Bio-computer diagnoses cancer and produces drug

The world’s smallest computer, made entirely of biological molecules, was developed by a team of scientists led by Prof. Ehud Shapiro at Weizmann Institute of Science, Rehovot, Israel. This computer was successfully programmed to identify in a test tube, changes in the balance of molecules in the body that indicated the presence of certain cancers, to diagnose the type of cancer, and to react by producing a drug molecule to fight the cancer cells.

            Input, output and software of the biological computer were all composed of DNA, while DNA manipulating enzymes were used as hardware. The input apparatus was designed to assess concentrations of specific RNA molecules, which might be over-or under-produced, depending on the type of cancer. Using pre-programmed medical knowledge, the computer then made its diagnosis based on the detected RNA levels. In response to a cancer diagnosis, the output unit of the computer could initiate the controlled release of a single-stranded DNA molecule that was known to interfere with the cancer cell’s activities, causing it to self-destruct.

            In one series of test-tube experiments, the team programmed the computer to identify RNA molecules that indicated the presence of prostate cancer and, following a correct diagnosis, to release the short DNA strands designed to kill cancer cells. Similarly, they were able to identify, in the test tube, the signs of one form of lung cancer. The scientists hope to create a “doctor in a cell”, which will be able to operate inside a living body, spot disease and apply the necessary treatment before external symptoms even appear.

May-June 2004, Vatis Update: Biotechnology

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Say “nuts” to high blood pressure

 

Here’s the kind of health news everybody likes to hear: Tasty, dry-roasted soy nuts can reduce your blood pressure and therefore lower your risk of heart disease. These snacks don’t merely nudge your blood pressure down a tad. According to research presented to the American Heart Association in November 2002, eating a half-cup a day can drop your blood pressure readings as much as some prescription blood pressure medications.

 Soy nuts aren’t nuts, of course. They’re simply roasted soybeans that taste and crunch like nuts. Plenty of research over the years has solidified soy’s reputation as a heart-healthy food. Recently, the attention turned from soy’s  cholesterol-lowering benefits to its effect  on blood pressure. In the second half of 2002, a Spanish study found that substituting soymilk for cow’s milk significantly lowered blood pressure.

 Canadian research found evidence that eating soy in any form-milk, beans, tofu, you name it-helps reduce blood pressure, at least in men.

2004, Reader’s Digest
Medical Breakthrough

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Scientists zero in on cancer’s genetic core

Dr. Arul Chinnaiyan and Dr. Daniel Rhodes scientists of United States have discovered that, out of approximately 35,000 genes in human genome, only 67 genes is required to change normal human cells into cancer. These 67 genes form cancer’s meta-signature – a core set of essential genes cause the transformation of normal cells to abnormally growing cells or neoplastic.

 Oncomine, the cancer microarray database used in the study, was developed by Dr. Chinnaiyan, Dr. Rhodes and colleagues in the U-M Medical School, Johns Hopkins University School of Medicine in Maryland, the United States, and the Institute of Bioinformatics in Bangalore, India. They used a statistical analysis method called comparative meta-profiling to examine 40 datasets from other scientists showing specific patterns of genetic activity associated with one of 12 types of cancer.

The researchers also identified another 69-gene meta-signature showing a common pattern of genetic activity in aggressive, invasive undifferentiated cancers. The pattern was different from the one found in well-differentiated cancers that grew slowly and were easier to control. The researchers tested the meta-signature validity by looking for the same patterns of genetic activity of 12 other gene expression databases, which were not available when the study began. 

July-August 2004, 
Vatis Update: Biotechnology

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World is at risk

With scientists undertaking controversial flu virus experiments: SCIENTISTS may be open the Pandora’s box if they given the go-ahead to create a new form of the flu virus. The article ponders over the effects of experiments soon to be undertaken to combine the genetic material of the fatal Asian bird flu virus   with that of  its equally lethal human counterpart. The controversial research is being undertaken as scientists and public health workers worldwide are concerned that the bird flu virus could combine with its human   form, creating an ‘immortal’ variety. If this happens, the world would face a virulent disease  that could kill millions. As per some experts, particularly those forms the World Health Organization (WHO), the only way to avert the crisis is to combine both the viruses in the laboratory, and then broadly study the new organism.

Many are planning such as investigation. In fact, in 2000, the US Centres for Disease Control and Prevention (CDC) had started experiments to create the crossover, but these were suspended when CDC’s flu researchers were overwhelmed by SARS. The agency plans to resume the work shortly. Others countries too are exploring the option. Virologist Albert Osterhaus of the Erasmus University in the Netherlands is eager to experiment on a range of bird flu strains. Researchers from UK’s Health Protection Agency and the National Institute for Biological Standards and Control are also discussing the idea.

            As per the article, these detection may spell ruin. “There is high risk of the virus escaping the laboratory. Moreover, the published results of these experiment might help those who want to set free a pandemic on purpose,” Mark Wheelis, a researcher at the Usbased University of California, was quoted as saying. But WHO’s principal flu scientist Klaus Stohr downplays these concerns: “You cannot create a monster. But it’s monster that nature could produce. Therefore, it is necessary to conduct the experiments.”

            Critics beg differ. “Though most countries have a system to review the safety and ethical aspect of run-of-the mill scientific studies, none have formal panels to weigh studies that could put the entire world at risk or be of potential help to bioterrorists,” they assert. As per flu researcher Karl Nicholson of the University of Leicester, the UK, there should be a more formal, global consensus on the necessity of studies and who should conduct them. But even in this regards, WHO’s attitude seems to be lax. “Studies have been discussed widely with scientists in WHO’s global flu lab network. The existing safeguards are sufficient enough”, asserts Stohr. Time will only tell whether he is right or not. If not, then the world will be in a fix.

August 31 2004, Down To Earth

 

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Gene expression assays predict responsiveness to drugs.

 

Scientists at DeCode Genetics, Iceland, have developed gene expression assays capable of predicting a patient’s responsiveness to common drugs given for asthma and hypertension, including corticosteroids, angiotensin II inhibitors, leukotriene inhibitors, calcium channel blockers and ACE inhibitors. Encode, DeCode’s pharmacogenomics and clinical trials subsidiary, states that assays developed through the company’s DNA diagnostics alliance with Roche, Switzerland, are based on fewer than a dozen genes, the expressions of which provides an 85 percent accurate prediction of responsiveness to such drugs. DeCode is now working with Roche to validate these findings, with a view to developing novel diagnostic tests that will help clinicians select individualized treatment options for patients.

March-April 2004, Vatis Update: Biotechnology

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Exercise your body to preserve your mind

 

For years now, “use it or lose it” has been sage advice for older men and women hoping to keep memory sharp. But while you’re challenging your intellect by solving crossword puzzles or mastering a foreign language, set aside some time for another mind-preserving activity: exercise. A six-year study of 349 adults age 55 and over has provided solid new evidence that staying physically fit as you age keeps your brain as well as your body in shape.

 The new findings should be enough to get just about anyone off the couch and onto the walking path or exercise bike. Simply put, the people in the study who were most physically fit maintained more of their mental acuity over the course of the study than those who were less fit. The most fit had the best scores on mental function tests, while the least fit scored the worst.

 Previous evidence had already linked poor physical fitness with poor mental fitness, but the latest study, published in April 2003 in the Journal of the American Geriatrics Society, gives the body-mind connection a big boost for two reasons, according to the authors.

 One is that it’s the first well-designed study that looked exclusively at older people (age 55 and up). The other is that instead of relaying on the subjects’ own reports of their fitness activity, the researchers measured their fitness levels by putting them through treadmill tests-which never lie. For healthy people, the more cardiorespiratory exercise they get, the better they’ll do on the treadmill test.

2004, Reader’s Digest
Medical Breakthrough

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Mitochondria and Diabetes

Type 2 diabetes affects 150 million people worldwide. With new estimates that this number may double by the year 2025.  One of the earliest symptoms of type 2 diabetes is the development of insulin resistance in muscle, a condition often accompanied by the unusual accumulation of intracellular fatty acids that are normally broken down by mitochondria. This and other facts have led researchers to focus increasingly on the mitochondrial dysfunction as a possible culprit in the disease.

 Support for this hypothesis is  provided  by  Petersen et al. who used  magnetic resonance spectroscopy to study skeletal muscle function in healthy young offspring of patients with type 2 diabetes. Compared with matched controls the muscle of these individuals was severely insulin-resistant and showed an 80% increase in the level of intracellular fatty acids as well a as 30% reduction in mitochondrial ATP production. The authors speculated that the insulin resistance is caused   by   an   inherited   defect in mitochondrial oxidative phosphorylation.

5 March, 2004 Science Vol. 303

 

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Cell fusion: New way to repair organs, deliver cancer vaccines

 Researchers led by Dr. Stephen Russell at Mayo Clinic, the United States, have developed a way to biologically fuse living cells through the use of a genetically engineered cell membrane. Named “biofusion”, this process represents a promising new technological platform for enlisting the natural properties of fused cells to kill cancers, stimulate immune responses or repair damaged tissues.

 The key to biological cell fusion is that when two cells come into contact, fusion proteins on the surface of one cell recognize a receptor on the other cell. This act of recognition triggers fusion of their respective outer lipid membranes, just like two bubbles merging into one big bubble. However, when cancer cells fuse with each other, they may grow dramatically, containing up to 1,000 cancer cells, which is unviable and the cancer cells therefore die. The fact that fused cancer cells kill each other has been known for quite some time. However, the missing element has been a way to direct fusion partners to exploit this tendency and use it as a basis for anti-cancer treatment. The ability to target fusion partners is important since if the wrong cells fuse, then healthy cells, instead of the cancerous cells, could be killed.

According to Dr. Russell, their biofusion research brings a new level of control to the system so that the right fusion matches are made to serve therapeutic ends. The study offers a biotechnological platform that provides a way to choose and direct the agents of fusion by getting tumour cells to fuse with dendritic cells, a type of cell in the immune system. The result is biofusion that prompts the immune system to attack the tumour. The ability to fuse tumour cells to treat cancers is one application that researchers have envisioned for their biofusion platform. Another possible application involves cancer vaccines that prevent cancer from progressing or developing. Biofusion involves putting genes inside the body’s dendritic cells that will cause them to fuse directly with tumours at multiple sites in the patient.

A third possible application, still in the concept stages, involves stem cells. Research has shown that some of the stem cells’ repair properties come from their ability to fuse with cells that are naturally resident in the organs they are repairing. The new biofusion technology can be exploited to genetically engineer stem cells so that they fuse quickly and efficiently to a target site and thereby direct the repair process.

March-April 2004, Vatis Update: Biotechnology

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Sugar-coated menance

Researchers link aerated drinks to diabetes in women: Woman who drink more than one soft drink a day are more likely to suffer from diabetes than females who consume less than one a month, according to a research. The study, is based on the analysis of data from a health study of 51,603 nurses. Researchers scrutinized survey forms filled in by the nurses in 1991, 1995 and 1999, detailing their eating habits, weight, physical activity and health problems. The researchers found there were 741 new cases of type-2 diabetes during the span, and women who drank one or more sugar-sweetened soft drinks a day were twice as likely to develop diabetes than those who consumed fewer than one a month. When factors such as weight, diet and lifestyle were considered, the researchers found that women drinking sugary sodas were 1.3 times more likely to develop the disease.

 “The findings led us to suggest that in addition to being the sources of extra calories, the beverages might also increase diabetes risk because their high amount of rapidly absorbed sugars causes a dramatic rise in glucose and insulin concentration in the body,” Therefore one has to keep the soda consumption low.

 Fruit juice consumption was not associated with the diabetes risk and diet soft drinks were not statistically important, but sugared fruit punch showed similar result to sugared soda. Diabetes experts agree with the findings. “The study must impel doctors to ask the patients about their soda consumption,” asserts Caroline M Apovian, associate professor of medicine at the Boston University School of Medicine, USA.

September 30, 2023 Down To Earth

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Babymaking after 50 gets the green light

 

At 50, many women are looking menopause square in the face. But a few are looking at a far different phenomenon: new motherhood, thanks to assisted reproductive techniques such as donor eggs and in vitro fertilization. And according to a study published in the Journal of the American Medical Association, for healthy women, there’s no clear medical reason not to.

The study looked at 77 women ages 50 to 63, all of whom were postmenopausal and used donated eggs. It found that the women’s rates of pregnancy, multiple gestation (twins, triplets, etc.), and spontaneous abortion were similar to those of younger women who received donated eggs. The older women did have a higher risk of preeclampsia (a serious condition involving high blood pressure and fluid retention) and gestational diabetes, and most of their babies were delivered by cesarean section.

 The numbers of women over 50 who give birth is small but growing. According to the Centres for Disease Control and Prevention, there were 255 births in the United States to women ages 50 to 54 in 2000, up from 174 in 1999-a 46 percent increase. That figure dropped slightly in 2001, to 239.

2004, Reader’s Digest
Medical Breakthrough

 

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FDA approves new biotech asthma drug

The United States Food and Drug Administration (FDA) has approved the first biotechnology for asthma. Xolair, a drug administered by injecting it into the body once or twice a month, was developed by Genetech Inc., Novartis AG and Tanox Inc., and is aimed at treating moderate to severe asthma triggered by allergies. Xolair works by disabling a naturally occurring antibody called IgE, which triggers the release of chemicals that cause inflammation, rather than the symptoms that inhaled corticosteroids address. At a wholesale price of US$433 a vial, Xolair’s annual cost per patient will work out around US$10,000-US$12,000 per year.

July-August 2003,Vatis Update: Biotechnology

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A better way to rule out heart attacks

You feel pressure in your chest, and you’re sweating and feeling panicky. You’re sure you’re having a heart attack-but are you? Almost four out of five people rushed to emergency rooms with heart attack symptoms are not actually having heart attacks. Now doctors have a new blood test at their disposal to help rule out false alarms. Approved by the FDA in February 2003, the test is known as albumin cobalt binding (ACB).

   When heart tissue is starved for oxygen, as it is during a heart attack, a blood protein called albumin changes properties, binding less easily to cobalt, a metallic element. For the ACB test, emergency room personnel simply add a bit of cobalt to the patient’s blood sample. The chemical reaction that takes place provides a good indication of whether a heart attack has taken place.

ACB can be used only negatively-that is, to rule out heart attacks rather than to confirm that one has occurred. Also, it isn’t foolproof, which is one reason it was approved for use only in conjunction with two existing tests–an electrocardiogram, which measures the heart’s electrical activity, and a test for toponin, another blood protein.

   The three tests make a good team. One study showed that when the ACB test was added to the other two, doctors were able to rule out heart attacks 70 percent of the time, up from 50 percent. That means more very relieved people can be sent home earlier, and precious emergency room resources can be better directed to where they’re needed most.

2004, Reader’s Digest
Medical Breakthrough

 

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Check it!

Medical products leach out toxic chemicals: Numerous people, including newborns, are being exposed to a toxin via medical products, indicates a recent reports. Di (2-ethylhexyl) phthalate (DEHP), the toxin, is found in products made of polyvinyl chloride (PVC). DEHP is added to PVC so that it gets softened to manufacture products, like blood bags, urine bags and tubes.

   The report, Preventing Harm from Phthalates, Avoiding PVC in Hospitals, has been released by Health Care Without Harm, a coalition of 437 organizations. At least 48 products used in European hospitals were tested. Almost 39 products contained DEHP, which accounted for 17 to 41 per cent of the total weight of the product. Since DEHP is not chemically bound to PVC, it leaches from PVC products depending on variety of factors, including storage and usage temperatures. Particularly troubling is the ‘potential’ exposure for premature babies. “These babies receive one or more blood transfusions per week…DEHP has been detected at levels as high as 174 milligrammes per litre (mg/l) of packed red blood cells and 889 mg/l of plasma.”

 Animal experiments indicate that exposure to DEHP leads to abnormal sexual development as well as skeletal, cardiovascular, eye and neural tube defects. Whereas the European Union has banned the use of DEHP in cosmetics, personal care products and certain toys, its use in medical products is out of control.  In India too there is no regulation on the use of phthalates and PVC.

August 31, 2023 Down To Earth

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RNA enzymes act like protein enzymes

Dr. Nils Walter and associates at the University of Michigan and his colleagues at Harvard University, Massachusetts, USA have studied how changes in ribozyme (RNA enzyme) molecules affect their activity, in order to understand how evolution had shaped ribozymes to function and to find ways of manipulating them for useful purposes.

Walter’s group combined a technique called single molecule fluorescence resonance energy transfer (FRET) with mathematical simulations to study a ribozyme involved in the replication of a tobacco-infecting virus. Like protein enzyme, ribozymes accelerate chemical reactions inside cells. Just as a protein enzyme is not a static structure, a ribozyme also changes shape, cycling back and forth between its compact, catalytically active form and its inactive, extended form. Single-molecule FRET allowed the scientists to directly observe and measure how quickly the ribozyme switched forms and how these rates changed when various parts of the molecule were altered.

The researchers observed that the modifications made anywhere on the molecule, even far from the site where the chemical reaction occurred, affected the rate of catalysis. Thus, the study gave the evidence for the first time that ribozymes behaved like protein enzymes and that there was a network of motions that made a ribozyme act as a whole, just like a protein enzyme. According to Dr. Walter, information on how ribozymes work is important for answering fundamental question of biology and the work may also lead to practical applications.

July-August 2004,
Vatis Update: Biotechnology

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Wonder leaf

A herb used for centuries in Indian cooking has the potential to control diabetes, according to scientists from king’s College, the UK. The curry leaf – a must in many south Indian dishes – contains agents that slow down the rate of the rate of starch-to-glucose breakdown in people suffering from diabetes. The leaves can also control the amount of glucose entering the bloodstream.

November 15, 2004 Down To Earth

 

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Human genome-wide RNAi library for research

A group of scientists led by Dr. Greg Hannon of Cold Spring Harbour Laboratory (CSHL), New York, US, has announced the creation of the first library of human RNA interference (RNAi) clones, which would finally provide users the ability to shut off virtually every gene in human genome. Based on short-hairpin RNA (shRNA) a versatile and powerful method for triggering RNAi, the library is the first DNA vector-based, human genome-wide RNAi library that is sequence-verified. Several leading pharmaceutical companies have entered into agreements with CSHL to take advantage of the strong potential for therapeutic discovery that this powerful library promises to deliver.

 RNAi phenomenon has the potential to shut off only individual genes. By individually targeting more than 10,000 human genes through this sequence-based method, companies could rapidly identify and validate target genes that cause disease, and develop drug to hit those targets.

 The shRNA method developed by Dr. Hannon and his colleagues is one of the most efficient method for triggering RNAi and has been validated in a large number of studies with different animal and human cell cultures, as well as in whole animals, where the method has been shown to trigger stable, heritable gene silencing. In addition, the sequence-validated library of shRNA molecules targets each one of more than 10,000 different human genes in triplicate, with three different gene specific interfering RNAs. According to Dr. Hannon, the method could be adopted by pharmaceutical and biotechnology industries to systematically search for targets for new drugs for cancer and other diseases.

May-June 2004, Vatis Update: Biotechnology

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Less lung, better life for some

To spot someone with the lung-destroying disease emphysema, just look for the characteristic barrel shaped chest. This physical oddity occurs as oxygen-starved lungs grow larger and take up more space in the chest cavity, causing the diaphragm to flatten and making it even harder for the lungs to move air in and out. In recent years, a potentially lifesaving surgery called lung volume reduction surgery, in which 20 to 30 percent of the lung is removed, has become popular. While not a cure, it seemed to improve breathing by creating more room in the chest.

 Evidence on the effectiveness of the surgery was mixed, and with a price tag of $35,000 or more, the procedure is expensive. Medicare, the government insurance program for the elderly, refused to cover it,  putting it out of reach for most people with the disease. Now, a landmark study, published in a May 2003 issue of the New England Journal of Medicine and paid for by Medicare and other government agencies, suggests that for about 10 percent of people with emphysema, the surgery not only improves quality of life but extends life as well.

2004, Reader’s Digest
Medical Breakthrough

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Male hormones for memory?

It’s no secret that aging men experience a decline in two things they’d just as soon hang onto-the male hormone testosterone and cognitive ability, including memory, reasoning, and learning. Now, a study of men between ages 51 and 91 has confirmed a long-suspected connection between the two.

 Scientists working with a research program known as the Baltimore Longitudinal Study of Aging followed some 400 men for 10 years, analyzing their blood levels of testosterone and their scores on a series of cognition tests. The results were clear: More testosterone in the blood meant better mental function. The researchers say the study shows a “beneficial relationship” between testosterone and mental performance in older men. Larger studies are needed to show whether testosterone replacement actually   protects mental function. Testosterone replacement therapy, like estrogen replacement therapy for women, poses serious safety concerns.

2004, Reader’s Digest
Medical Breakthr
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Healthy Appetite

           Since its discovery 5 years ago, the stomach-derived peptide ghrelin has been the subject of intense research. Dubbed the “hunger hormone”, ghrelin stimulates food intake and body weight gain when administered to rodents possibly through direct action on the brain.

     These observations prompted speculation that pharmacological inhibitors of ghrelin production would be valuable drugs for the treatment of obesity.

To study the physiological role of ghrelin, Wortley et al. generated ghrelin-deficient mice. Surprisingly, the mutant mice showed normal food in-take, basal metabolic rate, and body weight. In contrast to wild-type mice, however, ghrelin-deficient mice on a high-fat diet burned more fat than carbohydrate, suggesting that ghrelin may play a role in regulating the metabolic substrates used for the maintenance of energy balance. In a complementary study, Sun et al. found that mice deficient in the receptor for ghrelin also showed no major abnormalities in food intake or body composition. Together, the studies indicate that ghrelin is not an essential regulator of appetite, and its role in body weight regulation may be more complex than previously envisaged.

4 June 2004, Science Vol. 304

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Fixing broken genes

Gene therapy can cure genetic diseases by repairing the mutations that lie beneath them. A new federal database, dubbed the Genetic Modification Clinical Research Information System (GeMCRIS), holds protocols for more than 600 gene therapy trials completed or launched since 1990. Users can search the site by disease, investigator, vector, or location, and the database includes abstracts as well as details on methods. Some of the information was already on the web, but the new collection is “easier to navigate,” says  Allan  Shipp  of the  National  Institutes  of  Health, which  developed the  site  with the U.S. Food and Drug Administration.

GeMCRIS will also allow investigators to submit reports of harmful events during gene therapy trials directly to the database.  Although these reports won’t be posted on the public part of the Website, Shipp says this feature will make it easier for agency   officials to look across trials for safety problems.

April 9, 2004  Science Vol. 304

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Edited by Dr. A. M. Mehandale

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