Two new sickle cell syndromes: HbS, Hb Camden, and alpha-thalassemia; and HbS in combination with Hb Tacoma

Hemoglobin variants having electrophoretic mobility more rapid than that of HbA were identified in combination with sickle hemoglobin in two patients at the Cook County Hospital. Neither individual had symptomatic hematologic disease. In one patient, the rapidly migrating hemoglobin had the amino acid substitution characteristic of Hb Tacoma (beta-40 arg leads to ser), a mildly unstable variant. In the other patient, Hb Camden (beta-131 gln leads to glu) was identified, and the hematologic findings also indicated that he has alpha-thalassemia trait. In the patient with HbS-Camden--alpha-thalassemia, globin synthesis was unbalanced (alpha/beta 0.66), and HbS represented only 19.5% of the total hemoglobin. The latter finding suggests that under conditions of limited alpha-chain availability beta Camden may combine with alpha subunits at least as efficiently as does betaA. HbS represented 56% of the hemoglobin of the patient with HbS Tacoma, although the rate of synthesis of beta Tacoma by her reticulocytes was consistently greater than that of betaS. A time-course synthesis study demonstrated a progressive increase in the specific activity of beta Tacoma in relation to that of betaS, suggesting that the unstable beta- chains of Hb Tacoma underwent selective intracellular degradation. This process appears to explain the disparity between the rates of synthesis of the two beta chains and the relative representation of HbS and Hb Tacoma in the patient's erythrocytes.     

Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenic Escherichia coli as a prophylactic against diarrhea

ABSTRACT

Background

. Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A.     

Growth in Children with Steroid Sensitive Nephrotic Syndrome

Background

Nephrotic syndrome in children usually has an onset between 2-8 years of age and steroids form the mainstay of management. Therapy may affect growth in children with relapsing nephrotic syndrome. This study was carried out to correlate growth with the cumulative dose of steroids in children with steroid sensitive nephrotic syndrome (SSNS).

Methods

Data of 35 children with SSNS was analysed retrospectively. They were divided into two groups. Group I received prednisolone only and Group II received levamisole and or cyclophosphamide in addition to steroids. Their heights were recorded at the time of inclusion and again one year later. The SD scores for age were determined. Growth rate as a change in the SD score over one year (Δ SD score) was correlated to the cumulative dose of steroids over the same period using the Pearson''s correlation. Result: There were 24 (68.6 %) boys and 11 (31.4 %) girls (M:F ratio 2.18:1) in the age group of 17 months to 11 years at inclusion. Group I constituted 19 (54.2 %) and Group II, 16 (45.8 %). Pearson''s correlation coefficients for all children, Groups I and II were -0.341, -0.441 and -0.255 respectively indicating “Fair correlation”. This indicates that as the cumulative dose of steroid increases the growth retardation becomes more apparent.

Conclusion

Growth retardation is proportional to the cumulative dose of steroids in children with SSNS.Key Words: Steroids, Cumulative dose, Nephrotic syndrome, Growth     

Delayed expression of the NFH subunit in differentiating P19 cells.

Pluripotent embryonal carcinoma (P19) cells differentiate into a neural phenotype in response to retinoic acid (RA). Expression of the low and medium molecular weight neurofilament subunits, but not the high molecular weight subunit (NFH), has been reported following RA treatment. In this study NFH expression was detected by Western blotting and immunofluorescence microscopy, but lagged behind the expression of the other subunits in a manner similar to that reported during in vivo neuronal development.     

Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects

Spontaneous mutation rates at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were measured in human cancer cell lines defective in the mismatch repair (MMR) genes hMLH1, hPMS2, or GTBP, as well as in a cell line carrying mutations in both hMLH1 and hPMS2. The mutation rate was determined by quantitating mutant frequency increases within a single culture as a function of cell division. These MMR- deficient cell lines exhibited a 50- to 750-fold increase in mutation rate relative to a MMR-proficient cancer cell line. From lowest to highest, the spontaneous mutation rates relative to the MMR-gene defects studied here are as follows: hMLH1- < GTBP- < hPMS2- < hMLH1- / hPMS2-. In addition, a cell line in which MMR was restored by chromosome transfer exhibited a mutation rate 12-fold below the MMR- deficient parental cell line. These data support the notion that MMR plays an important role in controlling the rate of spontaneous mutation and suggest that different MMR-gene defects may vary in their ability to repair different types of DNA mismatches, thus leading to measurable quantitative differences in spontaneous mutagenesis. Furthermore, a difference in mutation rates was observed between a hPMS2-defective cell line (3.1 x 10(-5) mutations/cell/generation) and two hMLH1- defective cell lines (4.0 x 10(-6) and 7.3 x 10(-6) mutations/cell/generation). Assuming the hPMS2- and hMLH1-gene products only function in the proposed hMutL alpha heterodimer, then defects in either gene should yield comparable mutation rates. These data suggest that hPMS2 plays a critical role in MMR, while additional hMLH1 homologues or hPMS2 alone may function to partially complement defects in hMLH1.      

B细胞能够部分自主控制命运

最近,澳大利亚和爱尔兰科学家在B细胞研究中证实B细胞可在某种程度上控制自己的命运.这一发现在很大程度上会改变科学家们对于细胞命运决定因素的理解.在淋巴结中增殖的B细胞面临着多种命运的抉择：常见的包括细胞死亡、细胞分裂、成为能够分泌抗体的细胞或是改变它们产生的抗体.过去科学界普遍认可的观点是B细胞的命运取决于例如特定激素或细胞信号分子等外部信号.而新研究发现B细胞的命运在很大程度上是由内部的程序所决定.他们开发了新型技术与图像分析方法,通过重建B细胞分化形成不同细胞类型所需的条件,对B细胞进行了追踪成像观测.结果 表明不同的细胞命运是细胞内竞争的结果.即使这些细胞获得相同的外部信号,细胞群体中发生的事件仍会出现相当大的差异.这表明激素或细胞信号分子等外部因素并非是B细胞命运的主宰因子,它们只不过能改变细胞命运选择的概率.