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This data article presents details on the assessment of fracture parameters of laboratory asphalt mixtures produced using both natural and recycled concrete aggregates. The gap-graded stone matrix asphalt (SMA) is created by incorporating Trinidad Lake Asphalt (TLA) binder with carefully calibrated mixtures of recycled concrete aggregates (0 %, 10 %, 35 %, and 50 %) and natural aggregates (limestone and dust filler). The dataset variables were chosen based on the specifications of the single-edge notched beam (SENB) and semi-circular bending (SCB) tests, which are currently used for quality control and assurance (QC & QA) assessment of asphalt concrete mixtures. The data parameters provided include air void content, voids in mineral aggregates, voids filled with asphalt, density, Marshall Stability, Flow, test temperature, peak loads, RCA content, and notch depths. The fracture resistance of the mixes was studied by analysing the fracture energy, tensile strength, and fracture toughness for the collected dataset. The data shows that incorporating up to 10 % of RCA into SMA mixes, similar fracture properties can be achieved compared to traditional SMA mixtures. This presents a sustainable and environmentally advantageous option, however, it is important to exercise caution as the RCA content increases.
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This data article presents information on the measurement of Indirect Tensile Stiffness Modulus of laboratory and field asphalt mixtures. The asphalt mixes are composed of three distinct binders that were categorised by their penetration grade (40/55-TLA, 60/75-TLA, and 60/70-MB) and aggregates (limestone, sharp sand, and filler). The asphalt mixtures are called dense-graded hot mix asphalt (HMA) and gap-graded stone matrix asphalt (SMA). The variables in the dataset were selected in accordance with the specifications of the dynamic modulus models that are currently in use as well as the needs for the quality control and assurance (QC & QA) assessment of asphalt concrete mixes. The data parameters included are temperature, asphalt content, and binder viscosity, air void content, cumulative percent retained on 19, 12.5, and 4.75 mm sieves, maximum theoretical specific gravity, aggregate passing #200 sieve, effective asphalt content, density, flow, marshal stability, coarse-to-fine particle ratio and the Indirect Tensile Stiffness Modulus (ITSM). Utilising soft computing techniques, models were developed utilising the data thus eliminating the requirement for complex and time-consuming laboratory testing.
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Equine coital exanthema (ECE) is an infectious, venereally transmitted muco-cutaneous disease affecting mares and stallions, caused by equid alphaherpesvirus 3 (EHV3). Diagnostic tools for rapid identification of EHV3 are of primary importance to diminish the risk of EHV3 dissemination at the time of breeding. In the last years, it has been shown that the performance of the insulated-isothermal polymerase chain reaction (iiPCR) is comparable to virus isolation, nested PCR and real-time PCR (qPCR) in detecting pathogens of various animal species. Analytical sensitivity and specificity of the iiPCR were compared with a qPCR, using a plasmid containing the target region of the EHV3 glycoprotein G gene and an Argentinian EHV3 isolate (E/9283/07 C3A). In order to evaluate the diagnostic performance of the iiPCR, nucleic acids of 85 perineal and genital swabs (PGS) of mares and stallions were extracted by tacoTM mini and tested by both techniques. EHV3 was detected in 46 and 45 of the 85 PGS by the iiPCR and qPCR, respectively. There was almost perfect agreement between the two diagnostic methods (98.82%; 95% CI: 95.03-100%; κâ¯=â¯0.98). The iiPCR had a limit of detection of 95.00% at 6 genome equivalents per reaction and a detection endpoint for viral DNA comparable to that of the qPCR, and did not react with six non-targeted equine pathogens. The iiPCR represents a sensitive and specific method for the rapid on-site diagnosis of EHV3 infection. Its routinely implementation in breeding facilities, and artificial insemination and embryo transfer centers, will contribute to prevent the dissemination of this venereal, highly contagious disease in horses.
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Genitales/virología , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 3/aislamiento & purificación , Enfermedades de los Caballos/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Perineo/virología , Reacción en Cadena de la Polimerasa/métodos , Animales , Infecciones por Herpesviridae/diagnóstico , Enfermedades de los Caballos/virología , Caballos , Pruebas en el Punto de Atención , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Short-term neurectomy-induced disuse (SN) has been shown to restore load responses in aged mice. We examined whether this restoration was further enhanced in both cortical and trabecular bone by simply extending the SN. METHODS: Following load:strain calibration, tibiae in female C57BL/J6 mice at 8, 14 and 20 weeks and 18 months (n=8/group) were loaded and bone changes measured. Effects of long-term SN examined in twenty-six 18 months-old mice, neurectomised for 5 or 100 days with/without subsequent loading. Cortical and trabecular responses were measured histomorphometrically or by micro-computed tomography. RESULTS: Loading increased new cortical bone formation, elevating cross-sectional area in 8, 14 and 20 week-old (p ⟨0.05), but not 18 month-old aged mice. Histomorphometry showed that short-term SN reinstated load-responses in aged mice, with significant 33% and 117% increases in bone accrual at 47% and 37%, but not 27% of tibia length. Cortical responses to loading was heightened and widespread, now evident at all locations, following prolonged SN (108, 167 and 98% at 47, 37 and 27% of tibial length, respectively). In contrast, loading failed to modify trabecular bone mass or architecture. CONCLUSIONS: Mechanoadaptation become deficient with ageing and prolonging disuse amplifies this response in cortical but not trabecular bone.
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Adaptación Fisiológica/fisiología , Hueso Esponjoso/fisiopatología , Hueso Cortical/fisiopatología , Osteogénesis/fisiología , Animales , Femenino , Ratones , Ratones Endogámicos C57BL , Desnervación Muscular , Osteoporosis/fisiopatología , Estrés MecánicoRESUMEN
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Lymphocyte trafficking via chemokine receptors such as CCR5 plays a critical role in alloreactive responses, and previous data suggest that CCR5 blockade with maraviroc results in a low incidence of visceral GVHD. However, the full scope of clinical and immunologic effects of CCR5 blockade in HSCT has not been described. We compared a cohort of patients enrolled on a trial of reduced-intensity allo-HSCT with standard GVHD prophylaxis plus maraviroc to a contemporary control cohort receiving standard GVHD prophylaxis alone. Maraviroc treatment was associated with a lower incidence of acute GVHD without increased risk of disease relapse, as well as reduced levels of gut-specific markers. At day 30, maraviroc treatment increased CCR5 expression on T cells and dampened T-cell activation in peripheral blood without impairing early immune reconstitution or increasing risk for infections. Patients who developed acute GVHD despite maraviroc prophylaxis showed increased T-cell activation, naive T-cell skewing, and elevated serum CXCL9 and CXCL10 levels. Collectively, these data suggest that maraviroc effectively protects against GVHD by modulating alloreactive donor T-cell responses, and that CXCR3 signaling may be an important resistance mechanism to CCR5 blockade in GVHD.
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Antagonistas de los Receptores CCR5/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Activación de Linfocitos/efectos de los fármacos , Receptores CCR5/inmunología , Linfocitos T/efectos de los fármacos , Adulto , Anciano , Antígenos de Neoplasias/análisis , Antígenos de Neoplasias/inmunología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/inmunología , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunidad Celular/efectos de los fármacos , Interleucina-15/análisis , Interleucina-15/inmunología , Lectinas Tipo C/análisis , Lectinas Tipo C/inmunología , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Pancreatitis , Linfocitos T/inmunología , Linfocitos T/patología , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL- 6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TO-related dry eye or other ocular surface inflammatory disorders.
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Enfermedades Autoinmunes/diagnóstico , Conjuntiva/patología , Síndromes de Ojo Seco/diagnóstico , Enfermedades de la Tiroides/diagnóstico , Adolescente , Adulto , Anciano , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Estudios de Casos y Controles , Conjuntiva/metabolismo , Técnicas Citológicas , Síndromes de Ojo Seco/inmunología , Síndromes de Ojo Seco/metabolismo , Epitelio/metabolismo , Epitelio/patología , Femenino , Humanos , Técnicas Inmunológicas , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Most contraceptive methods present benefits beyond contraception; however, despite a large body of evidence, many healthcare professionals (HCPs), users and potential users are unaware of those benefits. This review evaluates the evidence for non-contraceptive benefits of hormonal and non-hormonal contraceptive methods. METHODS: We searched the medical publications in PubMed, POPLINE, CENTRAL, EMBASE and LILACS for relevant articles, on non-contraceptive benefits of the use of hormonal and intrauterine reversible contraceptive methods, which were published in English between 1980 and July 2014. Articles were identified using the following search terms: 'contraceptive methods', 'benefits', 'cancer', 'anaemia', 'heavy menstrual bleeding (HMB)', 'endometrial hyperplasia', 'endometriosis' and 'leiomyoma'. RESULTS: We identified, through the literature search, evidence that some combined oral contraceptives have benefits in controlling HMB and anaemia, reducing the rate of endometrial, ovarian and colorectal cancer and ectopic pregnancy as well as alleviating symptoms of premenstrual dysphoric disorder. Furthermore, the use of the levonorgestrel-releasing intrauterine system also controls HMB and anaemia and endometrial hyperplasia and cancer, reduces rates of endometrial polyps in users of tamoxifen and alleviates pain associated with endometriosis and adenomyosis. Depot medroxyprogesterone acetate controls crises of pain associated with sickle cell disease and endometriosis. Users of the etonogestrel-releasing contraceptive implant have the benefits of a reduction of pain associated with endometriosis, and users of the copper intrauterine device have reduced rates of endometrial and cervical cancer. CONCLUSIONS: Despite the high contraceptive effectiveness of many hormonal and intrauterine reversible contraceptive methods, many HCPs, users and potential users are concerned mainly about side effects and safety of both hormonal and non-hormonal contraceptive methods, and there is scarce information about the many benefits that these methods offer beyond contraception.
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Anticonceptivos Femeninos/uso terapéutico , Enfermedades Urogenitales Femeninas/tratamiento farmacológico , Dispositivos Intrauterinos Medicados , Anemia/tratamiento farmacológico , Anticoncepción/métodos , Anticonceptivos Orales Combinados/uso terapéutico , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Humanos , Levonorgestrel/uso terapéutico , Dolor/prevención & control , Embarazo , Embarazo Ectópico/tratamiento farmacológico , Trastorno Disfórico Premenstrual/tratamiento farmacológicoRESUMEN
PURPOSE: To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. PATIENTS AND METHODS: We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. RESULTS: Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 10(8) CD8 cells per kilogram optimally segregated patients receiving CD8(hi) and CD8(lo) grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8(hi) graft, whereas approximately half of younger donors provided CD8(hi) grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8(lo) doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8(hi) doses (P = .03), but not for recipients of younger unrelated donor CD8(lo) grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. CONCLUSION: Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT.
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Linfocitos T CD8-positivos , Selección de Donante , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Femenino , Citometría de Flujo , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Donante no EmparentadoRESUMEN
Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele-specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.
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Neoplasias Colorrectales/genética , Factor de Crecimiento Epidérmico/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Factor A de Crecimiento Endotelial Vascular/genética , Alelos , Pueblo Asiatico , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Frecuencia de los Genes , Genotipo , Humanos , Malasia/epidemiología , Oportunidad RelativaRESUMEN
Colorectal cancer (CRC) is one of the most common types of cancer in both developed and developing countries. This disease is triggered by and progresses via the sequential accumulation of multiple genetic alterations. In addition, the interaction between low-penetrance genes and environmental factors can also increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are one of the predisposing factors for CRC, IBD-related genes might, to a certain extent, be associated with cancer initiation. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most well-established gene to be associated with increased susceptibility to Crohn's disease. Thus, various studies have been performed to investigate the potential contribution of this gene to CRC risk. In this study, we aimed to determine the frequency of the Arg702Trp, Gly908Arg, 3020insC, Pro268Ser, and JW1 variants of NOD2/CARD15, and to investigate their association with CRC susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this study. Subsequently, real-time polymerase chain reaction with TaqMan was performed for the genotyping of these NOD2/ CARD15 variants. None of the NOD2/CARD15 variants was statistically associated to CRC susceptibility in our Malaysian population. Our findings were remarkably similar to those of other Asian cohorts, which indicated that these NOD2/CARD15 variants exhibit genetic heterogeneity between Caucasian and Asian populations.
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Pueblo Asiatico/genética , Neoplasias Colorrectales/genética , Variación Genética , Proteína Adaptadora de Señalización NOD2/genética , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes , Estudios de Asociación Genética , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Malasia , Oportunidad Relativa , Polimorfismo de Nucleótido SimpleRESUMEN
Mutations in the PAX6 gene that cause aniridia have been identified in various ethnicities but not in the Malaysian population. Therefore, the objective of this study was to investigate the PAX6 mutation in a Malaysian family with congenital aniridia. In this study, a complete ophthalmic examination was performed on a Dusun ethnic family with aniridia. Genomic DNA was extracted from the peripheral blood of the subjects and screened for the PAX6 gene mutation using polymerase chain reaction amplification high-resolution melting curve analysis (PCR-HRM) followed by confirmation via direct DNA sequencing. A heterozygous G deletion (c.857delG) in exon 7 causing a frame shift in PAX6 was identified in all affected family members. Genotype-phenotype correlation analysis revealed congenital cataract and all affected family members showed a similar spectrum of aniridia with no phenotypic variability but with differences in severity that were age-dependent. In summary, by using a PCR-HRM approach, this study is the first to report a PAX6 mutation in a Malaysian family. This mutation is the cause of the aniridia spectra observed in this family and of congenital cataract.
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Aniridia/genética , Proteínas del Ojo/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Homeodominio/genética , Factores de Transcripción Paired Box/genética , Polimorfismo Conformacional Retorcido-Simple/genética , Proteínas Represoras/genética , Aniridia/patología , Pueblo Asiatico/genética , Femenino , Estudios de Asociación Genética , Humanos , Malasia , Masculino , Mutación , Desnaturalización de Ácido Nucleico , Factor de Transcripción PAX6 , LinajeRESUMEN
Agonists of the TNF superfamily of receptors hold promise as novel therapy for cancer. Recent data on agonistic anti-murine TNF receptors (TNFR) such as CD40 suggest that the specific engagement of Fc-receptor (FcR) is required for optimal antitumor effects, prompting calls to engineer anti-human CD40 and other TNFR mAb accordingly. CP-870,893 is a fully human anti-CD40 mAb, selected in part because it is an IgG2 which is presumed to have poor reactivity with FcR; however, CP-870,893 has been evaluated in multiple clinical trials with beneficial activity in patients with melanoma, pancreatic and other cancers. Here, we confirmed that the activity of anti-murine CD40 mAb was dependent on FcγRIIB engagement, was decreased significantly in FcγRIIB (-/-) mice, and upon Fc-crosslinking anti-mouse CD40 mAb enhanced the activation of antigen presenting cells. In contrast, the CP-870,893-mediated activation of human B cells was not enhanced with anti-IgG-crosslinking nor abrogated when used as an F(ab)'2 reagent. Crosslinking of CP-870,893 using the CD32-expressing K562 cells yielded an Fc-dependent modest increase in the expression of some activation markers relative to that of the soluble CP-870,893 mAb. Classic Fc-dependent functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CMC) were minimal for CP-870,893 as compared to the IgG1 anti-CD20 mAb rituximab, which mediated both ADCC and CMC in parallel assays. Anti-mouse CD40 mAb competed for the CD40 ligand binding site, but CP-870,893 did not. Thus, Fc-crosslinking is not an essential requirement for agonistic anti-human CD40 mAb, whose potency is more dependent on the CD40 epitope recognized and the strength of the signal achieved.
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Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Antígenos CD40/agonistas , Neoplasias/inmunología , Animales , Anticuerpos Monoclonales/metabolismo , Especificidad de Anticuerpos/inmunología , Antineoplásicos/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Modelos Animales de Enfermedad , Humanos , Fragmentos Fc de Inmunoglobulinas/metabolismo , Inmunoterapia , Activación de Linfocitos/inmunología , Ratones , Ratones Noqueados , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Unión Proteica , Receptores de IgG/metabolismoRESUMEN
Allele frequencies of 15 short tandem repeat (STR) loci, namely D5S818, D7S820, D13S317, D16S539, TH01, TPOX, Penta D, Penta E, D3S1358, D8S1179, D18S51, D21S11, CSF1PO, vWA, and FGA, were determined for 154 individuals from the Kadazan-Dusun tribe, an indigenous population of East Malaysia. All loci were amplified by polymerase chain reaction, using the Powerplex 16 system. Alleles were typed using a gene analyzer and the Genemapper ID software. Various statistical parameters were calculated and the combined power of discrimination for the 15 loci in the population was calculated as 0.999999999999999. These loci are thus, informative and can be used effectively in forensic and genetic studies of this indigenous population.
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Frecuencia de los Genes/genética , Repeticiones de Microsatélite , Alelos , Sitios Genéticos , Genética de Población , Humanos , Malasia/etnología , Reacción en Cadena de la PolimerasaRESUMEN
We report on the first evidence of intra-community coalitionary lethal aggression in muriquis (Brachyteles). The event occurred in southern muriquis (Brachyteles arachnoides) during a long-term study (>15 years) of two social groups inhabiting mostly pristine Atlantic forest habitat in the Parque Estadual Carlos Botelho, southern São Paulo State, Brazil. The attack took place deep in the core area of the Group Caetê home range. Tense agonistic behaviors and vocalizations preceded the lethal coalitionary attack, and the tension increased over a 36-48 hr period. One adult female and two unidentified individuals also took part in a coalition led by six adult males. The members of the coalition collectively approached, embraced, immobilized and repeatedly bit the entire body of an adult male, resulting in severe bleeding injuries and the victim's death in less than 1 hr after the attack commenced. Combined ecological, behavioral and spatial data related to the event indicate that this was an intra-community attack and suggest social tensions related to mating competition as the proximate trigger of the coalitionary killing. The attack resembled those reported for chimpanzees, with clear numeric superiority and a low risk of injury to aggressors, resulting in the death of a lone conspecific victim. This observation (n=1) is suggestive of a capacity for escalated aggression in muriquis and reinforces arguments for the potential adaptive significance of intra-community aggression in male philopatric societies, as reported for spider monkeys and chimpanzees. These characteristics challenge the view of the muriquis as a peaceful primate and support the general hypothesis that imbalances of power contribute to intra-specific killing in primates, such as chimpanzees and humans.
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Conducta Agonística/fisiología , Atelinae/fisiología , Conducta Animal/fisiología , Conducta Cooperativa , Agresión , Animales , Brasil , Ecosistema , Femenino , Masculino , Predominio Social , ÁrbolesRESUMEN
An African American male of West Indies descent was diagnosed to have elevated transferrin saturation, hyperferritinemia, severe iron deposition in hepatocytes, and hepatic cirrhosis at age 4. He was treated with serial phlebotomy to maintain a normal serum ferritin concentration thereafter. We evaluated him at age 23 and confirmed that he had normal serum ferritin levels, severe iron deposition in hepatocytes, hepatic cirrhosis, and portal hypertension. He did not have endocrinopathy, cardiomyopathy, or arthropathy. He was homozygous for the novel hemojuvelin (HJV) premature stop-codon mutation R54X (exon 3; c.160A-->T). He did not have either HFE C282Y, H63D, or S65C, or deleterious coding region mutations of SLC40A1, TFR2, or HAMP. His erythrocyte measures and hemoglobin electrophoresis were consistent with alpha-thalassemia trait. We conclude that homozygosity for HJV R54X accounts for his severe, early age-of-onset hemochromatosis; his phenotype was probably modified by serial phlebotomy therapy.
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Hemocromatosis/genética , Sobrecarga de Hierro/genética , Proteínas de la Membrana/genética , Adulto , Negro o Afroamericano/genética , Edad de Inicio , Ferritinas/sangre , Proteínas Ligadas a GPI , Proteína de la Hemocromatosis , Humanos , Hipertensión Portal , Cirrosis Hepática , Masculino , Fenotipo , Flebotomía , Indias Occidentales/etnologíaRESUMEN
Wild capuchin monkeys inhabiting dry forest were found to customarily use tools as part of their extractive foraging techniques. Tools consisted of twigs and sticks, often modified, which were used to probe for insects and, most frequently, of stones of a variety of sizes and shapes used for cracking and digging. The use of tools for digging has been thought to be restricted to humans. These monkeys, living in a harsh dry habitat, survive food limitation and foraging time constraints through their extensive tool use.
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Conducta Animal , Cebus/psicología , Conducta Alimentaria , Alimentos , Animales , Conducta Apetitiva , Brasil , Ambiente , ÁrbolesRESUMEN
The possible occurrence of increased non-enzymatic glycosylation of serum insulin-like growth factor binding protein-3 (IGFBP-3) in vivo and the changes that would simultaneously occur in serum levels of IGFBP-3 and insulin-like growth factor-1 (IGF-I) were investigated. We measured levels of IGF-I and IGFBP-3 and the degree of glycation of total serum protein and IGFBP-3, in serum samples obtained from patients with poorly controlled non-insulin-dependent diabetes (type 2) and from age-matched non-diabetic controls. Type 2 diabetic patients had significantly higher glycated serum protein (GlyP) levels. GlyP significantly correlated with age in the control (r = 0.315, P<0.05) but not in the type 2 diabetes group. Control and diabetic subjects had comparable serum IGF-I levels and in both groups IGF-I levels tended to decrease with age (r = -0.567, P<0.001 and r = -0.465, P<0.05 for control and type 2 diabetic subjects, respectively). In the type 2 diabetes group, IGF-I levels showed a negative correlation with serum GlyP values (r = -0.476, P<0.05). Type 2 diabetic and control patients had comparable serum IGFBP-3 levels, which were significantly higher in diabetic patients in the older age subgroups. A negative correlation was found between IGFBP-3 levels and age in the control (r = -0.705, P<0.001) and in the type 2 diabetes groups (r = -0.463, P<0.05). A significant negative correlation was found between IGFBP-3 levels and GlyP in control (r = -0.449, P<0.002) but not in type 2 diabetic subjects. The mean glycated IGFBP-3 (GlyIGFBP-3) levels were higher in the oldest type 2 diabetic patients. In these patients, GlyIGFBP-3 was negatively associated with IGF-I levels (r = -0.447, P<0.05). The IGF-I/IGFBP-3 molar ratio was significantly reduced in the 46-60-year-old type 2 diabetic group, whereas the IGF-I/IGFBP-3 ratio was positively and significantly correlated with GlyP levels only in the control group (r = 0.489, P<0.01). Our results show that: a) increased non-enzymatic glycosylation of IGFBP-3 occurs in vivo; and b) this effect is accompanied by an increase in IGFBP-3 levels. These results suggest that the IGF-I/IGFBP-3 system is another target for the metabolic derangements of type 2 diabetes. Its alterations might play a role in diabetic complications.
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Diabetes Mellitus Tipo 2/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adulto , Anciano , Envejecimiento/sangre , Proteínas Sanguíneas/metabolismo , Femenino , Glicosilación , Humanos , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
OBJECTIVES: The identification of constitutional cytogenetic abnormalities in patients with cancer may indicate loci of genes, abnormalities of which are responsible for tumor development or progression. This study was undertaken to determine whether girls with Turner's syndrome (TS) (partial or complete deletion of an X chromosome, short stature, gonadal dysgenesis) are at increased risk of neural crest-derived tumors. STUDY DESIGN: Medical records of 394 patients with TS who were followed up at Thomas Jefferson Hospital and Children's Hospital of Pittsburgh were reviewed for documentation of TS phenotype, constitutional cytogenetics, and history of neuroblastoma or related tumors. Informative cases were reviewed for tumor pathology, primary site, disease stage, associated symptoms, treatment, and outcome. RESULTS: Three patients were found to have neuroblastoma. A fourth child who died of neurofibrosarcoma was found to have extensive areas of ganglioneuroma, the benign counterpart of neuroblastoma, at autopsy. An additional four girls with TS and neuroblastoma were identified in the literature, as were two more patients with ganglioneuroma. These 10 patients ranged in age from 1 week to 16 10/12 years (median age, 3 years), and all but two of the children had localized lesions. Two of the seven children with neuroblastoma had courses complicated by opsoclonus-myoclonus, a syndrome found in fewer than 5% of all patients with neuroblastoma. CONCLUSIONS: These data strongly suggest that girls with TS are predisposed to the development of neuroblastoma and related tumors. Because these tumors are often of limited stage and may be underdiagnosed, screening of urine of patients with TS for elevated catecholamine metabolite levels may strengthen this association.
Asunto(s)
Neuroblastoma/complicaciones , Síndrome de Turner/complicaciones , Adolescente , Niño , Preescolar , Aberraciones Cromosómicas/genética , Deleción Cromosómica , Trastornos de los Cromosomas , Femenino , Estudios de Seguimiento , Ligamiento Genético/genética , Humanos , Lactante , Recién Nacido , Cariotipificación , Neuroblastoma/genética , Síndrome de Turner/genética , Cromosoma X/genéticaRESUMEN
Blood samples for plasma steroid hormone determinations and molecular genotype analysis of the 21-hydroxylase gene (CYP21) were obtained from 15 infants identified through a voluntary newborn screening program. Mutations were identified on both CYP21 alleles in 12 (80%) of 15 infants; all had confirmatory plasma 17-hydroxyprogesterone concentrations > 3500 ng/dl. No patient was found to carry mutations associated with late-onset 21-hydroxylase deficiency. Newborn screening hastened diagnosis in eight infants.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Tamizaje Neonatal , 17-alfa-Hidroxiprogesterona/sangre , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Hiperplasia Suprarrenal Congénita/prevención & control , Alelos , Androstenodiona/sangre , Exones/genética , Femenino , Conversión Génica/genética , Genotipo , Humanos , Recién Nacido , Intrones/genética , Masculino , Mineralocorticoides/uso terapéutico , Biología Molecular , Mutación/genética , Hibridación de Ácido Nucleico , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , Progesterona/sangre , Empalme del ARN/genética , Análisis de Secuencia de ADN , Esteroide 21-Hidroxilasa/sangre , Esteroide 21-Hidroxilasa/genética , Virilismo/diagnósticoRESUMEN
OBJECTIVE: To investigate the safety, immunogenicity, and efficacy of a simplified hepatitis B vaccination schedule. METHODS: The second dose of hepatitis B vaccine and the first dose of diphtheria-tetanus-pertussis (DTP) vaccine were given simultaneously at age 6 weeks. The second dose of DTP vaccine was given at age 3.5 months. The third dose of DTP vaccine and the third dose of hepatitis B vaccine were given at age 5.5 months. One hundred three infants (group A) born to mothers without hepatitis B surface antigen (HBsAg) received DTP with whole-cell pertussis vaccine. Fifty-five infants (group B) born to mothers with HBsAg and hepatitis B e antigen received DTP with acellular pertussis vaccine. RESULTS: By age 9 months, none of group A and 4 (7%) group B infants were sero-positive for HBsAg. The protective efficacy against the hepatitis B carrier state in these infants at high risk was 92%. Antibody to hepatitis B surface antigen was 10 mlU/ml or greater in 99 (96%) of group A infants and in 50 (91%) of group B infants. Both the acellular and whole-cell DTP vaccines were immunogenic, and the incidences of adverse reactions were within an expected and acceptable range. CONCLUSIONS: The simplified vaccination schedule to integrate the hepatitis B vaccine into the Expanded Programme of Immunization was safe, Immunogenic, and effective. This schedule may improve vaccine compliance and be applied to DTP and hepatitis B combination vaccines now under investigation.