Rosalie Ber’s research while affiliated with Technion – Israel Institute of Technology and other places

Various hormones and growth factors have been implicated in progression of prostate cancer, but their role and the underlying molecular mechanism(s) involved remain poorly understood. In this study, we investigated the role of human growth hormone (GH) and its receptor (GHR) in human prostate cancer. We first demonstrated mRNA expression of GHR and of its exon 9-truncated isoform (GHR(tr)) in benign prostate hyperplasia (BPH) and prostate adenocarcinoma patient tissues, as well as in LNCaP, PC3 and DU145 human prostate cancer cell lines. GHR mRNA levels were 80% higher and GHR(tr) only 25% higher, in the carcinoma tissues than in BPH. Both isoforms were also expressed in LNCaP and PC3 cell lines and somewhat less so in DU145 cells. The LNCaP cell GHR protein was further characterized, on the basis of its M(r) of 120kDa, its binding to two different GHR monoclonal antibodies, its high affinity and purely somatogenic binding to (125)I-hGH and its ability to secrete GH binding protein, all characteristic of a functional GHR. Furthermore, GH induced rapid, time- and dose-dependent signaling events in LNCaP cells, including phosphorylation of JAK2 tyrosine kinase, of GHR itself and of STAT5A (JAK2-STAT5A pathway), of p42/p44 MAPK and of Akt/PKB. No effect of GH (72h) could be shown on basal or androgen-induced LNCaP cell proliferation nor on PSA secretion. Interestingly, however, GH caused a rapid (2-12h) though transient striking increase in immunoreactive androgen receptor (AR) levels (< or =5-fold), followed by a slower (24-48h) reduction (< or = 80%), with only modest parallel changes in serine-phosphorylated AR. In conclusion, the GH-induced activation of signaling pathways, its effects on AR protein in LNCaP cells and the isoform-specific regulation of GHR in prostate cancer patient tissues, suggest that GH, most likely in concert with other hormones and growth factors, may play an important role in progression of human prostate cancer.

In the light of the growing interest in professionalism and non-cognitive attributes in medical education, a focus group (FG) methodology was used to achieve a database of desired physician attributes. Ten FGs, consisting of medical faculty, service heads, residents, general practitioners, students and patients, took place, producing 169 desired attributes; further attributes were derived from a literature search, and the Mission and Vision Statement (MVS) of the authors' medical faculty. A total of 254 separate attributes finally emerged, after a process of combining and collapsing similar items. Attributes appearing with the highest frequency were: honest, empathic, patient, capacity to be an attentive listener, understanding, able to work in a team, intellectual curiosity, egalitarian. The high number of attributes generated in this study provides an indication of what the profession is wanting of itself. This database is multipotential and preliminary in nature and requires further processing before achieving full relevance.

Most U.S. medical schools offer courses in the behavioral and social sciences (BSS), but their implementation is frequently impeded by problems. First, medical students often fail to perceive the relevance of the BSS for clinical practice. Second, the BSS are vaguely defined and the multiplicity of the topics that they include creates confusion about teaching priorities. Third, there is a lack of qualified teachers, because physicians may have received little or no instruction in the BSS, while behavioral and social scientists lack experience in clinical medicine. The authors propose an approach that may be useful in overcoming these problems and in shaping a BSS curriculum according to the institutional values of various medical schools. This approach originates from insights gathered during their attempts to teach various BSS topics at four Israeli medical schools. They suggest that medical faculties (1) adopt an integrative approach to learning the biomedical, behavioral, and social sciences using Engel's "biopsychosocial model" as a link between the BSS and clinical practice, (2) define a hierarchy of learning objectives and assign the highest priority to acquisition of clinically relevant skills, and (3) develop clinical role models through teacher training programs. This approach emphasizes the clinical relevance of the BSS, defines learning priorities, and promotes cooperation between clinical faculty and behavioral scientists.

This paper describes a novel tool for assessment in medical education, the comprehensive integrative puzzle (CIP). The dual scoring system of the puzzle stresses the integrative elements of diagnostic thinking and clinical reasoning, while preserving the ability to discern proficiency in various disciplinary elements. The CIP has the format of an 'extended matching' crossword puzzle. Its answer sheet is a grid comprising rows and columns. The left-hand column contains diagnoses or brief clinical vignettes. To complete the cells of the grid the student is required to match, stepwise, the various 'disciplinary investigations' to the diagnoses or clinical vignettes. When the puzzle is completed each horizontal row reflects a coherent medical case. The completed horizontal rows reflect integrative ability (diagnostic thinking and clinical reasoning) and the vertical columns measure the student's proficiency in interpreting medical history data, physical examination findings, laboratory test results, ECG, imaging, special tests, pathology and pharmacology. The CIP has been well accepted by teachers and students during the last seven years at the Bruce Rappaport Faculty of Medicine in Haifa, and it has favorably affected both student assessment and teaching. The reliability of the test and its validity will be reported separately.

Medical professionalism includes expert knowledge, self-regulation and fiduciary responsibility to place the needs of patients ahead of the self-interest of physicians. In teaching medical professionalism to our medical students only the behavioural elements are dealt with. One of the challenges facing medical educators today is how medical professionalism can be taught. At the authors' faculty of medicine brief videotapes (trigger films) of amateur actor physician-patient encounters in various clinical settings (taken from genuine encounters) are used as a stimulus for discussion and instruction of medical professionalism. A series of 16 trigger films has been produced that raise many medical professional issues. The films and the issues raised are described in brief. These trigger films are viewed by small groups of medical students together with a physician tutor facilitator at various stages of their studies. It is noteworthy how fast the transition occurs in students, from observing the trigger films in their pre-clinical stage as a client, to observing them in their clinical years from the angle of a provider; from identifying with the patient's concerns to identifying with the physicians' behaviour; from being a critical person to becoming a person who accepts the rules and regulations of the guild. Most probably the power of the teaching of ethical and professional rules is overruled by the power of everyday clinical experience during their clinical clerkships. It is planned to run a series of trigger film sessions with senior and junior physicians of the major clerkships, in an attempt to promote an institutional environment/atmosphere/culture of professional behaviour.

The use of trigger films (TFs) for undergraduate teaching is well established in the Technion School of Medicine and elsewhere. These are typically based on a written script highlighting diverse issues within the patient-physician relationship (PPR). We report here on the staging of a filmed script-free encounter between a physician and an actress-patient as a further development of the TF approach. This involved the creation of a clinical interaction in which the patient's revealed cultural background demanded an adaptive response from the physician in order to achieve a stable PPR and to institute effective treatment. Considerable improvisation was thus required. Prior directorial manipulation of the conditions of the interview enhanced the didactic power and goals of the TF. After completion of the filming, the physician and the actress studied the video and then repeated the interview within the same situation free of directorial input. The two sequential videotaped interviews constitute the final product. These TFs appear to carry a wide spectrum of didactic messages at many levels including the need to relate effectively to the cultural aspects in the PPR, and the importance of self-observation as a tool for change and learning.

Trigger films or trigger videos that depict patient-physician encounters can be used to provoke reflection, stimulate discussion, help learners confront their feelings and give learners practice in responding to challenges. For more than 20 years at the B. Rappaport Faculty of Medicine, the authors have used trigger films to teach/demonstrate the doctor-patient relationship, medical ethics, diagnostic thinking, professional behavior, and the application of the principles of the Israeli Patient Bill of Rights, and have found them to be an excellent tool for provoking active participation in small-group discussions. The authors describe how they have effectively produced and used trigger films in an Introduction to Clinical Medicine course. They highly recommend the "homemade" production of trigger films.

The introduction of contraceptive technologies has resulted in the separation of sex and procreation. The introduction of new reproductive technologies (mainly IVF and embryo transfer) has led not only to the separation of procreation and sex, but also to the redefinition of the terms mother and family. For the purpose of this essay, I will distinguish between: 1. the genetic mother--the donor of the egg; 2. the gestational mother--she who bears and gives birth to the baby; 3. the social mother--the woman who raises the child. This essay will deal only with the form of gestational surrogacy in which the genetic parents intend to be the social parents, and the surrogate mother has no genetic relationship to the child she bears and delivers. I will raise questions regarding medical ethical aspects of surrogacy and the obligation(s) of the physician(s) to the parties involved. I will argue that the gestational surrogate is "a womb to rent," that there is great similarity between gestational commercial surrogacy and organ transplant marketing. Furthermore, despite claims to freedom of choice and free marketing, I will claim that gestational surrogacy is a form of prostitution and slavery, exploitation of the poor and needy by those who are better off. The right to be a parent, although not constitutional, is intuitive and deeply rooted. However, the issue remains whether this right overrules all other rights, and at what price to the parties involved. I will finally raise the following provocative question to society: In the interim period between today's limited technology and tomorrow's extra-corporeal gestation technology (ectogenesis), should utilizing females in PVS (persistent vehetative state) for gestational surrogacy be socially acceptable/permissible--provided they have left permission in writing?

The aim of this study is to further characterize the prolactin receptors (PRL-R) previously reported in the murine Leydig tumor MA-10 cell line, as well as to study their homologous and heterologous regulation. Two forms of PRL-R, a high and a low molecular weight form, were revealed by studies of covalent crosslinking of 125I-human GH to cultured MA-10 cells or cell membranes and immunoprecipitation of the solubilized PRL-R complexes with polyclonal anti PRL-R antibody, followed by SDS-PAGE and autoradiography. The long form had a molecular weight of 101 kDa and was predominant when the study was performed in the presence of protease inhibitors. The short form, with a molecular weight of 39 kDa, appeared, at least in part, to be a proteolytic product of the longer form. The same size forms of PRL-R were detected by crosslinking studies in the parental C57BL/6 mouse testicular Leydig cells, indicating the physiological relevance of the MA-10 cell model to the study of Leydig cell PRL-R. Homologous down-regulation of PRL-R was demonstrated in cultured MA-10 cells exposed for 24 h to increasing concentrations of PRL. In contrast, heterologous, 3–5-fold up-regulation of PRL-R was induced by various cAMP-elevating agents, including 8-bromo-cAMP (10−4–10−3 M), dibutyryl cAMP (3×10−3 M) and cholera toxin (1–10 ng/ml), although not by hCG (up to 100 ng/ml). This up-regulatory effect was apparently the result of a change in affinity, since cholera toxin caused a 2.4-fold increase in PRL-R affinity, with no change in the number of binding sites. In summary, these studies provide further evidence that MA-10 Leydig cells can serve as a physiologically relevant model for the study of PRL and PRL-R interactions, both at the functional level, as shown in our previous study, and at the structural and regulatory levels as shown in the current study.