RESUMEN
Food processing wears down teeth, thus affecting tooth functionality and evolutionary success. Other than intrinsic silica phytoliths, extrinsic mineral dust/grit adhering to plants causes tooth wear in mammalian herbivores. Dental microwear texture analysis (DMTA) is widely applied to infer diet from microscopic dental wear traces. The relationship between external abrasives and dental microwear texture (DMT) formation remains elusive. Feeding experiments with sheep have shown negligible effects of dust-laden grass and browse, suggesting that intrinsic properties of plants are more important. Here, we explore the effect of clay- to sand-sized mineral abrasives (quartz, volcanic ash, loess, kaolin) on DMT in a controlled feeding experiment with guinea pigs. By adding 1, 4, 5, or 8% mineral abrasives to a pelleted base diet, we test for the effect of particle size, shape, and amount on DMT. Wear by fine-grained quartz (>5/<50 µm), loess, and kaolin is not significantly different from the abrasive-free control diet. Fine silt-sized quartz (â¼5 µm) results in higher surface anisotropy and lower roughness (polishing effect). Coarse-grained volcanic ash leads to significantly higher complexity, while fine sands (130 to 166 µm) result in significantly higher roughness. Complexity and roughness values exceed those from feeding experiments with guinea pigs who received plants with different phytolith content. Our results highlight that large (>95-µm) external silicate abrasives lead to distinct microscopic wear with higher roughness and complexity than caused by mineral abrasive-free herbivorous diets. Hence, high loads of mineral dust and grit in natural diets might be identified by DMTA, also in the fossil record.
Asunto(s)
Alimentación Animal , Cobayas , Plantas , Abrasión de los Dientes/veterinaria , Desgaste de los Dientes/veterinaria , Animales , Dieta/veterinaria , Herbivoria , Tamaño de la Partícula , Abrasión de los Dientes/etiologíaRESUMEN
Rabbits (Oryctolagus cuniculus) and rodents possess continuously growing teeth, and dental problems are a major health issue in these species. Knowledge of tooth growth characteristics is required to adequately treat dental problems and advise owners concerning diets. Most research was performed using bur marks and measuring eruption and wear manually. However, this method cannot be applied to teeth less rostral than the first premolar; therefore, for evaluation of molars, other methods are needed. We evaluated the use of fluorochromes xylenol orange and calcein green to measure growth rates of rabbit teeth and compared this method to results obtained by manually measuring the distance between a bur mark and the gingival margin of the same tooth (eruption) and by measuring the distance between the bur mark and the apex of the same tooth on computed tomography scans (growth). Apical fluorochrome measurements correlated well with eruption and growth rates obtained with bur marks, whereas measurements coronal to the pulp cavity did not. Growth rates were approximately 1.9 mm/wk for maxillary and 2.2 mm/wk for mandibular incisors. Growth rates of premolars were 2.14 ± 0.28 mm/wk in rabbits on a grass/rice hulls/sand pelleted diet and 0.93 ± 0.18 mm/wk in rabbits on a hay diet. Growth of molars could only be assessed using the measurement in dentin on the wall of the pulp cavity, which does not account for the real growth. However, being similar to this measurement in premolars, one could hypothesize similar growth in molars as in premolars. We conclude that the application of fluorochrome staining can be used to measure tooth growth in teeth that are not accessible for bur marks or in animals that are too small to assess tooth eruption or growth by bur marks.
Asunto(s)
Odontología/veterinaria , Microscopía Fluorescente/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Erupción Dental , Diente/crecimiento & desarrollo , Animales , Femenino , Colorantes Fluorescentes/metabolismo , ConejosRESUMEN
Although patterns of tooth wear are crucial in palaeo-reconstructions, and dental wear abnormalities are important in veterinary medicine, experimental investigations on the relationship between diet abrasiveness and tooth wear are rare. Here, we investigated the effect of four different pelleted diets of increasing abrasiveness (due to both internal [phytoliths] and external abrasives [sand]) or whole grass hay fed for 2 weeks each in random order to 16 rabbits (Oryctolagus cuniculus) on incisor and premolar growth and wear, and incisor and cheek tooth length. Wear and tooth length differed between diets, with significant effects of both internal and external abrasives. While diet abrasiveness was linked to tooth length for all tooth positions, whole forage had an additional effect on upper incisor length only. Tooth growth was strongly related to tooth wear and differed correspondingly between diets and tooth positions. At 1.4-3.2 mm/week, the growth of cheek teeth measured in this study was higher than previously reported for rabbits. Dental abnormalities were most distinct on the diet with sand. This study demonstrates that concepts of constant tooth growth in rabbits requiring consistent wear are inappropriate, and that diet form (whole vs. pelleted) does not necessarily affect cheek teeth. Irrespective of the strong effect of external abrasives, internal abrasives have the potential to induce wear and hence exert selective pressure in evolution. Detailed differences in wear effects between tooth positions allow inferences about the mastication process. Elucidating feedback mechanisms that link growth to tooth-specific wear represents a promising area of future research.
Asunto(s)
Dieta/veterinaria , Desgaste de los Dientes/veterinaria , Diente/crecimiento & desarrollo , Diente/patología , Alimentación Animal , Animales , Dieta/efectos adversos , Masticación , ConejosRESUMEN
PURPOSE/OBJECTIVES: To determine the prevalence of malnutrition and chemotherapy-induced nausea and vomiting (CINV) limiting patients' dietary intake in a chemotherapy unit. DESIGN: Cross-sectional descriptive audit. SETTING: Chemotherapy ambulatory care unit in a teaching hospital in Australia. SAMPLE: 121 patients receiving chemotherapy for malignancies, aged 18 years and older, and able to provide verbal consent. METHODS: An accredited practicing dietitian collected all data. Chi-square tests were used to determine the relationship of malnutrition with variables and demographic data. MAIN RESEARCH VARIABLES: Nutritional status, weight change, body mass index, prior dietetic input, CINV, and CINV that limited dietary intake. FINDINGS: Thirty-one participants (26%) were malnourished, 12 (10%) had intake-limiting CINV, 22 (20%) reported significant weight loss, and 20 (18%) required improved nutrition symptom management. High nutrition risk diagnoses, CINV, body mass index, and weight loss were significantly associated with malnutrition. Thirteen participants (35%) with malnutrition, significant weight loss, intake-limiting CINV, and/or who critically required improved symptom management reported no prior dietetic contact; the majority of those participants were overweight or obese. CONCLUSIONS: Of patients receiving chemotherapy in this ambulatory setting, 26% were malnourished, as were the majority of patients reporting intake-limiting CINV. IMPLICATIONS FOR NURSING: Patients with malnutrition and/or intake-limiting CINV and in need of improved nutrition symptom management may be overlooked, particularly patients who are overweight or obese-an increasing proportion of the Australian population. Evidence-based practice guidelines recommend implementing validated nutrition screening tools, such as the Malnutrition Screening Tool, in patients undergoing chemotherapy to identify those at risk of malnutrition who require dietitian referral.
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Antineoplásicos/efectos adversos , Desnutrición/inducido químicamente , Desnutrición/enfermería , Neoplasias/tratamiento farmacológico , Neoplasias/enfermería , Enfermería Oncológica/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Índice de Masa Corporal , Estudios Transversales , Enfermería Basada en la Evidencia/métodos , Femenino , Humanos , Masculino , Desnutrición/epidemiología , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/epidemiología , Náusea/enfermería , Neoplasias/epidemiología , Estado Nutricional/efectos de los fármacos , Prevalencia , Factores de Riesgo , Vómitos/inducido químicamente , Vómitos/epidemiología , Vómitos/enfermería , Adulto JovenRESUMEN
Several studies have described the production of influenza virus-like particles (VLP) using a variety of platform systems. These VLPs are non-replicating particles that spontaneously self-assemble from expressed influenza virus proteins and have been proposed as vaccine candidates for both seasonal and pandemic influenza. Although still in the early stages of development and evaluation as influenza vaccines, influenza VLPs have a variety of other valuable uses such as examining and understanding correlates of protection against influenza and investigating virus-cell interactions. The most common production system for influenza VLPs is the baculovirus-insect cell expression which has several attractive features including the ease in which new gene combinations can be constructed, the immunogenicity elicited and protection afforded by the produced VLPs, and the scalability offered by the system. However, there are differences between the influenza VLPs produced by baculovirus expression systems in insect cells and the influenza viruses produced for use as current vaccines or the virus produced during a productive clinical infection. We describe here the development of a modified vaccinia virus Ankara (MVA) system to generate mammalian influenza VLPs containing influenza H5N1 proteins. The MVA vector system is flexible for manipulating and generating various VLP constructs, expresses high level of influenza hemagglutinin (HA), neuraminidase (NA), and matrix (M) proteins, and can be scaled up to produce VLPs in quantities sufficient for in vivo studies. We show that mammalian VLPs are generated from recombinant MVA vectors expressing H5N1 HA alone, but that increased VLP production can be achieved if NA is co-expressed. These mammalian H5N1 influenza VLPs have properties in common with live virus, as shown by electron microscopy analysis, their ability to hemagglutinate red blood cells, express neuraminidase activity, and to bind influenza specific antibodies. Importantly, these VLPs are able to elicit a protective immune response in a mouse challenge model, suggesting their utility in dissecting the correlates of immunity in such models. Mammalian derived VLPs may also provide a useful tool for studying virus-cell interactions and may have potential for development as pandemic vaccines.
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Vectores Genéticos , Hemaglutininas/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Neuraminidasa/inmunología , Virus Vaccinia/genética , Virosomas/biosíntesis , Animales , Hemaglutininas/genética , Subtipo H5N1 del Virus de la Influenza A/genética , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/genética , Ratones , Ratones Endogámicos BALB C , Neuraminidasa/genética , Infecciones por Orthomyxoviridae , Vacunas de Virosoma/administración & dosificación , Vacunas de Virosoma/genética , Vacunas de Virosoma/inmunología , Virosomas/inmunologíaRESUMEN
Human herpesvirus 8 (HHV-8) persists as episomal DNA in latently-infected cells and can establish two alternative life cycles, latent or lytic. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is a known inducer of HHV-8 in several human primary effusion lymphoma cell lines and has been widely used for HHV-8 reactivation; however, induction conditions have differed, resulting in varying levels of virus expression. We have used HHV-8 latently-infected BC-3 cells as a model to determine critical parameters for optimizing virus reactivation by TPA. We found that cell growth properties and drug treatment conditions were important for maximum reactivation of HHV-8. Addition of TPA to cells in the early log phase of a sigmoidal growth curve, which was tightly associated with high percentage of the cells in early S phase and with lower histone deacetylase activity in the cells, provided the optimum cell conditions for latent virus to switch to lytic replication. Furthermore, increasing TPA concentration (up to 320 ng per ml) at 48 h exposure time resulted in increased virus production. The results demonstrate the use of a step-wise strategy with chemical induction that may facilitate broad detection of latent DNA viruses and novel virus discovery.
Asunto(s)
Herpesvirus Humano 8/efectos de los fármacos , Herpesvirus Humano 8/fisiología , Acetato de Tetradecanoilforbol/farmacología , Secuencia de Bases , Ciclo Celular , Línea Celular , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , ADN Viral/genética , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/patogenicidad , Histona Desacetilasas/metabolismo , Humanos , Microscopía Electrónica de Transmisión , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Viral/biosíntesis , ARN Viral/genética , Activación Viral/efectos de los fármacos , Activación Viral/fisiología , Replicación Viral/efectos de los fármacosRESUMEN
Native hepatitis B surface antigen (HBsAg) spontaneously assembles into 22-nm subviral particles. The particles are lipoprotein micelles, in which HBsAg is believed to span the lipid layer four times. The first two transmembrane domains, TM1 and TM2, are required for particle assembly. We have probed the requirements for particle assembly by replacing the entire first or third TM domain of HBsAg with the transmembrane domain of HIV gp41. We found that either TM domain of HBsAg could be replaced, resulting in HBsAg-gp41 chimeras that formed particles efficiently. HBsAg formed particles even when both TM1 and TM3 were replaced with the gp41 domain. The results indicate remarkable flexibility in HBsAg particle formation and provide a novel way to express heterologous membrane proteins that are anchored to a lipid surface by their own membrane-spanning domain. The membrane-proximal exposed region (MPER) of gp41 is an important target of broadly reactive neutralizing antibodies against HIV-1, and HBsAg-MPER particles may provide a good platform for future vaccine development.
Asunto(s)
Antígenos de Superficie de la Hepatitis B/química , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/metabolismo , Secuencia de Aminoácidos , Línea Celular , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/química , Virus de la Hepatitis B/genética , Humanos , Estructura Terciaria de ProteínaRESUMEN
Replication-competent forms of herpes simplex virus 1 (HSV-1) defective in the viral neurovirulence factor infected cell protein 34.5 (ICP34.5) are under investigation for use in the therapeutic treatment of cancer. In mouse models, intratumoral injection of ICP34.5-defective oncolytic HSVs (oHSVs) has resulted in the infection and lysis of tumor cells, an associated decrease in tumor size, and increased survival times. The ability of these oHSVs to infect and lyse cells is frequently characterized as exclusive to or selective for tumor cells. However, the extent to which ICP34.5-deficient HSV-1 replicates in and may be neurotoxic to normal brain cell types in vivo is poorly understood. Here we report that HSV-1 defective in ICP34.5 expression is capable of establishing a productive infection in at least one normal mouse brain cell type. We show that γ34.5 deletion viruses replicate productively in and induce cellular damage in infected ependymal cells. Further evaluation of the effects of oHSVs on normal brain cells in animal models is needed to enhance our understanding of the risks associated with the use of current and future oHSVs in the brains of clinical trial subjects and to provide information that can be used to create improved oHSVs for future use.
Asunto(s)
Encéfalo/virología , Virus Defectuosos/patogenicidad , Herpesvirus Humano 1/patogenicidad , Proteínas Virales/genética , Animales , Encéfalo/patología , Virus Defectuosos/ultraestructura , Eliminación de Gen , Herpes Simple , Herpesvirus Humano 1/genética , Ratones , Viroterapia Oncolítica , Virus Oncolíticos/genética , Replicación ViralRESUMEN
The recent urgency to develop new vaccines for emerging and re-emerging diseases, such as pandemic influenza, has necessitated the use of cell substrates not previously used in the manufacture of licensed vaccines. A major safety concern in the use of novel cell substrates is the presence of potential adventitious agents, such as latent and occult viruses, that may not be detected by currently used conventional assays. In cases where the novel cell substrate is known to be tumorigenic, there are additional safety issues related to tumorigenicity of intact cells and oncogenicity of residual cellular DNA. We have developed a strategy for evaluating vaccine cell substrates for the presence of latent/occult viruses, including endogenous retroviruses, latent RNA viruses and oncogenic DNA viruses, by optimizing conditions for chemical induction of viruses and using a combination of broad and specific assays to enable detection of known and novel viruses.
Asunto(s)
Algoritmos , Vacunas , Virus/aislamiento & purificaciónRESUMEN
Rotavirus is a non-enveloped virus that depends on cellular lipids for cell entry and associates with lipid rafts during assembly. However, the effects of cellular lipids on rotavirus assembly are still not fully understood. The present study analyzes the effects of lovastatin, an inhibitor of cholesterol biosynthesis, during rotavirus infection in MA104 cells with regard to viral growth and particle assembly. Following viral infection, a 2-log relative reduction of viral titers was observed in drug-treated cells, while viral mRNA levels in infected cells remained unaltered in both groups. Furthermore, the levels of some viral proteins in drug-treated cells were elevated. The observed discordance between the viral RNA and protein levels and the decrease in infectivity titers of viral progeny in the drug-treated cells suggested that the drug affects viral assembly, the viral proteins not being properly incorporated into virions. Transmission electron microscopic (TEM) analysis revealed that in drug-treated cells there was an increase in "empty-looking" rotavirus particles devoid of an electron-dense core as compared to the normal, electron-dense particles seen in untreated infected cells. The present study thus provides visual evidence of defective rotavirus particle assembly as a result of cholesterol depletion.
Asunto(s)
Colesterol/metabolismo , Rotavirus/fisiología , Virión/fisiología , Ensamble de Virus/fisiología , Animales , Anticolesterolemiantes/farmacología , Línea Celular , Lovastatina/farmacología , Microscopía Electrónica de Transmisión , ARN Viral/efectos de los fármacos , ARN Viral/metabolismo , Rotavirus/efectos de los fármacos , Rotavirus/ultraestructura , Proteínas Estructurales Virales/efectos de los fármacos , Proteínas Estructurales Virales/metabolismo , Proteínas Estructurales Virales/ultraestructura , Virión/efectos de los fármacos , Virión/ultraestructura , Ensamble de Virus/efectos de los fármacosRESUMEN
OBJECTIVE: Multisomatoform disorder (MSD) is characterised by > or = 3 medically inexplicable, troublesome physical symptoms, together with a > or = 2-year history of somatisation. The aim of this study was to evaluate the prevalence of depressive and anxiety disorders in a South African sample MSD, and to compare demographic and clinical outcomes in those patients with and without co-morbidity. METHODS: Fifty-one adult outpatients with MSD were recruited from primary care clinics in the Cape Town metropolitan area. Participants were assessed for the presence of co-morbid depressive and anxiety disorders using the Mini Neuropsychiatric Interview-Plus (MINI-Plus). Outcomes included somatic symptom severity, disability, reported sick days and health care visits, pain experience, patient satisfaction with health services, and clinician-experienced difficulty. RESULTS: A current co-morbid depressive disorder was present in 29.4% (N = 15) of patients, and a current co-morbid anxiety disorder in 52.9% (N = 27). MSD patients with a co-morbid depressive disorder (current or lifetime) had significantly higher physical symptom counts, greater functional impairment, higher unemployment rates, more clinician-reported difficulties, and more dissatisfaction with health care services than those without the disorder. A larger number of co-morbid disorders was associated with greater overall disability. CONCLUSION: High rates of co-morbid depressive and anxiety disorders were present in a South African sample of primary care patients with MSD. Not all patients had co-morbidity, which is consistent with the view that MSD should be viewed as an independent disorder. However, co-morbid depressive disorders were associated with increased symptom severity and functional impairment, consistent with previous reports from developing countries, emphasising the importance of comorbidity in MSD.
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Ansiedad/epidemiología , Ansiedad/etiología , Depresión/epidemiología , Depresión/etiología , Atención Primaria de Salud/estadística & datos numéricos , Trastornos Somatomorfos/complicaciones , Adulto , Comorbilidad , Femenino , Humanos , Masculino , Neuropsicología , Dimensión del Dolor , Valor Predictivo de las Pruebas , Prevalencia , Pruebas Psicológicas , Psicometría , Factores de Riesgo , Trastornos Somatomorfos/epidemiología , Sudáfrica/epidemiología , Encuestas y CuestionariosRESUMEN
Somatization disorder is a somatoform disorder that overlaps with a number of functional somatic syndromes and has high comorbidity with major depression and anxiety disorders. Proposals have been made for revising the category of somatoform disorders, for simplifying the criteria for somatization disorder, and for emphasizing the unitary nature of the functional somatic syndromes in future classifications. A review of the cognitive-affective neuroscience of somatization disorder and related conditions suggests that overlapping psychobiological mechanisms mediate depression, anxiety, and somatization symptoms. Particular genes and environments may contribute to determining whether symptoms are predominantly depressive, anxious, or somatic, and there are perhaps also overlaps and distinctions in the distal evolutionary mechanisms that produce these symptoms.
Asunto(s)
Ansiedad , Terapia Cognitivo-Conductual/métodos , Depresión , Neurociencias/métodos , Trastornos Somatomorfos , Ansiedad/complicaciones , Ansiedad/fisiopatología , Ansiedad/psicología , Ansiedad/terapia , Evolución Biológica , Encéfalo/anatomía & histología , Depresión/complicaciones , Depresión/fisiopatología , Depresión/psicología , Depresión/terapia , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Genotipo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos Somatomorfos/complicaciones , Trastornos Somatomorfos/fisiopatología , Trastornos Somatomorfos/psicología , Trastornos Somatomorfos/terapiaRESUMEN
Despite the prevalence of multisomatoform disorder (MSD), there are few controlled trials of its pharmacotherapy. The aim of this study was to compare the efficacy and safety of escitalopram (10-20 mg/day) with that of placebo in treating patients with MSD over a 12-week period. Fifty-one outpatients aged from 18 to 65 years, with multiple medically unexplained symptoms, were recruited. The primary efficacy measure was a change on the Patient Health Questionnaire-15 scores from baseline to endpoint. Secondary efficacy endpoints included the Clinical Global Impression-Improvement score, the psychic and somatic subscales of the Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale, the Visual Analogue Pain Rating Scale, the Scale for the Assessment of Illness Behaviour and the Sheehan Disability Scale. On the primary analysis of covariance, escitalopram-treated patients had significantly greater reductions in Patient Health Questionnaire scores (P<0.0001) compared with placebo at week 12. Significant separation from placebo occurred from week 6 onwards. Escitalopram was superior to placebo on all secondary outcome endpoints, with the exception of the Scale for the Assessment of Illness Behaviour. The medication was well tolerated. In conclusion, in this 12-week, randomized, placebo-controlled study, escitalopram (10-20 mg/day) was both effective and well tolerated in the treatment of patients with MSD. Compared with placebo, escitalopram was associated with lower symptom scores, increased response and remission rates, and improved functioning.
Asunto(s)
Antidepresivos/uso terapéutico , Citalopram/uso terapéutico , Trastornos Somatomorfos/tratamiento farmacológico , Adulto , Antidepresivos/efectos adversos , Citalopram/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Encuestas y CuestionariosRESUMEN
Immunohistochemistry is an indispensable tool in human pathology enabling immunophenotypic characterization of tumor cells. Immunohistochemical analyses of mouse models of human hematopoietic neoplasias have become an important aspect for comparison of murine entities with their human counterparts. The aim of this study was to establish a diagnostic antibody panel for analysis of murine lymphomas/leukemias, useful in formalin-fixed/paraffin-embedded tissue. Overall, 48 antibodies (4 rabbit monoclonal, 12 rabbit polyclonal, 2 goat polyclonal, 11 rat, and 19 mouse monoclonal), which were either mouse-specific (14) or cross-reactive with murine tissue (34) were tested for staining quality and diagnostic value in 468 murine hematopoietic neoplasms. Specific staining was achieved with 29 antibodies, of which 18 were human antibodies cross-reactive with murine tissue. Only 23 (B220, BCL-2, BCL-6, CD117, CD138 (2x), CD3 (2x), CD43, CD45, CD5, CD79 alpha cy, cyclin D1, Ki-67 (2x), Mac-3, Mac-2, lysozyme, mast cell tryptase, MPO, Pax-5, TdT, and TER-119) were regarded as valuable for diagnostic evaluation. Immunohistochemistry was also established in an automated immunostainer for high throughput analysis. The antibody panel developed is useful for the classification of murine lymphomas and leukemias analyzed, and a valuable tool for human and veterinary pathologists involved in the diagnostic interpretation of murine models of hematopoietic neoplasias.
Asunto(s)
Envejecimiento/inmunología , Anticuerpos/inmunología , Reacciones Cruzadas , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/metabolismo , Inmunohistoquímica/métodos , Animales , Anticuerpos/genética , Femenino , Fijadores/química , Formaldehído/química , Neoplasias Hematológicas/clasificación , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos , Adhesión en ParafinaRESUMEN
BACKGROUND: Demonstrating an association between physical malformation and schizophrenia could be considered supportive of a neurodevelopmental origin of schizophrenia and may offer insights into a critical period for the development of this illness. The aim of our study was to investigate whether differences in the presence of minor physical anomalies could be demonstrated between schizophrenia sufferers and normal controls in a Xhosa population with a view to identifying a means of subtyping schizophrenia for use in future genetic studies. METHODS: Sixty-three subjects with schizophrenia (21 sibling pairs, 1 sibship of four and a group of probands with an affected non-participating sibling (n = 17)), 81 normal controls (37 singletons and 22 sibling pairs) of Xhosa ethnicity were recruited. Each participant was then examined for minor physical anomalies using the Modified Waldrop scale. The relationship between each of the morphological features and the presence of an affected sib was examined using the Chi-squared test, followed by an intra-pair concordance analysis in the sibling pairs. RESULTS: Gap between first and second toes was significantly more common in the affected sib pair group when compared to the non-affected sib pair group (p = 0.019) and non-affected singleton control group (p = 0.013). Concordance analysis also revealed increased concordance for this item in the affected sib pair group. CONCLUSION: These findings offer an intriguing possibility that in the Xhosa population, affected sib pair status may be linked to a neurodevelopmental insult during a specific period of the fetal developmental.
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Antropometría , Esquizofrenia/complicaciones , Dedos del Pie/anatomía & histología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Desarrollo Fetal , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/etnología , Esquizofrenia/genética , Hermanos , Sudáfrica/etnologíaRESUMEN
Over 125 pigmentation-related genes have been identified to date. Of those, PMEL17/GP100 has been widely studied as a melanoma-specific antigen as well as a protein required for the formation of fibrils in melanosomes. PMEL17 is synthesized, glycosylated, processed, and delivered to melanosomes, allowing them to mature from amorphous round vesicles to elongated fibrillar structures. In contrast to other melanosomal proteins such as TYR and TYRP1, the processing and sorting of PMEL17 is highly complex. Monoclonal antibody HMB45 is commonly used for melanoma detection, but has the added advantage that it specifically reacts with sialylated PMEL17 in the fibrillar matrix in melanosomes. In this study, we generated mutant forms of PMEL17 to clarify the subdomain of PMEL17 required for formation of the fibrillar matrix, a process critical to pigmentation. The internal proline/serine/threonine-rich repeat domain (called the RPT domain) of PMEL17 undergoes variable proteolytic cleavage. Deletion of the RPT domain abolished its recognition by HMB45 and its capacity to form fibrils. Truncation of the C-terminal domain did not significantly affect the processing or trafficking of PMEL17, but, in contrast, deletion of the N-terminal domain abrogated both. We conclude that the RPT domain is essential for its function in generating the fibrillar matrix of melanosomes and that the luminal domain is necessary for its correct processing and trafficking to those organelles.
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Melanosomas/metabolismo , Glicoproteínas de Membrana/fisiología , Secuencia de Aminoácidos , Antígenos de Neoplasias , Línea Celular Tumoral , Eliminación de Gen , Aparato de Golgi/metabolismo , Células HeLa , Humanos , Antígenos Específicos del Melanoma , Glicoproteínas de Membrana/química , Modelos Genéticos , Datos de Secuencia Molecular , Mutación , Proteínas de Neoplasias/química , Estructura Terciaria de Proteína , Transfección , Antígeno gp100 del MelanomaRESUMEN
When adenovirus vectors are injected intravenously, they are quickly taken up by Kupffer cells in the liver. We report that this causes rapid necrosis of Kupffer cells in mice at doses of 10(11) particles/kg or higher. By 10 min after intravenous vector injection, Kupffer cells were permeable to propidium iodide and trypan blue. This coincided with a sharp rise in serum lactate dehydrogenase. Ultrastructural examination showed degeneration of Kupffer cells, including complete disappearance of chromatin by 1 h. After an initial intravenous injection of vector, dead Kupffer cells were unable to take up a second dose of vector, and hepatic transgene expression from the second dose was augmented. Death of Kupffer cells did not affect serum levels of IL-6 or IL-12. There was no immediate change in the number of Kupffer cells in the liver, but a significant decline was found by 4 h after injection of vector. Interestingly, substantial numbers of vector-containing Kupffer cells were found in pulmonary capillaries, indicating that they had been swept out of the liver. Together these results show that an intravenous injection of adenovirus vector causes synchronous and surprisingly rapid Kupffer cell death.
Asunto(s)
Adenoviridae/genética , Macrófagos del Hígado/patología , Animales , Cromatina/metabolismo , Cromatina/ultraestructura , Colorantes , Vectores Genéticos/administración & dosificación , Inmunidad Innata , Inyecciones Intravenosas , Interleucina-12/sangre , Interleucina-6/sangre , Macrófagos del Hígado/ultraestructura , L-Lactato Deshidrogenasa/sangre , Hígado/patología , Hígado/ultraestructura , Pulmón/irrigación sanguínea , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Necrosis , Propidio , Azul de TripanoRESUMEN
Anxiety symptoms and disorders are associated with a range of general medical disorders. This association may be a physiologic consequence of the general medical disorder, a psychologic reaction to the experience of having a medical illness, a side effect of treatment, or a chance occurrence. This article briefly reviews the associations of panic disorder with seizure disorder, Klüver-Bucy syndrome, mitral valve prolapse, and respiratory disorders; of generalized anxiety disorder with chronic obstructive airway disease and cardiovascular and endocrine disorders; of social anxiety disorder with Parkinson's disease; of obsessive-compulsive disorder with striatal disorders; and of posttraumatic stress disorder with head injury and pain. Such associations provide important clues for understanding the neurobiology of anxiety disorders.
Asunto(s)
Ansiedad/epidemiología , Estado de Salud , Trastorno de Pánico/epidemiología , Enfermedades Cardiovasculares/epidemiología , Traumatismos Craneocerebrales/epidemiología , Humanos , Trastorno Obsesivo Compulsivo/epidemiología , Dolor/epidemiología , Trastornos Fóbicos/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
Careful phenotyping and the identification of subtypes of schizophrenia can contribute significantly to the success of genetic studies in schizophrenia. The phenomenology of schizophrenia in affected sib pairs has been well-described in Caucasian populations, however a paucity of data exists for African populations. This study therefore investigated symptom dimensions in a sizeable group of affected Xhosa sib pairs as a means of evaluating the role of shared familial factors in the psychosis of schizophrenia. Five hundred and thirteen participants were interviewed with the Diagnostic Interview for Genetic Studies (DIGS), which included the Schedules for the Assessment of Negative and Positive symptoms (SANS/SAPS). One hundred and four sib pairs were then extracted (N = 208) for analysis of concordance for lifetime psychotic symptoms and an exploratory factor analysis of the SANS/SAPS. Concordance analysis of life-time symptoms indicated a significant concordance for olfactory hallucinations, persecutory delusions, jealousy, somatic, reference and control delusions as well as thought insertion and withdrawal. The factor analysis of the global scores of the SAPS and SANS revealed a five factor best-fit model and accounted for 92.5% of variance. The factors included a negative symptom factor, a positive symptom factor, a positive thought disorder and a bizarre behaviour component. The core symptomatology of schizophrenia in this sib pair sample was similar to that reported in Caucasian populations with the exception of higher rates of auditory hallucinations and delusions of persecution. In summary therefore; although the factor analysis only supported the concept of the universality of psychotic symptoms in schizophrenia, the concordance analysis of these symptoms did reveal hallucinations as well as delusions of control as possible candidates relevant for future research into genotype-phenotype relationships.