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The University of Texas M.D. Anderson Cancer Center (UTMDACC), Department of Pathology and Laboratory Medicine is committed to the endless pursuit of innovative research, education, training and administration for the prevention, diagnosis and clinical management of cancer and associated diseases. The molecular genetic technology professional development model promotes personal development, recognizes increased competencies, and sets high standards for all skills and services provided. There are four competency levels that comprise our Professional Development Model (PDM): Discovery, Application, Maturation, and Expert. The skill, knowledge, education, and certification requirements for each level are defined based on the business needs of each lab. When a genetic technologist successfully completes all skills, knowledge, proficiency, education and certification requirements within the appropriate time frame for a particular competency level, his/her salary would be adjusted to the entry point for the competency level he/she has completed.
RESUMEN
Sublethal plasma membrane disruption (PMD) is an established mechanism for signaling in several cell types, including endothelial cells and skeletal muscle. We used a rat model of orthodontic tooth movement to test the hypothesis that periodontal ligament (PDL) cells communicate stretch to changes in bone cell activity in part via PMD. To produce PMD, we used a 50-g load from a spring activated in the buccal direction against the maxillary first molars for 5 min. Uptake of endogenous serum albumin was used as a PMD marker. Immunohistochemistry demonstrates albumin in PDL cells surrounding moved first molar tips. Image analysis shows significantly more albumin in cells of the buccal side (tension) of the moved teeth compared with those of the lingual, distal, and mesial sides, and those of the unmoved control. Albumin localization within cells of the PDL, after only 5 min of mechanical loading, suggests that PMD could promote uptake or release of signaling molecules.
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Membrana Celular/fisiología , Ligamento Periodontal/citología , Técnicas de Movimiento Dental , Análisis de Varianza , Animales , Western Blotting , Análisis del Estrés Dental , Femenino , Técnicas para Inmunoenzimas , Ratas , Ratas Endogámicas , Albúmina Sérica/análisis , Transducción de Señal , Estadísticas no Paramétricas , Estrés MecánicoRESUMEN
BACKGROUND: Hip fractures are the most devastating consequence of osteoporosis in humans. Since the ovariectomized (ovx) rat is a useful model of estrogen-deficient osteoporosis, the purposes of this study were to describe the histo-anatomical features of the rat hip and to determine changes in the proximal femur induced by ovariectomy to evaluate the use of this skeletal site for future bone studies. METHODS: Changes in body mass and composition and in bone mineral content and density were determined by DEXA at 12 weeks after ovariectomy. Gross and histo-anatomy of the rat hip was studied by light microscopy and histomorphometry. Cancellous and cortical bone changes induced by ovx at the femoral midneck were determine using dynamic, static, and structural histomorphometric techniques. The stiffness of the femoral neck was determined by biomechanical testing, and the results were correlated with histological observations and the histomorphometric data. RESULTS: The bony structures of the rat hip, articular cartilage, and muscular and capsular attachments are very similar to the human. Rats, however, have an active growth plate and a well-vascularized periosteum covering the intracapsular portion of the femoral neck, which is different from the adult humans. Rats in the sham and ovx groups exhibited similar biological variations in the thickness of the femoral neck and epiphyseal bone and cartilaginous composition. Ovariectomy promoted periosteal modeling and induced endocortical and cancellous bone remodeling, with a net loss of bone mass due to excess bone resorption. The ovx-induced increase in resorption resulted in reduced trabecular number, thickness, and endocortico-trabecular connectivity, which likely contributed to less bone stiffness in ovx rats relative to the sham controls. CONCLUSIONS: There are numerous similarities in the structure and histology of the rodent and human hip. Skeletal changes induced by ovariectomy in rats, particularly those at the endocortical surface and in the cancellous bone, are very similar to changes observed in the proximal femur in osteoporotic women. In addition, ovx in the rat had compromised the biomechanical properties at the femoral neck, similar to what occurs in the postmenopausal women. Data presented here confirmed responsiveness of the proximal femur in rat to ovarian hormone deficiency, which appears to be a useful and relevant site to investigate mechanisms and interventions relative to human disease.
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Huesos/anatomía & histología , Huesos/fisiología , Fémur/anatomía & histología , Ovariectomía , Ratas/anatomía & histología , Absorciometría de Fotón , Animales , Elasticidad , Femenino , Tamaño de los Órganos , Ratas Sprague-Dawley , Valores de ReferenciaRESUMEN
Sixteen-week-old Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated and housed for 8 weeks to develop osteopenia prior to systemic administration of rhIGF-I (0.9 and 2.6 mg/kg) alone or the rhIGF-I/IGFBP-3 (0.9, 2.6 and 7.5 mg/kg) complex. After 8 weeks of treatment, proximal femurs were fixed, embedded, and cut through the midneck region. Structural and dynamic histomorphometric analyses were performed using standard techniques. Ovx increased endocortical resorption and modeling-dependent periosteal formation which resulted in decreased cortical bone area. Despite increased bone formation, trabecular number, thickness, and area were all reduced due to increased resorption. Structural changes following Ovx included fewer struts and nodes, a higher percentage of the simpler strut forms, and reduced endocortico-trabecular connectivity. Eight weeks of treatment with rhIGF-I or rhIGF-I/IGFBP-3 promoted periosteal and endocortical bone formation and reduced the endocortical resorption induced by Ovx. Both rhIGF-I formulations stimulated bone formation on existing trabecular surfaces which increased trabecular thickness and area but not trabecular number. These treatments prevented further deterioration of the trabecular network caused by Ovx and preserved endocortico-trabecular connectivity. In summary, changes in the femoral neck following Ovx appear to be similar in rats and humans. The highest dose of rhIGF-I/IGFBP-3 used in this study showed the best results in promoting cortical and cancellous bone formation, and appears to be promising therapy for human osteopenias.
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Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Proteínas Portadoras/farmacología , Cuello Femoral/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/farmacología , Animales , Desarrollo Óseo/efectos de los fármacos , Enfermedades Óseas Metabólicas/patología , Remodelación Ósea/efectos de los fármacos , Femenino , Cuello Femoral/patología , Fracturas de Cadera/etiología , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Masculino , Ovariectomía , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacologíaRESUMEN
The purpose of this study was to compare dose-related effects on cortical bone and lean body mass following subcutaneous administration of rhIGF-I alone, or bound to an equimolar amount of rhIGFBP-3 to adult Ovx rats. At the age of 16 weeks, rats were ovariectomized or sham-operated and were allowed 8 weeks to develop osteopenia. After being divided into control (saline treated) or treatment groups, rats were injected daily during an 8-week period with 0.9 and 2.6 mg/kg of rhIGF-I, or with 0.9, 2.6, and 7.5 mg/kg of rhIGF-I bound to rhIGFBP-3. Fluorescent bone markers were given 9 and 2 days prior to necropsy. Body weights and lean body mass were monitored throughout the experiment. Cortical bone histomorphometry was performed on tibial cross-sections at the tibiofibular junction, and endochondral bone growth was measured at the distal femoral metaphysis. All rats treated with rhIGF-I or the rhIGF-I/IGFBP-3 complex had increased body weights, corresponding to a dose-dependent increase in lean body mass. Endochondral growth was slightly increased in all experimental groups, but was not dose-dependent. A dramatic increase in periosteal, modeling-dependent formation, coupled with decreased or unchanged resorption on the endocortical envelope resulted in a dose-dependent increase in cortical thickness and cross-sectional area in groups treated with the complex of rhIGF-I/IGFBP-3. This complex appeared to be more effective in promoting positive musculoskeletal changes than rhIGF-I alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Proteínas Portadoras/farmacología , Inhibidores de Crecimiento/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Absorciometría de Fotón , Animales , Peso Corporal/efectos de los fármacos , Desarrollo Óseo/efectos de los fármacos , Desarrollo Óseo/fisiología , Enfermedades Óseas Metabólicas/fisiopatología , Resorción Ósea/tratamiento farmacológico , Proteínas Portadoras/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Inhibidores de Crecimiento/administración & dosificación , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Músculo Esquelético/efectos de los fármacos , Ovariectomía , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Somatomedinas/administración & dosificación , Somatomedinas/farmacología , Tibia/efectos de los fármacos , Tibia/fisiologíaRESUMEN
Transforming growth factor beta is a multifunctional protein with known actions on bone and bone cells. The ability of TGF-beta to stimulate osteogenic parameters in vitro and osteogenesis adjacent to injection sites in vivo is well established. The purpose of this study was to determine if systemic administration of recombinant TGF-beta 2 (rTGF-beta 2) could stimulate bone formation in rats of different ages. Juvenile (25-day-old) and adult (160-day-old) rats were treated daily for 5 days and 14 days, respectively, with rTGF-beta 2 given by subcutaneous injection. Bone formation was measured in cancellous bone of the lumbar vertebrae in juvenile rats and the femoral epiphysis in adult rats. Endochondral bone growth rates were measured in the distal femurs from both juvenile and adult rats using histomorphometric methods. Systemic administration of rTGF-beta 2 resulted in substantial increases in bone formation rates (both surface and volume referent) in both juvenile and adult rats. In the juvenile rats, rTGF-beta 2 increased the percent double labeled surface and the mineral appositional rate. In the adult rats, TGF-beta 2 treatment increased the double labeled surface and also endochondral (longitudinal) growth parameters without changing the number of osteoclasts or the number of osteoclast nuclei per cell. These results demonstrate that short-term systemic administration of rTGF-beta 2 substantially increases cancellous bone formation rate in rats.
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Envejecimiento/fisiología , Desarrollo Óseo/efectos de los fármacos , Fémur/crecimiento & desarrollo , Vértebras Lumbares/crecimiento & desarrollo , Factor de Crecimiento Transformador beta/farmacología , Animales , Fémur/efectos de los fármacos , Vértebras Lumbares/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacologíaRESUMEN
The human homologue of the mouse double minute 2 (MDM-2) gene codes for a cellular protein that forms a complex with the mutant and wild-type p53 protein and modulates its trans-activation activity. Overexpression of the MDM-2 gene in cells increases their tumorigenic potential and overcomes the growth-suppressive activity of p53. Previous reports have shown that the MDM-2 gene is amplified in approximately one third of human sarcomas. To examine the role of MDM-2 in leukemia, we analyzed MDM-2 gene amplification and mRNA expression in various types of leukemias. We did not detect gene amplification in any of the 48 cases of leukemia that we examined. In contrast, we observed significant MDM-2 mRNA overexpression in 34 of 64 cases (53%). The level of mRNA overexpression in some cases of leukemias was comparable to that observed in some cases of sarcomas, which demonstrate more than 50-fold MDM-2 gene amplification. Furthermore, we divided these cases into different prognostic groups according to their karyotypic abnormalities. MDM-2 overexpression seemed to be associated with unfavorable chromosomal abnormalities. These findings suggest that the expression of the MDM-2 gene is altered in a significant fraction of human leukemias and MDM-2 may play a significant role in leukemogenesis. In addition, these results suggest that mechanisms other than gene amplification may play a significant role in deregulating the MDM-2 expression.
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Regulación Leucémica de la Expresión Génica , Leucemia/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares , Oncogenes , Proteínas Proto-Oncogénicas , Secuencia de Bases , Aberraciones Cromosómicas , Amplificación de Genes , Genes p53 , Humanos , Datos de Secuencia Molecular , Proteínas Proto-Oncogénicas c-mdm2 , ARN Mensajero/análisis , ARN Neoplásico/análisis , Células Tumorales CultivadasRESUMEN
The use of lineage and cytogenetic probes in diagnosis of oncologic disorders is reviewed. The presence of rearranged bands via Southern blot analysis may generate diagnostic support of hematopoietic malignancy in several instances. DNA probes can be used to demonstrate clonality, reveal lineage characteristics, or identify specific chromosomal aberrations. Lineage probes detect genetic events during normal lymphocyte differentiation, while cytogenetic probes detect a malignant characteristic. The number of translocations detectable using DNA probes will likely expand in the future.
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Sondas de ADN , Sondas Moleculares , Neoplasias/diagnóstico , Southern Blotting , Enfermedades Hematológicas/diagnóstico , Humanos , Translocación GenéticaRESUMEN
Basic concepts of molecular technology and diagnostic applications in the clinical laboratory are discussed. Advances in molecular biology have led to an increased number of clinical laboratories providing diagnostic support at the genetic level. The clinical applications of such a technology at present is broad, perhaps limited only by the regions mapped on the human genome. As the rapid discovery of new genes ignites a chain reaction of opportunities, the clinical laboratory scientist should be kept informed of the exciting technologic advances in the diagnosis of infectious diseases, genetic-related diseases, and leukemia and lymphomas. Many future diagnostic applications are now being researched.
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Biología Molecular/métodos , Autorradiografía , Southern Blotting , Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/tendencias , ADN/aislamiento & purificación , Sondas de ADN , Enzimas de Restricción del ADN , Predicción , Humanos , Biología Molecular/tendencias , Hibridación de Ácido Nucleico , Evaluación de la Tecnología BiomédicaAsunto(s)
Anestesia por Inhalación , Anestesia Local , Artroscopía , Bupivacaína , Traumatismos de la Rodilla/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Adolescente , Método Doble Ciego , Femenino , Fentanilo , Humanos , Masculino , Dimensión del Dolor , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The results of this single case report suggest that ceftizoxime may be an excellent antibiotic in the therapy of E. coli meningitis with ventriculitis.
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Ceftizoxima/uso terapéutico , Ventrículos Cerebrales , Encefalitis/tratamiento farmacológico , Infecciones por Escherichia coli/tratamiento farmacológico , Ceftizoxima/administración & dosificación , Humanos , Recién Nacido , Inyecciones Intravenosas , MasculinoRESUMEN
Biliary-bronchial fistula is an extremely unusual complication of thoracoabdominal trauma or suppurative hepatobiliary disease. We treated a patient with a biliary-bronchial fistula that developed after right hepatectomy for an infected traumatic intrahepatic hematoma. The diagnosis of biliary-bronchial fistula was confirmed by percutaneous transhepatic cholangiography. Surgical therapy included a primary transabdominal choledochostomy, with the insertion of a T-tube, sphincteroplasty, and open marsupialization of the chronic subphrenic abscess.