Induction of tyrosine phosphorylation of Vav and expression of Pim-1 correlates with Jak2-mediated growth signaling from the erythropoietin receptor

The receptor for erythropoietin (Epo) belongs to the cytokine receptor family and lacks a tyrosine kinase domain. However, it has been hypothesized that a tyrosine kinase, Jak2, associates with the membrane proximal cytoplasmic region of Epo receptor (EpoR) and mediates the growth signaling from the receptor through tyrosine phosphorylation of cellular substrates. To explore the growth signaling pathways from the EpoR, we analyzed substrates of tyrosine phosphorylation induced by Epo stimulation in cells expressing various mutant EpoRs. The vav proto- oncogene product was found to be tyrosine phosphorylated after Epo stimulation in cells expressing the wild-type EpoR or a truncated receptor, H mutant, that retains the growth signaling function. In these cells, Epo also induced the expression of a serine/threonine kinase, Pim-1. However, Epo stimulation did not have any effect on Vav or Pim-1 in cells expressing a mutant EpoR, PM4 mutant, inactivated by a point mutation, Trp282 to Arg, in the membrane proximal region, which abrogates the interaction with Jak2. On the other hand, both tyrosine phosphorylation of Vav and expression of Pim-1 were observed constitutively in cells expressing a mutant EpoR that is constitutively activated by a point mutation, Arg 129 to Cys, in the extracellular domain. Jak2 was also constitutively tyrosine phosphorylated and activated in cells expressing this mutant, which confirms the crucial role of Jak2 in growth signaling from the EpoR. Taken together, these observations suggest that the tyrosine phosphorylation of Vav and the expression of Pim-1 may play important roles in growth signaling from the EpoR.     

Psychosocial well-being of patients with skin diseases in general practice

BACKGROUND: Skin diseases are a substantial part of the problems dealt with by general practitioners. Although the psychosocial consequences of skin diseases in secondary care has been extensively studied, little is known about the psychosocial well-being of patients with skin diseases in primary care. OBJECTIVE: To investigate the psychosocial well-being of patients with skin diseases in primary care. PATIENTS/METHODS: Questionnaires about the psychosocial consequences of skin diseases were sent to patients with a skin disease who were registered within a research network (continuous morbidity registration) of general practices that continuously have recorded morbidity data since 1971. Questionnaires completed by 532 patients were eventually suitable for analyses. RESULTS: Compared with the general population, patients with skin diseases reported significantly lower scores for psychosocial well-being. Furthermore, a lower psychosocial wellbeing was significantly related with higher levels of disease-severity, lower disease-related quality of life, longer disease duration, more comorbidity and more physical symptoms of itch, pain and fatigue. After demographic variables and comorbidity were controlled for, sequential regression analyses showed that disease duration, disease severity and physical symptoms (itch, pain and fatigue) were significant predictors of psychosocial well-being. CONCLUSION: The psychosocial well-being of patients with skin diseases in primary care is lower than that of the general population. Special attention has to be directed to those patients with lowered psychosocial well-being who might be at risk of developing severe psychosocial impairments such as clinical depression.     

正常人视觉运动觉的测试

目的研究我国正常人视觉运动觉特性。方法在ＰＣ兼容机上，应用运动觉测试软件，由微机控制，于ＶＧＡ显示器产生棒状垂直视标，测定年龄１１～６８岁正常人５６例（１１２只眼）的视觉运动觉。结果当视标作２个象素的水平运动，从１０岁组至３０岁组，随年龄增长，视觉运动觉逐渐上升。４０岁以后年龄组逐渐降低，４个象素、６个象素水平运动和＞４０Ｈｚ闪烁运动状态不受年龄影响；性别和眼别与运动觉无相关关系。结论确定了我国正常人的运动觉特性，提供了正常参考值。     

Red cell antibody problems in 1000 liver transplants

Liver transplant patients frequently require large amounts of blood. The frequency and nature of their red cell (RBC) antibody problems were examined. Records were reviewed in 496 adults and 286 children undergoing 1000 consecutive transplants. Twenty-two percent of adults and 14 percent of children had RBC alloantibodies. Antibodies of potential clinical significance were found before transplant in 6.3 percent of adults and 1.0 percent of children; despite immunosuppression, they appeared 1 to 5 weeks after transplant in an additional 7.5 and 5.2 percent respectively. These antibodies probably represented secondary immune responses. Of 58 transplant patients with prior potentially significant antibodies, 8 required 7 to 110 units of antigen-untyped blood after 8 to 28 units of antigen-negative blood; of these patients, one had subsequent hemolysis. Positive direct antiglobulin tests in 24 percent of adults and 10 percent of children were most often thought to be due to nonspecific adsorption of IgG. Anti-recipient ABO antibodies developed in 22 of 60 (37%) evaluable ABO-unmatched grafts; 13 cases had associated hemolysis. In all, 36 percent of adults and 20 percent of children had diverse RBC antibody problems. Resolution of these problems is an important part of the laboratory support necessary for a liver transplantation program.     

Interleukin-1 (IL-1) directly and indirectly promotes hematopoietic cell growth through type I IL-1 receptor

Interleukin-1 (IL-1) has been shown to stimulate hematopoietic progenitor cell growth both in vitro and in vivo. Although IL-1 alone lacks the ability to promote hematopoietic progenitor growth in vitro, it is a potent synergistic factor in combination with other colony- stimulating factors (CSFs). Because it was unknown whether type I (p80), type II (p68), or other IL-1-binding proteins mediated the synergistic effects of IL-1 on purified progenitor cells, we used the difference in immunoreactivity between type I and type II IL-1 receptor (IL-1R) to better assess the role of these receptors in hematopoietic progenitor growth. Therefore, the synergistic effects of IL-1 alpha on IL-3-, CSF-1-, and granulocyte macrophage (GM)-CSF-induced progenitor growth, both in CFU-c and single-cell assays, were determined in the presence of monoclonal antibodies (MoAbs) 35F5 and 4E2 that block the binding of IL-1 alpha to type I and type II IL-1R, respectively. The synergistic effect of IL-1 alpha on IL-3 responsive Lin- and Lin(-)-Thy- 1+ progenitors was indirectly mediated and could be inhibited by MoAb 35F5. In contrast, IL-1 alpha directly synergized with CSF-1 and GM-CSF to promote progenitor cell growth. The direct synergistic effect of IL- 1 alpha on CSF-1-induced progenitor growth was observed in all progenitor populations examined (Lin-, Lin-Thy-1+, and Lin-Thy-1-) and was inhibited by MoAb 35F5. However, the direct synergistic effect of IL-1 alpha on GM-CSF-responsive progenitors. Lin- and Lin-Thy-1+, was partially inhibited by MoAb 35F5. In contrast, the MoAb antitype II IL- 1R (MoAb 4E2) could not inhibit the direct synergistic effects of IL-1 alpha on CSF-1- or GM-CSF-induced progenitor growth. Thus, IL-1 alpha directly and indirectly stimulates the growth and differentiation of purified progenitors through the type I IL-1R but not the type II IL-1R.     

Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor

Three cell lines of mature T cell origin derived from patients with cutaneous T cell lymphoma-leukemias (CTCL) were found to be constitutive producers of T cell growth factor (L-TCGF). These are the first reported human cell lines which constitutively produce TCGF. Biologically active TCGF could also be eluted from the surface of these cells using an acid glycine buffer under conditions that maintained cell viability, and subcellular fractionation showed that almost all the TCGF activity was associated with the plasma membrane. Over 30 other human hematopoietic cell lines derived from other disorders were unable to produce TCGF even after induction, and their acid eluates did not contain TCGF activity. L-TCGF from CTCL lines had the same biological activity as TCGF obtained from normal leukocytes (N-TCGF) in that they both supported the long-term growth of normal T cells only after the cells were previously activated by antigen or lectin. Both L-TCGF and N-TCGF increased the rate of proliferation of TCGF-independent and TCGF-dependent CTCL cell lines. The same three factor-independent cell lines that released TCGF adsorbed TCGF in a cell-concentration, time-, and temperature-dependent manner. Since the CTCL cell lines produce TCGF, adsorb TCGF, and increase their proliferative rate in response to TCGF or a related molecule, it is suggested that this endogenously produced factor plays a role in maintaining the abnormal proliferation of these cells in culture as permanently growing cell lines independent of exogenous TCGF. However, this does not mean that this is an essential aspect of neoplastic transformation. Since it is unusual to develop these cell lines in the absence of the continuous need for added TCGF, “autostimulation” may be one of the many unusual variant phenotypic properties sometimes associated with neoplastic cells that gives them a selective advantage for in vitro growth.