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.

Monday, October 10, 2016

Dr. Arnoldo Gabaldón

Malaria is one of the world’s deadliest diseases.  It is especially prevalent in the tropics.  The life cycle of the causative microbial parasite – members of the plasmodium genus i.e. Plasmodium vivax is complex involving the Anopheles mosquito as a vector (see images below).  The nature of the infection is such that it has eluded the development of an effective vaccine for many years. 

Human red cells infected by Plasmodium vivax

In light of this, it is quite surprising that Dr. Arnoldo Gabaldón, born in 1909, in Venezuela made a significant contribution to the understanding of this disease and its implications in regard to public health.
Gabaldón earned a doctorate in medical sciences at the Universidad Central de Venezuela. He continued his education internationally working in Hamburg and the United States at  the Rockefeller Foundation and ultimately received a doctorate from Johns Hopkins University in hygiene sciences with a specialty in protozoology. With this kind of medical background and expertise in infectious disease, he was asked to head the newly created Special Directorate of Malariology in his home country of Venezuela in 1936.  He held this post until 1950.
He successfully applied his understanding of the methodologies required to combat infectious disease to the rate and severity of malarial infection that gripped his country in the 1930s.  This included the emphasis on public hygiene and sanitation and the judicious application of anti-malarial drugs. His approach was so successful that mortality resulting from malarial infection was decreased significantly by 1944 and, more importantly, its control was seen as within reach.
This initial success was followed by an attempt to significantly reduce the Anopheles mosquito population.  For this purpose, the insecticide dichlorodiphenyltrichloroethane  (DDT) was used.  The historic data has revealed that “by 1950 the death rate from malaria in the country had been reduced to 9 per 100,000 inhabitants and was eradicated in an area of 132 000 km2. In 1955, 10 years after the program started the rate was lowered to 1 per 100 000 population and the eradicated area had increased to 305,414 km2.” On balance, it should be kept in mind that the discovery of the ecological burden posed by the use of DDT on the natural environment has effectively banned its application for many years.
Gabaldón is also credited with discovering a new species of malarial parasites and had focused a great deal of his efforts on further study of the Anopheles mosquito.  He was later appointed Minister of Health and Welfare between 1959 and 1964 in recognition of his premier understanding regarding issued of public health.  He died in September of 1990.

Arnoldo Gabaldón made a significant contribution to the principles and practices of public health around the area of infectious disease.  The example of his leadership has been emulated throughout the world and possibly has saved countless lives.