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Dr. Bortrum

 

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08/03/1999

Hamlet

Having dealt with Viagra and the role of NO, nitric oxide, in
enhancing the male''s sexual prowess, I feel obligated to discuss a
female-oriented subject. An obvious subject is the female breast.
Indeed, Brian Trumbore in his weekly review recently attempted
to correlate the financial market''s ups and downs with the
fluctuating bust measurements of someone named Pamela Lee
Anderson. I occasionally do my morning 3-mile walk at a local
mall and cannot help noting, as a scientist of course, larger-than-
life photos in the windows of Victoria''s Secret extolling the
enhanced presentation of a woman''s breasts by the engineering
design of the Wonderbra or its equivalent. In fairness, I should
point out that the male also has breasts. Indeed, a Seinfeld
aficionado will recall an episode in which George was upset that
his father, played by Jerry Stiller, had developed pronounced
breasts in his advancing years. This moved Kramer to invent the
"bro", counterpart to the more widely known "bra". To my
knowledge, the "bro" has not been a commercial success. On the
other hand, the Nike sports bra for women received an inordinate
amount of attention recently, thanks to Brandy Chastain''s
removal of her shirt. I don''t understand the media''s interest in
this happening inasmuch as I see many women jogging or
running in our area in their sports bras and no shirts. (OK, I do
understand that in between major tragedies the media does have
to fill their spaces and time with something.)

To keep you up to date on bras, I saw in the weekly Circuits
section of the New York Times that an industrial engineering
design student in London has invented a new "Techno Bra".
This new bra incorporates a heart monitor, wireless telephone
and Global Positioning System locator! The Techno Bra can
detect a sudden increase in heart rate, call the police and give the
wearer''s location. A stop button is included, presumably to
prevent false alarms, so prevalent in cars these days. The
designer of this security bra is a woman who felt that a feminine
touch was needed since many designers are men, whose designs
are more aimed at men than women. Will the Techno Bra fare
better than the "bro" in the marketplace?

For Dow Corning, the breast is not a subject for humor. Its
contribution to the silicone implants to enhance or perhaps
replace women''s breasts has meant bankruptcy. Only within the
past month does it look like the company will finally get
approval for a reorganization plan which takes into account the
liability, potential or actual, resulting from lawsuits filed on
behalf of over half a million women. These women claim to
have suffered from various complications and diseases resulting
from their breast implants. In fact, a number of scientific studies
have concluded there is no evidence that implanted woman have
any more problems of the types claimed than do women without
implants. Nevertheless, the court cases will probably drag on for
years and years. (Leakage from ruptured silicone implants is
acknowledged to be a problem in some cases.)

Because of the media''s obsession with breast cancer and with the
sensual aspects of the female breast, the primary function of this
organ tends to get short shrift. For many years the benefits of
breast-feeding versus formula feeding of infants have been well
known. The passage to the baby of various components of
mother''s milk enhances the baby''s immune system and the
infant''s development. I saw an article last week reporting that
formula babies were something like five times more likely to be
overweight by the age of 5 than those who were breast-fed. It is
clear that the biochemistry of mother''s milk remains a fertile
ground for exploration.

Of course, a prime concern of any woman these days is the
possibility of breast cancer. The incidence of breast cancer,
according to some studies, varies widely for different
geographical areas and is especially high in the northeastern
United States, with its large industrial base. A small study in
Ontario reported last December found for the first time certain
aromatic amines in human breast milk. Although only present in
parts per billion, these compounds, used in many industrial
processes, are known to cause cancer in rat''s mammary glands.
The authors emphasize that their work should not discourage
breast-feeding because of the great benefits to the infants
regardless of the trace contaminants. They plan to expand their
studies to other regions.

One reads almost daily of some promising new drug or treatment
that hopefully will lead to a cure for cancer but so often these
hopes turn out to be unfounded. However, I was intrigued by an
article by Peter Radetsky in the June issue of Discover magazine.
The article describes very exciting work of Catharina Svanborg
and associates at Lund University in Sweden. If this work pans
out, it could well be that a potent cancer killer might be hiding in,
of all places, the woman''s breast itself, i.e., in mother''s milk!

To understand cancer, researchers have found that a key player is
APOPTOSIS. Apoptosis is a form of programmed cell death;
that is, our healthy cells are programmed to commit suicide when
they receive the appropriate signal. Apoptosis under normal
conditions means that the cells tear themselves apart in a manner
that the leakage of their contents is minimized. Otherwise,
undesirable consequences may result. A key feature of cancer is
that the cancer cells don''t commit suicide, as they should, in spite
of being instructed to do so. Therefore, they keep growing and
multiplying to form tumors in the case of most cancers. Many
years of research have gone into identifying the proteins involved
in the sensing and regulation of apoptosis.

Back to Catharina Svanborg. Her Lund University website states
that her project goals include characterizing the apoptosis-
inducing molecules in human milk and evaluating the anti-tumor
effect in tumor bearing mice. How did this project come about?
According to the Discover article, Svanborg and her group had
been studying mother''s milk and its interactions with the cells
lining the gut of nursing infants. They found that mother''s milk
did a good job of blocking pneumococcus bacteria infection.
They also noted that breast-fed children had fewer ear and upper
respiratory infections. Other studies had shown that the risk of
childhood lymphoma is 9 times greater for those children who
had been formula-fed as compared to those who were breast-fed.

About 7 years ago, Svanborg''s student, Anders Hakansson told
Svanborg that something strange was happening. He had been
mixing cancer cells, bacteria and mother''s milk and found that
the volume of cancer cells was decreasing. Svanborg peered
through the microscope and deduced immediately that the cells
were committing suicide, apoptosis. If the finding had taken
place in a pharmaceutical company, a team of researchers would
have been placed on the project but Svanborg''s group numbered
less than 20. Everyone was engaged in studies on fighting
infectious diseases so it was left primarily to Svanborg and
Hakansson to continue the study. By late 1995, they had
identified the cancer cell killer as an abundant protein in breast
milk called alpha-lactalbumin, or alpha-lac for short. Alpha-lac
had been studied before and was known to help produce lactose,
the sugar found in milk, and nourish babies.

A hot topic in biochemistry these days is PROTEIN FOLDING.
It seems that proteins don''t hang around and do their jobs in
straight chains or linear molecules like you see in simple models
of DNA, with its entwined double helix. Rather the proteins will
fold up in all kinds of shapes and forms. The prion is an example
of a protein, whose function is not known, that apparently sits
around in the brain all folded up and happy. Unfold that prion,
however, and you get mad-cow disease! Svanborg and her
colleagues have come to the conclusion that the alpha-lac also
changes shape, sort of like Clark Kent changing into his
Superman cape. In its folded form it carries on its lactose bit but,
when partially unfolded, it''s transformed into a cancer fighter.
As often happens, serendipity came into play in this project.
When Svanborg prepared the milk to pour over cells, she added
acid to the solution. Well, it turns out that the acid unfolds the
alpha-lac. Actually, Svanborg''s group has found that another
"secret" ingredient in the mother''s milk also has to be present to
unfold the protein. Being Scandinavian, they''ve named the
unfolded alpha-lac HAMLET (Human Alpha-lactalbumin Made
LEthal to Tumor cells).

It turns out that the breast-fed infant''s stomach is at about the
same acid level as the experimental solution and Svanborg
postulates that the folded alpha-lac is unfolded in the stomach to
form HAMLET. HAMLET, now in its crime-fighting role,
searches out suspicious looking cells and persuades them to
commit suicide. Of course, growth is rapid in an infant and cells
are multiplying rapidly. It seems reasonable that in the vast
number of new cells there could be quite a few cells that didn''t
duplicate precisely the normal genetic code. These abnormal
cells, if not destroyed, could be latent cancer cells or cancer
promoters that might be activated years later. If Svanborg''s
scenario is correct, HAMLET and the secret ingredient could
emerge as the Supermen or, more appropriately, Superwomen of
cancer killers. Svanborg''s group has found that HAMLET kills
every form of cancer cell they''ve tested so far and the hope is for
beginning experimental trials in humans by next year. IF these
trials are successful, and it certainly is a big if, the 21st century
could be the century of HAMLET and the conquest of cancer.
Svanborg is just as excited about the possibility that alpha-lac
may be used to prevent bacterial infection, e.g., in hospitals.
Let''s all hope she''s right!

Allen F. Bortrum



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-08/03/1999-      
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Dr. Bortrum

08/03/1999

Hamlet

Having dealt with Viagra and the role of NO, nitric oxide, in
enhancing the male''s sexual prowess, I feel obligated to discuss a
female-oriented subject. An obvious subject is the female breast.
Indeed, Brian Trumbore in his weekly review recently attempted
to correlate the financial market''s ups and downs with the
fluctuating bust measurements of someone named Pamela Lee
Anderson. I occasionally do my morning 3-mile walk at a local
mall and cannot help noting, as a scientist of course, larger-than-
life photos in the windows of Victoria''s Secret extolling the
enhanced presentation of a woman''s breasts by the engineering
design of the Wonderbra or its equivalent. In fairness, I should
point out that the male also has breasts. Indeed, a Seinfeld
aficionado will recall an episode in which George was upset that
his father, played by Jerry Stiller, had developed pronounced
breasts in his advancing years. This moved Kramer to invent the
"bro", counterpart to the more widely known "bra". To my
knowledge, the "bro" has not been a commercial success. On the
other hand, the Nike sports bra for women received an inordinate
amount of attention recently, thanks to Brandy Chastain''s
removal of her shirt. I don''t understand the media''s interest in
this happening inasmuch as I see many women jogging or
running in our area in their sports bras and no shirts. (OK, I do
understand that in between major tragedies the media does have
to fill their spaces and time with something.)

To keep you up to date on bras, I saw in the weekly Circuits
section of the New York Times that an industrial engineering
design student in London has invented a new "Techno Bra".
This new bra incorporates a heart monitor, wireless telephone
and Global Positioning System locator! The Techno Bra can
detect a sudden increase in heart rate, call the police and give the
wearer''s location. A stop button is included, presumably to
prevent false alarms, so prevalent in cars these days. The
designer of this security bra is a woman who felt that a feminine
touch was needed since many designers are men, whose designs
are more aimed at men than women. Will the Techno Bra fare
better than the "bro" in the marketplace?

For Dow Corning, the breast is not a subject for humor. Its
contribution to the silicone implants to enhance or perhaps
replace women''s breasts has meant bankruptcy. Only within the
past month does it look like the company will finally get
approval for a reorganization plan which takes into account the
liability, potential or actual, resulting from lawsuits filed on
behalf of over half a million women. These women claim to
have suffered from various complications and diseases resulting
from their breast implants. In fact, a number of scientific studies
have concluded there is no evidence that implanted woman have
any more problems of the types claimed than do women without
implants. Nevertheless, the court cases will probably drag on for
years and years. (Leakage from ruptured silicone implants is
acknowledged to be a problem in some cases.)

Because of the media''s obsession with breast cancer and with the
sensual aspects of the female breast, the primary function of this
organ tends to get short shrift. For many years the benefits of
breast-feeding versus formula feeding of infants have been well
known. The passage to the baby of various components of
mother''s milk enhances the baby''s immune system and the
infant''s development. I saw an article last week reporting that
formula babies were something like five times more likely to be
overweight by the age of 5 than those who were breast-fed. It is
clear that the biochemistry of mother''s milk remains a fertile
ground for exploration.

Of course, a prime concern of any woman these days is the
possibility of breast cancer. The incidence of breast cancer,
according to some studies, varies widely for different
geographical areas and is especially high in the northeastern
United States, with its large industrial base. A small study in
Ontario reported last December found for the first time certain
aromatic amines in human breast milk. Although only present in
parts per billion, these compounds, used in many industrial
processes, are known to cause cancer in rat''s mammary glands.
The authors emphasize that their work should not discourage
breast-feeding because of the great benefits to the infants
regardless of the trace contaminants. They plan to expand their
studies to other regions.

One reads almost daily of some promising new drug or treatment
that hopefully will lead to a cure for cancer but so often these
hopes turn out to be unfounded. However, I was intrigued by an
article by Peter Radetsky in the June issue of Discover magazine.
The article describes very exciting work of Catharina Svanborg
and associates at Lund University in Sweden. If this work pans
out, it could well be that a potent cancer killer might be hiding in,
of all places, the woman''s breast itself, i.e., in mother''s milk!

To understand cancer, researchers have found that a key player is
APOPTOSIS. Apoptosis is a form of programmed cell death;
that is, our healthy cells are programmed to commit suicide when
they receive the appropriate signal. Apoptosis under normal
conditions means that the cells tear themselves apart in a manner
that the leakage of their contents is minimized. Otherwise,
undesirable consequences may result. A key feature of cancer is
that the cancer cells don''t commit suicide, as they should, in spite
of being instructed to do so. Therefore, they keep growing and
multiplying to form tumors in the case of most cancers. Many
years of research have gone into identifying the proteins involved
in the sensing and regulation of apoptosis.

Back to Catharina Svanborg. Her Lund University website states
that her project goals include characterizing the apoptosis-
inducing molecules in human milk and evaluating the anti-tumor
effect in tumor bearing mice. How did this project come about?
According to the Discover article, Svanborg and her group had
been studying mother''s milk and its interactions with the cells
lining the gut of nursing infants. They found that mother''s milk
did a good job of blocking pneumococcus bacteria infection.
They also noted that breast-fed children had fewer ear and upper
respiratory infections. Other studies had shown that the risk of
childhood lymphoma is 9 times greater for those children who
had been formula-fed as compared to those who were breast-fed.

About 7 years ago, Svanborg''s student, Anders Hakansson told
Svanborg that something strange was happening. He had been
mixing cancer cells, bacteria and mother''s milk and found that
the volume of cancer cells was decreasing. Svanborg peered
through the microscope and deduced immediately that the cells
were committing suicide, apoptosis. If the finding had taken
place in a pharmaceutical company, a team of researchers would
have been placed on the project but Svanborg''s group numbered
less than 20. Everyone was engaged in studies on fighting
infectious diseases so it was left primarily to Svanborg and
Hakansson to continue the study. By late 1995, they had
identified the cancer cell killer as an abundant protein in breast
milk called alpha-lactalbumin, or alpha-lac for short. Alpha-lac
had been studied before and was known to help produce lactose,
the sugar found in milk, and nourish babies.

A hot topic in biochemistry these days is PROTEIN FOLDING.
It seems that proteins don''t hang around and do their jobs in
straight chains or linear molecules like you see in simple models
of DNA, with its entwined double helix. Rather the proteins will
fold up in all kinds of shapes and forms. The prion is an example
of a protein, whose function is not known, that apparently sits
around in the brain all folded up and happy. Unfold that prion,
however, and you get mad-cow disease! Svanborg and her
colleagues have come to the conclusion that the alpha-lac also
changes shape, sort of like Clark Kent changing into his
Superman cape. In its folded form it carries on its lactose bit but,
when partially unfolded, it''s transformed into a cancer fighter.
As often happens, serendipity came into play in this project.
When Svanborg prepared the milk to pour over cells, she added
acid to the solution. Well, it turns out that the acid unfolds the
alpha-lac. Actually, Svanborg''s group has found that another
"secret" ingredient in the mother''s milk also has to be present to
unfold the protein. Being Scandinavian, they''ve named the
unfolded alpha-lac HAMLET (Human Alpha-lactalbumin Made
LEthal to Tumor cells).

It turns out that the breast-fed infant''s stomach is at about the
same acid level as the experimental solution and Svanborg
postulates that the folded alpha-lac is unfolded in the stomach to
form HAMLET. HAMLET, now in its crime-fighting role,
searches out suspicious looking cells and persuades them to
commit suicide. Of course, growth is rapid in an infant and cells
are multiplying rapidly. It seems reasonable that in the vast
number of new cells there could be quite a few cells that didn''t
duplicate precisely the normal genetic code. These abnormal
cells, if not destroyed, could be latent cancer cells or cancer
promoters that might be activated years later. If Svanborg''s
scenario is correct, HAMLET and the secret ingredient could
emerge as the Supermen or, more appropriately, Superwomen of
cancer killers. Svanborg''s group has found that HAMLET kills
every form of cancer cell they''ve tested so far and the hope is for
beginning experimental trials in humans by next year. IF these
trials are successful, and it certainly is a big if, the 21st century
could be the century of HAMLET and the conquest of cancer.
Svanborg is just as excited about the possibility that alpha-lac
may be used to prevent bacterial infection, e.g., in hospitals.
Let''s all hope she''s right!

Allen F. Bortrum