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.     

Behaviour of HPMC compacts investigated using UV-imaging

The aim of the study was to visualize the behaviour of the hydroxypropyl methylcellulose (HPMC) in a buffer solution using UV imaging. The obtained results were related to rheological measurements in order to gain insight into critical polymer properties affecting drug release. Two viscosity grades of HPMC, 15cP and 50 cP, were used. The behaviour of the polymer at the surface of the compact was observed by UV-imaging at 214 nm for 90 min in a stagnant buffer solution and in presence of flow. Steady shear and oscillatory shear measurements were conducted to determine the rheological characteristics. Three distinctive phases could be detected by real-time UV-imaging of the HPMC; gel formation due to water penetration, further expansion of the gel into solution and finally steady conditions, where a critical polymer concentration that can withstand the shear forces without eroding was observed. The critical concentration corresponded to the rheologically determined gel point, which is the lowest concentration where a 3D-network is obtained. Higher viscosity grade HPMC swelled more rapidly and lead to a thicker gel layer, which was more resistant towards the shear forces due to the applied flow. The results showed that UV imaging is suitable for obtaining both qualitative and quantitative information on polymer behaviour.     

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.     

C-reactive protein predicts future arterial and cardiovascular events in patients with symptomatic peripheral arterial disease

High-sensitivity C-reactive protein is associated with increased risk of cardiovascular events. Consequently, the predictive value of this protein in patients with symptomatic peripheral arterial disease was examined. In all, 452 patients with symptomatic peripheral arterial disease had high-sensitivity C-reactive protein measured at baseline (mean follow-up = 2.1 +/- 1.4 years). Events were defined as primary (death, amputation, or peripheral revascularization) or secondary (lower limb thrombosis, myocardial infarction, or stroke).The level of high-sensitivity C-reactive protein was significantly higher among those dying (P = .04), those who needed amputation (P = .01), and those developing an overall secondary endpoint (P = .02). By receiver-operating characteristic curve analysis, the optimal cutoff point was constantly approximately 10 to 20 mg/L with a sensitivity and specificity of 56% to 63% and 54% to 56%, respectively. Baseline levels of high-sensitivity C-reactive protein are associated with future arterial events in symptomatic peripheral arterial disease patients but cannot stand alone as a predictive tool.     

Absence of IFNγ expression induces neuronal degeneration in the spinal cord of adult mice

Background  

Interferon gamma (IFNγ) is a pro-inflammatory cytokine, which may be up-regulated after trauma to the peripheral or central nervous system. Such changes include reactive gliosis and synaptic plasticity that are considered important responses to the proper regenerative response after injury. Also, IFNγ is involved in the upregulation of the major histocompatibility complex class I (MHC class I), which has recently been shown to play an important role in the synaptic plasticity process following axotomy. There is also evidence that IFNγ may interfere in the differentiation and survival of neuronal cells. However, little is known about the effects of IFNγ absence on spinal cord neurons after injury.     

In vitro stability of lyophilized and reconstituted recombinant activated factor VII formulated for storage at room temperature

BACKGROUND: Recombinant activated factor VII (rFVIIa) is indicated to treat bleeding episodes or prevent bleeding related to surgery in patients with hemophilia A or B who have antibodies to coagulation factors VIII or IX. The first-generation rFVIIa formulation is stable when stored under refrigeration. A new formulation has been developed for storage at room temperature, which may improve patients' access to treatment during bleeding episodes. OBJECTIVE: These in vitro experiments were conducted to evaluate the stability of the new formulation of rFVIIa, both lyophilized and reconstituted, under the expected storage conditions, as well as at higher temperatures. METHODS: The stability of the new rFVIIa formulation when stored under various conditions before and after reconstitution was evaluated in terms of retained activity (clotting assay), rFVIIa content (high-performance liquid chromatography [HPLC]), and rFVIIa degradation products (HPLC), including aggregates (dimer/oligomer). Activity was analyzed within specific limits representing the allowable minimum/maximum for each test parameter at the end of the product's shelf-life, as adopted by the European Medicines Agency and the US Food and Drug Administration. Before reconstitution, vials from 9 lots of the new rFVIIa formulation, 3 of each size (1, 2, and 5 mg/vial), were stored at refrigerated temperature (5 degrees C) and at room temperature (25 degrees C) for 24 months, and at 30 degrees C for 12 months. To simulate short-term exposure to temperatures higher than recommended, samples were stored at 40 degrees C for 6 months, followed by storage at 25 degrees C for 12 months. To simulate the home setting, in which the product may be alternately stored in and out of the refrigerator, samples were stored at 30 degrees C for 8 hours and then at 5 degrees C for 16 hours, repeated daily for 5 days. To analyze the effect of storage at extremely elevated temperatures, samples were exposed to temperatures of 50 degrees C, 60 degrees C, and 70 degrees C for 12 hours. After reconstitution, samples were maintained at 25 degrees C for up to 6 hours or at 5 degrees C for up to 24 hours. RESULTS: The specific activity and rFVIIa content of the new lyophilized formulation remained stable after storage for 24 months at 5 degrees C and 25 degrees C, and for 12 months at 30 degrees C; after 5 days of daily alternation between storage at 5 degrees C and 30 degrees C; and after storage for 6 months at 40 degrees C followed by 12 months at 25 degrees C. When stored at 50 degrees C and 60 degrees C for 12 hours, activity remained constant, whereas rFVIIa aggregates increased within the specified limits; after storage at 70 degrees C for 12 hours, rFVIIa activity decreased in parallel with the formation of aggregates, which exceeded the specified limit for the 5-mg product. After reconstitution, samples of all vial sizes of the new rFVIIa formulation retained their activity when stored at 25 degrees C for 6 hours and at 5 degrees C for 24 hours. CONCLUSIONS: In these in vitro experiments, the new lyophilized formulation of rFVIIa was stable when stored for 24 months at 25 degrees C, 12 months at 30 degrees C, 6 months at 40 degrees C, and 12 hours at 50 degrees C and 60 degrees C without compromise to its activity or rFVIIa content. The reconstituted product retained activity when stored at 25 degrees C for 6 hours and at 5 degrees C for 24 hours.