Melanocyte culture lines from Tyr-SV40E transgenic mice: models for the molecular genetic evolution of malignant melanoma

Transgenic Tyr-SV40E mice previously produced on the C57BL/6 inbred-strain background, with SV40 oncogenic sequences specifically expressed in pigment cells, are predisposed to melanoma [Bradl, M., Klein-Szanto, A., Porter, S. & Mintz, B. (1991). Proc. Natl. Acad. Sci. USA, 88, 164-168]. Separate lines of these animals differ genetically only in the number of copies and chromosomal site of integration of the transgene. Skin melanocytes from young mice with no apparent skin lesions were established in continuous culture from hemizygous donors with low, medium and high numbers of transgene copies, and from a homozygous offspring of the low-copy mouse line. The standard culture conditions enable C57BL/6 wild-type melanocytes to become stably immortalized without transformation. The transgenic cell lines all changed over time in an orderly progression. However, with greater numbers of transgene copies, the cells more rapidly displayed shorter doubling times, increased anchorage independence, reduced serum and growth factor requirements, decreased tyrosinase expression and melanin content, increased oncogene expression, and capacity to form malignant melanomas when tested by grafting. Melanocytes with the lowest number of transgene copies were of special interest. They grew more rapidly than the wild-type cells from the outset, but did not become tumorigenic until an apparently small number of still-unknown genetic changes had spontaneously occurred, or until the number of transgene copies was increased slightly by homozygosity. In contrast to the hemizygous low-copy cells, the homozygous counterparts underwent striking and rapid transformational changes and early conversion to malignancy. Thus such low-copy transgenic melanocyte lines afford an exceptional opportunity for molecular analysis of somatic genetic evolution toward malignant melanoma.     

Expressed emotion and subclinical psychopathology observable within the transactions between schizophrenic patients and their family members.

The authors examined whether young, recently discharged schizophrenic patients from high (n?=?34) and low (n?=?14) expressed emotion (EE) families differ in their level of subclinical symptomatology during a direct interaction task. Compared with patients from low-EE homes, patients from high-EE homes showed significantly more odd and disruptive behavior with family members. High-EE relatives were more likely than low-EE relatives to respond with criticism to the first unusual thought verbalized by the patient; when this occurred, the probability of a second unusual thought was augmented. Results suggest that high-EE family members may display negative attitudes toward patients in part because they are exposed to higher levels of unusual or disruptive behavior than low-EE relatives. The data also support a bidirectional, transactional model of the relationship between relatives' EE and patient psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recognizing, assessing, and intervening with problems of professional competence.

Working collaboratively, psychologist educators and trainers at the doctoral, internship, and postdoctoral levels; credentialers; practitioners; and students offer 8 proposals for psychologists to consider in recognizing, assessing, and intervening with problems of professional competence in students and practicing professionals. In the proposals, the authors address the following topics: definitions and categories; preparing the system; self-assessment; remediation; diversity; communication across various levels of the system; confidentiality; and ethical, regulatory, and legal underpinnings. They also propose future directions for the assessment of problems in professional competence in both students and practicing psychologists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Two proto-oncogenes that play dual roles in embryonal cell growth and differentiation

BACKGROUND AND PURPOSE: Clinical and experimental data indicate that hyperglycemia can aggravate the consequences of stroke and cerebral ischemia. The purpose of this study was to examine the effects of moderate hyperglycemia on the response of the blood-brain barrier to normothermic (37 degrees C) and hypothermic (30 degrees C) global forebrain ischemia. METHODS: Sixteen rats underwent 20 minutes of four-vessel occlusion followed by 30 minutes of postischemic recirculation. We used the protein tracer horseradish peroxidase as an indicator of increased vascular permeability, and rats were perfusion-fixed for microscopic analysis. To produce moderate hyperglycemia, we gave an intraperitoneal injection of 50% dextrose 15 minutes before the ischemic insult. RESULTS: After normothermic brain ischemia, normoglycemic rats (plasma glucose level, 115 +/- 3 mg/dl) demonstrated extravasated horseradish peroxidase mainly restricted to the cerebral cortex. In contrast, more severe and widespread protein extravasation was documented throughout the neuraxis of hyperglycemic (plasma glucose level, 342 +/- 27) rats. Sites of protein leakage included the cerebral cortex, striatum, hippocampus, thalamus, and cerebellum. Foci of protein extravasation were associated with pial and large penetrating vessels. Intraischemic hypothermia significantly attenuated the blood-brain barrier consequences of hyperglycemic brain ischemia. CONCLUSIONS: Under normothermic ischemic conditions, hyperglycemia significantly worsens the degree of acute blood-brain barrier breakdown compared with normoglycemia. Postischemic blood-brain barrier disruption may play an important role in the pathogenesis of increased brain damage associated with systemic hyperglycemia.     

A formal curriculum in breast imaging for radiology residents

RATIONAL AND OBJECTIVES: Training in breast imaging is highly variable among radiology programs. The authors have developed a standardized breast imaging curriculum for radiology residents. METHODS: This curriculum has been implemented within the residency program at the University of North Carolina at Chapel Hill. It includes nine standardized components: 1) the clinical activities of the service; 2) the study of breast imaging teaching file films and contribution of new cases; 3) selected readings; 4) formal discussion with faculty on the readings; 5) review of this material using an interactive computer program; 6) formal conferences; 7) technical and quality control activities; 8) research activities; and 9) an evaluation. The participating residents have been surveyed regarding their opinions of their educational experience. RESULTS AND CONCLUSION: The standardized curriculum has been well received by the participating residents. Conclusions about the educational efficacy of such a curriculum cannot be made until more residents have used it.     

Prostate cancer clinical trials of the Southwest Oncology Group

The changing clinical dynamics of prostate cancer have resulted in a broadening of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease in its early years, SWOG prostate cancer trials now cover the entire spectrum of the disease: localized, locally advanced, metastatic and hormone-refractory disease. As the world's largest GU cancer research group, the GU committee of SWOG has pioneered studies in combined androgen therapy for metastatic disease, quality-of-life (QOL) assessments for patients with localized and advanced disease, adjuvant therapy models, and prostate cancer chemoprevention. The committee has also formed the GU Global Group, whose purpose is to convene the chairs of the GU committees of all the major national and international oncology cooperative groups. Meeting semiannually, this group discusses activities within their respective organizations, plans collaborative strategies and protocols, and establishes global strategy in prostate cancer clinical research. The future directions of national and international prostate cancer trials will build on this broad foundation of well-conceived, logically sequenced studies.     

Putative liver progenitor cells: conditions for long-term survival in culture

BACKGROUND AND OBJECTIVES: We operated on three patients with leiomyosarcoma of the inferior vena cava. METHODS: Complete excision was possible in all three patients. RESULTS: One patient developed widespread metastasis at 23 months, one patient is alive with no evidence of disease at 70 months, and one patient is alive at 15 months. The third patient had subcutaneous and pulmonary metastases at the time of presentation, which are radiologically nondetectable at present following postoperative chemotherapy. CONCLUSIONS: The clinicopathologic features, prognostic factors, and treatment of 130 cases found in a comprehensive literature search and our three cases are reported.