I have heard it was the opinion of others that it [the plague] might be distinguished by the party's breathing upon a piece of glass, where, the breath condensing, there might living creatures be seen by a microscope, of strange, monstrous, and frightful shapes, such as dragons, snakes, serpents, and devils, horrible to behold.
-Daniel Defoe
A Journal of the Plague Year, 1721

Our townsfolk were not more to blame than others; they forgot to be modest, that was all, and thought that everything was still possible for them; which presupposed that pestilences were impossible. They went on doing business, arranging for journeys, and formed views. How should they have given a thought to anything like plague, which rules out any future, cancels journeys, silences the exchange of views. They fancied themselves free, and no one will ever be free so long as there are pestilences.
-Albert Camus
The plague

I had a little bird,
Its name was Enza.
I opened the window,
And in-flu-enza.
-- Children's Skipping Rhyme, 1918

Assignment
Audesirk, Audesirk & Byers part of Chapter 19,

Today's music selection
Huey "Piano" Smith Rockin' pneumonia and the Boogie Woogie Flu

Prions

(conventional wisdom that DNA or RNA are required)

Figure (chapter 3 opener)
Prion diseases
Creutzfeldt - Jakob Disease (CJD) "Spongiform" (brain turns to sponge) degeneration.
There were seemingly esoteric* cases of spongiform encephalitis.
* for instance afflicting Jews in Lybia who thought raw sheep eyeballs were a delicacy.
Kuru was a disease in New Guinea among cannibals.
D. Carleton Gadjusek (1976 Nobel Prize) thought it was a slow virus.
Scrapie in sheep so named because they roll around with intense itching.

Personal reflection. Since we did a sheep brain dissection in physiological psychology lab at Hopkins, I wondered if rubber gloves were necessary. Since Baltimore was close to Bethesda, I called. Gadjusek was away, studying some remote tribe, but I spoke with his coworker (Gibbs) who thought formaldehyde might not kill the virus. Then I got on their mailing list and, once a month or so, got an inch thick envelope full of case studies of diseases in far away places. I had to move to Missouri (in 1979) to make it stop.

Stanley Pruisinger 1980's proposes "prion" (protenaceous infectious particle).
That a disease could be transmitted without virus or bactera was heresy at the time.
But he had strong evidence and won the 1997 Nobel Prize.
Normal protein (PrP-C [control]) is altered by altered form (PrP-Sc [scrapie])
In the 1990s when the term "mad cow disease," was applied to observations in Britain, it seemed like a joke.
Now "BSE" (bovine spongiform encephalitis) is no laughing matter.
In meat industry, having matter from other animals in the feed is really bad.
Can disease spread from animal to animal? (probably)
Can disease spread from animal to human? (probably)
Cases in Canada, mainland Europe, and even in the US are in the news.
Should "downers" ("cows" that have dropped to the ground) be slaughtered for food?
How is it that meat from one downer can be sold in many different states and, only later, the announcement is made that it had BSE?

Viruses

not in 5 kingdoms (recall question on whether viruses are "alive") makes it virtually impossible for an introductory textbook to have a good place to cover viruses

Figure 19-11
These are electron micrographs
Being small (Protein and DNA) they pass through fine filters, hence an old term, "filterable"

Figure 19-13
(review from first lecture)
Bacteriophage (phage-eat) protein and DNA
lytic cycle - bacterial cells lyse.

Viruses cause lots of disorders: measles, smallpox, chicken pox, mumps, rabies, flu = influenza, herpes, AIDS, mononucleosis, polio, colds, rubella (German measles), yellow fever, hepatitis

Immunity

Some very fundamental terminology:
Antigen - non-self protein (e.g. virus coat)
Antibody to antigen made by B lymphocytes (white blood cells)

History:

Vaccines - active immunity (like disease)
memory cells of immune system

Figure E36-1
Edward Jenner credited with "vaccination" -1796 "encowment" cowpox, smallpox
Actually the English aristocrat Lady Mary Wortley Montague introduced the Turkish technique of innoculating with weakened smallpox in the early 1700's
Smallpox is so completely eliminated that one issue is whether to get rid of lab virus.
Passive immunity - give antibodies

Flu

Figure Chapter 36 opener
Case study Chapter 36 Fighting the flu (p. 721) snd revisited (p. 738)

Figure E36-2
Box on fighting influenza
change (mutate) also exchange with birds (ducks) and pigs

Humanities Gina Kolata, Flu: The story of the great influenza pandemic of 1918 and the search for the virus that caused it, New York, Farrar Straus and Giroux, 1999

1918 20-200 million died worldwide, H1N1 (hemagglutinin, neuraminidase)
1957 Asian bad H2N2
1968 Hong Kong bad H3N2 (70,000 died in 6 wks)
Worry in 1973 that there would be a swine flu pandemic
Worry now that there will be an avian (bird) flu pandemic H5N1

Figure E19-2b
Herpes
Not always does cell burst. Here you see how the virus takes over the cells machinery to make its own DNA and to make proteins etc after transcription of its DNA into RNA

AIDS

Figure 19-12
HIV
Structurally (and chemically) not all viruses are as simple as bacteriophage, and sometimes RNA is the hereditary material

Figure E19-2a
The retrovirus, HIV (Human Immunodeficiency Virus that leads to AIDS, acquired immunodeficiency syndrome) deserves special attention. Its hereditary material is RNA. It is called a retrovirus because it comes pre-packaged with functional reverse transcriptase enzyme to make DNA out of RNA. The DNA that is made gets incorporated into the cell's own genome.

Figure (Chapter 18 opener)
Case study - origin of a killer, Chapter 18, p. 357

Figure 18-8
Case study revisited
Evolutionary relationships for HIV

Prokaryotes

2 of 3 domains
Kingdom? (monera)
bacteria, also blue-green algae (cyanobacteria)
(algae = aquatic plants)

Figure 1-5
Penicillin, an antibiotic, kills bacteria
Penicillin was discovered by Fleming and developed by Florey and Chain. They shared the 1945 Nobel Prize

Figure 19-1b
Here is a picture of E. coli (Escherichia coli), the most famous bacterium from genetics and molecular studies - this picture was found at the microbe zoo site
circular DNA
prokaryote, (karyon as in "karyotype," refers to the nucleus)
genophore - bacterial chromosome
Reproduction by fission, "Multiply and Divide"

also DNA transferred: (1) transformation (earlier coverage, DNA from smooth transforming rough) , transduction (from phage

Figure 19-8
conjugation (like mating)
Plasmids - little circles of DNA - very useful in molecular biology and easy to identify since they carry antibiotic resistance

Figure 19-1
Shape
cocci-blob
-diplococcus - two
-streptococci-string (e.g. strep throat)
-staphylococci-grapes (e.g. staph infections)
bacilli-rod
spirilla and spirochetes-spiral

One characteristic of monera is that they have a rigid cell wall made of peptidoglycan. That means that they must absorb, they cannot ingest. The chemiheterotrophs (saprobes) are therefore good at biodegradation because they must put out "digestive" enzyme

Figure 19-2
Even though they are rigid, they have flagella (very different from eukaryotic flagella), and organisms like the famous E. coli have positive and negative chemotaxes.

Figure 19-4
Endospores
Aerobic vs anaerobic -
The story about anaerobic bacteria that is so famous that everybody should know it. It is about botulism toxin from Clostridium botulinum, endospores killed only with high temperature. They are obligate anaerobes, and the endospores survive in improperly canned goods, 1 g kill 15 million by blocking release of vesicles that contain neurotransmitter substances. "Botox" is used as cosmetic, injected into face, blocks muscles, less wrinkles.

Figure 19-5
Archaebacteria
Thermoacidophyles hot sulfur (heat stability important in enzymes used for PCR, refer back to biotech lecture).

cell wall, Gram stain
Gram positive-heavy wall, Negative-stain wash out
Antibiotics like penicillin G for Gram + like strep, gonorrhea, syphilis

Disease-

Famous traditional STD's (VD's) gonorhea, syphilis (spirochete)
famous recent worry Lyme disease from ticks
recently understood that ulcers are caused by Helicobacter pylori
bubonic plague rats flea middle ages

Figure Chapter 15 opener
Tuberculosis TB consumption sanatoriums
Humanities suggestion - Eugene O"Neill Long day's journey into night
Current events - May 2007 - a patient with antibiotic resistant TB is quaranteened

diphtheria, some pneumonia, paratyphoid, scarlet fever
tetanus muscle clamp lockjaw anaerobic puncture (like botulism, toxin affects neural transmission)
whooping cough (pertussis) DPT vaccine (toxin very important in studying signal transduction)
strep throat (leads to rheumatic fever)
typhoid fever carriers*
cholera fatal diarrhea (toxin very important in studying signal transduction)
leprosy leper colonies,
Salmonella (food = "ptomane" poisoning),
(evolution of resistance in meat and eggs with antibiotics fed in animal husbandry)
evololution of antibiotic resistance in syphilis (spirochete), gonnorhea
toxic shock (tampons)
Leigionnaires' (1970's Philadelphia, took several years to find cause)
Staphylococcus = acne,
some pneumonia, paratyphoid, scarlet fever, dysentery
chlamydia like virus common STD (VD)
Rocky Mountain spotted fever typhus (Rickettsia like virus)
mycoplasmas - smallest cells

Figure - chapter opener
(Case study- agents of death Chaspter 19, p. 371 and case study revisited p. 384)
Anthrax (mostly cattle [also humans, mail terror attacks of Fall, 2001])
fire blight (apple, pear)
crown galls (plants)

*Typhoid Mary (Mary Mallon) Irish immigrant, in the 1900-1906 period, cases involved in her being a cook until epidemiological investigation found her. She had an infection in her gallbladder. Detained at Riverside Hospital for 3 years. Later, released then detained again for the rest of her life (25 years) - died in 1938. Caused 1300 cases of typhoid fever.

Advantages-biodegradation,sewage
nitrogen fixation,
actinomycetes produce streptomycin, chloramphenicol,
tetracycline, cyanobacteria (blue-green) algae
nitrogen fixation nodules - alfalfa, soy clover
for rice blue green algae - cyanobacteria heterocysts
yogart, cheeze, saurkraut, coco
enzymes for industry
Chemisynthetic use sulfur, ammonia, nitrite,
put out sulfates and nitrates for soil.
cows sheep goats cellulose
make vit K and B12

For further study: Here is a site entitled "Communicable Disease Surveillance and Response (CSR)" which is of relevance to this and other chapters. And here is Disease information from the Centers for Disease Control, also relevant to several chapters, especially this one.

Questions used in 2007 & 2008 relating to this outline

Vaccination is more successful for smallpox than flu because
(a) passive immunity is conferred for smallpox.
(b) antibiotics work so well for smallpox.
*(c) evolution in animal hosts takes place in flu.
(d) smallpox is a bacterium while flu is a retrovirus.
(e) flu is caused by a proteinaceous particle.

Mad cow disease is most closely related to
(a) typhoid.
(b) antibiotic resistance.
(c) herpes.
*(d) scrapie.
(e) the H1N1 strain.

Fleming accidentally dropped a colony of Penicillium onto a plate of
(a) viruses.
*(b) bacteria.
(c) algae.
(d) antibiotics.
(e) plasmids.

One particular concern about rubella (German measles) is that
(a) it is killing all the chimpanzees.
(b) it killed over 20 million people in 1918 and it could strike again.
(c) even though eliminated worldwide, we should not eliminate the last repositories of viruses in case terrorists have it in their possession.
(d) the DNA reverse transcribed from its RNA gets incorporated into the host cell's genome.
*(e) it can cross the placenta.

An important laboratory test is the Gram stain. What structure does it target?
(a) alleles for purple flowers
(b) eukaryotic chromosomes at the metaphase plate
(c) DNA in gel electrophoresis
(d) protein coat of virus
*(e) cell wall of bacteria

It has recently been understood that Helicobacter pylori causes what aliment in humans?
(a) sexually stransmitted diseases (STDs)
(b) Down syndrome
*(c) ulcers
(d) Bubonic plague
(e) Turner's syndrome

What is the proper scientific nomenclature for rod shaped bacteria?
(a) cocci
*(b) bacilli
(c) spirilla
(d) streptococci
(e) staphylococcus

The lytic cycle applies to reproduction
(a) of DNA during the S phase of the cell cycle.
(b) of herpes virus.
*(c) of bacteriophage.
(d) of the karyotype.
(e) of bacteria.

Evolution of antibiotic resistance is of particular concern in
(a) biodegradation.
(b) polymerase chain reaction (PCR).
(c) endospores.
*(d) the meat industry.
(e) the digestion of cellulose by ruminants.

What disorder would you be avoiding by making certain that your home-canned foods and the containers are hot enough?
(a) west Nile encephalitis
(b) polio
(c) tetanus
*(d) botulism
(e) ulcers

Shortly after the 9/11 attacks on the World Trade Center and the Pentagon, there were mail attacks with what disease?
(a) botox
(b) avian flu
(c) smallpox
*(d) anthrax
(e) fire blight

Plasmids are found in
*A) bacterial cells.
B) the virus that causes AIDS (acquired immunodeficiency syndrome).
C) vaccines.
D) hemaglutinin and neuraminidase.
E) antigens.

What allows Clostridium botulinum to flourish in improperly canned garden goods?
A) reverse transcriptase
B) flagella
*C) endospores
D) peptidoglycan
E) antibiotics

Cyanobacteria are _____________ .
A) saprobes.
*B) photosynthetic.
C) heterotrophic.
D) eukaryotic.
E) the cause of bovine spongiform encephalitis (mad cow disease).

Bacteria cause (or contribute to) which of these disorders?
A) tuberculosis (TB, consumption)
B) anthrax
C) ulcers
D) strep throat
*E) all of these

For which of the following diseases would antibiotics be useful?
A) smallpox
*B) plague
C) H1N1 ("Spanish") influenza
D) scrapie
E) measles

Creutzfeldt-Jacob disease (CJD) is caused by
*A) a protenacious infectious particle.
B) an anaerobic bacterium.
C) viruses that can also live in swine and birds.
D) an RNA-containing virus.
E) peptidoglycan.


Prions are known to cause
A) sickle cell anemia
B) colds
C) AIDS
*D) mad cow disease
E) influenza

Flagellated bacteria
A) have internal organelles such as mitochondria.
B) use the flagella to exchange sperm and eggs for sexual reproduction.
*C) can move toward attractants like nutrients.
D) are not considered to be officially "alive" by biologists.
E) are eukaryotes.

The bacterial cell wall contains
A) adrenalin.
*B) peptidoglycan.
C) chitin.
D) triglycerides.
E) glycogen.

How do Gram-positive bacteria necessarily differ from Gram-negative bacteria?
A) how much they weigh
B) whether they have DNA or not
C) whether they translate RNA to DNA or reverse translate DNA into RNA
*D) staining properties
E) whether they have a nucleus or not

Which of the following may be contained in a virus?
*A) RNA
B) mitochondria
C) cytoplasm
D) ribosomes
E) lysosomes


Questions used in 2002 relating to this outline (and other outlines)

The first vaccination, in the late 1700's was against
(a) polio.
(b) Asian flu.
*(c) small pox.
(d) a retrovirus.
(e) E. coli.

A Nobel Prize relates to mad cow disease, caused by a
(a) virus.
*(b) protein.
(c) bacterium.
(d) plasmid.
(e) transposon.

Reverse transcriptase would work on [A] to form [B].
(a) [A] bacteria; [B] bacteriophage
(b) [A] pre-mRNA; [B] mRNA
(c) [A] mRNA; [B] protein
(d) [A] DNA; [B] PCR reaction products
*(e) [A] RNA; [B] DNA

Which enzyme is the hallmark of HIV (human immunodeficiency virus) that causes AIDS (acquired immunodeficiency virus)?
(a) primase.
(b) nuclease.
(c) telomerase.
(d) hemoglobin.
*(e) reverse transcriptase.

Vaccination confers active immunity by
*(a) stimulating your immune system to make antibodies.
(b) stimulating your immune system to make antigens.
(c) stimulating your immune system to make prions.
(d) stimulating your immune system to make transposons.
(e) giving a person antibodies made by another person when (s)he overcame the disease.

Clostridium botulinum
(a) is a methanogen, making swamp gas.
(b) was used by terrorists in Fall, 2001 in the US Postal Service.
(c) is a photoautotroph.
*(d) have a toxin that, although deadly, is used as a cosmetic.
(e) reproduces sexually but, since the offspring are not fertile, is not considered to be a species.

Which live in salty areas like the Dead Sea?
(a) cyanobacteria
(b) Helicobacter pylori
*(c) extreme halophiles
(d) E. coli
(e) the bacterium whose DNA polymerase is used in the PCR reaction

Botulism
(a) causes ulcers
(b) is spread by the bite of a tick.
(c) caused the Black Plague in the Middle Ages.
*(d) comes from anaerobic bacteria.
(e) is a sexually transmitted disease

Mary Mallon, an Irish immigrant, worked as a cook in the early 1900's until she was incarcerated and is believed to have infected 1300 people with
(a) typhoid.
(b) small pox.
(c) hepatitis B.
(d) AIDS.
(e) syphilis.

Antibiotics
(a) are drugs that kill bacteria.
(b) are made by your immune system to attack microbes.
(c) are the portions of the antigen that antibodies attack
(d) are on red blood cells and are responsible for ABO blood groups.
(e) should be used to treat disorders like influenza.

Some viruses use the mosquito as an intermediate host. Of the following, this applies to the one causing
(a) Lyme disease
(b) small pox
(c) polio
(d) West Nile encephalitis
(e) Klinefelter's syndrome

Which is not caused by a virus?
(a) small pox
(b) AIDS
(c) polio
(d) cholera
(e) flu

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