Takumi Yasugi

The microvasculature of the 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumour. I, Vascular patterns as visualized by scanning electron microscopy of corrosion casts

We examined the microvasculature of the 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumour by scanning electron microscopy of corrosion casts. An elaborate vascular envelope predominantly consisting of sinusoidal and venular vessels was formed around each tumour nodule. These vessels exhibited various abnormal features, whereas arterioles appeared normal. The abnormal vessels possessed many globular outpouches, possibly representing the site of angiogenesis. An additional capillary layer was seen in the marginal boundary between the tumour and host tissue. The lack of centrifugally extruding vessels in this layer may indicate a poor potency for vascular spread of tumour cells into the adjacent normal tissue. Looplike or glomerular ingrowths were frequently found on the inner aspect of the vascular capsule, which eventually developed into a dense intranodular plexus. Intranodular vessels often showed focal narrowing, tapering and/ or rupturing, possibly due to increased tissue pressure caused by proliferating tumour cells. Those surrounding necrotic portions were extremely dilated with occasional periodic varicosities. The features may be associated with the lessening of the tissue pressure resulting from tumour cell collapse.

Transient ischemia-induced paresis and complete paraplegia displayed distinct reactions of microglia and macrophages

In this study, we perform a detailed analysis of the microglial and macrophage responses in a model of spinal cord ischemia and reperfusion (SCI/R) injury in Wistar rats. The rats underwent occlusion across the descending aorta for 13min, causing paraplegia or paresis of varying severity. They were divided into four groups based on neurological assessment: sham, mild paresis, moderate paresis, and severe (complete) paraplegia. To examine the origin of microglia and macrophages in the ischemic lesion, bone marrow from rats expressing green fluorescent protein (GFP) was transplanted into test subjects one month before performing SCI/R. Many GFP(+)/CD68(+) microglia and macrophages were present 7d after SCI/R. Resident (GFP(-)/Iba1(+)/CD68(-)) microglia and bone marrow-derived macrophages (BMDMs; GFP(+)/Iba1(+)/CD68(+)) colocalized in the mild group 7d after SCI/R. In the moderate group, BMDMs outnumbered resident microglia. A greater accumulation of BMDMs expressing insulin-like growth factor-1 (IGF-1) was observed in lesions in the severe group, relative to the moderate group. BMDMs in the severe group strongly expressed tumor necrosis factor α, interleukin-1β, and inducible nitric oxide synthase, in addition to IGF-1. A robust accumulation of BMDMs occupying the entire ischemic gray matter was observed only in the severe group. These results demonstrate that the magnitude of the microglial and BMDM responses varies considerably, and that it correlates with the severity of the neurological dysfunction. Remarkably, BMDMs appear to have a beneficial effect on the spinal cord in paresis. In contrast, BMDMs seem to exhibit both beneficial and harmful effects in severe paraplegia.

Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice

Background Liver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would provide greater insights into the genetic basis of the disease. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches. Methods Eight-week-old Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers was detected by western blot and microarray analyses. Results We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down-regulated proteins that were associated with angiogenesis. TNF-α and MMP-9 were highly expressed at 3 weeks after CBDL and were less expressed in the lungs of the control group. Conclusions We constructed a mouse lung injury model by using CBDL. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase. Thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome.

Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular Inflammation and Aneurysm FormationNovelty and Significance

Perivascular adipose tissue exhibits characteristics of active local inflammation, which contributes to the development of atherosclerotic disease as a complication of obesity/metabolic syndrome. However, the precise role of perivascular adipose tissue in the progression of abdominal aortic aneurysm remains unclear. To test the hypothesis that genetic deletion of angiotensin II type 1a (AT1a) receptor in perivascular visceral adipose tissue (VAT) can attenuate aortic aneurysm formation in apolipoprotein E–deficient (ApoE−/−) mice, we performed adipose tissue transplantation experiments by using an angiotensin II–induced aneurysm murine model, in which we transplanted VAT from ApoE−/− or ApoE−/− AT1a−/− donor mice onto the abdominal aorta of ApoE−/− recipient mice. Compared with ApoE−/− VAT transplantation, ApoE−/− AT1a−/− VAT transplantation markedly attenuated aortic aneurysm formation, macrophage infiltration, and gelatinolytic activity in the abdominal aorta. AT1a receptor activation led to the polarization of macrophages in perivascular VAT toward the proinflammatory phenotype. Moreover, osteopontin expression and gelatinolytic activity were considerably lower in ApoE−/− AT1a−/− perivascular VAT than in ApoE−/− perivascular VAT, and angiotensin II–induced osteopontin secretion from adipocytes was eliminated after deletion of AT1a receptor in adipocytes. Notably, induction of macrophage migration by conditioned medium from angiotensin II–stimulated wild-type adipocytes was suppressed by treatment with an osteopontin-neutralizing antibody, and ApoE−/− OPN−/− VAT transplantation more potently attenuated aortic aneurysm formation than ApoE−/− VAT transplantation. Our findings indicate a previously unrecognized effect of AT1a receptor in perivascular VAT on the pathogenesis of abdominal aortic aneurysm.

Pseudoaneurysm in the Left Groin due to Ruptured Knitted Dacron Graft

An 82-year-old man was admitted to our institution with a painful pulsating mass in the left groin. He had undergone bypass surgery with a bifurcated Cooley double velour knitted Dacron graft to treat aorto-iliac occlusive disease 21 years previously. Computed tomography demonstrated a 35-mm pseudoaneurysm near the distal anastomosis site of the graft. Opening the aneurysm revealed that the graft was disrupted along the guideline. We resected the aneurysm and interposed an expanded polytetrafluoroethylene (ePTFE) graft. Vascular surgeons should consider that grafts can fail in patients with long-term prosthetic grafts.

Polymorphisms of serum proteins in Japanese patients with vascular diseases. I. Factor XIIIB, plasminogen and complement types in primary varicose veins.

The polymorphisms of the B subunit of coagulation factor XIII (F13B), plasminogen (PLG), complement C6, C7, factor B (BF) and factor I (IF) were studied among 21 unrelated Japanese patients with primary varicose veins (PVV) by isoelectric focusing followed by immunoblotting. The allele frequencies for F13B*2 and IF*A in PVV patients were significantly higher (F13B*2, p = 0.0047; IF*A, p = 0.0006) than those in healthy controls (n = 60). Significant associations of F13B 2 allotype [p = 0.0220, relative risk (RR) = 13.9] and IF A allotype (p = 0.0006, RR = 10.0) with PVV were observed; however, no significant association of PLG, C6, C7 or BF allotype with the disease was found.

Redo cardiac surgery for active prosthetic valve endocarditis associated with hereditary hemorrhagic telangiectasia: report of a case

Abstract Hereditary hemorrhagic telangiectasia (HHT) is caused by an autosomal dominant gene and characterized by multiple arteriovenous malformations in several organs, leading to bleeding or shunting. These patients often suffer severe infections and heart failure, which should be managed in the perioperative period, when open heart surgery is indicated. We report a case of successful aortic root replacement for active prosthetic valve endocarditis and ventricular septal perforation in a patient with HHT, who had severe heart failure.

The analysis of ascending aortic dilatation in patients with a bicuspid aortic valve using the ratio of the diameters of the ascending and descending aorta.

BackgroundA bicuspid aortic valve (BAV) is associated with premature valve dysfunction and abnormalities of the ascending aorta. The aim of our study was to assess the degree of ascending aortic dilatation by measuring the ratio of the dimension of the AAo to that of the descending aorta (DAo) using preoperative computerized tomography (CT).MethodsA review of our institutional clinical database identified 76 patients undergoing aortic valve replacement (AVR) and 73 control patients undergoing off-pump coronary artery bypass (OPCAB group) between September 2009 and April 2012.ResultsThere were 17 patients diagnosed with BAV (BAV group), and the remaining 59 patients had a tricuspid aortic valve (TAV group). The ratios of the dimensions of the AAo to that of the DAo (AAo/DAo) for each group were: BAV, 1.58 ± 0.25; TAV, 1.32 ± 0.11; and OPCAB, 1.29 ± 0.12. Interestingly, the AAo/DAo of the BAV group was significantly larger than that of the other groups.ConclusionsAlthough progressive AAo dilatation for BAV is well documented, the diameter of the AAo is currently the only estimate of aortic dilatation. In this study, we report that the ratio of the AAo and DAo diameters in patients with BAV can be a new index for assessing the dilatation of the AAo and differentiating the patients with BAV from those with TAV.

Biochemical and histological evidence of deteriorated bioprosthetic valve leaflets: the accumulation of fibrinogen and plasminogen

ABSTRACT Calcification of bioprosthetic valves (BVs) implanted in aortic position can result in gradual deterioration and necessitate aortic valve replacement. The molecular mechanism of calcium deposition on BV leaflets has been investigated, but remains to be fully elucidated. The present study aimed to identify explanted bioprosthetic valve (eBV)-specific proteins using a proteomics approach and to unveil their biochemical and histological involvements in calcium deposition on BV leaflets. Calcification, fibrosis, and glycosylation of the valves were histologically assessed using Von Kossa, Massons Trichrome and Alcian Blue staining, as well as immunostaining. Protein expression in the explanted biological valves was analysed using proteomics and western blotting. In a histological evaluation, αSMA-positive myofibroblasts were not observed in eBV, whereas severe fibrosis occurred around calcified areas. SDS-PAGE revealed three major bands with considerably increased intensity in BV leaflets that were identified as plasminogen and fibrinogen gamma chain (100 kDa), and fibrinogen beta chain (50 and 37 kDa) by mass analysis. Immunohistochemistry showed that fibrinogen β-chain was distributed throughout the valve tissue. On the contrary, plasminogen was strongly stained in CD68-positive macrophages, as evidenced by immunofluorescence. The results suggest that two important blood coagulation-related proteins, plasminogen and fibrinogen, might affect the progression of BV degeneration. Summary: Fibrinogen was specifically deposited on whole deteriorated tissue valve leaflets, and plasminogen-positive macrophages strongly invaded the areas around calcified bioprosthetic and native tissues.

Combined ablation of atrial fibrillation and minimally invasive mitral valve surgery: a case report

A partial lower inverted J sternotomy and an extended transseptal incision provide excellent exposure for minimally invasive mitral valve surgery. However, the extended trasnsseptal incision causes dividing the sinus node artery, which may result in conduction system disturbance and need for permanent pacemaker implantation. Therefore, there is a challenge in the patient who requires concomitant ablation for atrial fibrillation because of possible conduction system disturbance caused by extended transseptal incision. We describe a new strategy for combined ablation of atrial fibrillation with minimally invasive cardiac surgery by a transseptal approach to the mitral valve through a partial lower sternotomy incision. Cryoablation was performed using a T-shaped cryoprobe with a lesion set of pulmonary vein isolation and ablation of the left and right isthmus in performing mitral annuloplasty, tricuspid annuloplasty, and atrial septal defect closure through a limited sternotomy incision. This technique might minimize possible conduction system disturbance and provide good surgical result for the patients who undergo mitral valve surgery and ablation of atrial fibrillation.