RESUMO
Cytotoxic T lymphocyte antigen-4-immunoglobulin (CTLA-4-Ig) exerts anti-rheumatic action via negative regulation of the co-stimulation process between antigen-presenting cells and T cells. CTLA-4-Ig also binds to CD80/CD86 on monocytes of osteoclast precursors. However, little is known about the effect of CTLA-4-Ig on osteoclastogenesis in rheumatoid arthritis (RA). In this study we evaluated the effects of CTLA-4-Ig on osteoclast generation from human blood monocytes (PBM) and rheumatoid synovial fluid monocytes (RSFM). Highly purified monocytes were cultured with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of CTLA-4-Ig. CTLA-4-Ig inhibited RANKL-induced osteoclast generation in PBM and RSFM, as determined by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay using osteo assay surface plates. In addition, CTLA-4-Ig reduced the gene and protein expressions of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and cathepsin K during osteoclastogenesis. Furthermore, CTLA-4-Ig significantly inhibited cell proliferation during osteoclastogenesis. Interestingly, the gene expression of indoleamine 2,3-dioxygenase-1, an inducer of apoptosis, was enhanced by CTLA-4-Ig. We next examined the effect of tumour necrosis factor (TNF)-α, a major inflammatory cytokine in rheumatoid synovium, on the expression of CD80 and CD86 by flow cytometric analysis. TNF-α potently induced the surface expression of CD80, which is known to have much higher affinity to CTLA-4-Ig than CD86, and this induction was observed at mRNA levels. Interestingly, freshly prepared rheumatoid synovial monocytes also expressed CD80 as much as TNF-α-treated PBM. Furthermore, TNF-α enhanced CTLA-4-Ig-induced inhibition of osteoclastogenesis and cell proliferation. Taken together, the TNF-α-induced CD80 may augment CTLA-4-Ig-induced inhibition of osteoclastogenesis, suggesting that CTLA-4-Ig potently inhibits osteoclast differentiation and protects bone destruction in rheumatoid inflamed joints.
Assuntos
Abatacepte/metabolismo , Artrite Reumatoide/imunologia , Antígeno B7-1/metabolismo , Monócitos/fisiologia , Osteoclastos/fisiologia , Líquido Sinovial/imunologia , Idoso , Diferenciação Celular , Células Cultivadas , Feminino , Humanos , Imunomodulação , Osteogênese , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
Chronic HCV-infected patients tend to have vitamin D deficiency, suggesting that vitamin D supplementation may enhance the efficacy of treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). We therefore assessed the effects of vitamin D supplementation on viral response to PEG-IFN/RBV. Eighty-four patients with HCV genotype 1b were randomized, 42 to oral vitamin D supplementation (1000 IU/day) and 42 to nonsupplementation (control), from week 8 to the end of PEG-IFN/RBV therapy. The primary end point was undetectable HCV RNA at week 24 (viral response [VR]). VR rate at week 24 was significantly higher in the vitamin D than in the control group (78.6% vs 54.8% P = 0.037). Adverse events were similar in both groups. When patients were subdivided by IL28B SNP rs8099917 genotype, those with the TT genotype group showed a significantly higher VR rate at week 24 with than without vitamin D supplementation (86.2% vs 63.3% vs P = 0.044). Although patients with the TG/GG genotype, who were relatively resistant to PEG-IFN treatment, had similar VR rates at week 24 with and without vitamin D supplementation, the decline in viral load from week 8 to week 24 was significantly greater with than without vitamin D supplementation. Multivariate analysis showed that rs8099917 genotype and vitamin D supplementation contributed significantly to VR at week 24. SVR rates were similar in the vitamin D and control groups [64.3% (27/42) vs 50% (21/42), P = 0.19]. Vitamin D supplementation may enhance the effects of PEG-IFN/RBV in HCV genotype 1b-infected patients.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Carga ViralRESUMO
The identification of human CD34-negative (CD34(-)) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. Previous studies demonstrated that CD34(-) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) are a distinct class of primitive HSCs in comparison to the well-characterized CD34(+)CD38(-) SRCs. However, the purification level of rare CD34(-) SRCs in 18 lineage marker-negative (Lin(-)) CD34(-) cells (1/1000) is still very low compared with that of CD34(+)CD38(-) SRCs (1/40). As in the mouse, it will be necessary to identify useful positive markers for a high degree of purification of rare human CD34(-) SRCs. Using 18Lin(-)CD34(-) cells, we analyzed the expression of candidate positive markers by flow cytometric analysis. We finally identified CD133 as a reliable positive marker of human CB-derived CD34(-) SRCs and succeeded in highly purifying primitive human CD34(-) HSCs. The limiting dilution analysis demonstrated that the incidence of CD34(-) SRCs in 18Lin(-)CD34(-)CD133(+) cells was 1/142, which is the highest level of purification of these unique CD34(-) HSCs to date. Furthermore, CD133 expression clearly segregated the SRC activities of 18Lin(-)CD34(-) cells, as well as 18Lin(-)CD34(+) cells, in their positive fractions, indicating its functional significance as a common cell surface maker to isolate effectively both CD34(+) and CD34(-) SRCs.
Assuntos
Antígenos CD34/metabolismo , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Separação Celular/métodos , Sangue Fetal/citologia , Glicoproteínas/metabolismo , Células-Tronco Hematopoéticas/citologia , Peptídeos/metabolismo , Antígeno AC133 , Animais , Linhagem da Célula , Células Cultivadas , Feminino , Sangue Fetal/metabolismo , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCIDRESUMO
Controlling the position of a magnetic domain wall with electric current may allow for new types of non-volatile memory and logic devices. To be practical, however, the threshold current density necessary for domain wall motion must be reduced below present values. Intrinsic pinning due to magnetic anisotropy, as recently observed in perpendicularly magnetized Co/Ni nanowires, has been shown to give rise to an intrinsic current threshold J(th)(0). Here, we show that domain wall motion can be induced at current densities 40% below J(th)(0) when an external magnetic field of the order of the domain wall pinning field is applied. We observe that the velocity of the domain wall motion is the vector sum of current- and field-induced velocities, and that the domain wall can be driven against the direction of a magnetic field as large as 2,000 Oe, even at currents below J(th)(0). We show that this counterintuitive phenomenon is triggered by Walker breakdown, and that the additive velocities provide a unique way of simultaneously determining the spin polarization of current and the Gilbert damping constant.
RESUMO
A change of magnetic flux through a circuit induces an electromotive force. By analogy, a recently predicted force that results from the motion of non-uniform spin structures has been termed the spin-motive force. Although recent experiments seem to confirm its presence, a direct signature of the spin-motive force has remained elusive. Here we report the observation of a real-time spin-motive force produced by the gyration of a magnetic vortex core. We find a good agreement between the experimental results, theory and micromagnetic simulations, which taken as a whole provide strong evidence in favour of a spin-motive force.
RESUMO
We herein report a case study of a female newborn with multiple pituitary hormone deficiencies who presented with generalized seizures, hypoglycemia and hyperammonemia at 18 h after birth. In addition, we review the association of hyperammonemia in neonates with multiple pituitary hormone deficiencies reported in the previous literature. This unrecognized association should be taken into account for the early diagnosis and treatment of these patients.
Assuntos
Hidrocortisona/administração & dosagem , Hiperamonemia/etiologia , Hipopituitarismo , Hipófise , Tiroxina/administração & dosagem , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/deficiência , Hipoglicemia/etiologia , Hipopituitarismo/complicações , Hipopituitarismo/congênito , Hipopituitarismo/diagnóstico , Hipopituitarismo/metabolismo , Hipopituitarismo/fisiopatologia , Hipopituitarismo/terapia , Recém-Nascido , Imageamento por Ressonância Magnética , Redes e Vias Metabólicas , Hipófise/anormalidades , Hipófise/metabolismo , Hipófise/fisiopatologia , Convulsões/etiologia , Tiroxina/deficiência , Resultado do TratamentoRESUMO
Electrical breakdowns of individual silicon nanochains, in which silicon nanoparticles are covered with and connected by oxide alternatively forming nanowires, are studied by in situ transmission electron microscopy using a microprobe system. Individual silicon nanochains can endure a current typically as large as 10(0) nA, and we found that a silicon nanochain can be converted to a nanotube by applying a current as large as 10(1) nA. In the nanotubes, some silicon particles are left. Experimental results suggest that nanotubes are heavily distorted carbon nanotubes, which are formed through the aggregation of contaminating carbon on the nanochain surface and the evaporation of the oxide core due to Joule heating.
RESUMO
Resistance switching in a semiconductor nanowire/metal nanoparticle system is demonstrated. SiC nanowires grown on a Si substrate and decorated with Au nanoparticles are measured using W microprobes in a scanning electron microscope, where one probe is grounded and the other is biased. HIGH and LOW states can be toggled by applying a negative or positive pulse voltage. The switching mechanism is attributed to a charge transfer between the SiC nanowires and the Au nanoparticles.
Assuntos
Compostos Inorgânicos de Carbono/química , Nanopartículas Metálicas/química , Nanofios/química , Compostos de Silício/química , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Nanofios/ultraestruturaRESUMO
This study is to elucidate whether the B- and T-lymphocyte attenuator (BTLA) gene is a new susceptibility gene for the development of type 1 diabetes (T1D) and systemic lupus erythematosus (SLE). As a result, this study did not find any genetic contribution of the BTLA gene to the development of T1D and SLE in Japanese population.
Assuntos
Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Receptores Imunológicos/genética , Alelos , Linfócitos B/metabolismo , Criança , Frequência do Gene/genética , Genótipo , Haplótipos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Linfócitos T/metabolismoRESUMO
This retrospective, observational study was designed to investigate factors affecting successful prosthetic ambulation in elderly amputees aged > or = 60 years. The study included 64 unilateral transfemoral or hip disarticulation amputees. Patients who were able to walk > or = 100 m with prosthesis were classified as successful and those who could walk < 100 m as failures. Age, comorbidities, cause of amputation, ability to stand on one leg, patient's motivation for walking and maximum oxygen uptake as a proportion of predicted maximum oxygen uptake (%VO(2max)) during an exercise load test were examined as indicators of physical fitness. Significant differences were noted between the two groups in the number of comorbidities, ability to stand on one leg, patient's motivation for walking and mean %VO(2max). A low number of comorbidities, the ability to stand on one leg, motivation for walking and adequate physical fitness allowing an exercise intensity of > or = 50% VO(2max) were considered to be predictive factors for successful prosthetic rehabilitation.
Assuntos
Amputados/reabilitação , Implantação de Prótese , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Resultado do TratamentoRESUMO
Juveniles of two Acentrogobius species collected in a mangrove estuary in Sikao Creek, southern Thailand, were identified by morphological and molecular methods. A total of 1315 Acentrogobius specimens were collected and grouped into types A (n = 1107, 4.4-12.0 mm standard length, L(S)) (melanophore absent or indistinct on posterodorsal contour of caudal peduncle; two rows of melanophore blotches on lateral midline) and B (n = 208, 4.8-12.6 mm L(S)) (distinct melanophore on posterodorsal contour of caudal peduncle; a single row of melanophore blotches on lateral midline). Based on the reverse series method, the melanophore patterns of larger juveniles were linked with the smallest specimens possessing adult characters. The homogeneities of mitochondrial cytochrome b region sequences between the two juvenile types and adult Acentrogobius species collected in the study area indicated type A to be A. kranjiensis (homogeneity between type A and A. kranjiensis: 99.3-100%), and type B to be A. malayanus (homogeneity between latter 98.1 and 99.7%). No Acentrogobius juveniles were collected from the surf zone outside the creek mouth, both species apparently spending most of their life histories within the estuarine habitat. During their pelagic phase, A. kranjiensis and A. malayanus dispersed in the upper, middle and lower reaches of the creek. On the other hand, occurrence patterns during the benthic phase of A. kranjiensis and A. malayanus differed, the former showing upstream movement and the latter downstream movement with growth. These results emphasize the necessity of analysing early fish life histories at the species level, and the collaboration between morphological and molecular methods should prove valuable in accurately identifying of larvae and juveniles.
Assuntos
Ecossistema , Perciformes/anatomia & histologia , Animais , DNA Mitocondrial/genética , Perciformes/genética , Perciformes/crescimento & desenvolvimento , Análise de Sequência de DNA , TailândiaRESUMO
OBJECTIVES: To assess the effects of a growth hormone (GH) replacement therapy using a GH dose regimen based on serum insulin-like growth factor (IGF-I) concentrations in Japanese adults with GH deficiency (GHD). DESIGN: In this multicentre, uncontrolled, open-label study, Japanese adults with GHD who had received either GH replacement therapy (GH-GH group, n=35) or placebo (Placebo-GH group, n=36) in a previous randomised, double-blind, placebo-controlled trial were treated with GH replacement therapy for 48 weeks. GH treatment was started at a dose of 0.003 mg/kg/day administered by subcutaneous injection for the first 8 weeks, after which the dose was adjusted to maintain patients' serum IGF-I levels within the reference range adjusted for age and gender. Body composition, serum lipids, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels were measured throughout study. Symptom and quality of life scores were also determined. RESULTS: Lean body mass (LBM) was increased compared with baseline (the end of the preceding double-blind trial) at 24 and 48 weeks, with a mean (+/-SD) increase of 1.3% (+/-4.2%) at week 48 in the GH-GH group (an increase of 6.6% [+/-6.0%] from the start of the preceding double-blind trial) and a larger increase of 4.7% (+/-5.9%) in the Placebo-GH group. Body fat mass (BFM) increased slightly from baseline in the GH-GH group with a mean increase of 2.9+/-10.6% at week 48 (a decrease from the start of the preceding double-blind trial at 48 weeks of 7.8% [+/-15.0%]) but decreased by 6.5% (+/-11.7%) at week 48 in the Placebo-GH group. Serum lipids were unchanged or slightly increased from baseline in the GH-GH group but patients' lipid profiles improved in the Placebo-GH group. In patients who received placebo during the double-blind study, individualised GH therapy in this open-label study increased mean LBM at 48 weeks by 6.2+/-6.8% in patients with CO GHD and by 3.0+/-4.4% in patients with AO GHD. Changes in mean LBM and mean BFM at week 48 were +4.1+/-4.5% and -2.4+/-10.5%, respectively, in females and +5.0+/-6.7% and -8.9+/-11.8%, respectively, in males. In patients who received GH treatment during the double-blind study, overall changes in LBM, BFM and IGF-I SD score after 24 weeks and 48 weeks were small, with no significant differences between subgroups. While the overall incidence of adverse events was broadly similar in the GH-GH and Placebo-GH groups (97% and 89%, respectively), the incidence of treatment-related events was higher in the GH-GH group (83% vs 42% in the Placebo-GH group). Most adverse events in both treatment groups were of mild or moderate severity and not clinically significant. The incidences of oedema and cases of high IGF-I during the IGF-I level-adjusted treatment regimen were lower than those during the preceding fixed dose titration. CONCLUSION: Long-term GH replacement therapy was well tolerated in Japanese adults with GHD. GH treatment maintained the improvements in body composition and lipid profiles in the patients previously treated in the double-blind study (GH-GH group) and improved these parameters in previously untreated patients (Placebo-GH group). Individualised GH administration based on IGF-I levels was well-tolerated and effective.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Adolescente , Adulto , Idoso , Algoritmos , Método Duplo-Cego , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Fator de Crescimento Insulin-Like I/análise , Japão , Masculino , Pessoa de Meia-Idade , Placebos , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Gefitinib shows prominent anti-tumor activity against advanced or recurrent non-small cell lung cancer (NSCLC). However, most gefitinib-responsive patients ultimately relapse. We reviewed postoperatively recurrent NSCLC patients who received gefitinib treatment, and analyzed both the clinical features and manifestations of treatment failure in patients who initially responded to gefitinib. METHODS: From 2002 to 2006, gefitinib was administered to in 34 postoperative recurrent lung adenocarcinoma patients. There were 13 men and 21 women with a mean age of 65 years. Twenty patients had never smoked while 14 were former smokers. Epidermal growth factor receptor (EGFR) gene mutation was measured using surgical specimens of the primary tumor. RESULTS: The study group showed 1 complete response, 16 partial responses, 7 stable diseases and 8 progressive diseases. Mutations of EGFR gene were detected in 20 of 34 patients. Only the presence of EGFR gene mutations was significantly associated with the clinical response of gefitinib in our limited study (p=0.036). In 9 of 12 responders, gefitinib treatment failed due to the appearance of new lesions. CONCLUSIONS: Gefitinib was significantly effective for patients with mutations of the EGFR gene and most responders failed due to the appearance of new lesions without progression of the pre-existent target lesions.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/complicações , Cuidados Pós-Operatórios , Quinazolinas/uso terapêutico , Adenocarcinoma/complicações , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Receptores ErbB/genética , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Mutação , Quinazolinas/efeitos adversos , Falha de TratamentoRESUMO
OBJECTIVE: The cellular effects of growth hormone (GH) are mediated by the interaction between GH and the GH receptor (GHR). We investigated the association between polymorphisms in GHR and changes in height standard deviation scores (SDS), and lipid metabolism during GH treatment for GH-deficient children. DESIGN: A 1-year study on growth rate and lipid metabolism under GH treatment. PATIENTS: Eighty-three children (61 boys and 22 girls) with GH deficiency were treated with GH for 1 year after diagnosis. INTERVENTION: The patients were treated with recombinant human GH (0.19 mg/kg/week) for at least 1 year after diagnosis. The growth rates and biochemical parameters for lipid metabolism were measured both before and during treatment. Four single nucleotide polymorphisms (SNPs) in the GHR gene, Cys440Phe, Pro495Thr, Leu544Ile and Pro579Thr, and exon 3 deletion polymorphisms were genotyped by direct sequencing and multiplex PCR. RESULTS: We found no significant association between GHR polymorphisms and changes in height SDS during GH treatment. The total cholesterol levels of the GH-deficient boys with Ile/Ile at codon 544 showed significantly higher cholesterol levels before GH treatment and then maintained high levels during the GH treatment, compared to those with other genotypes. No other polymorphisms seemed to have any apparent effects on lipid metabolism. CONCLUSION: The Leu544Ile polymorphism of the GHR gene is associated with cholesterol levels in boys with GH deficiency.
Assuntos
Colesterol/sangue , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/genética , Polimorfismo de Nucleotídeo Único , Receptores da Somatotropina/genética , Análise de Variância , Criança , HDL-Colesterol/sangue , Éxons , Feminino , Deleção de Genes , Crescimento , Hormônio do Crescimento/sangue , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/tratamento farmacológico , Fator de Crescimento Insulin-Like I/análise , Desequilíbrio de Ligação , Metabolismo dos Lipídeos , Masculino , Fatores SexuaisRESUMO
BACKGROUND: We have previously reported that troglitazone, a synthetic ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), and bitter gourd seed oil rich in 9cis,11trans,13trans-conjugated linolenic acid (9c,11t,13t-CLN) prevent colon carcinogenesis. To evaluate the chemotherapeutic effect and potency of these compounds on colon cancer cells, we investigated their antiproliferative and apoptosis-inducing effects using different human colon cancer cell lines. METHODS: The antiproliferative and apoptosis-inducing effects of troglitazone and 9c,11t,13t-CLN were evaluated and compared using HT-29, DLD-1 and Caco-2 cells at different stages of enterocytic differentiation. RESULTS: Troglitazone and 9c,11t,13t-CLN decreased cell viability and induced apoptosis in three colon cancer cell lines. The susceptibility of HT-29, which expresses PPARgamma at high levels, to troglitazone and 9c,11t,13t-CLN was higher than that of Caco-2 cells with low levels of PPARgamma. CONCLUSION: Troglitazone and 9c,11t,13t-CLN exhibited more effective chemotherapeutic effects on HT-29 cells than on Caco-2 cells.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromanos/farmacologia , Neoplasias do Colo/patologia , Ácidos Linolênicos/farmacologia , Tiazolidinedionas/farmacologia , Western Blotting , Células CACO-2 , Diferenciação Celular , Neoplasias do Colo/metabolismo , Células HT29 , Humanos , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Troglitazona , Ácido alfa-LinolênicoRESUMO
OBJECTIVE: The aim of this study was to assess the effect of growth hormone (GH) replacement therapy on lean body mass (LBM) and other variables including body fat mass, serum lipids and quality of life measures in GH-deficient Japanese adults. DESIGN: This was a multicentre, double-blind, placebo-controlled, parallel group study. Following initial screening, patients were randomly assigned to GH treatment (n=37) or placebo (n=36). GH treatment was started at an initial dose 0.003 mg/kg/day s.c. each day for the first 4 weeks after which the dose was increased to 0.006 mg/kg/day for 4 weeks and then to 0.012 mg/kg/day for the last 16 weeks (n=37). Body composition, serum lipids, serum IGF-I and IGFBP-3 levels were measured during the 24-week study. Short Form-36 and Quality of Life Assessment of GH Deficiency in Adults scores were also determined. RESULTS: LBM was significantly increased from baseline at 24 weeks in GH-treated patients, with a mean (+/-SD) increase of 4.7% (+/-5.3%) compared with an increase of 1.0% (+/-4.4%) in the placebo group (p<0.0001 versus baseline, p=0.0003 versus placebo). Percentage body fat decreased significantly from baseline in GH-treated patients (9.3%, p<0.0001), compared with a non-significant 0.2% increase in the placebo group (p<0.0004 for difference between treatment groups). In addition, significantly increased serum IGF-I and IGFBP-3 levels and improvements in the patients' serum lipid profiles were observed in patients who received GH therapy. Changes in quality of life measures did not differ between treatments, probably because of the small number of patients studied. GH therapy was well tolerated, with adverse events of any cause reported in 86.5% of the GH treatment group and 83.3% of the placebo group. CONCLUSION: GH treatment significantly improved body composition and serum lipid profiles in adult Japanese patients with GH deficiency compared with placebo and had no clinically relevant adverse effects.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adulto , Povo Asiático , Composição Corporal/efeitos dos fármacos , Método Duplo-Cego , Feminino , Transtornos do Crescimento/sangue , Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Japão , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placebos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêuticoRESUMO
Suppressors of cytokine signalling (SOCS) proteins play important roles in the negative regulation of cytokine signal. We first searched for polymorphisms in SOCS-1, SOCS-3 and SOCS-5 genes, and examined the association of the polymorphisms with type 1 diabetes (T1D). As a result, we did not find any significant associations between SOCS genes and T1D.
Assuntos
Diabetes Mellitus Tipo 1/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/etiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Fases de Leitura Aberta , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Tumor cells of lung cancer exhibit genetic abnormalities as well as high proliferative activity. The purpose of this study was to evaluate the relationship of genetic abnormalities and smoking status, histological type, and tumor proliferative activity in resected samples of stage I non-small cell lung cancer (NSCLC). METHODS: We evaluated 126 samples of stage I NSCLC from patients who underwent complete resection between 1988 and 1993. Loss of heterozygosity (LOH) was assessed using primers that amplified polymorphic microsatellite markers at D3S1300, D3S643, D3S1317, D9S171, IFNA, D13S153, and TP53. Expression of Ki-67 nuclear antigen was examined using immunohistochemical methods to assess tumor proliferative activity. RESULTS: The Fractional Regional Loss index (FRL) was significantly higher in squamous cell carcinoma samples than in adenocarcinoma samples (p < 0.0001). In smokers, Ki-67 labeling index (LI) in high-FRL cases was significantly higher than in low-FRL cases (p < 0.0001). CONCLUSION: The frequency of LOH at 3 p, 9 p, 13 q, and 17 p was related to proliferative activity in smokers with stage I non-small cell lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Perda de Heterozigosidade , Neoplasias Pulmonares/genética , Fumar/patologia , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 9/genética , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
We previously reported a powerful tumor-promoting ability of dextran sodium sulfate (DSS) in a novel mouse model for colitis-related colon carcinogenesis initiated with azoxymethane (AOM). To determine the dose-dependent influence of DSS in our animal model, male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight), followed by DSS at dose levels of 2, 1, 0.5, 0.25, and 0.1% (w/v) in drinking water for 1 week. All animals were sacrificed at week 14 and histological alterations in their colon and nitrotyrosine immunohistochemistry were examined to evaluate the nitrosative stress. In the mice which received AOM and 2% DSS, the incidences (multiplicity) of colonic tubular adenoma and adenocarcinoma were 75% (1.25+/-1.26/mouse) and 100% (2.75+/-2.22/mouse), respectively. Mice given AOM and 1% DSS had 80% incidence of adenoma (1.00+/-0.71/mouse) and 60% incidence of adenocarcinoma (1.40+/-2.07/mouse) in the colon. In a mouse treated with AOM and 0.5% DSS, only one colonic adenoma (20% incidence with 0.20+/-0.45 multiplicity) developed. Higher frequency of high-grade colonic dysplasia was noted in mice given AOM and 2% or 1% DSS when compared with mice treated with AOM and lower doses of DSS. Also, scoring of inflammation and nitrotyrosine immunoreactivity suggested that severe inflammation and nitrosation stress caused by high-doses (2% and 1%) of DSS contribute its tumor-promoting effects in mouse colon carcinogenesis initiated with a low dose of AOM. Thus, our findings indicate that a tumor-promoting effect of DSS was dose-dependent (1% or more) and the effect might occur under the condition of inflammation and nitrosation stress.
Assuntos
Carcinógenos/toxicidade , Neoplasias do Colo/induzido quimicamente , Sulfato de Dextrana/toxicidade , Tirosina/análogos & derivados , Animais , Azoximetano/administração & dosagem , Azoximetano/toxicidade , Carcinógenos/administração & dosagem , Cocarcinogênese , Colite/induzido quimicamente , Colite/patologia , Doenças do Colo/induzido quimicamente , Doenças do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Sulfato de Dextrana/administração & dosagem , Relação Dose-Resposta a Droga , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tirosina/metabolismo , Úlcera/induzido quimicamente , Úlcera/patologiaRESUMO
A 66-year-old woman underwent coronary artery bypass grafting (CABG). Postoperative angiography on postoperative day (POD) 11 revealed that right internal thoracic artery (RITA) anastomosed to left anterior descending artery (LAD) had a kinking. The angiography performed 30 months after operation revealed no specific changes in the kinking of RITA and in the left ventricular function. Another case was a 74-year-old man with chronic renal failure under hemodialysis. He underwent CABG with left internal thoracic artery (LITA) to LAD. Post-operatively he had chest pain during hemodialysis. On POD 10, angiography revealed that LITA had a kinking with moderate stenosis and normal left ventricular function. The angiography performed 10 months after operation revealed no specific changes in the kinking of LITA. However, left ventriculography revealed akinesis in the antero-apical region. It suggested that the viability was lost due to the graft kinking of LITA and steal phenomenon on hemodialysis.