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Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. PAPERCLIP:
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Antibacterianos/administração & dosagem , Modelos Animais de Doenças , Intestinos/microbiologia , Microbiota , Obesidade/microbiologia , Penicilinas/administração & dosagem , Animais , Bactérias/classificação , Bactérias/metabolismo , Feminino , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microbiota/efeitos dos fármacos , Obesidade/metabolismoRESUMO
OBJECTIVES: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan. RESULTS: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases. CONCLUSIONS: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.
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OBJECTIVES: This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies. RESULTS: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%. CONCLUSIONS: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA.
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Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.
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Adiposidade/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Colo/efeitos dos fármacos , Colo/microbiologia , Metagenoma/efeitos dos fármacos , Adiposidade/fisiologia , Fatores Etários , Animais , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/metabolismo , Colesterol/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Polipeptídeo Inibidor Gástrico/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , DesmameRESUMO
The most common cause of erythema multiforme (EM) in children is infectious diseases which account for approximately 90% of cases. Drug eruptions are another common cause. Here we are reporting about a male patient aged 14 years with lymphadenitis who developed severe diffuse erythema during the course of treatment with medications including several antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Based on the pathological findings of the skin biopsy, the skin rash was due to EM. Upon investigating the underlying cause of EM, viral antibody was positive for Coxsackie A6, lymphocyte transformation testing (LTT) was positive for one of the NSAIDs, and the patch test (PT) was positive for amoxicillin. Based on the pattern of distribution of the skin rash, the cause of EM was considered to be drug-induced eruption due to amoxicillin. In this case, we did not derive a diagnosis of drug eruption without investigating the possibility of drug induction, because most cases of EM in children are induced by infection and the antibody against Coxsackie A6 was elevated. To diagnose the possibility of amoxicillin-induced EM, it was important to distinguish between the distribution patterns of infectious versus drug-induced EM and to evaluate the possibility of drug induction by both LTT and PT. If the diagnosis of amoxicillin-induced EM, had not been made, the potential recurrence of EM with amoxicillin could have occurred.
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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.
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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.
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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
Helicobacter pylori infection is associated with several autoimmune diseases, in which autoantibody-producing B cells must be activated. Among these B cells, CD5-positive B-1a cells from BALB/c mice were confirmed to secrete autoantibodies when cocultured with purified H. pylori urease in the absence of T cells. To determine the mechanisms for autoantibody production, CD5-positive B-1a cells were sorted from murine spleen cells and stimulated with either purified H. pylori urease or H. pylori coated onto plates (referred to hereafter as plate-coated H. pylori), and autoantibody production was measured by enzyme-linked immunosorbent assay (ELISA). Complete urease was not secreted from H. pylori but was visually expressed over the bacterium-like endotoxin. Urease-positive plated-coated H. pylori stimulated B-1a cells to produce autoantibodies, although urease-deficient isotype-matched H. pylori did not. Autoantibody secretion by B-1a cells was inhibited when bacteria were pretreated with anti-H. pylori urease-specific antibody having neutralizing ability against urease enzymatic activity but not with anti-H. pylori urease-specific antibody without neutralizing capacity. The B-1a cells externally express various Toll-like receptors (TLRs): TLR1, TLR2, TLR4, and TLR6. Among the TLRs, blocking of TLR2 on B-1a cells with a specific monoclonal antibody (MAb), T2.5, inhibited autoantibody secretion when B-1a cells were stimulated with plate-coated H. pylori or H. pylori urease. Moreover, B-1a cells from TLR2-knockout mice did not produce those autoantibodies. The present study provides evidence that functional urease expressed on the surface of H. pylori will directly stimulate B-1a cells via innate TLR2 to produce various autoantibodies and may induce autoimmune disorders.
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Autoanticorpos/metabolismo , Linfócitos B/imunologia , Helicobacter pylori/enzimologia , Receptor 2 Toll-Like/metabolismo , Urease/metabolismo , Animais , Antígenos CD5/metabolismo , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Feminino , Mucosa Gástrica/citologia , Regulação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Coelhos , Transdução de Sinais , Receptor 2 Toll-Like/genéticaRESUMO
IgA vasculitis (IgAV) is the most frequent form of vasculitis in childhood which classically presents with purpura of the lower extremities, joint pain or swelling and abdominal pain. Though it is a self-limiting disease, and its prognosis is generally good, glomerulonephritis is one of the most important complications. IgAV is classified as a small vessel vasculitis, and though glomerulonephritis develops in IgAV, necrotizing arteritis is rarely seen. Here, we present a case of a 13-year-old girl with IgAV, glomerulonephritis, and necrotizing arteritis in the small renal arteries. There have been only a few reports of adult cases of IgAV with necrotizing arteritis in the kidneys, but there have been no pediatric cases. Some previous reports showed a high mortality rate and implied the possibility of overlap with other vasculitides. In the current report, a rare case of IgAV is described which exhibited necrotizing arteritis rather than overlap with another vasculitis, with a relatively typical clinical course for IgAV and laboratory tests.
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Glomerulonefrite/etiologia , Vasculite por IgA/complicações , Poliarterite Nodosa/etiologia , Adolescente , Feminino , Glomerulonefrite/patologia , Humanos , Glomérulos Renais/ultraestrutura , Poliarterite Nodosa/patologiaRESUMO
OBJECTIVES: Knowledge gaps exist in the use of biologics for pregnant patients with Crohn's disease (CD), especially the usage of ustekinumab (UST) and infliximab (IFX) infusion during the late gestation period. In this case series, we investigated perinatal and neonatal outcomes and pharmacokinetics of these biologics in pregnant CD patients. METHODS: Pregnant CD patients under treatment with IFX or UST during January 2017 to December 2019 were monitored. Growth and development of their babies were followed up to six months. Drug concentrations were measured in maternal peripheral and cord blood at delivery and infants' blood at six months of age. RESULTS: Four cases were kept IFX treatment until late gestation (median last dose: 31.2 weeks). One case received UST until 23 weeks of gestation. All cases were in clinical remission but moderately undernourished. Babies were delivered by cesarean section at full term without any complications or congenital abnormalities. No growth or developmental defects and no susceptibility to infections were observed by six months. However, two babies whose mothers received IFX after 30 weeks of gestation were detected IFX in their blood at six months of age (0.94 and 0.24 pg/ml). Concentrations of UST in maternal and cord blood were 267.7 and 756.5 ng/ml, respectively. UST was not detected in the infant at six months of age. CONCLUSIONS: Administration of UST or IFX to pregnant patients with CD is safe, particularly IFX to be given in the late gestation period. Understanding of the pharmacokinetics of biologics in maternal-infant interactions may improve the management of pregnant CD patients.
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PURPOSE OF REVIEW: The prevalence of chronic upper airway inflammatory diseases such as allergic rhinitis and chronic rhinosinusitis (CRS) is increasing markedly posing a potential health threat globally. The involvement of the upper respiratory microbiota in chronic inflammatory diseases of the upper airways has been of considerable interest. The purpose of this review is to understand the characteristics of upper respiratory microbiota in both healthy and chronic inflammatory diseases of the upper airways like allergic rhinitis and CRS and to know the potential role of interventions with probiotics. RECENT FINDINGS: We present here the studies on the nasal microbiota in healthy infants, allergic rhinitis, and CRS. The results demonstrate that there are stable and unstable profiles of microbiota during infancy. Decreased diversity or an imbalance of the microbial composition could be an important factor in the development of both allergic rhinitis and CRS. We also discuss here several recent animal and human studies that demonstrate the effect of probiotics in allergic rhinitis and chronic rhinosinusitis. Results from human studies (clinical trials) have demonstrated that probiotics may be effective for allergic rhinitis, but there are no consistent results in human CRS trials. SUMMARY: Several strains of probiotics revealed potential efficacy for allergic rhinitis but not for CRS. Large clinical trials are essential to establish robust data on probiotics for chronic inflammatory upper airways diseases like allergic rhinitis and CRS.
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Inflamação/microbiologia , Microbiota/imunologia , Sistema Respiratório/microbiologia , Rinite Alérgica/microbiologia , Rinite/microbiologia , Animais , Doença Crônica , Ensaios Clínicos como Assunto , Humanos , Probióticos/uso terapêutico , Sistema Respiratório/imunologia , Rinite/imunologia , Rinite/terapia , Rinite Alérgica/imunologia , Rinite Alérgica/terapiaRESUMO
Food-dependent exercise-induced anaphylaxis (FDEIA) is a life-threatening but relatively rare disorder which occurs mainly in older children and young adults and manifests with symptoms of anaphylaxis upon exercise following ingestion of certain kinds of food. We herewith report 3 cases of soybean-induced FDEIA. We also highlight 2 types of soybean-induced FDEIA, one caused by storage protein components Gly m 5 and Gly m 6 and the other caused by pollen-related allergen components.
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Hemophagocytic lymphohistiocytosis (HLH) associated with Epstein-Barr virus (EBV) infection can be self-limiting, severe/aggressive, or fatal. We report a case of EBV-HLH with persistent fever, severe pancytopenia, hypertriglyceridemia, and hypofibrinogenemia in a 4-year-old boy. Levels of plasma cytokines and chemokines were measured with a Bio-Plex system at 1, 2, 3, 4, 5, and 8 days after hospital admission. Administration of steroid and high-dose intravenous immunoglobulin (1 g/kg) did not alleviate fever or reduce cytokine production; however, after administration of etoposide (an antineoplastic agent), fever decreased immediately, the patient's general condition improved, and levels of IL-6, IL-10, IL-8, MCP-1, IFN-γ, and TNF-α declined after etoposide administration. In particular, IFN-γ production sharply declined, from 1,104.1 pg/mL to 101.5 pg/mL, and IL-6 level decreased from 229.8 pg/mL to 11.0 pg/mL, on the day after initial etoposide administration. There was no later recurrence of symptoms during treatment with dexamethasone, etoposide, and cyclosporine A. This case suggests that early etoposide administration is critical for treatment success and indicates that etoposide promptly inhibits cytokine production.
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Citocinas/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Etoposídeo/administração & dosagem , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Pré-Escolar , Infecções por Vírus Epstein-Barr/metabolismo , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoterapia , Linfo-Histiocitose Hemofagocítica/metabolismo , Masculino , Resultado do TratamentoRESUMO
X-Linked severe combined immunodeficiency (X-SCID) is a severe form of primary immunodeficiency characterized by absence of T cells and NK cells. X-SCID is caused by a loss-of-function mutation in the IL2RG gene that encodes common gamma chain (γc), which plays an essential role in lymphocyte development. We report the first case of hypomorphic X-SCID caused by a synonymous mutation in the IL2RG gene leading to a splice anomaly, in a family including two patients with diffuse cutaneous warts, recurrent molluscum contagiosum, and mild respiratory infections. The mutation caused aberrant splicing of IL2RG mRNA, subsequently resulted in reduced γc expression. The leaky production of normally spliced IL2RG mRNA produced undamaged protein; thus, T cells and NK cells were generated in the patients. Functional assays of the patients' T cells and NK cells revealed diminished cytokine response in the T cells and absent cytokine response in the NK cells. In addition, the TCR repertoire in these patients was limited. These data suggest that a fine balance between aberrant splicing and leaky production of normally spliced IL2RG mRNA resulted in late-onset combined immunodeficiency in these patients.
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Subunidade gama Comum de Receptores de Interleucina , Mutação , Sítios de Splice de RNA , Splicing de RNA , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/imunologia , Adolescente , Feminino , Humanos , Subunidade gama Comum de Receptores de Interleucina/genética , Subunidade gama Comum de Receptores de Interleucina/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Masculino , Splicing de RNA/genética , Splicing de RNA/imunologia , Linfócitos T/imunologia , Linfócitos T/patologia , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/patologiaRESUMO
BACKGROUND: Therapeutic outcomes for childhood malignancy have dramatically improved. However, secondary malignancies are a major concern, as they greatly affect the quality of life of survivors. This retrospective study evaluated the cumulative incidence, clinical features, and outcomes of secondary malignancies at Nippon Medical School Hospital. METHODS: We examined data from 275 cases of primary childhood malignancy diagnosed between 1980 and 2014. Information regarding treatment of the primary malignancy, including irradiation dose, site, and cumulative dose of anticancer drugs, was assessed. We also collected data on secondary malignancy, including patient sex, age at diagnosis, malignancy site, time from primary to secondary malignancy, and outcomes. RESULTS: Secondary malignancies developed in 11 patients and included acute myeloid leukemia (AML) (4), meningioma (4), Ewing sarcoma (1), germ cell tumor (1), and malignant parotid gland tumor (1). The primary malignancies included acute lymphoblastic leukemia (ALL) (9), non-Hodgkin lymphoma (1) and brain tumor (1). In 7 of the 9 ALL patients, chemoradiotherapy was the primary treatment. The meningiomas and 1 solid tumor developed within the radiation field. All AMLs and meningiomas developed within 5 years and after 20 years, respectively, of the primary diagnosis. The 10- and 20-year cumulative incidence rates for secondary malignancy in our hospital were 1.9% and 5.8%, respectively. CONCLUSIONS: Our results revealed that the type of secondary malignancy depends on the interval after the end of treatment for primary malignancy. Meningioma, notably, develops many years after completion of primary malignancy treatment. Early detection during long-term follow-up is therefore essential.
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Neoplasias Ósseas/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Sarcoma de Ewing/epidemiologia , Quimiorradioterapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
A 6-year-old female was admitted with abdominal pain and a mass in the right abdomen. Her lactose dehydrogenase level was 1,200 IU/L, and neuron specific enolase was 120 ng/ml. Computed tomography scan confirmed a large right renal mass with necrosis. A right radical nephrectomy was performed. The tumor was completely encapsulated. Based on small round cell histology, strong MIC-2 (CD99) positive tumor cells, and EWS-FLI-1 fusion transcript, Ewing sarcoma/primitive neuroectodermal tumor of the kidney was diagnosed. Induction and follow-up with seven cycles of chemotherapy were given after surgery. She has had no evidence of recurrence 90 months from diagnosis.
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Neoplasias Renais/diagnóstico , Tumores Neuroectodérmicos Primitivos Periféricos/diagnóstico , Sarcoma de Ewing/diagnóstico , Criança , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Tumores Neuroectodérmicos Primitivos Periféricos/terapia , Sarcoma de Ewing/patologia , Sarcoma de Ewing/terapiaRESUMO
Gastric colonization of Helicobacter pylori (H. pylori) occurs in a very early age via infected mothers having H. pylori-specific IgG antibodies that would be transplacentally transferred to infants. In addition, H. pylori urease-specific IgG was associated with chronic gastric atrophy and post-immunization gastritis is usually correlated with a strong local IgG response. These findings indicate that H. pylori-specific IgG antibodies, in particular its urease-specific IgG, may induce unfavorable influence on host resistance against H. pylori. Here, we show that we have found a unique H. pylori urease-specific IgG monoclonal antibody (MAb), termed S3, recognizing the conformational structure of the small subunit Ure-A, which enhanced the urease enzymatic activity. Such enhancement of the H. pylori urease activity induced by 1 microg of S3 was almost completely cancelled by simultaneously added the same amount of L2 MAb, which has a strong and specific inhibitory activity against H. pylori urease and recognizes a liner epitope of 8-mer peptide (F8: SIKEDVQF) within its large subunit Ure-B (Infect. Immun. 69: 6597, 2001). Intravenous pre-administration of purified S3 into BALB/c mice showed significant augmentation for gastric colonization with the susceptible strain Sydney Strain-1 (SS-1). To our knowledge, this is the first demonstration that a H. pylori urease-specific IgG MAb induced an augmentation of their gastric colonization in vivo.
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Helicobacter pylori/enzimologia , Helicobacter pylori/imunologia , Urease/imunologia , Urease/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Especificidade de Anticorpos , Antígenos de Bactérias/genética , Mapeamento de Epitopos , Feminino , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Gastrite/imunologia , Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/crescimento & desenvolvimento , Imunoglobulina G/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Urease/genéticaRESUMO
PURPOSE OF REVIEW: Cytokines are immunomodulatory proteins important in cell signaling. Complex interactions of innate and adaptive immune cells, as well as structural cells and their cytokines, play crucial roles in regulating allergic airway inflammation. Here, we summarize current knowledge about the potential roles of known and newly identified helper T cells and epithelial cell-derived cytokines [interleukin (IL)-9, IL-17, IL-22, IL-25, and IL-33] in allergic rhinitis and asthma. RECENT FINDINGS: Although T-helper (Th)2 cells were considered to be the main orchestrators of allergic airway inflammation, recent studies have revealed the potential interaction of other helper T cells and their cytokines in this process. Th17 cells may have a role in allergic rhinitis and asthma, and chronic rhinosinusitis with nasal polyps. An IL-9-producing subset called Th9 cells, Th22 cells which primarily secrete IL-22, IL-13, tumor necrosis factor-α, Th25 cells via producing IL-25 and epithelial cell-derived thymic stromal lymphopoietin, IL-33, IL-31, and IL-25 are believed to be important for the initiation of allergic reactions and inducing airway inflammation. SUMMARY: A new paradigm of an interplay of cytokines is important in allergic rhinitis and asthma in orchestrating the allergic inflammatory response. Potential therapeutic applications emerging from the roles of these cytokines are promising, but need further research.
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Asma/imunologia , Citocinas/imunologia , Mucosa Respiratória/imunologia , Rinite Alérgica/imunologia , Células Th2/imunologia , Animais , Humanos , Inflamação/imunologiaRESUMO
Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
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Envelhecimento , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Tilosina/farmacologia , Amoxicilina/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Metabolismo Energético/fisiologia , Fezes/química , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metagenômica , Camundongos , Camundongos Endogâmicos C57BL , Transcriptoma , Tilosina/administração & dosagemRESUMO
DnaK is required for adaptation to environmental stress and is also involved in bacterial growth under normal conditions. To examine whether DnaK plays a role in the expression of genes related to pathogenicity of Listeria monocytogenes, the transcription of flaA, iap and lmaA in a dnaK mutant was analyzed. Northern blot analysis showed that expression of flaA and lmaA mRNAs was reduced in the dnaK mutant, THY-LK1. A reporter assay revealed that transcription of lmaB in the dnaK mutant, LKS01, constructed in this study was lower than that in the parental strain. In contrast, the dnaK mutation had no effect on the transcription of iap. These results suggest that DnaK is involved in the transcription of flaA and lmaB.