Psychiatry

Maternal Antibodies May Trigger up to 25% of Autism Cases

Judy Van de Water, PhD, and colleagues have coined the term "maternal autoantibody–related," or MAR, autism

Maternal antibodies that interfere with fetal brain proteins during pregnancy may be responsible for roughly one quarter of cases of autism spectrum disorder (ASD), a new study suggests.

Critical Role in Brain Development
The antigens include the following: lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2), and Y-box-binding protein.
In 246 mothers of children with ASD and 149 mothers of typically developing children, maternal reactivity to any of these antigens, individually or in combination, was statistically significantly associated with having a child with ASD (odds ratio, 3.26; 95% confidence interval, 1.92 - 5.53), the researchers found.
Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of children with ASD and in only 1% of mothers of typically developing children.
Behaviorally, the researchers found that children with ASD whose mothers have autoantibodies targeting a subset of these antigens had greater overall impairment compared with children with ASD whose mothers lack these particular antibodies.
This study, coupled with several prior studies, provides "compelling evidence" that placental transfer of maternal antibodies could alter fetal neurodevelopment and could play a role in autism, they note.
"Each of the target autoantigens...is known to have a critical role in the developing brain and interference with the level or function of more than one of them could act synergistically to change the trajectory of brain development," the investigators write.
"The effect of MAR autoantibodies could occur through a direct antigen–antibody interaction, thereby either decreasing the abundance of or causing functional interference of the target proteins. Alternatively, the presence of these maternal antibodies may merely serve as a biomarker of cell destruction," they point out.
Clinical Implications
Dr. Van de Water told Medscape Medical News that their new findings have potential implications for diagnosis and treatment.
"We can work toward the development of a clinical test to determine the risk of having a child with autism preconception or during the early postnatal period, which would be especially important in the high-risk population of those women who already have at least 1 child on the spectrum," she said.
"It's important to note that this would be a rule-in test, as a negative result would not necessarily mean that you would have a typically developing child, but if you are positive, your risk of having a child with ASD is greater than 99%," she added.
"The second implication is that we can explore a target therapeutic approach in the future through a better understanding of the specific antibody targets," Dr. Van de Water said.
She said her group is now working on identifying the specific sites on the protein targets that are recognized by the MAR antibodies (the epitopes), "which will allow us to build a more specific animal model. We will use this model to determine the mechanism through which these antibodies affect neurodevelopment, or their true pathologic significance."

source from 

Medscape Medical News by M.Madan Mohan. Librarian, VMMC.

'Caution' Warranted if Consuming Artificial Sweeteners

Consumption of noncaloric, artificially sweetened beverages (ASBs) is associated with an increased risk for disease variety of chronic diseases, according to an opinion article by Susan E. Swithers, PhD, a professor of behavioral neuroscience at Purdue University in West Lafayette, Indiana, published online July 10 in Trends in Endocrinology & Metabolism.

"Frequent consumers of these sugar substitutes may...be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease,"

The prospective studies Dr. Swithers reviewed found an elevated risk for weight gain and obesity, metabolic syndrome, type 2 diabetes, coronary heart disease, and hypertension in those who consumed ASBs. No decreased risk for weight gain or increased body fat percentage was associated with ASB intake.

 "In [the] short-term, ASBs is preferable to the use of SSBs. For those who want to kick the habit of drinking sugary soda, diet soda may be the beverage equivalent of a nicotine patch: it can be used in small amounts, for a short time. For most people, plain water and unsweetened coffee or tea are more healthy alternatives to either SSBs or ASBs,"
Hormones, Brain Response Altered

Dr. Swithers reviewed 2 interventional studies. The first found that children of normal weight who consume ASBs may have decreased weight gain compared with those who consume SSBs. In the second study, overweight and obese adults who substituted water or ASBs for SSBs had no greater weight loss at 6 months than an attentional control group.

Brain responses are altered in those who consume artificial sweeteners compared with those who consume caloric sweeteners. In imaging studies of the human brain, sucrose activates dopaminergic midbrain areas involved with reward, but sucralose does not. Sucralose also reduces activation in other pathways related to taste when compared with sucrose.

 Dr. Swithers concludes "Current findings suggest that caution about the overall sweetening of the diet is warranted, regardless of whether the sweetener provides energy directly or not,"

Source from Medscape Medical News  by M.Madan Mohan. Librarian VMMC.

AVIAN INFLUENZA

Human infection with avian influenza A H7N9 virus: an assessment of clinical severity Hongjie Yu MD a †, Benjamin J Cowling PhD

Summary

Background

Characterisation of the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian influenza A H7N9 virus, which emerged in China in early 2013.

Methods

We obtained information about laboratory-confirmed cases of avian influenza A H7N9 virus infection reported as of May 28, 2013, from an integrated database built by the Chinese Center for Disease Control and Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confirmed cases detected through sentinel influenza-like illness surveillance to estimate the symptomatic case fatality risk.

Findings

Of 123 patients with laboratory-confirmed avian influenza A H7N9 virus infection who were admitted to hospital, 37 (30%) had died and 69 (56%) had recovered by May 28, 2013. After we accounted for incomplete data for 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26—45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60—77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76—90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with influenza-like illness associated with influenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63—460) and 2800 (1000—9400) per 100 000 symptomatic cases.

Interpretation

Human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human 

This article available The Lancet Journal 2013. Further details Contact: Librarian. VMMC

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HEPATIC ARTERY DOPPLER INDICES:

HEPATIC ARTERY DOPPLER INDICES:

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Hepatic Artery Resistive Index: (HARI): Peak systolic velocity minus end-diastolic velocity divided by the peak systolic velocity.

The Early Systolic Acceleration (ESA) in the hepatic artery is the slope of tangent of the initial systolic upsweep of the arterial waveform i.e. duration of upstroke from end-diastolic to peak systole, measured using calipers. The time corresponding to ESA was computed and this was referred to as the Hepatic Artery Acceleration Time (HAAT) in sec. The Value used in this study was obtained by taking an average of three measurements.

The Hepatic Artery Acceleration Index (HAAI) is the ratio between the acceleration of the Doppler special waveform and the relative peak systolic velocity. The systolic acceleration was calculated as a change in the distance between the beginning of systolic flow and the peak systolic velocity (cm/sec), divided by the acceleration time. The acceleration index is expressed in frequency units as KHz/sec or in velocity units as cm/sec^{2 .}

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STEM CELL RESEARCH

What are Stem Cells?

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources:

1. Embryos formed during the blastocyst phase of embryological development (embryonic stem cells) and
2. Adult tissue (adult stem cells).

Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

Adult stem cells

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.
Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Embryonic stem cells

Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.
Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

9-week Human Embryo from Ectopic Pregnancy [by Ed Uthman, MD]
creative commons license

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.
However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the "inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Stem cell cultures

Human embryonic stem cell colony
[Wikipedia]

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

Stem cell lines

Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher - a process known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem cells.

Potency

Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most potent since they must become every type of cell in the body. The full classification includes:

• Totipotent - the ability to differentiate into all possible cell types. Examples are the zygote formed at egg fertilization and the first few cells that result from the division of the zygote.
• Pluripotent - the ability to differentiate into almost all cell types. Examples include embryonic stem cells and cells that are derived from the mesoderm, endoderm, and ectoderm germ layers that are formed in the beginning stages of embryonic stem cell differentiation.
• Multipotent - the ability to differentiate into a closely related family of cells. Examples include hematopoietic (adult) stem cells that can become red and white blood cells or platelets.
• Oligopotent - the ability to differentiate into a few cells. Examples include (adult) lymphoid or myeloid stem cells.
• Unipotent - the ability to only produce cells of their own type, but have the property of self-renewal required to be labeled a stem cell. Examples include (adult) muscle stem cells.

Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta.

What are stem cells - Video

A video on how stem cells work and develop.

Identification of stem cells

Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the laboratory to check for these properties.
One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and immune cells, it demonstrates its potency.
Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated or they may examine chromosomes.
To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of differentiated cells).

Research with stem cells

Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body, for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore, stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells powerful enough to regenerate damaged tissue under the right conditions.

Organ and tissue regeneration

Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.

Brain disease treatment

Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson's and Alzheimer's by replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving. Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are promising.

Cell deficiency therapy

Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease, repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to replace the insulin-producing cells that have been lost or destroyed by the patient's own immune system. The only current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for transplant.

Blood disease treatments

Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types, such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make these powerful cells more easily obtainable and to decrease the chances of a body's rejecting therapy.

General scientific discovery

Stem cell research is also useful for learning about human development. Undifferentiated stem cells eventually differentiate partly because a particular gene is turned on or off. Stem cell researchers may help to clarify the role that genes play in determining what genetic traits or mutations we receive. Cancer and other birth defects are also affected by abnormal cell division and differentiation. New therapies for diseases may be developed if we better understand how these agents attack the human body. Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug's effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on human volunteers.

Stem cell controversy

The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a fully-developed human.

When does life begin?

The core of this debate - similar to debates about abortion, for example - centers on the question, "When does life begin?" Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark the beginning of life - after the development of certain organs or after a certain time period.

Chimeras

People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop. This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people, however, object to the creation of an organism that is "part human".

Legal issues

The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However, the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that were created after August 2001.

Stem cell research news

Medical News Today is a leading resource for the latest headlines on stem cell research. So, check out our stem cell research news section. You can also sign up to daily stem cell news alerts or our weekly digest newsletters to ensure that you stay up-to-date with the latest news.

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This what are stem cells? information section was written by Peter Crosta for Medical News Today, and may not be re-produced in any way without the permission of Medical News Today.

STEM CELL RESEARCH