EXERCISE !!

Exercise!

The New Year has arrived with bushels of resolutions, top amongst them is “I will exercise!”

Okay maybe here might be some incentives for you.

1. Exercise tones your body, sculpts your muscles and lubricates your joints and prevents the bone softening that come with age.
1. The facts are simple. Use them or lose them. Muscles like the brain need to be fed with some repetitive resistance to develop memory. Just like the brain when it is fed with knowledge it grows in intelligence and wherewithal.
2. Exercising the muscle leads to increasing the IGF-1Receptors that help store the glycogen within the muscle cells for use as energy. The higher the IGF-1R expressed by the muscle the less the Insulin floating around. Thus exercise leads to utilization of the consumed foods converted into sugars to be stored for use by the muscles. This leads to less sugar in the blood for insulin spikes.
3. Excess sugar floating in the blood stream is converted into fat and stored in the adipose tissue. So the larger the storage the fatter the person. This ultimately leads to resistance to insulin and Voila Type II Diabetes mellitus happens.
4. Of course the more unconverted sugars in the blood stream, the more filtration by the kidney and more sugar spills in the urine to the point that kidney damage results, ultimately leading to dialysis.
5. And if that was not enough more sugars in the blood stream floating through the eyes leads to impairment of vision.
6. And last but not least (since this is a simple primer) Excess sugars convert to triglycerides and those fatty molecules lining the arteries leads them to become rigid which leads to high blood pressure leading ultimately to strokes, heart attacks and other maladies that are not fitting for a New Year bloggersdom.

2. Exercise results in a IGF-1R expression in the heart muscle too which leads to allowance for cardiac myocyte (heart cell) hypertrophy (Or physical exercise leads to a tougher heart) So in a sedentary individual there is limited if any IGF-1R protein presence and faced with “fight-or-flight” scenario such as body-builder coming at you with a sledge hammer the heart would not be able to expand to function at peak capacity for the potential induced stress and outrace itself into an arrythmia. That is why athletes have a resting heart rate much lower than non-athletes.
1. If a sculpted “cool” body does not grab your attention let me try another approach that I know will get the point across:               Cancer Cell

1. Exercise leads to a lower death rate from Colon cancer. 
2. Exercise induces IGF-1R expression in patients with a specific type of Triple Negative Breast Cancer where those patient who had a higher expression of IGF-1R in their cells had a higher survival rate then those without. So exercise did make a difference in their survival and well-being.
3. Women who exercised regularly had lowered risk of developing breast cancer. Exercise was preventative!
4. Women who had breast cancer had a higher chance of increasing their overall survival and potentially cure.

4. This will not come as any surprise to anyone, but exercise induces the flow of neuro-chemicals in the brain, which lead to a feeling of well-being. These chemicals are called “Endorphins.” The feeling of well-being leads to a positive outlook on life and changes the approach to life.
1. Decision Making is on a moment-to-moment basis. We make decision at every level, at every turn of the screw and at every fork in the road. We survive through life living with the results of those decisions. Might it not be a good reason to make all decisions when we have a full score of endorphins circulating in our brains? Remember Charles Dickens he would walk the streets of London and those walks gave him the ideation of the Classics and the temper to toil writing such works as "Oliver Twist" and "A Christmas Carol".

5. Exercise also implicated in reducing the risk of lung cancer in current or former     women smokers.
6. Exercise with diet rich in vegetables, fruits are also implicated in reducing the risk of Prostate Cancer in Men.

Okay, so get off the couch, turn the TV off, put away the glasses, put your sweats on and roll with the endorphins.

Wish you all a happy healthy and endorphin-rich-proper-decision-making-New-Year 2011!

References:

1. Insulin-Like Growth Factor I Receptor Signalin is required for exercise induced Cardiac Hypertrophy, Jaetaek Kim et.al; Molecular Endocrinology 22 (11):2532-2543.
2. Enhanced muscle insulin receptor autophosphorylation with short-term aerobic exercise training, J.F. Youngren et. al: Am J Physiol Endocrinol Metab (2001) 280: E528-33.
3. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803, Meyerhardt JA et al. J Clin Oncol 2006 Aug1; 24(22): 3535-41 (Dana Farber Institute, Boston, MA)
4. Tao MH, Shu XO, Ruan ZX, et al: Association of overweight with breast cancer survival. Am J Epidemiol 163:101-107, 2006.
5.  Bianchini F, Kaaks R, Vainio H: Weight control and physical activity in cancer prevention. Obes Rev 3:5-8, 2002
6. Del Giudice ME, Fantus IG, Ezzat S, et al: Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 47:111-120, 1998
7. Holmes MD, Chen WY, Feskanich D, et al: Physical activity and survival after breast cancer diagnosis. JAMA 293:2479-2486, 2005.
8. The Association of Physical Activity with Lung Cancer Incidence in a cohort of Older Women: The Iowa Women’s Health Study. Sinner,P et. al. Cancer Epidemiol Biomarkers Prev 2006;15(12):2359–64.
9. Evidence of Inhibitory effect of Diet and Exercise on Prostate Cancer Cell Growth. Tymchuck, CN et.al. Journal of Urology Vol 166 (3): Pages 1185-1189, September 2001

Mammograms

Thought Experiment #2

The mammogram controversy is due to multiple competing issues: The desire to test and diagnose early, the excessive insults to the tissues from testing and surgical probing and the potential benefits overall. Lets look at the facts:

1. Mammograms in younger women age < 40 years have a higher “false positives,’ and therefore are subjected to un-needed needle biopsies and further radiation exposures for confirmation and re-testing. The NCI projects this false positive reading at 20% (2 in 10). This anomalous reading is primarily due to the increased breast density as a result of the milk ducts and fat ratio.

2. Mammograms initiated at an early age also expose the breast tissue to increased life-time radiation. With a risk of 1 Rad (mSv) causing a 2% (2 in 100)/ year risk would necessarily cause the risk to increase to 20% (2 in 10) in 10 years of annual mammography. The peak effect from a single intense source of radiation (Hiroshima and Nagasaki data) occurs in 15 years, the cumulative effects of annual mammography would account for similar peak/plateau to occur. Additional views of the breast to delineate “abnormal” tissues would add to that risk. A known but fortunately rare complication called malignant angiosarcoma occurs due to radiation therapy to the breast with an incidence of 2-5% over a 10-year period in treated patients.
1. Radiation from an X-Ray machine is a low-energy source focused-radiation as is in Computer Tomography scans. The energetics from the machine cause dislocation of the electrons within the cells that can disrupt the DNA molecule by changing one of the four Nucleotides: Adenine - Thymine, and Guanine - Cytosine and that form the backbone of the DNA helix. This change can lead to disrupted gene formation. (as in shutting down a tumor suppressor gene or accelerating a tumor promoter gene by changing the down-stream signal transduction via protein to cell propagation).

3. Digital Mammograms are no different than the Conventional Mammograms except in the mode of recording. The amount of radiation remains the same as does the light source in a digital camera, only the recording method differs; instead of a film it is recorded on a CMOS chip. Mammograms use low-energy radiation to a total value per test at -20KeV (1 eV or electron volt = 1.602×10⁻¹⁹ J and 20 KeV = 20 * 1 kiloelectron volt = 20 * 1.60217646 × 10^-16 joules) The absorbed dose is recorded as 0.56% mSv (millisievert (1 mSv = 10⁻³ Sv)

4. Taking into account all Mammograms, 9 in 10 abnormal mammograms when subjected to a biopsy are proven negative or said in another way; the yield is 10% (1 in 10) true positivity.

5. In younger women the risks of developing breast cancer is dependent upon genetics. The family history is extremely important and directive for extra vigilance. An individual whose mother or sister with a history of breast cancer especially at a younger age is high risk as are with known BRCA1 and/or  BRCA2 gene mutation are considered high risks. BRCA1 and 2 mutation increase the risk by 60% (6 in 10) up to the age of 90 and increased the risk of Ovarian cancer by 55% or (55 in100) Other factors such as menstrual history, breast feeding (protective?), alcohol (lobular breast cancer) radiation therapy, HRT (hormone replacement therapy), and diet/obesity are surrogates of environmental risks and therefore not taken into account for early age related cancer since the damage is limited and risks projected over time.

6. NCI data of risks of breast cancer diagnosis increase with age:
1. At age 30 the risk is 0.43 in 10 years
2. At age 40 the risk is 1.45 in 10 years or 1 in 233
3. At age 50 the risk is 2.38 in 10 years or 1 in 69
4. At age 60 the risk is 3.45 in 10 years or 1 in 38
5. At age 70 the risk is 3.74 in 10 years or 1 in 27
6. At age 80 the risk is 3.02 in 10 years

So in younger women a family history dictates the need for a diagnostic test. If such a test is needed then a MRI (Magnetic Resonance Imaging) may be the test of choice. Albeit the cost is high but the yield is identical to Mammography! The false negative or missing a diagnosis of cancer is roughly 20% (2 in 10) with all known testing procedures available today, including the MRI, however the radiation risks are mitigated.

In older women who do not have dense breasts a competent breast examination leads to an extremely high yield of discovery of malignancy – 83%.

The Incidence of Breast Cancer is increasing both due to diagnostic tests (cause or just discovery?) although a recent downward trend is due to cessation of the HRT and the death rate is also falling due to early diagnosis of DCIS (with mostly 98% 10-year survival) and better management of the disease. The question being is whether the diagnostic testing and disease discovery are just a self-fulfilling prophecy? (Annual mammography, with its inherent radiation effects, over time creates the disease that the test ultimately detects). More data and research definitely needs to be done to address this issue.

Developing non-ionized methods of detection are important for the future. Thermography and Infra-red imaging have yet to prove themselves. Unfortunately BSGI (Breast-specific gamma imaging by 23 times more) and PEM (Positron Emission Mammography by 20 times more) expose individuals to a higher radiation exposure than mammogram. 

However a portable MRI dedicated for the breast evaluation can easily be developed. The volume testing would lead to lower costs and limit the annual radiation exposure giving the benefit of 85-87% detection rate currently known and equivalent to mammography minus the risks.

Thought Experiment on PRDM

Thought Experiment #1

PRDM9 micro-satellites involved with human diversity by modulating the hotspots on the DNA. The PRDM (Positive Regulatory Domain Modulator) gene encodes for a protein which is a Zinc Finger transcriptor and this resides within the nucleus to modulate transcription into the DNA of the cell and modulate the proliferation of the cell with the variance to encode diversity – genetic for propagation and cellular to withstand stressors.

PRDM 16 on Chromosome 1

Interesting that PRDM16 is involved in a similar pathway but one of the known issues with PRDM16 is that in a t(1:3) (p36-q21) a subsets of MDS (Myelodysplastic Syndrome) and AML (Acute Myeloid Leukemia) cases have been identified.

Further viral infections lead to over-expression of the PRDM16 gene.

Question: DO sometimes clustering of Acute Leukemia cases represent a viral infection and the subsequent translocations through the PRDM genetic gateway?

Reference: Nature Genetics September 2010.