ACTIVIT OF HUMAN PLACENTAL GAMMA GLOBULININ BLOCKING IMMUNE FUNCTIONS IN VITRO AND IN ABROGATING THE XENOGENEIC, LOCAL GRAFT-VERSUS-HOST-REEACTEON

In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft – versus –host disease (GCHD) following bone marrow transplantation (BMT) ,we have examined the effect of PGG in vitro and in a model of the xenogeneic , local graft –ver- sus – host reaction (LGVHR) .PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P<0.005) and depressed interleukin -2 (IL-2) levels in such cultures at 72 hours (P<0.01) . In contrast phytohemagglutinin (PHA) –and pokeweed mitogen (PWM) –induced T and B lymphocyte blastogenesis was not affected by such PGG treatment .PGG treatment .PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability .Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation . An immunosuppressive effect of PGG on the LGCHR was tested in a model of intracutaneous transplantation of PGG –treat human lymphocytes into cyclophosphamide – immunosuppressed rats. Lymphoprep – separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing：（1）PGG,4mg/ml,(2) human plasma albumin,4mg/ml,(3)mitomycin-C,25ug/ml, or (4) no additive. Cell of each preparation (3x107cells in 0.1ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells ,each rat received [125 I]IUdR (10uCi) intraperitoneally and was killed after 5 hours. For each site of injection, the diameters of induration were measured and 125 I was counted . There was no difference between buffer – treated and a ibumin – treated groups either in the diameter of the area of induration (t=0.66;P>0.5)or in radioactive counts(t=0.22;P>0.05).In the PGG –treated group, the induration and radioactivity measurements were significantly less than in control groups (t=3.72 and P<0.1;t=2.62 and P<0.02,respectively ) Cytophilic antibodies in PGG were thought to inhibit an early phase of T cell activation, and not to be cytotoxicity .In the LGVHR, the immune response might be abrogated either by immuno- regulatory suppression of T cell function or by toxicity to the infused lymphoid cells. For some clinical purposes, immuno- modulating, human antibodies might be preferred to murine, monoclonal antibodies.     

Stability of poly(D,L-lactide-co-glycolide) and leuprolide acetate in in-situ forming drug delivery systems.

In-situ forming drug delivery systems are prepared by dissolving a drug and a biodegradable polymer (poly(D,L-lactide-co-glycolide), PLGA) in a biocompatible organic solvent (In-situ implant, ISI) or further emulsified into an external phase (oil or aqueous solution), resulting in oil-in-oil or oil-in-water emulsions (In-situ forming microparticles, ISM). The chemical stability of PLGA and the drug is a major concern. In this study, the stability of PLGA and leuprolide acetate in the in-situ forming systems and lyophilized sponges was investigated. The degradation of PLGA increased with increasing storage temperature and water content in the biocompatible solvents. A faster degradation occurred in polar protic solvents (2-pyrrolidone, PEG 400, triethyl citrate) than in polar aprotic solvents (N-methyl-2-pyrrolidone, DMSO, triacetin, ethyl acetate). The presence of leuprolide acetate significantly accelerated PLGA degradation, especially in solution state. PLGA was stable in oily suspensions at 4 degrees C and degraded only slightly faster than solid powder at 25 degrees C. No interaction between the oils and the PLGA was observed as indicated by an unchanged T(g) of approx. 47 degrees C. PLGA underwent a slight degradation at 4 degrees C after 150 days in water and saturated sodium chloride solution. The degradation was slower in saturated sodium chloride solution than in water at 25 degrees C. Residual acetic acid in lyophilized sponges facilitated the PLGA degradation in contrast to dioxane. Leuprolide acetate did not affect the PLGA stability negatively. However, lidocaine significantly enhanced the polymer degradation in the sponges. Finally, leuprolide acetate was chemically stable in the sponges, the oils and the polymer solutions in suspension state, but unstable (aggregation) when dissolved in the polymer solutions and stored at 25 degrees C and 40 degrees C.     

Effects of chelating agents on the rheological property of cervical mucus

As an ongoing effort to elucidate the mechanisms involved in the calcium-dependent fertility regulation process, the viscoelastic properties of the mucus obtained from lamb cervix and human semen, as well as their water and total protein contents after exposure to EDTA, a chelating agent, or Nonoxynol-9 (N-9), a spermicidal agent, were examined. The viscosity was measured using a Cone Plate Digital Viscometer, while the water and total protein contents were determined by the lyophilization process and the Lowry method, respectively. The significant changes in the rheological properties of mucus, such as its viscosity and the water content, upon exposure to EDTA were demonstrated. The viscosity of cervical mucus and human semen were significantly increased by EDTA treatment (as compared to the controls): lamb cervical mucus (2.9 ± 0.3 vs. 2.2 ± 0.3 cps) and human semen (5.0 ± 0.3 vs. 4.3 ± 0.3 cps), respectively. The hydration rate was decreased by EDTA treatment as compared with the control (93.6 ± 0.7 vs. 96.8 ± 0.8%). Among tested samples, the reduction in the percentage of sperm penetration through the cervical mucus was the highest in the mucus containing EDTA, which had the lowest water content (93.6 ± 0.7%), indicating that there is a positive relationship between the hydration rate of the cervical mucus and its ability to permit the penetration of spermatozoa. This result indicates that spermicidal activity exerted by high concentrations of EDTA is in part due to its effect on the rheological properties of cervical mucus or semen.     

Radiographic manifestations of bronchiolitis obliterans with organizing pneumonia vs usual interstitial pneumonia

The radiographic findings in 24 cases of bronchiolitis obliterans with organizing pneumonia and 16 cases of usual interstitial pneumonia were reviewed and compared. Some cases of bronchiolitis obliterans with organizing pneumonia have been mistaken for usual interstitial pneumonia, although the two diseases have distinct pathologic findings. Clinically, the diseases often have different manifestations. Bronchiolitis obliterans with organizing pneumonia has a better prognosis and often responds well to steroids. This study shows that the radiologic findings of bronchiolitis obliterans include alveolar opacities without lung-volume loss. Patients with usual interstitial pneumonia, however, have bilateral diffuse interstitial opacities with occasional honeycomb changes, and there is loss of lung volume in most patients. These findings suggest that the chest radiograph can aid in distinguishing the two diseases.     

管状膨体聚四氟乙烯用于组织工程支架材料的动物实验研究

目的：研究膨体聚四氟乙烯(ePTFE)植入动物体内后与机体的关系。方法：管状膨体聚四氟乙烯两端闭合，内充DMEM培养液，埋入家兔皮下，观察宿主生命情况，于术后1、2、4、6周取出标本，行大体及光镜下观察。结果：家兔在植入膨体聚四氟乙烯材料及DMEM培养液后存活情况良好，DMEM培养液在1周时即已完全无色透明；4周时膨体聚四氟乙烯与周围组织有粘连，6周时粘连紧密；光镜下观察，各时间点材料间隙均可见着色，1周时可见少量淋巴细胞浸润，无血管及组织细胞。材料内壁未见细胞附着。结论：植入膨体聚四氟乙烯材料及少量DMEM培养液对宿主动物存活无影响；管内外液体可相互交通，管状膨体聚四氟乙烯可作为组织工程化尿道的支架材料。     

不同脑缺血和再灌流过程中大鼠脑组织NO含量的动态变化

采用线栓法制成大鼠大脑中动脉梗塞 ( MCAO)模型 ,依 Hb O2 - NO法测定持续性脑缺血和缺血 /再灌流脑组织内 NO含量的变化 ,以探讨不同脑缺血和再灌流过程中 NO的变化规律及其意义。结果 :缺血 3小时受损脑组织 NO水平即增高 ,再灌流后 NO逐步升高 ,而持续性缺血状态下 NO则表现降低后再升高的变化。虽然两组 NO在 7天时均有明显降低 ,但仍高于缺血前水平。认为持续性脑缺血和缺血 /再灌流情况下 NO的变化规律有所不同 ,与缺血脑组织的缺氧及产生 NO所需底物供应缺乏有关 ,且可能与脑组织的损害密切相关