Northwestern Medicine scientists are continuing to unravel the molecular changes that underlie one of the world’s deadliest and most infamous respiratory infections.
When the bacterium Yersinia pestis enters the lungs, it causes pneumonic plague, a disease that is 100 percent fatal if untreated. The way in which Y. pestis evades the immune system and kills people in a matter of days has largely confounded scientists, until now.
Following a 2007 study demonstrating that the presence of a protein called the plasminogen activator protease (Pla) is required for Y. pestis to live inside the lungs, Wyndham Lathem, PhD, assistant professor in Microbiology-Immunology, has found what role Pla plays during disease.
The activator shuts down a molecule, Fas ligand (FasL), which stimulates a form ofprogrammed cell death known as apoptosis. The result is a disrupted immune response during infection. This allows Y. pestis to overwhelm the lungs, causing death.
"This is the first time anyone has shown how bacteria can subvert apoptotic cell death by directly destroying Fas ligand," said Lathem, a member of the Center for Genetic Medicine and Interdepartmental Immunobiology Center.
The findings were published April 9 in Cell Host & Microbe.
To study its effects, scientists added Pla to glass slides with various fluorescently-tagged proteins. If the protease showed an affinity for a specific protein, it would chew off pieces, making it appear less florescent when viewed under a microscope.
"We knew that Pla must be chopping up host proteins in some manner and we looked to discover exactly what proteins were being affected," said first author Adam Caulfield, a research associate in Lathem’s lab.
"As we reviewed possible hits, the ‘aha moment’ came when we saw Fas ligand on the list of affected proteins, because we know Fas is an integral receptor for controlling cell death," said Lathem. "The process of Pla degrading Fas ligand effectively prevents the lungs from being able to clear the infection."
After verifying their findings using cell cultures, Lathem conducted preclinical tests using mice, arriving at the same conclusion.
"Now that we have identified this as a method by which plague bacteria can manipulate the immune system, we have something to look for when studying other respiratory infections," Lathem said. "This could be a common feature, where we see other bacteria manipulating cell death pathways by altering Fas signaling."
Pneumonic plague is unique in that it is the only type of plague with an ability to spread from person to person. It is treatable if caught early, but after 24 hours, antibiotics are rendered useless.
Lathem believes that a restoration of Fas signaling may give antibiotics more time to work, and scientists in his lab are exploring that possibility. They will also be looking at different bacterial infections to see if any manipulate cell death by altering Fas signaling in a similar manner.
Journal reference: Cell Host & Microbe
The first transparent 3D-printed skull has been successfully implanted.Three months ago, surgeons in Holland implanted a transparent plastic skull in a woman whose skull has never stopped growing. Incredibly, the rare bone disease that was wrecking her vision and destroying her life has been been bested by a simple 3D printer. The team of surgeons, led by Dr. Bon Verweij at the University Medical Center in Utrecht, expect her new skull to last indefinitely, opening up new vistas for cranial transformation.
Read the entire article here.
Smart Solution To Stop Needle Reuse Wins Design Impact Award
Healthcare providers reusing unsterilized syringes and needles cause more than 1.3 million infections around the world every year, according to the World Health Organization. Ignorance of the dangers and a lack of supplies means that the average syringe is reused four times in the developing world, says advocacy and education charity Safepoint.
The problem, which spreads bloodborne pathogens like hepatitis and
AIDSHIV (h/t and good catch to sexeducationforprudes), led healthcare designer David Swann and his team at the University of Huddersfield in the United Kingdom to come up with a simple and cheap visual aid.
They created a syringe coated with a color-changing dye that turns red when exposed to carbon dioxide. The so-called A Behavior-Changing (ABC) syringe is stored in a nitrogen-filled pack and starts changing color only when the pack is punctured or the syringe is removed. Read more below and see the video.
The above image shows a coloured X-ray of pulmonary tuberculosis, caused specifically by the bacterium Mycobacterium tuberculosis.
TB is most commonly caused by the bacterium Mycobacterium tuberculosis (MTB), which is spread by droplet infection (transmitted in saliva, usually by coughing or sneezing). MTB is highly aerobic, requiring high levels of oxygen. It affects the respiratory system, particularly damaging and destroying lung tissue.
Only about 30% of people exposed to TB will become infected. This is much more likely to occur in individuals who are immunocompromised (hence TB often presenting itself in those whom are HIV positive).
The primary infection of TB is often asymptomatic, although occasionally it may cause fever and/or a dry cough. In an individual with a healthy immune system, a localised inflammatory response will occur, forming a nodule of tissue called a tubercule (containing dead bacteria and macrophages). Typically (in about 90% of cases) the condition will resolve itself without the individual ever having known they were infected.
However MTB may survive, as alveolar macrophages are unable to digest the bacteria, allowing it to remain in a state of dormant latency and multiply silently. After a period of time, when the host’s immunity is compromised (for example, due to infection or malnourishment) the bacteria will produce active tuberculosis.
When the infection presents itself in this way (referred to as miliary tuberculosis), symptoms may initially include loss of appetite, fever, productive cough and loss of energy, loss of weight/anorexia or night sweats however these are very non-specific. As the infection progresses, one may develop tuberculous pleuritis (causing chest pain, nonproductive cough and fever), increase in production of mucous and haemoptysis (coughing up blood).
As the infection spreads it may lead to symptoms such as abdominal pain, painful urination, sterility and brain damage (depending on which areas are affected and to what extent).
Treatment and prevention:
If left untreated, TB will eventually cause death. This may be because of hypoxia (due to severe lung damage) or organ failure (due to malnutrition). Also, as TB disarms a critical part of the immune system, it makes patients much more susceptible to opportunistic infections (such as pneumonia) therefore patients are often treated with antibiotic medication outside of a hospital environment. Vaccines are commonly administered as a form of prevention and are effective against severe forms of paediatric TB however adult pulmonary TB is still prevalent (there are currently more TB cases worldwide than ever before).
An X-ray may indicate the presence of TB however other infections appear similar so cultures must be taken to confirm the diagnosis.
Today (03/24/12) is World TB Day
1 out of every 3 people in the world is infected by tuberculosis and 95% of cases occur in developing countries where medication is largely unavailable or unaffordable. In addition, it’s becoming more resistant to treatment and only one drug is currently in the third stage of clinical trials - no pharmaceutical company wants to put money into a drug that they can’t put a huge price tag on and more so, a drug that is only taken for a relatively short period of time and will also eventually become ineffective too. People are dying needlessly because they can’t get the treatment that they need.
Please take some time out of your day to inform yourself about this condition and raise awareness to others. Just like the progress we are making with HIV treatment and prevention in developing countries, we can make a difference and there can be change.
Keratoconus of varying severity
Keratoconus is a weakening of the corneal tissue, allowing it to bulge outwards. It generally begins in the teens or early adulthood, and in many cases requires corneal transplant.
Many centers in the United States and Europe are exploring options for mild-to-moderate keratoconus that are less invasive than a corneal transplant, but for severe manifestations (such as the bottom image, where the corneal tissue is not only bulging, but bulging in an uneven pattern), donor or artificial corneas are still the most successful treatment.
When scientists made the stunning announcement last year that a baby born with H.I.V. had apparently been cured through aggressive drug treatment just 30 hours after birth, there was immediate skepticism that the child had been infected in the first place.
But on Wednesday, the existence of a second such baby was revealed at an AIDS conference here, leaving little doubt that the treatment works. A leading researcher said there might be five more such cases in Canada and three in South Africa.
And a clinical trial in which up to 60 babies who are born infected will be put on drugs within 48 hours is set to begin soon, another researcher added.
If that trial works — and it will take several years of following the babies to determine whether it has — the protocol for treating all 250,000 babies born infected each year worldwide will no doubt be rewritten.
“This could lead to major changes, for two reasons,” said Dr. Anthony S. Fauci, executive director of the National Institute for Allergy and Infectious Diseases. “Both for the welfare of the child, and because it is a huge proof of concept that you can cure someone if you can treat them early enough.”
The announcement was the third piece of hopeful news in two days about the virus that causes AIDS.
On Tuesday, scientists reported that injections of long-lasting AIDS drugs fended off infection in monkeys, and on Wednesday, researchers announced a “gene editing” advance that might enable immune cells to repel the virus.
The first infant to make an apparent recovery from H.I.V. infection, now famous as the “Mississippi baby,” was described last March at the Conference on Retroviruses and Opportunistic Infections, the same annual meeting where the new case was reported on Wednesday.
The Mississippi child, now more than 3 years old, is still virus-free, said Dr. Deborah Persaud, a virologist who has run ultrasensitive tests on both children in her lab at the Johns Hopkins Children’s Center in Baltimore.
The second baby, a girl born at Miller Children’s Hospital in Long Beach, Calif., is now 9 months old and apparently free of the virus that causes AIDS.
Her mother, who has advanced AIDS and is mentally ill, arrived in labor; she had been prescribed drugs to protect her baby but had not taken them.
Four hours after the birth, a pediatrician, Dr. Audra Deveikis, drew blood for an H.I.V. test and immediately started the baby on three drugs — AZT, 3TC and nevirapine — at the high doses usually used for treatment of the virus.
The normal preventive regimen for newborns would be lower doses of two drugs; doctors usually do not use the more aggressive treatment until they are sure the baby is infected, and then sometimes not in the first weeks.
“Of course I had worries,” Dr. Deveikis said in an interview here. “But the mother’s disease was not under control, and I had to weigh the risk of transmission against the toxicity of the meds.”
“I’d heard of the Mississippi baby, I’d watched the video,” she added. “I knew that if you want to prevent infection, early treatment is critical.”
The New York Times, "Early Treatment Is Found to Clear HIV In a Second Baby."
Heart surgery is an extremely difficult procedure. Even more so when the tiny anatomy of a small child is involved. When 14-month old Roland Lian Cung Bawi’s heart was failing him, his surgeon Erle Austin knew that he had to prepare meticulously for an intricate operation. Initially he consulted other surgeons, but this yielded conflicting advice. So Austin turned to 3D printing for help.
Using the facilities at the University of Louisville’s engineering school, Austin and his medical team produced a three dimensional model of little Ronald’s heart. Pediatric operations are difficult because the interior structures of a child’s organs are small and hard to see clearly. This model allowed the surgical team to come up with a precise plan to limit the amount of exploratory incisions, reduce operating time and prevent the need for follow-up operations.
When a copperhead sank its fangs into Eric Ferguson last August, the North Carolina printing-equipment salesman knew he needed treatment immediately.
Ferguson got it at the Lake Norman Regional Medical Center in Mooresville, about 30 miles from Charlotte. He received four intravenous vials of CroFab, an anti-venom harvested from the blood of toxin-exposed sheep. After 18 hours of observation, he got a clean bill of health — and a bill for $81,151.16, or more than $20,000 per vial.
“The staff there were second to none,” Ferguson said. “They did save my life.”
(Photo: James Robinson/The Fayetteville Observer/AP)