This enhanced phosphorylation was observed in proportion to the virus titer and E-selectin expression levels data not shown , suggesting that the constitutive activation of MAPK was an SR polymorphism-dependent phenomenon. Download figure Download PowerPoint Figure 4. After washing nonadhered HL60 cells, cell lysates were prepared as described in the Methods section. Bar graph represents the percentage of density of the phosphorylated band to that of the total protein band. Blots are representative of 3 independent experiments.
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Figure 5. After washing the nonadhered HL60 cells, cell lysates were prepared as described in the Methods section. Bar graph represents the density of the bands expressed in arbitrary densitometry units. Genetic mutations and polymorphisms are known to be risk factors for atherosclerosis and have been extensively studied for their potential association with atherogenic vascular diseases. Similarly, mutations in adhesion molecules, including P-selectin 19 and E-selectin, 5 and their association with cardiovascular diseases have recently been investigated.
In the present study, we demonstrated that a SerineArg mutation in the EGF domain of E-selectin is a potential risk factor for genetic susceptibility to MI in the Japanese population. Considering the possibility of selection bias, which may have an influence on the results of association studies, we carefully examined the genetic and ethnic homogeneity of our study population along with the competency of the control group. Our entire study population resided in Tokyo and adjacent areas within Japan, where individuals are considered to have a homogeneous genetic background.
Furthermore, the distribution of the E-selectin genotype in our control group showed Hardy-Weinberg equilibrium, which verified that the control group was statistically appropriate. In a study of the association between the E-selectin gene and atherosclerotic vascular diseases, Ye et al 6 reported that the SerArg mutation was associated with coronary artery disease in their patients. Wenzel et al 7 also found that both the SerArg and LeuPhe mutations in the transmembrane domain were related to early severe atherosclerosis in a German population. Results of these studies, conducted using subjects with different ethnic and genetic backgrounds, suggest the possibility that mutations found in the E-selectin gene SerArg and LeuPhe may play a functional role in the development of atherosclerosis.
Notably, recent findings have also demonstrated that the association between the E-selectin SR polymorphism and coronary artery calcification was prominent among younger women. Thus, as a coronary risk factor, the E-selectin SR polymorphism may be of particular importance for younger women. To functionally examine this issue, we created an experimental model that used vascular endothelium that overexpressed mutant E-selectin via a recombinant adenovirus.
It has also been reported that the SerArg mutation totally confers carbohydrate specificity to E-selectin, 8 and we also demonstrated such an effect by an anti-E-selectin mAb in SerArg mutant E-selectin—transduced HUVECs in the present study. These data also strongly indicate an altered ligand specificity of SR-E-selectin. The mechanism by which this mutation causes enhanced binding activity under flow requires additional study.
However, as revealed by a three-dimensional crystal-structural analysis of E-selectin, we now know that the position of the th amino acid in the EGF domain of E-selectin does not allow it to directly participate in the ligand-binding pocket.
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Recent observations suggest that the polymorphisms found in cell-surface receptors lead to a constitutive activation of the receptors in the absence of their ligands, 22,23 possibly through constitutive oligomerization, as has been suggested for the EGF receptor, or via induction of a conformational change, as reported with CD The presence of soluble ligands in the assay medium can be neglected, because an enhanced phosphorylation of ERK kinase was observed in the absence of serum in the media data not shown. A chemical cross-linking approach for potential oligomerization of E-selectin failed to show the difference between WT- and SR-E-selectin—transduced HUVECs data not shown ; therefore, the responsible mechanisms underlying the altered MAPK signaling pathway observed with SR mutant E-selectin seem to involve complex processes, which we hope to focus on in a future project.
We have begun a series of experiments to elucidate the detailed molecular mechanisms involved in the constitutive phosphorylation of MAPKs. Additional study of the pathological consequences of these disease-associated polymorphisms may provide a significant contribution to understanding the mechanisms of atherosclerosis as well as provide future diagnostic approaches to cardiovascular diseases. The authors wish to thank Yoshie Nakamura for her technical assistance.
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You are viewing the most recent version of this article. Previous versions: March 20, Previous Version 1. Abstract Objective— Polymorphisms found in genes encoding adhesion molecules have been reported to be associated with atherosclerosis. Download figure Download PowerPoint. References 1 Ross R.
Atherosclerosis: an inflammatory disease. N Engl J Med. She also loved being surrounded by friends, you could always count on a good cup of coffee at her house, the chairs at the kitchen table full with her daily coffee drinkers. Preceded in death by her husband Santy Ansotegui and daughter Theresa Dragoo, along with her parents and several brothers, and sisters.
Survived by son Leland Ansotegui Barbara.
Brother Phidel Larrrucea, sister Begonia Corta, many nephews, nieces and longtime friends including the wonderful loving staff at Burney Annex. Graveside services will be held March 25th, pm at the Burney Cemetery. Coffee and Dessert reception will follow at the Burney Lions Hall. In Loving Memory of Janice Marie Straub Oiler January 13, January 13, Our Mothers final wish was to make it to her 80th birthday, which she fought a courageous fight to accomplish that. Janice passed away at Copper Ridge Care Center with her family by her side.
Janice was a gifted seamstress, quilter, home maker and volunteer. She won Volunteer of the Year Award Oct. Janice loved camping, fishing, and going to the coast, she also enjoyed being part of Redding Quilting Guild and Skogen Lodge Preceded in death by her parents and her two sisters Loye Eller and Eunice Dietrich. She was raised on the family ranch in Round Valley hear Adin attending elementary and high school in Adin and graduating with her class of After the marriage ended she married Norman Tyrrell and celebrated 50 years of marriage together until his death on May 23, She enjoyed making craft decoration, crocheting edges on baby blankets, piercing quilts and watching athletic events involving family.
Graveside Services will be at the Adin Cemetery at 1 p. His family being his favorite pastime, Richard was also born an avid hunter and fisherman, traveling out of state for moose, elk and antelope and hunting locally for deer. When not engaged in these activities, he could be found in his shop building or repairing something. Richard grew up in Fort Bidwell, CA, cowboying on the family ranch as well as other ranches in the Surprise Valley area. He was a frequent rodeo participant as well. He graduated from Modoc High School in Alturas and attended UCS Davis for a short time before returning to the Intermountain Area where he worked on ranches and at local lumber mills until he landed a job at Louisiana-Pacific in Burney where he worked for 30 years, mostly as a millwright.
Per his request, no services were held. In Loving Memory of Delores J.
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Powell Delores J. Powell left us to be with the Lord on March 2, She left as the last of her family of siblings that included her older brother Franklin. Francis is her first younger sister and Jane her youngest sister. She has, or had, her youngest brother, John Davis.
Delores was born January 11, to Clifford W. Davis and Louise N. Davis in Santa Cruz, CA and where she was also educated and lived most of her life. She was first married to Loyal Harbison on August 25, They moved to Redding in or where Loyal passed away. She met Stephen Powell in late and they were officially married May 28, She was outgoing and was loved by all.
Guided by a terrific sense of humor, she made those who knew her very happy.
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She was a wonderful wife to Stephen and made him very happy. She also leaves four other nephews and two nieces of her sister Francis. From her brother John are three daughters. She will be missed by all who knew her. He was born in Louisville, Kentucky in and came to live in Big Valley in He was a manager and later a loan officer until his retirement.
Don was involved in a lot of Big Valley activities. He loved Big Valley and the people there. His favorite pastimes were eating, and talking with his buddies at breakfast and also being on his 40 acres on Big Valley Mountain. Don is survived by his wife of 61 years, Sue, his son Russ of Redding, daughter Beth McCain of Salem, Oregon, seven grandchildren and nine great-grandchildren. Memorial Services will be held on March 4, at the Lookout Fire hall at p. On February 17, a dear, brave and loving wife, mother, grandmother, aunt and friend passed away. Carla was a special person who loved everyone and was a friend to anyone she met.
Her laugh and smile will always be remembered. Carla, Leanna and their parents participated in many horse shows as a family group or the girls individually. Carla and Leanna went to grade school in Little Valley and then Carla went on to Fall River for the 7th and 8th grade. The summer before her freshman year in high school the family moved to Big Valley on one of the Connelly Ranches there. Carla went to high school in Bieber. She graduated from high school in in a huge class of seven.
Carla attended Lassen College in Susanville and studied Secretarial Science and was a whiz at short hand, which is now a lost art. She worked briefly as a switch board operator at Pacific Bell Telephone Company. Later on, she worked many years at C. Moffett Company as the administrative assistant to the owner, as well as salesperson for his wholesale hardware company.
Carla soon married and had two children, Dwight and Catherine Point. Carla never would have thought that 42 years later she would move back to Big Valley, which she always thought of as home. On one of her trips back to Bieber to visit family and friends she met up with an old school friend and on October 5, Carla and Roy Conner were married.