Scientists film HIV spreading for first time

Scientists have made a breakthrough in understanding how HIV spreads through the human body after filming the process for the first time ever.
Researchers found that the virus is transferred from infected cells to healthy ones in a previously unknown way.
It is hoped that the discovery will help researchers create a vaccine to combat the virus, which has led to the deaths of more than 25 million people.




Video Refered by Eddie Salinas

The study was made possible after experts created a molecular clone of infectious HIV and inserted a protein into its genetic code which glows green when exposed to blue light.

This allowed scientists to see the cells on digital video, and capture the way HIV-infected T-cells interact with uninfected ones.

They noted that when an infected cell came into contact with a healthy one, a bridge was created between them, called a virological synapse.

Researchers were then able to observe the fluorescent green viral particles moving towards the synapse and into the healthy cell.

The US study has broken new ground by revealing that it is the synapse through which the viral proteins are gathered and moved into uninfected cells.

The team, comprising scientists from UC Davis university in California, and Mount Sinai School of Medicine in New York, believe that this knowledge could help create new treatments for HIV and Aids.

Study author Dr Thomas Huser, chief scientist at the UC Davis Center for Biophotonics Science and Technology, said: "Our findings may explain why attempts to develop an HIV vaccine have so far been unsuccessful.

"The more we know about this mode of transfer, the better chance we have of figuring out how to block it and the spread of HIV and Aids."

For decades it was believed that HIV was mostly spread around the body through freely circulating particles, which attach themselves to a cell, take over its replication machinery and make multiple copies of themselves.

In 2004, scientists discovered that cell-to-cell transfer of HIV also occurred via virological synapses, but it was not understood why the process was so effective in spreading the virus.

Due to this, previous efforts to create an HIV vaccine have focused on priming the immune system to recognise and attack proteins of free-circulating virus.

The new video footage indicates that HIV avoids recognition by being directly transferred between cells.

Dr Huser said: "We should be developing vaccines that help the immune system recognise proteins involved in virological synapse formation and antiviral drugs that target the factors required for synapse formation."

Co-author Benjamin Chen, assistant professor of medicine and infectious diseases at the Mount Sinai School of Medicine, added: "Direct T-cell-to-T-cell transfer through a virological synapse is a highly efficient avenue of HIV infection, and it could be the predominant mode of dissemination."

Further research intends to discover what happens to viral particles once they are transferred into a newly infected cell.

The study's finding are published in the journal Science.

Engineering New Approaches to Cancer Detection and Therapy

With his 500-plus patents, Robert Langer, Jr. surely has dibs on the title of MIT’s Mr. Wizard. This talk, which concludes the series on cancer research, deals with Langer’s efforts to design materials for safer and more effective cancer treatment.

Langer describes his groundbreaking work of 30 years ago to inhibit angiogenesis, the growth of blood vessels on which tumors depend. He came up with a way of packaging proteins inside plastic polymers, essentially microspheres of drugs, which could be injected directly into a target site. These tiny beads released an angiogenic inhibitor in a slow and steady way, starving the tumor of nutrients. He notes dryly that it took the FDA 28 years from the time these results were published to approve the first implantable angiogenic inhibitors. Today, this approach is heartily embraced, says Langer, because it “gives you a whole new other avenue of attack” against tumors.

Because many large proteins are effective at combating cancers but can’t be swallowed, taken nasally, injected directly, or put in a patch, they now end up in Langer’s microspheres. One hormone-releasing microsphere attacks advanced prostate cancer. This drug delivery system has even spread to treatments for schizophrenia and alcoholism.


Langer’s recent forays in the lab have yielded dime-sized, gold-covered, degradable microchips conveying multiple, small quantities of a drug. In response to a one-volt zap (“via telemetry like a garage door opener”), these devices release just the right dose. Chips might someday also carry imaging agents. Says Langer, “The beauty of the chip is that information could be transmitted from the body to a computer, your house, doctor’s office, or hospital, so you could have a record of whatever happened.”

In the surgical arena, Langer’s come up with a “shape memory” polymer that can phase from a string at room temperature, to a coil at body temperature -- acting as a self-tying suture in hard-to-reach places.

Langer is now moving into even smaller domains, experimenting with nano-sized drugs for use in the blood stream. Coated with a polymer to prevent attack from the body’s immune system, these nanoparticles show promise in shrinking tumors.

Langer cites his career-long commitment to devise materials for medical treatment that are biologically and chemically compatible with the human body. (Dialysis tubing was based on sausage casing, and the artificial heart from ladies’ girdle material.) His polymers often faced opposition from the research establishment. “When you’re at a place like MIT, you often do speculative work, and when you do speculative work, you’re not always greeted that well in the scientific community,” he says.



About the Speaker
Robert S. Langer Jr. SCD '74
Institute Professor and Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering
2002 Draper Prize Award Recipient

Robert Langer has more than 500 issued or pending patents worldwide. In 2005, Langer received the $500,000 Albany Medical Center Prize in Medicine and Biomedical Research, America's top prize in medicine. In 2002, he received the Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers, from the National Academy of Engineering. Among numerous other awards Langer has received are the Heinz Award for Technology, Economy and Employment (2003), the John Fritz Award (2003) (given previously to inventors such as Thomas Edison and Orville Wright) and the General Motors Kettering Award for Cancer Research (2004). Langer is one of very few people ever elected to all three U.S. National Academies and the youngest in history (age 43) ever to receive this distinction.

He received his Bachelor’s Degree from Cornell University in 1970 and his Sc.D. from the Massachusetts Institute of Technology in 1974, both in Chemical Engineering.

Bacterial Flagellum

The bacterial flagellum is made up of the protein flagellin. Its shape is a 20 nanometer-thick hollow tube. It is helical and has a sharp bend just outside the outer membrane; this "hook" allows the helix to point directly away from the cell. A shaft runs between the hook and the basal body, passing through protein rings in the cell's membrane that act as bearings. Gram-positive organisms have 2 of these basal body rings, one in the peptidoglycan layer and one in the plasma membrane. Gram-negative organisms have 4 such rings: the L ring associates with the lipopolysaccharides, the P ring associates with peptidoglycan layer, the M ring is embedded in the plasma membrane, and the S ring is directly attached to the plasma membrane. The filament ends with a capping protein.



The bacterial flagellum is driven by a rotary engine made up of protein (Mot complex), located at the flagellum's anchor point on the inner cell membrane. The engine is powered by proton motive force, i.e., by the flow of protons (hydrogen ions) across the bacterial cell membrane due to a concentration gradient set up by the cell's metabolism (in Vibrio species there are two kinds of flagella, lateral and polar, and some are driven by a sodium ion pump rather than a proton pump). The rotor transports protons across the membrane, and is turned in the process. The rotor alone can operate at 6,000 to 17,000 rpm, but with the flagellar filament attached usually only reaches 200 to 1000 rpm.

Flagella do not rotate at a constant speed but instead can increase or decrease their rotational speed in relation to the strength of the proton motive force. Flagellar rotation can move bacteria through liquid media at speeds of up to 60 cell lengths/second (sec). Although this is only about 0.00017 km/h (0.00011 mph), when comparing this speed with that of higher organisms in terms of number of lengths moved per second, it is extremely fast. By comparison, the cheetah, the fastest land animal, can sprint at 110 km/h (68 mph), which is approximately 25 body lengths/sec.[18]

The components of the bacterial flagellum are capable of self-assembly without the aid of enzymes or other factors. Both the basal body and the filament have a hollow core, through which the component proteins of the flagellum are able to move into their respective positions. During assembly, protein components are added at the flagellar tip rather than at the base.
The basal body has several traits in common with some types of secretory pores, such as the hollow rod-like "plug" in their centers extending out through the plasma membrane. Given the structural similarities between bacterial flagella and bacterial secretory systems, it is thought that bacterial flagella may have evolved from the type three secretory system; however, it is not known for certain whether these pores are derived from the bacterial flagella or the bacterial secretory system

Inflammation in Alzheimer's Disease

Cynthia A. Lemere, Ph.D. Associate Professor of Neurology at Harvard Medical School and an Associate Neuroscientist at Brigham & Women’s Hospital in the Center for Neurologic Diseases (CND). She has been an active participant in the research field of Alzheimer's disease (AD) for more than sixteen years. Dr. Lemere received her B.A. from Mount Holyoke College, her M.S. in Neurobiology from State University of New York at Albany, and her Ph.D. in Pathology from Boston University School of Medicine. Her thesis research, conducted in the laboratory of Dr. Dennis Selkoe at the CND, focused on mechanisms of ß-amyloid generation and deposition in Alzheimer’s disease and models thereof, particularly in Down syndrome. During her years as Postdoctoral Fellow and Instructor at the CND, her research focused on the role of inflammation in Alzheimer’s disease. In particular, these studies involved examining brain tissue from APP transgenic mice, a transgenic or genetically-engineered mouse model of AD, and Down syndrome to examine the temporal accrual of amyloid-associated inflammatory proteins, such as complement protein, in relation to Aß deposition, gliosis and neuritic changes. In addition, she collaborated with scientists in Medellin, Colombia, to confirm in vivo that which was already known in vitro, that mutations in the presenilin 1 gene lead to overproduction of Aß42.


Cynthia Lemere of Harvard Medical School shares her findings on the link between inflammation and Alzheimer's disease.
About Speaker:

In 1997, she founded an independent laboratory at the CND and continued her research on the role of inflammation in AD by examining strategies for reducing amyloid ß-protein (Aß) protein, cerebral deposits of which are a key feature of AD, and its resultant inflammation in the AD brain. Her results showed that chronic nasal immunization with Aß peptide in APP transgenic mice led to anti-Aß antibody production and a lowering of the Aß burden in the brain. Dr. Lemere and her colleagues have optimized various treatment protocols in non-transgenic mice and then employed them to lower cerebral Aß levels in APP transgenic mice. In addition to pursuing the mechanism of these effects, much of her laboratory's work focuses on the humoral and cellular immune responses to Aß immunization in APP tg mice and in non-human primates. Recently, her lab completed a 10 month Aß immunization trial in Caribbean vervet monkeys and found a lowering of Aß protein in both CSF and brain.

Other projects in her laboratory have involved examining the temporal appearance of both intraneuronal Aß and P25 (the regulatory subunit for cdk5) in Down syndrome brain, characterization of a-synuclein following traumatic brain injury and characterization of sonic hedgehog in aged human control and AD brain.

Congestive Heart Failure

Congestive heart failure, is a life-threatening condition in which the heart can no longer pump enough blood to the rest of the body.
Causes
Heart failure is almost always a chronic, long-term condition, although it can sometimes develop suddenly. This condition may affect the right side, the left side, or both sides of the heart.



As the heart's pumping action is lost, blood may back up into other areas of the body, including the:

  • Gastrointestinal tract, arms, and legs (right-sided heart failure)
  • Liver
  • Lungs (left-sided heart failure)
Heart failure results in a lack of oxygen and nutrition to organs, which damages them and reduces their ability to function properly. Most areas of the body can be affected when both sides of the heart fail.

The most common causes of heart failure are:

  • Coronary artery disease
  • High blood pressure
Other structural or functional causes of heart failure include:

  • Cardiomyopathy
  • Dilated cardiomyopathy
  • Hypertropic cardiomyopathy
  • Restrictive cardiomyopathy
  • Congenital heart disease
  • Heart valve disease
  • Heart tumor
  • Lung disease
Heart failure becomes more common with advancing age. You are also at increased risk for developing heart failure if you are overweight, have diabetes, smoke cigarettes, abuse alcohol, or use cocaine.

Symptoms
  • Cough
  • Decreased alertness or concentration
  • Decreased urine production
  • Difficulty sleeping
  • Fatigue, weakness, faintness
  • Irregular or rapid pulse
  • Loss of appetite, indigestion
  • Nausea and vomiting
  • Neck veins that stick out
  • Need to urinate at night
  • Sensation of feeling the heart beat (palpitations)
  • Shortness of breath with activity, or after lying down for a while
  • Swelling of the abdomen
  • Swelling of feet and ankles
  • Weight gain

Pharmacology: Intra Venous Absorption

Intravenous medication is given in the way catheter inserted in the veins. IV catheter is placed in peripheral or central circulation. The medications are eluded in IV carrier fluid mixes with venous blood and is carried along the route of the blood vein, A medication administered in the bronchial vein is carried to the right side of heart, from there it is pumped toward lung and back to left side of heart, From the left side it pumped through the aorta and into the arterial tree of the body to the upper and lower parts of the body and then to the tissues.

Auditory Pathways

This sound information, now re-encoded, travels down the vestibulocochlear nerve, through intermediate stations such as the cochlear nuclei and superior olivary complex of the brainstem and the inferior colliculus of the midbrain, being further processed at each waypoint. The information eventually reaches the thalamus, and from there it is relayed to the cortex. In the human brain, the primary auditory cortex is located in the temporal lobe.


Cochlear nucleus
The cochlear nucleus is the first site of the neuronal processing of the newly converted “digital” data from the inner ear. This region is anatomically and physiologically split into two regions, the dorsal cochlear nucleus (DCN), and ventral cochlear nucleus (VCN).

Associated anatomical structures include:


Trapezoid body
The Trapezoid body is a bundle of decussating fibers in the ventral pons that carry information used for binaural computations in the brainstem.

Superior olivary complex

The superior olivary complex is located in the pons, and receives projections predominantly from the ventral cochlear nucleus, although the posterior cochlear nucleus projects there as well, via the ventral acoustic stria. Within the superior olivary complex lies the lateral superior olive (LSO) and the medial superior olive (MSO). The former is important in detecting interaural level differences while the latter is important in distinguishing interaural time difference.
Lateral lemniscus in red, as it connects the cochlear nucleus, superior olivary nucleus and the inferior colliculus. Seen from behind.

Lateral lemniscus
The lateral lemniscus is a tract of axons in the brainstem that carries information about sound from the cochlear nucleus to various brainstem nuclei and ultimately the contralateral inferior colliculus of the midbrain.

Inferior colliculi
The IC are located just below the visual processing centers known as the superior colliculi. The central nucleus of the IC is a nearly obligatory relay in the ascending auditory system, and most likely acts to integrate information (specifically regarding sound source localization from the superior olivary complex and dorsal cochlear nucleus) before sending it to the thalamus and cortex.

Medial geniculate nucleus


The medial geniculate nucleus is part of the thalamic relay system.

Primary auditory cortex
The primary auditory cortex is the first region of cerebral cortex to receive auditory input.

Perception of sound is associated with the right posterior superior temporal gyrus (STG). The superior temporal gyrus contains several important structures of the brain, including Brodmann areas 41 and 42, marking the location of the primary auditory cortex, the cortical region responsible for the sensation of basic characteristics of sound such as pitch and rhythm.

The auditory association area is located within the temporal lobe of the brain, in an area called the Wernicke's area, or area 22. This area, near the lateral cerebral sulcus, is an important region for the processing of acoustic signals so that they can be distinguished as speech, music, or noise.

Magnetic resonance Imaging

Magnetic resonance imaging (MRI), or nuclear magnetic resonance imaging (NMRI), is primarily a medical imaging technique most commonly used in radiology to visualize the internal structure and function of the body. MRI provides much greater contrast between the different soft tissues of the body than computed tomography (CT) does, making it especially useful in neurological (brain), musculoskeletal, cardiovascular, and oncological (cancer) imaging. Unlike CT, it uses no ionizing radiation, but uses a powerful magnetic field to align the nuclear magnetization of (usually) hydrogen atoms in water in the body. Radiofrequency fields are used to systematically alter the alignment of this magnetization, causing the hydrogen nuclei to produce a rotating magnetic field detectable by the scanner. This signal can be manipulated by additional magnetic fields to build up enough information to construct an image of the body.

How MRI works

The body is mainly composed of water molecules which each contain two hydrogen nuclei or protons. When a person goes inside the powerful magnetic field of the scanner these protons align with the direction of the field.

A second radiofrequency electromagnetic field is then briefly turned on causing the protons to absorb some of its energy. When this field is turned off the protons release this energy at a radiofrequency which can be detected by the scanner. The position of protons in the body can be determined by applying additional magnetic fields during the scan which allows an image of the body to be built up. These are created by turning gradients coils on and off which creates the knocking sounds heard during an MR scan.

Diseased tissue, such as tumors, can be detected because the protons in different tissues return to their equilibrium state at different rates. By changing the parameters on the scanner this effect is used to create contrast between different types of body tissue.

Contrast agents may be injected intravenously to enhance the appearance of blood vessels, tumors or inflammation. Contrast agents may also be directly injected into a joint, in the case of arthrograms, MR images of joints. Unlike CT scanning MRI uses no ionizing radiation and is generally a very safe procedure. Patients with some metal implants, cochlear implants, and cardiac pacemakers are prevented from having an MRI scan due to effects of the strong magnetic field and powerful radiofrequency pulses.

MRI is used to image every part of the body, and is particularly useful in neurological conditions, disorders of the muscles and joints, for evaluating tumors and showing abnormalities in the heart and blood vessels.

Nerve Physiology - sciatic nerve and gastrocnemius

The sciatic nerve (also known as the ischiatic nerve) is a large nerve that starts in the lower back and runs through the buttock and down the lower limb. It is the longest and widest single nerve in the body.

The sciatic supplies nearly the whole of the skin of the leg, the muscles of the back of the thigh, and those of the leg and foot.The nerve enters the lower limb by exiting the pelvis through the greater sciatic foramen, below the Piriformis muscle and above the superior gemellus muscle.



It descends midway between the greater trochanter of the femur and the tuberosity of the ischium, and along the back of the thigh to about its lower third, where it divides into two large branches, the tibial and common peroneal nerves. This division may take place at any point between the sacral plexus and the lower third of the thigh. When it occurs at the plexus, the common peroneal nerve usually pierces the Piriformis muscles.
Gastrocnemius muscle
Gastrocnemius muscle is a very powerful superficial muscle that is in the back part of the lower leg and also called the calf. It runs from its two heads just above the knee to the heel, and is involved in standing, walking, running and jumping. Along with the soleus muscle it forms the calf muscle.

BRAIN INJURY


Birth Stations of Presentation

This 3D medical animation shows the birth stations of presentation using the -5 to +5 positions. From an anterior (front) view, the baby is shown within the mother's pelvis, descending from -3 vertex station point by point to the +5 station.Stations of Presentation



Stations of Presentation (Third System)

Laparoscopic fundoplication video

Fundoplication is a surgical procedure to treat gastroesophageal reflux disease (GERD) and hiatus hernia. In GERD it is usually performed when medical therapy has failed, but with paraesophageal hiatus hernia, it is the first-line procedure. Partial fundoplications known as a Dor fundoplication or Toupet fundoplication may accompany surgery for achalasia.Fundoplication, the gastric fundus (upper part) of the stomach is wrapped, or plicated, around the inferior part of the esophagus and stitched in place, reinforcing the closing function of the lower esophageal sphincter: Whenever the stomach contracts, it also closes off the esophagus instead of squeezing stomach acids into it. This prevents the reflux of gastric acid (in GERD). A fundoplication can also prevent hiatal hernia, in which the fundus slides up through the enlarged esophageal hiatus of the diaphragm.

Shoulder Dystocia

Shoulder dystocia is a specific case of dystocia whereby after the delivery of the head, the anterior shoulder of the infant cannot pass below the pubic symphysis, or requires significant manipulation to pass below the pubic symphysis. It is diagnosed when the shoulders fail to deliver shortly after the fetal head. In shoulder dystocia, it is the chin that presses against the walls of the perineum.

Retinal Detachments

The retina is the light-sensitive layer of tissue that lines the inside of the eye and sends visual messages through the optic nerve to the brain. When the retina detaches, it is lifted or pulled from its normal position. If not promptly treated, retinal detachment can cause permanent vision loss.

In some cases there may be small areas of the retina that are torn. These areas, called retinal tears or retinal breaks, can lead to retinal detachment.


What are the symptoms of retinal detachment?
Symptoms include a sudden or gradual increase in either the number of floaters, which are little "cobwebs" or specks that float about in your field of vision, and/or light flashes in the eye. Another symptom is the appearance of a curtain over the field of vision. A retinal detachment is a medical emergency. Anyone experiencing the symptoms of a retinal detachment should see an eye care professional immediately.


What are the different types of retinal detachment?
There are three different types of retinal detachment:


Rhegmatogenous-- A tear or break in the retina allows fluid to get under the retina and separate it from the retinal pigment epithelium (RPE), the pigmented cell layer that nourishes the retina. These types of retinal detachments are the most common.


Tractional -- In this type of detachment, scar tissue on the retina's surface contracts and causes the retina to separate from the RPE. This type of detachment is less common.


Exudative -- Frequently caused by retinal diseases, including inflammatory disorders and injury/trauma to the eye. In this type, fluid leaks into the area underneath the retina, but there are no tears or breaks in the retina.


Who is at risk for retinal detachment?
A retinal detachment can occur at any age, but it is more common in people over age 40. It affects men more than women, and Whites more than African Americans.

A retinal detachment is also more likely to occur in people who:

  • Are extremely nearsighted
  • Have had a retinal detachment in the other eye
  • Have a family history of retinal detachment
  • Have had cataract surgery
  • Have other eye diseases or disorders, such as retinoschisis, uveitis, degenerative myopia, or lattice degeneration
  • Have had an eye injury

How is retinal detachment treated?
Small holes and tears are treated with laser surgery or a freeze treatment called cryopexy. These procedures are usually performed in the doctor's office. During laser surgery tiny burns are made around the hole to "weld" the retina back into place. Cryopexy freezes the area around the hole and helps reattach the retina.

Retinal detachments are treated with surgery that may require the patient to stay in the hospital. In some cases a scleral buckle, a tiny synthetic band, is attached to the outside of the eyeball to gently push the wall of the eye against the detached retina. If necessary, a vitrectomy may also be performed. During a vitrectomy, the doctor makes a tiny incision in the sclera (white of the eye). Next, a small instrument is placed into the eye to remove the vitreous, a gel-like substance that fills the center of the eye and helps the eye maintain a round shape. Gas is often injected to into the eye to replace the vitreous and reattach the retina; the gas pushes the retina back against the wall of the eye. During the healing process, the eye makes fluid that gradually replaces the gas and fills the eye. With all of these procedures, either laser or cryopexy is used to "weld" the retina back in place.

With modern therapy, over 90 percent of those with a retinal detachment can be successfully treated, although sometimes a second treatment is needed. However, the visual outcome is not always predictable. The final visual result may not be known for up to several months following surgery. Even under the best of circumstances, and even after multiple attempts at repair, treatment sometimes fails and vision may eventually be lost. Visual results are best if the retinal detachment is repaired before the macula (the center region of the retina responsible for fine, detailed vision) detaches. That is why it is important to contact an eye care professional immediately if you see a sudden or gradual increase in the number of floaters and/or light flashes, or a dark curtain over the field of vision.

Immunotherapy for Brain Tumors

Immunotherapy, refers to an array of treatment strategies based upon the concept of modulating the immune system to achieve a prophylactic and/or therapeutic goal.
Dr. Linda M. Liau is a neurosurgeon and Professor of Neurosurgery at the UCLA School of Medicine. She is Director of the Comprehensive Brain Tumor Program and Director of Neurosurgical Oncology at the UCLA Medical Center in Los Angeles. Dr. Liau received her B.S. degree in Biochemistry and B.A. degree in Political Science, both with honors, from Brown University in Providence, Rhode Island in 1987. She then received her M.D. degree from Stanford University in Palo Alto, California in 1991, and a Ph.D. degree in Molecular Neuroscience from UCLA in Los Angeles, California in 1999.


After completing her residency and fellowship training in neurosurgery at UCLA, she joined the faculty at the UCLA School of Medicine as an Assistant Professor of Neurosurgery in 1998. She was granted tenure at UCLA in 2003 and was promoted to Associate Professor of Neurosurgery. She is currently a board-certified neurosurgeon with both an active research laboratory and a busy clinical practice in the field of brain tumors and neurosurgical oncology. She is a member of the Executive Committee of the Congress of Neurological Surgeons and the Tumor Section of the American Association of Neurological Surgeons. She currently serves as a member of the NIH Clinical Neuroimmunolgoy and Brain Tumor (CNBT) study section, is on the Scientific Advisory Board of the Goldhirsh Foundation and the General Advisory Committee of the National Brain Tumor Foundation. She is currently Chairman of the Fellowship Awards committee of the Congress of Neurological Surgeons. Dr. Liau serves as Principal Investigator on two NIH R01 grants, and is the mentor for several NIH training grants (K01, K12, T32) for postdoctoral fellows in her laboratory. Her research interests include translational experimental therapeutics of cell-based therapies for brain tumors and characterization of molecular targets involved in brain tumor pathogenesis and progression. She has published dozens of peer-reviewed research articles, along with several book chapters and a textbook entitled Brain Tumor Immunotherapy (Humana Press, 2001). She is Editor-in-Chief of the Journal of Neuro-Oncology and is on the editorial boards of Neurosurgery, Surgical Neurology, and Neuro-Oncology.

Genetics and the Effect of Aging on Stem Cell Regulation

Genetics research is key to understanding the effects of aging and age-related diseases. How do stem cells change as we grow older, and can they be regulated to decrease cancer risk?

Mitotic spindle peptidase

Spindle apparatus (also called spindle fibers) is the structure that separates the chromosomes into the daughter cells during cell division. It is part of the cytoskeleton in eukaryotic cells. Depending on the type of cell division, it is also referred to as the mitotic spindle during mitosis.

The cellular spindle apparatus includes the spindle microtubules, associated proteins, and any centrosomes or asters present at the spindle poles. spindle apparatus is vaguely ellipsoid in shape and tapers at the ends but spreads out in the middle. In the wide middle portion, known as the spindle midzone, antiparallel microtubules are bundled by kinesins. At the pointed ends, known as spindle poles, microtubules are nucleated by the centrosomes in most animal cells. Acentrosomal or anastral spindles lack centrosomes or asters at the spindle poles, respectively, and occur for example during gametogenesis in animals.[2] In fungi, spindles form between spindle pole bodies embedded in the nuclear envelope. Most plants lack centrosomes or spindle pole bodies and instead spindle microtubules are nucleated on their nuclear envelopes.[3] Take chromosomes through most stages of mitosis. Start to form in early metaphase. Connected to the centrioles at each end of the cell.





Mitotic spindle assembly checkpoint

The completion of spindle formation is a crucial transition point in the cell cycle called the spindle assembly checkpoint. If some chromosomes are not properly attached to the mitotic spindle by the time of this checkpoint, the onset of anaphase will be delayed.[6] Failure of this spindle assembly checkpoint can result in aneuploidy and may be involved in aging and the formation of cancer.

Prostate Radiation Therapy

The prostate is the gland below a man's bladder that produces fluid for semen. Prostate cancer is the third most common cause of death from cancer in men of all ages. It is rare in men younger than 40.

Levels of a substance called prostate specific antigen (PSA) is often high in men with prostate cancer. However, PSA can also be high with other or prostate conditions. Since the PSA test became common, most prostate cancers are found before they cause symptoms. Symptoms of prostate cancer may include





Problems passing urine, such as pain, difficulty starting or stopping the stream, or dribbling
Low back pain
Pain with ejaculation
Prostate cancer treatment often depends on the stage of the cancer. How fast the cancer grows and how different it is from surrounding tissue helps determine the stage. Treatment may include surgery, radiation therapy, chemotherapy or control of hormones that affect the cancer

Macrophages Phagocytosis

Macrophage phagocytosis of micro-organisms is important in host immunity and activated macrophages kill ingested pathogens by production of reactive oxygen and nitrogen metabolites. Medically important pathogens including the mycobacteria which cause tuberculosis and leprosy evade immune destruction by surviving inside the macrophage. Survival of pathogens in macrophages is central to the pathogenesis and tissue injury in these important human diseases.

Overactive bladder

What is Overactive Bladder?
Overactive bladder (OAB) is a condition characterized by a sudden, uncomfortable need to urinate with or without urine leakage usually with daytime and nighttime frequency.
OAB occurs when smooth muscle of the detrusor muscle of the bladder squeezes or contracts more often than normal and at inappropriate times. Instead of staying at rest as urine fills the bladder, the detrusor contracts while the bladder is filling with urine.



Treatment for OAB includes lifestyle modification (fluid restriction, avoidance of caffeine), bladder retraining, antimuscarinic drugs (darifenacin, hyoscyamine, oxybutynin, tolterodine, solifenacin, trospium), and various devices (Urgent PC Neuromodulation System, InterStim). Intravesical botulinum toxin A is also used in some intractable cases, although not with formal FDA approval. The antimuscarinic fesoterodine was recommended for approval by the European Medicines Agency in February 2007, and will become available for use during 2008.

From Conception to Birth

Computational Challenges in the Era of Personal Genomics: A subjective View



A discussion of some of the computational problems in haplotype analysis and association mapping, as well as our own progress in addressing these problems and related possible future directions.

Neutrophil Chemotaxis Chasing a Bacterium

Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of white blood cells in humans and form an essential part of the immune system. They form part of the polymorphonuclear cell family (PMN's) together with basophils and eosinophils.
Neutrophils are normally found in the blood stream. However, during the beginning (acute) phase of inflammation, particularly as a result of bacterial infection and some cancers, neutrophils are one of the first group of inflammatory cells to migrate toward the site of inflammation, firstly through the blood vessels, then through interstitial tissue, following chemical signals (such as Interleukin-8 (IL-8), Interferon-gamma (IFN-gamma), and C5a) in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.






Neutrophils react within an hour of tissue injury and are the hallmark of acute inflammation.

Proteolytic Enzymes

Proteolytic Enzymes are a group of enzymes that break the long chainlike molecules of proteins into shorter fragments (peptides) and eventually into their components, amino acids
Proteolytic enzymes are present in bacteria and plants but are most abundant in animals. In the stomach, protein materials are attacked initially by the gastric enzyme pepsin. When the protein material is passed to the small intestine, proteins, which are only partially digested in the stomach, are further attacked by proteolytic enzymes secreted by the pancreas.

Computational Neuroimaging

Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain. It is a relatively new discipline within medicine and neuroscience/psychology.


Alzheimer's Disease

Bruce Reed, the Associate Director of the Alzheimer's Disease Research Center at UC Davis presents a comprehensive update on Alzhemier's Disease. What is Alzhemier's Disease and can it be cured or treated? Can one predict who will ultimately be afflicted by this disease? What is the current research being done on Alzheimier's Disease

Inside the Heart

Cataract Surgery

Dropped nucleus

Dropped nucleus - defined as loss of a part or the whole lens nucleus to the vitreous cavity -is an unusual but well known complication during modern cataract phaco-technique surgery. Most cases need re-operation with pars plana vitrectomy (ppv) in order to avoid serious complications and damage to the eye due to secondary glaucoma, prolonged intraoccular inflammation or retinal detachment.


Phaco chop


Cesarean Section Delivery

A Caesarean section , also known as C-section or Caesar, is a surgical procedure in which incisions are made through a mother's abdomen (laparotomy) and uterus (hysterotomy) to deliver one or more babies.
Types
There are several types of Caesarean section (CS). The differences between them lie primarily in the deep incision made on the uterus, apart from the type of laparotomy used to access the uterus.





  •  The classical Caesarean section involves a midline longitudinal incision which allows a larger space to deliver the baby. However, it is rarely performed today as it is more prone to complications.
  •  The lower uterine segment section is the procedure most commonly used today; it involves a transverse cut just above the edge of the bladder and results in less blood loss and is easier to repair.
  •  An emergency Caesarean section is a Caesarean performed once labour has commenced.
  •  A crash Caesarean section is a Caesarean performed in an obstetric emergency, where complications of pregnancy onset suddenly during the process of labour, and swift action is required to prevent the deaths of mother, child(ren) or both.
  •  A Caesarean hysterectomy consists of a Caesarean section followed by the removal of the uterus. This may be done in cases of intractable bleeding or when the placenta cannot be separated from the uterus.
  •  Traditionally other forms of Caesarean section have been used, such as extraperitoneal Caesarean section or Porro Caesarean section.
  •  a repeat Caesarean section is done when a patient had a previous Caesarean section. Typically it is performed through the old scar.

In many hospitals, especially in Argentina, the United States, United Kingdom, Canada, Norway, Australia, and New Zealand the mother's birth partner is encouraged to attend the surgery to support the mother and share the experience. The anaesthetist will usually lower the drape temporarily as the child is delivered so the parents can see their newborn.

Haversian System

The osteon, or Haversian system, is the fundamental functional unit of compact bone. Osteons are present in many of the bones of most mammals, birds, reptiles, and amphibians.

Each osteon consists of concentric layers, or lamellae, of compact bone tissue that surround a central canal, the Haversian canal. The Haversian canal contains the bone's nerve and blood supplies. Osteoblasts form the lamellae sequentially, from the most external inward toward the Haversian canal. Some of the osteoblasts develop into osteocytes, each living within its own small space, or lacuna. Osteocytes make contact with the cytoplasmic processes of their counterparts via a network of small canals, or canaliculi. This network facilitates the exchange of nutrients and metabolic waste.


Collagen fibers in a particular lamella run parallel to each other but the orientation of collagen fibers within other lamellae is oblique. The collagen fiber density is lowest at the seams between lamellae, accounting for the distinctive microscopic appearance of a transverse section of osteons.

Osteons are separated from each other by interstitial lamellae between systems.

The space between osteons is occupied by interstitial lamellae, which are the remnants of osteons that were partially resorbed during the process of bone remodelling.

Osteons are connected to each other and the periosteum by oblique channels called Volkmann's canals.

Alzheimer's Disease Neuropathology

Clinical differentiation of neurodegenerative diseases that produce dementia is imprecise. Neuropathology offers the only way to make a definite diagnosis. The CNS autopsy is also important for clinical quality control and for providing tissue that furthers research into these disabling disorders. This brief article summarizes the major neuropathologic features of largely sporadic disorders that present with late-life dementia. The common causes of dementia discussed are Alzheimer's disease, Lewy body disease, and vascular dementia; less common disorders described are dementia lacking distinctive histopathology, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, and Creutzfeldt-Jakob disease.

Drug Studies

Almost every American takes a drug every day; many take three or more. This series presented by the UCSF Osher Lifelong Learning Institute explores your medicine, your health and your money. In this episode join John Flaherty, director of medical affairs at Gilead Science, Inc, as he explores the use of drug studies.

Pseudomonas infection

Pseudomonas is a genus of gamma proteobacteria, belonging to the larger family of pseudomonads.
Pseudomonas infection refers to a disease caused by one of the species of the genus Pseudomonas.

P. aeruginosa is an opportunistic human pathogen, most commonly affecting immunocompromised patients, such as those with cystic fibrosis or AIDS. Infection can affect many different parts of the body, but infections typically target the respiratory tract (e.g. patients with CF or those on mechanical ventilation), causing bacterial pneumonia. Treatment of such infections can be difficult due to multiple antibiotic resistance.


P. oryzihabitans can also be a human pathogen, although infections are rare. It can cause peritonitis, endophthalmitis, septicemia and bacteremia. Similar symptoms although also very rare can be seen by infections of P. luteola.

P. plecoglossicida is a fish pathogenic species, causing hemorrhagic ascites in the ayu (Plecoglossus altivelis). P. anguilliseptica is also a fish pathogen.

Due to their hemolytic activity, even non-pathogenic species of Pseudomonas can occasionally become a problem in clinical settings, where they have been known to infect blood transfusions.

Adult Stem Cell Results & Embryonic Stem Cell Ethics Video

Adult Stem Cell Results & Embryonic Stem Cell Ethics Video


Pharmacology: Drug binding

Most drugs act at cellular level by binding to receptor surface of cell membrane or inside cells, the cell membrane contains receptor for many kinds of substances such as hormones and neural transmittors. Some receptors also interact with drug molecules, as a drug molecule binds to the receptor it inhibits regular cellular functions; one type of reaction activates, deactivates or alters the intra cellular enzymes. Enzymes catalize almost all cellular functions, therefore drug-induced alterations can greatly increase or decrease rate of cellular metabolism.
Most drugs act at cellular level by binding to receptor surface of cell membrane or inside cells, the cell membrane contains receptor for many kinds of substances such as hormones and neural transmittors. Some receptors also interact with drug molecules, as a drug molecule binds to the receptor it inhibits regular cellular functions; one type of reaction activates, deactivates or alters the intra cellular enzymes. Enzymes catalize almost all cellular functions, therefore drug-induced alterations can greatly increase or decrease rate of cellular metabolism.

Histone Deacetylation

Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. Its action is opposite to that of histone acetyltransferase.
Subtypes
HDAC proteins are found in three groups, the first two groups belong to the classical HDACs and their activities are inhibited by trichostatin A (TSA) whereas the third group is a family of NAD+-dependent proteins not affected by TSA. Homologues to all three groups are found in yeast having the names reduced potassium dependency 3 (Rpd3) - corresponds to class 1, histone deacetylase 1 (hda1) – to class 2 and silent information regulator 2(Sir2) – class3.



Function

Histone tails are normally positively charged due to amine groups present on their lysine and arginine amino acids. These positive charges help the histone tails to interact with and bind to the negatively charged phosphate groups on the DNA backbone. Acetylation, which occurs normally in a cell, neutralizes the positive charges on the histone by changing amines into amides and decreases the ability of the histones to bind to DNA. This process allows chromatin expansion, allowing for genetic transcription to take place. Histone deacetylases remove those acetyl groups, increasing the positive charge of histone tails and encouraging high-affinity binding between the histones and DNA backbone. This process condenses DNA structure, preventing transcription.

Histone deacetylase is involved in a series of pathways within the living system. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), these are:

  • Environmental information processing; signal transduction; notch signaling pathway PATH:ko04330
  • Cellular processes; cell growth and death; cell cycle PATH:ko04110
  • Human diseases; cancers; chronic myeloid leukemia PATH:ko05220

Histone acetylation plays an important role in the regulation of gene expression. Hyperacetylated chromatin is transcriptionally active, and hypoacetylated chromatin is silent. A study on mice found that a specific subset of mouse genes (7%) was deregulated in the absence of HDAC1.[5] Their study also found a regulatory crosstalk between HDAC1 and HDAC2 and suggest a novel function for HDAC1 as a transcriptional coactivator. HDAC1 expression was found to be increased in the prefrontal cortex of schizophrenia subjects,negatively correlating with the expression of GAD67 mRNA.

It is a mistake to regard HDACs solely in the context of regulating gene transcription by modifying histones and chromatin structure, although that appears to be the predominant function. The function, activity, and stability of proteins can be controlled by post-translational_modifications. Protein phosphorylation is perhaps the most widely studied and understood modification in which certain amino acid residues are phosphorylated by the action of protein_kinases or dephosphorylated by the action of phosphatases. The acetylation of lysine residues is emerging as an analogus mechanism, in which non-histone proteins are acted on by acetylases and deacetylases . It is in this context that HDACs are being found to interact with a variety of non-histone proteins -- some of these are transcription factors and co-regulators, some are not. Note the following four examples:
  •  HDAC6 is associated with aggresomes. Misfolded protein aggregates are tagged by ubiquitination and removed from the cytoplasm by dynein motors via the microtubule network to an organelle termed the aggresome. HDAC 6 binds polyubiquitinated misfolded proteins and links to dynein motors, thereby allowing the misfolded protein cargo to be physically transported to chaperones and proteasomes for subsequent destruction.
  •  PTEN is an important phosphatase involved in cell signaling via phosphoinositols and the AKT/PI3 kinase pathway. PTEN is subject to complex regulatory control via phosphorylation, ubiquitination, oxidation and acetylation. Acetylation of PTEN by the histone acetyltransferase p300/CBP-associated factor (PCAF) can stimulate its activity; conversely, deacetylation of PTEN by SIRT1 deacetylase and apparently by HDAC1 can repress its activity.
  •  APE1/Ref-1 (APEX) is a multifunctional protein possessing both DNA repair activity (on abasic and single strand break sites) and transcriptional regulatory activity associated with oxidative stress. APE1/Ref-1 is acetylated by PCAF; conversely it is stably associated with and deacetylated by Class I HDACs. The acetylation state of APE1/Ref-1 does not appear to affect its DNA repair activity, but it does regulate its transcriptional activity such as its ability to bind to the PTH promoter and initiate transcription of the parathyroid hormone gene.
  •  NF-kB is a key transcription factor and effector molecule involved in responses to cell stress, consisting of a p50/p65 heterodimer. The p65 subunit is controlled by acetylation via PCAF and by deacetylation via HDAC3 and HDAC6.

These are just some examples of constantly emerging non-histone, non-chromatin roles for HDACs.

HDAC inhibitors
Histone deacetylase inhibitors (HDIs) have a long history of use in psychiatry and neurology as mood stabilizers and anti-epilectics, for example, valproic acid. More recently, HDIs are being studied as a mitigator or treatment for neurodegenerative diseases.Also in recent years, there has been an effort to develop HDIs for cancer therapy, and Vorinostat (SAHA) has recently been approved for treatment of cutaneous T cell lymphoma (CTCL). The exact mechanisms by which the compounds may work are unclear, but epigenetic pathways are proposed. In addition, a clinical trial is studying valproic acid effects on the latent pools of HIV in infected persons.

HDAC inhibitors have effects on non-histone proteins that are related to acetylation. HDIs can alter the degree of acetylation of these molecules and thereby increase or repress their activity. For the four examples given above (see Function) on HDACs acting on non-histone proteins, in each of those instances the HDAC inhibitor Trichostatin A (TSA) blocks the effect. HDIs have been shown to alter the activity of many transcription factors, including ACTR, cMyb, E2F1, EKLF, FEN 1, GATA, HNF-4, HSP90, Ku70, NFκB, PCNA, p53, RB, Runx, SF1 Sp3, STAT, TFIIE, TCF, YY1.[

Selfish Sex Chromosomes

Part 1
Part2

Part 3

Co-Codamol

Co-codamol (BAN) is a non-proprietary name used to denote a compound analgesic, a combination of codeine phosphate and paracetamol (acetaminophen). Co-codamol tablets are used for the relief of mild/moderate (or in the case of 30/500mg - severe) pain.

Side effects can include: constipation, skin rashes, dizziness, sedation, shortness of breath, hypersensitivity reaction, fainting (syncope or near syncope), nausea and/or vomiting, confusion, loss of short-term memory, drowsiness, changes in blood, allergic reactions, euphoria, dysphoria, abdominal pain, pruritus (itching), easy bruising, bleeding gums, and addiction.


Genetic differences between people gives rise to differing rates of metabolism of codeine to morphine. In about 5% of people this may happen particularly fast, leading to higher levels of morphine being passed through breast milk in amounts potentially able to cause fatal respiratory depression of a breastfed baby.

Stroke

A stroke is the rapidly developing loss of brain function(s) due to a disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood supply) caused by thrombosis or embolism or due to a hemorrhage. As a result, the affected area of the brain is unable to function, leading to inability to move one or more limbs on one side of the body, inability to understand or formulate speech or inability to see one side of the visual field.In the past, stroke was referred to as cerebrovascular accident or CVA, but the term "stroke" is now preferred.

A stroke is a medical emergency and can cause permanent neurological damage, complications and death. It is the leading cause of adult disability in the United States and Europe. In the UK, it is the second most common cause of death, the first being heart attacks and third being cancer. It is the number two cause of death worldwide and may soon become the leading cause of death worldwide. Risk factors for stroke include advanced age, hypertension (high blood pressure), previous stroke or transient ischemic attack (TIA), diabetes, high cholesterol, cigarette smoking and atrial fibrillation. High blood pressure is the most important modifiable risk factor of stroke.

The traditional definition of stroke, devised by the World Health Organization in the 1970s, is a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours". This definition was supposed to reflect the reversibility of tissue damage and was devised for the purpose, with the time frame of 24 hours being chosen arbitrarily. The 24-hour limit divides stroke from transient ischemic attack, which is a related syndrome of stroke symptoms that resolve completely within 24 hours. With the availability of treatments that, when given early, can reduce stroke severity, many now prefer alternative concepts, such as brain attack and acute ischemic cerebrovascular syndrome (modeled after heart attack and acute coronary syndrome respectively), that reflect the urgency of stroke symptoms and the need to act swiftly.

A stroke is occasionally treated with thrombolysis ("clot buster"), but usually with supportive care (speech and language therapy, physiotherapy and occupational therapy) in a "stroke unit" and secondary prevention with antiplatelet drugs (aspirin and often dipyridamole), blood pressure control, statins, and in selected patients with carotid endarterectomy and anticoagulation.

Radial Keratotomy

Radial keratotomy (RK) is a refractive surgical procedure to correct myopia.In radial keratotomy (RK), incisions are made with a precision calibrated diamond knife. It has been found that incisions that penetrate only the superficial corneal stroma are less effective than those reaching deep into the cornea,and consequently incisions are made quite deep. One study cites incisions made to a depth equivalent to the thinnest of four corneal-thickness measurements made near the centre of the cornea. Other sources cite surgeries leaving 20 to 50 micrometres of corneal tissue unincised (roughly equivalent to 90% of corneal depth based on thickness norms).




Arcuate keratotomy is still popular to correct astigmatism. It is also done with a diamond knife but in these cases, cuts are made circumferentially, parallel to the edge of the cornea.

Postsurgical healing

Cross-section schematic of postsurgical epithelial plugs. Example of a desirable outcome left, and an undesirable outcome right.

The healing corneal wounds are comprised of newly abutting corneal stroma as well as fibroblastic cells and irregular fibrous tissue. Closer to the wound surface lies the epithelial plug, a bed of the cells that form the normal corneal epithelium, which have fallen into the wound. Often this plug is three to four times as deep as the normal corneal epithelium layer. As the cells migrate from the depth of the plug up to the surface, some die before reaching the surface, forming breaches in the otherwise healthy epithelial layer. This consequently leaves the cornea more susceptible to infection.This risk is estimated to be between 0.25%[7] and 0.7%[8] Healing of the RK incisions is very slow and unpredictable, often incomplete even years after surgery.[9] Similarly, infection of these chronic wounds can also occur years after surgery,[10][11][12] with 53% of ocular infections being 'late' in onset. The pathogen most commonly involved in such infections is the highly virulent bacterium Pseudomonas aeruginosa.

Chromosome to DNA

Understanding Memory

Memory is an organism's mental ability to store, retain and recall information. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing the memory.
Processes

From an information processing perspective there are three main stages in the formation and retrieval of memory:

* Encoding or registration (receiving, processing and combining of received information)
* Storage (creation of a permanent record of the encoded information)
* Retrieval or recall (calling back the stored information in response to some cue for use in a process or activity)



Sensory memory corresponds approximately to the initial 200 - 500 milliseconds after an item is perceived. The ability to look at an item, and remember what it looked like with just a second of observation, or memorization, is an example of sensory memory. With very short presentations, participants often report that they seem to "see" more than they can actually report. The first experiments exploring this form of sensory memory were conducted by George Sperling (1960) using the "partial report paradigm." Subjects were presented with a grid of 12 letters, arranged into three rows of 4. After a brief presentation, subjects were then played either a high, medium or low tone, cuing them which of the rows to report. Based on these partial report experiments, Sperling was able to show that the capacity of sensory memory was approximately 12 items, but that it degraded very quickly (within a few hundred milliseconds). Because this form of memory degrades so quickly, participants would see the display, but be unable to report all of the items (12 in the "whole report" procedure) before they decayed. This type of memory cannot be prolonged via rehearsal.

Neuroimmunity and Autism

Carlos A. Pardo,MD, discusses the hypothesis suggesting that the immune system may in some way play a role in triggering the onset of autism and how certain treatments may help. Series: "M.I.N.D. Institute Lecture Series on Neurodevelopmental Disorders.

Drug Metabolism

Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products. Its rate is an important determinant of the duration and intensity of the pharmacological action of drugs.

Presentation on the Genetics of Mental illnesses

Dr. Weinberger received his BA from Johns Hopkins University and MD from the University of Pennsylvania. After medical internship at UCLA-Harbor General Hospital, he did residencies in psychiatry at Harvard Medical School and in neurology at George Washington University and is board certified in both specialties. He was a research fellow at the NIMH in Richard Wyatt�s lab and became Chief of the Clinical Brain Disorders Branch in 1987. He is the recipient of the Research Prize of the World Federation of Societies of Biological Psychiatry, the Foundation's Fund Prize from the American Psychiatric Association, and the Lieber Prize from NARSAD, and is a member of the Institute of Medicine of the National Academy of Sciences. The work of his lab focuses on basic neurobiological and genetic mechanisms of neuropsychiatric disorders, especially schizophrenia.

Bleomycin Anti cancer agent

Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anti-cancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. Bleomycin A2 .The drug is used in the treatment of Hodgkin lymphoma (as a component of the ABVD regimen), squamous cell carcinomas, and testicular cancer, as well as in the treatment of pleurodesis and plantar warts.



Bleomycin was first discovered in 1966 when the Japanese scientist Hamao Umezawa found anti-cancer activity while screening culture filtrates of S. verticullus. Umezawa published his discovery in 1966. The drug was launched in Japan by Nippon Kayaku in 1969. In the US bleomycin gained Food and Drug Administration (FDA) approval in July 1973. It was initially marketed in the US by the Bristol-Myers Squibb precursor Bristol Laboratories under the brand name Blenoxane.

Mechanism of action

Bleomycin acts by induction of DNA strand breaks. Some studies suggest that bleomycin also inhibits incorporation of thymidine into DNA strands. DNA cleavage by bleomycin depends on oxygen and metal ions, at least in vitro. It is believed that bleomycin chelates metal ions (primarily iron) producing a pseudoenzyme that reacts with oxygen to produce superoxide and hydroxide free radicals that cleave DNA. In addition, these complexes also mediate lipid peroxidation and oxidation of other cellular molecules.


Bleomycin. . In Wikipedia, The Free Encyclopedia. from http://en.wikipedia.org/w/index.php?title=Bleomycin&oldid=270981622

Nucleotide excision repair of carcinogen

Nucleotide excision repair is a DNA repair mechanism. DNA constantly requires repair due to damage that can occur to bases from a vast variety of sources including chemicals but also ultraviolet (UV) light from the sun. Nucleotide excision repair (NER) is a particularly important mechanism by which the cell can prevent unwanted mutations by removing the vast majority of UV-induced DNA damage (mostly in the form of thymine dimers and 6-4-photoproducts). The importance of this repair mechanism is evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins including Xeroderma pigmentosum and Cockayne's syndrome.