RESUMO
PURPOSE: Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose-volume histograms with side-effects after proton radiation therapy (PT). PATIENTS AND METHODS: Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81%), sarcomas (16%) and meningiom (3%). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8-2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed. RESULTS: Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5-7 mm margins. Mean PTV was 560.22 cm(3). A mean of 93.2% of the PTV was covered by at least 90% of the prescribed dose. SB volumes (cm(3)) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5=0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of >70 Gy (RBE), SB received >50 and >60 Gy (RBE) in only 61 and 54% of patients, respectively. Mean SB volumes (cm(3)) covered by different dose levels (Gy, RBE) were: V20 (n=24): 45.1, V50 (n=19): 17.7, V60 (n=17): 7.6 and V70 (n=12): 2.4. No acute toxicity ≥ grade 2 or late SB sequelae were observed. CONCLUSION: Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology.
Assuntos
Enteropatias/etiologia , Intestino Delgado/efeitos da radiação , Lesões por Radiação/etiologia , Radioterapia de Alta Energia/efeitos adversos , Neoplasias Retroperitoneais/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Adolescente , Adulto , Idoso , Criança , Relação Dose-Resposta à Radiação , Feminino , Humanos , Enteropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Terapia com Prótons , Lesões por Radiação/diagnóstico , Neoplasias Retroperitoneais/complicações , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/complicações , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: This study investigated a novel approach to induce chondrogenic differentiation of human mesenchymal stem cells (hMSC). We hypothesized that a structured three-dimensional co-culture using hMSC and chondrocytes would provide chondroinductive cues to hMSC without inducing hypertrophy. METHOD: In an effort to promote optimal chondrogenic differentiation of hMSC, we created bilaminar cell pellets (BCPs), which consist of a spherical population of hMSC encased within a layer of juvenile chondrocytes (JC). In addition to histologic analyses, we examined proteoglycan content and expression of chondrogenic and hypertrophic genes in BCPs, JC pellets, and hMSC pellets grown in the presence or absence of transforming growth factor-ß (TGFß) following 21 days of culture in either growth or chondrogenic media. RESULTS: In either growth or chondrogenic media, we observed that BCPs and JC pellets produced more proteoglycan than hMSC pellets treated with TGFß. BCPs and JC pellets also exhibited higher expression of the chondrogenic genes Sox9, aggrecan, and collagen 2A1, and lower expression of the hypertrophic genes matrix metalloproteinase-13, Runx2, collagen 1A1, and collagen 10A1 than hMSC pellets. Histologic analyses suggest that JC promote chondrogenic differentiation of cells in BCPs without hypertrophy. Furthermore, when cultured in hypoxic and inflammatory conditions intended to mimic the injured joint microenvironment, BCPs produced significantly more proteoglycan than either JC pellets or hMSC pellets. CONCLUSION: The BCP co-culture promotes a chondrogenic phenotype without hypertrophy and, relative to pellet cultures of hMSCs or JCs alone, is more resistant to the adverse conditions anticipated at the site of articular cartilage repair.
Assuntos
Cartilagem Articular/citologia , Diferenciação Celular , Condrócitos/citologia , Células-Tronco Mesenquimais/citologia , Agrecanas/metabolismo , Cartilagem Articular/metabolismo , Técnicas de Cultura de Células/métodos , Condrócitos/metabolismo , Colágeno/genética , Colágeno/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteoglicanas/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fator de Crescimento Transformador beta/farmacologiaRESUMO
"Brachycephaly" is generally considered a phenotype in which the facial part of the head is pronouncedly shortened. While brachycephaly is characteristic for some domestic varieties and breeds (e.g., Bulldog, Persian cat, Niata cattle, Anglo-Nubian goat, Middle White pig), this phenotype can also be considered pathological. Despite the superficially similar appearance of "brachycephaly" in such varieties and breeds, closer examination reveals that "brachycephaly" includes a variety of different cranial modifications with likely different genetic and developmental underpinnings and related with specific breed histories. We review the various definitions and characteristics associated with brachycephaly in different domesticated species. We discern different types of brachycephaly ("bulldog-type," "katantognathic," and "allometric" brachycephaly) and discuss morphological conditions related to brachycephaly, including diseases (e.g., brachycephalic airway obstructive syndrome). Further, we examine the complex underlying genetic and developmental processes and the culturally and developmentally related reasons why brachycephalic varieties may or may not be prevalent in certain domesticated species. Knowledge on patterns and mechanisms associated with brachycephaly is relevant for domestication research, veterinary and human medicine, as well as evolutionary biology, and highlights the profound influence of artificial selection by humans on animal morphology, evolution, and welfare.
La braquicefalia generalmente se considera un fenotipo en el que el cráneo, específicamente el hocico, es notablemente acortado. Mientras que la braquicefalia es característica de algunas variedades domésticas y razas (p.e. Bulldog, gato persa, vaca ñata, cabra anglo nubiana, cerdo Middle White), también se puede interpretar como un fenotipo patológico. A pesar de que la braquicefalia tiene una apariencia semejante, por lo menos superficial, en estas variedades y razas, al examinarla más en detalle se descubre que la "braquicefalia" incluye una variedad de diferentes modificaciones del cráneo que probablemente tienen diferentes subyacentes genéticos y de desarrollo y que están relacionados con la historia de la raza. Revisamos las diferentes definiciones y propiedades relacionadas con la braquicefalia en varias especies domésticas. Describimos diferentes tipos de braquicefalia (tipo bulldog, "katantognático" y braquicefalia alométrica) y analizamos condiciones morfológicas relacionadas con la braquicefalia incluyendo enfermedades (p.e. síndrome obstructivo respiratorio). Además, examinamos los complejos procesos genéticos y de desarrollo subyacentes y los motivos culturales y de desarrollo por las que variedades braquicéfalas pueden ser más o menos prevalentes en ciertas especies domésticas. El conocimiento de patrones y mecanismos asociados a la braquicefalia son relevantes para la investigación sobre la domesticación, medicina veterinaria y humana, así como para la biología evolutiva y destaca la profunda influencia de la selección artificial sobre la morfología y bienestar de los animales y su evolución.
RESUMO
Amelogenins are a group of heterogenous proteins first identified in developing tooth enamel and reported to be present in odontoblasts. The objective of this study was to elucidate the expression and function of amelogenins in the human dentin-pulp complex. Developing human tooth buds were immunostained for amelogenin, and mRNA was detected by in situ hybridization. The effects of recombinant amelogenins on pulp and papilla cell proliferation were measured by Brd U immunoassay, and differentiation was monitored by alkaline phosphatase expression. Amelogenin protein was found in the forming dentin matrix, and amelogenin mRNA was localized in the dentin, presumably in the odontoblast processes. Proliferation of papilla cells was enhanced by recombinant human amelogenin rH72 (LRAP+ exon 4), while pulp cells responded to both rH72 and rH58 (LRAP), with no effect by rH174. These studies suggest that odontoblasts actively synthesize and secrete amelogenin protein during human tooth development, and that low-molecular-weight amelogenins can enhance pulp cell proliferation.
Assuntos
Amelogenina/biossíntese , Amelogenina/fisiologia , Papila Dentária/metabolismo , Polpa Dentária/metabolismo , Dentina/metabolismo , Odontoblastos/metabolismo , Processamento Alternativo , Amelogenina/química , Proteínas de Ciclo Celular/genética , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Papila Dentária/citologia , Papila Dentária/efeitos dos fármacos , Polpa Dentária/citologia , Dentina/citologia , Humanos , Peso Molecular , Odontogênese/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Proteínas Recombinantes/farmacologiaRESUMO
Fimbriae (pili) of enterotoxigenic Escherichia coli (ETEC), including K88, K99, 987P, and F41, are adhesins that facilitate intestinal colonization in neonatal pigs. K88 is also associated with some ETEC isolated from weaned pigs. Many ETEC isolates from weaned pigs do not express known adhesins and are termed 4P-. A novel bacterial adhesin, 2134P, was recently identified on two 4P- ETEC isolates from weaned pigs. In this study, we identified a 2134P-specific monoclonal antibody, mAb 6C7/C1, that blocked the binding of 2134P+ bacteria to intestinal epithelial cells. Indirect immunofluorescent antibody and immunoperoxidase assays using mAb 6C7/C1 confirmed that the 2134P adhesin is expressed in vivo by adherent bacteria in pigs challenge-exposed with 2134P+ ETEC. 2134P was detected on 31% of 189 postweaning diarrhea 4P- ETEC isolates from the National Animal Disease Center's culture collection by dot blot immunoperoxidase assays using mAb 6C7/C1. We conclude that 2134P is a bacterial adhesin and is an important virulence attribute of some ETEC that cause diarrhea in weaned pigs.
Assuntos
Antígenos de Bactérias/análise , Aderência Bacteriana/fisiologia , Proteínas da Membrana Bacteriana Externa/análise , Diarreia/veterinária , Infecções por Escherichia coli/veterinária , Fímbrias Bacterianas/fisiologia , Doenças dos Suínos/microbiologia , Adesinas de Escherichia coli , Animais , Anticorpos Monoclonais , Aderência Bacteriana/imunologia , Técnicas de Cultura , Diarreia/microbiologia , Escherichia coli/imunologia , Escherichia coli/patogenicidade , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Fímbrias Bacterianas/imunologia , Microvilosidades/microbiologia , Suínos , DesmameRESUMO
Escherichia coli isolates from 1,305 (of 6,894) fecal samples collected during the 1991-1992 USDA, Animal and Plant Health Inspection Service, National Health Monitoring System, Diary Heifer Evaluation Project were tested for virulence attributes associated with human enterohaemorrhagic E. coli (EHEC) and the enterotoxin commonly associated with diarrhoea in newborn calves. Single, random isolates from each heifer were hybridized to probes derived from the 60 mDa EHEC plasmid (CVD 419), E. coli attaching and effacing gene (eae), Shiga-like toxin (slt) genes I and II, and E. coli heat-stable enterotoxin a (STaP). Seventy-seven of the 1305 isolates (5.9%) were slt-positive. Most (81.8%) slt-positive E. coli were also CVD 419 and eae-positive. Only 2 of the slt-positive E. coli isolates were STaP-positive.
Assuntos
Bovinos/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/patogenicidade , Animais , Toxinas Bacterianas/genética , Sondas de DNA , Enterotoxinas/genética , Escherichia coli/classificação , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Feminino , Genes Bacterianos , Humanos , Hibridização de Ácido Nucleico , Plasmídeos , VirulênciaRESUMO
Cancer patients typically experience fatigue while undergoing treatment for their disease. This study was an effort to identify a reliable and economical measure of fatigue. In particular, scores on the five subscales of the Multidimensional Fatigue Inventory (MFI-20) were analyzed for internal consistency and then correlated with scores on the Rhoten Fatigue Inventory to establish a measure of validity. Moderate-to-high Cronbach alphas coefficients were established for the General Fatigue subscale of the MFI-20 using a sample of 97 rural oncology outpatients (1). Partial associations with the Rhoten Fatigue Scale lend evidence to the validity of the MFI-20 measures.
Assuntos
Fadiga/etiologia , Neoplasias/complicações , Neoplasias/enfermagem , Enfermagem Oncológica , Adulto , Idoso , Feminino , Humanos , Iowa , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Reprodutibilidade dos Testes , Saúde da População RuralRESUMO
Presence of Escherichia coli enterotoxin genes LT (heat-labile enterotoxin), STaP (heat-stable enterotoxin a, porcine genotype), STaH (heat-stable enterotoxin a, human genotype), and STb (heat-stable enterotoxin b) among 874 swine isolates of E coli was determined, using DNA probes and the DNA colony hybridization technique. Of the 874 isolates evaluated, 45% hybridized with at least one of the enterotoxin gene probes and were designated as enterotoxigenic E coli (ETEC). Eighty-five percent of the ETEC were from pigs with enteric colibacillosis. The remaining 15% were from pigs with edema disease or various other diseases, and from healthy swine. Seventy-four percent of the ETEC hybridized with the STb probe, 52% with STaP, and 31% with LT; ETEC did not hybridize with the STaH probe. Most of the ETEC hybridized with more than one enterotoxin gene probe. Isolates that hybridized with the LT probe also hybridized with STb. The most prevalent gene combination was LT-STb. However, 35% of the ETEC from neonatal (less than or equal to 1 week old) swine with enteric colibacillosis were of the STaP-only genotype, and 33% of the ETEC from older swine with enteric colibacillosis were of the STb-only genotype.
Assuntos
Enterotoxinas/genética , Infecções por Escherichia coli/veterinária , Escherichia coli/genética , Genes Bacterianos , Genes , Doenças dos Suínos/microbiologia , Animais , Infecções por Escherichia coli/microbiologia , Genótipo , SuínosRESUMO
Colony hybridizations with 4 enterotoxins (STaP, STaH, STb, and LT) and 1 adherence factor (K99) gene probes were done on Escherichia coli isolated from calves. Agreement between the K99 probing and a serologic assay to detect the K99 antigen was 99% for the identification of K99+ and K99- isolates. Ninety-five of the isolates (22%) hybridized with at least 1 enterotoxin gene probe (Ent+ isolates), and 82 (19%), with the K99 gene probe. The majority of Ent+ isolates (85%) reacted with probes for STaP and K99 genes. The STaP gene was present by itself in 4 of the Ent+ isolates (4%) and with the STb gene in 6 of the Ent+ isolates (6%). Five of the Ent+ isolates (5%) carried the STb and LT genes, and none (0%) of the isolates carried the STaH gene. All but 2 of the isolates with the K99 gene also had the STaP gene. Twenty-eight isolates shown to produce STa enterotoxin in previous studies failed to hybridize with any of the enterotoxin gene probes. These 28 isolates were also phenotypically negative when the tests for enterotoxin production were repeated. These isolates probably lost their genes for enterotoxin production during storage in the laboratory.
Assuntos
Proteínas de Bactérias/genética , Bovinos/microbiologia , Enterotoxinas/genética , Escherichia coli/genética , Genes Bacterianos , Adesinas de Escherichia coli , Animais , Clonagem Molecular , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Plasmídeos , VirulênciaRESUMO
OBJECTIVE: To examine the effects of fatigue on proprioception and neuromuscular control of the shoulder. DESIGN AND SETTING: Subjects were randomly assigned to either an experimental group or control group. Subjects were tested using either the active angle-reproduction or the single- arm dynamic stability test. The subjects were then fatigued using a dynamometer performing continuous, concentric rotation exercises of the shoulder. Once fatigued, the subjects were posttested using the same test. One week later, the subjects returned and were pretested, fatigued, and posttested using the other test. SUBJECTS: Thirty-two college-age (18 to 25 years) subjects (16 males, 16 females) with no history of glenohumeral instability or upper extremity injury volunteered for this study. MEASUREMENTS: Absolute angular error was measured using an electrogoniometer present within the isokinetic dynamometer, while sway velocity was measured using a force-plate system. RESULTS: Repeated-measures analysis of variance revealed a significant difference between the pretest and posttest values for absolute angular error in the experimental group, whereas no significant difference was revealed between pretest and posttest sway velocity for either the control or experimental group. CONCLUSIONS: Fatigue of the internal and external rotators of the shoulder decreased proprioception of the shoulder, while having no significant effect on neuromuscular control.
RESUMO
To test the reliability and concurrent validity of the Multidimensional Fatigue Inventory-20, 45 spouses or first-degree female caregivers of male hemodialysis patients in northern and eastern Iowa were administered the Multidimensional Fatigue Inventory-20 and the Rhoten Fatigue Scale. Four of the five subscales had a high Cronbach alpha (.76 to .82). There were low to moderate statistically significant Pearson correlations between scores on the Rhoten Fatigue Inventory and the MFI-20 subscales (.40 to .72). Limitations of generalizations are addressed.
Assuntos
Cuidadores/psicologia , Fadiga/psicologia , Fadiga Mental/psicologia , Inventário de Personalidade/estatística & dados numéricos , Diálise Renal/psicologia , Cônjuges/psicologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Fatores SexuaisRESUMO
Cancer patients experience both fatigue and depression while undergoing treatment for their disease. A number of authors have conceptualized such depression among this populations as secondary to fatigue. This study of 54 patients was done to test the concurrent validity of two inventories. Scores on the five subscales of the 20-item Multidimensional Fatigue Inventory were correlated with those on the 21-item Beck Depression Inventory. Moderate correlations are reported and the potential usefulness of the Multidimensional Fatigue Inventory is discussed.
Assuntos
Transtorno Depressivo/diagnóstico , Fadiga/diagnóstico , Neoplasias/psicologia , Inventário de Personalidade/estatística & dados numéricos , Papel do Doente , Adaptação Psicológica , Adulto , Idoso , Transtorno Depressivo/psicologia , Fadiga/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos TestesAssuntos
Eunuquismo/diagnóstico , Hipogonadismo/diagnóstico , Hipotálamo/fisiopatologia , Transtornos do Olfato/diagnóstico , Adulto , Biópsia , Mama/fisiopatologia , Defeitos da Visão Cromática/diagnóstico , Defeitos da Visão Cromática/fisiopatologia , Eunuquismo/fisiopatologia , Feminino , Glucocorticoides/metabolismo , Gonadotropinas/metabolismo , Humanos , Hipogonadismo/patologia , Masculino , Pessoa de Meia-Idade , Aberrações dos Cromossomos Sexuais/diagnóstico , Aberrações dos Cromossomos Sexuais/fisiopatologia , Síndrome , Testículo/patologia , Testosterona/metabolismoRESUMO
Rhinovirus (RV) infections trigger asthma exacerbations. Genome-wide expression analysis of RV1A-infected primary bronchial epithelial cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of RV-induced gene expression. Virus replication rates were similar in cells from normal and asthmatic donors. Overall, RV downregulated 975 and upregulated 69 genes. Comparisons of transcriptional profiles generated from microarrays and confirmed by quantitative reverse transcription PCR and cluster analysis showed some up- and downregulated genes in asthma cells involved in immune responses (IL1B, IL1F9, IL24, and IFI44) and airway remodeling (LOXL2, MMP10, FN1). Notably, most of the asthma-related differences in RV-infected cells were also present in the cells before infection. These findings suggest that differences in RV-induced gene expression profiles of cells from normal and mild asthmatic subjects could affect the acute inflammatory response to RV, and subsequent airway repair and remodeling.
Assuntos
Asma/imunologia , Infecções por Picornaviridae/imunologia , Mucosa Respiratória/metabolismo , Rhinovirus/fisiologia , Adulto , Remodelação das Vias Aéreas/genética , Aminoácido Oxirredutases/biossíntese , Aminoácido Oxirredutases/genética , Asma/complicações , Asma/genética , Asma/patologia , Células Cultivadas , Citocinas/biossíntese , Citocinas/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Masculino , Metaloproteinase 10 da Matriz/biossíntese , Metaloproteinase 10 da Matriz/genética , Análise em Microsséries , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/genética , Infecções por Picornaviridae/patologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Replicação ViralAssuntos
Olfato , Adaptação Fisiológica , Corticosteroides/fisiologia , Insuficiência Adrenal/fisiopatologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Defeitos da Visão Cromática/complicações , Estrogênios/fisiologia , Eunuquismo/genética , Feminino , Humanos , Hidrocortisona/sangue , Hipogonadismo/genética , Deficiência Intelectual/complicações , Menstruação , Distúrbios Menstruais/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Odorantes , Transtornos do Olfato/etiologia , Feromônios/fisiologia , Síndrome , Paladar , Zinco/deficiênciaAssuntos
Doenças dos Bovinos/microbiologia , Bovinos/microbiologia , Diarreia/veterinária , Escherichia coli/isolamento & purificação , Intestino Delgado/microbiologia , Animais , Meios de Cultura , Diarreia/microbiologia , Enterotoxinas/biossíntese , Escherichia coli/metabolismo , Escherichia coli/patogenicidade , Íleo/microbiologia , Jejuno/microbiologia , VirulênciaAssuntos
Fenômenos Fisiológicos Cardiovasculares , Hemodinâmica , Estações do Ano , Aclimatação , Adulto , Idoso , Pressão Sanguínea , Feminino , Resposta Galvânica da Pele , Frequência Cardíaca , Humanos , Umidade , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Temperatura , Resistência VascularRESUMO
Avian embryos, which have been studied scientifically since Aristotle, continue to persevere as invaluable research tools, especially for our understanding of the development and evolution of the craniofacial skeleton. Whether the topic is beak shape in Darwin's finches or signaling interactions that underlie bone and tooth formation, birds offer advantages for craniofacial biology that uniquely complement the strengths of other vertebrate model systems, such as fish, frogs, and mice. Several papers published during the past few years have helped pinpoint molecular and cellular mechanisms that pattern the face and jaws through experiments that could only have been done together with our feathered friends. Ultimately, such knowledge will be essential for devising novel clinical approaches to treat and/or prevent diseases, injuries, and birth defects that affect the human craniofacial skeleton. Here we review recent insights plucked from avians on key developmental processes that generate craniofacial diversity.