Friday, April 20, 2018

A Possible Effective Treatment for Ulcerative Colitis Using a Monoclonal Antibody


Ulcerative Colitis is serious ailment that has been shown to be an auto-immune disease that involves an attack by the ulcerative colitis patient’s own immune system against intestinal tissue.   According to a description of this disease as shown on the Mayo Clinic website –

“Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation and ulcers (sores) in your digestive tract. Ulcerative colitis affects the innermost lining of your large intestine (colon) and rectum. Symptoms usually develop over time, rather than suddenly.

“Ulcerative colitis can be debilitating and can sometimes lead to life-threatening complications. While it has no known cure, treatment can greatly reduce signs and symptoms of the disease and even bring about long-term remission.



“Ulcerative colitis symptoms can vary, depending on the severity of inflammation and where it occurs. Signs and symptoms may include:
·         Diarrhea, often with blood or pus
·         Abdominal pain and cramping
·         Rectal pain
·         Rectal bleeding — passing small amount of blood with stool
·         Urgency to defecate
·         Inability to defecate despite urgency
·         Weight loss
·         Fatigue
·         Fever
·         In children, failure to grow

“Most people with ulcerative colitis have mild to moderate symptoms. The course of ulcerative colitis may vary, with some people having long periods of remission.”

As stated above, this disease has no known cure.  However, there is strategy that is being investigated by Wendy J. Komocsar. and her colleagues in the laboratories of Eli Lilly and Company, Indianapolis, IN that utilizes the production of a monoclonal antibody that blocks the activity of BAFF.  BAFF is a natural B-cell activating factor – this factor effectively enhances B-cell survival.  B cells are a subset of the immune repertoire of circulating lymphocytes that are responsible for the production of antibodies.  In addition, it has been demonstrated that the overexpression of BAFF results in severe autoimmune disorders in mice.  Furthermore, elevated levels of BAFF have been shown to be present in some patients with autoimmune diseases.  The monoclonal antibody that has bee produced that blocks BAFF is a potential drug referred to as tabalumab.

This type of approach may provide the potential for providing relief for individual’s suffering from a variety of autoimmune disorders.

Tuesday, February 27, 2018

The Molecular Biology of Celiac Disease


Celiac disease is a so-called, “autoimmune disease” that impacts an estimated one percent of the population.  An auto-immune disease is caused by an individual’s immune system attacking its own tissue.  Other examples of diseases that fit this classification are multiple sclerosis (MS), pemphigus, rheumatoid arthritis and systemic lupus.

In Celiac disease, the tissue that is impacted involves the microscopic villi that line the lumen of the small intestine.  These structures provide the surface area through which digested nutrients are absorbed (see image below).  The patient with celiac disease presents with unexplained loss of weight and fatigue, anemia and constipation for example.  The destruction of these highly complex structures is irreversible; if, this condition is left untreated, it can be deadly.



The trigger for this auto-immune response is the presence of gluten - a protein found in wheat and related plants.  Gluten is a protein that is prevalent in Western diets.  In addition, research studies have demonstrated that the agent (antigen) that induces the autoimmune response is not the intact gluten protein but the protein after it is modified by the enzyme transglutaminase 2 (TG2) within the small intestine.  It seems that in normal tissues, although TR2 is an abundant enzyme, it exists primarily in the inactive state.
   
Chaitan Khosla and his colleagues at the University of California at Stafford have recently demonstrated that there is a cellular enzyme protein 57 (ERp57) that inactivates TG2.  Normally, ERp57 is involved in the process of protein folding within the cell.  Furthermore, it has been established that ERp57 inactivates TG2 outside the cell within the extra-cellular environment.  These data suggest that the etiology of celiac disease may relate to the functionality of ERp57.

These findings are significant; for, a more detailed understanding of the biological chemistry of celiac disease may open avenues of therapy that have heretofore remained elusive. 

Saturday, February 17, 2018

Stem Cells and the Risk of Atherosclerotic Cardiovascular Disease


Atherosclerosis is a condition often associated with age that involves a narrowing of the lumen of the arteries usually associated with age (see image below).  This condition often leads to coronary heart disease.  Traditionally there are a number of risk factors that are generally associated with this syndrome – high blood pressure (hypertension), high cholesterol, heredity, life style, diet etc.  However, a significant percentage of those individuals that show evidence of atherosclerosis have no known risk factors.  Research done by Dr. Siddhartha Jaiswal and his colleagues that has been published in the New England Journal of Medicine (July, 2017) sheds significant light on the possible etiology of this perplexing reality.



Within the bone marrow, reside stem cells that are so-called, pluripotent cells; they are responsible for the production of the body’s complement of immune-competent cells such as red blood cells, white blood cells including lymphocytes, neutrophils etc.  It has been well documented that over the lifetime of the individual these stem cell undergo mutations that can lead to blood – hematopoietic – cancers such as leukemia.
    
According to Jaiswal, “Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer.”

Jaiswal and his associates now have evidence that CHIP may be the underlying cause of atherosclerotic cardiovascular disease of no known etiology.  The results of their studies indicate that the presence of CHIP in the cell population of circulating blood was associated with a near doubling of the incidence of atherosclerotic cardiovascular disease.  Furthermore, the common mutations that were present in CHIP were found to be in the genes DNMT3A, TET2 AND ASXL1.  These genetic mutations have also been shown to be associated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).   These clones seem to be more prevalent with age – more that 10% of persons older than 70 years carry such a mutation.

This finding is significant in that it shed further light upon the etiology of atherosclerosis.

Tuesday, January 16, 2018

The Scientific Method

The scientific method is a proven way to find answers to questions regarding particular aspects of the natural world. It can be summarized in the following way –

• Question arises from known information – data
• Hypothesis proposed to explain data
• Experiment(s) conducted to prove or disprove the working hypothesis
• Experimental approach is precisely documented
• Results are reported
• Results are subject to peer-review.
• To be correct, the conclusion must explain all the data
• If correct, findings must be repeatable.

The following information is presented to highlight the theories that have been effectively discredited using the scientific method, the advances made through the application of the scientific method and the potential disasters that have been effectively averted through its application.


The Homunculus -There was a theory (proposed in the 16 century and popularized in the 19 century) that human sperm carried a miniature human (Homunculus) than subsequently developed into a fully developed infant at birth following fertilization

Image of Homunculus






 Image of an actual human spermatozoa showing DNA



 

The Martial Canals - Percival Lowell (1855 – 1916) proposed that there was intelligent life on Mars based upon sighting of purported Martian Canals

Image of Martian Canals as reported by Lowell
 

Image of Mars from space telemetry data







Spontaneous Generation – Theory that living organisms can arise spontaneously from decaying organic matter

Louis Pasteur’s (1822 1895) Classic Experiment that effectively refuted this belief.

The diagram below outlines his elegant approach






Earth’s Place in the Solar System – It was believed for many centuries that the earth was the center of the cosmos

Ptolemy’s (140 AD) Earth-Centric Model




Copernicus’ Model (1543) – Current Model




Ptolemy generated this convoluted model in attempting to fit the available astronomical data into the accepted belief that the earth was the center of the known universe.



HIV AIDS – In the early 1980’s a new, infectious and deadly disease appeared within human populations. In a just a few short years and with intense research efforts spear-headed by the Center for Disease Control (CDC), the cause was determined to be a so-called“retrovirus” (see diagrams below)– a discovery that ultimately averted a world-wide pandemic.

Image of an HIV virus





HIV AIDS Virus infecting human T-cell





George Washington’s Death (1799): An Example of Unscientific Medicine
His death was ultimately attributed to standard medical practice of that era. Washington came down with a respiratory infection. He underwent the following procedures via 3 different physicians –

• A half-pint of blood was extracted via leeches (see diagram below)



• Blisters were created on his throat to balance body fluids”
• Vinegar and sage tea mixtures were administered
• Emetics were given to induce vomiting.



The current understanding is that he died of iatrogenic causes – (caused by physician). His actual death was apparently caused by hypovolemic shock – a condition that occurs when more than 20% of the body’s fluid is lost. As a result, his heart was unable to pump sufficient blood volume to effectively deliver oxygen and nutriment to all the cells.
 
  
Rachel Carson – The Silent Spring (August 1972): The Inter-Connected Nature of the Natural World

In the 1950’s, DDT was sprayed to control beetles that are responsible for Dutch Elm Disease. Rachel Carson book documented the impact of DDT pesticide on natural environment especially on bird mortality. This book awakened the scientific community and the public to the ecological implications of human-caused environmental pollution. The Environmental Protection Agency was created in 1970 as a direct result of the growing concerns about the health of the natural environment.

Models of the DDT molecule



Ecological Implications –
• Earthworms ingest DDT from contaminated soil
• Robins (as an example) eat earthworms and concentrate DDT (biological magnification)
• DDT impacts shell production in the eggs – proves fatal to developing embryos
• DDT is an example of poly-chlorinated hydrocarbon (see diagrams above) that is fat
soluble with a long biological half-life.

DDT was ultimately banned for agricultural use – a policy that averted a catastrophic decline in bird populations due to DDT’s insidious effects.


Ozone Depletion - Ozone (O3) is a pollutant in the lower atmosphere. However, in the upper atmosphere, this molecule is vital for the filtering of dangerous UV radiation that normally bombards the earth. Holes in this protective layer was first report in 1985. As a result of intense scientific study, it was soon discovered that ozone was being destroyed by a by-product of a human-produced pollutant, chlorofluorocarbons (CFC - see diagram below). CFCs were once commonly used in refrigerants; until, they were banned in 1995. This ban ultimately helped replenish the ozone concentration in the upper atmosphere.

Diagram Illustrating this Process

  


The Examples cited above have been included in order to demonstrate the importance and relevance of science and the scientific method in everyday existence.

The End


Monday, January 8, 2018

The Bomb Cyclone

In the winter of 2018, the American Northeast was struck by fierce and extreme winter weather. This apparent weather anomaly was referred to as the “Bomb Cyclone.” It was characterized by a sudden and precipitous drop in barometric pressure accompanied by strong winds and cold arctic air.

Climate scientists have long predicted that accompanying the warming of the lower atomosphere and the oceans, one would expect an increase in the severity and frequency of extreme weather conditions...In a report found in the science section of Time magazine written by Bryan Walsh, the author suggests just such an explanation of this weather phenomenon.

"Sea ice is vanishing from the Arctic thanks to climate change, which leaves behind dark open ocean water, which absorbs more of the heat from the sun than reflective ice. That in turn is helping to cause the Arctic to warm faster than the rest of the planet, almost twice the global average. The jet stream—the belt of fast-flowing, westerly winds that essentially serves as the boundary between cold northern air and warmer southern air—is driven by temperature difference between the northerly latitudes and the tropical ones. Some scientists theorize that as that temperature difference narrows, it may weaken the jet stream, which in turns makes it more likely that cold Arctic air will escape the polar vortex and flow southward. Right now, an unusually large kink in the jet stream has that Arctic air flowing much further south than it usually would."

It should be kept in mind that this conclusion is preliminary: climate scientists would be first to admit that there is not enough accumulated data to unambiguously make this connection, However, numerous examples of extreme weather patterns have already been cited in the scientific literature.