Heterozygote advantage in Tay-Sachs carriers?

Chi-square analyses of new data as well as data previously reported by Myrianthopoulos have shown that grandparents of Tay-Sachs carriers die from proportionally the same causes as grandparents of noncarriers. It is unlikely that there is any advantage to being a Tay-Sachs carrier insofar as resistance to tuberculosis is concerned. Our results are further evidence to support Fraikor's claim that the high carrier frequency of the allele in Ashkenazi Jews is probably caused by a combination of founder effect, genetic drift, and differential immigration patterns.     

The β2 subunit of human placenta hexosaminidase (Hex) A and B is a non-random association of the two polypeptides αa and βb

The subunit structures of placental Hex A and B have previously been assigned as _a and _b, respectively. The ₂ subunit is composed of two non-identical polypeptide chains, _a and _b. Purified Hex A and B were fractionated on a chromatofocusing column, and the fractions were reduced and then alkylated with iodo-I-¹⁴C-acetamide. The polypeptide chains were separated by polyacrylamide-gel isoelectric focusing. From the radioactivity measurements of the polypeptides a constant value for ₂ was obtained in all the chromatofocusing fractions, demonstrating a non-random structure of (₂) in each ₂ subunit.     

Lectin-mediated uptake of lysosomal hydrolases by genetically deficient human fibroblasts.

A protein factor named S-II that stimulates RNA polymerase II was previously purified from Ehrlich ascites tumor cells [1]. In this work using an antibody prepared against purified S-II, the localization of S-II in the cell was investigated by an indirect immunofluorescence technique. In 3T3 cells, specific immunofluorescence was detected only in the nucleoplasm where RNA polymerase II is located, and not in the nucleoli where RNA polymerase I is present. In Ehrlich ascites tumor cells fluorescence was detected mainly in the nucleoplasm, although some fluorescence was also detectable in the cytoplasm, possibly due to leak of S-II from the nuclei during preparation of the immunofluorescent samples. In metaphase cells fluorescent was not found on chromosomes but throughout the cytoplasm. These findings suggest that S-II is a nuclear protein and that it spreads into the cytoplasm without being attached to chromosomes in metaphase, but is reassembled into the nucleoplasm in the interphase. Specific immunofluorescence was also detected in the nuclei of HeLa cells and salivary glands cells of flesh-fly larvae, suggesting that the nucleoplasm of these heterologous cells contains proteins immunologically cross-reactive with the antibody against S-II.     

Antenatal diagnosis of sphingolipid and mucopolysaccharide storage diseases.

In 4 years of 24 fetuses at risk for various sphingolipid and mucopolysaccharide storage diseases were examined. Amniocentesis at 16 weeks'' gestation was followed in most cases by culture of amniotic fluid cells and measurement in the cells of the activity of the enzyme suspected to be deficient. Six fetuses were affected; five were examined morphologically and biochemically after abortion. Two fetuses had Tay-Sachs disease, two had GM1 gangliosidosis and one had Hurler''s syndrome. Although in each affected detus the specific enzyme activity was absent, we found in the placenta 5 to 50% of the normal activity.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Recovery after Shift Work: Relation to Coronary Risk Factors in Women

Shift work increases the risk for developing cardiovascular disease. There is, however, little knowledge of what aspects of shift scheduling that are detrimental and what characteristics promote good health. The aim of the present study was to evaluate whether coronary risk factors deteriorate after a hard work period and whether recovery, in the form of a week off, was sufficient to improve them. A total of 19 women worked an extremely rapidly rotating and clockwise shift schedule at a paper and pulp factory. They underwent two health examinations, one at the end of the work period and one after the week off. In addition, the women were divided into a tolerant and a vulnerable group, depending on their satisfaction with their work hours. Most risk factors did not change, but total cholesterol and low‐density lipoprotein (LDL)‐cholesterol were lower after the working period than after the week‐off. In addition, vulnerable women had higher levels of total cholesterol and a higher ratio of total cholesterol/high‐density lipoprotein (HDL) than tolerant ones. In conclusion, the finding that a week‐off worsens cholesterol levels was against our hypothesis and suggests further studies on how activities/responsibilities outside the workplace affect shift‐working women. It was also shown that susceptible shift workers had worse lipid profiles.     

Reduction of product-related species during the fermentation and purification of a recombinant IL-1 receptor antagonist at the laboratory and pilot scale

Through a parallel approach of tracking product quality through fermentation and purification development, a robust process was designed to reduce the levels of product-related species. Three biochemically similar product-related species were identified as byproducts of host-cell enzymatic activity. To modulate intracellular proteolytic activity, key fermentation parameters (temperature, pH, trace metals, EDTA levels, and carbon source) were evaluated through bioreactor optimization, while balancing negative effects on growth, productivity, and oxygen demand. The purification process was based on three non-affinity steps and resolved product-related species by exploiting small charge differences. Using statistical design of experiments for elution conditions, a high-resolution cation exchange capture column was optimized for resolution and recovery. Further reduction of product-related species was achieved by evaluating a matrix of conditions for a ceramic hydroxyapatite column. The optimized fermentation process was transferred from the 2-L laboratory scale to the 100-L pilot scale and the purification process was scaled accordingly to process the fermentation harvest. The laboratory- and pilot-scale processes resulted in similar process recoveries of 60 and 65%, respectively, and in a product that was of equal quality and purity to that of small-scale development preparations. The parallel approach for up- and downstream development was paramount in achieving a robust and scalable clinical process.