Autis dan Sistem Kekebalan Tubuh Ibu.

Hasil penelitian dari UC Davis M.I.N.D. Institute and Center for Children's Environmental Health telah menemukan bahwa terdapat keterkaitan antara sistem kekebalan tubuh pada darah seorang ibu dan sel otak anaknya yang menderita autis, yang memiliki kemungkinan untuk mempengaruhi perkembangan otak si bayi. Penemuan ini meningkatkan kemungkinan pemberian kekebalan tubuh dari seorang ibu ketika mengandung merupakan salah satu faktor resiko penyakit autis dan pada saat yang sama, penanganan yang baik sebelum melahirkan dapat mencegah penyakit tersebut pada beberapa anak menurut Judy Van de Water professor rheumatology, allergy dan clinical immunology.

Judy dan timnya memulai penelitian terhadap sampel darah dari 123 orang ibu yang 61 orang diantaranya memiliki anak yang menderita autis. Mereka mengisolasi antibodi IgG dari sampel kemudian memberikan antibodinya kepada jaringan otak bayi menggunakan analisa western blot yang mendeteksi reaktifitas antibodi terhadap protein. Hasilnya mengungkapkan pola reaktifitas yang spesifik terhadap 2 protein pada 7 otak bayi dari 61 contoh dari anak penderita autis.

Judy dan timnya belum terlalu mengerti mengapa IgG merespon protein dari otak bayi dengan sangat baik, namun perkiraan mereka bahwa kemunculan ini diperoleh dari antibodi sang ibu ketika mengandung yang diberikan kepada si bayi dan juga pengaruh dari lingkungan semakin menguatkan munculnya autis.

Karakteristik dari autis - penurunan mental, keterbatasan bahasa, prilaku berulang - biasanya terlihat sangat jelas diawal kehidupan sang anak. Beberapa anak lainnya mulai menderita autis ketika usia 12-24 bulan.

Antibodi IgG bertanggungjawab terhadap sistem kekebalan tubuh untuk jangka panjang dalam merespon infeksi, namun dapat juga berkontribusi terhadap penyakit autoimmune seperti arthritis, multiple sclerosis dan lupus. IgG juga menembus plasenta untuk memberikan sistem kekebalan tubuh kepada fetus dan bayi yang baru lahir. Inilah yang menjadi salah satu alasa Judy meneliti peran IgG sebagai faktor potensial penyebab autis.

Untuk selanjutnya, Judy ingin mengetahui efek dari IgG terhadap wanita ketika mereka mengandung, apakah akan menghasilkan respons yang sama seperti respons terhadap protein pada otak bayi.

Sumber : Science Daily, 12 Februari 2008

Looking into the Brain with Light

By Michael Chorost

A new noninvasive diagnostic technology could give doctors the single most important sign of brain health: oxygen saturation. Made by an Israeli company called OrNim and slated for trials on patients in U.S. hospitals later this year, the technology, called targeted oximetry, could do what standard pulse oximeters can't.

A standard pulse oximeter is clipped onto a finger or an earlobe to measure oxygen levels under the skin. It works by transmitting a beam of light through blood vessels in order to measure the absorption of light by oxygenated and deoxygenated hemoglobin. The information allows physicians to know immediately if oxygen levels in the patient's blood are rising or falling.

Prior to the development of pulse oximeters, the only way to measure oxygen saturation was to take a blood sample from an artery and analyze it in a lab. By providing an immediate, noninvasive measure of oxygenation, pulse oximeters revolutionized anesthesia and other medical procedures.

While pulse oximeters have become accurate and reliable, they have a key limitation: they can't measure oxygen saturation in specific areas deep inside the body. Because pulse oximeters measure only the blood's overall oxygen levels, they have no way of monitoring oxygen saturation in a specific region. This is especially problematic in the case of brain injuries, since the brain's oxygenation can then differ from the rest of the body's.

Information on oxygenation in specific regions of the brain would be valuable to neurologists monitoring a brain-injured patient, as it could be used to search for localized hematomas and give immediate notice of hemorrhagic strokes. When a stroke occurs, an area of the brain is deprived of blood and thus oxygen, but there is no immediate way to detect the attack's occurrence.

CT and MRI scans give a snapshot of tissue damage, but they can't be used for continuous monitoring. It can also be very difficult to conduct such scans on unconscious patients hooked up to life-support devices.

Wade Smith, a neurologist at the University of California, San Francisco, and an advisor to OrNim, points out that, while cardiologists have devices to monitor hearts in detail, neurologists have no equivalent tool. With brain-injured patients, Smith says, "the state of the art is flying blind."

OrNim's new device uses a technique called ultrasonic light tagging to isolate and monitor an area of tissue the size of a sugar cube located between 1 and 2.5 centimeters under the skin. The probe, which rests on the scalp, contains three laser light sources of different wavelengths, a light detector, and an ultrasonic emitter.

The laser light diffuses through the skull and illuminates the tissue underneath it. The ultrasonic emitter sends highly directional pulses into the tissue. The pulses change the optical properties of the tissue in such a way that they modulate the laser light traveling through the tissue. In effect, the ultrasonic pulses "tag" a specific portion of tissue to be observed by the detector. Since the speed of the ultrasonic pulses is known, a specific depth can be selected for monitoring.

The modulated laser light is picked up by the detector and used to calculate the tissue's color. Since color is directly related to blood oxygen saturation (for example, arterial blood is bright red, while venous blood is dark red), it can be used to deduce the tissue's oxygen saturation. The measurement is absolute rather than relative, because color is an indicator of the spectral absorption of hemoglobin and is unaffected by the scalp.

Deeper areas could be illuminated with stronger laser beams, but light intensity has to be kept at levels that will not injure the skin. Given the technology's current practical depth of 2.5 centimeters, it is best suited for monitoring the upper layers of the brain. Smith suggests that the technology could be used to monitor specific clusters of blood vessels.

While the technology is designed to monitor a specific area, it could also be used to monitor an entire hemisphere of the brain. Measuring any area within the brain could yield better information about whole-brain oxygen saturation than a pulse oximeter elsewhere on the body would. Hilton Kaplan, a researcher at the University of Southern California's Medical Device Development Facility, says, "If this technology allows us to actually measure deep inside, then that's a big improvement over the limitations of decades of cutaneous versions."

Michal Balberg, the CEO and cofounder of OrNim, thinks that it may ultimately be feasible to deploy arrays of probes on the head to get a topographic map of brain oxygenation. In time, brain oxygenation may be considered a critical parameter that should be monitored routinely. Balberg says, "Our development is directed toward establishing a new brain vital sign that will be used to monitor any patient [who's] unconscious or under anesthesia. We believe that this will affect patient management in the coming decade in a manner comparable to pulse oximeters."

Michael Chorost covers medical devices for Technology Review. His book about cochlear implants, Rebuilt: How Becoming Part Computer Made Me More Human, was published in 2005.

From here

Sel Penyebab Leukemia Ditemukan

Selasa, 29 Januari 2008 | 13:28 WIB

TEMPO Interaktif, Oxford:
Tim peneliti menemukan bahwa kedua anak kembar tersebut memiliki sel tunas abnormal praleukemia dalam darah mereka. Sel itu bisa "tidur" dalam sumsum tulang atau berkembang menjadi sel tunas leukemia. Hasil ini dikonfirmasi oleh eksperimen yang menggunakan sel tali pusar manusia.

"Penelitian ini berarti kami dapat mengetes apakah penanganan leukemia lymphoblastic akut pada anak bisa dikaitkan dengan menghilangnya dan berkembangnya sel tunas leukemia," kata Profesor Tariq Enver dari Unit Hematologi Molekuler Universitas Oxford, yang memimpin penelitian tersebut. "Mulai saat ini, upaya penyembuhan bisa difokuskan pada upaya membidik sel tunas praleukemia dan sel tunas kanker dengan obat yang ada atau yang akan kita kembangkan."

Upaya penyembuhan yang terfokus, menurut Tariq, bisa menghindari efek samping pengobatan kanker kemoterapi yang menyakitkan dan terkadang justru membahayakan kondisi tubuh pasien. Hal ini sangat penting karena terbukti, Olivia, salah satu anak kembar yang terkena leukemia, mengalami kebutaan di sebelah matanya akibat infeksi yang tidak bisa dilawan tubuhnya saat kemoterapi.

Para ilmuwan telah melacak kemungkinan sel tunas prakanker itu akibat fusi abnormal dari dua gen yang terjadi selama kehamilan ibu. Fusi ini menghasilkan protein hibrida, sebuah "kesalahan" genetik yang terjadi secara acak dan menyebabkan sel menjadi terjangkit leukemia. Gen yang diambil dari si kembar lantas ditransplantasikan ke tikus laboratorium yang mengkonfirmasi adanya hubungan langsung antara malfungsi genetik dari sel tunas tersebut dan leukemia.

Lembaga donor Inggris yang membiayai penelitian itu, Leukemia Research and the Medical Research Council, dan Rumah Sakit Great Ormond Street menyatakan sangat gembira atas penemuan itu dan berharap penelitian dilanjutkan ke upaya mencegah dan mengobati penyakit tersebut.

AMAL IHSAN | SCIENCEDAILY

from here

Gadis Australia Pasien Pertama Dunia yang Berubah Golongan Darah

Canberra (ANTARA News) - Seorang gadis remaja Australia --Demi-Lee Brennan-- menjadi pasien pertama yang mengubah golongan darahnya dan menerima sistem kekebalan dari donor organnya.

Brennan yang kini berusia 15 tahun menerima transplantasi organ hati pada saat usianya 9 tahun karena organ harinya tidak berfungsi.

"Hal itu adalah kesempatan kedua saya untuk dapat bertahan hidup," kata Brennan kepada media massa setempat ketika menceriterakan bagaimana tubuhnya berhasil menerima dan beradaptasi bedah transplantasi yang dapat dikatakan "Mukjizat" yang datang dari Tuhan. "Sungguh sulit dipercaya."

Golongan darah Brennan mengalami perubahan dari "O" negatif menjadi "O" positif pada saat ia sakit dan diberikan pengobatan untuk menghindari penolakan terhadap organ hati donor oleh sistem kekebalan tubuhnya.

Sel batang pembuluh darah hatinya yang baru memasuki sumsum tulang belakangnya yang mengubah seluruh sistem kekebalan tubuhnya, berarti si remaja Brennan tak lagi memerlukan obat-obatan anti penolakan tubuh.

Para dokter dari Rumah Sakit Anak Westmead di Sydney mengatakan mereka belum dapat memberikan keterangan kasus Brennan yang mengalami kesembuhan, seperti yang mereka sampaikan dalam majalah kedokteran, The New England Journal of Medicine.

"Terus terang kami belum menemukan penjelasan untuk hal itu," kata Michel Stormon seorang ahli hepatologi pediatri seperti dikutip Reuters.

Sturat Dorrney, mantan kepala bagian unit transplantasi di rumah sakit itu mengatakan, kasus Brennan dapat membuka jalan bagi terapi transplantasi organ, karena biasanya sistem kekebalan tubuh pasien penerima menyerang transplantasi jaringan di donor.

"Kini kami harus kembali mengkaji ulang semua tahapan yang terjadi pada Demi-Lee dan melihat mengapa hal itu dapat terjadi dan kalau-kalau dapat melakukan pengulangan kembali," kata Dorney.

"Kami berpikir hal itu mungkin karena kami menggunakan organ hati dari seseorang yang usianya masih muda dan Demi-Lee memiliki sel darah putih dalam jumlah rendah mungkin karena dua faktor itulahyang menjadi alasan," katanya kepada harian Daily Telegraph.

Penolakan tubuh umumnya ditangani dengan kombinasi obat-obatan walaupun penolakan kronik tidak terjadi dua arah (bolak-balik).

Hanya tujuh dalam 10 operasi transplantasi di Australia yang berhasil setelah lima tahun berselang yang dikarenakan oleh penolakan tubuh di pasien. (*)

from here

Magnetic Cell Therapy

Stents are expandable stainless-steel scaffolds commonly used to prop open clogged arteries. But inserting a stent can damage an artery's inner lining, and stented arteries may reclose after several months, causing blood clots and possibly heart attacks. Now researchers at the Children's Hospital of Philadelphia have devised a way to use tiny iron-bearing nanoparticles and a magnetic field to direct cells with therapeutic properties to the sites of steel stents. The cells could help repair arterial damage and prevent clotting, among other things.

"Stents have been known to induce severe trauma," says Robert Levy, chair of pediatric cardiology at the Children's Hospital of Philadelphia. "Repairing blood vessels with cell therapy is a very important concept that can be realized with magnetic targeting."

Levy and his colleagues engineered nanoparticles, or tiny spheres, of polylactic acid, a biodegradable polymer used in sutures and other medical applications. The team then loaded each nanoparticle with a small dose of magnetically responsive iron oxide and inserted it into a bovine endothelial cell--a cell found in a blood vessel's inner lining. The bovine cells were genetically altered to express a fluorescent marker, making them easily detectable.

Next, the researchers surgically implanted small metal stents in the carotid arteries of live rats. They injected the rats with a solution of treated endothelial cells and created a steady magnetic field around each rat using two large, external electromagnetic coils. Levy says that the magnetic field he and his colleagues applied was less than a tenth of the strength of the fields generated by conventional MRI machines. After 48 hours, the team created images of the rat using bioluminescence imaging.

The researchers found that the magnetic field caused the cells to migrate to the metal stents under two scenarios: when cells were injected directly into the carotid artery, near the stent location, and when they were injected farther away, in the aortic arch, whence they could have branched out to all areas of the body. In tests that didn't use a magnetic field, the cells migrated throughout the body with little direction.

Magnetically directing cells, particularly endothelial cells, to the sites of metal stents may have a significant therapeutic effect, says Levy. During surgical implantation, stents tend to scrape off endothelial cells, whose normal functions include helping prevent blood clotting. Endothelial cells are also barriers to inflammatory cells. While inflammatory cells normally flock to an injury to help repair it, in the absence of endothelial cells, they build up excessively, creating arterial blockage. In recent years, stents have been engineered to release anticlotting drugs to prevent arteries from reclosing. But such drug-releasing stents have problems of their own, including preventing endothelial cells from regenerating.

"Two years ago, clinicians noticed that patients in significant numbers were having problems with these stents, probably because the endothelium wasn't properly healed," says Levy. "Clotting, myocardial infarctions, and sudden deaths occurred, and this has caused a big uproar over stent usage."

Levy hopes that magnetically directing new endothelial cells to blood vessels may solve many of the problems that stents currently face. His team plans to continue experimenting on rats, using endothelial cells derived from rats instead of cows, to minimize risk of rejection. Now that he has found a way to direct cells to metal stents, Levy is also looking at other potential therapies, including nitric oxide, which is known to relax and dilate blood vessels. He is currently engineering cells to genetically express enzymes that produce nitric oxide, and he will eventually load them with iron-oxide nanoparticles that will drive them to the sites of stents, further opening arteries.

Levy adds that the magnetic-based technique has applications outside of cardiovascular therapy. For example, in treating lung cancer, clinicians often use metal stents to keep airways open. However, a patient's tumor may continue to grow, eventually obstructing the passage despite the stenting. Magnetically targeted therapies could help deliver specific drugs to stent sites to treat tumors, in addition to keeping airways open.

"Metallic implants are also widely used in other areas, like orthopedics, for complex fractures, and correcting spinal curvature, where cell therapies could also be helpful," says Levy. "Steel implants are widely used in medicine, and there are all sorts of situations where applications could be used."

What's more, Levy envisions that such therapies can be applied using conventional MRI machines. The magnetic field generated by MRI cores is an order of magnitude more powerful than the ones Levy used in his experiments, so fewer iron-oxide nanoparticles could produce the same effect.

Robert Langer, Institute Professor at MIT, believes that Levy's technique is a promising step toward directed cell therapies. "They were able to localize more drugs into the targeted areas," he says. "I think it's a neat idea that has a lot of potential."

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