These results provide evidence that the transmembrane domain of CD44, more specifically the cysteine residue in the transmembrane domain, is important for both activation-induced and anti-CD44 antibody-induced binding of soluble HA.
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Cisteína , Receptores de Hialuranos/química , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/metabolismo , Secuencia de Aminoácidos , Animales , Antígenos CD/química , Antígenos CD/metabolismo , Sitios de Unión , Línea Celular , Membrana Celular/inmunología , Clonación Molecular , Secuencia Conservada , Citoplasma/inmunología , Humanos , Cinética , Mamíferos , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , TransfecciónRESUMEN
Serological analysis of idiotypic specificities present in azobenzenearsonate (ABA)-specific first-order suppressor T cell factors (TsF1) from C.AL-20 and BALB/c mice revealed a significant difference between TsF from these two strains of mice. The idiotypic composition of TsF1 from BALB/c mice appears to be more heterogeneous, and at least two different fractions can be readily identified. One bears the characteristic BALB/c-associated CRI(C) (crossreactive idiotype) determinants, and the other is non-CRI(C)-bearing. Analysis of ABA-specific TsF1 from animals lacking B cells uncovered a fundamental change in the expression of their idiotypic specificities. TsF from rabbit anti-mouse IgM (anti-mu)-treated C.AL-20 mice failed to express the characteristic CRI(A) determinants. Instead, they express CRI(C) specificities. Similarly, TsF1 from anti-mu-treated BALB/c mice did not express their characteristic CRI(C) specificities, but rather express CRI(A) determinants. These experiments provide strong evidence that the Igh restriction specificity of TsF is dictated by the particular idiotypic specificities expressed. They also clearly demonstrate that B cells and their products play an important role in establishing the idiotypic composition and repertoire of suppressor T cells.
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Linfocitos B/inmunología , Linfocinas/biosíntesis , Linfocitos T/inmunología , Animales , Reacciones Cruzadas , Idiotipos de Inmunoglobulinas/inmunología , Inmunoglobulina M/inmunología , Depleción Linfocítica , Linfocinas/genética , Linfocinas/inmunología , Ratones , Ratones Endogámicos BALB C , Conejos , Factores Supresores Inmunológicos , Linfocitos T Reguladores/inmunología , p-Azobencenoarsonato/inmunologíaRESUMEN
B cell-deficient (anti-mu-treated) mice have proven to be a valuable tool with which to examine the influence of Ig idiotypic determinants upon the development of the Ts repertoire. We have previously reported that ABA-specific Ts repertoires matured in normal and Ig-deficient environments differ from one another in their composition, and consequently, their functionally expressed Igh restrictions. The present report characterizes the impact of natural development of mature B cell activity upon the composition of the Ts repertoire. After stopping anti-mu treatment of C.AL-20 mice, ABA-specific Ts repertoires undergo a defined expansion shown by their acquisition of an additional Ts network that displays Igh restrictions characteristic of normal C.AL-20 mice. This Igh-1d-restricted repertoire can be readily shown within 2 wk of major increases in surface Ig spleen cells and total serum Ig levels in these mice. At the same time, the original Ts restriction specificity (Igh-1a-restricted) generated in the Ig-deficient environment of anti-mu. C.AL-20 mice, is not lost for at least 20 wk. The resulting dual Ts repertoire, characterized by expression of parallel, idiotypically restricted Ts networks, is demonstrable for at least 13 wk. These findings favor an important role for Ig determinants in determining the makeup of the T cell repertoire, and ultimately, the composition of immunologic networks as a whole.
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Anticuerpos Antiidiotipos/administración & dosificación , Cadenas Pesadas de Inmunoglobulina/genética , Inmunoglobulina M/administración & dosificación , Síndromes de Inmunodeficiencia/inmunología , Activación de Linfocitos , Linfocitos T Reguladores/inmunología , Animales , Linfocitos B/patología , Diferenciación Celular , Quimera , Inmunoglobulina G/biosíntesis , Inmunoglobulina M/biosíntesis , Síndromes de Inmunodeficiencia/patología , Ratones , Ratones Endogámicos BALB C , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/metabolismo , Factores de TiempoRESUMEN
Tumor growth is dependent in part on interactions between tumor cells and the extracellular matrix of host tissues. Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined. Recently, two isoforms of CD44 have been identified: an 80-90 kD form, which has high affinity for cell bound hyaluronate and a 150 kD form which does not mediate attachment to hyaluronate-coated surfaces. In this work, human B cell lymphoma cells stably transfected with cDNA clones encoding either of the two CD44 isoforms were compared for tumorigenicity and metastatic potential in nude mice. Expression of the 80-90 kD form but not the 150 kD form of CD44 greatly enhanced both local tumor formation and metastatic proclivity of the lymphoma cells. Our results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo.
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Linfoma de Burkitt/inmunología , Receptores Mensajeros de Linfocitos/fisiología , Animales , Linfoma de Burkitt/patología , División Celular , Línea Celular , Replicación del ADN , Técnica del Anticuerpo Fluorescente , Humanos , Ratones , Ratones Desnudos , Metástasis de la Neoplasia , Trasplante de Neoplasias , Receptores Mensajeros de Linfocitos/genética , Transfección , Trasplante HeterólogoRESUMEN
CD44H is the principal cell surface receptor for hyaluronate, which is a major glycosaminoglycan of the extracellular matrix. Expression of CD44H is enhanced in a variety of malignant tumors and correlates with tumor aggressiveness, supporting the notion that interaction between CD44H and hyaluronate may play an important role in tumor growth and dissemination. In this report we show that in vivo tumor formation by human lymphoma Namalwa cells, stably transfected with CD44H, can be suppressed by a soluble human CD44H-immunoglobulin fusion protein. Disruption of the interaction between CD44H and its physiologic ligands may provide a novel strategy for controlling tumor growth in vivo.
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Inmunoglobulinas/inmunología , Linfoma/inmunología , Receptores Mensajeros de Linfocitos/inmunología , Animales , Antígenos CD8/inmunología , División Celular , Semivida , Humanos , Inmunoglobulinas/administración & dosificación , Inmunoglobulinas/genética , Linfoma/terapia , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Receptores Mensajeros de Linfocitos/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/farmacología , Solubilidad , Transfección , Células Tumorales CultivadasRESUMEN
Suppressor T cells (Ts-1) induced with trinitrophenyl (TNP)-conjugated syngeneic spleen cells (TNP-SC) can be enriched on antigen-coated plates and are afferent suppressors. In addition, these suppressor cells produced soluble suppressor factors (TsF) that were active in vivo. Therefore, the Ts-1 cells in the TNP system are very similar to the Ts-1 cells in other systems we have studied earlier. Further characterization of these TsF-1 revealed that TsF-1 obtained from TNP-SC-induced Ts-1 is major histocompatibility complex restricted in its activity. Injection of TNP-specific TsF-1 into naive mice did not induce Ts-2 unless additional corresponding antigen was provided. Moreover, the Ts-2 cells induced by administration of both TsF-1 and trinitrobenzene sulfonic acid were antigen specific rather than antiidiotypic.
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Epítopos , Hipersensibilidad Tardía/inmunología , Activación de Linfocitos , Nitrobencenos/inmunología , Linfocitos T Reguladores/inmunología , Ácido Trinitrobencenosulfónico/inmunología , Animales , Sitios de Unión , Hipersensibilidad Tardía/diagnóstico , Inmunización Pasiva , Idiotipos de Inmunoglobulinas/genética , Idiotipos de Inmunoglobulinas/inmunología , Linfocinas/genética , Linfocinas/fisiología , Ratones , Ratones Endogámicos A , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Receptores de Antígenos de Linfocitos T/genética , Bazo/citología , Factores Supresores Inmunológicos , Linfocitos T Reguladores/clasificación , Linfocitos T Reguladores/metabolismo , Ácido Trinitrobencenosulfónico/administración & dosificaciónRESUMEN
Delayed-type hypersensitivity (DTH) to p-azobenzenearsonate (ABA) can be induced in A/J mice with intravenous injection of minute amounts of anti-cross-reactive idiotypic (CRI) antibodies, providing that the animals have been pretreated 2 d earlier with low doses of cyclophosphamide (50 mg/kg). However intravenous injection of the F(ab')2 fragments of the anti-CRI antibodies or subcutaneous administration with anti-CRI antibodies induces comparable immunity in both cyclophosphamide-pretreated and normal nontreated animals. Furthermore adoptive transfer experiments indicate that lymph node cells taken from animals sensitized with anti-CRI 4 d earlier can adoptively transfer immunity to naive recipients. Transfer of immunity is mediated by a population of thymus-dependent (T) cells, which express idiotypic structures on their surface. Treatment of effector cells with either anti-theta serum or anti-idiotypic antibodies plus complement completely abrogated their ability to transfer immunity. In addition idiotype-bearing suppressor T cells induced with ABA-coupled spleen cells inhibit the development of ABA-specific DTH induced with anti-CRI antibodies. Genetic analysis revealed that the ability of anti-CRI antibodies to induce ABA-specific DTH was linked to Igh-1 heavy-chain allotype. Anti-idiotypic antibodies to the major CRI associated with anti-ABA antibodies in A/J mice failed to induce significant immunity in BALB/c mice (H-2d, Igh-1a). Nevertheless, they were able to induce significant immunity in C.AL20 mice (H-2d, Igh-1d) which possess a heavy-chain allotype similar to that of A/J mice.
Asunto(s)
Compuestos Azo/inmunología , Hipersensibilidad Tardía/inmunología , Inmunidad Celular , Idiotipos de Inmunoglobulinas , Linfocitos T/inmunología , p-Azobencenoarsonato/inmunología , Animales , Anticuerpos Antiidiotipos , Reacciones Cruzadas , Ciclofosfamida/farmacología , Femenino , Inmunización Pasiva , Ratones , Ratones Endogámicos A/inmunología , Receptores Inmunológicos/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
Genetic restrictions governing the induction and expression of suppressor T cells (Ts) in tolerance to 1-fluoro-2,4-dinitrogenzene (DNFB) contract sensitivity were studied. Tolerance was induced by using 2,4-dinitrophenyl (DNP)-modified lymphoid cells (DNP-LC) as tolerogen. Two kinds of Ts were found-those produced by DNP-LC syngeneic to the donor of the Ts (syninduced Ts), and those produced by DNP-LC allogeneic to the donor of Ts (alloinduced Ts). Studies employing congenic resistant mouse strains indicated that recognition of DNP-modified-major histocompatibility region determinants on the tolerogenic DNP-LC was essential for the induction of both types of Ts. Non-H-2 genetic background was irrelevant to Ts induction. Mapping studies indicated that induction of both syninduced and alloinduced Ts was associated with recognition of DNP-modified-MHC region determinants which map to the right of the H-2G region (i.e., H-2D gene products). Tolerization of donor mice with DNP-LC which were H-2D region compatible, but not with H-2K or I region compatible DNP-LC, was both sufficient and required for the induction of hapten-specific syninduced Ts. Tolerization of donor mice with DNP-LC which were incompatible only at the H-2D region was sufficient for the induction of alloinduced Ts. These Ts were capable of suppressing recipient mice only if the recipients shared the H-2D region with the strain providing the DNP-LC tolerogen, and were not capable of suppressing recipients sharing all but the H-2D region with the tolerogen.