RESUMEN
Pycnodysostosis is a rare autosomal recessive disease due to a mutation in the gene for the enzyme Cathepsin K. It is characterized by short stature, craniofacial dysmorphias, osteosclerosis, and brittle bones. There are only a few reports in the literature describing surgical interventions for long bone fractures in pycnodysostosis patients, most of which describe intramedullary nail treatment of isolated long bone fractures. We describe a case in which a pregnant female with pycnodysostosis presented with a shaft fracture of the left femur following minor trauma and a history of increasing thigh pain. Radiographs obtained in the emergency room also revealed an impending subtrochanteric fracture of the contralateral side. The acute left femoral shaft fracture was treated with an adolescent-sized intramedullary nail; it was decided to defer surgery on the contralateral side until after pregnancy. Three months later, the patient had the contralateral femur prophylactically fixated with a plate and screws. One year after the index surgery, both methods demonstrated satisfactory healing both clinically and radiographically. Although we recommend use of an intramedullary nail for long bone fractures in patients with pycnodysostosis, a plate can be utilized if health conditions or skeletal morphology precludes use of a nail.
Asunto(s)
Fracturas del Fémur/etiología , Fracturas Espontáneas/etiología , Complicaciones del Embarazo , Picnodisostosis/complicaciones , Adulto , Placas Óseas , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas/métodos , Fijación Intramedular de Fracturas/métodos , Fracturas Espontáneas/diagnóstico por imagen , Fracturas Espontáneas/cirugía , Fracturas de Cadera/prevención & control , Humanos , Embarazo , RadiografíaRESUMEN
Amyloidosis is a rare but devastating condition caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. High clinical suspicion is required to facilitate early diagnosis. Correct identification of the causal amyloid protein is absolutely crucial for clinical management in order to avoid misdiagnosis and inappropriate, potentially harmful treatment, to assess prognosis, and to offer genetic counselling if relevant. This review summarises the current evidence on which the diagnosis and subtyping of amyloidosis is based, outlines the limitations of various diagnostic techniques, particularly in an Australian and New Zealand context, and discusses optimal strategies for the diagnostic approach to these patients. Recommendations are provided for when particularly to suspect amyloidosis, what investigations are required, as well as an approach to accurate subtyping of amyloidosis.
Asunto(s)
Amiloidosis/diagnóstico , Amiloide/análisis , Amiloidosis/clasificación , Amiloidosis/etiología , Amiloidosis/genética , Amiloidosis/patología , Australasia , Biopsia , Rojo Congo , Pruebas Genéticas , Humanos , Inmunohistoquímica , Inflamación/complicaciones , Especificidad de Órganos , Paraproteinemias/complicaciones , Fenotipo , Coloración y Etiquetado , Espectrometría de Masas en TándemRESUMEN
Treponema denticola, a periodontal pathogen, binds the complement regulatory protein Factor H (FH). Factor H binding protein B (FhbB) is the sole FH binding protein produced by T. denticola. The interaction of FhbB with FH is unique in that FH is bound to the cell and then cleaved by the T. denticola protease, dentilisin. A â¼ 50-kDa product generated by dentilisin cleavage is retained at the cell surface. Until this study, a direct role for the FhbB-FH interaction in complement evasion and serum sensitivity had not been demonstrated. Here we assess the serum resistance of T. denticola strain 35405 (Td35405wt) and isogenic mutants deficient in dentilisin (Td35405-CCE) and FhbB production (Td35405ΔfhbB), respectively. Both dentilisin and FhbB have been postulated to be key virulence factors that mediate complement evasion. Consistent with conditions in the subgingival crevice, an environment with a significant concentration of complement, Td35405wt was resistant to serum concentrations as high as 25%. Deletion of fhbB (Td35405ΔfhbB), which resulted in the complete loss of FH binding ability, but not inactivation of dentilisin activity (Td35405-CCE), rendered T. denticola highly sensitive to 25% human serum with 80% of the cells being disrupted after 4 h of incubation. Heat treatment of the serum to inactivate complement confirmed that killing was mediated by complement. These results indicate that the FH-FhbB interaction is required for serum resistance whereas dentilisin is not. This report provides new insight into the novel complement evasion mechanisms of T. denticola.
Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Factor H de Complemento/inmunología , Inactivadores del Complemento/inmunología , Evasión Inmune/inmunología , Treponema denticola/inmunología , Animales , Antígenos Bacterianos/genética , Antígenos Bacterianos/metabolismo , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Técnicas Bacteriológicas , Actividad Bactericida de la Sangre/genética , Actividad Bactericida de la Sangre/inmunología , Quimotripsina/genética , Quimotripsina/metabolismo , Factor H de Complemento/metabolismo , Inactivadores del Complemento/metabolismo , Electroforesis en Gel de Poliacrilamida , Humanos , Sueros Inmunes/inmunología , Factores Inmunológicos/inmunología , Ratones , Péptido Hidrolasas , Plásmidos/genética , Unión Proteica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Eliminación de Secuencia/genética , Treponema denticola/genética , Factores de Virulencia/genética , Factores de Virulencia/inmunología , Factores de Virulencia/metabolismoRESUMEN
Atopic dermatitis (AD) is a common inflammatory skin disease with recurring episodes of itching and a chronic relapsing course. The prevalence of AD has increased exponentially over the years, along with information on how it may occur. Diagnosis of AD is typically based on physical examination and history and may be confirmed based on chronicity of symptoms, itching, and age-specific morphology. Nonpharmacological approaches include psychological interventions such as behavior modification, stress reduction techniques, and group psychotherapeutic treatments or may also include dietary restrictions, ultraviolet (UV) phototherapy, house dust mite reduction, and avoidance of enzyme-enriched detergents. Herbal therapy has also showed some promise particularly Zemaphyte®, Kamillosan®, and Shiunko®. Pharmacological agents that show great efficacy include emollients, topical corticosteroids, and topical calcineurin inhibitors.
Asunto(s)
Productos Biológicos/uso terapéutico , Inhibidores de la Calcineurina , Enfermedad Crónica/tratamiento farmacológico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/fisiopatología , Emolientes/uso terapéutico , Prurito/tratamiento farmacológico , Administración Cutánea , Dermatitis Atópica/epidemiología , Dermatitis Atópica/terapia , Humanos , Prurito/fisiopatologíaRESUMEN
Heart failure is the usual cause of death in patients with amyloid cardiomyopathy. The commonest form of hereditary cardiac amyloidosis is associated with the Val122Ile variant of transthyretin (TTR), which is carried by 3-4% of the African American population. Here, we report the outcome of the first cardiac transplantation in a patient with TTR V122I. A 59-year-old Caribbean man presented with biventricular failure. Other than previous bilateral carpel tunnel syndrome, he had been well and had no evidence of extracardiac amyloidosis. An endomyocardial biopsy demonstrated amyloid of TTR type. Sequencing of TTR gene indicated homozygosity for V122I. He underwent cardiac transplantation and 3 years later, remains well with no evidence of allograft or systemic amyloid deposition.
Asunto(s)
Sustitución de Aminoácidos , Amiloidosis Familiar/genética , Trasplante de Corazón , Polimorfismo de Nucleótido Simple , Prealbúmina/genética , Amiloidosis Familiar/cirugía , Homocigoto , Humanos , Isoleucina , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , ValinaRESUMEN
AIMS: Bone marrow sampling is a key investigation in the work-up of amyloid light chain (AL) amyloidosis, but the relationship between bone marrow findings and the varied phenotype and clinical outcome of AL amyloidosis is unclear. The aim was to determine if bone marrow pathological parameters at diagnosis were related to clinical behaviour in AL amyloidosis patients. METHODS AND RESULTS: Bone marrow findings, clinical features and outcome of 80 patients referred with a diagnosis of systemic AL amyloidosis were evaluated; six patients were subsequently excluded due to re-categorization as other forms of amyloidosis. At latest follow-up (median 66 months), 11 of the 18 patients with no identifiable bone marrow neoplastic cells (61%) versus only seven of the 56 patients with neoplastic plasma cells or non-Hodgkin's lymphoma (13%) were alive (P = 0.0046). However, neither the quantity of the neoplastic cells nor the serum light chain levels were correlated with amyloid burden or patient survival. CONCLUSIONS: Identification of a neoplastic population in the bone marrow of AL amyloidosis patients by histology and immunohistochemistry correlates with poor outcome; however, the neoplastic cell burden is not prognostically significant, suggesting that additional factors are important in determining disease behaviour in AL amyloidosis.
Asunto(s)
Amiloide/metabolismo , Amiloidosis/patología , Células de la Médula Ósea/patología , Médula Ósea/patología , Adulto , Anciano , Anciano de 80 o más Años , Amiloide/inmunología , Amiloidosis/metabolismo , Amiloidosis/mortalidad , Médula Ósea/metabolismo , Células de la Médula Ósea/metabolismo , Análisis Mutacional de ADN , Femenino , Fibrinógeno/genética , Fibrinógeno/metabolismo , Genotipo , Humanos , Cadenas Ligeras de Inmunoglobulina/inmunología , Cadenas Ligeras de Inmunoglobulina/metabolismo , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Mutación Puntual , Prealbúmina/genética , Prealbúmina/metabolismo , Tasa de Supervivencia , Reino Unido/epidemiologíaRESUMEN
Patients with hereditary apolipoprotein AI (apoAI) amyloidosis often have extensive visceral amyloid deposits, and many develop end-stage renal failure as young adults. Solid organ transplantation to replace failing organ function in systemic amyloidosis is controversial due to the multisystem and progressive nature of the disease and the risk of recurrence of amyloid in the graft. We report the outcome of solid organ transplantation, including dual transplants in 4 cases, among 10 patients with apoAI amyloidosis who were followed for a median (range) of 16 (4-28) and 9 (0.2-27) years from diagnosis of amyloidosis and transplantation, respectively. Eight of 10 patients were alive, seven with a functioning graft at censor. Two patients died, one of disseminated cytomegalovirus infection 2 months after renal transplantation and the other of multisystem failure following severe trauma more than 13 years after renal transplantation. The renal transplant of one patient failed due to recurrence of amyloid after 25 years. Amyloid disease progression was very slow and the natural history of the condition was favorably altered in both cases in which the liver was transplanted. Failing organs in hereditary apoAI amyloidosis should be replaced since graft survival is excellent and confers substantial survival benefit.
Asunto(s)
Amiloidosis Familiar/complicaciones , Apolipoproteína A-I/genética , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Fallo Hepático/cirugía , Trasplante de Hígado , Mutación , Adolescente , Adulto , Amiloidosis Familiar/sangre , Amiloidosis Familiar/cirugía , Apolipoproteína A-I/sangre , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/etiología , Fallo Hepático/sangre , Fallo Hepático/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Prevención Secundaria , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Puente de Arteria Coronaria/métodos , Servicios de Atención de Salud a Domicilio/economía , Tiempo de Internación/economía , Alta del Paciente/economía , Puente de Arteria Coronaria/economía , Costos de Hospital , Humanos , Readmisión del Paciente/estadística & datos numéricos , Calidad de Vida , Factores de TiempoRESUMEN
AL amyloidosis is a rare disorder characterised by tissue deposition of a fibrillary proteinaceous material, formed from monoclonal immunoglobulin light (or exceptionally heavy) chains. Although it may complicate multiple myeloma or B-cell lymphomas, AL amyloidosis is often associated with a low burden of clonal plasma cells ("primitive" AL amyloidosis). The mechanisms involved in the formation of AL amyloid deposits remain unclear, but are probably related to structural peculiarities of monoclonal immunoglobulin light chains. AL amyloidosis is usually a systemic disease, often revealed by renal involvement, the most common complication of the disease. The longterm prognosis of AL amyloidosis is poor, mainly related to amyloid restrictive cardiomyopathy leading to congestive heart failure. Oral melphalan and prednisone is considered the standard treatment for AL amyloidosis, but with limited increase in the median survival. High-dose intra-venous melphalan with autologous stem cell transplantation is an effective treatment, aimed at eliminating the clonaly expanded plasma cells, which has been shown to induce complete hematologic remissions and to prolong survival. However, the tolerability of such treatment is low, limiting its use to selected patients. The development of new drugs, able to interfere with amyloid fibril deposition, may provide a new therapeutic approach.
Asunto(s)
Amiloidosis/inmunología , Amiloidosis/terapia , Cadenas Ligeras de Inmunoglobulina , Enfermedades Renales/inmunología , Amiloidosis/fisiopatología , Humanos , Trasplante de Células MadreRESUMEN
GH stimulates the phosphorylation of tyrosine residues in the GH receptor (GHR), Janus kinase 2 (JAK2), and other signaling proteins in a transient manner that subsides within 1 h. To assess the possible roles of cytokine-induced Src homology domain 2 (SH2) (CIS/SOCS) proteins in these transient responses, we studied the expression and disposition of CIS/SOCS proteins in rat adipocytes, a physiological target of GH action. A tyrosine-phosphorylated protein that appears to be the GHR was coprecipitated from extracts of GH-treated adipocytes with alpha-CIS. In contrast, no tyrosine-phosphorylated adipocyte proteins were recovered after immunoprecipitation with alpha-SOCS3, although coprecipitation of GHR with SOCS3 was readily detected in extracts of 3T3-F442A fibroblasts. Interaction of GHR with CIS peaked between 2 and 10 min after adipocytes were treated with GH, when tyrosine phosphorylation of the GHR was maximal. By 60 min after GH, tyrosine phosphorylation of the GHR declined to very low levels, and its interaction with CIS was reduced correspondingly. Proteasome inhibitors prevented the decline in tyrosine-phosphorylated GHR and prolonged interaction of GHR and CIS for at least 1 h. These findings demonstrate the interaction of CIS with the GHR in vivo and suggest that CIS may enhance degradation of the receptor by a proteasomal pathway.
Asunto(s)
Adipocitos/metabolismo , Citocinas/farmacología , Proteínas de Unión al ADN , Péptidos y Proteínas de Señalización Intracelular , Receptores de Somatotropina/metabolismo , Proteínas Represoras , Transactivadores , Factores de Transcripción , Dominios Homologos src/fisiología , Animales , Proteínas Portadoras/análisis , Proteínas Portadoras/genética , Línea Celular , Células Cultivadas , Cisteína Endopeptidasas/metabolismo , Expresión Génica/efectos de los fármacos , Hormona del Crecimiento/farmacología , Humanos , Técnicas de Inmunoadsorción , Riñón , Cinética , Masculino , Complejos Multienzimáticos/antagonistas & inhibidores , Complejos Multienzimáticos/metabolismo , Fosforilación , Fosfotirosina/metabolismo , Complejo de la Endopetidasa Proteasomal , Proteínas/análisis , Proteínas/genética , ARN Mensajero/análisis , Ratas , Receptores de Somatotropina/análisis , Receptores de Somatotropina/genética , Proteína 1 Supresora de la Señalización de Citocinas , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas , TransfecciónRESUMEN
AIMS: Research has demonstrated the beneficial impact that pre-operative education exerts on the postoperative recovery of patients having surgery but little work has focused specifically on cardiac surgery. Therefore a randomized controlled trial was designed to elucidate the consequences of pre-operative education, given before admission, on postoperative pain, anxiety, depression and wellbeing in the 6 months following a first episode of coronary artery surgery. METHOD AND RESULTS: Three hundred and fifty-six people were randomized into the study, with 188 in the experimental and 168 in the control arms. Patients in the experimental group received the intervention, a day of education by members of the multidisciplinary team, prior to admission for surgery. Experimental and control subjects had the usual care, which involved education on admission and throughout their stay in hospital. Measurement was conducted on entry to the study, before randomization, and at 3 days, 6 weeks, 3 months and 6 months following operation. A variety of tools were used: the SF-36 Health Status questionnaire, the Hospital Anxiety and Depression scale, the General Well-Being questionnaire and a pain measurement tool. Analysis was done using the intention-totreat principle and non-parametric statistics. There were no significant differences between groups in the primary outcomes namely anxiety (P=0.09) and pain (P=0.48), or in depression (P=0.62) and wellbeing ('worn out' P=0.11; 'tense and uptight' P=0.29) 6 months after operation. This was also the case 3 days after coronary artery surgery. There was a significant difference in length of hospital stay (P=0.01) with the experimental group having the longer stay. These findings contrast with much of the existing evidence. CONCLUSION: The findings demonstrate that there is no benefit to be gained from this form of pre-operative education and that there is an associated increase in length of hospital stay. Future research could examine an ongoing programme of education and support, and might use alternative methods such as CD-ROM or the Internet.
Asunto(s)
Puente de Arteria Coronaria , Educación del Paciente como Asunto , Cuidados Preoperatorios/educación , Recuperación de la Función/fisiología , Adulto , Anciano , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/psicología , Método Simple Ciego , Encuestas y Cuestionarios , Tiempo , Resultado del TratamientoRESUMEN
Using a structured outcome interview, this study addressed the validity and sensitivity to change of the Glasgow Outcome Scale (GOS) and the Extended GOS (GOSE) in a prospective study of patients who sustained mild (n = 30) to moderate (n = 13) traumatic brain injury (TBI) or general trauma (n = 44). The patients were recruited from the emergency center or inpatient units of Ben Taub General Hospital and invited to participate in follow-up examinations at 3 and 6 months. Using a series of functional outcome measures, assessment of affective status, and neuropsychological tests as criteria, the validity of the GOSE generally exceeded the GOS. Analysis of the outcome data for the patients who completed both the 3-month and 6-month assessments disclosed that the GOSE was more sensitive to change than the GOS. Comparison of the 3-month outcome data disclosed that the GOSE and GOS scores did not differ for the TBI and general trauma groups. These findings lend further support for utilization of the GOSE in clinical trials when it is based on a structured interview.
Asunto(s)
Lesiones Encefálicas/diagnóstico , Escala de Consecuencias de Glasgow/normas , Adulto , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Pronóstico , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%. CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.
Asunto(s)
Oxalatos/administración & dosificación , Oxalatos/orina , Adulto , Calcio de la Dieta/farmacología , Dieta , Relación Dosis-Respuesta a Droga , Electroforesis/métodos , Femenino , Alimentos Formulados , Humanos , Masculino , Oxalatos/farmacologíaRESUMEN
To investigate the frequency and risk factors of major depressive disorder (MDD) after mild to moderate traumatic brain injury (TBI), 69 TBI and 52 general trauma (GT) patients were prospectively recruited and studied at 3-months postinjury. There was a nonsignificant difference in the proportion of MDD patients in the TBI and GT groups. Therefore, a composite MDD group (TBI and GT patients) was compared to patients who were nondepressed. Female gender was related to MDD, but no other risk factors were identified. MDD was associated with disability (Glasgow Outcome Scale, Community Integration Questionnaire) and cognitive impairment. MDD was comorbid with posttraumatic stress disorder. Implications for postacute management of mild to moderate TBI are discussed.
Asunto(s)
Lesiones Encefálicas/psicología , Trastorno Depresivo Mayor/psicología , Trastornos por Estrés Postraumático/psicología , Adolescente , Adulto , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/terapia , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/etiología , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/etiología , Factores de TiempoRESUMEN
Mitral valve stenosis can lead to a range of symptoms that affect daily life. As many of the people with this problem are elderly, the difficulties resulting from age can be exacerbated by illness. A pilot descriptive study was designed to examine the differences in anxiety, depression and functional capacity in women with mitral valve stenosis who were aged over 60 years when compared to a similar group of volunteers who did not have any cardiac disease. Measurement was undertaken using the Hospital Anxiety and Depression scale, the SF-36 Health Status questionnaire and the Functional Limitations Profile. Forty women were recruited to the study: 20 women with mitral valve stenosis and 20 volunteers. Each person was asked to complete the three questionnaires on one occasion only. Non-parametric statistics were used for analysis. Patients fared worse than volunteers with significant differences between groups in respect of anxiety (P = 0.03), depression (P = 0.02) and overall function (P < 0.001), but not in physical (P = 0.52) or mental health (P = 0.32). Future research could focus on strategies that would help alleviate anxiety and depression and improve functional capacity in older women with mitral valve stenosis.
Asunto(s)
Ansiedad/psicología , Depresión/psicología , Estenosis de la Válvula Mitral/psicología , Mujeres/psicología , Anciano , Femenino , Humanos , Proyectos Piloto , Encuestas y CuestionariosRESUMEN
The role of GH in the developing fetus is poorly understood. Several studies have demonstrated a limited role for GH in late fetal life. In fact, few data are available regarding GH signal transduction in the late gestation fetus. We therefore focused on a comparison of hepatic GH signaling in near-term fetal rats [embryonic day 19 (E19)] and adult rats using a combination of in vitro studies employing hepatocytes in primary culture and in vivo studies. We found that GH receptor (GHr) binding was comparable in fetal liver and adult liver. The long isoform of the GHr underwent tyrosine phosphorylation in response to GH stimulation of E19 fetal hepatocytes in a manner similar to that seen in cultured adult hepatocytes. Furthermore, downstream signaling via the Janus kinase-2 tyrosine kinase, STAT1 (signal transducer and activator of transcription), and STAT5 was also intact in both, as demonstrated by the tyrosine phosphorylation of these signaling proteins. To confirm the relevance of these findings to the in vivo situation, GH was directly administered by ip injection to E 19 fetal and adult rats. In both cases, tyrosine phosphorylation of STAT5 was markedly and rapidly induced. Finally, transfection of E19 fetal hepatocytes with GH-responsive reporter elements [Spi2.1(-275/+85)-CAT and 8xGHRE-TKCAT] demonstrated intact transcriptional regulation. Our data indicate that GHr abundance and activity as well as downstream GH signaling are similar in the late gestation fetal rat and in the adult and that these mechanisms appear capable of supporting physiological GH functions in the developing liver.
Asunto(s)
Feto/fisiología , Hormona del Crecimiento/fisiología , Hígado/embriología , Transducción de Señal/fisiología , Envejecimiento/fisiología , Animales , Células Cultivadas , Proteínas de Unión al ADN/fisiología , Feto/metabolismo , Edad Gestacional , Hormona de Crecimiento Humana/farmacología , Humanos , Inyecciones Intraperitoneales , Hígado/citología , Hígado/fisiología , Fosforilación , Isoformas de Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Somatotropina/metabolismo , Factor de Transcripción STAT1 , Transactivadores/fisiología , Transcripción Genética , Tirosina/metabolismoRESUMEN
Comparative genome studies are important contributors to our understanding of genome evolution. Most comparative genome studies in plants have been based on genetic mapping of homologous DNA loci in different genomes. Large-scale comparative physical mapping has been hindered by the lack of efficient and affordable techniques. We report here the adaptation of fluorescence in situ hybridization (FISH) techniques for comparative physical mapping between Arabidopsis thaliana and Brassica rapa. A set of six bacterial artificial chromosomes (BACs) representing a 431-kb contiguous region of chromosome 2 of A. thaliana was mapped on both chromosomes and DNA fibers of B. rapa. This DNA fragment has a single location in the A. thaliana genome, but hybridized to four to six B. rapa chromosomes, indicating multiple duplications in the B. rapa genome. The sizes of the fiber-FISH signals from the same BACs were not longer in B. rapa than those in A. thaliana, suggesting that this genomic region is duplicated but not expanded in the B. rapa genome. The comparative fiber-FISH mapping results support that chromosomal duplications, rather than regional expansion due to accumulation of repetitive sequences in the intergenic regions, played the major role in the evolution of the B. rapa genome.