Core I
Terms
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- pseudohypoparathyroidism (type Ia)
- gene mut in G alpha; loss of GTPase activity or accelerated Guanine Nucleotide Exchange; since in body, the G protein is deactivated
- testotoxicosis
- mut. in Ga causing loss of GTPase activity or accelerated Guanine nucleotide exchange, testes are cooler so protein dn denature
- cholera toxin
- modifies a subunit on Gs that's critical for GTPase activity so STUCK ON
- pertussis toxin
- Gi protein, STUCK OFF
- B1--PKA phosphorylates VSCC
- +ve inotropic +ve chronotropic relax sm. m., secretion, steroidogenesis, hungry state
- B1 (heart) B2 (bronchiole)
- B1 E=NE B2 E>>>NE
- Evidence Cycle
- 1. asking foreground Q 2. Accessing best evidence 3. Appraising evidence critically 4. Applying evidence to pt sit 5. Assessing performance of plan
- Asking Foreground Q
- 1. Pt Popn 2. Intervention 3. Comparison or Control 4. Outcome 5. Methods
- Critically Appraise Article
- Is the study valid? (must face diagnostic uncertainty, blind v. gold standard) What are the Results? How can be applied to my situation?
- Congenital Adrenal Hyperplasia (CAH)
- Genetic defect in cortisol production -> elevated ACTH -> adrenal cortical hyperplasia -> intrauterine production of androgens -> masculinization of XX fetuses (female pseudohermaphrodite)
- Benign Prostatic Hypertrophy (BPH)
- Western⬝ male -> nodular hyperplasia -> urinary frequency, urgency, retention, UT infections, increased gland/stroma ratio
- Squamous metaplasia of bronchial epithelium
- columnar-->squamous
- Barrettʼs metaplasia of esophagus
- ⬢ Squamous -> columnar epithelia of intestinal type ⬢ Chronic reflux esophagitis ⬢ Increased risk of cancer
- Reversible subcellular response to injury
- Cell may recover if stimulus withdrawn – “Hydropic change†due to cell swelling – “Fatty change†due to altered fat metabolism – ER, mitochondrial swelling – Membrane blebs – Clumped chromatin
- Irreversible
- – Cell cannot recover if stimulus withdrawn – More swelling with breaks and ribosome detachment – Myelin figures (concentrically swirled membranes) – Fragmented chromatin • Pyknosis - condensation • Karyorrhexis - fragmentation • Karyolysis - dissolution
- Necrosis
- cell gets bigger karyolysis corrupt plasma membrane inflamm. c. engulf necrotic cell corpose tz destroyed always abN
- Apoptosis
- cell gets smaller nucleosome fragments plasma memb intact no inflamm, corpse may be engulfed by adj c. tz intact N or abN
- Coagulative Necrosis
- ischemia, toxic exposure w/o redundant Blood Supply pale&wedge shaped dual blood supply-wedge shaped hemorrhagic
- Caseous Necrosis
- TB, leprosy, myobacterial
- Fat necrosis
- pancreatic injury release lipases with saponified Ca salts and FA
- Fibrinoid Necrosis
- med. arteries following vasculitis
- metastatic v. dystrophic calcification
- hypercalcemia (metastatic), necrosis w/o abN serum Ca++ (dystrophic)
- Bcl2
- -oncogene block cell death -overexpressed in follicular lymphoma
- Apaf1/ced4
- apoptosome
- caspases/ced3
- activator, executioner, inflammatory
- Bcl2/ced9
- oncogene (promote growth) overexpressed in follicular lymphoma
- Autophagy
- prevent death in nutrient deprivation/accelerate cell death in stress
- Necroptosis
- RIP1 PARP1 (normally promote DNA stability)
- a1-antitrypsin mutation
- defect in protein folding reduce solubility and degradation resulting in accumulation in intracellular aggregates
- Mallory Bodies; Hyaline Glomerulosclerosis, hyaline in lung
- aggregated intermed. filament protein, fibrin and plasmaexcess glomerular bm
- RIP3
- switches TNF induced cell death from Apoptosis to Necrosis
- Niemann Pick Anthracotic Pigment
- lackof enzyme ingestion of undigestible material
- Insulin(IR, P13K, PDK1, AKT)--|FOXO1-->longevity, antiaging
- PTEN--longevity/antiaging SIRT1-longevity/antiaging
- Sirtuins
- NAD-dependent deacetylates histones (Acetylated histones-Active genes) Sir2 starved mice, longevity, Resveratrol-activates Sir2
- Huntington-Gilford Progeria
- deletion mutation in lamin A, an intermediate filament of nuclear envelope
- Werner Syndrome
- -mut DNA helicase WRN of the RecQ family -WRN-dna recomb repair/telomere maintenance -premature aging
- Telomerase deficiency
- hayflick limit (#celldivisions) BM failure and pulmonary fibrosis
- Klotho
- reg. insulin/FOXO, longevity reg. FGF23-->Phosphate reabsorption, leading to phosphate toxicity
- parvovirus
- --self-priming strand displacement --Small, linear ssDNA • Non-enveloped • Parvoviruses DNA information is insufficient,require helper virus or rapidly dividing cells. – Dependovirus (Adeno-associated virus (AAV)) Req. co-infection with a helper virus (adenovirus or herpesvirus) • No disease in humans • Common viral vector used in gene therapy – Parvovirus B19: Requires dividing cells for replication • Erythema infectiosum (childhood illness, fever, rash) • Aplastic anemia (sickle cell disease, hemolytic anemia) • Fetal loss
- Papovavirus
- Non-enveloped, icosahedral symmetry, dsDNA circular genome (5-8 kb). • Viral genome can persist in episomal [(papilloma (pa) or integrated (polyoma (po)]. • Replication/assembly in nucleus, virions released via cell lysis • Narrow host range – Papilloma replication only in differentiating cells • Multiple splicing events • Multiple promoters
- Strand displacement
- do not require RNA primer --adenovirus --parvovirus --pox virus
- Fork
- require RNA primer -papovirus -papilloma -polyomavirus