The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model.

Pertussis, also known as whooping cough, is a contagious respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. This disease is characterized by severe and uncontrollable coughing, which imposes a significant burden on patients. However, its etiological agent and the mechanism are totally unknown because of a lack of versatile animal models that reproduce the cough. Here, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components and demonstrate that lipooligosaccharide (LOS), pertussis toxin (PTx), and Vag8 of the bacterium cooperatively function to cause coughing. Bradykinin induced by LOS sensitized a transient receptor potential ion channel, TRPV1, which acts as a sensor to evoke the cough reflex. Vag8 further increased bradykinin levels by inhibiting the C1 esterase inhibitor, the major downregulator of the contact system, which generates bradykinin. PTx inhibits intrinsic negative regulation systems for TRPV1 through the inactivation of Gi GTPases. Our findings provide a basis to answer long-standing questions on the pathophysiology of pertussis cough. IMPORTANCE The Gram-negative bacterium Bordetella pertussis causes a respiratory disease called whooping cough, or pertussis. This disease is characterized by paroxysmal coughing, the mechanism of which has not been intensively studied because of a lack of versatile animal models that reproduce the cough. In this study, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components. Using this model, we demonstrate that lipooligosaccharide, Vag8, and pertussis toxin of the bacteria cooperatively function to cause coughing. Our results also indicate that bradykinin, an inflammatory mediator, and TRPV1, an ion channel linked to nociceptive signaling, are host factors involved in the coughing mechanism.

Spatial and single-cell transcriptome analysis reveals changes in gene expression in response to drug perturbation in rat kidney.

The kidney is a complex organ that consists of various types of cells. It is occasionally difficult to resolve molecular alterations and possible perturbations that the kidney experiences due to drug-induced damage. In this study, we performed spatial and single-cell transcriptome analysis of rat kidneys and constructed a precise rat renal cell atlas with spatial information. Using the constructed catalogue, we were able to characterize cells of several minor populations, such as macula densa or juxtaglomerular cells. Further inspection of the spatial gene expression data allowed us to identify the upregulation of genes involved in the renin regulating pathway in losartan-treated populations. Losartan is an angiotensin II receptor antagonist drug, and the observed upregulation of the renin pathway-related genes could be due to feedback from the hypotensive action of the drug. Furthermore, we found spatial heterogeneity in the response to losartan among the glomeruli. These results collectively indicate that integrated single-cell and spatial gene expression analysis is a powerful approach to reveal the detailed associations between the different cell types spanning the complicated renal compartments.

Identification of the minimum region of Bordetella pertussis Vag8 required for interaction with C1 inhibitor.

An autotransporter of Bordetella pertussis, virulence-associated gene 8 (Vag8), binds and inactivates the complement regulator, C1 inhibitor (C1-Inh), and plays a role in evasion of the complement system. However, the molecular interaction between Vag8 and C1-Inh remains unclear. Here, we localized the minimum region of Vag8 required for interaction with C1-Inh by examining the differently truncated Vag8 derivatives for the ability to bind and inactivate C1-Inh. The truncated Vag8 containing amino-acid residues 102-548, but not 102-479 and 202-648, showed the full activity of intact Vag8, suggesting that the separate 102-202 and 548-648 amino-acid regions of Vag8 mediate the interaction with C1-Inh.

A case of spontaneous coronary artery dissection complicated with pseudoaneurysm healed by medical treatment: Follow-up by multidetector computed tomography.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial ischemia. Identification of intimal flap, true and false lumens in coronary angiogram (CAG) is the standard method to diagnose SCAD. In cases of obscure intimal flap, intravascular ultrasound (IVUS) is a useful method to diagnose, although crossing the wire and IVUS in the dissected lesion is invasive. Multidetector computed tomography (MDCT) provides valuable information in any clinical setting less invasively. We report here a rare case of spontaneous dissecting coronary artery pseudoaneurysm diagnosed by CAG and MDCT, healed by medical treatment, and followed up by MDCT over a 2-year period. .

Postinfarct cardiac free wall rupture detected by multidetector computed tomography.

Cardiac free wall rupture after myocardial infarction is one of the life-threatening complications, which often results in sudden onset of cardiogenic shock caused by cardiac tamponade. Multidetector computed tomography (MDCT) provides valuable information in any clinical setting. There have been a few case reports on detecting cardiac rupture by means of CT. We report here a rare case of postinfarct cardiac free wall rupture, whose myocardial tear could be detected by MDCT.