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 S. Z. Rabin, Ph.D., Physics and Astronomy, UMass
Robert A.Goulart, M.D., Pathology, Baystate
Martin Bur, M.D., Pathology, Baystate
Joseph J. Regensburger, Graduate Student, Physics, UMass
We are studying a particular form of breast cancer - ductal carcinoma
insitu. We are
developing a computer-based approach that enables the pathologist
to record, in a
computer file, necessary information about each case (patient name,
case number,
dimensions of the excised tissue, etc.). The program will then find
the boundary of the
tissue for each slice, and enable the pathologist to indicate the
locations of disease. 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 probability
that there is residual
disease outside the margins of the excised tissue. 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, 2001
Exercise, Ischemia Reperfusion, Lipid Peroxidation and Antioxidant
Supplementation
Priscilla Clarkson, Ph.D., Exercise Science, UMass
Paul Lahti, Ph.D., Chemistry, UMass
Joel Berman, M.D., Vascular Service, Baystate
Amy Howell, Graduate Student, Exercise Science, UMass
The primary goal of this project is to determine the relationship
between blood flow and
oxidative stress during a novel exercise involving static contractions
of the forearm
muscles in human volunteers. This exercise can partially reduce
blood flow during the
contraction, and upon relaxation, there is an increase in blood
flow, known as hyperemia.
We believe that the hyperemic response may be the cause of the oxidative
stress that
has been observed with this exercise. To test our hypothesis, we
will assess blood
flow using Doppler technology , and we will measure novel markers
of oxidative stress.
A second experiment will determine if a unique combination of dietary
antioxidants will
reduce oxidative stress produced from this exercise. Results of
this experiment will
provide insight on how repetitive exercise can result in muscle
injury by oxidative stress
and whether a dietary intervention may prevent such injury.
Effective Date - June 1, 2001
Molecular Mechanisms of Early Pituitary Patterning in Zebrafish
and Human Embryos
Rolf Karlstrom, Ph.D., Biology, UMass
Theonia Boyd, M.D., Pathology, Baystate
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, 2001
Intermediate Filament Specific Auto-autobodies in Patient Specimen:
A Correlate of Anti-Chlamydial Antibody Titer?
Elizabeth Stuart, Ph.D., Microbiology, UMass
Chester Andrzejewski, Ph. D., M.D., Pathology, Baystate
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, 2001
Estimation and Tracking of the Left Ventricle Boundary in Ultrasound
Image Sequences
Patrick Kelly, Ph.D., Electrical & Computer Engineering, UMass
Haluk Derin, Ph.D., Electrical & Computer Engineering, UMass
Francis Lee, M.D., Surgery, Baystate
Dennis Tighe, M.D., Cardiology, Baystate
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 - January 1, 2001
Autoantibody Diversity and Pathogenicity in Autoimmune Disorders
Richard Goldsby, Ph.D., Biology, Amherst College
Chester Andrzejewski, Ph.D., M.D., Bone Marrow & Transplant
Unit, Baystate
The goals of this study are to investigate the pathogenic potentials
of autoantibodies directed against red blood cells (RBC) and the
cells producing them. The results of this investigation should bring
further insight into the etiopathogenesis of autoimmune diseases
and facilitate their diagnosis and clinical management.
Effective Date - January 1, 2001
Genetic Epidemiology of Fetal Growth Restriction
Ronald Adkins, Ph.D., Biology, UMass
Theonia Boyd, M.D., Pathology, Baystate
Gabriel Cohn, M.D., Obstetrics & Gynecology, Baystate
This project is the initial phase of a long-term study of the role
of genetic and hormonal variation in fetal growth. Fetal growth
restriction (FGR) is a serious health risk factor. Infants in the
lowest 7.5 percent of birth weight account for two-thirds of infant
deaths. Among the FGR infants that live, there is an increased frequency
of hypoglycemia, hypothemia, polycythemia, neurodevelopmental deficits
and cerebral palsy. Later in life the risk of hypertension, cardiovascular
disease, and non-insulin dependent diabetes is elevated. Therefore,
FGR infants account for a substantial proportion of early death
and mobidity and chronic illness. The ability to diagnose and to
treat FGR early in gestation has enormous potential to reduce childhood
death and suffering and to save considerable money devoted to its
outcomes.
Effective Date - January 1, 2001
Presentations:
Adkins, Ronald, (2001). Bioinformatic and Genomic Analyses of the
Growth Hormone Locus and Fetal Growth. University of Texas-San Antonio.
Adkins, Ronald, (2001). Genomics and Bioinformatics of the Growth
Hormone Locus and Fetal Growth, University of Tennessee-Memphis.
Effects of Estrogen and Progesterone on Substrate Utilization
During Exercise
Barry Braun, Ph.D., Exercise Science, UMass
Stuart Chipkin, M.D. Endocrinology, Diabetes and Metabolism, Baystate
Daniel Grow, M.D., InVitro Fertilization, Baystate
Halina Wiczyk, M.D., Reproductive Endocrinology, Baystate
Many researchers have speculated that, in women, the relative abundance
of the ovarian hormones estrogen and/or progesterone, may serve
to alter the regulation of metabolic pathways to favor fat oxidation
and conserve carbohydrate. The goal of this study is to gain a deeper
understanding to the roles played by estrogen and progesterone in
regulating substrate metabolism during exercise and their importance
in mediating the observed sex differences.
Effective Date - January 1, 2001
Publications:
D'Eon, T., and Braun, B. The role of the ovarian hormones in mediating
gender differences in carbohydrate and fat utilization at rest and
during exercise. Journal of Women's Health and Gender-Based Medicine,
in press.
Presentations:
D'Eon, T. M., Grow, D., Chipkin, S. R., Sharoff, C., and Braun B.
Effects of estrogen and progesterone on carbohydrate utilization
during exercise in women. Presented at the New England Chapter of
the American College of Sports Medicine, November 2001.
Sharoff, C., D'Eon, T. M., Chipkin, S. R., Grow, D., and Braun,
B. Regulation of insulin sensitivity and leptin concentrations by
estrogen and progesterone. Presented at the American College of
Sports Medicine, June 2002.
D'Eon, T.M., Grow, D., Chipkin, S. R., Sharoff, C., and Braun, B.
Regulation of carbohydrate kinetics and oxidation by estrogen and
progesterone during exercise in women. Presented at the American
College of Sports Medicine, June 2002.
Extramural Funding:
Glass Charitable Trust (9/01/01-8/31/03) $168,500
Genomic and Phenotypic Analysis of Clinical Isolates of the
Bacterium, Burkholderia cepacia.
Thomas Lessie, Ph.D., Microbiology, UMass
Robert Gerstle, M.D., Cystic Fibrosis Program, Baystate
Members of the Burkholderia cepacia complex have emerged as a serious
cause of respiratory tract infections in patients with cystic fibrosis.
The aims of this research are to examine whether cystic fibrosis
patients infected by bacteria belonging to the B. cepacia complex
have been colonized with the same or different strains and to gain
insight into mechanisms that contribute to the ability of members
of the B. cepacia complex to adapt from a free-living to a host-associated
state.
Effective Date - January 1, 2001
A Biomedical Evaluation of Lumbar Spine Fixation
Robert Gao, Ph.D., Mechanical & Industrial Engineering, UMass
Scott Cowan, M.D., Orthopedic Surgery, Baystate
Francis Lee, M.D., Surgery, Baystate
The goal is to develop an optimum fixation technique that maximizes
spine fusion potential and thereby improving patient care and reducing
health care expenditures by decreasing revision surgery rates. The
specific objective of this research is to develop a systematic biomechanical
evaluation procedure for investigating the stability of lumbar spine
fixation techniques.
Effective Date - January 1, 2001
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