Anti-citrullinated protein antibody titre as a predictor of abatacept treatment persistence in patients with rheumatoid arthritis: a prospective cohort study in Japan.

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment.Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation.Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months.Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

Complete renal response at 12 months after induction therapy is associated with renal relapse-free rate in lupus nephritis: a single-center, retrospective cohort study.

BACKGROUND: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. RESULTS: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum ß2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels. CONCLUSIONS: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum ß2MG levels were negative predictive factors of CR at 12 months.

National surveillance of Salmonella Enteritidis in commercial eggs in Japan.

A total of 105 033 eggs were collected across Japan from June 2010 to January 2011 and tested for Salmonella Enteritidis to provide data for the risk profiling of S. Enteritidis in eggs by the Food Safety Commission of Japan. S. Enteritidis isolates were recovered from three samples (20 eggs/sample) and these samples were different in regard to sampling period, grading and packaging centre and farm. The prevalence of S. Enteritidis in commercial eggs in Japan is estimated at ~0.003% which was a tenfold decrease in prevalence compared to similar surveillance in the mid 1990s. The decrease in the contamination in commercial eggs is considered a contributory factor in the decrease of foodborne diseases associated with S. Enteritidis in this period.

The use of warmed water treatment to induce protective immunity against the bacterial cold-water disease pathogen Flavobacterium psychrophilum in ayu (Plecoglossus altivelis).

We investigated the induction of protective immunity against bacterial cold-water disease (BCWD) caused by Flavobacterium psychrophilum by warmed water treatment in ayu (Plecoglossus altivelis). Fish were immersed in a live bacterial suspension (107 CFU mL⁻¹) for 30 min and placed in 700 L concrete tanks. The 28 °C warmed water treatment lasted 3 days and began 1, 6, and 24 h after immersion in the live bacterial suspension. A naïve control fish group was immersed in a sterilized modified Cytophaga (MCY) broth instead of the bacterial suspension. Fourteen days after the immersion, agglutination antibody titers against F. psychrophilum were measured by using micro-titer methods. Fish were then exposed to a bacterial bath to infect them with live F. psychrophilum, and cumulative mortality was monitored. Fish treated with warmed water at 1, 6, and 24 h after immersion in the live bacterial suspension had cumulative mortalities of 36%, 30%, and 18%, respectively, all of which were significantly lower than the cumulative mortality of the naïve control fish (90%). Treated fish also showed high antibody titers against F. psychrophilum in agglutination tests. These results demonstrate that warmed water treatment could not only cure BCWD but also immunize the fish against the causative agent F. psychrophilum.

A novel genotyping technique for distinguishing between Flavobacterium psychrophilum isolates virulent and avirulent to ayu, Plecoglossus altivelis altivelis (Temminck & Schlegel).

We developed a simple genotyping method for Flavobacterium psychrophilum for analysing two single nucleotide polymorphisms (SNPs) in the gyrA gene and to distinguish between isolates that are virulent and avirulent to ayu, Plecoglossus altivelis altivelis (Temminck & Schlegel). The genotyping method is an on/off switch assay and is based on the polymerase chain reaction technique with phosphorothioated primers. We classified 232 isolates from four families of fish (i.e. Plecoglossidae, Osmeridae, Cyprinidae and Salmonidae) into four genotypes (G-C, A-T, A-C and G-T). The G-C type isolates exhibited strong pathogenicity to ayu, whereas the A-T and G-T types did not show any pathogenicity to this species. The A-C type exhibited no or weak pathogenicity to ayu. These results indicate that genotyping F. psychrophilum isolates with two SNPs from gyrA can clearly distinguish between isolates potentially harmful to ayu (G-C type) and those that are potentially not harmful or less harmful (A-C, A-T and G-T type). The on/off switch assay provides a quick, simple, and very powerful DNA genotyping technique for F. psychrophilum isolates.

Lipopolysaccharide induces proinflammatory cytokines and chemokines in experimental otitis media through the prostaglandin D2 receptor (DP)-dependent pathway.

Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP⁻(/)⁻) mice, CRTH2 single gene-deficient (CRTH2⁻(/)⁻) mice and DP/CRTH2 double gene-deficient (DP⁻(/)⁻ CRTH2⁻(/)⁻) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1ß and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1ß and IL-6 induced by LPS, are reduced significantly in DP⁻(/)⁻ mice and DP⁻(/)⁻ CRTH2⁻(/)⁻ mice. CRTH2⁻(/)⁻ mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP.

Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors.

Using a clonal culture system, we investigated the hemopoietic effects of purified recombinant IL-5 obtained from conditioned media of transfected Xenopus oocytes. IL-5 alone acted on untreated bone marrow cells and supported the formation of a small number of colonies, all of which were predominantly eosinophilic. However, it did not support colony formation by spleen cells from 5-FU-treated mice, in which only primitive stem cells had survived, while IL-3 and G-CSF did. Eosinophil-containing colonies were formed from these cells in the presence of IL-5 and G-CSF together. In contrast, G-CSF alone did not support any eosinophil colonies. The eosinophilopoietic effect of IL-5 was dose-dependent, and was neutralized specifically by anti-IL-5 antibody. To exclude the possibility of interactions with accessory cells in the same culture dish, we replated a small number (200 cells/dish) of enriched hemopoietic progenitors, obtained from blast cell colonies, which were formed by cultivation of spleen cells from 5-FU-treated mice in the presence of IL-3 or G-CSF. From these replated blast cells, eosinophil colonies were induced in dishes containing IL-5 but not in those containing G-CSF alone. From these findings, it was concluded that IL-5 did not act on primitive hemopoietic cells, but on blast cells induced by IL-3 or G-CSF. IL-5 specifically facilitated the terminal differentiation and proliferation of eosinophils. In this respect, the role of IL-5 in eosinophilopoiesis seems to be analogous to erythropoietin, which promotes the terminal differentiation and amplification of erythroid cells. Moreover, IL-5 maintained the viability of mature eosinophils obtained from peritoneal exudate cells of the mice infected with parasites, indicating mature functional eosinophils carried IL-5 receptors. The synergistic effects of IL-5 and colony-stimulating factors on the expansion of eosinophils is supposed to contribute to the urgent mobilization of eosinophils at the time of helminthic infections and allergic responses.

Development and evaluation of a loop-mediated isothermal amplification assay for rapid and simple detection of Flavobacterium psychrophilum.

Flavobacterium psychrophilum is the causative agent of bacterial cold-water disease and rainbow trout fry syndrome of salmonids. The pathogen has been reported from all regions in the world involved in salmonid aquaculture, but also from natural fresh-water environments. We established a quantitative loop-mediated isothermal amplification of DNA (LAMP) method to estimate quantities of F. psychrophilum. LAMP primers were designed based on the sequence of the DNA topoisomerase IV subunit B gene, parE, of F. psychrophilum. parE LAMP exhibited a high specificity for the parE gene of F. psychrophilum but not for other related species. parE LAMP detected the gene in a wide range of concentrations from 2.0 x 10(1) to 2.0 x 10(9) copies/reaction within 70 min and revealed a good correlation between threshold times and gene copy number.

Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group.

We evaluated the efficacy of a treatment strategy in which infants with acute lymphoblastic leukemia (ALL) were stratified by their MLL gene status and then assigned to different risk-based therapies. A total of 102 patients were registered on two consecutive multicenter trials, designated MLL96 and MLL98, between 1995 and 2001. Those with a rearranged MLL gene (MLL-R, n=80) were assigned to receive intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT), while those with germline MLL (MLL-G, n=22) were treated with chemotherapy alone. The 5-year event-free survival (EFS) rate for all 102 infants was 50.9% (95% confidence interval, 41.0-60.8%). The most prominent late effect was growth impairment, observed in 58.9% of all evaluable patients in the MLL-R group. This plan of risk-based therapy appears to have improved the overall prognosis for infants with ALL, compared with previously reported results. However, over half the events in patients with MLL rearrangement occurred before the instigation of HSCT, and that HSCT-related toxic events comprised 36.3% (8/22) of post-transplantation events, suggesting that further stratification within the MLL-R group and the development of more effective early-phase intensification chemotherapy will be needed before the full potential of this strategy is realized.

Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk.

The aim of this study was to clarify the epidemiological association and bacteriological characteristics of human and animal Staphylococcus aureus isolates. Pulsed-field gel electrophoresis showed that pulsotypes (PT) of isolates from bulk milk differed from PT from human isolates, suggesting that there is no epidemiological association between isolates from these 2 sources. The absence of a common PT could result from the lack of contact between the sources. Methicillin-resistant S. aureus from human secretions and S. aureus from bulk milk in Japan consisted of 1 and 2 dominant clusters, respectively, whereas methicillin-susceptible S. aureus from humans consisted of assorted clusters. Isolates belonging to the dominant clusters showed the coagulase serotype, the capsule serotype, detection of exotoxin genes, and antimicrobial susceptibility. Isolates from bulk milk did not show the penicillin-binding protein 2a gene, and 252 of 275 isolates belonging to the 2 dominant clusters of bulk milk were susceptible to ampicillin, cefazolin, erythromycin, chloramphenicol, oxacillin, and vancomycin. Moreover, the LukM/LukF'-PV leukotoxin gene was detected in 233 of 275 isolates belonging to the dominant clusters in bulk milk isolates. These results support the hypothesis that a number of factors play a role in the adaptation of S. aureus isolates to specific hosts.

[Subtraction image for dynamic liver MRI using free breath-hold at functional residual capacity: a clinical trial].

PURPOSE: Dynamic liver MRI images have been obtained under expiration breath holding (BH). However, problems with obtaining reproducible liver positions often observed. This study investigated ways to improve the reproducibility of liver position on dynamic liver MRI. MATERIALS AND METHODS: After giving informed consent, 60 patients (32 males and 28 females, ages 33-85, median age 69) were examined by liver dynamic MRI under two types of BH. The BH phases were voluntary expiration (VE) phase without any explanations and functional residual capacity (FRC) phase after careful explanation was provided. Plain images, arterial phase images, portal phase images and parenchymal phase images were obtained. For statistical evaluation of reproducibility, the area of the 2nd or 3rd images from top of the liver was measured in each phase using a threshold value of half maximum. Misregistration areas were calculated by finding the remainder of the liver area in the plain-arterial (Pl-A) phase, arterial-portal (A-Po) phase, plain-parenchymal (Pl-Pa) phase. Contingency table analysis was done due to the misregistration was occurred or not. RESULTS: Misregistration of liver image on the VE and the FRC of three phase types were statistical significant on the Pl-A (p < 0.01), on the A-Po (p < 0.01) and on the Pl-Pa (p < 0.05), respectively. CONCLUSION: The FRC phase following careful explanation of the BH provided significantly improved reproducibility of liver position on dynamic liver MRI. Therefore, precise subtraction images could be obtained for routine clinical examinations without slice matching.

Control of fatty acid metabolism by leptin in L6 rat myoblasts is regulated by hyperinsulinemia.

The development of hypothalamic leptin resistance plays a role in the development of obesity, yet whether peripheral leptin resistance occurs in obesity and diabetes is controversial. Here we investigate whether hyperinsulinemia, as observed during the development of Type 2 diabetes, modifies the effects of leptin on long chain fatty acid metabolism in skeletal muscle cells. We used boron dipyrromethene difluoride (BODIPY)-labeled palmitate to show that leptin (60 nM) caused a time-dependent (0-60 min) increase in fatty acid uptake in L6 myoblasts. Quantitative analysis using 3H-palmitate showed that pre-incubation with insulin (100 nM, 24 h) prevented stimulation of fatty acid uptake by leptin. Insulin pre-treatment also attenuated the ability of leptin to phosphorylate acetyl Co-A carboxylase and increase palmitate oxidation. Suppressor of cytokine-3 (SOCS-3) has been proposed as a possible mediator of insulin-induced leptin resistance. Here we show that treatment of L6 cells with insulin elicited a time-dependent increase in both SOCS-3 mRNA and protein content. In summary, hyperinsulinemia can induce leptin resistance in L6 myoblasts and this may be mediated via a SOCS-3-dependent mechanism.

Computed tomography phantom for radiochromic film dosimetry.

To evaluate in detail the dose distribution during computed tomography (CT), a sheet roll CT dosimetry phantom (SRCT-P) with a radiochromic film (RF) was experimentally developed. The SRCT-P was made by rolling up a vinyl chloride sheet in a cylindrical shape to arbitrarily select the SRCT-P diameter, dose measurement position, and depth. The SRCT-P centre core consisted of a plastic hose in which a 10 mm acrylic bar with a RF was inserted. To determine the availability of the SRCT-P, the surface and centre doses (at a 5 mm radius) at each SRCT-P diameter (6-16 cm; every 2 cm) were measured. The ratios of the centre-to-surface doses (D(centre)/D(surface)) systematically increased, from 80 to 111%, for decreasing SRCT-P diameters, between 16 and 6 cm, respectively. The centre dose approached the surface dose as the SRCT-P diameter decreased. To use a RF for a CT dose measurement, further detailed research and analysis is necessary. However, this study has shown that a SRCT-P is useful and beneficial for the measurement of the dose distribution during a CT examination.

Establishment and characterization of a human leukemic cell line with megakaryocytic features: dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival.

A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and theta-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and beta-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.

Defective control of apoptosis, radiosensitivity, and spindle checkpoint in ataxia telangiectasia.

We examined the regulation of apoptosis, radiosensitivity, and spindle checkpoint in response to DNA-damaging agents in ataxia telangiectasia (AT)-derived lymphoblastoid cell lines (AT-LCLs), which lack AT mutated (ATM) protein expression. In addition to the previous findings that AT-LCLs are defective in regulation of cell cycle at the G1, S, and G2-M checkpoints in response to X-ray irradiation (X-IR) and are highly sensitive to X-IR (J. Biol. Chem., 271: 20486-20493, 1996), we showed for the first time that AT-LCLs were defective in X-IR-associated spindle checkpoint control. The cells were also resistant to early apoptosis as much as LCLs derived from patients with Li-Fraumeni syndrome (LFS-LCLs). Terminal deoxynucleotidyl transferase-mediated nick end labeling assay of LCLs, however, demonstrated a significant increase in apoptotic cells among AT-LCLs cultured over a longer period after X-IR. These findings were in contrast to those of LFS-LCL, which showed very little increase in terminal deoxynucleotidyl transferase-mediated nick end labeling-positive population, even in cells with hyperploidy. Thus, although early apoptosis and cell cycle controls in response to DNA damage are disrupted in both ATM and p53 mutations, cells from AT patients are much more susceptible to late-onset apoptosis than those of LFS. These differences may depend on the level of accumulation of DNA damage and/or threshold that triggers late-onset cell death in ATM or p53 mutations. Our findings allow a better understanding of the role of ATM in p53-dependent and independent signal transduction pathways in response to DNA damaging agents.

Defective control of apoptosis and mitotic spindle checkpoint in heterozygous carriers of ATM mutations.

Ataxia telangiectasia (AT) carrier-derived lymphoblastoid cell lines (AT-LCLs/hetero) with suboptimal ATM protein expression were examined for the regulation of radiosensitivity, apoptosis, and mitotic spindle checkpoint in response to DNA-damaging agents. Although AT-LCLs/hetero showed intermediate radiation sensitivity, as determined by clonogenic assay, they were resistant to early-onset apoptosis, as much as AT patient-derived LCLs (AT-LCLs/homo). Furthermore, two of three AT-LCLs/hetero showed defective mitotic spindle checkpoint control in response to X-ray irradiation, which is a recently characterized biological feature in AT-LCLs/homo. Our findings indicate that carriers of ATM mutation have biological abnormalities due to haploinsufficiency of ATM protein or dominant-negative effect of mutant ATM protein. Thus, although it is still controversial whether ATM mutation carriers are at higher risk for cancer during adulthood, our findings based on in vitro biological indicators support the notion that at least some of such carriers are at a higher risk for cancer development than those without ATM mutation. Our findings may help to reevaluate epidemiological studies on cancer susceptibility in AT carriers.

DNA damage-associated dysregulation of the cell cycle and apoptosis control in cells with germ-line p53 mutation.

Lymphoblastoid cell lines (LCLs) with heterozygous p53 mutations at residues 286A, 133R, 282W, 132E, and 213ter were established from five independent Li-Fraumeni syndrome families. When cell cycle regulation in response to gamma-irradiation was studied, these LCLs showed an abnormal G1 checkpoint associated with defective inhibition of cyclin E/cyclin-dependent kinase 2 activity in all cases except for 282W LCL, which showed a normal G1 checkpoint. On the other hand, the control of S-phase-G2 as determined by cyclin A/cyclin-dependent kinase 2 activity was defective in all these LCLs. The mitotic checkpoint was also defective in the two LCLs analyzed as either competent or incompetent for G1 arrest. When radiation-induced apoptosis, which requires wild-type p53 function under optimal conditions, was studied, all of these LCLs showed significant failure compared to normal LCLs. These findings indicate that although p53-dependent transactivation and G1-S-phase cell cycle control are variably dysregulated, the induction of apoptosis and control of the cell cycle at S-phase-G2 and the mitotic checkpoint in response to DNA-damaging agents are consistently dysregulated in heterozygous mutant LCLs. This suggests that these dysfunctions underlie, at least in part, the susceptibility of Li-Fraumeni syndrome families to cancer. Furthermore, the approach presented is a potentially useful method for studying individual carriers of different germ-line p53 mutations and different biological features.

Cloning and sequence analysis of membrane-bound alkaline phosphatase cDNA of the silkworm, Bombyx mori.

The nucleotide sequence (1974 bp) of cDNA coding for membrane-bound alkaline phosphatases (m-ALP) of Bombyx mori was isolated. The cDNA clone contained an open reading frame encoding a polypeptide (547 amino acids), which contains a hydrophobic signal peptide of 36 amino acids and the mature protein of 511 amino acids (Mr = 56,163). We found a highly hydrophobic domain presumed to be a membrane anchoring region at the C-terminus. Comparing analysis between Bombyx m-ALP and mammalian and Escherichia coli ALPs suggested an evolutionary relationship of sharing a common ancestral gene.

Right ventricular abnormalities assessed by myocardial single-photon emission computed tomography using technetium-99m sestamibi/tetrofosmin in right ventricle-originated ventricular tachyarrhythmias.

OBJECTIVES: We sought to determine whether right ventricular (RV) perfusion imaging with technetium-99m (Tc-99m) sestamibi or tetrofosmin single-photon emission computed tomography has diagnostic benefit for RV-originated ventricular tachyarrhythmias (RVT). BACKGROUND: Identification of RV abnormalities is clinically important to establish RVT etiology. METHODS: Forty-seven patients with RVT (23 with idiopathic and 24 with organic RVT due to arrhythmogenic RV or dilated cardiomyopathy, cardiac sarcoidosis or myocarditis) were compared to 25 control subjects. Right ventricular uptake score, as assessed by modified tomographic imaging, and regional RV count relative to peak left ventricular (LV) count (RV/LV count ratio) were compared with RV regional and global function. RESULTS: Regional RV uptake score correlated well with the RV/LV count ratio, and segmental abnormality was more frequently (p = 0.001) detected in the organic RVT group (22 [92%] of 24 patients) than in the idiopathic RVT group (4 [17%] of 23 patients) or the control group (8 [32%] of 25 patients). The total RV score (8.4+/-3.8) in the organic RVT group was significantly lower than that in the idiopathic RVT group (15.6+/-1.6) or the control group (15.1+/-1.8). The total RV score correlated with RV EF (r = 0.702, p<0.001). A total RV score <12 differentiated the organic RVT group from the other two groups, with a sensitivity of 79% and a specificity of 100%. The asynergic RV regions had a significantly lower RV/LV count ratio and RV score as compared with the nonasynergic regions and were identified by RV assessment, with a sensitivity of 76.1% and a specificity of 76.6%. CONCLUSIONS: Right ventricular perfusion tomography using a Tc-99m-labeled tracer is clinically useful for the noninvasive detection of RV myocardial damage in patients with RVT and for differentiating organic from idiopathic RVT.

Chloroquine induces basophilic differentiation of HL-60 cells.

Many agents have been known to induce the differentiation of HL-60 cells. However, only a small number of reports on the basophilic differentiation of this cell line are known. In this study we show that the exposure of HL-60 cells to chloroquine induces to differentiate into basophils. This chloroquine-induced change suggests that the increase in intracellular pH and the upregulation of p21 with subsequent downregulation of cdc2 kinase are triggers for basophilic differentiation of this cell line.