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Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental disabilities. Auto auditory brainstem response (AABR) is a simple hearing test and used for the purpose of neonatal hearing screening, but can use it for early detection hard of hearing within the study age of the model. We experienced two case of asymptomatic CMV infection in which congenital and late-onset hearing loss were diagnosed early with AABR, and hearing loss improved with valganciclovir.

In isotropic environments, an Escherichia coli cell exhibits coordinated rotational switching of its flagellar motors, produced by fluctuations in the intracellular concentration of phosphorylated CheY (CheY-P) emanating from chemoreceptor signaling arrays. In this study, we show that these CheY-P fluctuations arise through modifications of chemoreceptors by two sensory adaptation enzymes: the methyltransferase CheR and the methylesterase CheB. A cell containing CheR, CheB, and the serine chemoreceptor Tsr exhibited motor synchrony, whereas a cell lacking CheR and CheB or containing enzymatically inactive forms did not. Tsr variants with different combinations of methylation-mimicking Q residues at the adaptation sites also failed to show coordinated motor switching in cells lacking CheR and CheB. Cells containing CheR, CheB, and Tsr [NDND], a variant in which the adaptation site residues are not substrates for CheR or CheB modifications, also lacked motor synchrony. TsrΔNWETF, which lacks a C-terminal pentapeptide-binding site for CheR and CheB, and the ribose-galactose receptor Trg, which natively lacks this motif, failed to produce coordinated motor switching, despite the presence of CheR and CheB. However, addition of the NWETF sequence to Trg enabled Trg-NWETF to produce motor synchrony, as the sole receptor type in cells containing CheR and CheB. Finally, CheBc, the catalytic domain of CheB, supported motor coordination in combination with CheR and Tsr. These results indicate that the coordination of motor switching requires CheR/CheB-mediated changes in receptor modification state. We conclude that the opposing receptor substrate-site preferences of CheR and CheB produce spontaneous blinking of the chemoreceptor array’s output activity. IMPORTANCE Under steady-state conditions with no external stimuli, an Escherichia coli cell coordinately switches the rotational direction of its flagellar motors. Here, we demonstrate that the CheR and CheB enzymes of the chemoreceptor sensory adaptation system mediate this coordination. Stochastic fluctuations in receptor adaptation states trigger changes in signal output from the receptor array, and this array blinking generates fluctuations in CheY-P concentration that coordinate directional switching of the flagellar motors. Thus, in the absence of chemoeffector gradients, the sensory adaptation system controls run-tumble swimming of the cell, its optimal foraging strategy.

Chronic lung disease (CLD) is a major neonatal pulmonary disorder associated with inflammation. Recent studies have shown that protein C anticoagulant pathways, such as those for protein C (PC), protein S (PS), and thrombomodulin (TM), could be useful indices for reflecting pulmonary injury. However, the involvement of these factors in preterm infants with very low birthweight (VLBW) who have developed CLD remains to be investigated. Here, we investigated whether PC pathway-related factors could predict the development of CLD in preterm infants with VLBW.We collected plasma samples from 26 preterm infants with VLBW (13 each from those with and without CLD) at the time of birth and measured TM, PC, and PS levels in their plasmas. We analyzed prospectively the relationship between these factors in infants with and without CLD.There were significant differences in gestational age, birthweight, Apgar score (5 min), and duration of mechanical ventilation between the CLD and non-CLD groups. No significant differences in the PC and PS levels at birth were observed between the two groups, whereas the TM levels in the CLD group were significantly higher than those in the non-CLD group (P = 0.013). The TM levels correlated with gestational age and duration of mechanical ventilation. However, covariance analysis demonstrated that gestational age was significantly associated with TM levels, and consequently, development of CLD was not associated with TM level at birth.Thrombomodulin, PC, and PS levels at birth could not predict the development of CLD in preterm infants with VLBW.

Background Atypical hemolytic uremic syndrome (aHUS) is caused by complement overactivation, and its presentation and prognosis differ according to the underlying molecular defects. The aim of this study was to characterize the genetic backgrounds of aHUS patients in Japan and to elucidate the associations between their genetic backgrounds, clinical findings, and outcomes. Methods We conducted a nationwide epidemiological survey of clinically diagnosed aHUS patients and examined 118 patients enrolled from 1998 to 2016 in Japan. We screened variants of seven genes related to complement and coagulation, as well as positivity for anti-CFH antibodies, and assessed clinical manifestations, laboratory findings, and clinical course. Results The most frequent genetic abnormalities were in C3 (31%) and the frequency of CFH variants was relatively low (10%) compared to Western countries. The predominant variant in this cohort was C3 p.I1157T (23%), which was related to favorable outcomes despite frequent relapses. A total of 72% of patients received plasma therapy, while 42% were treated with eculizumab. The prognosis of Japanese aHUS patients was relatively favorable, with a total mortality rate of 5.4% and a renal mortality rate of 15%. Conclusions The common occurrence of genotype C3, especially the p.I1157T variant was the characteristic of the genetic backgrounds of Japanese aHUS patients that differed from those of Caucasian patients. In addition, the favorable prognosis of patients with the unique C3 p.I1157T variant indicates that understanding the clinical characteristics of individual gene alterations is important for predicting prognosis and determining therapeutic strategies in aHUS.

Significance The flagellar basal body contains a type III protein export machinery to construct the flagellar axial structure. ATP hydrolysis by FliI facilitates the flagellar protein export, and the ATPase activity is regulated by FliH. In this study, the structure of the homodimer of a FliH fragment (FliH C ) complexed with FliI has been solved at 3.0-Å resolution. FliH C2 shows a marked structural similarity to the peripheral stalk of the A/V-type ATPases, and the proposed FliH C2 –FliI hexamer model resembles in situ electron cryotomographic images. These results suggest that FliH 2 functions as a peripheral stalk of the type III ATPase complex and that the flagellar export system and F/A/V-type ATPases share a similar functional mechanism and close evolutionary relationship.

Phototherapy using blue light-emitting diodes (LED) is effective against neonatal jaundice. However, green light phototherapy also reduces unconjugated jaundice. We aimed to determine whether mixed blue and green light can relieve jaundice with minimal oxidative stress as effectively as either blue or green light alone in a rat model.Gunn rats were exposed to phototherapy with blue (420-520 nm), filtered blue (FB; 440-520 nm without440-nm wavelengths, FB50 (half the irradiance of filtered blue), mixed (filtered 50% blue and 50% green), and green (490-590 nm) LED irradiation for 24h. The effects of phototherapy are expressed as ratios of serum total (TB) and unbound (UB) bilirubin before and after exposure to each LED. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by HPLC before and after exposure to each LED to determine photo-oxidative stress.Values1.00 indicate effective phototherapy. The ratios of TB and UB were decreased to 0.85, 0.89, 1.07, 0.90, and 1.04, and 0.85, 0.94, 0.93, 0.89, and 1.09 after exposure to blue, filtered blue, FB50, and filtered blue mixed with green LED, respectively. In contrast, urinary 8-OHdG increased to 2.03, 1.25, 0.96, 1.36, 1.31, and 1.23 after exposure to blue, filtered blue, FB50, mixed, green LED, and control, indicating side-effects (1.00), respectively.Blue plus green phototherapy is as effective as blue phototherapy and it attenuates irradiation-induced oxidative stress.Combined blue and green spectra might be effective against neonatal hyperbilirubinemia.

Background Chorioamnionitis, or infiltration of the chorioamnion by neutrophils, is a risk factor associated with the development of bronchopulmonary dysplasia. Increased neutrophil elastase levels are observed in the tracheal aspirates of these patients. Aims To examine the effects of early administration of the selective neutrophil elastase inhibitor sivelestat, which is used to treat acute lung injury in adults, on bronchopulmonary dysplasia in extremely premature infants. Study design Retrospective cohort study. Subjects This study included extremely low-birth-weight infants born at a gestational age Outcome measures The primary outcome was the rate of bronchopulmonary dysplasia-free survival at a postmenstrual age of 36 weeks, and the secondary outcomes included various clinically significant factors of neonatal mortality and morbidity and adverse events. Results Of the 1031 included neonates, 124 (12.0%) were treated with sivelestat. Significant differences between the groups were noted for gestational age, delivery method, fetal number, the frequency of chorioamnionitis, immunoglobulin M levels, and WBC counts. No differences were identified concerning the bronchopulmonary dysplasia-free survival rate at a postmenstrual age of 36 weeks (adjusted odds ratio for sivelestat to control, 0.83; 95% confidence interval = 0.53–1.30). Secondary outcomes did not significantly differ between the groups. Conclusions In extremely premature infants, early sivelestat use was not associated with an improved rate of survival without bronchopulmonary dysplasia at a postmenstrual age of 36 weeks.

Atypical hemolytic uremic syndrome (aHUS), a form of thrombotic microangiopathy, is caused by the uncontrolled activation of the alternative pathway of complement on the cell surface that leads to microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. A recent genetic analysis of aHUS patients identified deleterious mutations not only in complement or complement regulatory genes but also in the plasminogen gene, suggesting that subnormal plasminogen activity may be related to the degradation of thrombi in aHUS. Dysplasminogenemia, which is caused by a genetic variant in the plasminogen gene, PLG:p.Ala620Thr, is commonly observed in the northeast Asian populations, including Japanese. To examine the association between dysplasminogenemia and aHUS, we genotyped PLG:p.Ala620Thr in 103 Japanese patients with aHUS. We identified five aHUS patients with PLG:p.Ala620Thr; the minor allele frequency (MAF) was thus 0.024. The MAF in the patient group was not significantly different from those obtained from a general Japanese population (MAF = 0.020) and the Japanese genetic variation HGDV database (MAF = 0.021) (P = 0.62 and 0.61, respectively). We concluded that, although carriers with PLG:p.Ala620Thr show low plasminogen activity, this is not a predisposing variant for aHUS and that individuals of dysplasminogenemia are not at significantly increased risk of aHUS.

Vibrio cholerae, the etiological agent of cholera, was found to be attracted by taurine (2-aminoethanesulfonic acid), a major constituent of human bile. Mlp37, the closest homolog of the previously identified amino acid chemoreceptor Mlp24, was found to mediate taxis to taurine as well as L-serine, L-alanine, L-arginine, and other amino acids. Methylation of Mlp37 was enhanced upon the addition of taurine and amino acids. Isothermal titration calorimetry demonstrated that a purified periplasmic fragment of Mlp37 binds directly to taurine, L-serine, L-alanine and L-arginine. Crystal structures of the periplamic domain of Mlp37 revealed that L-serine and taurine bind to the membrane-distal PAS domain in essentially in the same way. The structural information was supported by characterising the in vivo properties of alanine-substituted mutant forms of Mlp37. The fact that the ligand-binding domain of the L-serine complex had a small opening, which would accommodate a larger R group, accounts for the broad ligand specificity of Mlp37 and allowed us to visualise ligand binding to Mlp37 with fluorescently labelled L-serine. Taken together, we conclude that Mlp37 serves as the major chemoreceptor for taurine and various amino acids.

Objective Cardiac tamponade is a serious complication of central venous catheter (CVC) insertion. The position of the carina has been shown to be near the pericardial reflection and can easily be identified as a landmark on routine chest x-ray (CXR). The purpose of this study was to show a simple way to predict optimal CVC depth, thereby facilitating safe positioning of the CVC tip. Methods Subjects included 119 inpatients undergoing gastroenterologic surgery. Central venous catheterization was performed through the right internal jugular vein or the right subclavian vein. The insertion depth was measured. Postoperatively, the CVC tip position was confirmed by CXR and the distance between the CVC tip and the carina was measured. We compared the “original measurement” up to the carina from the insertion point with the “calculated measurement” derived by adding half the length of the right clavicle and the vertical length between the sternal head of the right clavicle and the carina on the CXR. Results There was a significant correlation between the original measurement and the calculated measurement when performed through the internal jugular vein and the subclavian vein. Conclusion The appropriate length of CVC inserted through the right internal jugular vein or right subclavian vein could be estimated by the calculated measurement of adding half the length of the right clavicle and the vertical length between the sternal head of the right clavicle and the carina.

Background: KL-6 in umbilical cord blood, including from premature infants, and perinatal factors that may affect these values have not yet been adequately discussed. The authors investigated factors affecting cord venous plasma levels of KL-6 in neonates, and to establish a normal range of values for KL-6 in neonatal cord blood. Methods: Cord plasma levels of KL-6 were measured in 75 neonates, and statistical analysis of factors affecting these levels was performed. A normal range for cord plasma KL-6 levels was calculated by statistical analysis methods based on guidelines by the National Committee for Clinical Laboratory Standards. Results: Data from a total of 75 neonates was analyzed. Gestational age ranged from 25 to 40 weeks (median, 33.4 weeks), and birthweight ranged from 776 to 3760 g (median, 1944 g). There was no statistically significant correlation between cord plasma KL-6 levels with gender, gestational age, birthweight, method of delivery, Apgar score 1 min, and postnatal respiratory distress. The normal range of values for cord plasma KL-6 was 44.3–148.2 U/mL (median, 73.0 U/mL). Conclusion: The cord plasma levels of KL-6 were about half the normal values reported in children and healthy adults and were not affected by various perinatal factors. The authors’ findings suggest that plasma KL-6 levels rise when respiratory function is established after birth and tend to further increase with age.

The human pathogen Legionella pneumophila delivers a large array of the effector proteins into host cells using the Dot/Icm type IVB secretion system. Among the proteins composing the Dot/Icm system, an inner membrane protein DotI is known to be crucial for the secretion function but its structure and role in type IV secretion had not been elucidated. We report here the crystal structures of the periplasmic domains of DotI and its ortholog in the conjugation system of plasmid R64, TraM. These structures reveal a striking similarity to VirB8, a component of type IVA secretion systems, suggesting that DotI/TraM is the type IVB counterpart of VirB8. We further show that DotI and its partial paralog DotJ form a stable heterocomplex. R64 TraM, encoded by the conjugative plasmid lacking DotJ ortholog, forms a homo-hexamer. The DotI-DotJ complex is distinct from the core complex, which spans both inner and outer membranes to form a substrate conduit and seems not to stably associate with the core complex. These results give insight into VirB8-family inner membrane proteins essential for type IV secretion and aid towards understanding the molecular basis of secretion systems essential for bacterial pathogenesis.

Waldenström's hypergammaglobulinemic purpura (HGP) is a rare chronic disorder characterized by recurrent purpura on the legs, a polyclonal increase in serum gamma-globulin, an elevated erythrocyte sedimentation rate and a positive rheumatoid factor. A 30-year-old primigravid woman with 14 years of HGP was found to have fetal bradycardia at 25 weeks' gestation. Laboratory investigations demonstrated positive anti-Ro/SSA and anti-La/SSB antibodies in the maternal serum. Cesarean delivery was performed at 39 weeks, and a 2750-g female infant was born with complete atrioventricular block. Fortunately, the neonatal period has been uneventful without need for pace-making. Maternal HGP exacerbated just after delivery, but resolved within 1 week without treatment. Physicians should be aware of the possible presence of neonatal lupus-related anti-Ro/SSA and anti-La/SSB autoantibodies in patients with HGP. Screening for these autoantibodies is important and could be used as a marker to identify and manage high-risk pregnancies.

Correspondence to: Dr. Toshiyuki Miyata Department of Molecular Pathogenesis National Cerebral and Cardiovascular Center 5-7–1 Fujishiro-dai, Suita, Osaka 565–8565, Japan Tel.: +81 6 6833 5012, Fax: +81 6 6835 1176 E-mail: miyata@ncvc.go.jp Financial support: This work was supported in part by grants-in-aid from the Ministry of Health, Labour and Welfare of Japan, the Japan Society for the Promotion of Science, and the Takeda Science Foundation.

Despite the recent introduction of a new class of anti-Aspergillus agents, no standard regimen for the prevention of invasive fungal disease (IFD) following allogeneic hematopoietic stem cell transplantation has been shown to be superior to fluconazole. The present prospective, single-arm study investigated the feasibility of voriconazole (VOR) administration as primary prophylaxis in 52 recipients of umbilical cord blood transplantation (CBT) with fludarabine-based conditioning, who had no previous IFD episodes. Proven or probable IFD was determined using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria were considered as breakthrough infections. VOR was administered as prophylaxis for a total of 6884 patient-days following CBT. The mean duration of VOR administration after transplantation was 132 days (range, 1-769); 44 patients (85 %) had advanced disease, 15 (29 %) had a history of allogeneic HSCT, and 29 (56 %) received systemic corticosteroid therapy for allogeneic immune-mediated complications. Under the prophylaxis with VOR, one patient developed probable invasive aspergillosis on day 71, and the cumulative incidence of IFD was 4.5 % at day 180. None of the patients developed breakthrough candida or zygomycetes infections. Under the extensive therapeutic dose monitoring, VOR was safely administered with a calcineurin inhibitor and was well tolerated. These results suggest that VOR represents a feasible primary prophylactic agent for IFD after CBT with fludarabine-based conditioning.

A practical synthetic method of d4T (3) from 5-methyluridine (2a) was developed. The Marumoto-Mansuri method was modified using 2′,3′-O-methoxy-ethylidene-5-methyluridine (10) as an intermediate to afford 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine (6a) in high yield with less formation of by-products. The reaction mechanism was also discussed. †Dedicated to Dr. Yoshihisa Mizuno on the occasion of his 75th birthday.

A convenient synthesis of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) from guanosine by chemical transpurination was developed. The isomerization of the 7-isomer to the desired 9-isomer and the purification of the 9-isomer was achieved simply by concentration, heating and further crystallization.

A soluble protein, FliJ, along with a membrane protein, FlhA, plays a role in the energy coupling mechanism for bacterial flagellar protein export. The water-soluble FliH(X)-FliI(6) ATPase ring complex allows FliJ to efficiently interact with FlhA. However, the FlhA binding site of FliJ remains unknown. Here, we carried out genetic analysis of a region formed by well-conserved residues-Gln38, Leu42, Tyr45, Tyr49, Phe72, Leu76, Ala79, and His83-of FliJ. A structural model of the FliI(6)-FliJ ring complex suggests that they extend out of the FliI(6) ring. Glutathione S-transferase (GST)-FliJ inhibited the motility of and flagellar protein export by both wild-type cells and a fliH-fliI flhB(P28T) bypass mutant. Pulldown assays revealed that the reduced export activity of the export apparatus results from the binding of GST-FliJ to FlhA. The F72A and L76A mutations of FliJ significantly reduced the binding affinity of FliJ for FlhA, thereby suppressing the inhibitory effect of GST-FliJ on the protein export. The F72A and L76A mutations were tolerated in the presence of FliH and FliI but considerably reduced motility in their absence. These two mutations affected neither the interaction with FliI nor the FliI ATPase activity. These results suggest that FliJ(F72A) and FliJ(L76A) require the support of FliH and FliI to exert their export function. Therefore, we propose that the well-conserved surface of FliJ is involved in the interaction with FlhA.

The bacterial flagellar proteins are translocated into the central channel of the flagellum by a specific protein-export apparatus for self-assembly at the distal growing end. FliH and FliI are soluble components of the export apparatus and form an FliH2–FliI heterotrimer in the cytoplasm. FliI is an ATPase and the FliH2–FliI complex delivers export substrates from the cytoplasm to an export gate made up of six integral membrane proteins of the export apparatus. In this study, an FliHCfragment consisting of residues 99–235 was co-purified with FliI and the FliHC2–FliI complex was crystallized. Crystals were obtained using the hanging-drop vapour-diffusion technique with PEG 400 as a precipitant. The crystals belonged to the orthorhombic space groupP212121, with unit-cell parametersa= 133.7,b= 147.3,c= 164.2 Å, and diffracted to 3.0 Å resolution.

We have various interesting time-varying data in our daily life, such as weather data (e.g., temperature and air pressure) and stock prices. Such time-varying data is often associated with other information: for example, temperatures can be associated with weather, and stock prices can be associated with social or economic incidents. Meanwhile, we often draw large-scale time-varying data by multiple polylines in one space to compare the time variation of multiple values. We think it should be interesting if such time-varying data is effectively visualized with their associated information. This paper presents a technique for polyline-based visualization and level-of-detail control of tagged time-varying data. Supposing the associated information is attached as tags of the time-varying values, the technique generates clusters of the time-varying values grouped by the tags, and selects representative values for each cluster, as a preprocessing. The technique then draws the representative values as polylines. It also provides a user interface so that users can interactively select interesting representatives, and explore the values which belong to the clusters of the representatives.

A 51-year-old man who underwent umbilical cord blood transplantation for acute lymphoblastic leukemia with a Philadelphia chromosome in April 2006 achieved complete remission. In June 2008, progressive renal dysfunction and melena emerged and the patient was diagnosed with B-cell-type malignant lymphoma. He presented with severe hypo-phosphate- mia(0. 1m g/dL)due to paraneoplastic syndrome, simultaneously. Because the development of tumor lysis syndrome followed by hyper-phophatemia was feared to occur after CHOP chemotherapy, we discontinued the adjustment of serum phosphorus. The serum phosphorus level was elevated to 11.6mg/dL after 3 days and decreased to 3. 8mg/dL after 5 days. We must be careful regarding hyper-phosphatemia and phosphorus adjustment even in patients with severe hypo-phosphatemia that is due to paraneoplastic syndrome.

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.

We report a patient with hairy cell leukemia Japanese variant (HCL-Jv) that developed after radiotherapy for orbital adnexal MALT lymphoma. A 78-year-old man was diagnosed as having MALT lymphoma in the left conjunctiva in December 2003. The patient was treated by local radiotherapy and the tumor disappeared. Thereafter, he gradually developed leukocytosis and mild splenomegaly. In May 2009, the leukocyte count was 34,300 with 80% lymphoid cells. A diagnosis of HCL-Jv was made since the lymphoid cells showed a hairy morphology with round nuclei and indistinct nucleoli. These cells expressed CD11c, CD19, CD20, CD103 and showed weak reaction for tartrate-resistant acid phosphatase (TRAP). Bone marrow was infiltrated by atypical cells with an intrasinusoidal pattern. No treatment was needed as the patient was asymptomatic without anemia, thrombocytopenia or lymphadenopathy. Results of the immunoglobulin light chain expression and the heavy chain rearrangement in the tumor cells indicated that the two mature B-lymphoid neoplasms, MALT lymphoma and HCL-Jv, in this patient were derived from independent clones. This appears to be the first reported case of HCL-Jv associated with other lymphoid tumor. Further analysis is needed to clarify the risk of secondary malignancy in HCL-Jv.

A convenient synthesis of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) from guanosine by chemical transpurination was developed. The isomerization of the 7-isomer to the desired 9-isomer and the purification of the 9-isomer was achieved simply by concentration, heating and further crystallization.

An economical synthesis of famciclovir from N-2-acetyl-7-benzylguanine by a novel regioselective alkylation with the diester cyclopropane compound was developed.

In this study, we investigated the level of gut absorption following oral beclomethasone dipropionate (BDP) administration by measuring the blood concentration of its metabolites measured by LC-MS/MS using the HPLC method. Five patients who were administered BDP orally for gut GVHD were included. The blood concentrations of beclomethasone-17-monopropionate (17BMP), which is one of the active metabolites of BDP, were 618 approximately 1, 749 pg/mL in 4 of the studied 5 patients, which was comparable to that after inhalation of BDP; however, it was relatively higher in one patient (2,439+/-161 pg/mL). As the blood concentration of 17BMP in this study patient was higher compared with healthy volunteers administered a single oral BDP 4 mg, GVHD patients might have a higher concentration than healthy volunteers. Given that a higher grade of gut GVHD was associated with a higher blood level of 17BMP, BDP absorption might be associated with gut mucosal injury. Thus, the systemic adverse effect following oral BDP administration might not be negligible especially in gut GVHD patients.

Regioselective 2′-O-deacetylation of 9-(2,5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)adenine (1) is achieved by treatment of 1 with β-cyclodextrin (β-CyD) / aq. NaHCO3 or N2H4·H2O / EtOH. The 9-(5-O-Acetyl-3-bromo-3-deoxy-β-D-xylo-furanosyl)adenine (2) obtained is a common intermediate for the synthesis of 2′,3′-dideoxy-adenosine (ddA) (7) and 9-(2-fluoro-2,3-dideoxy-β-D-threo-pentofuranosyl)-adenine (F-ddA) (9).

We have various interesting time series data in our daily life, such as weather data (e.g., temperature and air pressure)and stock prices. Polyline chart is one of the most common ways to represent such time series data. We often draw multiple polylines in one space to compare the time variation of multiple values. However, it is often difficult to read the values if the number of polylines gets larger. This paper presents a technique for visualization and level-of-detail control of large number of time series data. The technique generates clusters of time series values,and selects representative values for each cluster, as a preprocessing. The technique then draws the representative values as polylines. It also provides a user interface so that users can interactively select interesting representatives,and explore the time series values which belong to the clusters of the representatives.

Practicing pharmaceutical care is necessary to promote the appropriate use of medicines. In the practice of pharmaceutical care, monitoring the efficacy and safety of drugs from the pharmacists' point of view is an important role for clinical pharmacists and it is necessary to standardize clinical skills. We would like to introduce the monitoring skills of pharmacotherapy of clinical pharmacists by taking vancomycin injection and injectable anticancer drugs that have different monitoring points as examples.

Background: Among full-term neonates, the authors discovered infants who showed respiratory inhibition after crying which involved a marked decrease in SpO2. The infants were found to present increased echogenicity or a cyst in a cranial region termed the ganglionic eminence, or to have a subependymal cyst. The authors prospectively examined the relationship between respiratory inhibition after crying and these changes to examine the prevention and treatment of the episode. Methods: The authors conducted cranial ultrasonography to screen 381 full-term neonates who showed no abnormalities at birth and whose parents requested ultrasonographic screening of the head, followed by polygraphy of infants who showed increased echogenicity or a cyst in ganglionic eminence, or had a subependymal cyst. The authors similarly conducted polygraphy for 50 neonates without cranial ultrasound abnormalities; the former constituted the control group. Respiratory inhibition was defined to be central apnea immediately after crying with a decrease in SpO2 to

Background Arbekacin (ABK) is an aminoglycoside antibiotic that has a dose-dependent bactericidal action. Because it inhibits the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus (MRSA), it has attracted attention as a therapeutic drug for MRSA infection. In this study, the authors investigated the pharmacokinetics of ABK based on therapeutic drug monitoring (TDM), in order to establish an effective dosage regimen with minimal adverse reactions in MRSA infected newborns and infants. Methods Arbekacin was administered to nine MRSA infected newborns and infants between October 2000 and March 2002. Following the initial ABK administration, blood was collected and the blood concentration of ABK was measured. The blood concentrations of ABK were analyzed by the two-compartment model or by a model-independent method in order to elucidate the pharmacokinetics of ABK. Pharmacokinetic analysis was performed using WinNonlin Professional V3.1. Results The mean age at initial ABK administration was 24.0 +/- 26.0 days (postconceptional age: 39.2 +/- 3.9 weeks). The increase in the peak blood concentration of ABK was 2.40 +/- 0.20 microg/mL per mg ABK per kg bodyweight, showing great consistency among cases. The elimination half-life of ABK was 0.22-3.52 h in the alpha phase (T(1/2alpha)) and 2.42-33.44 h in the beta phase (T(1/2beta)), showing great variation among cases. The distribution volume was 0.75 +/- 0.13 L/kg, and systemic clearance was 0.054 +/- 0.012 L/h/kg. ABK alleviated clinical symptoms and inflammations in all cases. Conclusion Nine newborns and infants with MRSA infection and various underlying diseases were successfully treated with TDM-based administration of ABK with no severe adverse reactions.

Background: Polygraph recordings of neonatal apnea obtained using an Eden Trace II monitor were manually analyzed to devise a new desaturation index (DSI). Methods: Heart rate, thoracic respiratory movements, airflow, andblood oxygen saturation (SpO 2 ) of 25 neonates in intensive care were monitored using polygraphy. The DSI was defined as the number of SpO 2 decreases per hour of valid monitoring time. Neonates were divided into three groups according to DSI 8 5 : group A, DSI 8 5 less than one decrease per hour (n = 12); group B, DSI 8 5 ranging from one to nine decreases per hour (n = 8); and group C, DSI 8 5 ≥10 decreases per hour (n = 5). Clinical characteristics and type of apnea in each group were compared statistically. Group C neonates were treated with aminophylline, and the effects of treatment were evaluated. Results: Gestational age at birth, birthweight, age at monitoring and valid monitoring time did not differ significantly between the three groups, but mean SpO 2 , DSI 7 0 , the frequency of central apnea and periodic breathing did. Oxygen desaturation in group B and particularly group C was predominantly attributable to periodic breathing rather than central apnea. Aminophylline produced significant improvement in periodic breathing but exerted no significant effect on the other types of apnea. Both DSI 8 5 and DSI 7 0 were strongly correlated (r = 0.833). Conclusions: Polygraphic study of neonates at risk revealed marked arterial oxygen desaturation, even among those with periodic breathing. This novel DSI represents a useful tool for evaluating apnea and periodic breathing in neonates and for assessing treatment efficacy.