顺铂聚乳酸微球的药物释放特性及肝动脉栓塞研究

对顺铂聚乳酸微球进行了体外药物释放和家犬肝动脉栓塞研究。该微球粒径范围为50～200μm,平均粒径为115.76±35.94μm,顺铂含量为37.16%(W/W);体外药物释放机制符合Higuchi方程;肝动脉栓塞后8h,肝组织顺铂浓度高达21.55±12.18μg/g,明显高于肝动脉灌注顺铂组:3.16±0.09μg/g(P<0.05);肝动脉栓塞组的顺铂血浓峰值、各取血点浓度及曲线下面积AUC皆低于肝动脉灌注顺铂组。可望达到提高栓塞部位的药物疗效,降低全身毒副反应的作用。     

2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

Fine T-Cell Subsets in Alcoholics as Determined by the Expression of l-Selectin, Leukocyte Common Antigen, and β-Integrin

Alcoholics admitted to the hospital solely for detoxication have been studied by flow cytometry to evaluate changes in the surface markers of peripheral blood leukocytes. As we have shown previously, such patients have an elevated percentage of CD8^hl lymphocytes that are HLA DR⁺; we now demonstrate that they also have striking alterations in the quantitative relationships of the fine T-cell subsets. Both CD4⁺ and CD8^hl lymphocytes have a sharply reduced percentage of the l -selectin⁺ CD45RA⁺ subset, increased percentages of the CD45RA-subsets, and several other fine subset alterations. The fine subset profile suggests, according to current correlations of phenotype and function, that both CD4⁺ suppressor inducer and CD4-dependent CD8⁺ suppressor effector cells are reduced, whereas other subsets, including CD8⁺ CTL or their precursors, are increased in relative percentages. Some of the phenotypic changes are reversible over the several days following withdrawal. In other results, the percentage of CD8^hl lymphocytes expressing CD11b (β-integrin) is shown to be reciprocal with the percentage expressing l -selectin both in normals and alcoholics. However, the regression function of CD11b vs. l -selectin on CD8^hl cells is different for the alcoholics than for the normals, indicating an abnormality in the regulation of the expression of these two adhesion markers. Taken together, this abnormality of adhesion molecules and the fine subset alterations previously described indicate widespread changes in the peripheral lymphocytes of currently drinking alcoholics. These changes suggest functional deficiencies that may include alterations of lymphocyte traffic and other adhesion-dependent functions, and a shift in the balance of regulatory interactions.     

Spectrin autoantibodies in normal human serum and in polyclonal blood grouping sera

Naturally occurring spectrin autoantibody was detected in normal human sera and in polyclonal blood grouping sera by the immunoblotting technique. The autoantibody seems to be IgG, stable, of high titre and low affinity. It was detected in all sera tested. Preparations of monoclonal antibodies directed against some blood group antigens and anti-A1 lectin reagent were devoid of spectrin autoantibody as expected. This autoantibody may be instrumental in clearing red cell membrane components from the circulation during haemolysis. Care must be exercised in studies designed to determine the association of some blood group antigens with the red cell membrane skeleton, when using polyclonal sera which contain spectrin autoantibodies in addition to the antibodies against the blood group antigen in question.     

The significance of alpha-fetoprotein in the serum of patients with malignant teratomas and related gonadal neoplasms

Sera from eleven patients with gonadal germ cell tumors were tested for alpha-fetoprotein (AFP) by counterelectrophoresis. Ovarian neoplasms containing either the endodermal sinus tumor (EST) or dysgerminoma and half of the testicular embryonal carcinomas elaborated the protein into the serum. The presence of AFP in the serum seemed to correlate with early metastasis or a fatal outcome. That the highest levels of AFP were found in cases of EST was in keeping with the theory that the tumor originates in cells of the yolk sac, a principal embryonic site of AFP synthesis.     

Retinal projection to the nucleus of the optic tract in the cat as revealed by retrograde transport of horseradish peroxidase

Retrograde transport of horseradish peroxidase injected iontophoretically into the nucleus of the optic tract of cats revealed that the direction-selective cells in this pretectal nucleus receive direct retinal projections from small retinal ganglion cells, the so-called gamma-cells. These cells from a horizontal band on the contralateral retina. Few labeled cells are found in the ipsilateral temporal retina. The input from the contralateral retina is 10 times more numerous than from the ipsilateral one. In both retinae the highest concentration of labeled cells is near the area centralis.     

A patient with simultaneous absence of "classical" natural killer cells (CD3-, CD16+, and NKH1+) and expansion of CD3+, CD4-, CD8-, NKH1+ subset

The clinical manifestations of putative natural killer (NK) cell deficiency are not well-known but theoretically should include recurrent tumors and systemic viral infections. In this article, we discuss a patient with recurrent condylomata, vulvar and cervical carcinoma in situ, pulmonary infiltrates of unknown significance, and a hypercoagulable state. This patient has a dramatic persistent deficiency in her circulating "classic" NK cells (CD3-, CD16+, NKH1+) and a simultaneous persistent expansion of a normally minor lymphocyte cell subset (CD3+, CD4-, CD8-, NKH1+) that does not express the alpha beta heterodimer of the T cell receptor. T-lymphocyte function, as measured by mitogen and alloantigen responsiveness in vitro, was normal. The coexistence of this particular clinical complex with this unusual set of laboratory abnormalities tends to emphasize our meager understanding of the biologic role of NK cells. At the very least, these findings suggest that the clinical manifestations of NK cell deficiency need not be dominated by disseminated systemic viral infections and that perhaps there should be a higher index of suspicion for the scrutinization of NK cell function.     

Diverse locations of amino acids in HLA-DR beta chains involved in polymorphic antibody binding epitopes on DR(alpha, beta 1*0101), DR(alpha, beta 1*1101), and DR(alpha,beta 3*0202) molecules.

In a previous study, we used transfectants expressing hybrid HLA-DR(beta 1*0403)/DR(beta 1*0701) chains to map sequences involved in polymorphic antibody binding epitopes on DR(alpha, beta 1*0403) or DR(alpha, beta 1*0701) molecules. Amino acids 1-40 of the beta 1 domain were found to make the major contributions to most of the antibody binding epitopes studied. To begin to localize sequences that contribute to polymorphic antibody epitopes on DR(alpha,beta 1*0101), DR(alpha,beta 1*1101) and DR(alpha,beta 3*0202) molecules, we used indirect immunofluorescence and flow cytometry to assess the binding of mAb to transfectants expressing hybrid DR(beta 1*0101)/DR(beta 1*1101) or DR(beta 1*1101)/DR(beta 3*0202) chains that divide the DR beta chain into three segments: amino acids 1-40, 41-97, and the beta 2 domain. The results indicate that amino acids 41-97 of the beta 1 domain on DR(beta 1*0101), DR(beta 1*1101), or DR(beta 3*0202) are critical in most of the epitopes, including those recognized by human antibodies MP4 and MP12, and mouse mAb GS88.2, I-LR1, 21r5, and 7.3.19.1, whereas amino acids 1-40 of DR(beta 1*1101) are critical in the epitope recognized by the MCS-7 mAb, and both segments 1-40 and 41-97 of DR(beta 1*1101) are important in the epitopes recognized by the I-LR2 and UL-52 mAbs. Based on these data and comparison of DR beta allelic protein sequences, the residues that may play critical roles in these antibody binding epitopes are predicted.     

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD)

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha- synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha- synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.