Exam III new material Flashcards
1
Q
spontaneous lesion
A
small chemical modifications at a NT
depurination- sensitive to hydrolysis = missing base
deamination- C–> Uracil by addition of H2O
don’t distort backbone
2
Q
Bulky lesions
A
covalent interactions due to UV, carcinogens, oxidative damage. Distorts double helix
3
Q
copy errors
A
DNA pol incorporates incorrect base
4
Q
Mutagen
A
an agent that causes DNA damage
chemical or physical
carcinogenic if causes division
5
Q
chemical mutagens
A
intercalating agent- in between strands of DNA in helix causing stretching
base analogs- inserts into a base space but not actually a base
6
Q
Indirect activating mutagens
A
require metabolic process to cause damage
7
Q
Physical mutagens
A
UV radiation. shorter wavelengths=more damage. A->B->C long->short
A: oxidative
B: induces dimers in adjacent pyrimidines
C: germicide C doesn’t make it to surface of earth
Ionization radiation: ss breaks, ds breaks, cross linking
8
Q
Ionization radiation
A
electromagnetic we use in medicine. because can travel further.
gamma rays are used in cancer therapy– ds breaks are the purpose to kill cells
9
Q
Particulate radiation
A
not wavelengths, can’t travel very far. don’t use in medicine
10
Q
Two types of DNA Repair
A
repair bases directly
repair bases that are incorrectly paired or bulky lesions etc..
11
Q
3mechanisms of DNA repair
A
reverse, remove, tolerate
12
Q
Base excision repair
A
DNA glycosylase removes purine/pyrimidine but leaves backbone
AP endonuclease recognizes site and cuts our backbone
results in single NT nick so DNA pol comes along and ligase seals
13
Q
Nucleotide Excision repair, bulky
A
multienzyme complex
scans for distorted double helix and cleaves on either side of distortion
helicase removes ss between cleavage sites
pol and ligase come through
14
Q
mismatch repair
A
DNA mismatch by DNA pol. following behind replication fork. To locate new synthesized strand use okazaki fragments. MutS and MutL, direct excision of entire sequence near mismatch
15
Q
piece of DNA is super damaged what back up mech do we have
A
backup polymerases. less accurate, take guesses
trans-lesion synthesis
16
Q
Transcription coupled repair
A
coding regions- exons. RNA pol stalls-> mech for nucleotide excision repair proteins to cut out lesion.
17
Q
Double strand breaks
A
non homologous repair- Ku70/80 proteins recruit DNA PK.always lose NT
homologous repair, sister chromatid nearby and used as template. Holiday junction. Recognized by Rad51 and make 3’ overhangs.
18
Q
DNA damage checkpoints
A
G1/S
S
G2/M
19
Q
ATM
A
associates with damage and starts kinase cascade for Chk1 and Chk2 proteins to activate p53–>tumor suppressor
20
Q
p53
A
usually ubiquitinated my Mdm2
when p53 Pi it will Pi p21 which will inhibit Cyclin/cdk complexes in cell cycle
21
Q
2 major issues with stem cells
A
technological: Driving differentiation
and applying safety
22
Q
Stem cells
A
have to be able to differentiate into something else and have to be able to proliferate
23
Q
totipotent
A
total potential to be anything
24
Q
pleuripotent
A
more directed than totipotent
25
multipotent
more directed than pleuripotent (bone marrow cells)
26
unipotent
near end of cell proliferation stage. "Transant amplifying cell"
Progenitor cell ex: keratinocytes
27
embryonic stem cells
totipotent. ability to take a single cell and grow a complete organism
28
post-natally derived
new borns. umbilical cord blood.placenta-derived:
pleuripoteny/multipotent
cord blood cell banks
29
adult derived stem cells
bone marrow adipose tissue
30
Induced pleuripotent cell
take a cell, fibroblast, keratinocyte. treat with developmental genes. Ox4 Klf4 Sox2 CMyc
31
cloning
somatic cell nuclear transport. take egg, take out nucleus and put in nucleus from a cell.
concerns: aging of DNA, telomere length
32
Process of induced pleuripotent cells
harvest donor cells, place with feeder cells(provide nutrients). transfect with genes of choice and select after proliferation.
mouse experiment with sickle cell anemia
33
c-Myc function
tumorogenisity function. so take out once grown cells that you want
34
sources of fat for stem cells
from surgeries (like around kidney) or from liposuction
35
what type of cell is fat stem cell
mesenchymal stem cell
36
potential use of stem cells
wound healing, diabetes, cardiac infarcts, bladders
37
Immunomodulation and stem cells
T regulatory cells- replace these using stem cells
38
Ketchums work with Islets
using a combination of mouse islets and hASCs, 5-7 days return to normal glycemic level
these mice become diabetic spontaneously
39
describe experiment with mouse liver
co transfected hASC and MSC and endothelial cells to produce liver buds. bile was produced and hepatic proteins but no biliary tree
40
hESCs transplant
changed medium to drive differentiation In VITRO
then transplanted into diabetic mice 32 weeks post injection
bone had grown too.
41
prochymal and chonrogen
chondrogen- knee reconstruction, causes cartilage growth
| prochymal
42
regenexx
not used in USA because of FDA
| proliferative in vitro
43
Cell senescence
telomerase activity over time. limited number of cell divisions- hayflick limit
44
hybridoma
inject mouse with antigen. wait till makes ab then select ab in B lymphocytes and insert into a tumor cell. infinite ab
45
structure of antibody
2 fab domains- bind antigen
| 1 fc- functions in signaling
46
are lymphocytes specific to antigens
yes
47
polyclonal ab
ab produced by inoculating an animal against antigen. from multiple lymphocytes against multiple epitopes
48
ELISA
not microscopy, HIV and pregnancy
49
Proteins in electrophoresis
denatured then add SDS which adds negative charge
50
northern blotting
mRNA
51
southernblotting
DNA
52
western blotting
immunoblotting, antibodies
53
2 ways to replicate DNA
1: restrictive endonucleases on each side
2: mRNA--> cDNA via reverse transcriptase, more efficient for specific gene
54
DNA vector needs
Restriction endonuclease site
Autonomous origin of replication (has own machinery)
A gene for antibiotic resistance
55
Recombinant proteins
produce large amounts of protein for therapeutic use.
| Expression Vectors- require sequence to express protein. Need bacterial promoter and start site
56
gene therapy
introduce a normal copy of a gene into defective tissue
57
Retroviruses gene therapy
permanent because incorporate into host genome, problem is it can insert anywhere, not directed
Only used in cells that are actively dividing
no immune response
58
Adenoviruses gene therapy
not integrated in host DNA, very transient, constantly re-treat
can give to senescent cells
large immune response
59
Transgenic animals
insert or delete genes from animals using cDNA.Inject into ovuum and offspring will have the gene in all cells and germ line
60
Blastocyst
offspring is chimeric in somatic and stem cells next generation will not be
61
2 basic components of connective tissue
ECM and cells
62
ECM 3 constituents
fibers, ground substance, tissue fluid
63
2 types of cells in CT
"fixed" and hematogenous
64
3 traditional basic CT fibers
collagen
reticular (type III collagen)
and elastic
65
characteristics of collagen
fibrillar, some globular add tensile strength
66
Collagen I
fibril 67nm most abundant- tendon skin, fascia
67
Collagen II
fibril 67nm cartilage, nucleus pulposus, notochord
68
Collagen III
fibril 67nm skin, blood vessels, lymph nodes, spleen
69
Collagen IV
globular, basal lamina of epithelial cells
70
Collagen VII
small fibers 67nm, anchoring fibrils in basal laminae
71
procollagen
can self assemble. Type I collagen, triple helix formation. 2 chains of 1 alphaprocollagen and 1 chain of 2 alphaprocollagen
72
collagen fibril
show periodicity, staggered alignment of procollagen makes it very strong
73
collagen fiber
collagen fibril bundles
74
length of repeating banding pattern
67 nm
75
length of tropocollagen helix repeating unit
300nm
76
Elastic fibers composed of
elastin(amorphous globule protein) and fibrillin (fibrillar protein forms sheath)
elastin core, glycine and proline
surrounded by fibrillin microfibrils that are held together by desmosine and isodesmosine
77
Marfans
fibrillin mutation because elastin has no elasticity
78
ground substance of ECM
GAGs- unbranched polysacs
proteoglycans: GAGs+proteins covalent
adhesive glycoproteins: large multi-domain glycoproteins that interact with integrins, collagen fibers and proteoglycans
79
GAGs
repeating dissacharides
80
Types of GAGs
hyaluronic acid(HUGE) does not covalently bind because doesn't have sulfate, keratan sulfate heparan sulfate, heparin, chondroitin-4 sulfate, chondroitin-6 sulfate, dermatan
81
How GAGs function
over 100 units long, GAG has overall (-) charge and attracts cations- high [Na] = H2O content
H2O=turgor- resistance
82
Linking protein
used to attach matrix(other GAGs), which are on the core protein aggrecan(another GAG) onto hyaluronic
83
types of adhesive glycoproteins
fibronectin, laminin, integrins, entactin, tenascin, chondronectin, osteonectin
84
fibronectin
dimer of alpha subunits with weight 220kD. links cells and ground substances via integrins, collagen and heparin sulfate PG
embryonic cell migration
85
laminin
trimer, 1alpha 2 beta. Exclusively in basal laminae. 950kD
| binds GAGs proteoglycans and adhesive glycoproteins--Collagen IV! entactin integrins and heparan sulfate PG
86
Integrins
250kD heterodimeric. extracell domain binds parts of ground substance causing intracell cascade
COOH terminal binds to vinculin and talin bind to actin
87
bonds of integrins
much weaker than most R-ligand, so but many integrins together to strengthen btu still be mobile(taken apart easily)
88
entactin
collagen IV
89
tenascin
hexamer binds fibronectin
90
chondronectin
binds collagen II
91
osteonectin
binds collagen I
92
Mucus CT
loose CT with lots of ground substance
| jelly like matrix(wharton's jelly) found in umbilical cord and pulp of developing teeth,
93
Loose areolar CT
abundant ground substance
cells:fibroblasts adipose cells, macrophages and mast cells.
loosely woven collagen and elastic fibers. has small nerves and blood vessels.
Packs in tissues and organs
94
Dense CT. 2 types
greater density of loose fibers
| regular and irregular
95
dense irregular CT
random arrangement of collagen bundles
dermis
fascia
96
dense regular CT
ordered arrangement: tendon, ligaments, aponeuroses
97
Adipose CT
low fiber and little ground substance. Few fibroblasts hematogenous cells
98
unilocular
white- single lipid droplet
99
multilocular
brown- multiple lipid droplets
100
Elastic CT
fibroblasts, collagen fibers, elastic fibers
wall of large vessel
nuchal ligament
101
Reticular CT
same as collagen III, liver, adipose, lymph and spleen. fibroblasts and reticular fibers
102
Blood as CT
all CT components: cells, ECM
fibers: fibrinogen-->fibrin
ground substance-->GAGs(heparin) proteins(albumin)
fluid-->plasma
103
characterizations of cartilage
rigid flexible and resilient
104
3 subtypes of cartilage
hyaline, elastic, fibrous
105
articular cartilage
hyaline, collagen type II
106
elastic cartilage
type II cartilage, high [ ] elastic fibers
107
fibrous cartilage
intervertebral disc, tendon with chondrocytes replacing fibroblasts collagen I fibers
108
cartilage cell types
chondrogenic
chondroblasts
chondrocytes
109
fibers of cartilage
collagen II (hyaline and elastic) and elastic
110
ground substance of cartilage is made up of
aggrecan (GAG)
| chondronectin (adhesive glycoprotein)
111
development on cartilage
embryological mesenchymal cells-> chondroblasts->aggregate->secrete fibers and ground substance and separate to become chondrocytes surrounded by matrix
112
perichondrium, 2 layers
when mesenchymal cells around primordial cartilage condense
| fibrous perichondrium, cellular perichondrium
113
Cartilage growth mechanisms
interstitially (within) and appositionally(periphery and moves down)
114
hormones controlling cartilage growth
```
growth hormone, thyroid hormone, gluccocorticoids
sex hormones(testosterone, estradiol) Vitamins
```
115
Growth hormone-cartilage
stimulate growth thru IGF-1
116
Thyroid hormone-cartilage
hypertrophic growth, acts directly thru IGF-1
117
Gluccocorticoids-cartilage
inhibit cartilage growth, down regulate type I collagen.
118
Vitamin A deficiency
slows cartilage growth and calcification
119
Vitamin C deficiency
(scurvy) inhibits collagen synthesis
120
Vitamin D deficiency
inhibits calcification (rickets and osteomalacia)
121
Is bone inert?
mineralized portion is but the tissue is dynamic
122
2 types of bone
compact (cortical)
| cancellous (spongy)
123
Wolff's law
bone adapts to forces placed on it
124
Bone matrix composition
collagen I, majority inorganic, radially arranged collagen fibers of one lamella are perpendicular to those in next lamina
mostly hydroxyapatite salt-Ca2+: form crystals to increase strength
125
lacunae
throughout lamellae, small cavities, osteocytes found in lacunae
126
canaliculi
radiate from lacunae to transport nutrients cell to cell
127
4 types of lamallae
outer circumferential:below periosteum
inner circumferential: along endosteum
osteon: haversian system (functional unit)
interstitial lamellae: remnants of old osteons
128
Cancellous bone structure
trabeculae
| spicules-no haversian system
129
Osteon structure
6-8 lamellae
| connected by Volkmann's canal which are vascular channels at right angles to long axis of bone
130
Periosteum structure
fibrous CT tightly adhering to bone, fibrous (outer) cellular (inner) which contains osteogenic cells
131
Sharpey's fibers
fibrous CT tightly adherent to bone. connects periosteum to bone
attach tendons as well
132
endosteum
lines bony cavities like haversian canals and marrow spaces
| osteogenic potential
133
types of bone cells
osteoblasts, osteocytes, and osteoclasts
134
osteoblasts->osteocytes
not via differentiation. depends on surroundings what they are
135
osteoblasts
mesenchymal cells and osteoprogenitor (periosteum and endosteum) Lots of ribosomes, ER, golgi near surface. nucleus away from surface
136
Osteocytes
reside in lacunae, sparse rER and Golgi, long cytoplasmic processes reach through canaliculi
participates in Ca2+ and PO4- transport
137
Osteoclasts
large multinucleate, located in Howship's lacunae, stimulated by fusion of macrophages
138
osteogenesis specific conditions
loose mesenchymal form (development)
| cartilagenous model
139
Happens in osteogenesis
rearrangement of underlying CT, increased vascularity, osteogenic stem cells
140
deposition of bony matrix
osteoid is a thin layer of uncalcified preosseous tissue that surrounds the osteocyte, adjacent to active osteoblast
141
making cancellous bone
first deposition of bone is a spicule, trabeculae are the spicules that have merged radiating from ossification centers
142
Intramembranous bone formation
flat bones, pre existing scaffold:
mesenchymal cells cluster, proliferate and enlarge
cells differentiate and become osteoblasts and secrete matrix, when the matrix calcifies it becomes osteocytes
143
Endochondral bone formation- long bones
pre-existing cartilage, osseus cuff forms, midregion calcifies death and reabsorption of central chondrocytes, blood vessels penetrate cuff and form a cavity(for marrow) and the osteogenic cells migrate into cavity
blood vessels then penetrate epiphysis and epiphyseal cartilage plate forms
144
5 distinct zones of epiphyseal plate
```
zone of resting
zone of proliferating
zone of hypertrophying
zone of calcifying
zone of resorption/ossification
```
145
zone of resting cartilage
pool of chondrocytes- hyaline cartilage
| collagen type II
146
zone of proliferating
chondrocytes proliferate- stacked nickel
| collagen type II
147
zone of hypertrophying cartilage
chondrocyte proliferation slows, cells increase in size
collagen type I
cells secrete VEGF
148
Zone of calcifying cartilage
chondrocytes begin to degenerate-apoptosis
matrix calcified, scaffold for bone deposition
VEGF still secreting- osteoprogenitor cells arrive at neovascularization
149
Zone of Resorption/Ossification
chondrocytes dissapear, vessels invade cartilage source of osteoprogenitor cells. osteoblasts develop and osteoclasts degrade cartilage so new bone is deposited
150
repairing bone fracture
granulation tissue and hyaline tissue laid in wound
new tissue develops, cal us
fracture heals as new bony tissue laid down
151
3 ways to regulate Ca2+ metabolism
changes in bone turnover
changes in gut absorption
urinary secretion
152
Calcitonin
Increased Ca2+ blood levels: inhibits bone resorption. directly inhibits osteoclasts.
parafollicular cells in thyroid gland
153
Parathyroid hormone
low bloodCa2+ levels.
increases Ca resorption from bone
binds osteoblasts->releaseing cytokines which stimulate osteoclasts
chief cells in parathyroid hormone
154
Vitamin D
converted to calcitriol. regulates Ca2+ and PO4 in blood. promotes Ca2+ uptake from gut
UV exposure causes skin to produce it
ingested in food
155
where is epithelial found in body
```
endothelium proper: covers and lines surfaces
endothelium: blood and lymph vessels
mesothelium: lines serous cavities
glands: epithelial invaginations
nerve specializations
```
156
sterocilia
very very long microvilli. no motor used for absorption
157
Microvilli
brush border or striate border, membrane bound
| rooted down via microfilaments and IFs "terminal web"
158
Apical specialization
microvilli and sterocilia cilia and flagella
159
LAteral specializations
zona occludens, zona adherens: Terminal bars-LM
gap junctions and macula adherens
fascia adherens
160
zona occludens
tight junction- permeable seal
161
zona adherens
major resistance to shearing stress. dense plaques of myosin tropomyosin actinin and vinculin and E cadherins extra cell protein
162
different lateral specialization found predominantly in muscles
6connexin hydrophilic pore
| cell-cell communication- ions, cAMP, cGMP, small proteins
163
"spot weld" in cells
lateral specialization-macula adherens- tonofilaments which are IFs that anchor into cytoplasm
primarily desmoglein and desmocollin
164
fascia adherens
intercalated discs- stretched adherens
165
Basal specializations
Basement membrane, hemidesmosomes
166
Basement membrane
not phospholipid bilayer. thin acellular layer that separates epithelial cells from underlying CT
167
layers of BM&collagen found in each
reticular lamina: connects to basal lamina via collagen VII
| basal lamina: lamina rara(lucida) and lamina densa includes collagen IV
168
reticular lamina collagen
I II and III
169
hemidesmosome
binds epithelium to BM. IFs
170
glands
invaginated epithelial cells that begin to secrete
171
modes of secretion for glands
apocrine-->membrane bounds particles release in membrane
merocrine-->eccrine, fusion, exocytosis
holocrine--> whole cell lysed
172
classification of glands
unicellular vs multicellular mode of secretion
method of production.
nature of secretion
173
Method of gland production
exocrine(via ducts), endocrine(secrete into blood and lymphatics) paracrine(extracell space)
174
glandular morphology
tubular and acinar
175
ductal morphology
simple, coumpoun or branched, or coiled
176
nature of secretion of glands
serous- watery. (exocrine pancreas, parotid salivary gland)
mucus- viscouse (goblet, sublingual salivary glands and palantine salivary glands)
mixed- serous demilunes- submandibular salivary glands
177
2 elements of glands
parenchyma- functional tissue
| stroma- CT elements (lobes and lobule boundary)
178
parenchyma
functional tissue of gland. secretory cells and ducts
179
what suggests that ducts are involved in secretion
so much mitochondria is found in the infoldings
180
2 divisions of skin
Epidermis and dermis
181
hypodermis
subcu, attachment, padding, molds external appearance.
182
epidermis layer
stratified squamous epithelium. thick 400-600um hairless and thin 70-150um hairy
183
3 layers of epidermis
stratum granulosum(superficial) stratum spinosum and stratum basalis (germinativum)
184
Stratum basalis
cuiboidal cells dermal-epidermal junction. hemidesmosomes to attach
intense mitotic activity turnover 50-60 days
IFs
185
Mechanism to regulate stratum basalis
vitamin A and D required for differentiation and keratinocytes have R for GFs and synthesize GFs
186
stratum spinosum
spiney desmosomes all around it-> resist shear stress.
187
Stratum granulosum
very basophilic, keratohyalin granules(H2O barrier), keratinosomes present that function as a cement and create barrier to intracellular transport
these both form cell envelop and lipid envelop for H2O barrier
188
2 layers above granulosum
```
stratum lucidum(thick skin)
stratum corneum (no identifiable organelles) have tonofilaments with filaggrin to form bundles
```
189
desquamation
removing outer epidermal layer, not only due to abrasive forces- lipolytic enzymes
190
Melanocytes
specialized cells of epidermis- dendritic cell morphology that reach between keratinocytes to give melanin. via specialized lysosomes called melanosomes
191
melanin production
tyrosine converted to DOPA by tyrosine kinase
192
how many keratinocytes does 1 melanocyte associate with
about 36
193
4 stages of production of mature melanin granules
Stage I: tyrosine containing melanosomes form in melanocyte
Stage 2: melanin production initiatied by tyrosine kinase
stage 3: melanosomes excreted
stage 4: melanosomes phagocytksed by keratinocytes
194
Langerhans cells
marrow derived. Antigen presenting cells (APCs)
| migrate to T cells and present antigen so then make IL-1 which induces T cells to make IL-2 to T cell proliferation
195
Merkel cells
mechanoreceptors for cutaneous sensation found in stratum basalis, more prominent in thick skin with high acuity(fingers)
196
Dermal-epidermal junction
dense irregular CT, epidermal pegs and dermal papillae to amplify contact
197
2 layers of dermis
Papillary: CT, blood vessels, Meissners corpuscles(2 pt discrimination)
Reticular: hair follicles, pacinian corpuscles, blood and lymph, glands
198
number 1 regulator of body temp
heat evaporation and heat production(muscle)
199
Layers of dermal-epidermal junction
basal cell plasmalemma (lowest epidermis)
basal lamina(lucida and dense)
CT fibers of basal lamina: anchoring fibrils to dermis via collagen VII
200
Hair follicles
shares characteristic with epidermis
source of new epidermis.
arrector pili muscle goose bumps
sebaceous gland (secrete sebum into hair follicle via holocrine), preventing evaporation
201
Sweat glands
thermal regulation. most merocrin(eccrine) cholinergic control
simple coiled tubular glands
202
3 cell types in sweat glands
dark-pyramidal : secretion granules
clear-primary cells: no secretion granules but lots of mitochondria and glycogen
myoepithelial cells- contractile
203
Apocrine sweat glands
axilla, areola, perianal regions
empty into hair follicle, and can store product in the lumen. odorless product but when degraded by bacteria= odor
adrenergic influence
204
Meissners corpuscles
low freq vibration, touch sensation. Neuro sensory organs in dermis
205
Pacinian corpuscles
neuro sensory present in dermis
found in deep dermis
sense:high freq vibration and pressure
206
muscle fiber
muscle cell or myocyte
207
types of m cells
skeletal, cardiac, smooth, myoepithelial, myofibroblast
208
myofibroblasts
spindle shaped CT cell- intracell bundled of actin filaments, adherence to PM via vinculin
good for closing wounds and shrinking scars
209
myoepithelial cells
specialized and assoc with glandular because contain actin and myosin that contract out gland product
210
what glands utilize myoepithelial cells?
mammary gland, lacrimal gland, salivary gland and sweat glands
211
smooth muscle
sm mm cells. involuntary contraction. 20-200um 3 to 8 um. centrally located nucleus
212
structure of sm mm.
external lamina, exibits like rara and dense
| each cell had densa and share rara in middle
213
sm mm contraction
intercellular gap junctions: link cells
intracellular fingerlike tubules of sarcoplasmic reticulum.
microfilaments and IFs attach at dense bodies which pull and make cell blebbing and nucleus is pleated or coil
214
skeletal muscle composition
voluntary contraction, long cylindrical. variable size 1-4cm and 10-100mm HUGE
peripheral nuclei and multiple nuclei
215
striations in skel muscle cells
z line to z line line up
216
contractile unit of myofiber
sarcomere
217
very thin dark line in myofibers
Z line
218
H line in myofibers
light band in middle of A band
219
A band
dark band in between z lines
220
I band
light band on either side of Z line
221
Endomysium
surrounds individual cells (myofibers)
222
perimysium
surrounds fasicles (bundles of cells)
223
epimysium
surrounds muscles (bundles of fascicles)
224
Cardiac muscle
composed of cardiac m, involuntary contraction, pecialized striated muscle
225
characteristics of cardiac muscle
elongated 50-100um 15-20um, 1-2 nuclei centrally located
not as defined as skel m but have striations.
intercalated discs-fascia adherens: gap junctions
226
4 events that are involved in m contraction
Neuro-muscular junction
excitation-contraction coupling
filament sliding
transduction of contraction(muscle-bone)
226
4 events that are involved in m contraction
Neuro-muscular junction
excitation-contraction coupling
filament sliding
transduction of contraction(muscle-bone)
227
Neuro-muscular junction
excitation signal transfered from neurons to motor end plate
227
Neuro-muscular junction
excitation signal transfered from neurons to motor end plate
228
Impulse at Neuromuscular junction
change in membrane potential, Ca2+ released, acetylcholine released into synaptic cleft
free Ach binds to R in myocyte membrane to ligand gated channels- Ach opens channel and Na+ depolarizes myocyte membrane
228
Impulse at Neuromuscular junction
change in membrane potential, Ca2+ released, acetylcholine released into synaptic cleft
free Ach binds to R in myocyte membrane to ligand gated channels- Ach opens channel and Na+ depolarizes myocyte membrane
229
Excitation-contraction coupling
transmission of nerve impulse down T tubules"triads" located at A/I band junction
Na+ influx->Ca2+ release from sER into cytoplasm to bind myofibrils
229
Excitation-contraction coupling
transmission of nerve impulse down T tubules"triads" located at A/I band junction
Na+ influx->Ca2+ release from sER into cytoplasm to bind myofibrils
230
each myosin filament is surrounded by how many actin
6 actin thin filaments
231
structure of myosin filaments
light meromyosin has 2 heavy chains and a hinge region
232
Muscle-Bone Connection
tension induced by m contraction. transmitted into connecting bones. actin filaments(insert at z line) and surrounding CT(tendon bone and sharpeys fibers) facilitate transmission
233
describe contraction of skel muscle
binding of myosin head to tropomyosin(uncovered when Ca2+ binds troponin) causes release of ADP and Pi which induces contraction and at low energy state, need ATP to release myosin from actin and eventually converted back to ADP and Pi
234
why is rigor mortis at a contractile state
because this is the low energy state of muscle contraction
235
smooth muscle contraction
Ca2+ release from sER binds to calmodulin(on myosin light chain kinase) which will phosphorylate myosin allowing it to bind actin
236
Golgi tendon organs
sensory, but not motor. sense increased tension in entire muscle
237
Nissl bodies
rER stains very darkly
238
MSOs
belly of most skel mm, run parallel with main muscle fibers.sense length and tone
have own motor and sensory neurons.
annulospiral
239
Skel mm two types of fibers
extrafusal: make up bulk of muscles
intrafusal: modified
240
Golgi tendon organs
sensory, but not motor. sense increased tension in entire muscle
241
Nissl bodies
rER stains very darkly
242
axonal cytoplasm
do not contain organelles
| only cytoskeleton, mitochondria, and vesicles
243
antergrade and retrograde transport
antero: kinesin. from cell body to periphery
retro: dynein. from periphery to cell body
244
dendritic cytoplasm
does not have golgi apparatuses
245
synaptotagmin
activates t and v snares for fusion in presynaptic membrane
246
Astrocyles
CNS neuroglia: maintain tight junctions at blood/brain barrier. assoc with nodes of rangier and regulate [K+]
247
microglia
phagocytic cells-response to disease or injury
248
Inhibition of AP on postsynaptic membrane
NT gated Cl- channels--> hyperpolarization
249
types of ependymal cells
apical surface microvilli and cilia in production CSF
basal surface: infoldings that assoc with astrocyes
lateral surface: tight junctions
choroid plexus: modified and produce CSF
250
satellite cells
analogous to Schwann cells but do not produce myelin.
251
enteric neuroglia
located in ganglia, analogous to astrocytes
252
Inhibition of AP on postsynaptic membrane
NT gated Cl- channels--> hyperpolarization
253
saltatory conduction
in myelinated nerve, voltage reversal takes place at nodes of rangier where Na+ and K+ can be moved across membrane. jumps from node to node
254
Grey matter vs white
grey: nerve cell bodies, axons and dendrites and glial
white: nerve axons, assoc glial and blood vessels
255
Epineuriam
Dense irregular CT, cover peripheral nerve(vessels within this layer)
256
Blood brain barrier
Endothelial cells- elaborate tight junctions- continuous capillaries
endothelial basal lamina has pericytes and BM
astrocytes: foot processes close with BM, important for integrity of tight junctions
257
Endoneurium
loose CT, covers individual nerve cells
258
Perineurium
specialized CT, covers fascicles. perineurial cells maintain blood nerve barrier
259
Epineuriam
Dense irregular CT, cover peripheral nerve(vessels within this layer)
260
blood vessels
derived from mesenchymal cells
lined with endotehlial cells- mono layer localize immune response, ischemia etc. can change shape/number depending on stimuli
261
endothelial cell location on capillary
interior. usually smaller than RBC, so RBC have to squeeze- increasing contact for exchange of material
262
Do capillaries have sm muscle?
no, but have perictyes
263
pericytes
specialized cells located next to capillary- have processes to surround capillary
264
When does the sprout cell stop
when reach another sprout or vessel that is emitting signals to sprout if its the same type of vessel and can join.
265
angiogenesis
Sprout from existing vessel
neovascularization
happens in ischemic conditions, menstration, can be caused by tumor metastization of diabetic retinopathy
266
Capillary sprout
vasodialtion will occur, followed by Tip cell sprout, it is an existing endothelial cell that changes phenotype to express "pseudopodial" processes to guide into ECM
not dividing- require guidance signals
267
Tip cells are followed by what cells
stalk cells- actively dividing epithelial cells and hollowing out to create lumen of capillary
268
When does the sprout cell stop
when reach another sprout or vessel that is emitting signals to sprout if its the same type of vessel and can join.
269
Endothelial precursor cell EPCs
undifferentiated in bone marrow- signals can recruit these cells. Like ischemia from MI or other complications. Express VEGFR-2 and VE-cadherin
270
events of angiogenesis
vasodialtion via NO and VEGF
degradation: proteolytic cleavage of BM components to allow it to travel.
Migration: direct new growth
Proliferation: endothelial cells in stalk
Maturation: after contact of sprouts- laying down BM and recruiting perictyes(capillaries)
271
Matrix metalloproteinase
degrades components of ECM to make room for capillary sprout migration
272
VEGF-A
promoter of angiogensis: ligand that acts in paracrine manner(diffuses short distances)
VEGF-2 R which bind circulating isoforms->induce down stream signaling pathways. tyrosine kinase so Ras/Raf and MapK and PI3 signaling
273
VEGF
induces Endothelial precursor cells to migrate from marrow to local area. Tip cells detect VEGF and move towards it. Increase vascular permeability.
upregulate expression of proangiogenic proteins
274
Proangiogenic proteins
plasminogen activator
| collegenase
275
What stimulates VEGF
hypoxia- Hif1 gene regulatory. usually ubiquitlyated and degraded. but can upregulate VEGF in hypoxic conditions
TGF beta and alpha
PDGF
276
Notch R signaling
juxtacrine, membrane bound
Stalk cells. control branching by regulating proliferation. decrease response to VEGF
delta is endothelial cell specific and expressed by tip cells, induced by VEGF
277
Angiopoietins
Ang1: recruit periendothelial cells to promote vessel maturation.
Ang2: endogenous antagonist to Ang 1 R(Tie2)
increase response to VEGF- so not grown completely yet
278
PDGF
secreted by endothelial cells. R is on pericytes and sm m cells to function in recruitment for maturation. PDGF released after Ang1
279
bFGF
endothelial cells and macrophages express this. secreted and stored in ECM- affinity for heparin to help guide recruitment mech
bFGFR expressed in endothelial cells, fibroblasts, sm mm cells and neurons. Mitogenic Induce mitosis
280
TGF-beta
induces VEGF expression- fibroblast and endothelium
281
MMPs matrix metalloproteinases
contain zine, necessary for tissue remodeling. Induced by VEGF, GFs and mechanical stress
secreted as zymogens by endothelial cells
degrade BM of vessel and ECM components
release ECM bound proangiogenic factors(VEGF) (FGF)
degrade ECM components into fragments to interact with integrin pathways
282
Integrin pathway
fibronectin :degraded fragment bind integrin- start to cluster = FAK focal adhesion complexes.
cytoplasmic sides now start to act as transcription->allows cell to migrate via actin cytoskeleton
283
Thrombospondin-1
inhibitor of angiogenesis. Upregulated by p53 in fibroblasts
284
When platelet reaches cloth
regulators are released to control neovascularization. pro and then anti angiogenic
285
Angiostatin
degradation ECM, inhibitor of angiogensis. plasminogen, found in plasma. this is a fragment that could induce apoptosis and inhibit cell migration
286
Endostatin
collagen. BM vessel walls. Inhibits VEGF signaling, blocks tyrosine kinase Phosphorylation
287
Platelets
small fragemented portions of cells, sacs of proteins to be released when signaled.
14+ promoters angiogenesis and 12 inhibitors
288
When platelet reaches cloth
regulators are released to control neovascularization. pro and then anti angiogenic
289
Turn off angiogenesis
Degrade Hif-1 and keep [ ] low, this happens when Oxygen levels are good.
E3 von hippel lindau ligase responsible for marking Hif-1 for degradation
290
one dysfunctional allele Von Hippel Lindau
somatic mutation results in no functional VHL-> continually express Hif1, overexpression VEGF, hemanglioblastoma(blood vessel rich tumor)
291
Tumor angiogenesis
in order for a tumor to grow, needs more vascularization. there is a switch when it can actually stimulate neovascularization
292
Nonneovascularized tumors
not clinically detectable (unless skin) small in size, growth inhibited due to hypoxia--> so growth is slow because diffusion of O2 is limited. 100um
generally not metastatic
293
Bevacizumba Avastin.
anti VEGF antibody, no longer able to bind to Receptor
| shows increase visual activity in diabetic retinopathy. most effective when combined with laser therapy
294
Inhibiting angiogenesis via drugs
direct/indirect and biologics(ab and proteins created in living tissues)
295
direct manner of inhibit angiogenesis
inhibit endothelial cells from responding
296
indirect manner of inhibiting angiogenesis
inhibiting cells that release stimulatory factors like TGF-beta and GFs
297
Bevacizumba Avastin.
anti VEGF antibody, no longer able to bind to Receptor
| shows increase visual activity in diabetic retinopathy. most effective when combined with laser therapy
298
Trastazumab
indirect inhibitor, breast cancer ab antagonist drug
Her2/neu R are tyrosine kinases that are mutated to be on or over expression
younger women. we use ab antagonist in Her2. so halts production of angiogenesis promoters
