Quantification of left ventricular regional functions using ECG-gated myocardial perfusion SPECT--validation of left ventricular systolic functions--.

OBJECTIVE: We have developed a program to quantify regional left ventricular (LV) function and wall motion synchrony using ECG-gated myocardial perfusion SPECT (MPS). This preliminary study was undertaken to validate the use of this program for estimating regional LV systolic function. METHODS: Patients were subjected to MPS by 99mTc-sestamibi at rest. The study included 20 patients who were confirmed to have a low probability of coronary artery disease (LPG; low probability group), 19 heart disease patients who were examined by MPS and equilibrium radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The values of the ejection fraction (EF) and peak ejection rate (PER) were estimated. The global functions evaluated by this program were compared with those obtained by ERNA in the ERG. For regional assessment, the reference values of the functional indices were obtained for 17 LV segments in LPG. The Z score, (reference average value of the segment--patient's value of the segment)/reference standard deviation of the segment, was used for the evaluation of regional functions; a score equal to or greater than 2 was defined as abnormal. Semiquantitative visual interpretation of 2DE was used as the standard to assess wall motion. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these criteria and the relationship between 2DE grading and Z scoring were validated in 2DEG. RESULTS: The values of the global EF and PER evaluated by this program correlated with those determined by ERNA (r = 0.76 and 0.58, respectively; p < 0.005 and 0.01, respectively). The sensitivities of regional EF and PER for segmental wall motion abnormalities were 86.7% and 68.7%, respectively; their specificities were 86.7% and 95.5%, respectively; their PPVs were 64.3% and 79.2%, respectively; and their NPVs were 96.0% and 91.7%, respectively. The Z scores of these indices significantly correlated with the scores determined by 2DE (rs = 0.70 and 0.68, respectively; p < 10(-10)). CONCLUSION: The potential of this program to quantify the regional systolic function was validated.

Differential cellular and subcellular localization of heme-binding protein 23/peroxiredoxin I and heme oxygenase-1 in rat liver.

Heme-binding protein 23 (HBP23), also termed peroxiredoxin (Prx) I, and heme oxygenase-1 (HO-1) are distinct antioxidant stress proteins that are co-ordinately induced by oxidative stress. HBP23/Prx I has thioredoxin-dependent peroxidase activity with high binding affinity for the pro-oxidant heme, while HO-1 is the inducible isoform of the rate-limiting enzyme of heme degradation. We investigated the cellular and subcellular localization of both proteins in rat liver. Whereas by immunohistochemistry (IHC) a uniformly high level of HBP23/Prx I expression was observed in liver parenchymal and different sinusoidal cells, HO-1 expression was restricted to Kupffer cells. By immunoelectron microscopy using the protein A-gold technique, HBP23/Prx I immunoreactivity was detected in cytoplasm, nuclear matrix, mitochondria, and peroxisomes of parenchymal and non-parenchymal liver cell populations. In contrast, the secretory pathway, i.e., the endoplasmic reticulum and Golgi complex, was free of label. As determined by immunocytochemical (ICC) studies in liver cell cultures and by Western and Northern blotting analysis, HBP23/Prx I was highly expressed in cultures of isolated hepatocytes and Kupffer cells. In contrast, HO-1 was constitutively expressed only in Kupffer cell cultures but was also inducible in hepatocytes. These data suggest that HBP23/Prx I and HO-1 may have complementary antioxidant functions in different cell populations in rat liver.

Induction of heme-binding protein 23/peroxiredoxin I gene expression by okadaic acid in cultured rat hepatocytes.

Heme-binding protein 23 (HBP23), also termed peroxiredoxin I (Prx I), is an antioxidant protein that is induced by various oxidative stress stimuli. HBP23/Prx I has thioredoxin-dependent peroxidase activity and noncovalently binds the prooxidant heme with high affinity. To investigate the regulatory role of cellular phosphorylation and dephosphorylation events on hepatic HBP23/Prx I gene expression, primary cultures of rat hepatocytes were treated with okadaic acid (OA) which is a specific inhibitor of the serine threonine protein phosphatases 1 and 2A. In hepatocyte cultures HBP23/Prx I was highly expressed for up to 5 days and, both protein and mRNA levels of HBP23/Prx I were induced by OA. The time kinetics of OA-dependent HBP23/Prx I mRNA upregulation were coordinate to that of heme oxygenase (HO)-1, which is the inducible isoform of the rate-limiting enzyme of heme-degradation. In contrast to HO-1, however, induction of HBP23/Prx I mRNA by OA was downregulated by dibutyryl-cAMP, and was enhanced by the specific protein kinase A inhibitors KT5720 and H-89. HBP23/Prx I induction by OA occurred on the transcriptional level as determined by studies with actinomycin D and nuclear run-off assays.

Delayed plaque protrusion after carotid artery stenting for the patient with symptomatic bi-lateral carotid artery stenosis.

Carotid artery stenting (CAS) has been developed as an alternative therapeutic strategy for carotid endarterectomy (CEA) for the past several decades. One of the remaining issues of CAS is the relatively higher incidence of ipsi-lateral stroke after the procedure compared with CEA. Ischemic stroke after CAS sometimes occurred after catheterization, and a major cause of delayed stroke has been hypothesized to be stent-thrombosis. In this report, we present a case of a delayed plaque protrusion observed by contrast enhanced computed tomography and intravascular ultrasound, which could be the cause of the delayed recurrence of ischemic symptom. The lesion required an additional endovascular treatment to relieve the patient of the recurrence. This phenomenon might be a possible reason for the delayed ischemic stroke after CAS.

Dimer-oligomer interconversion of wild-type and mutant rat 2-Cys peroxiredoxin: disulfide formation at dimer-dimer interfaces is not essential for decamerization.

Rat heme-binding protein 23 (HBP23)/peroxiredoxin (Prx I) belongs to the 2-Cys peroxiredoxin type I family and exhibits peroxidase activity coupled with reduced thioredoxin (Trx) as an electron donor. We analyzed the dimer-oligomer interconversion of wild-type and mutant HBP23/Prx I by gel filtration and found that the C52S and C173S mutants existed mostly as decamers, whereas the wild type was a mixture of various forms, favoring the decamer at higher protein concentration and lower ionic salt concentration and in the presence of dithiothreitol. The C83S mutant was predominantly dimeric, in agreement with a previous crystallographic analysis (Hirotsu, S., Abe, Y., Okada, K., Nagahara, N., Hori, H., Nishino, T., and Hakoshima, T. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 12333-12338). X-ray diffraction analysis of the decameric C52S mutant revealed a toroidal structure (diameter, approximately 130A; inside diameter, approximately 55A; thickness, approximately 45A). In contrast to human Prx I, which was recently reported to exist predominantly as the decamer with Cys(83)-Cys(83) disulfide bonds at all dimer-dimer interfaces, rat HBP23/Prx I has a Cys(83)-Cys(83) disulfide bond at only one dimer-dimer interface (S-S separation of approximately 2.1A), whereas the interactions at the other interfaces (mean S-S separation of 3.6A) appear to involve hydrophobic and van der Waals forces. This finding is consistent with gel filtration analyses showing that the protein readily interconverts between dimer and oligomeric forms. The C83S mutant exhibited similar peroxidase activity to the wild type, which is exclusively dimeric, in the Trx/Trx reductase system. At higher concentrations, where the protein was mostly decameric, less efficient attack of reduced Trx was observed in a [(14)C]iodoacetamide incorporation experiment. We suggest that the dimerdecamer interconversion may have a regulatory role.

Vasospasms of the radial artery after the transradial approach for coronary angiography and angioplasty.

We examined vasospasms of the radial artery after a transradial approach was used for coronary angiography or angioplasty. In forty-eight patients (39 males and 9 females), arteriography of the radial artery was initially performed just after the transradial approach was used for coronary angiography and/or angioplasty. Then, five months later, a second arteriography of the radial artery was obtained after a transbrachial approach was used for coronary angiography. First and second arteriographies were compared to evaluate vaso-spasms of the radial artery. In the present study, more than 75% stenosis in the radial artery, 25-75% stenosis, and less than 25% stenosis were tentatively defined as severe spasms, moderate spasms, and mild spasms, respectively. In arteriographic studies on the radial artery, twenty-four patients (50%) had severe radial artery spasms, eleven patients (23%) had moderate spasms, and thirteen patients (27%) had mild spasms. The diameters of both the proximal and distal radial arteries in the severe spasm group were significantly smaller than those in the mild and moderate spasm groups (proximal site: severe group 2.39 +/- 0.70 mm versus mild group 2.98 +/- 0.46 mm, P < 0.05, and moderate group 2.96 +/- 0.77 mm, P < 0.05, distal site: severe group 2.26 +/- 0.60 mm versus mild group 2.73 +/- 0.47 mm, P < 0.05, and moderate group 2.86 +/- 0.71 mm, P < 0.05). We concluded that vasospasms of the radial artery occurred in most patients after the transradial approach. Furthermore, severe radial spasms were strongly correlated with the size of the diameter of the artery.