Extensive Ex Vivo Expansion of Functional Human Erythroid Precursors Established From Umbilical Cord Blood Cells by Defined Factors

There is a constant shortage of red blood cells (RBCs) from sufficiently matched donors for patients who need chronic transfusion. Ex vivo expansion and maturation of human erythroid precursors (erythroblasts) from the patients or optimally matched donors could represent a potential solution. Proliferating erythroblasts can be expanded from umbilical cord blood mononuclear cells (CB MNCs) ex vivo for 10⁶–10⁷-fold (in ~50 days) before proliferation arrest and reaching sufficient number for broad application. Here, we report that ectopic expression of three genetic factors (Sox2, c-Myc, and an shRNA against TP53 gene) associated with iPSC derivation enables CB-derived erythroblasts to undergo extended expansion (~10⁶⁸-fold in ~12 months) in a serum-free culture condition without change of cell identity or function. These expanding erythroblasts maintain immature erythroblast phenotypes and morphology, a normal diploid karyotype and dependence on a specific combination of growth factors for proliferation throughout expansion period. When being switched to a terminal differentiation condition, these immortalized erythroblasts gradually exit cell cycle, decrease cell size, accumulate hemoglobin, condense nuclei and eventually give rise to enucleated hemoglobin-containing erythrocytes that can bind and release oxygen. Our result may ultimately lead to an alternative approach to generate unlimited numbers of RBCs for personalized transfusion medicine.     

Bone mineral density enhances use of clinical risk factors in predicting ten-year risk of osteoporotic fractures in Chinese men: the Hong Kong Osteoporosis Study

Summary  

This prospective study aimed to determine the risk factors and the 10-year probability of osteoporotic fracture in Southern Chinese men. The findings show substantial population differences in fracture incidence and risk prediction compared to the FRAX^TM model, and the addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men.     

Family needs and burdens of mentally ill offenders

A growing number of research projects have been devoted to the study of needs, burdens and intervention programmes of families of psychiatric patients due to the emphasis on deinstitutionalization and community integration. Although it is noted that burdens for families when looking after a patient with a criminal history are even heavier and more complicated, studies on identifying family needs and burdens for mentally ill offenders have been very limited. This paper reviews literature on family burdens and studies on family needs for psychiatric patients with a forensic history. Methodological problems of available studies are discussed. In addition, a theoretical model that can be used as a conceptual guide for the study of burdens of families of mentally ill offenders is postulated. Directions for further research are discussed.     

Combined use of fasting plasma glucose and HbA1c predicts the progression to diabetes in Chinese subjects

OBJECTIVE: We have previously suggested using the paired values of fasting plasma glucose (FPG) and HbA1c to identify potential diabetic subjects. In this article, we followed up on 208 nondiabetic subjects and examined their rates of progression to diabetes. We analyzed their likelihood of becoming diabetic according to their baseline FPG and HbA1c concentrations. RESEARCH DESIGN AND METHODS: Between 1988 and 1995, 2,877 Chinese subjects with risk factors for diabetes underwent screening. Of these, 2,250 had FPG <7.8 mmol/l and 2-h plasma glucose (PG) <11.1 mmol/l. Of these 2,250 subjects, 265 were randomly recruited for an annual oral glucose tolerance test (OGTT) until they progressed to develop diabetes. Of those 265 subjects, 57 had baseline FPG > or =7.0 mmol/l and were excluded from the present analysis. Hence, the progression of glucose tolerance in 208 subjects who were nondiabetic according to the new American Diabetes Association diagnostic criteria (FPG < 7.0 mmol/l and 2-h PG < 11.1 mmol/l) was examined RESULTS: Of the 208 nondiabetic subjects, 26 (12.5%) were men and 182 (87.5%) were women. After a mean follow-up of 1.60 +/- 1.16 years (range 1-7, median 1), 44 (21.2%) progressed to develop diabetes and 164 (78.8%) remained nondiabetic. Those who were diabetic at the end of the study had a high likelihood ratio (LR) of 9.3 to have baseline FPG > or =6.1 mmol/l and baseline HbA1c > or =6.1%. This was compared with a low LR of 0.6-1.1 in diabetic subjects who had either FPG <6.1 mmol/l or HbA1c <6.1% or both at baseline. The crude rate of progression to diabetes was more than five times higher (44.1 vs. 8.1%) in those whose baseline FPG was > or =6.1 mmol/l and baseline HbA1c was > or =6.1% compared with those whose baseline FPG was <6.1 mmol/l and baseline HbA1c was <6.1%. CONCLUSIONS: For Chinese subjects with risk factors for glucose intolerance, the use of paired FPG and HbA1c values helped to identify potential diabetic subjects. Those with an FPG > or =6.1 mmol/l and HbA1c > or =6.1% had a rate of progression to diabetes more than five times higher than those with an FPG <6.1 mmol/l and an HbA1c <6.1% after a mean follow-up of 1.6 years. Those with an FPG > or =6.1 but <7.0 mmol/l, especially if their HbA1c was > or =6.1%, should undergo an OGTT to confirm diabetes. Subjects with an FPG <6.1 mmol/l and/or an HbA1c <6.1% should have regular screening using the paired values of FPG and HbA1c.     

Phenotypic and functional correlations in circulating lymphocytes of prodromal homosexuals and patients with AIDS

Findings of selected phenotypic and functional parameters demonstrated significant aberrations in both prodromal homosexual males and patients with AIDS. An impaired blastogenic response to T-cell dependent B-cell mitogen was associated with a significant decrease in percentage of helper T cells but appeared unrelated to the percentage of suppressor T cells. The functional subsets of the latter were further defined by a panel of monoclonal antibodies (Leu8, Leu15, and HLA-DR) applying dual color flow cytometric techniques. In both homosexuals at risk and in AIDS patients, activated suppressor cells with the phenotype Leu2+Leu15+ and Leu2+HLA-DR+ were elevated while the reciprocal cytotoxic Ts cells (Leu2+Leu15- and Leu2+HLA-DR-) were depressed. Both subsets of suppressor precursor cells and effector cells (Leu2+Leu8+ and Leu2+Leu8-) were elevated particularly in high risk homosexual males. These results suggest a defective feedback loop that regulate both helper and suppressor T cells as well as B-lymphocyte functions and may explain the clinical manifestation of AIDS.     

Activities of various quinolone antibiotics against Mycobacterium leprae in infected mice.

Previously, pefloxacin and ofloxacin were found to be active against Mycobacterium leprae in vitro, in experimental animals, and in clinical trials of lepromatous leprosy patients. In this study, we compared certain more recently developed fluoroquinolones (lomefloxacin, PD 124816, WIN 57273, temafloxacin, and sparfloxacin) with pefloxacin and ofloxacin in M. leprae-infected mice at doses of 50, 150, and 300 mg/kg given five times weekly. All seven of the fluoroquinolones studies were active against M. leprae; temafloxacin and sparfloxacin were the most active, being fully bactericidal at all three dosage schedules. Additionally, sparfloxacin was found to be fully bactericidal at 15 and 30 mg/kg given five times weekly.