Chromosomal AmpC β-lactamase induction by several types of β-lactams has been reported, but not enough data are available on DHA-1 β-lactamase, a plasmid-mediated AmpC β-lactamase. Therefore, we evaluated the DHA-1 β-lactamase induction by various antibiotics including piperacillin/tazobactam (PIP/TZB) in this study. Six strains (Enterobacter cloacae 2 strains, Citrobacter freundii 1 strain, Serratia marcescens 2 strain, and Morganella morganii 1 strain) possessing chromosomal inducible AmpC β-lactamase were used as controls. Four strains (Escherichia coli 2 strains, Klebsiella pneumoniae 1 strain, and C. koseri 1 strain) possessing DHA-1 β-lactamase were used. The β-lactamase activities were determined by a spectrophotometer using nitrocefin. β-lactamase induction by PIP, PIP/TZB was not observed in any strains and β-lactamase induction by third- and fourth-generation cephems was not observed in most strains. The induction ratios of the chromosomal AmpC β-lactamase in the reference group by PIP/TZB were <1.51, and those of the DHA-1 β-lactamase were <1.36, except for K. pneumoniae Rkp2004 (2.22). The β-lactamase induction by first- and second-generation cephems, flomoxef, and carbapenem differed in each strain. Cefmetazole (CMZ) strongly induced β-lactamase. This study demonstrated that the induction of DHA-1 β-lactamase was similar to that of chromosomal AmpC using various Enterobacteriaceae, although the induction of β-lactamase in both groups by PIP/TZB was low. We also reported that the induction of PIP/TZB, a β-lactamase inhibitor combination antibiotic, against various AmpC-producing Enterobacteriaceae, including DHA-1 producers, was low.
Background Lower respiratory tract infections (LRTI, bronchiectasis, bronchitis and bronchiolitis) are common comorbidities in patients with rheumatoid arthritis (RA). According to the recent advances of the treatment modalities of RA and other collagen vascular diseases (CVD) including anti-inflammatory biological agents, an aggressive diagnosis of LRTI including nontuberculous mycobacteriosis (NTM) is becoming more important. Patients and Methods From April 2008 to August 2011, patients with RA and other CVD with suspicion of NTM were enrolled. Additionally, patients with non-CVD with suspicion of NTM were also enrolled as controls. Bronchial washing were directly obtained from the pathological lesions, and bacteriological analyses were demonstrated. Chest CT findings were also evaluated. Results A total of 106 patients (41 with RA, 22 with CVD other than RA and 43 with non-CVD) were enrolled. P. aeruginosa (26.8%) were the most frequently detected in patients with RA, followed by S. aureus (19.5%) and NTM (7.3%). In patients with CVD other than RA, P. aeruginosa (9.1%), S. aureus (13.6%), NTM (4.5%) were detected. Additionally, P. aeruginosa (7.0%), S. aureus (11.6%) and NTM (25.6%) were detected in non-CVD patients. Chest CT findings of patients with RA complicating P. aeruginosa infection demonstrated that these patients showed more widespread of granular opacities and bronchiectasis and tendency of exacerbation of these pathological lesions. Conclusion P. aeruginosa was frequently detected in patients with RA complicating LRTI, and it is speculated that P. aeruginosa infection in patients with RA seemed to be an indicative factor of exacerbation of LRTI.
A 36-year-old Japanese man presented with cavities and nodular shadows in the lower lobes of his lungs and osteolytic lesions in the thoracic spine. He was diagnosed with multisystem Langerhans cell histiocytosis (LCH). Three years earlier, he had been noted to have small cavities and granular lesions noted in the upper lobes of his lungs, which later improved with smoking cessation. It was likely that his single-system pulmonary LCH (PLCH) progressed to multisystem LCH despite smoking cessation. Relapse or progression may occur in cases where PLCH lesions improve after smoking cessation. Thus, close follow-up is vital.
An eighty-nine-year-old Japanese male was admitted to our hospital due to dry cough and dyspnea.Respiratory symptoms appeared soon after an administration of an oriental medicine, Kamikihito for tinnitus.Upon admission, chest computed tomography showed patchy consolidations and ground-glass opacities in the right upper lobe of the lungs, and ground-glass opacities in the bilateral lower lobes.Sulbactam-ampicillin combination (SBT/ ABPC, 3 g × 2/day) was started in addition to the change or cessation of several other drugs, including Kamikihito, resulting in respiratory symptoms and chest radiographic exacerbations.Bronchoalveolar lavage fluid obtained from the right S 3 showed an increase in the total cell number of lymphocytes.A drug lymphocyte stimulation test (DLST) for Kamikihito was also positive.Kamikihito-induced lung injury was most likely, and treatment with prednisolone (50 mg/day) was started.His respiratory symptoms and chest radiographic findings improved rapidly soon after initiating oral prednisolone.This is the first report of Kamikihito-induced lung injury.
The advancement in generative AI could be boosted with more accessible mathematics. Beyond human-AI chat, large language models (LLMs) are emerging in programming, algorithm discovery, and theorem proving, yet their genomics application is limited. This project introduces Math Agents and mathematical embedding as fresh entries to the "Moore's Law of Mathematics", using a GPT-based workflow to convert equations from literature into LaTeX and Python formats. While many digital equation representations exist, there's a lack of automated large-scale evaluation tools. LLMs are pivotal as linguistic user interfaces, providing natural language access for human-AI chat and formal languages for large-scale AI-assisted computational infrastructure. Given the infinite formal possibility spaces, Math Agents, which interact with math, could potentially shift us from "big data" to "big math". Math, unlike the more flexible natural language, has properties subject to proof, enabling its use beyond traditional applications like high-validation math-certified icons for AI alignment aims. This project aims to use Math Agents and mathematical embeddings to address the ageing issue in information systems biology by applying multiscalar physics mathematics to disease models and genomic data. Generative AI with episodic memory could help analyse causal relations in longitudinal health records, using SIR Precision Health models. Genomic data is suggested for addressing the unsolved Alzheimer's disease problem.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.
