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1.
Biochem Biophys Res Commun ; 645: 47-54, 2023 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-36680936

RESUMEN

Interleukin (IL)-31 is a recently-identified cytokine with a well-defined role in the pathogenesis of pruritus. Previously, we reported that adenosine upregulates IL-17A secretion by T-helper (Th)17 cells; however, the effect of adenosine on T cell subsets other than Th17 remains unclear. In this report, we show that adenosine upregulated production of IL-31 by cluster of differentiation (CD)4+ T cells. IL-31 was also upregulated by administration of an adenosine A2a receptor (A2aR) agonist (PSB0777), and adenosine-mediated IL-31 production was inhibited by an A2aR antagonist (istradefylline). Production of Th2-related cytokines (IL-4, IL-10, and IL-13) by CD4+ T cells showed the same tendency. Immune subset analyses revealed that adenosine upregulated IL-31 secretion by CD4+ chemokine receptor 3high T cells, and that Th2 cells differentiated from naïve CD4+ T cells. Administration of istradefylline to mice with atopic dermatitis suppressed the symptoms, suggesting that A2aR antagonists are an effective treatment for inflammatory dermatitis. Taken together, the results indicate that adenosine upregulates secretion of Th2-related cytokines by effector T cells in the skin, thereby triggering atopic dermatitis and associated pruritus.


Asunto(s)
Adenosina , Dermatitis Atópica , Interleucinas , Células Th2 , Animales , Ratones , Adenosina/metabolismo , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Prurito , Interleucinas/metabolismo
2.
J Infect Chemother ; 29(8): 825-828, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37187412

RESUMEN

The promising diagnostic performance of rapid antigen tests (RATs) using non-invasive anterior nasal (AN) swab specimens to diagnose COVID-19 has been reported. A large number of RATs are commercially available; however, the careful assessment of RATs is essential prior to their implementation in clinical practice. We evaluated the clinical performance of the GLINE-2019-nCoV Ag Kit as a RAT using AN swabs in a prospective, blinded study. Adult patients who visited outpatient departments and received SARS-CoV-2 tests between August 16 and September 8, 2022, were eligible for this study. Patients who were aged under 18 years and patients without appropriate specimens were excluded. Two sets of AN and nasopharyngeal (NP) swabs were collected from all patients. Each set of specimens was tested by the RAT and quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Of the 138 recruited patients, 84 were positive and 54 were negative by RT-qPCR using NP swabs. The positive agreement rate between RT-qPCR using NP swabs and RAT using AN swabs was 78.6% (95% confidence interval [CI], 68.3%-86.8%), the negative agreement rate was 98.1% (95% CI, 90.1%-99.9%), and the overall agreement rate was 86.2% (95% CI, 79.3%-91.5%), with a κ coefficient of 0.73. The positive agreement rate in the early phase (≤3 days from symptom onset) was >80%, but this fell to 50% in the late phase (≥4 days). This study demonstrates that the GLINE-2019-nCoV Ag Kit using AN swabs has good clinical performance and might be a reliable alternative method for diagnosing COVID-19.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Cavidad Nasal , Estudios Prospectivos , Pruebas Inmunológicas , Nasofaringe , Sensibilidad y Especificidad
3.
Infect Prev Pract ; 6(1): 100332, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38292208

RESUMEN

Case: A 36-year-old female healthcare worker with no past medical history, accidentally injected her flexed right middle finger with live attenuated Mycobacterium bovis bacillus Calmette-Guérin (BCG). Swelling and erythema around the injured area appeared two days after the needlestick injury. She was referred to the hospital and presented approximately nine days after self-inoculation. Surgical debridement was immediately performed. After 38 days, colonies were observed on cultures of the removed tissue on Ogawa's medium. This isolate was identified as M. bovis BCG by polymerase chain reaction (PCR) based on RD1 gene deletion. She had a history of BCG vaccination and her skin lesion appeared immediately after the accidental injection of M. bovis BCG. Therefore, in the differential diagnosis, the possibility that the lesion was an allergic reaction to BCG was considered. The subsequent culture results came back positive for M. bovis BCG and acute tenosynovitis caused by M. bovis BCG was diagnosed. The skin lesion was treated with anti-mycobacterial drugs and resolved. Discussion: The allergic reactions to BCG should be considered in the differential diagnosis of skin lesions following BCG vaccination. It is important to promptly submit a specimen for culture as delayed initiation of appropriate treatment can lead to a poor prognosis. In patients with accidental injection of M. bovis BCG, it is important to consider timely surgical excision and appropriate antimycobacterial therapy.

4.
Microbiol Spectr ; 12(1): e0244423, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38100166

RESUMEN

IMPORTANCE: Our study emphasizes the efficacy of whole-genome sequencing (WGS) in addressing outbreaks of vancomycin-resistant enterococci. WGS enables the identification and tracking of resistant bacterial strains, early detection and management of novel infectious disease outbreaks, and the appropriate selection and use of antibiotics. Furthermore, our approach deepens our understanding of how resistant bacteria transfer genes and adapt to their environments or hosts. For modern medicine, these insights have significant implications for controlling infections and effectively managing antibiotic use in the current era, where antibiotic resistance is progressing.


Asunto(s)
Enterococcus faecium , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Humanos , Enterococos Resistentes a la Vancomicina/genética , Epidemiología Molecular , Vancomicina/farmacología , Vancomicina/uso terapéutico , Enterococcus faecium/genética , Japón/epidemiología , Tipificación de Secuencias Multilocus , Antibacterianos/farmacología , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Proteínas Bacterianas/genética
5.
IDCases ; 36: e01943, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646599

RESUMEN

Malignant syphilis (MS) is a rare variant of secondary syphilis. Also known as rupioid syphilis, MS is characterized by the presence of multiple papules, papulopustules, black lamellate crust that may resemble an oyster shell, or nodules with ulceration lacking central clearing. MS is often associated with immunodeficiency and frequently co-occurs with HIV infection. We here report a case of MS in a patient with HIV infection. HIV infection can cause atypical clinical symptoms of syphilis. In this case, unlike previous cases, cutaneous lesions of MS were limited to the face, making the diagnosis challenging based on clinical findings alone. However, his laboratory findings, appearance of the Jarisch-Herxheimer reaction, and a dramatic response to antibiotic therapy are characteristic of MS, making the diagnosis even more certain. Our case suggests the importance of physicians considering the possibility of MS when observing black-crusted lesions.

6.
Infect Dis Rep ; 16(2): 356-366, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38667753

RESUMEN

Candidemia, linked to high mortality rates, requires prompt antifungal therapy for better outcomes. Treatment is structured as an action bundle, which is beneficial when followed closely. However, the Japanese action bundle lacks detailed guidance on severe complications like endocarditis or ocular issues. To address this, we adjusted the action bundle and assessed outcomes with and without AFT intervention. We strengthened protocols for blood cultures and organ assessments, and the AFT contacted the primary physician when yeast-like fungi were detected in the patient's blood culture bottles. Analyzing 204 candidemia cases from 2008-2021, we observed increased adherence and reduced mortality post-AFT intervention. Ophthalmology consultations rose significantly, but many patients had only one visit, suggesting inadequate follow-up. If endophthalmitis is diagnosed, a change in the treatment approach may be necessary. There is a possibility that abnormal ocular findings will be detected during subsequent visits, which highlights the need for improvement in ophthalmology follow-up rates as a future challenge for our AFT activities.

7.
IDCases ; 31: e01654, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36478666

RESUMEN

We report a case of Talaromyces marneffei fungemia in a patient with HIV infection with a history of travelling to southern China. At first, Pneumocystis pneumonia was considered in this case because chest CT images showed typical ground-glass opacity and elevated ß-D-glucan levels. However, PCR testing of sputum for Pneumocystis jirovecii was negative and a filamentous fungus was isolated from blood cultures. The cultured fungus was subsequently identified as T. marneffei, and the patient was considered to have pneumonia caused by this organism. However, skin disease and lymphadenopathy, which are common in T. marneffei infections, were not observed during the disease course. This patient was successfully treated with voriconazole and consequently the chest CT shadow disappeared. In the present case, T. marneffei infection required differentiation from pneumonia with Pneumocystis jirovecii infection.

8.
Intern Med ; 62(13): 1989-1993, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36418098

RESUMEN

A 67-year-old woman with a 2-day history of a fever, headache and disturbed consciousness was admitted to our hospital. Bacillus subtilis was isolated from both the cerebrospinal fluid and blood. She was cured by the administration of vancomycin. Next-generation sequencing identified the strain as B. subtilis var. natto, the same strain found in natto, which this patient ate daily. We suspected that some of the B. subtilis that caused the infection may have actually been B. subtilis var. natto.


Asunto(s)
Bacillus subtilis , Meningitis Bacterianas , Femenino , Humanos , Anciano , Bacillus subtilis/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Meningitis Bacterianas/complicaciones , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/tratamiento farmacológico
9.
Immunol Med ; 45(4): 244-250, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35790489

RESUMEN

Extracellular adenosine produced from ATP plays a role in energy processes, neurotransmission, and inflammatory responses. Istradefylline is a selective adenosine A2a receptor (A2aR) antagonist used for the treatment of Parkinson's disease. We previously showed using mouse models that adenosine primes hypersecretion of interleukin (IL)-17A via A2aR, which plays a role in neutrophilic inflammation models in mice. This finding suggests that adenosine is an endogenous modulator of neutrophilic inflammation. We, therefore, investigated the in vitro effect of istradefylline in humans. In the present study, using human peripheral blood mononuclear cells (PBMCs), we tested the effect of adenosine, adenosine receptor agonists and istradefylline on cytokine responses using mixed lymphocyte reaction (MLR), PBMCs, CD4+ T cells, and Candida albicans antigen (Ag)-stimulated PBMCs. We showed that adenosine and an A2aR agonist (PSB0777) promoted IL-17A and IL-8 production from human PBMCs, and istradefylline suppressed this response. In addition, istradefylline inhibited not only the IL-17A and IL-8 production induced by adenosine but also that from C. albicans Ag-stimulated PBMCs. These results indicate that adenosine-mediated IL-17A and IL-8 production plays a role in neutrophilic inflammation, against which istradefylline should be effective.


Asunto(s)
Antagonistas del Receptor de Adenosina A2 , Receptor de Adenosina A2A , Animales , Humanos , Ratones , Antagonistas del Receptor de Adenosina A2/farmacología , Interleucina-17 , Interleucina-8/farmacología , Antagonistas de Receptores Purinérgicos P1/farmacología , Leucocitos Mononucleares , Linfocitos T , Adenosina/farmacología , Linfocitos T CD4-Positivos , Inflamación
10.
Brain Behav Immun Health ; 26: 100544, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36467126

RESUMEN

Extracellular adenosine, produced from ATP secreted by neuronal or immune cells, may play a role in endogenous regulation of inflammatory responses. Studies show that adenosine induces hypersecretion of IL-17A by CD4+ T cells upon treatment with an A2aR agonist (PSB0777), and that adenosine-mediated IL-17A hypersecretion is suppressed by the A2aR antagonist (Istradefylline) in humans. However, it is unclear whether A2aR downstream signaling is involved in IL-17A hypersecretion. Here, we show that inhibitors of adenyl cyclase (AC), protein kinase A (PKA), and cAMP response element binding protein (CREB) (which are signaling molecules downstream of the Gs protein coupled to the A2aR), suppress IL-17A production, suggesting that activation of A2aR signaling induces IL-17A production by CD4+ T cells. Furthermore, immune subset studies revealed that adenosine induces hypersecretion of IL-17A by T-helper (Th)17 cells. These results indicate that adenosine is an endogenous modulator of neutrophilic inflammation. Administration of an A2aR antagonist to mice with experimental autoimmune encephalomyelitis led to marked amelioration of symptoms. Thus, inhibitors of the novel A2aR-AC-cAMP-PKA-CREB signaling pathway for IL-17A hypersecretion by TCR-activated Th17 cells suppresses adenosine-mediated IL-17A production, suggesting that it may be an effective treatment for Th17-related autoimmune diseases.

11.
Immunol Med ; 45(3): 162-167, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35623041

RESUMEN

B-cell but not T-cell responses have been extensively studied using peripheral blood mononuclear cells (PBMCs) obtained from patients with coronavirus disease 2019 (COVID-19). Our recent study showed that not only T-helper (Th) 17 but also Th1 cells directly produce interleukin (IL)-8, a major source of neutrophilic inflammation, which is also known to induce disseminated intravascular coagulation (DIC) in COVID-19 patients. Neutrophilic inflammation caused by IL-17A or IL-8 can be fatal; thus, therapeutic intervention is highly expected. The present study aimed to investigate the T-cell responses in the Japanese patients. We synthesized spike protein-derived 15-mer peptides that are expected to bind to HLA class II allelic products frequently observed in the Japanese population, and checked the T-cell responses in Japanese patients with COVID-19. We have found that (i) patients show marked IL-8 but not IL-17A responses; (ii) these responses are restricted by HLA-DR; and (iii) IL-8 responses are abrogated by a dopamine D2 like receptor (D2R) agonist, ropinirole, and an adenosine A2a receptor (A2aR) antagonist, istradefylline. Compounds used for the treatment of Parkinson's disease may ease DIC in COVID-19. (183 words).


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Dopamina , Linfocitos T , Agonistas de Dopamina/farmacología , Humanos , Inflamación , Interleucina-8 , Leucocitos Mononucleares/metabolismo , Antagonistas de Receptores Purinérgicos P1 , Receptor de Adenosina A2A/metabolismo , Linfocitos T/inmunología
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