Hydrodynamic characteristics of a membrane oxygenator: modeling of pressure-flow characteristics and their influence on apparent viscosity.

The viscosity obtained from pressure-flow characteristics of an oxygenator may help to detect factors that change oxygenator resistance. The objective of this study was to model pressure-flow characteristics of a membrane oxygenator with an integrated arterial filter and to quantify their influence on apparent viscosity of non-Newtonian fluids. One Newtonian fluid (glycerin solution) and two non-Newtonian fluids (whole bovine blood and a human red blood cell suspension) were perfused through an oxygenator and their pressure-flow characteristics examined systematically. Four resistance parameters for the pressure gradient characteristics approximation equation were obtained by the least squares method from the relational expression of pressure-flow characteristics and viscosity. For all three fluids, a non-linear flow to pressure change was observed with a coefficient of determination of almost 1 by exponential approximation. The glycerin solution had a higher pressure gradient (10-70%) than the other fluids; the apparent viscosity of the non-Newtonian fluids was around 35% lower than the static one measured by a torsional oscillation viscometer. Overall, our study demonstrated that the influence on the apparent viscosity of non-Newtonian fluids can be quantified by pressure gradient differences in a membrane oxygenator with an integrated arterial filter.

Evaluation of weather-based rice yield models in India.

The objective of this study was to compare two different rice simulation models--standalone (Decision Support System for Agrotechnology Transfer [DSSAT]) and web based (SImulation Model for RIce-Weather relations [SIMRIW])--with agrometeorological data and agronomic parameters for estimation of rice crop production in southern semi-arid tropics of India. Studies were carried out on the BPT5204 rice variety to evaluate two crop simulation models. Long-term experiments were conducted in a research farm of Acharya N G Ranga Agricultural University (ANGRAU), Hyderabad, India. Initially, the results were obtained using 4 years (1994-1997) of data with weather parameters from a local weather station to evaluate DSSAT simulated results with observed values. Linear regression models used for the purpose showed a close relationship between DSSAT and observed yield. Subsequently, yield comparisons were also carried out with SIMRIW and DSSAT, and validated with actual observed values. Realizing the correlation coefficient values of SIMRIW simulation values in acceptable limits, further rice experiments in monsoon (Kharif) and post-monsoon (Rabi) agricultural seasons (2009, 2010 and 2011) were carried out with a location-specific distributed sensor network system. These proximal systems help to simulate dry weight, leaf area index and potential yield by the Java based SIMRIW on a daily/weekly/monthly/seasonal basis. These dynamic parameters are useful to the farming community for necessary decision making in a ubiquitous manner. However, SIMRIW requires fine tuning for better results/decision making.

A novel measurement and delivery system for synchronizing oxygen gas flow with blood flow during cardiopulmonary bypass.

Monitoring the blood pump and the oxygen gas flow meter are important maneuvers at the initiation of cardiopulmonary bypass (CPB). We present a novel system, designed to improve safety in the heart-lung machine by linking the control of blood flow and the oxygen gas flow meter. This system uses a mass flow controller to provide and control oxygen flow based on the ventilation-perfusion (V/Q) ratio, using the electronic signal of the blood flow. We tested the system, in vitro and in vivo, and examined the resulting level of blood oxygenation. When extracorporeal circulation was initiated, the oxygen flow was instantly linked to the circulating blood flow, providing an adequate V/Q ratio; the partial pressure of oxygen in the blood was maintained at a normal level. Although we have yet to confirm the safety of this system in clinical trials, the new safety assist device can automatically supply oxygen to the oxygenator at the beginning of CPB.

Integrated analysis of gene copy number, copy neutral LOH, and microRNA profiles in adult acute lymphoblastic leukemia.

We adopted an integrated analysis of gene copy number alterations (CNAs), copy number neutral loss of heterozygosity (CNN LOH), and microRNA (miRNA) profiling in 21 adult acute lymphoblastic leukemia (ALL) patients. This study revealed the most frequent CNAs to be at chromosomes 9p, 7, and 17 and recurrent CNN LOH at 5p, 9p, and Xq. As for the most differentially expressed miRNAs, they included 8 upregulated and 14 downregulated miRNAs, of which miR-148a at 7p15.2, miR-22 at 17p13.3, miR-223 at Xq12, as well as miR-101-2 at 9p24.1 exhibited recurrent CNAs or CNN LOH. miR-101-2 was recurrently downregulated, and although the related CNN LOH was detected only in BCR-ABL1 negative cases (2/14), deletions of miR-101-2 were observed solely in BCR-ABL1 positive cases (4/7). Finally, BCR-ABL1 positive cases, in contrast to negative ones, were characterized by slightly, but still significantly, higher expression levels of miR-29b.

The impulsive horse: Comparing genetic, physiological and behavioral indicators to those of human addiction.

Stress and genotype elicit changes in impulse control in a range of species that are attributable to adaptations in both the central and peripheral nervous system. We examined aspects of this mechanism in the horse by assessing the effect of a dopamine receptor genotype (DRD4) and central dopaminergic tone (measured via spontaneous blink rate [SBR] and behavioral initiation rate [BIR]), on measures of impulsivity, compulsivity (3-choice serial reaction time task) and sympathetic/ parasympathetic system balance (heart rate variability [HRV]). Genotype did not have a significant effect on any of the parameters measured. SBR but not BIR correlated significantly with levels of impulsivity. There was no clear association of HRV parameters with either measures of central dopaminergic activity or impulsivity/compulsivity. Overall, some elements of the data suggest that the horse may be a useful animal model for assessing the genetic and environmental factors that lead to the physiological and behavioral phenotype of human addiction, particularly when considering the relationship between central dopaminergic tone and impulsivity.

Organic depth profiling of a nanostructured delta layer reference material using large argon cluster ions.

Cluster ion beams have revolutionized the analysis of organic surfaces in time-of-flight secondary ion mass spectrometry and opened up new capabilities for organic depth profiling. Much effort has been devoted to understanding the capabilities and improving the performance of SF(5)(+) and C(60)(n+), which are successful for many, but not all, organic materials. Here, we explore the potential of organic depth profiling using novel argon cluster ions, Ar(500)(+) to Ar(1000)(+). We present results for an organic delta layer reference sample, consisting of ultrathin "delta" layers of Irganox 3114 (approximately 2.4 nm) embedded between thick layers of Irganox 1010 (approximately 46 or 91 nm). This indicates that, for the reference material, major benefits can be obtained with Ar cluster ions, including a constant high sputtering yield throughout a depth of approximately 390 nm, and an extremely low sputter-induced roughness of <5 nm. Although the depth resolution is currently limited by an instrumental artifact, and may not be the best attainable, these initial results strongly indicate the potential to achieve high depth resolution and suggest that Ar cluster ions may have a major role to play in the depth profiling of organic materials.

Super-atmospheric pressure ionization mass spectrometry and its application to ultrafast online protein digestion analysis.

Pressure is a key parameter for an ionization source. In this Special Feature article, Lee Chuin Chen and colleagues review super-atmospheric pressure ionization MS with electrospray, corona-discharge-based chemical ionization, and field desorption. They routinely run their mass spectrometer with ion source pressures ranging from several to several tens of atmospheres. A number of strategies have been used to preserve the high vacuum of the instrument while working with a high-pressure (HP) ion source. A recent prototype uses a booster pump with variable pumping speed added to the first pumping stage of the mass spectrometer to regulate a constant vacuum pressure. Further, a new HP-ESI source allowing rapid (a few seconds) online protein digestion MS is also reported. Dr. Lee Chuin Chen is Associate Professor in the Department of Interdisciplinary Research at the University of Yamanashi (Yamanashi, Japan). His main research interest is the development of novel mass spectrometric methods for in-situ medical diagnosis.

An informative linkage map of soybean reveals QTLs for flowering time, leaflet morphology and regions of segregation distortion.

A genetic linkage map covering a large region of the genome with informative markers is essential for plant genome analysis, including identification of quantitative trait loci (QTLs), map-based cloning, and construction of a physical map. We constructed a soybean genetic linkage map using 190 F2 plants derived from a single cross between the soybean varieties Misuzudaizu and Moshidou Gong 503, based on restriction-fragment-length polymorphisms (RFLPs) and simple-sequence-repeat polymorphisms (SSRPs). This linkage map has 503 markers, including 189 RFLP markers derived from expressed sequence tag (EST) clones, and consists of 20 major linkage groups that may correspond to the 20 pairs of soybean chromosomes, covering 2908.7 cM of the soybean genome in the Kosambi function. Using this linkage map, we identified 4 QTLs--FT1, FT2, FT3, and FT4--for flowering time, the QTLs for the 5 largest principal components determining leaflet shape, 6 QTLs for single leaflet area, and 18 regions of segregation distortion. All 503 analyzed markers identified were located on the map, and almost all phenotypic variations in flowering time were explained by the detected QTLs. These results indicate that this map covers a large region of the soybean genome.

Characterization of specific cytochrome P450 enzymes responsible for the metabolism of diazepam in hepatic microsomes of adult male rats.

The role of several P450 enzymes in the metabolism of diazepam (DZ) has been investigated. Hepatic microsomes of adult male rats were pretreated with antisera raised against the P450s CYP3A2, 2B1, 2C6, 2C11, 2D1 and 2E1, and their influence on the subsequent metabolism of DZ was determined by simultaneously measuring the changes in the relative rates of formation of its metabolites. Several forms of P450 were found to be positively involved in DZ metabolism. Antisera of the "male-specific" P450 enzyme CYP2C11 partially inhibited both DZ N-demethylase and C3 hydroxylase activities (60%) which resulted in decreased formations of N-desmethyl-DZ (NDZ) and 3-hydroxy-DZ (3HDZ), respectively. In a reconstitution experiment with the purified enzyme, CYP2C11 predominantly catalysed the formation of NDZ from DZ. Antisera of a further male-specific P450 CYP3A2 strongly inhibited (95%) the C3 hydroxylase of DZ and thus 3HDZ formation. A corresponding reconstitution experiment with this same P450 enzyme gave 3HDZ as principal product. CYP2D1 antisera inhibited the aromatic hydroxylation of DZ (98%) and subsequent formation of 4'-hydroxy-DZ (4'HDZ). This enzyme was also observed to inhibit DZ N-demethylase activity (60%). A reconstitution experiment with pure CYP2D1 catalysed the formation of both 4'HDZ and NDZ.

Renal and skin involvement in a patient with complete Kearns-Sayre syndrome.

We report on a 13-year-old girl with complete Kearns-Sayre syndrome (KSS) and unusual manifestations of anhidrosis and de Toni-Fanconi-Debré syndrome which preceded by several years the onset of KSS triad. Histochemical examination of skeletal muscle showed focal deficiency of cytochrome c oxidase (CCO). Southern blot analysis of mitochondrial DNA (mtDNA) demonstrated a deletion of 5.4 kb in 60% of the total mtDNAs isolated from the muscle and kidney. On electron microscopy, epithelial cells of the proximal and distal renal tubules and the sweat glands showed an increased number of giant mitochondria with complicated and concentric cristae. This appears to be the first report of complete KSS associated with renal and skin involvement. Data obtained in this patient provide important information on the clinical heterogeneity and tissue specificity of CCO deficiency.

Rapid screening method to detect mutations in CYP21, the gene for 21-hydroxylase.

To facilitate a rapid and practical molecular diagnosis of 21-hydroxylase deficiency (21-OHD), we developed a polymerase chain reaction (PCR) test in which only the 21-OH gene (CYP21) is amplified. We applied the test to diagnose 23 patients with salt-wasting type of 21-OHD. The upstream and downstream sequences of CYP21 have been specifically amplified by using a primer set containing the 8-bp deletion sequence of exon 3, which is distinct from its pseudogene CYP21P. The amplified PCR products were further subjected to mutation detection by restriction analysis: E1PL by AciI, I2g by PstI, E63a by DraIII, E7VL by ApaLI, E8non by PstI, and E8RW by AciI. To detect delections and/or gene conversions occurring on exon 3, we used the method described by Rumsby and Honour [1990: J Med Genet 27:676-678]. Our method is able to elucidate 8 common CYP21 mutations by using only 3 primer pairs and 4 restriction enzymes. The overall detection ratio of abnormal haplotypes by this method was over 95%, indicating that our method is practical and useful, particularly for carrier detection.

Case of ovarian dysgenesis and dilated cardiomyopathy supports existence of Malouf syndrome.

We describe an 18-year-old girl with ovarian dysgenesis, dilated cardiomyopathy, mild mental retardation, broad nasal base, blepharoptosis, and minor skeletal abnormalities. This unusual association of manifestations was first reported by Malouf et al. [1985]. Our patient, although a sporadic case, supports the existence of Malouf syndrome.

Acampomelic campomelic syndrome and sex reversal associated with de novo t(12;17) translocation.

The association of rare chromosomal rearrangements involving a specific 17q breakpoint with campomelic syndrome (CMPS) and/or sex reversal (SR) has led to an assignment of the CMPS1/SRA1 locus to 17q24.3-->q25.1. We describe a patient with multiple anomalies and SR, who had a de novo t(12;17) translocation. The phenotype was consistent with that of CMPS except for the lack of lower limb bowing and talipes equinovarus. Chromosome painting indicated that the breakpoints appeared to have occurred at 12q21.32 and 17q24.3 or q25.1. This study suggests that acampomelic CMPD with SR represents a variant of the CMPS1/SRA1 locus disorder. We emphasize the likelihood that CMPS may be a contiguous gene syndrome.

Craniosynostosis and hemizygosity for D7S135 caused by a de novo and apparently balanced t(6;7) translocation.

Craniosynostosis (CRS) is frequently seen in the del(7p) syndrome, and the gene for this cranial anomaly (CRS1) has been assigned to 7p21. We present a 3-year-old boy with CRS involving the sagittal and coronal sutures, who had a de novo and apparently balanced translocation, t(6;7)(q16.2;p15.3). Southern blot analysis of several loci on 7p14-->pter showed that the patient was heterozygous for HOX1I and IL6, possibly homozygous for D7S149, but hemizygous for D7S135 with a loss of the paternal allele. These findings suggest the localization of a candidate gene for CRS1 to be on 7p15.3 in the close proximity to the D7S135 locus.

Maternal origin of a unique extra chromosome, der(9)(pter-->q13::q13-->q12:) in a girl with typical trisomy 9p syndrome.

We report on a girl with the typical trisomy 9p syndrome who had an additional E-sized metacentric chromosome. On the basis of GTG- and CBG-banding, her karyotype was considered to be 47,XX,+der(9)(pter-->q13::q13-->q12:) de novo. Results of a fluorescence in situ hybridization study using a chromosome 9-specific painting probe were compatible with this cytogenetic interpretation. Molecular analyses of six highly polymorphic dinucleotide repeat loci on the short arm and the proximal long arm of chromosome 9 demonstrated that the girl inherited one allele from her father and two identical or different alleles from the mother. We speculated that the extra chromosome may have resulted from either nondisjunction of chromosome 9 followed by a U-type exchange and a crossing-over between different sister chromatids during maternal meiosis I and subsequent breakage and malsegregation during meiosis II, or nondisjunction during meiosis II followed by isochromosome formation in one of the two maternal chromosomes 9 and subsequent breakage.

Reproductive risk in mating between two translocation carriers: case report and review of the literature.

We conducted a study to determine the reproductive risk in a couple who were translocation carriers. This couple, who carried balanced reciprocal translocations, experienced habitual abortions. The wife had a karyotype of 46,XX,t(7;13)(p15.3;q12.3) and the husband of 46,XY,t(1;7)(p11.1;p11.1). Chromosome study of their fourth abortus demonstrated a chimera consisting of two cell lines with a 46,XY and a 46,XX,t(1;7)(p11.1;p11.1)pat, -13, + der(7)t(7;13)(p15.3;q12.3)mat, karyotype. A review of the literature indicates that the risk of having unbalanced live offspring or of spontaneous abortion/stillborns is similar in couples in whom both were translocation carriers and in couples in whom one individual was a translocation carrier. The apparent lack of increased reproductive failure may result from the selective disadvantage of aneusomic gametes at fertilization or very early spontaneous abortions of unbalanced conceptuses.

Growth hormone deficiency and empty sella syndrome in a boy with dup(X) (q13.3----q21.2).

A 2 8/12-year-old boy with severe growth failure and mental retardation was found to have a maternally derived tandem duplication of the long arm of X chromosome, dup(X) (q13.3----q21.2). Karyotypic interpretation was further confirmed in this patient by a double gene dose for red blood cell phosphoglycerate kinase. DNA replication study showed that the duplicated X chromosome was always late replicating in peripheral blood lymphocytes as well as in skin fibroblasts from the mother. Endocrine studies in the patient demonstrated growth hormone deficiency. Magnetic resonance imaging of the head then disclosed the empty sella syndrome. This appears to be the first report of a dup(Xq) patient associated with a growth hormone deficiency and the empty sella syndrome. We emphasize that duplication of the proximal Xq in males represents another microduplication syndrome (Thode-Leonard syndrome).

Unique karyotypes in two patients with Prader-Willi syndrome.

A physical disruption of the Prader-Willi syndrome (PWS) chromosome region is thought to cause PWS. We describe 2 girls with PWS phenotype, who had unique chromosome 15 abnormalities. The first patient showed mosaicism: 45,XX,t(15;15)(qter----p11.1::q11.200----qter)/46,XX,t(15;15)(qter----p1 1.1::q 11.200----qter), +mar. The band 15q11.2 apparently remained intact in the t(15;15) chromosome, and the mar chromosome was considered as r(15) (p11.1q11.1). The second patient had a karyotype of 47,XX,del(15)(q11.200----q11.207), +idic (15)(pter----q11.1::q11.1----pter). The complex breakage and reunion involving the 15q11.2 regions of the father's homologous chromosomes 15 at meiosis appeared to have resulted in the idic(15) and the del(15) chromosomes. These cytogenetic findings suggest that the PWS chromosome region may be localized on the very proximal portion of band 15q11.2.

Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis patients.

SETTING: Transforming growth factor-beta (TGF-beta) plays an important role in many diseases, influencing as it does such processes as immune responses, fibrosing processes, and angiogenesis. Recently, polymorphisms have been described for TGF-beta that are associated with the risk of several diseases. In this study, we investigated whether TGF-beta 1 polymorphism has an effect on sarcoidosis and tuberculosis. OBJECTIVE: TGF-beta 1 Codon 10 T869C polymorphism was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and 101 tuberculosis patients. DESIGN: The TGF-beta genotype was determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS: We found no significant differences in TGF-beta genotypes between sarcoidosis patients and healthy controls or tuberculosis patients and controls. The long axis of the tuberculin skin test was larger in the CC type compared with the CT type. However, there was no association between the TGF-beta genotype and the roentgenographic stage, the disappearance of shadows, or organ involvement in sarcoidosis, nor any association between genotype, the extent or type of roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis. CONCLUSION: From the results, we believe that TGF-beta polymorphisms on the whole do not have a strong influence on disease onset or clinical progression in sarcoidosis and tuberculosis, although this polymorphism might have an effect on the immune response in a tuberculosis host.