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Biomedical subjects

N Kume

Publications and source records attributed to N Kume.

At least 73 records · Page 4Linked to original sources

Visualization of functional improvement by 123I-IMP lung SPET after thromboendarterectomy for chronic pulmonary embolism.

We report on six patients with chronic pulmonary embolism who underwent 123I-IMP and 99Tcm-MAA lung SPET before and after thromboendarterectomy. 123I-IMP lung SPET can assess the viability of lung parenchyma, because it is a non-particulate agent that accumulates in the endothelial membranes of pulmonary capillaries. Chronic pulmonary thromboembolism accompanied by pulmonary hypertension has a poor prognosis that may be improved only by thromboendarterectomy. We compared 123I-IMP and 99Tcm-MAA lung SPET in terms of functional improvement after such surgery. After thromboendarterectomy, all six patients were functionally improved, according to the criteria of the New York Heart Association. The pre- and post-surgery percentage of vascular obstruction did not differ significantly with 99Tcm-MAA lung SPET (44.8 +/- 11.2% and 32.5 +/- 15.6% pre- and post-surgery, respectively). In contrast, 123I-IMP lung SPET revealed a significant pre- versus post-surgery difference (15.5 +/- 9.5% and 3.3 +/- 5.9% pre- and post-surgery, respectively). 123I-IMP lung SPET could be useful for evaluating thromboendarterectomy because pulmonary parenchymal viability owing to arterial microvasculature can be estimated.

Adult↗

Gallates inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of leukocyte adhesion molecules in vascular endothelial cells.

Gallates (gallic acid esters) belong to the class of phenolic compounds, which are abundant in red wine. In this study, we show that gallates can inhibit cytokine-induced activation of nuclear factor kappaB (NF-kappaB) and thereby reduce expression of endothelial-leukocyte adhesion molecules in cultured human umbilical vein endothelial cells (HUVECs). Pretreatment of HUVECs with ethyl gallate (3 to 10 micromol/L) significantly suppressed interleukin-1alpha (IL-1alpha)- or tumor necrosis factor-alpha (TNF-alpha)- induced mRNA and cell-surface expression of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and E-selectin, which was associated with reduced adhesion of leukocytes to HUVECs. Gel shift assays with the NF-kappaB consensus sequence showed the decreased densities of the shifted bands in gallate-treated HUVECs. Furthermore, gallate pretreatment inhibited cytokine-induced transcription of a fusion gene, which consisted of 4 repeats of the NF-kappaB consensus sequence and the luciferase reporter gene. Immunoblot analysis of nuclear extracts and whole-cell lysates demonstrated the decreased amounts of NF-kappaB p65 in nuclei but equal amounts of inhibitor-kappaBalpha (I-kappaBalpha) in whole-cell lysates of ethyl gallate-treated HUVECs. Incubation of the nuclear extracts from cytokine-activated HUVECs with ethyl gallate did not affect the NF-kappaB shifted bands induced by cytokines in gel shift assays. Taken together, these data demonstrate that ethyl gallate can inhibit cytokine-induced nuclear translocation of NF-kappaB p65 by way of a mechanism independent of I-kappaBalpha degradation and thereby suppress expression of VCAM-1, ICAM-1, and E-selectin, which was associated with reduced adhesion of leukocytes. These results in vitro demonstrate that gallates can exhibit anti-inflammatory properties by blocking activation of NF-kappaB and suggest that these natural compounds, abundant in red wine, may play important roles in the prevention of atherosclerosis and inflammatory responses in vivo.

Arteriosclerosis↗

Repeated 131I treatment of a residual ovarian teratoma containing malignant thyroid tissue.

A 49-year-old woman with ovarian teratoma received 131I treatment three times for an unresectable mass containing malignant thyroid tissue after surgery. Repeated 131I treatment effectively reduced serum thyroglobulin (Tg) level and tumour uptake of 131I, despite absence of any change in size of the treated tumour. Treatment did not inhibit the increase of serum CA-125 and tumour 201Tl uptake, associated with progression of a radioresistant intratumoral hyper-perfused tissue component, detected by colour Doppler ultrasound. Serum CA-125 level and tumour 201Tl uptake were not significantly changed despite temporary increases in serum Tg level after each 131I treatment. These observations indicate the importance of diagnostic measures using combined functional imaging and tumour markers in managing this rare tumour.

Biomarkers, Tumor↗

[Aspergillosis following influenza A infection].

An 83-year-old man had an influenza-like upper respiratory infection that progressed to pneumonia and respiratory insufficiency during a period two weeks. After admission, anti-influenza A antibody increased 32-fold and antibiotic treatment had little effect on the pneumonia. Aspergillus antigen was detected from his serum and pleural effusion, however, culture of sputum was negative for aspergillus. Administration of amphotericin B reduced the serum level of aspergillus antigen, however he died due to the progression of respiratory insufficiency and bloody sputum. Aspergillus infection is generally thought to occur in immunocompromised hosts, but this patient had no apparent immunosuppressive conditions except for his age before the influenza A infection. His WBC and lymphocyte count temporally decreased to 2,000 x 10(6)/L (lymphocytes 160 x 10(6)/L) followed by aspergillus infection. This temporally reduction of lymphocytes is thought to have been responsible for the aspergillus infection. Complications of influenza infection are sometimes fatal and vaccination against influenza seems necessary in high risk individuals such as elderly people.

Aged↗

Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages: upregulated expression by TNF-alpha.

Uptake of oxidized low density lipoprotein (Ox-LDL) and subsequent foam cell transformation have been implicated in early atherogenesis. Although multiple molecules, including class A and B scavenger receptors, have been identified as Ox-LDL receptors, additional receptors may also be involved in this process. Here, we provide evidence that lectin-like Ox-LDL receptor-1 (LOX-1), a novel Ox-LDL receptor initially identified in vascular endothelial cells, is also expressed in macrophages in humans and mice. Expression of LOX-1 can be induced after macrophage-like differentiation in vitro in human peripheral blood monocytes and the related cell line THP-1 cells. Furthermore, LOX-1 expression can also be detected in resident peritoneal macrophages, and can be upregulated by an inflammatory cytokine TNF-alpha. These results suggest that LOX-1 in macrophages may play an important role in Ox-LDL uptake and subsequent foam cell formation in this cell type.

Animals↗

Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes.

Accumulation of substantial numbers of activated T lymphocytes, as well as monocyte/macrophages, in focal areas of arterial intima appears to be a hallmark of atherogenesis. Our previous report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate the expression of heparin-binding epidermal growth factor-like growth factor and the interleukin (IL)-2 receptor in cultured human peripheral T lymphocytes. In this study, we show that lyso-PC can also enhance interferon gamma (IFN-gamma) secretion and gene expression in human T lymphocytes. Lyso-PC-induced upregulation of IFN-gamma depended on the presence of IL-2, IL-12, or phytohemagglutinin in culture media and was similarly observed in both CD4+ and CD8+ subsets. Actinomycin D chase by Northern blotting showed that lyso-PC significantly prolonged IFN-gamma mRNA half-lives in human T cells. Transient transfection of IFN-gamma promoter-reporter gene construct in the human T-cell line Jurkat cells demonstrated that lyso-PC stimulated the transcription of IFN-gamma promoter-driven luciferase gene. Analyses of serial deletion mutations of IFN-gamma promoter revealed that the lyso-PC-responsive element is located between base pairs - 102 and -78 of the transcription initiation site of the IFN-gamma gene. Enhanced expression of IFN-gamma in T lymphocytes by lyso-PC may play a crucial role in atherogenesis.

CD4-Positive T-Lymphocytes↗

Lysophosphatidylcholine upregulates CD40 ligand expression in newly activated human CD4+ T cells.

Lysophosphatidylcholine (lyso-PC) accumulates in tissues undergoing inflammation and atherosclerosis, where an infiltration of T cells is also seen. We found that lyso-PC increased IFN-gamma production and CD40L expression in CD4+ T cells stimulated with anti-CD3 Ab and recombinant CD80 molecules, whereas lyso-PC did not affect IL-2 and IL-4 production. These results suggest that lyso-PC, in combination with other stimuli, may regulate CD4+ T cell functions to propagate local inflammatory reactions and also imply a novel role played by a modified lipid in the selection of Th1/Th2 immune response as well as in the T cell mediated pathogenesis in atherosclerosis.

Antibodies↗

Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells.

Endothelial dysfunction, or activation, elicited by oxidized LDL (Ox-LDL) or its lipid constituent, has been implicated in the initiation and progression of atherosclerosis. We have recently identified a C-type lectin-like molecule, designated lectin-like Ox-LDL receptor-1 (LOX-1), which acts as a cell-surface receptor for Ox-LDL in cultured vascular endothelial cells. In this study, we provide evidence that LOX-1 expression can be upregulated by tumor necrosis factor-alpha (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA) in cultured bovine aortic endothelial cells. TNF-alpha and PMA upregulated LOX-1 protein and mRNA in a time- and dose-dependent manner. Nuclear runoff assay revealed that TNF-alpha stimulates transcription of the LOX-1 gene. Chinese hamster ovary K1 cells stably expressing LOX-1 internalized 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled Ox-LDL but did not significantly internalize acetylated LDL (Ac-LDL), which was effectively suppressed by excess amounts of unlabeled Ox-LDL but not by Ac-LDL. Upregulated expression of LOX-1 by TNF-alpha and PMA was associated with increased uptake of DiI-Ox-LDL that cannot be blocked by excess amounts of unlabeled Ac-LDL. Taken together, LOX-1 is a receptor specific for Ox-LDL, and enhanced uptake of Ox-LDL via this novel receptor on vascular endothelial cells may play an important role in endothelial activation in atherogenesis.

Animals↗

Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells.

Fluid shear stress has been shown to modulate various endothelial functions, including gene expression. In this study, we examined the effect of fluid shear stress on the expression of lectin-like oxidized LDL receptor-1 (LOX-1), a novel receptor for atherogenic oxidized LDL in cultured bovine aortic endothelial cells (BAECs). Exposure of BAECs to the physiological range of shear stress (1 to 15 dyne/cm2) upregulated LOX-1 protein and mRNA in a time-dependent fashion. LOX-1 mRNA levels peaked at 4 hours, and LOX-1 protein levels peaked at 8 hours. Inhibition of de novo RNA synthesis by actinomycin D totally abolished shear stress-induced LOX-1 mRNA expression. Furthermore, nuclear runoff assay showed that shear stress directly stimulates transcription of the LOX-1 gene. Chelation of intracellular Ca2+ with quin 2-AM completely reduced shear stress-induced LOX-1 mRNA expression; furthermore, the treatment of BAECs with ionomycin upregulated LOX-1 mRNA levels in a dose-dependent manner. Taken together, physiological levels of fluid shear stress can regulate LOX-1 expression by a mechanism dependent on intracellular Ca2+ mobilization. Inducible expression of LOX-1 by fluid mechanics may play a role in localized expression of LOX-1 and atherosclerotic lesion formation in vivo.

Animals↗

Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells.

Recognition of the exposure of phosphatidylserine (PS) on the outer surface of plasma membrane has been implicated in the phagocytosis of aged/apoptotic cells. Because oxidized low-density lipoprotein (OxLDL) has been reported to block the phagocytosis, here we examined whether lectin-like OxLDL receptor 1 (LOX-1), the OxLDL receptor in endothelial cells, mediates phagocytosis of aged/apoptotic cells by endothelial cells. Cultured bovine aortic endothelial cells (BAE) and Chinese hamster ovary (CHO) cells expressing bovine LOX-1 (BLOX-1-CHO), but not wild-type CHO-K1 cells, bound aged red blood cells (RBC) and apoptotic cells, which were further phagocytosed. The binding of aged RBC and the phagocytosis of apoptotic cells were inhibited by OxLDL, acetyl LDL, and other LOX-1 ligands in both BAE and BLOX-1-CHO. mAb against LOX-1 blocked the binding of aged RBC to BAE, suggesting a role for LOX-1 in the recognition of aged cells. The recombinant soluble LOX-1 inhibited the interactions of aged/apoptotic cells with both BLOX-1-CHO and BAE and distinguished aged RBC from native RBC and apoptotic cells from native cells. PS liposome inhibited these LOX-1-mediated interactions with aged/apoptotic cells, suggesting LOX-1 recognizes PS of the apoptotic cells. PS exposed on the surface of apoptotic cells is known to be procoagulant. Accordingly, increased OxLDL may be one of the reasons for enhanced coagulation in atherosclerosis, inhibiting the removal of apoptotic cells.

Animals↗

Lipoprotein(a) enhances the expression of intercellular adhesion molecule-1 in cultured human umbilical vein endothelial cells.

BACKGROUND: We reported an increase in serum lipoprotein(a) [Lp(a)] levels in patients with thromboangiitis obliterans, suggesting that Lp(a) could also contribute to the pathogenesis of cardiovascular diseases by a mechanism different from atherosclerosis. Adhesion molecules were shown to contribute to the development of not only atherosclerotic but also inflammatory vascular diseases. METHODS AND RESULTS: We evaluated the effect of Lp(a) on the expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in human umbilical vein endothelial cells by a cell ELISA. Lp(a) dramatically enhanced the levels of ICAM-1 in a dose-dependent manner. A discernible increase in ICAM-1 expression was observed at a physiological concentration of 0.26 mmol cholesterol/L Lp(a) after 48-hour incubation. A 1.8-fold increase in ICAM-1 expression was observed 48 hours after the addition of Lp(a) (1.04 mmol cholesterol/L). Northern blot analysis demonstrated that the amount of ICAM-1 mRNA was increased after treatment with Lp(a). In contrast to ICAM-1, the expression of VCAM-1 and E-selectin was not significantly affected by Lp(a). Lp(a-) [apolipoprotein(a)- removed Lp(a) by reduction with dithiothreitol] and LDL had no significant effect on the expression of ICAM-1. In contrast, recombinant apolipoprotein(a) protein alone significantly enhanced ICAM-1 expression. Lp(a) decreased the level of active transforming growth factor (TGF)-beta in the conditioned medium. Furthermore, recombinant TGF-beta significantly decreased the Lp(a)-induced ICAM-1 expression. These findings suggested that Lp(a) may enhance the ICAM-1 expression by decreasing active TGF-beta level. CONCLUSIONS: Lp(a) could contribute to the development of cardiovascular diseases by enhancing the expression of ICAM-1 in endothelial cells.

Antibodies↗

Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells.

Lysophosphatidylcholine (lyso-PC), a biologically active phospholipid, appears to modulate various endothelial cell functions through tyrosine kinase-dependent signaling pathways. In cultured bovine aortic endothelial cells (BAEC), we have found that a 130 kDa protein (p130) was rapidly tyrosine phosphorylated within 2 min and sustained for, at least, 1 hr in response to 10 mumol/L of lyso-PC but not to phorbol myristate acetate (PMA). Prolonged preexposure to PMA did not affect lyso-PC-induced p130 tyrosine phosphorylation, suggesting that mechanisms independent of protein kinase C may be involved. Fractionation of the cell lysates revealed that p130 was detectable in the membrane fraction but not in the cytosolic fraction. Immunoprecipitation followed by immunoblotting of lyso-PC-treated BAEC identified p130 as bovine PECAM-1. Tyrosine phosphorylation of PECAM-1 appears to be one of the earliest events elicited by lyso-PC, and may play a role in lyso-PC-induced modulation of endothelial functions.

Animals↗

Increased bone mineral turnover without increased glucose utilization in sclerotic and hyperplastic change in fibrous dysplasia.

Fibrous dysplasia is a benign bone disorder. It is diagnosed by distinctive X-ray radiography, CT, and MRI findings. Although bone scintigraphy helps to identify the tumor origin according to accelerated bone turnover, the glucose metabolism in fibrous dysplasia has not yet been investigated. We reported a case of fibrous dysplasia in craniofacial bone which showed signs of the acceleration of bone mineral turnover without elevated glucose utilization by Technetium-99m-HMDP SPECT and Fluorine-18-FDG PET. We concluded that the growth of fibrous dysplasia needed the acceleration of bone mineral turnover without an increase in glucose metabolism.

Bone Density↗

Visualization of pressure-dependent luxury perfusion in a patient with subacute cerebral infarction.

Luxury perfusion characterized by depressed metabolism compared with CBF might be changed by decreasing cerebral perfusion pressure during the sitting position. A 77-yr-old man with subacute cerebral infarction was studied with brain X-ray computed tomography (CT), raise-up test with 99mTc-d,1-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission tomography (SPECT) and positron emission tomography (PET). Brain X-ray CT revealed a low-density area in the left middle cerebral artery (MCA) anterior area. Raise-up 99mTc-HMPAO brain SPECT revealed decreased uptake in the left MCA anterior area in the sitting position and subsequent supine 99mTc-HMPAO brain SPECT revealed hot accumulation there. PET study in the supine position demonstrated some differences between CBF and the cerebral metabolic rate for oxygen in the left MCA anterior area, indicating luxury perfusion. CBF in the area of luxury perfusion might be decreased during the sitting or standing position and increased during the supine position by dysautoregulation of the cerebral vessels in the luxury perfusion during the subacute infarct.

Aged↗

Abnormal brain perfusion demonstrated by Tc-99m MAA total-body scan in two children with complex congenital heart disease.

This paper describes abnormal brain perfusion unexpectedly demonstrated by Tc-99m MAA total-body imaging in two children with intracardiac right-to-left shunt (RLS) associated with complex congenital heart disease. One child was a 12-year-old girl with asplenia cardiac syndrome and multiple cerebral infarctions caused by thromboembolism in the internal carotid artery, and the other child was a 6-month-old boy who developed focal cerebral infarction following shunt operation. In both children, the total-body imaging depicted the brain due to RLS, where radioactivity decreased unilaterally in the cerebral hemisphere. In the first patient, radioactivity also decreased in the contralateral cerebellum, suggesting the crossed cerebellar diaschisis phenomenon. These abnormalities in brain perfusion were confirmed by Tc-99m HMPAO brain SPECT. Careful review of the distribution of the radiotracer in the depicted brain on Tc-99m MAA total-body imaging may provide important information regarding brain perfusion in some patients with a high risk of stroke complication associated with RLS.

Brain↗

201Tl SPECT as an indicator for early prediction of therapeutic effects in patients with non-small cell lung cancer.

This study retrospectively investigated the good parameters on thallium-201 chloride (201Tl) SPECT for early assessment of the therapeutic effects in patients with non-small cell lung cancer. Based on tumor response as determined by chest CT scan about 9 weeks after the end of irradiation with adjuvant chemotherapy, the subjects were divided to the responder group (tumor regression > 50%, n = 13) and non-responder group (tumor regression < 50%, n = 13). 201Tl SPECT was performed before and at the halfway through the course of therapy (average tumor dose, 27.4 Gy +/- 4.5) in all the patients. SPECT was conducted twice 15 min (early scan) and 120 min (delayed scan) after intravenous injection of 148 MBq (4 mCi) of 201Tl. Tumor-to-contralateral normal lung tissue count ratios on both scans were calculated as early and delayed uptake ratios (EUR and DUR), and a retention index (RI) was also derived from these ratios. In the responder group, a significant decrease in DUR and RI halfway through the therapy was observed compared to pretreatment (2.6 +/- 0.6 vs. 3.5 +/- 1.0; p < 0.01, and -2.3% +/- 25.5 vs. 37.4% +/- 17.8; p < 0.001, respectively), even though EUR did not change significantly (N.S.). By contrast, in the non-responder group, there were no significant changes in any of these parameters (N.S.). When comparing DUR and RI for the two groups halfway through the therapy, DUR and RI were significantly lower in the responder group (both; p < 0.01), but no significant difference was noted in EUR (N.S.), and the percent reduction in tumor size did not correlate with the percent decrease in DUR or RI (N.S.). These results indicate that the extent of decrease in DUR and RI after therapy can be a useful parameter for early assessment of the therapeutic effects in patients with non-small cell lung cancer.

Aged↗

Acetazolamide induced myocardial ischemia in patients with severe coronary artery disease.

UNLABELLED: Acetazolamide (ACZ)-augmented brain SPECT is commonly used for evaluating cerebral vascular reserve in patients with cerebrovascular disease. ACZ may cause myocardial ischemia in patients with coronary artery disease. To evaluate the risk of induction of myocardial ischemia with ACZ-augmented myocardial SPECT, we performed combined ACZ-augmented Tl-201 myocardial SPECT (ACZ-myo SPECT) with Tc-99m HMPAO brain SPECT in patients with severe coronary artery disease. METHODS: Nine patients underwent combined ACZ-myo SPECT with Tc-99m HMPAO brain SPECT. (1) For qualitative analysis, SPECT images were divided into 13 segments to calculate the total defect scores. (2) Six ROIs were placed on the slices in the myocardial SPECT short-axis images and the regional uptake ratio was obtained as the ratio of the mean counts in the myocardium to the maximal count in the slice. The total defect score and regional uptake ratio of ACZ-myo SPECT were compared with those of early and delayed dipyridamole Tl-201 myocardial SPECT (DP-Tl SPECT) images. RESULTS: (1) In the 21 coronary artery territories with coronary stenosis > or = 75%, the total defect score in ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 3.52 +/- 4.14*, 4.19 +/- 4.65* and 2.25 +/- 3.34, respectively (*: p < 0.05 vs. delayed DP-Tl SPECT images). (2) In 44 of 54 ROIs with coronary stenosis > or = 75%, the regional uptake ratio of ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 0.670 +/- 0.166**, 0.677 +/- 0.194**, 0.721 +/- 0.178, respectively (**: p < 0.01 vs. delayed DP-Tl SPECT images). Systolic blood pressure fell at 11 min after ACZ infusion without electrocardiographic ST-T changes or chest pain. CONCLUSION: As ACZ has the potential to cause myocardial ischemia, ACZ-augmented brain SPECT should be performed with caution in patients with severe coronary artery disease associated with cerebrovascular disease.

Acetazolamide↗

Preliminary application of dynamic pulmonary xenon-133 single-photon emission tomography in the evaluation of patients with pulmonary emphysema for thoracoscopic lung volume reduction surgery.

Dynamic pulmonary xenon-133 single-photon emission tomography (SPET) with three-dimensional (3D) displays was preliminarily applied to select resection targets for thoracoscopic lung volume reduction surgery (LVRS) and to assess regional ventilatory changes following surgery. Dynamic SPET was performed using a triple-detector SPET system in 14 patients with pulmonary emphysema before and after LVRS. After reconstructing colour-illuminated, surface-rendered 3D images of equilibrium (EQ) and 3-min washout (WO3), a single 3D fusion display was created from these two different time-course image sets, in which the 3D WO3 image indicating 133Xe retention was visible through the overlying 3D EQ image delineating lung contours. Volumetric extent of retention on this display was quantified by a 133Xe retention index, defined as the ratio (%) of total pixel numbers of segmented 3-min WO data to those of EQ data. 133Xe SPET and appropriately thresholded 3D displays efficiently localized a total of 36 retention sites; 19 (52.7%) of these sites were not localized by CT because they were within the widely or homogeneously spreading non-bullous emphysematous lung tissues. The 3D displays enhanced the perception of anatomical configurations and the extent of 133Xe retention compared with multislice tomograms. Postoperatively, 3D fusion display visualized the details of regional changes in retention, and changes in the retention index on the 3D display with a standardized threshold correlated well with changes in 133Xe clearance time (T1/2) and %FEV1 (r = 0.881 and 0. 856, respectively; P<0.0001). This preliminary study indicates that 133Xe SPET and appropriately thresholded, topographic 3D displays are of potential use in selecting resection targets for LVRS, and in evaluating the treatment effects on regional ventilation.

Aged↗