Researchers in the laboratory of Dr. Jayakrishna Ambati at the University of Kentucky have discovered the first naturally occurring molecule that selectively blocks lymphatic vessel growth. In an article in the Aug. 9, 2009 online edition of Nature Medicine, they report the identification of a new molecule known as soluble VEGFR-2 that blocks lymphangiogenesis the growth of lymphatics but not blood vessel growth.

The twin circulatory systems of mammals blood and lymphatic are intricately intertwined, both anatomically and functionally. Until now it has been difficult to selectively target one without affecting the other. The lymphatic vessel network is essential for transporting fluids, molecules, and immune cells. It is crucial for wound healing and immune defense. Disturbances in the lymphatics are involved in diseases as varied as lymphedema, transplant rejection, and tumor metastasis, which collectively affect hundreds of millions of people worldwide.

This article, whose lead author is Dr. Romulo Albuquerque, currently a medical student in the UK College of Medicine, showed that soluble VEGFR-2 specifically blocks lymphatic vessel growth both during development and following injury by blocking VEGF-C, a powerful lymphatic growth factor. It also reports that loss of soluble VEGFR-2 during development led to the spontaneous invasion of lymphatic vessels, but not blood vessels, into the cornea, solving the long-standing mystery of why the cornea is normally devoid of lymphatics. Soluble VEGFR-2 was also required for normal development of lymphatics in the skin.

Importantly, administration of soluble VEGFR-2 to mice following corneal transplantation nearly eliminated graft rejection. This finding might also be applicable in kidney transplant rejection because it is known that lymphatic vessels are the culprit in the rejection of that organ as well. In addition, it challenges the prevailing dogma that abnormal blood vessels are responsible for transplant rejection.

The Ambati group also studied a childhood tumor known as lymphangioma, which is estimated to affect 1 in 50 babies and for which there is no satisfactory medical treatment. Administration of soluble VEGFR-2 blocked the growth of lymphangioma cells isolated from children with this tumor. Because this molecule spares blood vessels, it might offer a safer and more targeted treatment for this pediatric tumor. The potential benefit of modulating soluble VEGFR-2 in other diseases such lymphedema due to filariasis and or following surgery for breast cancer, as well as in tumor metastasis, are also under study.

"This paper by Dr. Ambati and his coworkers represents another in a line of highly novel and important findings from their laboratory," said Patricia A. D'Amore, Professor of Ophthalmology and Pathology, Harvard Medical School and Senior Scientist at the Schepens Eye Research Institute.

"The report of the first endogenous inhibitor of lymphangiogenesis is an exciting development and holds great therapeutic promise for a number of pathologies in which lymphatic growth is a serious complication."

This work was supported by research grants from the National Eye Institute of the National Institutes of Health and an unrestricted grant from Research to Prevent Blindness.

Researchers at the Center for Molecular and Behavioral Neuroscience (CMBN) at Rutgers University in Newark have identified the need to develop a new framework for understanding "perceptual stability" and how we see the world with their discovery that visual input obtained during eye movements is being processed by the brain but blocked from awareness.

The process of seeing requires the eyes to move so light can hit the photoreceptors at the center of each retina, which then pass that information to the brain. If we were cognizant of the stimulus that passes before the eyes during the two to three times they move every second, however, vision would consist of a series of sensations of rapid motion rather than a stable perception of the world. To achieve perceptual stability, current theory has held that visual information gained during an eye movement is eliminated, as if cut off by a camera's shutter, and removed from processing.

As published in Current Biology, significant new research conducted by assistant professor Bart Krekelberg and post-doctoral researcher Tamara L. Watson now shows that theory of saccadic suppression is incorrect and what the brain is doing instead is processing information gained during eye movement but blocking it from being reported.

"Rather than completely suppressing inputs during eye movements, the brain is processing that as information it does not need to report back to awareness," says Krekelberg.

The findings were obtained by making use of a visual illusion in which the presentation of a horizontal line makes a subsequent circle look like an ellipse. In Watson and Krekelberg's study, the line was presented to research participants immediately before an eye movement. Under current theory, the line would be eliminated from visual processing and one would expect participants to report a subsequently presented circle to look like a circle. While the research participants did not recall seeing the line, the image they reported seeing was not a circle but rather an ellipse. In other words, the participants experienced the illusion, even though they were not aware of the line that causes the illusion.

"Although they did not recall seeing the line, the brain apparently did process the line," says Watson. "What this shows is that perceptual stability is not accomplished by suppressing stimuli encountered during an eye movement, or removing them from processing, but rather that those signals are prevented from reaching awareness at a later stage of processing. Some suppression is also happening, but suppression is not enough to explain perceptual stability; it is not the whole story."

One reason why the brain does not discard visual input during eye movements could be that it provides useful information about eye movements. "We speculate that the visual signals generated by eye movement may be important for determining how much and how fast the eye moved so the brain can maintain perceptual stability," says Watson. "It may be that these signals are useful for improving perceptual stability as long as they do not enter into awareness."

The findings also show that a new approach is needed to gain additional understanding into the cognitive and neural functions involved in visual processing and perceptual stability. Until now, research largely has focused on pinpointing those areas of the brain that show lower activity during an eye movement. "What we are seeing now is that things are much more complex than we suspected," says Krekelberg. "We shouldn't just be looking at areas of reduced activity in the brain during eye movement, but for areas that may change their processing to make use of the input that arises during eye movements."

Providing a better understanding of those changes in processing could pave the way for earlier detection and more effective treatments for those who suffer from deficits associated with eye movements. For example, schizophrenic patients sometimes report a lack of perceptual stability. And while dyslexia traditionally has been interpreted as a deficit in language development, it also has been found to be associated with deficits in the control of eye movements.

A new diagnostic tool developed by Van Andel Research Institute (VARI) scientists has shown promising results when used with patients of pancreatic cancer, one of the deadliest forms of cancer due to the difficulty of diagnosing it in its early stages. The method, which studies carbohydrate structures in the bloodstream, could lead to the development of blood tests that can detect cancer more effectively.

"Tumor cells sometimes shed proteins into a patient's bloodstream," said VARI Senior Scientific Investigator Brian Haab, Ph.D., whose lab published its findings in the journal Molecular & Cellular Proteomics. "These proteins can have carbohydrate structures attached to them that might be able to tell us not only if a patient has cancer, but also more about the cancer and how to treat it."

Associating specific carbohydrate alterations on proteins with cancer could provide better cancer detection than the measuring of protein levels alone, the current, most-commonly-used method of blood testing for many types of cancer. Haab said that specific alterations also could be connected to specific cancer characteristics, such as the ability to spread or resistance to therapy. Some carbohydrate alterations also could have distinct functions in cancer progression, which might have therapeutic value.

Researchers used the method to study blood samples from pancreatic cancer patients at Evanston Northwestern Healthcare in Illinois. They identified the prevalence of a variety of alterations on different proteins.

"Interestingly, the protein with the most alterations was not previously recognized as a marker for pancreatic cancer, perhaps because the protein level alone did not provide good cancer detection," said Tingting Yue, a Michigan State University graduate student working at VARI and lead author of the study. "This protein is found in pre-malignant lesions and could be valuable for early detection if we can find unique alterations associated with it."

In response to a study published in the BMJ that examined the risk factors for deaths from heart disease for patients with angina, British Heart Foundation (BHF) Associate Medical Director Dr Mike Knapton said:

"This study of 1800 people living with angina in Scotland showed that those who were most likely to die from heart disease were male, older, obese or smokers.

"This is the first time this has been demonstrated in a large number of patients living in the community, rather than in hospital settings, and confirms that smoking and being obese greatly up your risk of dying from heart disease.

"This is good news for people living with angina, as it shows that it's never too late for them to change their lifestyles, or to stop smoking."

India has joined the international community’s effort to make a vaccine for the H1N1 pandemic that has affected 135 countries in the world.

The virus strains reached the country last week from the World Health Organisation and two New Delhi-based drug companies have started work. Officials said the indigenous vaccine will take about “three to four months” to manufacture — the same duration in which international drug manufacturers have promised to deliver the vaccine. The WHO has said that the vaccines will be available by this autumn.

As of now, the Government has granted licences for the H1N1 vaccine to three companies, Serum Institute of India, Panacea Biotec and Bharat Biotech.

While Serum Institute of India, already a WHO-recognised vaccine manufacturing unit and Panacea Biotec have got the “A” (H1N1) virus strains from WHO, Bharat Biotech is waiting for its strains.

Said V M Katoch, Secretary, Department of Health Research and DG ICMR: “Vaccine manufacture takes a minimum of three to four months, our vaccine will also take around the same time. It’s a part of international rapid response and things have to be hastened in response to a pandemic.” According to Katoch, this is part of the government’s plan to have its own indigenous vaccine.

With the pandemic spreading and over 70 per cent of the international manufacturing units being in Europe, the government wants to ensure that Indians get their vaccines on priority. “We have committees set up which will negotiate with the industry and also monitor the process. We want to ensure that our people get priority and once our need is met, firms can export the vaccines,” Katoch said.