Maspin expression inversely correlates with breast tumor progression in MMTV/TGF-alpha transgenic mouse model.

Maspin is a novel serine protease inhibitor (serpin) with tumor suppressive activity. To date, despite the mounting evidence implicating the potential diagnostic/prognostic and therapeutic value of maspin in breast and prostate carcinoma, the lack of a suitable animal model hampers the in vivo investigation on the role of maspin at different stages of tumor progression. In this study, we used MMTV/TGF-alpha transgenic mouse model to study the expression profile of maspin in mammary tumor progression. Histopathological examinations of MMTV/TGF-alpha transgenic mice revealed TGF-alpha expression leading to hyperproliferation, hyperplasia, and occasional carcinoma in mammary gland. Interestingly, when MMTV/TGF-alpha transgenic mice were breed to homozygocity, they also developed characteristic skin papillomas. Immunohistochemistry analysis of maspin expression in the breast tissues of TGF-alpha transgenic mice showed a direct correlation between down-regulation of maspin expression and tumor progression. The loss of maspin expression was concomitant with the critical transition from carcinoma in situ to invasive carcinoma. Subsequent in-situ hybridization analyses suggest that the down-regulation of maspin expression is primarily a transcriptional event. This data is consistent with the tumor suppressive role of maspin. Furthermore, our data suggests that MMTV/TGF-alpha transgenic mouse model is advantageous for in vivo evaluation of both the expression and the biological function of maspin during the slow multi-stage carcinogenesis of mammary gland.

Faculty development in communication skills instruction: insights from a longitudinal program with "real-time feedback".

Responsibility for teaching communication skills often falls to a multidisciplinary group of faculty who lack both a common model for teaching and prior experience teaching communication in small groups. This article describes East Tennessee State University's multifaceted faculty development program in teaching communication skills. The program was developed and implemented in three phases. First, a two-step Delphi approach helped identify core communication skills. Phase two gave faculty the opportunity to practice identifying communication teaching issues and effective strategies for working with small groups. The third phase involved the videotaping of faculty teaching small groups of students. These tapes were reviewed both individually and in faculty groups. The tapes were also reviewed by students, who provided realtime, moment-to-moment feedback to the faculty. Implementation and review of the program has helped to identify new strategies for effectively facilitating small-group teaching of communication skills.

The surface of prostate carcinoma DU145 cells mediates the inhibition of urokinase-type plasminogen activator by maspin.

Maspin is a novel serine protease inhibitor (serpin) with tumor suppressive potential in breast and prostate cancer, acting at the level of tumor invasion and metastasis. It was subsequently demonstrated that maspin inhibits tumor invasion, at least in part, by inhibiting cell motility. Interestingly, in cell-free solutions, maspin does not inhibit several serine proteases including tissue-type plasminogen activator and urokinase-type plasminogen activator (uPA). Despite the recent biochemical evidence that maspin specifically inhibits tissue-type plasminogen activator that is associated with fibrinogen or poly-L-lysine, the molecular mechanism underlying the tumor-suppressive effect of maspin remains elusive. The goal of this study was to investigate the effect of maspin on cell surface-associated uPA. In our experimental system, we chose prostate carcinoma DU145 cells because these cells mediate plasminogen activation primarily by uPA, as shown by two different colorimetric enzyme activity assays. Purified recombinant maspin produced in baculovirus-infected Spodoptera frugiperda Sf9 insect cells [rMaspin(i)] binds specifically to the surface of DU145 cells, inhibits the DU145 cell surface-bound uPA, and forms a stable complex with the uPA in DU145 cell lysate. The inhibitory effect of rMaspin(i) on cell surface-bound uPA was similar to that of an uPA-neutralizing antibody and was reversed by a polyclonal antibody against the reactive site loop sequence of maspin. The Ki value for rMaspin(i) in cell surface-mediated plasminogen activation was 20 nM, which was comparable to the Ki values for plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2, respectively. Furthermore, the proteolytic inhibitory effect of rMaspin(i) was quantitatively consistent with its inhibitory effect on the motility of DU145 cells in vitro. Our data demonstrate an important role for the prostate carcinoma cell surface in mediating the inhibitory interaction between rMaspin(i) and uPA. Thus, future maspin-based therapeutic strategies may prove useful in blocking the invasion and metastasis of uPA-positive prostate carcinoma.

The painful truth: physicians are not invincible.

Physicians are not immune to psychosocial problems but may face unique impediments to attending to them. Self-care among physicians is not a topic generally included as a part of professional training, nor is it a topic that readily receives consideration in professional practice. The stresses of professional practice can exact a great toll, however, and self-neglect can lead to tragic consequences. In some areas, particularly suicide rates, physicians have increased vulnerability, and in other areas problems may be unrecognized (depression, substance abuse, marital problems, and other stress-related concerns). Female physicians show some particular areas of risk. In this paper, we raise questions about how and why physicians may be particularly vulnerable, review the available literature about the extent and nature of such problems in physicians, discuss possible factors related to the development of these problems in physicians, and suggest a variety of solutions to improve physician self-care.

Genotoxicity of polychlorinated biphenyls (PCBs): recombinogenesis by biotransformation products.

A coplanar polychlorinated biphenyl (PCB) when eaten by test animals increased the rate of recombination in somatic cells, indicating a new mechanism of action for these compounds. Using the eye-mosaic test a high bioactivation strain of Drosophila that consumed 4,4'-dichlorobiphenyl (4,4'-DCB) manifested a genotoxicity rate that was three-fold greater than that in animals fed the solvent-spiked medium. This compound was not genotoxic in a suppressed bioactivation strain indicating that genotoxicity requires bioactivation of the compound. High bioactivation test strains made heterozygous for a paracentric inversion, a chromosomal rearrangement that suppresses homologous recombination, exhibited significantly reduced genotoxicity after treatment.

The selection of paraprofessional telephone counselors using the California Psychological Inventory.

Comparing groups of 36 veteran telephone counselors with 36 matched age and sex control subjects on the CPI revealed substantial differences on a number of scales. Subsequent development of weighted formulae via regression analysis led to very accurate predictions as to which individuals were telephone counselors or controls. Various cutoff scores and their uses are discussed.