Investigation of Fixation Techniques for Spine Stabilization
Robert Gao, Ph.D., Mechanical & Industrial Engineering, UMass
Amherst
Scott Cowan, M.D., New England Orthopedic Surgeons
K. Francis Lee, M.D., Biomedical Technology, Baystate Medical Center
The objective of this research is to investigate the effects of
several anterior fixation techniques on lumbar spine stabilization,
and establish a preliminary but systematic biomechanical evaluation
procedure. Rigid spine fixation is of critical importance to the
clinical outcome of spinal surgery and patient care, and an in-depth
understanding of the attributing mechanisms has significant impact
on the fundamental aspects of spinal rehabilitation.
Effective date – September 1, 2002
Development of a Novel Cell Encapsulation
System through the Evaluation of a Model Cell Line and Formulation
of Biocompatible Materials
Susan Roberts, Ph.D., Chemical Engineering, UMass Amherst
Surita Bhatia, Ph.D., Chemical Engineering, UMass Amherst
Stuart Chipkin, M.D., Endocrinology, Diabetes & Metabolism,
Baystate Medical Center
The encapsulation of cells/tissues in suitable matrices with retention
of viability and metabolic functionality has extensive clinical
applications and is likely to play a major role in cell and transplantation
therapies over the next decade. A successful implant is comprised
of cells or tissue surrounded by a biocompatible matrix permitting
the entry of small molecules such as oxygen, nutrients and electrolytes;
exit of toxic metabolites, hormones and other small bioactive compounds;
while excluding antibodies and T cells, thus protecting the encapsulated
cells/tissue. Systems of this type are currently being evaluated
for the treatment of a variety of disorders (e.g., type 1 diabetes
mellitus and kidney failure). Several key issues need to be addressed
before the clinical use of this technology can be realized: tissue
supply, protection from immune rejection and maintenance of cell
viability and functionality for extended periods of time. Metabolic
functionality is controlled by the transport of nutrients and oxygen,
with oxygen the primary dominant limitation. Maintenance of sufficient
oxygen levels in the encapsulation device is critical to avoid local
domains of necrotic and /or hypometabolic cells. This project was
established to develop a superior cell microencapsulation device
utilizing fluorocarbons to address current limitations in oxygen
transport and supply. This will be accomplished through the design
and testing of optimal materials formulation protocols to incorporate
fluorocarbons into FDA-approved alginate and Pluronic polymeric
systems.
Effective date – June 1, 2002
Intervention in Function of Tumor Cell Surface Membrane Receptors:
A Potential Role of Environmental Toxicants
Kathleen Arcaro, Ph. D., Vet & Animal Science, UMass Amherst
Christopher Otis, M.D., Pathology, Baystate Medical Center
Bert Zuckerman, Professor Emeritus, UMass Amherst
Surface membrane receptors play a vital role in the growth and proliferation
of cancer cells, and in signaling and recognition among these cells.
An objective of the current proposal is to broaden the understanding
of the mechanisms underlying carcinogenesis by experimentally perturbing
the functions of the glycolipid and/or glycoprotein membrane receptors
in primary human breast cultures and in a human breast-cancer cell
line. To achieve this objective we will establish primary breast
culture techniques, both dispersed-cell and explant culture, in
our laboratory. A second objective of this proposal is to investigate
the role of estrogens in the glycolipid/glycoprotein cell signaling
and adhesion. These studies will form the basis for future studies
on the role of environmental estrogens and anti-estrogens in tumor
formation.
It is only through advances in knowledge of the basic mechanisms
underlying breast cancer that there will be progress towards a cure.
The current project is designed to define parameters of recognition
and signaling between breast cells and breast-cancer cells, and
can lead to intervention in signals between these cells.
Effective Date – June 1, 2002
Role of Testosterone in Regulating Carbohydrate and Fat Utilization
during Exercise
Barry Braun, Ph.D., Exercise Science, UMass Amherst
Dan Grow, M.D., OB/GYN, Baystate Medical Center
Stuart Chipkin, M.D., Endocrinology, Gerontology, and Metabolism,
Baystate Medical
Robert Goulart, M.D., Baystate Medical Center
Compared with men, women "conserve carbohydrate" and use
more fat to provide energy for exercise at any given intensity.
The physiological mechanisms that explain this difference are unknown
but likely involve female (estrogen, progesterone) and/or male (testosterone)
sex hormones. We recently showed that boosting estrogen levels in
young women shifted energy use during exercise in the direction
of more fat by conserving both liver and muscle carbohydrate stores.
Adding progesterone completely reversed the estrogen effect by greatly
increasing use of muscle carbohydrate. We now propose to assess
the role of testosterone in regulating exercise substrate use by
greatly lowering its concentration in young men, and then adding
it back using transdermal patches.
The overall goal of this collaborative study is to gain a deeper
understanding of the roles played by the sex hormones in regulating
energy metabolism during exercise and their relative importance
in explaining differences between men and women. In addition to
shedding light on some basic biochemical mechanisms by which energy
use is mediated, results from these studies are expected to aid
in the design of nutrition and exercise recommendations for older
adults (who have low or non-existent levels of sex hormones) and
young amenorrheic women.
Effective Date – June 1, 2002
Molecular Mechanism of Early Pituitary Patterning in Zebrafish
and Human Embryos
Rolf Karlstrom, Ph.D., Biology, UMass Amherst
Theonia Boyd, M.D., Baystate Medical Center
The goal of this project is to apply our rapidly increasing knowledge
of
zebrafish pituitary development to our understanding of pituitary
formation in human embryos. More specifically, we are comparing
early
pituitary development between fish and humans and trying to understand
the
molecular mechanisms that help the pituitary become functionally
organized. We have shown that mutations in the hedgehog signaling
pathway
lead to a range of pituitary defects in zebrafish and that hedgehog
signaling is necessary for several discrete stages of zebrafish
pituitary
development. Importantly, there are a number of human developmental
disorders affecting pituitary development that have been linked
to
mutations in the hedgehog signaling pathway (e.g. Holoprosencephaly
and
Pallister-Hall syndrome). We are now comparing the development of
early
regionalization in the zebrafish pituitary to that in the human
pituitary
and ultimately hope to determine whether specific defects in Hh
signaling
can lead to specific human pituitary deficiencies. The analysis
of the
experimentally accessible zebrafish embryo, when combined with a
direct
comparison to human embryology, promises to greatly increase our
understanding of human pituitary development and birth defects that
affect the pituitary.
Effective Date – June 1, 2002
Automated Estimation of Left Ventricular Volume Using 3D Echocardiography
Patrick Kelly, Ph.D., Electrical and Computer Engineering UMass
Amherst
Francis Lee, M.D., Biomedical Technology, Baystate Medical Center
Despite recent clinical success with three-dimensional echocardiography
(3DE), the technology has been limited to use only by echocardiographers.
However, the clinical need for rapid non-invasive assessment of
cardiac function exists in a wider clinical setting, such as the
ICU and the emergency/trauma room. In those settings without specially
trained echocardiographers, differential diagnosis between the normal
and the diseased heart may require detailed quantitation of the
key parameters of the left ventricular (LV) functional mechanics.
Although three-dimensional echocardiography (3DE) has been used
recently to quantify global LV function, a reliable methodology
has not been developed for a rapid and detailed quantitative analysis
of both the regional and global LV function in attempts to differentiate
among the various cardiac conditions. The investigators of this
project propose to develop methods to make 3DE a quantitative cardiac
assessment tool, which may then be used independently.
Effective Date – June 1, 2002
Computer-Aided 3-Dimensional Evaluation of the Volume and Shape
of Ductal Carcinoma in Situ in Excisional Biopsies of the Breast
and their Relationship to Risks of Residual Disease and Recurrence
Monroe Rabin, Ph.D., Physics, UMass Amherst
Robert Goulart, M.D., Pathology, Baystate Medical Center
Franklin Periera, Graduate Student, Electrical & Computer Engineering,
UMass
Monroe S. Z. Rabin, Ph.D., Physics and Astronomy, UMass
Robert A.Goulart, M.D., Pathology, Baystate
Martin Bur, M.D., Pathology, Mercy Hospital
Franklin Periera, Graduate Student, Electrical & Computer Engineering,
UMass
We are studying a form of breast cancer called ductal carcinoma
in situ and are developing a computer-based approach to enable pathologists
to better record relevant data and predict the likelihood of residual
and recurrent disease. We begin by enabling the pathologist to record,
in a computer file, necessary information about each case (patient
name, case number, dimensions of the excised tissue, etc.). Then
the pathological slides are scanned into the computer and the program
will find the boundary of the tissue for each slice, and enable
the pathologist to indicate the locations of disease. After all
slides have been scanned a 3-dimensional reconstruction of the tissue
along with observed disease sites and their distances to the nearest
tissue margin will be generated and be visible on a computer monitor,
to enable the pathologist to better estimate the probabilities that
there is residual disease outside the margins of the excised tissue
and that the disease will recur. The computer file containing all
of this information will become part of the pathological report
and be accessible at a later time if re-evaluation of the case is
desired. If further treatment is needed, the 3-dimensional computer
reconstruction will aid the surgeon and radiation oncologist in
treatment planning.
Effective Date – June 1, 2002
Chlamydia Pneumoniae in Healthy Volunteer Donor Blood Samples:
An Unsuspected Source of Pathogen Transmission?
Elizabeth Stuart, Ph.D., Microbiology, UMass Amherst
Chet Andrzejewski, M.D., Ph.D., Transfusion Medicine, Blood Banking
and Immunology, Baystate Medical Center
Chlamydiae, especially C. pneumoniae, are intracellular
pathogens that
can disseminate to various sites and are associated with an array
of
symptoms and highly debilitating sequelae. In addition, chlamydial
infections frequently go undiagnosed. Earlier basic research demonstrated
intermediate filaments (IF), a normal class of host cell cytoplasmic
protein, accumulate in the inclusion as chlamydia replicate, are
released
along with the newly formed, infectious chlamydial elementary bodies
(EBs), and also adhere to the infectious EBs themselves. Therefore,
IF
would be presented to the host immune system along with highly antigenic
chlamydial surface proteins. The research examines serum specimens
exhibiting autoantibodies to cytoplasmic proteins during routine
ANA
screening. The aim is to detect possible occult chlamydial infections
in
this population and perhaps identify an unrecognized host target
of
antibody damage. Anti-chlamydia and anti-IF antibody titers will
be
assessed and levels compared with levels from the same assessments
carried
out with sera from patients with diagnosed chlamydia associated
pathologies, such as PID, cardiac disease, chronic obstructive pulmonary
disease (COPD) or atherosclerosis and with healthy controls.
Effective Date - June 1, 2002
Development of Computer Vision Techniques to Support the Clinical
Study of Ischemic
Stroke Treatment
Edward Riseman, Ph. D., Computer Science, UMass
Joseph Horowitz, Ph. D., Mathematics and Statistics, UMass
Allen Hanson, Ph. D., Computer Science, UMass
Richard Hicks, M.D., Radiology, Baystate Medical Center
Robert Kirkwood, M. D., Radiology, Baystate
George Howard, M. D., Neurology, Baystate
The goal of this study is automatic segmentation of stroke lesions
in MRI data so that lesion volumes can be tracked over time and
as a function of varying treatment. Multiple techniques and hybrid
versions have been developed and are being compared, including statistical
regularization (packing), deformable models (snakes), nonlinear
diffusion, and level sets. Results from these algorithms are being
compared with physician and radiologist manual segmentations.
Effective Date - January 1, 2002
Genetic Epidemiology of Fetal Growth Restriction
Ronald Adkins, Ph.D., Biology, UMass
Theonia Boyd, M.D., Pathology, Baystate
Low birth weight babies have a higher rate of newborn death and
illness, and people born at a low birth weight have higher rates
of heart disease, stroke and adult-onset diabetes. Many environmental
and genetic factors play a role in fetal growth restriction, and
our research focuses on the genetic contribution to fetal growth.
Recently, we have begun using a revolutionary new technique that
allows us to track the activity of thousands of genes simultaneously.
By using DNA microarrays, we will compare the activity of genes
in normal birth weight and low birth weight babies to find those
genes that behave differently in the two groups. This knowledge
will allow us to devote future research to those genes that may
be useful for predicting low birth weight early in pregnancy and
in providing medical treatments that may promote growth in the uterus.
Effective Date - January 1, 2002
Functional Investigations of Optic Input to the Serotonin System
Katherine Fite, Ph.D., Psychology, UMass
Warren Foote, Ph.D., Medical Research, Baystate
Our present research is designed to understand the functional role
of visual input to the
serotonin system using a highly visual rodent species for investigation.
Major research
objectives include: (1) investigation of how and where in the DRN
visual stimulation
may alter the metabolic activity of DRN neuron by using a metabolic
labeling technique
for glucose activity. Several kinds of visual stimulation will be
presented, including
exposure to a sustained, high-intensity stimulus, exposure to a
flashing light presented at different flash frequencies, and exposure
to a large-field, moving pattern presented at different velocities.
Experimental animals will be compared with controls exposed only
to dim illumination. (2) A second set of experiments involves the
development of experimental microdialysis techniques to determine
whether extracellular serotonin varies in the DRN over the 24-hour,
light:dark cycle. Also, visual stimulation will be used to determine
whether a 30-minute presentation of high-intensity light stimulation
presented at selected times in the 24-hour light:dark cycle can
alter baseline, extracellular serotonin levels in the DRN.
Effective - January 1, 2002
Publications:
Fite, K. V., Birkett, M., Smith, A., Bengston, L. and Foote, W.
Retinal ganglion cells projecting to the dorsal raphe nucleus and
lateral geniculate in Mongolian gerbils. Neuroscience Abstracts,
2002, 761.4 (Manuscript by same title: submitted for review to Brain
Research).
Fite, K. V. and Janusonis, S. Optic afferents to the parabrachial
nucleus. Brain Research 2002, 943: 9-14.
Janusonis, S., Fite, K. V. and Bengston, L. Subdivisions of the
dorsal raphe nucleus projecting to the lateral geniculate nucleus
and primary visual cortex of the Mongolian gerbil. NeuroReport (in
press)
Wu, P. (MS project) “The effects of Flashing Light on c-Fos
Expression in the Dorsal Raphe Nucleus of the Mongolian Gerbil.”
August 20, 2002. (journal manuscript in preparation)
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