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1.
Eur J Nucl Med Mol Imaging ; 41(9): 1673-82, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24663289

ABSTRACT

PURPOSE: Prediction of mortality risk is important in the management of chronic heart failure (CHF). The aim of this study was to create a prediction model for 5-year cardiac death including assessment of cardiac sympathetic innervation using data from a multicenter cohort study in Japan. METHODS: The original pooled database consisted of cohort studies from six sites in Japan. A total of 933 CHF patients who underwent (123)I-metaiodobenzylguanidine (MIBG) imaging and whose 5-year outcomes were known were selected from this database. The late MIBG heart-to-mediastinum ratio (HMR) was used for quantification of cardiac uptake. Cox proportional hazard and logistic regression analyses were used to select appropriate variables for predicting 5-year cardiac mortality. The formula for predicting 5-year mortality was created using a logistic regression model. RESULTS: During the 5-year follow-up, 205 patients (22 %) died of a cardiac event including heart failure death, sudden cardiac death and fatal acute myocardial infarction (64 %, 30 % and 6 %, respectively). Multivariate logistic analysis selected four parameters, including New York Heart Association (NYHA) functional class, age, gender and left ventricular ejection fraction, without HMR (model 1) and five parameters with the addition of HMR (model 2). The net reclassification improvement analysis for all subjects was 13.8 % (p < 0.0001) by including HMR and its inclusion was most effective in the downward reclassification of low-risk patients. Nomograms for predicting 5-year cardiac mortality were created from the five-parameter regression model. CONCLUSION: Cardiac MIBG imaging had a significant additive value for predicting cardiac mortality. The prediction formula and nomograms can be used for risk stratifying in patients with CHF.


Subject(s)
3-Iodobenzylguanidine , Death , Heart Failure/diagnostic imaging , Heart Failure/mortality , Models, Statistical , Analysis of Variance , Chronic Disease/mortality , Female , Humans , Logistic Models , Male , Middle Aged , Radionuclide Imaging , Risk
2.
JACC Cardiovasc Imaging ; 6(7): 772-84, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23845574

ABSTRACT

OBJECTIVES: The study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123-labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events. BACKGROUND: Although the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database. METHODS: Six prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death. RESULTS: Lethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic-determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001). CONCLUSIONS: Pooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk.


Subject(s)
3-Iodobenzylguanidine , Heart Failure/diagnostic imaging , Heart/diagnostic imaging , Heart/innervation , Radiopharmaceuticals , Sympathetic Nervous System/diagnostic imaging , Aged , Biomarkers/blood , Chi-Square Distribution , Databases as Topic , Disease Progression , Evidence-Based Medicine , Female , Heart Failure/blood , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Multicenter Studies as Topic , Multivariate Analysis , Natriuretic Peptide, Brain/blood , Predictive Value of Tests , Prognosis , Proportional Hazards Models , ROC Curve , Radionuclide Imaging , Risk Factors , Stroke Volume , Time Factors , Ventricular Function, Left
3.
Eur J Heart Fail ; 13(8): 892-8, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21602550

ABSTRACT

AIMS: Loop diuretics are essential for the treatment of chronic heart failure (CHF) but short-acting diuretics are reported to induce sympathetic nervous system (SNS) activation. This study was performed to compare therapeutic effects of two loop diuretics, long-acting azosemide and short-acting furosemide, using (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy. METHODS AND RESULTS: Twenty-two patients with New York Heart Association class II-III heart failure and left ventricular dysfunction, who required treatment with a loop diuretic, were included. In this crossover study, 11 patients were randomized to azosemide treatment first and the remaining 11 patients to furosemide. Treatments were administered for 6 months and then patients were crossed over to the second treatment. (123)I-MIBG scintigraphy was performed before and 6 months after the start of treatment with each loop diuretic. Early and delayed images were obtained 20 min and 4 h after administration of (123)I-MIBG, respectively; and the heart/mediastinum (H/M) ratio and washout rate (WR) were measured. In addition, left ventricular ejection fraction (LVEF), levels of brain natriuretic peptide (BNP), and norepinephrine were measured before and 6 months after the start of treatment. No differences were observed between the two groups in terms of concomitant medication, cause of heart failure, H/M ratio, WR, BNP, norepinephrine, or LVEF. The azosemide group exhibited a significant increase in delayed image H/M ratio, and a significant decrease in WR and norepinephrine after the final administration compared with the furosemide group. CONCLUSION: This study indicates that azosemide suppresses SNS activation compared with furosemide in patients with CHF, suggesting that long-acting loop diuretics may have more beneficial effects on the prognosis of CHF.


Subject(s)
Furosemide/therapeutic use , Heart Failure/diagnostic imaging , Heart Failure/drug therapy , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Sulfanilamides/therapeutic use , 3-Iodobenzylguanidine , Adult , Aged , Aged, 80 and over , Chronic Disease , Cross-Over Studies , Female , Humans , Male , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals
4.
Ann Nucl Med ; 25(2): 101-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21210256

ABSTRACT

BACKGROUND: The goals of this meta-analysis were to determine survival rates in patients with heart failure (HF) assessed by ¹²³I-MIBG imaging results using recently published studies and to determine the prognostic value of ¹²³I-MIBG imaging. METHODS: We reviewed published cohort studies carried out in Japan that compared the prognosis of patients with their ¹²³I-MIBG activity quantified as late heart-to-mediastinum ratio (H/M) or washout rate by performing a PubMed search for articles in English up to December 2006. Studies were selected if they analyzed a clearly defined lethal outcome (cardiovascular death) using life tables to estimate the odds ratio at 24 months after enrollment. RESULTS: Of 158 articles related to cardiac ¹²³I-MIBG, seven referred to studies that met the inclusion criteria: 5 evaluated H/M via ¹²³I-MIBG in a total of 866 patients and 4 calculated washout rate in a total of 491 patients. A low H/M indicated a high risk of cardiac death: pooled odds ratio, 5.2; 95% confidence interval (CI) of 3.1-5.7. A high washout was also associated with lethal events with a pooled odds ratio of 2.8 (CI: 1.6-5.0). The association between washout and cardiac death was heterogeneous (Chi-square = 11.0, P < 0.02), whereas that between late H/M and fatal events was homogeneous (Chi-square = 2.3, P = no significance). CONCLUSION: This meta-analysis of published studies of ¹²³I-MIBG studies conducted in Japan indicated that both a decreased cardiac ¹²³I-MIBG activity (H/M) and an increased washout rate are indicative of a poor prognosis in patients with chronic heart failure.


Subject(s)
3-Iodobenzylguanidine , Heart Failure/diagnostic imaging , Heart Failure/mortality , Humans , Japan , Prognosis , Radionuclide Imaging , Survival Rate , Time Factors
7.
Dev Dyn ; 239(6): 1739-47, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20503369

ABSTRACT

We cultured the rudimental submandibular gland (SMG) of mice with a non-cell-permeable fluorescent tracer, and observed cell behavior during epithelial branching morphogenesis using confocal time-lapse microscopy. We traced movements of individual cells as shadowgraph movies. Individual epithelial cells migrated dynamically but erratically. The epithelial cleft extended by wiggling and separated a cluster of cells into two buds during branching. We examined the ultrastructure of the clefts in SMG rudiments treated with the laminin peptide A5G77f, which induces epithelial clefting. A short cytoplasmic shelf with a core of microfilaments was found at the deep end of the cleft. We propose that epithelial clefting involves a dynamic movement of cells at the base of the cleft, and the formation of a shelf within a cleft cell. The shelf might form a matrix attachment point at the base of the cleft with a core of microfilaments driving cleft elongation.


Subject(s)
Morphogenesis/physiology , Submandibular Gland/cytology , Animals , Cells , Embryo, Mammalian , Epithelial Cells/cytology , Female , Laminin/physiology , Mice , Mice, Inbred ICR , Pregnancy
8.
Nucl Med Commun ; 31(6): 488-94, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20429093

ABSTRACT

OBJECTIVES: Although it has been reported that (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is useful for assessing the prognosis of dilated cardiomyopathy (DCM), there have been no reports regarding how interval MIBG imaging should be performed during follow-up. We investigated the significance of performing MIBG at different times for the long-term prediction of cardiac events in DCM patients. METHODS: The participants were 36 DCM patients who did not sustain cardiac events for 2 years after beta-blocker induction. MIBG was performed 6 months and 2 years after beta-blocker induction and the images analyzed to obtain the extent score, severity score (SEV), and the washout rate. Echocardiography was performed at the same time. RESULTS: Eight patients experienced a cardiac event during follow-up (cardiac death: two patients; heart failure requiring hospitalization: six patients). Although no significant difference was found in any MIBG parameters or left ventricular ejection fraction between patients who experienced a cardiac event and those who did not after 6 months, early extent score, early SEV, delayed SEV, and washout rate were found to be significantly higher for patients who experienced a cardiac event after 2 years. In multivariate analysis using Cox proportional hazard model, none of the MIBG parameters or left ventricular ejection fraction after 6 months was identified as a predictor of cardiac events. However, delayed SEV after 2 years (hazard ratio 1.067, P = 0.0435) was a significant predictor of cardiac events. CONCLUSION: The study suggested that performing MIBG at least once every 2 years allows long-term prediction of cardiac events in the follow-up of DCM patients.


Subject(s)
3-Iodobenzylguanidine , Cardiomyopathy, Dilated/diagnostic imaging , Myocardial Perfusion Imaging , Adrenergic beta-Antagonists/therapeutic use , Analysis of Variance , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/drug therapy , Female , Humans , Male , Middle Aged , Prognosis , Time Factors
9.
Kaibogaku Zasshi ; 85(4): 121-3, 2010 Dec.
Article in Japanese | MEDLINE | ID: mdl-21226318

ABSTRACT

In Japan, dissection of human body is generally prohibited by the Penal Code, i.e. the criminal law. However, the Postmortem Examination and Corpse Preservation Act allows for the dissection of the body in very limited situations, that include gross anatomy dissection and pathological and forensic autopsy in medical and dental schools. Growing numbers of co-medical schools have been founded more recently in Japan, and not a small number of co-medical schools try to adopt human body dissection in the course of anatomy education. The present short communication reminds us of the ways of thinking of the Postmortem Examination and Corpse Preservation Act and the Act on Body Donation for Medical and Dental Education in order that anatomy education in medical as well as co-medical schools takes place under the regulation by these two laws.


Subject(s)
Anatomy/education , Anatomy/legislation & jurisprudence , Cadaver , Dissection/education , Dissection/legislation & jurisprudence , Education, Medical/legislation & jurisprudence , Autopsy/legislation & jurisprudence , Forensic Pathology/education , Forensic Pathology/legislation & jurisprudence , Humans , Japan , Schools, Dental , Schools, Medical
10.
Ann Nucl Med ; 23(6): 517-22, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19521747

ABSTRACT

OBJECTIVE: The standard patterns of myocardial radiotracer distribution of (123)I-metaiodobenzylguanidine (MIBG) and (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) should be defined in a Japanese population. The purpose of this study was to present and provide data on the characteristics of MIBG and BMIPP with respect to myocardial single photon emission computed tomography. METHODS: The normal database included (123)I-MIBG and (123)I-BMIPP imaging and a (99m)Tc-sestamibi/tetrofosmin myocardial perfusion study. The projection images were transferred by digital imaging and communications in medicine (DICOM) format and reconstructed and analyzed with polar maps. RESULTS: The projection data from multiple centers were successfully transferred to a common format for SPECT reconstruction. When the average values were analyzed using a 17-segment model, MIBG uptake in the inferior and apical wall appeared to be slightly lower than anterior uptake (P < 0.05). The inferior and apical uptake of MIBG has a larger standard deviation (10.7 units in males, 12.6 units in females). BMIPP uptakes in the septal wall have higher than that of (99m)Tc-tracer uptake (P < 0.05). CONCLUSION: Myocardial sympathetic nerve and metabolic scintigraphy data that were specific for the Japanese population were generated and found to be different from that of perfusion tracers. The normal database can serve as a standard for nuclear cardiology work conducted in Japan.


Subject(s)
Heart/innervation , Myocardial Perfusion Imaging/methods , Myocardium/metabolism , Sympathetic Nervous System/diagnostic imaging , 3-Iodobenzylguanidine/metabolism , Aged , Fatty Acids/metabolism , Female , Heart/diagnostic imaging , Humans , Iodobenzenes/metabolism , Japan , Male , Mediastinum/diagnostic imaging , Middle Aged , Nuclear Medicine , Societies, Scientific , Tomography, Emission-Computed, Single-Photon
11.
Circ J ; 73(4): 686-90, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19261990

ABSTRACT

BACKGROUND: Because increased sympathetic nervous activity (SNA) in patients with dilated cardiomyopathy (DCM) associated with sleep breathing disorder (SBD) is known to deteriorate the prognosis of cardiac failure, (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was used as the investigative tool in the present study. METHODS AND RESULTS: The study group comprised 53 patients (47 men, 6 women; mean age 56+/-3 years) with chronic stable DCM. Patients were divided into SBD(+) or SBD(-) group according to 24-h pulse oximetry results. SBD(+) was defined when the 3% oxygen desaturation index was more than 15/h during sleep. In total, 32 patients were SBD(-) and 21 were SBD(+). In both groups, pulse oximetry were performed during sleep and awakening pulse rate, and measurement of the blood levels of catecholamines and B-type natriuretic peptide was performed. MIBG myocardial scintigraphy and echocardiography were performed at the same time. No significant difference was found between the 2 groups in catecholamine levels or left ventricular ejection fraction. However, MIBG had a significantly increased washout rate and a significantly decreased delayed heart to mediastinum ratio in the SBD(+) group compared with the SBD(-) group. CONCLUSIONS: SNA is increased in DCM patients when associated with SBD. MIBG myocardial scintigraphy may be a sensitive method of detecting increased SNA.


Subject(s)
3-Iodobenzylguanidine/administration & dosage , Cardiomyopathy, Dilated/physiopathology , Myocardial Perfusion Imaging , Radiopharmaceuticals/administration & dosage , Sleep Apnea Syndromes/physiopathology , Sympathetic Nervous System/physiopathology , Adult , Aged , Cardiomyopathy, Dilated/blood , Cardiomyopathy, Dilated/diagnostic imaging , Catecholamines/blood , Female , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Oximetry , Oxygen/blood , Radiography , Sleep , Sleep Apnea Syndromes/blood , Sleep Apnea Syndromes/diagnostic imaging
12.
Anat Sci Int ; 84(3): 148-54, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19274476

ABSTRACT

This study was conducted to determine whether intercalated duct cells in the rat parotid gland have the properties of tissue stem cells. After induction of cellular proliferation by repeated administration of isoproterenol (IPR), a beta-adrenergic agonist, proliferation activity in acinar, intralobular, and intercalated ductal cells was quantified using Ki-67 immunohistochemistry. The total number of each type of component cell in a gland was also estimated in the course of IPR treatment. IPR was found to induce proliferation of acinar and intercalated duct cells, but not intralobular duct cells. The total number of acinar cells in a gland on day 5 of IPR treatment was 1.6 times of that at day 0 (baseline). In contrast, the total numbers of intercalated and intralobular duct cells did not change from baseline, indicating a high possibility that the proliferated intercalated duct cells differentiated into acinar cells. On days 2 to 3 of IPR treatment, intercalated duct cells with amylase-positive secretory granules were recognized in a region very close to the acini, and were suspected of being transitional cells from intercalated duct to acinar cells. This quantitative study indicates that intercalated duct cells may have the properties of tissue stem cells upon IPR stimulation.


Subject(s)
Cell Proliferation/drug effects , Parotid Gland/cytology , Stem Cells/cytology , Adrenergic beta-Agonists/pharmacology , Animals , In Vitro Techniques , Isoproterenol/pharmacology , Male , Parotid Gland/drug effects , Rats , Rats, Wistar
13.
Wound Repair Regen ; 17(1): 127-35, 2009.
Article in English | MEDLINE | ID: mdl-19152660

ABSTRACT

Novel peptide-conjugated chitosan membranes were fabricated and used to deliver keratinocytes to dermal wounds in mice. Three active peptides of 12 or 13 amino acids each, RLVSYNGIIFFLK (A5G27), ASKAIQVFLLAG (A5G33), and AGTFALRGDNPQG (A99) were selected from a cell-adhesive peptide library of laminin, a major constituent of basement membrane. The peptides were synthesized and coupled to chitosan membranes, and the resulting peptide-chitosan membranes were tested for keratinocyte attachment. Two of the peptides that bind to cell surface heparin-like receptors (A5G27 and A5G33) were found to promote strong keratinocyte attachment, whereas the one that binds to integrin (A99) was inactive. Subsequently, A5G27- and A5G33-chitosan membranes were tested as vehicles for keratinocyte delivery in a wound model. We found that keratinocytes were delivered into the full-thickness wound with either membrane. Using the A5G33-chitosan membrane, we further evaluated the activity of the delivered keratinocytes in wound healing. Immunohistochemistry for granulation tissue markers, including tenascin and alpha-smooth muscle actin, showed that keratinocyte delivery by the present peptide-chitosan membranes in the wound bed provided a favorable condition for keratinocyte migration along the wound surface and reduced granulation tissue formation.


Subject(s)
Granulation Tissue/physiology , Keratinocytes/physiology , Skin/injuries , Wound Healing/physiology , Animals , Cell Adhesion/physiology , Cell Culture Techniques/methods , Chitosan/chemistry , Immunoenzyme Techniques , Laminin/chemistry , Male , Membranes, Artificial , Mice , Mice, Nude , Skin/cytology
14.
Proc Natl Acad Sci U S A ; 105(35): 12849-54, 2008 Sep 02.
Article in English | MEDLINE | ID: mdl-18757743

ABSTRACT

Extracellular matrix (ECM), which provides critical scaffolds for all adhesive cells, regulates proliferation, differentiation, and apoptosis. Different cell types employ customized ECMs, which are thought to play important roles in the generation of so-called niches that contribute to cell-specific functions. The molecular entities of these customized ECMs, however, have not been elucidated. Here, we describe a strategy for transcriptome-wide identification of ECM proteins based on computational screening of >60,000 full-length mouse cDNAs for secreted proteins, followed by in vitro functional assays. These assays screened the candidate proteins for ECM-assembling activities, interactions with other ECM molecules, modifications with glycosaminoglycans, and cell-adhesive activities, and were then complemented with immunohistochemical analysis. We identified 16 ECM proteins, of which seven were localized in basement membrane (BM) zones. The identification of these previously unknown BM proteins allowed us to construct a body map of BM proteins, which represents the comprehensive immunohistochemistry-based expression profiles of the tissue-specific customization of BMs.


Subject(s)
Extracellular Matrix Proteins/analysis , Gene Expression Profiling , Animals , Basement Membrane/cytology , Basement Membrane/metabolism , Cell Line , Computational Biology , Epithelium/metabolism , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Humans , Immunohistochemistry , Mice , Mice, Inbred ICR , Protein Transport , Tooth/cytology , Tooth/embryology
15.
J Cardiol ; 51(2): 121-30, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18522785

ABSTRACT

BACKGROUND: Although there are many reports on Ampulla Cardiomyopathy, its etiologic mechanisms are not well known. AIM: Etiology of Ampulla Cardiomyopathy was investigated by myocardial scintigraphy with various nuclear tracers. SUBJECTS AND METHODS: In nine patients with Ampulla Cardiomyopathy, myocardial scintigraphy was performed at acute, subacute and chronic phases. Total defect score (TDS) of tallium-201 (Tl) or technetrium-99m sestamibi (MIBI) myocardial perfusion and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) scintigraphies was calculated. Cardio-mediastinal ratio (H/M) and washout rate (WR) of early and delayed images of iodine-123-meta-iodobenzylguanidine (MIBG) scintigraphy were also calculated. The patients in whom TDS of myocardial perfusion scintigraphy at acute phase was 0, were classified into group N (n = 5) and those with TDS > or = 1 into group D (n = 4). RESULTS: TDS of BMIPP at acute, subacute and chronic phases was higher in D than in N; 28.8 +/- 10.3 vs. 7.2 4.7 (p = 0.0039), 15.5 +/- 2.1 vs. 1.0 +/- 0.8 (p < 0.0001) and 2.7 +/- 1.2 vs. 0 (p = 0.05), respectively. WR of MIBG at acute phase was also higher in D (50.3 +/- 5.7% vs. 36.6 +/- 10.5%, p = 0.05). H/M (dH/M) on the delayed images and WR at chronic phase were not different between the two groups. H/M (eH/M) on the early images was lower in D. Blood noradrenaLine (ng/ml) at acute phase was higher in D than in N (1.21 +/- 0.55 vs. 0.45 +/- 0.33, p < 0.05). Left ventricular ejection fraction (LVEF) was decreased in both at acute phase but it was lower in D than in N (48.1 +/- 3.7% vs. 69.9 +/- 9.7%, p < 0.05) at subacute phase. CONCLUSION: These findings suggest that the etiology of Ampulla Cardiomyopathy is neurologically stunned myocardium induced by coronary microcirculatory disorder. Due to the significant amount of time that was necessary for normalization of wall motion in the D group, myocardial scintigraphy is believed to be also useful in assessment of severity.


Subject(s)
Coronary Disease/complications , Myocardial Stunning/diagnostic imaging , Myocardial Stunning/etiology , Acute Disease , Aged , Aged, 80 and over , Chronic Disease , Coronary Disease/physiopathology , Female , Humans , Male , Microcirculation , Middle Aged , Radioisotopes , Radionuclide Imaging , Radiopharmaceuticals , Severity of Illness Index
16.
Dev Dyn ; 236(12): 3451-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17973333

ABSTRACT

The organogenesis of islets in rat pancreas was studied by three-dimensional reconstructions from serial section micrographs. On embryonic day (E) 12, an endocrine cluster consisting mainly of glucagon-expressing cells maintained connection with the pancreatic endoderm at several regions. On E15-E17, the cluster enlarged by fusion of newly formed buds. Although the proportion of insulin-expressing cells increased, they were located in the periphery of the cluster. On the day of birth, insulin-expressing cell clusters enlarged and fused to form several cores within the islet. The glucagon-expressing cell mass expanded to form a thin mantle covering the cores. During islet organogenesis, proliferation activity was high in the exocrine duct system. Moreover, the endocrine cell clusters maintained contact with the duct epithelium throughout. We conclude that the pancreatic islet is generated by the unification of multiple endocrine clusters originated from separate regions of the duct system. The mechanism of mantle-core formation is discussed.


Subject(s)
Islets of Langerhans/cytology , Islets of Langerhans/embryology , Animals , Cell Proliferation , Female , Gestational Age , Imaging, Three-Dimensional , Immunohistochemistry , Insulin/metabolism , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/metabolism , Islets of Langerhans/metabolism , Pregnancy , Rats , Rats, Wistar
17.
Ann Nucl Med ; 21(9): 505-11, 2007 Nov.
Article in English | MEDLINE | ID: mdl-18030582

ABSTRACT

OBJECTIVE: Standards for myocardial single-photon emission computed tomography (SPECT) adapted for a Japanese population were not available. The purpose of this study was to create standard files approved by the Japanese Society of Nuclear Medicine and to make known the characteristics of the myocardial perfusion pattern of this population. METHODS: With the collaboration of nine hospitals, a total of 326 sets of exercise-rest myocardial perfusion images were accumulated from subjects with a low likelihood of cardiac diseases. The normal database included a (99m)Tc-MIBI/tetrofosmin myocardial perfusion study with 360 degrees (n = 80) and 180 degrees (n = 56) rotations, (201)Tl study with 360 degrees (n = 115) and 180 degrees rotations (n = 54) and a dual-isotope study with 360 degrees rotation (n = 27). The projection images were transferred by digital imaging and communications in medicine (DICOM) format and reconstructed and analyzed with polar maps. RESULTS: The projection data from multiple centers were successfully transferred to a common format for SPECT reconstruction. When the average values were analyzed using a 17-segment model, myocardial counts in the septal segment differed significantly between 180 degrees and 360 degrees rotation acquisitions. Regional differences were observed between men and women in the inferior and anterior regions. A tracer difference between (99m)Tc and (201)Tl was also observed in some segments. The attenuation patterns differed significantly between subjects from the United States and those from Japan. CONCLUSIONS: Myocardial perfusion data that were specific for the Japanese population were generated. The normal database can serve a standard for nuclear cardiology work conducted in Japan.


Subject(s)
Coronary Vessels , Heart/diagnostic imaging , Radiopharmaceuticals/pharmacokinetics , Tomography, Emission-Computed, Single-Photon/standards , Adult , Aged , Aged, 80 and over , Coronary Vessels/diagnostic imaging , Coronary Vessels/physiology , Female , Gated Blood-Pool Imaging/standards , Heart/physiology , Humans , Image Processing, Computer-Assisted , Japan , Male , Middle Aged , Nuclear Medicine/organization & administration , Nuclear Medicine/standards , Radiopharmaceuticals/blood , Reference Standards , Sex Factors , Societies, Medical
18.
Ann Nucl Med ; 21(7): 399-404, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17876553

ABSTRACT

OBJECTIVE: Various clinical trials for dilated cardiomyopathy (DCM) have demonstrated that the prognosis as well as cardiac function is improved by the administration of beta-blocker therapy. On the other hand, 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) reflects myocardial fatty acid metabolism and is considered to be a more sensitive tracer than perfusion tracers. In this study, the efficacy of DCM for the evaluation of myocardial damage and the prediction of cardiac events was studied using 123I-BMIPP and 201TI (Tl) myocardial scintigraphy. METHODS: Study subjects comprised 33 DCM patients, divided into a cardiac event group (event, n = 9) and an event-free group (event free, n = 24). An extent score (ES) and severity score (SS) were calculated for each BMIPP image. BMIPP and Tl images were divided into 17 segments, and total defect scores (TDS) were calculated for each. The TDS of the BMIPP and Tl images were compared with score differences greater than or equal to 4 and less than 4 defined as mismatch and non-mismatch, respectively. RESULTS: The TDS of BMIPP was significantly higher in the event group than in the event-free group (P < 0.05). The ES and SS were significantly higher in the event group than in the event-free group (P < 0.01). The comparison in the 2 x 2 contingency tables showed that the occurrence of non-mismatch was significantly higher in the event-free group (chi2 test; P < 0.01). The ES of BMIPP was a significant predictor of cardiac events in the multivariate analysis (P < 0.01). CONCLUSIONS: These results suggest that the ES for BMIPP is useful as a predictor of cardiac events in DCM.


Subject(s)
Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/diagnostic imaging , Fatty Acids , Heart Arrest/diagnostic imaging , Heart Arrest/diagnosis , Heart Failure/diagnostic imaging , Heart Failure/diagnosis , Iodobenzenes , Tachycardia, Ventricular/diagnostic imaging , Tachycardia, Ventricular/diagnosis , Aged , Fatty Acids/metabolism , Fatty Acids/pharmacokinetics , Female , Follow-Up Studies , Heart Arrest/etiology , Heart Arrest/mortality , Heart Failure/etiology , Heart Failure/mortality , Humans , Image Interpretation, Computer-Assisted , Iodine Radioisotopes/pharmacokinetics , Iodobenzenes/pharmacokinetics , Male , Middle Aged , Multivariate Analysis , Myocardium/metabolism , Myocardium/pathology , Predictive Value of Tests , Prognosis , Radiopharmaceuticals/pharmacokinetics , Risk Factors , Survival Rate , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/mortality , Thallium Radioisotopes/pharmacokinetics , Tomography, Emission-Computed, Single-Photon
19.
J Biol Chem ; 282(34): 24806-15, 2007 Aug 24.
Article in English | MEDLINE | ID: mdl-17604280

ABSTRACT

A mechanism by which ubiquitinated cargo proteins are sorted into multivesicular bodies (MVBs) from plasma and trans-Golgi network (TGN) membranes is well established in yeast and mammalian somatic cells. However, the ubiquitin-dependent sorting pathway has not been clearly defined in germ cells. In this study we identified a novel member of the transmembrane RING-finger family of proteins, termed membrane-associated RING-CH (MARCH)-XI, that is expressed predominantly in developing spermatids and weakly in brain and pituitary. MARCH-XI possesses an E3 ubiquitin ligase activity that targets CD4 for ubiquitination. Immunoelectron microscopy of rat round spermatids showed that MARCH-XI is localized to TGN-derived vesicles and MVBs. Fluorescence staining of rat round spermatids and immunoprecipitation of rat testis demonstrated that MARCH-XI forms complexes with the adaptor protein complex-1 and with fucose-containing glycoproteins including ubiquitinated forms. Furthermore, the C-terminal region of MARCH-XI mediates its interaction with mu1-adaptin and Veli through a tyrosine-based motif and a PDZ binding motif, respectively. Our data suggest that MARCH-XI acts as a ubiquitin ligase with a role in ubiquitin-mediated protein sorting in the TGN-MVB transport pathway, which may be involved in mammalian spermiogenesis.


Subject(s)
Spermatids/metabolism , Ubiquitin-Protein Ligases/chemistry , Ubiquitin/metabolism , Amino Acid Motifs , Amino Acid Sequence , Animals , Brain/metabolism , Cloning, Molecular , Male , Microscopy, Immunoelectron , Molecular Sequence Data , Pituitary Gland/metabolism , Protein Binding , Rats , Recombinant Proteins/chemistry , Ubiquitin-Protein Ligases/physiology
20.
J Cardiol ; 49(5): 277-85, 2007 May.
Article in Japanese | MEDLINE | ID: mdl-17552294

ABSTRACT

A 58-year-old woman with chronic renal failure had been undergoing maintenance hemodialysis. Ampulla cardiomyopathy recurred in association with prolonged sympathetic nerve function disorder. Periodical evaluation of the patient's condition using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was continued since the first attack at age 55 years. The initial washout rate was high at 58.3%, and was still high at 33.0% when she was discharged following improvement in wall motion, and remained high at 45.4% 1 year after discharge. Recurrence occurred at age 58 years, when a high washout rate of 48.6% was observed. High washout rate values of 49.5% and 40.1% were also observed 2 and 9 months after discharge, respectively, following improvement in wall motion abnormalities. 123I-MIBG can be used to assess the course of recurrent ampulla cardiomyopathy, and can objectively evaluate sympathetic nerve function disorders. This interesting case suggests that sympathetic nerve function disorder is closely related to the pathophysiology of this disorder.


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Cardiomyopathies/diagnosis , Heart/diagnostic imaging , 3-Iodobenzylguanidine , Autonomic Nervous System Diseases/complications , Cardiomyopathies/etiology , Echocardiography , Electrocardiography , Female , Humans , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals , Recurrence , Renal Dialysis
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