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1.
Jpn J Radiol ; 41(9): 965-972, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37040023

RESUMO

PURPOSE: The right top pulmonary vein (RTPV) is defined as an anomalous branch of the right superior PV (SPV) draining into the PV or left atrium (LA). Several previous reports have described the RTPV, but only a few have mentioned the left top PV (LTPV). The present study aimed to evaluate the branching patterns of the RTPV and LTPV using thin-section CT images and three-dimensional CT angiography (3D-CTA). MATERIALS AND METHODS: This study included 1437 consecutive patients for evaluation of the right side and 1454 consecutive patients for the left side who were suspected of lung cancer and underwent CTA. We assessed the presence of each RTPV and LTPV and their branching patterns on the CTA images. When the RTPV or LTPV was identified, the maximum short-axis diameter was measured. RESULTS: RTPV was found in 9.1% (131/1437), whereas LTPV was found in 2.9% (42/1454) of the patients. RTPV was also observed in 17.1% (7/41) of LTPV cases, except for one case in which the right side could not be evaluated. The most common RTPV inflow site was the right inferior PV (IPV) in 64.9% (85/131) of the patients, whereas that of the LTPV was the left IPV in 100.0% (42/42) of the patients. The mean diameter of the RTPV and LTPV was 3.3 mm (range, 1.3-7.5 mm) and 2.4 mm (range, 0.9-6.3 mm), respectively (P < 0.01). CONCLUSION: The top PV branching pattern variations can be evaluated using thin-section CT and 3D-CTA images. RTPV is not a rare finding, and LTPV should also be identified in lung cancer cases scheduled for resection.


Assuntos
Neoplasias Pulmonares , Veias Pulmonares , Humanos , Angiografia por Tomografia Computadorizada , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/anormalidades , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Imageamento Tridimensional , Pulmão
2.
EJNMMI Phys ; 9(1): 83, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469149

RESUMO

BACKGROUND: The purpose of the present study was to elucidate the correlation between standardized uptake value (SUV) and volume-based parameters measured by quantitative [99mTc]Tc-methylene diphosphonate (MDP) single photon emission computed tomography (SPECT)/CT and [18F]-sodium fluoride ([18F]NaF) positron emission tomography (PET)/CT in the assessment of bone metastases in patients with prostate cancer. METHODS: The study included 26 male prostate cancer patients with confirmed or suspected bone metastases who underwent both [99mTc]Tc-MDP SPECT/CT and [18F]NaF PET/CT studies. Skeletal lesions visible on both SPECT/CT and PET/CT were classified as benign or metastases. The maximum SUV (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), metabolic bone volume (MBV), and total bone uptake (TBU) were calculated for every lesion showing abnormal uptake. RESULTS: A total of 202 skeletal lesions (147 benign and 55 metastases) were detected in the 26 patients. Strong significant correlations were noted between SPECT/CT and PET/CT for the SUV- and volume-based parameters (all P < 0.001). The SUVmax, SUVpeak, SUVmean, and TBU values obtained with SPECT/CT were significantly lower than the corresponding values obtained with PET/CT (all P < 0.001). The MBV in SPECT/CT was significantly higher than that in PET/CT (P < 0.001). All SUV- and volume-based parameters obtained with both SPECT/CT and PET/CT for metastatic lesions were significantly higher than the corresponding parameters for benign lesions (P values from 0.036 to < 0.001). CONCLUSIONS: These preliminary results demonstrate that the SUV- and volume-based parameters for bone uptake obtained with quantitative SPECT/CT and PET/CT are strongly correlated in patients with prostate cancer. The SUV parameters obtained with SPECT/CT were significantly lower than those obtained with PET/CT, whereas the uptake volume obtained with SPECT/CT was significantly higher than that obtained with PET/CT.

4.
J Nucl Cardiol ; 29(2): 569-577, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-32743752

RESUMO

BACKGROUND: This preliminary study was undertaken to evaluate relationship among the degree of internal carotid artery (ICA) stenosis, wall shear stress (WSS) by computational fluid dynamics (CFD) on magnetic resonance angiography (MRA) and 18F-FDG uptake of ICA on PET/CT. METHODS: A total of 40 carotid arteries in 20 patients with carotid atherosclerotic disease were examined with MRA and 18F-FDG PET/CT. Atherosclerotic risk factors were assessed in all patients. Degree of ICA stenosis was calculated according to NASCET method. CFD analysis was performed and maximum WSS (WSSmax) was measured. 18F-FDG uptake in ICA was quantified using maximum target-to-blood pool ratio (TBRmax). RESULTS: Atherosclerotic risk factors did not affect imaging findings. There were significant correlations between WSSmax and degree of ICA stenosis (ρ = .81, P < .001), WSSmax and TBRmax (ρ = .64, P < .001), and TBRmax and degree of ICA stenosis (ρ = .50, P = .001). CONCLUSIONS: These preliminary results indicate that there may be significant correlations among the degree of ICA stenosis, WSSmax and TBRmax in patients with carotid artery stenosis.


Assuntos
Aterosclerose , Estenose das Carótidas , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Constrição Patológica , Fluordesoxiglucose F18 , Humanos , Angiografia por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
6.
Acta Med Okayama ; 75(3): 351-356, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34176939

RESUMO

We assessed the role of 18F-FDG PET/CT texture indices for the differentiation of squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the oropharynx. 18F-FDG PET/CT data for 27 patients with SCC and 25 patients with NHL in the oropharynx were investigated. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and six texture indices (homogeneity, entropy, short-run emphasis, long-run emphasis, low gray-level zone emphasis [LGZE], and high graylevel zone emphasis [HGZE]) were derived from PET images. PET/CT parameters of the SCC patients were compared with those of the NHL patients. The diagnostic accuracy of the indices for differentiating SCC from NHL was calculated by a receiver operating characteristic curve analysis. 18F-FDG uptake in the oropharynx was observed in all of the patients. The SUVmax, MTV, and TLG did not differ significantly between the SCC and NHL groups, but two of the six texture indices (LGZE [p=0.004] and HGZE [p=0.03]) showed significant differences between the groups. LGZE was the best discriminative index for the differentiation of SCC and NHL (55.6% sensitivity, 88.0% specificity). The LGZE and HGZE texture indices derived from 18F-FDG PET/CT images may be useful in differentiating SCC and NHL in the oropharynx.


Assuntos
Carcinoma de Células Escamosas/patologia , Linfoma não Hodgkin/patologia , Neoplasias Orofaríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos
7.
Nucl Med Mol Imaging ; 55(1): 46-47, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33643489

RESUMO

We present a female in her sixties with mixed connective tissue disease who underwent 99mTc-human serum albumin diethylenetriaminepentaacetic acid (99mTc-HSA-DTPA) scintigraphy to clarify the cause of generalized edema. Scintigraphy findings directed the diagnosis to protein-losing gastroenteropathy. Various disorders are known to be associated with protein-losing gastroenteropathy; however, mixed connective tissue disease is a rare cause. 99mTc-HSA-DTPA scintigraphy is helpful in the diagnosis and following the response to therapy of protein-losing gastroenteropathy.

8.
EJNMMI Res ; 11(1): 13, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33566186

RESUMO

PURPOSE: We investigated the potential of interim 4'-[methyl-11C]thiothymidine ([11C]4DST) PET for predicting the chemoradiotherapeutic response for head and neck squamous cell carcinoma (HNSCC), in comparison with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET. METHODS: A total of 32 patients with HNSCC who underwent both [11C]4DST and [18F]FDG PET/CT before therapy (baseline) and at approximately 40 Gy point during chemoradiotherapy (interim) were available for a retrospective analysis of prospectively collected data. The baseline was treatment-naïve PET/CT scan as part of staging. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) from [18F]FDG PET or proliferative tumor volume (PTV) from [11C]4DST PET, and total lesion glycolysis (TLG) from [18F]FDG PET or total lesion proliferation (TLP) from [11C]4DST PET were measured. MTV or PTV was defined as the volume with an SUVmax greater than 2.5. The differences in SUVmax (ΔSUVmax), MTV (ΔMTV) or PTV (ΔPTV) and TLG (ΔTLG) or TLP (ΔTLP) from baseline to interim PET scans were calculated. Patients without or with evidence of residual or recurrent disease at 3 months after completion of chemoradiotherapy were classified as showing a complete response (CR) and non-CR, respectively. RESULTS: All patients showed increased uptake in primary tumor on baseline [11C]4DST and [18F]FDG PET studies. All patients showed increased uptake on interim [18F]FDG PET, whereas 18 patients showed no increased uptake on interim [11C]4DST PET. After chemoradiotherapy, 25 patients were found to be in CR group and 7 to be in non-CR group. [11C]4DST ΔSUVmax, ΔPTV, and ΔTLP for CR group showed significantly greater reductions than the corresponding values for non-CR group (P = 0.044, < 0.001, < 0.001, respectively). However, there were no significant differences in [18F]FDG ΔSUVmax, ΔMTV, or ΔTLG between CR group and non-CR group. [11C]4DST ΔMTV of -90 was the best cutoff value for the early identification of patients with non-CR. CONCLUSION: These preliminary results suggest that interim [11C]4DST PET might be useful for predicting the chemoradiotherapeutic response in patients with HNSCC, in comparison with [18F]FDG PET.

11.
Clin Nucl Med ; 46(5): e264-e265, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315671

RESUMO

ABSTRACT: Gitelman syndrome is an autosomal recessive renal tubulopathy. A 38-year-old woman was diagnosed with Gitelman syndrome. Eight years later, 18F-FDG PET/CT was performed to evaluate recurrence of endometrial cancer. FDG PET images showed an extremely abnormal FDG biodistribution. They showed decreased brain uptake, increased cardiac muscle uptake, and diffuse increased muscle and adipose tissue uptake. This pattern is similar to high insulin state; however, her glucose level was normal, and insulin level was very low.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Síndrome de Gitelman/metabolismo , Adulto , Feminino , Síndrome de Gitelman/diagnóstico por imagem , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição Tecidual
12.
Clin Nucl Med ; 46(4): e208-e209, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33181741

RESUMO

ABSTRACT: 18F-FDG accumulates not only in malignant lesions but also in infectious and inflammatory ones. 3'-deoxy-3'-18F-fluorothymidine (FLT) has been investigated as a promising PET tracer for evaluating tumor proliferating activity. We report a case of liver abscess during therapy of pancreatic cancer that underwent FDG PET/CT and FLT PET/CT studies. Although FDG PET/CT demonstrated several regions of increased uptake in the liver, FLT PET/CT showed no increased uptake in the liver.


Assuntos
Fluordesoxiglucose F18/metabolismo , Abscesso Hepático/metabolismo , Transporte Biológico , Didesoxinucleosídeos/metabolismo , Feminino , Humanos , Abscesso Hepático/complicações , Abscesso Hepático/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
13.
EJNMMI Res ; 10(1): 153, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296037

RESUMO

PURPOSE: The efficiency of [18F]FDG PET/CT using volume-based indices was evaluated to assess the disease activity and response to therapy in patients with immunoglobulin G4-related disease (IgG4-RD). METHODS: A total of 17 patients with IgG4-RD were examined with [18F]FDG PET/CT before and during treatment. The lesion boundary was determined using a fixed threshold of standardized uptake value (SUV) ≥ 2.5. The highest maximum SUV (SUVmax) among all affected lesions was calculated for individual patients. We summed metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of each affected lesion to generate a total MTV and total TLG. PET results were compared with those of serum IgG4 and soluble interleukin-2 receptor (sIL-2R) levels. RESULTS: The mean number of involved organs per patient was 3.8 as determined by [18F]FDG uptake. The number of involved organs, total MTV and total TLG were significantly correlated with IgG4 (P = 0.046, < 0.001, < 0.001, respectively) and sIL-2R (P < 0.001, = 0.031, 0.031, respectively). According to the clinical assessments for therapy response, all patients were classified as improved. The SUVmax, total MTV, and total TLG during therapy were all significantly lower than those before therapy (all P < 0.001). CONCLUSION: [18F]FDG PET/CT is valuable for assessing the extent of multi-organ involvement before therapy and monitoring subsequent therapy in patients with IgG4-RD. [18F]FDG PET/CT using volumetric indices correlated with serum IgG4 and sIL-2R levels.

14.
CVIR Endovasc ; 3(1): 74, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006699

RESUMO

BACKGROUND: The majority of maxillary sinus cancers are advanced at initial detection due to anatomical limitations and lack of early symptoms. In patients with orbital invasion, the feeding arteries of the tumor are often associated with the ophthalmic artery in addition to the maxillary artery. We describe a case of tumor bleeding in a patient with recurrent maxillary carcinoma that was treated with embolization from the maxillary and ophthalmic arteries. CASE PRESENTATION: A 70-year-old man was treated for left maxillary carcinoma from the maxillary artery with 6 cycles of selective intra-arterial cisplatin infusion with concomitant radiation therapy. He subsequently had epistaxis and underwent arterial embolization for hemostasis. He had almost no sight by this time. Angiography of the left external carotid artery and internal carotid artery revealed blood supply from the maxillary and ophthalmic arteries. Regarding the maxillary artery, coil embolization was performed after embolization with 300-500 µm Embosphere. On the other hand, for the ophthalmic artery, the 3rd portion, supratrochlear artery and dorsal nasal artery, were selected and embolized with coils. Final angiography revealed disappearance of tumor staining and a residual choroidoretinal blush. There was no bleeding that needed treatment up to 2 months after embolization. CONCLUSIONS: In embolization of the ophthalmic artery, it is necessary to embolize the second and subsequent parts because the arteries associated with visual function branch off from the first part. Even in patients whose visual acuity has been almost lost, like in this case, there is a risk of eye pain from embolization at the proximal end, and distal embolization is necessary.

15.
Jpn J Radiol ; 38(12): 1158-1168, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32729007

RESUMO

PURPOSE: The purpose of the present study was to analyze the left pulmonary artery (LPA) branching pattern of the interlobar portion using three-dimensional CT pulmonary angiography (3D-CTPA) and thin-section CT images, and to attempt to diagrammatize these patterns. MATERIALS AND METHODS: The study included 320 patients suspected of having lung cancer of the left upper/lower lobe who underwent CTPA. The number and origin of the LPA branches of the interlobar portion, A1 + 2c, A6, and lingular artery from pars interlobaris (PI), were identified meticulously using 3D-CTPA and thin-section images. We then diagrammatized the identified LPA branching patterns of the interlobar portion. RESULTS: The diagrammatized LPA branching patterns of the interlobar portion were broadly classified into seven types in the order of bifurcation from proximal to distal. Type 1 was the most frequent (120/320, 37.5%). PI originated from the lower portion, that is, from A8 or the common trunk of A8 and A9 in 95 cases (29.7%). We could also precisely diagrammatize the LPA branching patterns of the interlobar portion into 85 types in all 320 patients. CONCLUSION: 3D-CTPA and thin-section images provided precise preoperative information regarding the LPA branching patterns of the interlobar portion.


Assuntos
Angiografia por Tomografia Computadorizada , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Artéria Pulmonar/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Imageamento Tridimensional , Pulmão/anatomia & histologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem
16.
Eur J Hybrid Imaging ; 4(1): 20, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34191155

RESUMO

BACKGROUND: In oropharyngeal squamous cell carcinoma (OPSCC), human papillomavirus (HPV)/p16 status is important as a prognostic biomarker. PURPOSE: We evaluated the relationship between 4'-[methyl-11C]-thiothymidine (11C-4DST) and 18F-FDG PET texture indices and p16 status in patients with newly diagnosed OPSCC. METHODS: We retrospectively reviewed the collected data of 256 consecutive, previously untreated patients with primary head and neck tumors enrolled between November 2011 and October 2019. Complete data on both 11C-4DST and 18F-FDG PET/CT studies before therapy, patients with OPSCC, and p16 status were available for 34 patients. Six of them were excluded because they did not exhibit sufficient 11C-4DST and/or 18F-FDG tumor uptake to perform textural analysis. Finally, 28 patients with newly diagnosed OPSCC were investigated. The maximum standardized uptake value (SUVmax) and 6 texture indices (homogeneity, entropy, short-run emphasis, long-run emphasis, low gray-level zone emphasis, and high gray-level zone emphasis) were derived from PET images. The presence of p16 expression in tumor specimens was examined by immunohistochemistry and compared with the PET parameters. RESULTS: Using 11C-4DST, the expression of p16 was associated with a higher homogeneity (P = 0.012), lower short-run emphasis (P = 0.005), higher long-run emphasis (P = 0.009), and lower high-gray-level-zone emphasis (P = 0.042) values. There was no significant difference between 18F-FDG PET parameters and p16 status. CONCLUSION: Texture indices of the primary tumor on 11C-4DST PET, but not 18F-FDG PET, may be of value in predicting the condition's p16 status in patients with newly diagnosed OPSCC.

17.
Eur J Hybrid Imaging ; 4(1): 14, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34191182

RESUMO

BACKGROUND: Muscle enzymes are the major noninvasive diagnostic parameters useful in polymyositis/dermatomyositis (PM/DM). Few studies have yet correlated findings on 18F-FDG PET with disease activity in patients with PM/DM. PURPOSE: We evaluated 18F-FDG muscle uptake in patients with PM/DM compared with non-muscular diseases and correlated the results with serum muscle enzymes. METHODS: A total of 28 patients with untreated PM/DM and 28 control patients with non-muscular diseases were examined with 18F-FDG PET/CT. 18F-FDG uptake was evaluated in 9 proximal skeletal muscle regions bilaterally. The uptake was scored as follows: 0 = less than that of the mediastinal blood vessels, 1 = greater than or equal to that of the mediastinal blood vessels, and 2 = greater than or equal to that of the liver. A score 1 or 2 was considered positive. The mean and maximum standardized uptake values (SUV) were calculated in each muscle and were averaged for all muscle regions. PET findings were correlated with serum muscle enzymes. RESULTS: 18F-FDG uptake was observed in 82% of patients with PM/DM and 7% of control patients. The number of positive regions, total score, mean SUVmean, and mean SUVmax in patients with PM/DM were significantly higher than those in the control patients (all P < 0.001). The total score of 2 was the best cut-off value that could discriminate patients with PM/DM from control patients. The total score, mean SUVmean, and mean SUVmax showed significant correlations with creatine kinase (P = 0.047, 0.002, 0.010, respectively) and aldolase (P = 0.036, 0.005, 0.038, respectively). CONCLUSION: 18F-FDG PET/CT using visual and SUV methods demonstrated its usefulness by discriminating PM/DM from non-muscular diseases and correlating with serum muscle enzymes in patients with PM/DM.

18.
Ann Nucl Med ; 33(12): 907-915, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31571042

RESUMO

OBJECTIVE: Atherosclerosis is a dynamic and complex process characterized by the formation and progression of plaque mediated by various pathophysiologic steps including inflammation and calcification. The present study aimed to evaluate the association between carotid 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) uptake with the severity of ischemic vascular brain disease on MRI in patients with carotid artery disease. METHODS: A total of 28 patients who were scheduled to undergo clinically indicated carotid endarterectomy or stenting for carotid artery disease were examined with 18F-NaF and 18F-FDG PET/CT and brain MRI. The PET/CT images were evaluated by qualitative and semiquantitative analyses. The maximum standardized uptake value (SUV) for the plaque and the average of mean SUV within the lumen of both internal jugular veins was calculated, and the target-to-blood pool ratio (TBR) was determined. The ischemic vascular brain disease on MRI was graded separately in the bilateral hemisphere as 0, 1, 2, and 3, with 0 being absent and 3 being the most severe. RESULTS: In two patients, only a unilateral carotid artery was analyzed because of previous indwelling stent. 18F-NaF focal uptake was observed in 50 carotid arteries. 18F-FDG focal uptake was observed in 47 carotid arteries. The mean (± SD) 18F-NaF TBR (2.93 ± 0.89) was significantly higher than the mean (± SD) 18F-FDG TBR (2.41 ± 0.84) (p < 0.001). The mean (± SD) values of 18F-NaF TBR were 2.63 ± 0.76 in grade 1, 2.90 ± 0.91 in grade 2, and 3.81 ± 0.60 in grade 3. Significant differences in 18F-NaF TBR were observed between grades 1 and 3 (p < 0.001) and grades 2 and 3 (p = 0.02). The mean (± SD) values of 18F-FDG TBR were 2.35 ± 0.77 in grade 1, 2.23 ± 0.48 in grade 2, and 2.87 ± 1.32 in grade 3. No significant differences in 18F-FDG TBR were noted between any of the ischemic vascular brain disease grades. CONCLUSIONS: These preliminary results suggest that carotid 18F-NaF uptake in patients with carotid artery disease may be associated with the severity of the ischemic vascular brain disease observed on MRI.


Assuntos
Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Doenças das Artérias Carótidas/complicações , Fluordesoxiglucose F18/metabolismo , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluoreto de Sódio/metabolismo , Idoso , Transporte Biológico , Isquemia Encefálica/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
J Biol Chem ; 285(33): 25448-57, 2010 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-20547767

RESUMO

Caldecrin/chymotrypsin C is a novel secretory-type serine protease that was originally isolated as a serum calcium-decreasing factor from the pancreas. Previously, we reported that caldecrin suppressed the bone-resorbing activity of rabbit mature osteoclasts (Tomomura, A., Yamada, H., Fujimoto, K., Inaba, A., and Katoh, S. (2001) FEBS Lett. 508, 454-458). Here, we investigated the effects of caldecrin on mouse osteoclast differentiation induced by macrophage-colony stimulating factor and the receptor activator of NF-kappaB ligand (RANKL) from the monocyte/macrophage cell lineage of bone marrow cells. Wild-type and protease-deficient mutant caldecrin dose-dependently inhibited RANKL-stimulated tartrate-resistant acid phosphatase-positive osteoclast formation from bone marrow cells. Caldecrin did not affect macrophage colony formation from monocyte/macrophage lineage cells or osteoclast progenitor generation in cultures of bone marrow cells. Caldecrin inhibited accumulation of the RANKL-stimulated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) mRNA in bone marrow cells, which is a key transcription factor for the differentiation of osteoclasts. Caldecrin also suppressed RANKL-induced differentiation of the RAW264.7 monocyte/macrophage cell line into osteoclasts. Caldecrin reduced the transcriptional activity of NFATc1 in RAW264.7 cells, whereas those of NF-kappaB and c-Fos, which are also transcription factors involved in osteoclast differentiation, were unaffected. Caldecrin inhibited RANKL-stimulated nuclear translocation of NFATc1 and the activity of the calcium/calmodulin-dependent phosphatase, calcineurin. Caldecrin inhibited phospholipase Cgamma1-mediated Ca(2+) oscillation evoked by RANKL stimulation. RANKL-stimulated phosphorylation of spleen tyrosine kinase (Syk) was also attenuated by caldecrin. Taken together, these results indicate that caldecrin inhibits osteoclastogenesis, without its protease activity, by preventing a phospholipase Cgamma1-mediated Ca(2+)oscillation-calcineurin-NFATc1 pathway.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Serina Endopeptidases/farmacologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Calcineurina/metabolismo , Cálcio/metabolismo , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Immunoblotting , Imunoprecipitação , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos , Fatores de Transcrição NFATC/genética , Osteoclastos/metabolismo , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/genética , Proteínas Tirosina Quinases/metabolismo , Ligante RANK/farmacologia , Spodoptera , Quinase Syk
20.
Biochem Biophys Res Commun ; 367(4): 787-92, 2008 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-18201550

RESUMO

Sepiapterin reductase (SPR) is an enzyme that acts in the third and final step of tetrahydrobiopterin (BH4) biosynthesis. The human Spr gene locates within the region of 2.5MB mapped to PARK3, an autosomal dominant form of familial Parkinson's diseases. In order to explore the role of SPR in the metabolism of BH4, we produced and analyzed Spr-deficient mice. Most of Spr-null mice survived beyond two weeks. Whereas the BH4 contents in the homozygous mutant mice were greatly decreased than those in wild-type and heterozygous mice, the substantial amounts of BH4 were remained even 17 days after delivery. Spr-null mice exhibited severe monoamine deficiencies and a tremor-like phenotype after weaning. The amount of TH protein in the brain of Spr-null mice was less than 10% of wild-type, while TH protein in the adrenal, phenylalanine hydroxylase protein in the liver, and nNOS in the brain were not altered. These data suggest an essential role of SPR in the biosynthesis of BH4, and that the SPR gene could be a candidate gene for PARK3.


Assuntos
Oxirredutases do Álcool/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Tirosina 3-Mono-Oxigenase/metabolismo , Oxirredutases do Álcool/genética , Animais , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Tecidual
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