PHAR 1001E: Exam 3
Incapacitating agents
- Agent 15 - Dimethylheptylpyran (DMHP) which is a THC analog - EA-3167 - Kolokol-1 - PAVA spray - Sleeping gas Riot-control - Pepper spray (Capsaicin) - Mace (tear gas)
Which of the following is false?
Blue eyes first appeared a million years ago, they appeared about 10,000 years ago TRUE statements: - Blue eyes are due to a gene mutation - No eye pigment results in blue eyes - Two major genes determine eye color - Blue eyed people likely came from one ancestor
Which of the following potential bioterrorism agents causes our muscles to lose their ability to contract?
Botulinum toxin
What is the most common natural way that humans are exposed to anthrax?
Cutaneous - Pulmonary would be the most common bioterrorism exposure
Smallpox - Variola virus is an
Orthopoxvirus - maybe the family name of the virus
Altered substrate specifity
Other metabolites possibly formed (Simple Point Mutations), drug concentration is really low so not having a therapeutic effect
Which of the following is easily transmitted from person-to-person, causes high mortality and might cause public panic?
Plague
Which one of the following is not correctly grouped?
Plague: Only in humans, Clostridium, caused by Yersinia pestis and is in animals CORRECTLY MATCHED: - Anthrax: Zoonosis, Bacillus - Smallpox: Contagious, Variola - Botulism: Respiratory support, protein toxin - Tularemia: Zoonosis, Francisella
Unstable enzyme
Reduced metabolism (Simple Point Mutations), drug levels increased a little bit, might have adverse effects
Why are we no longer vaccinating people against Smallpox virus?
There is a significant health risk associated with vaccination - It is still considered very contagious - Most people are very susceptible to Smallpox - Smallpox is considered a significant bioterrorism threat
How do our cells repair DNA mutations?
They don't, they repair DNA damage, can't repair a mutation once it occurs
True or False: Electromagnetic radiation interacts with chemicals in different ways depending on its frequency?
True
True or False: Electromagnetic radiation interacts with chemicals in different ways depending on its wavelength?
True
Which of the following human diseases would most likely be acquired by humans after being bitten by the organism shown in the picture (Lone Star Tick)?
Tularemia
What is causing this effect?
UV radiation causing photoionization
Which of the following is not a type of electromagnetic radiation?
alpha-particles - infrared, UV, microwave, and X-rays are all EMR
Which of the following can pass through paper but not aluminum?
beta particles
What is the approximate acute dose of radiation that would cause no observable effect in humans?
0-250 mSv
What is the approximate energy (in eV) of visible light?
1
Exposure to Botulinum protein toxin occurs through the following mechanisms
1) Ingestion of preformed protein that is fairly large (dose dependent) 2) Inhalation of preformed protein (dose dependent) 3) Local production of protein toxin by C botulinum in the gastrointestinal tract of infants (<12 months old) so if you give somebody some honey that is contaminated with C. botulinum, it can grow in the gastrointestinal tract so that is why it is recommended not to give < 1 year old kids honey because there is a little bit of the bacteria in the honey and for some reason it grows really well in infants intestines but not in our intestines, but if we eat the preformed protein it affects us the bacteria doesn't do so well 4) Local production of protein toxin by C botulinum in anaerobic tissue at the site of a wound
Biological agents used in a bioterrorism attack would likely enter the human body through one of several routes
1) Inhalation of small particles into the lungs (easiest) 2) Ingestion of contaminated food or water (less likely) 3) Contamination of the skin or absorption through the skin (less likely)
Smallpox is a concern as a biological weapon for several reasons
1) much of the population is susceptible to infection since nobody is being vaccinated anymore, if you have smallpox you can't get it again, but there are few people left that have gotten it 2) the virus carries a high rate of morbidity and mortality (about 30%) 3) the virus is contagious 4) vaccine is not available for general use 5) past experience has demonstrated that smallpox creates a great deal of havoc and panic Aerosol release of virus is most likely method of weaponization of Smallpox
Critical Biologic Agents for Use in Bioterrorism - Category A agents
1. Bacillus anthracis (anthrax) - Bacteria 2. Clostridium botulinum toxin - Bacteria 3. Yersinia pestis (plague) - Bacteria 4. Francisella tularensis (tularemia) - Bacteria 5. Variola major (smallpox virus) - Viruses 6. Ebola, Marburg, Lassa and other viruses - There are also Category B and C Agents (other bacteria and viruses agents that could be used as bioterrorism agent)
Anthrax: Weaponization
1. Grow 2. Spores (resistant to desiccation and UV light, humidity, temperature, they are an ideal way to weaponize anthrax) 3. Purify 4. Dust (add some talcum powder to make it in like a dust powder material) 5. Deliver the spores or powder maybe in an envelope 6. Inhale the spores and get the disease - 2001 Anthrax Attacks
Chemicals used as Weapons
1. Lethal agents (most of them aren't lethal but with enough of them they can cause death) a. Blood agents b. Blister agents c. Nerve agents d. Pulmonary/choking agents e. Vomiting agents 2. Incapacitating agents
What is the approximate energy (in eV) of UV radiation
10
Historical use of Biological Weapons
1346 - plague infected corpses catapulted over city walls - "black death" because of these sores that developed in people that had the plague (killed at least 75 million people or about half of the people throughout Europe) spread through fleas 1767 - French and Indian War, Lord Amherst (British general) might have provided "gifts" of Smallpox laden blankets to American Indians loyal to the French (not certain that this is true, but it is possible)
US Epidemiology of Tularemia
150 case/yr. - South central and Western US, Transmitted by ticks/deer flies/ mosquitoes, or contact with infected animals (rodents/rabbits)
Approximately what percentage of mutations confer an advantage to an individual
2
Why are mutations significant?
A. Cancer (caused by mutations - about 1,500/day which is usually two or more mutations are required) is a major disease in Humans - Some cancers (about 10%) are due to germline mutations like BRCA, most cancers are due to somatic cell mutations that occur during our lifetime B. Other hereditary (germline) diseases such as Familial hypercholesterolemia (1 in 500), Polycystic kidney disease (1 in 1250), Sickle cell anemia (1 in 625), Cystic fibrosis (1 in 2,000), Tay-Sachs disease (1 in 3,000), Phenylketonuria (1 in 12,000), Duchenne muscular dystrophy (1 in 7,000), Hemophilia (1 in 10,000), Lots of other Hereditary Diseases C. All life on earth is due to mutations; major source of variation!!! - Other side of mutations; an enormous biological variability is due to mutations, we would not be here without mutations - In bacteria that were injected with a virus that was treated with a chemical that caused mutations and determined how well these viruses grew after they have been exposed to mutagenic chemicals: about almost 40% were lethal, about 25% had no effect or they didn't alter the growth of virus on the bacteria, only 2% of the mutations were advantageous meaning they either allowed the virus to grow faster, infect the bacteria better, the rest were sort of deleterious meaning that it caused the virus to grow slower but didn't really kill them - In us, an advantageous mutation could be better VO2 max, stronger muscles, an example of a lethal mutation is cystic fibrosis can be treated but eventually it's not good, Deleterious mutations include Sickle cell anemia which a person can live with but it is hard on them, Phenylketonuria, Hemophilia (have to be very careful if you have that)
How do our cells limit the formation of mutations (3 billion base pairs in each cell)?
A. DNA repair: DNA repair only recognizes damaged DNA, Repair of damaged DNA, not repair of mutations!!, can't repair blue eyes (a mutation) it doesn't recognize already occurred mutants or mutations, but can repair damage to DNA through UV light that forms a thymine dimer 1. Base excision repair: Cuts out the damaged base and replaces it with a new base 2. Nucleotide excision repair: Cuts out a bunch of bases so its a nucleotide length and not just one pair so it basically does the same thing, can repair damage from UV radiation, can cut out at least 30 bases, there are people who have mutations in their nucleotide excision repair and there are about 2000 of these people so if they go outside they are so sensitive to sunlight that it causes Xeroderma Pigmentosum (children of the night) which results in cancer in most people with this disease, can't even go outside in the sunlight without risking damage occurring in their epidermal cells on their skin, without the mutation we repair it before we even know that it happens 3. Mismatch repair: Occurs soon after a DNA replication error where the wrong base is added and the enzyme system recognizes the mismatch and in this case it cuts out a huge piece of the other strand up to 2000 bases and then fills it back in with the correct base, Important to recognize the damage before the second strand is synthesized or replicated to put in the wrong base and making a mutation
How can we use information about mutations to improve human health?
A. Disease diagnosis/screening 1. Cancer (e.g. BRCA1/2; germline mutations) - Can diagnose and prevent before it becomes a problem 2. Other Hereditary diseases: Familial hypercholesterolemia (1 in 500), Polycystic kidney disease (1 in 1250), Sickle cell anemia (1 in 625), Cystic fibrosis (1 in 2,000), Tay-Sachs disease (1 in 3,000), Phenylketonuria (1 in 12,000), Duchenne muscular dystrophy (1 in 7,000), Hemophilia (1 in 10,000), Xeroderma pigmentosum or XP (1 in 250,000) B. To optimize the use of prescription medications 1. For treating cancers caused by mutations 2. Drug Treatment Options for people a) Mutation in Drug metabolizing enzymes, some of the enzymes have mutations
Higher enzyme levels
Increased metabolism (Large Scale Mutations)
Vomiting agents (Lethal agents)
- Adamsite - Chloropicrin - Diphenylchlorarsine - Diphenylcyanoarsine - Diphenylaminocyanoarsine
Botulism (Clostridia Botulinum - strict anaerobe which means that it can only live in deep wounds or in places where there is no oxygen)
- C. botulinum is a natural contaminant of anaerobic soil throughout the United States, but it is found more frequently in the west (not a zoonosis so no real animal reservoir so not like it's constantly infecting animals and then we are getting it from animals, it is in the soil, out in nature so can pick it up occasionally) - Patient Alert - Postural Hypotension (when you stand and blood pressure drops and you get dizzy and could pass out) - Pupils Unreactive - Normal Sensation - Variable Muscle Weakness (limp), need respiratory support because the diaphragm can't contract - Blocks release of acetylcholine; muscles can't contract, blocks the binding of the vesicles that contain the neurotransmitter so they can't fuse with the membrane and can't release acetylcholine so there is just no connection and muscles can't contract, cleaves synaptobrevin in the vesicle containing acetylcholine so the vesicle can't bind and fuse to release acetylcholine - Botulinum toxin is one of the most toxic compounds (protein) that is used as a drug and it is very effective to get rid of wrinkles, depends on dose - a little is ok, but too much is not good - Case Fatality - High mortality without respiratory support - Most cases in the USA (about 30/year) are due to consumption of improperly cooked home-prepared foods (preformed toxin) so what happens is there is bacteria in the green beans or whatever and then somebody cans them and they don't sterilize them well enough, not heated long enough or high enough pressure or high enough temperature, and so the bacteria grow and produce the toxin, it is sealed in the can or the jar and it sits in the basement awhile and the bacteria keep growing and then you go to eat that and there are pretty high levels that can cause toxicity, Person to person transmission very unlikely - Toxin (a protein) can be inactivated by heating at ≥ 85 degrees C (about 185 degrees F) for 5 minutes so relatively easy to inactivate this protein and denatures the toxin and it is completely safe then - As a biological weapon, most likely dispersed as the preformed toxin (protein) as aerosol or distributed in foods or beverages, somebody would grow up the bacteria in an anaerobic condition, they would form the toxin, they would purify that and form it into an aerosol or less likely put it in some kind of food or beverage
Each of the Category A agents has some (or all) of the following characteristics (CDC)
- Can be easily disseminated or transmitted from person-to-person (i.e. is Contagious, in general viruses are highly contagious) - Causes high mortality with potential for major public health impact - Might cause public panic and social disruption - Requires special action for public health preparedness
Anthrax
- Caused by Bacillus anthracis - Zoonoses - infectious diseases caused by bacteria, viruses and parasites that spread between animals (i.e. a vertebrate animal reservoir where they have existed for hundreds of thousands of years and they will continue to exist here) and humans - Bacillus Anthracis infects cattle, sheep, horses and goats that feed on contaminated pasture - 2,000 to 20,000 human cases per year (worldwide) - almost no way to avoid this because to some extent these bacteria all over the world - No known person to person transmission (although possible) - Bacillis anthracis is a nonmotile, gram-positive rods, is a spore forming soil organism with spores formed in chains (boxcars), sporulate and bacteria start growing, kind of like the seed of a plant, its and waits until the right conditions and then it starts growing the organism, the spores are very stable and can last for years
Tularemia
- Caused by the bacterium Francisella tularensis found in animals (Zoonosis - animal reservoir, so in the environment always will be, been there for a long time so it is not something we will probably ever get rid of) from a vector like a mosquito or tick or something like that from especially rodents, rabbits, and hares, ("Rabbit Fever") from contaminated water, soil and vegetation (where bacteria live), At least 4 subspecies of F. tularensis - Person to person transmission is very unlikely - Outbreaks of waterborne disease in Europe in 1930s, Found on Martha's Vineyard in 2001 - about 150 cases/yr - South central and Western US, Transmitted by ticks/deer flies/mosquitoes, or occasionally contact with infected animals (rodents/rabbits) - Lone Star Tick transmits this from animal reservoirs to humans and it is in the spider family - Incubation: 1-10 days [average 3-5 days] - Duration of Illness: > 2 wks - Case Fatality: 10-35% if untreated, Due to sepsis (generalized infection on the bacteria) and can get into the nervous system and cause meningitis (the mechanisms that cause the sepsis and the meningitis and the virulence factors and why it is so deadly is unknown) - Responds well to antibiotics (once diagnosed!!) if it is caught soon enough, diagnosed soon enough, take the antibiotics you are usually fine, it is often difficult to diagnose diseases like this because often we are not aware that we are bitten by a tick or a mosquito or a deer fly we just feel kind of bad and a lot of things can cause that so diagnosis can take awhile - Aerosolized Francisella tularensis most likely as bioweapon
Pulmonary/choking agents (Lethal agents)
- Chlorine - Chloropicrin - Phosgene - Diphosgene - Disulfur decafluoride Cause asphyxiation basically
Which of the following is easily transmitted from person-to-person?
- Clostridium botulinum - Bacillus anthracis - Francisella tularensis - Anthrax spores - None of the above (CORRECT ANSWER)
Blood Agents (Lethal agents)
- Cyanogen chloride - Hydrogen cyanide - Arsine
Smallpox (Variola virus only in humans, not zoonosis)
- Different from chicken pox because the pox are developed on the extremities like the arms, hands, and legs, where in chicken pox they develop on the central part of your body Incubation Period - 7 to 19 days - Average 10-12 days - Rash 2 days after incubation period Duration of illness - 4 weeks (Contagious at around day 14 when pustules start to develop in the mouth) - Infectiousness is considered to be highest during the first week after rash onset when lesions in the mouth ulcerate and release large amounts of virus into the saliva and when you sneeze, cough, and talk the saliva has virus particles in it and it can be transmitted to other people Case Fatality (Two strains of smallpox) - Variola Minor (less severe illness) < 1% - Variola Major (more severe illness) up to 30% - Death most commonly results from overwhelming hypertension and edema (too much fluid in the body) Control by Identification, Isolation and Vaccination for prophylactic use in somebody who has smallpox
Blister Agents (Lethal agents - typically not lethal, but cause blistering and with enough can be lethal)
- Ethyldichloroarsine - Methyldichloroarsine - Phenyldichloroarsine - Lewisite - Sulfur mustard - Nitrogen mustard (derivatives are used for chemotherapy because they can damage DNA, have a lot of side effects)
Gastrointestinal Route of Exposure to Anthrax
- GI infection accounts for < 5% of Anthrax cases - Mortality: Treated 50%, Untreated approaches 100% - Ingestion of inadequately cooked contaminated meat (spores in meat that is killed out in the environment and it is not cooked very well and you eat it and get some spores in the meat) - Incubation period 2-5 days
Exposure to Botulinum toxin can occur through which of the following mechanisms?
- Ingestion of preformed protein - Inhalation of preformed protein - Local production of protein toxin by C. botulinum in the GI tract of infants - Local production of protein toxin by C. botulinum in anaerobic tissue at the site of a wound
Pulmonary Route of Exposure to Anthrax
- Inhalation of spores from wool or animal hair, hides or bones - Inhalation of particles < 5 micrometer - Antibiotic therapy must be instituted very early in clinical disease - Approaches 100% mortality - Antibiotics must be continued for 30-60 days while vaccine series started
Summary of Chemicals used for bioterrorism and as weapons of mass destruction
- Most are acetylcholinesterase inhibitors e.g., Sarin, Novichok (the ones that are really of most concern) - By inhibiting acetylcholinesterase, acetylcholine (the neurotransmitter) is not effectively removed from the neuromuscular junction; muscle contraction does not stop and the person suffocates - Toxicity/death is caused due to the inability of the diaphragm to relax - asphyxiation
Smallpox: Physical Exam
- Papules, pustules, or scabs of similar stage, many on: Face, Palms, Soles, Extremities
Possible Routes of Exposure to Anthrax
- Pulmonary (Inhalation) - Cutaneous - Gastrointestinal
Smallpox: Differential Diagnosis
- Relative density of rash on different parts of the body - Centrifugal (move away from center), more distal, on the extremities whereas chicken pox is more centripetal or on the center parts of the body
Which of the following is easily transmitted from person-to-person, causes high mortality and might cause public panic?
- Smallpox - Plague Not anthrax - would cause high mortality and public panic but only smallpox and the plague are contagious or transmitted from person to person
Sylvatic Cycle
- Sylvatic - a disease or pathogen in wild animals (sylvan means forest dwelling), there could be a sylvatic disease that never gets into humans and it just stays in the wild population, that wouldn't be a zoonosis - Zoonosis - a disease that can be transmitted from animals to humans with an animal reservoir so can also infect humans, can be said that it is a sylvatic disease that can also infect humans
Nerve Agents (Acetylcholine esterase (ACE) inhibitors) (Lethal agents)
- Tabun - Sarin - Novichok - Chlorosarin - Soman - Ethylsarin - Cyclosarin - many, many others
Which of the following countries does have regions where Plague occurs in animals?
- United States - China - South Africa - Brazile
Smallpox Treatment
- Vaccination within 4 days of exposure: Exposed people should be immunized immediately - Supportive Care: Dehydration and electrolyte imbalance, Skin care because of pustules - Routine vaccinations stopped in 1972 (prior to that everybody was basically vaccinated as a child and a mark on their arm) because, 1) the incidence of natural smallpox infection was/is extremely low and due to the WHO had this vaccination campaign across the world and basically eliminated it, 2) because of complications of the vaccine that were moderate to severe including Eczema Vaccinatum where susceptible patients display a chronic skin disease and it happened pretty frequently, Thus, routine vaccinations are no longer warranted, and the vaccine is no longer available for general use although there is one available
Other Related Viruses to Smallpox (Variola virus is an Orthopoxvirus)
- Varicella (chickenpox, varicella zoster virus, human herpes virus type 3, zoster virus, shingles - if somebody has chickenpox when they were younger that varicella virus can go into a latent phase and sort of not doing anything for many years and show up when somebody gets older as shingles and it is recommended to get a shingles shot if somebody had chicken pox as a child, a Herpesviridae virus not an Orthopoxvirus so a different virus but similar in that it causes pustules) - Vaccinia (similar to Variola, in animals, Orthopoxvirus, from cowpox virus??, source of vaccines) - Monkeypox (similar to Variola, in animals, would not cause very serious disease in humans, Orthopoxvirus) - Cowpox (similar to Variola in animals, would cause some pustules, but would not cause very serious disease because it does not infect humans as well as animals or less virulent in humans, Orthopoxvirus)
How are most mutations caused
- avoidable damage of DNA - chemical damage of DNA - unavoidable changes in cell death - by evolution - none of the above (CORRECT ANSWER) should be unavoidable damage of DNA
Large Scale Mutations in Chromosomes
- large scale mutations are rare in "normal" cells - Where big pieces of DNA get moved around, common in cancer cells, called karyotyping instability - Deletion: Blue piece is removed - Duplication: Blue piece doubles - Inversion: Blue piece is reversed - Insertion: Viruses?? viruses typically do this, they insert their DNA into our DNA if they infect us and you have this major insertion, about 8% of our DNA is made up of viral DNA that we have acquired over course of our evolution and are vital to our survival and vital to our evolution so without them we wouldn't be here - Translocation: where pieces of various chromosomes just switch around with each other, might be more common in cancer cells - A lot that is not known, but important in viruses and cancer
Nerve Gases
Acetylcholine Esterase Inhibitors, Muscle can't relax because without acetylcholine esterase, acetylcholine just stays there and so the muscle just stays contracted and can't relax, kind of just cramped up, opposite of Botulinum toxin, so if your diaphragm can't relax, can't breath and causes death - Really of most concern, used in WW1 and potentially thought to be used in WW2 - Sarin and all of the nerve agents bind to acetylcholinesterase in the catalytic site and it stays there and the enzyme can't metabolize acetylcholine because it has that sarin stuck on the enzyme which is why it is so toxic because it binds to that enzyme so well
The Bubonic Plague can be transmitted to humans via
An urban cycle - Lesions in the mouth at day 14 would be smallpox - Inhalation of spores would be anthrax
Bioterrorism Agents not considered contagious (really unlikely to transfer from person to person)
Anthrax, Tularemia, Botulinum Toxin
Which of the following is a type of DNA repair?
Base excision repair
What is the major reason that ionizing radiation is considered a health concern?
Because it can damage DNA
Which of the following is not true?
Beta particles: less energy than microwave radiation TRUE Statements: - Alpha particles: 2 protons and 2 neutrons ejected from the nucleus of an atom - Beta particles: neutron is transformed into a proton and an electron - Alpha particles: form all helium on earth
How are Mutations Caused?
By damaging DNA A. Unavoidable spontaneous alterations in the chemistry of DNA (probably major source of DNA mutations; 60-70%? for most people but for people who smoke or are exposed to aflatoxin this is different, throughout our lives this is occurring) 1. mispairing of bases (thymine can also bind to guanine in an enol-ketol equilibrium) 2. loss of nitrogen groups (every now and again because of the chemistry of the base pairs, the nitrogen groups can come off), happens all the time but at a very low rate) 3. loss of one of the bases - These bases are in equilibrium with slightly different structure, tautomers, so not exactly damaged DNA but strange DNA, can base pair with the wrong base, causes mispairing and mutations and if it is replicating - Sometimes these bases can just come off due to pH, temperature, can be hydrolyzed off - Loss of bases can result in single strand breaks in the DNA - Can happen all the time at an extremely low rate, inherent chemistry of DNA but we have so many cells B. Chemicals can damage DNA (not clear how common or significant this is; but is what people often think of, can happen throughout our lives as well) 1. Adducts-attachment of reactive chemicals to the DNA (e.g. makes G-x, C-x, A-x, or T-x: Forms a covalent bond with the DNA) - Used for chemotherapy: Binds to cancer cell and caner cell can't replicate Examples: Cisplatin forms a covalent bond with DNA and used to treat cancer because cancer cells can't replicate its DNA because of the huge molecule of cisplatin so can't replicate and divide and then it dies so basis of chemotherapy, Aflatoxin, Benzo(a)pyrene, Lipid peroxides, Glyphosate 2. Intercalation - binding of chemicals in the DNA, alters the chemistry of the bases a little bit and might alter DNA polymerase's ability to read the bases 3. ROS (actual chemicals that can react with DNA and DNA bases to damage it)/Ionizing Radiation (kind of indirect because it can form ROS that can damage DNA) damage of DNA - 8-oxoG - ketone is on guanine which is not normal guanine, an example of radiation is UV light causing two thymines that are next to each other to covalent bond together and that causes damage and it is called a thymine dimer C. Biological damage of DNA (important in some cases) 1. Mutations due to viruses is a good example of this a. Human Papillomavirus (HPV) which intercalates in the DNA and by doing that it changes some of the gene expression and could lead to cancer-responsible for >90% of cervical cancers in women - More of a large scale type of mutation, probably inflammation going on with that (Insertion - HPV?? - causes a large scale mutation) - DNA Damage through Unavoidable damage, Chemicals, or Biological damage could be to a base or section of DNA - Wrong Base added = potential for mutation
Which of the following states in the U.S. had the highest occurrence of foodborne botulism from 1990 to 2000?
California
Which of the following is not a characteristic of a Category A bioterrorism agent as defined by the CDC?
Can be found in the natural environment (they can be found in the natural environment but this is not a characteristic) TRUE characteristics: - Can be easily transmitted from person-to-person - Might cause public panic and social disruption (probably the biggest factor for most of the agents because it is unlikely that it will cause widespread mortality in terms of square mileage even through aerosolization) - Causes high mortality with potential for major public health impact - Requires special action for public health preparedness
What are DNA mutations (in humans/all organisms, same processes with some differences and will apply to plants, animals, bacteria, rates of mutations change maybe they are faster in some animals or some organisms but generally these principles generally apply to all living organisms that have DNA replication)?
Changes in our DNA sequence that can be humans have ver: 1) Inherited from our parents, These are called germline mutations, Each of us has about 30,000-40,000 of these mutations; we are born with these mutations (somewhat unique about all of us, come to us from our mother or father) 2) Acquired during our lifetime, In all the other (other than the eggs and sperm) cells of our body , These are called somatic cell mutations, These mutations are "in addition" to our germline mutations
How do our cells limit the formation of mutations
DNA repair
The absorption of visible light radiation (photons) by chemicals results in:
Electron transitions
Which of the following countries has the highest natural occurrence of anthrax?
Ethiopia where it is a hyperendemic
True or False: Electromagnetic radiation interacts with chemicals in different ways depending on its speed?
False (speed is constant)
It is relatively easy to develop "rabbit fever" from a person known to be infected with Francisella tularensis?
False, not contagious so not easy to get it from somebody who has it
Plague
In the 1300s in central Europe, half the people dying in a town or city, Yersinia pestis - gram-negative bacillus, facultative anaerobe, nonmotile - Incubation period: 2-3 days - Duration of illness: 1-6 days - Case fatality: Usually fatal unless treated in 12-24 hour - US epidemiology (Zoonosis-so always present): 2-3 cases/yr., mainly in Southwest US - Highly contagious - Aerosolization of Yersinia pestis (not spores) most likely method of weaponization - Called the "Black Death" because of these bubos in people that were infected with Yersinia pestis, these bacteria sort of accumulated in the lymph nodes not only on the neck but under the arm and the groin, these bulges filled with these Yersinia pestis bacteria would develop and they were black
An individual was found to have a mutation in an enzyme that metabolized a drug she was taking. Based on the evidence below showing serum drug concentrations over time, what is the most likely effect the mutation is having?
Increasing drug metabolizing enzyme levels, more enzyme so it metabolizes the drug faster and the concentration of the drug is lower
Which of the following routes of exposure is the greatest concern with bioterrorism agents?
Inhalation
How are [simple] Mutations Caused?
Insertion of the wrong G, A, T or C during DNA replication (the parental strand has to double its DNA to give one to each daughter cell), when something causes DNA damage (or changes to the chemistry) by either a chemical bound to it or a base that has fallen or come off the guanine so it is not a guanine, it is a slightly different chemical so now when DNA polymerase comes to the slightly altered guanine, it doesn't recognize it so it might not know what to put and put the wrong base because of the change in the structure of guanine and if it puts the wrong base there is a potential for mutation because then if that strand gets replicated a wrong base is put to match the wrong base
Which of the following is a mechanism by which unavoidable spontaneous DNA damage occurs
Loss of nitrogen groups - inherent chemistry of the DNA
The absorption of microwave radiation (photons) by chemical results in:
Molecular rotation and torsion
The absorption of infrared radiation (photons) by chemicals results in
Molecular vibrations
Smallpox is of concern as a biological weapon for several reasons. Which of the following is not one of them?
Most people are now resistant to infection because people are now susceptible to smallpox because it was eradicated in the 1970s so now very few people who are currently alive have been exposed to smallpox so most people are now susceptible TRUE reasons: - The virus carries a high rate of morbidity and mortality (maybe up to 30% mortality) - The virus is contagious - A vaccine is not available for general use - Past experience has demonstrated that "smallpox" creates a great deal of panic
No enzyme
No metabolism (Simple Point Mutations), Poor metabolism, drug concentration is way too high and that can result in toxicity or adverse drug effects
Normal enzyme
Normal metabolism (Simple Point Mutations), desire concentration, efficient therapy
Which of the following potential bioterrorism agents causes our muscles to lose their ability to relax?
Sarin nerve gas
Inserting or deleting 1 or 2 bases
Simple Point mutation - Encodes wrong amino acids or no amino acid - Can tell by counting the bases
Changing a base
Simple Point mutations - One base for another base so encodes no amino acid or wrong amino acid, whether it has any effect is unknown, sometimes it does, sometimes it doesn't
Although not for general use, currently there are vaccines available for
Smallpox
Currently there are FDA approved antibiotics available for all of the following except
Smallpox because it is a virus and you can't develop antibiotics against a virus There are FDA approved antibiotics available for - Anthrax - Tularemia - Plague
Contagious Bioterrorism Agents (from person to person)
Smallpox, Plague, Ebola, Marburg, Lassa Fever
Which one of the following is not correctly grouped?
Smallpox: Zoonosis, Clostridium because smallpox is only in humans and it is not caused by bacterial it is caused by the orthopox virus variola Correctly grouped: - Anthrax: Zoonosis, Bacillus - Plague: Zoonosis, Yersinia pestis
Which transmission route is of greatest concern?
The inhalation route since all of the Category A agents can be effectively disseminated through aerosolization, Use of aerosols is an efficient way to affect the maximum number of people with a single attack, but even as a aerosol it would be difficult to disseminate over a very large area more than about a square mile
Which one of the following is grouped correctly?
germline mutations/also called hereditary mutations
Which of the following is a mechanism by which chemicals damage DNA?
intercalation in the DNA
Somatic cell mutations
mutations in the DNA of all other cells in the body, These are acquired during our lifetime and are passed to "daughter" cells in a tissue or organ following DNA replication and cell division so not a lot of cells until a lot of cell division occurs, cell division typically decreases as we get older so it is usually a very low population
Germline mutations
mutations in the DNA of germ cells (eggs and sperm), Transmitted to offspring from parents; these mutations are thus in all cells of the offspring since all cells come from the sperm and the egg, Also called hereditary mutations
Which of the following are somatic mutations
mutations in the DNA of kidney (can be in any somatic cell besides the sperm and egg so pancreas, brain, liver, kidney, occurred after birth) cells (all mutations are due to DNA replication)
Isotopes of each of the elements have the same number of blank but different number of blank
protons, neutrons
Cutaneous Route of Exposure to Anthrax
spores infect through broken skin - Mortality: Untreated 10-20% (Spreads via lymphatics to regional nodes and develops to infection), Treated - low, Most common natural exposure to humans - Pustules formed by bacteria - Have a cut on skin and get exposed to spores from being around livestock or out in the pasture and the bacteria gets onto or into that cut
How are mutations most significant to human disease?
they can cause cancer
The electromagnetic radiation that reaches the earth from the sun is mainly composed of:
visible, UV and infrared radiation
