PATHOPHYSIOLOGY OF BILIRUBIN BOUND COVALENTLY TO ALBUMIN
PATHOPHYSIOLOGY OF BILIRUBIN BOUND COVALENTLY TO ALBUMIN
批准号:
3080388
负责人:
ANIL GAUTAM
金额:
$7.63万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-04-01 至 1987-03-31
中文摘要
这个研究项目的主要目的是调查
英文摘要
The major objective of this research project is to investigate the
pathophysiological significance of BIL-ALB, recently confirmed by us to be
a significant fraction of serum conjugated bilirubin (BR) that is
apparently covalently bound to albumin is sera from patients with
hepatobiliary diseases. Specific aims: To investigate the chemical nature
and site of formation of BIL-ALB and to determine if other organic anions
also bind covalently to albumin in the presence of cholestasis. Methods:
BIL-ALB and other BR fractions will be measured by a reverse-phase HPLC
method. BIL-ALB will be purified from pooled, jaundiced sera by sequential
column chromatography. The identity of the conjugated BR species will be
determined by thin-layer chromatography (TLC) of ethyl anthranilate
azoderivatives and products of methanolysis with sodium methoxide.
Proteolysis of BIL-ALB followed by purification and Edman-degradation of
BR-tagged 'chromopeptides' will be used to identify the amino acid site/s
of binding. Chromic acid oxidation and TLC separation of the liberated
imides would aid in identifying the nature of the BR-albumin bond. An
isolated perfused rat liver model will be used, along with detailed kinetic
studies of any non-enzymatic formation of BIL-ALB in in vitro systems to
determine the site of BIL-ALB synthesis- in the liver or in peripheral
circulation. Any alteration in the turnover rate of albumin resulting from
BIL-ALB formation will be studied. In addition, covalent binding of
estrogen and benzodiazepene metabolites to albumin will be looked for in
patients with cholestasis. Significance: These studies should better our
understanding of the metabolism, transport and protein-binding of BR and
other organic anions in the presence of hepatobiliary diseases and would
lead to a more complete study of protein binding of organic anions.
After completing 2 years of laboratory research supported by an NIH
Institutional Training grant in Hepatology, the candidate was appointed to
the Digestive Diseases Division faculty in July, 1983. The Yale Liver
Study Unit is an ideal environment for this project. The co-sponsors are
well experienced researchers in hepatocellular function and metabolism.
Dr. E. Gordon is an internationally renowned expert in bilirubin chemistry
and metabolism. Thus, both equipment and technical expertise are
excellent. Interaction with basic science department such as Biochemistry
and Chemistry is readily available
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会议论文
OPTICAL QUANTITATION OF CANALICULAR BILE SECRETION
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批准号:3238099
-
项目类别:
-
资助金额:$12.87万
-
财政年份:1987
-
负责人:ANIL GAUTAM
-
依托单位:
OPTICAL QUANTITATION OF CANALICULAR BILE SECRETION
-
批准号:3238097
-
项目类别:
-
资助金额:$20.31万
-
财政年份:1987
-
负责人:ANIL GAUTAM
-
依托单位:
OPTICAL QUANTITATION OF CANALICULAR BILE SECRETION
-
批准号:3238098
-
项目类别:
-
资助金额:$14.49万
-
财政年份:1987
-
负责人:ANIL GAUTAM
-
依托单位:
PATHOPHYSIOLOGY OF BILIRUBIN BOUND COVALENTLY TO ALBUMIN
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批准号:3079005
-
项目类别:
-
资助金额:$7.51万
-
财政年份:1984
-
负责人:ANIL GAUTAM
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依托单位:
CORE--PREPARATION AND USE OF ISOLATED HEPATOCYTES AND HEPATOCYTE CULTURES
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批准号:4689863
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:ANIL GAUTAM
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依托单位:
PILOT STUDY--CANALICULAR BILE FORMATION IN ISOLATED HEPATOCYTE COUPLETS
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批准号:4689853
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:ANIL GAUTAM
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依托单位: