Bioinspired Optical Sensor for Remote Measurement of Small Displacements at a Distance.

Identifying appropriate sites for landing a spacecraft or building permanent structures is critical for extraterrestrial exploration. By tracking the movement of land masses and structures on a planetary surface, scientists can better predict issues that could affect the integrity of the site or structures. A lightweight, low-cost, low-power bioinspired optical sensor is being developed at the National Aeronautics and Space Administration (NASA) Ames Research Center to remotely measure small displacements of land masses on either side of a fault. This paper describes the sensor, which is inspired by the compound eye vision system found in many insects, and the algorithms developed to estimate displacement. The results are presented for indoor and outdoor tests using the sensor to measure the displacement of a specially designed target that is located 0.35, 6, and 30 m from the sensor and is moved 10 mm to the left and right of a centered position, simulating the displacement of land masses on either side of a fault. Measurement uncertainties estimates were a few tenths of a millimeter when the target was located 0.35 and 6 m from the sensor. At the 30 m distance, corrections were required to obtain accuracies in the order of 1 mm.

Optimal strength and number of shocks at upper limit of vulnerability testing required to predict high defibrillation threshold without inducing ventricular fibrillation.

BACKGROUND: The upper limit of vulnerability (ULV) closely correlates with the defibrillation threshold (DFT). The aim of this study was to establish the optimal protocol for using the ULV test to predict high DFT (>20 J) without inducing ventricular fibrillation (VF). METHODS AND RESULTS: The 10-J and 15-J ULV test with 3 coupling intervals (-20, 0, and +20 ms to the peak of T-wave) and the DFT test were performed in 96 patients receiving implantable cardioverter defibrillator. ULV ≤ 10 J was confirmed in 47 (49%). ULV ≤ 15 J was confirmed in 70 (77%) of 91 patients (15-J ULV test could not be done in 5). The sensitivity and negative predictive value of both ULV >10 J and >15 J for predicting high DFT were 100%. The specificity and positive predictive value of ULV >15 J were higher than those for ULV >10 J (85% vs. 55%, 43% vs. 22%, respectively). The rate of VF inducibility for confirming ULV ≤ 15 J was lower than that for ULV ≤ 10 J (23% vs. 51%, P<0.0001). On analysis of single 15-J ULV test only at the peak of T-wave, VF was not induced in 79 of 91 patients, but 4 of these had high DFT. CONCLUSIONS: The 15-J ULV test with 3 coupling intervals could correctly identify high-DFT patients and reduce the necessity for VF induction at defibrillator implantation.

Rate-dependent and site-specific conduction block at the posterior right atrium and drug effects evaluated using a noncontact mapping system in patients with typical atrial flutter.

INTRODUCTION: Conduction block in the posterior right atrium (RA) plays an important role in perpetuating atrial flutter (AFL). Although conduction blocks have functional properties, it is not clear how the block line changes with the pacing rate, pacing site, and administration of antiarrhythmic drugs. METHODS AND RESULTS: Forty patients with typical AFL were enrolled. Pacing (110, 170, 230 ppm) from the coronary sinus ostium (CSo) and low lateral RA was performed. After 1 mg/kg pilsicainide (pure sodium channel blockade) administration, the pacing protocol was repeated. Conduction block was assessed based on a color-coded isopotential map and 20 points of virtual unipolar electrograms in the posterior RA using noncontact mapping. Block line proportion was defined as the percentage of length of the block line between the superior and inferior vena cava. The pacing rate-dependent extension of the block proportion was significant during pacing from both sides (pacing from the CSo: 59 ± 17% at 110 ppm, 69 ± 16% at 230 ppm, P < 0.05; pacing from the low lateral RA: 43 ± 19% at 110 ppm, 55 ± 22% at 230 ppm, P < 0.05). The block line was significantly longer during CSo pacing than during low lateral RA pacing at each rate (all P < 0.05). After pilsicainide administration, the block line extended further. CONCLUSION: In addition to pacing rate-dependent and site-dependent changes in the block line, pilsicainide further extended the block line length. This phenomenon explains the clinical observation that counterclockwise AFL occurs more frequently than clockwise AFL, and the mechanism of class IC AFL.

Recognition of inferiorly dislocated fast pathways guided by three-dimensional electro-anatomical mapping.

PURPOSE: Slow pathway (SP) ablation of atrioventricular (AV) nodal reentrant tachycardia (AVNRT) can be complicated by unexpected AV block even at sites >10 mm inferior to the bundle of His (HB), and one cause is thought to be the inferior dislocation of an antegrade fast pathway (A-FP). We assessed locations of FPs guided by CARTO. METHODS: Sites of FPs were mapped guided by CARTO before SP ablation in 18 patients with slow-fast AVNRT. The A-FP was defined as the site with the minimum interval between the stimulus and HB potential when pace mapping in the right atrial septum. RESULTS: The A-FP was 7.9 ± 7.5 mm inferior and 2.9 ± 5.0 mm posterior to the HB. In 6 of 18 patients (33%), the A-FP was inferiorly dislocated >10 mm to the HB. SP ablation was successfully performed in all patients at sites >10 mm from both the HB and the A-FP without AV block. In the inferiorly dislocated A-FP group, A-FPs seemed to be positioned much more on atrial sites and sufficiently posterior to SP ablation sites. CONCLUSIONS: The A-FP inferiorly dislocated >10 mm to the HB in one third of patients with AVNRT and seemed to be positioned deep on atrial sites. It is again emphasized that SP ablation within the triangle of Koch should be performed at a very ventricular annulus site, particularly in the inferiorly dislocated A-FP group.

Utility of virtual unipolar electrogram morphologies to detect transverse conduction block and turnaround points of typical atrial flutter.

BACKGROUND: Noncontact mapping is useful for the diagnosis of various arrhythmias. Virtual unipolar electrogram morphologies (VUEM) of the conduction block and the turnaround points, however, are not well defined. We compared the VUEM characteristics of a transverse conduction block in the posterior right atrium (RA) with those of contact bipolar electrograms obtained during typical atrial flutter (AFL). METHODS: Contact bipolar electrograms were used to map the posterior RA during typical AFL in 16 patients. Twenty points of the VUEM recorded along the block line were analyzed and compared with contact bipolar electrograms. RESULTS: Seventeen AFLs were analyzed. Fifteen AFLs showed an incomplete transverse conduction block in the posterior RA by contact bipolar mapping. A double potential on the block line corresponded to the two components of the VUEM, in which the second component showed an Rs, RS, or rS pattern. At the turnaround point, a fused double potential of the contact bipolar electrograms corresponded to a change of the second component of the VUEM from an rS to a QS morphology. Two AFLs showed a complete block line in the posterior RA. The contact bipolar electrogram showed double potentials from the inferior vena cava to the superior vena cava, whereas the second component of the VUEM remained in an unchanged Rs, RS, or rS pattern. CONCLUSION: VUEM analysis was a reliable method for identifying the posterior block line during AFL. This method may also be applicable for detecting block lines and turnaround points of circuits in other unmappable arrhythmias.

Late gadolinium enhancement on cardiac magnetic resonance imaging: is it associated with a higher incidence of nonsustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy?

PURPOSE: Late gadolinium enhancement (LGE) during cardiac magnetic resonance imaging (MRI) can be seen in patients with myocardial fibrosis accompanied by myocardial infarction and cardiomyopathy. Some idiopathic dilated cardiomyopathy (DCM) patients have fibrosis in the myocardium and show LGE during cardiac MRI. The purpose of this study was to investigate the clinical significance of LGE in patients with DCM. MATERIALS AND METHODS: We recruited 32 DCM patients who had a left ventricular ejection fraction (LVEF) of <40% by echocardiography and performed cardiac MRI. LGE images were obtained 15 min after injection of Gd-DTPA (0.1 mmol/kg) using an inversion recovery gradient echo sequence. We compared LGE(+) and LGE(-) groups in terms of their nonsustained ventricular tachycardia (NSVT) properties. We also compared LGE and the frequency of an implantable cardioverter defibrillator (ICD) implantation. RESULTS: In total, 18 patients (56.3%) had LGE and a higher incidence of NSVT (P = 0.01). ICD implantation was more frequent in the LGE(+) group (P = 0.04). CONCLUSION: Because the LGE(+) patients showed a higher incidence of NSVT and ICD implantation, cardiac MRI could prove to be a useful tool in the management of DCM patients.

Dilated phase of hypertrophic cardiomyopathy caused by Fabry disease with atrial flutter and ventricular tachycardia.

We describe a case of a 60-year-old male with dilated phase of hypertrophic cardiomyopathy caused by Fabry disease. He was diagnosed to have a cardiac variant of Fabry disease by an enzyme assay and a right ventricular endomyocardial biopsy which revealed specific features of this disease and cardiac involvement was the sole manifestation. He has developed dilated cardiomyopathy with sustained atrial flutter and frequent non-sustained ventricular tachycardia requiring isthmus ablation and cardiac resynchronization therapy with defibrillator.

The definition of fibrogenic processes in fibroblastic foci of idiopathic pulmonary fibrosis based on morphometric quantification of extracellular matrices.

There is limited information regarding the process of tissue remodeling in fibroblastic foci associated with idiopathic pulmonary fibrosis. The aim of this study was to identify the different pathologic stages of tissue remodeling in fibroblastic foci based on the histopathologic differences in the glycosaminoglycan distribution and collagen deposition. In addition, we also aimed at clarifying the stage-specific characteristics by taking into consideration the expression pattern of matrix metalloproteinase and angiogenesis. Lung biopsies of 16 patients with idiopathic pulmonary fibrosis were used. The presence of glycosaminoglycans was detected by Alcian blue staining, and type I collagen was detected by immunohistochemical analysis with a primary antibody specific to the cross-linked carboxyterminal telopeptide of type I collagen. The fibroblastic foci characterized by the expression intensity of Alcian blue and telopeptide of type I collagen were divided into 3 groups, namely, Alcian blue(+)telopeptide of type I collagen(weak), Alcian blue(+)telopeptide of type I collagen(+), and Alcian blue(weak)telopeptide of type I collagen(+); consequently, 3 new stages were defined--stages I, II, and III, respectively. A significant inverse correlation was observed between the area densities of Alcian blue(+) and telopeptide of type I collagen(+) in fibroblastic foci. Stage I was characterized by the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloprotease-2 in fibroblasts and the overlying epithelium of fibroblastic foci, and also the absence of capillary angiogenesis. In contrast, the expression of these proteins was attenuated in stage III, except for that of matrix metalloproteinase-2 in fibroblasts. In stages II and III, capillary angiogenesis was observed. Lymphangiogenesis was undetected in all the 3 stages. Thus, pathologic staging helps understand the roles of the factors involved in tissue remodeling in idiopathic pulmonary fibrosis.

Cysteinyl leukotrienes enhance the degranulation of bone marrow-derived mast cells through the autocrine mechanism.

The cysteinyl leukotrienes (LTs), LTC(4), LTD(4), and LTE(4), are potent inflammatory mediators and are involved in allergic reactions, such as bronchoconstriction, eosinophilic inflammation, and allergic cell proliferation. The present study aimed to elucidate the role of constitutively produced cysteinyl LTs in mast cell activation. We used a newly developed quantification method based on mass spectrometry to detect cysteinyl LTs in the cultured medium of mouse bone marrow-derived mast cells (BMMCs), which were obtained by interleukin (IL)-3-conditioned culture of mouse bone marrow. BMMCs were stimulated with immunoglobulin (Ig) E and antigen (IgE/Ag) or lipopolysaccharide for 1 or 24 h. This new quantification method revealed that unstimulated BMMCs produced and secreted LTB4 and LTE4 after 24 h of incubation. The treatment of unstimulated BMMCs for 2 h with montelukast, an antagonist of a cysteinyl LT receptor, CysLT1, resulted in the suppression of a downstream signaling event of this receptor, i.e., the decrease in phosphorylation of extracellular responsive kinases. Thus, cysteinyl LTs constitutively simulate BMMCs through the CysLT1 receptor in an autocrine manner. Treatment of BMMCs for 3 weeks with montelukast, which caused long-term inhibition of the autocrine cyteinyl LT-derived signal, significantly attenuated the IgE/Ag-dependent degranulation, as judged by the decrease in the release of beta-hexosaminidase, an enzyme contained in the granules, whereas the production of cytokines, such as IL-6 and tumor necrosis factor-alpha, were largely unaffected. In conclusion, an autocrine signal derived from constitutively produced cysteinyl LTs predisposes mast cells to the degranulation upon allergic stimulation.

Ceramidastin, a novel bacterial ceramidase inhibitor, produced by Penicillium sp. Mer-f17067.

Decrease of ceramide in the skin is one of the aggravating factors of atopic dermatitis. The skin is often infected by ceramidase-producing bacteria, such as Pseudomonas aeruginosa. The bacterial ceramidase then degrades ceramide in the skin. To develop anti-atopic dermatitis drugs, we searched for ceramidase inhibitors, which led to the discovery of ceramidastin, a novel inhibitor of bacterial ceramidase, from the culture broth of Penicillium sp. Mer-f17067. Ceramidastin inhibited the bacterial ceramidase with an IC(50) value of 6.25 microg ml(-1). Here we describe the isolation, physicochemical properties, structure determination and biological activity of ceramidastin.

Upper turnover portion of the reentry circuit for typical and reverse typical atrial flutter.

BACKGROUND: The posteromedial right atrium (PMRA) forms a block line during typical atrial flutter (AFL). However, whether upper turnover portion exists at the anterior or posterior superior vena cava (SVC) has not been determined. METHODS: We performed right atrial mapping during AFL in 20 patients (typical AFL, n = 17; reverse typical AFL, n = 3) using an electroanatomical mapping system. RESULTS: Mean AFL cycle length was 224 +/- 20 ms and mean number of mapping points was 140 +/- 27. PMRA formed a block line during both typical and reverse AFL in all patients. However, in 16 of 17 patients mapped with typical AFL, PMRA did not extend superiorly to the orifice of the SVC and AFL wave propagated between the upper limit of the PMRA and the posterior SVC. In the remaining patient mapped with typical AFL, a double potential was recorded along the PMRA continuously between the orifices of the inferior vena cava (IVC) and SVC. In the three patients mapped with reverse typical AFL, a posterior barrier was detected from IVC to the upper limit of the PMRA and AFL wave propagated between the upper limit of the PMRA and the posterior SVC. Mean length from IVC to upper limit of the PMRA was 81 +/- 8% of the length from IVC to SVC. CONCLUSIONS: PMRA forms a functional block line during both typical and reverse typical AFL. The upper turnover portion of reentry circuit for AFL was observed between the upper limit of the PMRA and the posterior SVC in the majority of isthmus-dependent AFL patients.

Endocardial substrate mapping for monomorphic ventricular tachycardia ablation in ischemic and non-ischemic cardiomyopathy.

We investigated the differences in the endocardial substrates between ischemic cardiomyopathy (ICM) and non-ICM (NICM) by using electro-anatomical mapping and pace-mapping. We studied 18 patients (ICM and NICM, 9 each) with monomorphic ventricular tachycardia (VT) documented by 12-leads ECG. Low voltage area was defined by signal amplitude <1.5 mV. A pace-map QRS morphology that matched VT in >10 of the 12-leads ECG was regarded as a pace-map match. And conduction delay during pace-mapping was defined as the stimulus to QRS interval >or=40 ms. Low voltage area was 53.8 +/- 21.5 and 20.8 +/- 16.7 cm2 in ICM and NICM patients, respectively (P = 0.002). Pace-mapping was assessed in 6 ICM and 9 NICM. Pace-map match with conduction delay were obtained in all the 6 ICM patients. But in NICM patients, pace-map match with conduction delay was obtained in 3 patients. Pace-map match sites where conduction delay was not observed were obtained in 5 patients. Pace-map match could not be obtained in 1 patient. We attempted ablation in 6 ICM and 7 NICM patients. Subsequently, VT recurrence was not observed in ICM but it was observed in 6 of 7 NICM patients (log-rank P = 0.0016). In NICM patients, the arrhythmogenic substrate that represented the abnormal electrogram and conduction delay was observed less within the endocardial surface when compared with that observed in ICM. VT recurrence rate subsequent to endocardial ablation was higher in NICM than in ICM patients.

Generation of new benanomicin analogues by biotransformation using Escherichia coli expressing actinomycete cytochrome P450.

Benanomicins were found as antifungal antibiotics from the culture of an actinomycete with potent antifungal activities in vitro and in vivo. We aimed to generate derivatives superior to benanomicin A by biotransformation using Escherichia coli constructed with bacterial P450 expression system. We found transformation of benanomicin A into two derivatives, 10-hydroxybenanomicin A and 11-O-demethylbenanomicin A by one of the P450-expressed strains which harbored a plasmid carrying a CYP105C1-homologous gene. Unexpectedly, the biotransformed compounds showed weak antifungal activities in vitro compared with those of benanomicin A.

Accuracy of nonstenotic coronary atherosclerosis assessment by multi-detector computed tomography.

BACKGROUND: The ability to evaluate coronary stenosis using multi-detector computed tomography (MDCT) has been well discussed. In contrast, several studies demonstrated that the plaque burden measured by intravascular ultrasound (IVUS) has a relationship to the risk of cardiovascular events. the accuracy of MDCT was studied to determine plaque and vessel size compared with IVUS. METHODS AND RESULTS: Fifty-six proximal lesions (American College of Cardiology/American Heart Association classification: segment 1, 5, 6) from 33 patients were assessed using MDCT and IVUS. The plaque and vessel area were measured from the cross-sectional image using both MDCT and IVUS. Eight coronary artery lesions with motion artifacts and heavily calcified plaques were excluded from the analysis. The vessel and lumen size evaluated using MDCT were closely correlated with those evaluated by IVUS (R(2)=0.614, 0.750 respectively). Furthermore, there was a strong correlation between percentage plaque area assessed by MDCT and IVUS (R(2)=0.824). CONCLUSION: MDCT can noninvasively quantify coronary atherosclerotic plaque with good correlation compared with IVUS in patients with atherosclerosis.

Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation.

Molecular mechanisms underlying migration of vascular smooth muscle cells (VSMCs) toward sphingosylphosphorylcholine (SPC) were analyzed in light of the hypothesis that remodeling of the actin cytoskeleton should be involved. After SPC stimulation, mitogen-activated protein kinases (MAPKs), including p38 MAPK (p38) and p42/44 MAPK (p42/44), were found to be phosphorylated. Migration of cells toward SPC was reduced in the presence of SB-203580, an inhibitor of p38, but not PD-98059, an inhibitor of p42/44. Pertussis toxin (PTX), a Gi protein inhibitor, induced an inhibitory effect on p38 phosphorylation and VSMC migration. Myosin light chain (MLC) phosphorylation occurred after SPC stimulation with or without pretreatment with SB-203580 or PTX. The MLC kinase inhibitor ML-7 and the Rho kinase inhibitor Y-27632 inhibited MLC phosphorylation but only partially inhibited SPC-directed migration. Complete inhibition was achieved with the addition of SB-203580. After SPC stimulation, the actin cytoskeleton formed thick bundles of actin filaments around the periphery of cells, and the cells were surrounded by elongated filopodia, i.e., magunapodia. The peripheral actin bundles consisted of alpha- and beta-actin, but magunapodia consisted exclusively of beta-actin. Such a remodeling of actin was reversed by addition of SB-203580 and PTX, but not ML-7 or Y-27632. Taken together, our biochemical and morphological data confirmed the regulation of actin remodeling and suggest that VSMCs migrate toward SPC, not only by an MLC phosphorylation-dependent pathway, but also by an MLC phosphorylation-independent pathway.

New naphthoquinones, f13102A and B, from a fungus strain F-13102.

Deficiency of Fas-mediated apoptosis is one of the mechanisms involved in the immune evasion by tumors. Thus, it might be a practical approach for cancer treatment that Fas-mediated apoptosis in tumor cells is modified by drugs. In the course of screening, we have isolated two new naphthoquinones, f13102A and B, from the culture broth of fungus strain F-13102. Coumpound f13102A sensitizes Fas-resistant human lung adenocarcinoma A549 cells to apoptosis.

A novel scheme of dystrophin disruption for the progression of advanced heart failure.

The precise mechanism of the progression of advanced heart failure is unknown. We assessed a new scheme in two heart failure models: (I) congenital dilated cardiomyopathy (DCM) in TO-2 strain hamsters lacking delta-sarcoglycan (SG) gene and (II) administration of a high-dose of isoproterenol, as an acute heart failure in normal rats. In TO-2 hamsters, we followed the time course of the histological, physiological and metabolic the progressions of heart failure to the end stage. Dystrophin localization detected by immunostaining age-dependently to the myoplasm and the in situ sarcolemma fragility evaluated by Evans blue entry was increased in the same cardiomyocytes. Western blotting revealed a limited cleavage of the dystrophin protein at the rod domain, strongly suggesting a contribution of endogenous protease(s). We found a remarkable up-regulation of the amount of calpain-1 and -2, and no change of their counterpart, calpastatin. After supplementing TO-2 hearts with the normal delta-SG gene in vivo, these pathological alterations and the animals' survival improved. Furthermore, dystrophin but not delta-SG was disrupted by a high dose of isoproterenol, translocated from the sarcolemma to the myoplasm and fragmented. These results of heart failure, irrespective of the hereditary or acquired origin, indicate a vicious cycle formed by the increased sarcolemma permeability, preferential activation of calpain over calpastatin, and translocation and cleavage of dystrophin would commonly lead to advanced heart failure.

A novel paradigm for therapeutic basis of advanced heart failure--assessment by gene therapy.

The precise mechanism(s) of the progression of advanced heart failure (HF) should be determined to establish strategies for its treatment or prevention. Based on pathological, molecular, and physiological findings in 3 animal models and human cases, we propose a novel scheme that a vicious cycle formed by increased sarcolemma (SL) permeability, preferential activation of calpain over calpastatin, and translocation and cleavage of dystrophin (Dys) commonly lead to advanced HF. The aim of this article was to assess our recent paradigm that disruption of myocardial Dys is a final common pathway to advanced HF, irrespective of its hereditary or acquired origin, but not intended to provide a comprehensive overview of the various factors that may be involved in the course of HF in different clinical settings. In addition, each component of Dys-associated proteins (DAP) was heterogeneously degraded in vivo and in vitro, i.e. Dys and alpha-sarcoglycan (SG) were markedly destroyed using isolated calpain 2, while delta-SG was not degraded at all. The up-regulation of calpain 2 was confirmed through previously published data that remain insufficient for precise evaluation, supporting our new scheme that the activation of calpain(s) is involved in the steady process of Dys cleavage. In addition, somatic gene therapy is discussed as a potential option to ameliorate the physiological/metabolic indices and to improve the prognosis.