Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively.
View Article and Find Full Text PDFThe SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID-19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations, and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.
View Article and Find Full Text PDFSARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated.
View Article and Find Full Text PDFSARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for the antibody system. Neutralizing antibodies targeting the RBD bind to several different sites on this domain.
View Article and Find Full Text PDFTranscription factors bind to their binding sites over a wide range of affinities, yet how differences in affinity are encoded in DNA sequences is not well understood. Here, we report X-ray crystal structures of four heterodimers of the Hox protein AbdominalB bound with its cofactor Extradenticle to four target DNA molecules that differ in affinity by up to ∼20-fold. Remarkably, despite large differences in affinity, the overall structures are very similar in all four complexes.
View Article and Find Full Text PDFType II cadherins are cell-cell adhesion proteins critical for tissue patterning and neuronal targeting but whose molecular binding code remains poorly understood. Here, we delineate binding preferences for type II cadherin cell-adhesive regions, revealing extensive heterophilic interactions between specific pairs, in addition to homophilic interactions. Three distinct specificity groups emerge from our analysis with members that share highly similar heterophilic binding patterns and favor binding to one another.
View Article and Find Full Text PDFThe direct-current electric shock is considered to be safe treatment of arrhythmias and rarely leads to serious hemodynamic complications. A 62-year-old patient was admitted to the hospital due to a first symptomatic episode of atrial fibrillation. Patient was diagnosed with apical hypertrophic cardiomyopathy 20 years ago.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2014
Type I cadherin cell-adhesion proteins are similar in sequence and structure and yet are different enough to mediate highly specific cell-cell recognition phenomena. It has previously been shown that small differences in the homophilic and heterophilic binding affinities of different type I family members can account for the differential cell-sorting behavior. Here we use a combination of X-ray crystallography, analytical ultracentrifugation, surface plasmon resonance and double electron-electron resonance (DEER) electron paramagnetic resonance spectroscopy to identify the molecular determinants of type I cadherin dimerization affinities.
View Article and Find Full Text PDFVisual interpretation of the Doppler waveform in the common femoral or distal external iliac artery (EIA) was reported to be useful in screening for proximal peripheral artery occlusive disease (PAOD) in patients with lower limb ischemia. Commonly patients with coronary artery disease (CAD) referred for echocardiography have coexistent arterial pathology. Therefore, we decided to study whether echocardiographic evaluation of the distal EIA flow can be useful for detection of PAOD in patients with CAD.
View Article and Find Full Text PDFSeveral studies demonstrated feasibility of visual assessment of the common femoral artery Doppler waveform, in an indirect evaluation of aorto-iliac segment stenosis. Patients with cardiac diseases referred for echocardiography often have coexistent arterial pathology. Since many of them are potential candidates for endovascular procedures, we decided to study, whether echocardiography can be useful for detection of aorto-iliac occlusive disease.
View Article and Find Full Text PDFBackground: Clinical picture of acute pulmonary embolism (APE), with wide range of electrocardiographic (ECG) abnormalities can mimic acute coronary syndromes.
Objectives: Assessment of standard 12-lead ECG usefulness in differentiation at the bedside between APE and non-ST elevation acute coronary syndrome (NSTE-ACS).
Methods: Retrospective analysis of 143 patients: 98 consecutive patients (mean age 63.
Myocardial stretch leads to the natriuretic peptides release in acute or chronic left ventricular dysfunction. However, there is an accumulating evidence that B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) may originate from right ventricle and their concentrations are elevated in patients with acute pulmonary embolism (APE) especially when resulting in right ventricular dysfunction (RVD). Recently it is underlined that severity assessment of APE as well as the risk stratification and therapy selection is based both on patients' hemodynamic status and markers of myocardial injury and RVD.
View Article and Find Full Text PDFBackground: Despite long-term anticoagulation in some patients after acute pulmonary embolism (APE) pulmonary thrombi are not completely resolved. We hypothesized that elevated D-dimer concentration reflecting increased endogenous fibrinolysis may indicate incomplete pulmonary thrombi resolution after the first episode of PE.
Methods: 55 patients aged 54.
Introduction: The mortality of untreated pulmonary embolism (PE) is estimated at approximately 30% of patients, whereas treatment decreases it to 2-8%. A specific combination of symptoms present in PE may suggest other cardiac or lung disorder.
Objectives: To evaluate frequencies of clinical symptoms and changes in diagnostic investigations misleading to the recognition of acute coronary syndrome (ACS) or lung diseases (Ld) in PE patients.
Aims: Low levels of brain natriuretic peptides on admission identify low-risk patients with acute pulmonary embolism (APE) through their high NPV for mortality. However, increased natriuretic peptide values on admission are less helpful for identifying high-risk patients due to their low PPV. The aim of the study was to test whether the PPV for mortality can be improved by performing serial NT-proBNP measurements on admission, at 12 h, and at 24 h.
View Article and Find Full Text PDFRight ventricular (RV) overload and hypoxia in acute pulmonary embolism (APE) may lead to RV myocardium injury reflected by elevated cardiac troponin levels. We studied 26 patients aged 57.2+/-17.
View Article and Find Full Text PDFBackground: Irreversible right ventricular (RV) failure with myocardial damage may precipitate fatal outcome in acute pulmonary embolism (APE). Cytoplasmic heart-type fatty acid binding protein (H-FABP) is a sensitive and specific biomarker of myocardial damage. We assessed which biomarker of myocardial damage or RV stretching is the most useful for short-term risk stratification in APE.
View Article and Find Full Text PDFAims: Despite growing interest in biomarkers application for risk evaluation in acute pulmonary embolism (APE), no decision-making levels have been defined.
Methods And Results: We developed a biomarker-based risk stratification in 100 consecutive, normotensive on admission, APE patients (35 males, 65 females, 62+/-18 years). On admission serum NT-proBNP and cardiac troponin T (cTnT) levels were assessed and echocardiography was performed.
Background: In some patients with acute pulmonary embolism (APE) thrombi may lodge at the levels of the bifurcation of pulmonary trunk and extend into both main pulmonary arteries, forming so-called saddle embolism (SE).
Aim: To assess the incidence of SE and whether it is associated with an increased risk of complicated clinical course.
Methods: We studied 150 consecutive patients (94 females, 56 males) aged 63.
Unlabelled: Acute pulmonary embolism (APE) may lead to myocardial necrosis detected by elevation of cardiac troponin levels. We tried to assess, if electrocardiographic abnormalities may help to define APE patients with myocardial damage and at high risk of complicated clinical course. Therefore we analyzed 50 patients (34F) aged 64.
View Article and Find Full Text PDFAlagille syndrome is characterized by paucity of bile ducts leading to cholestasis and may be accompanied by renal and cardiovascular abnormalities. We report 42-years old patient with hypertension, chronic renal failure and Alagille syndrome. Ischemic nephropathy was suspected, which was not confirmed on angio-CT.
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