fundamentals week 6 tutoring.pptx

8/14/2019 Fundamentals Week 6 Tutoring.pptx

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+

Fundamentals Week6Ashley and Kara

(best if viewed in full screen)


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+Blood Plasmatrin!er

Avera!e adult blood volume" # $ (%lasma" & $)

'ormal serum electrolyte values"

odium *# m+,-$

Potassium &.##./ m+,-$

0hloride 12/2 m+,-$

Albumin is the most abundant %rotein in the %lasma"

3rans%orts free fatty acids4 acidic dru!s (warfarin4 as%irin)4bilirubin4 metal ions4 and water (indirectly)


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+5f %rotein 0 and %rotein are

!enetically absent4 what ty%eof disease %resents

A. hemolytic anemia

B. sickle cell anemia

0. hy%ercoa!ulation disorder

7. hy%ocoa!ulation disorder

+. hemo%hilia


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+Anti!en %ecific 8ece%tors

0hoi B cells are made throu!hout the lifetime of humans and are at rest and ,uiescent until

stimulated by an anti!en

Light chain gene rearrangement:

+ncoded by 9 !ene se!ment and : !ene se!ment (occurs via somatic recombination)

Ka%%a and lambda code for the li!ht chains

Heavy chain gene rearrangement:

+ncoded by 9 !ene se!ment4 short 7 !ene se!ment4 and : se!ment (also occurs via somaticrecombination)

7ifferent B cells use different combinations of 94 74 and : to make the heavy chain variable re!ion

Junctional diversity" occurs at 97 and 7: ;unction of heavy chain and 9: ;unction of li!htchain

Somatic hypermutation" %oint mutations introduced into 9 re!ions of < and $ chains afterthe B cell is activated

occurs after B cell encounter with anti!en

=ost mutations are in the 078 re!ions


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+Anti!en %ecific 8ece%tors4

0ontinued3wo ty%es of 3 cells" al%ha-beta (more common) and

!amma-delta


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+What is the function of the

en>yme terminaldeo?ynucleotidyl transferase(3d3) A. Activates recombination of the li!ht chain. B. Addition of ' se,uences at the 9: ;unctions.

0. @sed as a marker for detectin! early linea!elym%hoid cells

7. Addition of ' se,uences at 97: ;unctions

+. Both 0 and 7

F. Both B and 0

. All of the above


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+What is the result of a 8A

recombinase deficiency A. 5!A deficiency

B. 7ieor!e yndrome

0. evere combined immunodeficieny (057)

7. 5! deficiency


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+i!nal 3ransduction$ieberman

Oncogene" !ain of function mutation (dominant mutation)

Tumor suppressor" loss of function mutation (recessive mutation)

rowth factors are re,uired to alter the conformation of the rece%tor so

that it can be activated

Antibodies to the rece%tor can activate the rece%tor so that it res%onds as if!rowth factor was %resent

ome !rowth factors must increase intracellular calcium levels in order to activatethe rece%tor (P7F4 +F)

Cell necrosis(abnormal event)" causin! cell swellin! which ru%tures the%lasma membrane4 causin! an inflammatory res%onse

Cell apoptosis (normal event)" causes cell shrinka!e and chromatincondensation. Pha!ocytosis results.


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Activation

(either G-protein mediated or

tyrosine kinase mediated)

Ras-GTP (active)

Growth Factor

Receptor

Raf activation

(MAPKKK)

Activate MAP kinase kinase

(MEK)

Activate MAP kinase

(ERK)

Phosphoryate Phosphoipase

A!" which activates A! and

eads to arachidonic acid

reease for second messen#er

prod$ction

Phosphoryate transcription

factors (%$n)& ater #ene

re#$ation

(Feed'ack inhi'ition () of

rafand MAPKK'y MAP

Kinase)


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+i!nal 3ransduction4 0ontinued

Retinolastoma" caused by tumor su%%ressor !ene

8b binds to +F and blocks the transcri%tion of !enes re,uired for to transition

When 8b is %hos%horylated4 it dissociates from +F and transcri%tion is initiated socells can enter the %hase

Phos%horylation is re!ulated by cyclin com%le?es

!sent R leads to loss o" regulation cell proli"eration

#RC!$ gene" tumor su%%ressor !ene which increases risk of breast-ovariancancer

Phos%horylated B80A inhibits cell cycle %ro!ression and blocks error %rone re%air ofdouble strand breaks in 7'A

Phos%horylated B80A can recruit B80A to the site of dama!e

#RC!% gene" tumor su%%ressor !ene found on chromosome &

5nvolved in re%airin! 7'A double strand breaks

5ncreases risk of breast and ovarian cancer


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+


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+Which of the followin! is false

re!ardin! colon cancer A. 0an be caused by inherited or s%ontaneous causes

B. 0an be treated with leevec and is caused by a bcrabl mutation

0. //C of %eo%le with a mutated AP0 !ene will !etcolon cancer without a colonectomy

7.


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+Which of the followin! is false

re!ardin! 3amo?ifen A. +8 %ositive breast cancers will res%ond to this dru!

B. 3amo?ifen is an estro!en anta!onist in breast cells4but an a!onist in the liver and bone

0. 0an be !iven %ro%hylactically to youn!er womenwith increased risk of breast cancer

7. 3amo?ifen increases the chance of lun! and colon

cancer

+. Both A and 0

F. Both B and 0


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+Anti!en Processin!=onaco

0ell mediated immunity uses 3 cells to fi!ht intracellular infections

0ytoto?ic 3 lym%hocytes e?%ress the 072 surface marker

5ntracellular anti!ens

3 cells that e?%ress the 07* surface marker (hel%er 3 cells) are anti!en %resentin! cells to other host cells (B cells4macro%ha!es)

+?tracellular anti!ens

3 cells have rece%tors that only reco!ni>e %rotein anti!ens

=


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+Anti!en Processin!

=


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+From which intracellularcom%artments do =


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+What would be the result of anabsence of the


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+=ilestones in Pharmacolo!yand =edicinetrin!er

Ascle%ius" ancient reek !od of medicine

Ascle%ius rod


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+What is evidence basedmedicine

3he conscientious4 e?%licit4 and ;udicious use of thecurrent best evidence in makin! decisions about thecare of individual %atients


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+Anti!en Processin! and =


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+Anti!en Processin! and =


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+Which


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+Amino Acid =etabolism4 @rea0ycle$ieberman

'itro!en derived from amino acids is incor%orated intourea4 which is easily e?creted

@rea cycle occurs in the liver

lutamate dehydro!enase kee%s ammonia levels low

Al%haketo!lutarate!lutamate

Ammonia is to?ic because it can inhibit !lutaminase in thebrain4 %reventin! the %roduction of !lutamate and ABA(neurotransmitters)

lutamine is the ma;or ammonia carrier in the body


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3he @rea 0ycle

NH2 C NH2

OArginase

urea

H C

2

C

H

NH

OHNH

(C )2 3H

O

(ornithine)

NH2

COOH

CH

CH

COOH

OH

H

NH

C N (CH )2 3 C C

H ONH

H

Argininosuccinate

Lyase

(arginine)

(fumarate)

2

C

OH

O

C N (CH )2 3 C

H

NH

H C N

HCH2

COOH

COHO

NH2

(argininosuccinate)

CH2

CH

COOH

COOH

2NH

(aspartic acid)

Argininosuccinate

Synthetase

ATP

AP

!

PPi

(CH )2 3 C

H

NH2

C

OH

O

NH

H N2

CO

(citru""ine)

OH

P O

O

#C O

OH

N

(car$amoy"#p)

Pi

OrnithineTranscar$amoy"ase


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+@rea 0ycle4 0ontinued

Regulation"

As !lutamate levels rise4 more 'acetyl!lutamate is made4 whichactivates 0P

Allows more carbamoyl %hos%hate to be %roduced to feed into the ureacycle

Ar!inine activates 'acetyl!lutamate synthase to make more 'acetyl!lutamate

3reatments for urea cycle disorders" want to !ive the %atients

a!ents that will con;u!ate with nitro!en containin! com%oundsand remove them from circulation

#en'oic acid" con;u!ates with !lycine to form hi%%uric acid

(henylacetate:con;u!ates with !lutamine to form%henylacetyl!luatmine (hel%s control hy%erammonemia)


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+3ransaminations re,uire whichvitamin

A. B

B. B6

0. B

7. 0


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+Which of the followin! is falseabout ornithinetranscarbamoylase defects A. 3his is the most common urea cycle defect

B. ym%toms include hy%erammonemia with oroticaciduria

0. Autosomal recessive disease

7. 7efective ornithine transcarbamoylase causes

carbamoyl %hos%hate to build u% in the mitochondriawhich results in elevated orotic acid

+. 'one of the above


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+Which ty%e of %erson would notbe in %ositive nitro!en balance

A. !rowin! children

B. bodybuilders

0. recoverin! burn %atients

7. starvin! %atients

+. both 0 and 7


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+What are the two e?clusivelyketo!enic amino acids

A. isoleucine and leucine

B. lysine and leucine

0. threonine and lysine

7. tyrosine and try%to%han


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+ene 3estin! and ene 3hera%y=enon

(opulation screening" identifies a subset of the %o%ulation in whomdia!nostic tests can be carried out

7oes not %rovide definitive dia!nosis4 tests should be chea% and fast

)iagnostic screening" identifies individuals in hi!h risk families

Provides definitive dia!nosis4 small scale screenin! for disease alleles

Sensitivity: true %ositive- (true %ositive H false ne!ative)

Speci"icity: true ne!ative- (true ne!ative H false %ositive)

(ositive (redictive *alue ((*," true %ositive- (true %ositive H false%ositive)

-egative (redictive *alue -(*," true ne!ative- (true ne!ative H falsene!ative)

8emember that !enetic tests reveal mutations4 not %resence of disease

=any disease causin! mutations have incom%lete %enetrance


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+When is linka!e analysisuseful

A. When the disease !ene se,uence is not available.

B. When the e?act !ene se,uence is known.

0. As a %o%ulation screenin! test for newborns.

7. When the %arents are refusin! other forms oftestin!.


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+Which of the followin! vitaminsis re,uired for calciumabsor%tion from the !ut A. 9itamin 7

B. 9itamin 0

0. 9itamin B

7. 3hiamin

+. 8iboflavin


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+5n a &1 year old woman who ;ust !ave birth4chorionic villus sam%lin! was %erformed4 and abattery of !enetic %anels was assessed in thenewborn. Dne marker indicated a defectivecystathionine B synthase. Which of thefollowin! com%ounds would you e?%ect to beelevated in the blood of the infant if the mother

was not %ro%erly treated

A. valine

B. homocysteine

0. threonine

7. !lutamine

+. cysteine


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+A child was brou!ht to 0hildrenIs with acom%laint of %assa!e of dark colored urine. Adisorder of %henylalanine metabolism wasdia!nosed. A low %henylalanine diet and asu%%lementation of vitamin 0 wasrecommended. What en>yme defect ise?%ected in this child

A. %henylalanine hydro?ylase

B. 3yrosine transaminase

0. homo!enistic acid o?idase

7. hydrolase


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+A & year old woman is seen for a lum% in herbreast that she %al%ated on self breaste?amination.


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+A *J year old man4 with no known history ofcancer4 develo%s chan!es in his bowel habits4includin! occasional blood in his stools. Acolonosco%y and bio%sy confirms the dia!nosisof adenocarcinoma of the colon. Furthermore4the tumor is found to have mutation in the ras%rotein. Which of the followin! best describes

the %rotein A. non rece%tor tyrosine kinase

B. nuclear transcri%tion factor

0. rece%tor kinase

7. 3P bindin! %rotein

+. %oly%e%tide !rowth factor


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+A homeless %erson is brou!ht into theemer!ency room with %sychotic illness

and smell of alcohol in his breath. Whichof the followin! vitamins is needed as%art of his treatment

A. Folate

B. 'iacin

0. 3hiamin

7. 8iboflavin

fundamentals week 6 tutoring.pptx

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