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Background: The wall motion abnormalities of the left ventricle (LV) in takotsubo syndrome (TTS) are known to be transient and completely recover within a few weeks. However, there is little information about the relationship between functional recovery and tissue characteristics. The aim of this study was to investigate the recovery process of TTS using cardiovascular magnetic resonance (CMR)., Methods: Consecutive patients with TTS were prospectively enrolled. We performed serial CMR in the acute phase (<72 h after admission), the subacute phase (7-10 days after admission) and the chronic phase (3 months later). To assess the degree of myocardial edema quantitatively, we evaluated the signal intensity of myocardium on T2-weighted images and calculated the signal intensity ratio compared with the skeletal muscle., Results: Fifteen patients with TTS were enrolled. CMR demonstrated reduced LV ejection fraction in the acute phase, and it recovered almost completely by the subacute phase. On the other hand, severe myocardial edema was still observed in the subacute phase, associated with increased LV mass. The highest signal intensity ratio in the subacute phase was correlated with the maximum voltage of negative T wave on electrocardiogram (r = 0.57, p = 0.03)., Conclusions: In patients with TTS, myocardial edema associated with increased LV mass still remained in the subacute phase despite functional recovery of the LV. Electrocardiogram may be useful to assess the degree of myocardial edema in the subacute phase. Our study suggests that myocardial ischemia might have a central role in developing TTS.

Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI 4mm ). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI 4mm (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI 4mm ). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI 4mm in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI 4mm in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.

Previous studies reported that elevated serum uric acid level was associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and is believed to play important roles in coronary atherosclerosis. However, the relation between XOR and coronary lipid plaque is unclear. Patients with stable coronary artery disease who underwent elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively included. They were divided into 3 groups according to plasma XOR activities based on a previous report: low, normal, and high. Quantitative coronary angiography and gray-scale IVUS were analyzed. The primary end point was coronary lipid plaques in a nontarget vessel assessed by NIRS-IVUS with lipid core burden index (LCBI) and maximum LCBI in 4 mm (maxLCBI 4mm ). Out of 68 patients, 26, 31, and 11 patients were classified as low, normal, and high XOR activity groups. Quantitative coronary angiography demonstrated that the high XOR activity group had longer lesion length, smaller minimum lumen diameter, and higher percentage of diameter stenosis in a nontarget vessel among the 3 groups. Gray-scale IVUS analysis also showed smaller lumen area in the high XOR activity group than the others. LCBI (102.1 ± 56.5 vs 65.6 ± 48.5 vs 55.6 ± 37.8, p = 0.04) and maxLCBI 4mm (474.4 ± 171.6 vs 347.4 ± 181.6, 294.0 ± 155.9, p = 0.04) in a nontarget vessel were significantly higher in the high XOR group than in the normal and low groups. In conclusion, elevated XOR activity was associated with coronary lipid-rich plaque in a nontarget vessel in patients with stable coronary artery disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The SYNERGY coronary stent is new-generation drug-eluting stents, which has a thin-strut platinum-chromium platform with everolimus in a biodegradable polymer applied to the abluminal surface. It would be speculated that favorable arterial healing with early strut coverage could be achieved. The present study investigated the degree of strut coverage using optical coherence tomography (OCT) 2 weeks after SYNERGY implantation and clinical factors contributing to strut coverage. A total of 29 patients who underwent staged percutaneous coronary intervention (PCI) to residual lesions 2 weeks after the index PCI with SYNERGY stent implantation were enrolled. At the time of staged PCI, OCT examinations of the SYNERGY stent were performed for conventional OCT analysis on both cross-sectional and strut level. SYNERGY stent showed a high level of strut coverage and apposition, and the percentage was 82.4 ± 12.4% and 96.2 ± 5.0%, respectively. The lesion complexity was significantly related to greater strut coverage on univariate analysis; however, it was found to be insignificant in multivariate analysis. Our findings suggest early arterial healing after SYNERGY stent implantation.

Aims: Residual SYNTAX score (rSS) is known to be associated with cardiac events. We sought to investigate the association between rSS and greyscale and virtual histology (VH)-intravascular ultrasound (IVUS) plaque morphology, and the association between rSS and non-culprit-related major adverse cardiac events (MACE) using data from the PROSPECT study., Methods and Results: A total of 697 patients with acute coronary syndromes were enrolled in the PROSPECT study. Three-vessel greyscale and VH-IVUS were performed. Among them, 688 patients with paired baseline SS or SYNTAX score and rSS were identified and divided into three groups - rSS=0 (n=184), 0 8 (n=140). MACE was defined as the composite of cardiac death, cardiac arrest, myocardial infarction, or rehospitalisation for unstable or progressive angina. There was a significant difference in the three-year non-culprit-related MACE rates among the three groups (5.7% versus 11.9% versus 19.7%, lowest to highest rSS; p=0.004) mainly due to rehospitalisation for unstable or progressive angina. On multivariable analysis, patients with ≥1 lesion with plaque burden ≥70% or ≥1 lesion with a minimum lumen area ≤4 mm2 and total dense calcium volume per patient were significantly correlated with rSS. Insulin-treated diabetes mellitus, rSS, and patients with ≥1 lesion with plaque burden ≥70% were independent predictors of non-culprit-related MACE., Conclusions: Plaque morphology based on greyscale IVUS and VH-IVUS was significantly correlated with rSS, and rSS and plaque burden ≥70% independently predicted non-culprit-related MACE.

Microvessels within neoatherosclerosis are associated with vulnerability and increase from the early to the very late phase after drug-eluting stent implantation. Microbubble contrast agents have been suggested to enhance tissue microvasculature for optical coherence tomography (OCT) imaging. The present study investigated whether OCT signal intensity of neointima within stented segments was enhanced after intracoronary administration of microbubble contrast agents. A total of 40 patients who underwent follow-up coronary angiography after drug-eluting stent implantation were enrolled. At the time of follow-up coronary angiography, OCT images of the stented segments were recorded before and after intracoronary administration of microbubble contrast agents. Mean OCT signal intensity of neointima after microbubble administration significantly increased [95.5 (85.7, 106.2) vs. 96.5 (88.7, 109.9), p = 0.001]. Multivariate analysis demonstrated the relationship between diabetes and greater neointima enhancement. The change in the OCT signal intensity of neointima following microbubble administration tended to be higher in diabetic patients than in non-diabetic patients [4.6 (0.6, 8.5) vs. 1.4 (- 1.1, 3.0), p = 0.05]. These findings suggest that this methodology may allow identification of neovascularization in neointima and evaluation of vulnerability of neoatherosclerosis. Microvessels in neointima may be a future target of pharmacological and interventional innovations for preventing stent failure.

Background: Vasospastic angina (VSA), which often causes acute coronary syndrome (ACS), can be diagnosed by intracoronary acetylcholine (ACh) provocation test. However, the safety and usefulness of ACh provocation test in ACS patients on emergency coronary angiography (CAG) compared to non-emergency settings are unclear., Methods: A total of 529 patients undergoing ACh provocation test during emergency or non-emergency CAG were included. Patients with resuscitated cardiac arrest were excluded. The primary endpoint was adverse events defined as a composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, cardiac tamponade, and stroke within 24 h after ACh provocation test., Results: There were no significant differences of the clinical characteristics between the groups of emergency (n = 84) and non-emergency (n = 445) ACh provocation test. The rate of positive ACh provocation test was similar between the 2 groups (50% vs. 49%, p = 0.81). Similarly, the incidence of adverse events in patients with emergency and non-emergency ACh provocation test did not significantly differ (1.2% vs. 1.3%, p = 1.00)., Conclusion: ACh provocation test can be safely performed in ACS patients with no obstructive culprit lesions on emergency CAG, and may be useful to diagnose VSA in those patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, we develop a computer-aided material design system to represent and extract knowledge related to material design from natural language texts. A machine learning model is trained on a text corpus weakly labeled by minimal annotated relationship data (~100 labeled relationships) to extract knowledge from scientific articles. The knowledge is represented by relationships between scientific concepts, such as { annealing, grain size, strength }. The extracted relationships are represented as a knowledge graph formatted according to design charts, inspired by the process-structure-property-performance (PSPP) reciprocity. The design chart provides an intuitive effect of processes on properties and prospective processes to achieve the certain desired properties. Our system semantically searches the scientific literature and provides knowledge in the form of a design chart, and we hope it contributes more efficient developments of new materials.

Objectives: This study assessed that the use of real-time monitoring and visualization of peak skin dose could reduce radiation dose during coronary angiography (CAG) and percutaneous coronary intervention (PCI)., Background: Exposure to ionizing radiation has dose related effects including skin damage. Reducing the radiation exposure is important during CAG and PCI. The skin dose-tracking system (DTS) has a real-time monitor of radiation peak skin dose., Methods: A total of 323 consecutive patients who underwent CAG and PCI between September 2014 and June 2015 were enrolled. Patients were classified into with DTS group (CAG alone in 104 and PCI in 57 patients) or without DTS group (CAG alone in 106 and PCI in 56 patients)., Results: There was no significant difference in reference air kerma between CAG alone with and without DTS groups. Reference air kerma with DTS group during PCI was lower than without DTS group (204.6 ± 141.1 mGy vs. 294.2 ± 237.4 mGy, P = 0.016). Moreover, kerma area product (17.8 ± 13.0 Gycm 2 vs. 25.2 ± 19.3 Gycm 2 , P = 0.019) and number of cine runs (12.8 ± 5.0 vs. 15.5 ± 6.5, P = 0.013) with DTS group were lower than without DTS group. Multiple regression analysis showed increased reference air kerma was associated with male gender, body mass index and type B2/C lesion. Conversely, DTS correlated with decreased reference air kerma., Conclusions: The use of DTS could reduce radiation dose during PCI. Real-time radiation monitoring and visualization of peak skin dose was effective for the patients with PCI., (© 2017 Wiley Periodicals, Inc.)

Excimer laser coronary atherectomy (ELCA) has been used for the treatment of complex percutaneous coronary intervention (PCI) such as in-stent restenosis (ISR). However, little information was provided about the clinical outcomes after treatment with ELCA for ISR of drug-eluting stents (DES). This study aimed to investigate the long-term clinical outcomes after PCI with ELCA for ISR of DES.A total of 81 consecutive patients with 87 lesions who underwent PCI for ISR of DES were included. Patients were classified into a PCI with ELCA group (23 patients with 24 lesions) and a PCI without ELCA group (58 patients with 63 lesions). The major adverse cardiac events (MACE) were evaluated. The mean duration of clinical follow-up was 29.8 ± 11.6 months. The incidences of diffuse restenosis and AHA/ACC type B2 or C lesion in the PCI with ELCA group were higher than in the PCI without ELCA group. Quantitative coronary angiography showed the acute luminal gain in the PCI with ELCA group was greater than in the PCI without ELCA group (1.64 ± 0.48 mm versus 1.26 ± 0.42 mm, P < 0.001). There were no significant differences in all-cause death, myocardial infarction, or target lesion revascularization between the 2 groups. Multivariate analysis due to a Cox proportional-hazards model showed that multivessel disease was an independent predictor of MACE (hazard ratio 3.05, 95% confidence interval 1.22 to 7.61, P = 0.02). ELCA was effective as an atherectomy device for lumen enlargement and optimal lesion preparation. Even though ELCA was used for ISR of DES in significantly more complex lesions, the long-term clinical outcomes were favorable and similar.

Objective: Previous intravascular ultrasound (IVUS) studies have not established a relationship between chronic statin use and plaque morphology and composition in patients undergoing percutaneous coronary intervention (PCI). We sought to use pre-PCI grayscale and virtual histology (VH)-IVUS to assess plaque morphology and composition in patients treated with chronic statin therapy compared with patients who were not taking statins before admission and PCI., Methods: In a prespecified substudy of the Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study, pre-PCI grayscale and VH-IVUS were performed in 780 patients with 916 culprit and 765 nonculprit lesions., Results: Overall, 338 patients were treated with chronic statin therapy before admission. Statin-treated patients were older and had a higher prevalence of coronary risk factors. Statin-treated patients were more likely to present with stable angina, whereas non-statin-treated patients more frequently presented with acute myocardial infarction. Grayscale and VH-IVUS findings showed that lesions in statin-treated patients had a smaller plaque burden, but more dense calcium. Statin-treated patients had more calcified thick-cap fibroatheromas (9.2 vs. 3.7%, P=0.0007), but fewer VH-defined thin-cap fibroatheromas (45.2 vs. 56.1%, P=0.001) or plaque ruptures (26.6 vs. 38.4%, P=0.0001). In a propensity-matched population (n=249 in each group), similar results were obtained as regards clinical presentation and grayscale and VH-IVUS findings., Conclusion: Chronic statin use in patients with coronary artery disease was associated with more stable clinical presentation and IVUS findings consistent with greater lesion stability (fewer VH-thin-cap fibroatheromas and plaque ruptures and more calcified thick-cap fibroatheromas).

Intravascular ultrasound (IVUS) is a reliable imaging tool to guide percutaneous coronary intervention. There has been increasing evidence supporting the clinical utility of IVUS-guided drug-eluting stent (DES) implantation, including randomized trials, observational studies, and meta-analyses of both. IVUS provides cross-sectional views of the coronary artery wall, and allows us to assess stenosis severity, identify plaque morphology, optimize stent implantation, and understand mechanism of stent failure. IVUS guidance can increase DES efficacy and decrease clinical events. In this review article, we summarize available evidence on IVUS-guided DES implantation.

We report the successful retrieval of an entrapped interventional guide wire between a newly deployed coronary stent and severely calcified vessel wall. Using a buddy wire technique, the stent was deployed at high pressure in a culprit lesion of the left anterior descending (LAD) artery. The buddy wire in the LAD artery was entrapped between the deployed stent and severely calcified vessel wall, as it was not removed before stent deployment, and could not be retrieved. Neither balloon catheters nor a microcatheter were able to be advanced behind the stent over the entrapped guide wire. Excimer laser coronary atherectomy (ELCA) was performed within the stent to modify and soften the calcification behind the deployed stent. Consequently, the entrapped guide wire was retrieved successfully and safely. This case illustrates that ELCA can be utilized to retrieve an entrapped guide wire between a deployed stent and calcified vessel wall., (© 2014 Wiley Periodicals, Inc.)

In Japan, a lower maintenance dose of ticlopidine is used than in the United States and Europe. Therefore a lower maintenance dose of clopidogrel may also be considered appropriate in Japanese patients. The present randomized pilot study evaluated the efficacy and safety of 50 mg clopidogrel in Japanese patients who underwent drug-eluting stent (DES) implantation. A total of 200 patients with 277 lesions who underwent intravascular ultrasound-guided DES implantation were enrolled. The subjects were allocated to the 50- or 75-mg clopidogrel group. All patients received 100 mg aspirin daily before the procedure, and this continued indefinitely. The duration of clinical follow-up was 21.8 ± 5.7 months in the 75-mg group and 21.9 ± 6.1 months in the 50-mg group (P = 0.96). During follow-up, no cardiac death, myocardial infarction, or stent thrombosis was observed in either group. Side effects of clopidogrel were observed in 4 patients (4.0 %) in the 75-mg group and in 4 patients (4.0 %) in the 50-mg group. Following this randomized pilot study, it may be justified to perform a large-scale randomized study comparing 50- and 75-mg dosing of clopidogrel in Japanese patients undergoing coronary stent implantation.

Whether endothelial dysfunction after sirolimus-eluting stent (SES) implantation is persistent has not been fully evaluated. Endothelial function was evaluated in 152 lesions that underwent follow-up coronary angiography after SES implantation. Lesions were classified into 2 groups according to the duration between SES implantation and follow-up: ≤12 months (n = 95) and >12 months (n = 57). Changes in coronary diameter in response to 10(-8) mol/L (-2.4% ± 6.3% vs -4.9% ± 3.8%, P < .01) and 10(-7) mol/L acetylcholine (Ach; -4.6% ± 7.6% vs -10.7% ± 9.1%, P < .001) in segment proximal to SES were significantly attenuated in the >12-month group than in the ≤12-month group. There were less changes in coronary diameter in response to 10(-8) mol/L (-2.3% ± 4.6% vs -6.9% ± 5.0%, P < .001) and 10(-7) mol/L Ach (-6.5% ± 11.4% vs -16.8% ± 10.5%, P < .001) in segment distal to SES in the >12-month group. Endothelial dysfunction may diminish long after SES implantation.

Background: Stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) has been shown to enhance endothelial healing after spontaneous or iatrogenic arterial disruption. Granulocyte colony-stimulating factor treatment might attenuate endothelial dysfunction after sirolimus-eluting stent (SES) implantation that may be associated with adverse cardiac events during follow-up. This prospective, double-blind, randomized, placebo-controlled study investigated whether G-CSF improved endothelial dysfunction after SES implantation., Methods: One hundred patients who underwent SES implantation were randomly assigned to the G-CSF (n = 50) or the placebo group (n = 50). They received daily subcutaneous injection of 300 μg G-CSF or saline for 5 days. Endothelial function was estimated by measuring the coronary vasoreactivity in the segments 15 mm proximal and distal to SES in response to intracoronary infusion of acetylcholine (10(-8) and 10(-7) mol/L) at 9-month follow-up., Results: Follow-up angiography was performed in 41 G-CSF patients (82%) and 46 placebo patients (92%) (P = .14). Changes in coronary diameter in response to acetylcholine infusion in the proximal segment were not significantly different between the 2 groups. However, vasoconstriction in the distal segment in response to 10(-8) mol/L (-3.9% ± 6.4% vs -7.0% ± 8.1%, P < .05) and 10(-7) mol/L (-8.8% ± 11.0% vs -15.2% ± 7.6%, P < .01) acetylcholine infusion was attenuated in the G-CSF group. Endothelium-independent vasodilatation after nitrate infusion did not differ between the 2 groups., Conclusion: Granulocyte colony-stimulating factor attenuates endothelial dysfunction after SES implantation., (Copyright © 2013 Mosby, Inc. All rights reserved.)

There is little information about coronary artery endothelial dysfunction in patients with sleep apnea. We evaluated relation between severity of sleep apnea and coronary artery endothelial dysfunction. In all, 26 patients without significant coronary stenoses were enrolled. Endothelial function was estimated by measuring coronary vasoreactivity in response to acetylcholine infusion (10(-7) mol/L) into coronary arteries. Vasoconstriction rate was defined as ([lumen diameter after isosorbide dinitrate injection - lumen diameter after acetylcholine injection]/lumen diameter after isosorbide dinitrate injection × 100). Vasoconstriction rate was calculated at each major coronary artery and the highest value was used for that patient. Overnight sleep study was performed and the apnea-hypopnea index (AHI) was calculated as the mean number of apneas and hypopneas per hour of sleep. There was significant correlation between AHI and vasoconstriction rate (P = .04). There is significant correlation between severity of sleep apnea and endothelial function of coronary arteries.

Cardiac rupture is a life-threatening complication during diagnostic cardiac catheterization, however, it rarely occurs nowadays. The present case report describes cardiac rupture during diagnostic cardiac catheterization using a 4F pigtail catheter and a 0.035" flexible guidewire, and global ST-segment elevation associated with impending cardiac rupture.

Stent thrombosis is an infrequent event but a potentially fatal complication of coronary stenting. Adherence to long-term antiplatelet therapy plays an important role in the prevention of late stent thrombosis after drug-eluting stent (DES) implantation. Poor glycemic control due to nonadherence to diabetic treatments is likely to result in severely diffuse coronary atherosclerosis and diabetic microvascular complications. This case report describes fatal very late stent thrombosis in a young diabetic patient, which teaches us about the potential risk of DES in patients with acute myocardial infarction and the importance of patient education about long-term dual antiplatelet therapy after DES implantation. Furthermore, it demonstrates severely diffuse atherosclerosis in a young diabetic patient with nonadherence to diabetic treatments.

We have observed the InSb(001)-c(8 x 2) surface by using high-resolution transmission electron microscopy in the profile-imaging geometry. All images observed at temperatures up to 420 degrees C agree well with the c(8 x 2) model reported by Kumpf et al. [Phys. Rev. Lett. 86, 3586 (2001)]]. 1/30 sec real-time observations at 420 degrees C evidence that a part of the subsurface and surface layers (called a gull-type segment) undergo switching to and from a bulk configuration. The finding is suggestive of large anisotropy in the mean square displacement of the c(8 x 2) surface.

The protein mu1B is a member of the medium chain family of the clathrin-associated adaptor complex and is expressed exclusively in epithelial cells. We determined the genomic structure of previously cloned murine genes for mu1B (Ap1m2) and its closely related homolog, mu1A (Ap1m1). Comparison of their genomic structures revealed that the positions of introns are identical between these two genes, except for the insertion of an additional intron in Ap1m1 (intron 4). By contrast, these structures are different from that of the more distantly related Ap2m1 gene encoding mu2. Taken together with the similarity of amino acid sequences among these genes, the data presented in this study suggest that Ap1m1/2 and Ap2m1 diverged long before the separation of Ap1m1 and Ap1m2, which most likely resulted from a relatively recent gene duplication. We also mapped AP1M2 to human chromosome 19p13.2 and Ap1m2 to the proximal region of mouse chromosome 9. The results are consistent with the fact that these regions are syntenic., (Copyright 1999 S. Karger AG, Basel)