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BACKGROUND: Diversity management has gained traction in Japan. The Pediatric Rheumatology Association of Japan (PRAJ) has an Advisory Committee for Diversity Promotion with a broader focus on promoting diversity. The objectives of this study were to better understand the problems faced by PRAJ members regarding the work environment, childcare and nursing care, and work-life balance. METHODS: A web-based questionnaire was administered to members of the PRAJ and 79 responses were evaluated. RESULTS: Of the respondents, 73% were male and 27% were female. A total of 14% worked for more than 12 h on weekdays, and 22% worked for more than 60 h per week and 38% had fewer than 4 days off per month. Regarding childcare, 54% of the respondents were raising preschool children and 83% had taken parental leave for less than 1 year. A total of 17% of participants had family members in need of care. For both childcare and caregiving, the burden was greater for women. Only 18% of the respondents reported a well-balanced work-life balance, and the most common reasons for a lack of balance were not having enough time, heavy workload, and heavy housework load. CONCLUSIONS: The working hours of the respondents were long, and female members had a greater burden of childcare and caregiving, which was considered a barrier to the career development of women. In the future, there will be a need to promote a sense of equality in diverse human resources, develop support for family life, and shorten working hours.
Assuntos
Reumatologia , Humanos , Masculino , Feminino , Japão , Família , Emprego , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.
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Artrite Juvenil , Dermatomiosite , Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Reumatologia , Síndrome de Sjogren , Criança , Humanos , Masculino , Feminino , Doenças Reumáticas/epidemiologia , Dermatomiosite/diagnóstico , Dermatomiosite/epidemiologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Japão/epidemiologia , Artrite Juvenil/epidemiologia , Sistema de Registros , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologiaRESUMO
OBJECTIVE: To update and revise the diagnostic criteria for mixed connective tissue disease (MCTD) issued by the Japan Research Committee of the Ministry of Health, Labor, and Welfare (MHLW), a round table discussion by experts from rheumatology, dermatology, and pediatric medicine was conducted in multiple occasions. METHODS: The definition of MCTD, and items included in the diagnostic criteria were generated by consensus method and evaluation using clinical data of typical and borderline cases of MCTD, by applying to the diagnostic criteria for MCTD proposed in 1996 and 2004 by the Research Committee of MHLW. RESULTS: To the end, all committee members reached consensus. Then, the criteria were assessed in an independent validation cohort and tested against preexisting criteria. The revised criteria facilitate an understanding of the overall picture of this disease by describing the concept of MCTD, common manifestations, immunological manifestation and characteristic organ involvement. Conditions with characteristic organ involvement include pulmonary arterial hypertension, aseptic meningitis and trigeminal neuropathy. Even if the overlapping manifestations are absent, MCTD can be diagnosed based on the presence of the characteristic organ involvement. Furthermore, the criteria were validated for applicability in actual clinical cases, and public comments were solicited from the Japan College of Rheumatology and other associated societies. CONCLUSION: After being reviewed through public comments, the revised diagnostic criteria have been finalized.
Assuntos
Doença Mista do Tecido Conjuntivo/diagnóstico , Reumatologia , Humanos , JapãoRESUMO
Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect.
Assuntos
Diagnóstico Tardio , Desnutrição/complicações , Doenças Negligenciadas , Púrpura Trombocitopênica Trombótica/etiologia , Deficiência de Vitamina B 12/complicações , Adolescente , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Desnutrição/sangue , Desnutrição/diagnóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Fatores de Tempo , Tomografia Computadorizada por Raios X , Deficiência de Vitamina B 12/sangueRESUMO
A 38-day-old infant was referred to our hospital for evaluation of apnea, fever, and pyuria. Invasive bacterial infection, including meningitis, was suspected because of the presence of apnea. A contrast-enhanced CT scan revealed acute localized bacterial nephritis, and meningitis was ruled out. Gram-positive cocci and Gram-negative rods, ie, Enterococcus raffinosus and Escherichia coli, were isolated from a urine culture at the referring hospital. This case report describes the youngest case of E. raffinosus infection. Apnea was the main complaint, but the origin of fever was infant acute focal bacterial nephritis (AFBN) with mixed infection. In infants, bacterial infections, especially invasive bacterial infections, can result in poor outcomes and require careful evaluation and treatment. Furthermore, the possibility of AFBN should not be overlooked, because bacteriuria or leukocyturia may be absent and can flare up if antimicrobials are not administered for an adequate duration. Although ampicillin-susceptible E. raffinosus infection in our patient responded well to treatment, there have been reports of vancomycin-resistant enterococci, which highlights the importance of proper use of antimicrobial agents to avoid producing drug-resistant bacteria.
RESUMO
Coronavirus disease 2019 (COVID-19) in children can be compounded by concurrent diseases and immunosuppressants. For the first time, we aimed to report the clinical features of concurrent COVID-19 and pediatric rheumatic disease (PRD) in Japan. Pediatric Rheumatology Association of Japan members were surveyed between 1 April 2020 and 31 August 2022. Outcome measurements included the clinical features of concurrent PRD and COVID-19. Questionnaire responses were obtained from 38 hospitals. Thirty-one hospitals (82%) had children with PRD and COVID-19. The female-to-male ratio in these children (n = 156) was 7:3, with half aged 11-15 years. The highest proportion of children with PRD and COVID-19 was accounted for by juvenile idiopathic arthritis (52%), followed by systemic lupus erythematosus (24%), juvenile dermatomyositis (5%), scleroderma (4%), and Takayasu arteritis (3%). Of children with PRD, a significant majority (97%) were found to be asymptomatic (10%) or presented with mild symptoms (87%) of the COVID-19 infection. No severe cases or deaths were observed. Regarding the use of glucocorticoids, immunosuppressants, or biologics for PRD treatment before COVID-19, no significant difference was found between asymptomatic/mild and moderate COVID-19 in children with PRD. Therefore, COVID-19 is not a threat to children with PRD in Japan.
Assuntos
COVID-19 , Doenças Reumáticas , Reumatologia , Criança , Humanos , Masculino , Feminino , COVID-19/epidemiologia , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/tratamento farmacológico , Japão/epidemiologia , Imunossupressores/uso terapêutico , Inquéritos e QuestionáriosRESUMO
In paediatric primary Sjögren's syndrome (SS), the initial symptoms manifest systemically, such as fever, general fatigue, and lymphadenopathy, rather than sicca symptoms. Most children with primary SS have autoantibodies, such as antinuclear, anti-Ro/SS-A, and/or anti-La/SS-B antibodies; however, some patients are seronegative. Similar to paediatric patients with primary SS, those with Takayasu arteritis (TAK) initially only present constitutional symptoms, making it difficult to suspect, unless characteristic features are present. To our knowledge, there have been no reports of the coexistence of both diseases in children. We present a rare case of seronegative SS complicated by TAK in a 9-year-old girl who presented with a persistent low-grade fever, general fatigue, cervical lymphadenopathy, and multiple caries. Although blood examination revealed all autoantibodies to be negative, a lip biopsy revealed lymphocytic sialadenitis, and a sialoscintigraphy indicated hypofunctional salivary glands, leading to the diagnosis of seronegative SS. The patient was treated with low-dose glucocorticoid and immunosuppressant administration to inhibit persistent inflammation and the progression of salivary gland dysfunction; although the symptoms resolved, inflammatory markers remained elevated. When the patient was 14 years old, cervical bruits were incidentally found, and TAK was suspected based on cervical ultrasonography and magnetic resonance angiography findings. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography results demonstrated increased fluorodeoxyglucose accumulation from the ascending to descending aorta. Therefore, she was diagnosed with SS complicated by TAK, which is rare. Aortitis should be suspected when the cause of persistent inflammation cannot be ascertained in patients with SS.
Assuntos
Linfadenopatia , Síndrome de Sjogren , Arterite de Takayasu , Adolescente , Feminino , Humanos , Autoanticorpos , População do Leste Asiático , Fluordesoxiglucose F18 , Inflamação/complicações , Linfadenopatia/complicações , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológicoRESUMO
Trisomy 21 (Down syndrome) is sometimes complicated by congenital heart disease; however, comorbid type I diabetes mellitus and diseases involving autoantibodies, such as Hashimoto disease and Graves disease, are not uncommon. Autoinflammatory diseases such as Kawasaki disease and systemic juvenile idiopathic arthritis are rare. We report a rare case of trisomy 21 with systemic juvenile idiopathic arthritis that responded well to the initial course of methylprednisolone pulse therapy but flared up and was complicated by macrophage activation syndrome (MAS). Subsequent methylprednisolone pulse therapy and cyclosporine resolved this condition. Cytokines were analyzed at several time points during the clinical course and revealed that interleukin-18, interleukin-6, and chemokine ligand 9 levels were elevated at MAS onset in the present patient, even though clinical symptoms had abated. Thus, early analysis of cytokine profiles should be performed to assess MAS risk and determine treatment intensity, even in T21 patients.
Assuntos
Artrite Juvenil , Síndrome de Down , Síndrome de Ativação Macrofágica , Humanos , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Síndrome de Down/complicações , Citocinas , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/tratamento farmacológico , Metilprednisolona , Progressão da DoençaRESUMO
Antigen-specific memory T cells (Tms) are essential in the immune surveillance of residual and metastatic tumors. Activation of Tms requires designing vaccines based on tumor rejection antigens, which are often not available to cancer patients. Therefore, it is desirable to have a general applicable approach to activate Tms without extensive knowledge of tumor antigens. Here, we report that activation of antigen-specific Tms could be achieved by the administration of agonistic anti-CD137 monoclonal antibody without additional tumor vaccination, leading to the prevention of recurrence and metastases after surgical resection of primary tumors in mouse models. By reconstitution with CD137-deficient Tms, we demonstrate that expression of CD137 on antigen-specific Tms is only partially required for the effect of anti-CD137 antibody. Other host cells, including those from hematopoietic and nonhematopoietic origins, are also important because ablation of CD137 from these cells partially but significantly eliminates antitumor effect of anti-CD137 antibody. Our findings implicate a potential new approach to prevent recurrence and metastases in cancer patients.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias/prevenção & controle , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/agonistas , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/fisiologia , Animais , Vacinas Anticâncer/uso terapêutico , Células Cultivadas , Feminino , Células-Tronco Hematopoéticas/metabolismo , Memória Imunológica/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Transgênicos , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/patologia , Prevenção Secundária , Análise de Sobrevida , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Linfócitos T Reguladores/fisiologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
T-cell tolerance is the central program that prevents harmful immune responses against self-antigens, in which inhibitory PD-1 signal given by B7-H1 interaction plays an important role. Recent studies demonstrated that B7-H1 binds CD80 besides PD-1, and B7-H1/CD80 interaction also delivers inhibitory signals in T cells. However, a role of B7-H1/CD80 signals in regulation of T-cell tolerance has yet to be explored. We report here that attenuation of B7-H1/CD80 signals by treatment with anti-B7-H1 monoclonal antibody, which specifically blocks B7-H1/CD80 but not B7-H1/PD-1, enhanced T-cell expansion and prevented T-cell anergy induction. In addition, B7-H1/CD80 blockade restored Ag responsiveness in the previously anergized T cells. Experiments using B7-H1 or CD80-deficient T cells indicated that an inhibitory signal through CD80, but not B7-H1, on T cells is responsible in part for these effects. Consistently, CD80 expression was detected on anergic T cells and further up-regulated when they were re-exposed to the antigen (Ag). Finally, blockade of B7-H1/CD80 interaction prevented oral tolerance induction and restored T-cell responsiveness to Ag previously tolerized by oral administration. Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance.
Assuntos
Autoantígenos/imunologia , Antígeno B7-1/fisiologia , Tolerância Imunológica/imunologia , Glicoproteínas de Membrana/fisiologia , Peptídeos/fisiologia , Linfócitos T/imunologia , Animais , Antígenos de Diferenciação/fisiologia , Antígeno B7-H1 , Western Blotting , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imunização , Imunoglobulina G/administração & dosagem , Imunoglobulina G/imunologia , Imunoglobulina G/farmacologia , Imunoprecipitação , Glicoproteínas de Membrana/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ovalbumina/metabolismo , Fragmentos de Peptídeos/imunologia , Peptídeos/antagonistas & inibidores , Receptor de Morte Celular Programada 1 , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos Lew , Receptores de Antígenos de Linfócitos T/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/citologia , Linfócitos T/metabolismo , Linfócitos T Citotóxicos/imunologiaRESUMO
PURPOSE: Drug resistance is a serious problem in leukemia therapy. A novel purine nucleoside analogue, nelarabine, is available for the treatment of children with T cell acute lymphoblastic leukemia. We investigated the mechanisms of drug resistance to nelarabine. METHODS: Nelarabine-resistant cells were selected by stepwise and continuous exposure to nelarabine using the limiting dilution method in human B and T cell lymphoblastic leukemia cell lines. Expression analysis was performed using real-time polymerase chain reaction, and epigenetic analysis was performed using methylation-specific polymerase chain reaction and chromatin immunoprecipitation. RESULTS: The RNA expression level for deoxycytidine kinase (dCK) was decreased in nelarabine-resistant leukemia cells. There were no differences between the parental and nelarabine-resistant leukemia cells in the methylation status of the promoter region of the dCK gene. In the chromatin immune precipitation assay, decreased acetylation of histones H3 and H4 bound to the dCK promoter was seen in the nelarabine-resistant cells when compared to the parental cells. Furthermore, treatment with a novel histone deacetylase inhibitor, vorinostat, promoted the cytotoxic effect of nelarabine along with increased expression of the dCK gene, and it increased acetylation of both histones H3 and H4 bound to the dCK promoter in nelarabine-resistant leukemia cells. The combination index showed that the effect of nelarabine and vorinostat was synergistic. CONCLUSION: This study reports that nelarabine with vorinostat can promote cytotoxicity in nelarabine-resistant leukemia cells through epigenetic mechanisms.
Assuntos
Antineoplásicos/farmacologia , Arabinonucleosídeos/farmacologia , Desoxicitidina Quinase/genética , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Acetilação , Linhagem Celular Tumoral , Ilhas de CpG , Metilação de DNA , Desoxicitidina Quinase/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histonas/genética , Histonas/metabolismo , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Regiões Promotoras Genéticas , Vorinostat/farmacologiaRESUMO
BACKGROUND: In preparation for the 2021 Tokyo Olympic/Paralympic Games, the Japanese government assessed the risks of infectious disease outbreaks and identified necessary preparations. This present study reviewed efforts made during a previous measles epidemic and describes the roles of hospitals. METHODS: This descriptive study investigated the records of 198 children with measles. All children were treated at a general hospital during the period from January 1997 through February 1998. We also examined the actions of pediatricians during and after a measles outbreak in the community. RESULTS: Of the 198 children, 145 (73%) were hospitalized. The measles vaccination rate in the previous year was approximately 75%. Of the patients examined, 53% were younger than 2 years of age; mean age was 2.75 years. Pneumonia and gastroenteritis accounted for 46% and 30% of the complications, respectively. Issues requiring attention included the number of hospital beds located in a negative pressure room or private room with a window, the need for gamma globulin preparations with high measles antibody titers, the necessity of increasing vaccination opportunities, and extension of physician working hours. CONCLUSIONS: Visitors from other countries could cause measles outbreaks in Japan. Measures that might mitigate an outbreak were maintenance of high vaccination rates, ready availability of information on the location of negative pressure hospital rooms, knowledge of the status of the measle outbreak, and flexible medical staffing. There is a risk of measles outbreaks among infants and among those who do not have a measles antibody titer.
Assuntos
Surtos de Doenças/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Sarampo/prevenção & controle , Vacinação/estatística & dados numéricos , Criança , Pré-Escolar , Epidemias , Feminino , Hospitais Comunitários , Humanos , Lactente , Masculino , Sarampo/epidemiologia , Pediatria , Cobertura VacinalRESUMO
PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), a respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), is a pandemic in over 120 countries worldwide. Risk factors for severe COVID-19 include older age, ethnicity, sex, comorbidities, and living conditions. Although asthmatics and those with allergies are susceptible to more severe outcomes to viral infections, interestingly, asthma has not been reported to be a major comorbidity of COVID-19. However, there are some conflicting reports on the impact of asthma on COVID-19. The underlying immunological and molecular mechanisms may explain at least in part these observations. Furthermore, environmental factors like air pollution that have detrimental effects on asthma and respiratory illnesses also have an impact on COVID-19. RECENT FINDINGS: Angiotensin-converting enzyme 2 (ACE2) is the receptor for the attachment and entry of SARS-CoV-2 into the host cells that is upregulated by Th1-mediated responses. In asthmatics, ACE2 gene expression is generally reduced and recent studies have shown a negative correlation between the levels of Th2 cytokines including IL-4, IL-5, and IL-13 in airway epithelial cells and other type 2 biomarkers with ACE2 expression. This may explain in part the potential protective role of asthma on COVID-19. Here, we review the relation of respiratory viral illnesses and asthma, the immune-molecular mechanisms of SARS-CoV-2 infection, the impact of asthma on COVID-19 and that of SARS-CoV-2 on asthma and allergic rhinitis, and the impact of environmental factors like air pollution on COVID-19. SUMMARY: Expression of ACE2 in airway epithelial cells in SARS-COV-2 is influenced by inflammatory profile. Respiratory allergic diseases like asthma appear to have a protective effect against SARS-COV-2 infection. However, the clinical association between asthma and SARS-COV-2 is not fully established and the underlying immune-molecular mechanisms may explain these observations.
Assuntos
Poluição do Ar/efeitos adversos , Asma/epidemiologia , Asma/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , Pandemias , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/virologia , Comorbidade , Citocinas/metabolismo , Humanos , Fatores de Risco , Células Th1/imunologia , Internalização do VírusRESUMO
BACKGROUND: There has been significant progress in reducing perinatal mortality in Japan. However, due to changes in social conditions, the total fertility rate and the number of births are decreasing, whereas the number of low birth weight infants is increasing along with the number of newborn babies that require intensive care. Further, although the number of high-level perinatal medical centers has increased, so has that of infants who need long-term hospitalization. Conversely, the number of regular obstetric facilities has decreased, thus resulting in insufficient beds for neonatal care. To fill this gap, we established a neonatal intensive care unit (NICU) at our hospital. This study aimed to evaluate our new type by comparing the data from ours with that from other facilities. METHODS: The other facilities assessed were two high-level NICU facilities and two regular obstetric facilities. Data, including sex, gestational age, birth weight, Apgar scores at 1 and 5 min, delivery method, and presence of breathing disorders, were extracted from medical records. RESULTS: The birth weight and gestational age distributions were significantly different in the institutions, except in one facility without a NICU. The new NICU saw more infants with low birth weight and respiratory disorders than the regular obstetric facilities. CONCLUSION: The comparison of birth weight and gestational age distributions, cases of respiratory disorders, and delivery methods indicate that our new NICU is positioned as an intermediate facility between a high-level NICU and a regular obstetrics facility.
Assuntos
Unidades de Terapia Intensiva Neonatal , Peso ao Nascer , Feminino , Idade Gestacional , Hospitais , Humanos , Lactente , Recém-Nascido , Japão , Gravidez , Faculdades de MedicinaRESUMO
In Japan, pneumococcal vaccine has been routinely administered since 2010 to prevent invasive pneumococcal diseases such as Streptococcus pneumoniae meningitis. We describe a case of pneumococcal meningitis in a 7-month-old girl who had received three doses of 13-valent pneumococcal conjugate vaccine. Brain magnetic resonance imaging showed infarcts in the right frontal region, and she was treated with antibiotics, intravenous immunoglobulin, dexamethasone, and edaravone. On day 27, an enhanced brain CT scan showed improvement of abnormal findings in the frontal region, except for slight atrophy. The S. pneumoniae serotype was 12F, which is not included in the 13-valent pneumococcal conjugate vaccine. A future vaccine is expected to use cross-reactivity to target common antigens.
Assuntos
Meningites Bacterianas/etiologia , Meningites Bacterianas/microbiologia , Infecções Pneumocócicas , Vacinas Pneumocócicas/efeitos adversos , Streptococcus pneumoniae , Vacinas Conjugadas/efeitos adversos , Antígenos de Bactérias/imunologia , Encéfalo/diagnóstico por imagem , Reações Cruzadas , Dexametasona/uso terapêutico , Edaravone/uso terapêutico , Feminino , Humanos , Imunoglobulinas Intravenosas , Lactente , Imageamento por Ressonância Magnética , Meningites Bacterianas/diagnóstico por imagem , Meningites Bacterianas/tratamento farmacológico , Infecções Pneumocócicas/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Tomografia Computadorizada por Raios XRESUMO
Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1-Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1-Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of naïve and memory T cells along with G(0)/G(1) cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions.
Assuntos
Dermatite Alérgica de Contato/imunologia , Receptores Imunológicos/imunologia , Animais , Ciclo Celular/imunologia , Células Cultivadas , Citocinas/biossíntese , Proteínas de Ligação a DNA/deficiência , Células Dendríticas/imunologia , Dermatite Alérgica de Contato/patologia , Modelos Animais de Doenças , Haptenos/imunologia , Tolerância Imunológica/imunologia , Memória Imunológica , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Transgênicos , Transdução de Sinais/imunologia , Baço/imunologia , Subpopulações de Linfócitos T/imunologiaRESUMO
Effective leukemia treatment is seriously hampered by drug resistance. We previously showed that aberrant methylation of the topoisomerase II α gene causes altered gene expression and acquired drug resistance in etoposide-resistant leukemia cells. In this study, we analyzed the genome-wide methylation status in resistant leukemia cells. We used MX2, which is a morpholino anthracycline derivative that functions as a topoisomerase II α inhibitor. We established a human myelogenous leukemia cell line (K562/P) and a related cell line with resistance to MX2 (K562/MX2). Using these cell lines, we investigated the genome-wide methylation status, compared expression profiles with a microarray, and analyzed the data using Gene Ontology and key node analysis. We demonstrate that the MX2-resistant cell line was globally hypermethylated. Gene Ontology analysis identified genes involved in the immunological response and gene silencing that were responsible for methylation-related altered gene expression in drug-resistant cells. Key node analysis showed that p38α mitogen-activated protein kinase was a novel enzyme involved in MX2-related resistance. p38 kinase activity in resistant cells was increased compared to MX2-sensitive parent cells. Blocking p38α activity using inhibitors and p38α knock down with small interfering RNA restored the sensitivity to MX2 in resistant cells with a decrease in p38 kinase activity as well as decreased expression of p38α mRNA and phosphorylated p38α protein. These findings may lead to a new strategy for treatment of drug-resistant leukemia cells.
RESUMO
Bacterial infections often cause fatal systemic infections in patients with primary immunodeficiency. To prevent unfortunate results, the selection, dose, and dosage of antibiotics are extremely important. Here, we report a case of Wiskott-Aldrich syndrome in a patient undergoing peritoneal dialysis because of chronic renal failure in whom methicillin-resistant Staphylococcus aureus sepsis developed. Because of the primary disease and complications, teicoplanin was the only chosen anti-S. aureus drug to prevent side effects. We used parameter estimation and dosage adjustment from a therapeutic drug monitoring simulation software program to overcome the challenges with teicoplanin treatment.