Categories
Uncategorized

Losing Control

The hardest patients to take care of are the ones my age. When a young 30 something guy with Cystic Fibrosis comes for surgery because he can’t breathe right, it is like a Chuck Norris kick to the gut. They say when Chuck Norris kicks you in the gut; your stomach apologizes to him in advance.

I digress.

I find it difficult because taking care of people my own age with significant medical problems makes me really introspect.  Youth is a time of misplaced invincibility. We think nothing can harm us, that the only thing we need to think about is increasing our wealth, starting a family, and going to the gym so you look good enough to start a family.

After taking care of many patients my age who are suffering from an ailment, I have learned one main lesson. Let them have some control.

Recently, I was taking care of a guy with Cystic Fibrosis. It is a genetic disease where difficulty to breathe is the often the most significant problem, leading to frequent lung infections, prolonged hospital stays, and multiple organ dysfunction. He came to have a procedure done to repair a hole in his stomach. He has had the procedure done multiple times. Each one was unsuccessful for one reason or another.

He was furious to find out that the outcome this time was also the same. At a time where you should be at your strongest, the feeling of helplessness can bring out real frustration. And that was exactly what he was feeling.

A mentor of mine told me as an intern that with these kinds of patients, you have to realize that they’re not trying to be difficult. They aren’t really angry with you. They’ve lost whatever control they have in their lives, and their anger is a mechanism to seize the moment.

So when he decided to yell at me after the procedure, I was ready to listen.

Sometimes doctors need to just shut up and listen.

I sat down next to him, heard him out, allowed him to vent his frustrations, and waited for him to be done. I even tried to wait a few moments after he was done to make sure. He goes, “Why aren’t you talking dude, stop being awkward.”

And we laughed.  It was a chance for him to express himself and process openly his concerns. His life has has been spiraling out of control.

In a lot of situations, be it in medicine or relationships, we’re not really listening to hear what the person in front of us is trying to say. We’re waiting for them to be done so we can say what we wanted to say 15 minutes ago. All of this while hoping not to forget our thoughts while they are talking.

You know its true.

It is imperative to listen, absorb, and reflect some positivity in these situations. This extends to all forms of relationships. Hear what they have to say, do what you can to help the situation. Their words to you, though in anger, may be far more compelling and beneficial to you than your treatment of their illness.

Give them some control.

(originally posted on Zafchat.com-visit Dr. Zaafran’s blog there for more original content)

Categories
Uncategorized

The Tryptophan Operon – A Repressible Operon System

The tryptophan (trp) operon system is a type of repressible operon system. It was worked out by Jacob and Monod in 1953.

The 20 amino acids are required in large amounts for protein synthesis and E.coli can synthesize all of them. The genes for the enzymes needed to synthesize tryptophan are generally clustered in trp operon and are expressed whenever existing supplies are limiting.

When tryptophan is present, it binds the trp repressor and induces a conformational change in that protein, enabling it to bind the trp operator and prevent transcription (operon is repressed).

The E.coli trp operon includes five trp genes (trp E, D, C, B, A) that encode enzymes required to convert chorismate to tryptophan.

The gene products are:

trpE – anthranilate synthetase

trpD – phosphoribosyl anthranilate transferase

trpC – phosphoribosyl anthranilate isomerase-indole glycerol phosphate synthetase

trpB – tryptophan synthetase β

trpA – tryptophan synthetase α

Mechanisms:

Transcription is initiated at the beginning of the 162 nucleotide mRNA leader encoded by a DNA region called trpL. Once repression is lifted and transcription begins, the rate of transcription is controlled by a second regulatory process, called transcription attenuation. This regulatory process determines whether transcription is attenuated (terminated) at the end of the leader or continues into the structural genes.

The trp operon attenuation mechanism uses signals encoded in four sequences within a 162 nucleotide leader region at the 5’-end of the mRNA, before the initiation codon of the first gene (trpE). Within the leader lies a region known as the attenuator, made up of sequences 3 and 4. The attenuator structure forms by the pairing of sequences 3 and 4. The attenuator structure acts as a transcription terminator.

Sequence 2 is an alternate complement for sequence 3. If sequences 2 and 3 base-pair, the attenuator structure cannot form and transcription continues into the trp genes. The 2:3 structure, unlike the 3:4 attenuator, does not prevent transcription.

The sequence encoding the leader peptide has two  tryptophan codons in a row. When tryptophan concentrations are high, concentrations of charged trp tRNA are also high. This allow ribosome to quickly translates sequence 1 and block sequence 2. Ribosome blocking sequence 2 allows formation of the 3:4 attenuator, aborting transcription at the end  of the  leader RNA. The leader peptide has no other known cellular function, its  synthesis is simply an operon regulatory device.

trp 1When tryptophan levels are low, there is very little charged tryptophan tRNA available, and the ribosome stuck when it reaches the tryptophan  codons. A ribosome caught at the tryptophan codons, masks region 1, leaving sequence 2 free to pair with sequence 3, thus the 3:4 attenuator hair-pin structure cannot be made. In this way, RNA polymerase passes the attenuator and moves on into the operon, allowing trp enzymes  expression.

trp 2


 

Categories
Uncategorized

The Human Genome Project

Francis Collins

The genome is the ultimate source of information about an organism. Advances in genetic engineering techniques made it possible for the scientists to isolate and clone DNA pieces and determine nucleotide sequences of these genome. After the development of practical DNA sequencing methods, serious discussions began about the prospects for sequencing the entire 3 billion base pairs of the human genome. The international Human Genome Project got underway with extensive funding in the late 1980s. The effort eventually included significant contributions from 20 sequencing centers distributed among six nations: the United States, Great Britain, Japan, France, China, and Germany. General coordination was provided by the Office of Genome Research at the National Institutes of Health, led first by James Watson and after 1992 by Francis Collins.

At the outset, the task of sequencing a 3 X 109 bp genome seemed to be a massive job, but it gradually yielded to advances in technology. The completed sequence of the human genome was published in April 2003, several years ahead of schedule. The sequence of chromosome 1 was completed only in May 2006. The Human Genome Project (HGP) was a 13-year project coordinated by the U.S. Department of Energy and National Institute of Health. Decades-old estimates that humans possessed about 100,000 genes within the approximately 3 X 109 bp in the human genome have been supplanted by the discovery that we have only 30,000 to 35,000 genes.

The Human Genome Project marks the culmination of twentieth-century biology and promises a vastly changed scientific landscape for the new century. The human genome is only part of the story, as the genomes of many other species are also being sequenced, including the yeasts Saccharomyces cerevisiae (completed in 1996) and Schizosaccharomyces pombe (2002), the nematode Caenorhabditis elegans (1998), the fruit fly Drosophila melanogaster (2000), the plant Arabidopsis thaliana (2000), the mouse Mus musculus (2002), zebrafish, and dozens of bacterial and archaebacterial species.