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2105 records – page 1 of 211.

2-substituted 1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. A new class of antitumor agent.

https://arctichealth.org/en/permalink/ahliterature24099
Source
J Med Chem. 1993 Mar 19;36(6):765-70
Publication Type
Article
Date
Mar-19-1993
Author
S M Sami
R T Dorr
D S Alberts
W A Remers
Author Affiliation
Department of Pharmaceutical Sciences and Cancer Center, University of Arizona, Tucson 85721.
Source
J Med Chem. 1993 Mar 19;36(6):765-70
Date
Mar-19-1993
Language
English
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - chemical synthesis - chemistry - therapeutic use
Female
Humans
Isoquinolines - chemical synthesis - chemistry - therapeutic use
Leukemia L1210 - drug therapy
Leukemia P388 - drug therapy
Male
Melanoma, Experimental - drug therapy
Mice
Mice, Inbred DBA
Ovarian Neoplasms - drug therapy
Research Support, U.S. Gov't, P.H.S.
Structure-Activity Relationship
Tumor Cells, Cultured - drug effects
Abstract
A new class of antitumor agents, having structural analogy to amonafide, but differing by the addition of a fourth ring in the nucleus, was synthesized conveniently from anthracene. Compounds with a variety of substituents, containing a basic nitrogen atom and located on the imide nitrogen, were prepared. Thirteen of 19 new compounds had greater growth inhibitory potency than amonafide in a panel of cultured murine and human tumor cells using the sulforhodamine B and MTT dye assays. The most active agents were similarly more toxic than amonafide to normal neonatal rat myocytes in vitro, but they had better chemotherapeutic indexes. From these compounds, the one with a 2-(dimethylamino)ethyl side chain (named azonafide) was chosen for further study. It showed high potency against a panel of cultured human colon cancer cells and it was active against ip P388 leukemia and subcutaneous B16 melanoma in mice. Preliminary structure-activity correlations suggest that the basicity of the side-chain nitrogen and the length of side chain are important determinants of antitumor potency in vitro. Steric hindrance and rigidity of the side chains might be other determinants.
PubMed ID
8459403 View in PubMed
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5-oxo-6,8,11,14-eicosatetraenoic acid induces the infiltration of granulocytes into human skin.

https://arctichealth.org/en/permalink/ahliterature15223
Source
J Allergy Clin Immunol. 2003 Oct;112(4):768-74
Publication Type
Article
Date
Oct-2003
Author
Shigeo Muro
Qutayba Hamid
Ronald Olivenstein
Rame Taha
Joshua Rokach
William S Powell
Author Affiliation
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Source
J Allergy Clin Immunol. 2003 Oct;112(4):768-74
Date
Oct-2003
Language
English
Publication Type
Article
Keywords
Arachidonic Acids - pharmacology
Asthma - physiopathology
Case-Control Studies
Cell Movement - drug effects
Chemotactic Factors - pharmacology
Granulocytes - drug effects - pathology
Humans
Macrophages - pathology
Mast Cells - pathology
Neutrophils - pathology
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Skin - pathology
Time Factors
Abstract
BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is an arachidonic acid metabolite with potent in vitro chemoattractant effects on eosinophils and neutrophils. It has also been shown to induce pulmonary eosinophilia in Brown Norway rats, but it is not known whether it is active in human beings in vivo. OBJECTIVE: To determine whether 5-oxo-ETE can induce cellular infiltration in patients with atopic asthma and nonatopic control subjects after intradermal administration. METHODS: 5-Oxo-ETE was administered intradermally to 11 patients with atopic asthma and 10 nonatopic control subjects. Skin biopsy specimens were taken 6 or 24 hours later and examined by immunocytochemistry for cells expressing specific markers for eosinophils (major basic protein), neutrophils (elastase), macrophages (CD68), lymphocytes (CD3), and mast cells (tryptase). RESULTS: 5-Oxo-ETE (1.5 and 5 microg) elicited the infiltration of both eosinophils and neutrophils into the skin in both control and atopic asthmatic subjects. Increased numbers of eosinophils were observed at 6 and 24 hours after injection, whereas significantly elevated neutrophil numbers were present only after 24 hours. Eosinophils were >3 times higher in patients with atopic asthma compared with control subjects after injection of the highest dose of 5-oxo-ETE. Macrophage numbers were also elevated, but only at the highest dose of 5-oxo-ETE. No effects were observed on the numbers of either lymphocytes or mast cells. CONCLUSIONS: 5-Oxo-ETE elicits the infiltration of eosinophils and neutrophils into the skin of human beings in vivo after intradermal administration. Asthmatic subjects are more responsive to this substance than nonallergic control subjects. These results suggest that 5-oxo-ETE may be an important mediator of inflammation.
PubMed ID
14564360 View in PubMed
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5-oxo-ETE induces pulmonary eosinophilia in an integrin-dependent manner in Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature10761
Source
J Clin Invest. 1998 Dec 15;102(12):2165-72
Publication Type
Article
Date
Dec-15-1998
Author
P. Stamatiou
Q. Hamid
R. Taha
W. Yu
T B Issekutz
J. Rokach
S P Khanapure
W S Powell
Author Affiliation
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.
Source
J Clin Invest. 1998 Dec 15;102(12):2165-72
Date
Dec-15-1998
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - pharmacology
Antigens, CD - metabolism
Arachidonic Acids - administration & dosage - pharmacology
Chemotactic Factors - pharmacology
Immunohistochemistry
Integrin alpha4
Integrins - metabolism
Intubation, Intratracheal - methods
Leukotrienes - pharmacology
Lung - cytology - drug effects
Macrophage-1 Antigen - metabolism
Male
Platelet Activating Factor - pharmacology
Pulmonary Eosinophilia - chemically induced
Rats
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Time Factors
Abstract
We have shown previously that the 5-lipoxygenase product 5-oxo-6,8, 11,14-eicosatetraenoic acid (5-oxo-ETE) is a highly potent eosinophil chemoattractant in vitro. To determine whether this substance can induce pulmonary eosinophil infiltration in vivo, it was administered to Brown Norway rats by tracheal insufflation. Eosinophils were then counted in lung sections that had been immunostained with an antibody to eosinophil major basic protein. 5-Oxo-ETE induced a dramatic increase in the numbers of eosinophils (ED50, 2.5 microg) around the walls of the airways, which reached maximal levels (five times control levels) between 15 and 24 h after administration, and then declined. LTB4 also induced pulmonary eosinophil infiltration with a similar ED50 but appeared to be somewhat less effective. In contrast, LTD4 and LTE4 were inactive. 5-Oxo-ETE-induced eosinophilia was unaffected by the LTB4 and PAF antagonists LY255283 and WEB 2170, respectively. However, it was inhibited by approximately 75% by monoclonal antibodies to CD49d (VLA-4) or CD11a (LFA-1) but was not significantly affected by an antibody to CD11b (Mac-1). In conclusion, 5-oxo-ETE induces pulmonary eosinophilia in Brown Norway rats, raising the possibility that it may be a physiological mediator of inflammation in asthma.
PubMed ID
9854052 View in PubMed
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6- and 7-substituted 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h] isoquinoline-1,3-diones: synthesis, nucleophilic displacements, antitumor activity, and quantitative structure-activity relationships.

https://arctichealth.org/en/permalink/ahliterature22674
Source
J Med Chem. 1996 Apr 12;39(8):1609-18
Publication Type
Article
Date
Apr-12-1996
Author
S M Sami
R T Dorr
A M Sòlyom
D S Alberts
B S Iyengar
W A Remers
Author Affiliation
Department of Pharmacology and Toxicology, University of Arizona, Tucson, 85721, USA.
Source
J Med Chem. 1996 Apr 12;39(8):1609-18
Date
Apr-12-1996
Language
English
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - chemical synthesis - pharmacology
Humans
Isoquinolines - chemical synthesis
Male
Mice
Mice, Inbred DBA
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Structure-Activity Relationship
Tumor Cells, Cultured
Abstract
New 2-[2'-(dimethylamino)ethyl]-3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at the 6- and 7-positions were prepared. Nucleophilic aromatic displacement was a key reaction in the syntheses. Ten of the new compounds were more potent than the unsubstituted compound, azonafide, in a panel of tumor cells including human melanoma and ovarian cancer and murine sensitive and MDR L1210 leukemia. They also were less cardiotoxic in cell culture. Four of these compounds were not cross-resistant with the MDR leukemia, and one of them, 6-ethoxyazonafide, was nearly as potent against solid tumor cells as leukemia cells. These compounds also had good potency against human breast, colon, and lung cancer cells, including doxorubicin and mitoxantrone resistant cell lines. Advantages of the new analogues over azonafide were less in vivo, but 6-ethoxyazonafide was more effective against L1210 leukemia and subcutaneous B16 melanoma in mice. Although correlations of antitumor potency in cells and physicochemical properties of substituents were not found, there were statistically significant correlations of DNA melt transition temperature (delta Tm) with potency in solid tumor cells and sensitive and MDR resistant L1210 leukemia cells for 6-substituted azonafides and with solid tumors for 7-substituted azonafides.
PubMed ID
8648600 View in PubMed
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The 20th century Danish facial cleft population--epidemiological and genetic-epidemiological studies.

https://arctichealth.org/en/permalink/ahliterature33384
Source
Cleft Palate Craniofac J. 1999 Mar;36(2):96-104
Publication Type
Article
Date
Mar-1999
Author
K. Christensen
Author Affiliation
Institute of Public Health, Epidemiology, Odense University, Denmark. k-christensen@win-chs.ou.dk
Source
Cleft Palate Craniofac J. 1999 Mar;36(2):96-104
Date
Mar-1999
Language
English
Publication Type
Article
Keywords
Child, Preschool
Cleft Lip - epidemiology - genetics
Cleft Palate - epidemiology - genetics
Cohort Studies
Denmark - epidemiology
Diseases in Twins - epidemiology - genetics
Epidemiology, Molecular
Female
Humans
Incidence
Infant
Infant, Newborn
Male
Pregnancy
Prevalence
Prospective Studies
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Risk factors
Seasons
Sex Factors
Twin Studies
Variation (Genetics)
Abstract
Since Dr. Fogh-Andersen's legendary 1942 thesis, the Danish facial cleft population has been one of the most extensively studied in terms of epidemiology and genetic-epidemiology. The etiology of cleft lip and/or palate (CLP) is still largely an enigma, and different results concerning environmental and genetic risk factors are obtained in different countries and regions. This may be due to etiological heterogeneity between settings. Therefore, an in-depth studied area with an ethnically homogeneous population, such as Denmark, has provided one of the best opportunities for progress in CLP etiological research. The present review summarizes epidemiological and genetic-epidemiological studies conducted in the 20th century Danish facial cleft population. Furthermore, analyses of sex differences, time trends and seasonality for more than 7000 CLP cases born in Denmark in the period 1936 to 1987 are presented. The review also points toward the excellent opportunities for continued etiological CLP research in Denmark in the 21st century using already established resources and an on-going prospective cohort study of 100,000 pregnant women.
PubMed ID
10213053 View in PubMed
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1991 Volvo Award in clinical sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins.

https://arctichealth.org/en/permalink/ahliterature65039
Source
Spine. 1991 Sep;16(9):1015-21
Publication Type
Article
Date
Sep-1991
Author
M C Battié
T. Videman
K. Gill
G B Moneta
R. Nyman
J. Kaprio
M. Koskenvuo
Author Affiliation
Department of Orthopaedics, University of Washington, Seattle.
Source
Spine. 1991 Sep;16(9):1015-21
Date
Sep-1991
Language
English
Publication Type
Article
Keywords
Awards and Prizes
Comparative Study
Diseases in Twins - epidemiology
Finland - epidemiology
Humans
Intervertebral Disk Displacement - diagnosis - epidemiology - etiology
Lumbar Vertebrae - pathology
Magnetic Resonance Imaging
Male
Middle Aged
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Smoking - adverse effects
Sweden
Twins, Monozygotic
Abstract
The primary objective of this study was to determine whether disc degeneration, as assessed through magnetic resonance imaging, is greater in smokers than in nonsmokers. To control for the maximum number of potentially confounding variables, pairs of identical twins highly discordant for cigarette smoking were selected as study subjects. Data analyses revealed 18% greater mean disc degeneration scores in the lumbar spines of smokers as compared with nonsmokers. The effect was present across the entire lumbar spine, implicating a mechanism acting systemically. This investigation demonstrates the efficiency of using carefully selected controls in studying conditions of multifactorial etiology, such as disc degeneration.
PubMed ID
1948392 View in PubMed
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Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation.

https://arctichealth.org/en/permalink/ahliterature61796
Source
Am J Physiol Endocrinol Metab. 2000 Jun;278(6):E985-91
Publication Type
Article
Date
Jun-2000
Author
G. Gupta
J A Cases
L. She
X H Ma
X M Yang
M. Hu
J. Wu
L. Rossetti
N. Barzilai
Author Affiliation
Department of Medicine, and the Diabetes Research and Training Center, Albert Einstein College of Medicine, New York, New York 10461, USA.
Source
Am J Physiol Endocrinol Metab. 2000 Jun;278(6):E985-91
Date
Jun-2000
Language
English
Publication Type
Article
Keywords
Adipose Tissue
Aging
Animals
Body Composition
Energy intake
Gluconeogenesis
Glucose - biosynthesis
Glycogen - metabolism
Insulin - pharmacology
Leptin - metabolism
Liver - drug effects - metabolism
Male
Rats
Rats, Inbred BN
Rats, Inbred F344
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Abstract
Increased total fat mass (FM) and visceral fat (VF) may account in part for age-associated decrease in hepatic insulin action. This study determined whether preventing the changes in body fat distribution abolished this defect throughout aging. We studied the F(1) hybrid of Brown Norway-Fischer 344 rats (n = 29), which we assigned to caloric restriction (CR) or fed ad libitum (AL). CR (55% of the calories consumed by AL) was initiated and used at 2 mo to prevent age-dependent increases in FM and VF. AL rats were studied at 2, 8, and 20 mo; CR rats were studied at 8 and 20 mo. VF and FM remained unchanged throughout aging in CR rats. AL-fed rats at 8 and 20 mo had over fourfold higher FM and VF compared with both CR groups. Insulin clamp studies (3 mU. kg(-1). min(-1) with somatostatin) were performed to assess hepatic insulin sensitivity. Prevention of fat accretion resulted in a marked improvement in insulin action in the suppression of hepatic glucose production (HGP) (6.3 +/- 0.3 and 7.2 +/- 1.2 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 8.3 +/- 0.5 and 10.8 +/- 0.9 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The rate of gluconeogenesis (by enrichment of hepatic uridine diphosphate glucose and phosphoenolpyruvate pools by [(14)C]lactate) was unchanged in all groups. The improvement in hepatic insulin action in the CR group was mostly due to effective suppression of glycogenolysis (4.4 +/- 0.3 and 4.9 +/- 0.3 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 5.8 +/- 0.6 and 8.2 +/- 1.0 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The results demonstrated the preservation of hepatic insulin action in aging CR rats. Therefore, body fat and its distribution are major determinants of age-associated hepatic insulin resistance.
PubMed ID
10826999 View in PubMed
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Abnormal Papanicolaou smears and colposcopic follow-up among American Indian and Alaska Native women in the Pacific northwest.

https://arctichealth.org/en/permalink/ahliterature4082
Source
J Am Board Fam Pract. 1995 May-Jun;8(3):183-8
Publication Type
Article
Author
T J Gilbert
J R Sugarman
N. Cobb
Author Affiliation
Fred Hutchinson Cancer Research Center, Division of Public Health Services, Seattle, WA, USA.
Source
J Am Board Fam Pract. 1995 May-Jun;8(3):183-8
Language
English
Publication Type
Article
Keywords
Alaska
Cervical Intraepithelial Neoplasia - ethnology - pathology
Colposcopy
Decision Trees
Female
Follow-Up Studies
Humans
Indians, North American
Northwestern United States
Prevalence
Research Support, U.S. Gov't, P.H.S.
Retrospective Studies
Uterine Cervical Neoplasms - ethnology - pathology
Vaginal Smears
Abstract
BACKGROUND: Mortality that is due to cervical cancer among American Indian and Alaska Native women in the Pacific Northwest exceeds that among women of other races. Nevertheless, little information is available regarding the prevalence and follow-up of abnormal Papanicolaou smears among American Indian and Alaska Native women in the region. METHODS: We conducted a retrospective review of medical records of American Indian and Alaska Native women seen at 12 Indian Health Service and tribally operated clinics in Washington, Oregon, and Idaho who had an abnormal Papanicolaou smear in 1992. RESULTS: Of 4547 Papanicolaou smear results reviewed, 280 (6.2 percent) had an abnormal result (dysplasia or carcinoma in situ). Of the recommended colposcopies, 167 of 224 (75 percent) were completed. Women with high-grade squamous intraepithelial lesions were more likely to obtain recommended colposcopy than were women with low-grade squamous intraepithelial lesions. Women treated at clinics that referred patients to outside providers for colposcopy were more likely to have colposcopy than were those who were offered the procedure on site. CONCLUSIONS: The proportion of Pacific Northwest American Indian and Alaska Native women in Indian Health Service and tribal clinics with abnormal Papanicolaou smears and the proportion who receive colposcopy are similar to those in other populations. The higher rate of cervical cancer mortality among American Indian and Alaska Native women could be due to failure to screen high-risk women. Cytologic screening rates, methods to improve adherence to colposcopy recommendations, and the contribution of other factors to the cause of cervical cancer mortality need to be characterized in this population.
PubMed ID
7618496 View in PubMed
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Aboriginal social organization, contemporary experience and American Indian adolescent alcohol use.

https://arctichealth.org/en/permalink/ahliterature9665
Source
J Stud Alcohol. 2003 Jul;64(4):450-7
Publication Type
Article
Date
Jul-2003
Author
Paul Spicer
Douglas K Novins
Christina M Mitchell
Janette Beals
Author Affiliation
American Indian and Alaska Native Programs, University of Colorado Health Sciences Center, Nighthorse Campbell Native Health Building, P.O. Box 6508, Mailstop F800, Aurora, Colorado 80045, USA. paul.spicer@uchsc.edu
Source
J Stud Alcohol. 2003 Jul;64(4):450-7
Date
Jul-2003
Language
English
Publication Type
Article
Keywords
Adolescent
Alcohol Drinking - ethnology - psychology
Analysis of Variance
Chi-Square Distribution
Comparative Study
Cross-Sectional Studies
Female
Humans
Indians, North American - psychology - statistics & numerical data
Longitudinal Studies
Male
Oceanic Ancestry Group - psychology - statistics & numerical data
Regression Analysis
Research Support, U.S. Gov't, P.H.S.
United States - ethnology
Abstract
OBJECTIVE: Anthropologists with an interest in American Indian alcohol use have long held that how native people drink has been conditioned by aspects of the social organization of their societies prior to the disruptive influences of European colonialism. Our goal in this article was to explicitly test the importance of these factors in four contemporary American Indian cultural groups. METHOD: Using data on adolescent alcohol use drawn from the first full wave of the longitudinal Voices of Indian Teens Project (N = 1,651, 51% female), we tested whether patterns of quantity-frequency of alcohol use and the negative consequences of alcohol use predicted by social organzational variables were found among contemporary adolescents and, subsequently, whether these differences persisted when other, more proximal, variables were included. RESULTS: Cultural differences appeared to account for a small percentage of the variance in both quantity-frequency of alcohol use and negative consequences in the initial steps of our analyses, but the pattern in these data was not consistent with the predictions of existing theories regarding aboriginal social organization. Moreover, these cultural differences were no longer significant in the final step of our analyses, suggesting that the cultural differences that did exist were better explained by other factors, at least among these adolescents. CONCLUSIONS: Although these analyses did not indicate that culture was irrelevant in understanding adolescent alcohol use in American Indian communities, classic formulations of these effects were of limited utility in understanding the experiences of contemporary American Indian adolescents.
Notes
Erratum In: J Stud Alcohol. 2004 Jan;65(1):153
PubMed ID
12921186 View in PubMed
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ABri peptide associated with familial British dementia forms annular and ring-like protofibrillar structures.

https://arctichealth.org/en/permalink/ahliterature3098
Source
Amyloid. 2004 Mar;11(1):10-3
Publication Type
Article
Date
Mar-2004
Author
Rekha Srinivasan
Roger E Marchant
Michael G Zagorski
Author Affiliation
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA.
Source
Amyloid. 2004 Mar;11(1):10-3
Date
Mar-2004
Language
English
Publication Type
Article
Keywords
Alzheimer Disease - metabolism
Amyloid - chemistry - metabolism
Amyloid beta-Protein - chemistry - metabolism
Diabetes Mellitus, Type 2 - metabolism
Humans
Microscopy, Atomic Force
Nerve Tissue Proteins - chemistry - metabolism
Parkinson Disease - metabolism
Peptides - chemistry - metabolism
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Senile Plaques - metabolism
Synucleins
alpha-Synuclein
Abstract
Amyloid plaque deposition involves the aggregation of normally soluble proteins into insoluble amyloid fibrils (fibrillization) and proceeds through intermediates with distinct morphologies, including spherical aggregates, protofibrils, and mature fibrils. Recently, a novel annular protofibril-like intermediate with unique pore-like properties was produced by alpha-synuclein, A beta-Arctic and amylin, which are proteins associated with Parkinson's disease, Alzheimer's disease, and type-II diabetes. The observation of annular structures coupled with size selective channel-like activity by these proteins suggests that these structures may be responsible for vesicle permeability by ion-channel formation. Using atomic force spectroscopy, we report here that the ABri peptide associated with familial British dementia produces similar annular and ring-like protofibril structures during the following sequence of events: spherical aggregates (0.4-1.5 nm height)-->chain-like protofibrils (1.5-2.3 nm height)-->ring-like protofibrils and annular protofibrils (1.5-2.3 nm height). This suggests that ABri fibrillization occurs in a similar fashion to other amyloidogenic proteins and that the annular protofibrillar structures may represent a common amyloid intermediate.
PubMed ID
15185493 View in PubMed
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2105 records – page 1 of 211.