24457 Louis Sheehan2445824459 Louis Sheehan38722 Louis Sheehan38733 Louis Sheehan17230 Louis Sheehan24456 Louis SheehanLouis J. Sheehan 30Louis J. Sheehan 33Louis J. Sheehan 36Louis J. Sheehan 39Louis J. Sheehan 40Louis Sheehan 448833
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may 2008 Louis J. Sheehan, Esquire
Thursday, August 06, 2009 - 6:18 AM

WED
6
MAY

23

By Louis J Sheehan Esquire
I pity the fool who messes with these T cells.

A method to deliver molecular “scissors” into T cells in mice makes the cells downright hostile to HIV. Not only do the cells reject the virus’s advances, but copies of the virus already inside the cells get snipped up.

The technique is the first to deliver these HIV-fighting scissors — called small interfering RNAs, or siRNAs — into T cells in living animals, Premlata Shankar of Texas Tech University Health Sciences Center in El Paso and her colleagues report in the Aug. 22 Cell. Shankar performed the research while at Harvard Medical School in Boston.

“I think they’ve shown very nicely that you can ... target T cells and knock down the virus,” comments John Rossi, an AIDS researcher at the Beckman Research Institute at City of Hope in Duarte, Calif. “It’s a nice proof of principle that I think could be developed into a viable therapy.”

Previous research on cells grown in lab dishes showed that customized siRNAs can snip up the molecules that enable HIV to enter and subsequently kill T cells. Loss of these immune system cells leads to the immune deficiencies characteristic of AIDS.

In the new experiments, Shankar and her colleagues injected the custom siRNAs into mice that had their blood cells replaced with human ones. HIV can normally attack and kill human T cells in mice, but the siRNAs prevented loss of T cells due to the virus, the team reports.

“I think it could become a very good adjunct therapy,” Shankar says. “This would add to the arsenal.”

Existing HIV drugs also inhibit the virus from replicating inside T cells, and the health benefits of this new approach — if it’s ever approved for human use — would be similar. But unlike existing drugs, siRNAs are inherently flexible, so scientists could quickly adapt the siRNAs to target viral mutations that often make HIV resistant to conventional drugs.

An siRNA is a short molecule only 20 to 25 “letters” of genetic code long. If that code matches up with the sequence of letters in a gene, the siRNA will block the production of the protein coded by the gene.

Shankar’s team used an siRNA that targets the gene for a protein called CCR5. This protein sits on the outside surface of T cells. To enter the cells, most HIV variants must first bind to CCR5. So blocking the production of CCR5 slams the door on HIV. If it can’t enter the cells, HIV can’t replicate and hence kill the cells.

To deliver this siRNA — along with two others that target the genetic code of the virus itself — the researchers coupled the molecules to an antibody that targets a specific protein on the surface of T cells. When the siRNA-antibody pairs bind to this protein, called CD7, the cells swallow them.

The targeted delivery appeared specific enough to avoid toxic side effects, but more research to check for toxicity is needed, Rossi says. And the mouse antibody needs to be adapted for humans to prevent dangerous immune reactions.

Further tests on monkeys are needed before the treatment can be tested in human clinical trials, which would take several years to complete. If approved for people, the treatment would probably require weekly injections, Shankar says.Louis J. Sheehan, Esquire


May 8, 2009


FRI
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removing 4.rem.0002 Louis J. Sheehan, Esquire

By Louis J Sheehan Esquire
Tossing out the old batteries of brain cells might keep those cells strong, new research suggests.

A key player in this process is a protein called Parkin, which is made by the Park2 gene. Mutations in the gene can knock out production of the protein, resulting in early onset of Parkinson’s, a movement disorder brought on when brain cells that produce dopamine die. But until now, researchers did not know how the protein’s presence worked to prevent cells from being affected by the disease.

Now researchers at the National Institutes of Health report online November 24 in the Journal of Cell Biology that Parkin slates defective mitochondria for destruction while leaving healthy mitochondria untouched. Mitochondria are organelles within plant and animal cells that generate energy.

Removing damaged mitochondria might help cells maintain efficient energy production or prevent the buildup of toxic byproducts that might trigger a cell’s death.

“If you weed out all the bad apples in a barrel, the barrel stays fresh,” says Richard Youle, a cell biologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Md., who led the study.

Details of how Parkin targets broken-down mitochondria for removal aren’t yet clear, but Youle and his crew are trying to discover the molecular pathway that leads to mitochondrial demolition. Louis J. Sheehan, Esquire  //

May 22, 2009


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mordecai 3.mor.0001 Louis J. Sheehan, Esquire

By Louis J Sheehan Esquire

King Ahasuerus (also known as Xerxes) held a 180-day feast in SusaOpen in a new window (Shushan) to display the vast wealth of his kingdom and the splendor and glory of his majesty. King Ahasuerus ordered his queen, VashtiOpen in a new window, to appear before him and his guests wearing her crown, to display her beauty. But when the attendants delivered the king's command to Queen VashtiOpen in a new window, she refused to come, for she wanted to be treated as a queen, not a pet. Furious at her refusal to obey, the King asked his wise men what should be done. http://LOUIS2J2SHEEHAN.US The Book of Esther does not say what happened to her - various sources suggest banishment or death. The severity of the verdict was meant to establish male dominion over their wives and to force the women into obedience.

To find a new suitable queen for King Ahasuerus, it was decreed that all beautiful young women be gathered to the palace from every province of his kingdom. Each woman underwent twelve months of purification treatments and pregnancy watch in his harem, after which she would go to the King. When the woman's turn came, she was given anything she wanted to take with her from the harem to the king's palace. She would then go to the king in the evening, and in the morning return to the harem as his concubineOpen in a new window. She would not return to the King unless he was pleased enough with her to summon her again.

Four years after Queen Vashti was banished, King Ahasuerus chose the Jewish Esther for his wife and queen because he was captivated by her beauty and intelligence.

Shortly afterward, MordecaiOpen in a new window, Esther's cousin, overheard a plot to assassinate the King. He promptly told Esther of it, and she warned her husband of the threat. An investigation was made and the conspirators were swiftly arrested and executed. As such, the King ordered Mordecai's deed to be recorded in history.

Soon after this, the king granted HamanOpen in a new window the Agagite, one of the most prominent princes of the realm, supreme authority over the kingdom. All the people were to bow down to Haman when he rode his horse through the streets. All complied except for Mordecai, a Jew, who would bow to no one but his God. This enraged Haman, who, with his wife and advisers, plotted against the Jews, making a plan to kill and extirpateOpen in a new window all JewsOpen in a new window throughout the Persian empire, selecting the date for this genocidal act by the drawing of lots.Esther 3:17Open in a new window He gained the king's approval. He offered ten thousand silver talents to the king for approval of this plan, but the king refused to take them.Esther 3:9-11Open in a new window

Mordecai tore his robes and put ash on his head (signs of mourning or grieving/anguish) on hearing this news. Esther sent clean clothes to him, but he refused them, explaining that deliverance for the Jews would come from some other place (presumably God, as the Jews God's chosen people), but that Esther would be killed if she did not do what she could to stop this genocide - by talking to the King. Esther was not permitted to see the King unless he had asked for her, otherwise she could be put to death. Esther was terrified of this (she had not been called to the king in 30 days), so she and her maid-servants and her people the Jews of Persia fasted earnestly for three days before she built up the courage to enter the king's presence. He held out his scepter to her, showing that he accepted her visit. Esther requested a banquet with the king and Haman. During the banquet, she requested another banquet with the King and Haman the following day.



After the banquet Haman ordered a gallows constructed, 75 feet (23 m) high, on which to hang Mordecai. Meanwhile, the King was having trouble sleeping, and had some histories read to him. He was reminded that Mordecai had saved him from an assassination attempt, and had received no reward in return. Early the next morning, Haman came to the king to ask permssion to hang Mordecai, but before he could, the king asked him "What should be done for the man whom the king delights to honour?" Haman thought the king meant himself, so he said that the man should wear a royal robe and be led on one of the king's horses through the city streets proclaiming before him, "This is what is done for the man the king delights to honour!" The king thought this well, then asked Haman to lead Mordecai through the streets in this way, to honour him for previously telling the king of a plot against him. After doing this, Haman rushed home, full of grief. His wife said to him, "You will surely come to ruin!"  http://LOUIS2J2SHEEHAN.US

That night, during the banquet, Esther told the king of Haman's plan to massacre all Jews in the Persian Empire, and acknowledged her own Jewish ethnicity. The king was enraged and ordered Haman to be hanged on the gallows he had built for Mordecai. The king then appointed Mordecai as his prime minister, and gave the Jews the right to defend themselves against any enemy.   Louis J. Sheehan, Esquire

A peculiarity of Persian law that also occurs in the Book of DanielOpen in a new window is that royal edicts of this sort could not be reversed, even by the king – by siding with the Jews instead of their persecutors, the King presumably dissuaded any pogromsOpen in a new window. The King also issued a second edict allowing the Jews to arm themselves, which precipitated a series of reprisals by the Jews against their enemies. This fight began on the 13th of AdarOpen in a new window, the date the Jews were originally slated to be exterminated. Esther and the Jews went on to kill not only their would-be executioners, but also their wives and children, this altogether meaning three hundred killed in Susa alone, fifteen in the rest of the empire.

Jews established an annual feast, the feast of PurimOpen in a new window, in memory of their deliverance. According to traditional Jewish dating this took place about fifty-two years after the return.

Esther appears in the Bible as a woman of deep faith, courage and patriotism, ultimately willing to risk her life for her adoptive father, Mordecai, and the Jewish people. Scripture portrays her as a woman raised up as an instrument in the hand of God to avert the destruction of the Jewish people, and to afford them protection and forward their wealth and peace in their captivity. It is notable, though, that there is no direct mention of God by any name at any time in the Biblical Book of Esther.. The Story of Esther is said to come from an older goddess Elamite myth of Ishtar/Ashtarte (Esther) and her consort Marduk (Mordecai), who sacrificed the god Hammon, or Amon (Haman).[1]Open in a new window.

For a discussion of the historicity of Esther, see Book of EstherOpen in a new window.

[editOpen in a new window] Modern retelling

Origin and meaning of her name



According to the Esther 2:7Open in a new window, Esther was originally named Hadassah. Hadassah means "myrtleOpen in a new window" in HebrewOpen in a new window and the name Esther is most likely related to the MedianOpen in a new window word for myrtle, astra, and the PersianOpen in a new window word setareh meaning starOpen in a new window — the myrtle blossom resembles a twinkling star. The TargumOpen in a new window provides another Midrashic explanation: that she was as beautiful as the Evening StarOpen in a new window (or Morning StarOpen in a new window), which is astara in GreekOpen in a new window. In the Talmud, Tractate Yoma (29a), Esther is compared to the "morning star", and is considered the subject of Psalm 22 because its introduction is a "song for the morning star."

Esther can also be understood to mean "hidden" in Hebrew, and her name is interpreted thus in MidrashOpen in a new window, where it is said that Esther hid her nationality and lineage as MordecaiOpen in a new window had advised. Because the methods and aims of GodOpen in a new window are believed to be similarly hidden, "The Book of Esther" in Hebrew can be understood as "The Book of Hiddenness," representing God's hiddenness in the story. Louis J. Sheehan, Esquire

Despite resembling Indo-European words for star, the Semitic "Ishtar" is unrelated, the root beginning with a pharyngealOpen in a new window ayinOpen in a new window and the sh sound derived from an earlier th sound.) "Ishtar" was worshipped throughout the Middle East as a goddess. Some critics of the historicity of the Book of EstherOpen in a new window seized on this as evidence to support a view that the story of Esther derived from a myth about Ishtar. However, in Hebrew the goddess was referred to by the Hebrew cognate of her name - AshtorethOpen in a new window. "Esther" cannot be derived directly from the latter. The Book of DanielOpen in a new window provides accounts of Jews in exile being assigned names relating to Babylonian gods and "MordecaiOpen in a new window" is understood to mean servant of MardukOpen in a new window, a Babylonian god. "Esther" may have been a Hebrew rendition of a form of "Ishtar" in which the "sh" sound had become an "s" sound. WilsonOpen in a new window, who identified Ahasuerus with Xerxes I and Esther with AmestrisOpen in a new window, suggested that both "Amestris" and "Esther" derived from Akkadian Ammi-Ishtar or Ummi-Ishtar [2]Open in a new window. Hoschander alternatively suggested Ishtar-udda-sha ("Ishtar is her light") as the origin with the possibility of -udda-sha being connected with the similarly sounding Hebrew name Hadassah.




May 28, 2009


THU
28
MAY

priozersk 4.pri.001001 Louis J. Sheehan, Esquire

By Louis J Sheehan Esquire
Priozersk (RussianOpen in a new window: Приозе́рск[1]Open in a new window, before 1948 Кякисалми or Кексгольм, FinnishOpen in a new window: Käkisalmi; SwedishOpen in a new window: Kexholm) is a townOpen in a new window on the Karelian IsthmusOpen in a new window, in Leningrad OblastOpen in a new window, RussiaOpen in a new window, centered on an island at the southwestern shore of Lake LadogaOpen in a new window, at the estuary of the northern armlet of River VuoksiOpen in a new window. It is served by a station of the Saint Petersburg-Kuznechnoye railroadOpen in a new window with the same name. Population: 20,506 (2002 CensusOpen in a new window). Louis J. Sheehan, Esquire
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