Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA

1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.     

吸虱和其啮齿动物宿主的关系—偕同进化的证据

采自贵州省猪尾鼠的吸虱具有特殊的形态。李氏欣奇虱独自成为一科。双叶盲鼠虱隶拟血虱科。拟血虱科中的拟血虱属和钩板虱属均寄生于鼹科,裂虱属和盲鼠虱属则寄生于睡鼠科和刺山鼠科。后者曾被置于睡鼠科。研究食虫目动物的吸虱将可能对吸虱与其宿主动物的偕同进化提供更多的证据。     

Evaluation of inpatient clinical training in AIDS care.

BACKGROUND: Studies of outpatient clinical training in AIDS care have shown positive effects on residents' knowledge, attitudes and intentions. In this study, residents' knowledge, attitudes and intentions regarding the care of HIV-infected patients were used as outcome measures to evaluate the effectiveness of a 1-month residency training in an AIDS inpatient unit. METHODS: From April 2000 through April 2001, 33 internal medicine residents completed pretest-posttest questionnaires evaluating changes in their knowledge, attitudes and intention to care for HIV-infected patients. Of these 33 residents, 25 participated in a posttest interview, reflecting on their learning experience during the 1-month clinical rotation. RESULTS: At the posttest, residents were significantly more accurate in assessing HIV-associated risk (p < 0.001), and were significantly more knowledgeable about the necessary protective equipment to prevent HIV transmission (p < 0.01). Residents were significantly less concerned about the risk of infection (p < 0.01) and interpersonal concerns (p < 0.05). Residents' reluctance to care for HIV-infected patients was significantly lower (p < 0.05), as was their tendency to avoid invasive procedures or treatment of HIV-infected patients (p < 0.001). Residents designated after their training were more likely to practice universal precautions and less likely to be afraid and to stereotype HIV-infected patients. They also reported gaining insight into HIV diseases and patients' multifaceted needs, and appreciating the importance of teamwork in AIDS care. CONCLUSION: A 1-month AIDS residency training can effectively enhance residents' HIV-related knowledge, attitudes and intention to care for patients infected with HIV.     

Activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) against guinea pig cytomegalovirus infection in cultured cells and in guinea pigs

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC, and two HPMPC-related nucleoside analogs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, HPMPA, and (2-phosphonylmethoxyethyl)guanine, PMEG, were evaluated for their antiviral activities against guinea pig cytomegalovirus (GPCMV) infection in guinea pig embryo (GPE) cells and human cytomegalovirus (HCMV) infection in human diploid fibroblast (MRC-5) cells. DHPG, 9-(1,3-dihydroxy-2-propoxymethyl)guanine, was used for comparison. The antiviral activity of HPMPC against GPCMV infection in vivo and its toxicity to Hartley guinea pigs were also evaluated. The 50% antiviral effective doses (ED50) of HPMPC, HPMPA, PMEG and DHPG against GPCMV infection in GPE cells were 0.22, 1.4, 0.07 and 62 microM, respectively; and against HCMV infection in MRC-5 cells, the ED50s were 0.51, 0.72, 0.01 and 17.5 microM, respectively. Their cytotoxic doses (CyD50) in GPE replicating cells were 84, 35, 1.4 and 700 microM, respectively and in MRC-5 cells were approximately 114, 31, 0.86 and 750 microM, respectively. Based on their calculated therapeutic indexes, HPMPC was the most potent and selective of the four compounds tested. In vivo, during acute infection, the spleen indexes of all infected animals that were treated with 1.25 to 5.0 mg/kg/day of HPMPC for 5 days were significantly reduced as compared with sham-treated animals. Virus infectivity titers in blood and various tissues of infected animals treated with HPMPC, 2.5 or 1.25 mg/kg/day were not significantly lower than those of the infected, sham-treated animals; with 5 mg/kg/day, infectivity titers in the blood, spleen, and salivary gland were significantly lower in HPMPC-treated than in sham-treated animals. However, HPMPC was toxic to guinea pigs especially at doses of 5 to 10 mg/kg/day. These data showed that HPMPC was highly active and selective in cultured guinea pig cells and human fibroblast cells against CMV infection but did not effectively inhibit GPCMV infection in guinea pigs at minimum toxic concentrations.     

Flow Cytometric Analysis of Lymphocyte Subsets of Mice Maintained on an Ethanol-Containing Liquid Diet

Alcoholic patients often have impaired immune function, yet little is known about the precise mechanism(s) of this impairment. We have previously shown that ethanol consumption by mice alters copolymer-specific humoral and cellular immune responses. In this study, we asked whether alcohol consumption by mice would phenotypically alter lymphocyte populations. Female C57BL/6 mice were fed a nutritionally complete liquid diet containing 35% ethanol-derived calories for up to 8 days. As controls, mice either were fed a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a standard solid diet and water ad libitum. Although mice fed ethanol-containing liquid or pair-fed control liquid diets have decreased numbers of spleen cells compared with solid diet controls, only the ethanol-containing diet allowed normally nonresponder C57BL/6 spleen cells to make antibody responses to the poly(Glu⁵⁰Tyr⁵⁰) synthetic copolymer antigen. Flow cytometric analysis of splenic lymphocyte populations of mice on the ethanol-containing diet shows an increase in the relative proportion of T-lymphocytes as compared with mice on either solid or liquid control diets. No such change is seen for either B-cell or natural killer cell populations in these same mice. Both liquid control and liquid ethanol diets caused a slight decrease in the CD4:CD8 ratios of splenic T-lymphocytes. We see the relative percentage of T-cells bearing the αβ-cell receptor (TcR) increases in the spleens of liquid ethanol diet mice; a smaller increase TcRαβ usage is seen in the spleens of liquid control mice, compared with solid diet mice. Flow cytometric analysis shows that little, if any, difference exists in TcRγδ expression between the liquid ethanol and either the liquid control or solid diet groups. Preliminary analysis of TcRαβ subsets suggest that ethanol increases the percentage of T-cells expressing Vβ5 and Vβ8, and decreases the percentage of Vβ11 expressing cells. These findings suggest that, in addition to modifying the immune response, ethanol alters the phenotypic expression of lymphocyte subsets.     

亮氨酸脑啡肽的电子结构及构效关系研究

对亮氨酸脑啡肽进行了量子化学(INDO)计算,研究其电子结构特征,讨论其活性部位、作用机理及构效关系。同吗啡和R31833进行了活性部位的电子结构与空间结构比较,推断它们的活性药效结构具有共同特点,与阿片受体相互作用时作用方式相同,作用部位有对应关系,因而具有相同的药理性质。