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LECTURE 1: Human Genome Project LECTURE 2: Small Molecule Drugs

Biggest Medical Advancement in the last 10 years - Very specific


- Human Genome Project, Microbiome project Biologics
- Stem cell research, iPSCs - Made by cells
- HIV cocktails - Acts in very small amounts
- Targeted cancer therapies Antibody
- Laparoscopic Surgery - Can initiate various deadly actions (effector function, signal
- Human Papillomavirus Vaccine transduction by itself or when modified with ligands)
Unmet Medical Needs - Molecules made of CHON
- Chronic pain - Has a variable region (Specific)
- Alzheimer's and other neurodegenerative disorders or conditions - Snake venom antibodies (from horses)
- Cystic fibrosis - Inject venom horse creates antibodies collect
- Immune system condition serum from blood
- TB, Malaria, Dengue, AIDS, Polio Antidote
- Hepatitis, Stroke, Drug Abuse - Reverses anything
- Reproductive disorder and endocrine disorder Serum
Pharmaceutical Industry - Part of the blood that contains tbe antibodies
- Antibiotics Mast Cells
Alexander Fleming - Detects antibodies
Discovered Penicillin in 1928 (London) - If B cells are stimulated, antibodies will be released
Fungi: Penicillium Pregnancy: Human Chorionic Gonadotropin
Pneumonia, Diphtheria ELISA Test
- Growing bacteria on a petri dish - Enzyme Linked Immunosorbent Assay
- Can kill bacteria, NOT viruses Specificity (SP)
Antibiotic action: destroy cell wall 0.61 0.31 False Positive Rate
- First man treated: Policeman
- Quinine - Bangladesh (Japanese) Sensitivity (SN)
- Chloroquine - industrial (Americans)
- Choosing the correct antibiotic 0.52 0.48 False Negative Rate
Sample body fluid is taken so that bacteria can be
grown on nutrient agar False Positive - wala pero sabi meron
Multidisc is placed on agar surface False Negative - meron pero sabi wala
- IMPORTANCE LR+ --> SN/FP or SN/(1-SP)
Version may be allergic to an antibiotic LR- --> FN/SP or (1-SN)/SP
Bacteria may become resistant = 0.52/0.39 = 1.3333
MAY CAUSE ANAPHYLACTIC SHOCK = 0.48/0.61 = 0.7869
- S. Aureus 0 abscess and boils Prior odds = 9
- MSRA - methicillin resistant Post odds = Prior x LR+ if positive, LR- if negative
Nosocomial Disease - any disease that comes from the hospital = 11.7/12.7 = 0.9213 or 92%
- Antifungals = 9 x 0.8 = 7.2
Epidemic
- CHARACTERISTICS Test
Density of population - Have an initial test
Contact - Get Lr+ and Lr-
Very few people are not immune - Apply the formula for post odss
- EBOLA VIRUS Problem in therapy
Blood and body fluids - Drugs are not effective
Mortality rate: 90% - They dont stay long in circulation
- BUBONIC PLAGUE Biologic Solutions: design
Fleas transmit the disease - Drugs that hit only targets
Kaffa, Turkey
Visa System:
- Who are exempted?
Clerics
University People
Pandemic
- HIV (1950s)
Very infectious and sensitive
Men having sex with men
Innovative Platforms
- Cell - based therapy: regeneration, drug delivery, immune
modulation (stem cell and mini organs)
- Support for aging population
- Pharmacogenomics
Future of Medicine
- Growing a heart and other organs
- DNA sequencing for routine check ups
- Pharmacogenetics and Pharmacogenomics
- Immunotherapy
LECTURE 3: Gene Therapy - All are injectable
- Normal gene inserted in non-specific location - No such thing as plant SC
- Normal gene snapped for abnormal homologous recombination - Form of adverse effect
- Reverse of abnormal - 4 hospitals accredited
- CRISPR cas9 - Medical City
Adenovirus - Makati Med
- Done by spraying - Lung Center
Virat Vectors - Cellular Therapeutics Center
- Retrovirus (HIV) - Good for medical tourism
- Most famous retrovirus is HIV DNA Vaccine
- WBC and muscle cells - Body produces the weakened virus peptide
- Insert genes into the genes Peptide Vaccine
- Adenovirus - Given directly
- Common colds
- Herpes Simplex Virus
- Chicken pox Bacteria Virus
- Targets neurons
Salmonella Rabies
Non-viral vectors
Pneumococcus Marburg
- Not very efficient Mycobacterium Lassa
- Direct injection of DNA into cells Bacillus Dengue
- Liposomes VIbrio - shrimp West Nile
- Ligand linked DNA Clostridium (Anaerobic) Japanese Encephalitis
- Artifical chromosome 47 Tetanus (Anaerobic) Measles (most common childhood virus)
Adjuvants Pimple or Acne Mumps (salivary glands and testes)
- Modifies the effect of other agents boosting effect or longer lasting Anthrax White spot virus (shrimp)
Rubella (like measles)
effect (increase immune response)
Nana or Pus is Yellow or Green Polio (ingested)
- Aluminum compounds Hepatitis
- Tuberculosis bacteria B- liver cancer
- Tumor suppressors C - liver, no vaccine
- oncogenes Conjunctivitis (caused by adenovirus in
Hemophilia the Eyes)
- Factor 9 Influenza
- Factor 8 Human Papillomavirus (Warts, benign but
ang malignant form is cervical cancer)
- engineer the liver to produce the factor
Throat, Oropharygneal Cancer
- Hepa A - good
- Hepa B and C - causes liver cancer Cloudy or clear bumps
- Insert DNA that codes for VIral Proteins
- Become immunogenic or stimulates immune response
- Immune Response Defect
- Cancer Candida - fungus
- May access naman to medical care Malaria - plasmodium, prokaryote
- Hepatitis vaccine Tummy Flu - over the counter drugs for flu
- Bacterial vaccine
- Smoking
- Lung cancer LECTURE 4: Biohazard
- Day of Pigs Disaster - Terrorism by intentional release of biological agents (bacteria,
- US failed to capture Cuba virus, toxins) in their natural or human modified form
Problems with Gene therapy History
- Short lived nature of treatment arising from problems of - Romans threw feces at their enemies
integration and rapid alterations - 14th century use of Bubonic Plague
- Pwedeng i-attack yung gene ng body - City of Kaffa, Turkey
- Pwedeng maging virus yung vector na nainstert (adenovirus) - World War I use of horse disease against Allies
- Immune response can attack - 1993 - Aum shinrikyo release anthrax
- Gelsinger -> died of massive organ failure - 1984 - Salmonella by Bhagwan S Rajneesh
- 2003 ( Banned ang gene therapy) - 2001 - Anthrax killed 5
- X-Severe Combined Immunodeficiency (X-SCID) Bacteria will form spores at time of stress
- 2003 Category A
- 11 french children participated in a study of gene - Anthrax (B)
therapy as a cure for severe combined - Smallpox (V)
immunodeficiency - Botulinum Toxin - pdt of B
- 3 children appear to have been cured but 4 developed - Bubonic Plague - B
leukemia-like symptoms and 1 died - Viral H fever: Marburg, Ebola, Lassa, Machupo (V)
PFDA: Stem Cell Anthrax
- Requires accreditation - Bacillus anthracis
- Bone marrow - Commonly affects animals
- Corneal resurfacing - Spread by spores
- Skin regeneration with epidermal cells - Tested by unit 731 in Manchuria in 1930
- Hematopoietic SCT - Accidental release in Russia killed 68 in 1979
- Benefits are still under investigation - 2001 bruce ivins allegedly killed 5
Smallpox Transplantation Antigens
- variola virus Antigens Degree of polymorphism (version)
- blood vessels in skin, mouth, throat ABO blood group Limited
- 30-100% mortality rate Major Histocompatibility Complex Very high
- scarring, blindness, limb deformities Minor HC (non-MHC antigen) Limited
- killed 300 to 500 M in the 20th C until eradicated by vaccination in Xeno antigens Extremely wide variety
1970 ABO Blood Groups
- close person-person fomites donor
- fomite: objects or materials that carry infection A B O
- chicken pox virus A / X /
- smallpox virus recipient B X / /
- cowpox rural form of smallpox O X X /
- bigpox bacterium (syphilis (STD))
AB / / /
- bacterium is Triponema
more T cells are activated in the immune response in grafting than in
- TROPISM (what is affected
infection
- HISTORY
Bone Marrow
- At least 10,000 years ago
- Transplant: stem cells
- First recorded in India (1500 BC) spread in Europe
- Insert by injection
during the Crusades brought by New World Colonists
- Old bone marrow exposed to radiation
in 16th Century
- Provide immunosuppressive drugs
- Allegedly used by British in the French and Indian
- FACS Machine
Wars and in the American Revolutionary War
- Used to separate stem cells
- Russian accident in 1970
Tissue Engineering
Variolation
- Engineering + biology bio substitutes
- Pre-vaccine treatment
- General approaches
- Live virus
- In-vivo
- Inhale or inject to get the disease DELIBERATELY
- Ex-vivo
Botulinum Toxin
- Killed 20 between 1989 to 2003, none linked to cosmetics
LECTURE 6: Evolution of Humans
- Paralytic
Molecular methods:
Bubonic Plague or Black Death
- DNA/RNA
- With antibiotics, black death is curable
- Single or multilocus
- Yersinia Pestis, attack lymph nodes (buboes)
- Sensitive and specific
- 50% mortality rate
- Directly on specimen
- Flea bites
Taxonomic Resolution
- Plague of Justinian 6th century
- Same appearance on the outside but when subjected to gel
- Black death of Europe killed to of population (14th century)
electrophoresis, magkaiba na yung pattern ng bands
- Used by Japanese in WW2
- Species and strain identification
Ebola
- Sub species
- A hemorrhagic rash appears over the entire body
Possible scenario
- Makes blood vessels open up
- 10 km rock at 100 000 kph generated million tons of TNT
- Spread through fluids
- destroyed everything within 400-500 km, followed by fires
- Immune system acts up
- Tidal waves (evidence exists), dust, vapor
Category B
- Series of volcanoes, earthquakes
- Brucellosis
- Fall of temp, then rise, then acid
- Salmonella
- Global cooling
- Glanders
- Effect on land: wipe out plants: about 25%, then herbivores
- Ricin
- Birds or mammals, ferns take over
-
Origin of Species, 1859
- Darwins diagram of the principle of divergence
LECTURE 5: Xenotransplantation and Tissue Engineering
- Early multicellular life
- Thomas Starza
- Ordovician
- From animals
- Silurian
- Xeno Foreign
- Devonian
- Use animals bred not to have immune suppressors
- Permian (early dinosaurs)
- Immune system detects transplant as foreign
- Feathered dinosaurs
24 year old victim, 30 M pig neural cells transplanted into damaged part
Cluster diagrams
of the brain
- cladogram
20 year old liver damage, hooked up to a series of transgenic ( pig livers
- Shows who are similar
until human donor was found
- Phylogeny
pig heart transplant; patient died in 2 days attributed to a small heart
- Phylogenic tree (common ancestor) -> cluster tree ->
GRAFT
ancestral tree
- Autograft (skin, self)
- Technical definition or phylogenetic
- Isograft (genetically identical individuals (twins)
- Common ancestry
- Allograft (genetically different but same species)
- Birds are reptiles
- Xenograft (different species)
Vessel surgical reconstruction
Angioplasty human lymphocyte antigen (HLA profile)
Bypass replace vessels in the heart using vessels from the foot

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