Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by a type of immune cell in people with multiple sclerosis (MS) may play a role in the disease’s progression. The finding could lead to new targeted therapies for MS treatment.
B cells, said Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study, are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy.
In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges — the covering of the brain and spinal cord — that attract them. Once within the meninges or central nervous system, Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins but that damage oligodendrocytes, the cells that produce a protective substance called myelin.
The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and, in part, why they are attracted to the meninges and the nervous system.
The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons and bring messages from the brain to the muscles. The white parts of the brain are white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons. The myelin’s function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can ‘leak’ and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons.
The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, and after removing the cells from the culture collected material produced by the cells. After adding the material produced by the B cells, including the cells that produce myelin, to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.
‘We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage,’ Lisak said. Wayne State University

If you look old, your heart may feel old, according to research presented at the American Heart Association’s Scientific Sessions 2012.

In a new study, those who had three to four ageing signs — receding hairline at the temples, baldness at the head’s crown, earlobe crease, or yellow fatty deposits around the eyelid (xanthelasmata) — had a 57 percent increased risk for heart attack and a 39 percent increased risk for heart disease .

‘The visible signs of ageing reflect physiologic or biological age, not chronological age, and are independent of chronological age,’ said Anne Tybjaerg-Hansen, M.D., the study’s senior author and professor of clinical biochemistry at the University of Copenhagen in Denmark.

Researchers analysed 10,885 participants 40 years and older (45 percent women) in the Copenhagen Heart Study. Of these, 7,537 had frontoparietal baldness (receding hairline at the temples), 3,938 had crown top baldness, 3,405 had earlobe crease, and 678 had fatty deposits around the eye.

In 35 years of follow-up, 3,401 participants developed heart disease and 1,708 had a heart attack.

Individually and combined, these signs predicted heart attack and heart disease independent of traditional risk factors. Fatty deposits around the eye were the strongest individual predictor of both heart attack and heart disease.

Heart attack and heart disease risk increased with each additional sign of ageing in all age groups and among men and women. The highest risk was for those in their 70s and those with multiple signs of ageing.

In the study, nurses and laboratory technicians noted the quantity of gray hair, prominence of wrinkles, the type and extent of baldness, the presence of earlobe crease and eyelid deposits.

‘Checking these visible ageing signs should be a routine part of every doctor’s physical examination,’ Tybjaerg-Hansen said. American Heart Association

​Unfortunately, newspaper articles about young athletes dying suddenly on the field are not unheard of. Such reports fuel discussions about compulsory screening, for example of young footballers, for heart failure. Research by scientists from Ghent (VIB/UGent) and Italy will benefit these screening methods. They have discovered a link between mutations in a certain gene and the heart condition Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC).
ARVC is a hereditary heart condition in which the heart muscle (particularly the right ventricle) is partly replaced by fatty tissue and connective tissue. Cardiac arrhythmias can occur as a result of the changes in the heart muscle. Severe arrhythmias can cause dizziness or even lead to fainting or an acute cardiac arrest (= sudden death). ARVC is a progressive disease that usually presents during the teenage years.
Mutations in various genes have already been linked to ARVC. These are primarily genes that are responsible for the production of proteins in the desmosomes. Desmosomes are structures in the heart that ensure that the heart muscle cells remain connected to each other. Therefore, it was assumed that defects in the desmosomes were the most important factors in developing ARVC.
Together with Italian scientists, Jolanda van Hengel, studied patients with ARVC who did not exhibit mutations in the desmosomal genes. The scientists identified mutations in the CTNNA3 gene in these patients, which codes for the protein αT-catenin – a component of the area composita. The area composita is a structure specifically modified to the heart, where extra strong connections between cardiac muscle cells occur.
The scientists’ findings indicate that there is a link between mutations in the CTNNA3 gene and ARVC. It was demonstrated for the first time that – in addition to desmosomal genes – an area composita gene also plays a role in the development of ARVC. Future genetic screening tests for ARVC should include the CTNNA3 gene as a standard part of the test. This would increase the value of the screening. VIB

A new ‘traffic light’ test devised by Dr Nick Sheron and colleagues at University of Southampton and Southampton General Hospital could be used in primary care to diagnose liver fibrosis and cirrhosis in high risk populations more easily than at present.
Liver disease develops silently without symptoms, and many people have no idea they have liver failure until it is too late – one-third of people admitted to hospital with end-stage liver disease die within the first few months. A simple test available in primary care could diagnose disease much earlier, enabling those at risk to change their behaviour and save lives.
The Southampton Traffic Light (STL) test combines several different tests and clinical markers which are given a score that indicates the patient’s likelihood of developing liver fibrosis and liver cirrhosis.
The result comes in three colours: red means that the patient has liver scarring (fibrosis) and may even have cirrhosis, green means that there is no cirrhosis and the patient is highly unlikely to die from liver disease over the next five years. Amber means there is at least a 50:50 chance of scarring with a significant possibility of death within five years, and patients are advised to stop drinking to avoid further disease and death.
The test was given to over 1,000 patients, and their progress was carefully followed and monitored afterwards, in some cases over several years, to assess the accuracy of the test in predicting whether they developed liver fibrosis or cirrhosis.
The test proved to be accurate in severe liver disease, and while not a substitute for clinical judgement or other liver function tests, can provide GPs with an objective means to accurately assess the potential severity of liver fibrosis in high-risk patients – for example, heavy drinkers, those with type II diabetes, or obese people.
Dr Nick Sheron, lead author and Head of Clinical Hepatology at the University of Southampton, and consultant hepatologist at Southampton General Hospital, said: ‘We are reliant on general practitioners detecting liver disease in the community so they can intervene to prevent serious liver problems developing, but so far we haven’t been able to give them the tools they need to do this. We hope that this type of test for liver scarring may start to change this because the earlier we can detect liver disease, the more liver deaths we should be able to prevent.’ University of Southampton

Researchers in the Taub Institute at Columbia University Medical Center (CUMC) have identified a mechanism that appears to underlie the common sporadic (non-familial) form of Parkinson’s disease, the progressive movement disorder. The discovery highlights potential new therapeutic targets for Parkinson’s and could lead to a blood test for the disease. The study was based mainly on analysis of human brain tissue.
Studies of rare, familial (heritable) forms of Parkinson’s show that a protein called alpha-synuclein plays a role in the development of the disease. People who have extra copies of the alpha-synuclein gene produce excess alpha-synuclein protein, which can damage neurons. The effect is most pronounced in dopamine neurons, a population of brain cells in the substantia nigra that plays a key role in controlling normal movement and is lost in Parkinson’s. Another key feature of Parkinson’s is the presence of excess alpha-synuclein aggregates in the brain.
As the vast majority of patients with Parkinson’s do not carry rare familial mutations, a key question has been why these individuals with common sporadic Parkinson’s nonetheless acquire excess alpha-synuclein protein and lose critical dopamine neurons, leading to the disease.
Using a variety of techniques, including gene-expression analysis and gene-network mapping, the CUMC researchers discovered how common forms of alpha-synuclein contribute to sporadic Parkinson’s. ‘It turns out multiple different alpha-synuclein transcript forms are generated during the initial step in making the disease protein; our study implicates the longer transcript forms as the major culprits,’ said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and cell biology and neurology at CUMC. ‘Some very common genetic variants in the alpha-synuclein gene, present in many people, are known to impact the likelihood that an individual will suffer from sporadic Parkinson’s. In our study, we show that people with ‘bad’ variants of the gene make more of the elongated alpha-synuclein transcript forms. This ultimately means that more of the disease protein is made and may accumulate in the brain.’
‘An unusual aspect of our study is that it is based largely on detailed analysis of actual patient tissue, rather than solely on animal models,’ said Dr. Abeliovich. ‘In fact, the longer forms of alpha-synuclein are human-specific, as are the disease-associated genetic variants. Animal models don’t really get Parkinson’s, which underscores the importance of including the analysis of human brain tissue.’
‘Furthermore, we found that exposure to toxins associated with Parkinson’s can increase the abundance of this longer transcript form of alpha-synuclein. Thus, this mechanism may represent a common pathway by which environmental and genetic factors impact the disease,’ said Dr. Abeliovich.
The findings suggest that drugs that reduce the accumulation of elongated alpha-synuclein transcripts in the brain might have therapeutic value in the treatment of Parkinson’s. The CUMC team is currently searching for drug candidates and has identified several possibilities.
The study also found elevated levels of the alpha-synuclein elongated transcripts in the blood of a group of patients with sporadic Parkinson’s, compared with unaffected controls. This would suggest that a test for alpha-synuclein may serve as a biomarker for the disease. ‘There is a tremendous need for a biomarker for Parkinson’s, which now can be diagnosed only on the basis of clinical symptoms. The finding is particularly intriguing, but needs to be validated in additional patient groups,’ said Dr. Abeliovich. A biomarker could also speed clinical trials by giving researchers a more timely measure of a drug’s effectiveness. Columbia University Medical Center