AdkPathCourse

Skeletal and Smooth Muscle Tumors

2008-04-24T15:37:00.000-04:00

Rhabdomyomas are rare benign tumors of skeletal muscle usually found in the area of the head and neck.

Rhabdomyosarcomas are malignant tumors of skeletal muscle. These tumors are typically found on the arms and legs. Over 85% of rhabdomyosarcomas occur in infants, children, and teenagers.

Leiomyomas are benign tumors of smooth muscle. These tumors are uncommon.

Leiomyosarcomas are malignant tumors of smooth muscle tissue. These are rare tumors in the USA.

Myasthenia gravis

2008-04-24T15:30:00.000-04:00

Myasthenia gravis is an autoimmune neuromuscular disease caused by defective nerve transmission to the muscles. It is first characterized by drooping eyelids and slack facial muscles. Autoantibodies block the attachment of acetycholine to acetycholine receptors. This interferes with transmission of the nerve impulse.

You can find a self-paced tutorial with questions on myasthenia gravis at this NIH website.

Disease of Muscle - Myositis and Myopathy

2008-04-24T15:14:00.000-04:00

Myositis is inflammation of muscle tissue due to injury, infection or autoimmune disease.

Myositis can be caused by infection with the parasitic nematode Trichinella spiralis. You become infected with this worm by eating poorly cooked, infected pork. The larvae produced by mating male and female worms invade muscle cells. The disease is characterized by abdominal pain, cramping, muscle pain and diarrhea.

Other infectious agents, including influenza virus, HIV, Lyme borrelia, and tapeworm can cause myositis.

Dermatomyositis is an autoimmune connective tissue disease that is characterized by inflammation of muscle and skin. This disease affects women more than men and usually occurs in people 40-60 yrs old.

Polymyositis is an ideopathic inflammatory disease that does not involve the skin. The cause is unknown.

Myopathy is a term used to describe neuromuscular diseases that are characterized by muscle weakness but are not muscular dystrophy. These diseases can be due to abnormalities in mitochondria or glycogen storage, a problem in metabolizing myoglobin or due to toxic effects of hormones or chemicals. One example is the muscle weakness or necrosis that can occur in some individuals taking cholesterol-lowering statin drugs.

Rhabdomyolysis is the sudden necrosis of skeletal muscle with the release of large amounts of myoglobin into the circulation. Myoglobin can be toxic to the kidneys and can result in their shutdown. This disease can result from any injury to the muscles, especially trauma.

Disease of Muscle - Muscular Dystrophy

2008-04-24T14:50:00.000-04:00

For muscle to remain healthy it must be innervated by a peripheral nerve. Denervation or loss of nerve stimulation results in atrophy of the muscle or loss of muscle tissue. Muscles can also atrophy due to decreased activity. This type of atrophy is reversable with exercise.

Muscular dystrophies are a group of diseases associated with increasing muscle weakness and loss of muscle tissue. The most common form of muscular dystophy is Duchenne muscular dystophy. This disease is inherited in an x-linked recessive pattern and is caused by a defect in the gene that encodes dystrophin. This results in an absence of dystrophin.

Another formof muscular dystrophy is Becker muscular dystrophy. In this form of the disease, dystrophin is present but abnormal. This disease is also x-linked, so both forms of muscular dystrophy occur most often in males.

You can learn more about muscular dystrophy at this NIH website and at the Muscular Dystrophy Association website.

Muscle Diseases con't

2008-04-24T14:17:00.000-04:00

Myasthenia gravis is a chronic neuromuscular disease characterized by muscle weakness. An NIH tutorial on myasthenia gravis can be found here.

Muscle tumors

Tumors of skeletal muscle are rare. Rhabdomyosarcoma is a fast growing malignant tumor found primarily in infants and children.

Rhabdomyoma is a benign tumor of striated muscle.

Leiomyoma and Leiomyosarcoma are benign and malignant tumors of smooth muscle. Leiomyomas are found in the uterus where they may be called "fibroids".

Muscular Diseases

2008-04-24T14:15:00.000-04:00

Muscular dystrophies. These are a group of progressive genetic noninflammatory diseases characterized by muscle weakness and degeneration.

Duchenne muscular dystrophy is the most common type of MD. It is an x-linked inherited disease caused by a defect in the dystrophin gene which results in an absence of dystrophin.

Becker muscular dystrophy is a milder form of Duchenne MD. It is also due to a genetic defect in the dystrophin gene but the protein is still produced in an abnormal form.

Myositis is inflammation of the muscles.

Myositis can be a result of autoimmune reactions as in Dermatomyositis and Polymyositis.

Trichinella spiralis larva in a muscle cell

Myositis can also be caused by infection. Trichinosis is a parasitic worm infection of the muscles. It is commonly caused by eating undercooked pork.

Infection with anaerobic bacteria can also result in myositis.

Gangrene results when a wound becomes infected with the bacterium Clostridium perfringens.

Tetanus result from infection with the bacterium Clostridium tetani.

Myopathy is a term used to describe noninflammatory muscle diseases that are not muscular dystrophy.

Rhabdomyolysis is the breakdown of muscle fibers resulting in the release of myoglobin in to the circulation resulting in kidney damage.

Muscle Anatomy

2008-04-24T14:04:00.000-04:00

The motor unit is the fundamental unit of the neuromusclular system.

It consists of:

Lower motor neuron which extends from the brain stem or spinal cord via a long axon to the skeletal muscle
The neuromuscular junction or motor end plate
A skeletal muscle cell

Where the motor end plate and muscle join is the neuromuscular junction - a synapse. Signals transmitted down the axon to the motor end plate cause the release of acetylcholine (a neurotransmitter) into the synaptic space. Acetylcholine interacts with the muscle cell causing contraction of muscle fibers. The acetylcholine must be immediately broken down by the enzyme cholinesterase before another signal can be transmitted.

You can find an excellent review of the physiology of muscle contraction here.

See an animation of the actin myosin crossbridge in action here.

Muscle fibers are either type 1 or type 2 (A and B). Go here to read a good review on muscle fiber types and training.

Tumors of Melanocytes

2008-04-24T13:38:00.001-04:00

Melanocytes are the cells that produce the pigment melanin. These cells are derived from the embryonic nervous system.

Nevi or moles are benign tumors of melanocytes. They are common and usually appear before age 20.

Dysplastic nevi are atypical moles. They are usually larger than common moles. Many pictures of moles here.

All nevi are important because they must be distinguished from malignant melanoma.

Malignant melanoma is the most dangerous type of skin cancer. They most commonly occure on sun-exposed skin surfaces. Half of melanomas arise spontaneously and half arise from pre-existing moles.

Tumors of the Dermis

2008-04-24T11:30:00.000-04:00

There are many tumors that occur in subepidermal tissues. Most of them are benign tumors.

Lipomas yellow, moveable subcutaneous masses that are not premalignant.

Dermatofibroma are benign fibrous tumors due to growth of dendritic cells.

Keloids are nodular masses of exaggerated scar tissue. They do not become malignant.

Hemangiomas are abnomal overgrowths of blood vessels.

Telangiectasis is a local collection of blood vessels that are often called spider angiomas. Often associated with hormonal imbalances.

Nevus flammeus (port wine stain) is a common congenital condition composed of a colleciton of dilated dermal blood vessels.

Neurofibroma is a benign tumor of peripheral nerves. See Von Recklinghausen neurofibromatosis.

Kaposi sarcoma is a malignant tumor of vascular endothelial cells caused by a type of Herpes virus.

Tumors of the Epidermis

2008-04-24T11:00:00.000-04:00

For more information on common types of skin cancer go here.

Epidermoid cysts are not true neoplasms. They form from occluded hair follicles.

Warts (verruca vulgaris)are common papillary growths of epidermis cause by papilloma virus infection.

Seborrheic keratosis is a non-cancerous growth of the epidermis. They are not premalignant.

Actinic keratosis is an early stage of skin cancer. They can be considered squamous carcinoma in situ.

Keratoacanthoma a common and generally considered benign tumor of sun-exposed skin.

Basal cell carcinoma is the most common skin cancer. It arises from basal cells and is associated with exposure to sunlight. It does not usually metastasize but can destroy surrounding skin.

Squamous cell carcinoma is a malignant tumor of epidermal cells (keratinocytes). Photos and more information here.

Acne

2008-04-23T23:43:00.000-04:00

Acne is an inflammatory disorder of hair follicles and associated sebaceous glands.

Acne vulgaris is a common skin condition seen in teenagers. More here.

Postadolescent acne is usually seen more in women than men. It's related to hormonal fluctuations.

Rosacea has been covered in a previous post several weeks ago.

Diseases of the Dermis - Contact Dermatitis

2008-04-23T22:45:00.000-04:00

Allergic contact dermatitis is a delayed type hypersensitivity (type 4). Also here. Click on links for photos and more information.

Allergic contact dermatitis is often called eczema. This is a descriptive word that is applied to a wide variety of skin diseases. The most common type of eczema is atopic dermatitis. It is an allergic condition that makes your skin dry and itchy. It is most common in babies and children.

Irritant contact dermatitis is caused by direct contact of certain chemicals with skin. No allergy is involved. Examples would be diaper rash or "dishpan hands".

Diseases of the Dermis - Noncontact Dermatitis

2008-04-23T22:11:00.000-04:00

Scleroderma is a chronic, systemic, autoimmune disease of the connective tissue characterized by severe fibrosis and tightening of skin.

Photoaging is a result of too much exposure to the sun resulting in breakdown of collagen.

Stasis dermatitis is a skin condition that accompanies severe varicose veins.

Urticaria and Angiodema (see here)

Diseases of the Epidermis

2008-04-23T20:11:00.000-04:00

Skin color is determined by the amount of melanin produced by melanocytes and deposited in basal cells.

There are several skin disorders of pigmentation. A good source of information on skin pigmentation disorders can be found here at Medline Plus (scroll down to specific disorders).

Here are some other specific disorders of pigmentation.

Vitiligo

Freckles and moles

Melasma

Lentigo

Some other diseases of the epidermis are:

Psoriasis Photo's here.

Seborrheic dermatitis Photos here (scroll down)

Lichen simplex chronicus

Pemphigus

Skin in Systemic Disease

2008-04-23T19:43:00.000-04:00

Many systemic diseases have skin manifestations. Below are links to some of them.

Skin signs of systemic disease (Cleveland Clinic)

Diabetes and skin.

Thyroid disease and skin.

HIV infection and skin. Photos here.

Blood lipid abnormalities and skin.

Systemic lupus erythematosus and skin

Sarcoidosis (scroll down to skin and click on various conditions)

Neurocutaneous syndromes

Skin Lesions 4

2008-04-23T18:51:00.000-04:00

Bacterial infection of the skin commonly seen in children

Ichthyosis vulgaris is a common inherited skin disorder causing dry, scaly skin

Keloid scars are an overgrowth of scar tissue at the site of a healed skin injury

Moles are benign neoplasms where melanocytes replicate

Contact dermatitis caused by contact with a material that causes an allergic reaction

Poison ivy (contact dermatitis)

Wart: a small benign neoplasm caused by infection with a type of human papilloma virus that does not cause genital warts

Skin Lesions 3

2008-04-23T15:12:00.000-04:00

Port wine stain birthmark usually present at birth

Psoriasis is a common, probably inherited skin condition probably related to an autoimmune inflammatory response

Seborrheic keartosis is a benign form of skin cancer ususally seen in those over age 40

Systemic lupus erythematosus is a chronic inflammatory autoimmune disorder

Actinic keratosis is a precancerous skin growth usually caused by sun exposure

Basal cell carcinoma is a slow growing skin cancer

Severe bedsore: an area of skin that breaks down due to the pressure caused by staying in one position too long (wheelchair, bedridden)

Early Lyme Disease lesion: an inflammatory disease caused by infection caused by the bacterium Borrelia burgdorferi (transmitted by tick bite)

Skin Lesions 2

2008-04-22T13:01:00.000-04:00

Cutaneous candidiasis (fungus) yeast infection of the skin

Necrobiosis diabeticorum (flesh eating skin disease) caused by infection with a variety of bacteria

Swimmer's itch caused by infection with bird Schistosome (worm)

Flea bite

2nd Degree burn

Pictures obtained from Medline Plus Encyclopedia

Skin Lesions

2008-04-20T14:43:00.000-04:00

Pictures from Medline Plus Encyclopedia

Blackheads caused by a small plug in the opening of a follicle on the skin

Cellulitis due to staph, strep or other bacterial infection

Atopic dermatitis chronic skin disorder categorized by scaly and itching rashes. Commonly seen in people that suffer allergies

Athletes foot due to Tinea (fungus) infection

Acne vulgaris occurs when tiny holes on the surface of the skin called pores become clogged

Shingles caused by infection with Herpes Zoster (virus)

Ringworm caused by Tinea corporis infection (fungus)

Skin Lesions

2008-04-20T09:23:00.000-04:00

Because the skin is so visible, there are more diseases described for the skin than for any other organ of the body. Most skin diseases are not life threatening but some are such as the flesh eating bacterial infection. Unfortunately there are many different types (names) of skin lesions. Just a few are:

Macule: a flat lesion that cannot be felt.

Papule: a bump smaller than 10 mm

Nodule: a bump larger than 10 mm

Vesicle: a fluid filled cavity under the skin smaller than 10 mm

Blister: a fluid filled cavity larger than 10 mm

Skin Anatomy

2008-04-19T20:44:00.000-04:00

Skin is made up of three layers, some of which contain more specialized cells:

1. Epidermis: is the outer layer of skin. It is made up of 5 layers. From bottom to top they are: stratum basale; stratum spinosum; stratum granulosum; stratum licidum and stratum corneum. The epidermis varies in thickness from .05 to 1.5 mm.

More information about each of these layers can be found here.

The epidermis contains 3 types of specialized cells. Melanocytes which are cells that produce the pigment melanin; Langerhans cells, a type of dendritic cell involved in immune function and Merkel's cells which are associate with sensory touch.

2. Dermis: consists of 3 types of tissue found in two layers; the upper papillary layer and the lower reticular layer . Collagen, elastic tissue and reticular tissue.

The reticular layer (RD) of the skin gives it strength and elasticity. It is also the home to glands and hair follicles. The papillary layer (PD) contains the vascular network important in regulating heat flow from the skin.

Specialized cells in the dermis include: hair follicles, sweat (sebaceous) and scent (apocrine) glands associated with hair follicles; sweat glands (eccrine) not associated with hair follicles, blood vessels and nerves and sensory nerve cells (touch) called Meissner's and Vater-Pacini corpuscles.

3. Subcutaneous tissue: a layer of fat and connective tissue containing blood vessels and nerves.

More articles and resources concerning skin anatomy can be found here.

Helminth Infection of the Skin

2008-04-18T11:21:00.000-04:00

Swimmer's itch is Cercarial Dermatitis. It results when bird (usually ducks, geese) schistosome eggs hatch and the resulting larvae infect a particular type of snail. Cercaria, from infected snails, are released into the water waiting to infect an unsuspecting duck. When the cercaria infect humans (the wrong host) a skin eruption occurs because the bird schistosome cercaria cannot develop further.

Cercarial dermatitis in a swimmer.

Another type of helminth skin infection that can be found in the USA is cutaneous larval migrans.

Cutaneous larval migrans results when roundworms that normally infect dogs or cats infect a human instead. The roundworm cannot develop normally because it is in the wrong host. Thus it wanders around under the skin.

Ectoparasites

2008-04-17T23:44:00.000-04:00

Top to bottom: human flea (Pulex), eyelash mite (Demodex) and a louse (Pediculus)

Here is a great medical entomology website. An ectoparasite is a parasite that lives on or in the skin rather than inside the body. Humans can become infested with many different ectoparasites. Some are pretty much harmless (head lice) and others can transmit disease (ticks, fleas, mites). Some ectoparasites live in the skin. For instance the scabies mite.

Learn more about scabies (mites) here, it's something you could possibly see. You can visit these websites to learn about head lice, ticks that spread Lyme Disease, body lice, and dust mites (not an ectoparasite but a cause of allergy). Here is a paper that discusses eyelash mites (demodex) and rosacea.

Some diseases spread by ectoparasites include: Babesiosis (ticks), Plague (fleas) and scrub typhus (mites).

Helminths

2008-04-17T16:50:00.000-04:00

Helminths are multicellular worms. The parasitic worms are found in several classes. The trematodes (flukes) and cestodes (tapeworms) contain the flatworms. The nematodes are the roundworms.

A good introduction to helminths can be found here. You can find plenty of pictures of helminths at this website if you click around.

Some important helminth diseases of man include Schistosomiasis, Oncocerciasis, Lymphatic Filariasis, Echinococcosis and Taeniasis. Some roundworm infections found in the USA include Pinworm (Enterobius), Whipworm (Trichuris), Ascariasis, Hookworm and Strongyliasis.

Protozoa

2008-04-15T14:25:00.000-04:00

A selection of parasitic protozoa from the UK Natural History Collection. From left to right: Entamoeba histolytica which cause amoebic dysentary; Trypanosoma brucei transmitted by Tetsi flies and causes sleeping sickness; Babesia sp in Red Blood Cells transmitted by ticks; Balantidium coli a very large protozoan of pigs that rarely causes disease; and then two ciliates of cattle both of which are symbionts and cause no disease.

Protozoa are unicellular, eukaryotic,usually motile organisms that are more "animal-like" than "plant-like". More than you need to know about parasitic protozoa can be found here and here.

Protozoa have complex life cycles, some requiring two different hosts for reproduction and/or transmission. You can see some animations of protozoan life cycles at this WHO website. Below is a dipiction of the malaria life cycle which takes place in a mosquito and a human.

Malaria parasites in red blood cells.

You can find out more about protozoa and parasites in general at this CDC website.

The most important protozoan diseases include: Malaria, Leishmaniasis, Trypanosomiasis (African and American), and Amoebiasis. Protozoal infections in the USA are more likely to be Toxoplasmosis, Giardiasis, Babesiosis and Trichomonas.

Bacteria

2008-04-15T14:20:00.000-04:00

Bacteria are unicellular, prokaryotic, microscopic organisms. They are found in many different shapes including rods, spheres and spirals.

For a short introduction to bacteria go here.

There is lots of information about bacteria, bacterial pathogenesis, bacterial genetics etc at this great website.

Everything you want to know about bacterial infections can be found at this CDC website.

LMT's should be aware of this website concerning skin diseases. Just click on the links to see pictures.

Viruses

2008-04-15T14:15:00.000-04:00

Rabies virus.

Viruses are small infectious particles that can only replicate inside of cells. The particle is made up of a protein capsid coat containing either RNA or DNA. Viruses are generally considered to be non-living.

There are many good websites that provide all the information you need to know about viruses. All the Virology on the WWW is a great place to start. Then visit The Big Picture Book of Viruses. Want to learn more about specific viral infections...then go here.

Influenza virus

Prion Diseases

2008-04-15T14:00:00.000-04:00

Prions are small proteinaceous infectious particles. They are non-living and lack DNA. Prion diseases are often called Spongiform encephalopathies because diseased brains often appear with large vacuoles. Prion diseases are usually rapidly progressive and are always fatal.

I highly recommend looking at this single page for more information about prions.

A free, full-text review on prions by Stanley Prusiner can be found here.

More about Creutzfieldt-Jacob disease here.

Go here for the CDC Prion Disease page.

Some info on Alzheimer disease here.

Genetic Disorders

2008-04-14T14:07:00.000-04:00

The University of Utah has provided an excellent website on genetics. There are animations and interactive projects to reinforce your learning. Make use of them!

Injured (mutated)DNA or abnormal chromosomes can result in genetic disease.
First, refresh your memory on mutations.
What is a mutation?
How do mutations occur?
How do mutations cause genetic disorders?

To learn more about genetic disorders go to this University of Utah website. Notice the distinction between single gene disorders, chromosome abnormalities and multifactorial disorders.

You should understand the genetic basis of sickle cell disease, PKUand cystic fibrosis.

Be sure to understand genetic traits characterized as:

Autosomal dominant

Autosomal recessive

Sex-linked (or X-linked)

To learn more about disorders caused by abnormal chromosomes go to another page at the same website.

You should understand the genetic basis of Down Syndrome, Turner Syndrome, and Klinefelter Syndrome.

Another great place to learn some genetics is at the Cold Spring Harbor DNA Learning Center. Here is the page for "Your Genes, Your Health".

There is also an excellent, easily understood, source of information on understanding genetic conditions at the National Library of Medicine. Your taxes paid for it, make use of it.

Genetics Definitions

2008-03-13T22:47:00.003-04:00

A locus is the specific place on a chromosome where a gene is located.

An allele is any one of an alternative forms of a given gene. Blood group antigens are an example. Blood types A, B and O are each alleles or slightly different version of genes that code for a blood surface antigen.

A gene is the portion of DNA that usually encodes a protein. Genes confer inheritable traits.

A genotype describes the genetic constitution of an individual.

A phenotype is the observed appearance or quality of an individual. Blue eyes, blond hair, six fingers. It is the product of the genotype and the environment.

A dominent allele (gene) expresses its phenotype even in the presence of a recessive allele. Thus genotype AA (two dominent alleles - homozygous) and Aa (one dominent and one recessive allele - heterozygous) have the same phenotype.

A recessive allele (gene) is expressed only if two copies of the recessive allele occurs.

A homozygous gene pair is an identical pair of alleles at the locus of each chromosome - eg. AA or aa but NOT Aa which is heterozygous.

A heterozygous gene pair has different alleles at the locus of each chromosome - eg. Aa

A gene mutation is a permanent change in the DNA sequence that makes up a gene.

A point mutation is single nucleotide base change in the DNA.

For more basics about chromosomes take this tour of the basics.

For more basics about genes take this tour of the basics.

Genetics Refresher

2008-03-13T14:44:00.000-04:00

First, refresh your memory about the cell and basic cell biology.

Then review the genome.

DNA is found in the nucleus

And in the mitochondria. Mitochondrial DNA is circular and carries the information for 37 genes. Almost all (99.9%) of your mitochondrial DNA is inherited from your mother.

DNA is transcribed into mRNA in the nucleus, and translated into protein in the cytoplasm.

A gene is the functional unit of heredity in an organism. A gene's nucleotide sequence encodes an RNA or polypeptide.

A gene mutation is a heritable change in the DNA sequence that makes up a gene.

A point mutation are those mutations that affect a single base pair of DNA. It occurs when 1 base on a DNA strand is replaced with a different one. There are four types of point mutations:

(1) missense mutation is where the point mutation results in a wrong codon and a wrong amino acid.

(2) nonsense mutation is where the point mutation results in a stop codon where the protein would be terminated at that point.

(3) silent (or sense) mutation is where the point mutation results in a new codon that still encodes the same amino acid

(4) frameshift mutation results from the addition or deletion of a base pair in a gene. Such additions or deletions shift the mRNA's reading frame by one base so that incorrect amino acids are added to the protein chain.

A chromosomal mutation occurs when a long segment of DNA is deleted, inserted, inverted or translocated.

Much more can be learned about the human genome at this Wellcome Trust website.

Immune System Disorders - Immune Deficiency

2008-03-13T13:21:00.000-04:00

Disorders related to defective immunity can be classified as follows:

1) Inadequate response to exposure to foreign antigen (congenital immunodeficiency).

2) An excessive or inappropriate immune response in response to foreign antigen (allergy).

3) The loss of the capacity to distinguish self from non-self (autoimmunity).

4) Cancer of the immune cells.

In this post we will deal with #1 above.

PRIMARY IMMUNE DEFICIENCY is a condition that results if one or more essential components of the immune system fails or is missing due to a congenital genetic defect.

Some examples of primary immune deficiency diseases include:

Reticular dysgenesis

Severe combined immune deficiency disease

Ataxia Telangiectasia

Wiskott-Aldrich Syndrome

DiGeorge Syndrome (affects primarily T cell function)

Bruton's congenital agammaglobulinemia (affects B cell function)

X-linked Hyper-IgM Syndrome

SECONDARY IMMUNE DEFICIENCY

Secondary immune deficiencies occur when damage is caused by an environmental factor.

Neoplastic disorder

Malnutrition

Iatrogenic

Infection

Vaccines

2008-02-28T14:50:00.000-05:00

If nothing else watch this very short video on how different vaccines are made.

Naturally Acquired Immunity is that immunity acquired upon exposure to a specific pathogen or foreign antigen.

Artificially Acquired Immunity is that immunity obtained via vaccination with a killed or live attenuated pathogen.

Vaccine is a preparation of killed or live attenuated pathogen or of specially derived pathogen antigenic determinants that is used to induce an immune response that protects an individual to a subsequent exposure to that pathogen.

Vaccination (immunization) is a means of inducing artifically acquired immunity. The goal of vaccination is to induce antibody or cell-mediated immune responses against a pathogen, without simultaneously inducing disease.

Edward Jenner was the army surgeon who is generally credited with advancing the art of "vaccination". On May 14, 1776, Jenner purposely exposed James Phipps with cowpox virus obtained from dairymaid Sarah Nelmes. Phipps became immune to smallpox as evidenced by survival of several purposeful attempts to infect him with the virus. Benjamin Jesty claims to have done the same thing 20 years prior to Jenner. Actually, the Chinese probably were vaccinating against smallpox hundreds of years before either of these men were born.

After the introduction of the smallpox vaccine in 1778 additional vaccines were introduced such as Rabies 1885, Plague 1897, Diptheria 1923, Pertussis 1926, Tuberculosis and Tetanus 1927 and Yellow fever 1935.

TYPES OF VACCINES

Inactivated Vaccines (killed) are vaccines consisting of an inactivated whole pathogen. Because the pathogen is dead these vaccines are considered very safe. However, they usually require several booster doses of the vaccine to induce sufficient immunity. An example of an inactivated vaccine is the Salk Polio vaccine and the Influenza vaccine.

Live, Attenuated Vaccines are vaccines that are made from a live pathogen that has been weakened so it cannot cause disease. These vaccines actually result in a mild infection, thus inducing a very strong protective immune response. A disadvantage of these vaccines is that they typically cannot be given to immunosuppressed individuals. An example of a live, attenuated vaccine is the oral Sabin Polio vaccine and the smallpox vaccine.

Toxoid Vaccine is a vaccine that is made from an inactivated toxin. Many infectious bacteria produce a toxin that is the cause of disease. Toxoid vaccines are made by treating the toxin chemically or with heat to inactivate it. Examples of toxoid vaccines are Diptheria and Tetanus vaccines.

SECOND GENERATION VACCINES

These vaccines are the result of recombinant DNA techology.

Subunit Vaccines are vaccines developed from well defined antigenic fragments of a pathogen.

Recombinant subunit vaccine are obtained using recombinant DNA techniques. Yeast cells are transfected with DNA which encodes an antigenic determinant of a pathogen. The yeast cells are grown in culture and the recombinant vaccine antigen is purified from the yeast cell culture. An example of this type of vaccine is the Hepatitis B vaccine.

Recombinant vector vaccines are made by inserting pathogen genes that encode protective antigens into a virus that does not cause disease (such as the vaccinia virus) but can express the pathogen genes. Although clinical trials are being done using these vaccines, there are no currently approved recombinant vector vaccines.

Conjugate Vaccine is a vaccine that is specially designed to induce immunity in babies who have an immature immune system. These vaccines consist of a polysaccharide (bacterial surface coat antigen) which is combined with an immunogenic protein that can be recognized by the baby's immune system. An example of this type of vaccine is the Haemophilus influenzae type b (Hib) vaccine.

FUTURE VACCINES

DNA Vaccines are made of a modified form of the pathogens DNA. When this DNA is injected into an individual, the pathogen DNA enters the cells which leads to the expression of the genes in the DNA (pathogen antigens). You can read more about DNA vaccines here.

Edible Vaccines are vaccines in which the pathgen antigens are expressed in edible plants such as potatoes and tomatoes. Read more about edible vaccines here.

VACCINE SIDE EFFECTS

Vaccination can result in side effects. These are typically local side effects including pain, redness, swelling, itching or a small lump at the site of injection.

However, occasionally systemic side effects can occur. These might include headache, fever, muscle aches or rashes. Very occasionally severe side effects might occur such as anaphylaxis shock.

Immunity - Lymphocytes

2008-02-28T14:36:00.000-05:00

Lymphocytes: these are the cells that are responsible for specific immune responses. There are two distinct classes of lymphocytes:

B lymphocytes: are the cells that produce antibodies. The specific antigen receptors on B cells are membrane-bound forms of antibodies. Antibody producing B cells are called plasma cells.

T lymphocytes: do not produce antibody molecules. They produce a wide variety of molecules called cytokines that mediate immune resistance and have the capacity to directly kill other cells. There are at least three main types of T cells:

Helper T lymphocytes: (CD4+) participate in th activation and development of B lymphocytes, the activation of macrophages and the inflammatory response. They recognize foreign antigens presented by cells displaying MHC Class II molecules. You can see an animation of how this works here.

Helper T lymphocytes can be further divided into TH1 and TH2 lymphocytes.

Pathways to TH1 and TH2 lymphocyte differentiation can be seen here.

TH1 and TH2 lymphocytes are differentiated by the cytokines that they secrete. Cytokines are small protein hormones that mediate and regulate immune responses and inflammation. Learn more about cytokines here, here and here.

Cytotoxic T lymphocytes: (CD8+) are the cells that have the capacity to kill virus-infected cells, tumor cells and allografts. They can also mediated other forms of cell-mediated immunity. They recognize foreign antigens presented by cells displaying MHC Class I molecules.

Regulatory T lymphocytes: (FoxP3+) are T cells that act to suppress or regulate the activation of the immune system. These cells are probably important in preventing the expression of autoimmune diseases. These cells are a relatively recent discovery and it is not yet known exactly how they work in many cases.

Lymphocytes can also be differentiated based on the surface proteins they express called clusters of differentiation.

Here is a pretty good representation of the overall immune response to a viral infection obtained from a U. of Texas website.

Down the left side of the picture:

1) A host cell becomes infected with a virus.
2) The cell processes and presents viral antigen epitopes bound to MHC Class I molecules to the antigen receptor on a CD8+ cytotoxic T cell.
3) Activated effector viral antigen-specific CD8+ cytotoxic T cell recognizes a virally infected cell and kills it.
4) After viral pathogen is cleared some CD8+ viral specific cytotoxic T cells become memory cells.

Down the right side of the picture:

1) Lysed virally infected cell releases viral particles.
2) Viral particles are engulfed by activated macrophages, processed and presented, bound to MHC Class II molecules, to the CD4+ helper T cells.
3) CD4+ helper T cell becomes activated, proliferates, differentiates and secretes cytokines to help B cells become antibody producing plasma cells and CD8+ cytotoxic cells to become better killers.
4) Later in the response, viral specific B lymphocytes become very potent antigen presenting cells due to their antigen receptors.
5) As virus is cleared, CD4+ T cells and B cells become either die or become memory cells.

Immunity - Overview

2008-02-28T14:15:00.001-05:00

Immune is from the latin immunitas refering to freedom from taxes or the exemption from service. We use the word to mean protection from disease, usually infectious disease.

Immunity is mediated by the immune system, a network of organs, tissues, cells and molecules. A brief introduction to the immune system can be found here.

The immune response is the collective and integrated response of the immune system to the introduction of a foreign antigen into the body.

NATURAL (INNATE) AND ACQUIRED (SPECIFIC) IMMUNITY

Natural or innate immunity are the barriers and mechanisms that mediate nonspecific resistance or defense in the body. Skin, mucous membranes, phagocytic cells and various molecules mediate innate immunity.

Acquired or specific immunity are those immune responses that are specific for distinct antigens and can increase in magnitude and capabilities with every exposure to the same antigen. An animation of specific immunity in action can be seen here.

Active Immunity is the type of specific immunity that is induced when an individual is exposed to an infectious agent or foreign antigen. This is the immunity that is generated in response to vaccination.

Passive Immunity is that immunity that can be transferred using cells or serum obtained from an immune individual. This is a means of rapidly inducing resistance to an individual.

The adaptive immune system is often classified into:

Humoral immunity which is mediated by antibodies. Go here to learn how lymphocytes make antibodies. Watch this animation on an allergic reaction that is mediated by IgE antibodies.

Cell-Mediated immunity which is mediated by T lymphocytes.

The immune response has several important features:

Specificity: immune response is specific for the antigen that induced the immune response.

Diversity: the number of antigen that can be recognized by the immune system is estimated to be 10,000,000,000.

Memory: exposure of the immune system to an antigen results in enhanced capacity to produce more antibodies or T cells to subsequent exposure to the same antigen.

Tolerance: individuals typically do not make immune responses to their own tissues. This is because the immune system is capable of discriminating self from non-self.

Self-limitation: immune responses normally decline after a period of time. This usually correlates with elimination of the antigen that originally induced the immune response.

Learn more about the immune system here and here.

A Human Endogenous Retrovirus Reconstituted

2008-02-21T21:12:00.001-05:00

Remember those HERVs we talked about in the previous post? A group from the Aaron Diamond AIDS Research Center at The Rockefeller University has reconstituted one of them using molecular techniques. The entire article is published in PLOS Pathogens, a free, full text, on-line journal.

These investigators have reconstitute a Class II HERV, HERV-K.

A pseudo-ancestral HERV-K DNA sequence was synthesized and used to produce viral proteins and RNA that could reconstitute the HERV-K replication cycle. Thus, the replication and biology of a once-extinct retrovirus can now be studied in the laboratory. Interestingly, reconstituted HERV-K replication experiments, and comparison of the reconstituted HERV-K DNA sequence with the dead HERV-Ks in modern human DNA, suggests that HERV-K may have been extinguished in humans in part by host defenses that induce mutation of retroviral DNA and that the reconstitution of the pseudo-ancestral HERV-K reversed these changes.

This further suggests that infection with ancient retroviruses induced selective pressure on the human immune system allowing us to resist infection with certain retroviruses.

Two major components of intrinsic defense against retrovirus and retroelement replication in primate cells are the TRIM5 and APOBEC3 gene products [40–42]. Analysis of these genes in modern primates indicates that these genes have likely been under positive selection pressure for significant portions of primate evolution [12–16]. As an endogenous retrovirus that has also apparently replicated exogenously and has been active for much of Old World primate evolutionary history, HERV-K is an excellent candidate for an agent that has imposed sustained evolutionary pressure on antiretroviral defenses present in modern primates.

The Introduction and Discussion in this article is very readable. Give it a try.

Human Endogenous Retroviruses

2008-02-21T20:00:00.000-05:00

I'm adding this post before I forget about it. We will discuss it more when we cover viruses.

Human Endogenous Retroviruses. These pieces of DNA are 'fossil's of retroviruses that were incorporated into the human germline DNA over thousands to hundreds of thousands to millions of years. They make up about 1% of the human genome. The first HERV was identified in 1981. So far, at least 20 HERV families have been identified (find free text article by M. Tristem here). There are lots of things cool about HERVs. First, they may be involved in the pathogenesis of some diseases, such as cancer, Sjogren's syndrome, Rheumatoid arthritis, Multiple sclerosis or Systemic Lupus Erythematosus, to name a few.

HERVs have been classified into 3 groups based on sequence identity with animal retroviruses.

Class I HERVs share sequence homology with infectious mammalian type C viruses. Examples would be porcine endogenous retrovirus, murine leukemia virus and baboon endogenous virus.

Class II HERVs share sequence homology to mammalian type A, B and D related retroviruses. HERV-K is a member of this group and is one of the most active HERVs. HERV-K can actually form virus-like particles.

Class III HERVs are foamy virus related HERVs and include only HERV-L. This is the oldest known genus of Retroviridae and more can be found about them here.

Why have HERVs been so successfully maintained in our genome? This person has one hypothesis. Is is possible that HERV's somehow serve the needs of the host? Also here.

Science fiction novelist Greg Bear has a series of novels in which HERV's play an important role in evolution.

Teratoma

2008-02-19T16:34:00.002-05:00

A teratoma is a tumor derived from pluripotent stem cells. The word teratoma is from the Greek meaning monstrous tumor. Teratomas are derived from germ cells, sperm and ova and thus can form tissue from endoderm, mesoderm and ectoderm. Thus these tumors can contain hair, bone and even teeth. Rarely, a more developed organ such as an eyeball or hand can be formed. Some forms of teratomas, Fetus in fetu and fetiform teratoma, can even resemble a malformed fetus. Pictures of these types of teratomas can be found here and can be quite shocking.

Here is a link to ovarian teratomas. There are two different kinds of ovarian teratomas. Mature teratomas which are benign and immature teratomas that are cancerous. A short review on teratomas can also be found here.

Pressure Ulcers

2008-02-19T09:22:00.003-05:00

There is a worthwhile article on pressure ulcers (bedsores) in todays New York Times Science section. An excellent review of this condition can be found at massage therapy. More information can be found here and here.

Cancer Biopsy and Risk of Metastases

2008-02-14T19:30:00.001-05:00

Last year someone asked if biopsy of a tumor could result in the spread of the cancer. There are a few unathorative websites that claim this is the case. Those sites also happen to be touting "alternative" treatments for cancer.

A recent publication The impact of preoperative breast biopsy on the risk of sentinel lymph node metastases: analysis of 2502 cases from the Austrian sentinel node biopsy study group by Peters-Engl et al (full free text here) concluded that:

based on the present data, is that preoperative breast biopsy does not cause artificial tumour cell spread to the SLN, with possible negative impact on the prognosis of breast cancer.

These results disagreed with those of Hansen et al in a paper titled Manipulation of the Primary Breast Tumor and the Incidence of Sentinel Node Metastases From Invasive Breast Cancer (summary here).

But go here and read what Dr. Hansen has to say about her study before you make a decision about the safety of cancer biopsy.

"This study does not link biopsy with spread [of breast cancer]," Hansen tells WebMD via email. "We have not changed our practice and do not plan to. We still prefer to perform a needle biopsy to confirm the diagnosis of cancer and then will proceed at another time to definitive surgical management."

Neoplasms

2008-02-14T19:13:00.001-05:00

For an excellent easily understood review about cancer proceed to this National Cancer Institute website and click through all 61 slides.

TERMS

Neoplasm: (neo= new; plasm= form) an uncontrolled growth of new cells, may be benign or malignant

Tumor: a mass; a neoplasm

Cancer: any kind of malignant neoplasm

Malignant: capable of spreading throughout the body and causing death

Carcinoma: a malignant neoplasm of epithelial cells

Sarcoma: a malignant neoplasm of mesenchymal (tissue derived from mesoderm) tissue

Our bodies are constantly shedding dead cells and growing new cells. Remember that a neoplasm is and uncontrolled growth of new cells. It is not normal growth.

Normal cell growth is controlled by proto-oncogenes. These genes generally encode proteins which control normal cell growth. But when proto-oncogenes undergo mutation, they may become oncogenes. You can learn much more about oncogenes here.

The body has evolved mechanisms to repair damaged DNA.

Cancer is caused by mutation of somatic cells. Some individuals have inherited genetic mutations that predispose them to develop certain types of cancer. It may take as few as 3 and as many as 20 mutations for a proto-oncogene to become an oncogene. Thus, cancers are frequently found in aged individuals.

How does DNA become damaged? Chemical carcinogens, ionizing radiation and viral infection have all been linked to DNA injury. Many, many more causes and risk factors for cancer can be found at this NIH website.

Does fluoridated water cause cancer? Experts at NIH say there is no evidence that it does.

In 1993, the Subcommittee on Health Effects of Ingested Fluoride of the National Research Council, part of the National Academy of Sciences, conducted an extensive literature review concerning the association between fluoridated drinking water and increased cancer risk. The review included data from more than 50 human epidemiological studies and six animal studies. The Subcommittee concluded that none of the data demonstrated an association between fluoridated drinking water and cancer (5). A 1999 report by the CDC supported these findings. The report concluded that studies to date have produced “no credible evidence” of an association between fluoridated drinking water and an increased risk for cancer (2).

However, if you do a google search you will find over 2.5 million links claiming differently. Could there really be a conspiracy to cover up the effects of fluoride treatment on cancer? I doubt it.

Tumor suppression genes can be thought of as genes that provide a "stop" signal. If these genes are mutated normal cell growth can become uninhibited. Much more about tumor suppressor genes here.

An important consideration in cancer biology is the speed of tumor growth. Go to this website to learn about cell growth and doubling time.

Angiogenesis is the process of growing a new blood supply. It's very important in tumor biology. There is a slide presentation on understanding the role of angiogenesis in cancer at this NCI website.

Grading and staging of neoplasms are done to aid in treatment decisions. Cancer grading is a pathologic exercise that determines the degree of differentiation of a tumor. Cancer staging is a clinical exercise that evaluates the behavior of a neoplasm. Learn more about grading and staging at this website.

Early detection of cancer is important for the most effective treatment. Learn about early detection of some cancers here, here and here.

Want further training in understanding cancer in general and specific tumors? Go to this government training website to continue your training.

Vaccination Via Tattoo

2008-02-07T19:32:00.000-05:00

German scientists have reported that vaccines delivered using a tattoo needle produce antibody responses 16 times greater than those delivered by intramuscular injection.

Hemodynamics - Thrombosis, Embolism, Shock

2008-02-05T18:40:00.000-05:00

A thrombus is a stationary mass of blood elements that remains attached to its place of origin along the wall of a blood vessel.

Thrombi are not clots although they are partially made up of clotted blood. Unlike most clots, a thrombus is always the result of a pathologic event. Clots are normal (usually) and occur outside a blood vessel.

The formation of a thrombus is not initially dependent on the clotting process. Thombi begin endothelial injury and an initial platelet clump. Layers of platelets are added followed by the adherence of white blood cells. A clot then adds volume as the thrombus grows.

You can find a full text article concerning deep vein thrombosis here and another full text article here.

An embolus is an intravascular object (air, tumor fragment, broken off thrombus, calcium fragments) that circulates in the bloodstream until it becomes lodged in a vessel obstructing the blood flow.

Ischemia is a lack of oxygen supply to a tissue usually due to obstruction of blood flow.

Lack of oxygen supply to a tissue can result in a tissue death called an infarct

See photos of an infarct of the heart here.

Shock is a state of systemic low blood flow. It can occur due to a loss of blood or because cardiac output is reduced.

Cardiogenic shock occurs when the heart is incapable of maintaining blood pressure. You can read much more about cardiogenic shock here.

Hypovolemic shock is a result of an underfilled vascular space, usually the result of hemorrhage. It can also be caused by fluid loss in cases of severe burns or diarrhea. Read more about hypovolemic shock here.

Septic shock is associated with systemic bacterial infections (sepsis) usually gram-negative bacterial infections. It is due to a massive inflammatory response to the infection. Read more about septic shock here.

Hemodynamics - Edema

2008-02-05T18:30:00.000-05:00

Above figure from Heartzine.Go there to learn about circulatory system.

To review your anatomy of the circulatory system go to this great website at the Texas Heart Institute.

60% of the human body is water. So an average person of 155 lbs is made up of 93 lbs of water and 62 lbs of solids. The 42 liters of water can be broken down this way:

Extracellular
Interstitial (space outside the blood vessels and in between cells) 8 liters
Plasma 3 liters
Cerebrospinal fluid and other 6 liters
For a total of 17 liters

Intracellular
A total of 25 liters (including Red Blood Cells)

Blood pressure is the force of blood pushing against the walls of arteries. It's expressed as the number of millimeters it can force a column of mercury upwards.

Normal blood pressure is a reading of 120/80 or lower. High blood pressure is a reading of 140/90 or greater.

Another type of pressure is osmotic pressure. Osmotic pressure is the amount of hemodynamic pressure that must be applied on the side with low water concentration to prevent water from passing into the saltier side.

Go to this Colorado State osmotic pressure simulator site and you can see the effects of increasing or decreasing solute on either side of a permeable membrane.

You can learn about osmotic pressure here (interactive) and here (physics).

Edema is a shift of water from the vascular space into another compartment, usually the interstitial compartment. Here is one website that discusses edema in general.

Low protein edema also called a transudate, occurs when there is excess venous pressure (hydrostatic edema) or low plasma osmotic pressure. Each of these conditions allows water to leave the vascular spaces and enter the tissue spaces.

One example of low protein edema is varicose veins due to excess venous pressure. Read more about varicose veins here.

Osmotic edema is another type of low protein edema. It occurs when plasma albumin levels are abnormally low allowing water to escape from the vascular space to the interstitial space. Osmotic edema is often associated with liver disease because the liver is the primary producer of albumin.

Generalized edema (anasarca) is another example of low protein edema.

High Protein Edema is the fluid accumulation seen in inflammation. Inflammatory edema would be seen in a sprained joint.

Lymphedema is due to obstucted lymphatics. See more here.

Cerebral and pulmonary edema can be fatal. Swelling of the brain results in increased pressure on the brain. Pulmonary edema can impair gas transport and exchange or encourage bacterial growth.

William Harvey and Blood Circulation

2008-02-05T18:25:00.000-05:00

William Harvey is the 17th century physician who hypothesized that blood moved in a circle. This was quite different from the accepted view of the time. Galen had postulated 1700 years previously that there were two kinds of blood, arterial and veinous, each with their own pathway to the tissues where it was consumed.

Harvey wrote: Since all things, both argument and ocular demonstration, show that the blood passes through the lungs and heart by the force of the ventricles, and is sent for distribution to all parts of the body, where it makes its way into the veins and porosites of the flesh, and then flows by the veins from the circumference on every side to the centre, from the lesser to the greater veins, and is by them finally discharged into the vena cava and right auricle of the heart, and this in such a quantity or in such a flux and reflux thither by the arteries, hither by the veins, as cannot possibly be supplied by the ingesta, and is much greater than can be required for mere purposes of nutrition; it is absolutely necessary to conclude that the blood in the animal body is impelled in a circle, and is in a state of ceaseless motion.
That is one hell of a sentence!

Harvey knew blood moved in a circle but he was unable to determine exactly how. He did not have the technology to observe the small capillaries that connected the arterial and veinous vessels.

Harvey was one of the first to use the scientific method in his work. He said:

I profess to learn and teach anatomy not from books but from dissections,not from the tenets for Philosophers but from the fabric of Nature.

You can learn more about William Harvey here.

Repair: Recovery from injury

2008-02-05T18:11:00.000-05:00

After injury and inflammation comes repair. Repair is the restoration of normal structure and function to injured tissue.

Read about it here.

Tissue regeneration requires an intact supporting stromal framework.

One element of this framework is the extracellular matrix. Read about extracellular matrix here.

The other stromal framework element is the basement membrane.

Photomicrograph from here.

Without the support of the extracellular matrix and basement membrane, tissues cannot return to normal and scarring occurs.

Angiogenesis is the growth of new blood vessels into the wound. View this NIH tutorial on angiogenesis in relation to tumor metastasis. It's a slide show, so just keep clicking on the arrow in the upper right corner.

There is also an entire issue of Nature devoted to angiogenesis with free text available here. This article is especially good.

Scar development follows angiogenesis. Read about scar development here.

What about tissue repair of the perineal region that is torn during childbirth?
You can read about this at these links here, here and here. Or you can listen to an NPR report on the topic here.

Stem Cells

2008-02-05T18:10:00.000-05:00

Above image from here.

Stem cells are primative, undifferentiated cells that have the capacity to proliferate and differentiate into more mature types of cells.

Some forms of tissue regeneration require stem cells.

You can go here to see animations about stem cells (you need Flash Player installed).

There is also stem cell information in lay terms at the NIH Stem Cell Information website.

Embryonic stem cells are obtained from human fertilized eggs called blastocysts. These stem cells are often refered to as "totipotent stem cells".

You can view an animated tutorial on human embryonic stem cells at this website and also at this website.

Adult stem cells are multipotent and are normally obtained from the bone marrow. A bone marrow transplant can be considered a stem cell transplant.

More recently, stem cells have been obtained from umbilical cords of recently born babies.

Stem cells were first cultured at my Alma Mater, The University of Wisconsin by James Thomson (paper cited above). Lots of stem cell info at this UW website.

Temperature Regulation

2008-02-05T18:02:00.000-05:00

The human body can regulate its core temperature to between 98 and 100 degrees F. If skin temperature drops below 37 degrees C. the body attempts to conserve heat by constricting the blood supply to the body surface. Shivering is the bodys attempt to produce more heat through muscle activity. Because no external work is performed during shivering, all the energy released is in the form of heat. Here is a short review on body temperature regulation. Also here.

Hypothermia (stage 1) occurs when the body temperature reaches 95 degrees or lower. Read about hypothermia at this Coast Guard website.

Hyperthermia occurs when the body produces more heat than it can dissipate. Body temperatures above 104 degrees F are life threatening. You can listen to scientist talk about how the human body copes with heat at this NPR website.

Fever (pyrexia)is an increase in body temperature as a response to bacterial or viral infection or to tissue injury. It's a temporary elevation in the bodies thermoregulatory setpoint. Generally, fever is not an illness because it's a defense response against infections. Body temperature can also increase due to hard exercise; ovulation; excess thyroid secretions and central nervous system damage. Cancer can also induce fever. More about fevers here.

Inflammation

2008-01-30T09:18:00.000-05:00

All disease is due to cell injury. Cell injury results in inflammation. The cardinal signs of inflammation were first described by Cornelius Celsus. You can actually read a translation of Celsus' De Medicina here.

You can learn a lot about Acute Inflammation at this website; chronic inflammation and healing and repair.

The pathogenesis of inflammation involves the leukocyte adhesion cascade. You can learn more about this process here.

This process is very important. Leukocyte Adhesion Deficiency Syndrome is a very rare genetic disorder caused by lack of, or deficiency in production of the cell surface molecule CD18.

Persistent injury can result in chronic inflammation. The above is one example. A Nobel Prize was awarded for this disovery.

The process of inflammation is very complex. There are many molecules involved and a few of them can be seen in the above figure showing airway smooth muscle mediators of inflammation.

More on molecular mediators of inflammation can be found HERE.

Plasma-derived mediators of inflammation:

Clotting system - read this.

Complement system - read this. We will discuss the complement system further under immunity. But the complement system generally has an under appreciated role in inflammation.

Kinin system - read this. [pdf available]

Cell-derived mediators of inflammation:

Vasoactive amines - read this and this.

Cell membrane factors - read this and this.

Cytokines (here and here)and Chemokines (here and here).

Reactive oxygen compounds - read this and this.

Chronic inflammation differs from acute inflammation. Read about it here.

Mitochondrial Diseases

2008-01-24T20:38:00.000-05:00

Yes there are diseases due to malfunctioning mitochondria. You can find an introduction here at the United Mitochondrial Disease Foundation. Many of these diseases are due to mutations in the mitochondrial DNA.

If you are really interested I found a free full text article about mitochondria and mitochondrial diseases here (but you have to register).

Healing Powers of Hyperbaric Oxygen

2008-01-24T20:20:00.000-05:00

Several diseases can be treated with hyperbaric oxygen. Read about some of them here at the Medical College of Wisconsin.

As for the use of hyperbaric oxygen therapy in cancer, there doesn't seem to be any firm evidence that it is useful. There is a fair bit of literature on the subject but I couldn't find any clinical trials that show the effectiveness of HBO treatment on cancer.

Necrosis

2008-01-24T19:45:00.000-05:00

Go here to see examples of coagulative necrosis and resulting infarcts both at the gross level and histological level. Keep clicking the 'right' arrow to see more examples. What is the most common cause of coagulative necrosis?

Examples of liquefactive necrosis can be seen starting here. Notice the photo of the macrophages cleaning up debris from an area of liquefactive necrosis in the brain.

Examples of fat necrosis start here.

Next is, you got it, the cheesy caseous necrosis seen in TB infected lung.

The Mycobacteria need to create these extensive areas of necrosis so they can be coughed out of the lungs and passed on to another individual.

Gangrene is next. Don't click on the link if you are feeling ill. The photo is of disembodied toes. We all know what can happen if you get frostbite.

Fibrinoid necrosis in hypertension.

Remember we talked about accumulation of abnormally folded proteins. Check out this photo of amyloid accumulation.

Then there is aging. Wear and tear (growing old) results in the accumulation of lipochrome in the liver. This is cellular debris that is sequestered within the cytoplasm.

Cell Adaptation

2008-01-24T19:33:00.000-05:00

Here are some examples of alterations in cell growth.

You can read more detail about muscle atrophy here.

Have you got that going problem? Maybe it's a growing problem. Benign prostate hyperplasia cartoon. Read more about BPH here.

Learn more about metaplasia here.

An example of cervical dysplasia. Keep clicking for more examples of dysplasia.

Here the entire epithelium is dysplastic so you have a full blown neoplasm. The basement membrane is intact however, so the cancer is not yet malignant.

APOPTOSIS

2008-01-24T18:55:00.000-05:00

More than you will ever want or need to know about apoptosis at this good website.

I borrowed this picture from the above website. It compares the process of apoptosis and necrosis.

You can read about the p53 tumor suppressor gene, apoptosis and prostate cancer here. We will cover this in more detail when we discuss neoplasms.

Guinea Worm and the Medical Practice Symbol

2008-01-22T23:15:00.000-05:00

I have mentioned that I am reading "Parasite Rex" by Carl Zimmer. The book is just as I expected. Wonderfully written, scary stories and anecdotes about parasites. I especially like his discussion of how the term "parasite" arose.

The word literally means "beside food," and the Greeks originally had something different in mind when they used it, referring to officials who served at temple feasts. At some point the word slipped its etymological harness and came to mean a hanger-on, someone who could get the occasional meal from a nobelman by pleasing him with good conversation....

But that is neither here nor there. Let's discuss guinea worm infection and its possible association with the symbol of medical practice....the Caduceus. The study of parasitology is filled with stories concerning history and especially biblical references.

Guinea worm, or Dracunculus medinensis, is a roundworm found in India, West and Central Africa and parts of the Middle East. The worms are found in the subcutaneous tissues of humans and the female worm can be over 30 inches in length. You become infected with guinea worm by drinking water that is contaminated with small, freshwater crustaceans that are themselves infected with guinea worm larvae. (Cyclops).

When the crustacean is consumed in contaminated drinking water, the guinea worm larvae in the Cyclops is released and makes its way through the intestinal wall, crosses the abdominal mesentaries, penetrates the abdominal muscles and make their way to the subcutaneous tissues. Fertilized females release their live larvae by penetrating the skin about a year after infection. Infected individuals often wind the body of the emerging female around a small stick so as to collect the entire adult worm rather than breaking it off in the body.

Obviously, the way to prevent this infection is to provide a clean, uncontaminated, source of drinking water. Also, the live larvae of the adult female need to be released into fresh water in order to find a Cyclops to infect as an intermediate host. So please do not go swimming or wading in fresh water if you find yourself with a female guinea worm emerging from your body.

Now, what you ask does this have to do with the symbol of medical practice? Well, you need to open your bible to Numbers 21:6-9:

And the Lord sent fiery serpents among the people, and they bit the people; and much people of Israel died.

Therefore the people came to Moses and said, We have sinned, for we have spoken against the Lord, and against thee; pray unto the Lord, that he take away the serpents from us. And Moses prayed for the people.

And the Lord said unto Moses, Make thee a fiery serpent, and set it upon a pole; and it shall come to pass, that every one that is bitten, when he looketh upon it, shall live.

And Moses made a serpent of brass, and put it upon a pole; and it came to pass, that if a serpent had bitten any man, when he beheld the serpent of brass, he lived.

Here we have talk of a serpent on a pole. Guinea worm, by the way, causes intense pain (like fire) when it emerges from a blister on an arm or leg.

Where Zimmer gets it wrong is stating that "But it may be that that person's invention was remembered in the symbol of medicine, known as the caduceus: two serpents wound around a staff." [Chapt. 1, pg. 2]

Actually, the symbol of medicine is not the winged staff with two serpents. That would be the "Caduceus of Mercury" or the "Karykeion of Hermes". This is actually a symbol of commerce.

The actual symbol of medicine is the Staff of Asclepius. A staff, or stick, with a single snake wrapped around it. You can find all you want to know about the difference between a caduceus and the staff of Asclepius here at the website of New Zealand physician Dr. Blayney.

Why is the caduceus a symbol of medicine in the USA? Blame it on the US Army Medical Corps.

Prefixes and Suffixes

2008-01-22T19:37:00.000-05:00

PREFIXES

a - without or not

an - without

angio - vessel

arthro - joint

brady - slow

dys - difficult or bad

homeo - similar

hyper - above or excessive

hypo - deficiency or beneath

inter - between

intra - within

mal - bad

micro - small

mega - large

necro - death

neo - new

para - beside

peri - around

osteo - bone

para - beside

peri - around

phleb - vein

poly - many

pro - before

pseudo - false

pyo - pus

steno - narrow, compressed

syn - together with

tachy - rapid

SUFFIXES

algia - pain

emia - blood

genesis - generation of

iasis - a process, especially a morbid one

ism - condition

itis - inflammation of the part named

lysis - to dissolve

megaly - large

oma - tumor

osis - full of

pathy - disease

penia - poverty, a deficiency

plasia - to form

plegia - a paralyzed state

ptosis - downward displacement

sclerosis - hardening

stasis - standing still

trophy - nourish

Some Terms

2008-01-22T19:33:00.000-05:00

Etiology. The cause of disease. Disease is either caused by genetic or acquired factors. Disease results from cell injury.

Pathogenesis. How the disease develops. The sequence of events or physiologic processes that result in disease.

What is disease? One definition is: An interruption, cessation, or disorder of body functions, systems, or organs. Another is the pattern of response of a living organism to some form of injury with a resultant alteration in normal function.

For a long list of diseases and information about them go to the disease list at CDC.

Injury. Damage or harm caused to the structure or function of the body.

Infection. A detrimental colonization of a host organism by a foreign species.

Angiogenesis. The process of blood vessel formation.

Apoptosis. Programmed cell death. Usually a normal biological function.

Atherosclerosis. A disease of arteries characterized by chronic inflammation, scarring and cholesterol deposits in large and medium-sized arteries.

Atrophy. A shrinkage in the size of cells, organs and tissues.

Dysplasia. An abnormal development of a body tissue.

Embolism. Obstruction of a blood vessel by an abnormal mass formed elsewhere in the circulation and transported to its point of impaction.

Fibrosis. The formation of fibrous tissuek, usually as a reaction to chronic inflammation.

Gangrene. Combination of tissue necrosis with infection.

Homeostasis. The maintenance of a steady state in respect of physiologic function in the face of environmental variation.

Hyperplasia. An increase in the number of cells in a given population.

Hypertrophy. An increase in the size of individual cells usually due to increase workload.

Hypoxia. A reduction in the supply of oxygen.

Impaction. The lodgement of some abnormal mass in a hollow muscular tube causing blockage of the lumen.

Infarct. An area of tissue necrosis caused by a lack of blood supply to the affected region.

Ischemia. The pathophysiologic state in which the blood supply of an organ or tissue is reduced below its metabolic needs.

Metaplasia. A change in a cell population from one fully differentiated form to another fully differentiated form.

Necrosis. The death of a tissue within a circumscribed area.

Thrombosis. The formation of an abnormal intravascular mass from the constituents of flowing blood.

Thrombus. An abnomal intravascular mass formed from the constituents of flowing blood.

A Short History of Pathology

2008-01-22T19:31:00.000-05:00

Cornelius Celsus (30 BC - 38 AD) describes clinical features of inflammation. Calor, rubor, dolor, tumor.

Galen (131 - 201 AD) a physician to the Roman gladiators. He didn't dissect human cadavors but Galen's great powers of observation allowed him to study, classify, and record anatomic and pathologic observations. Some of his observations, like the crab-like growth of cancers, were correct.

Leonardo da Vinci (1452 -1519) was one of the first to dissect humans in the quest for answers about the human form.

Andreas Vesalius (1514 - 1564) dissected humans and published a book De Humani Corporis Fabrica, 1543. His drawings of the human skeleton are especially noted for their detail and artestry.

More images and pages of his book can be seen here.

Antonio Benivieni (1443 - 1502) is credited for performing the first autopsies on humans to determine the cause of death. Not much is known about Benivieni's life.

Anatomy as a subject of study became acceptible in the 17th century.

Marie-Francois-Xavier Bichat (1771 - 1802), a French physcian was one of the first 'modern' pathologists and is considered by many to be the father of histology and pathology.

John Hunter (1728 - 1793), an Englishman who devised a method for preserving diseased tissues so they could be studied in the future.

Carl Rokitansky (1804 – 1878) is said to have performed over 20,000 autopsies and oversaw the performance of 60,000 more. He made important observations concerning multiple sclerosis.

Rudolf Virchow (1821 - 1905), used the microscope to learn that diseases arise from alterations within tissues and cells.

Julius Cohnheim (1839–1884), Virchow's student, devised experiments to study inflammation as it happened rather than after the tissue was dead. The Father of Experimental Pathology.

Some information about these pathologists was obtained here.

How to Use PubMed

2008-01-18T19:46:00.001-05:00

First go HERE to the PubMed website.

In the empty "search box" at the top, middle of the page, type your search term.

For example, type cellular injury. Then hit enter or click on "go".

You will see that there are 105635 articles that refer to cellular injury. Of these 105635 articles, 15099 are review articles (these numbers change as new articles are added to the database).

Clicking on article #2 will bring up the title, authors, abstract and tell you which journal published the article. To the left of the abstract, you will see links to a series of related journal articles.

Go to the top of the page and click on the History tab. On this page you will see #1 Search cellular injury. To the far left you will see the number of journal articles.

Now type ischemic in the empty search box at the top of the page and click on "go".

You see that there are 114951 articles referring to the term "ischemic". [Note: this number can change daily with the addition of new journal articles into the library.]

Click on the History tab again.

Now you see a list of both your search terms - cellular injury and ischemic.

Type this exactly in the empty search box: #1 AND #3 ("AND must be captalized), then click on "go".

Now you see that there are 8856 journal articles that contain both terms. If you had typed #1 OR #3 you would have obtained 211730 articles that contain one term or the other. If you had typed #1 NOT #3, you would have obtained 96779 articles containing the term "cellular injury" but not containing the term ischemic

Go to the upper left hand part of the page where the 'tabs' are located and click on "Limits".

This page allows you to greatly refine your search of cellular injury AND/OR/NOT ischemic. Let's say you only want to see articles printed in english. Under "Language" click the box marked english.

Let's say you only want to see articles referencing female humans. Just click on the "Human" and "Female" boxes. Click the box that says "links to free full text" to find the entire article for free.

Go to the bottom of the page and click on "Go". Up pops the 1216 articles in english about "cellular injury" but without the word "ischemia" specifically concerning "human" "females".

Click on article #1 and the abstract pops up. Notice that on the right hand side of the page containing the abstract, there is a box that says Journal of Invasive Cardiology. If you click on that box the entire article will pop up. More often there will be a free text box in that location and you can download a pdf file of the article.

If you start a search with new terms, remember to unclick the 'Limits' box or you will only get articles in english that reference humans and females.

There are many, many other databases (accessible on the library computers) and search engines (Google) that can be used to find information. But how do you know which information or articles to trust?

Here are a few general rules:

Expertise: Most of the papers you find in PubMed have been written by experts and then peer reviewed by experts. Websites that end in .gov, .org, .edu are surely more likely to provide valid information than what you find in many .com websites. Resources like Quackwatch are useful in determining the value of many medical information websites.

Experience: People tend to trust the advice of "experienced" individuals. This is because they are expected to have accumulated knowledge over time. One has to be careful here because in rapidly changing situations (like science), you need to be sure the "experienced" person has kept up with the changes and new discoveries.

Verifiability: Claims of medicine and science need to be verified or scientifically repeatible. That is why we can typically be assured that FDA approved drugs will do what the drug company claims they will do. Remember Ronald Reagans advice to trust, but verify.

Disinterest: A car salesman tells you that the car that he is about to sell you is the best in the world and will be trouble free for 15 yrs. Maybe it will, but do you believe the car salesman? No, because he is about to make money upon selling you the car. That is why most journals require full disclosure of whether scientists are funded by companies that have an interest in the publication.

A simple Google search is also well worth doing. A Google search will bring up the names of many government and non-government websites that contain a lot of useful information. The advantage of these sites are that they present information in layman terms.