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WordNet

in or to a high position, amount, or degree; "prices have gone up far too high"
a state of altered consciousness induced by alcohol or narcotics; "they took drugs to get a high on"
a state of sustained elation; "Im on a permanent high these days"
an air mass of higher than normal pressure; "the east coast benefits from a Bermuda high"
a lofty level or position or degree; "summer temperatures reached an all-time high"
a high place; "they stood on high and observed the countryside"; "he doesnt like heights" (同)heights
at a great altitude; "he climbed high on the ladder" (同)high up
used of sounds and voices; high in pitch or frequency (同)high-pitched
happy and excited and energetic (同)in high spirits
slightly and pleasantly intoxicated from alcohol or a drug (especially marijuana) (同)mellow
in a rich manner; "he lives high" (同)richly, luxuriously
(literal meaning) being at or having a relatively great or specific elevation or upward extension (sometimes used in combinations like `knee-high'
far up toward the source; "he lives high up the river"
greater than normal in degree or intensity or amount; "a high temperature"; "a high price"; "the high point of his career"; "high risks"; "has high hopes"; "the river is high"; "he has a high opinion of himself"
(statistics) a coefficient assigned to elements of a frequency distribution in order to represent their relative importance (同)weighting
sports equipment used in calisthenic exercises and weightlifting; it is not attached to anything and is raised and lowered by use of the hands and arms (同)free weight, exercising weight
an artifact that is heavy
the vertical force exerted by a mass as a result of gravity
the relative importance granted to something; "his opinion carries great weight"; "the progression implied an increasing weightiness of the items listed" (同)weightiness
an oppressive feeling of heavy force; "bowed down by the weight of responsibility"
have a certain weight
determine the weight of; "The butcher weighed the chicken" (同)librate
to be oppressive or burdensome; "weigh heavily on the mind", "Something pressed on his mind" (同)press
relating to simple or elementary organization; "proceed by more and more detailed analysis to the molecular facts of perception"--G.A. Miller
relating to or produced by or consisting of molecules; "molecular structure"; "molecular oxygen"; "molecular weight is the sum of all the atoms in a molecule"
adjusted to reflect value or proportion; "votes weighted according to the size of constituencies"; "a law weighted in favor of landlords"; "a weighted average"

PrepTutorEJDIC

『高い』,高い所にある / 《数の後に置いて》高さが…ある / (数量・程度などが標準より)『高い』,大きい,激しい / (身分・地位が)『高い』,高貴な / 『気高い』,高潔な / (声の調子が)『高い』,鋭い / 値段の高い,金の掛かる,ぜいたくな / 楽しい,陽気な,上得意の / (時・季節が)盛りの,たけなわの / (色が)濃い,赤い / 《話》(酒・麻薬などに)酔って / 『高く』,高い所に / (価値・程度などが)高く,高度に,激しく / 〈C〉《話》高水準,高値 / 〈U〉(自動車の)高速ギア / 〈C〉《話》(麻薬などによる)酔った状態
〈u〉『重さ』,重量,目方;体重;《a weight》(…の)重さ《+of+名》 / 〈u〉重さ(重力が物体に及ぼす力) / 〈u〉衡法(重量を示す体係) / 〈c〉重量単位 / 〈c〉(はかりの)おもり,分銅;(一般に)重いもの,おもし / 〈u〉重要性,価値 / 〈u〉《しばしば a weight》精神的な重荷,負担 / (…で)…‘に'重荷を負わせる;…‘を'圧迫する;苦しめる《+名+with+名》 / …‘を'重くする
…‘の'『重さを計る』 / 〈ある重さ〉‘を'『計量する』,計る / (…と比較して)…‘を'『検討する』,考慮する〈+名 against+名〉 / 『重さがある』,目方がかかる / (…にとって)『重要である』,(‥に)重要糸される〈+with+名〉
分子の,分子による
《補語にのみ用いて》(…に)有利な《+toward+名》

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/11 11:02:34」(JST)

wiki en

High molecular weight kininogen (HMWK or HK) is a circulating plasma protein which participates in the initiation of blood coagulation, and in the generation of the vasodilator bradykinin via the Kallikrein-kinin system. HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or it binds to intact endothelial cells or platelets for functions other than coagulation.

Other names

In the past, HMWK has been called HMWK-kallikrein factor, Flaujeac factor (1975),^[1] Fitzgerald factor (1975),^[2] and Williams-Fitzgerald-Flaujeac factor, - the eponyms being for people first reported to have HMWK deficiency. Its current accepted name is to contrast it with low molecular weight kininogen (LMWK) which has a similar function to HMWK in the tissue (as opposed to serum) kinin-kallikrein system.

Structure and Function

HMWK is an alpha-globulin with six functional domains. It circulates as a single-chain 626 amino acid polypeptide . The heavy chain contains domains 1, 2, and 3; the light chain, domains 5 and 6. Domain 4 links the heavy and light chains.

The domains contain the following functional sites:

Domain 1 - calcium binding
Domain 2 - cysteine protease inhibition
Domain 3 - cysteine protease inhibition; platelet and endothelial cell binding
Domain 4 - bradykinin generation
Domain 5 - heparin and cell binding; antiangiogenic properties; binding to negatively charged surfaces
Domain 6 - prekallikrein and factor XI binding (amino acids 420 to 510)(histidine rich)

HMWK is one of four proteins which interact to initiate the contact activation pathway (also called the intrinsic pathway) of coagulation: the other three are Factor XII, Factor XI and prekallikrein. HMWK is not enzymatically active, and functions only as a cofactor for the activation of kallikrein and factor XII. It is also necessary for the activation of factor XI by factor XIIa.

HMWK is also a precursor of bradykinin;^[3] this vasodilator is released through positive feedback by kallikrein.

HMWK is a strong inhibitor of cysteine proteinases. Responsible for this activity are domains 2 and 3 on its heavy chain.^[4]

Genetics

The gene for both LMWK and HMWK is located on the 3rd chromosome (3q26).^[5]

Measurement

Measurement of HMWK is usually done with mixing studies, in which plasma deficient in HMWK is mixed with the patient's sample and a partial thromboplastin time (PTT) is determined. Results are expressed in % of normal - a value under 60% indicates a deficiency.

Clinical features

The existence of HMWK was hypothesised in 1975 when several patients were described with a deficiency of a class of plasma protein and a prolonged bleeding time and PTT.^[6] There is no increased risk of bleeding or any other symptoms, so the deficiency is a trait, not a disease.

References

^ Wuepper KD, Miller DR, Lacombe MJ (1975). "Flaujeac trait. Deficiency of human plasma kininogen". J. Clin. Invest. 56 (6): 1663–72. doi:10.1172/JCI108248. PMC 333145. PMID 127805.
^ Waldmann R, Abraham JP, Rebuck JW, Caldwell J, Saito H, Ratnoff OD (1975). "Fitzgerald factor: a hitherto unrecognised coagulation factor". Lancet 1 (7913): 949–51. PMID 48123.
^ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. Retrieved 11 December 2010.
^ Higashiyama S, Ohkubo I, Ishiguro H, Kunimatsu M, Sawaki K, Sasaki M (April 1986). "Human high molecular weight kininogen as a thiol proteinase inhibitor: presence of the entire inhibition capacity in the native form of heavy chain". Biochemistry 25 (7): 1669–75. doi:10.1021/bi00355a034. PMID 3635411.
^ Fong D, Smith DI, Hsieh WT (1991). "The human kininogen gene (KNG) mapped to chromosome 3q26-qter by analysis of somatic cell hybrids using the polymerase chain reaction". Hum. Genet. 87 (2): 189–92. PMID 2066106.
^ Colman RW, Bagdasarian A, Talamo RC, Scott CF, Seavey M, Guimaraes JA, Pierce JV, Kaplan AP (1975). "Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways". J. Clin. Invest. 56 (6): 1650–62. doi:10.1172/JCI108247. PMC 333144. PMID 1202089.

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English Journal

Prolylcarboxypeptidase gene expression in the heart and kidney: Effects of obesity and diabetes.

Tabrizian T, Hataway F, Murray D, Shariat-Madar Z1.
Cardiovascular & hematological agents in medicinal chemistry.Cardiovasc Hematol Agents Med Chem.2015 Sep 11. [Epub ahead of print]
Prolylcarboxypeptidase (PRCP) regulates plasma prekallikrein/high molecular weight kininogen/bradykinin axis. It also modulates angiotensin II (Ang II), angiotensin III (Ang III), and alpha-stimulating hormone (a-MSH) physiological effects. Study suggests that increased plasma PRCP level is associat
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The polyphosphate-factor XII pathway drives coagulation in prostate cancer-associated thrombosis.

Nickel KF1, Ronquist G2, Langer F3, Labberton L4, Fuchs TA5, Bokemeyer C3, Sauter G6, Graefen M7, Mackman N8, Stavrou EX9, Ronquist G2, Renné T1.
Blood.Blood.2015 Sep 10;126(11):1379-89. doi: 10.1182/blood-2015-01-622811. Epub 2015 Jul 7.
Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its s
PMID 26153520

Histidine-rich glycoprotein binds DNA and RNA and attenuates their capacity to activate the intrinsic coagulation pathway.

Vu T, Leslie BA, Stafford AR, Zhou J, Fredenburgh JC1, Weitz JI.
Thrombosis and haemostasis.Thromb Haemost.2015 Sep 10;115(1). [Epub ahead of print]
When triggered by factor (F) XII and nucleic acids, we showed that thrombosis in HRG-deficient mice is accelerated compared with that in wild-type mice. In this study, we set out to identify the mechanisms by which nucleic acids promote contact activation, and to determine whether HRG attenuates the
PMID 26354857

Japanese Journal

A Novel Frameshift Mutation in Exon 4 Causing a Deficiency of High-molecular-weight Kininogen in a Patient with Splenic Infarction

Internal Medicine 53(3), 253-257, 2014
NAID 130003392631

血漿および腺性キニン前駆体である高分子および低分子キニノーゲンのcDNA構造解析と遺伝子の形態学的解析

尚絅大学研究紀要. B, 自然科学編 (45), 107-122, 2013-03-31
NAID 110009579121

血漿および腺性キニン前駆体である高分子および低分子キニノーゲンのcDNA構造解析と遺伝子の形態学的解析 (尚絅学園創立百二十五周年記念号)

尚絅大学研究紀要. A, 人文・社会科学編 (45), 107-122, 2013
NAID 40019644490

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