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Aims: This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology., Methods and Results: A total of 902 pathological cross-sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross-sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well-delineated heterogeneous signal-poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high-backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses <893 µm as cut points for the prediction of measurable calcification (72% sensitivity and 91% specificity, area under the curve = 0.893, P < 0.001)., Conclusion: Our study demonstrated the potential capability of OFDI to characterize various types of coronary calcifications, which may contribute to the understanding of the pathogenesis of coronary atherosclerosis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Chronic intussusception, defined as intussusception continuing over 14 days, is rare in children. We herein report a case of chronic ileocolic intussusception caused by the transmural infiltration of diffuse large B cell lymphoma in a 14-year-old boy. The patient had been suffering from anorexia and intermittent abdominal pain for 5 weeks, during which his body weight decreased by around 7 kg. Upon admission to our hospital, ultrasonography and enhanced computed tomography (CT) of the abdomen showed ileocolic intussusception. A retrospective examination of abdominal CT led us to suspect that the intussusception had initially appeared 5 weeks before admission, presumably coinciding with the beginning of the patient's abdominal symptoms. Since hydrostatic reduction was unsuccessful, laparotomy was performed, which showed unreducible ileocolic intussusception with a marked edematous ileum and mesentery. Ileocecal resection without lymph node dissection was carried out, and a histological examination of the resected specimen revealed the transmural infiltration of diffuse large B-cell lymphoma of the terminal ileum. The patient's postoperative course was uneventful, and adjuvant chemotherapy was administered. This case illustrates the diagnostic challenges of confirming 'chronic' intussusception in older children.

The great majority of gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the c-kit gene, which encodes KIT receptor tyrosine kinase. Most of the mutations are located at exon 11, but some are at exon 9 or at other exons. Mutation types at exon 11 vary, while most mutations at exon 9 are a particular duplication of Ala502Tyr503 (KIT-Dup-Ala502Tyr503). Recently a duplication of Ser501Ala502 (KIT-Dup-Ser501Ala502) at exon 9 has been reported in two cases of pediatric mastocytosis and one case of adult mast cell leukemia. Although KIT-Dup-Ser501Ala502 had not been reported in GISTs, we found two GIST cases possessing the mutation in 45 GIST cases with exon 9 c-kit gene mutations, among a total of approximately 500 GIST cases examined. In this report, we briefly summarize clinicopathological findings of the two cases, and characterize the biology of the mutation. When autophosphorylation of KIT-Dup-Ser501Ala502 was examined by transient transfection of c-kit cDNA with Dup-Ser501Ala502 into CHO-K1 cells, KIT-Dup-Ser501Ala502 was ligand-independently activating. The inhibitory effect of selective tyrosine kinase inhibitors, imatinib and nilotinib, on KIT-Dup-Ser501Ala502 was examined and compared with that of KIT-Dup-Ala502Tyr503. Imatinib efficiently inhibited constitutive activation of KIT-Dup-Ser501Ala502 at a concentration of 0.1 μM, whereas it inhibited that of KIT-Dup-Ala502Tyr503 at a concentration of 10 μM. Constitutive activation of KIT-Dup-Ser502Ala503 was not inhibited by nilotinib even at a concentration of 10 μM but that of KIT-Dup-Ala501Tyr502 was almost completely inhibited at a concentration of 1 μM. The results suggest that imatinib and nilotinib could be more effective on GISTs with KIT-Dup-Ser501Ala502 than those with KIT-Dup-Ala502Tyr503. In fact, a patient with KIT-Dup-Ser501Ala502 showed long-term stable disease with administration of the usual dose of 400 mg imatinib. Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503.

During upper endoscopic screening, a 71-year-old asymptomatic woman was found to have a small, yellowish, superficial elevated lesion in the upper third of her stomach, without any signs of atrophic mucosa. The patient underwent endoscopic follow-up once a year for approximately five years; however, changes in the tumor were barely detectable. Endoscopic mucosal resection was performed, and a histological examination confirmed the diagnosis of gastric adenocarcinoma with chief cell differentiation (GA-CCD). GA-CCD is rare; therefore, its clinicopathological features remain unknown. This case suggests that only barely detectable endoscopic changes may be observed in GA-CCD during long-term follow-up.

We found a novel type germline mutation at exon 11 of the c-kit gene, which results in a substitution of Tyr to Cys at codon 553 of the c-kit gene product (KIT-Tyr553Cys), in a 68-year-old female patient with multiple gastrointestinal stromal tumors (GISTs). In the present study, we carried out mutational analysis in her family members to determine the carriers and characterized the mutation by introducing the corresponding mutation (murine KIT-Tyr552Cys) into expression vector possessing murine c-kit cDNA. Mutational analysis of peripheral blood leukocytes of her family members revealed that a 44-year-old son had the same mutation, but at present he had neither apparent symptoms nor images of multiple GISTs. By transfection with the expression vector possessing the murine mutant c-kit cDNA, interleukin-3-dependent Ba/F3 murine lymphoid cells started growing autonomously without any growth factors, indicating that the mutation was considered to be of gain-of-function. Imatinib, a small molecule of tyrosine kinase inhibitor, effectively inhibited autophosphorylation of KIT-Tyr552Cys. Nilotinib, another small molecule of the KIT inhibitor, also effectively inhibited autophosphorylation of KIT-Tyr552Cys. In fact, proliferation of Ba/F3 cells expressing KIT-Tyr552Cys was effectively inhibited by both imatinib and nilotinib. These findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family.

Sodium alginate oligosaccharides (NaAOs) consisting of a mixture of eight oligosaccharides have previously been reported to lower blood pressure. We investigated in this study the excretion of NaAOs into the urine or feces, and attempted to elucidate the mechanism for lowering blood pressure by using isolated mesenteric arteries from the rabbit. The recovery rate of P8, which is the main component of NaAOs, was 5.2% and 58.9% over 48 hours in the urine and feces, respectively. The mechanism for lowering blood pressure appeared to be NaAOs having calcium antagonist activity, especially voltage-operated calcium channels. Our results suggest that NaAOs are substantially excreted into the feces, although some of them may be absorbed internally, exerting antagonist activity towards the calcium channels, especially voltage-operated calcium channels.

The relaxant effects of calcitonin gene-related peptide (CGRP) and other drugs were compared in basilar artery rings obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). In addition, the relaxant effect of CGRP on basilar arteries from spontaneously hypertensive rats (SHR) was examined. Relaxation induced by CGRP was independent of the presence of endothelium, and it was markedly increased in SHRSP when compared to WKY. In contrast, acetylcholine-induced relaxation was endothelium-dependent and did not differ between the two groups. Enhanced CGRP-induced relaxation was also found in SHR when compared to WKY. However, the relaxant response was greater in SHRSP than in SHR. No significant differences were found in the relaxation induced by isoproterenol, forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine in endothelium-rubbed arteries of WKY and SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the rat basilar artery, and that the enhanced CGRP-induced relaxation found in SHRSP may not be associated with alterations of vasodilation mediated by cyclic AMP.

Phenylephrine-induced oscillatory contractions in rabbit mesenteric arteries were investigated in vitro. Adrenergic, cholinergic, or histamine antagonists as well as cyclooxygenase and lipoxygenase inhibitors had no effect on this phenylephrine-induced oscillation. The removal of extracellular calcium ions or treatment with a calcium antagonist reduced the amplitude and frequency of the oscillation. Removal of the endothelium or treatment with inhibitors of the synthesis or the target enzyme of endothelium-derived relaxing factor (EDRF) also reduced the amplitude and frequency of the oscillation. In a perfusion bioassay, the perfusate from an endothelium-intact arterial segment induced oscillation of an endothelium-denuded arterial ring recipient. These results suggest that phenylephrine-induced oscillation is mediated by an endothelium-derived factor such as EDRF and depends on the influx of extracellular calcium ions.

The fourth heart sound was clearly recorded by using the signal averaging method. Furthermore, the simultaneous recording of the Doppler signal with the fourth heart sound was performed. Thus, it was demonstrated that the Doppler signal started after the P wave and followed by the fourth heart sound. In 2 cases, the effect of the double Master's test and taking a bath was studied on the computer averaged phonocardiogram. After the exercise, the amplitude of the fourth heart sound was increased, whereas after taking a bath it was almost unchanged. The above results show that the simultaneous recordings of a computer averaged phonocardiogram and Doppler signal that is associated with cardiac activity can greatly facilitate the interpretation of small vibrations such as the fourth heart sound.

A possible mechanism of infertility by Cd was investigated from the standpoint of influence of Cd on the contractile responses of isolated seminal vesicle from guinea pigs to K, acetylcholine, noradrenaline, Ba and Ca by using the Magnus method. Cd inhibited the contractile responses to the contractile agents tested in a dose-dependent manner. Cd showed the preferential inhibition against the contractile responses to K and Ca. The inhibitory effect of Cd on the contractile responses to noradrenaline and acetylcholine was hardly removed. The effect of Cd was inhibited by the thiol compounds, glutathione and thiola. The active mechanism of Cd was discussed in relation to Ca mobilization.