Melissa A. Kacena

Bio: Melissa A. Kacena is an academic researcher from Indiana University. The author has contributed to research in topics: Haematopoiesis & Bone healing. The author has an hindex of 27, co-authored 107 publications receiving 2493 citations. Previous affiliations of Melissa A. Kacena include University of Colorado Boulder & Indiana University – Purdue University Indianapolis.

Megakaryocyte-osteoblast interaction revealed in mice deficient in transcription factors GATA-1 and NF-E2

Abstract: Mice deficient in GATA-1 or NF-E2 have a 200–300% increase in bone volume and formation parameters. Osteoblasts and osteoclasts generated in vitro from mutant and control animals were similar in number and function. Osteoblast proliferation increased up to 6-fold when cultured with megakaryocytes. A megakaryocyte-osteoblast interaction plays a role in the increased bone formation in these mice. Introduction: GATA-1 and NF-E2 are transcription factors required for the differentiation of megakaryocytes. Mice deficient in these factors have phenotypes characterized by markedly increased numbers of immature megakaryocytes, a concomitant drastic reduction of platelets, and a striking increased bone mass. The similar bone phenotype in both animal models led us to explore the interaction between osteoblasts and megakaryocytes. Materials and Methods: Histomorphometry, μCT, and serum and urine biochemistries were used to assess the bone phenotype in these mice. Wildtype and mutant osteoblasts were examined for differences in proliferation, alkaline phosphatase activity, and osteocalcin secretion. In vitro osteoclast numbers and resorption were measured. Because mutant osteoblasts and osteoclasts were similar to control cells, and because of the similar bone phenotype, we explored the interaction between cells of the osteoblast lineage and megakaryocytes. Results: A marked 2- to 3-fold increase in trabecular bone volume and bone formation indices were observed in these mice. A 20- to 150-fold increase in trabecular bone volume was measured for the entire femoral medullary canal. The increased bone mass phenotype in these animals was not caused by osteoclast defects, because osteoclast number and function were not compromised in vitro or in vivo. In contrast, in vivo osteoblast number and bone formation parameters were significantly elevated. When wildtype or mutant osteoblasts were cultured with megakaryocytes from GATA-1- or NF-E2-deficient mice, osteoblast proliferation increased over 3- to 6-fold by a mechanism that required cell-to-cell contact. Conclusions: These observations show an interaction between megakaryocytes and osteoblasts, which results in osteoblast proliferation and increased bone mass, and may represent heretofore unrecognized anabolic pathways in bone.

Bacterial growth in space flight: logistic growth curve parameters for Escherichia coli and Bacillus subtilis.

Abstract: Previous investigations have reported that bacterial suspension cultures grow to higher stationary concentrations in space flight than on Earth; however, none of these investigations included extensive ground controls under varied inertial conditions. This study includes extensive controls and cell-growth data taken at several times during lag phase, log phase, and stationary phase of Escherichia coli and Bacillus subtilis. The Marquardt-Levenberg, least-squares fitting algorithm was used to calculate kinetic growth parameters from the logistic bacterial growth equations for space-flight and control growth curves. Space-flight cultures grew to higher stationary-phase concentrations and had shorter lag-phase durations. Also, evidence was found for increased exponential growth rate in space.

The Association of American Medical Colleges

Abstract: BIOMEDICAL RESEARCH POLICY COMMITTEE REPORT WAS PUBLISHED AS A SUPPLEMENT TO THE AUGUSTJOURNAL OF MEDICAL EDUCATION. A REPRINT IS ENCLOSED. REQUESTS FOR ADDITIONAL COPIES SHOULD BE ADDRESSED TO THISOFFICE. -COPIES ARE BEING SENT TO MEMBERS OF CONGRESS AND THE KEY MEMBERS OF THE ADMINISTRATION. CALLING UPON-YOUR SENATORSAND CONGRESSMEN TO TELL THE STORY OF THE ROLE. OF MEDICAL SCHOOLS IN BIOMEDICAL RESEARCH AND HEALTH CARE IS IMPORTANT.I STRONGLY URGE THAT YOU MAKE AN 411 APPOINTMENT TO SEE YOUR CONGRESSIONAL REPRESENTATIVES WHILE YOU ARE IN WASHINGTON FOR THE COUNCIL MEETINGON OCTOBER 29. UPON REQUEST WE CAN SUPPLY THE NAMES OF APPOINTMENT SECRETARIES AND PHONE NUMBERS OF YOUR SENATORS AND CONGRESSMEN. APPROPRIATIONS COMMITTEE ACTED WITH EXTRAORDINARY ALACRITY THIS YEAR. THE-NIH APPROPRIATION WAS INCREASED BY 242 MILLION DOLLARSOVER 1971, REPRESENTING A 142 MILLION DOLLAR INCREASE OVER. THE ADMINISTRATION BUDGET, THE BLUE SHEET ASCRIBES APPROPRIATIONS OUTCOME TO THE EFFECTIVENESS OF THE COALITION FOR HEALTH FUNDING UNDER THE LEADERSHIP OF JOHN A. D. COOPER.

Cancer to bone: a fatal attraction

Abstract: When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and invasion, is central to the pathophysiology of bone metastases. Basic findings of tumour–bone interactions have uncovered numerous therapeutic opportunities that focus on the bone microenvironment to prevent and treat bone metastases.