RESUMO
Tuning of the anisotropic Gilbert damping Δα has been realized in ultrathin single-crystalline Fe films grown on GaAs (001). A nonmonotonic dependence of Δα on film thickness t is observed upon varying t about 10 ML (â¼1.4 nm). Δα increases for 16 ML>t>8.5 ML, and then decreases for 8.5 ML>t>6.5 ML accompanied by a sign reversal of Δα for t=6.5 ML. The sign reversal of Δα is captured by first-principle calculations, which show that the anisotropic density of states changes sign upon decreasing t. Moreover, t^{-1} dependence of the anisotropic damping indicates the emergence of an anisotropic effective spin mixing conductance according to the theory of spin pumping. The results establish new opportunities for controlling the Gilbert damping and for fundamental studies of magnetization dynamics in reduced dimension.
RESUMO
BACKGROUND: Obesity is closely linked to increased markers of metabolic syndrome and development of diabetes. Roux-en-Y bariatric surgery reduces hyperinsulinemia and improves insulin sensitivity and hence benefits morbidly obese patients. AIM: To determine changes in markers of metabolic syndrome, pancreatic function, and hepatic insulin sensitivity in patients before and 1 year after undergoing Roux-en-Y gastric bypass surgery. METHODS: We enrolled 43 consecutive patients in a single center. Markers for metabolic syndrome included proinsulin, insulin, C-peptide, liver enzymes, and serum levels of selected microRNAs hsa-miR-122, hsa-miR-130, hsa-miR-132, and hsa-miR-375. RESULTS: After surgery, all patients showed a significant 37% drop of body mass index (p < 0.001). Furthermore, proinsulin (59% reduction, p < 0.001), insulin (76% reduction, p < 0.001), and C-peptide (56% reduction, p < 0.001) were all reduced 1 year after surgery. Using the hepatic insulin clearance score, we determined a significant increase in hepatic insulin clearance after surgery (76% increase, p < 0.001). Especially diabetic patients showed a marked 2.1-fold increase after surgery. Hepatic enzymes ALT (35% reduction, p = 0.002) and γGT (48% reduction, p < 0.001) were significantly reduced in all patients with similar improvement in diabetic and non-diabetic patients. miRNAs hsa-miR-122, hsa-miR-130, and hsa-miR-132 were all significantly reduced whereas hsa-miR-375 was increased after gastric bypass surgery (p < 0.001 for all miRNAs). CONCLUSION: Both liver and pancreatic stress parameters were reduced significantly 1 year after Roux-en-Y gastric bypass surgery suggesting an overall amelioration of the metabolic syndrome in all patients regardless of previous health status.
Assuntos
Biomarcadores/sangue , Derivação Gástrica , Síndrome Metabólica/prevenção & controle , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/cirurgia , Adulto , Idoso , Anastomose em-Y de Roux , Biomarcadores/metabolismo , Índice de Massa Corporal , Feminino , Derivação Gástrica/métodos , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , MicroRNAs/sangue , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Prognóstico , Fatores de Risco , Redução de Peso/fisiologia , Adulto JovemRESUMO
Despite similar ecology, mating systems and female preferences for supernormal tails, the 17 species of African widowbirds and bishops (Euplectes spp.) show astonishing variation in male tail ornamentation. Whereas bishops retain their brown nonbreeding tails in nuptial plumage, widowbirds grow black nuptial tails, varying in length from a few centimetres in E. axillaris to the extreme half metre train of E. progne. Here, we phylogenetically reconstruct the evolution of the discrete trait, nuptial tail and the continuous trait, tail length, using a molecular phylogeny of 33 Euplectes subspecies. Unlike many recent findings of labile evolution of plumage ornaments, our results suggest that the nuptial tail of Euplectes is a derived and phylogenetically conserved ornamental trait that, once gained, shows directional evolution in its expression. Directionality is demonstrated in the trivial sense of a short-tailed ancestor, and by contingency and randomization tests suggesting that branches with increasing tail length are overrepresented. This supports an early origin and strong retention of directional female mate choice in widowbirds and bishops, as previously indicated by empirical and experimental results, and provides a less labile, yet rapid scenario of sexually selected diversification.
Assuntos
Plumas , Passeriformes/classificação , Filogenia , Seleção Genética , Animais , Feminino , Masculino , Passeriformes/genética , Fatores Sexuais , CaudaRESUMO
Methyl group rotations in methyl fluoride were studied using the high flux backscattering spectrometer SPHERES at FRM-II. The asymmetry and width of the low temperature tunneling peak was used to determine if coupled rotations between neighboring methyl fluoride molecules exist. The temperature dependent broadening of the tunneling peak was used to determine the first librational transition and compared to the temperature dependent shift of the position of the tunneling peak. The results obtained by using inelastic neutron scattering confirm previous models that assume rotational coupling. This is the first neutron backscattering experiment with sub-microeV resolution at energy transfers up to 31 microeV.
RESUMO
Diaminodurene crystallizes in the orthorhombic space group Pbca, with eight molecules in the unit cell. Four inequivalent methyl groups with different environments exist in a molecule. The amino groups are also different, which is well reflected in infrared spectra. Two tunneling modes are resolved at 23.7 and 7.0 microeV at 4.5 K. Their intensities are consistent with the presence of two further unresolved tunneling modes. Quasielastic spectra are composed of three Lorentzians of equal intensities. The two low activation energies and tunnel modes are modeled into consistent rotational potentials. The third activation energy and a librational band are used to guess the strength of the two stronger rotational potentials. The internal modes related to the torsional/librational vibrations mix with ring torsions in the range of 70-220 cm(-1). This way the tunnel modes couple to ring torsions whose energy determines the broadening of both tunnel bands. The calculations for free molecules yield mode frequencies a little bit lower than the experimental inelastic neutron scattering (INS) values. Application of theoretical methods elaborated for the crystalline state leads to a satisfactory consistency. It is also valid for bending modes of NH(2) groups, which in the solid state show much higher frequencies than in the gas phase, as expected.
RESUMO
BACKGROUND: Epidemiological data on individuals suffering from severe primary hyperhidrosis are scarce. OBJECTIVE: This study aims to prospectively assess disease-specific characteristics of patients with severe, mostly therapy-resistant hyperhidrosis presenting for sympathetic surgery. METHODS: We evaluated a total of 227 patients (69.6% women) with a mean age of 30 years (standard deviation, 9.5 years) using a standardized questionnaire. Severity of disease was rated on a visual analogue scale (VAS) graded between 0 (no symptoms) and 10 (worst symptom). Age, sex, previous therapies, hormonal therapies and body mass index were analysed for their possible influence on severity of the disease and on hyperhidrosis sites. In addition, allergies were investigated for the first time in this patient population. RESULTS: There was a positive correlation between age of onset and sites of hyperhidrosis. The most commonly affected areas were palmar-axillary-plantar (51.1%) and palmar-plantar (15.0%), with sex-specific differences. Two hundred and twelve patients (93.4%) had previous conservative therapies; 219 patients (96.5%) reported VAS scores between 8 and 10. Female patients stated higher VAS scores for palmar (P = 0.009) and axillary (P = 0.012) sites. Type IV allergies were found to be much higher than in the general Austrian female population. Hormonal therapies and the body mass index had no influence on severity of hyperhidrosis after analysis of VAS scores. CONCLUSION: Sex-dependent aspects can be found in patients strongly affected by primary upper limb hyperhidrosis.
Assuntos
Hiperidrose/cirurgia , Sistema Nervoso Simpático/cirurgia , Adulto , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To compare the efficacy and safety of induction of labour by vaginal application of dinoprostone or misoprostol or transcervical insertion of a balloon (Bard) catheter. DESIGN: A non-blinded, randomised, controlled trial. SETTING: A tertiary level Swedish hospital. POPULATION: A total of 592 women who had undergone full-term pregnancies, not previously been subjected to a caesarean section, and required induction of labour for common, routine indications. METHODS: Women were randomly assigned to induction of labour using intravaginal dinoprostone (2 mg once every 6 hours) or misoprostol (25 micrograms once every 4 hours) or a transcervical balloon catheter. MAIN OUTCOME MEASURES: The time interval between induction to delivery in general and vaginal delivery in particular, the mode of delivery, maternal and neonatal parameters of outcome. RESULTS: Of the 588 subjects included in the final intention-to-treat analysis, 191 were assigned to treatment with dinoprostone, 199 with misoprostol and 198 with the balloon catheter. The shortest mean induction-to-delivery interval was obtained with the catheter (12.9 hours versus 16.8 and 17.3 hours for dinoprostone and misoprostol, respectively). The efficacies of the two prostaglandins were similar. The maternal and neonatal outcomes associated with each of the three procedures were similar. CONCLUSIONS: Induction of labour with a transcervical balloon catheter is effective and safe and can be recommended as the first choice. The two prostaglandins, dinoprostone and misoprostol, were shown to be equally effective and safe, while misoprostol costs significantly less and is easier to store.
Assuntos
Cateterismo , Dinoprostona/administração & dosagem , Primeira Fase do Trabalho de Parto/fisiologia , Trabalho de Parto Induzido/métodos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Administração Intravaginal , Adulto , Peso ao Nascer , Feminino , Humanos , Primeira Fase do Trabalho de Parto/efeitos dos fármacos , Gravidez , Resultado da GravidezRESUMO
BACKGROUND AND PURPOSE: The incidence of metallic dental restorations and implants is increasing, and head and neck MR imaging is becoming challenging regarding artifacts. Our aim was to evaluate whether multiple-slab acquisition with view angle tilting gradient based on a sampling perfection with application-optimized contrasts by using different flip angle evolution (MSVAT-SPACE)-STIR and slice-encoding for metal artifact correction (SEMAC)-STIR are beneficial regarding artifact suppression compared with the SPACE-STIR and TSE-STIR in vitro and in vivo. MATERIALS AND METHODS: At 3T, 3D artifacts of 2 dental implants, supporting different single crowns, were evaluated. Image quality was evaluated quantitatively (normalized signal-to-noise ratio) and qualitatively (2 reads by 2 blinded radiologists). Feasibility was tested in vivo in 5 volunteers and 5 patients, respectively. RESULTS: Maximum achievable resolution and the normalized signal-to-noise ratio of MSVAT-SPACE-STIR were higher compared with SEMAC-STIR. Performance in terms of artifact correction was dependent on the material composition. For highly paramagnetic materials, SEMAC-STIR was superior to MSVAT-SPACE-STIR (27.8% smaller artifact volume) and TSE-STIR (93.2% less slice distortion). However, MSVAT-SPACE-STIR reduced the artifact size compared with SPACE-STIR by 71.5%. For low-paramagnetic materials, MSVAT-SPACE-STIR performed as well as SEMAC-STIR. Furthermore, MSVAT-SPACE-STIR decreased artifact volume by 69.5% compared with SPACE-STIR. The image quality of all sequences did not differ systematically. In vivo results were comparable with in vitro results. CONCLUSIONS: Regarding susceptibility artifacts and acquisition time, MSVAT-SPACE-STIR might be advantageous over SPACE-STIR for high-resolution and isotropic head and neck imaging. Only for materials with high-susceptibility differences to soft tissue, the use of SEMAC-STIR might be beneficial. Within limited acquisition times, SEMAC-STIR cannot exploit its full advantage over TSE-STIR regarding artifact suppression.
Assuntos
Artefatos , Implantes Dentários/efeitos adversos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Metais , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Obesity is considered to be a major comorbidity. Obese patients suffer from an increased proinflammatory state associated with a premature aging phenotype including increased secretion of senescence-associated secretory proteins (SASP) and reduced telomere length. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that could modify the post-transcriptional process. Several studies have reported associations between miRNAs and metabolic unhealthy conditions. AIM: To determine if bariatric surgery and the resulting weight loss could reverse the premature aging phenotype. METHODS: We enrolled 58 morbidly obese patients undergoing bariatric surgery. Markers of premature aging including the SASP IL-6, CRP and PAI-1, 7 miRNAs, as well as telomere length and telomere oxidation in mononuclear cells were evaluated. RESULTS: Patients showed a significant drop of body mass index (BMI; 43.98 ± 3.5 versus 28.02 ± 4.1, p < 0.001). We observed a significant reduction in SASP including a reduction of 55% of plasma IL-6 levels (p = 0 < 0.001), 83% of CRP levels (p = 0.001) and 15% of plasma PAI-1 levels (p < 0.001). Telomere length doubled in the patient cohort (p < 0.001) and was accompanied by a reduction in the telomere oxidation index by 70% (p < 0.001). Telomere length was inversely correlated with telomere oxidation. The aging-associated miRNA miR10a_5p was upregulated significantly (p = 0.039), while the other tested miRNAs showed no difference. CONCLUSION: Our data indicate a significant reduction of the proinflammatory SASP after bariatric surgery. We observed an increase in telomere length and reduced oxidative stress at telomeres. miR10a_5p which is downregulated during aging was upregulated after surgery. Overall, bariatric surgery ameliorated the premature aging phenotype.
Assuntos
Senilidade Prematura , Derivação Gástrica/estatística & dados numéricos , Obesidade Mórbida , Senilidade Prematura/sangue , Senilidade Prematura/complicações , Senilidade Prematura/epidemiologia , Senilidade Prematura/genética , Biomarcadores , Índice de Massa Corporal , Humanos , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgiaRESUMO
PURPOSE: Purpose of our research was the evaluation of a dedicated dental surface coil in comparison with a standard head and neck coil for the improvement of dental magnetic resonance imaging (MRI). MATERIALS AND METHODS: Axial T1-weighted spin echo MRI was performed by using a newly developed dental coil for MRI and a standard head and neck coil on five volunteers. In addition, MRI was implemented with dental coil on five patients. Using the Wilcoxon test, we compared the volunteers' signal-to-noise ratio (SNR) of a variety of anatomical structures (e.g., hard tooth tissue, pulp tissue, bone, muscle tissue). Also subjective evaluation of image quality was performed on both volunteers and patients. RESULTS: Compared with the head and neck coil, the mean SNR was 3.5-fold higher on an average with the dental coil (range: from 2.7 [masseter muscle] to 4.6 [pulp tissue]). That difference was statistically significant for all evaluated structures. The higher SNR also resulted in a superior image quality as determined by subjective evaluation. CONCLUSION: Dental MRI benefits profoundly from using a dedicated dental coil.
Assuntos
Implantes Dentários , Imageamento por Ressonância Magnética/instrumentação , Adolescente , Adulto , Idoso , Polpa Dentária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Articulação Temporomandibular/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: That infections with certain pathogens, by initiating an inflammatory response, may contribute to the development of atherosclerosis is suggested by clinical and experimental evidence. AIM: To analyse atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins and circulating leucocytes from the same individual patients for the presence of Helicobacter pylori and Mycoplasma pneumoniae. METHODS: Samples from 36 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis were analysed by polymerase chain reaction for the presence of DNA specific for H. pylori and M. pneumoniae. IgG antibody titres against H. pylori and M pneumoniae and plasma levels of soluble E-selectin, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 were determined. RESULTS: M. pneumoniae-specific DNA was detected in the atherosclerotic plaques of 13 of 36 (36.1%) patients, in the saphenous veins of 9 of 36 (25%) patients and in the leucocytes of 27 of 36 (75%) patients. No salient association was observed between the presence of M. pneumoniae-specific DNA in leucocytes and atherosclerotic plaques or veins. A marked correlation between the presence of M. pneumoniae in the respective specimens and the studied inflammatory markers or the presence of anti-M. pneumoniae antibodies was not observed. H. pylori-specific DNA could not be detected in the specimens tested. CONCLUSIONS: The absence of H. pylori and the random distribution of M. pneumoniae in tissue samples obtained from patients with symptomatic carotid artery stenosis do not support a role for these pathogens in the development of atherosclerosis due to a direct interaction of the bacteria with the vasculature.
Assuntos
Aterosclerose/microbiologia , Doenças das Artérias Carótidas/microbiologia , Helicobacter pylori/isolamento & purificação , Mycoplasma pneumoniae/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/cirurgia , Doenças das Artérias Carótidas/cirurgia , Moléculas de Adesão Celular/sangue , DNA Bacteriano/análise , Feminino , Infecções por Helicobacter/complicações , Humanos , Mediadores da Inflamação/sangue , Leucócitos/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycoplasma/complicações , Reação em Cadeia da Polimerase/métodos , Veia Safena/microbiologiaRESUMO
Levamisole enhanced transformation of murine lymphocytes stimulated either by mitogens or allogeneic lymphocytes. In a similar dose-dependent pattern it stimulated in vitro growth of L1210, P1798, and 6C3HED but not YAC lymphoma cells. Stimulation of growth of lymphoma cells was greater by peritoneal cells harvested from normal mice 4 days after levamisole injection than by peritoneal cells from untreated mice. This effect correlated with the shortened survival time of BALB/c mice treated with levamisole prior to P1798 implantation compared to that of a control group not pretreated. Administration of levamisole with iodoacetamide-modified tumor cells in immunoprophylaxis studies had no effect on the rejection of a tumor implant or on development of tumor-specific antibody. Levamisole was added to regimens involving asparaginase therapy of 6C3HED-bearing C3H mice and chemoimmunotherapy of BALB/c mice bearing P1798 with methotrexate and iodoacetamide-modified P1798 cells. In neither case were there increased numbers of survivors, and mean survival time was generally decreased for the levamisole-treated groups. The stimulated tumor growth may have been mediated by a direct effect of levamisole on the lymphoma cells, through an effect on other cell types, or by both effects; these effects apparently outweighed potentially beneficial effects of levamisole on the immune system.
Assuntos
Levamisol/farmacologia , Linfócitos/efeitos dos fármacos , Linfoma/terapia , Animais , Antígenos de Neoplasias/administração & dosagem , Asparaginase/uso terapêutico , Quimioterapia Combinada , Feminino , Imunoterapia , Técnicas In Vitro , Ativação Linfocitária/efeitos dos fármacos , Linfoma/imunologia , Metotrexato/uso terapêutico , Camundongos , Camundongos Endogâmicos , Neoplasias Experimentais/terapiaRESUMO
Bacterial endotoxin was administered with iodoacetamide-modified P1798 lymphoma cells to immunize syngenic BALB/cJ mice against this lymphoma to which they are naturally unresponsive. Three or four vaccinations with endotoxin (6.6 mug/injection) alone or the modified cells alone did not produce host resistance. A significant number (30 percent) of mice receiving both endotoxin and modified cells rejected a subsequent implant of viable tumor cells. Even those mice having progressive tumor growth exhibited prolonged survival. High doses of endotoxin given with the modified P1798 cells caused 70-75 percent of the mice to reject the tumor implants. When resistance developed, antibodies reacting with tumor cell membrane were demonstrable. These results indicate that B-lymphocyte stimulators can produce an effective immune response against lymphoma cells.
Assuntos
Antígenos de Neoplasias , Endotoxinas/imunologia , Linfoma/prevenção & controle , Vacinação , Animais , Anticorpos Antineoplásicos/análise , Membrana Celular/imunologia , Rejeição de Enxerto , Iodoacetamida/farmacologia , Linfoma/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/prevenção & controle , Transplante HomólogoRESUMO
DNA synthesis by murine lymphoma cells was stimulated up to 20-fold in vitro by syngeneic or allogeneic peritoneal cells (PEC) and peripheral blood lymphocytes, as measured by [3H]thymidine incorporation in a 44-hr assay. The increase in DNA synthesis correlated with an increase in tumor cell number in the cultures. The adherent PEC population was responsible for most of the enhancement. This effect was abrogated by pretreating the adherent cells with the metabolic inhibitors iodoacetamide, KCN, NaF, and dinitrophenol, or with glutaraldehyde, or by heating at 56 degrees. Pretreatment with mitomycin C did not eliminate the stimulatory effect. PEC supernatants did not enhance tumor growth, but effector-to-target cell proximity was shown to be necessary for stimulation. PEC from tumor-immunized mice also stimulated tumor target cell growth, but to a consistently smaller degree than did nonimmune PEC. This immune inhibition correlated with in vivo survival of mice to live tumor challenge and with ability of effector cells to increase life-span in adoptive immunity tests. Differential production of thymidine by normal and immune PEC appeared not to be a factor in these assays. Fractionation of PEC showed that the immune nonadherent cells were inhibitory in vitro and were able to increase survival time in adoptive immunity tests. On the other hand, the adherent PEC from immune mice either inhibited, stimulated, or had no effect on tumor cell DNA synthesis, compared with nonimmune adherent PEC, thus exhibiting no correlation with the immune status of the donor. In one example, administration of the macrophage activator lipopolysaccharide to mice resulted in PEC that were inhibitory in the in vitro assay, although the agent did not produce in vivo immunity. The inhibition of tumor DNA synthesis assay, with unfractionated PEC, exhibited a consistent correlation with the immune status of the host when mice were sensitized to lymphoma cells. However, the variable influence of the adherent PEC population on tumor growth reduced or nullified the immune inhibitory effect in a few cases.
Assuntos
DNA de Neoplasias/biossíntese , Imunidade Celular , Leucemia L1210/imunologia , Linfoma/imunologia , Animais , Líquido Ascítico/citologia , Adesão Celular , Células Cultivadas , Feminino , Imunização , Imunização Passiva , Leucemia L1210/metabolismo , Linfócitos/imunologia , Linfoma/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Transplante de Neoplasias , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/metabolismo , Transplante Homólogo , Transplante IsogênicoRESUMO
Dimethyldioctadecylammonium bromide (DDA) stimulates immune responses, primes (or activates) macrophages, and binds to antigens. Because relatively little is known about the binding of adjuvants to antigens, the nature of the interaction of DDA with soluble protein and cellular antigens was investigated. Dose-dependent, stable complexes are formed between cells and the lipoidal cation of DDA. Since the interaction is independent of negatively charged sialic acid residues of the cell membrane and little DDA binds to intracellular structures, it is suggested that binding occurs primarily at the cell membrane, probably through hydrophobic interaction with lipids. The idea of membrane perturbation is supported by the leak of macromolecules (lactic dehydrogenase) from treated cells. Reaction of varying amounts of DDA with a constant amount of ovalbumin was also dose dependent. Because of a minimal effect of ionic strength on the reaction, it is concluded that ionic interaction may make a minor contribution to product formation. Complexes of DDA and antigen are articularly effective in eliciting a delayed hypersensitivity reaction, which has been postulated to be desirable for an antitumor effect.
Assuntos
Adjuvantes Imunológicos , Antígenos , Leucemia L1210/imunologia , Compostos de Amônio Quaternário , Animais , Eritrócitos/imunologia , Cinética , Camundongos , Camundongos Endogâmicos DBA , Compostos de Amônio Quaternário/metabolismo , Ovinos , Ácidos Siálicos/sangueRESUMO
Treating iodoacetamide (IAD)-modified lymphoma cells with the lipophilic agent dimethyldioctadecylammonium bromide (DDA) increased their immunogenicity as evidenced by the increased capacity of syngeneic, vaccinated hosts to reject subsequent implants of the same lymphoma. Under conditions of suboptimal immunization to facilitate comparison, there were 61% survivors among mice challenged with tumor implants after immunization with modified cells and DDA compared to 20% survivors among those immunized in the absence of DDA. The enhanced immune response was dependent on DDA dosage and was most striking when DDA was directly complexed to the IAD-treated cells. DDA was also effective with solubilized tumor antigen and with lymphoma cells not pretreated with IAD, but the latter had to be heat killed to assure that they were nontumorigenic. In therapy experiments BALB/c mice bearing P1798 were treated with methotrexate followed by immunotherapy with IAD-P1798 alone or complexed to DDA. With two and three cycles of therapy, methotrexate alone yielded 5 and 13% survivors, while adding immunotherapy with the DDA complex gave survival rates of 63 and 71%. In the absence of DDA, chemoimmunotherapy with methotrexate and IAD-P1798 gave intermediate results. In the absence of antigen, DDA was ineffective in either immunoprophylaxis or therapy experiments.
Assuntos
Antígenos de Neoplasias/administração & dosagem , Linfoma/terapia , Metotrexato/uso terapêutico , Compostos de Amônio Quaternário/farmacologia , Adjuvantes Imunológicos , Animais , Antígenos de Neoplasias/isolamento & purificação , Feminino , Rejeição de Enxerto/efeitos dos fármacos , Imunoterapia , Iodoacetamida , Linfoma/imunologia , Camundongos , Camundongos Endogâmicos , Transplante de Neoplasias , Neoplasias Experimentais/terapia , Transplante IsogênicoRESUMO
The extent of blast transformation for human and BALB/c mouse lymphocytes has been examined over a wide range of glutamine concentrations with several agents which initiate blastogenesis. Maximum [3H] thymidine incorporation was seen at 0.5 mM glutamine for lymphoid tissues stimulated in the following manner: human and BALB/c splenic and peripheral blood lymphocytes with phytohemagglutinin, BALB/c splenic lymphocytes with lipopolysaccharide, and BALB/c vs C3H/HeJ two-way mixed lymphocyte cultures. The inhibition of blastogenesis exerted by glutamine concentrations greater than 0.5 mM could not be reversed by washing and reculturing the cells at 0.5 mM glutamine. To elucidate the reason for inhibition by higher glutamine concentrations, the products of spontaneous glutamine decomposition, L-2-pyrrolidone-5-carboxylic acid and ammonia were tested for their in vitro influence on BALB/c splenocyte blastogenesis. Pyrrolidone-carboxylic acid, in concentrations up to 5 mM, was without effect. In contrast, ammonia concentrations exceeding 1 mM became increasingly more inhibitory. The genesis of inhibitory levels of ammonia in culture medium was confirmed and has been considered as primarily responsible for inhibiton by high glutamine. Addition of Escherichia coli glutaminase (pH optimum 4.9) to cultures of BALB/c splenocytes or human peripheral blood lymphocytes had no effect on either the extent of blastogenesis of these tissues or the glutamine levels in their culture medium.
Assuntos
Glutaminase/farmacologia , Glutamina/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Adulto , Amônia/farmacologia , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Feminino , Humanos , Lectinas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Ácido Pirrolidonocarboxílico/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Timidina/metabolismoRESUMO
BACKGROUND: Symptoms of anxiety and depression in patients with restless legs syndrome (RLS) have been observed. However, it is unclear whether rates of threshold depression and anxiety disorders according to DSM-IV criteria in such patients are also elevated. METHODS: 238 RLS patients were assessed with a standardized diagnostic interview (Munich-Composite International Diagnostic Interview for DSM-IV) validated for subjects aged 18-65 years. Rates of anxiety and depressive disorders were compared between 130 RLS patients within this age range and 2265 community respondents from a nationally representative sample with somatic morbidity of other types. RESULTS: RLS patients revealed an increased risk of having 12-month anxiety and depressive disorders with particularly strong associations with panic disorder (OR=4.7; 95% CI=2.1-10.1), generalized anxiety disorder (OR=3.5; 95% CI= 1.7-7.1), and major depression (OR=2.6; 95% CI=1.5-4.4). In addition, lifetime rates of panic disorder and most depressive disorders as well as comorbid depression and anxiety disorders were considerably increased among RLS patients compared with controls. CONCLUSIONS: The results suggest that RLS patients are at increased risk of having specific anxiety and depressive disorders. Causal attributions of patients suggest that a considerable proportion of the excess morbidity for depression and panic disorder might be due to RLS symptomatology.
Assuntos
Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Comorbidade , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Transtorno de Pânico/etiologia , Transtorno de Pânico/fisiopatologia , Prevalência , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/psicologia , Fatores de RiscoRESUMO
A human renal carcinoma cell line (Caki-1) was examined for asparagine (Asn) dependence and susceptibility to Escherichia coli asparaginase. Because this enzyme hydrolyzes glutamine (Gln) as well as Asn, even though at only 2-3% the rate, Asn- Gln+ and Asn- Gln- media were prepared. Only the former supported Caki growth. The Asn- Gln- medium was then repleted with Asn, Gln, or both. Although Asn repletion failed to promote growth, addition of Gln alone or the combination supported growth as well as complete medium. With [3H]leucine and [3H]mannose incorporation to indicate protein and glycoprotein synthesis, respectively, the Gln repleted medium supported these processes as well as complete medium. Asparaginase added to complete medium was highly toxic to the Caki cells, but this is a reflection of Gln depletion rather than Asn depletion.
Assuntos
Asparaginase/farmacologia , Aspartato-Amônia Ligase/metabolismo , Neoplasias Renais/enzimologia , Ligases/metabolismo , Divisão Celular , Linhagem Celular , Meios de Cultura , Glutamina/metabolismo , Humanos , Neoplasias Renais/patologia , Biossíntese de Proteínas , Células Tumorais CultivadasRESUMO
The effect of dimethylsulfoxide (DMSO) and butyrate, agents which induce differentiation of certain cancer cells, on membrane associated 5'-nucleotidase (5'-NT) of 2 human renal carcinoma cell lines (Cur and Caki) was investigated. Under a variety of conditions of agent addition, 5'-NT specific activity increased in Cur and decreased in Caki cells. This opposite response pattern was observed for assays performed on lysates at pH 9.0 and 7.4 and assays with intact cell monolayers, even under conditions of identical cellular growth inhibition. It is concluded that the cell lines responded in a fundamentally different way to the chemical agents. An increase in 5'-NT has correlated with cell maturation for a number of processes. The DMSO induced increase in Cur 5'-NT was dependent on protein synthesis.