Cardiac surgery using cardiopulmonary bypass in a patient with sickle-cell trait

The sickle-cell gene is most concentrated in West Central Africa, the northeast corner of Saudi Arabia and East Central India. Sickle cell trait is the heterozygous condition for Hb S gene. Thirty to fifty per cent of their hemoglobin is Hb S and the remainder is Hb A. The sickle-cell crisis is induced by hypoxia, hypercarbia, acidosis, low flow condition, and hypothermia, which leads to vasoocclusion. A 39-year-old black man from Burkina Faso located in West Africa with left ventricular rupture was admitted for operation using cardiopulmonary bypass (CPB). He had been diagnosed as sickle-cell trait. The Hb S concentration was 36.2 per cent before operation with hemoglobin electrophoresis. During CPB, the minimum blood temperature was 31 degrees C and an aortic cross-clamp was not done. Total CPB time was 1 hour 31 minutes. Use of vasodilator and hyperventilation was effective. No neurological sequelae were observed.     

Testing for segregation distortion in the HLA complex

One of the long-standing issues in HLA research is whether there is segregation distortion in the HLA complex in human populations. In this paper we study some simple statistical models aimed at detecting segregation distortion. We present a statistic to test the Mendelian null hypothesis of equal transmission probabilities. To assess the possible contribution of multiple alleles to segregation distortion, we employ a specific log-linear model for transmission probabilities equivalent to the Bradley-Terry model in the literature of paired comparisons. We also provide a simple method for detecting a single allele effect, if present.     

Quenching distortion induced by ingot segregation in gear steel

The influence of ingot segregation on quenching distortion of gear steel was investigated in this paper.The results show that the shape of ingot segregation of rod steel depends on the shape of continuous casting (CC) molds,and that the distortion of gear steel with square ingot segregation is uniform,while that of gear steel with rectangular ingot segregation is anisotropic.After quenching,the outer circle of the ring sample with a large rectangular segregation area is distorted into an oval shape.No obvious element segregation has been found in the rod steel produced through the rectangular CC mold.Obvious difference in density has been detected at the cross section of rod steel.It suggests that center porosity may be the main reason for the strong impact of segregation on heat treatment distortion of gear steel.     

Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait

BACKGROUND: The sickle-cell trait protects against severe Plasmodium falciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects. MATERIALS AND METHODS: Blood was collected from asymptomatic individuals living in two different regions of Africa. The polymorphic MSP-1 and MSP-2 loci were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specific probes. Multivariate logistic regression was used to analyze allele distribution. RESULTS: In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families and had an impact on distinct individual alleles, whereas the distribution of MSP-2 alleles was marginally affected. There was no influence of other genetic traits, including the HLA Bw53 genotype, or factors such as place of residence within the village. In a cohort of Gabonese schoolchildren in which the influence of age was abrogated, a similar imbalance in the MSP-1 allelic distribution but not of MSP-2 allelic distribution by hemoglobin type was observed. CONCLUSIONS: The influence of the host's hemoglobin type on P. falciparum genotypes suggests that parasite fitness for a specific host is strain-dependent, which is consistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle-cell traits.     

Selection of T-DNA-tagged male and female gametophytic mutants by segregation distortion in Arabidopsis

As a strategy for the identification of T-DNA-tagged gametophytic mutants, we have used T-DNA insertional mutagenesis based on screening for distorted segregation ratios by antibiotic selection. Screening of approximately 1000 transgenic Arabidopsis families led to the isolation of eight lines showing reproducible segregation ratios of approximately 1:1, suggesting that these lines are putative gametophytic mutants caused by T-DNA insertion at a single locus. Genetic analysis of T-DNA transmission through reciprocal backcrosses with wild type showed severe reductions in genetic transmission of the T-DNA through the male and/or female gametes. Direct evidence for mutant phenotypes in these lines was investigated by DAPI staining of mature pollen grains and by the analysis of seed set and embryo sac morphology in cleared ovules. One line, termed limpet pollen, showed a novel pollen phenotype in that the generative cell failed to migrate inward after pollen mitosis I, such that the generative or sperm cells remained against the pollen wall. Two other lines, andarta and tistrya, were defective in female transmission and showed an early arrest of embryo sac development with the viable megaspore not initiating the nuclear division cycles. These data demonstrate the efficacy of a segregation ratio distortion strategy for the identification of T-DNA-tagged gametophytic mutants in Arabidopsis.     

The sex-ratio trait in Drosophila simulans: genetic analysis of distortion and suppression

The sex-ratio trait described in several Drosophila species is a type of naturally occurring X-linked meiotic drive that causes males bearing a sex-ratio X chromosome to produce progenies with a large excess of females. We have previously reported the occurrence of sex-ratio X chromosomes in Drosophila simulans. In this species, because of the co-occurrence of drive suppressors, the natural populations and the derived laboratory strains show an equal sex-ratio even when sex-ratio X chromosomes are present at a high frequency. The presence of sex-ratio X chromosomes is established via crosses with a standard strain that is devoid of drive suppressors. In this article, we show first that the sex-ratio trait in D. simulans results from the action of several X-linked loci. Second we describe drive suppressors on each major autosome as well as on the Y chromosome. The Y-linked factors suppress the drive partially whereas the autosomal suppression can be complete.     

Microstructural effects on distortion and solid-liquid segregation during liquid phase sintering under microgravity conditions

Tungsten heavy alloys with compositions ranging from 78 to 98 wt pct tungsten were liquid phase sintered at 1507 °C under microgravity conditions for 120 minutes. The sintered microstructures were quantitatively measured for solid volume fraction, grain size, connectivity, and contiguity. Links between these microstructural parameters were analyzed and compared to previously derived empirical equations. The macrostructures of the samples were also quantified and correlated to the underlying microstructures. Critical values of solid volume fraction, contiguity, and connectivity required for free-standing structural rigidity were defined for various degrees of bond rigidity as represented by the dihedral angle. The results are used to predict the degree of solid-liquid segregation due to density differences between the solid and the liquid.     

Dynamic balance of segregation distortion and selection maintains normal allele sizes at the myotonic dystrophy locus

Myotonic dystrophy (DM), an autosomal dominant neurological disorder, is caused by CTG-repeat expansions at the DMPK locus, with affected individuals having > or = 50 repeats of this trinucleotide. Reduced reproductive fitness of affected individuals and decreased viability of congenital DM have been noted. Expanded CTG-repeat alleles are highly unstable, predominantly yielding even higher repeat sizes. Preferential transmission of longer alleles from heterozygous mothers within the normal size range of alleles also is observed. In view of these observations, it is worth examining how DM has been maintained in human populations for hundreds of generations. We present an analysis of the dynamic properties of a model of joint effects of segregation distortion and selection (intensity of which increases with allele sizes of an individual's genotype). Our mathematical formulation and numerical analyses demonstrate that a weak segregation distortion during female meiosis, together with selection of comparable intensity (within the normal allele size range), can maintain an equilibrium distribution of allele frequencies. Genetic drift, acting in conjunction with the occasional contraction of alleles by mutation, can contribute to the balance of segregation distortion and mutation, in the sense that even weaker selection can explain the observed allele frequencies. The model is applied to CTG-repeat size distributions at the DMPK locus, observed in normal individuals from world populations.     

Pain from sickle-cell crisis

A qualitative questionnaire survey was carried out to identify the perceptions and expectations of pain management of patients with sickle-cell disease, and of nurses. The study illustrates that the present sample of nurses contributed to the poor pain control of sickle-cell patients because of their misconceptions about narcotic addiction, inadequate formal pain assessment and their neglect of attention to the psychosocial implications of this chronic disease.     

Cyanate-induced cataracts in patients with sickle-cell hemoglobinopathies

Two young patients developed bilateral posterior subcapsular cataracts while receiving oral sodium cyanate for treatment of sickle cell hemoglobinopathy. In one of the patients, lens opacities regressed spontaneously after cyanate therapy was discontinued.     

Acupuncture and blood studies in sickle-cell anemia

The effect of testosterone on the activity of ornithine decarboxylase (ODC), its protein level and immunocytochemical distribution were examined in the mouse kidney. Male BALB C mice at 8 weeks of age were used throughout. Fourteen hours before death, they received a subcutaneous injection of testosterone (1 mg/animal) or solvent to measure renal ODC activity or to detect the distribution of ODC immunoreactivity in the kidney. Renal ODC activity and the content of the enzyme were markedly increased after testosterone treatment. Histologically, few cells that were obviously immunoreactive to ODC were observed in the control animals and in the testosterone-treated animals a marked increase in ODC immunoreactivity was observed only in the cortex. ODC immunoreactive cells were located diffusely in the proximal tubule. In the pars recta, cells were stained weakly and homogeneously, while in the pars convoluta, the luminal surface of the cells showed stronger immunoreactivity. Moreover, many granule-like particles that were strongly ODC immunoreactive were observed inside the lumen of the pars convoluta. These results show that testosterone treatment induces an increase in ODC content in certain cells located in the proximal tubule of the cortex.     

FRAXA and FRAXE: evidence against segregation distortion and for an effect of intermediate alleles on learning disability

There have been several claims of segregation distortion (meiotic drive) for loci associated with diseases caused by trinucleotide repeats, leading us to test for this phenomenon in a large study of the X-linked loci FRAXA and FRAXE. We found no evidence of meiotic drive in females and no convincing evidence in males, where the limitation of risk to daughters creates a testing bias for alleles of interest. Alleles for pre- and full mutation, intermediate alleles, and common alleles were analyzed separately, with the same negative results that are extended in the discussion to claims of meiotic drive for other diseases. On the other hand, an excess risk of learning difficulties was confirmed for intermediate FRAXA alleles (relative risk, 2.58 +/- .74) and suggested for intermediate FRAXE alleles. The penetrance of learning difficulty is low, the risk being estimated as .039 for FRAXA common alleles and .101 for intermediate alleles. Because of their lower gene frequency, full mutations are a less frequent cause of learning difficulty than intermediate alleles, which contribute .0020 to total prevalence and .0012 to attributable prevalence of learning difficulty.     

The intergranular segregation of boron in Ni3Al: Equilibrium segregation and segregation kinetics

The grain boundary B content of high-purity Ni-24 at.% Al alloys containing 0.048, 0.144, 0.240 and 0.480 at.% B (100, 300, 500, 1000 ppm mass) has been determined for samples aged from 1323 to 873 K for sufficient times to attain equilibrium. The B content was derived from Auger electron spectra of the intergranular fracture facets. Many facets were exposed during fracture at ≈ 300 K, and additional facets were formed upon fracturing following hydrogen charging after heat treatment. For each alloy sample, about 25 facets were analyzed. The grain boundary B contents were in the range of 0.5–2.5 at.%. The grain boundary B content increased with decreasing temperature and with increasing bulk B content in the alloys. The energy of binding of a B atom to the grain boundary was calculated using McLean's segregation theory and assuming a unique binding energy for each alloy. The values were in the range of 0.15–0.45 eV/atom, and increased with increasing temperature and with decreasing bulk B content. These results have been rationalized in terms of a spectrum of binding energies for a given alloy. However, when the entropy of adsorption was taken into account, an enthalpy of adsorption of B to the grain boundary of 0.13 eV/atom was obtained, independent of temperatire and bulk B content. This is interpreted to mean that the spectrum of binding energies is quite restricted. The grain boundary B content of these alloys has also been measured as a function of annealing time at 773, 873, 973 and 1173 K. The diffusion coefficient of B in Ni₃Al at 773 K is about 5 × 10⁻²¹ m²/s, and the equilibrium grain boundary B content is attained at about 3000 s. The diffusion coefficient at 973 K is between 10⁻¹⁶ and 10⁻¹⁷ m²/s. The activation energy for diffusion of B in Ni₃Al is between 200,000 and 300,000 J/mol.     

Diagnosis of sickle-cell disease by DNA analysis in Nigeria

OBJECTIVE: To compare genotyping of leucocyte DNA by PCR and Dde I with the conventional genotyping of haemoglobin of the same subject. DESIGN: Comparative study. SUBJECTS: 25 adults, 16 males and nine females. MAIN OUTCOME MEASURES: Predictability. RESULTS: In all cases the results were comparable. CONCLUSIONS: The technology can be applied locally to prenatal diagnosis of sickle-cell disease by chorionic sampling and, therefore, improve the management of sickle-cell disease in Nigeria.     

Free energy simulations of axial contacts in sickle-cell hemoglobin

Molecular dynamics simulations have been used to investigate the thermodynamic stability of axial contacts in sickle-cell hemoglobin (HbS). Free energy changes were evaluated for the point mutation beta 121 Glu --> Gln in the axial contact region of HbS crystals. The calculations predict a free energy change of-3.6 kcal/mol per contact for the mutation, which is in qualitative agreement with experimental observations of aggravated sickling found in the double mutant Hb D Los Angeles (beta 6 Glu --> Val. beta 121 Glu --> Gln) relative to HbS (beta 6 Glu --> Val). The beta 121 Glu is sequestered in a salt link with beta 17 Lys located on the same polypeptide chain, making the Glu interactions with its surroundings similar in aggregates and individual hemoglobins. Due to this cancellation of the large electrostatic Glu contributions, the weak nonspecific interactions between the Gln and the neighboring polypeptide chain are the main contributing factor to the enhanced aggregation of Hb D Los Angeles relative to HbS. Together with the previous study of the lateral contact [K. Kuczera et al. (1990) Proceedings of the National Academy of Science USA, Vol. 87, pp, 8481-8485], the present results provide a more complete picture of the forces driving the sickling aggregation. A comparison of different treatments of internal flexibility in free energy simulations and analysis of rate of convergence of the different calculated properties has also been performed.     

Inverse segregation

Inverse, segregation at the chill face and the region adjacent to the chill face has been calculated for the AlCu,AlZn, and SbBi alloys using a finite difference analysis. In the calculations the effect of changes in composition and temperature, as well as the volume change on freezing, were considered during the solidification process. The calculations agree in general with the reported values of chill face segregation in the AlCu and SbBi alloys. They differ appreciably in the 40 pet composition region of the AlZn alloy, where a depression in the chill face segregation/composition curve is obtained instead of a peak. In the region adjacent to the chill face, the inverse segregation is found to drop rapidly with distance from the face, the rate decreasing with increasing solute concentration. The presence of an air gap between the solidifying metal and the chill can markedly influence the chill face and adjacent segregation. The air gap size in turn is dependent on the pouring temperature of the melt and the chill material. In one case the calculated air gap size was 3 Μm.