Production of D∗+(2010)D^{*+}(2010) mesons by high energy neutrinos from the Tevatron

Charged vector $D^{*+}(2010)$ meson production is studied in a high energy neutrino bubble chamber experiment with mean neutrino energy of 141 GeV. The $D^{*+}$ are produced in $(5.6 \pm 1.8)\%$ of the neutrino charged current interactions, indicating a steep increase of cross section with energy. The mean fractional hadronic energy of the $D^{*+}$ meson is $0.55 \pm 0.06$

Three Linked Vasculopathic Processes Characterize Kawasaki Disease: A Light and Transmission Electron Microscopic Study

Kawasaki disease is recognized as the most common cause of acquired heart disease in children in the developed world. Clinical, epidemiologic, and pathologic evidence supports an infectious agent, likely entering through the lung. Pathologic studies proposing an acute coronary arteritis followed by healing fail to account for the complex vasculopathy and clinical course.Specimens from 32 autopsies, 8 cardiac transplants, and an excised coronary aneurysm were studied by light (n=41) and transmission electron microscopy (n=7). Three characteristic vasculopathic processes were identified in coronary (CA) and non-coronary arteries: acute self-limited necrotizing arteritis (NA), subacute/chronic (SA/C) vasculitis, and luminal myofibroblastic proliferation (LMP). NA is a synchronous neutrophilic process of the endothelium, beginning and ending within the first two weeks of fever onset, and progressively destroying the wall into the adventitia causing saccular aneurysms, which can thrombose or rupture. SA/C vasculitis is an asynchronous process that can commence within the first two weeks onward, starting in the adventitia/perivascular tissue and variably inflaming/damaging the wall during progression to the lumen. Besides fusiform and saccular aneurysms that can thrombose, SA/C vasculitis likely causes the transition of medial and adventitial smooth muscle cells (SMC) into classic myofibroblasts, which combined with their matrix products and inflammation create progressive stenosing luminal lesions (SA/C-LMP). Remote LMP apparently results from circulating factors. Veins, pulmonary arteries, and aorta can develop subclinical SA/C vasculitis and SA/C-LMP, but not NA. The earliest death (day 10) had both CA SA/C vasculitis and SA/C-LMP, and an "eosinophilic-type" myocarditis.NA is the only self-limiting process of the three, is responsible for the earliest morbidity/mortality, and is consistent with acute viral infection. SA/C vasculitis can begin as early as NA, but can occur/persist for months to years; LMP causes progressive arterial stenosis and thrombosis and is composed of unique SMC-derived pathologic myofibroblasts

Myocarditis.

<p>A. Low magnification H&E of a poorly-preserved hourglass-shaped epicardial CA showing varying degrees of SA/C peri-arteritis, transmural SA/C, and minimal preserved media. H&E, case 1, original magnification 10×. B. Perivascular and transmural SA/C inflamed adventitia and heavily damaged media with some discernible SMC and IEL, and SA/C-LMP with scattered pleomorphic myofibroblasts. There are some eosinophils intermixed with the small lymphocytes. H&E, case 1, original magnification 16×. C. A higher magnification of a typical area of SA/C-LMP with prominent amphophilic myofibroblasts in a background of mostly small lymphocytes, scattered eosinophils, and likely macrophages in a fibrillar ECM that shows some artifactual spaces. H&E, case 1, original magnification 25×. D. A typical area of the highly edematous interstitial myocarditis especially rich in eosinophils, with scattered lymphocytes, macrophages, and plasma cells. Note the longitudinally-sectioned caterpillar-shaped and cross-sectioned, owl eye-shaped (unidentified) Anitschkow chromatin pattern in a myocyte and two unidentified cell nuclei, respectively. H&E, case 1, original magnification 40×. L=lumen, NV=nerve, IEL=internal elastic lamina, Eo=eosinophil, AM=Anitschkow myocyte, MF=myofibroblast, V=vein, ADV=adventitia, M=media.</p

Clinical implications of this study.

<p>Clinical implications of this study.</p

SA/C-Luminal Myofibroblastic Proliferation (LMP) causes narrowing of CA in KD patients.

<p>A. A tear drop-shaped CA with SA/C-LMP is about 50% narrowed. The actin-rich myofibroblasts and medial and adventitial SMCs stain brown. The residual media is variably thinned. Alpha-SMA IHC, case 11, original magnification 10×. B. Oval-shaped SA/C-LMP CA is virtually occluded. The MF and medial SMC stain red and there is a relatively little ECM (blue) in the LMP. Except for some thinning, the media is almost completely intact. The adventitia is densely collagenized. Trichrome stain, case 28, original magnification 10×. C. The SA/C-LMP in this elongated CA is eccentric having started at the end (top) where the media and IEL had been destroyed and progressed toward the end, which still contains media and IEL (bottom). H&E, case 26, original magnification 10×. D. An oval CA is occluded by SA/C-LMP, of relatively low SA/C cellularity concentrated around the lumen. There are several small areas of minimally preserved media. No media is present on the side with the hyper-vascular adventitia, where the process likely began. H&E, case 27, original magnification 10×. E. The SA/C-LMP progressed from the inflamed/damaged end (bottom) of this tangentially-sectioned renal artery almost reaching the opposite end (top), where the lumen is visible and there is intact media and IEL are intact. H&E, case 27, original magnification 10×. L=lumen, M=media, ADV=adventitia, LMP=luminal myofibroblastic proliferation, RBC=red blood cells, IEL=internal elastic lamina, V=vein, I=inflammation, T=renal tubules, P=pericardium, My=myocardium.</p

Newly described pathologic features observed in the 41 KD patients.

<p>Newly described pathologic features observed in the 41 KD patients.</p

Pathologic findings in patients with Kawasaki Disease.

<p>RCIA=right common iliac artery, SA/C=subacute/chronic inflammation, CA=coronary artery, CAA=coronary artery aneurysm, LMP=luminal myofibroblastic proliferation, MI=myocardial infarction, TX=transplant, Mac=macrophage, SI=small intestine, RCA=right coronary artery, LAD=left anterior descending artery, LCx=left circumflex artery, IMA=inferior mesenteric artery, GB=gallbladder, MV=mitral valve, TV=tricuspid valve, PV=pulmonary valve, GT=granulation tissue, eos=eosinophils, SMA=superior mesenteric artery, PA=pulmonary arteries, macs=macrophages, PMNL=predominantly neutrophils, U=unknown, N/A=not available, EFE=endocardial fibroelastosis, ECMO=extracorporeal membrane oxygenation, IVC=inferior vena cava. Notes: CA sections usually contained myocardium, epicardium, and some endocardium. All patients had active SA/C plus LMP in coronary and also in available non-coronary arteries. Varying degrees of chronic hypoxia (hydropic change) seen in all cases. Anitschkow cells always seen, if case had at least two sections of myocardium. EFE always seen, if specimens included more than focal endocardium. By report=slides not available, but description sufficient to derive pathology.</p

Thrombi in coronary artery aneurysms (CAA) of KD patients.

<p>A. A CA already severely compromised by SA/C-LMP is virtually occluded by a superimposed fresh thrombus (dark red) that blends into the SA/C-LMP. Trichrome stain, case 18, original magnification 16×. B. Part of a NA CAA occluded by a fresh thrombus. There is a small area of organizing thrombus. Since only mildly inflamed fibrotic adventitia remains, it is not possible in this section to distinguish between NA and SA/C as the etiology. H&E, case 11, original magnification 10×. C. A small portion of CAA thrombus. The vascular granulation tissue has a loose matrix containing few free RBC, spindle cells and mononuclear cells, a few of which are macrophages containing brown hemosiderin blood pigment. Spindle cells are reaching into the luminal RBCs. H&E, case 22, original magnification 63×. D. The oldest peripheral thrombus in this CAA is re-canalizing. There are superimposed fresher thrombi. Since the CAA still has some remaining media, the aneurysm likely resulted from severe SA/C pan-arteritis. H&E, case 37, original magnification 10×. E. This organized SA/C CAA thrombus has peripheral clumps of calcium. Some of the media is still visible (upper right). H&E, case 19, original magnification 16×. L=lumen, LMP=luminal myofibroblastic proliferation, M=media, ADV=adventitia, ORG=organizing thrombi, R=recanalized, Ca=calcium, V=vessel.</p

Pathologic observations that differ from those previously reported.

<p>Pathologic observations that differ from those previously reported.</p