U.S. patent application number 13/609537 was filed with the patent office on 2013-01-10 for libraries and data structures of materials removed by debulking catheters.
This patent application is currently assigned to TYCO HEALTHCARE GROUP LP. Invention is credited to John B. SIMPSON, Angela SOITO.
Application Number | 20130013216 13/609537 |
Document ID | / |
Family ID | 37889556 |
Filed Date | 2013-01-10 |
United States Patent
Application |
20130013216 |
Kind Code |
A1 |
SOITO; Angela ; et
al. |
January 10, 2013 |
LIBRARIES AND DATA STRUCTURES OF MATERIALS REMOVED BY DEBULKING
CATHETERS
Abstract
Material removed by a debulking catheter from a body lumen can
be preserved. Materials can be collected from many different
patients and/or from multiple procedures on individual patients.
Data which describe the properties or qualities of the removed
material and/or the patient and/or the patient's family or
environment can be stored on computer readable media. The stored
data can be used to draw correlations, to stratify groups of
patients, to provide risk assessments, to provide diagnoses and/or
prognoses. Further tests can be done on the stored materials at
later times after the procedures have been completed.
Inventors: |
SOITO; Angela; (Oakland,
CA) ; SIMPSON; John B.; (Woodside, CA) |
Assignee: |
TYCO HEALTHCARE GROUP LP
Mansfield
MA
|
Family ID: |
37889556 |
Appl. No.: |
13/609537 |
Filed: |
September 11, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12880010 |
Sep 10, 2010 |
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13609537 |
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11230924 |
Sep 21, 2005 |
7794413 |
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12880010 |
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11108887 |
Apr 19, 2005 |
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11230924 |
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Current U.S.
Class: |
702/19 |
Current CPC
Class: |
A61B 10/0096 20130101;
A61B 10/02 20130101; A61B 17/320758 20130101; A61B 90/90 20160201;
A61B 10/0266 20130101; A61B 2017/320791 20130101; A61B 17/320783
20130101; A61B 2017/00778 20130101; G16H 50/20 20180101; G16H 10/60
20180101; A61B 10/04 20130101; G16H 10/40 20180101; Y02A 90/10
20180101; A61B 17/320725 20130101 |
Class at
Publication: |
702/19 |
International
Class: |
G06F 19/10 20110101
G06F019/10 |
Claims
1. An article of manufacture, said article comprising: a computer
readable media having computer executable instructions stored
thereon, which when executed by a computer causes the computer to
perform an operation comprising: receiving a set of data fields
derived from a patient sample, wherein the set of data fields
comprise: a first value corresponding to a property of a first
tissue sample comprising tissue excised from an inner surface of a
vascular lumen of a patient, and a second value corresponding to
data identifying the patient; storing the set of data fields;
correlating the first and second values; and diagnosing the
patient.
2. The computer readable media of claim 1 further comprising: a
third data field comprising a value corresponding to cardiac health
of the patient.
3. The computer readable media of claim 1 wherein the property is a
level of a marker in the tissue.
4. The computer readable media of claim 1 wherein the property is
composition of the tissue sample.
5. The computer readable media of claim 1 wherein the property is
histologic characterization of the tissue.
6. The computer readable media of claim 1 wherein the property is
an immunochemical characterization of the tissue.
7. The computer readable media of claim 1 wherein the property is a
genomic characteristic.
8. The computer readable media of claim 1 wherein the property is
level of a mRNA.
9. The computer readable media of claim 1 wherein the property is
location of the vascular lumen from which the tissue was
excised.
10. The computer readable media of claim 1 wherein the property is
volume or mass of the excised tissue.
11. The computer readable media of claim 1 further comprising: a
fourth data field comprising a value corresponding to a
characteristic of the patient's blood.
12. The computer readable media of claim 11 wherein the patient's
blood was withdrawn at the time of or before tissue excision.
13. The computer readable media of claim 1 further comprising: a
fifth data field comprising a value corresponding to family history
of the patient.
14. The computer readable media of claim 1 further comprising: a
sixth data field comprising a value corresponding to the patient's
medical history.
15. The computer readable media of claim 1 further comprising: a
seventh data field comprising a value corresponding to a property
of a second tissue sample excised from a vascular lumen of the
patient at a distinct time.
16. The computer readable media of claim 15 wherein the second
tissue sample is excised from the same vascular lumen as the first
tissue sample.
17. The computer readable media of claim 1 further comprising: an
eighth data field comprising a value corresponding to a property of
a second tissue sample excised from distinct vascular lumen of the
patient on the same day as the first tissue sample.
18. The computer readable media of claim 1 wherein said media are
associated with one or more excised tissue samples in labeled
storage containers, wherein the computer readable media comprise a
ninth data field which comprises a value which links the labeled
storage containers with a value in the second data field.
19. The computer readable media of claim 1 wherein said media are
associated with one or more excised tissue samples in labeled
storage containers, wherein the storage containers are labeled with
a value in the second data field.
20. The computer readable media of claim 1 wherein said media are
associated with one or more samples in labeled storage containers,
wherein the one or more samples comprise a component extracted or
processed from an excised vascular tissue from a vascular lumen of
the patient, wherein the component is selected from the group
consisting of DNA, RNA, cDNA, and protein, and wherein the computer
readable media comprise a tenth data field which comprises a value
which links the labeled storage containers with a value in the
second data field.
21. The computer readable media of claim 1 wherein said media are
associated with one or more samples in labeled storage containers,
wherein the storage containers are labeled with a value in the
second data field, wherein the samples comprise a component
extracted or processed from an excised vascular tissue from a
vascular lumen of the patient, wherein the component is selected
from the group consisting of DNA, RNA, cDNA, and protein.
Description
CROSS-REFERENCES TO RELATED APPLICATION
[0001] This application is a continuation and claims the benefit of
priority under 35 U.S.C. .sctn.120 of U.S. patent application Ser.
No. 12/880,010, filed Sep. 10, 2010, which is a continuation of
U.S. patent application Ser. No. 11/230,924, filed Sep. 21, 2005,
now U.S. Pat. No. 7,794,413 B2, issued Sep. 14, 2010, which is a
continuation-in-part of U.S. patent application Ser. No.
11/108,887, filed Apr. 19, 2005, now abandoned, the contents of
each of which are hereby incorporated by reference herein.
TECHNICAL FIELD OF THE INVENTION
[0002] The present invention relates generally to computer readable
media for storing data relating to patients and tissue samples
excised from their vascular or other lumens. The data may be used
to analyze current, past, or future patient health, to assess
treatments, to evaluate drugs, to evaluate risk factors, and to
determine proposed treatments or assessments.
BACKGROUND OF THE INVENTION
[0003] Cardiovascular disease frequently arises from the
accumulation of atheromatous material on the inner walls of
vascular lumens, particularly arterial lumens of the coronary and
other vasculature, resulting in a condition known as
atherosclerosis. Atherosclerosis occurs naturally as a result of
aging, but may also be aggravated by factors such as diet,
hypertension, heredity, vascular injury, and the like. Atheromatous
and other vascular deposits restrict blood flow and can cause
ischemia which, in acute cases, can result in myocardial
infarction. Atheromatous deposits can have widely varying
properties, with some deposits being relatively soft and others
being fibrous and/or calcified. In the latter case, the deposits
are frequently referred to as plaque.
[0004] One conventional treatment for cardiovascular disease is the
use of stents. Endoluminal stents are commonly used to treat
obstructed or weakened body lumens, such as blood vessels and other
vascular lumens. Once deployed in the blood vessel, the stent can
remain in the body lumen where it will maintain the patency of the
lumen and/or support the walls of the lumen which surround it. One
factor impeding the success of stent technology in endoluminal
treatments is the frequent occurrence of in-stent restenosis,
characterized by proliferation and migration of smooth muscle cells
within and/or adjacent to the implanted stent, causing reclosure or
blockage of the body lumen.
[0005] Atherosclerosis and restenosis can be treated in a variety
of ways, including drugs, bypass surgery, and a variety of
catheter-based approaches which rely on intravascular debulking or
removal of the atheromatous or other material occluding a blood
vessel. Of particular interest to the present invention, a variety
of methods for cutting or dislodging material and removing such
material from the blood vessel have been proposed, generally being
referred to as atherectomy procedures. Atherectomy catheters
intended to excise material from the blood vessel lumen generally
employ a rotatable and/or axially translatable cutting blade which
can be advanced into or past the occlusive material in order to cut
and separate such material from the blood vessel lumen.
[0006] There is a need in the art for methods and tools for
managing and storing materials removed from body lumens. There is a
need in the art for methods and tools for managing and storing
information related to and/or derived from materials removed from
body lumens.
BRIEF SUMMARY OF THE INVENTION
[0007] One aspect of the invention provides one or more computer
readable media having a data structure stored thereon. The data
structure comprises a first data field comprising a value
corresponding to a property of a first tissue sample excised from a
vascular lumen of a patient and a second data field comprising data
identifying the patient. Optional additional data fields include a
third data field comprising a value corresponding to cardiac health
of the patient, a fourth data field comprising a value
corresponding to a characteristic of the patient's blood, a fifth
data field comprising a value corresponding to family history of
the patient, a sixth data field comprising a value corresponding to
the patient's medical history, a seventh data field comprising a
value corresponding to a property of a second tissue sample excised
from a vascular lumen of the patient at a distinct time, an eighth
data field comprising a value corresponding to a property of a
second tissue sample excised from distinct vascular lumen of the
patient on the same day as the first tissue sample, a ninth data
field which comprises a value which links a labeled storage
container comprising excised tissue with a value in the second data
field, a tenth data field which comprises a value which links the
labeled storage containers comprising a component extracted or
processed from an extracted tissue with a value in the second data
field. These can be used separately or cumulatively. These data
fields are not an exclusive list of possible useful data
fields.
[0008] For a further understanding of the nature and advantages of
the invention, reference should be made to the following
description.
DETAILED DESCRIPTION OF THE INVENTION
[0009] Data collected related to samples of materials removed from
body lumens can be stored in data structures. The stored data can
be used to draw correlations, to stratify groups of patients, to
provide risk assessments, to provide diagnoses and/or prognoses.
Libraries of samples can be assembled to be used for studies of
drugs, candidate drugs, toxins, therapeutic treatments, etc. The
samples can be preserved according to any method known in the art.
Samples may be frozen, for example, in liquid nitrogen. They may be
preserved in paraffin, dried, freeze dried, etc. Samples may be
treated to achieve a purified or semi-purified component of the
sample. Samples may be treated, for example to extract DNA or
protein. Samples may be treated to extract mRNA and to preserve it
or "convert" it to cDNA. Desirably, samples are stored in a
consistent and systematic way so that patient information remains
associated with the samples so that patient outcome or other data
collected at a later time can be associated with the sample
concurrently or at a later time.
[0010] Samples within a library can be stored and associated with
information related to the sample itself, e.g., its properties, and
the patient from whom the sample was excised. Other information
that can be associated with the sample include results of analyses
of the sample, patient history information, patient outcome
information, drug efficacy information, therapeutic efficacy
information, family history, factors of the patient related to
cardiac disease, factors of the patient related to non-cardiac
disease. In some cases this information may be stored without
association with the physical samples. Patient identifying
information may be coded so that confidentiality can be maintained
while still permitting correlation of various patient attributes
with the samples.
[0011] One or more aspects of the invention may be embodied in
computer-usable data and computer-executable instructions, such as
in one or more program modules, executed by one or more computers
or other devices. Generally, program modules include routines,
programs, objects, components, data structures, etc. that perform
particular tasks or implement particular abstract data types when
executed by a processor in a computer or other device. The computer
executable instructions may be stored on a computer readable medium
such as a hard disk, optical disk, removable storage media, solid
state memory, RAM, etc. As will be appreciated by one of skill in
the art, the functionality of the program modules may be combined
or distributed as desired in various catheters. In addition, the
functionality may be embodied in whole or in part in firmware or
hardware equivalents such as integrated circuits, field
programmable gate arrays (FPGA), and the like. Particular data
structures may be used to more effectively implement one or more
aspects of the invention, and such data structures are contemplated
within the scope of computer executable instructions and
computer-usable data described herein.
[0012] Data fields which are present in the data structures of the
present invention may include one or more of those discussed below.
A first data field comprises a value corresponding to a property of
a first tissue sample excised from a vascular lumen of a patient.
The tissue sample is typically material that has been excised from
a body lumen. The body lumen is often a vascular lumen. The
property may be, for example, level of a marker in the tissue,
composition of the tissue sample, histologic characterization,
immunochemical characterization of the tissue, a genomic
characteristic of the tissue, level of a mRNA in the tissue,
location of the vascular lumen from which the tissue was excised,
or volume or mass of the excised tissue. Any property of the tissue
may be stored in this data field. A second data field may comprise
data identifying a patient. The patient data may be anonymous or
identify a person. If anonymous, the code will uniquely identify a
patient's characteristics, without actually identifying the
patient. Thus data can be used for studies, without divulging
identities of the patients.
[0013] An optional third data field comprises a value corresponding
to cardiac health of the patient. Such values may, for example,
relate to past infarct history, past angioplasty procedures, or
past cholesterol values. A possible fourth data field comprises a
value corresponding to a characteristic of the patient's blood. The
blood may have been withdrawn at the time of or before tissue
excision. The blood characteristic may be any known in the art,
including but not limited to, sedimentation rate, red blood cell
count, white blood cell count, triglycerides, and C-reactive
protein.
[0014] An optional fifth data field comprises a value corresponding
to family history of the patient. Thus a value can be assigned to
family history events based on degree of relatedness of the family
member and the severity of the event. An optional sixth data field
comprises a value corresponding to the patient's own medical
history. This history includes but is not limited to cardiac
related events. Thus other medical history events can be recorded
which may not be currently known to be associated with vascular
occlusion, but which may in fact have a correlation. Such data will
make the data structure useful for discovering new associations,
risks, and mechanisms. Such data may also be useful in stratifying
patients for treatment regimens and for drug trials.
[0015] An optional seventh data field comprises a value
corresponding to a property of a second tissue sample excised from
a vascular lumen of the patient at a distinct time from the first
tissue sample. The second tissue sample can be excised from the
same vascular lumen as the first tissue sample or from a different
vascular lumen of the patient. An optional eighth data field
comprises a value corresponding to a property of a second tissue
sample excised from a distinct vascular lumen of the patient on the
same day as the first tissue sample.
[0016] The computer readable media can optionally be associated
with one or more excised tissue samples in labeled storage
containers. Labeled storage containers includes storage containers
that are in fixed positions or parts of a machine or apparatus
which positions are themselves labeled. If such stored tissue
samples are associated with the data structure, an optional ninth
data field can be used which comprises a value which links the
labeled storage containers with a value in the second data field.
Alternatively, the labeled storage containers may be labeled with a
value in the second data field. Alternatively or optionally the
data structure can be associated with labeled storage containers in
which one or more samples comprise a component extracted or
processed from an excised vascular tissue from a vascular lumen of
the patient. Such components include DNA, RNA, cDNA, lipid,
carbohydrate, and protein. In such a case, the data structure can
optionally comprise a tenth data field in which a value which links
the labeled storage containers with a value in the second data
field is present. Alternatively, such labeled storage containers
can be labeled with a value in the second data field. There is no
significance to the numbers of the data fields as used herein. Data
fields with sequential numbers need not be used. Thus, for example,
a structure can comprise data fields with fields 1, 2, 5, and 6
without data fields 3, 4, 7, 8, 9, and 10.
[0017] Catheters can be used to debulk atheroma and other occlusive
material from diseased body lumens, and in particular coronary
arteries, de novo lesions, and in-stent restenosis lesions.
Catheters are also suitable for treating stenoses of body lumens
and other hyperplastic and neoplastic conditions in other body
lumens, such as the ureter, the biliary duct, respiratory passages,
the pancreatic duct, the lymphatic duct, and the like. Neoplastic
cell growth will often occur as a result of a tumor surrounding and
intruding into a body lumen. Debulking of such material can thus be
beneficial to maintain patency of the body lumen. The debulked
material is typically a continuous strip of tissue removed from the
lumen interior wall that ranges from about 1 mg to about 2000 mg;
it retains the structure of the tissue prior to removal. The
continuous strip or strand of tissue removed will typically have a
length that is longer than a length of the cutting window. The data
storage and access structures of the present invention can be
applied to a variety of occlusive, stenotic, or hyperplastic
material in a variety of body lumens.
[0018] Apparati will generally comprise catheters having catheter
bodies adapted for intraluminal introduction to the target body
lumen. The dimensions and other physical characteristics of the
catheter bodies will vary significantly depending on the body lumen
which is to be accessed. In the exemplary case of atherectomy
catheters intended for intravascular introduction, the proximal
portions of the catheter bodies will typically be very flexible and
suitable for introduction over a guidewire to a target site within
the vasculature.
[0019] Generally, the smooth muscle cells of the stenotic material
show a range of phenotypes, but most of the cells contained
myofilaments as well as a relatively high amount of synthetic
organelles, such as rough endoplasmic reticulum, Golgi apparatus
and mitochondria. One can determine how much stenotic tissue is
retrieved in an access procedure. One can determine presence or
absence of inflammatory cells in excised tissue. One can determine
the presence of inflammatory cells within critical areas of plaque.
Determination of the location and degree of inflammatory cells
present may facilitate a more informed characterization or
diagnosis.
[0020] The material removed from a catheter collection chamber, or
a portion thereof, can be placed in a preserving agent, a tissue
fixative, and or a preparation agent suitable for a desired test
prior to testing the material. The material removed from the
patient by this method is typically at least one or more continuous
strip(s) of material that maintains the structure of the material
in vivo. The quantity of material removed by the method can be from
about 1 mg to about 2000 mg. Typically the amount of material is
about 1 mg to about 100 mg, about 100 mg to about 200 mg, about 200
mg to about 300 mg, 300 mg to about 400 mg, 400 mg to about 500 mg,
500 mg to about 600 mg, about 600 mg to about 700 mg, 700 mg to
about 800 mg, or about 800 mg to about 2000 mg. In a typical
procedure about 400 mg to about 600 mg of material is removed and
available for testing and/or storage. Collection of one or more
continuous strips of material from the inner surface of a lumen may
be longer than a largest dimension of the cutting window of a
catheter used to remove the material. In a particular example, the
material can comprise plaque tissue. The material can be collected
from a single site or at least one additional site in the same or a
different body lumen.
[0021] Excised material can be stored to permit later confirmatory
or additional testing without having to subject the patient to
another percutaneous translumenal lumenectomy procedure. The
material can be tested by genomic screening, DNA hybridization, RNA
hybridization, gene expression analysis, PCR amplification,
proteomic testing, drug efficacy screening, presence of one or more
protein markers, presence of one or more DNA markers, presence of
one or more RNA markers, histological testing, histopathology,
cytopathology, cell and tissue type analysis, biopsy, and the like.
Additionally, the material can also be cultured and/or tested to
determine sensitivity to drugs, toxins, and the like. The material
can be tested for the presence of DNA, RNA, or protein markers
comprising a smooth muscle proliferative promoter, a smooth muscle
proliferative inhibitor, a cellular marker, an apoptotic marker, a
cell cycle protein, a transcriptional factor, a proliferative
marker, an endothelial growth factor, an adhesion molecule, a
cytokine, a chemokine, a chemokine receptor, an inflammation
marker, a coagulation factor, a fibrinolytic factor, an oxidative
stress related molecule, an extracellular matrix molecule, an
interleukin, a growth factor, a glycoprotein, a proteoglycan, a
cell-surface marker, a serum marker, and or an immune factor, and
the like. Tests for each of these molecules and others are well
known to the skilled artisan as are methods and preservatives,
fixatives and preparation agents for adding to all or a portion of
the material collected. The results of any of the tests for
properties of the removed material can be stored in a data
structure according to the invention.
[0022] The material produced by a lumenectomy comprises at least
one continuous tissue stand collected in vivo from an inner surface
of the body lumen of a subject. The body lumen can be an artery or
other lumen or vessel of the circulatory system and the material
can comprise arterial plaque and associated tissue. The continuous
strand of tissue provided by the disclosed methods provide a
sufficient amount of high quality material to successfully perform
at least one or more tests comprising, for example, genomic
screening, DNA hybridization, RNA hybridization, gene expression
analysis (including serial analysis of gene expression), PCR
amplification, proteomic testing, drug efficacy screening, a
determination of the presence of one or more protein markers, a
determination of the presence of one or more DNA markers, a
determination of the presence of one or more RNA markers,
histological testing, histopathology, cytopathology, cell type
analysis, tissue type analysis, biopsy, and the like. Methods for
performing each of the tests are well known to the skilled artisan.
It is also well known that material collected from a patient can be
added to a preserving agent, tissue fixative, or a preparation
agent in order to prepare at least a portion of collected material
for the desired test. Agents known in the art for preserving,
fixing or preparing the material for later use include, for
example, saline, heparinized saline, liquid nitrogen, formalin, a
membrane lysis agent, a RNA or DNA preparation agent, and the like.
Particular tests that can be carried out successfully on the
excised lumenectomy material include, but are not limited to,
histology techniques including hematoxylin and eosin staining,
connective tissue staining, carbohydrate staining, and lipid
staining, and the like. In addition, tissue array testing, enzyme
histochemistry, transmission electron microscopy, immunohistology,
immunocytochemistry, immunoassays, immunofluorescent assays,
immunoprecipitation assays, ELISA, flow cytometry, fluorescent
activated cell sorting, radioimmunochemistry, electrophoresis,
two-dimensional gel electrophoresis, Western blotting, protein
sequencing, mass spectrometry, proteomic analysis, and protein
microarray analysis can be carried out. Further, cytogenetic
testing, Nothern blotting, RNase protection assays, in situ
hybridization assays, DNA microarray testing, reverse transcription
polymerase chain reaction PCR (RT-PCR), Southern blotting, DNA
sequencing, PCR amplification, single strand conformational
polymorphism assays, single strand polymorphism (SNP) assays, and
serial analysis of gene expression (SAGE) assays can be
successfully carried out with the lumenectomy materials
compositions. The compositions can also be prepared for storage for
later testing.
[0023] Table 1 shows relevant markers for which the excised
vascular material can be tested for expression, and about which
data can be stored.
TABLE-US-00001 TABLE 1 Markers upregulated in vascular disease
AA775616 osteopontin AA682386 oxidised low density lipoprotein
(lectin-like) receptor 1 AA969504 interferon, gamma AA102526
interleukin 8 BU631490 tissue inhibitor of metalloproteinase 2 NM
002356 myristoylated alanine-rich protein kinase C substrate NM
000930 plasminogen activator, tissue NM 002117 major
histocompatibility complex, class I, C AI129421 interleukin 18
(interferon-gamma-inducing factor) W51794 matrix metalloproteinase
3 (stromelysin 1, progelatinase) AA143201 matrix metalloproteinase
1 (interstitial collagenase) N94616 laminin, alpha 4 NM 021999
integral membrane protein 2B NM 000584 interleukin 8 NM 002510
glycoprotein (transmembrane) nmb N53447 integral membrane protein
2A NM_002659 plasminogen activator, urokinase receptor AL133111
SII3-domain binding protein 5 (BTK-associated) NM_147780 cathepsin
B W46577 endothelial cell-specific molecule 1 AA857496 matrix
metalloproteinase 10 (stromelysin 2) NM_005502 ATP-binding
cassette, sub-family A (ABC1), member 1 AI342012 macrophage
scavenger receptor 1 AA490846 integrin, alpha 4 (antigen CD49D,
alpha 4 subunit of VLA-4 receptor) AA454999 hypothetical protein
FLJ10111 AK093984 hypothetical protein MGC5618 AA666269 integrin,
beta 3 (platelet glycoprotein IIIa, antigen CD61) NM_005625
syndecan binding protein (syntenin) BC014989 phospholipid
scramblase 3 AI279830 protein phosphatase 1, regulatory (inhibitor)
subunit 16B AA936768 interleukin 1, alpha NM_ 001920 decorin
AK055130 calmodulin 2 (phosphorylase kinase, delta) NM_016497
mitochondrial ribosomal protein L51 AA451863 CD4 antigen (p55)
NM_058197 cyclin-dependent kinase inhibitor 2A R10284
hyaluronan-mediated motility receptor (RHAMM) AI309439 integrin,
alpha M (complement component receptor 3, alpha) AI334914 integrin,
alpha 2b AF001893 multiple endocrine neoplasia I N36136 endomucin-2
AW772163 hypothetical protein FLJ20401 NM_001964 early growth
response 1 AA454668 prostaglandin-endoperoxide synthase 1 NM 004530
matrix metalloproteinase 2 AK027663 stanniocalcin 2 AA057204
interleukin 2 receptor, beta NM_001444 Fatty acid binding protein 5
(psoriasis-associated) AA873792 small inducible cytokine A5
(RANTES) Markers upregulated in diabetes AA936768 interleukin 1,
alpha NM_000600 interleukin 6 (interferon, beta 2) N98591
interleukin 6 (interferon, beta 2) AA156031 metallothionein 2A
NM_001235 serine (or cysteine) proteinase inhibitor, Glade H
BF131637 metallothionein 2A NM_006216 serine (or cysteine)
proteinase inhibitor, Glade E NM_001552 insulin-like growth factor
binding protein 4 NM_004530 matrix metalloproteinase 2 NM_000088
collagen, type I, alpha 1 NM_023009 MARCKS-like protein NM_003670
basic helix-loop-helix domain containing, class B, 2 T8095 Hs.
clone 24707 mRNA sequence NM_002993 chemokine C-X-C motif,
granulocyte chemotactic protein 2 NM_006756 transcription
elongation factor A (SII), 1 AI983239 Hs. cDNA FLJ32163 fis, clone
PLACE6000371 NM_005110 glutamine-fructose-6-phosphate transaminase
2 NM_000584 interleukin 8 AK092836 Homo sapiens cDNA FLJ35517 fis,
clone SPLEN2000698 NM_000104 cytochrome P450, subfamily I
(dioxin-inducible), peptide NM_004966 heterogeneous nuclear
ribonucleoprotein F AK025599 mannosidase, alpha, class 1A, member 1
NM_002923 regulator of G-protein signalling 2, 24kDa AW005755
macrophage migration inhibitory factor AA873792 small inducible
cytokine AS (RANTES) U72621 pleiomorphic adenoma gene-like 1
NM_000358 transforming growth factor, beta-induced, 68kDa AK054688
Homo sapiens cDNA FLJ30126 fis, clone BRACE1000114 BC007583 Homo
sapiens, clone MGC: 15572 IMAGE: 3140342 NM_000089 collagen, type
I, alpha 2 NM_004404 neural precursor cell expressed, developmental
regulated 5 NM_078467 cyclin-dependent kinase inhibitor 1A (p21,
Cip1) U97105 Homo sapiens N2A3 mRNA, complete cds AI356451 CD19
antigen BF732465 tissue inhibitor of metalloproteinase 2 NM_001554
cysteine-rich, angiogenic inducer, 61 BQ890604 Homo sapiens URB
mRNA, complete cds NM_002631 phosphogluconate dehydrogenase N94503
pregnancy-associated plasma protein A NM_001710 B-factor, properdin
Markers upregulated in normal (non0diabetic) vessel segments
NM_000584 interleukin 8 N98591 interleukin 6 (interferon, beta 2)
AA936768 interleukin 1, alpha BM803108 ESTs NM_000600 interleukin 6
(interferon, beta 2) AI359876 EST AA156031 metallothionein 2A
BF131637 metallothionein 2A NM_003670 basic helix-loop-helix
domain, class B, 2 NM_001235 serine (or cysteine) proteinase
inhibitor, Glade H NM_004530 matrix metalloproteinase 2 NM_002982
monocyte chemotactic protein 1 NM_002631 phosphogluconate
dehydrogenase NM_078467 cyclin-dependent kinase inhibitor 1 A (p21,
Cipl) NM_152862 actin related protein 2/3 complex, subunit 2
NM_002923 regulator of G-protein signalling 2, 24kDa A1983239 Hs.
cDNA FLJ32163 fis, clone PLACE6000371 NM_005415 solute carrier
family 20, member 1 AW772163 hypothetical protein FLJ20401 R21535
Hs. cDNA FLJ11724 fis, clone HEMBA1005331 NM_005110
glutamine-fructose-6-phosphate transaminase 2 AK092836 cDNA
FLJ35517 fis, clone SPLEN2000698 NM_006216 serine (or cysteine)
proteinase inhibitor, clade E Markers which are downregulated with
statin treatment NM 000600 interleukin 6 (interferon, beta 2)
N98591 interleukin 6 (interferon, beta 2) NM_005746 pre-B-cell
colony-enhancing factor NM_ 002852 pentaxin-related gene, rapidly
induced by IL-1 beta N9201 fatty acid binding protein 4, adipocyte
NM_005110 glutamine-fructose-6-phosphate transaminase 2 AK094728
cDNA FLJ37409 fis, similar to COMPLEMENT C3 NM_004000 chitinase
3-like 2 NM_002923 regulator of G-protein signalling 2, 24kDa
T80495 Hs. clone 24707 mRNA sequence AA936768 interleukin 1, alpha
NM_145791 microsomal glutathione-S-transferase 1 NM_006169
nicotinamide N-methyltransferase AW007736 UDP-glucose ceramide
glucosyltransferase NM_005420 sulfotransferase, estrogen-preferring
NM_003670 basic helix-loop-helix domain containing, class B, 2
AA425102 monocyte chemotactic protein 1 NM_003254 tissue inhibitor
of metalloproteinase 1 BF131637 metallothionein 2A NM_000104
cytochrome P450, subfamily I (dioxin-inducible) NM_001733
complement component 1, r subcomponent NM_032849 hypothetical
protein FLJ14834 NM_005328 hyaluronan synthase 2 NM_002009
fibroblast growth factor 7 (keratinocyte growth factor) NM_002615
serine (or cysteine) proteinase inhibitor, Glade F NM_002658
plasminogen activator, urokinase NM_033439 DVS27-related protein
AA381343 interleukin 6 (interferon, beta 2) AW780123 ribosomal
protein S26 M14219 chondroitin/dermatan sulfate proteoglycan (PG40)
core AF495759 Homo sapiens unknown mRNA NM_001679 ATPase, Na+/K+
transporting, beta 3 polypeptide NM_001029 ribosomal protein S26
NM_002074 guanine nucleotide binding protein, beta polypeptide 1
NM_001552 insulin-like growth factor binding protein 4 AF208043
interferon, gamma-inducible protein 16 AI268937 monocyte
chemotactic protein 2 AA040170 monocyte chemotactic protein 3
AW131311 EST NM_005415 solute carrier family 20 (phosphate
transporter), member 1 NM_006988 a disintegrin-like and
metalloprotease (reprolysin type) NM_006307 sushi-repeat-containing
protein, X chromosome NM_000584 interleukin 8 D31887 KIAA0062
protein NM_002229 jun B proto-oncogene NM_002982 monocyte
chemotactic protein 1 Markers downregulated with statin treatment
NM_002615 serine (or cysteine) proteinase inhibitor, Glade F
AK094728 Homo sapiens cDNA FLJ37409 fis, clone BRAMY2028516
NM_001552 insulin-like growth factor binding protein 4 N92901 fatty
acid binding protein 4, adipocyte N98591 interleukin 6 (interferon,
beta 2) NM_000104 cytochrome P450, subfamily I (dioxin-inducible)
NM_006756 transcription elongation factor A (SII), 1 NM_000600
interleukin 6 (interferon, beta 2) AF506819 Homo sapiens URB mRNA,
complete cds NM_145791 microsomal glutathione S-transferase 1
N39161 CD36 antigen (thrombospondin receptor) M14219 Human
chondroitin sulfate proteoglycan core protein NM_031476
hypothetical protein DKFZp434B044 NM_000186 H factor 1 (complement)
NM_003254 tissue inhibitor of metalloproteinase 1 N98.sup.-391
interleukin 6 (interferon, beta 2) AJ318805 ESTs, Weakly similar to
hypothetical protein FLJ20378 AA284954 colony stimulating factor 1
receptor NM_002923 regulator of G-protein signalling 2, 24kDa
NM_001920 decorin B160199 likely ortholog of mouse Urb AA451863 CD4
antigen (p55) AA464526 interleukin 1 receptor, type I AW192258
sprouty homolog 4 (Drosophila) N68859 intercellular adhesion
molecule 1 (CD54) BC007552 Homo sapiens, clone MGC: 15473 IMAGE:
2967168, mRNA NM_001733 complement component 1, r subcomponent
NM_006288 Thy-1 cell surface antigen NM_000201 intercellular
adhesion molecule 1 (CD54) R22412 platelet/endothelial cell
adhesion molecule (CD31 antigen) NM_013417 isoleucine-tRNA
synthetase NM_004000 chitinase 3-like 2 R70506 growth factor
receptor-bound protein 2 NM_030781 collectin sub-family member 12
NM_001710 B-factor, properdin NM_006216 serine (or cysteine)
proteinase inhibitor, Glade E NM_005110
glutamine-fructose-6-phosphate transaminase 2 AF506819 Homo sapiens
URB mRNA, complete cds NM_002074 guanine nucleotide binding
protein, beta polypeptide 1 H26022 fractalkine, inducible cytokine
subfamily D (Cys-X3-Cys) AK092836 Homo sapiens cDNA FLJ35517 fis,
clone SPLEN2000698 BQ890604 Homo sapiens URB mRNA, complete cds
AA057204 interleukin 2 receptor, beta AI524093 myosin, heavy
polypeptide 11, smooth muscle AI655374 stromal cell-derived factor
1
[0024] The material collected can be analyzed for the presence of
DNA, RNA, or protein markers comprising smooth muscle proliferative
promoters (platelet-derived growth factor (PDGF), and PDGF
receptor), basic fibroblast growth factor (FGF) and FGF receptor,
interleukin 1 (IL-1), or transforming growth factor .alpha.
(TGF.alpha.), and the like), smooth muscle proliferative inhibitors
(nitric oxide/endothelial-derived relaxing factors (NO/EDRF),
interferon .gamma. (IF.gamma.), transforming growth factor .beta.
(TGF.beta.), or TGF.beta. receptor, and the like), cellular markers
(including CD68, CD3, CD4, CD8, CD20, smooth muscle actin, or CD31,
and the like), apoptotic markers (Bcl-x, Bcl-2, Bax, Bak, or P53,
and the like), cell cycle proteins (cyclin A, cyclin B, cyclin D,
or cyclin E, and the like), transcriptional factors (transcription
factor NF.kappa.B, transcription factor E2F, transcription factor
CREB, or transcription factor KLF5/BTEB2, and the like),
proliferative markers (Ki-67 or proliferating cell nuclear antigen
(PCNA), and the like), endothelial growth factors (vascular
endothelial growth factor (VEGF), and the like), adhesion molecules
(intercellular adhesion molecule-1 (ICAM-1), CD11a/CD18 (LFA-1),
CD11b/CD18 (MAC-1), vascular cell adhesion molecule-1 (VCAM-1),
p-selectin (CD62P), or integrin, and the like), cytokines
(interleukin 6 (IL-6) or interleukin 8 (IL-8), and the like),
chemokines and chemokine receptors (monocyte chemoattractant
protein 1 (MCP-1) and its receptor CCR2, CX3C chemokine fractalkine
and its receptor CX3CR1, or eotaxin and its receptor CCR3, and the
like), inflammation markers (C-reactive protein, myeloperoxidase,
or complement proteins, and the like), coagulation factors and
fibrinolytic factors (fibrinogen, prothrombinogen, plasminogen
activator, tissue factor, or glycoprotein receptor on platelets
(GpIIb-IIIa), and the like), oxidative stress related molecules
(oxidized LDL and its receptor CD36, or lipoxygenase, and the
like), extracellular matrix molecules (collagen, matrix
metalloproteinase (MMP), FK506-binding protein 12 (FKBP12),
endothelial differentiation gene receptors (EDG receptors),
ephrins, elastin, lamin receptor, monocyte colony stimulating
factor (M-CSF), tumor necrosis factor (TNF), or PDZ domain
proteins, and the like), interleukins (interleukin 1 (IL-1),
interleukin 6 (IL-6), or interleukin 8 (IL-8), and the like),
growth factors (platelet-derived frowth factor (PDGF), basic
fibroblast growth factor (FGF), transforming growth factor .alpha.
(TGF.alpha.), or transforming growth factor .beta.(TGF.beta.), and
the like), glycoproteins, proteoglycans (versican, hyluronan,
biglycan, or deorin, and the like), cell-surface markers, serum
markers, and/or immune factors (stromal cell-derived factor 1a
(SDP-1)), and the like). Analysis of the excised material by any of
the above tests can be used for diagnosis of a condition in a
patient, to design a treatment directive or protocol for a subject,
to monitor progress of a treatment regimen, or if tests from a
number of individuals are compared, the information can be used in
a multi-patient analysis, such as a cardiovascular disease
population study.
[0025] While all the above is a complete description of the
preferred embodiments of the inventions, various alternatives,
modifications, and equivalents may be used. Therefore, although the
foregoing invention has been described in detail for purposes of
clarity of understanding, it will be obvious that certain
modifications may be practiced within the scope of the appended
claims.
* * * * *