Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.     

ALAS, our frailty is the cause … of a new for form of protoporphyria

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload
Whatley et al. (2008)
The American Journal of Human Genetics 83: 408–414     

缺血性脑卒中的A-S-C-O(表型)分类

背景和目的:国际5国脑血管病专家提出一种新的腩卒中亚型分类法,旨在介绍完整的"脑卒中表型"分类的新观念,该分类是包括脑卒中的病因和存在的所有病因相关的疾病,并将病因疾病按严重程度分成3级.     

Dentomaxillofacial manifestations of Gaucher's disease: preliminary clinical and radiographic findings

Objectives

A wide variety of manifestations is presented in patients with Gaucher''s disease (GD), including bone, haematology and visceral disturbances. This study was conducted to ascertain the main maxillofacial abnormalities by means of clinical survey, panoramic and cone beam CT (CBCT); to compare the patient''s group with an age–sex matched control group; and to correlate clinical and radiological data.

Methods

Ten patients previously diagnosed with GD were submitted to clinical and radiological surveys (CBCT and panoramic radiographs). The examination consisted of anamnesis, extra- and intraoral examinations and analyses of each patient''s records. Imaging data were collected from the point of view of 3 observers, and the results compared with a healthy group (20 individuals) by means of statistical analysis (Fisher''s exact test).

Results

Gaucher patients had significantly more manifestations than otherwise healthy carriers. The most prevalent findings were enlarged marrow spaces, generalized osteopenia and effacement of jaw structures (mandibular canal, lamina dura and mental foramen). Here we describe a case in which thickening of the maxillary sinus mucosa was observed on CBCT rather than opacification of the sinus as seen on panoramic radiographs. Pathological fractures, root resorption and delay on tooth eruption were not observed.

Conclusions

A poor relationship could be observed between clinical and radiological data. Patients showed important bone manifestations, which require careful diagnostic and surgical planning whenever necessary. Although panoramic radiographs have shown significant differences, CBCT is more effective in pointing out differences between patients and a control group, thus showing it as an important tool for evaluation of Gaucher patients.     

Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia

Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B- cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.     

Pretreatment hematocrit as an independent prognostic variable in Hodgkin's disease

Pretreatment hematocrit in 117 advanced-stage Hodgkin's disease patients treated with a combined modality therapy program was evaluated as an independent prognostic variable with regard to survival and relapse-free survival. Age greater than 40 years, and multiple extranodal sites of involvement were found to be statistically significant independent negative prognostic factors with regard to survival. Pretreatment hematocrit, however, was not an independent negative prognostic variable.