Tuesday, February 21, 2017

The Metabolic Syndrome

The metabolic syndrome refers to that constellation of risk factors that increase the likelihood of such potentially life-threatening conditions as coronary heart disease (CHD), stroke and diabetes.  It is now estimated that some forty-seven million individuals currently suffer from metabolic syndrome within the United States.  The size of this at-risk population is a cause for concern from a public health perspective.  On account of the fact that this population is growing strongly suggest that there are environmental factors involved and that need to be explored.

The five conditions enumerated below are referred to as metabolic risk factors and they are -
  • ·         “A large waistline. This also is called abdominal obesity.  Excess fat in the stomach area is a greater risk factor for heart disease than excess fat in other parts of the body, such as on the hips.
  • ·         A high triglyceride level (or you're on medicine to treat high triglycerides). Triglycerides are a type of fat found in the blood.
  • ·         A low HDL cholesterol level (or you're on medicine to treat low HDL cholesterol). HDL sometimes is called "good" cholesterol. This is because it helps remove cholesterol from your arteries. A low HDL cholesterol level raises your risk for heart disease.
  • ·         High blood pressure (or you're on medicine to treat high blood pressure). Blood pressure is the force of blood pushing against the walls of your arteries as your heart pumps blood. If this pressure rises and stays high over time, it can damage your heart and lead to plaque buildup.
  • ·         High fasting blood sugar (or you're on medicine to treat high blood sugar). Mildly high blood sugar may be an early sign of diabetes.”

The projected risk for heart disease, diabetes, and stroke increases with the number of metabolic risk factors presented. The risk of having metabolic syndrome is also closely linked to obesity and a lack of physical activity.


Insulin resistance is a definitive risk factor for the metabolic syndrome and is strongly associated with Type II Diabetes.  Insulin is the small protein hormone produced by specialized cells of the pancreas (Islets of Langerhans).  Insulin (see image below) is produced in response to the presence of elevated glucose in the blood – usually following a meal – and is responsible for regulating glucose levels in the blood.  Insulin resistance refers to that condition in which the body fails to use this hormone properly.

    Structure of Human Insulin

Tuesday, January 17, 2017

Human Pancreatic Cancer and CD155 Expression

The cell surface transmembrane glycoprotein CD 155 is expressed in many different human tissue cells. This protein has also been shown to be expressed in pancreatic cells in patients suffering from pancreatic cancer. CD 155 is also referred to as a poliovirus receptor (PVR) on account of the fact that it has been implicated in infection with poliovirus in the primate animal model. Current evidence suggests that its function within normal cells is associated with maintaining cohesion between epithelial cells.

S. Nishiwada and his colleagues from the Department of Surgery, Nara Medical University in Kashihara Nara, Japapn have put considerable effort into the study of the role CD 155 expression in human pancreatic cancer within a clinical setting.

In their study of 134 patients with pancreatic cancer, they found that those patients that demonstrated high levels of CD 155 expression also showed a poorer postoperative prognosis than those with low expression of this protein. In addition, they have found an inverse relationship between the expression of CD 155 and the body’s ability to dispatch tumor-infiltrating lymphocytes to the site of the tumor in order to destroy cancerous cells. Furthermore, expression of CD 155 positively correlated with increased growth of the malignancy and angiogenesis – growth of new blood vessels towards the growing tumor. Both of these effects enhances tumor growth. As would be expected, suppression of CD 155 expression, inhibited cell division within pancreatic cancer cells.

Given these important findings, CD 155 may prove to be an important target in pancreatic cancer therapy.

Monday, December 19, 2016

Plasma Membrane Compartments and Cytokine Signaling

The cell (plasma) membrane is a complex array of lipids and proteins that plays an essential role in the communication between the cell and its external environment (see image below).  In complex multi-cellular organisms, individual tissue cells communicate with vast varieties of factors including hormones and cytokines that are found in the tissue fluids that bathe cells and within the circulatory system that delivers nutrients to these cells.


Cytokines are a special class of compounds including interferon (IFN) (see structure below) and interleukins.  These substances are low molecular weight proteins often bound to sugar molecules (glycoproteins) that promote cell to cell communication within the immune system in response to inflammation, infectious agents and trauma.

Interferon


Changiiang You and his colleagues from *the Universitat Osnabruck, Germany, studied in detail the interaction dynamics of the complex array of signaling components and receptors on the plasma membrane especially in regard to IFN.  Interferons augment the immune system response to viral infections and impede the growth of cancerous cells through the regulation of specific genes whose gene products impact cell growth.

The results of their extensive investigation demonstrated that microcompartmentalization plays an essential role in facilitating binding of IFN to its specific receptor on the plasma membrane and the resulting cascade of signaling events that leads to gene expression (see image below).  They found that the maintenance of the integrity of the membrane skeleton (MSK) is of crucial importance.




These finding are of value; because, they help elucidate the complex interactions that are required to insure the successful role of key factors like interferon in proper cell function.

Monday, November 21, 2016

Site Specific Phosphorylation of Tau Inhibits Alzheimer’s in Mice

Alzheimer’s disease impacts many individuals in the latter stages of life.  It is a form of dementia that is very devastating to the individuals affected and their families.  On the molecular level, the disease is indicated by extracellular protein “plaques” that are composed of amyloid-β (Aβ) and an accumulation of so-called, “neurofibrillary tangles” within the neurons (see images below).  These tangles are composed of tau protein.  Amyloids represent aggregates of proteins that are stuck together and pose problems for cellular health and development in tissues.  This is especially important within the central nervous system since communication between neurons is of such vital importance.





The accumulated evidence suggests that it is the combined impact of Aβ and tau that lead to the neuronal dysfunction that is indicated by the severe cognitive deficits exhibited by individual with this disease.  Furthermore, the production of Aβ seems to trigger the subsequent phosphorylation of tau protein that lead to its deposition and ultimately to cognitive deficits.  In mouse animal models, the depletion of tau prevents Aβ toxicity.  It seems that by the time the symptoms are evident, significant cell damage has already occurred.

However, recent studies by Dr. Arne Ittner and his colleagues from the School of Medical Sciences at UNSW Australia have shown that site-specific phosphorylation of tau directed by the neuronal p38 mitogen-activated protein kinase enzyme (p38γ) actually inhibited Aβ toxicity.  Furthermore, the depletion of p38γ worsened cognitive defects and increasing p38γ eliminated these deficits.
 

These results are of importance; for, they demonstrate that phosphorylation of tau may or may not be detrimental depending upon the site(s) on the protein structure that are impacted.

Saturday, November 5, 2016

The Impact of Climate Change on Desertification

Climate Change and Desertification - The following is a link to an extensive New York Times article regarding the expansion of the Tengger desert in China and the impact of this change on the affected population - 


Saturday, October 29, 2016

Integration of Newly-Formed Neurons within the Adult Human Brain

The learning process that proceeds within the adult human brain has long been an intense interest of study for neuroscientists especially in regards to the events that unfold on a cellular and molecular level.  It has been shown that physical activity as well as the experience that comes with being in novel environments triggers the production, development and eventual connectivity of newly-formed neurons within the adult human brain.

Diego D. Alvarez and his colleagues (Laboratorio de Plasticidad Neuronal, Fundación Instituto Leloir–Instituto de Investigaciones Bioquímicas de Buenos Aires–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Patricias Argentinas 435, Buenos Aires C1405BWE, Argentina) focused their studies on the mechanism through which the experience of an enriched environment (EE) impacts the incorporation of newly-formed adult neurons into the hippocampal network – an area of the human brain involved in retaining declarative (explicit) memory.  Declarative memory refers to the memory of facts and events.

The cells of interest are referred to as granule cells (GCs) (see image below).  In the investigators’ study of newly-formed GCs using the mouse animal model, they found that exposing the test animal subjects to EE accelerated the incorporation of these neurons into the microcircuits of the dentate gyrus – the apparent site for the establishment of new memories.


Granule Cells

In addition, further study demonstrated that in order for this incorporation of new GCs to proceed, the process required the participation of parvalbumin y-aminobutyric acid-releasing interneurons (PV-INs).  Inactivation of PV-INs effectively prevented the effects of EE.  Neuronal stem cells (NSC) of the adult hippocampus are the precursors of GCs of the dentate gyrus.  
  

These results further our understanding of the complex cellular and molecular mechanisms involved in incorporating new memories in the adult human brain.

Friday, October 14, 2016

Natural Killer Cells in the Treatment of Cancer

It has been well established that the human immune system has the inherent capability to recognize and eliminate aberrant tissue cells in the body that have become transformed into cancerous cells capable of metastasis.  The natural process of finding and eliminating these cells is referred to as cancer surveillance.  It is this understanding that has led to the development of clinical approaches taking advantage of this phenomenon.  The techniques employed in this regard are classified under the heading, cancer immunotherapy.

There is a particular subset of circulating immuno-competent white blood cells referred to as natural killer cells that play a significant role in the body’s response to infectious pathogens as well as in cancer surveillance (see image below).  Dr. Rizwan Rowee and is colleagues from the Department of Medicine, Oncology Division Washington University School of Medicine in St. Louis investigated the properties of natural killer cells in regard to their ability to identify and destroy cancerous cells.  They were particularly interested in their “memory” capacity.  It has long been known that subsets of immuno-competent cells retain the capacity to recognize and attack particular targets from previous encounters.  This is an indispensable feature of a normal immune system.


Natural Killer Cells Attacking a Target Cell

Following exhaustive study and analysis of these natural killer cells with human leukemic cells in culture, the investigators discovered that natural killer cells with memory-like capability actually demonstrated an anti-leukemic effect against patients with acute myeloid leukemia (AML).  In some cases, this treatment led to clinical remissions.  The investigators reported that, “Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML.”


These are very important findings especially in regard to the treatment of patients with AML; since, this disease is a particularly aggressive form of leukemia.