Frederick S. Southwick

Bio: Frederick S. Southwick is an academic researcher from University of Florida. The author has contributed to research in topics: Actin & Arp2/3 complex. The author has an hindex of 40, co-authored 104 publications receiving 9613 citations. Previous affiliations of Frederick S. Southwick include University of Pennsylvania & Harvard University.

Multifactorial Index of Cardiac Risk in Noncardiac Surgical Procedures

Abstract: To determine which preoperative factors might affect the development of cardiac complications after major noncardiac operations, we prospectively studied 1001 patients over 40 years of age. By multivariate discriminant analysis, we identified nine independent significant correlates of life-threatening and fatal cardiac complications: preoperative third heart sound or jugular venous distention; myocardial infarction in the preceding six months; more than five premature ventricular contractions per minute documented at any time before operation; rhythm other than sinus or presence of premature atrial contractions on preoperative electrocardiogram; age over 70 years; intraperitoneal, intrathoracic or aortic operation; emergency operation; important valvular aortic stenosis; and poor general medical condition. Patients could be separated into four classes of significantly different risk. Ten of the 19 postoperative cardiac fatalities occurred in the 18 patients at highest risk. If validated by prospective application, the multifactorial index may allow preoperative estimation of cardiac risk independent of direct surgical risk.

Acute Bacterial Meningitis in Adults -- A Review of 493 Episodes

Abstract: Background and Methods To characterize acute bacterial meningitis in adults, we reviewed the charts of all persons 16 years of age or older in whom acute bacterial meningitis was diagnosed at Massachusetts General Hospital from 1962 through 1988. We included patients who were admitted after initial treatment at other hospitals. Results During the 27-year period, 445 adults were treated for 493 episodes of acute bacterial meningitis, of which 197 (40 percent) were nosocomial. Gram-negative bacilli (other than Haemophilus influenzae) caused 33 percent of the nosocomial episodes but only 3 percent of the community-acquired episodes. In the 296 episodes of community-acquired meningitis, the most common pathogens were Streptococcus pneumoniae (37 percent), Neisseria meningitidis (13 percent), and Listeria monocytogenes (10 percent); these organisms accounted for only 8 percent of the nosocomial episodes. Only 19 of the 493 episodes of meningitis (4 percent) were due to H. influenzae. Nine percent of all patien...

N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.

Abstract: The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12. N-WASP is not required for the actin-based movement of the intracellular pathogen Listeria but is absolutely required for the motility of Shigella and vaccinia virus. Despite these distinct defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by using lamellipodia and can protrude filopodia. These results imply a crucial and non-redundant role for N-WASP in murine embryogenesis and in the actin-based motility of certain pathogens but not in the general formation of actin-containing structures.

Listeria monocytogenes moves rapidly through the host-cell cytoplasm by inducing directional actin assembly.

Abstract: Listeria monocytogenes is an intracellular parasite that can readily infect the macrophage-like cell line J774 and the kidney epithelial cell PtK2 After being ingested, the organism escapes from the phagolysosome into the host-cell cytoplasm N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-phallacidin, a specific stain for actin filaments (F-actin), demonstrates that within 1 hr of initiation of infection, the bacteria become surrounded by host-cell cytoplasmic actin filaments By 3 hr, long projections of F-actin begin to form at one end of the bacteria These actin structures colocalize with the actin-bundling protein alpha-actinin as well as with tropomyosin Microinjection of fluorescently labeled alpha-actinin in living cells demonstrates that the formation of these F-actin projections is associated with bacterial movement, actin filaments rapidly assembling behind the bacteria as they migrate through the cytoplasm These F-actin tails attain lengths up to 40 microns The movement of the bacteria through the cytoplasm is rapid, 012-146 microns/sec Within 2 min of cytochalasin D (05 micrograms/ml) treatment, all bacterial intracellular movement stops, and additional bacteria-associated actin assembly is blocked A nonmotile Listeria mutant induces comparable actin assembly and moves at speeds similar to the wild type, indicating that the forces required for intracellular bacterial movement are generated by the host cell L monocytogenes can dramatically stimulate host-cell actin assembly in a directional manner, which serves to rapidly propel the bacteria through the cytoplasm, allowing the organisms to move to peripheral membranes and spread to uninfected cells

Cell migration: integrating signals from front to back.

Abstract: Cell migration is a highly integrated multistep process that orchestrates embryonic morphogenesis; contributes to tissue repair and regeneration; and drives disease progression in cancer, mental retardation, atherosclerosis, and arthritis. The migrating cell is highly polarized with complex regulatory pathways that spatially and temporally integrate its component processes. This review describes the mechanisms underlying the major steps of migration and the signaling pathways that regulate them, and outlines recent advances investigating the nature of polarity in migrating cells and the pathways that establish it.

2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk

Abstract: Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S50 The goals of the American College of Cardiology (ACC) and the American Heart Association (AHA) are to prevent cardiovascular diseases (CVD); improve the management of people who have these diseases through professional education and research; and develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health. Toward these objectives, the ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to develop …