Assessment of Heating on Titanium Alloy Cerebral Aneurysm Clips during 7T MRI.

BACKGROUND AND PURPOSE: Patients with cerebral aneurysms often undergo MR imaging after microsurgical clipping. Ultra-high-field MR imaging at 7T may provide high diagnostic capability in such clinical situations. However, titanium alloy clips have safety issues such as adverse interactions with static magnetic fields and radiofrequency-induced heating during 7T MR imaging. The purpose of this study was to quantitatively assess temperature increases on various types of titanium alloy aneurysm clips during 7T MR imaging. MATERIALS AND METHODS: Five types of titanium alloy aneurysm clips were tested, including combinations of short, long, straight, angled, and fenestrated types. Each clip was set in a phantom filled with gelled saline mixed with polyacrylic acid and underwent 7T MR imaging with 3D T1WI with a spoiled gradient recalled acquisition in the steady-state technique. Temperature was chronologically measured at the tips of the clip blade and head, angled part of the clip, and 5 mm from the tip of the clip head using MR imaging-compatible fiber-optic thermometers. RESULTS: Temperature increases at all locations for right-angled and short straight clips were <1°C. Temperature increases at the angled part for the 45° angled clip and the tip of the clip head for the straight fenestrated clip were >1°C. Temperature increases at all locations for the long straight clip were >2°C. CONCLUSIONS: Temperature increases on the right-angled and short straight clips remained below the regulatory limit during 7T MR imaging, but temperature increases on the 45° angled, straight fenestrated, and long straight clips exceeded this limit.

The KANNO blood group system.

The KANNO blood group system (International Society of Blood Transfusion [ISBT] 037) includes one high-prevalence antigen, KANNO1, across ethnic groups. Sporadic KANNO1- cases among East and South Asians are theoretically estimated by the DNA database library. Anti-KANNO1 has been found most often among Japanese women with current or prior pregnancy. Thus far, there are no reported cases of hemolytic transfusion reaction or hemolytic disease of the fetus and newborn due to anti-KANNO1.

Diagnostic Accuracy of Screening Arterial Spin-Labeling MRI Using Hadamard Encoding for the Detection of Reduced CBF in Adult Patients with Ischemic Moyamoya Disease.

BACKGROUND AND PURPOSE: Adult patients with ischemic Moyamoya disease are advised to undergo selective revascularization surgery based on cerebral hemodynamics. The purpose of this study was to determine the diagnostic accuracy of arterial spin-labeling MR imaging using Hadamard-encoded multiple postlabeling delays for the detection of reduced CBF in such patients. MATERIALS AND METHODS: Thirty-seven patients underwent brain perfusion SPECT and pseudocontinuous arterial spin-labeling MR imaging using standard postlabeling delay (1525 ms) and Hadamard-encoded multiple postlabeling delays. For Hadamard-encoded multiple postlabeling delays, based on data obtained from the 7 sub-boluses with combinations of different labeling durations and postlabeling delays, CBF corrected by the arterial transit time was calculated on a voxel-by-voxel basis. Using a 3D stereotaxic template, we automatically placed ROIs in the ipsilateral cerebellar hemisphere and 5 MCA territories in the symptomatic cerebral hemisphere; then, the ratio of the MCA to cerebellar ROI was calculated. RESULTS: The area under the receiver operating characteristic curve for detecting reduced SPECT-CBF ratios (<0.686) was significantly greater for the Hadamard-encoded multiple postlabeling delays-CBF ratios (0.885) than for the standard postlabeling delay-CBF ratios (0.786) (P = .001). The sensitivity and negative predictive value for the Hadamard-encoded multiple postlabeling delays-CBF ratios were 100% (95% confidence interval, 100%-100%) and significantly higher than the sensitivity (95% CI, 44%-80%) and negative predictive value (95% CI, 88%-97%) for the standard postlabeling delay-CBF ratio, respectively. CONCLUSIONS: ASL MR imaging using Hadamard-encoded multiple postlabeling delays may be applicable as a screening tool because it can detect reduced CBF on brain perfusion SPECT with 100% sensitivity and a 100% negative predictive value in adult patients with ischemic Moyamoya disease.

Probing the Magnetosheath Boundaries Using Interstellar Boundary Explorer (IBEX) Orbital Encounters.

Inside the magnetosheath, the IBEX-Hi energetic neutral atom (ENA) imager measures a distinct background count rate that is more than 10 times the typical heliospheric ENA emissions observed when IBEX is outside the magnetosheath. The source of this enhancement is magnetosheath ions of solar wind (SW) origin that deflect around the Earth's magnetopause (MP), scatter and neutralize from the anti-sunward part of the IBEX-Hi sunshade, and continue into the instrument as neutral atoms, behaving indistinguishably from ENAs emitted from distant plasma sources. While this background pollutes observations of outer heliospheric ENAs, it provides a clear signature of IBEX crossings over the magnetospheric boundaries. In this study, we investigate IBEX encounters with the magnetosheath boundaries using ∼8 yr of orbital data, and we determine the MP and bow shock (BS) locations derived from this background signal. We find 280 BS crossings from X GSE ∼ 11 Re to X GSE âˆ¼ -36 Re and 241 MP crossings from X GSE ∼ 6 Re to X GSE âˆ¼ -48 Re. We compare IBEX BS and MP crossing locations to those from IMP-8, Geotail, Cluster, Magion-4, ISEE, and Magnetospheric Multiscale Mission, and we find that IBEX crossing locations overlap with the BS and MP locations inferred from these other data sets. In this paper, we demonstrate how IBEX can be used to identify magnetosheath crossings, and extend boundary observations well past the terminator, thus further constraining future models of magnetosheath boundaries. Furthermore, we use the IBEX data set to show observational evidence of near-Earth magnetotail squeezing during periods of strong interplanetary magnetic field B y.

Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: The fetal brain is vulnerable to severe and sustained hypoxia during and after birth, which can lead to hypoxic-ischemic encephalopathy (HIE). HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury. The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates are not fully understood. In this study, we investigated cytokine profile related to cerebral palsy (CP) with neonatal hypoxic ischemic encephalopathy (HIE) and HIE severity. METHODS: Eligible subjects were HIE newborns with a gestational age between 36 and 42 weeks. We included newborns who was born at our NICU and did not admit to NICU as healthy controls. The study comprised 52 newborns, including 13 with mild to severe HIE and 39 healthy control. Serum cytokine profiles were performed using a LUMINEX cytokine kit (R&D Systems). RESULTS: VEGF, MCP-1, IL-15, IL-12p70, IL-12p40, IL-1Ra, IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, G-CSF and eotaxin in the HIE patients were significantly increased compared with the healthy neonates. In the subgroup analysis, IL-6 and G-CSF were significantly increased in CP infants (n = 5) compared with non-CP infants (n = 8). Five and eight HIE patients were classified into the mild HIE and moderate-severe HIE groups, respectively. IL-6, 10, 1Ra, and G-CSF in the moderate-severe HIE group were significantly higher than those in the mild HIE group. CONCLUSION: We demonstrated that higher serum IL-6 and G-CSF at birth in HIE patients were associated with CP and moderate-severe HIE.

First Global Images of Ion Energization in the Terrestrial Foreshock by the Interstellar Boundary Explorer.

The Interstellar Boundary Explorer (IBEX) mission provides global energetic neutral atom (ENA) observations from the heliosphere and the Earth's magnetosphere, including spatial, temporal, and energy information. IBEX views the magnetosphere from the sides and almost always perpendicular to noon-midnight plane. We report the first ENA images of the energization process in the Earth's ion foreshock and magnetosheath regions. We show ENA flux and spectral images of the dayside magnetosphere with significant energization of ENA plasma sources (above ~2.7 keV) in the region magnetically connected to the Earth's bow shock (BS) in its quasi-parallel configuration of the interplanetary magnetic field (IMF). We also show that the ion energization increases gradually with decreasing IMF-BS angle, suggesting more efficient suprathermal ion acceleration deeper in the quasi-parallel foreshock.

Acetazolamide-Loaded Dynamic 7T MR Quantitative Susceptibility Mapping in Major Cerebral Artery Steno-Occlusive Disease: Comparison with PET.

BACKGROUND AND PURPOSE: Dynamic changes in cerebrovascular reactivity after acetazolamide administration vary markedly among patients with major cerebral arterial steno-occlusive disease. MR quantitative susceptibility mapping can dynamically quantify the cerebral magnetic susceptibility. The purpose of this study was to determine whether dynamic changes in susceptibility after administration of acetazolamide on 7T quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in the cerebral hemispheres with major cerebral arterial steno-occlusive disease. MATERIALS AND METHODS: Sixty-five patients underwent 7T MR imaging at baseline and at 5, 10, 15, and 20 minutes after acetazolamide administration. Differences between the susceptibility of venous structures and surrounding brain tissue were calculated in the quantitative susceptibility mapping images. Susceptibility differences at 5, 10, 15, and 20 minutes after acetazolamide administration relative to baseline were calculated in 97 cerebral hemispheres with major cerebral arterial steno-occlusive disease. CBV and the cerebral metabolic rate of oxygen were also calculated using 15O-gas PET in the resting state. RESULTS: Dynamic changes of susceptibility after acetazolamide administration were classified into 3 patterns: abnormally increasing 5 or 10 minutes after acetazolamide administration; abnormally decreasing within 20 minutes after acetazolamide administration; and remaining unchanged after acetazolamide administration. CBV was significantly greater in the first pattern than in the latter 2. The cerebral metabolic rate of oxygen differed significantly in descending order from the first to middle to last pattern. CONCLUSIONS: Dynamic changes of susceptibility after acetazolamide administration on 7T MR quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in major cerebral arterial steno-occlusive disease.

The B allele with a 5·8 kb deletion in intron 1 of the ABO gene is the major allele in Japanese individuals with Bm and A1 Bm phenotypes.

Bm and A1 Bm phenotypes are the most frequent ABO variants in the Japanese population. The B antigen on Bm red blood cells is only detectable by adsorption and elution tests, and plasma B-transferase activity is usually detected at half or less levels compared with that of common B. Recently, a B allele lacking an erythroid cell-specific transcription enhancer in intron 1 of the ABO gene was identified from individuals with Bm and A1 Bm phenotypes, which could explain the unique serologic properties of Bm . In the Japanese Red Cross Society, eight Blood Centers tested blood samples from donors throughout Japan and collected blood samples from 888 Bm and 415 A1 Bm individuals. DNA analysis revealed that 1300 of 1303 (99·77%) individuals had the B allele with a 5·8 kb deletion (c.28 + 5110_10889del), which included the enhancer element.

Silent KEL alleles identified from Japanese individuals with the Ko phenotype.

BACKGROUND AND OBJECTIVE: The rare Ko phenotype lacks all 36 antigens in the Kell blood system. The molecular basis of the Ko phenotype has been investigated, and more than 40 silent KEL alleles are reported by many investigators. The majority of silent alleles are the KEL*02 background. Here, we report molecular genetic analysis of the KEL gene in Japanese individuals with the Ko phenotype. MATERIALS AND METHODS: The Ko phenotype was screened from Japanese blood donors for several years using monoclonal anti-Ku or anti-K14 by an automated blood grouping system PK7300. Kell-related antigens were typed by standard tube tests. Genomic DNA was extracted from the blood samples, and KEL gene was analysed by polymerase chain reaction (PCR) and Sanger sequencing. RESULTS: We collected 35 Ko blood samples with K-k-, Kp(a-b-), Js(a-b-) and K14-. PCR and sequence analysis revealed that 11 individuals were homozygous for a mutant KEL allele with a c.299G>C (p.Cys100Ser) mutation (rs. 200268316). Three individuals were homozygous for the KEL*02N.24 allele that is c.715G>T (p.Glu239*), and one individual was homozygous for the KEL*02N.40 allele that is c.1474C>T (p.Arg492*). Five individuals were homozygous for novel KEL alleles with single-nucleotide mutations, four individuals had a c.2175delC (p.Pro725 fs*43), and one individual had a c.328delA (p.Arg110 fs*79). The remaining 15 individuals were compound heterozygous, and eight new alleles were identified from them. CONCLUSIONS: We identified three known and ten new silent KEL alleles from Japanese individuals with the Ko phenotype. The KEL allele with the c.299G>C (p.Cys100Ser) mutation was the most frequent.

Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy.

BACKGROUND AND PURPOSE: Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy. MATERIALS AND METHODS: Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping-oxygen extraction fraction images. RESULTS: Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping-oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5-249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping-oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively. CONCLUSIONS: Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy.

Serum cytokine concentrations, chorioamnionitis and the onset of bronchopulmonary dysplasia in premature infants.

OBJECTIVE: To investigate the relationships between serum cytokine concentrations and chorioamnionitis (CAM) and CAM-related bronchopulmonary dysplasia (BPD) in premature infants. METHODS: Serum was collected at 0 and 7 days after birth from 36 premature infants born at <32 weeks of gestation. We examined the relationships between 30 cytokine concentrations and CAM, BPD, and other perinatal factors. RESULTS: On day 0, GM-CSF, IL-15, IL-17, IL-2, IL-2R, VEGF, and MIG concentrations were significantly higher in the CAM group (n = 17) than in the non-CAM group (n = 19). These concentrations had decreased by day 7 and were similar in both groups. The IL-12p70 concentration on day 0 was significantly lower in the BPD group (n = 16) than in the non-BPD group (n = 15). BPD incidence was similar between the CAM and non-CAM groups. CONCLUSIONS: These data support the hypothesis that intrauterine inflammation is not a primary risk factor for BPD. The immunological environment at birth or soon after, rather than intrauterine fetal inflammation (e.g., CAM), is a primary risk factor for BPD onset in preterm infants. Decreased inflammatory responses are particularly relevant, as indicated by the relationship between BPD and low serum IL-12p70 concentrations on day 0.

Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model.

Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell-mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti-NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin-KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D-ligand in allografts and demonstrated the significance of this using grafts expressing Rae-1, a murine NKG2D-ligand, which induced severe bronchiolitis obliterans in WT and Rag-1 KO recipients. This effect was ameliorated by injection of anti-NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans.

Prevalence of RHD alleles in Japanese individuals with weak D phenotype: Identification of 20 new RHD alleles.

We identified 46 different RHD alleles from 226 Japanese individuals with weak D phenotype, 26 of which had been previously described and 20 that were novel. Among these weak D individuals, the alleles with c.960G>A, c.845G>A (RHD*15) or c.1013T>C (RHD*01W.24) mutations were most prevalent with relative occurrences of 36·7%, 15·9% and 9·7%, respectively. These findings demonstrate that the prevalence of common weak D alleles in the Japanese population significantly differs from that of Caucasian populations.

Optimal MR Plaque Imaging for Cervical Carotid Artery Stenosis in Predicting the Development of Microembolic Signals during Exposure of Carotid Arteries in Endarterectomy: Comparison of 4 T1-Weighted Imaging Techniques.

BACKGROUND AND PURPOSE: Preoperative identification of plaque vulnerability may allow improved risk stratification for patients considered for carotid endarterectomy. The present study aimed to determine which plaque imaging technique, cardiac-gated black-blood fast spin-echo, magnetization-prepared rapid acquisition of gradient echo, source image of 3D time-of-flight MR angiography, or noncardiac-gated spin-echo, most accurately predicts development of microembolic signals during exposure of carotid arteries in carotid endarterectomy. MATERIALS AND METHODS: Eighty patients with ICA stenosis (≥70%) underwent the 4 sequences of preoperative MR plaque imaging of the affected carotid bifurcation and then carotid endarterectomy under transcranial Doppler monitoring of microembolic signals in the ipsilateral middle cerebral artery. The contrast ratio of the carotid plaque was calculated by dividing plaque signal intensity by sternocleidomastoid muscle signal intensity. RESULTS: Microembolic signals during exposure of carotid arteries were detected in 23 patients (29%), 3 of whom developed new neurologic deficits postoperatively. Those deficits remained at 24 hours after surgery in only 1 patient. The area under the receiver operating characteristic curve to discriminate between the presence and absence of microembolic signals during exposure of the carotid arteries was significantly greater with nongated spin-echo than with black-blood fast spin-echo (difference between areas, 0.258; P < .0001), MPRAGE (difference between areas, 0.106; P = .0023), or source image of 3D time-of-flight MR angiography (difference between areas, 0.128; P = .0010). Negative binomial regression showed that in the 23 patients with microembolic signals, the contrast ratio was associated with the number of microembolic signals only in nongated spin-echo (risk ratio, 1.36; 95% confidence interval, 1.01-1.97; P < .001). CONCLUSIONS: Nongated spin-echo may predict the development of microembolic signals during exposure of the carotid arteries in carotid endarterectomy more accurately than other MR plaque imaging techniques.

Presence of nucleotide substitutions in the ABO promoter in individuals with phenotypes A3 and B3.

Recently, the involvement of mutation and deletion of transcription regulatory elements in the Bm , Am , A3 and B3 phenotypes has been reported. In the present study, we carried out genetic analysis of individuals with A3 and B3 using peptide nucleic acid-clamping PCR to exclude amplification of O alleles. Two single-point mutations, -76G>C and -68G>T, were found in the ABO promoter on the A-allele in three A3 individuals and on the B allele in a B3 individual, respectively. Transient transfection of luciferase reporter plasmids carrying the same mutations into K562 cells revealed decreased luciferase activity in comparison with that carrying the wild-type promoter. These observations suggest that the mutations downregulate the promoter activity, leading to reduction in A- or B-antigen expression on red blood cells in individuals with the A3 and B3 phenotypes.

Weak D alleles in Japanese: a c.960G>A silent mutation in exon 7 of the RHD gene that affects D expression.

BACKGROUND AND OBJECTIVES: The molecular basis of the weak D phenotype has been investigated for many years, and more than 80 different alleles producing weak D phenotypes have been identified. Most alleles producing weak D phenotypes have a single missense mutation in exons corresponding to a transmembrane domain of the RhD polypeptide. We report here RHD alleles with single nucleotide mutations in Japanese accounting for weak expression of D antigen. METHODS: Seventy-five blood samples with a weak D phenotype were detected from 763 408 blood donors by standard serological methods. Forty-five of the 75 blood donors were available for RHD gene analysis by PCR and sequencing using genomic DNA and reticulocyte mRNA. Real-time PCR was performed to estimate the relative amounts of the RHD transcripts. RESULTS: We detected 16 different RHD alleles in the 45 individuals with weak D by nucleotide sequencing; 12 were newly identified. Thirty-two of the 45 individuals had an RHD allele with a single missense mutation, while the other 13 individuals had RHD with a c.960G>A silent mutation in exon 7. Red blood cells of these 13 individuals showed direct agglutination with anti-D at a strength of 3+ or less. Semi-quantitative analysis of the RHD transcripts by real-time PCR revealed that the cDNA samples with the c.960G>A mutation showed a significant increment of exon 7 skipping compared with the common RHD. CONCLUSION: Reduced expression of D antigen is caused not only by missense mutation of the RHD gene, but also by silent mutation that may affect splicing.

An integrated time-of-flight versus residual energy subsystem for a compact dual ion composition experiment for space plasmas.

We have developed a novel concept for a Compact Dual Ion Composition Experiment (CoDICE) that simultaneously provides high quality plasma and energetic ion composition measurements over 6 decades in ion energy in a wide variety of space plasma environments. CoDICE measures the two critical ion populations in space plasmas: (1) mass and ionic charge state composition and 3D velocity and angular distributions of ∼10 eV/q-40 keV/q plasma ions­CoDICE-Lo and (2) mass composition, energy spectra, and angular distributions of ∼30 keV-10 MeV energetic ions­CoDICE-Hi. CoDICE uses a common, integrated Time-of-Flight (TOF) versus residual energy (E) subsystem for measuring the two distinct ion populations. This paper describes the CoDICE design concept, and presents results of the laboratory tests of the TOF portion of the TOF vs. E subsystem, focusing specifically on (1) investigation of spill-over and contamination rates on the start and stop microchannel plate (MCP) anodes vs. secondary electron steering and focusing voltages, scanned around their corresponding model-optimized values, (2) TOF measurements and resolution and angular resolution, and (3) cross-contamination of the start and stop MCPs' singles rates from CoDICE-Lo and -Hi, and (4) energy resolution of avalanche photodiodes near the lower end of the CoDICE-Lo energy range. We also discuss physical effects that could impact the performance of the TOF vs. E subsystem in a flight instrument. Finally, we discuss advantages of the CoDICE design concept by comparing with capabilities and resources of existing flight instruments.

Molecular basis for D- Japanese: identification of novel DEL and D- alleles.

BACKGROUND AND OBJECTIVES: The occurrence of D- is approximately 0.5% in Japanese, but DEL in apparently D- individuals is relatively common compared with that in Caucasian populations. On the basis of molecular genetics, we examined D- Japanese blood donors. METHODS: A standard serological technique was used for RhD typing, and we selected 3526 D- blood samples. Genomic DNA obtained from whole blood was used for RHD analysis by polymerase chain reaction (PCR) and sequencing. Multiplex PCR to detect all of the RHD exons and use of PCR-sequence-specific primer (PCR-SSP) to detect RHD deletion (RHD*01N.01) and c.1227G>A mutation (for RHD*01EL.01) were performed. RESULTS: Multiplex PCR and PCR-SSP revealed that 3091 of 3526 D- individuals (87.7%) were homozygous for RHD*01N.01, and 318 individuals (9.0%) had the RHD*01EL.01/RHD*01N.01 or RHD*01EL.01/RHD*01EL.01 genotype. The other 103 in the 3526 individuals (2.9%) had the known D-CE-D hybrid allele, RHD*01N.04, and the association of RHCE*Ce with RHD*01EL.01 as well as RHD*01N.04 was observed. The remaining 14 individuals had RHD*01N.01 hemizygous with one of the following alleles: RHD*01N.06 (3), RHD*01N.07 (1), RHD*04N.01 (1), RHD*DEL8 (1), RHD with c.761C>G (p.Ser254Ter) (2), RHD with c.1252T>A (p.Ter418Lysex26) (2) and apparently common RHD (4). Adsorption and elution tests with anti-D revealed that the individuals with c.761C>G mutation were D- while the individuals with c.1252T>A mutation were DEL. CONCLUSIONS: The RHD genotype of more than 96% of D- Japanese could be determined by conventional PCR-SSP. In addition, we identified a novel DEL allele having c.1252T>A mutation and a novel RHD silencing allele having c.761C>G nonsense mutation.

A novel DO null allele with a c.268C>T (p.Gln90Stop) mutation in Japanese.

The Dombrock blood group system consists of two antithetical antigens, Do(a) (DO1) and Do(b) (DO2), and seven high-prevalence antigens, Gy(a) (DO3), Hy (DO4), Jo(a) (DO5), DOYA (DO6), DOMR (DO7), DOLG (DO8) and DOLC (DO9). Do(a) /Do(b) polymorphism is associated with c.793A>G (p.Asn265Asp) in exon 2 of the DO (ART4) gene, and the corresponding alleles are named DO*01 and DO*02. The rare Donull or Gy(a-) phenotype lacks all Dombrock antigens, and the DO null alleles vary with both DO*01 and DO*02 backgrounds. We report a novel DO null allele, which has a c.268C>T (p.Gln90Stop) nonsense mutation with a DO*02 background identified from four unrelated Gy(a-) Japanese individuals.