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1.
Tech Coloproctol ; 28(1): 66, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850445

RESUMO

BACKGROUND: We aimed to compare outcomes and cost effectiveness of extra-corporeal anastomosis (ECA) versus intra-corporeal anastomosis (ICA) for laparoscopic right hemicolectomy using the National Surgical Quality Improvement Programme data. METHODS: Patients who underwent elective laparoscopic right hemicolectomy for colon cancer from January 2018 to December 2022 were identified. Non-cancer diagnoses, emergency procedures or synchronous resection of other organs were excluded. Surgical characteristics, peri-operative outcomes, long-term survival and hospitalisation costs were compared. Incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness. RESULTS: A total of 223 patients (175 ECA, 48 ICA) were included in the analysis. Both cohorts exhibited comparable baseline patient, comorbidity, and tumour characteristics. Distribution of pathological TMN stage, tumour largest dimension, total lymph node harvest and resection margin lengths were statistically similar. ICA was associated with a longer median operative duration compared with ECA (255 min vs. 220 min, P < 0.001). There was a quicker time to gastrointestinal recovery, with a shorter median hospital stay in the ICA group (4.0 versus 5.0 days, P = 0.001). Overall complication rates were comparable. ICA was associated with a higher surgical procedure cost (£6301.57 versus £4998.52, P < 0.001), but lower costs for ward accommodation (£1679.05 versus £2420.15, P = 0.001) and treatment (£3774.55 versus £4895.14, P = 0.009), with a 4.5% reduced overall cost compared with ECA. The ICER of -£3323.58 showed ICA to be more cost effective than ECA, across a range of willingness-to-pay thresholds. CONCLUSION: ICA in laparoscopic right hemicolectomy is associated with quicker post-operative recovery and may be more cost effective compared with ECA, despite increased operative costs.


Assuntos
Anastomose Cirúrgica , Colectomia , Neoplasias do Colo , Laparoscopia , Duração da Cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anastomose Cirúrgica/economia , Anastomose Cirúrgica/métodos , Colectomia/economia , Colectomia/métodos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/economia , Análise de Custo-Efetividade , Procedimentos Cirúrgicos Eletivos/economia , Procedimentos Cirúrgicos Eletivos/métodos , Custos Hospitalares/estatística & dados numéricos , Laparoscopia/economia , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/economia , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
2.
Phys Rev Lett ; 131(2): 022502, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37505949

RESUMO

The excitation energy of the 1/2^{-} isomer in ^{99}In at N=50 is measured to be 671(37) keV and the mass uncertainty of the 9/2^{+} ground state is significantly reduced using the ISOLTRAP mass spectrometer at ISOLDE/CERN. The measurements exploit a major improvement in the resolution of the multireflection time-of-flight mass spectrometer. The results reveal an intriguing constancy of the 1/2^{-} isomer excitation energies in neutron-deficient indium that persists down to the N=50 shell closure, even when all neutrons are removed from the valence shell. This trend is used to test large-scale shell model, ab initio, and density functional theory calculations. The models have difficulties describing both the isomer excitation energies and ground-state electromagnetic moments along the indium chain.

3.
Scand J Gastroenterol ; 58(12): 1499-1504, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37464727

RESUMO

BACKGROUND: Drug-induced liver injury (DILI) remains a challenging diagnosis due to an absence of specific biomarkers. DILI due to volatile anaesthetics (VA-DILI) is characterised by trifluoroacetyl and CYP2E1 antibodies, but may not be seen for weeks after injury. Interleukin-4 (IL-4) may be involved in the production of these antibodies and may serve as a clinically useful early biomarker of VA-DILI. AIM: To prospectively compare serum IL-4 levels between patients who develop VA-DILI and controls following exposure to the volatile anaesthetic. METHODS: A nested case-control study of patients exposed to VA during surgery was conducted. Thirteen DILI cases were identified from the original cohort, and 26 controls were matched according to age, sex and VA agent. Serum samples were collected before and 48-96 h after VA exposure, and analysed for IL-4 using quantitative enzyme-linked immunosorbent assay techniques. RESULTS: There was a statistically significant difference in serum IL-4 in post-VA samples between DILI cases and controls (control: 0.030 pg/mL, IQR: 0.030 - 0.030 pg/mL vs DILI: 0.044 pg/mL, IQR: 0.030 - 0.061 pg/mL; p = 0.039). A greater proportion of DILI cases had post-VA IL-4 levels above the assay lower limit of detection compared to controls (control: 23% vs DILI: 69%; p = 0.013). CONCLUSION: IL-4 is a potential biomarker of DILI. Clinical diagnosis and understanding of DILI disease mechanisms may be improved by further investigation of novel biomarkers, and this IL-4 signal in serum is important as proof of concept for prospective study designs.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Interleucina-4 , Humanos , Estudos de Casos e Controles , Estudos Prospectivos , Biomarcadores , Anticorpos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Fígado
4.
Osteoarthritis Cartilage ; 28(12): 1559-1571, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32858189

RESUMO

OBJECTIVES: This study aimed to investigate the role of endothelin-1 (ET-1), originally known as the potent vasoconstrictor, and its receptors in chondrocyte senescence and osteoarthritis (OA) development. METHOD: Temporal changes of ET-1 and its receptors with OA development were characterized in a posttraumatic OA (PTOA) mouse model at time zero, 1-month and 4-month after surgical induction via destabilization of medial meniscus (DMM). A transgenic ET-1 overexpression (TET-1) mouse model was deployed to assess the impact of upregulated ET-1 on chondrocyte senescence and cartilage degradation. Effects of endothelin receptor blockade on chondrocyte senescence and OA development were further examined both in vitro and in vivo. RESULTS: Local expression of ET-1 in subchondral bone and synovium upregulated after DMM with an increase of plasma ET-1 level from 3.18 ± 0.21 pg/ml at time zero to 6.47 ± 0.34 pg/ml at 4-month post-surgery. Meanwhile, endothelin type B receptor (ETBR) (53.31 ± 2.42% to 83.8 ± 2.65%) and p16INK4a (10.91 ± 1.07% to 28.2 ± 1.0%) positve chondrocytes accumulated in articular cartilage since 1-month prior to cartilage loss at 4-month post-surgery. Overexpressed ET-1 promoted p16INK4a-positive senescent chondrocytes accumulation and cartilage degradation in TET-1 mice. Selective blockade of ETBR, but not ETAR, lowered the expression of p16INK4a in ET-1 or H2O2-induced chondrocyte senescence model, and mitigated the severity of murine PTOA. Intriguingly, reactive oxygen species (ROS) scavenger, Vitamin C, could rescue ET-1-induced chondrocyte senescence in vitro associated with restoration of mitochondrial dynamics. CONCLUSION: ET-1 could induce chondrocytes senescence and cartilage damages via ETBR in PTOA.


Assuntos
Cartilagem Articular/metabolismo , Senescência Celular/fisiologia , Condrócitos/fisiologia , Endotelina-1/metabolismo , Osteoartrite/fisiopatologia , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Senescência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Receptores de Endotelina/metabolismo , Regulação para Cima/fisiologia
5.
Genet Med ; 21(4): 1008-1014, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30166628

RESUMO

PURPOSE: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures. Because DEEs are clinically and genetically heterogeneous, next-generation sequencing, especially exome sequencing (ES), is becoming a first-tier strategy to identify the molecular etiologies of these disorders. METHODS: We combined ES analysis and international data sharing. RESULTS: We identified 11 unrelated individuals with DEE and de novo heterozygous truncating variants in the interferon regulatory factor 2-binding protein-like gene (IRF2BPL). The 11 individuals allowed for delineation of a consistent neurodevelopmental disorder characterized by mostly normal initial psychomotor development followed by severe global neurological regression and epilepsy with nonspecific electroencephalogram (EEG) abnormalities and variable central nervous system (CNS) anomalies. IRF2BPL, also known as enhanced at puberty protein 1 (EAP1), encodes a transcriptional regulator containing a C-terminal RING-finger domain common to E3 ubiquitin ligases. This domain is required for its repressive and transactivating transcriptional properties. The variants identified are expected to encode a protein lacking the C-terminal RING-finger domain. CONCLUSIONS: These data support the causative role of truncating IRF2BPL variants in pediatric neurodegeneration and expand the spectrum of transcriptional regulators identified as molecular factors implicated in genetic developmental and epileptic encephalopathies.


Assuntos
Proteínas de Transporte/genética , Epilepsia/genética , Transtornos do Neurodesenvolvimento/genética , Proteínas Nucleares/genética , Convulsões/genética , Adolescente , Adulto , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/patologia , Criança , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Feminino , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenótipo , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Sequenciamento do Exoma , Adulto Jovem
6.
Sci Rep ; 14(1): 11033, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744912

RESUMO

The presented paper discusses the production of radioactive ion beams of francium, radium, and actinium from thick uranium carbide (UC x ) targets at ISOLDE, CERN. This study focuses on the release curves and extractable yields of francium, radium and actinium isotopes. The ion source temperature was varied in order to study the relative contributions of surface and laser ionization to the production of the actinium ion beams. The experimental results are presented in the form of release parameters. Representative extractable yields per µ C are presented for 222 - 231 Ac, several Ra and Fr isotopes in the mass ranges 214 ≤ A ≤ 233 and 205 ≤ A ≤ 231 respectively. The release efficiency for several isotopes of each of the studied elements was calculated by comparing their yields to the estimated in-target production rates modeled by CERN-FLUKA. The maximal extraction efficiency of actinium was calculated to be 2.1(6)% for a combination of surface ionization using a Ta ion source and resonant laser ionization using the two-step 438.58 nm, and 424.69 nm scheme.

7.
Nat Genet ; 23(2): 203-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10508518

RESUMO

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.


Assuntos
Arabidopsis/genética , Marcadores Genéticos/genética , Genoma de Planta , Ascomicetos/crescimento & desenvolvimento , Mapeamento Cromossômico , DNA de Plantas/genética , Genes de Plantas/genética , Predisposição Genética para Doença , Genótipo , Análise de Sequência com Séries de Oligonucleotídeos , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Polimorfismo Genético
9.
Arch Orthop Trauma Surg ; 131(11): 1509-18, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21805361

RESUMO

AIM: Delayed fracture healing and non-unions of the femoral neck after lag screw osteosynthesis occur particularly in multiply injured young patients, and then surgical revision is often required. Currently no evidence-based treatment guidelines exist and therapeutic options include both hip arthroplasties and femoral head-maintaining operations. Here we report on young patients with delayed fracture healing of the femoral neck. Patients underwent revision surgery by autologous bone cylinder transplantation with mechanical re-stabilisation by cannulated lag screws. MATERIAL AND METHODS: We reviewed all patients after femoral neck screw osteosynthesis and identified eight patients at 7.3 [3-24] months after initial osteosynthesis with persisting, or reoccurring postoperative pain. Average patient age was 43 [35-57] years and patient Harris Hip Score (HHS) numbers were low (52 ± 19). Before revision surgery the preoperative CT scans showed a partial bone consolidation (anterior and/or posterior cortices) in the absence of a complete bone consolidation of all cortices. Seven patients were treated by bone cylinder transplantation from the patient's own iliac crest; one patient underwent an inverse bone cylinder procedure. Seven patients were additionally treated by re-insertion of 1-2 lag screws to increase mechanical stability. RESULTS: After revision surgery the average patient follow-up period was 42 [12-89] months. Five patients achieved favourable clinical and radiographic outcome with both complete bone union and return to work within 7.2 ± 2.75 months. One patient showed fracture healing but developed an aseptic femoral head osteonecrosis. Two patients failed to achieve complete bone consolidation. The postoperative HHS was 92 ± 4 in patients with favourable clinical outcome (n = 5) and 89 ± 2 after second revision surgery (2 hip arthroplasties; 1 valgus osteotomy). Both groups had significantly better HHS numbers compared with before surgical revision (p < 0.05). DISCUSSION: These data show that in this difficult-to-treat subset of young patients with delayed fracture healing of the femoral neck, autologous bone cylinder transplantation with mechanical re-stabilisation should be considered as a promising surgical revision strategy before hip arthroplasty.


Assuntos
Parafusos Ósseos , Transplante Ósseo/instrumentação , Fraturas do Colo Femoral/cirurgia , Consolidação da Fratura , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
11.
Eur Rev Med Pharmacol Sci ; 24(21): 11365-11373, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33215457

RESUMO

OBJECTIVE: This experimental study explored the potential of oral zinc sulfate to protect the gut mucosa from 5-fluorouracil (5-FU)-induced degenerative lesions in Wistar rats. MATERIALS AND METHODS: Female Wistar rats were used and divided into 2 interventional groups (Z with 6 animals and F with 5 animals) and one control group (M with 5 rats). After 2 hours of fasting, group Z received via oral gavage 1.5 ml of solution, corresponding to 15 mg zinc sulfate for 9 consecutive days. Groups F and M received only the vehicles. On day 3, 400 mg/kg of 5-FU was administered intraperitoneally to groups Z and F. Tissue samples were collected from the duodenum, jejunum, colon and liver. Histological assessment for each gastrointestinal tract segment was determined semi-quantitatively by rating 11 histological features from normal (0) to severe (3). The independent groups were analyzed using the Kruskal-Wallis test and the Mann-Whitney U-test, with a Bonferroni correction for alpha (p ≤ 0.016). RESULTS: In group F the jejunum was the most affected area with a mean histological score of  27 (25-32). In the Z group, significantly lower histological scores were obtained compared with group F (duodenum Z vs. F: U = 0, p = 0.004; jejunum Z vs. F: U = 0, p = 0.006 and colon: Z vs. F: U = 0, p = 0.005). Graded liver necro-inflammatory lesions were significantly lower in group Z compared with group F (U = 0, p = 0.004), suggesting fewer bacterial intestinal translocation processes. CONCLUSIONS: Zinc sulfate has a beneficial role, decreasing the severity of gut mucosal injuries induced by 5-FU in Wistar rats.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Mucosite/tratamento farmacológico , Sulfato de Zinco/farmacologia , Administração Oral , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Modelos Animais de Doenças , Feminino , Fluoruracila/administração & dosagem , Trato Gastrointestinal/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Mucosite/induzido quimicamente , Mucosite/patologia , Ratos , Ratos Wistar , Sulfato de Zinco/administração & dosagem
12.
Science ; 243(4894 Pt 1): 1027-33, 1989 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-2646709

RESUMO

The genetic control of neuronal differentiation has been studied by examining mutations that affect the development and function of the six touch receptor neurons of the nematode Caenorhabditis elegans. By screening for touch-insensitive mutants, it has been possible to identify 18 genes (represented by 417 mutations) that are required at various stages in the developmental program for touch cell differentiation. Two of the genes are needed for the generation of precursors in the touch cell lineages; without the precursors, touch cells are not made. A third gene, mec-3, specifies the differentiation of the touch cells, probably by acting as a transcription factor. The remaining 15 genes are likely targets of mec-3 action; mutants defective in these genes have nonfunctioning, yet differentiated, touch cells. Some of these latter genes are needed for the formation of cell-specific components of the touch cells, such as a set of microtubules that are only found in these cells. The study of the touch genes should help us understand how touch cell fate is determined, how microtubule form is specified, and, perhaps, how mechanical stimuli are transduced.


Assuntos
Caenorhabditis/genética , Regulação da Expressão Gênica , Neurônios/citologia , Animais , Caenorhabditis/citologia , Caenorhabditis/crescimento & desenvolvimento , Diferenciação Celular , Mecanorreceptores/citologia , Mutação , Tato
13.
Nanoscale ; 10(27): 13074-13082, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-29961799

RESUMO

The large-scale production and ecotoxicity of urea make its removal from wastewater a health and environmental challenge. Whereas the industrial removal of urea relies on hydrolysis at elevated temperatures and high pressure, nature solves the urea disposal problem with the enzyme urease under ambient conditions. We show that CeO2-x nanorods (NRs) act as the first and efficient green urease mimic that catalyzes the hydrolysis of urea under ambient conditions with an activity (kcat = 9.58 × 101 s-1) about one order of magnitude lower than that of the native jack bean urease. The surface properties of CeO2-x NRs were probed by varying the Ce4+/Ce3+ ratio through La doping. Although La substitution increased the number of surface defects, the reduced number of Ce4+ sites with higher Lewis acidity led to a slight decrease of their catalytic activity. CeO2-x NRs are stable against pH changes and even to the presence of transition metal ions like Cu2+, one of the strongest urease inhibitors. The low costs and environmental compatibility make CeO2-x NRs a green urease substitute that may be applied in polymer membranes for water processing or filters for the waste water reclamation. The biomimicry approach allows the application of CeO2-x NRs as functional enzyme mimics where the use of native or recombinant enzyme is hampered because of its costs or operational stability.


Assuntos
Cério/química , Nanotubos , Ureia/isolamento & purificação , Urease , Hidrólise , Água , Purificação da Água
14.
Leukemia ; 20(4): 715-23, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16453006

RESUMO

The processes mediating genomic instability and clonal evolution are obscure in multiple myeloma (MM). Acquisition of new chromosomal translocations into the switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in MM, often heralds transformation to more aggressive disease. Since the combined effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch recombination (CSR), and this process involves DNA double strand break repair (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this study, we show that MM cell lines that are optimally triggered via CD40 and/or IL-4 demonstrate abnormal decoupling of IL-4 signal transduction from CD40. Specifically, CD40 alone was sufficient to trigger maximal growth of tumor cells. We further demonstrate that CD40 triggering induced both DNA DSBs as well as newly acquired karyotypic abnormalities in MM cell lines. Importantly, these observations were accompanied by induction of activation induced cytidine deaminase expression, but not gross apoptosis. These data support the role of abnormal CD40 signal transduction in mediating genomic instability, suggesting a role for the CD40 pathway and intermediates in myelomagenesis and clonal evolution in vivo.


Assuntos
Antígenos CD40/imunologia , Ligante de CD40/farmacologia , Instabilidade Genômica , Cadeias Pesadas de Imunoglobulinas/imunologia , Interleucina-4/imunologia , Mieloma Múltiplo/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Aberrações Cromossômicas , Citidina Desaminase/biossíntese , Citidina Desaminase/efeitos dos fármacos , DNA/biossíntese , DNA/efeitos dos fármacos , Humanos , Cadeias Pesadas de Imunoglobulinas/efeitos dos fármacos , Cadeias Pesadas de Imunoglobulinas/genética , Interleucina-4/farmacologia , Mieloma Múltiplo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Regulação para Cima
15.
Mol Endocrinol ; 3(10): 1610-26, 1989 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2558297

RESUMO

The thyroid hormones and retinoic acid are potent modulators of differentiation, development, and gene expression. The transcriptional activities of these ligands are mediated by closely related nuclear receptors which bind and activate identical hormone responsive DNA elements. We noticed that a region within the ligand binding or E domain is well conserved between receptors for these hormones. This region contains hydrophobic heptad repeats that are structurally similar to the leucine-zipper dimerization domain. To study the function of this conserved domain, we examined the transcriptional responses of thyroid hormone receptor/c-erbA deletion mutants which lacked the heptad repeats. We previously reported that the chick c-erbA-alpha possesses hormone-independent (constitutive) activity in cells which express endogenous rat thyroid hormone receptor. We now demonstrate that this activity is abolished upon deletion of the conserved heptad repeats. This suggests that the heptad repeats mediate in vivo interactions between chick c-erbA and rat thyroid hormone receptors. To further test this hypothesis deletion mutants of chick c-erbA were constructed which contained all eight heptad repeats but which lacked the zinc-finger DNA binding domain. Although these mutants are transcriptionally inactive, they act in a dominant-negative fashion to block trans-activation by both the chick c-erbA-alpha and the endogenous thyroid hormone and retinoic acid receptors. We suggest that the heptad repeats mediate the formation of inactive mutant/wild-type hetero-dimers. Dimer formation suggests a mechanism to account for the dominant-negative phenotypes displayed by nonhormone binding variants of c-erbA, the proto-oncoprotein v-erbA and patients with the generalized thyroid hormone resistance syndrome.


Assuntos
Proteínas de Transporte/metabolismo , Leucina/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Tretinoína/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Transporte/genética , Células Cultivadas , Embrião de Galinha , DNA/genética , Dados de Sequência Molecular , Mutação , Plasmídeos , Testes de Precipitina , Proteínas Proto-Oncogênicas/genética , Receptores do Ácido Retinoico , Receptores dos Hormônios Tireóideos/genética
16.
Am J Med Genet ; 18(3): 493-507, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6332533

RESUMO

We have studied various properties of the binding of 5 alpha-dihydrotestosterone (DHT) or the synthetic, nonmetabolizable androgen methyltrienolone (R1881; 17 beta-hydroxy-17 alpha-methylestra-4,9,11-trien-3-one) to the androgen receptor of genital skin fibroblasts (GSF) from controls and a subject with familial, receptor-positive, partial androgen insensitivity. The mutant cells form R1881-receptor complexes that dissociate 7 times more rapidly than normal at 30 degrees C, and they do not increase their specific R1881-receptor activity in response to a 72-hr period of incubation with R1881, whereas the cells from normal individuals do so two- to three-fold. As previously reported [Pinsky et al, 1981; Kaufman et al, 1981], the mutant cells have similar abnormalities with DHT as with R1881. When the patient's cells are incubated for 120 min with varying concentrations (0.05-3 nM) of R1881 or DHT, Scatchard analysis shows that their androgen-receptor activity has an apparent equilibrium dissociation constant (Kd) for each ligand that is six-fold greater than that of normal cells (approximately 0.2 nM). Normal GSF have higher, more variable values of Kd (0.3-1.8 nM) for either ligand after 30 compared to 120 min of incubation, and the 60-min values are intermediate. This explains why we previously reported that the patient's cells had a 30-min Kd for DHT in the normal range [Pinsky et al, 1981]. Sucrose gradient centrifugation of mutant GSF cytosol incubated with DHT in the presence of 10 mM sodium molybdate yields a normal 6.5-8S peak of DHT-receptor complexes. From these data we conclude that normal GSF form initial, low-affinity androgen-receptor complexes that are transformed into one (or more) higher-affinity (? activated) states by a process that depends on time and initial concentration of androgen; the subject's GSF can form low-affinity androgen-receptor complexes but cannot generate the normal high-affinity state of the complexes, and this lack precludes augmentation of their androgen-receptor activity in response to prolonged incubation with either androgen; and failure of molybdate to stabilize the androgen-receptor activity in GSF cytosol is not a more sensitive indicator of structurally altered androgen-receptor proteins than are other qualities described heretofore.


Assuntos
Di-Hidrotestosterona/metabolismo , Transtornos do Desenvolvimento Sexual/genética , Estrenos/metabolismo , Regulação da Expressão Gênica , Receptores Androgênicos/genética , Receptores de Esteroides/genética , Adolescente , Criança , Transtornos do Desenvolvimento Sexual/tratamento farmacológico , Fibroblastos/metabolismo , Seguimentos , Ginecomastia/genética , Humanos , Cinética , Masculino , Metribolona , Receptores Androgênicos/metabolismo , Testosterona/análogos & derivados , Testosterona/uso terapêutico
17.
Spine (Phila Pa 1976) ; 21(19): 2260-6; discussion 2267, 1996 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-8902972

RESUMO

STUDY DESIGN: Rigid post-traumatic kyphosis after fracture of the thoracolumbar and lumbar spine represents a failure of initial management of the injury. Kyphosis moves the center of gravity anterior. The kyphosis and instability may result in pain, deformity, and increased neurologic deficits. Management for symptomatic post-traumatic kyphosis always has presented a challenge to orthopedic surgeons. OBJECTIVES: To evaluate the surgical results of one stage posterior correction for rigid symptomatic post-traumatic kyphosis of the thoracolumbar and lumbar spine. SUMMARY OF BACKGROUND DATA: The management for post-traumatic kyphosis remains controversial. Anterior, posterior, or combined anterior and posterior procedures have been advocated by different authors and show various degrees of success. METHODS: One vertebra immediately above and below the level of the deformity was instrumented posteriorly by a transpedicular system (internal fixator AO). Posterior decompression was performed by excision of the spinal process and bilateral laminectomy. With the deformed vertebra through the pedicle, the vertebral body carefully is removed around the pedicle level, approximating a wedge shape. The extent to which the deformed vertebral body should be removed is determined by the attempted correction. Correction of the deformity is achieved by manipulation of the operating table and compression of the adjacent Schanz screws above and below the lesion. RESULTS: Thirteen patients with post-traumatic kyphosis with symptoms of fatigue and pain caused by slow progression of kyphotic deformities received posterior decompression, correction, and stabilization as a definitive treatment. The precorrection kyphosis ranged from 30-60 degrees, with a mean of 40 degrees +/- 10.8 degrees. After correction, kyphosis was reduced to an average of 1.5 degrees +/- 3.8 degrees, with a range from -5 degrees to 5 degrees. The average angle of correction was 38.8 degrees +/- 10.4 degrees, with a range from 25 degrees to 60 degrees. Significant difference was found between pre- and post-operative kyphosis measures (P < 0.001). The follow-up period for all patients was 2 years, and the average kyphosis angle measured at the moment was 3.8 degrees +/- 3 degrees with a range from -3 degrees to 8 degrees. Substantial overall improvement was achieved in the 13 patients. CONCLUSION: This method provides single-stage posterior decompression, correction, and stabilization on as definitive management for post traumatic kyphosis of the thoracolumbar and lumbar spine.


Assuntos
Cifose/etiologia , Cifose/cirurgia , Vértebras Lombares/cirurgia , Ortopedia/métodos , Fraturas da Coluna Vertebral/complicações , Vértebras Torácicas/cirurgia , Adulto , Seguimentos , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Tomografia Computadorizada por Raios X
18.
Clin Oncol (R Coll Radiol) ; 10(4): 231-6, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9764374

RESUMO

High dose rate (HDR) interstitial tongue brachytherapy is a new treatment modality. This study describes important technical details required for its successful use. Thirteen patients with carcinoma of the oral tongue were treated solely with interstitial brachytherapy using HDR remote afterloading techniques during the years 1994-1997. The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Custom-made mandibular lead shields were inserted prior to treatment. Special reusable Tuen Mun Hospital (TMH) lead buttons were made for improved radiation protection. The median dose given was 55 Gy in ten fractions over 6 days. The interfraction interval was 7 hours for the first seven patients treated and was extended to 8 hours for the other six. Shrinking field techniques were employed and the treatment length of the last fraction was reduced by 5 mm. Commencing with the second patient treated with double planar implants, the medial plane was treated with eight fractions while the lateral plane received ten fractions. To reduce further the potential risk of tract seeding, additional coverage to the implantation tracts was given for the last four patients, with the resultant isodose curves resembling a 'comb rake/brush'. The mean and median measured doses on the inner face of the mandibular shields were 113% and 93% of the reference dose respectively (range 77-247). The dose to the corresponding sites on the gingival surface can be reduced by 75% if the 3 mm thick lead shield is placed successfully. With the use of the TMH button, the transmitted dose to the tissue in direct contact can be reduced by one-third. With the 'comb rake/brush' dose distribution, the high dose volume of the single planar implants could be reduced by 44%, compared with the low dose rate technique, if loading to just 5 mm short of the submandibular skin was required. The mean doses for the combination of eight double planar plus two single planar implants, and ten double planar implants, are on average 29% and 37% greater than the reference dose respectively. An 8% reduction in absolute dose in the region between the planes of the catheters would lead to an even greater magnitude of reduction in morbidity to late responding tissue. The prerequisite for the success of HDR interstitial implants is to develop a good technique in positioning the afterloading catheters and protection of the normal tissue. Its importance merits special attention if HDR remote afterloading interstitial tongue brachytherapy is to realize its full potential.


Assuntos
Braquiterapia , Neoplasias da Língua/radioterapia , Braquiterapia/métodos , Humanos , Dosagem Radioterapêutica
19.
Sci Total Environ ; 93: 385-92, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2360021

RESUMO

25 substances were determined in runoff, wet and bulk deposition samples from different sampling sites in Hamburg, (a street in an industrial area, a thoroughfare and a small street in a residential area). The runoff from the industrial road and the main street showed similar pollution levels. The surface water from the industrial area contained higher concentrations of As, whereas the main street showed higher concentrations of Pb, Sb and Zn. The runoff from the residential area was loaded substantially lower. Several elements e.g. Co, Cr, V were found to be almost completely adsorbed to particles, but some more toxical elements e.g. Cd, Cu were found at a high percentage in the soluble phase.


Assuntos
Meios de Transporte , Poluentes Químicos da Água/análise , Poluentes da Água/análise , Alemanha Ocidental , Humanos , Indústrias , Chuva , População Urbana
20.
Disabil Rehabil ; 22(1-2): 43-56, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10661757

RESUMO

A community survey of 271 Chinese migrants aged 15 years and older living in Auckland was conducted to assess self-rated adjustment and health. The majority of respondents came from Hong Kong and Taiwan. Despite significant changes in their lives, including the absence of family members, unemployment and underemployment, most did not report major adjustment problems or regret having come to New Zealand. Few considered their health to be poor. Forty-two per cent reported having consulted a doctor within the past 12 weeks. Factors significantly associated with having experienced major problems included being aged 26-35 years, rejection from locals and having low English proficiency. Factors associated with poor adjustment included expectations not having been met, regretting coming, low proficiency in English, recent arrival in New Zealand, unemployment, younger age and lower levels of education. Self-rated fair or poor health was found to be associated with Chinese-only reading knowledge, residency of more than 5 years and regretting having come to New Zealand.


Assuntos
Aculturação , Emigração e Imigração , Nível de Saúde , Saúde Mental , Adaptação Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/etnologia , Feminino , Serviços de Saúde/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nova Zelândia/epidemiologia , Razão de Chances , Fatores Socioeconômicos
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