RESUMO
This study investigated the effects of raloxifene and alendronate to follow parathyroid hormone (PTH) on bone collagen and biomechanical properties in ovariectomized rabbits. Sequential treatments of raloxifene and alendronate after hPTH(1-34) treatment improved biomechanical properties with and without bone collagen improvement, respectively. INTRODUCTION: The standard sequential treatment to follow human parathyroid hormone (hPTH) (1-34) therapy for osteoporosis has yet to be determined. The objective of this study was to compare the effects of raloxifene and alendronate treatments to follow daily hPTH(1-34) treatment on non-enzymatic collagen cross-links, bone mass, and bone strength in ovariectomized (OVX) rabbits. METHODS: From 3 months after ovariectomy, seven month-old female New Zealand white rabbits were given either vehicle or hPTH(1-34) (8 µg/kg/day), once daily for 5 months. After hPTH(1-34) treatment, the hPTH(1-34)-treated animals were divided into two groups, and given raloxifene (10 mg/kg, daily) orally or alendronate (100 µg/kg, twice weekly) subcutaneously for 5 months. We evaluated bone mineral density (BMD), bone structural parameters, advanced glycation end product (AGE) content in collagen, and bone mechanical parameters including intrinsic parameters in the femur. RESULTS: Raloxifene (hPTH/RLX) and alendronate (hPTH/ALN) to follow hPTH(1-34) increased cortical thickness, maximum load, and maximum stress and decreased endocortical surface in the diaphysis, in addition to increasing total BMD in the distal metaphysis. Decreased trabecular AGE, pentosidine, and homocysteine contents and increased toughness and breaking energy were noted with hPTH/RLX treatment only. With hPTH/ALN treatment, no effects on non-enzymatic collagen cross-link AGEs were noted although increases in stiffness and elastic modulus were observed. CONCLUSION: These results suggest that sequential treatments with hPTH(1-34) and antiresorptive drugs (raloxifene and alendronate) have a beneficial effect on bone mass and biomechanical properties in OVX rabbits.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Colágeno/efeitos dos fármacos , Alendronato/administração & dosagem , Alendronato/farmacologia , Animais , Biomarcadores/metabolismo , Fenômenos Biomecânicos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/administração & dosagem , Colágeno/metabolismo , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Feminino , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fêmur/fisiopatologia , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Ovariectomia , Coelhos , Cloridrato de Raloxifeno/administração & dosagem , Cloridrato de Raloxifeno/farmacologia , Estresse Mecânico , Teriparatida/farmacologia , Suporte de CargaRESUMO
Pseudomonas aeruginosa possesses an arsenal of both cell-associated (flagella, pili, alginate, etc.) and extracellular (exotoxin A, proteases, type III secretion effectors, etc.) virulence factors. Among them, secreted proteases that damage host tissues are considered to play an important role in the pathogenesis of P. aeruginosa infections. We previously reported that EprS, an autotransporter protease of P. aeruginosa, induces host inflammatory responses through protease-activated receptors. However, little is known about the role of EprS as a virulence factor of P. aeruginosa. In this study, to investigate whether EprS participates in the pathogenicity of P. aeruginosa, we characterized various pathogenic phenotypes of the wild-type PAO1 strain and its eprS-disrupted mutant. The growth assays demonstrated that the growth of the eprS mutant was somewhat lower than that of the wild-type strain in a minimal medium containing BSA as the sole carbon and nitrogen source. Thus, these results indicate that eprS would have a role in the growth of P. aeruginosa in the presence of limited nutrients, such as a medium containing proteinaceous materials as a sole nutrient source. Furthermore, disruption of eprS resulted in a decreased production of elastase, pigments, autoinducers and surfactants, and a reduction of swimming and swarming motilities. In addition, the eprS mutant exhibited a reduction in the ability to associate with A549 cells and an attenuation of virulence in leucopenic mice as compared with the wild-type strain. Collectively, these results suggest that EprS exerts pleiotropic effects on various pathogenic phenotypes of P. aeruginosa.
Assuntos
Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/patogenicidade , Serina Proteases/genética , Fatores de Virulência/genética , Animais , Aderência Bacteriana/genética , Linhagem Celular , Humanos , Camundongos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Tensoativos/metabolismoRESUMO
UNLABELLED: Improvements in total content of enzymatic cross-linking, the ratio of hydroxylysine-derived enzymatic cross-links, and non-enzymatic advanced glycation end product cross-link formation from once-weekly administration of hPTH(1-34) for 18 months in OVX cynomolgus monkeys contributed to the improvement of bone strength. INTRODUCTION: Parathyroid hormone (PTH) is used for the treatment of osteoporosis. To elucidate the contribution of material properties to bone strength after once-weekly treatment with hPTH(1-34) in an ovariectomized (OVX) primate model, the content of collagen and enzymatic immature, mature, and non-enzymatic cross-links, collagen maturity, trabecular architecture, and mineralization in vertebrae were simultaneously estimated. METHODS: Adult female cynomolgus monkeys were divided into four groups (n = 18-20 each) as follows: SHAM group, OVX group, and OVX monkeys given once-weekly subcutaneous injections of hPTH(1-34) either at 1.2 or 6.0 µg/kg (low- or high-PTH groups) for 18 months. The content of collagen, enzymatic and non-enzymatic cross-linking pentosidine, collagen maturity, trabecular architecture, mineralization, and cancellous bone strength of vertebrae were analyzed. RESULTS: Low-PTH and high-hPTH treatments increased the content of enzymatic immature and mature cross-links, bone volume (BV/TV), and trabecular thickness, and decreased pentosidine, compared with the OVX group. Stepwise logistic regression analysis revealed that BV/TV, the content of total enzymatic cross-links, and calcium content independently affected ultimate load (model R (2) = 0.748, p < 0.001) and breaking energy (model R (2) = 0.702, p < 0.001). BV/TV was the most powerful and enzymatic cross-link content was the second powerful determinant of both ultimate load and breaking energy. The most powerful determinant of stiffness was the enzymatic cross-link content (model R (2) = 0.270, p < 0.001). CONCLUSION: Once-weekly preventive administration of hPTH(1-34) increased the total contents of immature and mature enzymatic cross-links, which contributed significantly to vertebral cancellous bone strength.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Colágeno/metabolismo , Osteoporose/metabolismo , Teriparatida/farmacologia , Animais , Arginina/análogos & derivados , Arginina/metabolismo , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Cálcio/metabolismo , Força Compressiva/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/metabolismo , Vértebras Lombares/fisiologia , Lisina/análogos & derivados , Lisina/metabolismo , Macaca fascicularis , Osteoporose/fisiopatologia , Osteoporose/prevenção & controle , Ovariectomia , Fosfatos/metabolismo , Teriparatida/administração & dosagem , Teriparatida/uso terapêutico , Microtomografia por Raio-X/métodosRESUMO
UNLABELLED: We demonstrate a reduction in enzymatic divalent immature and trivalent pyridinium cross-links and an increase in the nonenzymatic cross-link, pentosidine (Pen), in rabbits with methionine (Met)-induced hyperhomocysteinemia. Such detrimental cross-link formation in bone was ameliorated by raloxifene (RLX) treatment. INTRODUCTION: Collagen cross-links are determinants of bone quality. Homocysteine (Hcys) interferes with collagen cross-linking. Because RLX is thought to ameliorate bone quality, we investigated whether RLX ameliorated hyperhomocysteinemia-induced cross-link abnormalities using a Met-rich diet rabbit model. METHODS: We divided New Zealand white rabbits into six groups (n = 6 per group): baseline control, sham operation, sham + 1% Met diet, ovariectomy (OVX), 1% Met diet + OVX, OVX + RLX (10 mg/kg/day), and 1% Met diet + OVX + RLX. RLX was administered for 16 weeks. We measured the amount of enzymatic immature and mature pyridinium cross-links and the nonenzymatic cross-link, Pen, and correlated the cross-link content to bone strength. RESULTS: Hcys levels were significantly higher in the Met diet groups than in the normal diet groups. Met-fed rabbits with or without OVX showed a significant reduction of enzymatic cross-links, whereas an increase in Pen was observed in Met-fed rabbits with OVX. The cross-link content of the RLX-treated Met-fed rabbits with OVX was restored to similar levels as the sham group, accompanied by an improvement of bone strength. CONCLUSION: These results demonstrate that hyperhomocysteinemia reduced bone strength via a reduction of enzymatic cross-links and an increase of nonenzymatic cross-links. RLX may ameliorate hyperhomocysteinemia-induced detrimental cross-linking in rabbits with OVX and may improve bone strength via the amelioration of collagen cross-links.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Hiper-Homocisteinemia/complicações , Osteoporose/prevenção & controle , Cloridrato de Raloxifeno/uso terapêutico , Animais , Arginina/análogos & derivados , Arginina/metabolismo , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Colágeno/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/fisiopatologia , Lisina/análogos & derivados , Lisina/metabolismo , Metionina , Osteoporose/etiologia , Osteoporose/metabolismo , Coelhos , Estresse MecânicoRESUMO
BACKGROUND: Scabies is a contagious dermatosis. The risk factors for its transmission remain unclear. A scabies outbreak, involving patients who were receiving chemotherapy for haematological malignancies, occurred at our hospital. METHODS: The outbreak population was analysed to determine whether the incidence of scabies was higher among contact patients receiving chemotherapy for haematological malignancies. RESULTS: A patient with crusted scabies was the index case, and 18 of 78 contact healthcare workers (HCWs) and 22 of 135 contact patients were diagnosed with classical scabies. Ten of 17 contact patients with haematological malignancies and 12 of 118 contact patients with other diseases were infected with scabies. The incidence rate was significantly higher among the patients with haematological malignancies (P<0.001). The patients with haematological malignancies had a significantly lower mean minimum neutrophil count than those with other diseases (1159/µL vs 3761/µL, P=0.0012). Most haematological patients did not require special nursing assistance, suggesting that the higher incidence of scabies among these patients resulted from their immunodeficiency rather than greater skin-to-skin contact with infected HCWs. CONCLUSION: Our study suggests that patients receiving chemotherapy for haematological malignancies are more susceptible to scabies than patients with other diseases, and require stricter protection.
Assuntos
Suscetibilidade a Doenças/induzido quimicamente , Tratamento Farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Escabiose/etiologia , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Suscetibilidade a Doenças/parasitologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Pessoal de Saúde/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Escabiose/epidemiologia , Escabiose/transmissãoRESUMO
Tom20 is a major receptor of the mitochondrial preprotein translocation system and is bound to the outer membrane through the NH(2)-terminal transmembrane domain (TMD) in an Nin-Ccyt orientation. We analyzed the mitochondria-targeting signal of rat Tom20 (rTom20) in COS-7 cells, using green fluorescent protein (GFP) as the reporter by systematically introducing deletions or mutations into the TMD or the flanking regions. Moderate TMD hydrophobicity and a net positive charge within five residues of the COOH-terminal flanking region were both critical for mitochondria targeting. Constructs without net positive charges within the flanking region, as well as those with high TMD hydrophobicity, were targeted to the ER-Golgi compartments. Intracellular localization of rTom20-GFP fusions, determined by fluorescence microscopy, was further verified by cell fractionation. The signal recognition particle (SRP)-induced translation arrest and photo-cross-linking demonstrated that SRP recognized the TMD of rTom20-GFP, but with reduced affinity, while the positive charge at the COOH-terminal flanking segment inhibited the translation arrest. The mitochondria-targeting signal identified in vivo also functioned in the in vitro system. We conclude that NH(2)-terminal TMD with a moderate hydrophobicity and a net positive charge in the COOH-terminal flanking region function as the mitochondria-targeting signal of the outer membrane proteins, evading SRP-dependent ER targeting.
Assuntos
Membranas Intracelulares/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Mitocôndrias/metabolismo , Sinais Direcionadores de Proteínas , Receptores de Superfície Celular , Sequência de Aminoácidos , Animais , Transporte Biológico , Células COS , Compartimento Celular , Cisteína Endopeptidases/efeitos dos fármacos , Inibidores de Cisteína Proteinase/farmacologia , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Proteínas de Fluorescência Verde , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas de Membrana/genética , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Dados de Sequência Molecular , Complexos Multienzimáticos/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma , Estrutura Terciária de Proteína , Ratos , Proteínas Recombinantes de Fusão/metabolismo , Partícula de Reconhecimento de Sinal/metabolismoRESUMO
Synaptotagmin II is a type I signal-anchor protein, in which the NH(2)-terminal domain of 60 residues (N-domain) is located within the lumenal space of the membrane and the following hydrophobic region (H-region) shows transmembrane topology. We explored the early steps of cotranslational integration of this molecule on the endoplasmic reticulum membrane and demonstrated the following: (a) The translocation of the N-domain occurs immediately after the H-region and the successive positively charged residues emerge from the ribosome. (b) Positively charged residues that follow the H-region are essential for maintaining the correct topology. (c) It is possible to dissect the lengths of the nascent polypeptide chains which are required for ER targeting of the ribosome and for translocation of the N-domain, thereby demonstrating that different nascent polypeptide chain lengths are required for membrane targeting and N-domain translocation. (d) The H-region is sufficiently long for membrane integration. (e) Proline residues preceding H-region are critical for N-domain translocation, but not for ER targeting. The proline can be replaced with amino acid with low helical propensity.
Assuntos
Retículo Endoplasmático/metabolismo , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Sequência de Aminoácidos , Animais , Células COS , Clonagem Molecular , Sequência Consenso , Retículo Endoplasmático/ultraestrutura , Glicosilação , Membranas Intracelulares/metabolismo , Membranas Intracelulares/ultraestrutura , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Camundongos , Microssomos/metabolismo , Microssomos/ultraestrutura , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Proteínas do Tecido Nervoso/genética , Fragmentos de Peptídeos/química , Biossíntese de Proteínas , Conformação Proteica , Coelhos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Sinaptotagmina II , TransfecçãoRESUMO
We present the development of a frequency-domain multiplexing readout of kinetic inductance detectors (KIDs) for pulse signals with a self-trigger system. The KIDs consist of an array of superconducting resonators that have different resonant frequencies individually, allowing us to read out multiple channels in the frequency domain with a single wire using a microwave-frequency comb. The energy deposited to the resonators break Cooper pairs, changing the kinetic inductance and, hence, the amplitude and the phase of the probing microwaves. For some applications such as X-ray detections, the deposited energy is detected as a pulse signal shaped by the time constants of the quasiparticle lifetime, the resonator quality factor, and the ballistic phonon lifetime in the substrate, ranging from microseconds to milliseconds. A readout system commonly used converts the frequency-domain data to the time-domain data. For the short pulse signals, the data rate may exceed the data transfer bandwidth, as the short time constant pulses require us to have a high sampling rate. In order to overcome this circumstance, we have developed a KID readout system that contains a self-trigger system to extract relevant signal data and reduces the total data rate with a commercial off-the-shelf FPGA board. We have demonstrated that the system can read out pulse signals of 15 resonators simultaneously with about 10 Hz event rate by irradiating α particles from 241 Am to the silicon substrate on whose surface aluminum KID resonators are formed.
RESUMO
Insulin-stimulated glycogen synthase activity in human skeletal muscle correlates with insulin-mediated glucose disposal rate (M) and is reduced in insulin-resistant subjects. We have previously reported reduced insulin-stimulated glycogen synthase activity associated with reduced fasting glycogen synthase phosphatase activity in skeletal muscle of insulin-resistant Pima Indians. In this study we investigated the time course for insulin stimulation of glycogen synthase and synthase phosphatase during a 2-h high-dose insulin infusion (600 mU/min per m2) in six insulin-sensitive caucasians (group S) and in five insulin-resistant Pima Indians (group R). Percutaneous muscle biopsies were obtained from the quadriceps femoris muscle after insulin infusion for 0, 10, 20, 40, and 120 min. In group S, insulin-stimulated glycogen synthase activity increased with time and was significantly higher than in group R. In group S, synthase phosphatase activity increased significantly by 25% at 10 min and then decreased gradually. No significant change in synthase phosphatase was seen in group R and activity was lower than group S at 0 to 20 min. These data suggest that a low basal synthase phosphatase activity and a defect in its response to insulin explain, at least in part, reduced insulin stimulation of skeletal muscle glycogen synthase associated with insulin resistance.
Assuntos
Glicogênio Sintase-D Fosfatase/análise , Resistência à Insulina , Insulina/farmacologia , Músculos/enzimologia , Fosfoproteínas Fosfatases/análise , Trifosfato de Adenosina/análise , Adulto , Ativação Enzimática , Jejum , Feminino , Glucose/metabolismo , Glucose-6-Fosfato , Glucofosfatos/análise , Glicogênio Sintase/análise , Humanos , Masculino , FosforilaçãoRESUMO
Insulin-stimulated glycogen synthase activity in human muscle correlates with insulin-mediated glucose disposal and is reduced in insulin-resistant subjects. Inhibition of the cyclic AMP-dependent protein kinase (A-kinase) is considered as a possible mechanism of insulin action for glycogen synthase activation. In this study, we investigated the time course of insulin action on human muscle A-kinase activity during a 2-h insulin infusion in 13 insulin-sensitive (group S) and 7 insulin-resistant subjects (group R). Muscle biopsies were obtained from quadriceps femoris muscle at times 0, 10, 20, 40, and 120 min. Insulin infusion resulted in significant inhibition of A-kinase activity at 20 and/or 40 min using 0.2, 0.6, and 1.0 microM cyclic AMP in group S. A-kinase activities both before and after insulin administration were lower in group S than in group R using 0.6 microM cyclic AMP. The decrease in apparent affinity for cyclic AMP during insulin infusion was larger for group S compared with group R. Glycogen synthase activity increased significantly after insulin infusion in both groups and was higher in group S compared with group R. The data suggest that a defective response of A-kinase to insulin in insulin-resistant subjects could contribute to their reduced insulin stimulation of skeletal muscle glycogen synthase.
Assuntos
AMP Cíclico/metabolismo , Resistência à Insulina , Insulina/metabolismo , Inibidores de Proteínas Quinases , Adulto , Glicemia/análise , Feminino , Glicogênio Sintase/metabolismo , Humanos , Insulina/sangue , Insulina/farmacologia , Masculino , Músculos/efeitos dos fármacos , Músculos/enzimologia , Grupos RaciaisRESUMO
Insulin-stimulated glycogen synthase activity in human muscle is reduced in insulin-resistant subjects. Insulin regulation of human muscle glycogen synthase may require activation of a type-1 protein phosphatase (PP-1). We investigated the change of phosphorylase phosphatase and glycogen synthase activities in muscle biopsies obtained during a 2-h hyperinsulinemic euglycemic clamp in 12 insulin-sensitive (group S) and 8 insulin-resistant (group R) subjects. Fasting phosphorylase phosphatase activity was lower in group R than in group S, and did not increase significantly with insulin infusion in group R until 20 min. In group S, phosphorylase phosphatase was significantly stimulated by 10 min, remaining significantly higher than in group R at all time points. The insulin-mediated changes in phosphatase activities were not decreased by 3 nM okadaic acid but were completely inhibited by 1 microM okadaic acid, thereby verifying that insulin-stimulated phosphorylase phosphatase is accounted for by a PP-1. Subcellular fractionation demonstrated reduced fasting PP-1 activities in both the glycogen and cytosolic fractions of muscle obtained from subjects in group R compared to those in group S. These results suggest that insulin activation of PP-1 could contribute to the stimulation of glycogen synthase by this hormone in human muscle. Lower fasting PP-1 activity in cytosol and glycogen fractions plus lower insulin-stimulated PP-1 activity could explain, in part, reduced insulin-stimulated glycogen synthase in skeletal muscle of insulin-resistant subjects.
Assuntos
Resistência à Insulina , Insulina/farmacologia , Fosforilase Fosfatase/análise , Adulto , Éteres Cíclicos/farmacologia , Feminino , Glicogênio Sintase/análise , Humanos , Masculino , Músculos/enzimologia , Ácido Okadáico , FosforilaçãoRESUMO
It is well known that interferon (IFN) has various side effects including neuropsychiatric complications such as depression. We examined the relationship between neuropsychological impairment and regional cerebral blood flow (CBF) in chronic hepatitis patients treated with and without IFN-alpha. Eight patients with chronic hepatitis participated in this study. Four patients were treated with IFN-alpha (IFN group) and 4 patients were not treated (control group). The entire IFN group and half of the control group were diagnosed with hepatitis C and the rests of the control group had hepatitis B. Neuropsychological tests were conducted. The Self-Rating Depression Scale and the State-Trait Anxiety Inventory were also completed by the subjects. In addition, cerebral single photon emission computed tomography (SPECT; 3DSRT) was performed in all patients. Neuropsychological tests and SPECT were performed in the IFN group 2 months after starting IFN treatment and in the control group 2 months after starting follow-up. A significant reduction of regional CBF in the IFN group was observed in two cerebral regions (lt-angular and lt-temporal region) (P < 0.05), which have reported associations with memory and language function. In addition, the Auditory-Verbal Learning Test (AVLT), a measure of memory function, showed a decreased tendency in the IFN group. A decrease of regional CBF by IFN treatment was shown, suggesting that a decrease of regional CBF may contribute to the neuropsychological impairment by IFN treatment.
Assuntos
Antivirais/efeitos adversos , Circulação Cerebrovascular/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Idoso , Feminino , Hepatite C Crônica/fisiopatologia , Hepatite C Crônica/psicologia , Humanos , Interferon alfa-2 , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Proteínas RecombinantesRESUMO
Although the short arm of chromosome 17, which contains the p53 gene, is frequently affected by loss of heterozygosity (LOH) in lung cancer, little is known about similar changes on the long arm. We found that LOH affected one or more of six loci along chromosome 17 in 59% of 102 informative non-small cell lung cancer (NSCLC) cases. Specifically, the frequency of LOH at 17q was 42%, approaching that at 17p (54%), and two distinct 17q regions were implicated. LOH at D17S4 on 17q was more frequent in adenocarcinomas than in squamous cell carcinomas, whereas squamous cell carcinomas had more LOH at 17p than at 17q, findings that indicate molecular genetic heterogeneity between the major NSCLC subtypes. In addition, LOH at 17q correlated with higher T stages and a significantly worse prognosis. In comparison, 25% of cases had mutations of p53 exons 5-8 but these were not associated with stage or survival. The data suggest that independent of p53, there are important tumor suppressor gene(s) on 17q that may influence NSCLC pathogenesis, progression, and survival.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Deleção Cromossômica , Cromossomos Humanos Par 17 , Neoplasias Pulmonares/genética , Adulto , Idoso , Feminino , Genes p53 , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
Paralabral cysts in the shoulder are a relatively rare pathology. It is sometimes difficult to detect the location of a paralabral cyst in the shoulder using arthroscopy, and it can be difficult to confirm sufficient decompression by arthroscopy. We describe the case of a 64-year-old woman who underwent arthroscopic decompression for a paralabral cyst in the shoulder. Indigo carmine was injected into the cyst under ultrasonography guidance just before the operation. The leakage point of indigo carmine was detected using arthroscopy. Arthroscopic decompression was performed until the indigo carmine was completely discharged. Her shoulder pain, limited range of motion, and muscle weakness during abduction and external rotation improved postoperatively. Magnetic resonance imaging confirmed the disappearance of the cyst. Arthroscopic decompression using an ultrasonography-guided injection of indigo carmine is a useful treatment for a paralabral cyst in the shoulder.
Assuntos
Artroscopia/métodos , Corantes , Cistos/cirurgia , Descompressão Cirúrgica/métodos , Índigo Carmim , Cistos/complicações , Cistos/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Articulação do Ombro/fisiopatologia , Articulação do Ombro/cirurgia , Dor de Ombro/etiologiaRESUMO
BACKGROUND: A vancomycin-intermediate Staphylococcus aureus (VISA) (vancomycin minimum inhibitory concentration: 4mg/L) outbreak occurred in an advanced emergency medical service centre [hereafter referred to as the intensive care unit (ICU)] between 2013 and 2014. AIM: Our objective was to evaluate the infection control measures that were successful. METHODS: Seventeen VISA strains were isolated from the sputum of 15 inpatients and the skin of two inpatients. Fourteen VISA strains were recognized as colonization. However, three VISA strains were isolated from the sputum of three inpatients with pneumonia. Environmental cultures were performed and VISA strains were detected in five of 65 sites. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) was performed on 21 VISA strains. FINDINGS: Molecular typing including PFGE and MLST showed that the patterns of 19 VISA strains were identical and those of the other two VISA strains were possibly related. This meant that a horizontal transmission of VISA strains had occurred in the ICU. In August 2013, the infection control team began interventions. However, new inpatients with VISA strains continued to appear. Therefore, in October 2013, the ICU was partially closed in order to try to prevent further horizontal transmission, and existing inpatients with the VISA strain were isolated. Although new cases quickly dissipated after the partial closure, it took approximately five months to eradicate the VISA outbreak. CONCLUSION: Our data suggest that despite the employment of various other infection control measures, partial closure of the ICU was essential in terminating this VISA outbreak.
Assuntos
Infecção Hospitalar/prevenção & controle , Surtos de Doenças , Controle de Infecções/métodos , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Resistência a Vancomicina , Adulto , Idoso , Idoso de 80 Anos ou mais , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Transmissão de Doença Infecciosa/prevenção & controle , Eletroforese em Gel de Campo Pulsado , Serviços Médicos de Emergência , Microbiologia Ambiental , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Pneumonia Bacteriana/epidemiologia , Pneumonia Bacteriana/microbiologia , Pele/microbiologia , Escarro/microbiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Uncontrolled expression of matrix metalloproteinases 2, 3 and 9 (MMP-2, -3 and -9) is believed to be a critical part of the invasive potential of tumor cells because of their ability to degrade type IV collagen, a major structural component of basement membranes. Availability of proteolytic activity in the vicinity of the cell surface is further affected by a local balance between the enzymes and their inhibitors produced by the cell. To determine how frequently deregulated expression of the MMPs and tissue inhibitors of metalloproteinases (TIMPs) is associated with tumor cells, 26 human tumor cell lines were examined by Northern blotting. Transcripts for MMP-2 and MMP-9 were more frequently expressed in mesenchymal tumor cells (9/9 for MMP-2 and 6/9 for MMP-9) than in epithelial tumor cells (4/17 for MMP-2 and 2/17 for MMP-9). Although expression of MMP-2 mRNA was clearly cell type-specific, MMP-9 mRNA expression in mesenchymal cells correlated well with the reported tumorigenicity of the cells. Enhanced expression of MMP-9 mRNA was also associated with the tumorigenic transformation of cells by an activated c-H-ras gene in human embryonic fibroblasts. Only 3 of the 26 tumor cells expressed MMP-3 mRNA, and 2 of the 3 were epithelial tumor cells which coordinately expressed MMP-9 and TIMP-1 mRNAs. TIMP-1 mRNA was almost undetectable in 50% of the tumor cells, but TIMP-2 mRNA was expressed in the majority of the cells. These findings provide comprehensive information about mRNA expression of the MMPs and TIMPs in tumor cells, the deregulation of which is thought to be an integral part of the invasive potential of tumor cells.
Assuntos
Transformação Celular Neoplásica/metabolismo , Regulação Enzimológica da Expressão Gênica , Glicoproteínas/metabolismo , Colagenase Microbiana/metabolismo , Neoplasias/enzimologia , RNA Mensageiro/metabolismo , Fibroblastos/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/genética , Humanos , Metaloproteinase 9 da Matriz , Colagenase Microbiana/genética , Neoplasias/genética , Acetato de Tetradecanoilforbol/toxicidade , Inibidores Teciduais de Metaloproteinases , Células Tumorais CultivadasRESUMO
The number of beta-adrenergic receptors in cardiac myocytes isolated from rats made diabetic with streptozocin (STZ) for 10 wk was measured by use of a hydrophilic nonselective antagonist [3H]CGP 12177 and was found to decrease to 59% of the number in control rats (P less than .05), without any change in affinity. Similarly, using [125I]iodocyanopindolol as a ligand, we found a decrease in the beta-adrenergic-receptor number on cardiac plasma membrane isolated from the diabetic rats [29% decrease (P less than .05) at 1 wk, 50% (P less than .01) at 3 wk, and 49% (P less than .01) at 10 wk compared with control rats]. However, the serum triiodothyronine level that had been known to modulate the beta-adrenergic-receptor-adenylate cyclase system was decreased in the 1-wk-diabetic rats but not in the 10-wk-diabetic rats compared with each control group. Furthermore, there was no difference in urinary catecholamine excretion between diabetic and control groups. In the 10-wk-diabetic rats, the response of adenylate cyclase to isoproterenol was significantly defective (56% decrease compared with control rats; P less than .05), although both the basal and the forskolin-stimulated maximum adenylate cyclase activities and a half-maximum concentration of isoproterenol for the stimulation of adenylate cyclase were similar in control and diabetic rats. On the other hand, both cholera toxin-dependent and islet-activating protein-dependent [32P]NAD incorporations into cardiac plasma membrane were markedly increased in the diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diabetes Mellitus Experimental/metabolismo , Miocárdio/metabolismo , Receptores Adrenérgicos beta/metabolismo , Adenilil Ciclases/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Toxina da Cólera/farmacologia , Cinética , Masculino , Proteínas de Membrana/biossíntese , Proteínas de Membrana/isolamento & purificação , NAD/metabolismo , Ratos , Ratos Endogâmicos , Valores de ReferênciaRESUMO
We demonstrate compression of ultrashort light pulses in the ultraviolet (UV) by impulsively excited molecular wave-packets in nitrogen filled in a 25 cm long hollow waveguide of 128 microm diameter. After compression with CaF2 prisms the pulse duration was determined by XFROG to be 23 fs with a time-bandwidth product of 0.50. The advantages of our technique are high efficiency and the possibility to use it also for pulses at wavelength shorter than 200 nm. The experimental observations are explained by a theoretical model.
RESUMO
The tumor inhibitor of metalloproteinase (TIMP) family is a natural inhibitor of several matrix metalloproteinase enzymes which are involved in the process of tumor cell invasion through the extracellular matrix. The aim of this study was to examine TIMP1 RNA expression levels in relation to the clinicopathological features in resected primary non-small cell lung cancer (NSCLC). Total cellular RNA, obtained from 45 cases of NSCLC and adjacent normal lung tissue, was examined using Northern blot analysis. TIMP1 RNA expression levels were heterogeneous in NSCLC but was significantly higher in the adenocarcinoma compared to the squamous cell carcinoma subtype. Although the TIMP1 RNA levels did not correlate with sex, smoking, tumor, node, or TNM stage, there was a statistically significant survival disadvantage for cases with relatively high TIMP1 RNA expression, suggesting a role for TIMP1 in determining the prognosis of resected NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA/análise , Inibidor Tecidual de Metaloproteinase-1/fisiologiaRESUMO
Translational diffusion coefficients of diphenylcyclopropenone (DPCP), diphenylacetylene (DPA), and carbon monoxide (CO) in 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([BMIm][NTf2]) and 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([EMIm][NTf2]) were determined by the transient grating (TG) spectroscopy under pressure from 0.1 to 200 MPa at 298 K and from 298 to 373 K under 0.1 MPa. Diffusion coefficients of these molecules at high temperatures in tributylmethylphosphonium bis(trifluoromethanesulfonyl)imide ([P4441][NTf2]), and tetraoctylphosphonium bis(trifluoromethanesulfonyl)imide ([P8888][NTf2]), and also in the mixtures of [BMIm][NTf2], N-methyl-N-propylpiperidinium bis(trifluoromethanesulfonyl)imide ([Pp13][NTf2]), and trihexyltetradecylphosphonium bis(trifluoromethanesulfonyl)imide ([P66614][NTf2]) with ethanol or chloroform have been determined. Diffusion coefficients except in ILs of phosphonium cations were well scaled by the power law of T/η, i.e., (T/η)(P), where T and η are the absolute temperature and the viscosity, irrespective of the solvent species, pressure and temperature, and the compositions of mixtures. The values of the exponent P were smaller for the smaller size of the molecules. On the other hand, the diffusion coefficients in ILs of phosphonium cations with longer alkyl chains were larger than the values expected from the correlation obtained by other ILs and conventional liquids. The deviation becomes larger with increasing the number of carbon atoms of alkyl-chain of cation, and with decreasing the molecular size of diffusing molecules. The molecular size dependence of the diffusion coefficient was correlated by the ratio of the volume of the solute to that of the solvent as demonstrated by the preceding work (Kaintz et al., J. Phys. Chem. B 2013 , 117 , 11697 ). Diffusion coefficients have been well correlated with the power laws of both T/η and the relative volume of the solute to the solvent.