RESUMO
BACKGROUND: Motocross is a recreational and competitive sport involving motorcycle racing on off-road circuits. Participants have enjoyed their sport worldwide for over 100 years. In the United Kingdom, there are over 200 clubs, with over 900 events annually. Unfortunately, little evidence exists on motocross injuries and their prevention. The aim of this study is to report and to quantify the different foot and ankle injuries observed in motocross. METHODS: Data was collected prospectively between August 2010 to August 2015 at our regional trauma unit, regardless of whether the sport was performed competitively or recreationally. RESULTS: Foot and ankle related injuries were identified in 210 patients (age range 4-78 years), with the majority being male participants (189, 90%). The majority of injuries occurred within the 21- to 30-year-old-age group. Most injuries were sustained around the start of the motocross season, in early spring and the summer months. A total of 76 patients (36%) required operative intervention. The most common injury was ankle fracture (49, 23%), followed by ankle sprain (44, 21%). CONCLUSION: This is the first epidemiological study in the United Kingdom documenting foot and ankle injuries in motocross. The frequency and severity of motocross-related injuries is presented. This may serve to provide recommendations and guidelines in the governing bodies of this sport. The surge in motocross popularity is correlates with an increase in injuries and inevitably the resources required to treat them. LEVEL OF EVIDENCE: Prospective descriptive epidemiological study. Level 1.
Assuntos
Traumatismos do Tornozelo/epidemiologia , Traumatismos em Atletas/epidemiologia , Motocicletas , Centros de Traumatologia/estatística & dados numéricos , Adulto , Traumatismos do Tornozelo/etiologia , Estudos Epidemiológicos , Feminino , Traumatismos do Pé/epidemiologia , Traumatismos do Pé/etiologia , Humanos , Incidência , Masculino , Estudos Prospectivos , Reino Unido/epidemiologia , Adulto JovemRESUMO
Highly efficient fluorescent and biocompatible europium doped sodium zinc molybdate (NZMOE) nanoprobes were successfully synthesized via Polyol method. Non-radiative defect centres get reduced with Li+ co-doping in NZMOE nanoprobes. XRD spectra and Rietveld refinement confirmed successful incorporation of lithium ion and crystallinity was also improved with Li+ co-doping. The shape of phosphor is rod shaped, as determined by TEM. Significant enhancement in photoluminescence intensity was observed with 266, 395 and 465 nm excitations. Profound red emission was recorded for 5 at% Li+ co-doped NZMOE nanoprobes with 266 nm excitation. It shows high asymmetry ratio (~15), color purity (94.90%) and good quantum efficiency (~70%). Judd Ofelt parameters have been calculated to measure intensity parameters and radiative transition rates. In order to measure biocompatibility of the nanoprobes, cytotoxicity assays were performed with HePG2 cells. The fluorescence emitted from phosphor material treated HePG2 cells was also measured by Laser Scanning Confocal Microscopy. The bright red fluorescence in HePG2 cells treated with very low concentration (20 µg/ml) of phosphor material indicates that it could be a promising phosphor for biological detection or bio-imaging.
Assuntos
Európio/química , Lítio/química , Substâncias Luminescentes/síntese química , Molibdênio/química , Zinco/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Substâncias Luminescentes/química , Substâncias Luminescentes/farmacologia , Nanopartículas Metálicas , Microscopia Confocal , Fósforo/químicaRESUMO
Lanthanide ions, Ln(3+) (Dy(3+), Eu(3+) and Sm(3+)) doped SrWO4 nanoparticles were synthesized using ethylene glycol (EG) as a capping agent as well as reaction medium. The X-ray diffraction (XRD) study reveals that all the Ln(3+) (Dy(3+), Eu(3+) and Sm(3+)) doped samples are well crystalline in nature with a tetragonal scheelite structure of SrWO4 phase. TG study reveals that the nanophosphors are thermally stable. Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy techniques were used to obtain the information about internal and external vibrational modes present in the SrWO4 structure. Optical properties were investigated using UV-vis and photoluminescence (PL) spectroscopy. The average crystallite size was calculated using Debye-Scherrer's for as-prepared and 800°C annealed samples and is found to be in the range of â¼35-70nm. The luminescence intensity of Eu(3+) doped SrWO4 nanoparticles under 364nm excitation wavelength reveals that (5)D0â(7)F2 transition at â¼613nm (red) is more prominent than that of (5)D0â(7)F1 transition at â¼590nm (orange). Also upon excitation by UV radiation, the SrWO4:Dy(3+) phosphor shows the yellow and blue transition lines appearing at â¼572 and 484nm which are the characteristic electronic transitions of (4)F9/2-(6)H13/2 and (4)F9/2-(6)H15/2 emission line of Dy(3+), respectively. Also Sm(3+) doped SrWO4 nanophosphor shows its characteristic emission lines in the range of 550-720nm, corresponding to (4)G5/2â(6)HJ (J=5/2, 7/2, 9/2 and 11/2) transitions of Sm(3+) ions. The predominant orange red color can be attributed to (4)G5/2â(6)H9/2 located at â¼642nm. This is related to the polarizing effect due to the energy transfer from WO4(2-) to the Eu(3+), Dy(3+) and Sm(3+) sites, respectively. Effect of annealing on the photoluminescence properties of samples has been studied and it was found that luminescence intensity increases up to â¼3 times on heating the samples at 800°C. This may be due to reduction in non-radiative decay channels pathways and reduced surface defects associated with the samples. These studies show that these Ln(3+) (Dy(3+), Eu(3+) and Sm(3+)) doped SrWO4 nanophosphors may be used as potential candidates for the advancement in LEDs.
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Primary hepatic angiosarcoma is a rare, aggressive tumor; composed of spindle or pleomorphic cells that line, or grow into, the lumina of pre-existing vascular spaces like sinusoids and terminal hepatic venules; with only about 200 cases diagnosed annually worldwide but it is the most common primary malignant mesenchymal tumor of the liver in adults and accounts for 2% of all primary hepatic malignancies. HAS occurs in association with known chemical carcinogens, but 75% of the tumors have no known etiology. Patients present with vague symptoms like abdominal pain, weight loss, fatigue or an abdominal mass. Hepatic angiosarcoma is usually multicentric and involves both lobes, entire liver may also found to be involved. CD31 is the most reliable marker. These tumors lack specific features on imaging, so, pathological diagnosis is necessary. There are no established treatment guidelines because of low frequency and aggressive nature of tumor, chemotherapy is only palliative, liver resection is indicated for solitary mass and liver transplant is contraindicated. The aim of this article is to comprehensively review all the available literature and to present detailed information and an update on primary hepatic angiosarcoma.
Assuntos
Hemangiossarcoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Diagnóstico Tardio , Hemangiossarcoma/metabolismo , Hemangiossarcoma/terapia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Guias de Prática Clínica como AssuntoRESUMO
Sudden and intermittent locking of the elbow joint is a com- mon complaint among patients who commonly demonstrate degenerative changes in the elbow. Common causes of elbow locking include acute trauma, osteochondritis dessicans, synovial chondromatosis, and osteoarthritis. Two cases involving patients with symptoms of elbow locking secondary to reasons other than loose bodies within the joint are presented: a synovial cyst within the posterior aspect of the elbow, specifically within the olecranon fossa causing their painful symptoms of locking. These cases present unique features in the diagnostic approaches of elbow locking due to the unexpected association with synovial cysts. We believe that these findings can shed new light on the pathogenesis of this disease.
Assuntos
Cartilagem Articular/patologia , Condromatose Sinovial/etiologia , Articulação do Cotovelo , Corpos Livres Articulares/etiologia , Cisto Sinovial/complicações , Adulto , Artroscopia , Biópsia , Condromatose Sinovial/diagnóstico , Diagnóstico Diferencial , Humanos , Corpos Livres Articulares/diagnóstico , Masculino , Cisto Sinovial/diagnóstico , Adulto JovemRESUMO
The Foley catheter is described in the emergency treatment of penetrating cardiac injuries, and its intra-operative use to control bleeding while definitive measures for intravascular embolization are being made. We present the first reported case of the use of a urinary catheter to control haemorrhage in an extremity stab injury to obtain haemodynamic stability while awaiting definitive surgical treatment. This quick, easy and useful technique can be used for junctional vascular injuries and wounds with a narrow neck, and can be easily removed once in the operating theatre. This life-saving, simple and cost-effective technique 'internalises' the externally applied pressure to control massive haemorrhage while awaiting definitive operative intervention. The catheter can be sutured in place if the patient is to be transferred to another department or hospital.
RESUMO
The opioidergic hypothesis suggests an association between genetic variations at the opioid receptor mu 1 (OPRM1) gene locus and opiate addiction. The OPRM1 gene, which encodes for mu opioid receptor, contains several single nucleotide polymorphisms (SNPs) in exon I. Two of these, C17T and A118G, have been reported to be associated with substance abuse. The present study aims to delineate the frequency of these variants in the subjects of Indian origin and study their association with the phenotype of opioid dependence. A118G (rs 1799971) and C17T (rs 1799972) were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. For 118G allele, the control subjects (n = 156) showed a frequency of 0.12 while the opioid dependents (n = 126) had an approximately 2.5-fold higher frequency of 0.31 (Odds Ratio 3.501; CI(95%) 2.212-5.555; p < 0.0001). For C17T polymorphism, the controls (n = 57) showed a frequency of 0.89 for C allele versus 0.83 seen in dependents (n = 123; odds ratio of 0.555; CI(95%) 0.264-1.147; p = 0.121). A significant association was observed between the 118G allele and no association was seen with C17T polymorphism and opioid dependence.
Assuntos
Predisposição Genética para Doença , Transtornos Relacionados ao Uso de Opioides/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Opioides mu/genética , Adulto , Distribuição de Qui-Quadrado , Intervalos de Confiança , Frequência do Gene , Genótipo , Humanos , Índia/etnologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de RestriçãoRESUMO
Opiates are known to induce immunosuppression in their users (addicts). Evidences supporting their role in suppressing a variety of immunological end points in addicts have been reported by several investigators. In the present study, we investigated the changes in serum immunoglobulin (Ig) levels and their correlation with Mu opiate receptor (MOR) genotypes. Eighty-seven users and forty-five non-users were recruited for the study. Genomic DNA, isolated from the peripheral blood, was used for genotyping for C17T and A118G polymorphism using PCR-RFLP method. The frequency of A and G alleles in non-users was 89% and 11% respectively, whereas in addicts, it was 67% and 33% respectively. Case control analysis between groups revealed that 118G allele was associated with opioid dependence [Chi square (chi2) = 13.56, odds ratio (OR) = 3.90, confidence interval 95% (CI 95%) = 1.80-8.67, p = 0.000231]. C17T polymorphism showed no association with opioid dependence [(chi2) = 0.9, OR = 2.49, CI 95% = 0.528-16.12, p = 0.343]. Mean Ig levels, both IgG (student's t-test = 2.2738, p = 0.007) and IgA (student's t-test = 2.848, p = 0.0051) differed between opiate users and nonusers. IgG and IgA levels were also significantly different in individuals with different MOR genotypes. Immunosuppression was observed in AA genotype-bearing individuals, while no suppression was seen in AG and GG genotypes bearing individuals. In case of C17T polymorphism, both CC and CT genotypes bearing individuals showed immunosuppression, as judged by circulating Ig levels.
Assuntos
Imunoglobulina A/sangue , Imunoglobulina G/sangue , Transtornos Relacionados ao Uso de Opioides/genética , Transtornos Relacionados ao Uso de Opioides/imunologia , Polimorfismo de Nucleotídeo Único/genética , Receptores Opioides mu/genética , Adulto , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Receptores Opioides mu/imunologia , Estatística como AssuntoRESUMO
A stable monolayer of N-octadecylaniline containing stearic acid at the air-water interface has been obtained. However, the Langmuir monolayer of pure poly(N-octadecylaniline) was not stable, but mixed Langmuir-Blodgett films of this polymer with stearic acid in different ratios as a spreading aid were stable. The electrical conductivity of these films increased by five orders of magnitude after doping with iodine as compared to that before iodine doping (5.8x10(-7) S cm(-1)). Temperature-dependent electrical conductivity suggested that these films were semiconducting in nature with low thermal activation energy. Impedance analyses of these films revealed that the equivalent circuit for poly(N-octadecylaniline) was (RQ) whereas that for mixed poly(N-octadecylaniline) with stearic acid was (RQ)(RQ).
Assuntos
Transtornos Mentais , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Colo do Útero/citologia , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Displasia do Colo do Útero/patologia , Esfregaço VaginalRESUMO
The information about Urban Mental Health Services has been nearly nonexistent in India, although the developed countries have been focusing on programmes for "Healthy Cities". The initiative taken as part of the WHO-ICMR Pilot Project on Urban Mental Health Services, with a public health perspective is being shared. The objectives of the Health Services Research (HSR) Arm of the project were to study the distribution and the availability of tertiary Mental Health Services, availability of human resources, average service load, mental health service gap, and perceptions of the users and the service providers, regarding the barriers in accessibility of mental health services, unmet service needs and strategies for improvement.The Research Methods involved Mapping Exercises with estimation of Service Loads and Qualitative Research Methods (QRM) like In-Depth Interviews (IDIs), Key Informant Interviews (KIIs), Free Listing and Focused Group Discussions (FGDs). The results indicate uneven availability of mental health services, human resource deficit specially for non-medical mental health professionals and mental health service gap (82% to96%). The average service load in the specialist mental health services is largely carried by the Govt. sector (half to two thirds), followed by the private sector (one third to half), with only a small portion by the NGO sector. The average mental health service load in the primary care general health services is largely carried by the private sector, with significant contribution from the non-formal service providers. The barriers to access, unmet needs and possible strategies as perceived by the community, users and service providers have been identified. The findings are discussed in the context of the mental health programmes and the public policy issues. The implications of the conclusions which suggest that Urban Mental Health Services are far from complete are highlighted.
RESUMO
Pathways to psychiatric care were evaluated among three hundred and eighty four first-contact psychiatric patients from five socio-culturally different regions of India by a modified version of World Health Organization encounter form for 'pathways in psychiatric care'. Concerning first caregivers, out of 384 respondents 34.1% had chosen the psychiatrists, 29.4% the general practitioners and 26% had chosen faith healers and exorcists. Choice for the first caregiver was not influenced by gender differences, literacy status and family type. Mostly the subjects hailing from rural areas and those presenting with somatic symptoms chose psychiatrist as their first caregivers.
Assuntos
Cuidadores/classificação , Serviços de Saúde Mental , Pessoas Mentalmente Doentes , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Cuidadores/estatística & dados numéricos , Comportamento de Escolha , Feminino , Humanos , Índia , Masculino , Fatores Socioeconômicos , Recursos HumanosRESUMO
Two hundred and thirty men, being treated for ICD-10 diagnosed dependence on alcohol, opioids or both, were studied 2-4 weeks after the last use of alcohol or opioids. Alienation Scale, Sensation Seeking Scale and Muliphasic Personality Questionnaire (MPQ), and selected sociodemographic and family history data were studied. All three groups showed high alienation (more in opioid cases), high sensation seeking (more in alcohol cases, more for boredom susceptibility), and a disturbed MPQ profile. The dual dependence group was similar to opioid group for age, but closer to alcohol group in terms of personality profile. Only alcohol cases showed a significantly positive correlation between alienation and sensation seeking- in terms of total scale, and boredom susceptibility and disinhibition subscales only. Thus, substance specificity was not reflected prominently in the inter-relationships between alienation, sensation seeking and MPQ scores, and sociodemographic variables.
RESUMO
Multiple sclerosis (MS) is a demyelinating disease of presumed T cell autoimmunity against self myelin. We hypothesized that if myelin-reactive T cells are associated with the disease processes, they may undergo activation and expansion during acute exacerbation. In this study, we examined the precursor frequency, epitope recognition and cytokine profile of myelin-reactive T cells in 14 relapsing/remitting MS patients during exacerbation and remission. The study revealed that T cells recognizing the immunodominant peptides of candidate myelin antigens, including myelin basic protein (MBP), proteolipid protein and myelin oligodendrocyte glycoprotein, occurred at increased precursor frequency during acute exacerbation. The T cell responses to MBP focused on the immunodominant regions (residues 83-99 and 151-170) during exacerbation and shifted toward other epitopes of MBP at the time of remission. Furthermore, there was a marked increase in the production of T(h)1 cytokines among T cell lines obtained during exacerbation compared to those obtained during remission. The study demonstrated that myelin-reactive T cells underwent selective activation and expansion during acute MS exacerbation. In contrast, myelin-reactive T cells found during remission in the same patients generally resembled those identified in healthy controls with some discrepancies. The findings suggest potential association of aberrant myelin-reactive T cell responses with acute exacerbation in MS, which may reflect transient activation of myelin-reactive T cell populations of pathogenic potential.
Assuntos
Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Células Cultivadas , Citocinas/análise , Epitopos/imunologia , Células Precursoras Eritroides/imunologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Proteína Básica da Mielina/farmacologia , Proteína Proteolipídica de Mielina/imunologia , Remissão Espontânea , Células Th1RESUMO
The putative replication origin of Azotobacter vinelandii was cloned as an autonomously replicating fragment after ligation to an antibiotic resistance cartridge. The resulting plasmids could be isolated and labelled by Southern hybridisation with the antibiotic resistance cartridge as probe and also visualised by electron microscopy. These plasmids integrated into the chromosome after a few generations, even in the recA mutant of A. vinelandii. The integrated copy of the plasmid was re-isolated from the chromosome and the DNA and its subfragments were cloned in the plasmid vector pBR322. A 200-bp DNA fragment was sufficient to allow the replication of pBR322 in an Escherichia coli polA strain. Electron microscopic analysis of this plasmid showed that replication initiated mostly within the A. vinelandii DNA fragment. The nucleotide sequence of the putative replication origin and its flanking regions was determined. In the sequence of the 200-bp fragment many of the distinctive features found in other replication origins are lacking. A greater variation from the consensus DnaA binding sequence was observed in A. vinelandii. Direct sequencing of the relevant genomic fragment was also carried after amplifying it from A. vinelandii chromosomal DNA by PCR. This confirmed that no rearrangements had taken place while the cloned fragment was resident in E. coli. It was shown by hybridisation that the 200-bp chromosomal origin fragment of A. vinelandii was present in three other field strains of Azotobacter spp.
Assuntos
Azotobacter vinelandii/genética , Origem de Replicação , Sequência de Bases , Clonagem Molecular , Replicação do DNA/genética , DNA Bacteriano/biossíntese , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Técnicas Genéticas , Microscopia Eletrônica , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Plasmídeos/genética , Plasmídeos/isolamento & purificação , Plasmídeos/ultraestrutura , Análise de Sequência de DNARESUMO
Long term intravenous drug abuse is associated with recurrent femoral pseudoaneurysm in a 36-year-old man. The clinical features alongwith a suitable discussion is described in this case report.
Assuntos
Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Veia Femoral , Entorpecentes , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Seguimentos , Humanos , Ligadura/métodos , Masculino , Recidiva , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Th0 clones recognizing an immunodominant peptide of myelin basic protein (residues 83-99) were derived from patients with multiple sclerosis. We demonstrate that analogue peptides with alanine substitution at Val86 and His88 had a unique partial agonistic property in inducing Th0 -->Th1 and Th0 -->Th2 deviation of the myelin basic protein-reactive T cell clones, respectively. Th0 to Th1 deviation induced by peptide 86V-->A correlated with up-regulation of Fyn and ZAP-70 kinase activities. Conversely, Th0 to Th2 deviation induced by peptide 88H-->A was associated with complete failure to activate Fyn and ZAP-70 kinases. The observed Th1 and Th2 shift also correlated, to a lesser extent, with Lck kinase activity that was down-regulated with Th1 deviation and increased with Th2 deviation in some T cell clones. We demonstrated that the Th1 and Th2 shift induced by the analogue peptides was a reversible process, as the T cell clones previously exposed to either 86V-->A or 88H-->A peptide could revert to an opposite phenotype when rechallenged reciprocally with a different analogue peptide. The study has important implications in our understanding of regulation of TCR-associated tyrosine kinases by altered peptide ligands and its role in cytokine regulation of autoreactive T cells.
Assuntos
Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Proteína Básica da Mielina/imunologia , Fragmentos de Peptídeos/imunologia , Peptídeos/imunologia , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Células Th1/imunologia , Células Th2/imunologia , Alanina/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos/imunologia , Células Clonais , Ativação Enzimática/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Imunofenotipagem , Dados de Sequência Molecular , Proteína Básica da Mielina/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeos/agonistas , Peptídeos/metabolismo , Proteínas Proto-Oncogênicas c-fyn , Células Th1/enzimologia , Células Th1/metabolismo , Células Th2/enzimologia , Células Th2/metabolismo , Proteína-Tirosina Quinase ZAP-70RESUMO
T cell responses to the immunodominant peptide (residues 83-99) of myelin basic protein are potentially associated with multiple sclerosis (MS). This study was undertaken to examine whether a common sequence motif(s) exists within the TCR complementarity-determining region (CDR)-3 of T cells recognizing the MBP83-99 peptide. Twenty MBP83-99-reactive T cell clones derived from patients with MS were analyzed for CDR3 sequences, which revealed several shared motifs. Some V beta 13.1 T cell clones derived from different patients with MS were found to contain an identical CDR3 motif, V beta 13.1-LGRAGLTY. Oligonucleotides complementary to the shared CDR3 motifs were used as specific probes to detect identical target CDR3 sequences in a large panel of T cell lines reactive to MBP83-99 and unprimed PBMC. The results revealed that, in contrast to other CDR3 motifs examined, the LGRAGLTY motif was common to T cells recognizing the MBP83-99 peptide, as evident by its expression in the majority of MBP83-99-reactive T cell lines (36/44) and PBMC specimens (15/48) obtained from randomly selected MS patients. The motif was also detected in lower expression in some PBMC specimens from healthy individuals, suggesting the presence of low precursor frequency of T cells expressing this motif in healthy individuals. This study provides new evidence indicating that the identified LGRAGLTY motif is preferentially expressed in MBP83-99-reactive T cells. The findings have important implications in monitoring and targeting MBP83-99-reactive T cells in MS.
Assuntos
Epitopos Imunodominantes/metabolismo , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/metabolismo , Fragmentos de Peptídeos/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Células Clonais , Clonagem Molecular , Primers do DNA/genética , DNA Recombinante/isolamento & purificação , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/metabolismo , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Humanos , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Dados de Sequência Molecular , Esclerose Múltipla/metabolismo , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/imunologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Subpopulações de Linfócitos T/imunologiaRESUMO
Cisplatin (cis-dichlorodiammineplatinum II), a potent antitumour compound, stimulates immune responses by activating monocytes/macrophages and other cells of the immune system. However, the exact mechanism by which cisplatin activates these cells is poorly characterized and attempts are being made to understand this mechanism. Previous studies from this laboratory have shown that Lyn, a protein tyrosine kinase of the src family, and nuclear factor (NF)-kappaB are involved in cisplatin-induced macrophage activation. Recent studies suggest that the RAS and mitogen-activated protein (MAP) kinases function as a connecting link between activated lyn and NF-kB, which raises the possibility of their involvement in cisplatin-induced macrophage activation. Therefore, this study was undertaken to investigate the effect of cisplatin treatment on the expression/activation of RAS (a low molecular weight GTP-binding protein) and MAP kinases in murine peritoneal macrophages. The underlying mechanism of expression/activation of RAS and MAP kinases in cisplatin-treated macrophages was also investigated. Immunoblotting and immune-complex kinase assays revealed that cisplatin treatment of macrophages leads to increased expression/activation of RAS and MAP kinases, with optimal expression/activation at 15 min of treatment. Using a battery of specific inhibitor/modulators of different signalling molecules, this study shows that expression and activation of MAP kinases are two unrelated processes. It was also observed that kinase (protein tyrosine and protein kinase C) inhibitor and Ca2+/calmodulin antagonist inhibit expression/activation of RAS/MAP kinases in macrophages, whereas phosphatases (protein tyrosine and serine/threonine) inhibitor up-regulate these kinases.