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Degradation of (S)-1,3-butanediol in Pseudomonas putida KT2440 reveals a CoA-activation route and enantiomeric crosstalk between (R)- and (S)-3-hydroxybutyrate catabolism.

1,3-Butanediol (1,3-BDO) exists as (R)- and (S)-enantiomers, yet how aerobic bacteria catabolize the (S)-form has been unknown. Here, we define (S)-1,3-BDO degradation pathway in Pseudomonas putida KT2440 and uncover an enantioselective enzyme that both controls the pathway and enables a chiral resolution. Transcriptomics, quantitative RT-PCR, and systematic gene deletions show that the ped cluster oxidizes (S)-1,3-BDO to (S)-3-hydroxybutyrate [(S)-3-HB] using the same upstream machinery as (R)-1,3-BDO and 1,4-BDO, but that the downstream route then diverges sharply. Rather than the free-acid

Severe Orolingual and Laryngeal Angioedema after Thrombolysis with Alteplase: Angiotensin II Receptor Blockers Should Not Be Underestimated.

INTRODUCTION: Alteplase is a recombinant tissue plasminogen activator (rt-PA), used for intravenous thrombolysis in ischaemic strokes. Orolingual angioedema is a rare but potentially lifethreatening complication of alteplase. Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors has been identified as a primary risk factor. Angiotensin II receptor blockers (ARBs) have been rarely related to angioedema. CASE PRESENTATION: A 72-year-old woman with a personal history of type 1 diabetes mellitus, dyslipidemia, stage 3 CKD, and arterial hypertension, in treatment with valsartan

Abnormal immunity of non-survivors with COVID-19: predictors for mortality.

BACKGROUND: The number of coronavirus disease 2019 (COVID-19) cases has rapidly increased all over the world. Specific information about immunity in non-survivors with COVID-19 is scarce. This study aimed to analyse the clinical characteristics and abnormal immunity of the confirmed COVID-19 non-survivors. METHODS: In this single-centered, retrospective, observational study, we enrolled 125 patients with COVID-19 who were died between January 13 and March 4, 2020 in Renmin Hospital of Wuhan University. A total of 414 randomly recruited patients with confirmed COVID-19 who were discharged from

[Adrenal hemorrhage in a patient with systemic lupus erythematosus].

A 58-year-old female was referred to our department with intermittent suffocation for 1.5 years, aggravated for a month. 1.5 years before she developed oral ulcer, raynaud phenomenon, proteinuria, bilateral pleural effusion, ANA and anti-dsDNA positive. This patient was diagnosed with systemic lupus erythematosus (SLE). After given hormones, hydroxychloroquine sulfate (HCQ), her symptom relieved soon. The patient stopped her pills 1 year ago. One month ago, she had chest tightness, increased urine foam, and suffered from oliguria. Her admission medical examination: blood pressure (BP) 130/80 m

Dietary vitamin C deficiency depressed the gill physical barriers and immune barriers referring to Nrf2, apoptosis, MLCK, NF-κB and TOR signaling in grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare.

This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activitie

[Skin diseases and hepatitis virus C infection].

INTRODUCTION: Using a creative molecularbiologic technique in 1989 Choo and co-workers isolated a new virus of hepatitis C, an agent responsible for numerous cases of parenterally transmissible viral hepatitis. Hepatitis C virus is a RNA virus with unique genomic organisation. Six genotypes of hepatitis C virus have been identified, which differ in geographical distribution, tendency towards chronicity and sensitivity to antiviral therapy. Transmission occurs due to apparent and inapparent parenteral procedures (after transfusion, transplantation, transplacentally, during lactation, sexually o

Genetics of immune response: a survey.

The mouse has served as an invaluable model for investigations of immune response (Ir) genes. Of most importance has been major histocompatibility complex (MHC) linked Ir genes. The MHC genes have been demonstrated to be the prime factor in determination of the ability to respond to an antigenic stimulus. One of the more intriguing findings has been the capacity of a relatively small number of Ir genes to determine immune reactivity to a diverse collection of antigens. This review will deal with the extent of the antigen diversity and the nature of the antigenic determinants. Data are summariz

Stromal cell independent B cell development in vitro: generation and recovery of autoreactive clones.

We describe and characterize a stromal cell independent culture system that efficiently supports pro-B cell to IgM+ B cell development with near normal levels of IgH and Igkappa diversity. Pro-B cells present in non-adherent bone marrow cells proliferate in the presence of IL-7 and subsequent to the removal of IL-7 and addition of BAFF, differentiate normally into IgM+ B cells. B cell development in vitro closely follows the patterns of development in vivo with culture-derived (CD) B cells demonstrating characteristic patterns of surface antigen expression and gene activation. IgM+ CD B cells

Erlotinib-induced Perioral Lesions Resembling Scleroderma.

Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is currently used in the therapy of several solid malignancies. This agent has been associated with several dermatological side-effects, the most common being papulo-pustular acneiform rash. Herein we describe a unique skin effect in a patient treated with erlotinib for non-small cell lung cancer. A 68-year-old Caucasian woman presented with complaints of an unusual perioral rash associated with redness and pain. A "feeling of tension" that interfered with chewing was described by the patient. She denied myalg

Vasculitis in systemic lupus erythematosus (SLE)--assessment of peripheral blood mononuclear cell activation and the degree of endothelial dysfunction: initial report.

BACKGROUND: Inflammatory-immune changes in the vascular endothelium are one of the main factors initiating vessel wall damage. Enhanced expression of endothelial adhesion molecules and their receptors on the surface of circulating leukocytes seems to play an important role in the pathogenesis of vasculitis. Increasing evidence indicates endothelial cell activation/damage in SLE. In patients with SLE complicated by vasculitis, enhanced expression of integrin activation markers on the surface of peripheral blood mononuclear cells (PBMCs) has been reported. It seems relevant to assess the mechani

Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management.

Drug-induced thrombotic microangiopathy (DITMA) represents 10%-13% of all thrombotic microangiopathy (TMA) cases and about 20%-30% of secondary TMAs, just behind pregnancy-related and infection-related forms. Although the list of drugs potentially involved as causative for TMA are rapidly increasing, the scientific literature on DITMA is quite scarce (mostly as individual case reports or little case series), leading to poor knowledge of pathophysiological mechanisms and clinical management. In this review, we focused on these critical aspects regarding DITMA. We provided an updated list of TMA

Combined Immune Defect in B-Cell Lymphoproliferative Disorders Is Associated with Severe Infection and Cancer Progression.

B cell chronic lymphoproliferative diseases (B-CLPD) are associated with secondary antibody deficiency and other innate and adaptive immune defects, whose impact on infectious risk has not been systematically addressed. We performed an immunological analysis of a cohort of 83 B-CLPD patients with recurrent and/or severe infections to ascertain the clinical relevance of the immune deficiency expression. B-cell defects were present in all patients. Patients with combined immune defect had a 3.69-fold higher risk for severe infection (p = 0.001) than those with predominantly antibody defect. Inte

Excessive diagnostic testing in acute kidney injury.

BACKGROUND: The patterns, performance characteristics, and yield of diagnostic tests ordered for the evaluation of acute kidney injury (AKI) have not been rigorously evaluated. METHODS: We characterized the frequency of AKI diagnostic testing for urine, blood, radiology, and pathology tests in all adult inpatients who were admitted with or developed AKI (N = 4903 patients with 5731 AKI episodes) during a single calendar year. We assessed the frequency of abnormal test results overall and by AKI stage. We manually reviewed electronic medical records to evaluate the diagnostic yield of selected

Clinical Predictors of Non-Diabetic Kidney Disease in Patients with Diabetes: Insights from a Biopsy-Proven Cohort.

Background: Distinguishing diabetic nephropathy (DN) from non-diabetic kidney disease (NDKD) in patients with diabetes remains clinically challenging, particularly when renal biopsy is not routinely performed. We aimed to identify clinical predictors of biopsy-proven NDKD. Methods: We conducted a retrospective cohort study of patients with type 2 diabetes who underwent native kidney biopsy at a tertiary referral center. Patients were classified as DN alone, mixed DN with NDKD, or pure NDKD. Baseline clinical and laboratory variables were analyzed. Logistic regression models were used to identi

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… Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA, positive/negative), anti-double-stranded DNA (dsDNA, positive/negative), complement C3 (mg/dL), and complement C4 (mg/dL). … HbA1c showed the largest difference, followed by complement C4, renal function parameters (eGFR and creatinine), and immunologic markers, including anti-double-stranded DNA and lupus. …

Rituximab-Associated Flare of Cryoglobulinemic Vasculitis.

BackgroundPatients with cryoglobulinemic vasculitis (CV) can develop disease flare after rituximab administration. The objective of our study was to describe the prevalence, clinical characteristics, predisposing factors, and outcomes of patients with rituximab-associated flare of CV.MethodsWe conducted a retrospective study in a tertiary referral center until March 25, 2020.ResultsAmong 64 patients with CV who received rituximab therapy in our center, 14 (22%) developed disease flare. Median age was 67.5 years. Seven patients (50%) had type II CV and the other half had either type I (n = 6) o

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… Table 1 Comparison of patients with cryoglobulinemic vasculitis according to the presence of a disease flare following rituximab C4, complement C4; CKD, chronic kidney disease; CNS, central nervous system; Cr, creatinine; cryo, cryoglobulin; ESKD, end-stage kidney disease; GI, gastrointestinal; HCV, …

Risk factors for relapse in non-infectious cryoglobulinemic vasculitis, including type I cryoglobulinemia: a systematic review.

BackgroundData on non-infectious cryoglobulinemic vasculitis (NICV) is scarce, especially concerning the management of relapses, which are troublesome. We aimed to investigate risk factors for relapse in NICV.MethodsA systematic literature search of CINAHL, Embase, MEDLINE, Scopus, and the Web of Science databases was implemented until April 2023. Eligible studies included randomized control trials, observational studies, and case series with ≥4 patients. Two reviewers independently extracted data and assessed the quality of the eligible studies.ResultsA total of 3,724 articles were retrieved

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… Immunological findings such as elevated cryoglobulin levels, low complement C4 levels, and positive RF activity in MC were commonly detected. Treatment strategies varied and included CS, RTX, cyclophosphamide (CYC), AZA, PLEX, and others. … Circulating cryoglobulins activate complements, forming immune complexes with subsequent complement C4 consumption. Another plausible mechanism postulated for low C4 levels is competent cryoglobulin interaction with the C1q protein ( 47 ). …

Дополнительные обновления в оптическом неврите.

Оптический неврит (ON) является воспалительным состоянием зрительного нерва, связанным с демиелинизирующими заболеваниями, такими, как множественный склероз, спектральный расстройство нейромиелита, и болезнь, связанная с антителами, миэлина олигодендроцита. Система дополнения имеет решающее значение для патогенеза, нарушения зрительного нерва в крови, воспаления и повреждения тканей. В настоящем обзоре рассматриваются дополнительные пути активации - классические, альтернативные и лектиновые - и их роли в развитии. Ключевые белки, такие, как C3, C5, и компоненты конечной трассы, выделены в каче

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

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… Serum levels of complement C4 were detected at notably higher levels in the HCC group than in controls. Further analysis showed that a combination of AFP and C4 significantly improved the detection of HCC in HCV-related liver cirrhosis patients ( 295 ). … Complement C4 also represents a component that can distinguish HCC and liver cirrhosis with the highest accuracy ( 300 , 301 ). Increased levels of serum C4a were also found in HCV-infected alcoholic patients with progressive cirrhosis and HCC ( 302 ). …

Case report: Single infusion of combined anti-CD20 and anti-CD38 monoclonal antibodies in pediatric refractory lupus nephritis.

Lupus nephritis (LN), present in 30%-50% of systemic lupus erythematosus (SLE) patients, often necessitates standard immunosuppressive therapy (glucocorticoids, MMF, CYC) as suggested by the European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) and Kidney Disease Improving Global Outcomes (KDIGO) guidelines. However, a subset of subjects remains refractory. Recent findings suggested the efficacy of targeting CD38-long-lived plasma cells in LN and SLE refractory to standard treatment. However, previous experiences were limite

Cryoglobulinemia Type II: Sustained Remission After B-Cell-Directed Therapy.

BACKGROUND Cryoglobulinemia is a rare disease with a prevalence of <5 cases per 10 000. In many cases there is significant diagnostic delay, leading to years of morbidity. There are no randomized trials on non-infectious type II cryoglobulinemia, and choice of therapy is based on clinical expertise and observational data. Therapy based on the monoclonal anti-CD20 antibody rituximab in combination with glucocorticosteroids is the preferred choice in many centers. This strategy induces clinical remission in two-thirds of patients. However, one-third of the initially-responding patients experienc

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… Laboratory findings revealed a slightly elevated erythrocyte sedimentation rate (ESR) of 34 mm/h [ref. 3–20] and a decreased complement C4 at 0.02 g/L [ref. 0.1–0.4]. A tentative diagnosis of undifferentiated connective tissue disease (UCTD) was made. … A positive rheumatoid factor IgM test and a low complement C4 level may raise suspicion of cryoglobulinemic vasculitis. The definitive test for cryoglobulinemia is demonstrating cryoglobulins in blood. …