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241 Cards in this Set
- Front
- Back
Hypertrophy
|
↑(inc.) size of cells
|
|
Hyperplasia
|
↑ (inc.) # of fully differentiated cells
∴ fully fxn cells, but more than usual |
|
Anaplasia
|
loss of differentiated form and function
refers to degree of differentiation of cells |
|
Regeneration
|
1:1 replacement by cells of same type
healthy, non-pathogenic |
|
Angioplasty
|
scrapes off plaque and endothelium lining arterial walls
|
|
Endothelium (blood)
|
Only blood compatible surface in body
clotting occurs when blood contacts any other tissue type |
|
Restenosis
|
from stenosis -- the abnormal narrowing of a vessel or tubular organ
ex. hyperplasia (excessive smooth muscle proliferation) after angioplasty re-obstructs the vessel, leaving a relatively small lumen through which blood can pass. |
|
Grave's Disease
|
hyperplasia of thyroid, caused by autoimmune attack producing Ab which bind TSH receptor and turn in constitutively on
symp: protruding eyes, non-pitting edema, fatigue, weight loss w/ high appetite, weakness, tachycardia treat via surgical removal, anti-thyroid drugs |
|
Metaplasia
|
Replacement of 1 cell type with another
common in airway & reproductive tract (as a result of chronic environmental insults) |
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Dysplasia
|
expansion of immature cells at the expense of location / number of mature cells
last step before cancer freq. large nuclei, much mitotic activity, pleomorphic, loss of orientation |
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Pleiotropy
|
1 gene is responsible for more than one phenotypic characteristic
|
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Neoplasia
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loss of growth control (remove growth signals and growth continues)
|
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Benign Neoplasia
|
loss of proliferation control only
freq. stay as encapsulated tumors, however benign≠harmless |
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Malignant Neoplasia
|
cancer
loss of both proliferation & positional control (will invade other tissues and establish tumors there as well) |
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Normal Cell Proliferation Roles
|
new blood vessel formation
wound healing liver regeneration epithelial cell regrowth lymphoid cell maintenance |
|
Pathological States -- Fibroblast Proliferation
|
Fibroplasia
Neurofibromatosis Psoriasis |
|
Pathological States -- Endothelial Cell Proliferation
|
Diabetic Retinopathy
Hemangioma (blood vessel tumor) |
|
Pathological States -- Smooth Muscle Cell Proliferation
|
arteriosclerosis, restenosis, pulmonary hypertension
uterine fibroids asthma pyloric stenosis megaureter |
|
Differentiation vs. Proliferation
|
Cannot proliferate once differentiated (neurons, cardiac muscle)
Don't proliferate (but can) once differentiated (liver, EC) High normal turnover/proliferation after differentiation (intestinal crypt cells, bone marrow cells) |
|
Shear Forces
|
cells will proliferate on agar until a monolayer is formed
application of fresh medium pumped across cells stimulates further growth |
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Shape Regulates Proliferation
|
shape gives important input in proliferation decisions; each cell has optimal shape for division
|
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Size Matters for Proliferation
|
cells must reach requisite size before division occurs
if continually cut before reaching threshold, will not divide. |
|
R-Point
|
Cells need to make a decision to continue through cell cycle or to exit and enter quiescent state (Go)
*committed step -- last point cell is still sensitive to external environment |
|
Positive Cell Cycle Effectors
|
peptide growth factors = hormones
|
|
Negative Cell Cycle Effectors
|
interferon
TGF-B retinoids heparin sulfates |
|
G1 Checkpoint
|
Is cell big enough?
Is DNA damaged? Is environment favorable? Nutrition status OK? |
|
S Checkpoint
|
Has the cell gone through mitosis since the last round of DNA replication?
|
|
G2 Checkpoint
|
Is all the DNA replicated?
Is the environment favorable? |
|
M checkpoint
|
Is spindle formed properly?
Are all chromosomes aligned on the spindle? |
|
MPF
|
Mitosis Promoting Factor
controls entry into mitosis (through oscillation of concentration and activity) regulated by phosphorylation/dephos. 2 subunits: cyclin B & CDK1 |
|
Go
|
growth-arrested state
↓ prot. synth ↑ prot. degradation ↓ RNA synth ↓ # polyribosomes ↓ S6 Phos. flatter shape |
|
R-point response delay
|
regulated by labil prot. w/ 2h half-lives
long delay indicates presence of inhibitory signals that must be overcome before cell proceeds through cell cycle |
|
Cyclin-CDK connection
|
monitoring mechanism in cell division
Reg. by multiple phosphorylation events (inhibitory > activating) Phophatase cleavage of inhibitory P yields rapid activation |
|
Cyclin-CDK Partners
|
G1: cyclin D --- CDK 4 / CDK 6
G1/S: cyclin E -- CDK2 S: cyclin A -- CDK2 M: cyclin B -- CDK1 (MPF) |
|
Why we need cell death?
|
a) nec. for normal devlopment (ex. limb dev.)
b) protection against viral infection (ex. prevent viral replication) c) immune sys. regulation d) elimination of genetic damage (ex. pot. cancerous cells) e) ↑ cell death assoc. w/ degenerative neurological diseases (ex. Parkinson's, Alzheimers) |
|
Immune Cell Death (Pathology)
|
↑ cell death assoc. w/ SCID or AIDS
↓ cell death assoc. w/ autoimmune disease |
|
Types of Cell Death
|
programmed vs. accidental
apoptosis: programmed -- "death on schedule" necrosis: accidental; ex. ischemia |
|
Apoptosis
|
cells do not degenerate randomly, but are broken into cell fragments, then phagocytosed by neighboring epithelial cells
*in normal and diseased tissue, can counterbalance mitosis |
|
Apoptosis (mech)
|
cell shrinks, chromatin condenses against nuc. membrane, karyorhexis
cell sheds buds (blebs) including nuc. fragments cell shrinks to single apoptotic body mito, organelles unaffected DNA cut into 185 bp fragments rapid (30-60min) no inflammatory response |
|
Karyorhexis
|
breaking up of nucleus in apoptosis
chromatin has already condensed in curved profiles against nuclear membrane |
|
DNA Laddering
|
cutting of DNA into 185 bp fragments
*represents size of a nucleosome unit (can see "ladder" pattern when run on gel; necrosis shows a smear) |
|
Ischemic Cell Death
|
begins w/ swelling of cells and organelles
non-specific DNA degradation necrosis (lysis) 12-24 hours after death large inflammatory response as cells are exposed to immune sys |
|
Apoptotic Regulators
|
Fas/TNF receptor family
Capsases Bcl-2 family members |
|
Fas L
|
immunologically privileged sites block B & T cell access (eyes, scrotum/testes, brain)
if Fas R binds Fas L as immune cell tries to cross epithelial tissue, triggers apoptosis |
|
Capsase
|
(Cytosolic Aspartate-Specific Cysteine Protease family)
zymogen activation cascade, eventually clips nuclear membrane and cytoskeletal proteins regulated by bcl-2 *executioners |
|
ICE
|
Interleukin Converting Enzyme
|
|
null mutation caspase-3
|
defective telencephalic (anterior forebrain) development
(cells don't die on schedule) |
|
deletion of caspase 1
|
↓↓ reduction of Interleukin-1 (IL-1) prod.
|
|
Bcl-2 Family
|
overexpression confers resistance to apoptosis, prolonged B lymphocytes survival
deletion leads to massive B cell apoptosis and loss of thymus and spleen, kidney disease deletion of pro-apoptotic members (Bad, Bcl-2s, Bax) → hyperplasia lymphocytes, oocytes, and neurons |
|
Pro-apoptotic Bcl-2 members
|
Bad, Bax, Bak, Bik, Bid, Bcl-Xs
|
|
Anti-apoptotic Bcl-2 members
|
Bcl-2, Bcl-W, McL-1, A1, Ced9, Bcl-XL, E1B 19k, Bhrf1, KSHV ORF16, Lmw5-hl
|
|
Human Follicular Lymphoma
|
Bcl-2 locus at t(14:18) translocation breakpoint
places Bcl-2 prot. just downstream of IgG (↑ expression locus) leades to prolonged survival of B lymphocytes, oncogenic |
|
Mitochondria in Apoptosis
|
death signals dephosphorylate Bad, which binds to BCL-Xs on mito. outer membrane
BCL-Xs forms channels, when activated, loss of fxn permeability control, Cytochrome C released to cyto. Cytochrome C binds Apaf-1 in cyto, cleaves proenzyme capsase9 active capsase 9 accelarates cascade |
|
Apaf-1
|
apoptotic protease-activating factor 1
binds cytosolic cytochrome C, cleaves pro-enzyme segments from capsase 9 |
|
Early Embryonic Development
|
days 1 → 17
trilayer (3 cell embryo) |
|
Blastomeres
|
1st 7 days
formed from mitotic cell divisions, no change in size of embryo |
|
Morula
|
formed at day 3
outer cells (trophoblast) → placenta inner cells mass → embryo *ICM cells also for amnion, yolk sac, parts of the placenta. These are the source of ES. |
|
Early Blastocyst
|
days 3-7
filling of blastocoel → ↑ size, bursts out of zona pelucida ("zona hatching") *ZP prevents adhearance to fallopian tube walls |
|
Late Blastocyst
|
days 7-17
begins just before implantation, ends with gastrulation |
|
Early Cleavages
|
begin in fallopian tube 24-30 hours after fertilization
inside ZP, prevents adherence to fallopian tube walls 48 hours: 8 cell stage (blastomeres) |
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Embryology
|
Embryonic Period (weeks 1-8)
Prenatal Period (weeks 9-38) |
|
Teratology
|
study of abnormal development
birth defects anomalies congenital malformations |
|
Gametes
|
specialized germ cells (♂ & ♀)
haploid (direct result of Meiosis) |
|
Gametogenesis
|
formation of fully-developed gametes
begins at gonad differentiation in the embryo, ends at fertilization Mitosis: Amplifies primordial germ cell lines Meiosis: germ cells undergo meiosis to make gametes |
|
Mitosis
|
produces all somatic cells
1 S phase -- creates exact copies of chromosome 1 M phase -- duplicated chromosomes attach to spindle, align, separate into 2 complete sets *parent and daughter cells identical, diploid |
|
Meiosis
|
only produces gametes
1 S phase Interphase w/ genetic recombination, followed by 2 divisions parents diploid, daughters haploid |
|
Spermatogenesis
|
occurs in seminiferous tubules
*acrosome - specialized golgi *mid-piece houses mitochondria (GTP → flagella) *occurs throughout lifetime of male |
|
Spermatogonia
|
dormant in seminiferous tubules until puberty
multiply by mitosis, mature into primary spermatocytes |
|
Secondary Spermatocytes
|
products of Meiosis I of primary spermatocytes
|
|
Spermatids
|
4 haploid cells created after completion of Meiosis II
|
|
Spermatozoa
|
mature sperm developing from haploid spermatids
*acrosome is specialized glogi at tip of sperm *mid-piece houses mitochondria to supply GTP as energy for flagella *nucleus is highly condensed |
|
Epididymis
|
long coiled duct on posterior border of testes
continues to ductus (vas) deferens mature spermatozoa migrate here from seminiferous tubules, stay for storage |
|
Sertoli Cells
|
line periphery of seminiferous tubules
support / nurture germ cells |
|
Leydig Cells
|
make testosterone
|
|
H-P-O axis
|
Hypothalamus - Pituitary - Ovary
hormonal "chain of command" |
|
Oogenesis (before puberty)
|
oogonia --> mature oocytes begins before birth, completed after puberty
oogonia proliferate via mitosis in untero |
|
Primary Oocytes
|
develop from oogonia
store mRNA, prot, ribosomes for post-fertilization **reason for maternal inheritance |
|
Follicular Epithelial Cells
|
ovarian stromal cells form layer of cells surrounding each primary oocyte
|
|
Zona Pellucida
|
specialized extracellular glycoprotein matrix coat
tough cross-linked protein lamina surrounding oocyte req. for species specific sperm recognition |
|
Cortical Granules
|
placed near edges of oocyte
secretory granules upon fertilization, dump enzymes into extracellular space to cross link ZP, create slow block to polyspermy |
|
Primordial Follicle
|
ZP + single layer follicle cells surround primary oocyte
|
|
Primary Oocyte Division
|
suspended in early prophase I until puberty
|
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Primary Follicle
|
Granulose Cells
formed from follicular epithelial cells as primary oocytes enlarge in puberty *respond to pituitary gonadotropin hormones |
|
Ovulation
|
initiated by FSH (follicle stimulating hormone)
FSH → follicular release of estrogen 10-12 weeks for development from pre-ovulatory (Graafian) follicle after puberty, one follicle / mo, one oocyte ovulated MI comp. --> secondary oocyte, disgard polar body |
|
Secondary Ooctye
|
created from primary oocyte just before ovulation
polar body degenerates arrested in Metaphase II (completes MII only if fertilized) |
|
Oocyte Chromosomal Damage
|
at ovulation, oocytes are 12-55 years of age
* this means there has been plenty of time for environmental factors to damage the chromosomes --> birth defects |
|
Atresia
|
enormous attrition due to apoptosis of oocytes
2000000 primary oocytes at birth, 400000 at adolescence, 400 ovulated |
|
GnRH
|
Gonadotropin Releasing Hormone
s: hypothalamus (brain) t: anterior pituitary a: synth. & secretion of FSH / LH |
|
FSH
|
Follicle Stimulating Hormone
s: anterior pituitary t: ovary a: stim. ovarian follicle growth, differentiation, and steroidogenesis |
|
LH
|
Luteinizing Hormone
s: anterior pituitary t: ovary a: stimulates ovulation, corpus luteum formation, and steroidogenesis |
|
Estrogens
|
s: ovary / folllicle cells
t: uterus, vagina, oviduct, mammary glands a: target growth and differentiation |
|
Progetins
|
s: corpus luteum
t: uterus, vagina, oviduct, mammary glands a: target growth and differentiation |
|
Down's Syndrome
|
Caused by non-disjunction / translocation chromosome 21
|
|
Angelman Syndrome
|
Deletion Ch. 15
severe developmental delay speech impairment (little use of words), mvmt/balance disorder unique behavior, happy demeanor (freq. laughter, smiling, easily excitable, flapping hand mvmts.) delayed head growth, microcephaly by age 2 seizures, onset <3 y |
|
Prader-Willi Syndrome
|
Deletion Ch 15
developmental delay, poor muscle tone, short stature, small hands and feet incomplete sexual development *insatiable appetite |
|
Preimplantation Genetic Diagnosis (PGD)
|
*blastomere biopsy
can remove 1 or 2 blastomeres from 8 cell stage; test for genetic abnomalities remaining blastomeres will still form normal embryo / placenta |
|
Early Mitotic Non-disjunction / Translocation
|
embryo will have 2 or more genetically unique cell lines
*mosaic phenotypes less severe then total non-isjunction/translocation events |
|
Decidual Cells
|
endometrial cells around implantation site
day 8-14, ↑ levels glycogen & lipids develop distinctive polyhedral shape nourish embryo, provide immunologically privileged status {prod. prostaglandin E2, ┤T cell, NK cell activation, maternal rejection} |
|
Early Cleavage
|
24-30h, first mitotic division
48h, 8 cell stage (blastomeres) w/ no change in overall size *zygote still in ZP (prevents adherence to fallopian tube) |
|
Day 3
|
Morula forms by compaction, mediated by cadherin
trophoblast --> placenta inner cell mass (ICM) --> embryo |
|
Day 6
|
Early Blastocyst attaches
blastocoel (fluid filled cavity) begins to form and increase in size ↑ size puts pressure on ZP, --> zona hatching |
|
Day 7
|
Late Blastocyst, begins implantation
|
|
Days 8-12
|
Mid-Implantation
syncitiotrophoblasts invade endometrium to nourish embryo embryo forms bilaminar disc (hypoblast & epiblast) |
|
Days 12-14
|
Completion of Implantation
syncitiotrophoblast → hCG → C.L. |
|
hCG
|
ad detectable levels < 10 days after fert.
ensures survival of CL (and ∴ progesterone production, essential to maintenance of pregnancy) |
|
Gastrulation
|
2 layers become 3
begins in implantation hypoblast delaminates (moves) and space is filled by rapid, directed movement of epiblast epiblast forms: endoderm, mesoderm, and ectoderm (3 primordial germ layers) *takes 2-3 days, perhaps the most important step in development |
|
Spontaneous Abortion of Abnormal Embryos
|
may appear as late / profuse menses
*33-50% rate (of all pregnancies) most grossly abnormal causes early abor: chromosomal abnormalities (60%) cleavage problems (25%) progesterone insufficiency (15%) *likelihood ↑ w/ ↑ maternal age |
|
Ectopic Pregnancy
|
blastocyst implants outside of uterus
1/200 (highest in women >35) 95% implant in fallopian tubes (ampulla or isthmus) -- "tubal preg." ab. pain, tenderness, bleeding, (sim. to appendicitis) rarely carry to full term, high risk of maternal death |
|
Inhibition of Implantation
|
large doses estrogen --| blastocyst implantation (Δ progesterone balance disrupts endometrium)
*"Plan B" RU486 and other drugs work w/ sim. mech |
|
Intrauterine Devices (IUDs)
|
cause chronic inflammation, interferes w/ implantation
|
|
Infertility
|
the inability to achieve pregnancy after one year of unprotected sex
*affect 8 million American couples, or ~12% of the reproductive age population |
|
Hysterosalpingography (HSG)
|
dye injected into cervex; should flow through uterus and out of fallopian tubes
can locate blockages potentially preventing fertilization |
|
Causes of Infertility
|
disruption of any steps between gametogenesis and implantation
♂ 40% ♀ anatomic: 35% ♀ hormonal: 15% unexplained: 20% |
|
Ovulation Defects
|
irregular ovulation caused by hypothalamic abnormalities (i.e. Δ GnRH release)
↓ FSH/LH *stress & extreme athletic activity, eating disorders, hormonal imbalances |
|
Polycystic Ovary Syndrome (PCOS)
|
apoptotic error → cyst formation
↑ LH : FSH ↑ androgen levels ... leads to chronic weight gain, excessive hair growth, irregular ovulation |
|
♀ Reproductive Tract Abnormalities
|
anatomical barriers to fertilization / implantation
ex. endometriosis, Pelvic Inflammatory Disease (PID), tubal obstructions, fibroids |
|
Uterine Fibroids
|
Leiomyomas
benign overgrowths of uterine smooth muscles, project into cavity |
|
Mayer-Rokitansky-Kuster-Hauser Syndrome
|
complete absence of uterus
|
|
Asherman's Syndrome
|
excessive scar tissue in uterine cavity
*freq. occurs after surgeries such as D & C or myomectomy |
|
D & C
|
dilation and curettage
scraping out of the uterus used to remove fibroids (although they will regrow), can cause scarring |
|
Recurrent Pregnancy Loss
|
3 or more consecutive miscarriages
*only counts "known" pregnancies may be from a hormone imbalance, ex. failure to maintain progesterone levels |
|
♂ Factors Causing Infertility
|
azoospermia -- no sperm
oligospermia -- low sperm counts caused by testicular defects, hormonal abnormalities, high Temp |
|
Varicocele
|
blown out vein in scrotum, bleed
↑T in scrotum, negatively affects sperm growth and development |
|
Infertility Treatment
|
1) Diagnose Cause
2) Treat w/ ↓ expensive, ↓ invasive therapy appropriate 3) Progress until successful treatment found |
|
Order of Infertility Treatment
|
Surgical correction of reproductive tract defects
1) oral drugs (clomiphene citrate) 2) clomiphene w/ intrauterine insemination (IUI) 3) injectable drugs (hMG, FSH) and IUI 4) IVF |
|
Clomiphene Citrrate
|
+cheap, oral
--| estrogen receptors in hypothalamus → FSH / LH prod, stim follicle growth one week after last dose, hypothalamus senses estrogen threshold for pituitary LH surge --> ovulation |
|
hMG
Human Menopausal Gonadotropins |
injection
req. follicle size monitoring (via ultrasound) → multiple dominant follicles, ↑ P (mult. births) when mature follicles detected, ovulation triggered w/ hCG (mimics LH surge) equal FSH/LH, derived from urine of postmenopausal women *used: women w/ no luck w/ clomiphene c. & women w/ ↓ FSH / LH |
|
FSH
(Follicle Stimulation Hormone) |
subcutaneous injection
stim. ovaries to prod. mult. follicles and oocytes *used: PCOS patients (high LH/ low FSH levels) |
|
GnRH
Gonadotropin Releasing Hormone |
pump, releases GnRH @ 90 min. intervals ('mimic' hypothalamus)
*used: anovulatory b/c of abnormal FSH/LH release |
|
hCG
(Human Chorionic Gonadotropin) |
one subcutaneous injection at end of treatment to induce ovulation (comes 36-72 h later)
*used: triggers ovulation |
|
IUI
(Intrauterine Insemination) |
*used: ↓ ♂ infert. fact., ♀ w/ cervical mucus abnormalities (wrong pH)
perf. w/ ovulatory induction (↑ efficacy) 24-36 hours after LH surge induced *sperm washed (mimics capacitation) |
|
IVF
(In Vitro Fertilization) |
gonadotropins induce ovulation for egg retrieval (laproscopic proc. w/ ultrasound)
mature eggs incubated w/ washed sperm, early cleavages obs. w/in 2-3 days normal embryos implanted into uterus |
|
ICSI
(Intracytoplasmic Sperm Injection) |
"zona drilling"
*No membrane fusion *No normal Ca++ wave using pipet, sperm injected directly into cytoplasm of oocyte |
|
Embryo Transfer (IVF)
|
2-3 days after retrieval, 1-4 best embryos transf. to uterus
cath. inserted through vagina, cervix, and into uterus ultrasound helps placement of embryos in uterus woman lays in bed for several hours, 4-6 hours later discharged *progesterone given to max. chances of good uterine lining |
|
Homotypic Cell-Cell Interactions
|
involve a single cell type
ex. formation of epithelial layers |
|
Heterotypic Cell-Cell Interactions
|
involving 2 or more cell types
ex. mesenchymal-epithelial interactions |
|
Homophilic Molecular Interactions
|
self-association
ex. Uvumorulin (mouse embryo compaction) |
|
Heterophilic Molecular Interactions
|
involving 2 or more macromolecules
|
|
Matrix Crossbridging
|
cell surface receptors bind extracellular matrix mol. in multivalent manner
ex. basal lamina between epithelium and mesenchyme |
|
Dynamic Interactions
|
making and breaking of contacts
ex. neural crest w/ fibronectin (migration) |
|
Stabilized adhesions
|
redistribution of surface receptors following primary interactions
ex. neuromuscular jxn |
|
Tissue-Specific Adherence
|
homotypic
dissociated cells adhere preferentially w/ cells of same tissue type can mix cells of multiple types, will reassemble into tissue specific aggregates |
|
Mesenchymal-Epithelial Interactions
|
heterotypic
* if mammary gland epithelia is combined w/ salivary mesenchyme, will appear to be a salivary gland, but will produce milk development involves ingrowth of epithelial cells into underlying mesenchyme mesenchyme : morphology epithelium : fxn |
|
Compaction of the Early Mouse Embryo
|
homophilic
blastomeres held together by ZP Ca++ dependent adhesion at 8 cell stage Ab against uvomorulin (a cadherin) --| compaction, blastomeres continue to divide, do not form blastocyst |
|
Binding of Metastatic Cells to Basement Membranes
|
matrix cross-bridging
2` tumor as conseq. of metastasis a. binding to basement membrane b. secretion of degradation enzymes c. movement into adjacent tissues laminin binds itself, t. IV collagen, heparan sulfate proteoglycan, and entactin, *cell surface receptors *metastatic cells ↑ binding to laminin-coated surf. & ↑# receptors Ab against laminin --| metastases |
|
Interaction of Neural Crest Cells with Fibronectin
|
dynamic
originate along dorsal border of neural tube at closure, n. crest cells break loose from epithelium, migrate --> give rise to many tissues (peripheral neurons, schwann cells, pigment cells, connective tissue) *cells follow pthwys lined w/ large adhesive glycoprotein fibronectin Ab against fibronectin interrupt interaction w/ crest cells, blocks migration |
|
Neuromuscular Junction
|
stabilized
|
|
EC
|
endothelial cells
surround lumen in arterial walls -- only blood-compatible surface in body |
|
ECM
|
extracellular matrix
underlies EC monolayer in vessel wall |
|
IEL
|
internal elastic lamina
tough, fenestrated elastin-containing lamina |
|
Intima
|
portion of vessel wall composed of EC and ECM
|
|
Arteriosclerosis
|
response to injury to the arterial wall (from hypertension, hypercholesterolemia, hyperlipidemia, surgery, ...)
platelet aggregation followed by deposits of granular products & growth factors --> SMC hyperplasia/proliferation *may eventually occlude vessel |
|
Marfan's Syndrome
|
elastin cross-linking defect (usually from defective fibrillin)
fibrillin forms "spring" connecting elastin fibers constant pressure changes in large vessels causes progressive stretching out of wall --> aneurysm |
|
Pemphigus
|
autoimmune
Ab to desmoglein (a cadherin) blistering disease; desmosomes and hemidesmosomes in skin are destroyed |
|
Glansmann's thrombasthenia
|
defective integrin
clotting disease (integrins essential for platelet aggregation) freq. fatal by 2-3 years |
|
Metastatic Cancer
|
fibronectin, laminin, MPPs
|
|
Arteriosclerosis
|
multiple-proteoglycans, CAMs, etc., ...
|
|
Scurvy
|
vitamin C def. --| cross-linking
collagen cross-linking defect |
|
Ehler-Danlos Syndrome
|
collagen synthesis & fibril assembly
hyperflexibility & vascular weakness |
|
Menkes
|
Cu def. / non fxn
--| cross linking w/ lysyl oxidase |
|
Alport Syndrome
|
col. type IV def. (mutation)
inherited kidney failure |
|
Goodpasture Syndrome
|
autoimmune
Ab attack type IV collagen destroys basement membrane in lungs and kidneys manage w/ corticosteroids / immunosuppressants |
|
Osteogenesis Imperfecta
|
mut. type I collagen
*social issues -- can appear as abuse in infants presenting with broken bones |
|
Collagen Type I
|
fibrilar (long, thin)
bone, skin, tendons, ligaments, internal organs |
|
Collagen Type II
|
fibrilar (long, thin)
cartilage, invertebral disc, notochord, vitreous humor (eye) |
|
Collagen Type III
|
fibrilar (long, thin)
skin, blood vessels, internal organs |
|
Collagen Type IV
|
network forming, sheetlike
basal lamina / basement membrane |
|
Basal Lamina
|
"basement membrane"
found underneath epithelial tissue, separates epithelium from connective tissue |
|
Proteoglycan Structure
|
cushing, ↑ structural support {~hydration state}
*like a sponge for matrix |
|
Chondrodysplasia
|
collagen def.
extremely flattened nose, oddly shaped legs, hip dysplasia (leg and knee problems), malformed fingers |
|
Fibronectin Structure
|
between cell membrane & collagen
binds integrins collagen binding site and cell binding site |
|
Carcinoma
|
cancer of epithelial cells
must break contacts w/ laminins to metastasize |
|
Integrins
|
everywhere!
fxn specific to cell types can combine in any # of combinations ↑ variability ↑ specificity for specific integrin |
|
Cadherins
|
regulate compaction
cells bind one another of same kind "glue between epithelial cells" |
|
CCN5
|
--| smooth muscle proliferation
|
|
MMPs
|
Matrix Metalloproteases
metal req. enzymes, imp. for angiogenesis ∴--| MMP, blocks tumor angiogenesis & growth |
|
Diabetic Retinopathy
|
from unwanted angiogenesis
|
|
Prenatal Period
|
before birth
|
|
Postnatal period
|
after birth
|
|
Infancy
|
first year after birth
|
|
Newborn / Neonatal
|
first 4 weeks after birth
|
|
Childhood
|
13 mo. to puberty
primary deciduous teeth active ossification |
|
Puberty
|
♂ 13-16 y
♀ 12-15 y (onset of menarche) |
|
Adolescence
|
11-19 y
earliest signs of puberty to attainment of physical, mental, and emotional maturity |
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Adulthood
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begins at 18-21 y
full growth and maturity usually reached ossification complete by 21-25 y |
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Menstrual Phase
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days 1-5
shedding of lining wall breaks off in pieces w/ 20-80 ml blood *necrosis as a planned event |
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Proliferative phase
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days 5-14
estrogenic phase; estrongen levels rise, stimulate re-growth of fxn layer glands increase in number and length, spiral arteries elongate coincides w/ follicles growth |
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Secretory phase
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days 14-27
estrogen levels peak and fall progesterone stays high formation, fxn, growth of corpus luteum in ovary epithelium secretes glycogen rich mucous fluid, endometrium thickens, spiral arteries coil, venous network forms lacunae implantation on day 20 |
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Ischemic phase
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days 27-28 (if not fertilization)
estrogen / progesterone levels fall rapidly, fxn endometrium becomes ischemic spiral arteries constrict, glandular secretion stops, fluid decreases, endometrium shrinks necrosis of superficial tissues |
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Ovarian Cycle
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GnRH made in neurosecretory cells in hypothalamus
secreted in rhythmic waves and carried by hypophyseal portal system to anterior pituitary |
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Ovarian Cycle (2)
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ant. pit. releases FSH, stimulates 4-12 primordial follicles to develop
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Primary Follicle Development
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a) growth and differentiation of a primary oocyte
b) proliferation of follicle cells c) formation of zona pellucda d) development of the theca folliculi |
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Dominant Follicle
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fastest growing follicle in stimulated group
becomes secondary follicle / primary oocyte and ultimately is ovulated as a secondary oocyte |
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theca folliculi
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stroma cells adjacent to primary follices form a capsule
internal vascular/glandular layer: theca interna capsule like outer layer: theca externa promote angiogenesis make follicular fluid, some estrogen, and androgens |
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Antrum
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follicular fluid-filled region
when present, primary follicle becomes secondary follicle surrounded by mass of cells called cumulus oophorus |
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LH surge
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stimulates ovulation 12-24 later
elicited by rising estrogen levels reaching a threshold |
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stigma
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visible cystic swelling on ovarian suface -- marks rapid growth of follicle
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Graafian follicle
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mature
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Corona Radiata
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one or more layers of follicle cells suoorounding ovulated secondary oocyte
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Corpus Luteum
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follicle walls and theca folliculi collapse to form glandular corpus luteum
secretes progesterone and some estrogen degeneration prevented by hCG |
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Progesterone
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causes endometrial glands to secrete glycogen-rich mucous fluid to prepare endometrium for implantation
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Corpus Albicans
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a small patch of white scar tissue left over from CL if no fertilization occurs
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Oocyte transport
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fimbriae and infundibulum at end of fallopian tube sweep secondary oocyte into tube
peristalsis & ciliar mvmt bring oocyte to ampulla |
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Anovulation
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failure to ovulate
freq. caused by inadequate levels of gonadotropins can treat w/ clomiphene citrate |
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Sperm Production
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occurs throughout lifetime of ♂
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Sperm Counts
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normal 100 million / ml, >40% motile
infertile <10 million/ml, <20% motile |
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Capacitation
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glycoprotein coat and seminal proteins are removed from acrosomal surface of sperm
activates sperm for acrosomal rxn |
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ACE
Angiotensin Converting Enzyme |
in acrosome, req. to induce acrosomal rxn
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♂ Contraception
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Vasectomy
reversible 50% of the time |
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Sperm Mvmt in ♀
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swim 2-3 mm / min
muscular contractions in ♀ reproductive tract stimulated by prostaglandins (*most of the mvmt) |
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Fertilization
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occurs in ampulla of fallopian tube, take 24 hours
begins w/ penetration of zona pellucida |
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ZP3
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primary CHO mol. rec. on oocyte by sperm
binding initiates acrosomal rxn |
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Hyaluronidase
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from the acrosome disperses follicular cells surrounding oocyte by eating ECM (degrades hyaluronan)
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Zona Reaction
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sperm contacts oocyte membrane, cortical granules exocytose contents, cross link zona proteins
*slow block to polyspermy |
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Membrane Fusion / Fertilization
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triggers completion of Meiosis II, release of second polar body
sperm brings centriole for mitotic spindle pronuclei formed, membranes break down, chromosomes condense, begin metaphase |
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Zygote
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unicellular embryo, 46 chromosomes (2n)
G prot, Ca++, IP3, prot kinases trigger activation of new zygotic genome |
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Parthenogenesis
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embryonic development without sperm
artificial induction of oocyte cleavage possible in some animals, not humans |
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Polyspermy
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several sperm fertilize oocyte
severe intrauterine growth retardation and developmental anomalies not compatible w/ life |
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Selective Reduction of Multiple Pregnancies
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presents ethical issues in IVF
mult. embryos ↑ mother's risk of complications |
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Ethical Issues w/ Infertility Treatments
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Limited access due to high costs
unknown long term medical risks (ex. ICSI) Are infertility treatments a health right or a privilege? |
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Somatic cell
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cell of the body other than egg or sperm
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SCNT
(Somatic Cell Nuclear Transfer) |
the transfer of a cell nucleus from a somatic cell into an egg from which the nulceus has been removed
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Stem Cells
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cells that have the ability to divide for indefinite periods in culture and to give rise to specialized cells
*self-renewing |
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Totipotent
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unlimited capacity to specialize into any and all cell types or tissues
"omnipotent" |
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Pluripotent
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capable of giving rise to most cells and tissues of an organism
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Multipotent
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capable of giving rise to several/many cell types
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Progenitor cells
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cells that are committed to differentiate
NOT self-renewing, (not stem cells) |
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Clone
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an organism, colony, or group of organisms derived from a single organism or cell by asexual reproduction
*all have identical genetic make-ups |
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Reproductive Cloning
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cloning to produce a pregnancy resulting in the birth of a baby
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Therapeutic Cloning
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cloning to produce embryonic stem cells for treatment of disease
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Properties of a good stem cell
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survive in liquid nitrogen freezing for years
survive and proliferate indefinitely in cell culture maintain stable and normal DNA and chromosomes differentiate predictably into many types of cells |
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ES
(Embryonic Stem Cells) |
+ low cost, unlimited #, pathogen free, non-carcinogenic, reduced immune rejection
++ more plastic - ethical issues! |
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Adult Stem Cells
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+found in most tissues, isolated from live of cadaver tissues
++ few ethical concerns - less plastic |
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Umbilical Cord Blood Stem Cells
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+ fewer ethical concerns
+possibility of a matched set of stem cells for autotransplantation later in life |
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Transgenic Animals
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substitute genetically modified cell into 8 cell embryo
modified trait will show up in some cells/tissues/organs genetic crosses of those chimeras having alteration in germ-line will yield animals w/ genes for new trait in all cells -also, inject modified DNA into male pronucleus of fertilized egg |
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tPA
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tissue plasminogen activator
*clot buster* can tie to mammary gland specific activator in goat, ∴ tPA rich in goat's milk, ... milk it and purify enzyme |
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Rubella (German Measles)
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causes birth defects
used to map progression of development (stage of development at time of infection determines specific defects) |
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Thalidomide
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used in leprosy treatments
powerful teratogen, many birth defects also used to map developmental progression |
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Burkitt's Lymphoma
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c-myc translocation
reveals mol. and mech. for pro- & anti-apoptotic events Bcl-2 misregulation, anti-apoptotic signals, --> massive outgrowths |
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Syndactyly
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lack of apoptosis
webbed fingers / toes no apoptosis to differentiate structures |
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Polydactyly
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wrong timing or wrong amount of apoptosis
make too many fingers or toes |