透皮促进剂对胰岛素离子导入大鼠体内血糖水平的影响

研究了几种常用透皮促进剂如月桂氮　酮(azone,AZ),油酸(oleicacid,OA),泊洛沙姆(poloxamer188,POL188)和丙二醇(propyleneglycol,PG)等对胰岛素离子导入大鼠体内血糖水平的影响。结果显示:离子导入3h后,100%AZ和5%AZ/PG处理组,处理后对处理前的大鼠血糖变化百分率(D%)分别为38.58%和25.28%,而对照组的为45.48%。100%OA,10%OA/PG,10%POL188%和100%PG处理组的D%分别为66.28%,60.47%,76.75%和57.93%。表明月桂氮　酮与离子导入有协同作用,丙二醇能够增强这种作用,3者并用有特别显著的促渗作用。而油酸、泊洛沙姆、丙二醇不增强离子导入的作用。离子导入和某些透皮促进剂并用,为多肽类药物的体内给药提供了新的思路和可能性。     

Noninterference of isosulfan blue on estrogen-receptor activity

Because a 1% sterile solution of methylene blue used for occult breast tumor localization has been shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay, isosulfan blue in a 1% injection was studied as a potential alternate stain. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with isosulfan blue. No modification of the ERP-specific binding capacity was found with this stain. The use of isosulfan blue for localization of occult breast tumor is suggested when an ERP binding capacity assay is anticipated.     

Targeting of an activated T-cell subset using a bispecific antibody- toxin conjugate directed against CD4 and CD26

We have developed a bispecific antibody that recognizes the CD4 and CD26 antigens simultaneously and that was examined for its ability to target CD4+CD26+T cells. These latter cells constitute the activated component of the CD4+ CD29highCD45RO+ memory T-cell subset that provides help for B-cell Ig synthesis and help for responses against recall antigens. The purified bispecific antibody exhibited an estimated dissociation constant (kd) of 2.4 x 10(-9) mol/L, on comparison with 1.1 x 10(-9) mol/L for anti-CD26, and 1.6 x 10(-10) mol/L for anti-CD4. Surface plasmon resonance was used to show the bifunctional capacity of the antibody. On binding 125I-bispecific antibody to phytohemagglutinin (PHA)-activated T cells, 54.4% of the bound antibody was internalized. This was the result of bispecific binding, because monovalent fragments of anti-CD4 and anti-CD26 were not able to modulate antigen or induce internalization using both a fluorescent assay and an 125I-internalization assay. The ability of the bispecific antibody to be internalized was used to deliver a toxin, blocked ricin, specifically to cells that are CD4+CD26+. The inability of monovalent fragments to be internalized formed the basis for our hypothesis that monovalent binding by the bispecific immunotoxin would not result in internalization. Against resting E+ T cells, the bispecific immunotoxin developed a minimal effect. On preactivating the same cells, using phorbol myristate acetate (PMA)/ionomycin on concanavalin A (ConA) or especially PHA, levels of CD26 were upregulated and the immunotoxin effectively inhibited the ability to provide help for B-cell Ig synthesis while leaving intact the CD4-CD26+ and CD4+CD26- populations; an effect observed both functionally and by phenotype. The bispecific antibody proved to be most effective at inhibiting a heterologous mixed leukocyte reaction. We propose that this reagent may form the basis for the rational design of toxins designed to modulate activated T cells from, or directed against, tissue grafts.     

Melanin Pigment Uptake Within Paget Cells

Cutaneous leiomyosarcoma typically presents as solitary, well‐circumscribed, firm plaques or nodules. We describe a case of cutaneous leiomyosarcoma clinically presenting as a skin tag on the thigh of a 50‐year‐old male. Histological examination of the lesion revealed a dome‐shaped tumor with interlacing fascicles of smooth muscle with pleomorphism, cellular atypia and multiple mitoses. Malignant tumors may rarely present as a skin tag, and these are most frequently basal cell carcinomas. We are unaware of previously reported leiomyosarcoma clinically presenting as a skin tag. This case suggests that solitary, wide‐based, papilloma‐like lesions or skin tags should be submitted for histologic examination to rule out malignancy.     

Research, ethics and privacy: the limits of knowledge

This paper considers the need for personal privacy within the context of epidemiological research. It concludes that privacy can be protected by early anonymisation and aggregation of personal health data without prejudicing the viability of a research project. During the period before anonymisation, however, a secure legal framework is necessary to prevent unauthorised access to potentially sensitive information. Within such a framework ethical codes need to be identified and monitored by an appropriate Local Research Ethics Committee (or a Multicentre Ethics Committee acting on behalf of a number of local committees). Present arrangements within the health care system in the UK for the handling of such data remain very unsatisfactory and put patient privacy at risk.