RESUMO
This paper reviews the literature to assess the effectiveness of oral health interventions in influencing oral health-related quality of life (OHRQoL) in older adults. Clinical studies published in 2010 onwards reporting oral health interventions in older adults and subsequent changes in OHRQoL were systematically searched in Medline, Web of Science and EMBASE databases. Reporting followed Preferred Reporting Items for Systematic Review and Meta-Analysis criteria. Eligibility evaluation and data abstraction from eligible studies were guided by predefined PICO questions and bias assessment by the Quality in Prognosis Studies tool. The search retrieved 144 articles. Of the 20 articles that met the eligibility criteria, 45% (9) reported a statistically significant improvement in OHRQoL. The majority of studies were conducted in adults with complete edentulism (70%) and mainly focused on implant provision to support a removable prosthesis (30%). The search indicates the limited scope of current literature on geriatric dental interventions, focusing mainly on denture realignments, denture fabrication and implant placement. Although the majority of the oral health interventions focused on edentulism and removable prostheses, there are many areas of oral health interventions and their potential impact on OHRQoL in this demographic group that have yet to be explored. © 2022 Australian Dental Association.
Assuntos
Saúde Bucal , Qualidade de Vida , Humanos , Idoso , AustráliaRESUMO
Providing evidence of potential changes in the climate has become increasingly important as it is the first step towards adopting mitigation and adaptation measures and planning for urban resilience. In this study a statistical analysis of the ambient air temperature time series over Sydney, Australia during 1970-2016 has been carried out with the aim to investigate potential changes towards higher temperatures. The dataset has been statistically analyzed using different techniques, concluding that the investigation should be performed on a monthly basis. A persistence analysis was conducted using different statistical approaches to investigate the dependence between consecutive monthly and daily ambient air temperature values. A trend analysis of the ambient air temperature and degree days time series has been conducted using linear regression to estimate the linear trend (slope) and its statistical significance (using a Student-t-test) and the Kendall-Mann test to identify the time at which the tendency starts to occur as well as the time after which it becomes statistically significant.
RESUMO
The manufactured in "cotto" is typical of Chianti Fiorentino with about 400 employees. In 2005. the UF PISLL encountered an exposure to silica more than TLV, particularly for some tasks; were prescribed interventions of prevention and was undertaken an investigation of the occupational health status with occupational health physician. We observed 227 workers, 208 males and 19 females, with average age of 43 years and average age working of 15 years. The habit of smoking tobacco was higher than for the general population. The assessment of exposure to silica has been detected for 59 workers (mean 0.05 mg / mc); at pulmonary function testing resulted: 10 with airway obstruction and 4 airflow limitation; by 140 chest X - ray acquired 1 was interstitial pulmonary disease and 1 was bronchopneumonia. Among the diseases not related to exposure to silica, emerging 42 cases of low back pain, 28 hearing loss, 7 with hypertension. Non uniformity in health surveillance and diagnostic criteria highlights the need to cooperate between occupational doctor in public prevention and control service and qualified occupational doctor to ensure a standard of quality in the prevention of disease in exposed to silica.
Assuntos
Nível de Saúde , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Dióxido de Silício/efeitos adversos , Silicose/epidemiologia , Silicose/etiologia , Adulto , Idoso , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-IdadeRESUMO
Prostatic endoscopic resection (TURP) is a reference method in the treatment of prostatic obstruction. In the past decades, the method used a monopolar resectoscope. In the last years, various technologies have been studied to improve the efficacy of endoscopic resection. As per our experience, we have thence ascertained the variations of the hematic crasis and of the mictional asset in TURP patients treated with bipolar knives. 20 patients underwent bipolar plasmakinetic resection of the prostate. Their age ranged between 58 yrs and 82 yrs (av.: 70.2 yrs), the adenoma volume, checked with TR ultrasound scanning, was between 33 and 44 cc (av.: 37.6), the Qmax was between 6.4 and 9.0 mL/min (av.: 7.42 mL/min). A 24Ch resectoscope and spinal anesthesia were used. Bleeding during resection was never relevant; therefore resection never had to be stopped. After about 36 hours from surgery, the patients' sanguification was checked again: a 6.53% reduction of the number of erythrocytes, compared to pre-surgery data, was observed, together with a 6.73% decrease of hemoglobin concentration, and a 6.3% decrease of hematocrit. Continuous irrigation was suspended during the first day, catheter was removed on the 48th hour in 15 cases, and on the 72nd in 5 cases: the patients were discharged on day 3 in 16 cases, and on day 4 in 4 cases. A flux evaluation was performed after 3 months, which showed a Qmax between 16.6 and 24 mL/min (av.: 19.11), with a significant increase in the maximum flow rate. The use of the new technologies in prostatic endoscopic resection has allowed us to improve the efficacy of such a method. Above all, the use of a bipolar electrosurgical knife enables us to associate a basal hemostasis with the resection of the prostatic tissue. Thus, the hematic loss is low, as we have been able to ascertain also in our own experience. This gave us the possibility to quickly stop continuous irrigation and to early remove the catheter. This way, hospitalization was sensibly reduced (av. 76.8 hours). The maximum flow rate, in the short term, has been good. We have been able, in our experience, to assess that this technology represents a useful guarantee to improve the results of prostatic endoscopic resection.
RESUMO
Diabetes is an important risk factor in erectile dysfunction (ED), acting via several mechanisms. We assessed the efficacy of intracavernous injections (ICI) rehabilitation and oral systematic therapy in diabetic patients, as well as the response of controls to oral therapy 'on demand'. MATERIALS AND METHODS. Sixteen diabetic patients with ED were treated with vasoactive drugs orally when needed, without satisfactory erections. The patients underwent then ICI rehabilitation with PGE1 20 mcg twice weekly for 4 weeks, followed by the administration of oral drugs twice weekly for 4 weeks. Before and after rehabilitation, the patients completed a detailed anamnestic protocol to study their libido (always present); they answered questions Q3 and Q4 of the IIEF questionnaire. During ICI, a study with dynamic echocolordoppler (ECCD) was carried out. All patients had Type 2 diabetes: 10 were treated with oral antidiabetics, 4 were treated with insulin, and in the other 2 patients, treated with insulin, a sensitive neuropathy of the lower limbs was diagnosed. Fourteen patients were treated with antihypertensive drugs. RESULTS. Before rehabilitation, the mean responses to questions 3 and 4 of the IIEF (International Index of Erectile Function) questionnaire were 1.6 and 1.5 respectively; after rehabilitation, the mean responses were 2.68 and 2.5, respectively. The ECCD test showed an arterial component in 4 cases and a high end-diastolic velocity (EDV) in 14 cases. Four patients (25%), 2 of which had neuropathy, and 2 were in advanced age, did not respond to PGE1 or to oral therapy, 4 patients (25%) (2 treated with insulin and 2 by oral therapy) responded to ICI but not to oral therapy, while 8 patients (50%) showed a good response to both injectable and oral therapy, with good Q3 and Q4 scores. CONCLUSIONS. Good endothelial function appears to be essential for the maintenance of acceptable erectile function. Diabetes has a negative effect on this function, as does hypoxia and low perfusion. Based on the principle that a good erection improves endothelial function, we tried to determine if oral systematic and intracavernous rehabilitation would improve erectile function in diabetic patients. The results indicate that diabetes interferes with erectile function, compromising the effects of the vasoactive drugs. However, integrated systematic rehabilitation appears to allow a good erectile response to both intracavernous and oral therapy in a large number of cases. Therefore, we support this kind of rehabilitative protocol in the treatment of ED in diabetic patients.
RESUMO
Porphyromonas gingivalis is a key periodontal pathogen that has been implicated in the aetiology of chronic adult periodontitis. The aim of this study was to characterize two potential vaccine candidates (PG32 and PG33) identified from a previous genomic sequence analysis. Gene knockout studies suggested that these proteins play an important role in bacterial growth and are transcriptionally linked. Analysis of 14 laboratory and clinical isolates of P. gingivalis found that in all strains, both genes were present with a high level of conservation and that the two proteins were also expressed in vitro. Truncated recombinant PG32 and PG33 proteins were produced in Escherichia coli in an attempt to increase the solubility of the proteins while retaining their native conformation. While most of the truncated proteins remained insoluble, two truncated proteins showed good solubility and high levels of protection in the P. gingivalis murine lesion model and may be considered as potential vaccine candidates for further testing in models of human periodontal disease.
Assuntos
Antígenos de Bactérias/isolamento & purificação , Proteínas da Membrana Bacteriana Externa/isolamento & purificação , Porphyromonas gingivalis/imunologia , Substâncias Protetoras/isolamento & purificação , Sequência de Aminoácidos , Animais , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Sequência Conservada , Modelos Animais de Doenças , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Inativação Gênica , Vetores Genéticos , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Porinas/imunologia , Porinas/isolamento & purificação , Porphyromonas gingivalis/genética , Proteínas Recombinantes , Solubilidade , Transformação Genética/genética , Vacinas Acelulares/imunologiaAssuntos
Aberrações Cromossômicas , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Análise Citogenética , Rearranjo Gênico/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , TrombocitoseRESUMO
Prophylactic antibiotics are used routinely in otolaryngology. Little objective data exist concerning their use in sinonasal procedures. We wished to determine the practice patterns of otolaryngologists regarding prophylactic antibiotics for septoplasty patients. A survey of 743 (60.3% responded) members of the American Rhinologic Society was used to get information about their practice habits and rationale for using antibiotics after septoplasty. Sixty-six percent of respondents routinely used antibiotics. Postoperative infection and toxic shock syndrome (TSS) were the primary indications. Forty-four percent of respondents used some form of packing and 38% used a splint. There was no relationship between the annual number of procedures and the reasons for using antibiotics. Doctors who performed more than 50 cases a year were less likely to use packing or splints (p < 0.001). Older surgeons used less younger surgeons a packing/splints (p < 0.001). Respondents who used packing/ splints were more likely to use antibiotics (p = 0.008). Older respondents used packing whereas younger respondents used splints (p = 0.002). The rationale for antibiotics varied by age; re more concerned with TSS and older physicians were more concerned with infection (p = 0.005). This survey shows great variability in the usage and rationale for antibiotics after septoplasty.
Assuntos
Antibioticoprofilaxia , Padrões de Prática Médica , Rinoplastia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Otolaringologia , Período Pós-Operatório , Choque Séptico/prevenção & controleRESUMO
Extracellular Arg-x- and Lys-x-specific cysteine proteinases are considered important virulence factors and pathogenic markers for Porphyromonas gingivalis, a bacterium implicated as a major etiological agent of chronic periodontitis. Three genes. rgpA, rgpB, and kgp, encode an Arg-x-specific proteinase and adhesins (RgpA), an Arg-x-specific proteinase (RgpB), and a Lys-x-specific proteinase and adhesins (Kgp), respectively. The contribution to pathogenicity of each of the proteinase genes of P. gingivalis W50 was investigated in a murine lesion model using isogenic mutants lacking RgpA, RgpB, and Kgp. Whole-cell Arg-x-specific proteolytic activity of both the RgpA(-) and RgpB(-) isogenic mutants was significantly reduced (3- to 4-fold) relative to that of the wild-type W50. However, for the Kgp(-) isogenic mutant, whole-cell Arg-x activity was similar to that of the wild-type strain. Whole-cell Lys-x proteolytic activity of the RgpA(-) and RgpB(-) mutants was not significantly different from that of wild-type W50, whereas the Kgp(-) mutant was devoid of Lys-x whole-cell proteolytic activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis using proteinase-specific antibodies of cell sonicates of the wild-type and mutant strains showed that the proteinase catalytic domain of each of the mutants was not expressed. This analysis further showed that RgpB appeared as 72- and 80-kDa bands, and the catalytic domains of RgpA and Kgp appeared as processed 45-kDa and 48-kDa bands, respectively. In the murine lesion model, mice were challenged with three doses of each mutant and wild-type strain. At the lower dose (3.0 x 10(9) viable-cells), no lesions were recorded for each of the mutants, whereas wild-type W50 induced large ulcerative lesions. At a dose of 6.0 x 10(9) viable-cells, all the mice challenged with the wild-type strain died, whereas mice challenged with the RgpA(-) and RgpB(-) isogenic mutants did not die but developed lesions. Mice challenged with the Kgp(-) isogenic mutant at this dose did not develop lesions. At a 1.2 x 10(10) viable-cell dose, only 40% of mice challenged with the Kgp(-) mutant developed lesions, and these lesions were significantly smaller than lesions induced by the wild-type strain at the 3.0 x 10(9) viable-cell dose. All the mice challenged with the RgpA(-) mutant died at the 1.2 x 10(10) viable-cell dose, whereas only 20% died when challenged with the RgpB(-) mutant at this dose. Wild-type phenotype was restored to the RgpB(-) mutant by complementation with plasmid pNJR12::rgpB containing the rgpB gene. There was no difference between the pNJR12::rgpB-complemented RgpB(-) mutant and the wild-type W50 strain in whole-cell Arg-x activity, protein profile, or virulence in the murine lesion model. These results show that the three proteinases, RgpA, RgpB, and Kgp, all contributed to virulence of P. gingivalis W50 in the murine lesion model and that the order in which they contributed was Kgp >> RgpB > or = RgpA.
Assuntos
Adesinas Bacterianas/metabolismo , Infecções por Bacteroidaceae/etiologia , Cisteína Endopeptidases/metabolismo , Hemaglutininas/metabolismo , Porphyromonas gingivalis/patogenicidade , Adesinas Bacterianas/genética , Animais , Cisteína Endopeptidases/genética , Teste de Complementação Genética , Cisteína Endopeptidases Gingipaínas , Hemaglutininas/genética , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Periodontite/etiologia , Porphyromonas gingivalis/genéticaRESUMO
Syk and ZAP-70 nonreceptor protein tyrosine kinases (PTKs) are essential elements in several cascades coupling immune receptors to intracellular responses. The critical role of these kinases in promoting the propagation of intracellular signaling requires a tight regulation of their activity, thus the existence of a negative feedback loop regulating their expression can be hypothesized. Herein, we have investigated whether ubiquitin-dependent proteolysis could be a mechanism responsible for controlling the fate of Syk and ZAP-70 after their immunoreceptor-induced activation. We found that both Syk and ZAP-70 become ubiquitinated in response to aggregation of the low affinity Fc receptor for IgG (CD16) on human natural killer cells. We confirmed the identity of the major in vivo ubiquitinated kinase species by performing an in vitro ubiquitination assay. In addition, we found that after CD16 stimulation, ubiquitinated forms of Syk and ZAP-70 associate with the receptor complex. After CD16 engagement, we also observed a decrease in the stability of Syk and ZAP-70 PTKs that is counteracted by pretreatment with either proteasome or lysosomal inhibitors. Moreover, in the presence of the proteasome inhibitor, epoxomicin, we observed an accumulation of ubiquitinated forms of both kinases. Our findings provide evidence of ligand-induced ubiquitination of nonreceptor PTKs belonging to the Syk family and propose the ubiquitin-dependent proteasome-mediated degradation pathway as a mechanism for attenuating the propagation of intracellular signaling initiated by immune receptor engagement.
Assuntos
Precursores Enzimáticos/metabolismo , Células Matadoras Naturais/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptores de IgG/imunologia , Transdução de Sinais/fisiologia , Ubiquitinas/metabolismo , Células Cultivadas , Cicloeximida/farmacologia , Cisteína Endopeptidases/metabolismo , Ativação Enzimática , Retroalimentação , Humanos , Imunoglobulina G/imunologia , Peptídeos e Proteínas de Sinalização Intracelular , Células Matadoras Naturais/imunologia , Lisossomos/enzimologia , Substâncias Macromoleculares , Complexos Multienzimáticos/antagonistas & inibidores , Complexos Multienzimáticos/metabolismo , Oligopeptídeos/farmacologia , Inibidores de Proteases/farmacologia , Complexo de Endopeptidases do Proteassoma , Subunidades Proteicas , Quinase Syk , Proteína-Tirosina Quinase ZAP-70Assuntos
Imunoglobulinas Intravenosas/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Púrpura Trombocitopênica Idiopática/complicações , Fatores Etários , Idoso , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Fatores de TempoRESUMO
A primary cutaneous form of peripheral T-cell lymphoma (PTCL) and a low grade B-cell non-Hodgkin's lymphoma that was classified as a variant of hairy cell leukemia (HCL) were simultaneously diagnosed in a 79-year-old woman by both phenotypic and genotypic analyses. The coexistence of a T- and B-cell lymphoma in the same patient is rare, and, to our knowledge, this particular association has not been previously described. The patient was referred to our Department for evaluation of multiple cutaneous itchy, reddish plaques; laboratory analyses disclosed a lymphocytosis, that presented 6 years earlier. A bone marrow aspirate showed a 50% B-cell interstitial infiltrate, while a skin biopsy surprisingly revealed a PTCL. Clonality of both neoplastic processes was assessed by Southern blot analysis. The indolent clinical course of the cutaneous disease, and the low and stable number of circulating neoplastic T cells supported the diagnosis of a mycosis fungoides (MF)-like PTCL. Possible oncogenic events and/or putative underlying viral infections which could have played a role in the occurrence of B- and T-cell non-Hodgkin's lymphomas in the same patient are discussed.
Assuntos
Leucemia de Células B/complicações , Leucemia de Células Pilosas/complicações , Linfoma Cutâneo de Células T/complicações , Neoplasias Cutâneas/complicações , Idoso , Biópsia , Southern Blotting , Medula Óssea/patologia , DNA/sangue , Feminino , Humanos , Imunofenotipagem , Pele/patologiaRESUMO
Porphyromonas gingivalis, a gram-negative bacterium, has been linked to the onset and progression of periodontitis, a chronic inflammatory disease of the supporting tissues of the teeth. A major virulence factor of P. gingivalis is an extracellular complex of Arg- and Lys-specific proteinases and adhesins designated the RgpA-Kgp complex (formerly the PrtR-PrtK complex). In this study we show that the RgpA-Kgp complex, when used as an immunogen with incomplete Freund adjuvant (IFA), protects against challenge with invasive and noninvasive strains of P. gingivalis in the murine lesion model. We identified a variety of peptide vaccine candidates from the RgpA and Kgp polyprotein sequences that involved the putative active site histidine of both proteinases and five repeat motifs in the adhesin domains of both polyproteins implicated in aggregation and binding to host substrates, designated adhesin-binding motif (ABM) peptides. These peptides were synthesized using standard, solid-phase protocols for 9-fluorenylmethoxy carbonyl chemistry with S-acetylmercaptoacetic acid (SAMA) as the N-terminal residue. The SAMA-peptides were then conjugated to diphtheria toxoid and used with IFA to immunize BALB/c mice. Both active-site peptides and three of the five ABM peptides gave protection (P < 0.005) against challenge with P. gingivalis in the murine lesion model. The three ABM peptide sequences that conferred protection exist within a 100-residue span in the RgpA44 and Kgp39 adhesins of the RgpA-Kgp complex. Protective anti-RgpA-Kgp complex mouse antisera recognized the RgpA27, Kgp39, and RgpA44 adhesins in an immunoblot. Epitope mapping of the RgpA27 adhesin using the protective anti-RgpA-Kgp antisera identified a major protective epitope that mapped immediately N terminal to one of the protective ABM peptides in the 100-residue span in RgpA44 and Kgp39. This identified protective epitope contains clusters of basic residues spatially surrounded by hydrophobic amino acids, a finding which is characteristic of a heparin binding motif.
Assuntos
Infecções por Bacteroidaceae/prevenção & controle , Cisteína Endopeptidases/imunologia , Hemaglutininas/imunologia , Porphyromonas gingivalis/imunologia , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Adesinas Bacterianas/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/biossíntese , Vacinas Bacterianas/administração & dosagem , Infecções por Bacteroidaceae/imunologia , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Toxoide Diftérico/administração & dosagem , Modelos Animais de Doenças , Mapeamento de Epitopos , Epitopos/química , Epitopos/genética , Cisteína Endopeptidases Gingipaínas , Hemaglutininas/química , Hemaglutininas/genética , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/patogenicidade , Vacinas Conjugadas/administração & dosagem , VirulênciaRESUMO
Protein tyrosine kinase activation is one of the first biochemical events in the signaling pathway leading to activation of NK cell cytolytic machinery. Here we investigated whether proline-rich tyrosine kinase 2 (Pyk2), the nonreceptor protein tyrosine kinase belonging to the focal adhesion kinase family, could play a role in NK cell-mediated cytotoxicity. Our results demonstrate that binding of NK cells to sensitive target cells or ligation of beta2 integrins results in a rapid induction of Pyk2 phosphorylation and activation. By contrast, no detectable Pyk2 tyrosine phosphorylation is found upon CD16 stimulation mediated by either mAb or interaction with Ab-coated P815 cells. A functional role for Pyk2 in natural but not Ab-mediated cytotoxicity was demonstrated by the use of recombinant vaccinia viruses encoding the kinase dead mutant of Pyk2. Finally, we provide evidence that Pyk2 is involved in the beta2 integrin-triggered extracellular signal-regulated kinase activation, supporting the hypothesis that Pyk2 plays a role in the natural cytotoxicity by controlling extracellular signal-regulated kinase activation.
Assuntos
Citotoxicidade Imunológica , Células Matadoras Naturais/enzimologia , Células Matadoras Naturais/imunologia , Proteínas Tirosina Quinases/fisiologia , Citotoxicidade Celular Dependente de Anticorpos , Antígenos CD18/metabolismo , Adesão Celular/imunologia , Testes Imunológicos de Citotoxicidade , Ativação Enzimática/imunologia , Indução Enzimática/imunologia , Quinase 2 de Adesão Focal , Humanos , Células K562 , Células Matadoras Naturais/metabolismo , Fosforilação , Proteínas Tirosina Quinases/biossíntese , Proteínas Tirosina Quinases/metabolismo , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Transdução de Sinais/imunologia , Tirosina/metabolismoRESUMO
Murine mast cells adhere spontaneously to plate-bound vitronectin (VNPB) via alphav-containing integrins, and this adhesive interaction results in an augmented interleukin-3 (IL-3)-dependent mast-cell proliferation. In this report we demonstrate that the activation of murine mast cells through alphav-integrin, as well as through the high affinity immunoglobulin E (IgE) receptor (FcepsilonRI), results in enhanced tyrosine phosphorylation of focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase involved in mitogenic and oncogenic signal transduction. While mast cell adhesion to VNPB resulted in enhanced FAK phosphorylation, treatment with soluble vitronectin (VNSOL) failed to do so. Spontaneous mast cell adhesion to entactin (EN) did not induce tyrosine phosphorylation of FAK, demonstrating that not all adhesive interactions lead to the same sequence of biochemical events. Because FAK has intrinsic tyrosine kinase activity, we examined whether activating mast cells via alphav-integrins, or via FcepsilonRI-cross-linking stimulated the in vitro kinase activity of FAK. Both pathways were found independently to activate FAK in mast cells and together appeared additive. Protein kinase C depletion in mast cells and calcium depletion in the medium caused decreased tyrosine phosphorylation of FAK, indicating that optimal tyrosine phosphorylation of FAK is regulated by both pathways. These data are consistent with the conclusion that the tyrosine phosphorylation of FAK represents at least one example of a point of convergence in the intracellular tyrosine phosphorylation cascades induced by alphav integrin-and FcepsilonRI-mediated signal transduction pathways in mast cells.
Assuntos
Moléculas de Adesão Celular/metabolismo , Mastócitos/fisiologia , Proteínas Tirosina Quinases/metabolismo , Receptores de IgE/metabolismo , Transdução de Sinais , Vitronectina/metabolismo , Animais , Antígenos CD/metabolismo , Western Blotting , Cálcio/metabolismo , Adesão Celular , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Integrina alfaV , Líquido Intracelular/metabolismo , Medições Luminescentes , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Proteína Quinase C/metabolismo , Receptor Cross-TalkRESUMO
Several studies suggest that the 24 hour ambulatory blood pressure monitoring (ABPM) predicts left ventricular hypertrophy more accurately than conventional blood pressure measurement (CBPM) with mercury sphygmomanometer. We estimated the left ventricular mass by M-mode echocardiography in 58 patients on regular haemodialysis treatment during the midweek haemodialysis (HD) interval. ABPM was recorded during the 24 hours preceding the dialysis session and the average of values were compared with the average of the 13 pre HD CBPM recorded by nurses during the month preceding the echocardiography study. The two types of BP measurements correlated significantly with each other, (systolic BP r = 0.62; p < 0.001 and diastolic BP r = 0.74; p < 0.001). The correlation of left ventricular mass with pre-HD systolic BP was stronger (r = 0.54; p < 0.001) than with 24h-systolic BP (r = 0.33; p < 0.01). The overall accuracy of prediction was also similar (68% for pre HD-CBPM; 67% for 24h-ABPM). Measurements of diastolic BP did not correlate significantly with LVM. Our data suggest that 24h-ABPM does not offer any advantage over pre HD-CBPM in predicting left ventricular hypertrophy in HD patients.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertrofia Ventricular Esquerda/diagnóstico , Diálise Renal , Uremia/complicações , Idoso , Feminino , Humanos , Hipertrofia Ventricular Esquerda/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Uremia/terapiaRESUMO
We investigated whether aggregation of the low-affinity immunoglobulin G receptor (CD16) on human NK cells results in receptor ubiquitination. We found that the CD16 zeta subunit becomes ubiquitinated in response to receptor engagement. We then investigated whether protein tyrosine kinase (PTK) activation is required for CD16-mediated receptor ubiquitination. Pretreatment with the PTK inhibitor genistein substantially decreased ligand-induced zeta ubiquitination, suggesting a requirement for PTK activation in receptor ubiquitination. We further analyzed PTK involvement in controlling receptor ubiquitination by using the vaccinia virus expression system. Overexpression of wild-type active lck, but not a kinase-deficient mutant, enhanced both ligand-induced tyrosine phosphorylation and ubiquitination of the CD16 zeta subunit. Taken together, our data demonstrate that CD16 engagement induces zeta chain ubiquitination and strongly suggest a role for lck in regulating this modification.
Assuntos
Células Matadoras Naturais/imunologia , Proteínas Tirosina Quinases/imunologia , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Ubiquitinas/metabolismo , Antígenos CD/imunologia , Antígenos CD/metabolismo , Humanos , Células Matadoras Naturais/metabolismo , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/biossíntese , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais/imunologia , Tirosina/metabolismoRESUMO
We report the case of a 65-year-old man affected by idiopathic thrombocytopenic purpura, who developed an acute myocardial infarction after 2 years of steroid therapy. Thrombocytopenia was initially recognized 11 years earlier, and became severe during the past 2 years [platelets (PLTS) 10000-30000/microl]. He was treated with steroids, initially to perform a surgical procedure (prednisone 75 mg/day), subsequently to maintain a platelet count of about 50000/microl (prednisone 12.5 mg/day). After 1 year of treatment, he began to complain about exertional angina and dyspnea. His blood pressure became elevated and cholesterol level raised. The exercise electrocardiogram, previously manifesting ischaemic changes, normalized after 1 month of steroid wash-out; however, steroid therapy was reinstituted (prednisone 5 mg per day). One year later, he suffered an infero-lateral non-Q-wave myocardial infarction. It seems likely that the severe coronary atherosclerosis present in our patient developed despite a low platelet count, under the spur of a heavier risk factor profile. Steroid therapy could have had a role as a precipitating agent of the acute event, and the opportunity of alternative treatments is considered.
Assuntos
Infarto do Miocárdio/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Esteroides/uso terapêutico , Idoso , Humanos , Masculino , Infarto do Miocárdio/sangue , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Fatores de RiscoRESUMO
Fc gamma RIII (CD16) is a hetero-oligomeric receptor composed of a ligand-binding alpha subunit associated with homo- or heterodimers of the TCR zeta- and Fc epsilon RI gamma-chains. We have previously demonstrated that CD16 ligation promotes complex formation between tyrosine-phosphorylated shc and Grb2, leading to activation of ras signaling pathway in human NK cells. Here we report that CD16 engagement induces rapid shc association with the tyrosine-phosphorylated receptor complex in human NK cells. In vitro binding studies demonstrate that this interaction is mediated by the shc-SH2 domain, and immunodepletion experiments indicate that the zeta- but not the gamma-chain has the capability to mediate this association. Jurkat cell clones expressing CD16-zeta or -gamma homodimers have been used to gain more information about the mechanism of shc/CD16 association. Our data show that, while engagement of both receptors induces tyrosine phosphorylation of shc and Grb2 recruitment, shc-SH2/receptor complex association is evident only in CD16-zeta but not in CD16-gamma transfectants. Overall, our data demonstrate that the adaptor protein shc can be recruited to the activated CD16 complex by interaction with tyrosine-phosphorylated zeta-chain in a SH2-dependent manner. These results also provide further support to the notion that zeta- and gamma-chains might couple to different biochemical pathways.
Assuntos
Células Matadoras Naturais/metabolismo , Proteínas de Membrana/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de IgG/metabolismo , Tirosina/metabolismo , Domínios de Homologia de src/imunologia , Células Cultivadas , Humanos , Células Jurkat , Ligantes , Fosforilação , Ligação Proteica/imunologia , Transfecção/imunologiaRESUMO
We report the case of a 65-year-old man who developed a symptomatic splenomegaly due to spleen metastasis from thyroid follicular carcinoma. In 1982, at the age of 53, the patient had undergone a thyroid lobectomy for a cold node, followed one year later by a second intervention for a microfollicular adenoma. He was subsequently administered thyroid suppressive therapy with no further follow-up. The diagnosis of spleen metastases from thyroid cancer was first suspected on the basis of history, high serum thyroglobulin (Tg) levels, and the presence of pulmonary 99Tc uptake. The patient underwent a splenectomy, during which vast infiltration involving the diaphragm, spleen, stomach, colon and pancreas, was found. Histological and immunohistochemical results showed that the spleen and diaphragm metastases derived from thyroid follicular carcinoma. Radioiodine uptake by the pulmonary metastases confirmed the thyroid source. Retrospective re-evaluation of the thyroid tissue removed in 1983 revealed a histological pattern consistent with follicular carcinoma, which could not be unequivocally attributed to the widely or minimally invasive form. To our knowledge this is the first report of splenomegaly as the first manifestation of thyroid cancer metastases. In this paper cases of splenomegaly due to metastatic spread are reviewed and the management of the present case is discussed.