No abstract

Several classified documents saved after the collapse of the German Democratic Republic (GDR) in 1990 describe the promotion by the government of the use of drugs, notably androgenic steroids, in high-performance sports (doping). Top-secret doctoral theses, scientific reports, progress reports of grants, proceedings from symposia of experts, and reports of physicians and scientists who served as unofficial collaborators for the Ministry for State Security (“Stasi”) reveal that from 1966 on, hundreds of physicians and scientists, including top-ranking professors, performed doping research and administered prescription drugs as well as unapproved experimental drug preparations. Several thousand athletes were treated with androgens every year, including minors of each sex. Special emphasis was placed on administering androgens to women and adolescent girls because this practice proved to be particularly effective for sports performance. Damaging side effects were recorded, some of which required surgical or medical intervention. In addition, several prominent scientists and sports physicians of the GDR contributed to the development of methods of drug administration that would evade detection by international doping controls.

1 n order to review the contradictory statements on the ultrast ru cture o f the nuclear envelope, a study was undertaken combining section and negat ive stai ning electron microscopy on manually isolated oocyte nuclei and nuclear envelopes from six amphibian species including Anura as well as Urodela.The a ppeara nce of the negatively stained iso lated nuclear envelopes is described in deta il a nd the dependence on the preparation co nditio ns used is emphas ized . Pore complex structures such as pore perimeter, centra l granule, an nul ar components, interna l fibrils , a nd annu lus-attached fibril s could be identified by both techniques, negat ive staining a nd sect ions.Comparati ve studies show that no marked diffe rences ex ist in the structural data of the nuclear envelope among the investigated amphibians and the significance of the structura l components is discussed. A model of the nuclea r po re complex based o n the findings of the present investigation is prese nted.To o btai n a n in sight into the mech a ni s ms invol ved in nucl eocyto pl asm ic interactio n, a thorough knowledge of the exchange sites of macromolecules between th ese two compartments is a prior condition. Since Calla n a nd Tomlin (1/) have shown that th e nuclear envelope is interrupted by di scontinuities of co nsta nt size a nd cha racteristi c structura l features, it is wid ely accepted that s uch nucl ear "pore co mpl exes" (80) a re th e gateways through which nucleocyto plasmic interactio ns c hiefl y take place. This is at least in line with the evidence hith erto acc umul a ted (fo r reviews, see e.g., 32, 7/). Co nsiderabl e research on the structure a nd function of th e nucl ear membra ne has been concerned with oocytes, part icula rl y with a mphibi a n oocy tes (20 , 29-34, 36, 37, 43, 55, 64, 66, 74, 79, 82, 84). Despite the large number of ultrastr uctura l studies o n the nuclear pore complex, there ex ist ma ny as toni shing ly diverse model s describin g the spati a l and functional relationship o f th e a nnulus a nd the membra nes limiting th e nuclear pores (e.g., 2, 5, 32, 34, 43, 55, 62, 68, 77,8 1, 82). Furthermore, recent articles (e.g., 33, 34) on structura l d eta il s of the a mphibian oocyte nuclear pore

Plakophilin 2 (PKP2) is a widespread protein which shows a remarkable dual location: On the one hand, it appears as a constitutive karyoplasmic protein and on the other it is a desmosomal plaque component of most, probably all, desmosome-possessing tissues and cell culture lines. Here we report on its desmosomal occurrence as revealed by immunocytochemical results obtained with three PKP2-specific murine monoclonal antibodies (mAbs) PP2-62, PP2-86 and PP2-150. These mAbs detect PKP2 in characteristic desmosomes of most normal cells, including simple and stratified epithelia as well as non-epithelial tissues such as myocardium and lymph node follicles. In addition, however, several normal tissues consistently display a differentiation-related PKP2 distribution, for example an absence of immunostaining in the "keratinizing" local specializations of the thymic epithelial reticulum, i. e. Hassall's corpuscles, and the restriction of PKP2 to the stratum basale of most stratified squamous epithelia, in contrast to its absence in upper strata, which contain PKP1-or PKP3-rich desmosomes instead. Taking advantage of the reactivity of mAb PP2-150 with formalin-fixed, paraffin-embedded material, a series of human carcinomas (n=37) has also been analyzed. The results suggest that mAbs to PKP2 may serve as markers for the identification and characterization of carcinomas derived from -or corresponding to -simple or complex epithelia. Thus consistent PKP2 immunostaining has been observed in all 18 cases of adenocarcinomas tested, but more variable and heterogeneous staining has been noted in squamous cell carcinomas, depending on the specific tumor type. The potential value of such mAbs for cell typing in normal and embry-onic tissues and for detecting cell subpopulations with different degrees of differentiation is discussed with respect to their possible application in tumor diagnosis.& b d y :