Sunday, May 28, 2017

We have an obligation to fulfill


Every May, we have the opportunity to remember those who have given the ultimate sacrifice for their country. Many of us know comrades-in-arms who never returned home. Yet, for every one we know, there are tens of thousands more who served and never returned. It is often called, “The Price of Freedom.”  That is why we must never forget to honor them.

In these divisive times, it is easy to become entangled in the Left and the Right’s rhetoric. Too often, when this happens, we can forget what actions gave us the right to vote, to challenge, to protest, and to change what needs to be improved.

This weekend, we need to put aside our differences for a few moments and honor all those who served and never returned. General Logan’s words below say it far better.   

John A. Logan, Commander and Chief
HEADQUARTERS GRAND ARMY OF THE REPUBLIC

General Orders No.11, WASHINGTON, D.C., May 5, 1868

1. The 30th day of May, 1868, is designated for the purpose of strewing with flowers or otherwise decorating the graves of comrades who died in defense of their country during the late rebellion, and whose bodies now lie in almost every city, village, and hamlet church-yard in the land. In this observance, no form of ceremony is prescribed, but posts and comrades will in their own way arrange such fitting services and testimonials of respect as circumstances may permit.

We are organized, comrades, as our regulations tell us, for the purpose among other things, “of preserving and strengthening those kind and fraternal feelings which have bound together the soldiers, sailors, and marines who united to suppress the late rebellion.” What can aid more to assure this result than cherishing tenderly the memory of our heroic dead, who made their breasts a barricade between our country and its foes? Their soldier lives were the reveille of freedom to a race in chains, and their deaths the tattoo of rebellious tyranny in arms. We should guard their graves with sacred vigilance. All that the consecrated wealth and taste of the nation can add to their adornment and security is but a fitting tribute to the memory of her slain defenders. Let no wanton foot tread rudely on such hallowed grounds. Let pleasant paths invite the coming and going of reverent visitors and fond mourners. Let no vandalism of avarice or neglect, no ravages of time testify to the present or to the coming generations that we have forgotten as a people the cost of a free and undivided republic.

If other eyes grow dull, other hands slack, and other hearts cold in the solemn trust, ours shall keep it well as long as the light and warmth of life remain to us.
Let us, then, at the time appointed gather around their sacred remains and garland the passionless mounds above them with the choicest flowers of spring-time; let us raise above them the dear old flag they saved from his honor; let us in this solemn presence renew our pledges to aid and assist those whom they have left among us a sacred charge upon a nation’s gratitude, the soldier’s and sailor’s widow and orphan.

2. It is the purpose of the Commander-in-Chief to inaugurate this observance with the hope that it will be kept up from year to year, while a survivor of the war remains to honor the memory of his departed comrades. He earnestly desires the public press to lend its friendly aid in bringing to the notice of comrades in all parts of the country in time for simultaneous compliance therewith.

3. Department commanders will use efforts to make this order effective.

Photos: Military.com

General Order from Memorial Day website

Wednesday, May 24, 2017

New Research Paper Published on Kennedy's Disease

The World Journal of Biological Chemistry published another interesting Kennedy’s Disease study this week. Below is a portion of the abstract. The entire paper can be read by following the link below. This is preliminary research and more study is required to determine the potential benefits and possible side effects.

Background - The AR gene contains CAG repeats which affect receptor function, where fewer repeats leads to increased receptor sensitivity to circulating androgens and more repeats leads to decreased receptor sensitivity.

Identification of neuron selective androgen receptor inhibitors

World J Biol Chem. May 26, 2017; 8(2): 138-150

AIM

To identify neuron-selective androgen receptor (AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness.

METHODS

Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell type-selective AR inhibitors. Secondary screening in luciferase assays was used to identify the best cell-type specific AR inhibitors. The mechanism of action of a neuron-selective AR inhibitor was examined in vitro using luciferase reporter assays, immunofluorescence microscopy, and immunoprecipitations. Rats were treated with the most potent compound and tissue-selective AR inhibition was examined using RT-qPCR of AR-regulated genes and immunohistochemistry.

RESULTS

We identified the thiazole class of antibiotics as compounds able to inhibit AR signaling in a neuronal cell line but not a muscle cell line. One of these antibiotics, thiostrepton is able to inhibit the activity of both wild type and polyglutamine expanded AR in neuronal GT1-7 cells with nanomolar potency. The thiazole antibiotics are known to inhibit FOXM1 activity and accordingly, a novel FOXM1 inhibitor FDI-6 also inhibited AR activity in a neuron-selective fashion. The selective inhibition of AR is likely indirect as the varied structures of these compounds would not suggest that they are competitive antagonists. Indeed, we found that FOXM1 expression correlates with cell-type selectivity, FOXM1 co-localizes with AR in the nucleus, and that shRNA-mediated knock down of FOXM1 reduces AR activity and thiostrepton sensitivity in a neuronal cell line. Thiostrepton treatment reduces FOXM1 levels and the nuclear localization of beta-catenin, a known co-activator of both FOXM1 and AR, and reduces the association between beta-catenin and AR. Treatment of rats with thiostrepton demonstrated AR signaling inhibition in neurons, but not muscles.

CONCLUSION

Our results suggest that thiazole antibiotics, or other inhibitors of the AR-FOXM1 axis, can inhibit AR signaling selectively in motor neurons and may be useful in the treatment or prevention of SBMA symptoms.

Friday, May 19, 2017

What is Kennedy's Disease?

Back to the Basics

The Androgen Receptor Gene

The AR gene provides instructions for making a protein called an androgen receptor. Androgens are hormones (such as testosterone) that are important for normal male sexual development before birth and during puberty. Androgen receptors allow the body to respond appropriately to these hormones. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.

The receptors are present in many of the body's tissues, where they attach (bind) to androgens. The resulting androgen-receptor complex then binds to DNA and regulates the activity of androgen-responsive genes. By turning the genes on or off as necessary, the androgen receptor helps direct the development of male sexual characteristics. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.

In one region of the AR gene, a DNA segment known as CAG is repeated multiple times. This CAG segment is called a triplet or trinucleotide repeat. In most people, the number of CAG repeats in the AR gene ranges from fewer than 10 to about 37.

The AR Gene and Spinal Bulbar Muscular Atrophy

Kennedy’s Disease, aka, Spinal Bulbar Muscular Atrophy, results from a particular type of mutation, an expansion of the CAG trinucleotide repeat, in the AR gene. This receptor attaches (binds) to a class of hormones called androgens.

With Kennedy’s Disease, the CAG is abnormally repeated from 38 to more than 60 times causing a disorder of the specialized nerve cells that control muscle movement. Researchers believe that a fragment of the androgen receptor protein containing the CAG repeats accumulates within these cells and interferes with normal cell functions. This buildup leads to the gradual loss of motor neurons, which results in muscle weakness and wasting (atrophy).

People with a higher number of CAG repeats tend to develop signs and symptoms of Kennedy’s Disease at an earlier age. [ FrequentlyAsked Questions about KD ]

Characteristics of Spinal Bulbar Muscular Atrophy

Spinal Bulbar Muscular Atrophy mainly affects males and is characterized by muscle weakness and wasting (atrophy) that usually begins in adulthood and worsens slowly over time. Muscle wasting in the arms and legs results in cramping; leg muscle weakness can also lead to difficulty walking and a tendency to fall.

Certain muscles in the face and throat (bulbar muscles) are also affected, which causes progressive problems with swallowing and speech. Additionally, muscle twitches (fasciculations) are common. Some males with the disorder experience unusual breast development (gynecomastia) and may be unable to father a child (infertile).  [ CommonSymptoms ]

Inheritance Pattern

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females (who have two X chromosomes). [ GeneticChart ]

DNA Test

Fortunately, today there is a DNA test to determine if a person has Kennedy’s Disease. Your doctor can draw some blood and send it to a DNA lab for testing. Test results are normally returned within three-to-six weeks. [ TestDetails ]



Note: Most information provided by the Genetics Home Reference

Sunday, May 7, 2017

Great News - A Treatment for ALS


In case you missed it, the big news this week is the FDA fast-tracked the approval of a treatment for ALS. You can read about it here:  CNN Health and here:  FDAPress Release.

This is fantastic news for those living with ALS.

I have received a few inquiries asking if this drug could be helpful for treating Kennedy’s Disease.

First off, I am not a doctor and not as knowledgeable as some others with KD concerning this topic. What I do know is that ALS is a condition that attacks the upper motor neurons. Kennedy’s Disease attacks the lower motor neurons. For this reason, I do not believe the new drug will be beneficial for those of us living with KD.

So what is the difference between the two upper and lower motor neurons? I found the following explanation to be helpful.

Upper motor neurons originate in the motor region of the brain stem. They are not responsible for the stimulation of the muscle which is targeted as they do not carry information down to the final common pathway. They work through a neurotransmitter called glutamate which transmits the nerve impulses from upper to lower motor neurons where it is detected by glutamatergic receptors. On the other hand, lower motor neurons receive impulses from the upper motor neurons and connect the spinal cord and brain stem to the muscle fibers. They are the cranial and spinal nerves. They work by making use of the glutamate which is released from the upper motor neurons, and this triggers depolarization in the lower motor neurons. A series of actions occur which end up signalling the muscle to contract. The cell bodies of the lower motor neurons are located in the neuraxis, and their axons leave and synapse with the muscles in the body. On the other hand, the upper motor neurons synapse with the lower motor neurons as they are unable to leave the central nervous system.


Nonetheless, even if this new treatment is not the answer, it is progress and a help for those living with ALS. 

Friday, May 5, 2017

What—Me Worry?

Many of my friends and family believe I accept living with Kennedy’s Disease better than most. I’m not so certain about that. I know of many men that are well centered and accepting. Perhaps we just hide it better than others do. Or, we aren’t smart enough to understand what is happening. Whatever the reason, I’m comfortable being this way.

I have my down days. I still wonder what the future has in store for me. Probably the only difference is that I don’t dwell on these thoughts. I am too busy ‘living’ to wallow in the muck of uncertainty.

Meditation helps put things in perspective. There is something called ‘noting’ that works for me. Whenever I find myself dwelling on a thought, I notice it (acknowledge it), apply a label to it (oh, that’s a fear of what might happen to me), and move on. I don’t study it or try to understand it; I just notice the thought and then discard it by refocusing on my breathing. If I tell myself to forget it, or force myself to think of something else, it won’t work. But, by just acknowledging the thought and then refocusing on my breath, it no longer is important and stops nagging me.

I also have a couple of good hobbies and social events that allow me to focus on something productive. If I’m engaged in an activity or a conversation, negativity can’t seem to wedge its way into my thoughts.

I’ll give you an example of a recent event. At the beginning of the year, I was in a long slide that had me concerned. If things didn’t change, my daily life would be transformed—and not in a positive way. After a couple of days of wallowing, I ‘noted’ it, and then refocused.

Almost immediately, my thoughts redirected to what I could do and what has helped in the past. I gradually worked my way through the issue and am better now (stronger) than before I started.

We are all human. We have concerns and fears. However, that doesn’t mean they have to control our lives.