ABSTRACT
Cell death in B cell terminal differentiation rapidly follows cell cycle arrest in IL-6 differentiation of EBV-immortalized, IgG-bearing human lymphoblastoid cells in vitro. G1 arrest is now found to coincide with repression of EBNA2 and LMP1, two EBV genes essential for B cell transformation, without activation of the viral lytic cycle. IL-6-differentiated B cells die by apoptosis, as evidenced by increases in Annexin V binding activity, PARP cleavage, and chromatin disorganization. Expression of Mcl-1, a Bcl-2 family member, was specifically induced during IL-6 differentiation and down-regulated during apoptosis. Thus, IL-6 reverses EBV immortalization and activates the terminal differentiation program in IgG-bearing human B lymphoblastoid cells, including regulation of an anti-apoptotic gene to coordinate differentiation, cell cycle arrest, and cell death.
Subject(s)
Apoptosis , B-Lymphocytes/cytology , Cell Transformation, Viral/drug effects , Gene Expression Regulation, Viral/drug effects , Herpesvirus 4, Human/genetics , Interleukin-6/pharmacology , Proto-Oncogene Proteins c-bcl-2 , Animals , Apoptosis/drug effects , B-Lymphocytes/virology , Callithrix , Cell Differentiation/drug effects , Cells, Cultured , Epstein-Barr Virus Nuclear Antigens/genetics , G1 Phase , Humans , Myeloid Cell Leukemia Sequence 1 Protein , Neoplasm Proteins/genetics , Plasma Cells/cytology , Viral Matrix Proteins/metabolismABSTRACT
Patients have infrequently been assessed about their desire for their family physician to possess a certain level of expertise in managing a wide range of behavioral science problems. This has led to inconsistencies in the type of behavioral science training offered to family physicians and thence to a marked discrepancy between the amount of training offered (relatively large) and the amount of mental health care provided (relatively small). This study reports the result of a study of patient attitudes concerning the level of involvement by their family physician for each of 45 psychosocial problems. The levels offered were (1) no help, (2) referral, (3) compassion, concern, and minor advice, and (4) expert therapeutic help. The mean responses place a majority (25 of the 45) of the problems in level 3. Certain obvious problems appeared in level 1 (religious/church problems) and level 4 (pregnancy). Child behavioral problems dominated in level 2. Certain surprises were also found, such as the presence of problems of marital discord in level 1, and the problem of long-term pain in level 4.
