Inherited unbalanced subtelomeric translocation in a child with 8p- and Angelman syndromes

A 10 1/2-month-old boy was found to have an unbalanced karyotype, 45,XY,der(8)t(8;15) (p23.3;q13). One of 83 analyzed cells also contained an unidentified small marker. Fluorescence in situ hybridization (FISH) using cosmic probes for SNRPN, D15S10, and GABRB3 for the Prader-Willi syndrome (PWS)/Angelman syndrome (AS) critical region were not present on the derived chromosome. The child had some physical findings compatible with monosomy 8p. The mother also was a balanced carrier for the translocation. She also had 2/80 cells with an additional small marker chromosome, similar in size to the extra chromosome in the one cell of the propositus. FISH using an 8 paint did not show the reciprocal exchange on the der(15) but was demonstrated by using an 8p telomeric probe. At 18 months of age the child has some manifestations of AS. Earlier diagnosis may have been masked by the 8p- phenotype, or related to difficulty in diagnosing AS in infants. Am. J. Med. Genet. 70:150–154, 1997. © 1997 Wiley-Liss, Inc.     

Genetic polymorphisms of human platelet antigens in Euro-African and Japanese descendants from Parana,Southern Brazil

The frequency distributions of HPA-1 to HPA-6 and HPA-15 were evaluated in two Brazilian populations from Parana: a mixed population of predominantly Caucasians and a population of Japanese descendants. Genotyping was performed by PCR-SSP in 364 unrelated individuals. Differences in the distribution of HPA highlight diversity in Brazilian miscegenation and the importance of formation of the HPA panel composed of regional blood donors.     

Characterization of mammary cancer stem cells in the MMTV-PyMT mouse model

Breast cancer stem cells, the root of tumor growth, present challenges to investigate: Primary human breast cancer cells are difficult to establish in culture and inconsistently yield tumors after transplantation into immune-deficient recipient mice. Furthermore, there is limited characterization of mammary cancer stem cells in mice, the ideal model for the study of breast cancer. We herein describe a pre-clinical breast cancer stem cell model, based on the properties of cancer stem cells, derived from transgenic MMTV-PyMT mice. Using a defined set of cell surface markers to identify cancer stem cells by flow cytometry, at least four cell populations were recovered from primary mammary cancers. Only two of the four populations, one epithelial and one mesenchymal, were able to survive and proliferate in vitro. The epithelial population exhibited tumor initiation potential with as few as 10 cells injected into syngeneic immune-competent recipients. Tumors initiated from injected cell lines recapitulated the morphological and physiological components of the primary tumor. To highlight the stemness potential of the putative cancer stem cells, B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) expression was knocked down via shRNA targeting Bmi-1. Without Bmi-1 expression, putative cancer stem cells could no longer initiate tumors, but tumor initiation was rescued with the introduction of a Bmi-1 overexpression vector in the Bmi-1 knockdown cells. In conclusion, our data show that primary mammary cancers from MMTV-PyMT mice contain putative cancer stem cells that survive in culture and can be used to create a model for study of mammary cancer stem cells.     

Direct and indirect contribution of bone marrow‐derived cells to cancer

Stromal‐epithelial interactions may control the growth and initiation of cancers. Here, we not only test the hypothesis that bone marrow‐derived cells may effect development of cancers arising from other tissue cells by forming tumor stroma but also that sarcomas may arise by transformation of stem cells from the bone marrow and epithelial cancers may arise by transdifferentiation of bone marrow stem cells to epithelial cancers. Lethally irradiated female FVB/N mice were restored with bone marrow (BM) transplants from a male transgenic mouse carrying the polyoma middle T‐oncoprotein under the control of the mouse mammary tumor virus promoter (MMTV‐PyMT) and followed for development of lesions. All of 8 lethally irradiated female FVB/N recipient mice, restored with BM transplants from a male MMTV‐PyMT transgenic mouse, developed Y‐chromosome negative (Y−) cancers of various organs surrounded by Y+ stroma. One of the female FVB/N recipient mice also developed fibrosarcoma and 1, a diploid breast adenocarcinoma containing Y chromosomes. In contrast, only 1 of 12 control female mice restored with normal male BM developed a tumor (lymphoma) during the same time period. These results indicate not only that the transgenic BM‐derived stromal cells may indirectly contribute to development of tumors in recipient mice but also that sarcomas may arise by transformation of BM stem cells and that breast cancers arise by transdifferentiation of BM stem cells, presumably by mesenchymal‐epithelial transition.     

The effect of direction and reaction on the neuromuscular and biomechanical characteristics of the knee during tasks that simulate the noncontact anterior cruciate ligament injury mechanism

BACKGROUND: Jumping and landing tasks that have a change in direction have been implicated as a mechanism of noncontact anterior cruciate ligament injury. Yet, to date, neuromuscular and biomechanical research has focused primarily on straight landing tasks during planned jumps. HYPOTHESIS: Lateral and reactive jumps increase the neuromuscular and biomechanical demands placed on the anterior cruciate ligament, and women perform these tasks differently from men. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 18 male and 17 female healthy high school basketball players underwent an analysis of the knee during planned and reactive 2-legged stop-jump tasks in 3 different directions that included novel methodology to incorporate a reactive component. Ground-reaction forces, joint kinematics, joint kinetics, and electromyographic activity were assessed during the tasks. RESULTS: Jump direction and task (planned or reactive) significantly affected joint angles, ground-reaction forces, knee joint moments, and proximal anterior tibia shear forces; female players demonstrated different kinematic, kinetic, and electromyographic characteristics during these tasks.Conclusion and CLINICAL RELEVANCE: Jump direction significantly influenced knee biomechanics, suggesting that lateral jumps are the most dangerous of the stop-jumps. Reactive jumps were also significantly different, suggesting differences between planned laboratory experiments and actual athletic competition. The results of this study indicate that directional and reactive jumps should be included in research methodology and injury-prevention programs.