The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

International Nuclear Information System (INIS)

Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

2007-01-01

Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to

Diagnostic value of glypican-3 in alpha fetoprotein negative ...

African Journals Online (AJOL)

EB

2013-09-03

Sep 3, 2013 ... School of Basic Medical Sciences, Capital Medical University, 100069, China. Abstract ... alpha fetoprotein(AFP) negative HCC and cirrhotic nodules is still difficult. Objectives: ..... Asia-Pacific Working Party on Prevention of.

[The alpha-fetoprotein in prognosis of survival of and functional rehabilitation of patients with ischemic stroke].

Science.gov (United States)

Arkhipkin, A A; Liang, O V; Kochetov, A G

2014-10-01

The study was carried out to determine the prognostic value of alpha-fetoprotein in development of lethal outcome and degree of functional rehabilitation of patients with ischemic stroke. The sampling included 216 patients in acute period of ischemic stroke. At the first day of development of disease they were measured the level of human alpha-fetoprotein. At the second day of disease patients were evaluated the degree of functional rehabilitation and the rate of lethal outcomes was calculated. Previously, the reference interval for alpha-fetoprotein was calculated according the guidelines of the International federation of clinical chemistry and national standard. The reference interval amounted to 0.59-3.78 mE/l. The study results demonstrated that low level of alpha-fetoprotein is related to higher risk of lethal outcome (SE=1.7, p=0.012). The increasing of level of alpha-fetoprotein over mentioned threshold value statistically significant increases probability of survival of patients. The further increasing more than 2.28 mE/l is related to subsequent good functional rehabilitation according the modifies Rankine scale (SE=1.4, p=0.001) and Barthel index (SE=1.49, p<0.001).

Direct analysis of the lectin reactivity of alpha-fetoprotein in maternal serum by crossed affinity radio-immunoelectrophoresis

International Nuclear Information System (INIS)

Kerckaert, J.P.; Bayard, B.; Biserte, G.; Puech, F.; Codaccioni, X.

1980-01-01

Affinity experiments with the lentil (Lens culinaris) lectin have revealed the existence of two distinct molecular populations of alpha-fetoprotein: lectin reactive and lectin non-reactive. Using a combination of crossed lectin immunoelectrophoresis and radio-immunoelectrophoresis, it has been possible to obtain directly the lentil lectin affinity patterns of alpha-fetoprotein present in maternal sera. The lentil lectin reactivity of maternal alpha-fetoprotein decreases almost linearly with the gestational age from week 15 to 35. (Auth.)

Immunohistochemical and radioimmunological demonstration of alpha/sub 1/-fetoprotein in nonmalignant changes of human gastric mucosa

Energy Technology Data Exchange (ETDEWEB)

Falser, N; Lederer, B; Reissigl, H [Innsbruck Univ. (Austria). Pathologisch-Anatomisches Lab.; Innsbruck Univ. (Austria). Gastroenterologisches Lab.)

1977-07-01

The occurence of ..cap alpha../sub 1/ fetoprotein in nonmalignant changes of the gastric mucosa was investigated by means of immunohistochemistry and radioimmunonoassay. The investigations were performed in tissue sections, cytological imprint preparations as well as in homogenized tissue samples (obtained by gastroscopy). ..cap alpha../sub 1/ fetoprotein could be demonstrated by immuno-histochemistry in about 90% of the samples originating from the surroundings of gastric ulcer and the region of gastrojejunostomy after B II-resection. The RIA was positive in about 75% of the tissue samples, whereas from gastric juice only 40% of positive results could be obtained. No ..cap alpha../sub 1/ fetoprotein-activity could be demonstrated in serum samples. These investigations indicate that ..cap alpha../sub 1/ fetoprotein is not exclusively synthesized by embryonic or neoplastic tissues and also can be synthesized also by regenerating cell-systems. It may be supposed that this synthesis represents an unspecific answer to growth-stimulation.

Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration

International Nuclear Information System (INIS)

Panduro, A.; Shalaby, F.; Weiner, F.R.; Biempica, L.; Zern, M.A.; Shafritz, D.A.

1986-01-01

During liver regeneration induced by CCl 4 administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl 4 administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal [ 3 H]thymidine incorporation into DNA which peaks at 48 h. Other genes related to liver-specific functions, such as ligandin, alpha 1-antitrypsin, and cytochrome P-450's, as well as general cellular genes pro alpha 1- and pro alpha 2-collagen, beta-actin, and alpha-tubulin, respond in kinetic patterns often distinct from each other and from albumin and alpha-fetoprotein. Changes in the steady-state levels of albumin and alpha-fetoprotein mRNA correlate with changes in transcription, but there is a lag in alpha-fetoprotein mRNA accumulation, which peaks at 72 h following CCl 4 administration. These studies indicate that reciprocal changes in albumin and alpha-fetoprotein gene transcription occur during CCl 4 -induced liver regeneration, leading to changes in the level of these specific mRNAs. These changes precede DNA synthesis and would appear to represent an alteration in differentiated function of hepatocytes in conjunction with the liver regenerative process

Equine alpha-fetoprotein levels in Lipizzaner mares with normal pregnancies and with pregnancy loss.

Science.gov (United States)

Vincze, Boglárka; Gáspárdy, András; Kulcsár, Margit; Baska, Ferenc; Bálint, Ádám; Hegedűs, György Tamás; Szenci, Ottó

2015-12-01

Alpha-fetoprotein has proved to be a good indicator of fetal well-being in human medicine for decades. Although this molecule is present in most of the mammalian species including horses, reference values in healthy and high-risk pregnant mares have not yet been published. The aim of the present study was to determine whether equine alpha-fetoprotein (eqAFP) is a good indicator of complicated pregnancies in Lipizzaner mares. A total of 111 serum samples from 30 mares have been analyzed for eqAFP levels throughout gestation (Days 60-325). After the pregnancy was confirmed, 23 mares had normal pregnancies with viable foals, six had late embryonic loss, and one of the mares aborted in the ninth gestational month. Equine alpha-fetoprotein concentrations significantly differed in the normal group (72.93 ± 49.25 pg/mL; mean ± standard deviation) and in the complicated pregnancy loss group (152 ± 36.48 pg/mL; mean ± standard deviation). The mares' age, gestational age, and the conception rate significantly affected the alpha-fetoprotein concentrations in the normal group. Furthermore, notable individual differences occurred in eqAFP concentrations between mares. Equine alpha-fetoprotein seems to be an important indicator of fetal well-being in horses, but there are still some unanswered questions (levels in foals of different age, ponies, and draft horses) regarding this serum protein. Large-scale studies are needed to assess the specificity, sensitivity, and reliability of this test as a possible future diagnostic tool for fetal well-being in horses. Copyright © 2015 Elsevier Inc. All rights reserved.

Prenatal radiographic diagnosis of alpha-fetoprotein positive malformations in early pregnancy

International Nuclear Information System (INIS)

Probst, F.P.; Sigurd, J.

1980-01-01

Early diagnosis of two malformed fetuses with positive alpha-fetoprotein test of the amniotic fluid with the aid of amniography is reported. Radiographic, diagnostic and prognostic aspects are discussed. (Auth.)

Diagnostic value of glypican-3 in alpha fetoprotein negative ...

African Journals Online (AJOL)

Background: The prognosis of patients with hepatocellular carcinoma(HCC) is generally very poor with a 5-year survival rate of less than 15% since most of them are diagnosed clinically at their late stage.However,the differential diagnosis between alpha fetoprotein(AFP) negative HCC and cirrhotic nodules is still difficult.

ALPHA-FETOPROTEIN IN FETAL SERUM, AMNIOTIC-FLUID, AND MATERNAL SERUM

NARCIS (Netherlands)

VANLITH, JMM; BEEKHUIS, [No Value; VANLOON, AJ; MANTINGH, A; DEWOLF, BTHM; BREED, ASPM

In order to gain more insight into the association between alpha-fetoprotein (AFP) and fetal chromosomal disorders, especially Down's syndrome, we measured AFP in fetal serum, amniotic fluid, and maternal serum at cordocentesis. We compared the concentration and gradient of AFP in these three

Nonpalpable testicular pure seminoma with elevated serum alpha-fetoprotein presenting with retroperitoneal metastasis: a case report.

Science.gov (United States)

Iwatsuki, Shoichiro; Naiki, Taku; Kawai, Noriyasu; Etani, Toshiki; Iida, Keitaro; Ando, Ryosuke; Nagai, Takashi; Okada, Atsushi; Tozawa, Keiichi; Sugiyama, Yosuke; Yasui, Takahiro

2016-05-05

Patients with a primary pure seminoma in the testis who have elevated serum alpha-fetoprotein are rare and should be treated as patients with nonseminomatous germ cell tumors. However, nonpalpable testicular tumors in this condition have never been reported. We describe a case of nonpalpable pure testicular seminoma with elevated serum alpha-fetoprotein presenting retroperitoneal metastasis. A 29-year-old Asian man was referred to our hospital with right flank pain. Computed tomography showed a mass located between his aorta and inferior vena cava, but a testicular tumor was not detected. His serum levels of lactate dehydrogenase, alpha-fetoprotein, and DUPAN-2 were high. Although no tumor or nodule was palpable in his testis, ultrasonography revealed multiple low echoic lesions in his right testicular parenchyma. He was diagnosed with right testicular cancer with retroperitoneal lymph node metastasis and underwent right high orchiectomy. A pathological examination revealed pure seminoma and no nonseminomatous components were found in the specimen. Three courses of induction systemic chemotherapy (cisplatin, etoposide, and bleomycin) normalized his serum alpha-fetoprotein and DUPAN-2 levels. Three additional courses of chemotherapy (etoposide and bleomycin) were performed, and treatment was completed with laparoscopic retroperitoneal lymph node dissection. Pathology of the dissected specimen showed fibrous and necrotic tissue with no viable cells. He is alive without recurrence 54 months after orchiectomy. We report a case of pure testicular seminoma with elevated serum alpha-fetoprotein and DUPAN-2 presenting retroperitoneal metastasis. We recommend an ultrasound examination of bilateral testes when large retroperitoneal tumors are detected in young men, even if a mass is not palpable in the scrotum.

Validation of the alpha-fetoprotein model for hepatocellular carcinoma recurrence after transplantation in an Asian population.

Science.gov (United States)

Rhu, Jinsoo; Kim, Jong Man; Choi, Gyu Seong; Kwon, Choon Hyuck David; Joh, Jae-Won

2018-02-20

This study was designed to validate the alpha-fetoprotein model for predicting recurrence after liver transplantation in Korean hepatocellular carcinoma patients. Patients who underwent liver transplantation for hepatocellular carcinoma at Samsung Medical Center between 2007 and 2015 were included. Recurrence, overall survival, and disease-specific survival of patients divided by both the Milan criteria and the alpha-fetoprotein model were compared using Kaplan-Meier log-rank test. The predictability of the alpha-fetoprotein model compared to the Milan criteria was tested by means of net reclassification improvement analysis applied to patients with a follow-up of at least 2 years. A total of 400 patients were included in the study. Patients within Milan criteria had 5-year recurrence, and overall survival rates of 20.9% and 76.3% respectively, compared to corresponding rates of 50.3% and 55.7%, respectively, for patients who were beyond Milan criteria. Alpha-fetoprotein model low risk patients had 5-year recurrence and overall survival rates of 21.1% and 76.2%, respectively, compared to corresponding rates of 57.7% and 52.2%, respectively, in high risk patients (P<0.001, all). Although overall net reclassification improvements were statistically nonsignificant for recurrence (NRI=1.7%, Z=0.30, p=0.7624), and overall survival (NRI=9.0%, Z=1.60, p=0.1098), they were significantly better for predicting no recurrence (NRI=6.6%, Z=3.16, p=0.0016) and no death. (NRI=7.7%, Z=3.65, p=0.0003) CONCLUSIONS: The alpha-fetoprotein model seems to be a promising tool for liver transplantation candidacy, but further investigation is needed.

Fifty years of discovery of alpha-fetoprotein as the first tumor marker

Directory of Open Access Journals (Sweden)

Nikulina Dina

2015-01-01

Full Text Available Alpha-fetoprotein represents the most prominent oncobiomarker, widely used in the diagnosis of hepatocellular carcinoma for monitoring of tumor progression, presence of metastasis, assessment of cancer prognosis and successful antitumor therapeutic measures. Yuri Semenovich Tatarinov is a Russian scientist who first published antigen specific for human hepatocellular carcinoma in 1963. To commemorate the 50th anniversary of the discovery of alpha-fetoprotein, 9th International Scientific- Practical Conference entitled “Achievements of fundamental science and translational medicine capabilities in solving actual problems of practical public health”, was held from May 6-8th, 2013 in Astrakhan, Russia. The conference was held in memory of historical scientific work of Yuri Semenovich Tatarinov. [Projekat Ministarstva nauke Republike Srbije, br. 175056

Diagnostic value of alpha-fetoprotein in liver cancer

International Nuclear Information System (INIS)

Pervez, T.; Anwar, S.M.

2001-01-01

Objective: To determine diagnostic value of alpha-fetoproteins (alpha-FP) in liver cancer. Design: Prospective study. Place and duration of study: Department of clinical oncology services Hospital Lahore, during the period from February 1998 to February 2001. Subjects and Methods: Among 200 persons studied, 100 presented with liver mass, jaundice and other symptoms directing toward liver pathology, later confirmed histopathologically, as suffering from hepatocellular carcinoma (HCC) while the other 100 healthy subject came to the department for blood donation and were HBs Ag pasitive on blood screening. All these subjects under went blood test for alpha-FP. This tumor marker was analyzed by using enzyme immunoassay-based kit. Results: The alpha-FP positivity was statistically evaluated. In HCC this test was statistically significant with p value of <0.001. In this study sensitivity of alpha-FP was 72% specificity 89%, positive predictive value 86.7% and negative predictive value of 76.1%. Conclusion: This study showed that alpha-FP was a useful diagnostic tool in the diagnosis of HCC. (author)

Interferometer immunosensor based on porous silicon for determining alpha-fetoprotein

Science.gov (United States)

Lv, Xiaoyi; Jiang, Jing; Lv, Guodong; Mo, Jiaqing; Jia, Zhenhong

2016-10-01

An increased level of alpha-fetoprotein ( AFP) in the blood may be a sign of liver cancer. Porous silicon based optical microcavities structure is prepared as a label-free immunosensor platform for detecting AFP. After the antigen-antibody reaction, it is monitored that the red shift of the reflection spectrum of the immunosensor increases

Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury

DEFF Research Database (Denmark)

Schmidt, Lars E; Dalhoff, Kim

2005-01-01

An increase in alpha-fetoprotein (AFP) following hepatic necrosis is considered indicative of hepatic regeneration. This study evaluated the prognostic value of serial AFP measurements in patients with severe acetaminophen-induced liver injury. Prospectively, serial measurements of AFP were...

Alpha-fetoprotein as a tool to distinguish amniotic fluid from urine, vaginal discharge, and semen.

Science.gov (United States)

Mor, Amir; Tal, Reshef; Haberman, Shoshana; McCalla, Sandra; Irani, Mohamad; Perlman, Jaqueline; Seifer, David B; Minkoff, Howard

2015-02-01

To estimate whether alpha-fetoprotein (AFP) can be used to distinguish amniotic fluid absorbed in sanitary pads from other similarly absorbed substances (semen, urine, and normal vaginal discharge). A prospective cohort study. Urine and amniotic fluid specimens were collected from 52 pregnant women admitted for labor. Semen specimens were collected from 17 men undergoing infertility evaluation. Alpha-fetoprotein concentrations were measured directly from urine, amniotic fluid, and semen and from pads instilled with samples from these specimens. Alpha-fetoprotein concentrations were also measured from pads absorbed with normal vaginal discharge collected from 27 pregnant women. Alpha-fetoprotein levels in amniotic fluid (245.38 ± 21.03 ng/mL, n = 52) were significantly higher than those measured in maternal urine (0.84 ± 0.17 ng/mL, n = 52, P < .001), or semen (1.52 ± 0.35 ng/mL, n = 17, P < .001). The same trend was seen when AFP was extracted from pads: amniotic fluid levels (19.44 ± 1.98 ng/mL, n=52) were significantly higher than those of urine (undetectable, n=52), semen (undetectable, n = 17), or normal vaginal discharge (0.53 ± 0.16 ng/mL, n = 27, P < .001). Receiver operator characteristic curve analysis demonstrated 96.2% sensitivity and 100% specificity for distinguishing the presence of amniotic fluid from normal vaginal discharge on sanitary pads (cutoff 3.88 ng/mL, area under the curve 0.99). When the diagnosis of rupture of membranes is in doubt, AFP levels can assist in differentiating amniotic fluid from other bodily fluids. A method that utilizes sanitary pads and an assay for AFP quantification may be an accurate and convenient way to confirm the diagnosis of rupture of membranes.

Acute Exacerbation of Hepatitis in Liver Cirrhosis with Very High Levels of alpha-Fetoprotein But No Occurrence of Hepatocellular Carcinoma

Science.gov (United States)

Park, Sang Jong; Park, Kwang Bo; Paik, So Ya; Ryu, Jin Kyung; Choi, Chang Kyu; Hwang, Tae Joon

2005-01-01

Aminotransferase levels do not always increase during acute hepatitis or during an acute flare-up of chronic hepatitis. Persistently increased levels of serum alpha-Fetoprotein in an adult with liver disease suggest not only the presence or progression of hepatocellular carcinoma or its recurrence after hepatic resection or after other therapeutic approaches such as chemotherapy or chemoembolization, but also it suggests that there is an acute exacerbation of hepatitis or liver cirrhosis. We report here on two unusual cases of HBV- & HCV-related liver cirrhosis with acute exacerbation of hepatitis in which there was an insignificant elevation of the aminotransferase levels, but there were markedly increased alpha-Fetoprotein levels observed. The levels of alpha-Fetoprotein decreased gradually in both cases since the beginning of antiviral therapy, which implies that the increased levels were due to aggravation of the accompanying hepatitis. These cases also emphasize that using only the measurement of alpha-Fetoprotein is not sufficient for the diagnosis of hepatocellular carcinoma, and that this diagnosis also requires a more specific measurement such as AFP L3 along with the standard imaging studies. PMID:15906959

Subtle Hepatocellular Carcinoma: A Persisting Role for Alpha-Fetoprotein Monitoring in High-Risk Patients with Cirrhosis

Directory of Open Access Journals (Sweden)

Barry Schlansky

2011-10-01

Full Text Available Hepatocellular carcinoma (HCC is a common, aggressive malignancy that usually develops in a background of liver cirrhosis. Practice guidelines recommend screening of cirrhotic patients with ultrasound and more detailed imaging (computed tomography or magnetic resonance imaging if abnormalities are detected. The utility of alpha-fetoprotein levels in HCC surveillance is controversial. Although HCC risk differs by etiology of cirrhosis, screening and surveillance guidelines are uniform after cirrhosis is established. We report a case of rapidly progressive HCC occurring in a cirrhotic patient with multiple unique risk factors for neoplasia, detected by a rising alpha-fetoprotein level without imaging features of liver cancer.

FIRST-TRIMESTER MATERNAL SERUM ALPHA-FETOPROTEIN AS A MARKER FOR FETAL CHROMOSOMAL DISORDERS

NARCIS (Netherlands)

VANLITH, JMM

1994-01-01

We evaluated first-trimester maternal serum alpha-fetoprotein (MS-AFP) as a marker for fetal chromosomal disorders. The multicentre study was performed under the auspices of the Dutch Working Party on Prenatal Diagnosis. MS-AFP was measured in 2404 normal pregnancies and 72 chromosomally abnormal

ORIGIN OF RAISED MATERNAL SERUM ALPHA-FETOPROTEIN LEVELS IN 2ND-TRIMESTER OLIGOHYDRAMNIOS

NARCIS (Netherlands)

LOS, FJ; BEEKHUIS, [No Value; MARRINK, J; HAGENAARS, AM; REUSS, A; SACHS, ES; JAHODA, MGJ; WLADIMIROFF, JW

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a

Regression of hepatocarcinoma cells using RNA aptamer specific to alpha-fetoprotein

Energy Technology Data Exchange (ETDEWEB)

Lee, Young Ju [Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin 448-701 (Korea, Republic of); Lee, Seong-Wook, E-mail: SWL0208@dankook.ac.kr [Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin 448-701 (Korea, Republic of)

2012-01-06

Highlights: Black-Right-Pointing-Pointer Identification of RNA aptamer specific to AFP with high affinity. Black-Right-Pointing-Pointer Specific induction of HCC proliferation by AFP. Black-Right-Pointing-Pointer Efficient increase in oncogene expression by AFP. Black-Right-Pointing-Pointer Efficient inhibition of AFP-mediated HCC proliferation by the aptamer. Black-Right-Pointing-Pointer Efficient suppression of AFP-induced oncogene expression of by the aptamer. -- Abstract: Alpha-fetoprotein (AFP) is a cancer-associated fetal protein and has long been utilized as a serum fetal defect/tumor marker to monitor distress/disease progression. In addition, AFP is closely associated with the proliferation of hepatocellular carcinoma. Thus, direct targeting of AFP has been recommended for a therapeutic strategy against hepatocellular carcinoma. In this study, we developed and characterized an RNA aptamer that specifically bound to the alpha-fetoprotein using SELEX technology. The aptamer interacted with the AFP with a K{sub D} of {approx}33 nM. Importantly, the identified aptamer specifically and efficiently inhibited the AFP-mediated proliferation of hepatocarcinoma cells in a dose dependent manner. Moreover, the aptamer efficiently down-regulated AFP-induced expression of oncogenes in the cells. These results indicate that an AFP-specific RNA aptamer could be a useful therapeutic and diagnostic agent against AFP-related hepatocellular carcinoma.

Regression of hepatocarcinoma cells using RNA aptamer specific to alpha-fetoprotein

International Nuclear Information System (INIS)

Lee, Young Ju; Lee, Seong-Wook

2012-01-01

Highlights: ► Identification of RNA aptamer specific to AFP with high affinity. ► Specific induction of HCC proliferation by AFP. ► Efficient increase in oncogene expression by AFP. ► Efficient inhibition of AFP-mediated HCC proliferation by the aptamer. ► Efficient suppression of AFP-induced oncogene expression of by the aptamer. -- Abstract: Alpha-fetoprotein (AFP) is a cancer-associated fetal protein and has long been utilized as a serum fetal defect/tumor marker to monitor distress/disease progression. In addition, AFP is closely associated with the proliferation of hepatocellular carcinoma. Thus, direct targeting of AFP has been recommended for a therapeutic strategy against hepatocellular carcinoma. In this study, we developed and characterized an RNA aptamer that specifically bound to the alpha-fetoprotein using SELEX technology. The aptamer interacted with the AFP with a K D of ∼33 nM. Importantly, the identified aptamer specifically and efficiently inhibited the AFP-mediated proliferation of hepatocarcinoma cells in a dose dependent manner. Moreover, the aptamer efficiently down-regulated AFP-induced expression of oncogenes in the cells. These results indicate that an AFP-specific RNA aptamer could be a useful therapeutic and diagnostic agent against AFP-related hepatocellular carcinoma.

Clinical evaluation of anti-alpha-fetoprotein radioimmunodetection

International Nuclear Information System (INIS)

Chapman, C.E.; Keeling, A.A.; Bradwell, A.R.; Chandler, S.T.; Dykes, P.W.

1986-01-01

Anti-alpha-fetoprotein (AFP) radioimmunodetection was performed in response to clinical requests in 16 patients. In two patients, assessment of a known tumour was required; the anti-AFP scans were accurate and provided useful clinical information in both cases. In the remaining 14 patients the request was for localisation of suspected recurrent tumour. Accurate information was provided in four of these patients. In this latter group, various conventional methods of investigation had failed to disclose the site of recurrence. However, of a total of 21 sites reported as positive in these 14 patients, eight proved to be false positives. Two false negative results also occurred in this group and nine could not be evaluated. Although occasionally patients were usefully scanned, improvements are necessary before consistently reliable information can be obtained using this technique. (author)

MATERNAL SERUM ALPHA-FETOPROTEIN LEVELS AND FETAL-OUTCOME IN EARLY 2ND-TRIMESTER OLIGOHYDRAMNIOS

NARCIS (Netherlands)

LOS, FJ; HAGENAARS, AM; MARRINK, J; COHENOVERBEEK, TE; GAILLARD, JLJ; BRANDENBURG, H

Early second-trimester oligohydramnios was associated with normal maternal serum alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent). Congenital malformations of the fetal urinary tract resulting in fetal anuria were present in nine cases; in seven of them, normal MSAFP levels

Alpha-fetoprotein: methodology and clinical experiences with a new radioimmunoassay

International Nuclear Information System (INIS)

Lamerz, R.; Rjosk, H.; Schmalhorst, U.; Fateh-Moghadam, A.; Muenchen Univ.

1976-01-01

The clinical-diagnostical value of alpha-fetoproteins (AFP) compared with the use of common less sensitive methods was tested. The results obtained clearly showed that in the clinical-internal-surgical sphere the main importance of radioimmunological AFP-determinations lies in the improved supervision of the development of hepatomas in patients suffering from hepatic cirrhosis. In the pre-operative differential diagnosis of testicle tumors, these determinations help to optimize the therapeutic measures and are also useful for the case control of hepatoma and teratoma patients. (GSE) [de

99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

National Research Council Canada - National Science Library

Line, Bruce

1998-01-01

.... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

National Research Council Canada - National Science Library

Line, Bruce

1999-01-01

.... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

Female Mice Deficient in Alpha-Fetoprotein Show Female-Typical Neural Responses to Conspecific-Derived Pheromones

NARCIS (Netherlands)

Brock, O.; Keller, M.; Douhard, Q.; Bakker, J.

2012-01-01

The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to

Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients

Directory of Open Access Journals (Sweden)

Rino A Gani

2016-05-01

Full Text Available Aim: to evaluate the use of alpha-1-acid glycoprotein (AAG for diagnosing hepatocellular carcinoma (HCC, and to combine with alpha fetoprotein (AFP as part of routine examination in liver cirrhosis patients. Methods: this is a diagnostic study using cross-sectional design. A hundred and six patients were included in this study. Baseline data such as age, gender, AFP, AAG, peripheral blood count, AST and ALT were consecutively collected from liver cirrhosis patients with or without HCC. Serum AAG were measured quantitatively using immunoturboditimetric assay and AFP with enzyme immune assay (EIA. Statistical analysis were done using SPSS 13.0. Data comparisons between group were done using Mann-Whitney test. Diagnostic performance for each marker alone was compared to the surrogate use of both markers (combined parallel approach in HCC cases. Results: receiver operating characteristic (ROC analysis showed that area under the curve for AFP AAG combination was 88.1% and higher than AFP only (86.2% or AAG only (76.5% with sensitivity of 83%, 73% and 44%, respectively, at specificity of >80%. Conclusion: our study showed that combination of AFP and AAG is superior than either marker alone in diagnosing HCC in liver cirrhosis patients. Combination of AFP and AAG may be used to prompt early diagnosis screening of HCC. Key words: alpha fetoprotein, alpha-1-acid glycoprotein, biomarker, liver cancer

Alpha-fetoprotein-producing Gastric Cancer with Metastasis to the Scrotum: Case Report

International Nuclear Information System (INIS)

Cho, Young Joon; Chung, Jae Joon; Yu, Jeong Sik; Kim, Joo Hee; Kim, Dae Jung; Ahn, Jhii Hyun; Cho, Eun Suk

2010-01-01

An alpha-fetoprotein-producing gastric cancer is rare, making up only about 3% of all gastric cancers. Further, gastric cancer with metastasis to the scrotum via a transperitoneal route is extremely rare. We report a case of metastatic scrotal mass in a 68-year-old man who had undergone a subtotal gastrectomy and gastroduodenostomy due to signet ring cell type gastric cancer with a description focusing on the radiologic findings

Alpha-fetoprotein-producing Gastric Cancer with Metastasis to the Scrotum: Case Report

Energy Technology Data Exchange (ETDEWEB)

Cho, Young Joon [Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Jae Joon; Yu, Jeong Sik; Kim, Joo Hee; Kim, Dae Jung; Ahn, Jhii Hyun; Cho, Eun Suk [Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2010-11-15

An alpha-fetoprotein-producing gastric cancer is rare, making up only about 3% of all gastric cancers. Further, gastric cancer with metastasis to the scrotum via a transperitoneal route is extremely rare. We report a case of metastatic scrotal mass in a 68-year-old man who had undergone a subtotal gastrectomy and gastroduodenostomy due to signet ring cell type gastric cancer with a description focusing on the radiologic findings

DETECTION OF FETOMATERNAL HEMORRHAGE ASSOCIATED WITH CORDOCENTESIS USING SERUM ALPHA-FETOPROTEIN AND THE KLEIHAUER TECHNIQUE

NARCIS (Netherlands)

VANSELM, M; KANHAI, HHH; VANLOON, AJ

Fetomaternal haemorrhage (FMH) was studied after 46 cordocenteses. alpha-Fetoprotein (AFP) concentration and Kleihauer staining of maternal blood, taken both before and after the procedure, revealed increases in AFP values of more than 40 per cent in 30 per cent of the patients examined; fetal

Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review.

Science.gov (United States)

Horta, Mariana; Cunha, Teresa Margarida; Marques, Rita Canas; Félix, Ana

2014-11-01

Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker.

Dosage of alpha-fetoprotein for radioimmunoassay in maternal blood

International Nuclear Information System (INIS)

Pandolfo, J.; Jaumandreu, C.A.; Aguirre de Garcia, B.; Robles, A.M.; Touya, E.

1981-01-01

Leigthon, Gordon and col. showed that the determination of serum levels of alpha-fetoprotein was useful as a method for the detection of fetal malformations of the neural tube. Due to its important clinical significance, the study of this simple test in women in different stages of pregnancy has been started. A total of 34 patients from the obstetrical external service were studied, with pregnancy stages between 10 and 40 weeks. Having established the incidence and implications of false positive and principally of false negative results, it has been concluded that this technique should be imposed as routine in the evolutive control of pregnancy. (M.B.) [es

[Engineering of a System for the Production of Mutant Human Alpha-Fetoprotein in the Methylotrophic Yeast Pichia pastoris].

Science.gov (United States)

Morozkina, E V; Vavilova, E A; Zatsepin, S S; Klyachko, E V; Yagudin, T A; Chulkin, A M; Dudich, I V; Semenkova, L N; Churilova, I V; Benevolenskii, S V

2016-01-01

A system for the production of mutant recombinant human alpha-fetoprotein (rhAFPO) lacking the glycosylation site has been engineered in the yeast Pichia pastoris. A strain of the methylotrophic yeast Pichia pastoris GS 115/pPICZ?A/rhAFP0, which produces unglycosylated rhAFPO and secretes it to the culture medium, has been constructed. Optimization and scale-up of the fermentation technology have resulted in an increase in the rhAFP0 yield to 20 mg/L. A scheme of isolation and purification of biologically active rhAFP0 has been developed. The synthesized protein has the antitumor activity, which is analogous to the activity of natural human embryonic alpha-fetoprotein.

Preoperative Alpha-Fetoprotein Slope is Predictive of Hepatocellular Carcinoma Recurrence after Liver Transplantation

Directory of Open Access Journals (Sweden)

Kathy Han

2007-01-01

Full Text Available BACKGROUND: Liver transplantation (LT offers a possible cure for patients with hepatocellular carcinoma (HCC and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP levels.

Removal Of Labeled ALPHA-Fetoprotein (AFP) Using Rice Husk-Based Activated Carbon

International Nuclear Information System (INIS)

ABDEL-MOUHTY, N.R.

2009-01-01

Biomass agricultural waste materials, rice husk (RH) or saw dust (SD), were used for the preparation of activated carbons. RH was activated by chemical activation using phosphoric acid or potassium hydroxide. The prepared activated carbons were characterized and used for the adsorption of labeled alpha-fetoprotein ( 125 I-AFP) from the lab waste of iodine labeled alpha-fetoprotein tracer. The effects of various factors, e.g. carbon type, carbon dosage, temperature, particle size of carbon, effect of different waste volumes on the adsorption capacity, were quantitatively determined. Desorption of activated carbon was also investigated. From the experimental results, it was found that SDK had the lowest ability for adsorption of 125I-AFP and the highest uptake was 83% by carbon RHH. The amount of adsorption accomplished per unit weight of a solid adsorbent was greater, the more finely divided and the more porous the solid. 0.5 g for RHH carbon was found to be optimum dose of adsorbent for the removal of 125I-AFP. The optimum volume of waste with 0.5 g dose of RHH was 15 ml. The increased adsorption with temperature may be due to the increase of the intra-particle diffusion rate of sorbate ions into the pores at higher temperature as diffusion is an endothermic process.

Autism Spectrum Disorders and Maternal Serum alpha-Fetoprotein Levels During Pregnancy

DEFF Research Database (Denmark)

Abdallah, Morsi; Grove, Jakob; Hougaard, David M

2011-01-01

Objective: Numerous studies have been trying to disentangle the complex pathophysiology of autism spectrum disorders (ASD). In our study, we explored the potential role of maternal serum (MS) alpha-fetoprotein (AFP) in the prediction and the pathophysiology of ASD. Methods: A total of 112 patients...... role in the pathophysiology of ASD makes AFP a good candidate for further larger-scale studies to confirm such an association and to determine whether this pattern is unique to ASD or related to other psychiatric disorders as well....

Improvement and multicenter evaluation of the analytical performance of an automated chemiluminescent immunoassay for alpha fetoprotein

NARCIS (Netherlands)

Morota, Kaori; Komori, Makoto; Fujinami, Ryo; Yamada, Koji; Kuribayashi, Kageaki; Watanabe, Naoki; Sokoll, Lori J.; Elliott, Debra; Chan, Daniel W.; Martens, Frans; Heijboer, Annemieke C.; Blankenstein, Marinus A.; Hershberger, Stefan J.; Pfeiffer, Zachary A.; Vaidya, Shyam V.; Dowell, Barry L.

2012-01-01

A new ARCHITECT® alpha fetoprotein (AFP) assay was developed to improve the linearity at the upper end of the calibration curve and to enhance other performance characteristics. In addition, this reformulation eliminated the possibility of falsely depressed samples at high AFP concentrations. The

The radioimmunoassay of serum alpha-fetoprotein levels

International Nuclear Information System (INIS)

Kim, Y. H.; Choi, K. A.; Ahn, K. S.; Suh, W. H.; Lee, M. J.

1982-01-01

Alpha-fetoprotein (AFP) was first described in the human fetus in 1956 and became a marker protein of primary liver cancer in adults. Serum AFP levels were measured by radioimmunoassay in 212 patients with a variety of malignant and nonmalignant diseases to determine the incidence of leveis elevated above 40 ng/ml. The results obtained are as follows: In 44 cases of total 212 patients, abnormal AFP levels above 40 ng/ml in serum were measured; 24 of 31 patients with primary hepatocellular carcinoma and primary hepatocellular carcinoma with liver cirrhosis (77.4%), 7 of 51 patients with only liver cirrhosis (13.7%), 4 of 10 patients with metastatic liver cancer (40.0%), 4 of 15 patients with chronic hepatitis (26.7%), 2 of 23 patients with acute hepatitis (8.7%), and each one patient with 6 pancreatic carcinoma and 9 cholangiocarcinoma had elevated serum AFP levels. One pregnant woman with gestation 35 weeks had elevated level, but within normal limit during pregnancy

The radioimmunoassay of serum alpha-fetoprotein levels

Energy Technology Data Exchange (ETDEWEB)

Kim, Y H; Choi, K A; Ahn, K S; Suh, W H; Lee, M J [Korea University College of Medicine, Seoul (Korea, Republic of)

1982-06-15

Alpha-fetoprotein (AFP) was first described in the human fetus in 1956 and became a marker protein of primary liver cancer in adults. Serum AFP levels were measured by radioimmunoassay in 212 patients with a variety of malignant and nonmalignant diseases to determine the incidence of leveis elevated above 40 ng/ml. The results obtained are as follows: In 44 cases of total 212 patients, abnormal AFP levels above 40 ng/ml in serum were measured; 24 of 31 patients with primary hepatocellular carcinoma and primary hepatocellular carcinoma with liver cirrhosis (77.4%), 7 of 51 patients with only liver cirrhosis (13.7%), 4 of 10 patients with metastatic liver cancer (40.0%), 4 of 15 patients with chronic hepatitis (26.7%), 2 of 23 patients with acute hepatitis (8.7%), and each one patient with 6 pancreatic carcinoma and 9 cholangiocarcinoma had elevated serum AFP levels. One pregnant woman with gestation 35 weeks had elevated level, but within normal limit during pregnancy.

Correlation between preoperative serum alpha-fetoprotein levels and survival with respect to the surgical treatment of hepatocellular carcinoma at a tertiary care hospital in Veracruz, Mexico

Directory of Open Access Journals (Sweden)

G. Martínez-Mier

2017-10-01

Full Text Available Introduction: Preoperative serum alpha-fetoprotein levels can have predictive value for hepatocellular carcinoma survival. Aim: Our aim was to analyze the correlation between preoperative serum alpha-fetoprotein levels and survival, following the surgical treatment of hepatocellular carcinoma. Methods: Nineteen patients were prospectively followed (07/2005-01/2016. An ROC curve was created to determine the sensitivity and specificity of alpha-fetoprotein in relation to survival (Kaplan-Meier. Results: Of the 19 patients evaluated, 57.9% were men. The mean patient age was 68.1 ± 8.5 years and survival at 1, 3, and 5 years was 89.4, 55.9, and 55.9%. The alpha-fetoprotein cutoff point was 15.1 ng/ml (sensitivity 100%, specificity 99.23%. Preoperative alpha-fetoprotein levels below 15.1, 200, 400, and 463 ng/ml correlated with better 1 and 5-year survival rates than levels above 15.1, 200, 400, and 463 ng/ml (P<.05. Conclusions: Elevated preoperative serum alpha-fetoprotein levels have predictive value for hepatocellular carcinoma survival. Resumen: Introducción: Los niveles séricos de alfafetoproteína (AFP preoperatoria pueden tener valor predictivo para la sobrevida del hepatocarcinoma (HCC. Objetivo: Analizar la correlación entre los niveles séricos de AFP preoperatoria y la sobrevida posterior al tratamiento quirúrgico del HCC. Métodos: Diecinueve pacientes fueron seguidos prospectivamente (julio del 2005-enero del 2016. Se realizó una curva ROC para determinar la sensibilidad y la especificidad de la AFP con relación con la sobrevida (Kaplan-Meier. Resultados: Se evaluó a 19 pacientes, 57.9% hombres, edad media 68.1 ± 8.5 años con sobrevida a 1, 3 y 5 años del 89.4, el 55.9 y el 55.9%. El punto de corte de AFP fue 15.1 ng/ml (sensibilidad 100%, especificidad 99.23%. Los niveles preoperatorios de AFP menores de 15.1, 200, 400 y 463 ng/ml correlacionaron con mejor sobrevida a 1 y 5 años que niveles mayores de AFP (p < 0

CONCANAVALIN-A VARIANTS OF ALPHA-FETOPROTEIN IN FIRST TRIMESTER FETUSES WITH TRISOMY-21 AND WITH NORMAL KARYOTYPES

NARCIS (Netherlands)

LOS, FJ; JANSE, HC; BRANDENBURG, H; DEVRIJ, RW; DEBRUIJN, HWA

1995-01-01

Total alpha-fetoprotein (AFP) concentrations and proportions of AFP non-reactive with the lectin concanavalin A (Con A) were studied in extracellular fluid of 22 first-trimester fetuses. Total AFP concentrations were significantly lower in fetuses with Down's syndrome than in those with

Validity of Alpha Fetoprotein for Diagnosis of Hepatocellular Carcinoma in Cirrhosis

International Nuclear Information System (INIS)

Sarwar, S.; Tarique, S.; Khan, A. A.

2014-01-01

Objective: To determine the accuracy of serum alpha fetoprotein (AFP) for diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. Study Design: Observational study. Place and Duration of Study: Department of Medicine, The King Edward Medical University, Lahore, from November 2007 to August 2011. Methodology: Consecutive patients, diagnosed with HCC by contrast enhanced CT, MRI or biopsy were included as cases. Patients of cirrhosis with no evidence of HCC were enrolled as controls. Demographic, laboratory and radiological data were recorded. Serum AFP was determined in all patients at outset and was analyzed using ROC curve for its accuracy in diagnosing HCC. Results: A total of 275 patients were included; of them 173 had HCC and 102 had cirrhosis. One hundred and thirty nine cases (80.3%) with HCC and 86 (84.3%) without HCC had cirrhosis due to HCV. Stage of liver disease, as determined by Child Turcotte Pugh (CTP) score, was comparable; mean CTP value 7.97 A +- 2.1A +- 2.21 in control group (p 0.41). Area under curve (AUC) for AFP was 0.85 (95%, CI: 0.80 - 0.90) with optimum cut off value of 20.85 ng/ml which showed 72.2% sensitivity, 86.2% specificity, 89.9% positive predictive value, 64.7% negative predictive value and 77.4% overall accuracy in diagnosing patients with HCC. Conclusion: Despite sub-optimal sensitivity, alpha fetoprotein is still a valid screening test for diagnosis of hepatocellular carcinoma till other more sensitive markers are developed. Till then, it should be used in conjunction with ultrasound. (author)

Elevated alpha-fetoprotein: differential diagnosis - hepatocellular carcinoma and other disorders.

Science.gov (United States)

Wong, Robert J; Ahmed, Aijaz; Gish, Robert G

2015-05-01

The incidence of cirrhosis-related hepatocellular carcinoma (HCC) is rising. Curative surgical options are available; outcomes are acceptable with early diagnosis. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are HCC risk markers. A high or increasing serum biomarker level can be predictive of the eventual development of HCC, large tumor size, advanced stage, extrahepatic metastases, portal vein thrombosis, and postoperative HCC recurrence. Based on FDA guidelines for HCC risk assessment, clinicians can consider using either the combination of AFP-L3 with DCP, or the combination of AFP-L3 with AFP and DCP. Copyright © 2015 Elsevier Inc. All rights reserved.

The evaluation of domestic immunoradiometric assay kit for alpha-fetoprotein

International Nuclear Information System (INIS)

Won, Kyoung Sook; Ryu, Jin Sook; Moon, Dae Hyuk; Lee, Hee Kyung

2000-01-01

Although α-fetoprotein is one of the most commonly used tumor markers in Korea, most of the radioimmunoassay kits for α-fetoprotein have been imported from foreign countries. The purpose of this study was to evaluate the performance of a recently developed domestic immunoradiometric kit for α-fetoprotein (Riakey AFP IRMA CT R , Sin-Jin Medics, Seoul, Korea). We evaluated intra-and inter-assay precision, recovery rate, parallelism, and sensitivity of serum α-fetoprotein measurement using Riakey AFP IRMA CT R kit. The values of α-fetoprotein measured by Riakey AFP IRMA CT R kit were compared with those measured by two foreign commercial kits (α-fetoproteina of Radim and α-feto.riabead of Abbott). Intra-assay coefficients of variation on three different levels were 5.3% for 18.9 ng/ml, 3.4% for 133 ng/ml and 1.6% for 330 ng/ml. Inter-assay coefficients of variation were 9.7% for 20.9 ng/ml, 3.2% for 137 ng/ml and 4.1% for 330 ng/ml respectively. Recovery rate tests on all three different levels showed within 100±10%. Parallelism was also good and the sensitivity was 0.63 ng/ml. There was strong correlation between the measurement of α-fetoprotein by Riakey AFP IRMA CT R and that by two foreign commercial kits(r=3D0.98). The first Korean domestic immunoradiometric kit for α-fetoprotein, Riakey AFP IRMA CT R , performed well for clinical use.=20

Fabrication of protein microarrays for alpha fetoprotein detection by using a rapid photo-immobilization process

Directory of Open Access Journals (Sweden)

Sirasa Yodmongkol

2016-03-01

Full Text Available In this study, protein microarrays based on sandwich immunoassays are generated to quantify the amount of alpha fetoprotein (AFP in blood serum. For chip generation a mixture of capture antibody and a photoactive copolymer consisting of N,N-dimethylacrylamide (DMAA, methacryloyloxy benzophenone (MaBP, and Na-4-styrenesulfonate (SSNa was spotted onto unmodified polymethyl methacrylate (PMMA substrates. Subsequently to printing of the microarray, the polymer and protein were photochemically cross-linked and the forming, biofunctionalized hydrogels simultaneously bound to the chip surface by short UV- irradiation. The obtained biochip was incubated with AFP antigen, followed by biotinylated AFP antibody and streptavidin-Cy5 and the fluorescence signal read-out. The developed microarray biochip covers the range of AFP in serum samples such as maternal serum in the range of 5 and 100 ng/ml. The chip production process is based on a fast and simple immobilization process, which can be applied to conventional plastic surfaces. Therefore, this protein microarray production process is a promising method to fabricate biochips for AFP screening processes. Keywords: Photo-immobilization, Protein microarray, Alpha fetoprotein, Hydrogel, 3D surface, Down syndrome

Frequency of deaths in hepatitis C virus infected hepatocellular carcinoma patients and its relationship with raised serum alpha-fetoprotein levels.

Science.gov (United States)

Shaikh, Fida Hussain; Zeb, Shaista; Chandio, Sultan Ahmed; Munaf, Alvina; Ghori, Muhamad Aamir; Memon, Mohammad Sadik; Burney, Asif Ali

2016-01-01

To determine the frequency of deaths in hepatitis C virus infected hepatocellular carcinoma patients, and its relationship with raised serum alpha-fetoprotein levels. The cross-sectional study was conducted at Isra University Hospital, Hyderabad, Pakistan, between March 2013 and April 2014, and comprised all patients diagnosed with hepatitis C virus and hepatocellular carcinoma over 30 years ofage. Blood sample was drawn for the measurement of serum Alfa fetoprotein levels. Data was analysed using SPSS 16. The mean age of the 165 patients was55.49±11.67 years. The mean tumour size was 5.63 ± 2.14cm. Of the total, 31(18.8%) patients had tumour size 5cm. The mean serum Alfa fetoprotein level was 7641.0±3665.32 IU/ml. Overall mortality rate was 70(41.9%). Tumour size >5cm was significantly associated with mortality (p=0.016). Serum Alfa fetoprotein levels were a useful tool for the detection of hepatocellular carcinoma in hepatitis C virus patients.

Intrinsic labeling of alpha-fetoprotein with 65Zn

International Nuclear Information System (INIS)

Preiss, I.L.

1994-01-01

Many enzymes, proteins, and large molecules bind a variety of inorganic ions. The replacement of a specific metal ion with another element can disrupt the biodistribution and biochemistry of the host molecule. Alpha-fetoprotein (AFP) is a known oncofetal antigen. The authors have demonstrated that the substitution of Cu or Pb on AFP inhibits the transplacental migration of AFP and may lead to fetal demise. It is evident that in labeling with a radiotracer in order to observe the true distribution of a molecule, one must select a radioisotope of an element which is naturally bound to the host molecule. It has been demonstrated that AFP binds Zn in vivo. Thus, substituting 65 Zn for natural Zn produces an intrinsic label for AFP. The authors discuss the methodology for stripping and labeling of AFP with 65 Zn. The biodistribution of labeled AFP is compared with that of 65 Zn 2+ in healthy and diseased (hepatoma) animals

Serum concentration of alpha-1-fetoprotein suggestive of, or pathognomonic for hepatoma

International Nuclear Information System (INIS)

Polterauer, P.; Horak, W.; Legenstein, E.; Mueller, M.

1979-01-01

A short review of alpha-1-fetoprotein (AFP), is followed by a presentation of the serum AFP concentrations obtained in healthy subjects and in patients with hepatoma, cirrhosis of the liver or metastatic liver cancer, measured by radioimmunoassay (RIA). A calculation is made from these results of the upper limit of normal (9 ng/ml), a limit which is suggestive of hepatome (215 ng/ml) and a limit which is pathognomonic for hepatoma (7500 ng/ml). It is concluded that the quantitative determination of AFP by RIA represents a sensitive method which provides valuable clinical information for the early diagnosis of hepatoma. (author)

comparative study between different oxidizing agents to prepare radioiodinated alpha fetoprotein (AFP)

International Nuclear Information System (INIS)

El-Kolaly, M.T.; Ragab, M.T.; El-Mohty, A.A.; Sallam, K.M.; Arief, M.H.

2004-01-01

the aim of the present study was designed to prepare four different preparation of radioiodinated alpha fetoprotein ( 125 I-Afp) using different oxidizing agents. the oxidizing agents were chloramine-T (Ch-T), lodogen (1,3,4 , 6-tetrachloro 3 α ,6α diphenyl glycoluril ), N-bromosuccinimide (NBS) and lactoperoxidase (LPS). the product was purified by gel filtration using sephadex G-25. then the tracers obtained were tested by radioimmunoassay (RIA) technique. different affecting factors were extensively studied including reaction time, reaction volume, oxidizing agent content and Ph of reaction. it was found that the Ch-T method is the best one

Serum alpha fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance

NARCIS (Netherlands)

de Wit, R; Collette, L; Sylvester, R; de Mulder, PHM; Sleijfer, DT; Huinink, WWT; Kaye, SB; van Oosterom, AT; Boven, E; Stoter, G

It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a

Concentration of carcinoembryonic antigen alpha-fetoprotein and beta-subunit of human chorionic gonadotropin in the serum of coke oven workers

Energy Technology Data Exchange (ETDEWEB)

Snit, M. [Silesian Medical Academy, Zabrze (Poland)

1993-01-01

Increased levels of carcinoembryonic antigen and {alpha}-fetoprotein were found in blood serum of coke oven workers, and also to some extent in smokers and in residents of industrial cities. The {beta} subunit of chorionic gonadotropin was barely detectable.

Gold nanoparticles and polyethylene glycols functionalized conducting polyaniline nanowires for ultrasensitive and low fouling immunosensing of alpha-fetoprotein.

Science.gov (United States)

Hui, Ni; Sun, Xiaotian; Song, Zhiling; Niu, Shuyan; Luo, Xiliang

2016-12-15

An ultrasensitive biosensor for alpha-fetoprotein was developed based on electrochemically synthesized polyaniline (PANI) nanowires, which were functionalized with gold nanoparticles (AuNPs) and polyethylene glycols (PEG). The prepared PEG/AuNPs/PANI composite, combining the electrical conductivity of the AuNPs/PANI with the robust antifouling ability of PEG, offered an ideal substrate for the development of low fouling electrochemical biosensors. Alpha-fetoprotein (AFP), a well-known hepatocellular carcinoma biomarker, was used as a model analyte, and its antibody was immobilized on the PEG/AuNPs/PANI for the construction of the AFP immunosensor. Using the redox current of PANI as the sensing signal, in addition to the good biocompatibility of PEG/AuNPs and the anti-biofouling property of PEG, the developed immunosensor showed improved biosensing performances, such as wide linear range and ultralow detection limit (0.007pgmL(-1)). More importantly, it is label-free, reagentless and low fouling, making it capable of assaying AFP in real serum samples without suffering from significant interference or biofouling. Copyright © 2016 Elsevier B.V. All rights reserved.

Hepatocellular carcinoma (HCC) and diagnostic significance of alpha-fetoprotein (AFP)

International Nuclear Information System (INIS)

Baig, J.A.; Alam, J.M.; Baig, M.; Mahmood, S.R.; Shaheen, R.; Waheed, A.

2009-01-01

Alpha-fetoprotein (alpha-fetoprotein, AFP) is a Glycoprotein, belonging to the intriguing class of onco-development protein. Generally designated as tumour marker, AFP is recognized as an important blood component, having specific diagnostic utilities Elevation of its level up to pathological range in adults correlate with the appearance of several malignant and chronic conditions, such as hepatocellular carcinoma (HCC) and chronic liver disease, respectively. To evaluate the diagnostic significance of AFP in HCC, a study was carried out for a period of two years (Jan. 2004 to Dec. 2005) A brief history of Patients was taken with clinical symptoms and signs and initial diagnosis. Patients admitted in wards or visiting OPDs with diagnosis or suspicions of HCC and additional conditions of Chronic Liver disease (CLDs), hepatitis C (HCV) and hepatitis B viral (HBV) infections, were selected and classified according to gender. When confirmed, their HCC status was evaluated and classified according to clinical condition. In 1012 adults including, males 762 (75.3%) and females 250 (24.7%) patients suspected of or diagnosed with HCC and presence of HBV and HCV infections. Out of 480 males, who depicted elevated AFP levels, 39 (8.13%) were diagnosed with HCC. Similarly, 7 (5.34%) females out of 131 with elevated levels of AFP were diagnosed with HCC. Mean elevated AFP levels in all HCC patients were, 421+-59 mu g/ml (range 157-4019 mu g/ml) in males and 163+-32 mu g/ml (range 101-2341 mu g/ml) in females. In males, the overall estimated mean AFP elevated values were analyzed to be 514 mu g/ml (range 67-4019+-59 mu g/ml), whereas in females it was 396+-42 mu g/ml (range 21-2341 mu g/ml). It was also noted that 43 (8.96%) males and 7 (5.34%) female patients, exhibited elevated levels of AFP, however, found negative for HCV and HBV infections. It is concluded that AFP is a significant markers for Hepatocellular carcinoma, helpful in assessing problems in management of HCC and

INCREASED MATERNAL SERUM ALPHA-FETOPROTEIN AND HUMAN CHORIONIC-GONADOTROPIN IN COMPROMISED PREGNANCIES OTHER THAN FOR NEURAL-TUBE DEFECTS OR DOWN-SYNDROME

NARCIS (Netherlands)

BEEKHUIS, [No Value; VANLITH, JMM; DEWOLF, BTHM; MANTINGH, A

Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore,

Clinical value of combined measurement of serum alpha-fetoprotein, alpha-L-fucosidase and ferritin levels in the diagnosis of primary liver cancer

International Nuclear Information System (INIS)

Zhang Aimin; Chai Xiaohong; Jin Ying; Dong Xuemei

2005-01-01

Objective: To investigate the clinical value of combined measurement of serum alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU) and ferritin (SF) levels in the diagnosis of primary liver cancer. Methods: Serum AFP, AFU (with RIA) and SF (with biochemical method) were determined in 52 patients with primary liver cancer and 40 controls. Results: The positive rates of AFP, AFU and SF in patient with liver cancer were 82.7%, 86.6% and 76.9%, respectively. Positive rates with combined measurement of AFP plus AFU, AFP plus SF, and AFP plus AFU, SF were 94.2%, 90.4% and 98.1% respectively. Conclusion: Combined measurement of AFP, AFU and SF can significantly increase the positive rate in the diagnosis of primary liver cancer. (authors)

Immunoradiometric versus radioimmunoassay: a comparison using alpha-fetoprotein as the model analyte

International Nuclear Information System (INIS)

Hunter, W.M.; Budd, P.S.

1981-01-01

With alpha-fetoprotein as a model a formal comparison has been made between inhibition type radioimmunoassay with radioiodinated antigen, liquid-phase incubation and double antibody separation (RIA) and variants of the sandwich immunoradiometric assay (IRMA). 125 I-antibody was prepared (expensively) by labelling the IgG fraction and subsequently undertaking immunopurification to yield a reproducibly-high quality reagent, 70-75% being reactive with antigen. The same antiserum was coupled to Sepharose 4B for use in the IRMA and separation was by the sucrose layer procedure (Hunter, 1980) which obviates the need for centrifugation. The principal basis used for the comparison was computer-generated precision profiles (Ekins, 1976), each of which was derived from 10 assays of each kind. (Auth.)

Quantitative Alpha Fetoprotein Detection with a Piezoelectric Microcantilever Mass Sensor

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Kyu; Cho, Jong Yun; Jeon, Sang Min; Cha, Hyung Joon; Moon, Won Kyu [Pohang University of Science and Technology, Pohang (Korea, Republic of); Lee, Yeol Ho [Samsung Advanced Institute of Technology, Yongin (Korea, Republic of)

2011-10-15

Alpha fetoprotein(AFP), which is serological marker for hepatocellular carcinoma, was quantitatively measured by its normal concentration, 10 ng/ml, with a label-free piezoelectric microcantilever mass sensor. The principle of detection is based on changes in the resonant frequency of the piezoelectric microcantilever before and after target molecules are attached to it, and its resonant frequency is measured electrically using a conductance spectrum. The resonant frequency of the developed sensor is approximately 1.34 MHz and the mass sensitivity is approximately 175 Hz/pg. The sensor has high reliability as mass sensor by reducing the effect of surface stress on resonant frequency due to attached proteins. 'Dip and dry' technique was used to react the sensor with reagents for immobilizing AFP antibody on the sensor and detecting AFP antigen. The measured mass of the detected AFP antigen was 6.02 pg at the concentration of 10 ng/ml, and 10.67 pg at 50 ng/ml when the immunoreaction time was 10 min.

Quantitative Alpha Fetoprotein Detection with a Piezoelectric Microcantilever Mass Sensor

International Nuclear Information System (INIS)

Lee, Sang Kyu; Cho, Jong Yun; Jeon, Sang Min; Cha, Hyung Joon; Moon, Won Kyu; Lee, Yeol Ho

2011-01-01

Alpha fetoprotein(AFP), which is serological marker for hepatocellular carcinoma, was quantitatively measured by its normal concentration, 10 ng/ml, with a label-free piezoelectric microcantilever mass sensor. The principle of detection is based on changes in the resonant frequency of the piezoelectric microcantilever before and after target molecules are attached to it, and its resonant frequency is measured electrically using a conductance spectrum. The resonant frequency of the developed sensor is approximately 1.34 MHz and the mass sensitivity is approximately 175 Hz/pg. The sensor has high reliability as mass sensor by reducing the effect of surface stress on resonant frequency due to attached proteins. 'Dip and dry' technique was used to react the sensor with reagents for immobilizing AFP antibody on the sensor and detecting AFP antigen. The measured mass of the detected AFP antigen was 6.02 pg at the concentration of 10 ng/ml, and 10.67 pg at 50 ng/ml when the immunoreaction time was 10 min

Alpha-Fetoprotein: From a Diagnostic Biomarker to a Key Role in Female Fertility

Directory of Open Access Journals (Sweden)

Christelle De Mees

2006-01-01

Full Text Available Alpha-fetoprotein (AFP is a well-known diagnostic biomarker used in medicine to detect fetal developmental anomalies such as neural tube defects or Down's syndrome, or to follow up the development of tumors such as hepatocellular carcinomas. However, and despite the fact that the protein was discovered almost half a century ago, little was known about its physiological function. The study of Afp knock-out mice uncovered a surprising function of AFP: it is essential for female fertility and for expression of normal female behaviors, and this action is mediated through its estrogen binding capacity. AFP sequestrates estrogens and by so doing protects the female developing brain from deleterious (defeminizing/ masculinizing effects of these hormones

A novel label-free voltammetric immunosensor for the detection of {alpha}-fetoprotein using functional titanium dioxide nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Liang Wenbin [Chongqing Key Laboratory of Analytical Chemistry, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Yuan Ruo [Chongqing Key Laboratory of Analytical Chemistry, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)], E-mail: yuanruo@swu.edu.cn; Chai Yaqin; Li Yan; Zhuo Ying [Chongqing Key Laboratory of Analytical Chemistry, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)

2008-01-01

A highly sensitive label-free voltammetric immunosensor was developed based on the functional titanium dioxide nanoparticles (PV-NTiP), which was prepared by capping 1,1'-bis-(2-phosphonoethyl)-4,4'-bipyridinium dibromide (PV) on the surface of the titanium dioxide nanoparticles (NTiP) with covalent attachment. The PV-NTiP has prominent biocompatibility, good electron transfer ability, primarily excellent adsorption, large specific surface area and positively charged environment. As a result, the negatively charged gold nanoparticles (NGP) could be adsorbed on the PV-NTiP modified electrode surface by electrostatic adsorption, and then to immobilize {alpha}-1-fetoprotein antibody (anti-AFP) for the assay of {alpha}-1-fetoprotein (AFP). The fabricated procedures and electrochemical behaviors of the immunosensor were characterized by electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and cyclic voltammetry (CV). The anti-AFP/NGP/PV-NTiP modified electrode was sensitive to AFP in linear relation between 1.25 and 200 ng/mL with the correlation coefficient of 0.9982, and the detection limit (S/N = 3) is 0.6 ng/mL under the optimal conditions. In addition, the proposed immunosensor exhibits good sensitivity, selectivity, stability and long-term maintenance of bioactivity and it may be used to immobilize other biomoleculars to develop biosensor for the detection of other antigens or biocompounds.

ABNORMAL LEVELS OF MATERNAL SERUM HUMAN CHORIONIC-GONADOTROPIN AND ALPHA-FETOPROTEIN IN THE 2ND-TRIMESTER - RELATION TO FETAL WEIGHT AND PRETERM DELIVERY

NARCIS (Netherlands)

MORSSINK, LP; KORNMAN, LH; BEEKHUIS, [No Value; DEWOLF, BTHM; MANTINGH, A

The aim of this prospective descriptive cross-sectional study was to examine the clinical significance of abnormal maternal serum human chorionic gonadotropin (MShCG) and alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. The study group comprised 8892 women with a singleton pregnancy,

Intermethod discordance for alpha-fetoprotein measurements in Fanconi anemia.

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Cassinat, B; Darsin, D; Guardiola, P; Toubert, M E; Rain, J D; Gluckman, E; Schlageter, M H

2001-08-01

The significantly higher serum alpha-fetoprotein (AFP) in patients with Fanconi anemia (FA) than in non-FA aplastic patients has potential diagnostic utility, but the increase is method-dependent. The aim of this study was to compare five AFP assays on FA and non-FA samples and to investigate possible explanations for FA-specific discrepancies. Two methods available in our laboratory (Kryptor and IMx) were compared on 59 FA and 27 non-FA patient samples. Kryptor, Immulite, Elecsys, Immuno-I, and Elsa-2 methods were then compared on 14 FA and 14 non-FA patient samples. The AFP glycosylation profile was analyzed by electrophoretic separation in a lectin-containing gel. With all six methods, AFP values were significantly higher in FA than in non-FA patients, but the diagnostic precision and optimal cutoff values varied. Indeed, two methods reached 100% sensitivity and specificity, but in other methods, one or both of these parameters were significantly <100%. Neither heterophilic antibodies nor a specific glycosylation profile was detected in FA samples. AFP results are method-dependent in FA. New methods must be evaluated before use in differential diagnosis of aplastic patients.

Replacing Alpha-Fetoprotein With Alpha-Fetoprotein-L3 Increases the Sensitivity of Prenatal Screening for Trisomy 21.

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Huai, Lei; Leng, Jianhang; Ma, Shenglin; Huang, Fang; Shen, Junya; Ding, Yu

This study aimed to investigate the serum concentration of alpha-fetoprotein (AFP)-L3 in midterm pregnancies and its potential application in prenatal trisomy screening. The serum samples from 27 women with trisomy 21 fetuses and 800 women with normal fetuses were examined to measure the concentrations of AFP, AFP-L3, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The screening results of various tests consisting of these markers were analyzed. In normal pregnancies within 15-20 weeks of gestation, the medians of serum AFP-L3 were 4.63, 5.70, 5.78, 6.58, 7.03, and 7.25 pg/mL. The median of AFP-L3 MoM in the trisomy 21 group was 0.46, which was significantly lower than the value of 1 in the normal group (P < 0.05). When using a cutoff value of 1/270, the sensitivity of the triple marker test (AFP, hCG, uE3) was improved from 74% to 81% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 5.4% to 6.8%. Similarly, the sensitivity of the quad marker test (AFP, hCG, uE3, inhibin-A) was improved from 81% to 89% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 4.6% to 5.6%. Serum AFP-L3 concentration increases along with more weeks of gestation in the midterm pregnancies. Trisomy 21 screening tests with AFP replaced by AFP-L3 have higher sensitivities at the expense of slightly increased false-positive rates. This improvement in screening may help to better prepare the parents and caregivers for the special needs of newborns with trisomy 21.

Late solitary pelvic metastasis of hepatocellular carcinoma mimicking alpha-fetoprotein-producing gynaecologic tumour

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Ji He Kim

2018-01-01

Full Text Available Extrahepatic spread of hepatocellular carcinoma (HCC is uncommon; and, pelvic metastasis, in particular, is extremely rare. A 71-year-old woman was admitted for evaluation of pelvic solitary solid mass. She had undergone a left lobectomy 28 years previously. Magnetic resonance imaging of the abdomen and pelvis demonstrated a heterogeneous mass in the right pelvic cavity, whereas no space-occupying lesions or ascites were detected in the liver. CA 125 levels were within normal limits; however, serum alpha-fetoprotein levels were markedly elevated. She underwent laparoscopic pelvic mass excision, total hysterectomy, and bilateral salpingo-oophorectomy. Histopathologic findings and immunochemical staining results indicated metastatic HCC. Herein, we report an unusual case of a patient with solitary recurrence in the pelvic cavity 28 years after initial diagnosis and treatment.

Measurement of alpha-fetoprotein in maternal serum: three commercial radioimmunoassay kits and two non-commercial radioimmunoassays compared

International Nuclear Information System (INIS)

Forest, J.C.; Verreault, F.; Pouliot, M.

1982-01-01

We evaluated three commercial radioimmunoassay kits (Amersham, Dainabot, Clinical Assays) and two non-commercial methods for determining alpha-fetoprotein in maternal serum during pregnancy. All five procedures were found to be acceptable with respect to practicability, sensitivity, linearity, and precision. Similar results were obtained with Dainabot, Clinical Assays, and the two non-commercial methods, but the Amersham method revealed a proportional error, results being about 20% lower than those by the other methods. Use of the international unit system is suggested for reporting results for AFP, to facilitate comparison between methods and laboratories

Human alpha-fetoprotein and prostaglandins suppress human lymphocyte transformation by different mechanisms

International Nuclear Information System (INIS)

Yachnin, S.; Lester, E.P.

1979-01-01

The capacity of human alpha-fetoprotein (HAFP) to suppress human lymphocyte transformation is well established, although some investigators have reported negative results in their efforts to demonstrate this phenomenon. This discrepancy may reside in the fact that not all isolates of HAFP are potent inhibitors of lymphocyte transformation and that the immunosuppressive potency of various HAFP isolates may be correlated with the proportion of certain negatively charged HAFP isomers which they contain. The possibility was considered that noncovalent binding of low-molecular-weight, negatively charged molecules might be partially responsible. Since fatty acids, including certain prostaglandins (PG), are capable of binding to a partly related serum protein, namely, human serum albumin, and since certain prostaglandins are known to be potent suppressors of human lymphocyte transformation, a study was undertaken of the role which prostaglandins might play in HAFP-induced suppression of human lymphocyte transformation

Alpha-fetoprotein, a fascinating protein and biomarker in neurology.

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Schieving, J H; de Vries, M; van Vugt, J M G; Weemaes, C; van Deuren, M; Nicolai, J; Wevers, R A; Willemsen, M A

2014-05-01

Alpha-fetoprotein (AFP) is present in fetal serum in concentrations up to 5,000,000 μg/l. After birth, AFP gene expression is turned down with a subsequent fall of the serum concentrations of this albumin-like protein to 'adult values' of circa 0.5-15 μg/l from the age of 2 years onwards. Irrespective of its assumed important functions, individuals with AFP deficiency appear fully healthy. The other way around, the presence of AFP in the circulation after the first years of life doesn't seem to harm, since individuals with 'hereditary persistence of AFP' are also without clinical abnormalities. During pregnancy, AFP (in maternal serum) has long been recognized as a marker for congenital anomalies of the fetus. Equally well known is AFP as biomarker for hepatocellular carcinoma and some other malignancies. There are at least four neurodegenerative disorders, all inherited as autosomal recessive traits and characterized by the presence of cerebellar ataxia, abnormal ocular movements, and neuropathy, for which an elevated concentration of serum AFP is an important diagnostic biomarker. The availability of a reliable biomarker is not only important during screening or diagnostic processes, but is also relevant for objective follow-up during (future) therapeutic interventions. Copyright © 2013. Published by Elsevier Ltd.

The utility of alpha-fetoprotein screening in Beckwith-Wiedemann syndrome.

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Duffy, Kelly A; Deardorff, Matthew A; Kalish, Jennifer M

2017-03-01

Beckwith-Wiedemann syndrome (BWS) is one of the most common cancer predisposition disorders. As a result, BWS patients receive tumor screening as part of their clinical management. Until recently, this screening has been employed uniformly across all genetic and epigenetic causes of BWS, including the utilization of ultrasonography to detect abdominal tumors and alpha-fetoprotein (AFP) to detect hepatoblastoma. The advancements in our understanding of the genetics and epigenetics leading to BWS has evolved over time, and has led to the development of genotype/phenotype correlations. As tumor risk appears to correlate with genetic and epigenetic causes of BWS, several groups have proposed alterations to tumor screening protocols based on the etiology of BWS, with the elimination of AFP as a screening measure and the elimination of all screening measures in BWS patients with loss of methylation at the KCNQ1OT1:TSS-DMR 2 (IC2). There are many challenges to this suggestion, as IC2 patients may have additional factors that contribute to risk of hepatoblastoma including fetal growth patterns, relationship with assisted reproductive technologies, and the regulation of the IC2 locus. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Specific Genetic Immunotherapy Induced by Recombinant Vaccine Alpha-Fetoprotein-Heat Shock Protein 70 Complex

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Wang, Xiaoping; Lin, Huanping; Wang, Qiaoxia

Purposes: To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific CTL response and its protective effect against AFP-producing tumor. Material/Methods: A recombinant vaccine was constructed by conjugating mouse alpha-fetoprotein to heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-γ in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. Results: By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-γ and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50±11.70 IFN-γ spots/106 cells vs 41.60±10.40 IFN-γ spots/106 cells, 7.32±3.14 IFN-γ spots/106 cells, P<0.01; 156.32±10.42 μg/mL vs 66.52±7.35 μg/mL, 5.73±2.89 μg/mL, P<0.01). The tumor volume in mAFP/HSP70 group was significantly smaller than that in mAFP and HSP70 groups (42.44±7.14 mm3 vs 392.23±12.46 mm3, 838.63±13.84 mm3, P<0.01). Conclusions: The study further confirmed the function of heat shock protein 70's immune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for hepatocellular carcinoma.

Fluorescence Quenching of Alpha-Fetoprotein by Gold Nanoparticles: Effect of Dielectric Shell on Non-Radiative Decay

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Zhu, Jian; Li, Jian-Jun; Wang, A.-Qing; Chen, Yu; Zhao, Jun-Wu

2010-09-01

Fluorescence quenching spectrometry was applied to study the interactions between gold colloidal nanoparticles and alpha-fetoprotein (AFP). Experimental results show that the gold nanoparticles can quench the fluorescence emission of adsorbed AFP effectively. Furthermore, the intensity of fluorescence emission peak decreases monotonously with the increasing gold nanoparticles content. A mechanism based on surface plasmon resonance-induced non-radiative decay was investigated to illuminate the effect of a dielectric shell on the fluorescence quenching ability of gold nanoparticles. The calculation results show that the increasing dielectric shell thickness may improve the monochromaticity of fluorescence quenching. However, high energy transfer efficiency can be obtained within a wide wavelength band by coating a thinner dielectric shell.

Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma.

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Wang, Jeremy; Liu, Wendy; Parikh, Keyur; Post, Anthony Benjamin

2017-02-01

Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.

Appraisal of radioimmunotherapy with 131I anti-alpha fetoprotein monoclonal antibody in patients with primary liver cancer

International Nuclear Information System (INIS)

Huang Yaozhang

1992-01-01

Mixed anti-alpha-fetoprotein monoclonal antibodies (AFPMcAb) labeled with 131 I were used in the treatment of 23 patients of moderate to advanced primary liver cancer. In 16 cases treated with 24 doses, the survival periods were 18-605 days with a mean of 135 days. Two patients with moderately advanced liver cancer had a mean survival period of 465 days. According to our experience, the larger dose of 131 I and of anti-AFPMcAb, the longer the survival period and the better the therapeutic results were observed. The relationship between the ratio of cancer/liver radioactivity and the survival period remains to be elucidated

Alpha-fetoprotein and Fanconi Anemia: Relevance to DNA Repair and Breast Cancer Susceptibility.

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Lakhi, Nisha A; Mizejewski, Gerald J

2017-02-01

Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic instability disorders which lack the capability to repair DNA breaks. The lesion occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing FA cells to override cell-cycle arrest. FA DNA repair pathways contain complementation groups known as FANC proteins. FANC proteins form multi-protein complexes with BRCA proteins and are involved in homologous DNA repair. An impaired cascade in these events imparts an increased breast cancer susceptibility to female FA patients. Elevations of sAFP have availed this fetal protein to serve as a biomarker for FA disease. However, the origin of the synthesis of sAFA has not been determined in FA patients. We hypothesize that hematopoietic multipotent progenitor stem cells in the bone marrow are the source of sAFP production in FA patients.

Label-free immunosensor based on Pd nanoplates for amperometric immunoassay of alpha-fetoprotein.

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Wang, Huan; Li, He; Zhang, Yihe; Wei, Qin; Ma, Hongmin; Wu, Dan; Li, Yan; Zhang, Yong; Du, Bin

2014-03-15

In this paper, Pd nanoplates were used as a kind of electrode materials for fabrication of an electrochemical immunosensor, which was applied for detection of cancer biomarker alpha-fetoprotein (AFP). Thanks to the unique structure and properties of Pd nanoplates, the antibody of AFP (Ab) was effectively immobilized onto the surface of the Pd nanoplates modified glassy carbon electrode (GCE). Moreover, the good electrochemical properties of Pd nanoplates greatly improved the electronic transmission rate and enhanced the electrochemical signal, which led to an increase of the detection sensitivity. Based on the specific antibody-antigen interaction, a label-free immunosensor based on Pd nanoplates was developed for sensing of AFP. The current method allows us to detect AFP over a wide concentration range from 0.01 to 75.0 ng/mL with a detection limit of 4 pg/mL. The proposed immunosensor has been used to determine AFP in human serum with satisfactory results. © 2013 Elsevier B.V. All rights reserved.

Immunohistochemical and radioimmunological demonstration of alpha1-fetoprotein in nonmalignant changes of human gastric mucosa

International Nuclear Information System (INIS)

Falser, N.; Lederer, B.; Reissigl, H.; Innsbruck Univ.

1977-01-01

The occurence of α 1 fetoprotein in nonmalignant changes of the gastric mucosa was investigated by means of immunohistochemistry and radioimmunonoassay. The investigations were performed in tissue sections, cytological imprint preparations as well as in homogenized tissue samples (obtained by gastroscopy). α 1 fetoprotein could be demonstrated by immuno-histochemistry in about 90% of the samples originating from the surroundings of gastric ulcer and the region of gastrojejunostomy after B II-resection. The RIA was positive in about 75% of the tissue samples, whereas from gastric juice only 40% of positive results could be obtained. No α 1 fetoprotein-activity could be demonstrated in serum samples. These investigations indicate that α 1 fetoprotein is not exclusively synthesized by embryonic or neoplastic tissues and also can be synthesized also by regenerating cell-systems. It may be supposed that this synthesis represents an unspecific answer to growth-stimulation. (orig.) [de

Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol

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2013-01-01

Background Diagnosis of early-stage hepatocellular carcinoma (HCC) followed by curative resection or liver transplantation offers the best chance for long-term patient survival. Clinically, ultrasonography has suboptimal sensitivity for detecting early-stage HCC. Several serological tests including alpha-fetoprotein (AFP), the ratio of lens culinaris agglutinin-reactive alpha-fetoprotein to total AFP (AFP-L3/AFP), des-gamma carboxyprothrombin (DCP), and glypican-3 (GPC-3) have been widely investigated as diagnostic biomarkers for early-stage HCC in at-risk populations. However, these tests are not recommended for routine HCC screening. Our objective is to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of HCC, particularly early-stage tumors meeting the Milan criteria. Methods/design We will include cross-sectional studies that consecutively or randomly recruit target populations. We will search the Cochrane Library, Medline, Embase, Science Citation Index, and the Chinese National Knowledge Infrastructure. We will also search the MEDION and ARIF databases to identify diagnostic systematic reviews that include primary studies. Reference lists of relevant reviews will be searched for additional trials. Language restrictions will not be applied. Two reviewers will independently screen study eligibility and extract data. Methodological quality will be assessed according to the revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Two authors will apply the QUADAS-2 assessment to all the included studies, and any discrepancies will be resolved by the third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. When possible, we will use the bivariate random

Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma

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Lipika Lipi

2014-01-01

Full Text Available A 50-year-old male patient presented with pain abdomen of 6 months duration. Computed tomography scan revealed a large mass in the stomach occluding the lumen. Histopathology revealed a triple composite tumor comprising of tubular adenocarcinoma arising on a background of high-grade dysplasia, hepatoid adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein and large cell neuroendocrine carcinoma (positive for synaptophysin and chromogranin with nodal metastasis.Triple composite tumors are distinctly rare with few reports in literature.

Alpha-fetoprotein detection by using a localized surface plasmon coupled fluorescence fiber-optic biosensor

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Chang, Ying-Feng; Chen, Ran-Chou; Li, Ying-Chang; Yu, Chih-Jen; Hsieh, Bao-Yu; Chou, Chien

2007-11-01

Alpha-fetoprotein (AFP) detection by using a localized surface plasmon coupled fluorescence (LSPCF) fiber-optic biosensor is setup and experimentally demonstrated. It is based on gold nanoparticle (GNP) and coupled with localized surface plasmon wave on the surface of GNP. In this experiment, the fluorophores are labeled on anti-AFP which are bound to protein A conjugated GNP. Thus, LSPCF is excited with high efficiency in the near field of localized surface plasmon wave. Therefore, not only the sensitivity of LSPCF biosensor is enhanced but also the specific selectivity of AFP is improved. Experimentally, the ability of real time measurement in the range of AFP concentration from 0.1ng/ml to 100ng/ml was detected. To compare with conventional methods such as enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA), the LSPCF fiber-optic biosensor performs higher or comparable detection sensitivity, respectively.

Significance of radioimmunoassay of human chorionic gonadotropin and alpha fetoprotein in nonseminomatous germ cell tumors of the testis

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Kausitz, J.; Hupka, S. (Institute for Postgradual Training of Physicians and Pharmaceutists, Bratislava (Czechoslovakia)); Cerny, V.; Bohunicky, L.; Korec, S. (Ustav Klinickej Onkologie, Bratislava (Czechoslovakia))

1980-01-01

Radioimmunoassays human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) made in 49 patients with nonseminomatous testicular tumors showed that these investigations make the diagnosis more precise, permit to follow up the dynamics of the course of the disease and the effectiveness of treatment and may help to reveal the presence of otherwise undetectable tumorous metastases. The significance of these assays is enhanced if the two tumorous proteins are investigated in parallel. The results proved positive in 43 (87.8%) and false negative in 6 (12.2%) of the patients. The absence of HCG and AFP production in some patients with active disorder has not as yet been elucidated.

Significance of radioimmunoassay of human chorionic gonadotropin and alpha fetoprotein in nonseminomatous germ cell tumors of the testis

International Nuclear Information System (INIS)

Kausitz, J.; Hupka, S.; Cerny, V.; Bohunicky, L.; Korec, S.

1980-01-01

Radioimmunoassays human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) made in 49 patients with nonseminomatous testicular tumors showed that these investigations make the diagnosis more precise, permit to follow up the dynamics of the course of the disease and the effectiveness of treatment and may help to reveal the presence of otherwise undetectable tumorous metastases. The significance of these assays is enhanced if the two tumorous proteins are investigated in parallel. The results proved positive in 43 (87.8%) and false negative in 6 (12.2%) of the patients. The absence of HCG and AFP production in some patients with active disorder has not as yet been elucidated. (author)

Serum albumin and globulin analysis for hepatocellular carcinoma detection avoiding false-negative results from alpha-fetoprotein test negative subjects

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Wang, Jing; Feng, Shangyuan; Lin, Juqiang; Zeng, Yongyi; Li, Ling; Huang, Zufang; Li, Buhong; Zeng, Haishan; Chen, Rong

2013-11-01

Surface-enhanced Raman spectroscopy (SERS) of serum albumin and globulin were employed to detect hepatocellular carcinoma (HCC). Tentative assignments of SERS bands show specific biomolecular changes associated with cancer development. These changes include a decrease in relative amounts of tryptophan, glutamine, glycine, and serine, indicating excessive consumption of amino acids for protein duplication. Principal component analysis was also introduced to analyze the obtained spectra, resulting in both diagnostic sensitivity and specificity of 100%. More importantly, it reveals that this method can detect HCC patients with alpha-fetoprotein negative test results, suggesting its great potential as a new alternative to detect HCC.

Experimental study on 131I-labelled anti-alpha-fetoprotein antibodies in the diagnosis of rat hepatoma

International Nuclear Information System (INIS)

Terashima, Hiromi

1980-01-01

The tumor-specificity of 131 I-labelled anti-α-fetoprotein antibodies was evaluated in rats using α-fetoprotein-producing AH66C4 rat hepatoma as a model. 1) Following the 12 hour incubation of 125 I-labelled anti-α-fetoprotein antibodies and tumor cells, microautoradiography revealed marked radioactivity in and around the tumor cells. This suggested that the labelled antibodies accumulated around the cells and were combined with the α-fetoprotein secreted from the cells. 2) The tumor was transplanted subcutaneously into the thighs of rats. There was marked accumulation of 131 I-antibodies in the tumor with cyst formation, but there was none in the tumor without cyst formation. The accumulation was enhanced by the administration of non-labelled antibodies to the rats before the administration of 131 I-antibodies. The α-fetoprotein level was higher in the cyst than in any other organ. 131 I-labelled horse-γ-globulins administered as a control, also accumulated in the tumor with cyst but the degree of accumulation did not exceed that of the 131 I-antibodies. The amount of 131 I-antibodies accumulated increased, while that of 131 I-horse-γ-globulins decreased with time. This indicated that the accumulation of the γ-globulins in the tumor was nonspecific and that it was related to the blood pool. These results strongly suggest that the accumulation of 131 I-antibodies in the tumor with cyst formation was a specific antigen-antibody reaction, and the present procedure reported is applicable in the specific diagnosis of such kinds of α-fetoprotein secreting tumor. (author)

Increasing of sensitivity of fluorescent immunoassay analysis of alpha-fetoprotein by means of plasmonical silver nanoparticles

International Nuclear Information System (INIS)

Vashchenko, S.V.; Min'ko, A.A.; Romanenko, A.A.; Gaponenko, S.V.; Kulakovich, O.S.

2014-01-01

A test system is proposed based on metal enhanced fluorescence to analyze low concentrations of alpha-fetoprotein (AFP), a tumor marker. Antigen-antibody reaction was performed on polystyrene plates coated with silver nanoparticles to increase sensitivity of fluorescent immunoassay and signal-to-noise ratio as compared to silver-free system. As compared to widely used ELISA technique and other immunoassay techniques the proposed approach is characterized by smaller probe volume, fast analysis and simplicity. The proposed test system uses layer-by-layer assembly approach, LED excitation and nanowatt photodetection set-up. The proposed test system offers AFP detection at concentrations used in clinical practice. Fluorescence enhancement for labeled AFP antibodies on a silver substrate was found to depend on antibodies concentration and was up to 6 times. (authors)

Purification and characterization of a bioactive alpha-fetoprotein produced by HEK-293 cells.

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Lin, Bo; Peng, Guoqing; Feng, Haipeng; Li, Wei; Dong, Xu; Chen, Yi; Lu, Yan; Wang, Qiaoyun; Xie, Xieju; Zhu, Mingyue; Li, Mengsen

2017-08-01

Alpha-fetoprotein (AFP) is a biomarker that is used to diagnose hepatocellular carcinoma (HCC) and can promote malignancy in HCC. AFP is an important target in the treatment of liver cancer. To obtain enough AFP to screen for AFP inhibitors, we expressed and purified AFP in HEK-293 cells. In the present study, we produced AFP in the cells and harvested highly pure rAFP (or recombinant expression AFP in HEK-293 cells). We also analysed the bioactivity of rAFP and found that rAFP promoted growth of the human HCC cells, antagonize paclitaxel inhibition of HCC cell proliferation, suppress expression of active caspase-3, and promote expression of Ras and survivin. This study provides a method to produce significant amounts of AFP for use in biochemical assays and functional studies and to screen AFP inhibitors for use in HCC therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Studies of an alpha-fetoprotein assay using dry blood-spot samples to be used for the detection of fetal neural tube defects.

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Wong, P Y; Mee, A V; Doran, T A

1982-06-01

We modified the Pharmacia serum alpha-fetoprotein (AFP) kit to enable its use with dry blood-spots on filter paper. Reference values were established for blood from 253 women in the 16th to 18th weeks of gestation. The result by the present technique in a woman with a confirmed anencephalic fetus was elevated, and in agreement with the results of AFP assays in serum and amniotic fluid. Blood AFP was stable on dried filter paper sent by mail.

Serial Changes in Alpha-Fetoprotein Levels During Therapy for Chronic Hepatitis C

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Altug Senol

2014-12-01

Full Text Available Aim: Alpha-fetoprotein (AFP has been widely used as a diagnostic marker for hepatocellular carcinoma. Some patients with hepatitis C show high AFP values, but no evidence of hepatocellular carcinoma. The aim of this study is to assess the influence of antiviral treatment on the serum AFP in patients with chronic hepatitis C without hepatocellular carcinoma. Material and Method: Thirty seven chronic hepatitis C patients (20 females and 17 males were included in the study. All patients were given a combined treatment of pegylated or conventional interferon (IFN and ribavirin. Serum AFP was measured at baseline and on months 3-6-12 of the therapy. Results: Compared to the pretreatment levels of ALT (88,59 ± 57,22 IU, those at 3, 6 and 12 months were statistically lower (p0,05, to 4,34 ± 4,64 (p>0,05 and to 2,63 ± 2,17 (p10 ng/ml. In these patients, mean serum AFP levels were decreased from pretreatment level of 15,09 ± 5,92 ng/ml to 11,39±3,30, to 6,97±2,53 (p

Alpha-fetoprotein as a prognostic marker in acute liver failure: a pilot study.

Science.gov (United States)

Varshney, Anshul; Gupta, Rohit; Verma, Sanjiv K; Ahmad, Sohaib

2017-07-01

Prognostic markers of acute liver failure (ALF) are based on clinical, laboratory or radiological parameters. Most of the biochemical markers are based on hepatic degeneration. We studied the impact of serial serum alpha-fetoprotein (AFP) levels, a marker of liver regeneration, on the outcome of the patients with ALF. AFP levels were estimated on days 1 and 3 of hospitalisation of 32 patients with ALF and the ratio (AFP day3/day1) was calculated. All subjects were categorised as group A (expired) or group B (survived). The AFP ratio was 0.84  +  0.15 in group A (n = 20) versus 1.55  +  0.70 in group B (n = 10); P < 0.001. However, the absolute initial AFP values were not associated with the outcome, favourable or unfavourable. We conclude that AFP levels change dynamically during ALF and have the potential to be used as a predictor of outcome in isolation or in combination with well-established prognostic markers.

Three-site sandwich radioimmunoassay with monoclonal antibodies for a sensitive determination of human alpha-fetoprotein

International Nuclear Information System (INIS)

Nomura, M.; Imai, M.; Takahashi, K.; Kumakura, T.; Tachibana, K.; Aoyagi, S.; Usuda, S.; Nakamura, T.; Miyakawa, Y.; Mayumi, M.

1983-01-01

Utilizing monoclonal antibodies against human alpha-fetoprotein, 3 distinct antigenic determinants were identified. These antigenic determinants, provisionally designated a, b and c, were arranged in such a manner that the binding of one determinant with the corresponding antibody did not inhibit, or only barely inhibited the binding of antibodies directed to the other 2 determinants. Monoclonal antibodies with 3 different specificities were, therefore, applied to develop a sandwich-type solid-phase radioimmunoassay of the antigen in which wells were coated with anti-a, and radiolabeled anti-b together with radiolabeled anti-c was employed to detect the bound antigen. The 3-site sandwich radioimmunoassay involving 3 different determinants gave a higher sensitivity than 2-site assays in which only anti-b or anti-c was employed as a radiolabeled reagent, because the radioactivity of the 2 labeled antibodies was added on the antigen bound to immobilized anti-a. (Auth.)

Clinicopathologic and prognostic characteristics of alpha-fetoprotein-producing gastric cancer.

Science.gov (United States)

He, Ruji; Yang, Qinyi; Dong, Xuqiang; Wang, Yao; Zhang, Weiming; Shen, Lizong; Zhang, Zhihong

2017-04-04

Alpha-fetoprotein-producing gastric cancer (AFPGC) accounts for 1.5%-7.1% of all gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor prognosis. To improve understanding of AFPGC we reviewed a consecutive series of 82 AFPGC patients and investigated the prognostic factors. The incidence of AFPGC among our gastric cancer patients was 1.95%, and 29.27% of AFPGCs were diagnosed with metastasis at the time of presentation, mainly liver metastasis. The serum AFP level of patients with AFPGC was significantly associated with tumor differentiation. Histologically, these AFPGC patients were composed of 34.55% hapatiod type, 58.18% fetal gastrointestinal type, 9.09% yolk sac tumor-like type, and 14.55% mixed type. Patient gender, tumor differentiation, Lauren classification, and number of metastatic lymph nodes showed significant differences among these four subtypes. The overall survival time was 42.02 months and the 3-year cumulative survival rate was 53.13%. Age, American Joint Committee on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and surgery were prognostic factors for overall survival; however, TNM stage was the only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare, unique, and heterogeneous entity, and its proper identification and treatment remain a challenge. More attention should be paid to AFPGC to improve patient care and the dismal prognosis.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

Science.gov (United States)

Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

2016-07-21

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

Science.gov (United States)

Silva, Jack P; Gorman, Richard A; Berger, Nicholas G; Tsai, Susan; Christians, Kathleen K; Clarke, Callisia N; Mogal, Harveshp; Gamblin, T Clark

2017-12-01

Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients. © 2017 Wiley Periodicals, Inc.

Nanosilver-penetrated polyion graphene complex membrane for mediator-free amperometric immunoassay of alpha-fetoprotein using nanosilver-coated silica nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Tang Juan [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, Department of Chemistry, Fuzhou University, Fuzhou 350108 (China); Tang Dianping, E-mail: dianping.tang@fzu.edu.c [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, Department of Chemistry, Fuzhou University, Fuzhou 350108 (China); Su Biling; Li Qunfang; Qiu Bin [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, Department of Chemistry, Fuzhou University, Fuzhou 350108 (China); Chen Guonan, E-mail: gnchen@fzu.edu.c [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, Department of Chemistry, Fuzhou University, Fuzhou 350108 (China)

2011-04-15

Research highlights: {yields} We fabricate a polyion graphene complex membrane-based immunosensing platform for sensitive electrochemical immunoassay of alpha-fetoprotein. {yields} Nanosilver-coated silica nanocomposites as bionanolabels. {yields} Graphene nanosheets, single-stranded DNA and silver nanoparticles as matrices. {yields} Direct electron transfer without electron mediator. {yields} Analysis of real samples and method comparison. - Abstract: A facile and sensitive mediator-free electrochemical immunosensor for detection of alpha-fetoprotein (AFP) was designed by using nanosilver-coated silica nanoparticles (Ag-SiO{sub 2}) as bionanolabels. To construct such an electrochemical immunosensor, silver ions/single-stranded DNA/graphene nanosheets were initially immobilized on a gold electrode in turn, then silver ions were in situ reduced to silver nanoparticles with the aid of NaBH{sub 4}, and anti-AFP antibodies conjugated to silver nanoparticles were used. In the presence of AFP analyte, the sandwiched immunocomplex was formed on the electrode surface by using horseradish peroxidase-anti-AFP conjugate-labeled Ag-SiO{sub 2} (HRP-anti-AFP-Ag-SiO{sub 2}) as secondary antibodies. Compared with pure silver nanoparticles, Ag-SiO{sub 2} nanocomposites could provide a large room for the immobilization of HRP-anti-AFP, and improve the electrochemical responses of the immunosensor. Meanwhile, the presence of highly conductive graphene nanosheets and silver nanoparticles provided a good pathway for electron transfer. Under optimal conditions, the immunosensor exhibited good electrochemical responses toward AFP ranging from 0.3 to 200 ng/mL with a detection limit (LOD) of 0.05 ng/mL (at 3{sigma}) in pH 6.0 PBS-H{sub 2}O{sub 2} system. Intra- and inter-assay displayed good precisions with coefficient of variation below 9.5%. In addition, the method was evaluated with 23 clinical serum samples, receiving good correlation with results from commercially available

Nanosilver-penetrated polyion graphene complex membrane for mediator-free amperometric immunoassay of alpha-fetoprotein using nanosilver-coated silica nanoparticles

International Nuclear Information System (INIS)

Tang Juan; Tang Dianping; Su Biling; Li Qunfang; Qiu Bin; Chen Guonan

2011-01-01

Research highlights: → We fabricate a polyion graphene complex membrane-based immunosensing platform for sensitive electrochemical immunoassay of alpha-fetoprotein. → Nanosilver-coated silica nanocomposites as bionanolabels. → Graphene nanosheets, single-stranded DNA and silver nanoparticles as matrices. → Direct electron transfer without electron mediator. → Analysis of real samples and method comparison. - Abstract: A facile and sensitive mediator-free electrochemical immunosensor for detection of alpha-fetoprotein (AFP) was designed by using nanosilver-coated silica nanoparticles (Ag-SiO 2 ) as bionanolabels. To construct such an electrochemical immunosensor, silver ions/single-stranded DNA/graphene nanosheets were initially immobilized on a gold electrode in turn, then silver ions were in situ reduced to silver nanoparticles with the aid of NaBH 4 , and anti-AFP antibodies conjugated to silver nanoparticles were used. In the presence of AFP analyte, the sandwiched immunocomplex was formed on the electrode surface by using horseradish peroxidase-anti-AFP conjugate-labeled Ag-SiO 2 (HRP-anti-AFP-Ag-SiO 2 ) as secondary antibodies. Compared with pure silver nanoparticles, Ag-SiO 2 nanocomposites could provide a large room for the immobilization of HRP-anti-AFP, and improve the electrochemical responses of the immunosensor. Meanwhile, the presence of highly conductive graphene nanosheets and silver nanoparticles provided a good pathway for electron transfer. Under optimal conditions, the immunosensor exhibited good electrochemical responses toward AFP ranging from 0.3 to 200 ng/mL with a detection limit (LOD) of 0.05 ng/mL (at 3σ) in pH 6.0 PBS-H 2 O 2 system. Intra- and inter-assay displayed good precisions with coefficient of variation below 9.5%. In addition, the method was evaluated with 23 clinical serum samples, receiving good correlation with results from commercially available electrochemiluminescent analyzer.

Radioimmunoassay for carcinoembryonic antigen and alpha1-fetoprotein in the qualitative evaluation of focal hepatic lesions in Japan

International Nuclear Information System (INIS)

Aburano, T.; Tonami, N.; Tada, A.; Hisada, K.

1980-01-01

The combined tests of serum alpha 1 -fetoprotein (AFP) und carcinoembryonic antigen (CEA) were routinely performed in 210 patients with focal hepatic lesions on a 99 sup(m)Tc-colloid liver scan in order to determine whether these could provide more useful information that AFP test alone in the qualitative evaluation of focal hepatic lesions. The predictive value of hepatoma with positive AFP alone remained 80%. However, when the negative CEA was combined with positive AFP, the predictive value of hepatoma (91%) with both was greatly increased. On the other hand, the predictive value of metastatic liver cancer with positive CEA showed 92%. The combined Test of AFP and CEA may be useful for preserving high predictive values of hepatoma and metastatic liver disease. (orig.) [de

Antibody modified gold nano-mushroom arrays for rapid detection of alpha-fetoprotein.

Science.gov (United States)

Li, Wanbo; Jiang, Xueqin; Xue, Jiancai; Zhou, Zhangkai; Zhou, Jianhua

2015-06-15

Localized surface plasmon resonance (LSPR) combined with immunoassay shows greatly potential in fast detection of tumor markers. In this paper, a highly sensitive LSPR substrate has been fabricated and modified for direct detection of alpha-fetoprotein (AFP). The biosensor was prepared by interference lithography, and modified by covalently immobilizing anti-AFP on the surface of gold nano-mushroom arrays (GNMA). The modification process was investigated by Vis-NIR reflectance spectra and cyclic voltammogram measurements. We revealed the optical properties of the modified GNMA by measuring the Vis-NIR reflectance spectra and simulating its electric intensity field distribution under light illumination. The GNMA substrate was highly sensitive, with a refractive index sensitivity of ~465 nm/RIU. The substrate can be applied to label-free detection of AFP, with the linear range and the limit of detection determined to be 20-200 ng/mL and 24 ng/mL (S/N=3), respectively. We also demonstrated its clinical application by directly detecting AFP in human serum samples. It is expected that our biosensor could be integrated on microfluidic chips for high-throughput detection in portable early diagnosis, post-operative and point-of-care (POC) in clinical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Radioimmunological analysis of the levels of the carcinoembryonic antigen and alpha-fetoprotein in the blood of patients with lung cancer

International Nuclear Information System (INIS)

Barbolin, V.I.; Abramov, V.F.; Tkacheva, G.A.

1980-01-01

The level of the carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) are determined in the blood of 41 patients with lung cancer and 70 healthy individuals (donors). It has been found that the CEA content in the blood of patients with lung cancer 2.6-4 times exceeds normal. No variations in the CEA and AFP levels depending upon the age and sex of the donors are revealed. A histological diagnosis of lung cancer has been made in 83.8% of the patients with CEA high concentration in the blood. Determination of the CEA level in the blood may be of diagnostic significance in the clinical picture of lung cancer

Association between serum alpha-fetoprotein levels and fatty liver disease: A cross-sectional study

Science.gov (United States)

Xu, Ping; Xu, Cheng-Fu; Wan, Xing-Yong; Yu, Chao-Hui; Shen, Chao; Chen, Peng; Xu, Gen-Yun; Li, You-Ming

2014-01-01

AIM: To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population. METHODS: A cross-sectional study was performed among subjects who presented for a health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University in 2013. FLD was diagnosed based on an ultrasonography examination. Serum AFP levels were measured with a chemiluminescence immunoassay. RESULTS: Of the 9800 subjects enrolled, 2601 were diagnosed with FLD. Subjects with FLD had higher serum AFP levels than those without the disease. Subjects with high serum AFP levels had a higher prevalence of FLD, metabolic syndrome, and its components. Univariate logistic analysis showed that elevated serum AFP levels were associated with an increased risk of FLD (OR = 1.057, 95%CI: 1.031-1.084). However, after adjusting for covariates, AFP no longer remained significantly associated with the risk factors for FLD. CONCLUSION: Our results suggest that serum AFP levels are significantly associated with FLD and that AFP acts as a cofactor, but not as an independent factor, for FLD. PMID:25206293

Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population.

Science.gov (United States)

Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

2016-12-12

BACKGROUND The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. MATERIAL AND METHODS Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. RESULTS We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31-7.89 ng/ml (males) and 1.01-7.10 ng/ml (females); CEA, 0.51-4.86 ng/ml (males) and 0.35-3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). CONCLUSIONS Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups.

Clinical value of imaging using antibody to alpha fetoprotein in germ cell tumours

International Nuclear Information System (INIS)

Hitchins, R.N.; Begent, R.H.J.; Green, A.J.; Searle, F.; Bagshawe, K.D.; Charing Cross Group of Hospitals, London; Van Heyningen, V.

1989-01-01

Germ cell tumours (GCT) producing alpha fetoprotein (aFP) can be imaged by external scintigraphy after intraveneous administration of radiolabelled antibody directed against aFP. Antibody imaging (AI) by this method was used in an attempt to guide surgical resection of deposits of drug-resistant or recurrent GCT. 30 patients with GCT and raised aFP in whom site of tumour was not known were investigated by AI and conventional imaging methods. All but one were heavily pretreated. Where tumour appeared localised, resection was attempted. Tumour was found in all sites positive by both AI and conventional imaging. AI produced false-positive results in one of 30 patients and false-negative results in 9 patients. Computerised tomography was false-positive in one case and false-negative in three. In these patients, AI gave true-negative and true-positive results, respectively. Of 11 patients with positive AI in whom resection was attempted, 6 achieved sustained complete response with up to 5 years follow-up. We conclude AI and conventional imaging methods to be complementary in selection for surgery of patients with drug-resistant or recurrent GCT. (orig.) [de

Comparative studies of Iodo-bead and chloramine-T methods for the radioiodination of human alpha-fetoprotein

International Nuclear Information System (INIS)

Lee, D.S.C.; Griffiths, B.W.

1984-01-01

Human alpha-fetoprotein (h-AFP) of iodination grade was radiolabeled with Na 125 I by chloramine-T (conventional method) and by Iodo-bead (solid-phase method) under standard and varied conditions, such as quantity of h-AFP and volume of the reaction mixture. The authors have modified the chloramine-T method and developed a protocol for the Iodo-bead method of iodination. The results show that while the chloramine-T method yields radiolabeled h-AFP of apparently 40% higher specific radioactivity (SR) than those of the Iodo-bead method, the latter appears to be a simpler, more controllable and milder method, giving rise to a more stable population of [ 125 I]h-AFP. This is supported by the results of radioactive counting of [ 125 I]h-AFP collected from a Sephadex G-50 column after radioiodination, storage stability and immunoreactivity with anti-h-AFP. (Auth.)

Diagnosis of hepatocellular carcinoma by serial determination of serum alpha-fetoprotein concentration

Energy Technology Data Exchange (ETDEWEB)

Yumoto, Y; Namba, T; Tanaka, Y; Taketa, K; Ohta, Y [Okayama Univ. (Japan). School of Medicine

1976-06-01

This communication describes the clinical significance of serum ..cap alpha..-fetoprotein (S-AFP) determined by radioimmunoassay (RIA) in the diagnosis of hepatocellular carcinoma (HCC). The sensitivity of the AFP assay with the ..cap alpha..-Feto-125 kit produced by the Dainabot RI laboratories was over 2.5 ng/ml. Reproducibility of the kit was satisfactory; coefficient of variation was 6-10% within assays and 13% between assays. The mean and standard deviation of S-AFP in the sera of 30 healthy controls was 5.6+-2.6 ng/ml. When serum with a high level of S-AFP (2.9x10/sup 5/ ng/ml) was diluted with normal horse serum, the actual concentrations of AFP in the diluted serum were consistent with those determined. Thus, normal horse serum was employed to dilute the sera with high levels of AFP. Levels of S-AFP were over 2000 ng/ml in 75.5% of 49 cases with HCC, in 0.64% of 157 patients with hepatitis and cirrhosis of the liver, and in 3.8% of 52 cases of metastatic gastric cancer to the liver. In 20 patients with HCC, levels of S-AFP ranged widely from 7.5 to 9.5x10/sup 5/ ng/ml. In serial determinations of S-AFP in the clinical courses of patients such as those with S-AFP over 2000 ng/ml, the continuous increase of AFP was strongly suggestive of the presence of HCC. In 4 of 20 cases of HCC, the S-AFP levels remained under 300 ng/ml. Histological examination of these 4 cases of HCC showed Classes I and II, but no III in Edmondson's classification. Other cases of HCC with S-AFP levels over 300 ng/ml showed Edmondson's Classes II and III.

Binding of alpha-fetoprotein by immobilized monoclonal antibodies during episodes of zero-gravity obtained by parabolic flight

Science.gov (United States)

Spooner, Brian S.; Guikema, James A.; Barnes, Grady

1990-01-01

Alpha-fetoprotein (AFP), a single-chain polypeptide which is synthesized by the liver and yolk sac of the human fetus, provided a model ligand for assessing the effects of microgravity on ligand binding to surface-immobilized model receptor molecules. Monoclonal antibodies, used as receptors for AFP, were immobilized by covalent attachment to latex microparticles. Zero gravity environment was obtained by parabolic flight aboard NASA 930, a modified KC-135 aircraft. Buring the onset of an episode of zero gravity, ligand and receptor were mixed. Timed incubation (20 s) was terminated by centrifugation, the supernatant removed, and microparticies were assessed for bound AFP by immunochemical methods. The extent of binding was not influenced by microgravity, when compared with 1-G controls, which suggests that aberrant cellular activities observed in microgravity are not the simple expression of altered macromolecular interactions.

Nanobody medicated immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein.

Science.gov (United States)

Chen, Jing; He, Qing-hua; Xu, Yang; Fu, Jin-heng; Li, Yan-ping; Tu, Zhui; Wang, Dan; Shu, Mei; Qiu, Yu-lou; Yang, Hong-wei; Liu, Yuan-yuan

2016-01-15

Immunoassay for cancer biomarkers plays an important role in cancer prevention and early diagnosis. To the development of immunoassay, the quality and stability of applied antibody is one of the key points to obtain reliability and high sensitivity for immunoassay. The main purpose of this study was to develop a novel immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein (AFP) based on nanobody against AFP. Two nanobodies which bind to AFP were selected from a phage display nanobody library by biopanning strategy. The prepared nanobodies are clonable, thermally stable and applied in both sandwich enzyme linked immunoassay (ELISA) and immuno-PCR assay for ultrasensitive detection of AFP. The limit detection of sandwich ELISA setup with optimized nanobodies was 0.48ng mL(-1), and the half of saturation concentration (SC50) value was 6.68±0.56ng mL(-1). These nanobodies were also used to develop an immuno-PCR assay for ultrasensitive detection of AFP, its limit detection values was 0.005ng mL(-1), and the linear range was 0.01-10,000ng mL(-1). These established immunoassays based on nanobodies were highly specific to AFP and with negligible cross reactivity with other tested caner biomarkers. Furthermore, this novel concept of nanobodies mediated immunoassay may provide potential applications in a general method for the ultrasensitive detection of various cancer biomarkers. Copyright © 2015 Elsevier B.V. All rights reserved.

Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Zhang ZG

2015-12-01

Full Text Available Zhiguo Zhang,1 Yanying Zhang,2 Yeying Wang,1 Lingling Xu,3 Wanju Xu3 1Department of Clinical Laboratory, Zhangqiu Maternity and Child Care Hospital, Zhangqiu, 2Department of Clinical Laboratory, Zaozhuang City Wangkai Infection Hospital, Zaozhuang, 3Department of Clinical Laboratory, Qianfoshan Hospital, Jinan, People’s Republic of China Abstract: Currently, there is no reliable biomarker for use in diagnosing alpha-fetoprotein (AFP-negative hepatocellular carcinoma (HCC. Such a biomarker would aid in making an early diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. This study examined AFP-L3 and Golgi protein 73 (GP73 as candidate biomarkers for AFP-negative HCC. The affinity adsorption method and enzyme-linked immunoassays were separately used to determine serum levels of AFP-L3 and GP73 in 50 patients with AFP-negative HCC, 30 non-HCC patients, and 50 healthy subjects. Fifty percent of patients with AFP-negative HCC tested positive for AFP-L3, while 3.33% of non-HCC patients and 2.00% of healthy subjects were AFP-L3 positive. Patients with AFP-negative HCC had significantly higher serum levels of AFP-L3 compared to non-HCC patients and healthy individuals; however, there was no significant difference in the AFP-L3 levels of non-HCC patients and healthy subjects. Sixty-six percent of patients with AFP-negative HCC tested positive for GP73, while 10% of non-HCC patients and 0% of healthy subjects were GP73-positive. Patients with AFP-negative HCC had significantly higher serum levels of GP73 compared to non-HCC patients and healthy subjects, but there was no significant difference between the GP73 levels of non-HCC patients and healthy individuals. Moreover, 20 patients with AFP-negative HCC were both AFP-L3- and GP73-positive, while no non-HCC patients or healthy subjects tested positive for both markers. Either AFP-L3 or GP73 may be used as a biomarker for diagnosing AFP-negative HCC, while their combined use

Detection of alpha-fetoprotein in magnetic immunoassay of thin channels using biofunctional nanoparticles

Science.gov (United States)

Tsai, H. Y.; Gao, B. Z.; Yang, S. F.; Li, C. S.; Fuh, C. Bor

2014-01-01

This paper presents the use of fluorescent biofunctional nanoparticles (10-30 nm) to detect alpha-fetoprotein (AFP) in a thin-channel magnetic immunoassay. We used an AFP model biomarker and s-shaped deposition zones to test the proposed detection method. The results show that the detection using fluorescent biofunctional nanoparticle has a higher throughput than that of functional microparticle used in previous experiments on affinity reactions. The proposed method takes about 3 min (versus 150 min of previous method) to detect 100 samples. The proposed method is useful for screening biomarkers in clinical applications, and can reduce the run time for sandwich immunoassays to less than 20 min. The detection limits (0.06 pg/ml) and linear ranges (0.068 pg/ml-0.68 ng/ml) of AFP using fluorescent biofunctional nanoparticles are the same as those of using functional microparticles within experimental errors. This detection limit is substantially lower and the linear range is considerably wider than those of enzyme-linked immunosorbent assay (ELISA) and other methods in sandwich immunoassay methods. The differences between this method and an ELISA in AFP measurements of serum samples were less than 12 %. The proposed method provides simple, fast, and sensitive detection with a high throughput for biomarkers.

Localization of radioiodinated antibody to alpha-fetoprotein in rats with transplanted hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Koji, T; Ishii, N; Munehisa, T; Kusumoto, Y; Nakamura, S; Tamenishi, A [Nagasaki Univ. (Japan). School of Medicine; Kobayashi, K; Hara, A; Tsukada, Y; Nishi, S

1980-01-01

Total body scintigraphy, organ and subcellular distribution of radioactivity and autoradiography of tissue sections has been assessed in an animal model using radioiodinated horse antibody to rat alpha-fetoprotein (AFP). Rats bearing subcutaneous transplants of AH-7974 ascites hepatoma were injected with /sup 125/I-labeled anti-AFP and scintigraphed. Localization of radioactivity in the tumors was observed 48-168 h after injection. Scintigraphy using /sup 125/I-labeled F(ab')/sub 2/ fragment of the antibody gave approximately the same results as that with the intact anti-AFP antibody. /sup 125/I-labeled normal horse IgG was used as control. The tumor/blood radioactivity ratio after a week after injection was approximately four times higher in the antibody group than that in the control group. This ratio suggested an active accumulation of radioactive antibody in the tumor tissue. In its subcellular distribution, about 30 to 60% of the total radioactivity administered was found in a fraction of the cell membrane plus nucleus. The specific activity of this fraction increased in the antibody group with time over 10 days. In autoradiograms of the fixed tissue sections specific localization of the antibody was observed on the tumor cell surface. The specific uptake of radiolabeled antibody to AFP into AFP producing tumor cells was confirmed.

p55PIK regulates alpha-fetoprotein expression through the NF-κB signaling pathway.

Science.gov (United States)

Ye, Guoguo; Sun, Ge; Cheng, Zhikui; Zhang, Lei; Hu, Kanghong; Xia, Xianmin; Zhou, Yin

2017-12-15

Alpha-fetoprotein (AFP) is regarded as a diagnostic and prognostic biomarker and a potential therapeutic target for hepatocellular carcinoma (HCC). However, the regulation of AFP expression in HCC remains poorly understood. This study aimed to investigate the mechanism by which AFP expression is regulated by p55PIK, an isoform of PI3K. Human HCC cell lines (HepG2 and Huh-7) were treated with p55PIK specific competitive inhibitor or shRNA, or p55PIK overexpression vector, in the absence or presence of NF-κB inhibitor PDTC. AFP expression was detected by quantitative real-time PCR and Western blotting. NF-κB responsive elements in AFP enhancer region were characterized by luciferase reporter assay. p55PIK significantly stimulated the expression of AFP by activating NF-κB signaling pathway in HCC cells. Furthermore, two NF-κB binding sites in AFP enhancer region were identified to be primarily responsible for p55PIK mediated upregulation of AFP expression. p55PIK/NF-κB signaling plays an important role in the upregulation of AFP expression in HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Capillary electrochromatography immunoassay for alpha-fetoprotein based on poly(guanidinium ionic liquid) monolithic material.

Science.gov (United States)

Liu, Cuicui; Deng, Qiliang; Fang, Guozhen; Dang, Meng; Wang, Shuo

2017-08-01

Alpha-fetoprotein (AFP) is widely used as a tumor marker for the serum diagnosis of primary hepatoma. Sensitive detection of AFP level plays an important role in the early diagnosis of disease and highly reliable prediction. In this study, a novel non-competitive immunoassay (IA) based on poly(guanidinium ionic liquid) monolithic material was developed for detecting ultra trace levels of AFP in capillary electrochromatography (CEC) mode. The AFP was mixed with an excess amount of fluorescently labeled antibody. After incubation, the immunocomplex was separated from the free labeled antibody and detected by CEC coupled with laser-induced fluorescence detector. Under the optimized conditions, the developed CEC-IA performed a low detection limit of 0.05 μg L -1  (S/N = 3) and a wide linearity ranging from 0.1 to 1000 μg L -1 for AFP, which can be largely attributed to the high separation and enrichment efficiency of poly(guanidinium ionic liquid) monolithic material for the targets. The application of this method was demonstrated by determining AFP in human serum. Copyright © 2017. Published by Elsevier Inc.

Zhx2 and Zbtb20: Novel regulators of postnatal alpha-fetoprotein repression and their potential role in gene reactivation during liver cancer

Science.gov (United States)

Peterson, Martha L.; Ma, Chunhong; Spear, Brett T.

2012-01-01

The mouse alpha-fetoprotein (AFP) gene is abundantly expressed in the fetal liver, normally silent in the adult liver but is frequently reactivated in hepatocellular carcinoma. The basis for AFP expression in the fetal liver has been studied extensively. However, the basis for AFP reactivation during hepatocarcinogenesis is not well understood. Two novel factors that control postnatal AFP repression, Zhx2 and Zbtb20, were recently identified. Here, we review the transcription factors that regulate AFP in the fetal liver, as well as Zhx2 and Zbtb20, and raise the possibility that the loss of these postnatal repressors may be involved in AFP reactivation in liver cancer. PMID:21216289

Radioimmunodetection of hepatocellular carcinoma with a radiolabeled antibody to alpha fetoprotein

Energy Technology Data Exchange (ETDEWEB)

Ishii, N; Nakata, K; Muro, T [Nagasaki Univ. (Japan). School of Medicine

1982-03-01

The present study was undertaken to investigate whether or not radiolabeled antibody to Alpha-fetoprotein (AFP) intravenously administered accumulates in AFP-producing tumors. Rats with subcutaneously transplanted hepatoma or with heptoma produced in liver by 3'-Me-DAB, and 12 patients with hepatocellular carcinoma (HCC) were studied. In animal experiments, the tumor localization was clearly demonstrated by total body scintigraphy 48 to 168 hours after the injection of the radioiodinated antibody. The rats were sacrificed and radioactivity in tissues was counted. Tumor tissues showed the highest counts. In patients with HCC, the imaging was made with a gamma camera usually 24 and 48 hours after injection of I-131-labeled antibody. In order to make the contrast of tumor image clear, nonspecific background images obtained by administration of Tc-99m-labeled serum albumin were subtracted from the images obtained by I-131 labeled antibody with a computer. In 6 of 12 patients with HCC, the tumor location could successfully demonstrated. However, tumor with sizes below 2 cm in diameter which were able to be detected by the celiac angiography were not detectable. Interestingly the images were more clear in patients with relatively higher serum AFP levels. In the blood of patient given injection of AFP radioantibody, both immune complex and free antibody were able to be detected at least for 120 hours so that the presence of free antigen (AFP) did not appear to prevent tumor radioimmunodetection. The information obtained concerning the biochemical factors which influence antibody localization in the tumor would provide better method for radioimmunodetection with antitumor antibodies.

Small and asymptomatic hepatocellular carcinoma detected by alpha-fetoprotein screening in black hepatitus B carriers. A report of 2 cases

Energy Technology Data Exchange (ETDEWEB)

Dusheiko, G M; Bowyer, S M; Epstein, B; Levien, L J; Beale, P; Kew, M C; Conradie, J C; Simjee, A

1986-01-01

Two patients in whom asymptomatic and small hepatocellular carcinomas (HCC) were detected by ..cap alpha..-fetoprotein (AFP) screening are reported. Both patients were hepatitis B surface antigen-positive. In the first patient, the tumour grew slowly and was resected more than 2 years after a significant elevation in serum AFP levels had been first detected and 13 months after hepatic angiography confirmed the presence of a vascular tumour. In the second patient, a small encapsulated HCC was diagnosed by AFP screening and hepatic imaging. Phosphorus 32 was used. The clinical course in these 2 patients illustrates that small, asymptomatic and encapsulated HCCs do occur in Southern African black hepatitis B carriers. Regular screening of patients at risk may be justified.

Radioimmunological assay of alpha-fetoprotein concentrations in blood serum samples from women in the first half of gestation

International Nuclear Information System (INIS)

Chomanski, M.; Grzes, A.

1977-01-01

In 66 unpregnant women and in 199 pregnant subjects (in the first half of pregnancy) the alpha-fetoprotein (α-FP) concentrations were determined in peripheric blood-serum samples. The α-FP was determined using radioimmunoo-assay technique where the addition of I 125 labelled protein was preceded by 3 hours lasting preincubation period. The free protein was separated from the bound by means of precipitation with a mixture of 96% ethanol and 34.5% ammonium acetate in a ratio 77.5 : 22.5. The patients were grouped into 5 subgroups according to the gestational age. The mean values of α-FP concentration demonstrated a steady increase along with the advancement of gestation. It is suggested that the concentration of this protein in the blood-serum samples may serve as a valuable parameter for the study of gestation development and the state of the fetus. (author)

Radiolabelled monoclonal antibodies against alpha-fetoprotein for in vivo localization of human hepatocellular carcinoma by immunotomoscintigraphy

International Nuclear Information System (INIS)

Bergmann, J.F.; Lumbroso, J.D.; Manil, L.; Saccavini, J.C.; Rougier, P.; Assicot, M.; Mathieu, A.; Bellet, D.; Bohuon, C.

1987-01-01

Two high affinity monoclonal antibodies, designated AF01 and AF04, directed against distinct epitopes of human alpha-fetoprotein (AFP) and the Fab fragments of one of them, were labelled with 131 I and injected into 18 patients with AFP producing hepatocellular carcinoma (HCC) in order to carry out imaging studies by tomoscintigraphy. Twelve patients were injected with whole antibody, only three of seven patients injected with AF01 and two of five patients injected with AF04 had a positive scan. In contrast, five out of six patients injected with labelled Fab fragments of AF04 had positive imaging. These results confirm that tumour imaging of HCC using 131 I labelled monoclonal antibody against AFP is feasible. Moreover, utilization of tomoscintigraphy in place of linear scintigraphy and Fab fragments instead of whole immunoglobulin may improve the sensitivity of radioimmunolocalization. This technique provides useful information on the in vivo distribution of monoclonal antibodies directed against AFP and on the practicability of the eventual therapeutic use of anti-AFP antibodies in HCC. (orig.)

Rapid and label-free bioanalytical method of alpha fetoprotein detection using LSPR chip

Science.gov (United States)

Kim, Dongjoo; Kim, Jinwoon; Kwak, Cheol Hwan; Heo, Nam Su; Oh, Seo Yeong; Lee, Hoomin; Lee, Go-Woon; Vilian, A. T. Ezhil; Han, Young-Kyu; Kim, Woo-Sik; Kim, Gi-bum; Kwon, Soonjo; Huh, Yun Suk

2017-07-01

Alpha fetoprotein (AFP) is a cancer marker, particularly for hepatocellular carcinoma. Normal levels of AFP are less than 20 ng/mL; however, its levels can reach more than 400 ng/mL in patients with HCC. Enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) have been employed for clinical diagnosis of AFP; however, these methods are time consuming and labor intensive. In this study, we developed a localized surface plasmon resonance (LSPR) based biosensor for simple and rapid detection of AFP. This biosensor consists of a UV-Vis spectrometer, a cuvette cell, and a biosensor chip nanopatterned with gold nanoparticles (AuNPs). In our LSPR biosensor, binding of AFP to the surface of the sensor chip led to an increasing magnitude of the LSPR signals, which was measured by an ultraviolet-visible (UV-Vis) spectrometer. Our LSPR biosensor showed sufficient detectability of AFP at concentrations of 1 ng/mL to 1 μg/mL. Moreover, the overall procedure for detection of AFP was completed within 20 min. This biosensor could also be utilized for a point of care test (POCT) by employing a portable UV-Vis spectrometer. Owing to the simplicity and rapidity of the detection process, our LSPR biosensor is expected to replace traditional diagnostic methods for the early detection of diseases.

Phenylboronic acid immunoaffinity reactor coupled with flow injection chemiluminescence for determination of {alpha}-fetoprotein

Energy Technology Data Exchange (ETDEWEB)

Wu Yafeng [Jiangsu Provincial Key Lab of Biomaterials and Biodevices, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210096 (China); Zhuang Yafeng [Department of Chemistry, Changzhou Institute of Technology, Changzhou 213022 (China); Liu Songqin [Jiangsu Provincial Key Lab of Biomaterials and Biodevices, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210096 (China)], E-mail: liusq@seu.edu.cn; He Lin [Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204 (United States)

2008-12-23

A reusable and sensitive immunoassay based on phenylboronic acid immunoaffinity reactor in combination with flow injection chemiluminescence (CL) for determination of glycoprotein was described. The reactor was fabricated by immobilizing 3-aminophenylboronic acid (APBA) on glass microbeads with {gamma}-glycidoxypropyltrimethoxysilane (GPMS) as linkage. The {alpha}-fetoprotein (AFP) could be easily immobilized on the APBA coated beads through sugar-boronic interaction. After an off-line incubation, the mixture of the analyte AFP with horseradish peroxidase-labeled AFP antibody (HRP-anti-AFP) was injected into the reactor. This led the trapping of free HRP-anti-AFP by the surface coated AFP on glass beads. The trapped HRP-anti-AFP was detected by chemiluminescence due to its sensitizing effect on the reaction of luminol and hydrogen peroxide. Under optimal conditions, the chemiluminescent signal was proportional to AFP concentration in the range of 10-100 ng mL{sup -1}. The whole assay process including regeneration of the reactor could be completed within 31 min. The proposed system showed acceptable detection and fabrication reproducibility, and the results obtained with the present method were in acceptable agreement with those from parallel single-analyte test of practical clinical sera. The described method enabled a low-cost, time saving and was potential to detect the serum AFP level in clinical diagnosis.

Screening and Identifying a Novel ssDNA Aptamer against Alpha-fetoprotein Using CE-SELEX

Science.gov (United States)

Dong, Lili; Tan, Qiwen; Ye, Wei; Liu, Dongli; Chen, Haifeng; Hu, Hongwei; Wen, Duo; Liu, Yang; Cao, Ya; Kang, Jingwu; Fan, Jia; Guo, Wei; Wu, Weizhong

2015-01-01

Alpha-fetoprotein (AFP) is a liver cancer associated protein and has long been utilized as a serum tumor biomarker of disease progression. AFP is usually detected in HCC patients by an antibody based system. Recently, however, aptamers generated from systematic evolution of ligands by exponential enrichment (SELEX) were reported to have an alternative potential in targeted imaging, diagnosis and therapy. In this study, AFP-bound ssDNA aptamers were screened and identified using capillary electrophoresis (CE) SELEX technology. After cloning, sequencing and motif analysis, we successfully confirmed an aptamer, named AP273, specifically targeting AFP. The aptamer could be used as a probe in AFP immunofluorescence imaging in HepG2, one AFP positive cancer cell line, but not in A549, an AFP negative cancer cell line. More interesting, the aptamer efficiently inhibited the migration and invasion of HCC cells after in vivo transfection. Motif analysis revealed that AP273 had several stable secondary motifs in its structure. Our results indicate that CE-SELEX technology is an efficient method to screen specific protein-bound ssDNA, and AP273 could be used as an agent in AFP-based staining, diagnosis and therapy, although more works are still needed. PMID:26497223

Alpha-fetoprotein and hepatitis B virus infection in chronic liver disease

International Nuclear Information System (INIS)

Solina, A.

1987-01-01

Among 177 patients with chronic non-malignant liver disease, the prevalence of raised levels of alpha-fetoprotein (AFP) was 11.2 percent. A close association between the severity of the liver disease and AFP concentrations was observed. The most frequent pattern of hepatitis B virus (HBV) infection in these patients was the presence of antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc), whilst only 5 cases were positive for hepatitis B surface antigen (HBsAg). Sixty seven patients, 18 of whom with high AFP, were longitudinally studied over a period ranging from 1 to 6 years. The evaluation of AFP was transient in 6 cases and persistent in 12 cases. The patients in the former group had high activity of liver disease and none of them developed primary liver cell cancer during the follow-up. In contrast, only two patients in the latter group had high activity, and 3 developed PLC. Active HBV replication was significantly more frequent among those with transient elevation of AFP, whereas anti-HBs and anti-HBc positive cases were significantly more frequent among those with persistent elevation of AFP. It is concluded that the severity of the liver disease is the major factor of elevation of AFP. Transiently raised levels of AFP are not related with PLC, whereas persistently high levels represent a premalignant condition. At variance with data obtained in areas with high prevalence of PLC, HBsAg seems not to be related with persistent elevation of AFP. The high rate positive for anti-HBs and anti-HBc in this group remains to be clarified

Radioimmunodetection of hepatocellular carcinoma with a radiolabeled antibody to alpha fetoprotein

International Nuclear Information System (INIS)

Ishii, Nobuko; Nakata, Keisuke; Muro, Toyokichi

1982-01-01

The present study was undertaken to investigate whether or not radiolabeled antibody to Alpha-fetoprotein (AFP) intravenously administered is accumulate in AFP-producing tumors. Rats with subcutaneously transplanted hepatoma or with heptoma produced in liver by 3'-Me-DAB, and 12 patients with hepatocellular carcinoma (HCC) were studied. In animal experiments, the tumor localization was clearly demonstrated by total body scintigraphy 48 to 168 hours after the injection of the radioiodinated antibody. The rats were sacrificed and radioactivity in tissues was counted. Tumor tissues showed the highest counts. In patients with HCC, the imaging was made with a gamma camera usually 24 and 48 hours after injection of I-131-labeled antibody. In order to make the contrast of tumor image clear, nonspecific background images obtained by administration of Tc-99m-labeled serum albumin were subtracted from the images obtained by I-131 labeled antibody with a computer. In 6 of 12 patients with HCC, the tumor location could successfully demonstrated. However, tumor with sizes below 2 cm in diameter which were able to be detected by the celiac angiography were not detectable. Interes tingly the images were more clear in patients with relatively higher serum AFP levels. In the blood of patient given injection of AFP radioantibody, both immune complex and free antibody were able to be detected at least for 120 hours so that the presence of free antigen (AFP) did not appear to prevent tumor radioimmunodetection. The information obtained concerning the biochemical factors which influence antibody localization in the tumor would provide better method for radioimmunodetection with antitumor antibodies. (author)

Preparation of Double Antibody Radioimmunoassay for Determination of Alpha fetoprotein as a Tumor Marker using BALB/C Mice as Host Animals

International Nuclear Information System (INIS)

Abdel-Ghany, I.Y.; EI- Mouhty, N.R.A.; Shafil, H.M.; Mehany, N.L.

2009-01-01

The aim of the present work was to prepare liquid phase radioimmunoassay system (RIA) reagents. Development as well as optimization and validation of this RIA system for the measurement of alpha fetoprotein (AFP) in human serum are described. The production of polyclonal antibodies was carried out by immunizing four BALB/C mice subcutaneously. The preparation of 125 I-AFP tracer was performed using chloramine-T oxidation method. The preparation of AFP standards was done by diluting cord sera using assay buffer. The results obtained provide a highly sensitive,precise and accurate RIA system of AFP based on liquid phase separation. In conclusion, this assay could be used for the diagnosis and management of patients with certain malignant diseases and in prenatal diagnosis of neural tube defects

Alfa-fetoprotein secreting ovarian sex cord-stromal tumor

Directory of Open Access Journals (Sweden)

Kusum D Jashnani

2013-01-01

Full Text Available Ovarian sex cord-stromal tumors are relatively infrequent neoplasms that account for approximately 8% of all primary ovarian tumors. They are a heterogeneous group of neoplasms composed of cells derived from gonadal sex cords (granulosa and Sertoli cells, specialized gonadal stroma (theca and Leydig cells, and fibroblasts. They may show androgenic or estrogenic manifestations. We report such a tumor associated with markedly raised serum alpha-fetoprotein (AFP levels in a young female presenting with a mass and defeminising symptoms. Serum AFP levels returned to normal on removal of tumor.

Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

Directory of Open Access Journals (Sweden)

Akira Suzuki

2012-01-01

Full Text Available Alpha-fetoprotein-producing carcinoma (AFPC/hepatoid adenocarcinoma (HAC and neuroendocrine carcinoma (NEC are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

Intrahepatic bile duct adenoma in a patient with chronic hepatitis B accompanied by elevation of alpha-fetoprotein.

Science.gov (United States)

Ahn, Jem Ma; Paik, Yong-Han; Lee, Jun Hee; Cho, Ju Yeon; Sohn, Won; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

2015-12-01

A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.

Shrink-induced graphene sensor for alpha-fetoprotein detection with low-cost self-assembly and label-free assay

Science.gov (United States)

Sando, Shota; Zhang, Bo; Cui, Tianhong

2017-12-01

Combination of shrink induced nano-composites technique and layer-by-layer (LbL) self-assembled graphene challenges controlling surface morphology. Adjusting shrink temperature achieves tunability on graphene surface morphology on shape memory polymers, and it promises to be an alternative in fields of high-surface-area conductors and molecular detection. In this study, self-assembled graphene on a shrink polymer substrate exhibits nanowrinkles after heating. Induced nanowrinkles on graphene with different shrink temperature shows distinct surface roughness and wettability. As a result, it becomes more hydrophilic with higher shrink temperatures. The tunable wettability promises to be utilized in, for example, microfluidic devices. The graphene on shrink polymer also exhibits capability of being used in sensing applications for pH and alpha-fetoprotein (AFP) detection with advantages of label free and low cost, due to self-assembly technique, easy functionalization, and antigen-antibody reaction on graphene surface. The detection limit of AFP detection is down to 1 pg/mL, and therefore the sensor also has a significant potential for biosensing as it relies on low-cost self-assembly and label-free assay.

Intrahepatic bile duct adenoma in a patient with chronic hepatitis B accompanied by elevation of alpha-fetoprotein

Directory of Open Access Journals (Sweden)

Jem Ma Ahn

2015-12-01

Full Text Available A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.

A cyclic peptide derived from alpha-fetoprotein inhibits the proliferative effects of the epidermal growth factor and estradiol in MCF7 cells.

Science.gov (United States)

Torres, Cristian; Antileo, Elmer; Epuñán, Maráa José; Pino, Ana María; Valladares, Luis Emilio; Sierralta, Walter Daniel

2008-06-01

A cyclic peptide derived from the active domain of alpha-fetoprotein (AFP) significantly inhibited the proliferation of MCF7 cells stimulated with the epidermal growth factor (EGF) or estradiol (E2). The action of these three agents on cell growth was independent of the presence of calf serum in the culture medium. Our results demonstrated that the cyclic peptide interfered markedly with the regulation of MAPK by activated c-erbB2. The cyclic peptide showed no effect on the E2-stimulated release of matrix metalloproteinases 2 and 9 nor on the shedding of heparin-binding EGF into the culture medium. We propose that the AFP-derived cyclic peptide represents a valuable novel antiproliferative agent for treating breast cancer.

Diagnosis and screening of small hepatocellular carcinomas. Comparison of radionuclide imaging, ultrasound, computed tomography, hepatic angiography, and alpha 1-fetoprotein assay

International Nuclear Information System (INIS)

Takashima, T.; Matsui, O.; Suzuki, M.; Ida, M.

1982-01-01

Twenty-nine small (less than 5 cm) hepatocellular carcinomas in 18 patients were examined by radionuclide imaging (RN), ultrasound (US), computed tomography (CT), hepatic angiography, and serum alpha 1-fetoprotein (AFP) assay. Sensitivity was 39% with RN, 50% with US, 56% with CT, and 94% with angiography, including infusion hepatic angiography (IHA). Lesions larger than 3 cm could be detected by all of these methods; those between 2 and 3 cm were generally shown by US and CT but not RN. IHA was essential for diagnosis of lesions less than 2 cm, which were otherwise difficult or impossible to detect except with angiography. As a screening method, AFP was best, followed by US and CT. The authors recommend using AFP and US to minimize expense and radiation exposure. In questionable cases, IHA should be performed

Determination of α-fetoprotein levels in maternal serum and its application in prenatal diagnosis

International Nuclear Information System (INIS)

Rokos, A.; Jedlickova, B.; Hradil, M.

1989-01-01

Alpha-fetoprotein determination is described in the screening of neural tube (NT) disorders. The benefits and constraints are described of the AFP-NT screening and the possibilities are assessed of revealing Down's syndrome fetuses. The use is evaluated of the RIA-test-AFP kit in Czechoslovakia. (E.J.). 1 fig., 3 tabs., 10 refs

Structural basis for alpha fetoprotein-mediated inhibition of caspase-3 activity in hepatocellular carcinoma cells.

Science.gov (United States)

Lin, Bo; Zhu, Mingyue; Wang, Wenting; Li, Wei; Dong, Xu; Chen, Yi; Lu, Yan; Guo, Junli; Li, Mengsen

2017-10-01

Alpha-fetoprotein (AFP) is an early serum growth factor in the foetal liver development and hepatic carcinogenesis; However, the precise biological role of cytoplasmic AFP remains elusive. Although we recently demonstrated that cytoplasmic AFP might interact with caspase-3 and inhibit the signal transduction of apoptosis in human hepatocellular carcinoma (HCC) cells, the details of this interaction are not clear. To reveal the molecular relationship between AFP and caspase-3, we performed molecular docking, co-immunoprecipitation (Co-IP), laser confocal microscopy, site-directed mutagenesis and functional experiments to analyse the key amino acid residues in the binding site of caspase-3. The results of Co-IP, laser confocal microscopy and functional analyses were consistent with the computational model. We also used the model to explain why AFP cannot bind to caspase-8. These results provide the molecular basis for the AFP-mediated inhibition of caspase-3 activity in HCC cells. Altogether, we found that AFP interacts with caspase-3 through precise amino acids, namely loop-4 residues Glu-248, Asp-253 and His-257. The results further demonstrated that AFP plays a critical role in the inhibition of the apoptotic signal transduction that mediated by caspase-3. Thus, AFP might represent a novel biotarget for the therapy of HCC patients. © 2017 UICC.

Maternal serum alpha-fetoprotein levels are normal in Fanconi anemia: Can it be a lack of postnatal inhibition of AFP gene resulting in the elevation?

Science.gov (United States)

Aslan, Deniz; Karabacak, Recep Onur; Aslan, Oner Deniz

2017-04-01

We investigated the feasibility of using serum alpha-fetoprotein (AFP) levels as a screening test for prenatal diagnosis of Fanconi anemia (FA). Serial measurements in maternal serum were recorded. Parents, both heterozygous for FA, had declined prenatal molecular testing. The infant was born with no somatic abnormalities, and FA was confirmed by postnatal molecular analysis. Maternal serum AFP levels during each trimester of pregnancy were normal indicating that these levels cannot be used as a screening test in prenatal diagnosis. Three-year follow-up after birth showed constantly elevated serum levels in the patient from the start, suggesting a lack of postnatal inhibition on AFP gene. © 2016 Wiley Periodicals, Inc.

Synthesis of CdTe/CdS/ZnS quantum dots and their application in imaging of hepatocellular carcinoma cells and immunoassay for alpha fetoprotein

Energy Technology Data Exchange (ETDEWEB)

Tian Jianniao; Liu Rongjun; Zhao Yanchun; Peng Yan; Hong Xue; Zhao Shulin [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), College of Chemistry and Chemical Engineering of Guangxi Normal University, Guilin 541004 (China); Xu Qing, E-mail: tianjn58@yahoo.com.cn [Pharmacology Department of Guilin Medical College, Guilin 541004 (China)

2010-07-30

We report the imaging of hepatocellular carcinoma cells and the immunoassay for alpha fetoprotein (AFP) using CdTe/CdS/ZnS core-shell-shell QDs. Stable and high PLQY (20%-48%) CdTe/CdS/ZnS core-shell-shell QDs were synthesized by a stepwise process. Bioconjugation of the core-shell-shell QDs with streptavidin (SA) was successfully applied in immunofluorescent imaging of the human hepatocellular carcinoma (HCC) cell line HepG2.2.15. Furthermore, the thioglycolic acid (TGA)-capped CdTe/CdS/ZnS core-shell-shell QDs fluorescence lifetime is longer than fluorescein, so it was first engaged to conjugate with antigen for the determination of protein (AFP) by fluorescence polarization immunoassay.

Synthesis of CdTe/CdS/ZnS quantum dots and their application in imaging of hepatocellular carcinoma cells and immunoassay for alpha fetoprotein

International Nuclear Information System (INIS)

Tian Jianniao; Liu Rongjun; Zhao Yanchun; Peng Yan; Hong Xue; Zhao Shulin; Xu Qing

2010-01-01

We report the imaging of hepatocellular carcinoma cells and the immunoassay for alpha fetoprotein (AFP) using CdTe/CdS/ZnS core-shell-shell QDs. Stable and high PLQY (20%-48%) CdTe/CdS/ZnS core-shell-shell QDs were synthesized by a stepwise process. Bioconjugation of the core-shell-shell QDs with streptavidin (SA) was successfully applied in immunofluorescent imaging of the human hepatocellular carcinoma (HCC) cell line HepG2.2.15. Furthermore, the thioglycolic acid (TGA)-capped CdTe/CdS/ZnS core-shell-shell QDs fluorescence lifetime is longer than fluorescein, so it was first engaged to conjugate with antigen for the determination of protein (AFP) by fluorescence polarization immunoassay.

Elevated serum alpha-fetoprotein in poorly differentiated adenocarcinoma with neuroendocrine differentiation of the ascending colon: a case report.

Science.gov (United States)

Lin, Hung-Hsin; Chang, Chia-Chu; Yang, Shung-Haur; Chang, Shih-Ching; Chen, Wei-Shone; Liang, Wen-Yih; Lin, Jen-Kou; Jiang, Jeng-Kai

2016-03-15

Colorectal cancer (CRC) is the most common form of cancer and the third leading cause of death in Taiwan. Serum alpha-fetoprotein (AFP) has been extensively used as a biomarker for hepatocellular carcinoma (HCC) and yolk sac tumors. This case report presents a 90-year-old woman with right abdominal pain and poor appetite for 1 week. The computed tomography (CT) showed wall thickening in the proximal ascending colon with ruptured appendicitis. Preoperative serum AFP was high. There was no definite liver metastasis or other abnormal findings in the hepatobiliary systems. After initial empirical antibiotic treatment, we performed laparoscopic right hemicolectomy. The pathological assessment was poorly differentiated adenocarcinoma with neuroendocrine differentiation in the ascending colon. The tumor cells did not produce AFP. Amazingly, the follow-up serum AFP level 1 month after the surgery declined to normal range. The patient had an uneventful course after the surgery and was free of recurrence or metastasis within 5 months of follow-up. AFP may be a useful tumor marker in poorly differentiated colorectal cancer with neuroendocrine component patients and a prediction of early treatment response.

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma.

Science.gov (United States)

Ilikhan, Sevil Uygun; Bilici, Muammer; Sahin, Hatice; Akca, Ayşe Semra Demir; Can, Murat; Oz, Ibrahim Ilker; Guven, Berrak; Buyukuysal, M Cagatay; Ustundag, Yucel

2015-06-14

To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma (HCC). Sixty-eight patients with HCC (mean age of 69.1 ± 10.1), 31 cirrhosis patients (mean age of 59.3 ± 6.3) and 33 healthy volunteers (mean age of 51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein (AFP) values with HCC clinicopathological features, such as tumor size, number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion (diameters; ≤ 3 cm, 3-5 cm and ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer (BCLC) criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alpha-fetoprotein levels were kept at -80 °C until use. Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay. In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number, presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls (P < 0.001). Prolidase levels were significantly associated with tumor size and number (P < 0.001, P = 0.002, respectively). Prolidase levels also differed in patients in terms of BCLC staging classification (P < 0.001). Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis (P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately (P = 0.032, P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation (r = 0.616; P < 0.001) between

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

Energy Technology Data Exchange (ETDEWEB)

Guo, S.J. [Beijing Institute of Pharmacology and Toxicology, Beijing (China); Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Qi, C.H.; Zhou, W.X.; Zhang, Y.X. [Beijing Institute of Pharmacology and Toxicology, Beijing (China); Zhang, X.M.; Wang, J.; Wang, H.X. [National Center of Biomedical Analysis, Beijing (China)

2013-04-12

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2-A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4{sup +} T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

International Nuclear Information System (INIS)

Guo, S.J.; Qi, C.H.; Zhou, W.X.; Zhang, Y.X.; Zhang, X.M.; Wang, J.; Wang, H.X.

2013-01-01

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2-A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4 + T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging

A sensitive fluorescent sensor for quantification of alpha-fetoprotein based on immunosorbent assay and click chemistry.

Science.gov (United States)

Xie, Qunfang; Weng, Xiuhua; Lu, Lijun; Lin, Zhenyu; Xu, Xiongwei; Fu, Caili

2016-03-15

A novel fluoresencent immunosensor for determination of cancer biomarkers such as alpha-fetoprotein (AFP) was designed by utilizing both the high specificity of antigen-antibody sandwich structure and the high sensitivity of the click chemistry based fluorescence detection. Instead of an enzyme or fluorophore, the CuO nanoparticles are labeled on the detection antibody, which was not susceptible to the change of the external environments. The CuO nanoparticles which were modified on the sandwich structure can be dissolved to produce Cu(2+) ions with the help of HCl and then the Cu(2+) ions were reduced by sodium ascorbate to produce Cu(+) ions which triggered the Cu(+) catalyzed alkyne-azide cycloaddition (CuAAC) reaction between the weak fluorescent compound (3-azido-7-hydroxycoumarin) and propargyl alcohol to form a strong fluorescent compound. A good linear relationship was observed between the fluorescence increase factor of the system and the concentration of AFP in the range of 0.025-5.0 ng/mL with a detection limit of 12 pg/mL (S/N=3). The proposed fluorescent sensor had been applied to detect AFP in the human serum samples and gave satisfactory results. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation.

Science.gov (United States)

Matsumoto, Kohei; Ueyama, Hiroya; Matsumoto, Kenshi; Akazawa, Yoichi; Komori, Hiroyuki; Takeda, Tsutomu; Murakami, Takashi; Asaoka, Daisuke; Hojo, Mariko; Tomita, Natsumi; Nagahara, Akihito; Kajiyama, Yoshiaki; Yao, Takashi; Watanabe, Sumio

2016-09-28

To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation (GCED). We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer (CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital. GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate. Six cases (5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases (139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC (66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED (positivity, 83.3%), immunohistochemically. Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type

A synthetic peptide derived from alpha-fetoprotein inhibits the estradiol-induced proliferation of mammary tumor cells in culture through the modulation of p21.

Science.gov (United States)

Sierralta, Walter D; Epuñan, María J; Reyes, José M; Valladares, Luis E; Pino, Ana M

2008-01-01

A stable cyclized 9-mer peptide (cP) containing the active site of alpha-alpha fetoprotein (alphaFP) has been shown to be effective for prevention of estrogen-stimulated tumor cell proliferation in culture or of xenographt growth in immunodeficient mice. cP does not block 17beta-estradiol (E2) binding to its receptors, but rather appears to interfere with intracellular processing of the signal that supports growth. To obtain insight on that mechanism we studied the effect of cP on the proliferation of MCF-7 cells in culture. Proliferation in the presence of 2 microM E2 is decreased up to 40% upon addition of 2 microg ml(-1) cP to the medium; the presence of cP did not increase cell death, cP reduced also the proliferation of estrogen-dependent ZR75-1 cells but had no effect on autonomous MDA-MB-231 cells, cP did not modify the number of binding sites for labeled E2 or affected cell death. We detected increased nuclear p21Cip1 immunoreactivity after cP treatment. Our results suggest that cP acts via p21Cip1 to slow the process of MCF-7 cells through the cycle.

Development of graphite carbon nitride based fluorescent immune sensor for detection of alpha fetoprotein

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Li, Yike; Dong, Lingyu; Wang, Xiangfeng; Liu, Yuan; Liu, Hailing; Xie, Mengxia

2018-05-01

A novel fluorescent immunosensor for determination of alpha fetoprotein (AFP) in serum samples has been developed based on the nano graphite carbon nitride (g-C3N4) as fluorophore and immunomagnetic beads (MBs) as separation material. The bulk g-C3N4 was obtained by thermal polymerization of melamine, and then carboxylated and exfoliated to acquire the carboxylated nano g-C3N4 (c-n-g-C3N4), which has been characterized and the results showed that it had excellent fluorescent properties. The antibodies of AFP (Ab1, Ab2) were conjugated to the MBs and the c-n-g-C3N4, respectively. In assay of AFP detection, the magnetic part of the immunosensor, MBs-Ab1, would form the sandwich type complex with the signal part of the sensor, c-n-g-C3N4-Ab2. The developed immunosensor could simplify the process of separation due to the MBs. The results illustrated that proposed approach held a good linearity between the fluorescence intensity of the sensor and the AFP concentration ranging from 5-600 ng/mL with the limit of detection as low as 0.43 ng/mL, and its spiking recoveries ranged from 98.2% to 105.9% with RSD from 2.1% to 3.5%. The fabricated fluorescent immunosensor possesses the merits of good sensitivity, excellent selectivity, high biocompatibility and low cost, and the results provide a novel clue to develop immunosensor for determination of the biomarkers in complex matrices.

Fullerol-fluorescein isothiocyanate-concanavalin agglutinin phosphorescent sensor for the detection of alpha-fetoprotein and forecast of human diseases

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Liu, Jia-ming; Lin, Li-ping; Jiang, Shu-Lian; Cui, Ma Lin; Jiao, Li; Zhang, Xiao Yang; Zhang, Li-hong; Zheng, Zhi Yong; Lin, Xuan; Lin, Shao-qin

2013-11-01

Based on the reaction of the active -OH group in fullerol (F) with the dissociated -COOH group in fluorescein isothiocyanate (FITC) to form an F-FITC and the enhanced effect of N, N-dimethylaniline (DMA) on phosphorescence signal of F-FITC, a new phosphorescent labeling reagent (DMA-F-FITC) was developed. What's more, a phosphorescent sensor for the determination of alpha-fetoprotein variant (AFP-V) has been designed via the coupling technique of the high sensitivity for affinity adsorption-solid substrate-room temperature phosphorimetry (AA-SS-RTP) with the strong specificity reaction between DMA-F-FITC-Con A and AFP-V. The DMA-F-FITC increased the number of luminescent molecules in the biological target which improved the sensitivity of phosphorescent sensor. The proposed sensor was responsive, simple, selective and sensitive, and it has been applied to the determination of trace AFP-V in human serum and the forecast of human diseases using phosphorescence emission wavelength of F or FITC, with the results agreed well with those obtained by enzyme-linked immunoassay (ELISA). Meanwhile, the mechanisms for the labeling reaction and the sensing detection of AFP-V were discussed.

Sandwich immunoassay for alpha-fetoprotein in human sera using gold nanoparticle and magnetic bead labels along with resonance Rayleigh scattering readout

International Nuclear Information System (INIS)

Lu, Yao; Huang, Xiangyi; Ren, Jicun

2013-01-01

We describe a sensitive sandwich immunoassay for alpha-fetoprotein (AFP). It is making use of gold nanoparticles (GNPs) and magnetic beads (MBs) as labels, and of resonance Rayleigh scattering for detection. Two antibodies were labeled with GNPs and MBs, respectively, and MB-antigen-GNP complexes were formed in the presence of antigens. The MB labels also serve as solid phase carriers that can be used to magnetically separate the immuno complex. The GNP labels are used as optical probes, and Rayleigh scattering was used to determine the concentration of free GNPs-antibody after separation of the MB-antigen-GNP complexes. The concentration of AFP is related to the intensity of light scattered by free GNPs in the 13.6 pM to 436 pM concentration range, and the limit of detection is 13.6 pM. The method was applied to the determination of AFP in sera of cancer patients, and the results agree well with those obtained by conventional ELISA. (author)

Improvement of insertion loss and quality factor of flexural plate-wave-based alpha-fetoprotein biosensor using groove-type reflective grating structures

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Lin, Chang-Yu; Huang, I.-Yu; Lan, Je-Wei

2013-01-01

Conventional flexural plate-wave (FPW) transducers have limited applications in biomedical sensing due to their disadvantages such as high insertion loss and low quality factor. To overcome these shortcomings, we propose a FPW transducer on a low phase velocity insulator membrane (5-μm-thick SiO2) with a novel groove-type reflective grating structure design. Additionally, a cystamine self-assembly monolayer and a glutaraldehyde cross-linking layer are implemented on the backside of the FPW device to immobilize alpha-fetoprotein (AFP) antibody. A FPW-based AFP biosensor with low detection limit (5 ng/mL) can be achieved and used to measure the extreme low concentration of AFP antigen in human serum for early detection of hepatocellular carcinoma. The proposed FPW-based AFP biosensor also demonstrates a very high quality factor (206), low insertion loss (-40.854 dB), low operating frequency (6.388 MHz), and high sensing linearity (90.7%).

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

Science.gov (United States)

Mizejewski, G J

2015-01-01

Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

Golgi protein 73 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta- analysis

International Nuclear Information System (INIS)

Zhou, Ying; Yin, Xin; Ying, Jun; Zhang, BoHeng

2012-01-01

There have been conflicting reports about serum golgi protein 73 (GP73) as one of the most promising serum markers for the diagnosis of hepatocellular carcinoma (HCC). This study was to make a systematic review about the diagnostic accuracy of serum GP73 versus alpha-fetoprotein (AFP) for HCC. After a systematic review of related studies, sensitivity, specificity and other measures about the accuracy of serum GP73 and AFP in the diagnosis of HCC were pooled using random-effects models. Summary receiver operating characteristic curve analysis was used to summarize the overall test performance. Eight studies were included in our meta-analysis. The summary estimates for serum GP73 and AFP in diagnosing HCC in the studies included were as follows: sensitivity, 76% (95% confidence interval (CI) 51-91%) vs. 70% (47-86%); specificity, 86% (95%CI 65-95%) vs. 89% (69-96%); diagnostic odds ratio (DOR), 18.59 (95%CI 5.33-64.91) vs. 18.00(9.41-34.46); and area under sROC, 0.88 (95%CI 0.77-0.99) vs. 0.86 (95%CI 0.84-0.87). The current evidence indicates that serum GP73 has a comparable accuracy to AFP for the diagnosis of HCC, while the value of serum GP73 in combination with AFP for HCC detection deserves further investigation

Immunohistochemical expression profiles of solute carrier transporters in alpha-fetoprotein-producing gastric cancer.

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Shimakata, Takaaki; Kamoshida, Shingo; Kawamura, Jumpei; Ogane, Naoki; Kameda, Yoichi; Yanagita, Emmy; Itoh, Tomoo; Takeda, Risa; Naka, Ayano; Sakamaki, Kuniko; Hayashi, Yurie; Kuwao, Sadahito

2016-11-01

Alpha-fetoprotein (AFP)-producing gastric cancer (GC) is an aggressive tumour with high rates of liver metastasis and poor prognosis, and for which a validated chemotherapy regimen has not been established. Drug uptake by solute carrier (SLC) transporters is proposed as one of the mechanisms involved in sensitivity to chemotherapy. In this study, we aimed to develop important insights into effective chemotherapeutic regimens for AFP-producing GC. We evaluated immunohistochemically the expression levels of a panel of SLC transporters in 20 AFP-producing GCs and 130 conventional GCs. SLC transporters examined were human equilibrative nucleoside transporter 1 (hENT1), organic anion transporter 2 (OAT2), organic cation transporter (OCT) 2, OCT6 and organic anion-transporting polypeptide 1B3 (OATP1B3). The rates of high expression levels of hENT1 (hENT1 high ) and OAT2 (OAT2 high ) were statistically higher in AFP-producing GC, compared with conventional GC. When analysing hENT1 and OAT2 in combination, hENT1 high /OAT2 high was the most particular expression profile for AFP-producing GC, with a greater significance than hENT1 or OAT2 alone. However, no significant differences in OCT2, OCT6 or OATP1B3 levels were detected between AFP-producing and conventional GCs. However, immunoreactivity for hENT1, OAT2 and OCT6 tended to be increased in GC tissues compared with non-neoplastic epithelia. Because hENT1 and OAT2 are crucial for the uptake of gemcitabine and 5-fluorouracil, respectively, our results suggest that patients with AFP-producing GC could potentially benefit from gemcitabine/fluoropyrimidine combination chemotherapy. Increased expression of hENT1, OAT2 and OCT6 may also be associated with the progression of GC. © 2016 John Wiley & Sons Ltd.

Quantum-dot-based homogeneous time-resolved fluoroimmunoassay of alpha-fetoprotein

Energy Technology Data Exchange (ETDEWEB)

Chen Meijun; Wu Yingsong; Lin Guanfeng; Hou Jingyuan; Li Ming [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515 (China); Liu Tiancai, E-mail: liutc@smu.edu.cn [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515 (China)

2012-09-05

Highlights: Black-Right-Pointing-Pointer QDs-based homogeneous time-resolved fluoroimmunoassay was developed to detect AFP. Black-Right-Pointing-Pointer The conjugates were prepared with QDs-doped microspheres and anti-AFP McAb. Black-Right-Pointing-Pointer The conjugates were prepared with LTCs and another anti-AFP McAb. Black-Right-Pointing-Pointer Excess amounts of conjugates were used for detecting AFP without rinsing. Black-Right-Pointing-Pointer The wedding of QPs and LTCs was suitable for HTRFIA to detect AFP. - Abstract: Quantum dots (QDs) with novel photoproperties are not widely used in clinic diagnosis, and homogeneous time-resolved fluorescence assays possess many advantages over current methods for alpha-fetoprotein (AFP) detection. A novel QD-based homogeneous time-resolved fluorescence assay was developed and used for detection of AFP, a primary marker for many cancers and diseases. QD-doped carboxyl-modified polystyrene microparticles (QPs) were prepared by doping oil-soluble QDs possessing a 605 nm emission peak. The antibody conjugates (QPs-E014) were prepared from QPs and an anti-AFP monoclonal antibody, and luminescent terbium chelates (LTCs) were prepared and conjugated to a second anti-AFP monoclonal antibody (LTCs-E010). In a double-antibodies sandwich structure, QPs-E014 and LTCs-E010 were used for detection of AFP, serving as energy acceptor and donor, respectively, with an AFP bridge. The results demonstrated that the luminescence lifetime of these QPs was sufficiently long for use in a time-resolved fluoroassay, with the efficiency of time-resolved Foerster resonance transfer (TR-FRET) at 67.3% and the spatial distance of the donor to acceptor calculated to be 66.1 Angstrom-Sign . Signals from TR-FRET were found to be proportional to AFP concentrations. The resulting standard curve was log Y = 3.65786 + 0.43863{center_dot}log X (R = 0.996) with Y the QPs fluorescence intensity and X the AFP concentration; the calculated sensitivity was 0

Gallium-67-citrate scanning in primary cancer of the liver: diagnostic value in the presence of cirrhosis and relation to alpha-fetoprotein

International Nuclear Information System (INIS)

Levin, J.; Kew, M.C.

1975-01-01

Gallium-67-citrate and /sup 99m/Tc-sulfur colloid scans were performed in 38 South African blacks with primary hepatocellular cancer. Selective uptake of the radionuclide by the tumor occurred in 27 patients (70 percent). In 12 out of 18 patients with associated cirrhosis, 67 Ga was concentrated in the defect or defects visible on the /sup 99m/Tc-sulfur colloid scan, but in the remaining 6 cases (33 percent), the 2 scans were identical and the defects may have been attributed wrongly to cirrhosis. Alpha-fetoprotein (AFP) was detected by immunodiffusion in the serum of 26 patients. Twenty-one of these showed selective uptake of 67 Ga by the tumor as compared with 6 out of 12 patients in whom this protein could not be detected. We were therefore unable to confirm a previous finding of a greater uptake of the radionuclide in AFP-negative primary liver cancer. (auth)

Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

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Seo, Seung In; Kim, Hyoung Su; Kim, Won Jin; Shin, Woon Geon; Kim, Doo Jin; Kim, Kyung Ho; Jang, Myoung Kuk; Lee, Jin Heon; Kim, Joo Seop; Kim, Hak Yang; Kim, Dong Joon; Lee, Myung Seok; Park, Choong Kee

2015-01-01

AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB). METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their combination were calculated and compared. RESULTS: The optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-II and AFP were not significantly different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB (P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION: Serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB. PMID:25852278

Development and application of a fluorescence protein microarray for detecting serum alpha-fetoprotein in patients with hepatocellular carcinoma.

Science.gov (United States)

Zhang, Aiying; Yin, Chengzeng; Wang, Zhenshun; Zhang, Yonghong; Zhao, Yuanshun; Li, Ang; Sun, Huanqin; Lin, Dongdong; Li, Ning

2016-12-01

Objective To develop a simple, effective, time-saving and low-cost fluorescence protein microarray method for detecting serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC). Method Non-contact piezoelectric print techniques were applied to fluorescence protein microarray to reduce the cost of prey antibody. Serum samples from patients with HCC and healthy control subjects were collected and evaluated for the presence of AFP using a novel fluorescence protein microarray. To validate the fluorescence protein microarray, serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA). Results A total of 110 serum samples from patients with HCC ( n = 65) and healthy control subjects ( n = 45) were analysed. When the AFP cut-off value was set at 20 ng/ml, the fluorescence protein microarray had a sensitivity of 91.67% and a specificity of 93.24% for detecting serum AFP. Serum AFP quantified via fluorescence protein microarray had a similar diagnostic performance compared with ELISA in distinguishing patients with HCC from healthy control subjects (area under receiver operating characteristic curve: 0.906 for fluorescence protein microarray; 0.880 for ELISA). Conclusion A fluorescence protein microarray method was developed for detecting serum AFP in patients with HCC.

A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture.

Science.gov (United States)

Sierralta, Walter D; Epuñan, Maria J; Reyes, José M; Valladares, Luis E; Andersen, Thomas T; Bennett, James A; Jacobson, Herbert I; Pino, Ana M

2008-01-01

This study was aimed to obtain additional information on the activity of a cyclized 9-amino acid peptide (cP) containing the active site of alpha fetoprotein, which inhibits the estrogen-stimulated proliferation of tumor cells in culture and of xenografts in immunodeficient mice. Breast cancer cells cultured in the presence of 2 nM estradiol were exposed to cP for different periods and their proliferation, estradiol binding parameters, clustering tendency and expression of E-cadherin and p21Cip1 were analyzed by biochemical and cell biology methods. The proliferation of MCF7 cells was significantly decreased by the addition of 2 microg/ml cP to the medium. cP did not increase cell death rate nor alter the number of binding sites for estradiol nor the endogenous aromatase activity of MCF7 cells. cP also decreased the proliferation of estrogen-dependent ZR75-1 cells but had no effect on estrogen-independent MDA-MB-231 cells. An increased nuclear p21Cip1 expression detected after cP treatment suggests that cP slows MCF7 cell proliferation via this regulator. We propose that cP could represent a novel breast cancer therapeutic agent whose mechanism of action is different from that of tamoxifen or of inhibitors of aromatase.

Horseradish peroxidase functionalized gold nanorods as a label for sensitive electrochemical detection of alpha-fetoprotein antigen.

Science.gov (United States)

Guo, Jinjin; Han, Xiaowei; Wang, Junchun; Zhao, Junqing; Guo, Zilin; Zhang, Yuzhong

2015-12-15

In this study, a novel tracer, horseradish peroxidase (HRP) functionalized gold nanorods (Au NRs) nanocomposites (HRP-Au NRs), was designed to label the signal antibodies for sensitive electrochemical measurement of alpha-fetoprotein (AFP). The preparation of HRP-Au NRs nanocomposites and the labeling of secondary antibody (Ab2) were performed by one-pot assembly of HRP and Ab2 on the surface of Au NRs. The immunosensor was fabricated by assembling carbon nanotubes (CNTs), Au NRs, and capture antibodies (Ab1) on the glassy carbon electrode. In the presence of AFP antigen, the labels were captured on the surface of the Au NRs/CNTs via specific recognition of antigen-antibody, resulting in the signal intensity being clearly increased. Differential pulse voltammetry (DPV) was employed to record the response signal of the immunosensor in phosphate-buffered saline (PBS) containing hydrogen peroxide (H2O2) and 3,3',5,5'-tetramethylbenzidine (TMB). Under optimal conditions, the signal intensity was linearly related to the concentration of AFP in the range of 0.1-100 ng ml(-1), and the limit of detection was 30 pg ml(-1) (at signal/noise [S/N] = 3). Furthermore, the immunoassay method was evaluated using human serum samples, and the recovery obtained was within 99.0 and 102.7%, indicating that the immunosensor has potential clinical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

Facile fabrication of a silicon nanowire sensor by two size reduction steps for detection of alpha-fetoprotein biomarker of liver cancer

International Nuclear Information System (INIS)

Pham, Van Binh; Pham, Xuan ThanhTung; Phan, Thanh Nhat Khoa; Le, Thi Thanh Tuyen; Dang, Mau Chien

2015-01-01

We present a facile technique that only uses conventional micro-techniques and two size-reduction steps to fabricate wafer-scale silicon nanowire (SiNW) with widths of 200 nm. Initially, conventional lithography was used to pattern SiNW with 2 μm width. Then the nanowire width was decreased to 200 nm by two size-reduction steps with isotropic wet etching. The fabricated SiNW was further investigated when used with nanowire field-effect sensors. The electrical characteristics of the fabricated SiNW devices were characterized and pH sensitivity was investigated. Then a simple and effective surface modification process was carried out to modify SiNW for subsequent binding of a desired receptor. The complete SiNW-based biosensor was then used to detect alpha-fetoprotein (AFP), one of the medically approved biomarkers for liver cancer diagnosis. Electrical measurements showed that the developed SiNW biosensor could detect AFP with concentrations of about 100 ng mL"−"1. This concentration is lower than the necessary AFP concentration for liver cancer diagnosis. (paper)

Facile fabrication of a silicon nanowire sensor by two size reduction steps for detection of alpha-fetoprotein biomarker of liver cancer

Science.gov (United States)

Binh Pham, Van; ThanhTung Pham, Xuan; Nhat Khoa Phan, Thanh; Thanh Tuyen Le, Thi; Chien Dang, Mau

2015-12-01

We present a facile technique that only uses conventional micro-techniques and two size-reduction steps to fabricate wafer-scale silicon nanowire (SiNW) with widths of 200 nm. Initially, conventional lithography was used to pattern SiNW with 2 μm width. Then the nanowire width was decreased to 200 nm by two size-reduction steps with isotropic wet etching. The fabricated SiNW was further investigated when used with nanowire field-effect sensors. The electrical characteristics of the fabricated SiNW devices were characterized and pH sensitivity was investigated. Then a simple and effective surface modification process was carried out to modify SiNW for subsequent binding of a desired receptor. The complete SiNW-based biosensor was then used to detect alpha-fetoprotein (AFP), one of the medically approved biomarkers for liver cancer diagnosis. Electrical measurements showed that the developed SiNW biosensor could detect AFP with concentrations of about 100 ng mL-1. This concentration is lower than the necessary AFP concentration for liver cancer diagnosis.

Targeting Alpha-Fetoprotein (AFP)-MHC Complex with CAR T-Cell Therapy for Liver Cancer.

Science.gov (United States)

Liu, Hong; Xu, Yiyang; Xiang, Jingyi; Long, Li; Green, Shon; Yang, Zhiyuan; Zimdahl, Bryan; Lu, Jingwei; Cheng, Neal; Horan, Lucas H; Liu, Bin; Yan, Su; Wang, Pei; Diaz, Juan; Jin, Lu; Nakano, Yoko; Morales, Javier F; Zhang, Pengbo; Liu, Lian-Xing; Staley, Binnaz K; Priceman, Saul J; Brown, Christine E; Forman, Stephen J; Chan, Vivien W; Liu, Cheng

2017-01-15

The majority of tumor-specific antigens are intracellular and/or secreted and therefore inaccessible by conventional chimeric antigen receptor (CAR) T-cell therapy. Given that all intracellular/secreted proteins are processed into peptides and presented by class I MHC on the surface of tumor cells, we used alpha-fetoprotein (AFP), a specific liver cancer marker, as an example to determine whether peptide-MHC complexes can be targets for CAR T-cell therapy against solid tumors. We generated a fully human chimeric antigen receptor, ET1402L1-CAR (AFP-CAR), with exquisite selectivity and specificity for the AFP 158-166 peptide complexed with human leukocyte antigen (HLA)-A*02:01. We report that T cells expressing AFP-CAR selectively degranulated, released cytokines, and lysed liver cancer cells that were HLA-A*02:01 + /AFP + while sparing cells from multiple tissue types that were negative for either expressed proteins. In vivo, intratumoral injection of AFP-CAR T cells significantly regressed both Hep G2 and AFP 158 -expressing SK-HEP-1 tumors in SCID-Beige mice (n = 8 for each). Moreover, intravenous administration of AFP-CAR T cells in Hep G2 tumor-bearing NSG mice lead to rapid and profound tumor growth inhibition (n = 6). Finally, in an established intraperitoneal liver cancer xenograft model, AFP-CAR T cells showed robust antitumor activity (n = 6). This study demonstrates that CAR T-cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent antitumor response. Our approach expands the spectrum of antigens available for redirected T-cell therapy against solid malignancies and offers a promising new avenue for liver cancer immunotherapy. Clin Cancer Res; 23(2); 478-88. ©2016 AACR. ©2016 American Association for Cancer Research.

Gold nanoparticle labeling with tyramide signal amplification for highly sensitive detection of alpha fetoprotein in human serum by ICP-MS.

Science.gov (United States)

Li, Xiaoting; Chen, Beibei; He, Man; Xiao, Guangyang; Hu, Bin

2018-01-01

In this work, we developed an immunoassay based on tyramide signal amplification (TSA) and gold nanoparticles (Au NPs) labeling for highly sensitive detection of alpha fetoprotein (AFP) by inductively coupled plasma mass spectrometry (ICP-MS). AFP was captured by anti-AFP1 coating on the 96-well plate and labeled by anti-AFP2-horseradish peroxidase (HRP), in which the HRP can catalyze the deposition of biotinylated tyramine on the nearby protein. Then the streptavidin (SA)-Au NPs was labeled on the deposited biotinylated tyramine as the intensive signal probe for ICP-MS measurement. Under the optimal experimental conditions, the limit of detection of the developed method for AFP was 1.85pg/mL and the linear range was 0.005-2ng/mL. The relative standard deviation for seven replicate detections of 0.01ng/mL AFP was 5.2%. The proposed method was successfully applied to the detection of AFP in human serum with good recoveries. This strategy is highly sensitive and easy to operate, and can be extended to the sensitive detection of other biomolecules in human serum. Copyright © 2017 Elsevier B.V. All rights reserved.

Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib.

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Houessinon, Aline; Gicquel, Albane; Bochereau, Flora; Louandre, Christophe; Nyga, Rémy; Godin, Corinne; Degonville, James; Fournier, Emma; Saidak, Zuzana; Drullion, Claire; Barbare, Jean-Claude; Chauffert, Bruno; François, Catherine; Pluquet, Olivier; Galmiche, Antoine

2016-01-28

Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC). A decrease in the serum levels of Alpha-fetoprotein (AFP) is reported to be the biological parameter that is best associated with disease control by sorafenib. In order to provide a biological rationale for the variations of AFP, we analyzed the various steps of AFP production in human HCC cell lines exposed to sorafenib. Sorafenib dramatically reduced the levels of AFP produced by HCC cells independently of its effect on cell viability. The mRNA levels of AFP decreased upon sorafenib treatment, while the AFP protein remained localized in the Golgi apparatus. Sorafenib activated the Regulated Inositol-Requiring Enzyme-1α (IRE-1α) and the PKR-like ER Kinase (PERK)-dependent arms of the Unfolded Protein Response (UPR). The inhibition of IRE-1α partially restored the mRNA levels of AFP upon treatment with sorafenib. The inhibition of both pathways partially prevented the drop in the production of AFP induced by sorafenib. The findings provide new insights on the regulation of AFP, and identify it as a biomarker suitable for the exploration of HCC cell proteostasis in the context of therapeutic targeting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Immunoprecipitation assay of alpha-fetoprotein synthesis by cultured mouse hepatoma cells treated with estrogens and glucocorticoids.

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Rosebrock, J A; Parker, C L; Kute, T E

1981-01-01

This investigation was to study the biosynthesis of 3H-labeled alpha-fetoprotein (AFP) by cultured mouse hepatoma (HEPA-2) cells. Both the function and regulation of this oncodevelopmental gene are unknown. However, evidence indicates that mechanisms controlling the expression of AFP involve aspects of both normal embryonic development and neoplastic transformation. the secretion of AFP was analyzed during different phases of the growth cycle to provide information on AFP production using standard culture conditions. The highest rate of secretion occurred during the stationary phase, followed by the late logarithmic and early logarithmic phases of growth, respectively. The production of AFP was then determined following the addition of glucocorticoids and estrogens in an attempt to understand hormonal factors that may be involved. Studies utilizing estradiol-17 beta indicated that the secretion of AFP did not appear to be sensitive to this steroid even though sucrose density gradient analysis of HEPA-2 cytosol, for estrogenic receptors, revealed competitive binding moieties on the 8S and 4S regions of the gradient. In contrast, the secretion of the total complement of proteins, including AFP, was significantly stimulated by the glucocorticoids, dexamethasone and corticosterone. Analysis of HEPA-2 cytosol for glucocorticoid receptors revealed binding components in the 7S and 3-4S regions of the gradient. The 3H-dexamethasone binding appeared to be stereospecific since nonlabeled dexamethasone, but not nonlabeled estradiol-17 beta, effectively displaced the bound radioactivity. The glucocorticoid-binding component in HEPA-2 therefore displayed characteristics reported for glucocorticoid receptors in normal liver and other hepatomas.

[The Clinical Significance of Serum Alpha-fetoprotein in Diagnosing Hepatocellular Carcinoma in a Health Screening Population].

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Ko, Young Sun; Bae, Joo Hwan; Sinn, Dong Hyun; Gwak, Geum Youn; Kang, Wonseok; Paik, Yong Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

2017-04-25

Serum alpha-fetoprotein (AFP) measurement is commonly included in a health check-up program in Korea. However, its benefits remain uncertain. We analyzed whether AFP measurement should be included in a general health check-up program to screen for hepatocellular carcinoma (HCC). A total of 36,552 adults aged 18 years or older-who participated in a routine health examination including AFP determination between January 2009 and December 2009 at the Health Promotion Center, Samsung Medical Center, South Korea-were analyzed. High risk of HCC was defined as positivity for hepatitis B surface antigen, anti-hepatitis C virus antibody or having liver cirrhosis. AFP level >10 ng/mL was observed in 27 participants (0.1%) and primary liver cancer was diagnosed in 9 patients (6 HCC and 3 cholangiocarcinoma). Among 1,619 participants with high risk factors of HCC, AFP level >10 ng/mL was observed in 16 participants, of which, 4 diagnoses were made. Sensitivity, specificity, positive predictive value, and negative predictive value of AFP for HCC was 0.66, 0.99, 0.25 and 0.99, respectively, for high risk participants. Among 34,933 participants without risk factors for HCC, 11 patients (<0.1%) showed elevated AFP levels above 10 ng/mL, and no case was diagnosed with primary liver cancer during a median follow-up period of 36 months (range: 0-48 months). AFP elevation was rare in participants without risk factors for HCC, and was unable to screen for HCC in this population. We discourage routine AFP measurements for asymptomatic adults without risk factors of HCC.

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

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Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

Hepatoid adenocarcinoma of the stomach: an unusual case of elevated alpha-fetoprotein with prior treatment for hepatocellular carcinoma

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Joon Seong Ahn

2013-06-01

Full Text Available Hepatoid adenocarcinoma (HAC is a rare type of extrahepatic carcinoma whose morphology is similar to that of hepatocellular carcinoma (HCC. Metachronous HCC and HAC in the same patient is extremely rare. The case of a 68-year-old man with chronic hepatitis B infection who had both HCC and HAC of the stomach is reported herein. Nine years previously this patient had been diagnosed with HCC and received a right lobectomy. HCC that recurred at the caudate lobe at 6 months after the operation was successfully treated with transarterial chemoembolization. The patient was followed up regularly thereafter without evidence of tumor recurrence for 9 years. In July 2010 his serum alpha-fetoprotein (AFP level elevated from 6.5 ng/mL to 625.4 ng/mL, and he developed a probable single metastatic lymph node around the hepatic artery without intrahepatic lesions. Subsequent evaluation with upper endoscopy revealed a 4-cm ulcerative lesion on the antrum of the stomach. Subtotal gastrectomy was performed with lymph-node dissection. Histologic examination revealed a special type of extrahepatic AFP-producing adenocarcinoma-HAC with lymph-node metastasis-which indicates that HAC can be a cause of elevated AFP even in patients with HCC. HAC should be considered if a patient with stable HCC exhibits unusual elevation of AFP.

Recombinant heat shock protein 70 functional peptide and alpha-fetoprotein epitope peptide vaccine elicits specific anti-tumor immunity.

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Wang, Xiao-Ping; Wang, Qiao-Xia; Lin, Huan-Ping; Xu, Bing; Zhao, Qian; Chen, Kun

2016-11-01

Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P. This novel peptide was administered into BALB/c mice to observe the effects. Quantification of AFP-specific CD8 + T cells that secrete IFN-γ in these mice via ELISPOT revealed the synergistic effects of HSP70-P/AFP-P with increased numbers of AFP-specific CD8 + T cells. Similarly, ELISA analysis showed increased granzyme B and perforin released by natural killer cells. Moreover, in vitro cytotoxic T-lymphocyte assays and in vivo tumor preventive experiments clearly showed the higher antitumor effects of HSP70-P/AFP-P against AFP-expressing tumors. These results show that treatment of BALB/c mice with HSP70-P/AFP-P induced stronger T-cells responses and improved protective immunity. Our data suggest that HSP70-P/AFP-P may be used as a therapeutic approach in the treatment of AFP-expressing cancers.

Alcoholic hepatitis with negligible sup(99m)Tc uptake and transient elevation of serum alpha-fetoprotein

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Hoshino, Hirosuke; Okumura, Makoto; Shimizu, Masanori; Eimoto, Tadaaki

1981-01-01

A 35 year old male with typical alcoholic hepatitis presented almost negligible uptake of sup(99m)Tc on the liver scan. Electron microscopic findings disclosing decreased number of Kupffer cells and impaired blood flow in the sinusoids may elucidate extremely diminshed uptake of isotope by the liver. Transient elevation of serum α-fetoprotein up to 3200 ng/ml observed during the active stage may indicate a regeneration process of hepatic necrosis occurred following the acute alcoholic hepatitis. (author)

Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy

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Kao, W.-Y. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Chiou, Y.-Y., E-mail: yychiou@vghtpe.gov.tw [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hung, H.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Su, C.-W., E-mail: cwsu2@vghtpe.gov.tw [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Chou, Y.-H. [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, J.-C. [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China); Huo, T.-I. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Huang, Y.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, W.-C. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China)

2012-05-15

Aims: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and methods: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of {>=}100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results: After a median follow-up of 26.7 {+-} 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and {>=}100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of {>=}100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count {<=}10{sup 5}/mm{sup 3} (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

Direct-acting antiviral-based triple therapy on alpha-fetoprotein level in chronic hepatitis C patients.

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Takayama, Koji; Furusyo, Norihiro; Ogawa, Eiichi; Ikezaki, Hiroaki; Shimizu, Motohiro; Murata, Masayuki; Hayashi, Jun

2015-04-21

To investigate the impact of telaprevir-based triple therapy on the serum alpha-fetoprotein (AFP) level of chronic hepatitis C patients. A total of 210 patients with chronic hepatitis C genotype 1 of high viral load (baseline serum hepatitis C virus RNA > 5.0 log10 IU/mL) were divided into two groups by type of treatment: triple therapy with telaprevir, pegylated-interferon-α (PEG-IFNα), and ribavirin (RBV) for 24 wk (n = 88), or dual therapy with PEG-IFNα and RBV for 48 wk (n = 122). The relationship between virological response and the change in the serum AFP level from baseline to 24 wk after the end of treatment was examined. No significant difference in mean baseline AFP level was found between the triple and dual therapy groups (8.8 ng/mL vs 7.8 ng/mL). Triple therapy produced significant declines in the AFP level in sustained virological response (SVR) and non-SVR patients (7.8 ng/mL at baseline to 3.5 ng/mL at 24 wk after the end of treatment, P < 0.001 and 14.3 ng/mL to 9.5 ng/mL, P = 0.004, respectively). In contrast, dual therapy resulted in a significant decline in AFP level only in SVR patients (4.7 ng/mL to 2.8 ng/mL, P < 0.001), but not in non-SVR patients (10.2 ng/mL to 10.1 ng/mL). Among patients with a high-baseline AFP level (≥ 10 ng/mL), the decline in the AFP level was significantly higher in the triple therapy than in the dual therapy group (15.9 ng/mL vs 1.6 ng/mL, P = 0.037). Regardless of virological response, telaprevir-based triple therapy reduced the serum AFP level.

Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

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Olivier Brock

Full Text Available The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus, as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

Serum reference interval of ARCHITECT alpha-fetoprotein in healthy Chinese Han adults: Sub-analysis of a prospective multi-center study.

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Yan, Cunling; Yang, Jia; Wei, Lianhua; Hu, Jian; Song, Jiaqi; Wang, Xiaoqin; Han, Ruilin; Huang, Ying; Zhang, Wei; Soh, Andrew; Beshiri, Agim; Fan, Zhuping; Zheng, Yijie; Chen, Wei

2018-02-01

Alpha-fetoprotein (AFP) has been widely used in clinical practice for decades. However, large-scale survey of serum reference interval for ARCHITECT AFP is still absent in Chinese population. This study aimed to measure serum AFP levels in healthy Chinese Han subjects, which is a sub-analysis of an ongoing prospective, cross-sectional, multi-center study (ClinicalTrials.gov Identifier: NCT03047603). This analysis included a total of 530 participants (41.43±12.14years of age on average, 48.49% males), enrolled from 5 regional centers. Serum AFP level was measured by ARCHITECT immunoassay. Statistical analysis was performed using SAS 9.4 and R software. AFP distribution did not show significant correlation with age or sex. The overall median and interquartile range of AFP was 2.87 (2.09, 3.83) ng/mL. AFP level did not show a trend of increasing with age. The new reference interval was 2.0-7.07ng/mL (LOQ- 97.5th percentiles). The reference interval for ARCHITECT AFP is updated with the data of adequate number of healthy Han adults. This new reference interval is more practical and applicable in Chinese adults. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Nonsecreted cytoplasmic alpha-fetoprotein: a newly discovered role in intracellular signaling and regulation. An update and commentary.

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Mizejewski, G J

2015-12-01

The concept of a non-secreted cytoplasmic-bound form of alpha-fetoprotein is not a new notion in AFP biological activities. Cytoplasmic AFP (CyAFP) is a long known but forgotten protein in search of a function other than a histochemical biomarker. In this report, CyAFP is presented as an "old" protein with a newly described intracellular function. In 1976, CyAFP was shown to be a product of hepatoma cells utilizing 14Cleucine incorporation and demonstrated by autoradiographic procedures. The synthesis of CyAFP without secretion was demonstrated to occur in both malignant and non-malignant cells encompassing hepatomas, ascite fluid cells, immature rodent uterus, MCF-7 breast cancers, and cytosols from human breast cancer patients. Using computer protein matching and alignments in AFP versus members of the nuclear receptor superfamily, a consecutive series of leucine zipper (heptad) repeats in AFP was previously reported, suggesting the possibility for protein-to-protein interactions. The potential for heptad heterodimerization between protein-binding partners provided the rationale for proposing that CyAFP might have the capability to form molecular hetero-complexes with cytoplasmic based transcription factors. More recent investigations have now provided experimental evidence that CyAFP is capable of colocalizing and interacting with transcription-associated factors. Such proteins can modulate intracellular signaling leading to regulation of transcription factors and initiation of growth in human cancer cells. Although circulating serum AFP is known as a growth-enhancing factor during development, cytoplasmic AFP has a lethal role in the oncogenesis, growth, and metastasis of adult liver cancer.

Morphologic alterations and immunohistochemical analysis of alpha-fetoprotein and CD34 in chorionic villi of anembryonic pregnancy

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Aydin, S.; Yenilmez, E.; Yulug, E.; Arvas, H.; Ozeren, M.; Cobanoglu, U.

2006-01-01

To investigate the morphology of chorionic villi using light and electron microscopy, especially the expression of alpha-fetoprotein (AFP) in trophoblastic cells and the process of maturation and margination vasculogenesis proper using CD34 immunohistochemistry in tissues from the first trimester of pregnancy loss due to anembryonic pregnancy in comparison with embryonic pregnancy. The study consisted of 2 groups: 9 patients with anembryonic pregnancies and 9 patients with embryonic pregnancies between 6 and 10 weeks of gestational age registered at the Department of Gynecology and Obstetrics, University Hospital of Karadeniz Technical University, Turkey, from March 2003 to December 2004. We examined the chorionic villi using light and electron microscopy. For immunohistochemical staining, we used AFP and CD 34. Microscopically, pathologic changes were shown in syncytiotrophoblast cells of anembryonic pregnancies and AFP was strongly expressed by villous trophoblastic cells compared to embryonic pregnancies. We determined the CD34 positivity in both groups. In anembryonic pregnancies, vascular elements were much fewer in number compared with embryonic pregnancies (p<0.001) and were located in the formed of hemangioblastic cords. Placental vasculogenesis is a basic feature in all types of pregnancy and a relationship exists between trophoblast cells and vessels in the chorionic villi with the potential to influence each other's functions. Defective chorionic villus vascularization is associated with embryonic death. This study may support the hypothesis, as suggested by previous studies, that anembryonic pregnancy results from early embryonic death and subsequent reabsorption rather than from the nondevelopment of an embryo. (author)

Diagnostic utility of alpha-fetoprotein and des-gamma-carboxyprothrombin in nigerians with hepatocellular carcinoma.

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Ette, Akpakip Ikpong; Ndububa, D A; Adekanle, O; Ekrikpo, U

2017-10-01

Alpha-fetoprotein (AFP) and Des-gamma-carboxyprothrombin (DCP) have been extensively studied as biomarkers for the diagnosis of and prognostication in hepatocellular carcinoma (HCC). However there are only few reports on the clinical characteristics of hepatocellular carcinoma in relation to the combination of the two tumor markers in hepatitis B virus-related HCC. The aim of this study was to investigate the clinical characteristics of HBV-related HCC in relation to different sets of AFP and DCP values. Sixty-two patients with untreated HCC were studied. The positive value of AFP was set at 20 1U/L while DCP positive value was set at 150 mAU/ml. Patients were divided into three groups: Group 1(n=36) with AFP ≥ 20 IU/L and DCP ≥ 150 mAU/ml. Group 2(n=24) with AFP <20 1U/L and DCP ≥ 150 mAU/ml. Group 3 (n=2) with AFP < 20 1U/L and DCP < 150 mAU/ml. There were no patients in group 4 meant for those with AFP ≥ 20 1U/L and DCP < 150 mAU/ml. Clinical and laboratory variables were compared among the groups. Clinical and laboratory variables were comparable among the groups with the exception of gender and values of serum alanine aminotransferase (ALT). Males were significantly more than females among the groups (p<0.03). ALT values were significantly different among the groups (p<0.006). Paired comparisons between the groups showed the mean values of serum ALT were significantly higher in group 2 than in group 1(p<0.003). The mean serum ALT values were also higher in group 2 than in group 3 (p <0.014). There was no significant difference between group 1 and group 3 (P = 0.124). HCC patients who are sero-positive for DCP and sero-negative for AFP have significantly higher levels of serum ALT; serum ALT levels may be of diagnostic importance in AFP-negative, HBV-related HCC patients.

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

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Mohamed Ahmed Khedr

2015-01-01

Full Text Available Background & Aims. The currently available treatment for chronic hepatitis C (CHC in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p<0.0001, p=0.071, and p=0.87, resp.. In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p<0.0001 and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p<0.0001 and p=0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p=0.044. Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

A novel electrochemical immunosensor using β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase as labels for ultrasensitive detection of alpha-fetoprotein.

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Gao, Jian; Ma, Hongmin; Lv, Xiaohui; Yan, Tao; Li, Na; Cao, Wei; Wei, Qin

2015-09-17

In this work, a novel sandwich-type electrochemical immunosensor based on host-guest interaction was fabricated for the detection of alpha-fetoprotein (AFP). Due to the large specific surface area of multiwalled carbon nanotubes and the unique supramolecular recognition ability of β-cyclodextrins, ferrocenecarboxylic acid (Fc) was incorporated into this sensor platform by host-guest interaction to generate an electrochemical signal. And β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase (GOD-CD-Ag), was used as a label to improve the analytical performance of the immunosensor by the dual amplification strategy. The obtained GOD-CD-Ag conjugates could convert glucose into gluconic acid with the formation of hydrogen peroxide (H2O2). And then silver nanoparticles could in situ catalyze the reduction of the generated H2O2, dramatically improving the oxidation reaction of Fc. The developed immunosensor shows a wide linear calibration range from 0.001 to 5.0 ng/mL with a low detection limit (0.2 pg/mL) for the detection of AFP. The method, with ideal reproducibility and selectivity, has a wide application prospect in clinical research. Copyright © 2015 Elsevier B.V. All rights reserved.

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

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Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

2015-12-01

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

Alpha-fetoprotein in the routine clinical laboratory: evaluation of a simple radioimmunoassay and review of current concepts in its clinical application

International Nuclear Information System (INIS)

Brummund, W.; Mennuti, M.T.; Arvan, D.A.; Starkovsky, N.A.

1980-01-01

The authors have assessed the clinical utility of a radioimmunoassay for alpha-fetoprotein (AFP). The method, which relies on ammonium sulfate precipitation for the separation of 'bound' and 'free' radiolabeled antigen, can be completed in one working day. The assay is specific for AFP, has a sensitivity of <10 ng/ml, and has intra- and inter-assay precision of 5-8% and 9-11%, respectively. They have conducted a three-year study of 472 pregnancies in which physicians wished to detect neural tube defects, and of 400 non-pregnant patients to assess the value of serum AFP as a marker for certain benign and malignant diseases. Six of 6 fetal open neural-tube defects (NTD'S) and 3 of 3 intrauterine fetal deaths were correctly identified by their association with marked AFP elevations in both maternal serum and amniotic fluid. Thirty non-pregnant patients were found to have AFP elevations greater than 20 ng/ml. Malignancies associated with these elevations were hepatoma, germ cell tumors, Wilms' tumor, and carcinoma of unknown origin. Carcinoma metastatic to the liver was not associated with AFP elevations. In AFP-associated tumors they found serial measurements of serum AFP to be of value in assessing therapeutic response. (Auth.)

The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins.

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Mizejewski, G J

2016-09-01

The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins. The cell cycle proteins identified were (1) cyclins, (2) cyclin-dependent kinases, (3) cell cycle-associated proteins (inhibitors, checkpoints, initiators), and (4) ubiquitin ligases. Following detection of the AFP-3D to cell cycle protein interaction sites, the computer-derived AFP localization AA sequences were compared and aligned with previously reported hydrophobic ligand and receptor interaction sites on AFP-3D. A literature survey of the association of cell cycle proteins with AFP showed both positive relationships and correlations. Previous reports of experimental AFP-derived peptides effects on various cell cycle proteins served to confirm and verify the present computer cell cycle protein identifications. Cell cycle protein interactions with AFP-CD peptides have been reported in cultured MCF-7 breast cancer cells subjected to mRNA microarray analysis. After 7 days in culture with MCF-7 cells, the AFP-derived peptides were shown to downregulate cyclin E, SKP2, checkpoint suppressors, cyclin-dependent kinases, and ubiquitin ligases that modulate cyclin E/CdK2 transition from the G1 to the S-phase of the cell cycle. Thus, the experimental data on AFP-CD interaction with cell cycle proteins were consistent with the "in silico" findings.

Maternal serum alpha-fetoprotein at 12, 22 and 32 weeks' gestation in screening for pre-eclampsia.

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Bredaki, F E; Matalliotakis, M; Wright, A; Wright, D; Nicolaides, K H

2016-04-01

To examine the distribution of maternal serum alpha-fetoprotein (AFP) at 12, 22 and 32 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. Serum AFP was measured in 17 071 cases at 11-13 weeks, in 8583 cases at 19-24 weeks and 8609 cases at 30-34 weeks' gestation. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with AFP. The performance of screening for PE requiring delivery < 32, at 32 + 0 to 36 + 6, < 37 and ≥ 37 weeks' gestation was estimated. In pregnancies that developed PE, serum AFP multiples of the median (MoM) was increased at 11-13 and 19-24 weeks' gestation, but not at 30-34 weeks, and the values were inversely related to gestational age at delivery. Combined screening with maternal factors and serum AFP improved the prediction provided by maternal factors alone for PE delivering < 37 weeks, but not for PE delivering ≥ 37 weeks. The performance of screening for preterm PE was better at 19-24 weeks than at 11-13 weeks and the detection rate (DR) for a given false-positive rate (FPR) was higher for PE delivering < 32 weeks than for PE delivering at 32 + 0 to 36 + 6 weeks. The DRs, at 10% FPR, of combined screening at 11-13 weeks for PE delivering < 32 and at 32 + 0 to 36 + 6 weeks were 54% and 45%, respectively, and these improved to 72% and 53% with screening at 19-24 weeks. Measurement of serum AFP at 11-13 and 19-24 weeks' gestation improves the prediction of preterm PE provided by maternal factors alone. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Serum alpha-fetoprotein in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

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Bredaki, F E; Sciorio, C; Wright, A; Wright, D; Nicolaides, K H

2015-07-01

To define the contribution of maternal variables which influence the measured level of maternal serum alpha-fetoprotein (AFP) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and serum AFP was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of AFP were determined from a linear mixed-effects multiple regression. Serum AFP was measured in 17 071 cases in the first trimester, 8583 in the second trimester and 8607 in the third trimester. Significant independent contributions to serum AFP were provided by gestational age, maternal weight, racial origin, gestational age at delivery and birth-weight Z-score of the neonate of the previous pregnancy and interpregnancy interval. Cigarette smoking was found to significantly affect serum AFP in the first trimester only. The machine used to measure serum AFP was also found to have a significant effect. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum AFP and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed pre-eclampsia and in those without this pregnancy complication. A model was fitted to express measured serum AFP across the three trimesters of pregnancy as MoMs, after adjusting for variables from maternal characteristics and medical history that affect this measurement. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Prussian blue-gold nanoparticles-ionic liquid functionalized reduced graphene oxide nanocomposite as label for ultrasensitive electrochemical immunoassay of alpha-fetoprotein.

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Gao, Qi; Liu, Na; Ma, Zhanfang

2014-06-04

In this work, poly(diallyldimethylammonium chloride) (PDDA) protected Prussian blue/gold nanoparticles/ionic liquid functionalized reduced graphene oxide (IL-rGO-Au-PDDA-PB) nanocomposite was fabricated. The resulting nanocomposite exhibited high biocompatibility, conductivity and catalytic activity. To assess the performance of the nanocomposite, a sensitive sandwich-type immunosensor was constructed for detecting alpha-fetoprotein (AFP). Greatly enhanced sensitivity for this immunosensor was based on triple signal amplification strategies. Firstly, IL-rGO modified electrode was used as biosensor platform to capture a large amount of antibody due to its increased surface area, thus amplifying the detection response. Secondly, a large number of Au-PDDA-PB was conjugated on the surface of IL-rGO, which meant the enrichment of the signal and the more immobilization of label antibody. Finally, the catalytic reaction between H2O2 and the IL-rGO-Au-PDDA-PB nanocomposite further enhanced the signal response. The signals increased linearly with AFP concentrations in the range of 0.01-100 ng mL(-1). The detection limit for AFP was 4.6 pg mL(-1). The immunosensor showed high sensitivity, excellent selectivity and good stability. Moreover, the immunosensor was applied to the analysis of AFP in serum sample with satisfactory result. Copyright © 2014 Elsevier B.V. All rights reserved.

Upconversion nanoparticle as elemental tag for the determination of alpha-fetoprotein in human serum by inductively coupled plasma mass spectrometry.

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Liu, Zhengru; Yang, Bin; Chen, Beibei; He, Man; Hu, Bin

2016-12-19

Upconversion nanoparticles (UCNPs) have received increasing attention due to their unique optical properties. Recognizing that UCNPs are lanthanide-doped nanoparticles, we incorporated UCNPs into an immunoassay with inductively coupled plasma mass spectrometry (ICP-MS) detection for the determination of specific proteins, e.g., alpha-fetoprotein (AFP). The sensitivity of the assay was enhanced because of the ICP-MS detection of UCNPs that contained large numbers of lanthanide elemental tags. Conjugates of UCNPs and antibodies were prepared and the morphology of the conjugates was characterized by transmission electron microscopy. After a sandwich immunoreaction, the AFP was determined by the ICP-MS analysis of UCNPs. Under the optimized conditions, a limit of detection (3σ) of 0.31 ng mL -1 based on 89 Y signal and 0.22 ng mL -1 based on 174 Yb signal was obtained for AFP, with a dynamic range of 0.5-35 ng mL -1 and a relative standard deviation of 4.8% (c = 5 ng mL -1 , n = 9). The developed method was applied to the determination of AFP in human serum and the recovery for the spiked sample was in the range of 98.6-123%. The proposed method is simple, rapid, selective and sensitive, and has a good tolerance for the complex biological matrix, indicating great potential for the application of UCNP in biological research as an elemental tag.

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors.

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de la Motte Rouge, Thibault; Pautier, Patricia; Genestie, Catherine; Rey, Annie; Gouy, Sébastien; Leary, Alexandra; Haie-Meder, Christine; Kerbrat, Pierre; Culine, Stéphane; Fizazi, Karim; Lhommé, Catherine

2016-09-01

The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. No conflict of interest. Copyright © 2016. Published by Elsevier Inc.

Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma.

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Yao, Mingjie; Zhao, Jingmin; Lu, Fengmin

2016-01-26

Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia.

Measurement of Glycosylated Alpha-Fetoprotein Improves Diagnostic Power over the Native Form in Hepatocellular Carcinoma

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Jin, Jonghwa; Park, Jiyoung; Yu, Su Jong; Yoon, Jung-Hwan; Kim, Youngsoo

2014-01-01

Serum alpha-fetoprotein (AFP) has long been used as a diagnostic marker for hepatocellular carcinoma (HCC), albeit controversially. Although it remains widely used in clinics, the value of AFP in HCC diagnosis has recently been challenged due to its significant rates of false positive and false negative findings. To improve the efficacy of AFP as HCC diagnostic marker, we developed a method of measuring total and glycosylated AFP by multiple reaction monitoring (MRM)-MS. In this study, we verified the total amount of AFP (nonglycopeptide levels) and the degree of glycosylated AFP (deglycopeptide levels) in 60 normal (41 men and 19 women; mean age 53 years; range 32–74 years), 35 LC (23 men and 12 women; mean age 56 years; range 43–78 years; HBV-related), and 60 HCC subjects (42 men and 18 women; mean age 58 years; range 38–76 years; HBV-related; 30 stage I, 15 stage II, and 10 stage III). By MRM-MS analysis, the nonglycopeptide had 56.7% sensitivity, 68.3% specificity, and an AUC of 0.687 [cutoff value: ≥0.02 (light/heavy ratio)], comparing the normal and HCC group, whereas the deglycopeptide had 93.3% sensitivity, 68.3% specificity, and an AUC of 0.859 [cutoff value: ≥0.02 (light/heavy ratio)]. In comparing the stage I HCC subgroup with the LC group, the nonglycopeptide had a sensitivity of 66.7%, specificity of 80.0%, and an AUC of 0.712 [cutoff value: ≥0.02 (light/heavy ratio)], whereas the deglycopeptide had a sensitivity of 96.7%, specificity of 80.0%, and an AUC of 0.918 [cutoff value: ≥0.02 (light/heavy ratio)]. These data demonstrate that the discriminatory power of the deglycopeptide is greater than that of the nonglycopeptide. We conclude that deglycopeptide can distinguish cancer status between normal subjects and HCC patients better than nonglycopeptide. PMID:25310463

Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

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Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin

2015-04-01

The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L- 1 and 0.054 μg L- 1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L- 1) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2-50 μg L- 1. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications.

Homogeneous immunoassay for the cancer marker alpha-fetoprotein using single wavelength excitation fluorescence cross-correlation spectroscopy and CdSe/ZnS quantum dots and fluorescent dyes as labels

International Nuclear Information System (INIS)

Wang, Jinjie; Liu, Heng; Huang, Xiangyi; Ren, Jicun

2016-01-01

The article describes sensitive and selective homogeneous immunoassays for the liver cancer biomarker alpha-fetoprotein (AFP) in human serum by using single wavelength excitation fluorescence cross-correlation spectroscopy (SW-FCCS). Both competitive and sandwich immunoassay modes were applied, and AFP served as a model analyte. Fluorescent CdSe/ZnS quantum dots (with a 655 nm emission peak) and the fluorophore Alexa Fluor 488 (520 nm emission) were chosen to label the antibodies in the sandwich mode, and the antibody and the antigen in the competitive mode. Under optimized conditions, the sandwich assay has a linear dynamic range that covers the 20 pM to 5.0 nM concentration range. The competitive assay, in turn, extends from 180 pM to 15.0 nM. The respective detection limits are 20 pM and 180 pM. The method was successfully applied to directly determine AFP in (spiked) clinical samples, and results were in good agreement with data obtained via ELISAs. (author)

Clinical characteristics of hepatocellular carcinoma patients with normal serum alpha-fetoprotein level: A study of 112 consecutive cases.

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Li, Li; Chen, Jinglong; Xu, Weiran; Ding, Xiaosheng; Wang, Xiangyi; Liang, Jun

2017-10-26

Serum alpha-fetoprotein (AFP) level is normal in 30-40% of hepatocellular carcinoma (HCC) patients, and knowledge on its characteristics and clinical outcome is limited. The purpose of this observational study was to determine the clinical presentation, biological behavior and outcome of HCC patients with normal AFP level. Data of 112 consecutive HCC patients with normal AFP level were analyzed retrospectively. Statistical analysis including survival and factors associated with serum AFP level were performed by Kaplan-Meier method and t-test, respectively. Hepatitis B virus infection exited in 83.0% of all 112 HCC patients with normal AFP level. During a mean 52 ± 20 months (range 5-85 months) follow-up, the 1-, 2-, 3-year overall survival (OS) rate was 97.2%, 85.3% and 81.7%, respectively. The OS rates at 3 years stratified by stages at diagnosis were 100%, 96.2%, 85.7%, 11.1% and 0%, respectively for Barcelona Clinic Liver Cancer (BCLC) stage 0-D diseases. Significant difference in OS was observed among patients with BCLC stage 0-D diseases, P level elevated beyond normal figure during follow-up (AFP conversion) in 16 patients, which related with deterioration of liver function, quantitative changes of T helper cell subsets, rapid tumor progression and shorter survival. Patients with sustained normal AFP level had better survival than patients with AFP conversion, P level elevation and the time of AFP elevation to death, P level was relatively optimal. Serum AFP level elevation during follow-up was significantly associated with clinical outcome in terms of OS. © 2017 John Wiley & Sons Australia, Ltd.

Hepatocellular carcinoma in children and young patients with chronic HBV infection and the usefulness of alpha-fetoprotein assessment.

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Tajiri, Hitoshi; Takano, Tomoko; Tanaka, Hideo; Ushijima, Kosuke; Inui, Ayano; Miyoshi, Yoko; Ozono, Keiichi; Abukawa, Daiki; Endo, Takeshi; Brooks, Stephen; Tanaka, Yasuhito

2016-11-01

The aims of the study were to elucidate the clinical characteristics of patients who developed hepatocellular carcinoma (HCC) related to persistent HBV infection since childhood and to investigate usefulness of assessing alpha-fetoprotein (AFP) in this population. A nationwide multicenter survey of children with chronic HBV infection was performed. Among 548 patients, 15 patients developed HCC at the median age of 15 years (range 9-36), including 13 males and 2 females. A case-control comparison showed that HBeAg seroconversion and liver cirrhosis were associated with the occurrence of HCC. Of the 15 HCC patients, 5 were treated with interferon and none of them responded to interferon therapy as compared with 12 of the 17 responders in the control group. Of the 15 patients, 10 died and 9 of the 10 who died never visited any medical facilities until diagnosis of HCC, while the remaining 5 surviving patients never stopped their clinic visits. The usefulness of AFP assessment was shown by the findings that AFP levels were elevated in all HCC cases, that elevations in AFP levels were detected prior to the diagnosis in the surviving patients, and that sensitivity of AFP as a diagnostic test for HCC was very high among 40 patients including our 14 and an additional 26 collected from the literature. HBeAg seroconversion and liver cirrhosis are associated with the occurrence of HCC. Regular measurement of AFP might be helpful to watch for the occurrence of HCC when following children and young patients with chronic HBV infection since childhood. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Time of hepatocellular carcinoma recurrence after liver resection and alpha-fetoprotein are important prognostic factors for salvage liver transplantation.

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Lee, Sanghoon; Hyuck David Kwon, Choon; Man Kim, Jong; Joh, Jae-Won; Woon Paik, Seung; Kim, Bong-Wan; Wang, Hee-Jung; Lee, Kwang-Woong; Suh, Kyung-Suk; Lee, Suk-Koo

2014-09-01

Salvage liver transplantation (LT) is considered a feasible option for the treatment of recurrent hepatocellular carcinoma (HCC). We performed this multicenter study to assess the risk factors associated with the recurrence of HCC and patient survival after salvage LT. Between January 2000 and December 2011, 101 patients who had previously undergone liver resection (LR) for HCC underwent LT at 3 transplant centers in Korea. Sixty-nine patients' data were retrospectively reviewed for the analysis. The recurrence of HCC was diagnosed at a median of 10.6 months after the initial LR, and patients underwent salvage LT. Recurrences were within the Milan criteria in 48 cases and were outside the Milan criteria in 21 cases. After salvage LT, 31 patients had HCC recurrence during a median follow-up period of 24.5 months. There were 24 deaths, and 20 were due to HCC recurrence. The 5-year overall survival rate was approximately 54.6%, and the 5-year recurrence-free survival rate was 49.3%. HCC recurrence within the 8 months after LR [hazard ratio (HR) = 3.124, P = 0.009], an alpha-fetoprotein level higher than 200 ng/mL (HR = 2.609, P = 0.02), and HCC outside the Milan criteria at salvage LT (HR = 2.219, P = 0.03) were independent risk factors for poor recurrence-free survival after salvage LT. In conclusion, the timing and extent of HCC recurrence after primary LR both play significant roles in the outcome of salvage LT. © 2014 American Association for the Study of Liver Diseases.

A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel.

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Ji, Xiaonan; Shen, Yanli; Sun, Hao; Gao, Xiangdong

2016-08-01

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

Amperometric immunosensor for {alpha}-fetoprotein antigen in human serum based on co-immobilizing dinuclear copper complex and gold nanoparticle doped chitosan film

Energy Technology Data Exchange (ETDEWEB)

Gan Ning; Meng Linghua; Wang Feng [State Key Laboratory Base of Novel Functional Materials and Preparation science, Faculty of Material Science and Chemical Engineering of Ninbo University, Ningbo, 315211 (China)], E-mail: ganning@nbu.edu.cn

2009-09-01

A sensitive amperometric immunosensor for {alpha}-fetoprotein (AFP), a tumor marker for the diagnosis of hepatocellular carcinoma (HCC), was constructed, The immunosensor is prepared by co-immobilizing [Cu{sub 2}(phen){sub 2}Cl{sub 2}] ({mu}-Cl){sub 2} (CuL), nano-Au/Chitosan(Chit) composite, horseradish peroxidase (HRP) and AFP antibody(anti-AFP) on a glassy carbon electrode (GCE). Firstly, CuL was irreversibly absorb on GCE electrode through {pi}-{pi} stacking interaction; then nano-Au/Chit composite was immobilized onto the electrode because of its excellent membrane-forming ability, finally HRP and anti-AFP was adsorbed onto the surface of the gold nanoparticles to construct GCE | CuL/nanoAu-chit/HRP/anti-AFP immunosensor. The preparation procedure of the electrode was characterized by electrochemical and spectroscopy method. The results showed that this immunosensor exhibited an excellent electrocatalytic response to the reduction of hydrogen peroxide (H{sub 2}O{sub 2}) without the aid of an electron mediator, offers a high-sensitivity (1710 nA {center_dot} ng{sup -1} {center_dot} ml{sup -1}) for the detection of AFP and has good correlation for detection of AFP in the range of 0.2 to 120.0 ng/ml with a detection limit of 0.05 ng/ml. The biosensor showed high selectivity as well as good stability and reproductivity.

Prognostic value of determination of carcinoembryonic antigen and α-fetoprotein level in blood plasma in patients with cancer stomach

International Nuclear Information System (INIS)

Smyslova, V.N.; Vygonnyj, I.I.

1986-01-01

60 donors and 129 patients with cancer stomach were examined. Tumor antigens were determined in blood plasma by the method of radioimmunoassay. The upper boundary of the norm of alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) is 12 ng/ml. Increased concentration of antigens studied is detected in most patients. It is established that the level of antigens increases depending on generalization of the process, cancer stage, tumor propagation in the stomach wall, patient's age. High volumes of AFP and CEA after operation give evidence about non-radicality of operation and bad prognosis

Nanogram per milliliter-level immunologic detection of alpha-fetoprotein with integrated rotating-resonance microcantilevers for early-stage diagnosis of heptocellular carcinoma.

Science.gov (United States)

Liu, Yongjing; Li, Xinxin; Zhang, Zhixiang; Zuo, Guomin; Cheng, Zhenxing; Yu, Haitao

2009-02-01

Nanogram per milliliter-level ultra-low concentration detection of alpha-fetoprotein (AFP), which is an important marker for heptocellular carcinoma, is in favor of early-stage prognosis and disease diagnosis. On-the-spot rapid detection of such antigens as AFP highly requires innovative micro/nano techniques. To meet this requirement, an advanced resonant microcantilever is developed and used for screening the tumor marker at nanogram per milliliter level. The sensing principle of the resonant microcantilever is measuring frequency-shift versus specific-adsorbed mass. With both electromagnetic resonance-exciting and piezoresistive readout elements on-chip integrated, the microcantilever sensor is operated in a rotating resonance mode to improve sensitivity and resolution to specific mass adsorption. Prior to detection of AFP with previously immobilized anti-AFP antibody, the antigen-antibody specific-binding is confirmed with an enzyme linked immunosorbent assay experiment. By implementing the specific reaction in liquid and reading out the sensor signal in lab air environment, the micromechanical sensor has achieved the sensitive scale between 2 and 20 ng/ml. To effectively depress cross-talk signal and improve resolution, the insensitive regions of the cantilever surface are pre-modified with 2-[methoxy (polyethyleneoxy) propyl] trimethoxysilane for nonspecific bio-adsorption minimization. Finally, a better AFP detecting limit than 2 ng/mL is experimentally achieved. The label-free resonant microcantilever sensor is promising in low-cost or even disposable early-stage prognosis and diagnosis of tumors.

Ataxia Telangiectasia

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... is the measurement of "fetal proteins," or serum alpha-fetoprotein , in the blood. These are proteins that are ... than 95 percent) have elevated levels of serum alpha-fetoprotein. When other causes of elevations of alpha-fetoprotein ...

Liver transplantation for hepatocellular carcinoma: evaluation of the alpha-fetoprotein model in a multicenter cohort from Latin America.

Science.gov (United States)

Piñero, Federico; Tisi Baña, Matías; de Ataide, Elaine Cristina; Hoyos Duque, Sergio; Marciano, Sebastian; Varón, Adriana; Anders, Margarita; Zerega, Alina; Menéndez, Josemaría; Zapata, Rodrigo; Muñoz, Linda; Padilla Machaca, Martín; Soza, Alejandro; McCormack, Lucas; Poniachik, Jaime; Podestá, Luis G; Gadano, Adrian; Boin, Ilka S F Fatima; Duvoux, Christophe; Silva, Marcelo

2016-11-01

The French alpha-fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort. Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement (NRI) method. Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio (HR) of 3.15 (P = 0.0001) and lower patient survival (HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence (HR 2.2, P = 0.12) and lower survival rate (HR 2.25, P = 0.03). A comparative analysis between HBV and non-HBV patients showed that the AFP model performed better in non-HBV patients. The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alpha-fetoprotein-producing ovarian clear cell adenocarcinoma with fetal gut differentiation: a rare case report and literature review.

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Chao, Wei-Ting; Liu, Chia-Hao; Lai, Chiung-Ru; Chen, Yi-Jen; Chuang, Chi-Mu; Wang, Peng-Hui

2018-06-22

Alpha-fetoprotein (AFP) is a useful tumor marker for ovarian germ cell tumors, particularly yolk sac tumor (YST). It is valuable for both diagnosis and further follow-up. Epithelial ovarian carcinoma (EOC) rarely secretes AFP, especially for clear cell type and in the postmenopausal women. Based on the limited knowledge about AFP-producing clear cell type EOC, a case and literature review on this topic is extensively reviewed. We report a 55-year-old postmenopausal woman experienced vaginal spotting for one month, and serum level of AFP was 60,721 ng/ml initially. Histological examination was clear cell type EOC. Tumor cells revealed strong immunoreactivity for glypican-3 (GPC3) and AFP and weak for hepatocyte nuclear factor-1 beta (HNF-1 beta), but negative for CD30, making the diagnosis of AFP-producing clear cell type EOC with fetal gut differentiation in focal areas, FIGO (International Federation of Gynecology and Obstetrics) IIIc. Although the patient underwent an intensive treatment, including optimal debulking surgery and multi-agent chemotherapy, the patient died of disease. To provide a better understanding of clinical and molecular characteristics of the AFP-producing clear cell type EOC, we conducted a systematic literature review. A total of three papers described the AFP-producing clear cell type EOC are available. The overall survival rate of these cases, including the current case is 50%. Although immunohistochemical examination is not always needed in routine for the diagnosis of clear cell type EOC, to distinguish from other tumors, especially germ cell tumors, or to provide the better way to monitor therapeutic response or to evaluate the disease status, immunostaining, including GPC3, HNF-1 beta, CD30, cytokeratin 7 or 20, and AFP is taken into account. Due to rarity, the appropriate chemotherapy regimen and the biological behavior of AFP-producing clear cell type EOC are still unclear.

Alpha-fetoprotein is present in the fetal fluids and is increased in plasma of mares with experimentally induced ascending placentitis.

Science.gov (United States)

Canisso, Igor F; Ball, Barry A; Scoggin, Kirsten E; Squires, Edward L; Williams, Neil M; Troedsson, Mats H

2015-03-01

The objectives of this study were to: (i) determine alpha-fetoprotein (AFP) concentrations in fetal fluids (FF), and (ii) compare plasma concentrations of AFP in mares with placentitis (n=17) and gestationally age-matched control mares (n=17). Fetal fluid sampling (FFS, n=7/group) was performed at 0, 5 and 12 days post inoculation (DPI) or until abortion. Plasma was harvested daily for 12 days or until abortion. Placentitis was induced via intracervical inoculation of Streptococcus equi ssp. zooepidemicus. Proteins present in the FF were resolved by 1D-SDS-PAGE, and immunoblotting was used to detect the presence of AFP in fetal fluids. Concentrations of AFP in FF and plasma were determined with a chemiluminescence immunoassay. Mixed models for DPI, and for days from abortion (DFA) were used to analyze plasma concentrations of AFP. A protein band ∼68kDa consistent with the AFP size was present in all samples of fetal fluids examined. Immunoblotting for AFP revealed a single protein band (∼68kDa) in all samples. Concentrations of AFP in FF appeared higher than those in maternal plasma. There were effects of time (DPI p<0.0001; DFA p=0.0002) and time-by-group interactions (DPI*Group p<0.06; Group*DFA p<0.001). This study confirmed that AFP is present in the FF of mares during the third trimester of pregnancy. Experimentally induced placentitis was associated with an elevation in maternal plasma concentrations of AFP. Copyright © 2015 Elsevier B.V. All rights reserved.

Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy

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Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Ito, Takanori; Maeda, Atsuyuki; Kaneoka, Yuji; Kagebayashi, Chiaki; Satomura, Shinji

2014-01-01

We investigated changes in highly sensitive lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (hsAFP-L3) measured using a novel method and its predictive ability for prognosis in patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy, comparing to other HCC tumor markers, that is, AFP, des-gamma-carboxy prothrombin (DCP), and AFP-L3 measured with conventional method (cAFP-L3). AFP, DCP, and AFP-L3 including both cAFP-L3 and hsAFP-L3 were measured before and after curative hepatectomy in 187 patients. The percentage of patients with elevated tumor marker levels pre- and postoperatively was compared, and recurrence-free and overall survival rates were analyzed based on changes in tumor markers. The percentages of patients with elevated AFP, DCP, and cAFP-L3 decreased postoperatively. In contrast, the percentage of patients with elevated hsAFP-L3 did not decrease postoperatively. Both recurrence-free and overall survival rates were significantly lower in patients whose tumor marker levels remained elevated postoperatively than patients without tumor marker elevation postoperatively. Recurrence-free and overall survival rates of patients in whom hsAFP-L3 became elevated postoperatively despite normal preoperative hsAFP-L3 levels were significantly lower than those of patients with normal hsAFP-L3 postoperatively, and were similar to those of patients with persistent elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many patients postoperatively, but not for hsAFP-L3. The elevation of hsAFP-L3 identifies patients with poor prognosis despite the normalization of AFP and DCP

Clinical and molecular sub-classification of hepatocellular carcinoma relative to alpha-fetoprotein level in an Asia-Pacific island cohort.

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Nishioka, Scott T; Sato, Miles M; Wong, Linda L; Tiirikainen, Maarit; Kwee, Sandi A

2018-01-01

Increased serum alpha-fetoprotein (AFP) levels are associated with specific molecular sub-classes of hepatocellular carcinoma (HCC), supporting AFP as a predictive or therapeutic biomarker for precision treatment of this disease. Considering recent efforts to validate HCC molecular classification systems across different populations, we applied existing signature-based classification templates to Hawaii cohorts and examined whether associations between HCC molecular sub-class, AFP levels, and clinical features found elsewhere can also be found in Hawaii, a region with a unique demographic and risk factor profile for HCC. Whole-genome expression profiling was performed on HCC tumors collected from 40 patients following partial hepatectomy. Tumors underwent transcriptome-based categorization into 3 molecular sub-classes (S1, S2, and S3). Patient groups based on molecular sub-class and AFP level were then compared with regards to clinical features and survival. Differences associated with AFP level and other clinical parameters were also examined at the gene signature level by gene set enrichment analysis. Statistically confident (false discovery rate 400 ng/mL predicted significant tumor enrichment for genes corresponding to MYC target activation, high cell proliferation, poor clinical prognosis, and the S2 sub-class. AFP > 400 ng/mL and non-S3 tumor classification were found to be significant predictors of overall survival. Distinct sub-classes of HCC associated with different molecular features and survival outcomes can be detected with statistical confidence in a Pacific Island cohort. Molecular classification signatures and other predictive markers for HCC that are valid for all patient populations are needed to support multi-center efforts to develop targeted therapies for HCC.

Forkhead box protein A2, a pioneer factor for hepatogenesis, is involved in the expression of hepatic phenotype of alpha-fetoprotein-producing adenocarcinoma.

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Yamamura, Nobuhisa; Fugo, Kazunori; Kishimoto, Takashi

2017-09-01

Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1β were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas. Copyright © 2017 Elsevier GmbH. All rights reserved.

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging.

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Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

2015-05-14

To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200

Characterization of Alpha-fetoprotein Levels in Three Dolphin Species: Development of Sensitive Immunoassays for Analysis of the Pregnancy-associated Variations

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MORITA, Yuka; HIRAMATSU, Naoshi; FUJITA, Toshiaki; AMANO, Haruna; KATSUMATA, Etsuko; ARAI, Kazutoshi; IWASAKI, Toshihide; TODO, Takashi; HARA, Akihiko

2013-01-01

Abstract A single radial immunodiffusion (SRID) assay and a chemiluminescent immunoassay (CLIA) were initially developed for alpha-fetoprotein (AFP) of the striped dolphin. Utilizing these developed assays, we investigated pregnancy-associated changes in the levels of AFP in the sera of fetuses and pregnant females of three dolphin species; samples were either collected from captive individuals or obtained as fishery by-products. The concentrations of AFP in the fetal serum ranged from 419.0 to 2026.3 μg/ml in the striped dolphin, 12.6 to 1218.7 μg/ml (for an AFP equivalent; eqAFP) in the common bottlenose dolphin and 770.6 to 3129.1 μg eqAFP/ml in the Risso's dolphin. AFP levels decreased with increased fetal size in fetuses over 20 cm in length. The concentrations of AFP in sera of pregnant females ranged from 7.18 to 8068.7 ng/ml in the striped dolphin, 6.6 to 1241.1 ng eqAFP/ml in the common bottlenose dolphin and 3.4 to 2868.7 ng eqAFP/ml in the Risso's dolphin. The levels in most pregnant females were equal to or lower than those found in males and nonpregnant individuals, although a few pregnant females exhibited extremely high levels (in the range of hundreds to thousands of nanograms per milliliter). Such high levels of AFP were not observed during pseudopregnancy. To our knowledge, this is the first report on basal profiles for serum AFP levels in small odontocetes. The profiles indicated that AFP may play a significant role during embryonic development, although maternal levels do not appear to be a diagnostic biomarker for monitoring pregnancy. PMID:23656975

Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis.

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Jeon, Yejoo; Jang, Eun Sun; Choi, Yun Suk; Kim, Jin-Wook; Jeong, Sook-Hyang

2016-09-01

Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. Plasma GPC3 levels in HCC patients were very low (0-3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.

Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPep). Updates and Prospects

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Mizejewski, Gerald J. [Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States)

2011-06-20

The Alpha-fetoprotein (AFP) derived Growth Inhibitory Peptide (GIP) is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic peptides against nine different human cancer types. Following the uptake of GIP-34 and GIP-8 into the cell cytoplasm, each follows slightly different signal transduction cascades en route to inhibitory pathways of tumor cell growth and proliferation. The parallel mechanisms of action of GIP-34 versus GIP-8 are demonstrated to involve interference of signaling transduction cascades that ultimately result in: (1) cell cycle S-phase/G2-phase arrest; (2) prevention of cyclin inhibitor degradation; (3) protection of p53 from inactivation by phosphorylation; and (4) blockage of K{sup +} ion channels opened by estradiol and epidermal growth factor (EGF). The overall mechanisms of action of both peptides are discussed in light of their differing modes of cell attachment and uptake fortified by RNA microarray analysis and electrophysiologic measurements of cell membrane conductance and resistance. As a chemotherapeutic adjunct, the GIPs could potentially aid in alleviating the negative side effects of: (1) tamoxifen resistance, uterine hyperplasia/cancer, and blood clotting; (2) Herceptin antibody resistance and cardiac (arrest) arrhythmias; and (3) doxorubicin's bystander cell toxicity.

Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

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Huang, Shujing; Jiang, Feifei; Wang, Ying; Yu, Yanhua; Ren, Siqian; Wang, Xiaowei; Yin, Peng; Lou, Jinli

2017-06-01

Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase.

Directory of Open Access Journals (Sweden)

Young-Il Kim

Full Text Available The role of serum alpha-fetoprotein (AFP levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment.A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4-8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence.The etiology of HCC was related to chronic hepatitis B virus (HBV infection in 562 patients (77.8%, chronic hepatitis C virus (HCV infection in 74 (10.2%, and non-viral cause in 86 (11.9%. There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001 and non-viral causes (p<0.05, and limited only to patients who had normal alanine aminotransferase (ALT levels.Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT.

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

Science.gov (United States)

Park, Joong-Won

2016-01-01

Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

Basic studies on the tumor imaging using antibodies to human alpha-fetoprotein

International Nuclear Information System (INIS)

Sakahara, Harumi; Endo, Keigo; Nakashima, Tetsuo; Ohta, Hitoya; Torizuka, Kanji

1984-01-01

Using polyclonal antibodies to human α-fetoprotein (AFP), the effect of iodination on the antibody activity and tumor accumulation of radioiodinated antibodies in tumor bearing nude mice were examined. Antibodies, obtained from horse antiserum and purified by affinity chromatography, were iodinated by the chloramine-T method and their antibody activity was evaluated using RIA and Scatchard plot analysis. When high concentrations of chloramine-T were used or more than 2.6 iodine atoms were incorporated per antibody molecule, the antigen binding capacity rather than the affinity constant was affected by the iodination. The antibody activity was completely destroyed at an iodine to antibody molar ratio of 15.4. Antibodies, however, which were iodinated under low concentrations of chloramine-T and contained less than 0.8 iodines per antibody molecule, showed almost full retention of their antibody activity. Nude mice transplanted with AFP producing human testicular tumor or AFP non-producing human urinary bladder tumor were administered intravenously with 131 I-labeled antibodies to human AFP. Scintigrams were taken at 1, 2, 4 and 7 days after the injection of labeled antibodies. At day 7, nude mice were sacrificed and organs and tumor were removed, weighed and counted. In nude mice bearing testicular tumor, tumor image became gradually clear with decreasing background activity and tumor to blood ratio, obtained, was 0.82 for testicular tumor compared to 0.42 for bladder tumor. These results indicated a specific in vivo localization of 131 I-labeled antihuman AFP antibodies in AFP producing tumor. (author)

Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain development by restraining the neurotrophic effect of oleic acid.

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García-García, Alejandro G; Polo-Hernández, Erica; Tabernero, Arantxa; Medina, José M

2015-10-22

We have previously shown that serum albumin controls perinatal rat brain development through the regulation of oleic acid synthesis by astrocytes. In fact, oleic acid synthesized and released by astrocytes promoted neurite growth, neuron migration and the arrangement of prospective synapses. In this work we show that alpha-fetoprotein (AFP) is also present in the brain during embryonic development, its concentrations peaking at E15.5 and at E19.5. However, after E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum albumin concentrations. At E15.5, AFP is present in caudal regions of the brain, particularly in brain areas undergoing differentiation during this period, such as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala and the hippocampus. Albumin was not detected in the brain at E15.5 but stained brain cells substantially on day E19.5, showing a very similar distribution to that of AFP under the same circumstances. The concentrations of free oleic acid in the brain were inversely correlated with those of AFP, suggesting that the signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a marker of axonal growth that is highly expressed by the presence of oleic acid, was not co-localized with AFP except in the marginal zone and areas delimiting the subplate. AFP prevented the increase in GAP-43 expression caused by the presence of oleic acid in neurons in primary culture in vitro and in organotypic cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the effect of serum albumin on brain development. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Horseradish peroxidase-loaded nanospheres attached to hollow gold nanoparticles as signal enhancers in an ultrasensitive immunoassay for alpha-fetoprotein

International Nuclear Information System (INIS)

Li, Ya; Yuan, Ruo; Chai, Yaqin; Zhuo, Ying; Su, Huilan; Zhang, Yuxia

2014-01-01

We report on a novel electrochemical signal amplification strategy for use in immunoassays. The highly responsive immunoelectrode was constructed in the following way: (1) The surface of a gold electrode was covered with a layer single-walled carbon nanotubes dispersed in chitosane functionalized with L-cysteine; (2) Gold nanoparticles containing protein A and anti-alpha-fetoprotein (anti-AFP) were then covalently attached to the surface via the thiol groups of the chitosane. The electrode is then exposed to the analyte (AFP) which then is bound by the antibody. In the next step, a gold-conjugated secondary antibody is added that was prepared in the following way: (1) Horseradish peroxidase was crosslinked and the resulting spheres were coated with hollow gold nanoparticles (hollow Au-NPs) to give nanospheres of ∼100 nm in diameter. (2) These were the coated with thionine and, in a last step, with secondary antibody. The use of these materials has several attractive features: The HRP-NPs functionalized with hollow Au-NPs possess a large surface area that can load the large amount of secondary antibody. Thionine (Thi) is highly redox active and improves the intensity of the signal. Carbon nanotubes were used because they possess an excellent electron transfer rate and large surface area. Following incubation of the modified electrode (a) with a sample containing AFP, (b) then with the secondary antibody, and (c) with washing buffer, the electrode is placed in a solution containing H 2 O 2 . The HRP in the smart secondary antibody causes the catalytic decomposition of H 2 O 2 and the results in an electrical current that is linearly related to the concentration of AFP in the 0.025 to 5.0 ng mL −1 concentration range. The detection limit for AFP is as low as 8.3 pg mL −1 . We believe that this novel kind of immunoassay represents a promising tool for use in sensitive clinical assays. (author)

Alpha-Fetoprotein, Identified as a Novel Marker for the Antioxidant Effect of Placental Extract, Exhibits Synergistic Antioxidant Activity in the Presence of Estradiol

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Choi, Hye Yeon; Kim, Seung Woo; Kim, BongWoo; Lee, Hae Na; Kim, Su-Jeong; Song, Minjung; Kim, Sol; Kim, Jungho; Kim, Young Bong; Kim, Jin-Hoi; Cho, Ssang-Goo

2014-01-01

Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. PMID:24922551

Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol.

Directory of Open Access Journals (Sweden)

Hye Yeon Choi

Full Text Available Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol.

8-Quinolineboronic acid as a potential phosphorescent molecular switch for the determination of alpha-fetoprotein variant for the prediction of primary hepatocellular carcinoma

International Nuclear Information System (INIS)

Liu Jiaming; Li Feiming; Liu Zhenbo; Lin Changqing; Lin Shaoqin; Lin Liping; Wang Xinxing; Li Zhiming

2010-01-01

8-Quinolineboronic acid phosphorescent molecular switch (8-QBA-PMS) in the 'off' state emitted weak room temperature phosphorescence (RTP) of 8-QBA on the acetylcellulose membrane (ACM) with the perturbation of Pb 2+ . When 8-QBA-PMS was used to label concanavalin agglutinin (Con A) to form 8-QBA-PMS-Con A based on the reaction between -OH of 8-QBA-PMS and -COOH of Con A, 8-QBA-PMS turned 'on' automatically due to its structure change, and RTP of the system increased 2.7 times. Besides, -NH 2 of 8-QBA-PMS-Con A could carry out affinity adsorption (AA) reaction with the -COOH of alpha-fetoprotein variant (AFP-V) to form the product Con A-AFP-V-Con A-8-QBA-PMS containing -NH-CO- bond, causing the RTP of the system to further increase. Moreover, the amount of AFP-V was linear to the ΔI p of the system in the range of 0.012-2.40 (fg spot -1 ). Thus, a new affinity sensitive adsorption solid substrate room temperature phosphorimetry using 8-QBA-PMS as labelling reagent (8-QBA-PMS-AASSRTP) for the determination of AFP-V was proposed with the detection limit (LD) of 9 x 10 -15 g mL -1 . It had been used to determine AFP-V in human serum with the results agreeing with enzyme-link immunoassay (ELISA), showing promise for the prediction of PHC due to the intimate association between AFP-V and primary hepatocellular carcinoma (PHC). The mechanism of the promethod was also discussed.

In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha fetoprotein producing hepatocellular carcinoma by targeted sodium iodide symporter gene expression

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Kim, Kwang Il; Lee, Yong Jin; Lee, Tae Sup; Song, Inho; Cheon, Gi Jeong; Lim, Sang Moo; Kang, Joo Hyun [Korea Institute of Radiological and Medical and Medical Sciences, Seoul (Korea, Republic of); Chung, June Key [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2012-03-15

This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha fetoprotein (AFP) producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter. The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP producing cells and in AFP nonproducing cells was investigated using {sup 125}I uptake assay and semi quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of {sup 131}I vitro clonogenic assay. In addition, tumor bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained. The expression of hNIS was efficiently demonstrated by {sup 125}I uptake assay in AFP producing cells, but not in AFP nonproducing cells. AFP producing HCC targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP producing cells caused more sensitivity to {sup 131}I than that in AFP nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging. An AFP producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP producing HCC specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system.

In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha fetoprotein producing hepatocellular carcinoma by targeted sodium iodide symporter gene expression

International Nuclear Information System (INIS)

Kim, Kwang Il; Lee, Yong Jin; Lee, Tae Sup; Song, Inho; Cheon, Gi Jeong; Lim, Sang Moo; Kang, Joo Hyun; Chung, June Key

2012-01-01

This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha fetoprotein (AFP) producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter. The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP producing cells and in AFP nonproducing cells was investigated using 125 I uptake assay and semi quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of 131 I vitro clonogenic assay. In addition, tumor bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained. The expression of hNIS was efficiently demonstrated by 125 I uptake assay in AFP producing cells, but not in AFP nonproducing cells. AFP producing HCC targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP producing cells caused more sensitivity to 131 I than that in AFP nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging. An AFP producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP producing HCC specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system

Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

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Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin, E-mail: binhu@whu.edu.cn

2015-04-01

The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L{sup −1} and 0.054 μg L{sup −1} with the relative standard deviations (RSDs, n = 7, c = 5 μg L{sup −1}) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2–50 μg L{sup −1}. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications. - Highlights: • 4-Mercaptophenylboronic acid functionalized magnetic beads were prepared and characterized. • ICP-MS based magnetic immunoassay approach was developed for quantification of glycoproteins. • AFP and CEA were quantified simultaneously with Au and Ag NPs as element tags. • The developed method exhibited good selectivity and sensitivity for target glycoproteins.

Tumor necrosis factor-alpha-independent downregulation of hepatic cholesterol 7alpha-hydroxylase gene in mice treated with lead nitrate.

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Kojima, Misaki; Sekikawa, Kenji; Nemoto, Kiyomitsu; Degawa, Masakuni

2005-10-01

We previously reported that lead nitrate (LN), an inducer of hepatic tumor necrosis factor-alpha (TNF-alpha), downregulated gene expression of cholesterol 7alpha-hydroxylase. Herein, to clarify the role of TNF-alpha in LN-induced downregulation of cholesterol 7alpha-hydroxylase, effects of LN on gene expression of hepatic cholesterol 7alpha-hydroxylase (Cyp7a1) in TNF-alpha-knockout (KO) and TNF-alpha-wild-type (WT) mice were comparatively examined. Gene expression of hepatic Cyp7a1 in both WT and KO mice decreased to less than 5% of the corresponding controls at 6-12 h after treatment with LN (100 mumol/kg body weight, iv). Levels of hepatic TNF-alpha protein in either WT or KO mice were below the detection limit, although expression levels of the TNF-alpha gene markedly increased at 6 h in WT mice by LN treatment, but not in KO mice. In contrast, in both WT and KO mice, levels of hepatic IL-1beta protein, which is known to be a suppressor of the cholesterol 7alpha-hydroxylase gene in hamsters, were significantly increased 3-6 h after LN treatment. Furthermore, LN-induced downregulation of the Cyp7a1 gene did not necessarily result from altered gene expression of hepatic transcription factors, including positive regulators (liver X receptor alpha, retinoid X receptor alpha, fetoprotein transcription factor, and hepatocyte nuclear factor 4alpha) and a negative regulator small heterodimer partner responsible for expression of the Cyp7a1 gene. The present findings indicated that LN-induced downregulation of the Cyp7a1 gene in mice did not necessarily occur through a TNF-alpha-dependent pathway and might occur mainly through an IL-1beta-dependent pathway.

Amniocentesis

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Culture - amniotic fluid; Culture - amniotic cells; Alpha-fetoprotein - amniocentesis ... laboratory. Testing may include: Genetic studies Measurement of alpha-fetoprotein (AFP) levels (a substance produced in the liver ...

Radioimmunoimaging using F(ab')2 fragment of monoclonal antibodies against human alpha-fetoprotein

International Nuclear Information System (INIS)

Sakahara, Harumi; Endo, Keigo; Nakashima, Tetsuo; Koizumi, Mitsuru; Ohta, Hitoya; Torizuka, Kanji; Okada, Kenichiro; Yoshida, Osamu; Nishi, Shinzo.

1985-01-01

Using monoclonal antibodies against human α-fetoprotein (AFP), radioiodinated F(ab') 2 fragments were compared with whole IgG as a radiotracer for radioimmunoimaging of cancer. F(ab') 2 fragments were obtained by pepsin digestion of whole IgG (IgGl). IgG and F(ab') 2 were labeled with 125 I or 131 I by the chloramine-T method with almost full retention of antibody activity. F(ab') 2 fragments were cleared more rapidly from the circulation in normal mice with a half life of 6.3 hours than whole IgG with a half life of 5.5 days. Radioactivity of F(ab') 2 in various organs also decreased faster than IgG. In nude mice transplanted with AFP-producing human testicular tumor, F(ab') 2 fragments demonstrated superior scintigrams to whole IgG at 2 days after the injection, because of the fast disappearance of background radioactivity. Although absolute accumulation of 131 I labeled F(ab') 2 in the tumor was less than that of 131 I labeled IgG, tumor to other organ ratios were much higher with F(ab') 2 than those of IgG. The tumor to blood ratio of 131 I labeled F(ab') 2 was 1.04 at day 2, whereas tumor to blood ratio of 131 I labeled IgG was 0.55 at day 2 and 0.92 at day 4, respectively. These results indicated that for the radiolabeling of monoclonal antibodies, F(ab') 2 fragments would be superior to whole IgG in the radioimmunoimaging of cancer. (author)

A sensitive label–free amperometric immunosensor for alpha-fetoprotein based on gold nanorods with different aspect ratio

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Zhou, Chunyang; Liu, Dali; Xu, Lin; Li, Qingling; Song, Jian; Xu, Sai; Xing, Ruiqing; Song, Hongwei

2015-01-01

A simple and accurate label–free amperometric immunosensor for α–fetoprotein (AFP) detection is developed based on gold nanorods (GNRs) with different aspect ratio and compared with gold particles (GNPs). The positively charged GNRs and GNPs due to the surface immobilized cetyltrimethyl ammonium bromide (CTAB) can adsorb the negatively charged AFP antibody (Ab) directly. The presence of the GNRs not only enhanced the immobilized amount of biomolecules, but also improved the electrochemical properties of the immunosensor. With the aid of GNRs, the electrochemical signal was greatly enhanced in comparison with GNPs. Under optimal conditions, the proposed immunosensor could detect AFP in a linear range from 0.1 to 200 ng/mL with a detection limit of 0.04 ng/mL (signal–to–noise ratio = 3), and it also possessed good reproducibility and storage stability. Moreover, the detection of AFP in five human serum samples also showed satisfactory accuracy. The proposed methodology was potentially attractive for clinical immunoassay. PMID:25909588

Development of on-chip fully automated immunoassay system "μTASWako i30" to measure the changes in glycosylation profiles of alpha-fetoprotein in patients with hepatocellular carcinoma.

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Kurosawa, Tatsuo; Watanabe, Mitsuo

2016-12-01

Glycosylation profiles significantly change during oncogenesis. Aberrant glycosylation can be used as a cancer biomarker in clinical settings. Different glycoforms can be separately detected using lectin affinity electrophoresis and lectin array-based methods. However, most methodologies and procedures need experienced technique to perform the assays and expertise to interpret the results. To apply glycomarkers for clinical practice, a robust assay system with an easy-to-use workflow is required. Wako's μTASWako i30, a fully automated immunoanalyzer, was developed for in vitro diagnostics based on microfluidic technology. It utilizes the principles of liquid-phase binding assay, where immunoreactions are performed in a liquid phase, and electrokinetic analyte transport assay. Capillary electrophoresis on microfluidic chip has enabled the detection of different glycoform types of alpha-fetoprotein (AFP), a serum biomarker for hepatocellular carcinoma. AFP with altered glycosylation can be separated based on the reactivity to Lens culinaris agglutinin on electrophoresis. The glycoform AFP-L3 was reportedly more specific in hepatocellular carcinoma. This assay system can provide a high sensitivity and rapid results in 9 min. The test results for ratio of AFP-L3 to total AFP using μTASWako i30 are correlated with those of conventional methodology. The μTASWako assay system and the technology can be utilized for glycosylation analysis in the postgenomic era. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of an alpha-fetoprotein and Golgi protein 73 multiplex detection assay using xMAP technology.

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Wu, Yun; Ma, Jie; Wang, Yipeng; Zhang, Yonghong; Hou, Yongjin; Zhang, Chunming; Sun, Huanqin; Sun, Jianping; Wang, Zikang; Li, Ning

2018-04-06

Development of a new method to simultaneously detect Alpha-fetoprotein (AFP) and Golgi protein 73 (GP73) from peripheral blood. Anti human AFP and GP73 monoclonal antibodies was used to develop a sandwich immunity reaction using xMAP technology for the simultaneous detection of plasma AFP and GP73. The assay evaluated the sensitivity, cross reactivity, range of detection, precision, recovery and linearity dilution effect. The assay utilized plasma samples and compared its performance with commercially available Enzyme Linked Immunosorbent Assay (ELISA) kits. The assay was successful in detecting AFP and GP73 simultaneously. Validation experiments demonstrated the limit of detection was AFP 0.006 μg/l and GP73 0.482 μg/l. The functional sensitivity was AFP 0.010 μg/l and GP73 0.640 μg/l. The range of detection was AFP 0.01-50 μg/l and GP73 0.64-100 μg/l. No cross reactivity was observed. The intra- and inter-assay variation for AFP was 0.19-3.46% and 3.1-5.8% and for GP73 was 1.5-3.2% and 1.1-7.6% respectively. The recovery for AFP was 96-106% and GP73 was 89-110%. 80 clinical plasma samples from healthy controls, and patients with liver cirrhosis and Hepatocellular Carcinoma (HCC) were evaluated. For healthy controls (n = 25), the AFP was 2.40 (1.55, 3.30) μg/l and GP73 was 42.60 (39.10, 57.40) μg/l. For patients with liver cirrhosis (n = 19), the AFP was 2.60 (1.70, 4.20) μg/l and GP73 was 136.10 (92.10, 261.70) μg/l, and for HCC patients (n = 36), the AFP was 13.65 (3.35, 158.88) μg/l and GP73 was 186.25 (96.73, 262.03) μg/l. The new assay demonstrated a good correlation with commercially available ELISA kits (correlation coefficients (r) were 0.997 (AFP, p < 0.001) and 0.959 (GP73, p < 0.001). The method demonstrated a sensitive, effective and accurate method for the simultaneous detection of AFP and GP73, and could be used clinically for routine detection and monitoring of patients with chronic hepatitis B

8-Quinolineboronic acid as a potential phosphorescent molecular switch for the determination of alpha-fetoprotein variant for the prediction of primary hepatocellular carcinoma

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Liu Jiaming, E-mail: zzsyliujiaming@163.com [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Xianzhiqian Street, 36 Zhangzhou, Fujian 363000 (China); Li Feiming [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Xianzhiqian Street, 36 Zhangzhou, Fujian 363000 (China); Liu Zhenbo [Third Hospital of Xiamen, Xiamen 316000 (China); Lin Changqing [Department of Food and Biological Engineering, Zhangzhou Institute of Technology, Zhangzhou 363000 (China); Lin Shaoqin [Department of Biochemistry, Fujian Education College, Fuzhou 350001 (China); Lin Liping [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Xianzhiqian Street, 36 Zhangzhou, Fujian 363000 (China); Wang Xinxing [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Xianzhiqian Street, 36 Zhangzhou, Fujian 363000 (China); Department of Food and Biological Engineering, Zhangzhou Institute of Technology, Zhangzhou 363000 (China); Li Zhiming [Department of Food and Biological Engineering, Zhangzhou Institute of Technology, Zhangzhou 363000 (China)

2010-03-24

8-Quinolineboronic acid phosphorescent molecular switch (8-QBA-PMS) in the 'off' state emitted weak room temperature phosphorescence (RTP) of 8-QBA on the acetylcellulose membrane (ACM) with the perturbation of Pb{sup 2+}. When 8-QBA-PMS was used to label concanavalin agglutinin (Con A) to form 8-QBA-PMS-Con A based on the reaction between -OH of 8-QBA-PMS and -COOH of Con A, 8-QBA-PMS turned 'on' automatically due to its structure change, and RTP of the system increased 2.7 times. Besides, -NH{sub 2} of 8-QBA-PMS-Con A could carry out affinity adsorption (AA) reaction with the -COOH of alpha-fetoprotein variant (AFP-V) to form the product Con A-AFP-V-Con A-8-QBA-PMS containing -NH-CO- bond, causing the RTP of the system to further increase. Moreover, the amount of AFP-V was linear to the {Delta}I{sub p} of the system in the range of 0.012-2.40 (fg spot{sup -1}). Thus, a new affinity sensitive adsorption solid substrate room temperature phosphorimetry using 8-QBA-PMS as labelling reagent (8-QBA-PMS-AASSRTP) for the determination of AFP-V was proposed with the detection limit (LD) of 9 x 10{sup -15} g mL{sup -1}. It had been used to determine AFP-V in human serum with the results agreeing with enzyme-link immunoassay (ELISA), showing promise for the prediction of PHC due to the intimate association between AFP-V and primary hepatocellular carcinoma (PHC). The mechanism of the promethod was also discussed.

Propensity Score Matching Analysis of Changes in Alpha-Fetoprotein Levels after Combined Radiotherapy and Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

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Yuri Jeong

Full Text Available To investigate the value of changes in alpha-fetoprotein (AFP levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC patients with portal vein tumor thrombus (PVTT who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT and transarterial chemoembolization (TACE.A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS, and progression-free survival (PFS rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.The median follow-up period was 11.1 months (range, 3.1-82.7 months. In the propensity-score matching cohort (92 pairs, a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001. OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001.AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.

Alpha-fetoprotein and (18)F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation.

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Hong, Geun; Suh, Kyung-Suk; Suh, Suk-Won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Paeng, Jin Chul; Yi, Nam-Joon; Lee, Kwang-Woong

2016-04-01

Given the organ shortage for liver transplantation (LT) and the limitations of the current morphology-based selection criteria, improved criteria are needed to achieve the maximum benefit of LT for hepatocellular carcinoma (HCC). We hypothesized that a combination of biological markers may better predict the prognosis than the Milan criteria. HCC patients (n=123) with preoperative data on serum alpha-fetoprotein (AFP) levels and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) positivity underwent live-donor LT between January 2003 and December 2009. The cut-off values for serum AFP levels (200 ng/ml) and (18)F-FDG PET positivity (1.10) for tumor recurrence were determined by c-statistics using receiver operating characteristic curves. Univariate and multivariate analyses with preoperative variables were performed to find pre-transplant prognostic factors. Disease-free survival rates and overall survival rates were analysed with regard to serum AFP levels and (18)F-FDG PET positivity. The 5-year disease-free survival rates and overall survival rates were 80.3% and 81.6% respectively. (18)F-FDG PET positivity (hazard ratio (HR) 9.766, 95% CI 3.557-26.816; p<0.001) and serum AFP level (HR 6.234, 95% CI 2.643-14.707; p<0.001) were the only significant pre-transplant prognostic factors in the multivariate analysis; tumor number and size were not significant. A combination of criteria showed that the biologically high-risk group (AFP level ⩾200 ng/ml and PET-positive) had an HR of 29.069 (95% CI 8.797-96.053; p<0.001) compared with the double-negative group. Use of the Milan criteria yielded an HR of 1.351 (95% CI 0.500-3.652; p=0.553). The combination of the serum AFP level and (18)F-FDG PET data predicted better outcomes than those using the Milan criteria, improving objectivity when adult-to-adult living donor LT is contemplated. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma

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Bozkaya, Yakup; Doğan, Mutlu; Yazıcı, Ozan; Erdem, Gökmen Umut; Demirci, Nebi Serkan; Zengin, Nurullah

2017-01-01

Alpha-fetoprotein producing gastric carcinoma (AFP-PGC) is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF) as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC) were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001). A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001). Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%), and 82.2% (complete response - 3%, PR - 36.2%, SD - 43%) in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively). Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area. PMID:28273032

Application of PET-CT in monitoring residual and extrahepatic metastatic lesions for hepatocellular carcinoma with positive alpha fetoproteins after interventional therapy

International Nuclear Information System (INIS)

Zhu Guangyu; Teng Gaojun; Guo Jinhe; Deng Gang; He Shicheng; Fang Wen; Li Guozhao; Chen Xiaohui; Wei Xiaoying

2010-01-01

Objective: To investigate the value of positron emission tomography-computed tomography (PET-CT) in monitoring the residual lesions in lipiodol sedimentary region and extrahepatic metastastic lesions of hepatocellular carcinoma (HCC) with alpha fetoproteins (AFP) positive after interventional therapy. Methods: The data of 20 cases with primary HCC confirmed by histopathology were retrospectively analyzed. Their AFP levels decreased to normal range after interventional treatments, but rose to abnormal high level during following-up. After the abdominal routine imaging examinations, the definite diagnosis of the residual lesions in lipiodol sedimentary region or extrahepatic lesions can't be made confidently. All cases were scanned by PET-CT, and according to their PET-CT results, the further treatments were given and the therapeutic results were monitored with radiology and AFP tests. Results: In all 20 cases, 10 of them were detected to have the extrahepatic metastastic lesions by PET-CT, including 4 with abdominal wall metastasis upon the liver, 3 with solitary pulmonary metastasis with diameter less than 1 cm, 2 with mesenteric metastasis, 1 with metastasis of operative incisions, but these lesions were neglected by abdominal routine imaging examinations. Eight cases showed the uneven lipiodol sedimentary region in the primary lesion by CT or MRI examination, but can't be diagnosed whether it was residual lesion with other examinations including DSA. A definite diagnosis was obtained by PET-CT. In 2 cases, lymph nodes less than 1.5 cm were found in the hepatic portal area (PHA) and retroperitoneum on CT images, which was determined to be metastatic by PET-CT. All the detected lesions were given further treatments of surgery or interventional therapy. Most patients showed decreased AFP levels except the 2 patients with lymph node metastasis. The imaging examinations also indicated that the treatments had a good effect on lesions. Conclusion: In the patients with

The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma

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Yakup Bozkaya

2017-05-01

Full Text Available Alpha-fetoprotein producing gastric carcinoma (AFP-PGC is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001. A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001.Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%, and 82.2% (complete response - 3%, PR - 36.2%, SD - 43% in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively. Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area.

Childhood Central Nervous System Germ Cell Tumors Treatment

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... make hormones. Yolk sac tumors make the hormone alpha-fetoprotein (AFP). Mixed germ cell tumors are made of ... used to diagnose some CNS germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). Blood ...

Treatment Options for Childhood Extracranial Germ Cell Tumors

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... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

Stages of Childhood Extracranial Germ Cell Tumors

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... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

General Information about Childhood Extracranial Germ Cell Tumors

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... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

Birth Defects Diagnosis

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... screen tests the levels of 4 proteins AFP (alpha-fetoprotein), hCG, estriol, and inhibin-A. Generally, the maternal ... which an amniocentesis tests. AFP AFP stands for alpha-fetoprotein, a protein the unborn baby produces. A high ...

General Information about Testicular Cancer

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... tumor markers are used to detect testicular cancer: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). Tumor ... tumor markers are used in staging testicular cancer : Alpha-fetoprotein (AFP) Beta-human chorionic gonadotropin (β-hCG). Lactate ...

Maternal and fetal mechanisms of B cell regulation during pregnancy: human Chorionic Gonadotropin stimulates B cells to produce IL-10 while alpha-fetoprotein drives them into apoptosis

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Franziska Fettke

2016-12-01

Full Text Available Maternal immune tolerance towards the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10 producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10 producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP in B cell modulation. Human Chorionic Gonadotropin (hCG, but not progesterone, estrogen or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10 production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmented galactosylation, sialylation or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetrically glycosylated antibodies in their Fab region. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding to maternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was able to drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus.Our data suggests that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interesting aspects of B cell function and modulation by pregnancy hormones and fetal proteins.

Autism Spectrum Disorders and Maternal Serum α-Fetoprotein Levels During Pregnancy

DEFF Research Database (Denmark)

Abdallah, Morsi; Grove, Jakob; Hougaard, David M

2011-01-01

Objective: Numerous studies have been trying to disentangle the complex pathophysiology of autism spectrum disorders (ASD). In our study, we explored the potential role of maternal serum (MS) α-fetoprotein (AFP) in the prediction and the pathophysiology of ASD. Methods: A total of 112 patients...

Expression of β-catenin protein in hepatocellular carcinoma and its relationship with alpha-fetoprotein.

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Ren, Ya-Jun; Huang, Tao; Yu, Hong-Lu; Zhang, Li; He, Qian-Jin; Xiong, Zhi-Fan; Peng, Hua

2016-12-01

This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma (HCC) tissues and its relationship with α-fetoprotein (AFP) in HCC. Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues (n=10), liver cirrhosis tissues (n=20), and primary HCC tissues (n=60). The relationship between β-catenin expression and clinical parameters of HCC was investigated. Real-time PCR and Western blotting were used to detect the mRNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP, and also the mRNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP shRNA plasmids. The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues. Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues, and such ectopic expression of β-catenin was predominant in HCC tissues. The abnormal expression of β-catenin was correlated with serum AFP levels, cancer cell differentiation and vascular invasion (P<0.05). Additionally, the increased expression of AFP resulted in the upregulation of β-catenin mRNA and protein levels, while knockdown of AFP with AFP shRNA led to significantly decreased β-catenin mRNA and protein levels (P<0.05). It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development. AFP can lead to increased expression of β-catenin, which may account for the poor prognosis of AFP-associated HCC patients.

Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.

Science.gov (United States)

Liu, Yang; Wang, Yue-ru; Wang, Long; Song, Rui-mei; Zhou, Bo; Song, Zhen-shun

2014-01-01

Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating

ENDODERMAL SINUS TUMOR OF THE OVARY DURING PREGNANCY - A CASE-REPORT

NARCIS (Netherlands)

VANDERZEE, AGJ; DEBRUIJN, HWA; BOUMA, J; AALDERS, JG; OOSTERHUIS, JW; DEVRIES, EGE

Serum alpha-fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24-year-old female in week 17 of pregnancy. After surgery, chemotherapy was postponed. In week 28 levels of serum alpha-fetoprotein increased, but delivery was delayed until 33 weeks' gestation.

Cost-effectiveness analysis of hepatocellular carcinoma screening by combinations of ultrasound and alpha-fetoprotein among Alaska Native people, 1983–2012

Directory of Open Access Journals (Sweden)

Prabhu P. Gounder

2016-05-01

Full Text Available Background: The American Association for the Study of Liver Diseases (AASLD recommends semi-annual hepatocellular carcinoma (HCC screening using ultrasound (US in persons with chronic hepatitis B (CHB virus infection at high risk for HCC such as Asian males aged ≥40 years and Asian females aged ≥50 years. Objective: To analyse the cost-effectiveness of 2 HCC screening methods in the Alaska Native (AN health system: US-alone, or screening by alpha-fetoprotein (AFP initially and switching to US for subsequent screenings if AFP >10 ng/mL (AFP→US. Design: A spreadsheet-based model was developed for accounting the costs of 2 hypothetical HCC screening methods. We used epidemiologic data from a cohort of 839 AN persons with CHB who were offered HCC screening by AFP/US semi-annually during 1983–2012. We assumed that compared with AFP→US, US-alone identifies 33% more tumours at an early stage (defined as a single tumour ≤5 cm or ≤3 tumours ≤3 cm in diameter. Years of life gained (YLG attributed to screening was estimated by comparing additional years of survival among persons with early- compared with late-stage tumours. Screening costs were calculated using Medicare reimbursement rates in 2012. Future screening costs and YLG were projected over a 30-year time horizon using a 3% discount rate. Results: The total cost of screening for the cohort by AFP→US would have been approximately $357,000 ($36,000/early-stage tumour detected compared to $814,000 ($59,000/early-stage tumour detected by US-alone. The AFP→US method would have yielded an additional 27.8 YLG ($13,000/YLG compared with 38.9 YLG ($21,000/YLG for US-alone. Screening by US-alone would incur an additional $114,000 per extra early-tumour detected compared with AFP→US and $41,000 per extra YLG. Conclusions: Although US-alone HCC screening might have yielded more YLG than AFP→US, the reduced costs of the AFP→US method could expand access to HCC screening in resource

Rapid and sensitive lateral flow immunoassay method for determining alpha fetoprotein in serum using europium (III) chelate microparticles-based lateral flow test strips

Energy Technology Data Exchange (ETDEWEB)

Liang, Rong-Liang; Xu, Xu-Ping; Liu, Tian-Cai; Zhou, Jian-Wei; Wang, Xian-Guo; Ren, Zhi-Qi [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong (China); Hao, Fen [DaAn Gene Co. Ltd. of Sun Yat-sen University, 19 Xiangshan Road, Guangzhou 510515 (China); Wu, Ying-Song, E-mail: wg@smu.edu.cn [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong (China)

2015-09-03

Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips. A fluorescence strip reader was used to measure the fluorescence peak heights of the test line (H{sub T}) and the control line (H{sub C}); the H{sub T}/H{sub C} ratio was used for quantitation. The Eu (III) chelate microparticles-based LFIA assay exhibited a wide linear range (1.0–1000 IU mL{sup −1}) for AFP with a low limit of detection (0.1 IU mL{sup −1}) based on 5ul of serum. Satisfactory specificity and accuracy were demonstrated and the intra- and inter-assay coefficients of variation (CV) for AFP were both <10%. Furthermore, in the analysis of human serum samples, excellent correlation (n = 284, r = 0.9860, p < 0.0001) was obtained between the proposed method and a commercially available CLIA kit. Results indicated that the Eu (III) chelate microparticles-based LFIA system provided a rapid, sensitive and reliable method for determining AFP in serum, indicating that it would be suitable for development in point-of-care testing. - Highlights: • Europium (III) chelate microparticles was used as a label for LIFA. • Quantitative detection by using H{sub T}/H{sub C} ratio was achieved. • LIFA for simple and rapid AFP detection in human serum. • The sensitivity and linearity was more excellent compared with QD-based ICTS. • This method could be developed for rapid point-of-care screening.

Expression of human α-fetoprotein in yeast

International Nuclear Information System (INIS)

Yamamoto, Ritsu; Sakamoto, Takashi; Nishi, Shinzo; Sakai, Masaharu; Morinaga, Tomonori; Tamaoki, Taiki

1990-01-01

Human α-fetoprotein (AFP) was expressed in Saccharomyces cerevisiae, with a plasmid containing the cDNA sequence for human AFP fused with the rat AFP signal peptide. The recombinant AFP was purified from the yeast lysate by DEAE-cellulose and immunoaffinity chromatography. The amino acid composition and the molecular weight of the recombinant AFP were similar to those of hepatoma AFP. N-terminal amino acids sequence analysis indicated that the signal peptide had been processed. The recombinant and hepatoma AFP reacted identically in Ouchterlony immunodiffusion and radioimmunoassay tests. These observations indicated that the yeast recombinant protein had the properties of native AFP

A novel signal-on photoelectrochemical immunosensor for detection of alpha-fetoprotein by in situ releasing electron donor.

Science.gov (United States)

Chen, Jiexia; Zhao, Guang-Chao

2017-12-15

A signal-on photoelectrochemical (PEC) immunosensor was constructed for detecting tumor marker in this work. α-fetoprotein (AFP) was chosen as a model analyte to investigate the prepared procedure and the analytical performance of the exploited sensor. In order to construct the sensor, CdSe QDs were used as photoactive material, biotin conjugated AFP antibody (Bio-anti-AFP) as detecting probe, streptavidin (SA) as signal capturing unit, biotin functionalized apoferritin encapsulated ascorbic acid (Bio-APOAA) as amplification unit, which were assembled onto the electrodes. The sensing strategy was based on in situ enzymatic hydrolysis of Bio-APOAA to release ascorbic acid (AA) as sacrificial electron donor to produce photocurrent. The photocurrent from the immunosensor was monitored as a result of AFP concentrations. The constructed sensing platform displayed high selectivity and good sensitivity for detecting AFP. Under optimal conditions, a wide linear range from 0.001 to 1000ng/mL and a low detection limit of 0.31pg/mL were obtained. The developed immunosensor is expected to be used to determine AFP and other tumor markers in human plasma in clinical laboratories either for pre-cancer screening or cancer monitoring. Moreover, this sensing platform further has the potential to use for the detection of trypsin activity and the corresponding inhibitor-screening. Copyright © 2017 Elsevier B.V. All rights reserved.

A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas.

Science.gov (United States)

Kwon, Oh-Joon; Kim, Pyung-Hwan; Huyn, Steven; Wu, Lily; Kim, Minjung; Yun, Chae-Ok

2010-12-15

Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE). We constructed Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 that incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter activity and specificity to hepatoma were examined by luciferase assay and fluorescence-activated cell sorting analysis. In addition, the AFP expression- and hypoxia-dependent in vitro cytotoxicity of Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo tumoricidal activity on subcutaneous and liver orthotopic model was monitored by noninvasive molecular imaging. Ad-HRE(12)/hAFPΔ19 exhibited enhanced tumor selectivity and cell-killing activity when compared with Ad-hAFPΔ19. The tumoricidal activity of Ad-HRE(12)/hAFPΔ19 resulted in significant inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic examination of the primary tumor after treatment confirmed accumulation of viral particles near hypoxic areas. Furthermore, Ad-HRE(12)/hAFPΔ19 did not cause severe inflammatory immune response and toxicity after systemic injection. The results presented here show the advantages of incorporating HREs into a hAFP promoter-driven oncolytic virus. This system is unique in that it acts in both a tissue-specific and tumor environment-selective manner. The greatly enhanced selectivity and tumoricidal activity of Ad-HRE(12)/hAFPΔ19 make it a promising therapeutic agent in the treatment

Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization

International Nuclear Information System (INIS)

Kumakura, M.; Kaetsu, I.; Suzuki, M.; Adachi, S.

1983-01-01

Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization at low temperatures was studied. The antibody activity of antibody was not affected by irradiation at an irradiation dose of below 8 MR and low temperatures. Immobilization of peroxidase-labeled anti-rabbit IgG goat IgG, anti-peroxidase, peroxidase, and anti-alpha-fetoprotein was carried out with hydrophilic and hydrophobic monomers. The activity of the immobilized enzyme-labeled antibody membranes varied with the thickness of the membranes and increased with decreasing membrane thickness. The activity of the immobilized antibody particles was varied by particle size. Immobilized anti-alpha-fetoprotein particles and membranes can be used for the assay of alpha-fetoprotein by the antigen-antibody reaction, such as a solid-phase sandwich method with high sensitivity

Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria.

Science.gov (United States)

Hameed, Bilal; Mehta, Neil; Sapisochin, Gonzalo; Roberts, John P; Yao, Francis Y

2014-08-01

Serum alpha-fetoprotein (AFP) has been increasingly recognized as a marker for a poor prognosis after liver transplantation (LT) for hepatocellular carcinoma (HCC). Many published reports, however, have included a large proportion of patients with HCC beyond the Milan criteria, and the effects of incorporating AFP as an exclusion criterion for LT remain unclear. We studied 211 consecutive patients undergoing LT for HCC within the Milan criteria according to imaging under the Model for End-Stage Liver Disease organ allocation system between June 2002 and January 2009. The majority (93.4%) had locoregional therapy before LT. The median follow-up was 4.5 years (minimum = 2 years). The Kaplan-Meier 1- and 5-year patient survival rates were 94.3% and 83.4%, respectively. In a univariate analysis, significant predictors of HCC recurrence included vascular invasion [hazard ratio (HR) = 10, 95% confidence interval (CI) = 3.9-26, P 1000 ng/mL (HR = 4.5, 95% CI = 1.3-15.3, P = 0.02), and an AFP level > 500 ng/mL (HR = 3.1, 95% CI = 1.04-9.4, P = 0.04). In a multivariate analysis, vascular invasion was the only significant predictor of tumor recurrence (HR = 5.6, 95% CI = 1.9-19, P = 0.02). An AFP level > 1000 ng/mL was the strongest pretransplant variable predicting vascular invasion (odds ratio = 6.8, 95% CI = 1.6-19.1, P = 0.006). The 1- and 5-year rates of survival without recurrence were 90% and 52.7%, respectively, for patients with an AFP level > 1000 ng/mL and 95% and 80.3%, respectively, for patients with an AFP level ≤ 1000 ng/mL (P = 0.026). Applying an AFP level > 1000 ng/mL as a cutoff would have resulted in the exclusion of 4.7% of the patients fr m LT and a 20% reduction in HCC recurrence. In conclusion, an AFP level > 1000 ng/mL may be a surrogate for vascular invasion and may be used to predict posttransplant HCC recurrence. Incorporating an AFP level > 1000 ng/mL as an exclusion criterion for LT within the Milan criteria may further improve posttransplant

Evaluation of a second trimester triple marker screening test for fetal status using alpha-fetoprotein (aFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3)

International Nuclear Information System (INIS)

Mi, Seong Young; Kim, Jong Ho; Choi, Seung Hun

1997-01-01

Our purpose was to assess the utility of maternal serum triple-marker screening test using alpha-fetoprotein (aFP), human Chorionic Gonadotropin (hCG) and unconjugated Estriol (uE 3 ) for fetal chromosomal abnormalities. 1,767 venous blood samples (4ml) between 15 and 20 week's gestation for maternal serum screening from January to October 1996, were tested with Kodak Amerix-M triple marker radioimmunoassay kits. Risk analysis was achieved with interpretive software such as Alpha (LMS, Kodak Clinical Diagnostics). Marker levels are transformed into multiples of median (MOM), which represent an interpretation of (weight regressed) patient marker levels relative to regressed median levels for stated gestation. By multivariate anaysis, the three MOM values are combined to generate a liklihood ratio. Calculation of a patient, risk is the product of liklihood ratio and age-related risk. Risk assessment is weight for maternal age. The median values of aFP, hCG and uE 3 were well correlated with gestational age, respectively (r=0.94, p=0.003; r=-0.97, p=0.029; r=0.99, p 3 weren't (r=-0.17, p=0.22; r=0.36, p=0.09, respectively). The values of aFP, CG and uE 3 between pregnancy younger than 35 years-old (n=87) and older than that (n=1640) were 51.67±27.44, vs 54.65±126.36, 46.45±30.08 vs 51.33±38.50 and 8.01±11.01 vs 6.68±7.23, respectively but all of them failed to show significant differences. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 21 if aFP or 2.1 MOM and E 3 2.5 MOM. The initial screen-positive rate for both Down' syndrome and neural tube defect were 1.46% (26/1767); 0.73% (13/1767) with each other. Among screen positive 26 patients, three and nine were normal karyotype and normal phenotype, respectively and five patients had still births. Reamining 9 patients underwent terminations. In conclusion, compared with the other group's data even in Koreans (Whang et al, and Song et al

Sensitive electrochemical immunosensor for α-fetoprotein based on graphene/SnO2/Au nanocomposite.

Science.gov (United States)

Liu, Junfeng; Lin, Guanhua; Xiao, Can; Xue, Ying; Yang, Ankang; Ren, Hongxuan; Lu, Wensheng; Zhao, Hong; Li, Xiangjun; Yuan, Zhuobin

2015-09-15

A label-free electrochemical immunosensor for sensitive detection of α-fetoprotein (AFP) was developed based on graphene/SnO2/Au nanocomposite. The graphene/SnO2/Au nanocomposite modified glassy carbon electrode was used to immobilize α-fetoprotein antibody (anti-AFP) and to construct the immunosensor. Results demonstrated that the peak currents of [Ru(NH3)6](3+) decreased due to the interaction between antibody and antigen on the modified electrode. Thus, a label-free immunosensor for the detection of AFP was realized by monitoring the peak current change of [Ru(NH3)6](3+). The factors influencing the performance of the immunosensor were investigated in details. Under optimal conditions, the peak currents obtained by DPV decreased linearly with the increasing AFP concentrations in the range from 0.02 to 50 ng mL(-1) with a linear coefficient of 0.9959. This electrochemical immunoassay has a low detection limit of 0.01 ng mL(-1) (S/N=3) and was successfully applied to the determination of AFP in serum samples. Copyright © 2015 Elsevier B.V. All rights reserved.

An Ultrasensitive Electrochemical Immunosensor for Alpha-Fetoprotein Using an Envision Complex-Antibody Copolymer as a Sensitive Label

Science.gov (United States)

Xiong, Ping; Gan, Ning; Cao, Yuting; Hu, Futao; Li, Tianhua; Zheng, Lei

2012-01-01

A novel strategy is presented for sensitive detection of alfa-fetoprotein (AFP), using a horseradish peroxidase (HRP)-functionalized Envision antibody complex (EVC) as the label. The Envision-AFP signal antibody copolymer (EVC-AFP Ab2) was composed of a dextran amine skeleton anchoring more than 100 molecules of HRP and 15 molecules of secondary antibody, and acted as a signal tag in the immunosensor. The sensor was constructed using the following steps: First, gold electrode (GE) was modified with nano-gold (AuNPs) by electro-deposition in HAuCl4 solution. The high affinity of the AuNPs surface facilitates direct formation of a self-assembled thiolated protein G layer. Next, the coated GE was incubated in a solution of AFP capture antibody (AFP Ab1); these antibodies attach to the thiolated protein G layer through their non-antigenic regions, leaving the antigen binding sites for binding of target analyte. Following a sandwich immunoreaction, an EVC-AFP Ab2-AFP-AFP Ab1 immunocomplex was formed on the electrode surface, allowing large amounts of HRP on the complex to produce an amplified electrocatalytic current of hydroquinone (HQ) in the presence of hydrogen peroxide (H2O2). Highly amplified detection was achieved, with a detection limit of 2 pg/mL and a linear range of 0.005–0.2 ng/mL for AFP in 10 μL undiluted serum; this is near or below the normal levels of most cancer biomarker proteins in human serum. Measurements of AFP in the serum of cancer patients correlated strongly with standard enzyme-linked immunosorbent assays. These easily fabricated EVC-modified immunosensors show excellent promise for future fabrication of bioelectronic arrays. By varying the target biomolecules, this technique may be easily extended for use with other immunoassays, and thus represents a versatile design route.

Autism Spectrum Disorders and Maternal Serum α-Fetoprotein Levels During Pregnancy

DEFF Research Database (Denmark)

Abdallah, Morsi; Grove, Jakob; Hougaard, David M

2011-01-01

Objective: Numerous studies have been trying to disentangle the complex pathophysiology of autism spectrum disorders (ASD). In our study, we explored the potential role of maternal serum (MS) α-fetoprotein (AFP) in the prediction and the pathophysiology of ASD. Methods: A total of 112 patients...... role in the pathophysiology of ASD makes AFP a good candidate for further larger scale studies to confirm such an association and to determine whether this pattern is unique to ASD or related to other psychiatric disorders as well....

ASO: Antistreptolysin O titer

Science.gov (United States)

... Phosphatase (ALP) Allergy Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/PR3 Antibodies Androstenedione Angiotensin-Converting Enzyme ( ...

Hepatoid adenocarcinoma of the stomach: a case report

Energy Technology Data Exchange (ETDEWEB)

Chung, Eun A; Yang, Ik; Lee, Yul; Chung, Soo Young; Kim, Ju Seup [College of Medicine, Hallym University, Seoul (Korea, Republic of)

1995-01-15

Hepatoid adenocarcinoma of the stomach is a gastric carcinoma with both adenocarcinomatous and hepatocellular carcinomatous differentiation. It usually produces large amount of serum alpha-fetoprotein. It often occurs in aged person, commonly located in the gastric antrum. Because of early lymph node and liver metastasis, prognosis is poor. A case of hepatoid adenocarcinoma of the stomach in a 49-year-old man is reported. The patient's serum alpha-fetoprotein level was high (3380 ng/ml). Liver function test was normal, otherwise. A mass was observed in right lobe of the liver on US and CT. It was hypervascular with increased uptake of lipiodol on hepatic arteriography. A large ulcerative tumor involving the gastric antrum and body was also found at barium study of the stomach. Subtotal gastrectomy nad right lobectomy of the liver resulted in rapid decrease in serum alpha-fetoprotein. Histopathologically the diagnosis was hepatoid adenocarcinoma of the stomach with liver metastasis.

Hepatoid adenocarcinoma of the stomach: a case report

International Nuclear Information System (INIS)

Chung, Eun A; Yang, Ik; Lee, Yul; Chung, Soo Young; Kim, Ju Seup

1995-01-01

Hepatoid adenocarcinoma of the stomach is a gastric carcinoma with both adenocarcinomatous and hepatocellular carcinomatous differentiation. It usually produces large amount of serum alpha-fetoprotein. It often occurs in aged person, commonly located in the gastric antrum. Because of early lymph node and liver metastasis, prognosis is poor. A case of hepatoid adenocarcinoma of the stomach in a 49-year-old man is reported. The patient's serum alpha-fetoprotein level was high (3380 ng/ml). Liver function test was normal, otherwise. A mass was observed in right lobe of the liver on US and CT. It was hypervascular with increased uptake of lipiodol on hepatic arteriography. A large ulcerative tumor involving the gastric antrum and body was also found at barium study of the stomach. Subtotal gastrectomy nad right lobectomy of the liver resulted in rapid decrease in serum alpha-fetoprotein. Histopathologically the diagnosis was hepatoid adenocarcinoma of the stomach with liver metastasis

common laboratory investigations in obstetrics and gynaecology

African Journals Online (AJOL)

Enrique

HIV diagnosis and monitoring. These 'universal' tests are often requested as screening labora- tory tests ... Rapid plasma reagin (for syphilis). • Hepatitis B. • HIV. • Alpha fetoprotein and Down's screen (α-fetoprotein, ... The biochemical diagnosis of early pregnancy is now taken for granted with the advent of the monoclonal ...

Feto-maternal haemorrhage associated with genetic amniocentesis

DEFF Research Database (Denmark)

Tabor, A; Bang, J; Nørgaard-Pedersen, B

1987-01-01

Maternal serum alpha-fetoprotein (AFP) levels were determined before and after genetic amniocentesis (n = 283) or ultrasound scan (n = 268) in a group of women participating in a randomized trial of genetic amniocentesis. Increases in AFP levels were seen significantly more often after amniocente......Maternal serum alpha-fetoprotein (AFP) levels were determined before and after genetic amniocentesis (n = 283) or ultrasound scan (n = 268) in a group of women participating in a randomized trial of genetic amniocentesis. Increases in AFP levels were seen significantly more often after...

A novel embryological theory of autism causation involving endogenous biochemicals capable of initiating cellular gene transcription: a possible link between twelve autism risk factors and the autism 'epidemic'.

Science.gov (United States)

King, Chiara R

2011-05-01

Human alpha-fetoprotein is a pregnancy-associated protein with an undetermined physiological role. As human alpha-fetoprotein binds retinoids and inhibits estrogen-dependent cancer cell proliferation, and because retinoic acid (a retinol metabolite) and estradiol (an estrogen) can both initiate cellular gene transcription, it is hypothesized here that alpha-fetoprotein functions during critical gestational periods to prevent retinoic acid and maternal estradiol from inappropriately stimulating gene expression in developing brain regions which are sensitive to these chemicals. Prenatal/maternal factors linked to increased autism risk include valproic acid, thalidomide, alcohol, rubella, cytomegalovirus, depression, schizophrenia, obsessive-compulsive disorder, autoimmune disease, stress, allergic reaction, and hypothyroidism. It will be shown how each of these risk factors may initiate expression of genes which are sensitive to retinoic acid and/or estradiol - whether by direct promotion or by reducing production of alpha-fetoprotein. It is thus hypothesized here that autism is not a genetic disorder, but is rather an epigenetic disruption in brain development caused by gestational exposure to chemicals and/or conditions which either inhibit alpha-fetoprotein production or directly promote retinoic acid-sensitive or estradiol-sensitive gene expression. This causation model leads to potential chemical explanations for autistic brain morphology, the distinct symptomatology of Asperger's syndrome, and the differences between high-functioning and low-functioning autism with regard to mental retardation, physical malformation, and sex ratio. It will be discussed how folic acid may cause autism under the retinoic acid/estradiol model, and the history of prenatal folic acid supplementation will be shown to coincide with the history of what is popularly known as the autism epidemic. It is thus hypothesized here that prenatal folic acid supplementation has contributed to the

Irregular vascular pattern by contrast-enhanced ultrasonography and high serum Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.

Science.gov (United States)

Takada, Hitomi; Tsuchiya, Kaoru; Yasui, Yutaka; Nakakuki, Natsuko; Tamaki, Nobuharu; Suzuki, Shoko; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Asahina, Yasuhiro; Enomoto, Nobuyuki; Izumi, Namiki

2016-11-01

Radiofrequency ablation (RFA) is considered the most effective treatment for early-stage hepatocellular carcinoma (HCC) patients unsuitable for resection. However, poor outcome after RFA has occasionally been reported worldwide. To predict such an outcome, we investigated imaging findings using contrast-enhanced ultrasonography (CEUS) with Sonazoid and serum tumor markers before RFA. This study included 176 early-stage HCC patients who had initially achieved successful RFA. Patients were examined using CEUS; their levels of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin before RFA were measured. Sonazoid provided parenchyma-specific contrast imaging and facilitated tumor vascular architecture imaging through maximum intensity projection (MIP). Kaplan-Meier analysis examined cumulative rates of local tumor progression, intrasubsegmental recurrence, and survival; factors associated with these were determined with Cox proportional hazards analysis. Local tumor progression (n = 15), intrasubsegmental recurrence (n = 46), and death (n = 18) were observed. Irregular pattern in MIP classification and serum AFP-L3 level (>10%) before RFA were identified as independent risk factors for local tumor progression and intrasubsegmental recurrence. These two factors were independently associated with poor survival after RFA (irregular pattern in MIP: hazard ratio, (HR) = 8.26; 95% confidence interval, (CI) = 2.24-30.3; P = 0.002 and AFP-L3 > 10%: HR = 2.94; 95% CI = 1.09-7.94; P = 0.033). Irregular MIP pattern by CEUS and high level of serum AFP-L3 were independent risk factors for poor outcome after successful RFA. The Patients with these findings should be considered as special high-risk group in early-stage HCC. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Evaluation of a second trimester triple marker screening test for fetal status using alpha-fetoprotein (aFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE{sub 3})

Energy Technology Data Exchange (ETDEWEB)

Mi, Seong Young; Kim, Jong Ho; Choi, Seung Hun [Chung Ang Gil Hospital, Inchon (Korea, Republic of)

1997-07-01

Our purpose was to assess the utility of maternal serum triple-marker screening test using alpha-fetoprotein (aFP), human Chorionic Gonadotropin (hCG) and unconjugated Estriol (uE{sub 3}) for fetal chromosomal abnormalities. 1,767 venous blood samples (4ml) between 15 and 20 week's gestation for maternal serum screening from January to October 1996, were tested with Kodak Amerix-M triple marker radioimmunoassay kits. Risk analysis was achieved with interpretive software such as Alpha (LMS, Kodak Clinical Diagnostics). Marker levels are transformed into multiples of median (MOM), which represent an interpretation of (weight regressed) patient marker levels relative to regressed median levels for stated gestation. By multivariate anaysis, the three MOM values are combined to generate a liklihood ratio. Calculation of a patient, risk is the product of liklihood ratio and age-related risk. Risk assessment is weight for maternal age. The median values of aFP, hCG and uE{sub 3} were well correlated with gestational age, respectively (r=0.94, p=0.003; r=-0.97, p=0.029; r=0.99, p<0.001, respectively). The median value of hCG were correlated withmateral age (r=0.13, p=0.04) but those of aFP and eU{sub 3} weren't (r=-0.17, p=0.22; r=0.36, p=0.09, respectively). The values of aFP, CG and uE{sub 3} between pregnancy younger than 35 years-old (n=87) and older than that (n=1640) were 51.67{+-}27.44, vs 54.65{+-}126.36, 46.45{+-}30.08 vs 51.33{+-}38.50 and 8.01{+-}11.01 vs 6.68{+-}7.23, respectively but all of them failed to show significant differences. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 21 if aFP < or 0.7 multiples of median (MOM), hCG> or 2.1 MOM and E{sub 3} < or 0.7 MOM. Patients were screen positive for neural tube defect if aFP >2.5 MOM. The initial screen-positive rate for both Down' syndrome and neural tube defect were 1.46% (26/1767); 0.73% (13/1767) with each other

Clinicopathologic features of hepatic neoplasms in explanted livers: a single institution experience

International Nuclear Information System (INIS)

Mourad, W.; Tulbah, A.; Al-Omari, M.; Al-Mana, H.; Khalaf, H.; Neiamatallah, M.

2007-01-01

Hepatic neoplasms can be the primary indication for hepatic transplantation. The tumors can also be incidentally identified in explanted livers. We explored the clinicopathologic features of hepatic neoplasms identified in explanted livers. All explanted livers resected between 2001 and 2006 were evaluated for the presence of neoplasms and their clinicopathologic features were examined. In 198 liver transplants, 15 neoplasms (15.3%) were identified. Patient ages ranged from 5 to 63 years (median, 56 years). The primary etiology of hepatic disease was hepatitis C virus in 12 cases, hepatitis B virus in 1 case, cryptogenic cirrhosis in 1 case and congenital hepatic fibrosis in 1 case. Serum alpha-fetoprotein was significantly elevated (>400 U/L) in only 2 cases. CA19-9 was not elevated in any of the cases. The tumors included hepatocellular carcinoma (HCC) in 13 cases, 1 case of cholangiocarcinoma and 1 case of combined HCC and hepatoblastoma. The tumors ranged in size from 0.5 to 5 cm (median 1.4 cm) and were multifocal in 5 of the cases (33%). Tissue alpha-fetoprotein expression was only seen in the cases associated with elevated serum levels. In our institution hepatic neoplasma are seen in more than 15% of explanted livers. They can be incidentally identified, are frequently not associated with elevated serum levels of alpha-fetoprotein and CA19-9, are commonly multifocal but small and are associated with good prognosis. Elevated serum alpha-fetoprotein, albeit specific, is not a very sensitive marker in the detection of hepatic neoplasms. (author)

Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors

International Nuclear Information System (INIS)

Kim, Young-sun; Rhim, Hyunchul; Cho, On Koo; Koh, Byung Hee; Kim, Yongsoo

2006-01-01

Purpose: To evaluate the pattern and risks for intrahepatic recurrence after percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC). Materials and methods: We studied 62 patients with 72 HCCs (≤4 cm) who were treated with percutaneous RF ablation. The mean follow-up period was 19.1 months (6.0-49.1). We assessed the incidence and cumulative disease-free survival of local tumor progression (LTP) and intrahepatic distant recurrence (IDR). To analyze the risk factors, we examined the following, for the LTP: (1) tumor diameter, (2) contact with vessels, (3) degree of approximation to hepatic hilum, (4) contact with hepatic capsule, (5) presence of ablative safety margin, (6) degree of benign periablational enhancement and (7) serum alpha-fetoprotein; for the IDR: (1) severity of hepatic disease, (2) presence of HBsAg, (3) serum alpha-fetoprotein, (4) whether RF ablation was the initial treatment and (5) multiplicity of tumor for IDR. Results: The incidence of overall recurrence, LTP and IDR was 62.9%, 26.4% and 53.2%, respectively. The cumulative disease-free survival rates were 52%, 82% and 56% at 1 year, 26%, 63% and 30% at 2 years, respectively. Univariate analysis showed that the significant risk factors for LTP were: a tumor with a diameter >3 cm, contact of HCC with a vessel and an insufficient safety margin (p 3 cm and insufficient safety margin were independent factors. Only the increased serum alpha-fetoprotein was a significant risk factor for IDR (p 3 cm) with high serum alpha-fetoprotein should be treated more aggressively because of higher risk for recurrence

Coagulation Factors Test

Science.gov (United States)

... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

Acridinium esters as high-specific-activity labels in immunoassay

International Nuclear Information System (INIS)

Weeks, I.; Beheshti, I.; McCapra, F.; Campbell, A.K.; Woodhead, J.S.

1983-01-01

A chemiluminescent acridinium ester has been synthesized that reacts spontaneously with proteins to yield stable, immunoreactive derivatives of high specific activity. The compound has been used to prepare chemiluminescent monoclonal antibodies to human alpha 1-fetoprotein having average incorporation ratios as great as 2.8 mol of label per mole of antibody, which corresponds to a detection limit of approximately 8 X 10(-19) mol. These antibodies have been used in the preliminary development of a two-site immunochemiluminometric assay for human alpha 1-fetoprotein, which requires only a 30-min incubation and a quantification time of 5 s per sample

The Relationship between Preeclampsia and Quadruple Screening Test in Nuliparous

Directory of Open Access Journals (Sweden)

Farnaz Zand Vakili

2017-01-01

Full Text Available Introduction: Early diagnosis and prediction of preeclampsia needs appropriate obstetric care. Preeclampsia predicting methods are important. This study was designed to determine the correlation between preeclampsia and quadruple screening test in the nulliparous. Materials and Methods:  This case - control study was conducted on 54 pregnant women with preeclampsia (case group and 108 healthy pregnant women (control group who referred to health centers in Sanandaj, Iran. Ultrasonography was performed to determine the gestational age by a radiologist. Maternal serum levels of alpha fetoprotein (AFP, human chorionic gonadotropin (hCG, unconjugated estriol (uE3, and inhibin-A were measured in the second trimester of pregnancy. Data were analyzed using SPSS statistical software and Chi-square test, T-test, sensitivity, specificity, positive and negative predictive values. Results: The results showed that the sensitivity and specificity for the diagnosis of preeclampsia in pregnant women for hCG were 35.2% and 79.6 respectively. These findings for estriol were 20.4% and 88.9%, for inhibin-A were 38.8% and 88% and for alpha fetoprotein were 38.8% and 74.1%. The positive predictive value for hCG, estriol, inhibin-A and alpha fetoprotein were 46.3%, 47.8%, 61.8% and 42.9% respectively. The negative predictive value for hCG, estriol, inhibin-A and alpha fetoprotein were also 71%, 69.1%, 74.2% and 70.8% respectively. Conclusion: There was a relationship between preeclampsia and high levels of inhibin-A and hCG. Further studies on these markers and evaluating their usefulness in the diagnosis and management of preeclampsia are recommended.

Clinical evaluation of sup(99m)Tc-N-pyridoxyl-5-methyltryptophan hepatobiliary scintigraphy in hepatocellular carcinoma

International Nuclear Information System (INIS)

Kashiwagi, Toru; Azuma, Masayoshi; Matsuda, Hiroyuki; Yoshioka, Hiroaki; Ishizu, Hiroshi; Mitsutani, Natsuki; Koizumi, Takeo; Kobayashi, Yasushi

1985-01-01

We have assessed the diagnostic value of sup(99m)Tc-N-pyridoxyl-5-methyltryptophan (sup(99m)Tc-PMT) hepatobiliary scintigraphy in 28 patients with hepatocellular carcinoma (HCC) who had obvious filling defects on sup(99m)Tc-phytate liver scintigram. Uptake of sup(99m)Tc-PMT in obvious defects on sup(99m)Tc-phytate liver scintigram was observed in 16 out of 28 patients (57.1 %). Most of HCC with sup(99m)Tc-PMT uptake were histologically well-differenciated. However, well-differenciated HCC did not always take up sup(99m)Tc-PMT. No correlation was observed between sup(99m)Tc-PMT uptake in the tumor and levels of serum alpha-fetoprotein. Patients with high alpha-fetoprotein level (>3000 ng/ml) were only 9 patients (32.1 %) in our study. By the combined results of sup(99m)Tc-PMT hepatobiliary scintigraphy and alpha-fetoprotein level (>3000 ng/ml), diagnostic rate for HCC was markedly elevated up to 75 %. Therefore, it is considered that sup(99m)Tc-PMT hepatobiliary scintigraphy is clinically useful for specific diagnosis of HCC. Furthermore, it provides the information for invasion of HCC into the bile duct. (author)

Clinical evaluation of sup(99m)Tc-N-pyridoxyl-5-methyltryptophan hepatobiliary scintigraphy in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Kashiwagi, Toru; Azuma, Masayoshi; Matsuda, Hiroyuki; Yoshioka, Hiroaki; Ishizu, Hiroshi; Mitsutani, Natsuki; Koizumi, Takeo; Kobayashi, Yasushi

1985-09-01

We have assessed the diagnostic value of sup(99m)Tc-N-pyridoxyl-5-methyltryptophan (sup(99m)Tc-PMT) hepatobiliary scintigraphy in 28 patients with hepatocellular carcinoma (HCC) who had obvious filling defects on sup(99m)Tc-phytate liver scintigram. Uptake of sup(99m)Tc-PMT in obvious defects on sup(99m)Tc-phytate liver scintigram was observed in 16 out of 28 patients (57.1 %). Most of HCC with sup(99m)Tc-PMT uptake were histologically well-differenciated. However, well-differenciated HCC did not always take up sup(99m)Tc-PMT. No correlation was observed between sup(99m)Tc-PMT uptake in the tumor and levels of serum alpha-fetoprotein. Patients with high alpha-fetoprotein level (>3000 ng/ml) were only 9 patients (32.1 %) in our study. By the combined results of sup(99m)Tc-PMT hepatobiliary scintigraphy and alpha-fetoprotein level (>3000 ng/ml), diagnostic rate for HCC was markedly elevated up to 75 %. Therefore, it is considered that sup(99m)Tc-PMT hepatobiliary scintigraphy is clinically useful for specific diagnosis of HCC. Furthermore, it provides the information for invasion of HCC into the bile duct.

Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors

Energy Technology Data Exchange (ETDEWEB)

Kim, Young-sun [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine (Korea, Republic of); Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of); Rhim, Hyunchul [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine (Korea, Republic of) and Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of)]. E-mail: forest@smc.samsung.co.kr; Cho, On Koo [Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of); Koh, Byung Hee [Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of); Kim, Yongsoo [Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of)

2006-09-15

Purpose: To evaluate the pattern and risks for intrahepatic recurrence after percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC). Materials and methods: We studied 62 patients with 72 HCCs ({<=}4 cm) who were treated with percutaneous RF ablation. The mean follow-up period was 19.1 months (6.0-49.1). We assessed the incidence and cumulative disease-free survival of local tumor progression (LTP) and intrahepatic distant recurrence (IDR). To analyze the risk factors, we examined the following, for the LTP: (1) tumor diameter, (2) contact with vessels, (3) degree of approximation to hepatic hilum, (4) contact with hepatic capsule, (5) presence of ablative safety margin, (6) degree of benign periablational enhancement and (7) serum alpha-fetoprotein; for the IDR: (1) severity of hepatic disease, (2) presence of HBsAg, (3) serum alpha-fetoprotein, (4) whether RF ablation was the initial treatment and (5) multiplicity of tumor for IDR. Results: The incidence of overall recurrence, LTP and IDR was 62.9%, 26.4% and 53.2%, respectively. The cumulative disease-free survival rates were 52%, 82% and 56% at 1 year, 26%, 63% and 30% at 2 years, respectively. Univariate analysis showed that the significant risk factors for LTP were: a tumor with a diameter >3 cm, contact of HCC with a vessel and an insufficient safety margin (p < 0.05). A multivariate stepwise Cox hazard model showed that the measurement of a tumor diameter >3 cm and insufficient safety margin were independent factors. Only the increased serum alpha-fetoprotein was a significant risk factor for IDR (p < 0.05). Conclusion: Intrahepatic recurrence after percutaneous RF ablation is common. Large HCC (>3 cm) with high serum alpha-fetoprotein should be treated more aggressively because of higher risk for recurrence.

Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Mary Ann Comunale

2010-08-01

Full Text Available We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT. To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC.Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (alpha-1,3 fucosylation. Increases in core (alpha-1,6 fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL, specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific.This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification.

Serological diagnosis of hepatocellular carcinoma: challenges and opportunities

Directory of Open Access Journals (Sweden)

LU Fengmin

2017-07-01

Full Text Available Serological markers have the features of noninvasiveness and simple operation and thus have become a research hotspot in the diagnosis of hepatocellular carcinoma. This article briefly introduces the role of the conventional serological marker alpha-fetoprotein (AFP in assisting the diagnosis and predicting the prognosis of HBV-related liver cancer, as well as the clinical value of new markers such as alpha-fetoprotein-L3 and abnormal prothrombin/des-γ-carboxy prothrombin. Based on literature review, the possibility of serum Golgi protein 73 used for laboratory auxiliary diagnosis of hepatocellular carcinoma has been denied. The results of the author′s experiment suggest that serum GP73 measurement can be used as a laboratory diagnostic index for progressive liver fibrosis and liver cirrhosis.

A three-parameter langmuir-type model for fitting standard curves of sandwich enzyme immunoassays with special attention to the α-fetoprotein assay

NARCIS (Netherlands)

Kortlandt, W.; Endeman, H.J.; Hoeke, J.O.O.

In a simplified approach to the reaction kinetics of enzyme-linked immunoassays, a Langmuir-type equation y = [ax/(b + x)] + c was derived. This model proved to be superior to logit-log and semilog models in the curve-fitting of standard curves. An assay for α-fetoprotein developed in our laboratory

Rapid and simple half-quantitative measurement alpha-fetoprotein by poly(dimethylsiloxane) microfluidic chip immunochromatographic assay

Science.gov (United States)

Tong, Chao; Jin, Qinghui; Zhao, Jianlong

2008-03-01

In this article, a kind of microfluidic method based on MEMS technology combined with gold immunochromatographic assay (GICA) is developed and discussed. Compared to the traditional GICA, this method supplies us convenient, multi-channel, in-parallel, low cost and similar efficiency approach in the fields of alpha-fetopro-tei (AFP)detection. Firstly, we improved the adhesion between the model material SU-8 and Silicon wafer, optimized approaches of the fabrication of the SU-8 model systematically, and fabricate the PDMS micro fluid chip with good reproduction successfully. Secondly, Surface modification and antibody immobilization methods with the GICA on the PDMS micro fluid analysis chip are studied, we choose the PDMS material and transfer GICA to the PDMS micro fluid chip successfully after researching the antibody immobilization efficiency of different materials utilized in fabrication of the micro fluid chip. In order to improve the reaction efficiency of the immobilized antibody, we studied the characteristics of micro fluid without the gas drive, and the fluid velocity control in our design; we also design structure of grove to strengthen the ability of immobilizing the antibody. The stimulation of the structure shows that it achieves great improvement and experiments prove the design is feasible.

Spina Bifida

Science.gov (United States)

... with language and reading comprehension, and trouble learning math. Additional problems such as latex allergies, skin problems, ... and fetal ultrasound. The MSAFP screen measures the level of a protein called alpha-fetoprotein (AFP), which ...

Expression and location of α-fetoprotein during rat colon development

Science.gov (United States)

Liu, Xiao-Yan; Dong, Dan; Sun, Peng; Du, Jun; Gu, Luo; Ge, Ying-Bin

2009-01-01

AIM: To investigate the expression of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, and its involvement during rat colon development. METHODS: Colons from Sprague-Dawley rat fetuses, young and adult (8 wk old) animals were used in this study. Expression levels of AFP in colons of different development stage were detected by reverse-transcriptase PCR (RT-PCR) and Western blotting. To identify the cell location of AFP in the developing rat colons, double-immunofluorescent staining was performed using antibodies to specific cell markers and AFP, respectively. RESULTS: The highest levels of AFP mRNA were detected in colons of rats at embryonic day 18.5 (e18.5). Compared to e18.5 d, the AFP expression was significantly decreased during rat development [85% for e20.5, P colon from the embryo to the weaning stage by immunofluorescence and presents 72-kDa isoform in the developing rat colons by Western blotting. The dynamic expression of AFP in the various developmental stages of the colon indicates that AFP might be involved in many aspects of colon development. PMID:19360917

Radial-velocity variations in Alpha Ori, Alpha Sco, and Alpha Her

International Nuclear Information System (INIS)

Smith, M.A.; Patten, B.M.; Goldberg, L.

1989-01-01

Radial-velocity observations of Alpha Ori, Alpha Sco A, and Alpha Her A are used to study radial-velocity periodicities in M supergiants. The data refer to several metallic lines in the H-alpha region and to H-alpha itself. It is shown that Alpha Ori and Alpha Sco A have cycle lengths of about 1 yr and semiamplitudes of 2 km/s. It is suggested that many semiregular red supergiant varibles such as Alpha Ori may be heading toward chaos. All three stars show short-term stochastic flucutations with an amplitude of 1-2 km/s. It is found that the long-term variability of H-alpha velocities may be a consequence of intermittent failed ejections. 58 refs

Construction of Expression Vector for Anti-Alpha-Fetoprotein Gene and Its Inhibition Effects on Alpha-Fetoprotein Positive Hepg2 Cells

Science.gov (United States)

Wang, Ze; Zhang, Hui

As research previously demonstrated, suppression of AFP expression or its biological activities might inhibit the proliferation of AFP positive human hepatocellular carcinoma cells. In this study, we constructed an anti-AFP gene vector and transfected it to HepG2 cells. RT-PCR showed AFP gene expression in the transfected cells was reduced. MTT assay suggested the proliferation of the transfected cells was also inhibited comparing with the untransfected cells. This result provides a new insight into AFP as the target for preventing and treating hepatocellular carcinoma.

Diagnostic value of α-fetoprotein in hepatocellular carcinoma

International Nuclear Information System (INIS)

Hernández Perera, Julio César

2009-01-01

In the world the hepatocellular carcinoma (HCC) is the fifth to sixth most common malignancy. An increase in its incidence is looming in Cuba as a result of the population aging and the increase of morbi-mortality due to liver cirrhosis (CH). α-fetoprotein (AFP) by SUMA®, was used in this work as a tumor marker technique in 189 Cirrhotic patients evaluated at the CIMEQ, between January 1999 and September 2005. The main factors associated with an elevation of AFP were HCC, viral cirrhosis, and the age of 50 years or more. Presented CHC 22 (11.64%) patients, who had an average age of 55 years and the predominant sex was male (86,36%). The most important cause associated with this malignant disease was viral CH, mainly the virus of hepatitis C. This tumor marker showed a sensitivity and specificity of 68.18% and 92.17%, respectively. When combined with abdominal ultrasound was increase 86.36% sensitivity and 100% specificity. Elevated AFP levels associated with tumor prognosis factors. It can be concluded that the AFP had value in the diagnosis of HCC. This work is the first of its kind carried out in Cuba, and allows the design of a workable strategy for the research, monitoring and prognosis of HCC, having a wide network of laboratories SUMA®,, with a low cost per each determination. (author)

A cyclized peptide derived from alpha fetoprotein inhibits the proliferation of ER-positive canine mammary cancer cells.

Science.gov (United States)

Torres, Cristian Gabriel; Pino, Ana María; Sierralta, Walter Daniel

2009-06-01

The effects of estradiol (E2) and of an AFP-derived cyclized peptide (cP) on the proliferation of primary cultures of cancer cells isolated from spontaneous canine mammary tumors were studied. The cellular response to E2 and cP was related to the expression of estradiol receptor (isoforms alpha and beta). In ER-positive cells, 2 nM estradiol increased cell proliferation and the phosphorylation of ERK1/2; 2 microg/ml cP inhibited all these effects. Estradiol also increased HER2 immunoreactivity in ER-positive cells, an effect that was reverted to its basal values by cP. Estradiol stimulated in these cells the release of MMP2 and MMP9 and the shedding of HB-EGF, effects that the cP did not affect. ER-negative cells were refractory to estradiol or cP. All canine mammary tumor cells in culture responded to treatments analogously to human mammary cancer cells. Our results support the proposal of cP as a new, potentially effective therapeutic agent for the management of mammary cancer.

Gender impact on first trimester markers in Down syndrome screening

DEFF Research Database (Denmark)

Larsen, Severin Olesen; Wøjdemann, Karen R; Shalmi, Anne-Cathrine

2002-01-01

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with nor......The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies...... with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male...

Diagnostic Utility of Alpha-fetoprotein and Des-gamma ...

African Journals Online (AJOL)

2018-02-07

] High DCP levels also reflect .... using the multiple logistic regression models. P < 0.05 was considered statistically significant. .... that C-reactive protein has significant diagnostic power in AFP-negative, HBV-related HCC.[23].

Diagnostic Utility of Alpha-fetoprotein and Des-gamma ...

African Journals Online (AJOL)

2017-12-05

Dec 5, 2017 ... reports on the clinical characteristics of hepatocellular carcinoma in relation to the combination of the ... This is an open access article distributed under the terms of the Creative Commons .... Microsoft Excel and then transferred to STATA 10 software ..... Sohn W, Paik Y, Kim J, Kwon C, Job J, Cho J, et al.

The α-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol

Science.gov (United States)

Keller, Matthieu; Pawluski, Jodi L.; Brock, Olivier; Douhard, Quentin; Bakker, Julie

2010-01-01

In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the α-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of α-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice. PMID:20109458

Browse Title Index

African Journals Online (AJOL)

Items 1 - 50 of 150 ... Vol 15, No 1 (2006), Alpha-Fetoprotein in Asymptomatic Hepatitis B Virus Infected ... Vol 14, No 1 (2005), Antibiotic Resistance Among Genital Tract Isolates ... JJ Abdulahi, MIJ Okoye, DE Agbonlahor, GO Nwobu, JE Njab, C ...

A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals.

Science.gov (United States)

Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

2016-03-25

Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold² software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed.

The HELLP syndrome : Its association with unexplained elevation of MSAFP and MShCG in the second trimester

NARCIS (Netherlands)

Morssink, LP; Heringa, MP; Beekhuis, [No Value; DeWolf, BTHM; Mantingh, A

In this study, we examined the relationship between concentrations of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) in the second trimester and the 'haemolysis, elevated liver enzymes, low platelet count' (HELLP) syndrome. The concentrations of both

Randomised controlled trial of genetic amniocentesis in 4606 low-risk women

DEFF Research Database (Denmark)

Tabor, A; Philip, J; Madsen, Mette

1986-01-01

2.3). In the study group, increased levels of maternal serum alpha-fetoprotein before amniocentesis, perforation of the placenta during amniocentesis, and withdrawal of discoloured amniotic fluid were associated with an increased risk of spontaneous abortion. In the first six weeks after...

45,X karyotype

DEFF Research Database (Denmark)

Tabor, A; Bang, J; Philip, J

1981-01-01

We report three cases of Turner's syndrome with cystic hygromata, which were diagnosed by routine ultrasound scanning before amniocentesis in the second trimester of pregnancy. Maternal and amniotic level of alpha-fetoprotein were normal. Karyotyping carried out afterwards showed a 45,X karyotype...

Diagnostic utility of leptin and insulin-like growth factor binding ...

African Journals Online (AJOL)

Serum levels of leptin, insulin growth factor binding protein-2 (IGFBP-2) and alpha fetoprotein (AFP) were measured. ... renewal in response to nutrients. IGF pathway is not only involved in cell growth in tissue culture, but it is also involved in ...

The sandwich-type electrochemiluminescence immunosensor for {alpha}-fetoprotein based on enrichment by Fe{sub 3}O{sub 4}-Au magnetic nano probes and signal amplification by CdS-Au composite nanoparticles labeled anti-AFP

Energy Technology Data Exchange (ETDEWEB)

Zhou Hankun [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Gan Ning, E-mail: ganning@nbu.edu.cn [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Li Tianhua; Cao Yuting; Zeng Saolin [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Zheng Lei, E-mail: nfyyzl@163.com [Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Guo Zhiyong [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China)

2012-10-09

Highlights: Black-Right-Pointing-Pointer Sandwich immunoreaction, testing a large number of samples simultaneously. Black-Right-Pointing-Pointer The magnetic separation and enrichment by Fe{sub 3}O{sub 4}-Au magnetic nano probes. Black-Right-Pointing-Pointer The amplification of detection signal by CdS-Au composite nanoparticles labeled anti-AFP. Black-Right-Pointing-Pointer Almost no background signal, which greatly improve the sensitivity of detection. - Abstract: A novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated on a glassy carbon electrode (GCE) for ultra trace levels of {alpha}-fetoprotein (AFP) based on sandwich immunoreaction strategy by enrichment using magnetic capture probes and quantum dots coated with Au shell (CdS-Au) as the signal tag. The capture probe was prepared by immobilizing the primary antibody of AFP (Ab1) on the core/shell Fe{sub 3}O{sub 4}-Au nanoparticles, which was first employed to capture AFP antigens to form Fe{sub 3}O{sub 4}-Au/Ab1/AFP complex from the serum after incubation. The product can be separated from the background solution through the magnetic separation. Then the CdS-Au labeled secondary antibody (Ab2) as signal tag (CdS-Au/Ab2) was conjugated successfully with Fe{sub 3}O{sub 4}-Au/Ab1/AFP complex to form a sandwich-type immunocomplex (Fe{sub 3}O{sub 4}-Au/Ab1/AFP/Ab2/CdS-Au), which can be further separated by an external magnetic field and produce ECL signals at a fixed voltage. The signal was proportional to a certain concentration range of AFP for quantification. Thus, an easy-to-use immunosensor with magnetic probes and a quantum dots signal tag was obtained. The immunosensor performed at a level of high sensitivity and a broad concentration range for AFP between 0.0005 and 5.0 ng mL{sup -1} with a detection limit of 0.2 pg mL{sup -1}. The use of magnetic probes was combined with pre-concentration and separation for trace levels of tumor markers in the serum. Due to the

Treatment of hepatocellular carcinoma by transarterial injection of anticancer agents in iodized oil suspension or of radioactive iodized oil solution

International Nuclear Information System (INIS)

Kobayashi, H.; Hidaka, H.; Kajiya, Y.; Tanoue, P.; Inoue, H.; Ikeda, K.; Nakajo, M.; Shinohara, S.

1986-01-01

Transarterial injection of modified iodized oil was performed in 48 patients with hepatoma. In 41 cases an adriamycin and/or mitomycin C-iodized oil suspension was administered into the proper hepatic artery or peripheral hepatic branches. A reduction in tumor size of over 50% was obtained in 14 of the 33 patients in whom CT examination was performed before and after treatment. Serum alpha-fetoprotein levels decreased in 20 of 21 cases within the first month after injection. The one-year survival rate was estimated at 55% in advanced hepatoma. In 7 patients, transarterial internal irradiation using radioactive iodized oil was carried out. A decrease in tumor size was observed in all cases and in alpha-fetoprotein levels in 6 cases. One patient with severe liver cirrhosis died in hepatorenal failure. No severe complications or other adverse reactions were encountered with either of the methods. (orig.)

Twin Pregnancy with Gastroschisis in Both Twins

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Hui-Fen Kao

2007-12-01

Conclusion: The cause of gastroschisis is unknown, although possible exogenous causes have been studied. The diagnosis of gastroschisis in twin pregnancy is always in late gestation. Therefore, maternal serum alpha feto-protein screening and a detailed prenatal ultrasound evaluation are recommended in multifetal pregnancies.

1ST-TRIMESTER SCREENING FOR FETAL CHROMOSOMAL-ABNORMALITIES - PRELIMINARY-RESULTS

NARCIS (Netherlands)

VANLITH, JMM

We have started a multicentre trial to study the possibilities of first-trimester maternal serum screening for fetal chromosomal abnormalities. Maternal blood samples were obtained before 13 weeks of gestation. We present the preliminary results of the first 950 patients on alpha-fetoprotein (AFP).

Characteristic of expression levels of HepPar-1, alpha-fetoprotein, cytokeratin 7 and 20 by the cells of cholangiocellular cancer in trephine biopsy of the liver

Directory of Open Access Journals (Sweden)

V. A. Tumanskiy

2014-10-01

Full Text Available Aim. Expression level of immunohistochemical markers such as HepPar-1, AFP, CK7, CK20 and the area of immunopositive cells in cholangiocellular liver cancer, and their differences from hepatocellular carcinoma Methods and results. Histopathological, histochemical and immunohistochemical research of trephine was determined in the liver in 90 patients with biopsy. Among them 53 patients had hepatocellular, 36 – сholangiocellular liver cancer, 1 patient had mixed hepato-cholangiocellular carcinoma. Level of expression of immunohistochemical markers of tumor cells and the area of immunopositive tumor cells in the tumor was determined by photo-digital morphometry. It was established that expression of α-fetoprotein is determined in 47.22% of patients with cholangiocellular liver carcinoma in tumor cells, when AFP-immunopositive cells represent 17,25 ± 9,67% of the total area of tumor cells. Positive expression of HepPar-1 cells in cholangiocellular liver cancer wasn’t detected (unlike hepatocellular carcinoma, when cytoplasmic expression of HepPar-1 by tumor hepatocytes is determined in 92.45% of cases. Expression of СK7 by cholangiocellular carcinoma cells was observed in 97.22% of patients, and the expression of CK20 – in 45.29% patients, immunopositive cells represent 43,55 ± 9,93% and 50,28 ± 16,35% of the tumor area, respectively. Medium strength correlation was determined between the level of AFP and CK7 expression by tumor cells in cholangiocellular carcinoma. Direct strong bond was determined between level of AFP and CK20 expression. Negative weak correlation was determined between the level of CK7 and CK20.

A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours

NARCIS (Netherlands)

M.J. Murray (Matthew); E. Bell (Emma); K.L. Raby (Katie L.); M.A. Rijlaarsdam (Martin); A.J.M. Gillis (Ad); L.H.J. Looijenga (Leendert); H. Brown (Helen); B. Destenaves (Benoit); J.C. Nicholson (James); N. Coleman (Nicholas)

2016-01-01

textabstractBackground:The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and

Effective treatment for malignant mediastinal teratoma.

Science.gov (United States)

Parker, D; Holford, C P; Begent, R H; Newlands, E S; Rustin, G J; Makey, A R; Bagshawe, K D

1983-12-01

Primary malignant mediastinal teratoma is a rare tumour previously regarded as inevitably fatal. In a series of eight male patients with a mean age of 24 years five remain alive and well. All patients showed raised serum concentrations of human chorionic gonadotrophin or alpha fetoprotein. The patients were treated with intermittent combination chemotherapy that included cisplatin. Six patients responded to chemotherapy with a fall in human chorionic gonadotrophin or alpha fetoprotein to near normal levels and they then had radical excision of the remaining tumour. Living malignant tumour was found in four of the specimens and these patients received postoperative chemotherapy. One patient died after eight months and the remaining five patients are alive and well 13-136 months after the start of treatment. The two patients who did not undergo surgery died at one month and 15 months. Intermittent combination chemotherapy and carefully timed radical excision of these tumours would appear to have produced better results than have been reported in other series.

Basic concepts of medical genetics, pathogenetics, part 3

African Journals Online (AJOL)

Mohammad Saad Zaghloul Salem

2013-01-30

Jan 30, 2013 ... The genetic material controls life activities of the cell through regulating the synthesis .... work reactions and interactions: signal transduction disorders: e.g. ... Obviously, the balance between the pathological effects of mutation and the ... e- b-thalssemia. 6- Maternal serum level of alpha-fetoprotein (AFP) is.

Distribution of alpha3, alpha5 and alpha(v) integrin subunits in mature and immature human oocytes.

Science.gov (United States)

Capmany, G; Mart, M; Santaló, J; Bolton, V N

1998-10-01

The distribution of three integrin subunits, alpha3, alpha5 and alpha(v), in immature and mature human oocytes has been examined using immunofluorescence and confocal microscopy. The results demonstrate that both alpha5 and alpha(v) are present at the germinal vesicle stage, while alpha3 was only detected in oocytes after germinal vesicle breakdown, in metaphase I and II stage oocytes. The cortical concentration of integrin subunits alpha3 and alpha5 is consistent with their localization in the oolemma. In contrast, the homogeneous distribution of alpha(v) throughout the oocyte suggests the existence of cytoplasmic reservoirs of this protein in the oocyte.

NUT midline carcinoma mimicking a germ cell tumor: a case report

International Nuclear Information System (INIS)

Harada, Yohei; Koyama, Takafumi; Takeuchi, Kengo; Shoji, Kazufusa; Hoshi, Kazuei; Oyama, Yu

2016-01-01

NUT midline carcinoma (NMC) is a rare and highly aggressive malignancy. Although more information on NMC has been recently accumulating in the literature, most oncologists and pathologists remain unfamiliar with the clinical and pathologic features of this disease. The clinical features of NMC sometimes mimic those of other malignancies, and NMC can therefore be overlooked if the diagnosis is not suspected. We present the case of a young male with NMC arising in the mediastinum with elevated serum alpha-fetoprotein levels suggestive of an extragonadal nonseminomatous germ-cell tumor. A 28-year-old Japanese male presented with cough and left-sided chest pain for 6 weeks. The patient had a mediastinal tumor with metastases to the right lung, lymph nodes, and bones at initial presentation. Nonseminomatous germ cell tumor was suspected due to the young age, location of the tumors, and elevated serum alpha-fetoprotein. However, biopsy confirmed the diagnosis of NMC with immunohistochemistry. The tumor briefly responded to cytotoxic chemotherapy but subsequently progressed and became refractory to the chemotherapy regimen. External beam radiotherapy was administered with dramatic shrinkage of the tumor and a metabolic response on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) scan. However, the patient died 4.5 months after the diagnosis of NMC. Serum levels of alpha-fetoprotein may be elevated in patients with NMC. Regardless of the level of tumor markers, immunohistochemistry for NUT should be performed in cases of poorly differentiated carcinomas without glandular differentiation arising in the midline structures. 18 F-FDG PET/CT is useful for staging and assessing responses to therapy

The determination of $\\alpha_s$ by the ALPHA collaboration

CERN Document Server

Bruno, Mattia

2016-01-01

We review the ALPHA collaboration strategy for obtaining the QCD coupling at high scale. In the three-flavor effective theory it avoids the use of perturbation theory at $\\alpha > 0.2$ and at the same time has the physical scales small compared to the cutoff $1/a$ in all stages of the computation. The result $\\Lambda_\\overline{MS}^{(3)}=332(14)$~MeV is translated to $\\alpha_\\overline{MS}(m_Z)=0.1179(10)(2)$ by use of (high order) perturbative relations between the effective theory couplings at the charm and beauty quark "thresholds". The error of this perturbative step is discussed and estimated as $0.0002$.

RIA of alpha-fetoprotein in serum and amniotic fluid

Energy Technology Data Exchange (ETDEWEB)

Fingerova, H; Talas, M; Stroufova, A [Palackeho Univ., Olomouc (Czechoslovakia). Lekarska Fakulta; Santavy, J; Krikal, Z [Ustav pro Peci o Matku a Dite, Prague (Czechoslovakia)

1979-01-01

An own modification of the double antibody radioimmunoassay for AFP using /sup 125/I-labelled AFP as a tracer, rabbit anti-AFP obtained from SEVAC, Prague and precipitating antibodies prepared by the authors is described. The AFP levels measured in the serum and the amniotic fluid using the method were in agreement with those obtained by the means of the AFPK RIA kit by SORIN in the Institute for the Care of Mother and Child in Prague. The AFP concentrations found in the cord serum and the amniotic fluid were confirmed also by the rocket electroimmunoassay according to Laurell. The described AFP RIA seems suitable for the clinical application in prenatal screening for congenital malformations, in difficult pregnancies, in hepatology and the diagnosis and the evaluation of therapy of some human malignancies.

RIA of alpha-fetoprotein in serum and amniotic fluid

International Nuclear Information System (INIS)

Fingerova, H.; Talas, M.; Stroufova, A.

1979-01-01

An own modification of the double antibody radioimmunoassay for AFP using 125 I-labelled AFP as a tracer, rabbit anti-AFP obtained from SEVAC, Prague and precipitating antibodies prepared by the authors is described. The AFP levels measured in the serum and the amniotic fluid using the method were in agreement with those obtained by the means of the AFPK RIA kit by SORIN in the Institute for the Care of Mother and Child in Prague. The AFP concentrations found in the cord serum and the amniotic fluid were confirmed also by the rocket electroimmunoassay according to Laurell. The described AFP RIA seems suitable for the clinical application in prenatal screening for congenital malformations, in difficult pregnancies, in hepatology and the diagnosis and the evaluation of therapy of some human malignancies. (author)

The role of unexplained high serum alpha-fetoprotein (AFP and human chorionic gonadotropin (hCG levels in the second trimester to determine poor obstetric outcomes

Directory of Open Access Journals (Sweden)

Hümeyra Öztürk

2014-09-01

Full Text Available Objective: To investigate the relationship between gestational complications and high levels of maternal serum alfa-fetoprotein (MSAFP and/or beta human chorionic gonadotropin (hCG and to determine whether these markers are effective predictors of poor pregnancy outcomes. Materials and Methods: In this study, we enrolled a total of 679 women at 15-20 gestational weeks with MSAFP and hCG below or above 2.0 multiples of the median (MoM; of those, 200 women with normal MSAFP and hCG MoM formed the control group. Pre-eclampsia, intrauterine growth retardation (IUGR, preterm labor, preterm delivery, placental abruption, placenta previa, placenta accreta, preterm premature rupture of the membranes (PPROM, intrauterine fetal death, as well as neonatal and perinatal morbidity rates were evaluated. Results: A significant relationship was found between adverse pregnancy outcomes and abnormal elevation of hCG and AFP levels in the second trimester. In cases of isolated elevation of hCG, preeclampsia and preterm labor/spontaneous preterm birth rate were slightly higher than in the control group (p=0.043, p=0.015, while IUGR, PPROM, placental abruption, and intrauterine fetal death rates were all similar (p=0.063, p=0.318, p=1.00, p=0.556. In case having an elevation in both markers, increased rate of obstetric complications have been observed. A significant relationship was found between the high levels of maternal serum AFP and hCG MoM and poor pregnancy outcomes like preeclampsia, IUGR, PPROM, intrauterine fetal death (p=0.003, p=0.001, p=0.040, p=0.006. Conclusion: To our knowledge, up to now, no definitive follow-up and treatment protocols have been established for patients at increased risk. In light of these findings, it is recommended to inform and educate patients about the most likely signs and symptoms of complications, to make more often antenatal visits, to perform more frequent ultrasound examination (fetal growth, AFI, etc., NST, arterial

Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics.

OpenAIRE

Liebhaber, S A; Kan, Y W

1981-01-01

The alpha-globin polypeptide is encoded by two adjacent genes, alpha 1 and alpha 2. In the normal diploid state (alpha alpha/alpha alpha) all four alpha-globin genes are expressed. Loss or dysfunction of one or more of these genes leads to deficient alpha-globin production and results in alpha-thalassemia. We present a technique to differentially assess the steady-state levels of the alpha 1- and alpha-2-globin messenger RNA (mRNA) transcripts and thus delineate the relative level of expressi...

Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing V alpha 1 or V alpha 14 elements.

Science.gov (United States)

Mahotka, C; Hansen-Hagge, T E; Bartram, C R

1995-10-01

Human acute lymphoblastic leukemia cell lines represent valuable tools to investigate distinct steps of the complex regulatory pathways underlying T cell receptor recombination and expression. A case in point are V delta 2D delta 3 and subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic pre-B cells as well as in normal lymphopoiesis. The functional expression of these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by alternative splicing events. In this report we show that alternative splicing at cryptic splice donor sites within V elements is not a unique feature of hybrid TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR, alternatively spliced products were observed in TCR alpha recombinations containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral blood cells and thymocytes, the leukemia cell line JM expressing functional V alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA species.

ALPHA/AMPU, Radionuclide Radioactivity from Alpha Spectrometer Measurements

International Nuclear Information System (INIS)

Sill, D.S.

1990-01-01

1 - Description of program or function: The two computer programs, ALPHA and AMPU, take raw data obtained from alpha spectrometry and from these calculate activities and uncertainties of the radionuclides present in the sample. ALPHA determines activities of any alpha emitter in a sample that has been directly precipitated with NdF 3 . AMPU determines the Pu-239, Pu-238,and Am-241 activities using Pu-236 and Am-243 tracers. 2 - Method of solution: These programs propagate all random and systematic uncertainties, found anywhere in the experimental process, to the final result. The result is rounded and is in decimal agreement with the uncertainty. 3 - Restrictions on the complexity of the problem: In ALPHA, a chemical yield of 98% is assumed

Resting alpha activity predicts learning ability in alpha neurofeedback

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Wenya eNan

2014-07-01

Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

Intrahepatic chemoembolization in unresectable pediatric liver malignancies

International Nuclear Information System (INIS)

Arcement, C.M.; Towbin, R.B.; Meza, M.P.; Kaye, R.D.; Carr, B.I.; Gerber, D.A.; Mazariegos, G.V.; Reyes, J.

2000-01-01

Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy. Materials and methods. From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery. Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size. Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization. Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert

Intrahepatic chemoembolization in unresectable pediatric liver malignancies

Energy Technology Data Exchange (ETDEWEB)

Arcement, C.M.; Towbin, R.B.; Meza, M.P.; Kaye, R.D.; Carr, B.I. [Department of Radiology, Children' s Hospital of Pittsburgh, PA (United States); Gerber, D.A.; Mazariegos, G.V.; Reyes, J. [Department of Transplant Surgery, Children' s Hospital of Pittsburgh, PA (United States)

2000-11-01

Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy. Materials and methods. From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery. Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size. Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization. Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert

Hepatocellular carcinoma after radiofrequency ablation: recurrent pattern and influenting factor

Energy Technology Data Exchange (ETDEWEB)

Kang, Myong Jin; Nam, Kyung Jin; Oh, Jong Young; Choi, Jong Chul; Park, Byeong Ho; Lee, Yung Il [College of Medicine, DongA Univ., Pusan (Korea, Republic of)

2002-02-01

To evaluate patterns of recurrence and factors which influence them in radiofreqency (RF) ablation for the treatment of hepatocellular carcinoma (HCC). Between May 1999 and March 2000, 69 patients with 82 HCCs underwent RF ablation for complete necrosis. They were diagnosed by tissue biopsy or tumor marker, and the results of triphasic spiral CT. The indications were that nodular lesions were clearly visualized at sonography, less than 5 cm in size and less than four in number, and that patients had no history of previous treatment. Local therapeutic efficacy such as complete necrosis and marginal recurrence, and new lesions were evaluated by means of triphasic spiral CT performed at least six months after the completion of ablation. We then analyzed the correlation between local therapeutic efficacy and various influential factors such as tumor size, whether the tumor was attached to the portal vein, gross morphology, Child-Pugh classification, and {alpha}-fetoprotein level vefore the procedure, as well as the correlation between new lesions and influential factors which included the {alpha}-fetoprotein level before the procedure, Child-Pugh classification, and multiplicity per person. During a mean follow-up period of 8.95 (range, 6-14) months after RF ablation, the rate of complete necrosis and of marginal recurrence was 91% and 12%, respectively. When a tumor was larger and was attached to a large branch of the portal vien, the incidence of incomplete necrosis and marginal recurrence was greater. The occurrence rate of new lesion was 19.4%. When the {alpha}-fetoprotein level before the procedure was higher and a tumor was multiple in number, new lesions occurred more frequently. Sufficient knowledge of patterns of recurrence and the factors which influence them might improve the therapeutic effects of RF ablation in patients with HCC.

α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.

Directory of Open Access Journals (Sweden)

Yuan-Fei Peng

Full Text Available RNA interference (RNAi has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment.Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1 was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3 and non-HCC cell lines (L-02, Hela and SW1116 were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5 was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo.The AFP-miRNA system could silence target gene (Beclin 1 but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1 in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo.An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA was successfully established. The system provides a usable tool for HCC-specific RNAi

Evaluation of serum protein markers in diagnosis of hepatocellular carcinoma and carcinogenesis risk assessment in chronic liver disease patients

Directory of Open Access Journals (Sweden)

Essraa Adel Aly Aly Hegazy

2017-09-01

Full Text Available Objective: To assess the diagnostic value of the protein markers in both cirrhotic patients on top of hepatitis C virus (HCV and in hepatocellular carcinoma (HCC patients on top of HCV in comparison to normal controls. Methods: A total number of 100 subjects including HCC, cirrhotic patients on top of HCV and normal controls were subjected to serum protein markers analysis for alpha-fetoprotein, apolipoprotein A1, apolipoprotein A2, insulin like growth factor 1 and insulin like growth factor 1 receptor by western blotting technique. Results: It was found that alpha-fetoprotein alone could not be used as a screening test while apolipoprotein A2 as a serum marker could be used as a non invasive screening test to differentiate a case of HCC from cirrhotic HCV patient. The all four markers were able to discriminate normal persons from HCC and cirrhotic HCV patients effectively. Conclusions: We concluded that proteomics analysis being non invasive, rapid and sensitive is a novel gate that can serve in early diagnosis and screening of HCC and cirrhotic HCV patients

Analysis of Prognostic Factors After Yttrium-90 Radioembolization of Advanced Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Inarrairaegui, Mercedes; Martinez-Cuesta, Antonio; Rodriguez, Macarena; Bilbao, J. Ignacio

2010-01-01

Purpose: To analyze which patient-, tumor-, and treatment-related factors may influence outcome after 90 Y radioembolization ( 90 Y-RE) for hepatocellular carcinoma (HCC). Patients and Methods: Seventy-two consecutive patients with advanced HCC treated with 90 Y-RE were studied to detect which factors may have influenced response to treatment and survival. Results: Median overall survival was 13 months (95% confidence interval, 9.6-16.3 months). In univariate analysis, survival was significantly better in patients with one to five lesions (19 vs. 8 months, p = 0.001) and in patients with alpha-fetoprotein 52 UI/mL, and their survival in the multivariate analysis was significantly worse (hazard ratio, 4.7; 95% confidence interval, 13-1.73) (p = 0.002). Conclusions: Yttrium-90 radioembolization results in control of target lesions in the majority of patients with HCC but does not prevent the development of new lesions. Survival of patients treated with 90 Y-RE seems to depend largely on factors related to the aggressiveness of the disease (number of nodules, levels of alpha-fetoprotein, and presence of microscopic disease).

Prognostic factors in transcatheter arterial chemoembolization of hepatocellular carcinoma : analysis of more than 3 year survivors

Energy Technology Data Exchange (ETDEWEB)

Seo, Heung Suk [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)

1999-06-01

To determine which prognostic factors contribute to long-term survival after transcatheter arterial chemoembolization(TACE) of hepatocellular carcinoma. In 100 patients who expired within one year and 84 who survived or have survived for more than 3 years after TACE, prognostic factors were retrospectively evaluated. TACE was accomplished by hepatic arterial infusion of a suspension of Lipiodol and anticancer drugs(Mitomycin-C and Adriamycin), either alone or followed by gelfoam embolization. Fisher's exact test of probability was used to determine which prognostic factors were statistically significant. Statistically significant prognostic factors were as follows : Child classification(p<0.01), alpha-fetoprotein value(p<0.05), type of tumor(p<0.01), portal vein status(p<0.01), and vascularity of the tumor(p<0.05). HBsAg, tumor size, and method of chemoembolization were not statistically significant(p>0.05). The prognosis of patients with hepatocellular carcinoma treated by TACE was affected favorably by good liver function(Child classification A), low alpha-fetoprotein value, nodular or massive-type tumor, patent main and first-order portal vein, and hypervascular tumor.

Case of small hepatocellular carcinoma detected only by dynamic sequential computed tomography with table incrementation during arterial portography (DSCTI-AP)

Energy Technology Data Exchange (ETDEWEB)

Nishijima, Hiroshi; Ida, Masahiro; Takayama, Shigeru; Yanaghi, Sekiya; Kuroda, Yuzuru [Fukui Saiseikai Hospital (Japan)

1984-05-01

A 62 years old woman was admitted for liver cirrhosis with esophageal varix. Radionuclide liver scintigram, ultrasonogram, computed tomography and infusion hepatic angiography showed no signs of hepatocellular carcinoma (HCC). But DSCTI-AP detected a small solid mass lesion about 1.5cm in diameter in the right lobe of the liver. It was difficult to diagnose this lesion as HCC because of low titer of serum ..cap alpha../sub 1/-fetoprotein. After the esophageal transection for esophageal varices, she was followed as an outpatient. Six months later, serum ..cap alpha../sub 1/-fetoprotein was slightly elevated (130 ng/ml), and all imaging methods were carried out for the detection of HCC. Ultrasonogram, computed tomography, infusion hepatic angiography, DSCTI-AP all showed hepatocellular carcinoma, about 4.5cm in diameter in the same site where a small nodule was visualized by DSCTI-AP performed 5 months ago. This case suggests that DSCTI-AP is a sensitive and useful method for detection of some type of small liver cancer.

Molecular basis for nondeletion alpha-thalassemia in American blacks. Alpha 2(116GAG----UAG).

OpenAIRE

Liebhaber, S A; Coleman, M B; Adams, J G; Cash, F E; Steinberg, M H

1987-01-01

An American black woman was found to have the phenotype of moderately severe alpha-thalassemia normally associated with the loss of two to three alpha-globin genes despite an alpha-globin gene map that demonstrated the loss of only a single alpha-globin gene (-alpha/alpha alpha). Several individuals in her kindred with normal alpha-globin gene mapping studies (alpha alpha/alpha alpha) had mild alpha-thalassemia hematologic values consistent with the loss of one to two alpha-globin genes. Thes...

Occipital Encephalocele: A Case Report

OpenAIRE

Aslanova, Rakhshanda; Dolgun, Zehra Nihal; Turhan, Emrah; Ökten, Sabri Berkem

2015-01-01

Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the covering membranes through an opening in the skull. In this case we presented a 21-year old 20 weeks pregnant woman with fetal occipital encephalocele accompanying lemon sign, normal posterior fossa imaging and normal level of maternal serum alpha-fetoprotein (MSAFP).

Anti-pp,. cap alpha cap alpha. and p. cap alpha. elastic scattering at high energies and Chou-Yang conjecture

Energy Technology Data Exchange (ETDEWEB)

Saleem, M.; Fazal-e-Aleem; Rifique, M.

1987-03-01

The recent experimental measurements for anti-pp and ..cap alpha cap alpha.. elastic scattering at high energies have shown that the Chou-Yang conjecture regarding the relationship between the electromagnetic and the hadronic form factor of a particle is only an approximation. A new ansatz has been proposed to obtain hadronic form factors of proton and the ..cap alpha..-particle. These form factors have been used to explain the various characteristics of anti-pp, ..cap alpha cap alpha.. and p..cap alpha.. elastic scattering at high energies.

Contribution to the study of alpha-alpha interaction; Contribution a l'etude de l'interaction alpha - alpha

Energy Technology Data Exchange (ETDEWEB)

Darriulai, P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1965-03-01

Two sets of measurements of the {alpha}-{alpha} elastic scattering differential cross section are presented. The first set - angular distributions from 50 up to 120 MeV - shows two new resonances, 6{sup +} and 8{sup +}, at 25 and 57 MeV. Complex phase shifts are extracted from the data and a phenomenological potential is given. A description of the 3 {alpha}-particle 0{sup +} states in C{sup 12} is made with this interaction potential. The second set - excitation curves between 20 and 50 MeV - allows investigation of the Be{sup 8} level structure within this energy range - It identifies the 16.6 and 16.9 MeV states as 2{sup +}, but the rise of inelastic processes at higher energies makes further identification of spins and parities more and more difficult. (author) [French] Deux series de mesures de la section efficace differentielle de diffusion {alpha}-{alpha} sont presentees. La premiere - distributions angulaires entre 50 et 120 MeV - fait apparaitre deux nouvelles resonances, 6{sup +} et 8{sup +}, a 25 et 57 MeV d'excitation. Des dephasages complexes en sont extraits et un potentiel phenomenologique est presente. Une etude des etats 0{sup +} a parentage (3{alpha}) de {sup 12}C est faite a partir de ce potentiel. La seconde - courbes d'excitation s'etendant de 20 a 50 MeV - met en evidence la structure de {sup 8}Be dans cette region. Elle montre que les niveaux a 16,6 et 16,9 MeV sont des 2{sup +} mais l'importance des processus inelastiques rend difficile l'identification des niveaux d'excitation plus elevee. (auteur)

Hepatocellular carcinoma with extensive hepatic artery injury: transcatheter arterial chemoembolization through collaterals after coil embolizatoin of gastric arteries

International Nuclear Information System (INIS)

Kim, Gab Choul; Yoon, Hyun Ki; Hwang, Jae Cheol; Lee, Duck Hee; Song, Ho Young; Suh, Dong Jin; Lee, Yung Sang; Chung, Young Hwa; Sung, Gyu Bo; Ko, Ki Young

1999-01-01

To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) after coil embolization of the gastroduodenal artery in hepatocellular carcinoma cases with multiple collateral arteries caused by proper hepatic artery injury. Between March 1997 and November 1998, a prospective trial of transcatheter arterial chemoembolization (TACE) was performed through collaterals from the gastroduodenal artery of 31 hepatocellular carcinoma patients with extensive proper hepatic artery injury due to repeated TACE. Among this number, 16 (group A) underwent TACE after coil embolization of the right gastric and gastroduodenal artery. The other 15 patients (group B) underwent TACE without coil embolization. The two groups had the same TNM stage and Clild-Pugh status. During the follow-up period, group A underwent additional TACE 3.3 times, and group B 2.8 times. The therapeutic effect of TACE was evaluated with computed tomography and by measuring alpha-fetoprotein levels. Complications were evaluated by means of gastrofibroscopy, laboratory data, and evaluation of the patients' clinical symptoms. The results obtained after six months and one year were compared within and between each group. At six months follow-up, CT findings had improved or were unchanged in 11 patients(69 %) in group A, and four patients(27 %) in group B(p = 0.032). In ten patients in each group, the level of alpha-fetoprotein was above 200 ng/ml. Its level was decreased in five patients(50 %) and three patients(30 %), respectively. The six-month survival rate was 81 % (13/16) in group A and 67% (10/15) in group B (p 0.43), while the one-year survival figures for these two groups were 50 % (8/16) and 20 % (3/15), respectively(p = 0.135). In group A, the CT findings were steady in five out of eight patients(63 %), while in groupB, CT findings showed that tumors with increased alpha-fetoprotein levels had increased in size and/or number. In group A, it was found that in two (33 %) of six

Hepatocellular carcinoma with extensive hepatic artery injury: transcatheter arterial chemoembolization through collaterals after coil embolizatoin of gastric arteries

Energy Technology Data Exchange (ETDEWEB)

Kim, Gab Choul; Yoon, Hyun Ki; Hwang, Jae Cheol; Lee, Duck Hee; Song, Ho Young; Suh, Dong Jin; Lee, Yung Sang; Chung, Young Hwa; Sung, Gyu Bo [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Ko, Ki Young [Catholic Univ. College of Medicine, Seoul (Korea, Republic of)

1999-09-01

To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) after coil embolization of the gastroduodenal artery in hepatocellular carcinoma cases with multiple collateral arteries caused by proper hepatic artery injury. Between March 1997 and November 1998, a prospective trial of transcatheter arterial chemoembolization (TACE) was performed through collaterals from the gastroduodenal artery of 31 hepatocellular carcinoma patients with extensive proper hepatic artery injury due to repeated TACE. Among this number, 16 (group A) underwent TACE after coil embolization of the right gastric and gastroduodenal artery. The other 15 patients (group B) underwent TACE without coil embolization. The two groups had the same TNM stage and Clild-Pugh status. During the follow-up period, group A underwent additional TACE 3.3 times, and group B 2.8 times. The therapeutic effect of TACE was evaluated with computed tomography and by measuring alpha-fetoprotein levels. Complications were evaluated by means of gastrofibroscopy, laboratory data, and evaluation of the patients' clinical symptoms. The results obtained after six months and one year were compared within and between each group. At six months follow-up, CT findings had improved or were unchanged in 11 patients(69 %) in group A, and four patients(27 %) in group B(p = 0.032). In ten patients in each group, the level of alpha-fetoprotein was above 200 ng/ml. Its level was decreased in five patients(50 %) and three patients(30 %), respectively. The six-month survival rate was 81 % (13/16) in group A and 67% (10/15) in group B (p 0.43), while the one-year survival figures for these two groups were 50 % (8/16) and 20 % (3/15), respectively(p = 0.135). In group A, the CT findings were steady in five out of eight patients(63 %), while in groupB, CT findings showed that tumors with increased alpha-fetoprotein levels had increased in size and/or number. In group A, it was found that in two (33 %) of six

Investigation of the Pygmy Dipole Resonance in (alpha, alpha 'gamma) coincidence experiments

NARCIS (Netherlands)

Savran, D.; Babilon, M.; van den Berg, A. M.; Harakeh, M. N.; Hasper, J.; Wortche, H. J.; Zilges, A.

2007-01-01

We report on first results from experiments using the (alpha, alpha'gamma) reaction at E alpha = 136 MeV to investigate bound electric dipole (El) excitations building the so-called Pygmy Dipole Resonance (PDR) in the semi-magic nucleus Ce-140. The method of (alpha, alpha'gamma) allows the

Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.

Science.gov (United States)

Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R

2005-04-01

The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

Energy Technology Data Exchange (ETDEWEB)

Hayes, Matthew [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France); Oestlin, Goeran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Schaerer, Daniel [CNRS, IRAP, 14, avenue Edouard Belin, F-31400 Toulouse (France); Verhamme, Anne; Orlitova, Ivana [Geneva Observatory, University of Geneva, 51 Chemin des Maillettes, CH-1290 Versoix (Switzerland); Mas-Hesse, J. Miguel; Oti-Floranes, Hector [Centro de Astrobiologia (CSIC-INTA), Departamento de Astrofisica, POB 78, 28691 Villanueva de la Canada (Spain); Adamo, Angela [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Atek, Hakim [Laboratoire d' Astrophysique, Ecole Polytechnique Federale de Lausanne (EPFL), Observatoire, CH-1290 Sauverny (Switzerland); Cannon, John M. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Herenz, E. Christian [Leibniz-Institut fuer Astrophysik (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Kunth, Daniel [Institut d' Astrophysique de Paris, UMR 7095 CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France); Laursen, Peter, E-mail: matthew@astro.su.se [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark)

2013-03-10

We report on new imaging observations of the Lyman alpha emission line (Ly{alpha}), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly{alpha}, H{alpha}, and the far ultraviolet continuum. We show that Ly{alpha} is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, R{sub P20}, Ly{alpha} radii are larger than those of H{alpha} by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Ly{alpha}-to-FUV radii is 2.9. This suggests that much of the Ly{alpha} light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly{alpha} compared to H{alpha}, {xi}{sub Ly{alpha}} = R {sup Ly{alpha}}{sub P20}/R {sup H{alpha}}{sub P20}, we find {xi}{sub Ly{alpha}} to be uncorrelated with total Ly{alpha} luminosity. However, {xi}{sub Ly{alpha}} is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly{alpha} photons throughout the interstellar medium and drive a large extended Ly{alpha} halo.

Synthesis and antimicrobial evaluation of new 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinones.

Science.gov (United States)

Güzeldemirci, Nuray Ulusoy; Ilhan, Eser; Küçükbasmaci, Omer; Satana, Dilek

2010-01-01

New 4-thiazolidinone derivatives of benzilic acid (alpha,alpha-diphenyl-alpha-hydroxyacetic acid) have been synthesized and evaluated for antibacterial and antifungal activities. The reaction of 1- (alpha,alpha-diphenyl-alpha-hydroxy)acetyl-4-alkyl/arylthiosemicarbazides with ethyl 2-bromopropionate gave 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinone derivatives. Their antibacterial and antifungal activities were evaluated against S. aureus ATCC 29213, P. aeruginosa ATCC 27853, E. coli ATCC 25922, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, T. mentagrophytes var. erinacei NCPF 375, M. gypseum NCPF 580 and T. tonsurans NCPF 245. 3e, 3f, 3g and 3h showed the highest antibacterial activity. Particularly 3a and 3e showed the highest antifungal activities against C. parapsilosis ATCC 22019, T. tonsurans NCPF 245 and M. gypseum NCPF 580.

Lyman Alpha Control

CERN Document Server

Nielsen, Daniel Stefaniak

2015-01-01

This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

Increased α-Fetoprotein Predicts Steatosis among Patients with Chronic Hepatitis C Genotype 4

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Nasser Mousa

2012-01-01

Full Text Available Background. The prognostic importance of α-fetoprotein (AFP level elevation in patients with chronic hepatitis C and its clinical significance in steatosis associated with HCV infection remain to be determined. The present paper assessed clinical significance of elevated AFP in patients with CHC with and without steatosis. Methods. One hundred patients with CHC were divided into 50 patients with CHC and steatosis and 50 patients with CHC and no steatosis based on liver biopsy. Results. AFP was significantly increased in CHC with steatosis than patients without steatosis (P<0.001. Highly significant positive correlation was found between serum AFP and necroinflammation as well as the severity of fibrosis/cirrhosis and negative significant correlation with albumin level in chronic HCV with steatosis (P<0.001 but negative nonsignificant correlation with ALT and AST level (P≤0.778 and 0.398, respectively. Highly significant increase was found in chronic hepatitis patients with steatosis than CHC without steatosis regarding necroinflammation as well as the severity of fibrosis/cirrhosis and AFP (P<0.001. Conclusion. Patients with chronic HCV and steatosis have a higher AFP levels than those without steatosis. In chronic HCV with steatosis, elevated AFP levels correlated positively with HAI and negative significant correlation with albumin level.

Alpha-fetoprotein, HCV and HBV infections in Nigerian patients with ...

African Journals Online (AJOL)

The aim of this study was to determine the relationship of serum AFP with HBV and HCV infections among Nigerian patients with, Primary Hepato-Cellular Carcinoma . Forty-two Nigerian adults comprising of 3 groups – PHCC, Liver cirrhosis (LC) and Controls were recruited into the study. The findings showed that only nine ...

Alpha - Skew Pi - Armendariz Rings

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Areej M Abduldaim

2018-03-01

Full Text Available In this article we introduce a new concept called Alpha-skew Pi-Armendariz rings (Alpha - S Pi - ARas a generalization of the notion of Alpha-skew Armendariz rings.Another important goal behind studying this class of rings is to employ it in order to design a modern algorithm of an identification scheme according to the evolution of using modern algebra in the applications of the field of cryptography.We investigate general properties of this concept and give examples for illustration. Furthermore, this paperstudy the relationship between this concept and some previous notions related to Alpha-skew Armendariz rings. It clearly presents that every weak Alpha-skew Armendariz ring is Alpha-skew Pi-Armendariz (Alpha-S Pi-AR. Also, thisarticle showsthat the concepts of Alpha-skew Armendariz rings and Alpha-skew Pi- Armendariz rings are equivalent in case R is 2-primal and semiprime ring.Moreover, this paper proves for a semicommutative Alpha-compatible ringR that if R[x;Alpha] is nil-Armendariz, thenR is an Alpha-S Pi-AR. In addition, if R is an Alpha - S Pi -AR, 2-primal and semiprime ring, then N(R[x;Alpha]=N(R[x;Alpha]. Finally, we look forwardthat Alpha-skew Pi-Armendariz rings (Alpha-S Pi-ARbe more effect (due to their properties in the field of cryptography than Pi-Armendariz rings, weak Armendariz rings and others.For these properties and characterizations of the introduced concept Alpha-S Pi-AR, we aspire to design a novel algorithm of an identification scheme.

Feto portador de síndrome de turner e tetralogia de fallot associadas à elevação de alfafetoproteína materna Fetal turner syndrome and tetralogy of fallot associated with elevated maternal serum alpha-fetoprotein levels

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Eduardo Vieira Neto

1998-06-01

Full Text Available A síndrome de Turner fetal e suas complicações, a hidropisia e o higroma cístico, podem produzir alteração dos marcadores bioquímicos de soro materno inicialmente utilizados no rastreamento de síndrome de Down e de defeitos de tubo neural (DTN. Os autores relatam o caso de uma gestante de 37 anos, que foi rastreada para síndrome de Down e DTN no início do 2º trimestre. Foi constatado aumento da alfafetoproteína de soro materno (MSAFP e o rastreamento foi considerado positivo para DTN. Foi realizado exame ultra-sonográfico tridimensional, que não demonstrou nenhuma anormalidade fetal ou placentária, caracterizando o caso como elevação idiopática de MSAFP. No 3º trimestre, a gravidez evoluiu com acentuada oligoidrâmnia e alteração do fluxo uteroplacentário, obrigando à instituição de terapia com corticosteróides e parto cesáreo na 34ª semana gestacional. O concepto do sexo feminino foi encaminhado à UTI neonatal, onde foram diagnosticadas tetralogia de Fallot e síndrome de Turner. Esse caso incentivou os autores a rever a literatura sobre marcadores bioquímicos de soro materno na síndrome de Turner e nas malformações cardíacas congênitas. Ao final, propõe-se um protocolo para elevação idiopática de MSAFP.Turner syndrome and its complications, hydrops and cystic hygroma, can produce alterations in maternal serum biochemical markers used in screening for Down's syndrome and neural tube defects (NTD. The authors report the case of a 37-year-old pregnant woman, screened for Down's syndrome and NTD in the second trimester of pregnancy. The maternal serum alpha-fetoprotein (MSAFP level was increased and the test was considered screen positive for NTD. A three-dimensional ultrasound investigation was performed, but no fetal or placental anomalies were found, indicating a case of unexplained increased msafp. In the third trimester severe oligohydramnios and disturbances in uteroplacental arterial circulation

The tree-alpha Faddeev calculation on 12C bound states with a Pauli correct alpha-alpha potential

International Nuclear Information System (INIS)

Kamada, Hiroyuki; Oryu, Shinsho

1986-01-01

The three-alpha model of 12 C is investigated by the Faddeev formalism with the UIM alpha-alpha potential, in which the Pauli effect between two-alpha system was taken into account adequately. The potential can reproduce the on- and off-shell effects of the alpha-alpha interaction by the rank-4 separable type for the S-wave, the rank-3 one for the D-wave, and the rank-2 one for the G-wave, in which two of the ranks in the S-wave, and one in the D-wave are prepared to eliminate the Pauli forbidden states. We obtained three even states J π = 0 + , 2 + , 4 + , and two odd states 1 - , 3 - , below the alpha- 8 Be(0 + g.s) threshold energy. The even parity states gain larger binding energies than those which have been obtained by former Faddeev calculation with the rank-1 Kukulin and Neudatchin (KN) potential. On the other hand, for the odd parity states, we obtained smaller binding energies than the former one. It is found that our Faddeev calculation with the UIM potential does not miss any important low-lying levels of 12 C, in which any spurious states do not appear. (author)

Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

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Lee SH

2015-04-01

Full Text Available Sangheun Lee,1,* Beom Kyung Kim,2–5,* Seung Up Kim,2–5 Jun Yong Park,2–5 Do Young Kim,2–5 Sang Hoon Ahn,2–6 Kwang-Hyub Han2–6 1Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea; 2Department of Internal Medicine, 3Institute of Gastroenterology, 4Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea; 6Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea.   *These authors contributed equally to this work Background: It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC. We investigated whether the α-fetoprotein (AFP response is associated with survival in patients with advanced HCC treated with sorafenib. Methods: We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6–8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors. Results: The median overall survival (OS and progression-free survival (PFS were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR was identified in 5 patients (4.0%, stable disease (SD in 65 patients (51.6%, and progressive disease (PD in 57 patients (44.4%, respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response, together with Child-Pugh B, tumor diameter ≥10 cm, and portal vein invasion (all P<0.05, and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response, together with tumor diameter ≥10 cm and portal vein invasion (all P<0.05. SD or PR was more frequently found

Synthesis of tritiated 1-alpha-methadol and 1-alpha-acetylmethadol

Energy Technology Data Exchange (ETDEWEB)

Thang, D.C.; Nam, N.H.; Pontikis, R. (Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Fernand Widal, 75 - Paris (France)); Pichat, L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

1982-04-01

dl-Methadone was resolved by crystallization of its ammonium d- ..cap alpha.. -bromocamphor-..pi..-sulfonate salt to give d-methadone. The latter in ethyl acetate solution was reduced with tritium gas to 1-..cap alpha..-methadol /sup 3/H in presence of Adams platinum oxide at normal temperature and pressure. Acetylation of 1-..cap alpha..-carbinol hydrochloride by means of acetyl chloride afforded 1-..cap alpha..-acetylmethadol /sup 3/H, specific activity: 20 Ci/mMole. The positions and extent of tritium labelling were determined by /sup 3/H NMR spectroscopy.

Fucosylation Is a Promising Target for Cancer Diagnosis and Therapy

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Shinichiro Shinzaki

2012-01-01

Full Text Available Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. Recent advances in glycomics have identified several types of glyco-biomarkers containing fucosylation that are linked to certain types of cancer. Fucosylated alpha-fetoprotein (AFP is widely used in the diagnosis of hepatocellular carcinoma because it is more specific than alpha-fetoprotein. High levels of fucosylated haptoglobin have also been found in sera of patients with various carcinomas. We have recently established a simple lectin-antibody ELISA to measure fucosylated haptoglobin and to investigate its clinical use. Cellular fucosylation is dependent upon fucosyltransferase activity and the level of its donor substrate, guanosine diphosphate (GDP-fucose. GDP-mannose-4,6-dehydratase (GMDS is a key enzyme involved in the synthesis of GDP-fucose. Mutations of GMDS found in colon cancer cells induced a malignant phenotype, leading to rapid growth in athymic mice resistant to natural killer cells. This review describes the role of fucosylated haptoglobin as a cancer biomarker, and discusses the possible biological role of fucosylation in cancer development.

Bartter syndrome prenatal diagnosis based on amniotic fluid biochemical analysis.

Science.gov (United States)

Garnier, Arnaud; Dreux, Sophie; Vargas-Poussou, Rosa; Oury, Jean-François; Benachi, Alexandra; Deschênes, Georges; Muller, Françoise

2010-03-01

Bartter syndrome is an autosomic recessive disease characterized by severe polyuria and sodium renal loss. The responsible genes encode proteins involved in electrolyte tubular reabsorption. Prenatal manifestations, mainly recurrent polyhydramnios because of fetal polyuria, lead to premature delivery. After birth, polyuria leads to life-threatening dehydration. Prenatal genetic diagnosis needs an index case. The aim of this study was to analyze amniotic fluid biochemistry for the prediction of Bartter syndrome. We retrospectively studied 16 amniotic fluids of Bartter syndrome-affected fetuses diagnosed after birth, only six of them being genetically proven. We assayed total proteins, alpha-fetoprotein, and electrolytes and defined a Bartter index corresponding to the multiplication of total protein and of alpha-fetoprotein. Results were compared with two control groups matched for gestational age-non-Bartter polyhydramnios (n = 30) and nonpolyhydramnios (n = 60). In Bartter syndrome, we observed significant differences (p Bartter index (0.16, 0.82, and 1.0, respectively). No statistical difference was observed for electrolytes. In conclusion, Bartter syndrome can be prenatally suspected on amniotic fluid biochemistry (sensitivity 93% and specificity 100%), allowing appropriate management before and after birth.

Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and lactating rats.

Science.gov (United States)

Frye, Cheryl A; Walf, Alicia A

2004-07-01

The 5alpha-reduced metabolite of progesterone (P), 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), may mediate progestins' effects to reduce depressive behavior of female rats in part through actions in the hippocampus. To investigate, forced swim test behavior and plasma and hippocampal progestin levels were assessed in groups of rats expected to differ in their 3alpha,5alpha-THP levels due to endogenous differences (pregnant and postpartum), administration of a 5alpha-reductase inhibitor (finasteride; 50 mg/kg sc), and/or gestational stress [prenatal stress (PNS)], an animal model of depression. Pregnant rats had higher plasma and hippocampal 3alpha,5alpha-THP levels and less depressive behavior (decreased immobility, increased struggling and swimming) in the forced swim test than did postpartum rats. Finasteride, compared to vehicle-administration, reduced plasma and hippocampal 3alpha,5alpha-THP levels and increased depressive behavior (increased immobility, decreased struggling and swimming). PNS was associated with lower hippocampal, but not plasma, 3alpha,5alpha-THP levels and increased swimming compared to that observed in control rats. Together, these data suggest that 3alpha,5alpha-THP in the hippocampus may mediate antidepressive behavior of female rats.

The heavy quarkonium spectrum at order $m\\alpha_{s}^{5}\\ln\\alpha_{s}$

CERN Document Server

Brambilla, Nora; Soto, Joan; Vairo, Antonio

1999-01-01

We compute the complete leading-log terms of the next-to-next-to-next-to-leading-order corrections to potential NRQCD. As a by-product we obtain the leading logs at $O(m\\alpha_s^5)$ in the heavy quarkonium spectrum. These leading logs, when $\\Lambda_{QCD} \\ll m\\alpha_s^2$, give the complete $O(m\\alpha_s^5 \\ln \\alpha_s)$ corrections to the heavy quarkonium spectrum.

Crystalline anhydrous {alpha},{alpha}-trehalose (polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose: A calorimetric study

Energy Technology Data Exchange (ETDEWEB)

Pinto, Susana S. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: susanapinto@ist.utl.pt; Diogo, Herminio P. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: hdiogo@ist.utl.pt; Moura-Ramos, Joaquim J. [Centro de Quimica-Fisica Molecular, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: mouraramos@ist.utl.pt

2006-09-15

The mean values of the standard massic energy of combustion of crystalline anhydrous {alpha},{alpha}-trehalose (C{sub 12}H{sub 22}O{sub 11}, polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose (C{sub 12}H{sub 26}O{sub 13}) measured by static-bomb combustion calorimetry in oxygen, at the temperature T=298.15K, are {delta}{sub c}u{sup o}=-(16434.05+/-4.50)J.g{sup -1} and {delta}{sub c}u{sup o}=-(14816.05+/-3.52)J.g{sup -1}, respectively. The standard (p{sup o}=0.1MPa) molar enthalpy of formation of these compounds were derived from the corresponding standard molar enthalpies of combustion, respectively, {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 22}O{sub 11},cr)=-(2240.9+/-3.9)kJ.mol{sup -1}, and {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 26}O{sub 13},cr)=-(2832.6+/-3.6)kJ.mol{sup -1}. The values of the standard enthalpies of formation obtained in this work, together with data on enthalpies of solution at infinite dilution ({delta}{sub sol}H{sup {approx}}) for crystalline dihydrate and amorphous anhydrous trehalose, allow a better insight on the thermodynamic description of the trehalose system which can provide, together with the future research on the subject, a contribution for understanding the metabolism in several organisms, as well as the phase transition between the different polymorphs.

Energy dependence of event shapes and of $\\alpha_s$ at LEP 2

CERN Document Server

Abreu, P; Adye, T; Adzic, P; Albrecht, Z; Alderweireld, T; Alekseev, G D; Alemany, R; Allmendinger, T; Allport, P P; Almehed, S; Amaldi, Ugo; Amapane, N; Amato, S; Anassontzis, E G; Andersson, P; Andreazza, A; Andringa, S; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barbiellini, Guido; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Beillière, P; Belokopytov, Yu A; Belous, K S; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Bizouard, M A; Bloch, D; Blom, H M; Bonesini, M; Bonivento, W; Boonekamp, M; Booth, P S L; Borgland, A W; Borisov, G; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Boyko, I; Bozovic, I; Bozzo, M; Branchini, P; Brenke, T; Brenner, R A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschbeck, Brigitte; Buschmann, P; Cabrera, S; Caccia, M; Calvi, M; Camporesi, T; Canale, V; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Chapkin, M M; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cieslik, K; Collins, P; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crépé, S; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Davenport, Martyn; Da Silva, W; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Min, A; De Paula, L S; Dijkstra, H; Di Ciaccio, Lucia; Dolbeau, J; Doroba, K; Dracos, M; Drees, J; Dris, M; Duperrin, A; Durand, J D; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Ellert, M; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fanourakis, G K; Fassouliotis, D; Fayot, J; Feindt, Michael; Fenyuk, A; Ferrari, P; Ferrer, A; Ferrer-Ribas, E; Ferro, F; Fichet, S; Firestone, A; Flagmeyer, U; Föth, H; Fokitis, E; Fontanelli, F; Franek, B J; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gamblin, S; Gandelman, M; García, C; Gaspar, C; Gaspar, M; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Ghodbane, N; Gil, I; Glege, F; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; González-Caballero, I; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Grahl, J; Graziani, E; Green, C; Grimm, H J; Gris, P; Grosdidier, G; Grzelak, K; Günther, M; Guy, J; Hahn, F; Hahn, S; Haider, S; Hallgren, A; Hamacher, K; Hansen, J; Harris, F J; Hedberg, V; Heising, S; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Heuser, J M; Higón, E; Holmgren, S O; Holt, P J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hughes, G J; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, P E; Joram, C; Juillot, P; Kapusta, F; Karafasoulis, K; Katsanevas, S; Katsoufis, E C; Keränen, R; Kersevan, Borut P; Khomenko, B A; Khovanskii, N N; Kiiskinen, A P; King, B J; Kinvig, A; Kjaer, N J; Klapp, O; Klein, H; Kluit, P M; Kokkinias, P; Koratzinos, M; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Krammer, Manfred; Kriznic, E; Krstic, J; Krumshtein, Z; Kubinec, P; Kurowska, J; Kurvinen, K L; Lamsa, J; Lane, D W; Langefeld, P; Lapin, V; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Leinonen, L; Leisos, A; Leitner, R; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Lethuillier, M; Libby, J; Liko, D; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; Lopes, J H; López, J M; López-Fernandez, R; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Mahon, J R; Maio, A; Malek, A; Malmgren, T G M; Maltezos, S; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Masik, J; Mazzucato, F; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; McPherson, G; Meroni, C; Meyer, W T; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Moch, M; Møller, R; Mönig, K; Monge, M R; Moreau, X; Morettini, P; Morton, G A; Müller, U; Münich, K; Mulders, M; Mulet-Marquis, C; Muresan, R; Murray, W J; Muryn, B; Myatt, Gerald; Myklebust, T; Naraghi, F; Nassiakou, M; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Némécek, S; Neufeld, N; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nikolenko, M; Nomokonov, V P; Normand, Ainsley; Nygren, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Orazi, G; Österberg, K; Ouraou, A; Paganoni, M; Paiano, S; Pain, R; Paiva, R; Palacios, J; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Pegoraro, M; Peralta, L; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Phillips, H T; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Ratoff, P N; Read, A L; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Reinhardt, R; Renton, P B; Resvanis, L K; Richard, F; Rídky, J; Rinaudo, G; Røhne, O M; Romero, A; Ronchese, P; Rosenberg, E I; Rosinsky, P; Roudeau, Patrick; Rovelli, T; Royon, C; Ruhlmann-Kleider, V; Ruiz, A; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sampsonidis, D; Sannino, M; Schneider, H; Schwemling, P; Schwering, B; Schwickerath, U; Schyns, M A E; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Sekulin, R L; Shellard, R C; Sheridan, A; Siebel, M; Simard, L C; Simonetto, F; Sissakian, A N; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Sopczak, André; Sosnowski, R; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stanic, S; Stevenson, K; Stocchi, A; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tegenfeldt, F; Terranova, F; Thomas, J; Timmermans, J; Tinti, N; Tkatchev, L G; Todorova-Nová, S; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tzamarias, S; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; Van der Velde, C; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Van Lysebetten, A; Van Vulpen, I B; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Verzi, V; Vilanova, D; Vitale, L; Vlasov, E; Vodopyanov, A S; Vollmer, C F; Voulgaris, G; Vrba, V; Wahlen, H; Walck, C; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G R; Winter, M; Witek, M; Wolf, G; Yi, J; Yushchenko, O P; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zucchelli, G C; Zumerle, G

1999-01-01

Infrared and collinear safe event shape distributions and their mean values are determined using the data taken at ve di erent centre of mass energies above $M_Z$ with the DELPHI detector at LEP. From the event shapes, the strong coupling $\\alpha_s$ is extracted in $O(\\alpha^2_s)$, NLLA and a combined scheme using hadronisation corrections evaluated with fragmentation model generators as well as using an analytical power ansatz. Comparing these measurements to those obtained at MZ, the energy dependence (running) of $\\alpha_s$ is accessible. The logarithmic energy slope of the inverse strong coupling is measured to be $d\\alpha_{s}^{-1}/d log(E_{cm}) = 1.39 \\pm 0.34(stat) \\pm 0.17(syst)$, in good agreement with the QCD expectation of 1.27.

Alpha Blockers

Science.gov (United States)

... quickly, but their effects last only a few hours. Long-acting medications take longer to work, but their effects last longer. Which alpha blocker is best for you depends on your health and the condition being treated. Alpha blockers are ...

Uranium analysis in Cypriot groundwaters by total alpha-radiometry and alpha-spectroscopy

International Nuclear Information System (INIS)

Efstathiou, Maria; Kiliari, Tasoula; Pashalidis, Ioannis

2011-01-01

Two different alpha-radiometric methods (e.g. alpha-spectroscopy and alpha-particle counting) have been applied to the determination of uranium in Cypriot groundwater samples after separation of the radionuclides by cation exchange using Chelex-100 and its electrodeposition on stainless steel planchettes. The data obtained were compared to show the advantages and disadvantages of the two radiometric methods, determine the alpha-radioactivity concentration and the radiation dose associated with the use of the studied groundwaters. Calibration of the methods was performed by means of uranium standard solutions and the corresponding data were used to evaluate linear range, detector efficiency, detection limits, value of the information obtained, and time of analysis of the methods. Comparison of the data obtained from calibration and natural sample measurements has shown that alpha-particle counting with a simple alpha-radiometer (equipped with a semiconductor detector) may offer only an activity value and not detailed information about the isotopic composition but it is the fastest method and the method of choice if only a screening method for the alpha-radioactivity measurement is required. Based on the alpha-radioactivity data, the corresponding radiation dose was estimated for situations where the groundwaters are used for drinking water purposes.

The Immunogenicity of the Tumor-Associated Antigen α-Fetoprotein Is Enhanced by a Fusion with a Transmembrane Domain

Directory of Open Access Journals (Sweden)

Lucile Tran

2012-01-01

Full Text Available Aim. To investigate the ability of recombinant modified vaccinia virus Ankara (rMVA vector to induce an immune response against a well-tolerated self-antigen. Methods. rMVA vectors expressing different form of α-fetoprotein (AFP were produced and characterized. Naïve mice were vaccinated with MVA vectors expressing the AFP antigen in either a secreted, or a membrane-bound, or an intracellular form. The immune response was monitored by an IFNΓ ELISpot assay and antibody detection. Results. Vaccination with the membrane-associated form of AFP induced a stronger CD8+ T-cell response compared to the ones obtained with the MVA encoding the secreted or the intracellular forms of AFP. Moreover, the vaccination with the membrane-bound AFP elicited the production of AFP-specific antibodies. Conclusions. The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen.

Influence of fast alpha diffusion and thermal alpha buildup on tokamak reactor performance

International Nuclear Information System (INIS)

Uckan, N.A.; Tolliver, J.S.; Houlberg, W.A.; Attenberger, S.E.

1988-01-01

The effect of fast alpha diffusion and thermal alpha accumulation on the confinement capability of a candidate Engineering Test Reactor plasma (Tokamak Ignition/Burn Experimental Reactor) in achieving ignition and steady-state driven operation has been assessed using both global and 1-1/2-dimensional transport models. Estimates are made of the threshold for radial diffusion of fast alphas and thermal alpha buildup. It is shown that a relatively low level of radial transport, when combined with large gradients in the fast alpha density, leads to a significant radial flow with a deleterious effect on plasma performance. Similarly, modest levels of thermal alpha concentration significantly influence the ignition and steady-state burn capability

[Age-related change in the alpha-tocopherolquinone/alpha-tocopherol ratio in the rat erythrocyte membrane].

Science.gov (United States)

Yanagawa, K; Takeda, H; Matsumiya, T; Takasaki, M

1999-05-01

alpha-Tocopherol (alpha-Toc), a lipophilic phenolic antioxidant that is localized mainly in the biomembrane, protects cells against oxidation-associated cytotoxicity by prevention of membrane lipid peroxidation, maintenance of the redox balance intracellular thiols and stabilization of the membrane structure. We investigated the age-related changes in redox dynamics of alpha-Toc in plasma and erythrocyte membrane of an elderly (66 weeks old) and young group (10 weeks old). Total, alpha-, beta + gamma-, delta-Toc and alpha-tocopherolquinone (alpha-TocQ) in plasma and erythrocyte membrane were determined by high-performance liquid chromatography (HPLC) with a series of multiple coulometric working electrodes (CWE). Rat venous blood sample was divided into plasma and erythrocyte layers by centrifugation, and then erythrocyte membrane sample was prepared according to the method of Dodge et al. under a stream of nitrogen. In plasma, total and alpha-Toc concentrations were increased, and beta + gamma-, delta-Toc and alpha-TocQ concentrations were decreased age-dependently. In the erythrocyte membrane, total, alpha-TocQ concentrations and three fractions of tocopherols decreased age-dependently. Also, a decrease in the alpha-TocQ/alpha-Toc ratio in erythrocyte membrane was observed in the elderly group. These findings suggest that the alpha-Toc uptake in erythrocyte membrane and utilization rate of alpha-Toc in erythrocyte membrane decline age-dependently. This decline may promote membrane lipid peroxidation. alpha-Toc redox dynamics in erythrocyte membrane were useful to investigate the pathophysiology of aging mechanisms related to oxidative stress.

Identification of a novel bile acid in swans, tree ducks, and geese: 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid.

Science.gov (United States)

Kakiyama, Genta; Iida, Takashi; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio; Hagey, Lee R; Schteingart, Claudio D; Hofmann, Alan F

2006-07-01

By HPLC, a taurine-conjugated bile acid with a retention time different from that of taurocholate was found to be present in the bile of the black-necked swan, Cygnus melanocoryphus. The bile acid was isolated and its structure, established by (1)H and (13)C NMR and mass spectrometry, was that of the taurine N-acyl amidate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid. The compound was shown to have chromatographic and spectroscopic properties that were identical to those of the taurine conjugate of authentic 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid, previously synthesized by us from ursodeoxycholic acid. By HPLC, the taurine conjugate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid was found to be present in 6 of 6 species in the subfamily Dendrocygninae (tree ducks) and in 10 of 13 species in the subfamily Anserinae (swans and geese) but not in other subfamilies in the Anatidae family. It was also not present in species from the other two families of the order Anseriformes. 3alpha,7alpha,15alpha-Trihydroxy-5beta-cholan-24-oic acid is a new primary bile acid that is present in the biliary bile acids of swans, tree ducks, and geese and may be termed 15alpha-hydroxy-chenodeoxycholic acid.

Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt

Science.gov (United States)

Abdel-Moneim, Adel; Morsy, Basant M.; Mahmoud, Ayman M.; Abo-Seif, Mohamed A.; Zanaty, Mohamed I.

2013-01-01

Hepatitis C is a major global health burden and Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. The current study was designed to evaluate the beneficial therapeutic effects of ethanolic extracts of Nigella sativa, Zingiber officinale and their mixture in Egyptian HCV patients. Sixty volunteer patients with proven HCV and fifteen age matched healthy subjects were included in this study. Exclusion criteria included patients on interferon alpha (IFN-α) therapy, infection with hepatitis B virus, drug-induced liver diseases, advanced cirrhosis, hepatocellular carcinoma (HCC) or other malignancies, blood picture abnormalities and major severe illness. Liver function enzymes, albumin, total bilirubin, prothrombin time and concentration, international normalized ratio, alpha fetoprotein and viral load were all assessed at baseline and at the end of the study. Ethanolic extracts of Nigella sativa and Zingiber officinale were prepared and formulated into gelatinous capsules, each containing 500 mg of Nigella sativa and/or Zingiber officinale. Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. Both extracts as well as their mixture significantly ameliorated the altered viral load, alpha fetoprotein, liver function parameters; with more potent effect for the combined therapy. In conclusion, administration of Nigella sativa and/or Zingiber officinale ethanolic extracts to HCV patients exhibited potential therapeutic benefits via decreasing viral load and alleviating the altered liver function, with more potent effect offered by the mixture. PMID:27298610

Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt.

Science.gov (United States)

Abdel-Moneim, Adel; Morsy, Basant M; Mahmoud, Ayman M; Abo-Seif, Mohamed A; Zanaty, Mohamed I

2013-01-01

Hepatitis C is a major global health burden and Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. The current study was designed to evaluate the beneficial therapeutic effects of ethanolic extracts of Nigella sativa, Zingiber officinale and their mixture in Egyptian HCV patients. Sixty volunteer patients with proven HCV and fifteen age matched healthy subjects were included in this study. Exclusion criteria included patients on interferon alpha (IFN-α) therapy, infection with hepatitis B virus, drug-induced liver diseases, advanced cirrhosis, hepatocellular carcinoma (HCC) or other malignancies, blood picture abnormalities and major severe illness. Liver function enzymes, albumin, total bilirubin, prothrombin time and concentration, international normalized ratio, alpha fetoprotein and viral load were all assessed at baseline and at the end of the study. Ethanolic extracts of Nigella sativa and Zingiber officinale were prepared and formulated into gelatinous capsules, each containing 500 mg of Nigella sativa and/or Zingiber officinale. Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. Both extracts as well as their mixture significantly ameliorated the altered viral load, alpha fetoprotein, liver function parameters; with more potent effect for the combined therapy. In conclusion, administration of Nigella sativa and/or Zingiber officinale ethanolic extracts to HCV patients exhibited potential therapeutic benefits via decreasing viral load and alleviating the altered liver function, with more potent effect offered by the mixture.

Storage of the complement components C4, C3, and C 3-activator in the human liver as PAS-negative globular hyaline bodies.

Science.gov (United States)

Storch, W; Riedel, H; Trautmann, B; Justus, J; Hiemann, D

1982-01-01

Liver biopsies of a 58-year-old clinically healthy patient with a hepatomegaly and intracisternal PAS-negative globular hyaline bodies were immunofluorescent-optically examined for the content of the complement components C 1 q, C 4, C 9, C 1-inactivator, C 3-activator. Further examinations were performed for fibrinogen, IgG, IgA, IgM, IgD, IgE, L-chain (type chi and lambda), alpha 1-antitrypsin, alpha 1-fetoprotein, alpha 1- and alpha 2-glycoprotein, cholinesterase, ceruloplasmin, myoglobin, hemopexin, HBsAg and HBsAg. Th inclusion bodies reacted with antisera against the complement components C 4, C 3 and C 3-activator, as also identified by double immunofluorescence. Probably this is a disturbance of the protein metabolism of the liver cell with abnormal complement storage in the presence of normal total complement and normal complement components in the serum.

Buffett's Alpha

DEFF Research Database (Denmark)

Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

Sterol synthesis. A novel reductive rearrangement of an alpha,beta-unsaturated steroidal epoxide; a new chemical synthesis of 5alpha-cholest-8(14)-en-3beta, 15alpha-diol.

Science.gov (United States)

Parish, E J; Schroepfer, G J

1977-04-01

Reduction of 3beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with either lithium triethylboro-hydride or lithium aluminum hydride (4 molar excess) gave 5-alpha-cholest-8(14)-en-3beta,15alpha-diol in high yield. Reduction of the epoxy ester with lithium triethylborodeuteride or lithium aluminum deuteride (4 molar excess) gave [7alpha-2-H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol. Reduction of 2beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with a large excess (24 molar excess) of lithium aluminum hydride gave, in addition to the expected 5alpha-cholest-8(14)-en-3beta,15alpha-diol, a significant yield (33%) of 5alpha-cholest-8(14)-en-3beta-o1. Reduction of the epoxy ester with a large excess (24 molar excess) of lithium aluminum deuteride gave [7alpha-2H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol and 5alpha-cholest-8(14)-en-3beta-o1 which contained two atoms of stably bound deuterium.

Posterior midline cervical fetal cystic hygroma.

Directory of Open Access Journals (Sweden)

Oak S

1992-04-01

Full Text Available Posterior midline cervical cystic hygromas (PMC are frequently found associated with chromosomal aberrations and usually do not survive. The present report illustrates diagnosis of this condition by sonography in an 18 weeks old fetus and an amniocentesis revealed 45 x0 karyotype and increased concentration of alpha-fetoproteins. Pregnancy was terminated in view of Turner′s syndrome. The etiology and natural history of the condition is reviewed.

Bioelectromagnetics 2005

Science.gov (United States)

2006-08-14

Ireland P-A-154 STUDENT POWER FREQUENCY MAGNETIC FIELDS BLOCK MELATONIN-INDUCED CHANGES IN ALPHA-FETOPROTEIN AND ALBUMIN IN HUMAN HEPATOCARCINOMA ...effects of a physiological dose of MEL on the human hepatocarcinoma line HepG2, and to determine whether the induced cellular response is affected...currently used as a tumor-marker in the prognosis of different cancer types, including hepatocarcinoma . As for Albumin, it expresses in normal

Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

Science.gov (United States)

Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

2009-10-15

Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

Drugs interacting with alpha adrenoceptors

NARCIS (Netherlands)

van Zwieten, P. A.

1989-01-01

Alpha adrenoceptors should be divided into various subtypes, comprising pre/postsynaptic and alpha 1/alpha 2-subpopulations, respectively. This classification implicates important functional differences between the various alpha-receptor subtypes, including certain differences in signal transduction

Alpha-in-air monitor for continuous monitoring based on alpha to beta ratio

International Nuclear Information System (INIS)

Somayaji, K.S.; Venkataramani, R.; Swaminathan, N.; Pushparaja

1997-01-01

Measurement of long-lived alpha activity collected on a filter paper in continuous air monitoring of ambient working environment is difficult due to interference from much larger concentrations of short-lived alpha emitting daughter products of 222 Rn and 220 Rn. However, the ratio between the natural alpha and beta activity is approximately constant and this constancy of the ratio is used to discriminate against short-lived natural radioactivity in continuous air monitoring. Detection system was specially designed for the purpose of simultaneous counting of alpha and beta activity deposited on the filter paper during continuous monitoring. The activity ratios were calculated and plotted against the monitoring duration up to about six hours. Monitoring was carried out in three facilities with different ventilation conditions. Presence of any long-lived alpha contamination on the filter paper results in increase in the alpha to beta ratio. Long-lived 239 Pu contamination of about 16 DAC.h could be detected after about 45 minutes of commencement of the sampling. The experimental results using prototype units have shown that the approach of using alpha to beta activity ratio method to detect long-lived alpha activity in the presence of short-lived natural activity is satisfactory. (author)

Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

Science.gov (United States)

Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

2015-01-01

The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

Long-range alpha detector

International Nuclear Information System (INIS)

MacArthur, D.W.; McAtee, J.L.

1991-01-01

Historically, alpha-particle and alpha-contamination detectors have been limited by the very short range of alpha particles in air and by relatively poor sensitivity even if the particles are intercepted. Alpha detectors have had to be operated in a vacuum or in close proximity to the source if reasonable efficiency is desired. Alpha particles interact with the ambient air, producing ionization in the air at the rate of ∼30,000 ion pairs per mega-electron-volt of alpha energy. These charges can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions. The long-range alpha detector (LRAD) offers several advantages over more traditional alpha detectors. First and foremost, it can operate efficiently even if the contamination is not easily accessible. Second, ions generated by contamination in crevices and other unmonitorable locations can be detected if the airflow penetrates those areas. Third, all of the contamination on a large surface will generate ions that can be detected in a single detector; hence, the detector's sensitivity to distributed sources is not limited by the size of the probe. Finally, a simple ion chamber can detect very small electric currents, making this technique potentially quite sensitive

Treatment of alpha bearing wastes

International Nuclear Information System (INIS)

1988-01-01

This report deals with the current state of the art of alpha waste treatment, which is an integral part of the overall nuclear waste management system. The International Atomic Energy Agency (IAEA) defines alpha bearing waste as 'waste containing one or more alpha emitting radionuclides, usually actinides, in quantities above acceptable limits'. The limits are established by national regulatory bodies. The limits above which wastes are considered as alpha contaminated refer to the concentrations of alpha emitters that need special consideration for occupational exposures and/or potential safety, health, or environmental impact during one or more steps from generation through disposal. Owing to the widespread use of waste segregation by source - that is, based upon the 'suspect origin' of the material - significant volumes of waste are being handled as alpha contaminated which, in fact, do not require such consideration by reason of risk or environmental concern. The quantification of de minimis concepts by national regulatory bodies could largely contribute to the safe reduction of waste volumes and associated costs. Other factors which could significantly contribute to the reduction of alpha waste arisings are an increased application of assaying and sorting, instrumentation and the use of feedback mechanisms to control or modify the processes which generate these wastes. Alpha bearing wastes are generated during fabrication and reprocessing of nuclear fuels, decommissioning of alpha contaminated facilities, and other activities. Most alpha wastes are contact handled, but a small portion may require shielding or remote handling because of high levels of neutron (n), beta (β), or gamma (γ) emissions associated with the waste material. This report describes the sources and characteristics of alpha wastes and strategies for alpha waste management. General descriptions of treatment processes for solid and liquid alpha wastes are included. 71 refs, 14 figs, 9 tabs

Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors

Directory of Open Access Journals (Sweden)

Kuiyu Zhu

2015-08-01

Full Text Available Primary hepatic carcinoma (PHC is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP and carcinoembryonic antigen (CEA have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs with polydimethylsiloxane (PDMS microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.

New ALPHA-2 magnet

CERN Multimedia

Anaïs Schaeffer

2012-01-01

On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

ALPHA-2: the sequel

CERN Multimedia

Katarina Anthony

2012-01-01

While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.   The ALPHA team lower the new superconducting solenoid magnet into place. The ALPHA collaboration is working at full speed to complete the ALPHA-2 set-up for mid-November – this will give them a few weeks of running before the AD shutdown on 17 December. “We really want to get some experience with this device this year so that, if we need to make any changes, we will have time during the long shutdown in which to make them,” says Jeffrey Hangst, ALPHA spokesperson. “Rather than starting the 2014 run in the commissioning stage, we will be up and running from the get go.&...

Technical Basis for the Use of Alpha Absorption Corrections on RCF Gross Alpha Data

International Nuclear Information System (INIS)

Ceffalo, G.M.

1999-01-01

This document provides the supporting data and rationale for making absorption corrections to gross alpha data to correct alpha data for loss due to absorption in the sample matrix. For some time there has been concern that the gross alpha data produced by the Environmental Restoration Contractor Radiological Counting Facility, particularly gross alpha analysis on soils, has been biased toward low results, as no correction for self-absorption was applied to the counting data. The process was investigated, and a new methodology for alpha self-absorption has been developed

Cloning, expression, and mapping of allergenic determinants of alphaS1-casein, a major cow's milk allergen.

Science.gov (United States)

Schulmeister, Ulrike; Hochwallner, Heidrun; Swoboda, Ines; Focke-Tejkl, Margarete; Geller, Beate; Nystrand, Mats; Härlin, Annika; Thalhamer, Josef; Scheiblhofer, Sandra; Keller, Walter; Niggemann, Bodo; Quirce, Santiago; Ebner, Christoph; Mari, Adriano; Pauli, Gabrielle; Herz, Udo; Valenta, Rudolf; Spitzauer, Susanne

2009-06-01

Milk is one of the first components introduced into human diet. It also represents one of the first allergen sources, which induces IgE-mediated allergies in childhood ranging from gastrointestinal, skin, and respiratory manifestations to severe life-threatening manifestations, such as anaphylaxis. Here we isolated a cDNA coding for a major cow's milk allergen, alphaS1-casein, from a bovine mammary gland cDNA library with allergic patients' IgE Abs. Recombinant alphaS1-casein was expressed in Escherichia coli, purified, and characterized by circular dichroism as a folded protein. IgE epitopes of alphaS1-casein were determined with recombinant fragments and synthetic peptides spanning the alphaS1-casein sequence using microarrayed components and sera from 66 cow's milk-sensitized patients. The allergenic activity of ralphaS1-casein and the alphaS1-casein-derived peptides was determined using rat basophil leukemia cells transfected with human FcepsilonRI, which had been loaded with the patients' serum IgE. Our results demonstrate that ralphaS1-casein as well as alphaS1-casein-derived peptides exhibit IgE reactivity, but mainly the intact ralphaS1-casein induced strong basophil degranulation. These results suggest that primarily intact alphaS1-casein or larger IgE-reactive portions thereof are responsible for IgE-mediated symptoms of food allergy. Recombinant alphaS1-casein as well as alphaS1-casein-derived peptides may be used in clinical studies to further explore pathomechanisms of food allergy as well as for the development of new diagnostic and therapeutic strategies for milk allergy.

Hepatocellular carcinoma: a retrospective analysis of 118 cases

International Nuclear Information System (INIS)

Aman-ur-Rehman; Murad, S.

2002-01-01

Objective: This study aimed at documenting the spectrum of clinico pathological variations in hepatocellular carcinoma (HCC). Design: It was a retrospective study. Place and duration of Study: This study was conducted at the Institute of Nuclear Medicine and Oncology (INMOL) Hospital, Lahore from March 1997 to December 2000. Patients and Methods: The profiles of 118 patients with a biopsy proven hepatocellular carcinoma were analyzed in this period. The data collected was age, sex, clinical presentation and laboratory investigations including liver function tests, alpha fetoprotein and hepatitis profile. Results: Weight loss, jaundice and right upper quadrant abdominal pain were the main presenting symptoms. Out of 118 patients, alpha fetoprotein values were raised in 63(53.38%) patients 106 (89.83%) patients were found to have or have had HBV infections, and 92 (77.96%) patients were anti-HCV positive. Eighty-three (70.33%) patients were cirrhotic. History of alcohol abuse was bound in three patients. Conclusion: The common association of HCC with cirrhosis and hepatitis B and C suggests that vaccination against HBV on nationwide basis can decrease prevalence of this malignancy. There is a need to generate public awareness regarding the transmission of these viruses. Early diagnosis and intervention is also important to the successful management of HCC. (author)

Alpha Shapes and Proteins

DEFF Research Database (Denmark)

Winter, Pawel; Sterner, Henrik; Sterner, Peter

2009-01-01

We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

Alpha Momentum and Price Momentum

Directory of Open Access Journals (Sweden)

Hannah Lea Hühn

2018-05-01

Full Text Available We analyze a novel alpha momentum strategy that invests in stocks based on three-factor alphas which we estimate using daily returns. The empirical analysis for the U.S. and for Europe shows that (i past alpha has power in predicting the cross-section of stock returns; (ii alpha momentum exhibits less dynamic factor exposures than price momentum and (iii alpha momentum dominates price momentum only in the U.S. Connecting both strategies to behavioral explanations, alpha momentum is more related to an underreaction to firm-specific news while price momentum is primarily driven by price overshooting due to momentum trading.

/sup 58,60,62/Ni (. cap alpha. ,p) three--nucleon transfer reactions and. cap alpha. optical potential ambiguities

Energy Technology Data Exchange (ETDEWEB)

Yuanda, Wang; Xiuming, Bao; Zhiqiang, Mao; Rongfang, Yuan; Keling, Wen; Binyin, Huang; Zhifu, Wang; Shuming, Li; Jianan, Wang; Zuxun, Sun; others, and

1985-11-01

The differential cross sections are measured using 26.0 MeV ..cap alpha.. particle for /sup 58,62/Ni(..cap alpha.., ..cap alpha..) /sup 58,62/Ni and /sup 58,62/Ni(..cap alpha..,p) /sup 61,65/Cu reactions as well as 25.4 MeV ..cap alpha.. particle for /sup 60/Ni(..cap alpha.., ..cap alpha..)/sup 69/Ni and /sup 60/Ni(..cap alpha.., p)/sup 63/Cu reactions. Consistent calculations with optical model and ZR DWBA are made for (..cap alpha.., ..cap alpha..) and (..cap alpha.., p) reactions by using of single, two, three and four nucleon optical potential parameters. For elastic scattering due to the ..cap alpha.. optical potential ambiguities, all the above optical potential can reproduce the experimental angular distributions. However, the single, two and three nucleon potential, including the Baird's mass systematics and the Chang's energy systematics of ..cap alpha.. potentials, obviously can not provide a reasonable fitting with the (..cap alpha..,p) reaction experimental data. Only the results from the four nucleon potential is in good agreement with the (..cap alpha..,p) reaction experimental data. This reveals that in the ..cap alpha..-particle induced transfer reactions, the real depth of the ..cap alpha..-nucleus optical potential should be rather deep.

Targeted Alpha Therapy: From Alpha to Omega

International Nuclear Information System (INIS)

Allen, Barry J; Clarke, Raymond; Huang Chenyu

2013-01-01

This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer.

Science.gov (United States)

Uemura, Motohide; Honma, Seijiro; Chung, Suyoun; Takata, Ryo; Furihata, Mutsuo; Nishimura, Kazuo; Nonomura, Norio; Nasu, Yasutomo; Miki, Tsuneharu; Shuin, Taro; Fujioka, Tomoaki; Okuyama, Akihiko; Nakamura, Yusuke; Nakagawa, Hidewaki

2010-08-01

Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

The alpha channeling effect

Science.gov (United States)

Fisch, N. J.

2015-12-01

Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

Compensatory increase in alpha 1-globin gene expression in individuals heterozygous for the alpha-thalassemia-2 deletion.

OpenAIRE

Liebhaber, S A; Cash, F E; Main, D M

1985-01-01

alpha-Globin is encoded by the two adjacent genes, alpha 1 and alpha 2. Although it is clearly established that both alpha-globin genes are expressed, their relative contributions to alpha-globin messenger RNA (mRNA) and protein synthesis are not fully defined. Furthermore, changes that may occur in alpha-globin gene activity secondarily to the loss of function of one or more of these genes (alpha-thalassemia [Thal]) have not been directly investigated. This study further defines the expressi...

Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume

Science.gov (United States)

Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.

2015-01-01

Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…

Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

DEFF Research Database (Denmark)

Svenson, M; Hansen, M B; Thomsen, Allan Randrup

2000-01-01

with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...

Proceedings, High-Precision $\\alpha_s$ Measurements from LHC to FCC-ee

Energy Technology Data Exchange (ETDEWEB)

d' Enterria, David [CERN; Skands, Peter Z. [Monash U.

2015-01-01

This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\\alpha_s(m_Z)$ = 0.1177 $\\pm$ 0.0013, is about 1\\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.

Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha

NARCIS (Netherlands)

Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P.; Li, Dan L.; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F.; Tschöp, Matthias H.; Clegg, Deborah J.

2014-01-01

High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha

Workshop on Precision Measurements of $\\alpha_s$

Energy Technology Data Exchange (ETDEWEB)

Bethke, Siegfried; /Munich, Max Planck Inst.; Hoang, Andre H.; /Vienna U.; Kluth, Stefan; /Munich, Max Planck Inst.; Schieck, Jochen; /Munich U.; Stewart, Iain W.; Aoki, S.; Beneke, M.; Bethke, S.; Blumlein, J.; Brambilla, N.; Brodsky, S.; /MIT, LNS

2011-10-01

These are the proceedings of the Workshop on Precision Measurements of {alpha}{sub s} held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of {alpha}{sub s}(m{sub Z}) in the {ovr MS} scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, {tau}-decays, electro-weak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

Combining Alphas via Bounded Regression

Directory of Open Access Journals (Sweden)

Zura Kakushadze

2015-11-01

Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

Genetics Home Reference: alpha thalassemia

Science.gov (United States)

... Facebook Twitter Home Health Conditions Alpha thalassemia Alpha thalassemia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alpha thalassemia is a blood disorder that reduces the production ...

Coaching the alpha male.

Science.gov (United States)

Ludeman, Kate; Erlandson, Eddie

2004-05-01

Highly intelligent, confident, and successful, alpha males represent about 70% of all senior executives. Natural leaders, they willingly take on levels of responsibility most rational people would find overwhelming. But many of their quintessential strengths can also make alphas difficult to work with. Their self-confidence can appear domineering. Their high expectations can make them excessively critical. Their unemotional style can keep them from inspiring their teams. That's why alphas need coaching to broaden their interpersonal tool kits while preserving their strengths. Drawing from their experience coaching more than 1,000 senior executives, the authors outline an approach tailored specifically for the alpha. Coaches get the alpha's attention by inundating him with data from 360-degree feedback presented in ways he will find compelling--both hard-boiled metrics and vivid verbatim comments from colleagues about his strengths and weaknesses. A 360-degree assessment is a wake-up call for most alphas, providing undeniable proof that their behavior doesn't work nearly as well as they think it does. That paves the way for a genuine commitment to change. In order to change, the alpha must venture into unfamiliar--and often uncomfortable--psychological territory. He must admit vulnerability, accept accountability not just for his own work for others', connect with his underlying emotions, learn to motivate through a balance of criticism and validation, and become aware of unproductive behavior patterns. The goal of executive coaching is not simply to treat the alpha as an individual problem but to improve the entire team dynamic. Initial success creates an incentive to persevere, and the virtuous cycle reverberates throughout the entire organization.

Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

Science.gov (United States)

Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

2004-01-16

Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

The 14th quality control survey for radioisotope in vitro tests in Japan, 1992

Energy Technology Data Exchange (ETDEWEB)

1993-11-01

This report presents the results of the 14th quality control nationwide survey. Of 490 facilities performing RI in vitro tests as of December 1992, 261 (53.3%) participated in the present 1992 survey. Free testosterone and renin were added to the following conventional 37 test items: adrenocorticotropic hormone (ACTH), growth hormone (GH), somatomedin C, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid stimulating hormone (TSH), triiodothyronine (T[sub 3]), free T[sub 3], thyroxine (T[sub 4]), free T[sub 4], T[sub 3] uptake, thyroglobulin, T[sub 3] binding globulin (TBG), parathyroid hormone (PTH), calcitonin, insulin, C-peptide, glucagon, gastrin, testosterone, estradiol, progesterone, 17[alpha]-hydroxyprogesterone, aldosterone, cortisol, immunoglobulin E (IgE), digoxin, [alpha]-fetoprotein, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), CA125, CA19-9, CA15-3, prostatic acid phosphatase (PAP), [beta][sub 2]-microglobulin, and ferritin. Measurement data for each kit were analyzed by a mean value of measurements, standard deviation, and coefficient of variation (CV). Both 'within kit variation' between facilities and 'between kit variation' showed a CV of 20% or less for GH, somatomedin C, TSH, T[sub 3], T[sub 4], T[sub 3] uptake, TBG, cortisol, IgE, CA125, PAP, and [beta][sub 2]-microglobulin, revealing satisfactory results. There was a great 'within kit variation' between facilities in ACTH, free T[sub 4], and calcitonin; and there was a great 'between kit variation' in ACTH, LH, free T[sub 4], thyroglobulin, PTH, calcitonin, and [alpha]-fetoprotein. (N.K.).

Immunodetection of Thyroid Hormone Receptor (Alpha1/Alpha2) in the Rat Uterus and Oviduct

International Nuclear Information System (INIS)

Öner, Jale; Öner, Hakan

2007-01-01

The aim of this study was to investigate the immunolocalization and the existence of thyroid hormone receptors (THR) (alpha1/alpha2) in rat uterus and oviduct. For this purpose 6 female Wistar albino rats found in estrous period were used. Tissue samples fixed in 10% neutral formalin were examined immunohistochemically. Sections were incubated with primary mouse-monoclonal THR (alpha1/alpha2) antibody. In uterus, THR (alpha1/alpha2) immunoreacted strongly with uterine luminal epithelium, endometrial gland epithelium and endometrial stromal cells and, moderately with myometrial smooth muscle. In oviduct, they were observed moderately in the epithelium of the tube and the smooth muscle cells of the muscular layer. In conclusion, the presence of THR in uterus and oviduct suggests that these organs are an active site of thyroid hormones

Alpha particle emitters in medicine

International Nuclear Information System (INIS)

Fisher, D.R.

1989-09-01

Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ( 211 At) and natural bismuth-212 ( 212 Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ( 223 Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs

Monte Carlo alpha calculation

Energy Technology Data Exchange (ETDEWEB)

Brockway, D.; Soran, P.; Whalen, P.

1985-01-01

A Monte Carlo algorithm to efficiently calculate static alpha eigenvalues, N = ne/sup ..cap alpha..t/, for supercritical systems has been developed and tested. A direct Monte Carlo approach to calculating a static alpha is to simply follow the buildup in time of neutrons in a supercritical system and evaluate the logarithmic derivative of the neutron population with respect to time. This procedure is expensive, and the solution is very noisy and almost useless for a system near critical. The modified approach is to convert the time-dependent problem to a static ..cap alpha../sup -/eigenvalue problem and regress ..cap alpha.. on solutions of a/sup -/ k/sup -/eigenvalue problem. In practice, this procedure is much more efficient than the direct calculation, and produces much more accurate results. Because the Monte Carlo codes are intrinsically three-dimensional and use elaborate continuous-energy cross sections, this technique is now used as a standard for evaluating other calculational techniques in odd geometries or with group cross sections.

Antihydrogen detection in ALPHA

Energy Technology Data Exchange (ETDEWEB)

Hydomako, Richard, E-mail: rhydomako@phas.ucalgary.ca [University of Calgary, Department of Physics and Astronomy (Canada); Bruun Andresen, Gorm [Aarhus University, Department of Physics and Astronomy (Denmark); Ashkezari, Mohammad Dehghani [Simon Fraser University, Department of Physics (Canada); Baquero-Ruiz, Marcelo [University of California, Department of Physics (United States); Bertsche, William [Swansea University, Department of Physics (United Kingdom); Butler, Eoin [CERN, European Laboratory for Particle Physics (Switzerland); Bowe, Paul David [Aarhus University, Department of Physics and Astronomy (Denmark); Cesar, Claudo Lenz [Universidade Federal do Rio de Janeiro, Instituto de Fsica (Brazil); Chapman, Steve [University of California, Department of Physics (United States); Charlton, Michael [Swansea University, Department of Physics (United Kingdom); Fajans, Joel [University of California, Department of Physics (United States); Friesen, Tim; Fujiwara, Makoto C. [University of Calgary, Department of Physics and Astronomy (Canada); Gill, David Russell [TRIUMF (Canada); Hangst, Jeffrey Scott [Aarhus University, Department of Physics and Astronomy (Denmark); Hardy, Walter Newbold [University of British Columbia, Department of Physics and Astronomy (Canada); Hayano, Ryugo S. [University of Tokyo, Department of Physics (Japan); Hayden, Michael Edward [Simon Fraser University, Department of Physics (Canada); Humphries, Andrew James [Swansea University, Department of Physics (United Kingdom); Jonsell, Svante [Stockholm University, Fysikum (Sweden); Collaboration: ALPHA Collaboration; and others

2012-12-15

The ALPHA project is an international collaboration, based at CERN, with the experimental goal of performing precision spectroscopic measurements on antihydrogen. As part of this endeavor, the ALPHA experiment includes a silicon tracking detector. This detector consists of a three-layer array of silicon modules surrounding the antihydrogen trapping region of the ALPHA apparatus. Using this device, the antihydrogen annihilation position can be determined with a spatial resolution of better than 5 mm. Knowledge of the annihilation distribution was a critical component in the recently successful antihydrogen trapping effort. This paper will describe the methods used to reconstruct annihilation events in the ALPHA detector. Particular attention will be given to the description of the background rejection criteria.

Buffett’s Alpha

DEFF Research Database (Denmark)

Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

Energy Technology Data Exchange (ETDEWEB)

Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

1998-06-29

Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

Determination of $\\alpha_{s}$ using Jet Rates at LEP with the OPAL detector

CERN Document Server

Abbiendi, G.; Akesson, P.F.; Alexander, G.; Anagnostou, G.; Anderson, K.J.; Asai, S.; Axen, D.; Bailey, I.; Barberio, E.; Barillari, T.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Boeriu, O.; Bock, P.; Boutemeur, M.; Braibant, S.; Brown, Robert M.; Burckhart, H.J.; Campana, S.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, D.G.; Ciocca, C.; Csilling, A.; Cuffiani, M.; Dado, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Etzion, E.; Fabbri, F.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Gagnon, P.; Gary, John William; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harel, A.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hill, J.C.; Horvath, D.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanzaki, J.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kramer, T.; Krasznahorkay, A.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lellouch, D.; Lettso, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, A.; Ludwig, J.; Mader, W.; Marcellini, S.; Martin, A.J.; Mashimo, T.; Mattig, Peter; McKenna, J.; McPherson, R.A.; Meijers, F.; Menges, W.; Merritt, F.S.; Mes, H.; Meyer, Niels T.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Nanjo, H.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Roney, J.M.; Rossi, A.M.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schorner-Sadenius, T.; Schroder, Matthias; Schumacher, M.; Seuster, R.; Shears, T.G.; Shen, B.C.; Sherwood, P.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spano, F.; Stahl, A.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vollmer, C.F.; Vannerem, P.; Vertesi, R.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija

2006-01-01

Hadronic events produced in e+e- collisions by the LEP collider and recorded by the OPAL detector were used to form distributions based on the number of reconstructed jets. The data were collected between 1995 and 2000 and correspond to energies of 91 GeV, 130-136 GeV and 161-209 GeV. The jet rates were determined using four different jet-finding algorithms (Cone, JADE, Durham and Cambridge). The differential two-jet rate and the average jet rate with the Durham and Cambridge algorithms were used to measure alpha(s) in the LEP energy range by fitting an expression in which order alpah_2s calculations were matched to a NLLA prediction and fitted to the data. Combining the measurements at different centre-of-mass energies, the value of alpha_s (Mz) was determined to be alpha(s)(Mz)=0.1177+-0.0006(stat.)+-0.0012$(expt.)+-0.0010(had.)+-0.0032

Coincidence study of alpha particle fragmentation at E/sub alpha/ = 140 MeV

International Nuclear Information System (INIS)

Koontz, R.W.

1980-01-01

Results of an experimental study of the interaction of 140 MeV alpha particles with 90 Zr nuclei resulting in fragmentation of the alpha particle are reported. The experimental observations of the study are analyzed and are found to show that alpha particle breakup reactions leading to at least 4-body final states, composed of two charged alpha particle fragments, contribute significantly to the singles yield of charged fragments observed at a fixed forward angle. The conclusions are based on coincidence measurements where one charged fragment is detected at a small forward angle which remains fixed, while the second charged fragment is detected at a series of coplanar secondary angles. The largest coincidence charged particle yield for the multiparticle final state events results from 90 Zr(α,pp)X reactions, where both of the measured protons have energy distributions similar to the proton singles energy distributions. The second largest observed coincidence yield involving two charged fragments arises from 90 Zr(α,pd)X reactions, where the p and d fragments, as in the 90 Zr(α,pp)X reactions also have energy distribution similar to the singles energy distributions. Analysis of additional measurements, where alpha particle fragments at the fixed angle are detected in coincidence with evaporation and nonequilibrium particles at many coplanar angles, show that the alpha particle fragmentation reactions are also generally associated with large energy transfer to the target nucleus. A multiple scattering model of the fragmentation reaction is employed, in conjunction with the experimental observations, to estimate the cross sections for alpha particle fragmentation into multi-particle final states resulting in n, 2n, p, pp, d, dn, dp, t and 3 He fragments. The estimated total cross section for all fragmentation reactions is 755 mb or approximately 38% of the total reaction cross section for 140 MeV alpha particle interactions with 90 Zr

alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages.

Science.gov (United States)

Taherzadeh, S; Sharma, S; Chhajlani, V; Gantz, I; Rajora, N; Demitri, M T; Kelly, L; Zhao, H; Ichiyama, T; Catania, A; Lipton, J M

1999-05-01

The hypothesis that macrophages contain an autocrine circuit based on melanocortin [ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH)] peptides has major implications for neuroimmunomodulation research and inflammation therapy. To test this hypothesis, cells of the THP-1 human monocyte/macrophage line were stimulated with lipopolysaccharide (LPS) in the presence and absence of alpha-MSH. The inflammatory cytokine tumor necrosis factor (TNF)-alpha was inhibited in relation to alpha-MSH concentration. Similar inhibitory effects on TNF-alpha were observed with ACTH peptides that contain the alpha-MSH amino acid sequence and act on melanocortin receptors. Nuclease protection assays indicated that expression of the human melanocortin-1 receptor subtype (hMC-1R) occurs in THP-1 cells; Southern blots of RT-PCR product revealed that additional subtypes, hMC-3R and hMC-5R, also occur. Incubation of resting macrophages with antibody to hMC-1R increased TNF-alpha concentration; the antibody also markedly reduced the inhibitory influence of alpha-MSH on TNF-alpha in macrophages treated with LPS. These results in cells known to produce alpha-MSH at rest and to increase secretion of the peptide when challenged are consistent with an endogenous regulatory circuit based on melanocortin peptides and their receptors. Targeting of this neuroimmunomodulatory circuit in inflammatory diseases in which myelomonocytic cells are prominent should be beneficial.

Recurrence of acute myeloid leukemia in cryptorchid testis: case report

OpenAIRE

Góes, Luccas Santos Patto de; Lopes, Roberto Iglesias; Campos, Octavio Henrique Arcos; Oliveira, Luiz Carlos Neves de; Sant’Anna, Alexandre Crippa; Dall’Oglio, Marcos Francisco; Srougi, Miguel

2014-01-01

A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associat...

Test of the Flavour Independence of $\\alpha_{s}$ using Next-to-Leading Order Calculations for Heavy Quarks

CERN Document Server

Abbiendi, G.; Alexander, G.; Allison, John; Altekamp, N.; Anderson, K.J.; Anderson, S.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Batley, J.R.; Baumann, S.; Bechtluft, J.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bellerive, A.; Bentvelsen, S.; Bethke, S.; Betts, S.; Biebel, O.; Biguzzi, A.; Bloodworth, I.J.; Bock, P.; Bohme, J.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Bright-Thomas, P.; Brigliadori, L.; Brown, Robert M.; Burckhart, H.J.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Ciocca, C.; Clarke, P.E.L.; Clay, E.; Cohen, I.; Conboy, J.E.; Cooke, O.C.; Couchman, J.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Davis, R.; De Jong, S.; de Roeck, A.; Dervan, P.; Desch, K.; Dienes, B.; Dixit, M.S.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Estabrooks, P.G.; Etzion, E.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Fiedler, F.; Fierro, M.; Fleck, I.; Frey, A.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gascon-Shotkin, S.M.; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Gibson, V.; Gibson, W.R.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Gorn, W.; Grandi, C.; Graham, K.; Gross, E.; Grunhaus, J.; Gruwe, M.; Hajdu, C.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Harder, K.; Harel, A.; Hargrove, C.K.; Harin-Dirac, M.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herndon, M.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hobson, P.R.; Hocker, James Andrew; Hoffman, Kara Dion; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jacob, F.R.; Jawahery, A.; Jeremie, H.; Jimack, M.; Jones, C.R.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klier, A.; Kobayashi, T.; Kobel, M.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kyberd, P.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lauber, J.; Lawson, I.; Layter, J.G.; Lellouch, D.; Letts, J.; Levinson, L.; Liebisch, R.; List, B.; Littlewood, C.; Lloyd, A.W.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Lu, J.; Ludwig, J.; Lui, D.; Macchiolo, A.; Macpherson, A.; Mader, W.; Mannelli, M.; Marcellini, S.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; Mckigney, E.A.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Mendez-Lorenzo, P.; Merritt, F.S.; Mes, H.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Petzold, S.; Pfeifenschneider, P.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poffenberger, P.; Poli, B.; Polok, J.; Przybycien, M.; Quadt, A.; Rembser, C.; Rick, H.; Robertson, S.; Robins, S.A.; Rodning, N.; Roney, J.M.; Rosati, S.; Roscoe, K.; Rossi, A.M.; Rozen, Y.; Runge, K.; Runolfsson, O.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schmitt, S.; Schoning, A.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Sittler, A.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Spagnolo, S.; Sproston, M.; Stahl, A.; Stephens, K.; Steuerer, J.; Stoll, K.; Strom, David M.; Strohmer, R.; Surrow, B.; Talbot, S.D.; Taras, P.; Tarem, S.; Teuscher, R.; Thiergen, M.; Thomas, J.; Thomson, M.A.; Torrence, E.; Towers, S.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Voss, H.; Wackerle, F.; Wagner, A.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wermes, N.; Wetterling, D.; White, J.S.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Zacek, V.; Zer-Zion, D.

1999-01-01

We present a test of the flavour independence of the strong coupling constant for charm and bottom quarks with respect to light (uds) quarks, based on a hadronic event sample obtained with the OPAL detector at LEP. Five observables related to global event shapes were used to measure alpha_s in three flavour tagged samples (uds, c and b). The event shape distributions were fitted by Order(alpha_s**2) calculations of jet production taking into account mass effects for the c and b quarks. We find: = 0.997 +- 0.038(stat.) +- 0.030(syst.) +- 0.012(theory) and = 0.993 +- 0.008(stat.) +- 0.006(syst.) +- 0.011(theory) for the ratios alpha_s(charm)/alpha_s(uds) and alpha_s(b)/alpha_s(uds) respectively.

Classification of alpha 1-adrenoceptor subtypes

NARCIS (Netherlands)

Michel, M. C.; Kenny, B.; Schwinn, D. A.

1995-01-01

Two alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) have been detected in various tissues by pharmacological techniques, and three distinct cDNAs encoding alpha 1-adrenoceptor subtypes have been cloned. The profile of an increasing number of subtype-selective compounds at cloned and endogenous

Liquid scintillation alpha spectrometry techniques

International Nuclear Information System (INIS)

McKlveen, J.W.; McDowell, W.J.

1984-01-01

Accurate, quantitative determinations of alpha emitting nuclides by conventional plate counting methods are difficult, because of sample self-absorption problems in counting and because of non-reproducible losses in conventional sample separation methods. Liquid scintillation alpha spectrometry offers an attractive alternative with no sample self-absorption or geometry problems and with 100% counting efficiency. Sample preparation may include extraction of the alpha emitter of interest by a specific organic phase-soluble compound directly into the liquid scintillation counting medium. Detection electronics use energy and pulse-shape discrimination, to yield alpha spectra without beta and gamma background interference. Specific procedures have been developed for gross alpha, uranium, plutonium, thorium and colonium assay. Possibilities for a large number of other applications exist. Accuracy and reproducibility are typically in the 1% range. Backgrounds of the order of 0.01 cpm are readily achievable. The paper will present an overview of liquid scintillation alpha counting techniques and some of the results achieved for specific applications. (orig.)

Dynamical chaos in a linear 3. alpha. system. Dinamicheskij khaos v linejnoj 3. alpha. -sisteme

Energy Technology Data Exchange (ETDEWEB)

Bolotin, Yu L; Gonchar, V Yu; Chekanov, N A [AN Ukrainskoj SSR, Kharkov (Ukrainian SSR). Fiziko-Tekhnicheskij Inst.; Vinitskij, S I [Joint Inst. for Nuclear Research, Dubna (USSR)

1989-01-01

Classical dynamics of the motion of a molecular model of the carbon nucleus, which is a linear 3{alpha} system with realistic {alpha}{alpha} interaction is studied. Transition from a regular to a chaos motion in the nuclear molecule is shown to occur with growing energy more rapidly than in model problems with polynomial potentials. It is found that in a small region of the phase space the motion remains regular at energies higher than the 3{alpha}-system dissociation threshold. This is probably related to the C{sub 3v}-symmetry violation. Formulas for the quasiclassical spectrum of the 3{alpha} system are obtained with the use of the Birkhoff normal form.

Alpha detection on moving surfaces

International Nuclear Information System (INIS)

MacArthur, D.; Orr, C.; Luff, C.

1998-01-01

Both environmental restoration (ER) and decontamination and decommissioning (D and D) require characterization of large surface areas (walls, floors, in situ soil, soil and rubble on a conveyor belt, etc.) for radioactive contamination. Many facilities which have processed alpha active material such as plutonium or uranium require effective and efficient characterization for alpha contamination. Traditional methods for alpha surface characterization are limited by the short range and poor penetration of alpha particles. These probes are only sensitive to contamination located directly under the probe. Furthermore, the probe must be held close to the surface to be monitored in order to avoid excessive losses in the ambient air. The combination of proximity and thin detector windows can easily cause instrument damage unless extreme care is taken. The long-range alpha detection (LRAD) system addresses these problems by detecting the ions generated by alpha particles interacting with ambient air rather than the alpha particle directly. Thus, detectors based on LRAD overcome the limitations due to alpha particle range (the ions can travel many meters as opposed to the several-centimeter alpha particle range) and penetrating ability (an LRAD-based detector has no window). Unfortunately, all LRAD-based detectors described previously are static devices, i.e., these detectors cannot be used over surfaces which are continuously moving. In this paper, the authors report on the first tests of two techniques (the electrostatic ion seal and the gridded electrostatic LRAD detector) which extend the capabilities of LRAD surface monitors to use over moving surfaces. This dynamic surface monitoring system was developed jointly by Los Alamos National Laboratory and at BNFL Instruments. All testing was performed at the BNFL Instruments facility in the UK

Study of ({alpha}, {sup 3}He) and ({alpha}, t) reactions on {sup 28}Si at 45 MeV

Energy Technology Data Exchange (ETDEWEB)

Darshan, V.P.; Sathyavathiamma, M.P.; Ramaswamy, C.R.; Raja Rao, M.; Puttaswamy, N.G.; Banerjee, S.R.; Chintalapudi, S.N. [Dept. of Phys., Bangalore Univ. (India)

1995-03-01

The {sup 28}Si({alpha}, {sup 3}He){sup 29}Si, {sup 28}Si({alpha}, t){sup 29}P and Si({alpha}, {alpha})Si reactions were studied at E{sub {alpha}} = 45 MeV. Exact finite-range (EFR) DWBA analysis was carried out for the transitions to the ground state and to five excited states in {sup 29}Si and {sup 29}P. Spectroscopic strengths G were extracted for all the states and were compared with the predictions from shell-model and quasi-particle core-coupling calculations. Similar EFR-DWBA analyses were carried out from available (unpublished) data for the {sup 28}Si({alpha}, {sup 3}He){sup 29}Si reaction at E{sub {alpha}} = 64.9 and 120 MeV, and for the {sup 28}Si({alpha}, t){sup 29}P reaction at E{sub {alpha}} = 50 and 64.9 MeV. The comparison of experimental and theoretical values of G are provided. (author)

alpha AD alpha hybrids of Cryptococcus neoformans: evidence of same-sex mating in nature and hybrid fitness.

Directory of Open Access Journals (Sweden)

Xiaorong Lin

2007-10-01

Full Text Available Cryptococcus neoformans is a ubiquitous human fungal pathogen that causes meningoencephalitis in predominantly immunocompromised hosts. The fungus is typically haploid, and sexual reproduction involves two individuals with opposite mating types/sexes, alpha and a. However, the overwhelming predominance of mating type (MAT alpha over a in C. neoformans populations limits alpha-a mating in nature. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions, especially between alpha isolates. Whether same-sex mating occurs in nature and contributes to the current population structure was unknown. In this study, natural alpha AD alpha hybrids that arose by fusion between two alpha cells of different serotypes (A and D were identified and characterized, providing definitive evidence that same-sex mating occurs naturally. A novel truncated allele of the mating-type-specific cell identity determinant SXI1 alpha was also identified as a genetic factor likely involved in this process. In addition, laboratory-constructed alpha AD alpha strains exhibited hybrid vigor both in vitro and in vivo, providing a plausible explanation for their relative abundance in nature despite the fact that AD hybrids are inefficient in meiosis/sporulation and are trapped in the diploid state. These findings provide insights on the origins, genetic mechanisms, and fitness impact of unisexual hybridization in the Cryptococcus population.

Biochemical characterization of CK2alpha and alpha' paralogues and their derived holoenzymes: evidence for the existence of a heterotrimeric CK2alpha'-holoenzyme forming trimeric complexes

DEFF Research Database (Denmark)

Olsen, Birgitte; Rasmussen, Tine; Niefind, Karsten

2008-01-01

Altogether 2 holoenzymes and 4 catalytic CK2 constructs were expressed and characterized i.e. CK2alpha (2) (1-335) beta(2); CK2alpha'-derived holoenzyme; CK2alpha(1-335); MBP-CK2alpha'; His-tagged CK2alpha and His-tagged CK2alpha'. The two His-tagged catalytic subunits were expressed in insect...... cells, all others in Escherichia coli. IC(50) studies involving the established CK2 inhibitors DMAT, TBBt, TBBz, apigenin and emodin were carried out and the K(i) values calculated. Although the differences in the K(i) values found were modest, there was a general tendency showing that the CK2...... holoenzymes were more sensitive towards the inhibitors than the free catalytic subunits. Thermal inactivation experiments involving the individual catalytic subunits showed an almost complete loss of activity after only 2 min at 45 degrees C. In the case of the two holoenzymes, the CK2alpha...

Flavonoids-induced accumulation of hypoxia-inducible factor (HIF)-1alpha/2alpha is mediated through chelation of iron.

Science.gov (United States)

Park, Sung-Soo; Bae, Insoo; Lee, Yong J

2008-04-15

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1 that is the key regulator of cellular response to low oxygen tension. Under normoxic conditions, HIF-1alpha is continuously degraded by the ubiquitin-proteasome pathway through pVHL (von Hippel-Lindau tumor suppressor protein). Under hypoxic conditions, HIF-1alpha is stabilized and induces the transcription of HIF-1 target genes. Quercetin, a flavonoid with anti-oxidant, anti-inflammatory, and kinase modulating properties, has been found to induce HIF-1alpha accumulation and VEGF secretion in normoxia. In this study, the molecular mechanisms of quercetin-mediated HIF-1alpha accumulation were investigated. Previous studies have shown that, in addition to being induced by hypoxia, HIF-1alpha can be induced through the phosphatidylinositol 3-kinase (PI3K)/Akt and p53 signaling pathways. But our study revealed, through p53 mutant-type as well as p53 null cell lines, that neither the PI3K/Akt nor the p53 signaling pathway is required for quercetin-induced HIF-1alpha accumulation. And we observed that HIF-1alpha accumulated by quercetin is not ubiquitinated and the interaction of HIF-1alpha with pVHL is reduced, compared with HIF-1alpha accumulated by the proteasome inhibitor MG132. The use of quercetin's analogues showed that only quercetin and galangin induce HIF-1/2alpha accumulation and this effect is completely reversed by additional iron ions. This is because quercetin and galangin are able to chelate cellular iron ions that are cofactors of HIF-1/2alpha proline hydroxylase (PHD). These data suggest that quercetin inhibits the ubiquitination of HIF-1/2alpha in normoxia by hindering PHD through chelating iron ions.

Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

International Nuclear Information System (INIS)

Bae, Hyun-Mi; Lee, Jeong-Hoon; Yoon, Jung-Hwan; Kim, Yoon Jun; Heo, Dae Seog; Lee, Hyo-Suk

2011-01-01

Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers. A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II production ≥ 300 mAU/mL had a 2.7-fold (95% confidence interval; 1.5-4.8; P < 0.001) and 3.7-fold (95% confidence interval; 2.0-6.6; P < 0.001) increased risk for extrahepatic metastases after adjustment for stage, platelet count, alpha-fetoprotein ≥ 400 ng/mL, and portal vein thrombosis according to the AJCC and BCLC staging systems, respectively. PIVKA-II production levels might be a good candidate predictive marker for extrahepatic HCC metastases, especially in patients with smaller and/or fewer tumors in the liver with in stages regardless of serum alpha-fetoprotein

HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

Directory of Open Access Journals (Sweden)

Freya M Mowat

2010-06-01

Full Text Available Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators.We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF and erythropoietin (Epo by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO.Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation plays a key role in regulating the response of Müller glia to hypoxia.

Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

International Nuclear Information System (INIS)

Andersson, G.; Lundgren, E.; Ekre, H.P.

1991-01-01

Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition of the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity

Alpha and beta detection and spectrometry

International Nuclear Information System (INIS)

Saro, S.

1984-01-01

The theory of alpha and beta radioactive decay, the interaction of alpha and beta particles with matter, and their detection and spectrometry are dealt with in seven chapters: 1. Alpha transformation of atomic nuclei; 2. Basic properties of detectors and statistics of detection; 3. Alpha detectors and spectrometers; 4. Applications of alpha detection and spectrometry; 5. Beta transformation of atomic nuclei; 6. Beta particle detectors and spectrometers; 7. Detection of low energy beta particles. Chapter 8 is devoted to sampling and preparation of samples for radiometry. (E.F.)

Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy?

NARCIS (Netherlands)

Bakker, H. D.; de Sonnaville, M. L.; Vreken, P.; Abeling, N. G.; Groener, J. E.; Keulemans, J. L.; van Diggelen, O. P.

2001-01-01

Two new individuals with alpha-NAGA deficiency are presented. The index patient, 3 years old, has congenital cataract, slight motor retardation and secondary demyelinisation. Screening of his sibs revealed an alpha-NAGA deficiency in his 7-year-old healthy brother who had no clinical or neurological

Applying alpha-channeling to mirror machines

Energy Technology Data Exchange (ETDEWEB)

Zhmoginov, A. I.; Fisch, N. J. [Department of Astrophysical Sciences, Princeton University, Princeton, New Jersey 08544 (United States)

2012-05-15

The {alpha}-channeling effect entails the use of radio-frequency waves to expel and cool high-energetic {alpha} particles born in a fusion reactor; the device reactivity can then be increased even further by redirecting the extracted energy to fuel ions. Originally proposed for tokamaks, this technique has also been shown to benefit open-ended fusion devices. Here, the fundamental theory and practical aspects of {alpha} channeling in mirror machines are reviewed, including the influence of magnetic field inhomogeneity and the effect of a finite wave region on the {alpha}-channeling mechanism. For practical implementation of the {alpha}-channeling effect in mirror geometry, suitable contained weakly damped modes are identified. In addition, the parameter space of candidate waves for implementing the {alpha}-channeling effect can be significantly extended through the introduction of a suitable minority ion species that has the catalytic effect of moderating the transfer of power from the {alpha}-channeling wave to the fuel ions.

DT results of TFTR's alpha collector

International Nuclear Information System (INIS)

Herrmann, H.W.; Zweben, S.J.; Darrow, D.S.; Timberlake, J.R.; Macaulay-Newcombe, R.G.

1996-01-01

An escaping alpha collector probe has been developed for TFTR's DT phase to complement the results of the lost alpha scintillator detectors which have been operating on TFTR since 1988. Measurements of the energy distribution of escaping alphas have been made by measuring the range of alphas implanted into nickel foils located within the alpha collector. Exposed samples have been analyzed for 4 DT plasma discharges at plasma currents of 1.0 and 1.8 MA. The results at 1.0 MA are in good agreement with predictions for first orbit alpha loss at 3.5 MeV. The 1.8 MA results, however, indicate a large anomalous loss of partially thermalized alphas at an energy ∼30% below the birth energy and at a total fluence nearly an order of magnitude above expected first orbit loss. This anomalous loss is not observed with the lost alpha scintillator detectors in DT plasmas but does resemble the anomalous delayed loss seen in DD plasmas. Several potential explanations for this loss process are examined. None of the candidate explanations proposed thus far are fully consistent with the anomalous loss observations

Alpha Thalassemia (For Parents)

Science.gov (United States)

... Safe Videos for Educators Search English Español Alpha Thalassemia KidsHealth / For Parents / Alpha Thalassemia What's in this ... Symptoms Diagnosis Treatment Print en español Alfa talasemia Thalassemias Thalassemias are a group of blood disorders that ...

Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

Science.gov (United States)

Rutault, K; Hazzalin, C A; Mahadevan, L C

2001-03-02

Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

Development of thermal conditioning technology for Alpha-containment wastes: Alpha-contaminated waste incineration technology

Energy Technology Data Exchange (ETDEWEB)

Kim, Joon Hyung; Kim, Jeong Guk; Yang, Hee Chul; Choi, Byung Seon; Jeong, Myeong Soo

1999-03-01

As the first step of a 3-year project named 'development of alpha-contaminated waste incineration technology', the basic information and data were reviewed, while focusing on establishment of R and D direction to develop the final goal, self-supporting treatment of {alpha}- wastes that would be generated from domestic nuclear industries. The status on {alpha} waste incineration technology of advanced states was reviewed. A conceptual design for {alpha} waste incineration process was suggested. Besides, removal characteristics of volatile metals and radionuclides in a low-temperature dry off-gas system were investigated. Radiation dose assessments and some modification for the Demonstration-scale Incineration Plant (DSIP) at Korea Atomic Energy Research Institute (KAERI) were also done.

Reverse-phase HPLC analysis of human alpha crystallin.

Science.gov (United States)

Swamy, M S; Abraham, E C

1991-03-01

A rapid and highly sensitive reverse-phase HPLC (RP-HPLC) method was used to separate crystallin subunits from human alpha crystallin. Three distinct peaks were separated; by electrophoretic and immunological analyses the first and second peaks were identified as alpha B and alpha A respectively. On the other hand, peak 3 appeared to be a modified form of alpha crystallin. The ratio of alpha A and alpha B proteins was 3:1 in 1 day old lenses which gradually changed to 2:1 in 17 year old lenses and to 1:1 in the 50 and 82 year old whole lenses and 82 year old lens cortex, with a concomitant increase in the modified alpha, suggesting that alpha A subunits are relatively more involved in aggregation. Analysis of the 82 year old lens nucleus also supported this conclusion. The RP-HPLC analysis of the HMW aggregate fraction showed substantial enrichment of the modified alpha. The alpha A and alpha B subunits independently reassociated to form polymeric alpha crystallin whereas the modified alpha reassociated to form HMW aggregates as shown by molecular sieve HPLC. Hence it appears that the HMW aggregate peak was constituted by modified alpha crystallin. Only in the peak 3 material the 280 nm absorbance was about 2-fold higher than what was expected from the actual protein content. The data suggest that the changes induced by post-translational modifications may have some role in the formation of modified alpha. The present RP-HPLC method is useful in separating these modified alpha from the unmodified alpha A and alpha B subunits.

Proteinaceous alpha-araylase inhibitors

DEFF Research Database (Denmark)

Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.

2004-01-01

-amylase inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha...

Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation.

Science.gov (United States)

Matousek, P; Novotný, J; Svoboda, P

2004-01-01

Low-density membrane-domain fractions were prepared from S49 lymphoma cells and clone e2m11 of HEK293 cells expressing a large number of thyrotropin-releasing hormone receptor (TRH-R) and G(11)alpha by flotation on sucrose density gradients. The intact cell structure was broken by detergent-extraction, alkaline-treatment or drastic homogenization. Three types of low-density membranes were resolved by two-dimensional electrophoresis and analyzed for G(s)alpha (S49) or G(q)alpha/G11) (e2m11) content. Four individual immunoblot signals of Gsalpha protein were identified in S49 lymphoma cells indicating complete resolution of the long G(s)alpha L+/-ser and short G(s)alpha S+/-ser variants of G(s)alpha. All these were diminished by prolonged agonist (isoprenaline) stimulation. In e2m11-HEK cells, five different immunoblot signals were detected indicating post-translational modification of G proteins of G(q)alpha/G(11)alpha family. The two major spots corresponding to exogenously (over)expressed G(11)alpha and endogenous G(q)alpha were reduced; the minor spots diminished by hormonal stimulation. Parallel analysis by silver staining of the total protein content indicated that no major changes in protein composition occurred under these conditions. Our data thus indicate that agonist-stimulation of target cells results in down-regulation of all different members of G(s) and G(q)/G(11) families. This agonist-specific effect may be demonstrated in crude membrane as well as domain/raft preparations and it is not accompanied by changes in overall protein composition.

Echography of congenital malformations of the central nervous system

International Nuclear Information System (INIS)

Toirac Romani, Carlos Andres; Salmon Cruzata, Acelia; Musle Acosta, Mirelvis; Rosales Fargie, Yamile; Dosouto Infante, Vivian

2010-01-01

A descriptive and prospective study was conducted in 173 pregnant women attended at the Provincial Department of Clinical Genetics of Santiago de Cuba, from January, 2000 to December, 2004, to identify congenital malformations of the central nervous system detected by means of echography. The most frequent malformation was the hydrocephaly, followed by the fusion defects of the spine, associated with the hydrocephaly and the absence of cranial cavity. There was a prevalence of altered alpha fetoprotein and of elevated amniotic fluid

Recurrent hepatoblastoma with localization by PET-CT

Energy Technology Data Exchange (ETDEWEB)

Figarola, Maria S.; McQuiston, Samuel A. [University of South Alabama, Department of Radiology, Mobile, AL (United States); Wilson, Felicia [University of South Alabama, Pediatric Hematology-Oncology, Mobile, AL (United States); Powell, Randall [University of South Alabama, Surgery Department, Mobile, AL (United States)

2005-12-01

Hepatoblastoma is the most common primary liver tumor in children, accounting for 79% of pediatric liver malignancies in children younger than 15 years, with most cases reported before the age of 5 years. Localization of primary and recurrent disease is necessary for appropriate clinical decision-making and treatment. We present a case of recurrent hepatoblastoma heralded by rising alpha-fetoprotein levels. After unsuccessful localization by conventional CT and MRI, positron emission tomography CT imaging localized the sites of recurrence. (orig.)

Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2.

Science.gov (United States)

Moreira, Maria-Céu; Klur, Sandra; Watanabe, Mitsunori; Németh, Andrea H; Le Ber, Isabelle; Moniz, José-Carlos; Tranchant, Christine; Aubourg, Patrick; Tazir, Meriem; Schöls, Lüdger; Pandolfo, Massimo; Schulz, Jörg B; Pouget, Jean; Calvas, Patrick; Shizuka-Ikeda, Masami; Shoji, Mikio; Tanaka, Makoto; Izatt, Louise; Shaw, Christopher E; M'Zahem, Abderrahim; Dunne, Eimear; Bomont, Pascale; Benhassine, Traki; Bouslam, Naïma; Stevanin, Giovanni; Brice, Alexis; Guimarães, João; Mendonça, Pedro; Barbot, Clara; Coutinho, Paula; Sequeiros, Jorge; Dürr, Alexandra; Warter, Jean-Marie; Koenig, Michel

2004-03-01

Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.

Alpha 1A and alpha 1B-adrenoceptors enhance inositol phosphate generation in rat renal cortex

NARCIS (Netherlands)

Michel, M. C.; Büscher, R.; Philipp, T.; Brodde, O. E.

1993-01-01

We have studied the role of alpha 1A- and alpha 1B-adrenoceptors in noradrenaline- and methoxamine-stimulated inositol phosphate accumulation in rat renal cortical slices. [3H]Prazosin binding studies with and without inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment suggested

Alpha-particle emission probabilities of ²³⁶U obtained by alpha spectrometry.

Science.gov (United States)

Marouli, M; Pommé, S; Jobbágy, V; Van Ammel, R; Paepen, J; Stroh, H; Benedik, L

2014-05-01

High-resolution alpha-particle spectrometry was performed with an ion-implanted silicon detector in vacuum on a homogeneously electrodeposited (236)U source. The source was measured at different solid angles subtended by the detector, varying between 0.8% and 2.4% of 4π sr, to assess the influence of coincidental detection of alpha-particles and conversion electrons on the measured alpha-particle emission probabilities. Additional measurements were performed using a bending magnet to eliminate conversion electrons, the results of which coincide with normal measurements extrapolated to an infinitely small solid angle. The measured alpha emission probabilities for the three main peaks - 74.20 (5)%, 25.68 (5)% and 0.123 (5)%, respectively - are consistent with literature data, but their precision has been improved by at least one order of magnitude in this work. © 2013 Published by Elsevier Ltd.

Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

DEFF Research Database (Denmark)

Andersen, J T

1995-01-01

During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... of patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... and improvement in objective parameters for bladder outflow obstruction. Approximately 30 to 50% of patients will respond to treatment with 5 alpha-reductase inhibitors. The definitive role of pharmacological treatment in symptomatic BPH remains to be established, although it seems that patients unfit...

Interactions of foot-and-mouth disease virus with soluble bovine alphaVbeta3 and alphaVbeta6 integrins.

Science.gov (United States)

Duque, Hernando; LaRocco, Michael; Golde, William T; Baxt, Barry

2004-09-01

At least four members of the integrin family of receptors, alphaVbeta1, alphaVbeta3, alphaVbeta6, and alphaVbeta8, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. Our investigators have recently shown that the efficiency of receptor usage appears to be related to the viral serotype and may be influenced by structural differences on the viral surface (H. Duque and B. Baxt, J. Virol. 77:2500-2511, 2003). To further examine these differences, we generated soluble alphaVbeta3 and alphaVbeta6 integrins. cDNA plasmids encoding the individual complete integrin alphaV, beta3, and beta6 subunits were used to amplify sequences encoding the subunits' signal peptide and ectodomain, resulting in subunits lacking transmembrane and cytoplasmic domains. COS-1 cells were transfected with plasmids encoding the soluble alphaV subunit and either the soluble beta3 or beta6 subunit and labeled with [35S]methionine-cysteine. Complete subunit heterodimeric integrins were secreted into the medium, as determined by radioimmunoprecipitation with specific monoclonal and polyclonal antibodies. For the examination of the integrins' biological activities, stable cell lines producing the soluble integrins were generated in HEK 293A cells. In the presence of divalent cations, soluble alphaVbeta6 bound to representatives of type A or O viruses, immobilized on plastic dishes, and significantly inhibited viral replication, as determined by plaque reduction assays. In contrast, soluble alphaVbeta3 was unable to bind to immobilized virus of either serotype; however, virus bound to the immobilized integrin, suggesting that FMDV binding to alphaVbeta3 is a low-affinity interaction. In addition, soluble alphaVbeta3 did not neutralize virus infectivity. Incubation of soluble alphaVbeta6 with labeled type A12 or O1 resulted in a significant inhibition of virus adsorption to BHK cells, while soluble alphaVbeta3 caused a low (20 to 30%), but consistent, inhibition of virus

Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis

International Nuclear Information System (INIS)

Fida, Nadia M.; Fadelallah, Mohamed F.; Al-Mughales, Jamil A.

2006-01-01

To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n=28), meningitis (n=7), and healthy controls (n=16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n=6), group 2 = clinical sepsis (n=14), and group 3 = possible-infected (n=8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer: In sepsis and meningitis patients, serum levels of CRP (p<0.01, p<0.05,) and IL-1alpha (p<0.001, p<0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p<0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p<0.05, p<0.001, p<0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis. (author)

Alpha1-antitrypsin deficiency

DEFF Research Database (Denmark)

Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

2006-01-01

The Alpha One International Registry (AIR), a multinational research program focused on alpha1-antitrypsin (AAT) deficiency, was formed in response to a World Health Organization recommendation. Each of the nearly 20 participating countries maintains a national registry of patients with AAT defic...

15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers.

Science.gov (United States)

Reeder, A Y; Joannou, G E

1995-12-01

In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.

Enzyme replacement therapy for alpha-mannosidosis

DEFF Research Database (Denmark)

Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J

2013-01-01

Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly...

IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

DEFF Research Database (Denmark)

Ross, Christian; Engler, Claus Bødker; Sander, Birgit

2002-01-01

We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2...

IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

DEFF Research Database (Denmark)

Ross, Christian; Engler, Claus Bødker; Sander, Birgit

2002-01-01

We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a...

Alpha-amino acid derivatives and alpha-fluoro ketones by enantioselective decarboxylation

OpenAIRE

Baur, Markus A.

2003-01-01

Die Methode der enantioselektiven Decarboxylierung wurde angewendet, um Enantiomeren-angereicherte alpha-Aminosäurederivate und alpha-Fluorketone zu erhalten. Als Substrate wurden 2-N-Acetylamino-2-alkylmalonsäuremonoethylester beziehungsweise beta-Keto-benzylester verwendet. China-Alkaloide und Derivate davon wurden als Katalysatoren eingesetzt. Die besten erhaltenen Ergebnisse waren N-Acetyl-L-phenylalaninethylester mit 70% Enantiomerenüberschuß unter Verwendung der katalytisch aktiven Base...

Complete primary structure of rainbow trout type I collagen consisting of alpha1(I)alpha2(I)alpha3(I) heterotrimers.

Science.gov (United States)

Saito, M; Takenouchi, Y; Kunisaki, N; Kimura, S

2001-05-01

The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be alpha1(I)alpha2(I)alpha3(I) and [alpha1(I)](2)alpha2(I), respectively. The occurrence of alpha3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 degrees C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proalpha(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proalpha(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific alpha(I) chain, proalpha3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proalpha1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proalpha3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proalpha3(I) had diverged from proalpha1(I). This study is the first report of the complete primary structure of fish type I procollagen.

TFTR alpha extraction and measurement: Development and testing of advanced alpha detectors: Final report

International Nuclear Information System (INIS)

Wehring, B.W.

1988-01-01

Advanced alpha-particle detectors made of heavy elements were investigated as alternatives to silicon surface-barrier detectors for the ''foil-neutralization technique'' of alpha-particle diagnostics in fusion reactors with high neutron backgrounds. From an extensive literature review, it was decided that HgI 2 would make a more suitable detector for alpha-particle diagnostics than other heavy element detectors such as CdTe. Thus, HgI 2 detectors were designed and fabricated. Experimental tests were performed to determine detector characteristics and detector responses to alpha particles. Radiation noise measurements were also performed using the North Carolina State University PULSTAR nuclear reactor for both the HgI 2 detectors and commercial Si(Au) surface barrier detectors. 15 refs., 1 fig

Synthesis and evaluation of phytotoxic activity of {alpha}-Santonin derivatives; Sintese e avaliacao da atividade fitotoxica de derivados da {alpha}-Santonina

Energy Technology Data Exchange (ETDEWEB)

Alvarenga, Elson S.; Barbosa, Luiz C.A.; Saliba, William A.; Arantes, Francisco F.P.; Demuner, Antonio J. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Quimica]. E-mail: elson@ufv.br; Silva, Antonio A. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Fitotecnia

2009-07-01

Mixtures of {alpha}-Santonin and various solvents were irradiated by either high or low pressure mercury lamps. The photochemical reactions afforded lumisantonin (11) (76% in acetonitrile), (3 S,3a S,9{beta}S)-3,6,6-trimethyl-3,3a,4,5-tetrahydronafto[1,2-b]furan-2,7({eta}6,9{beta}{eta}) dione (12) (100% in acetonitrile), 10{alpha}-acetoxy-3-oxo-1,7{alpha}H{eta},6,11{alpha}a{eta}-guaia-4-en-6,12-oli= de (8) (26% in acetic acid), 10{alpha}-hydroxy-3-oxo-1,7{alpha}a{eta},6,11{alpha}{eta}-guaia-4-en-6,12-olid= e (10) (32%) and (E)-3-((3 S,3a S,7{alpha}S)-3-methyl-2-oxo-6-(propan-2-ylidene)hexahydrobenzofuran- 7 - (7{alpha}{eta})-ylidene)propanoic acid (9) (44%) (in water/ acetic acid 1:1, v/v). Lactone 12 was also prepared by irradiation of lumisantonin in diethyl ether. Lactones 8 and 10 were converted, respectively, into the 10 {alpha}-acetoxy-3{alpha}-hydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olid= e (13) (87%) and 3a,10a-dihydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olide (14) (75%) by sodium borohydride reduction. The effects of the compounds on the development of radicle of Sorghum bicolor and Cucumis sativus were evaluated. (author)

A survey of the alpha-nucleon interaction

International Nuclear Information System (INIS)

Ali, S.; Ahmad, A.A.Z.; Ferdous, N.

1984-10-01

A survey of the alpha-nucleon interaction is made. The experimental work on angular distributions of differential scattering cross-sections and polarizations in proton-alpha and neutron-alpha scattering is described. The phenomenological approach which includes the study of both local and non-local potentials reproducing the experimental alpha-nucleon scattering data, is discussed. Basic studies of the alpha-nucleon interaction attempting to build an interaction between an alpha particle and a nucleon from first principles are then described. A critical discussion of the results with some concluding remarks suggesting the direction for further investigation is made. (author)

Remarks on tilde g_{alpha}-irresolute maps

Directory of Open Access Journals (Sweden)

Nirmala Rebecca Paul

2011-12-01

Full Text Available Only a few of the class of generalized closed sets form a topology. The class of tilde g_{alpha}-closed sets is one among them. The aim of this paper is to introduce the different notions of irresolute function using tilde g_{alpha}-closed sets and study some of their basic properties.We also study the relation between strongly tilde g_{alpha}- continuous and perfectly eg-continuous functions. We also introduce tilde g_{alpha}-compact and ilde g_{alpha}-connectedspaces and study their properties using tilde g_{alpha}-continuous and eg-irresolute functions.

Long-range alpha detector (LRAD)

International Nuclear Information System (INIS)

MacArthur, D.W.; McAtee, J.L.

1991-01-01

Historically, alpha detectors have been limited by the very short range of alpha particles in air and by relatively poor sensitivity, even if the particles are intercepted. Of necessity, these detectors are operated in a vacuum or in close proximity to the source if reasonable efficiency is desired. In our new long-range alpha detector (LRAD), alpha particles interact with the ambient air, producing ionization in the air at the rate of about 30,000 ion pairs per MeV of alpha energy. These charges can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions. The LRAD-based monitor is more sensitive and more thorough than conventional monitors. We present current LRAD sensitivity limits and results, practical monitor designs, and proposed uses for LRAD monitors. 4 refs., 7 figs

Beta/alpha continuous air monitor

Science.gov (United States)

Becker, G.K.; Martz, D.E.

1988-06-27

A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinquishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts. 7 figs.

ALPHA experiment facility and Prof. Jeffrey Hangst.

CERN Multimedia

Maximilien Brice

2010-01-01

Picture 01-07: General views of the ALPHA experiment Picture 5: Andrea Gutierrez, a PhD student from UBC, transfers liquid helium from a storage dewar into the cryostat containing the superconducting magnetic trap used by the ALPHA experiment.Picture 08-11: Jeffery Hangst, spokesperson for ALPHA Picture 12: The ALPHA silicon detector, which surrounds the trapping resion and is used for imaging antiproton annihilations (Credit University of Liverpool) Picture 13: Untrapped antihydrogen atoms annihilating on the inner surface of the ALPHA trap. These are measured by the ALPHA annihilation detector. The events are concentrated at the electrode radius of about 22.3 mm. The coordinates are defined in the Nature article, Figure 1b. Picture 14: The electrodes (gold) for the ALPHA Penning trap being inserted into the vacuum chamber and cryostat assembly. This is the trap used to combine or "mix" positrons and antiprotons to make antihydrogen. (Credit: Niels Madsen ALPHA/Swansea.) Picture 15: Top, a diagram of the...

Alpha-Driven MHD and MHD-Induced Alpha Loss in TFTR DT Experiments

Science.gov (United States)

Chang, Zuoyang

1996-11-01

Theoretical calculation and numerical simulation indicate that there can be interesting interactions between alpha particles and MHD activity which can adversely affect the performance of a tokamak reactor (e.g., ITER). These interactions include alpha-driven MHD, like the toroidicity-induced-Alfven-eigenmode (TAE) and MHD induced alpha particle losses or redistribution. Both phenomena have been observed in recent TFTR DT experiments. Weak alpha-driven TAE activity was observed in a NBI-heated DT experiment characterized by high q0 ( >= 2) and low core magnetic shear. The TAE mode appears at ~30-100 ms after the neutral beam turning off approximately as predicted by theory. The mode has an amplitude measured by magnetic coils at the edge tildeB_p ~1 mG, frequency ~150-190 kHz and toroidal mode number ~2-3. It lasts only ~ 30-70 ms and has been seen only in DT discharges with fusion power level about 1.5-2.0 MW. Numerical calculation using NOVA-K code shows that this type of plasma has a big TAE gap. The calculated TAE frequency and mode number are close to the observation. (2) KBM-induced alpha particle loss^1. In some high-β, high fusion power DT experiments, enhanced alpha particle losses were observed to be correlated to the high frequency MHD modes with f ~100-200 kHz (the TAE frequency would be two-times higher) and n ~5-10. These modes are localized around the peak plasma pressure gradient and have ballooning characteristics. Alpha loss increases by 30-100% during the modes. Particle orbit simulations show the added loss results from wave-particle resonance. Linear instability analysis indicates that the plasma is unstable to the kinetic MHD ballooning modes (KBM) driven primarily by strong local pressure gradients. ----------------- ^1Z. Chang, et al, Phys. Rev. Lett. 76 (1996) 1071. In collaberation with R. Nazikian, G.-Y. Fu, S. Batha, R. Budny, L. Chen, D. Darrow, E. Fredrickson, R. Majeski, D. Mansfield, K. McGuire, G. Rewoldt, G. Taylor, R. White, K

Alpha decay and various problems related to it

International Nuclear Information System (INIS)

Katori, Kenji

1992-01-01

On the proton-excessive nucleus side of lanthanide and actinide, alpha decay is the main decay mode. In lanthanide region, alpha decay has been measured to the drip line for most even-even nuclei. In the measurement of alpha decay, emitted energy and life are measured, but the measurement of converted alpha width remains in the limited range. In order to obtain the converted alpha width of high accuracy, the nucleus formation in larger quantity on the drip line and the simultaneous measurement with a multiple detector system including gamma ray and beta ray are required. In this paper, three topics related to alpha cluster and alpha decay and the problems that confront at present are discussed. The continuation to exist of alpha cluster structure to heavy nuclei, the analysis of lanthanide nucleus region by the alpha giant resonance model, and the new data on the alpha ray decaying from the mass of 175, 176 and 177 are reported. In lanthanide nucleus region, remarkable interference was not observed between beta-2 and beta-3 modes in the converted alpha width measured between the ground states. The present problems in alpha decay are enumerated. (K.I.)

Cortical Alpha Activity in Schizoaffective Patients.

Science.gov (United States)

Moeini, Mahdi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Zarafshan, Hadi; Fazio, Rachel L; Majidi, Hamid

2017-01-01

Objective: Electrophysiological studies have identified abnormal oscillatory activities in the cerebral cortex in schizophrenia and mood disorders. Biological and pathophysiological evidence suggests specific deficits in serotonin (5-HT) receptor function in schizoaffective disorder (SA), a clinical syndrome with characteristics of both schizophrenia and bipolar disorder. This study investigated alpha oscillations in patients with SA. Method: Electroencephalography was used to measure ongoing and evoked alpha oscillations in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for SA, and in 39 healthy controls. Results: Spontaneous alpha power of the participants with SA was significantly lower than that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025]. Conclusion : A strong reduction of alpha power in the posterior regions may reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and reduced cerebral blood flow is associated with reduced alpha activity among different regions of the brain. Therefore, it can be concluded that greatly decreased alpha activity, particularly in centro-parietal and occipital regions, is related to SA symptoms such as hallucinations.

Alpha 1 B- but not alpha 1 A-adrenoceptors mediate inositol phosphate generation

NARCIS (Netherlands)

Michel, M. C.; Hanft, G.; Gross, G.

1990-01-01

We used novel highly subtype-selective antagonists to study whether alpha 1A- and/or alpha 1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 microM) and prazosin (100 nM) completely abolished the stimulated inositol

Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

Science.gov (United States)

Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

2007-09-01

Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors.

Science.gov (United States)

Kelley, Joshua B; Talley, Ashley M; Spencer, Adam; Gioeli, Daniel; Paschal, Bryce M

2010-08-11

Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin alpha and importin beta. NLS cargo is recognized by importin alpha, which is bound by importin beta. Importin beta mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin beta triggers disassembly of the complex. To date, six importin alpha family members, encoded by separate genes, have been described in humans. We sequenced and characterized a seventh member of the importin alpha family of transport factors, karyopherin alpha 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin beta (IBB) is divergent, and shows stronger binding to importin beta than the IBB domains from of other importin alpha family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. KPNA7 is a novel importin alpha family member in humans that belongs to the importin alpha2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin alpha family. These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation.

Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments

NARCIS (Netherlands)

Baer, R.; Boehm, T.; Yssel, H.; Spits, H.; Rabbitts, T. H.

1988-01-01

We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one

Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function

DEFF Research Database (Denmark)

Hansen, Sara K; Párrizas, Marcelina; Jensen, Maria L

2002-01-01

Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. More recent data demonstrates that HNF-4alpha...... in human islets and exocrine cells is primarily mediated by the P2 promoter. Furthermore, we describe a G --> A mutation in a conserved nucleotide position of the HNF-1alpha binding site of the P2 promoter, which cosegregates with MODY. The mutation results in decreased affinity for HNF-1alpha...

The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin

DEFF Research Database (Denmark)

Goldfinger, L E; Hopkinson, S B; deHart, G W

1999-01-01

Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found in epithe......-inhibiting antibodies, we provide evidence that LN5 and its two integrin receptors (alpha6beta4 and alpha3beta1) appear necessary for wound healing to occur in MCF-10A cell culture wounds. We propose a model for healing of wounded epithelial tissues based on these results....... in epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 subunit as a consequence of proteolytic processing. Antibody 12C4 stains throughout the matrix...... the wound site. A similar phenomenon is observed in human skin wounds, since we also detect expression of the unprocessed alpha3 laminin subunit at the leading tip of the sheet of epidermal cells that epithelializes skin wounds in vivo. In addition, using alpha3 laminin subunit and integrin function...

Assessment and association of two useful tumour markers: alpha feto protein and human chornionic gonodotropin (beta hCG) hormone

International Nuclear Information System (INIS)

Subhan, F.; Tahir, F.; Sultan, S.; Subhan, K.

2008-01-01

This study was designed to determine serum Alpha-fetoprotein (AFP) and beta-h Chornionic Gonodotropin hormone (beta-hCG) levels among adult Pakistani population, and to observe their correlation. Serum AFP and beta-hCG levels were evaluated, using Micro-particle Enzyme Immuno Assay (MEIA) technology of M/s Abbott Laboratories. Data were compared using students t-test and correlation was computed. In the patients advised serum AFP assessment, 52% had normal AFP levels. comprising 37% male and 63% female subjects. For patients having a non-pathological picture, AFP levels varied non-significantly (p>0.05) between the Genders however, age varied highly significantly (p 0.05) and highly significant (p 0.05). Comparison of the population in the same age groups of both genders revealed significant (p 0.05), due to a large standard error. Although the differences in beta-hCG levels were highly significant (p 0.05). Among the studied cases, 67% patients had normal and 33% patients had raised beta-hCG levels. Beta-hCG levels show a decreasing trend with increasing age and beta-hCG levels were statistically significant (p<0.05) when patients under 50 years of age were compared with patients above 50 years. The coefficient of correlation between serum AFP and beta- hCG levels was 0.996454, which indicated a very strong. Significant positive correlation between the two tumour markers. The study showed that both serum AFP and beta-hCG are useful tumour markers and had a very strong positive correlation. (author)

Remote Optical Detection of Alpha Radiation

International Nuclear Information System (INIS)

Sand, J.; Hannuksela, V.; Toivonen, J.; Ihantola, S.; Peraejaervi, K.; Toivonen, H.

2010-01-01

Alpha emitting radiation sources are typically hard to detect with conventional detectors due to the short range of alpha particles in the air. However, previous studies have shown that remote detection of alpha radiation is possible by measuring the ionization-induced fluorescence of air molecules. The alpha-induced ultraviolet (UV) light is mainly emitted by molecular nitrogen and its fluorescence properties are well known. The benefit of this method is the long range of UV photons in the air. Secondly, the detection is possible also under a strong beta and gamma radiation backgrounds as they do not cause localized molecular excitation. In this work, the optical detection was studied using two different detection schemes; spectral separation of fluorescence from the background lighting and coincidence detection of UV photons originating from a single radiative decay event. Our spectrally integrated measurements have shown that one alpha decay event yields up to 400 fluorescence photons in the air and all these UV photons are induced in a 5 ns time-window. On the other hand, the probability of a background coincidence event in 5 ns scale is very rare compared to the number of background photons. This information can be applied in fluorescence coincidence filtering to discriminate the alpha radiation initiated fluorescence signal from much more intense background lighting. A device called HAUVA (Handheld Alpha UV Application) was built during this work for demonstration purposes. HAUVA utilizes spectral filtering and it is designed to detect alpha emitters from a distance of about 40 cm. Using specially selected room lighting, the device is able to separate 1 kBq alpha emitter from the background lighting with 1 second integration time. (author)

Monitor for alpha beta contamination of hands; Moniteur de contamination alpha beta des mains

Energy Technology Data Exchange (ETDEWEB)

Guitton, J

1958-07-01

The following specifications of hands alpha beta contamination monitor are presented: the position of the hands, the detection and separation of alpha and beta, the information processing, the programming, the results presentation and general characteristics. (A.L.B.)

[Anti-TNF alpha in dermatology].

Science.gov (United States)

Mahe, E; Descamps, V

2002-12-01

The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.

Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

International Nuclear Information System (INIS)

Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

1989-01-01

This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [ 3 H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

PLE CATALYZED HYDROLYZES OF ALPHA-SUBSTITUTED ALPHA-HYDROXY ESTERS - THE INFLUENCE OF THE SUBSTITUENTS

NARCIS (Netherlands)

MOORLAG, H; KELLOGG, RM

1991-01-01

The enzymatic hydrolyses of a variety of alpha-substituted mandelic and lactic esters using pig liver esterase (PLE) have been investigated. High to moderate enantioselectivity was found for various alpha-substituted mandelic esters, whereas PLE showed low to no enantioselectivity for

Alpha particle studies during JET DT experiments

International Nuclear Information System (INIS)

1999-01-01

The 1997 DT experiment (DTE1) at the Joint European Torus included studies of the behaviour of alpha particles in high temperature plasmas. Clear alpha particle heating was observed in a series of otherwise similar 10MW hot-ion H-modes by scanning the DT mixture from 0%T to 93%T. Maxima in central temperature and energy content were obtained which corresponded with the maximum in fusion yield. Alfven Eigenmodes (AEs) have been detected in JET, driven by NBI or ICRH fast ions. However, in agreement with theory, no AE activity was observed in DT plasmas which could be attributed to alpha particle drive, except in the afterglow of some Optimised Shear pulses. Ion Cyclotron Emission (ICE) was detected at harmonics of the alpha particle cyclotron frequency at the outer edge of the plasma. The ICE is interpreted as being close to magnetoacoustic cyclotron instability, driven by inverted alpha distributions at the plasma edge. The high-energy neutral particle spectra showed features, which are ascribed to a mixture of alphas, neutralised by helium-like impurities, and deuterons, born from elastic collisions with alpha particles and neutralised by hydrogen-like impurities. The results of all these studies are consistent with classical alpha particle trapping and slowing-down. Future DT experiments will aim to increase alpha particle pressure, so interactions with plasma instabilities can be studied. The measurement of knock-on neutral triton spectra offers a clean way to determine confined alpha densities in these future experiments. (author)

Alpha particle studies during JET DT experiments

International Nuclear Information System (INIS)

2001-01-01

The 1997 DT experiment (DTE1) at the Joint European Torus included studies of the behaviour of alpha particles in high temperature plasmas. Clear alpha particle heating was observed in a series of otherwise similar 10MW hot-ion H-modes by scanning the DT mixture from 0%T to 93%T. Maxima in central temperature and energy content were obtained which corresponded with the maximum in fusion yield. Alfven Eigenmodes (AEs) have been detected in JET, driven by NBI or ICRH fast ions. However, in agreement with theory, no AE activity was observed in DT plasmas which could be attributed to alpha particle drive, except in the afterglow of some Optimised Shear pulses. Ion Cyclotron Emission (ICE) was detected at harmonics of the alpha particle cyclotron frequency at the outer edge of the plasma. The ICE is interpreted as being close to magnetoacoustic cyclotron instability, driven by inverted alpha distributions at the plasma edge. The high-energy neutral particle spectra showed features, which are ascribed to a mixture of alphas, neutralised by helium-like impurities, and deuterons, born from elastic collisions with alpha particles and neutralised by hydrogen-like impurities. The results of all these studies are consistent with classical alpha particle trapping and slowing-down. Future DT experiments will aim to increase alpha particle pressure, so interactions with plasma instabilities can be studied. The measurement of knock-on neutral triton spectra offers a clean way to determine confined alpha densities in these future experiments. (author)

Alpha-driven magnetohydrodynamics (MHD) and MHD-induced alpha loss in the Tokamak Fusion Test Reactor

International Nuclear Information System (INIS)

Chang, Z.; Nazikian, R.; Fu, G.Y.

1997-02-01

Alpha-driven toroidal Alfven eigenmodes (TAEs) are observed as predicted by theory in the post neutral beam phase in high central q (safety factor) deuterium-tritium (D-T) plasmas in the Tokamak Fusion Test Reactor (TFTR). The mode location, poloidal structure and the importance of q profile for TAE instability are discussed. So far no alpha particle loss due to these modes was detected due to the small mode amplitude. However, alpha loss induced by kinetic ballooning modes (KBMs) was observed in high confinement D-T discharges. Particle orbit simulation demonstrates that the wave-particle resonant interaction can explain the observed correlation between the increase in alpha loss and appearance of multiple high-n (n ≥ 6, n is the toroidal mode number) modes

Summary of alpha-neutron sources in GADRAS

International Nuclear Information System (INIS)

Mitchell, Dean James; Thoreson, Gregory G.; Harding, Lee T.

2012-01-01

A common source of neutrons for calibration and testing is alpha-neutron material, named for the alpha-neutron nuclear reaction that occurs within. This material contains a long-lived alpha-emitter and a lighter target element. When the alpha particle from the emitter is absorbed by the target, neutrons and gamma rays are released. Gamma Detector Response and Analysis Software (GADRAS) includes built-in alpha-neutron source definitions for AcC, AmB, AmBe, AmF, AmLi, CmC, and PuC. In addition, GADRAS users may create their own alpha-neutron sources by placing valid alpha-emitters and target elements in materials within their one-dimensional models (1DModel). GADRAS has the ability to use pre-built alpha-neutron sources for plotting or as trace-sources in 1D models. In addition, if any material (existing or user-defined) specified in a 1D model contains both an alpha emitter in conjunction with a target nuclide, or there is an interface between such materials, then the appropriate neutron-emission rate from the alpha-neutron reaction will be computed. The gamma-emissions from these sources are also computed, but are limited to a subset of nine target nuclides. If a user has experimental data to contribute to the alpha-neutron gamma emission database, it may be added directly or submitted to the GADRAS developers for inclusion. The gadras.exe.config file will be replaced when GADRAS updates are installed, so sending the information to the GADRAS developers is the preferred method for updating the database. This is also preferable because it enables other users to benefit from your efforts.

Exhaustive Weakly Wandering Sequences and Alpha-type Transformations

Directory of Open Access Journals (Sweden)

Stanley Eigen

2015-12-01

Full Text Available An increasing sequence of integers, $\\mathbb{B}$, is given for which there exists a family of ergodic, infinite measure preserving transformations $T_\\alpha$, $0 \\leq \\alpha \\leq 1$ so that (1 $T_\\alpha$ is of $\\alpha$-type and (2 $\\mathbb{B}$ is an exhaustive weakly wandering sequence for each $T_\\alpha$.

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon.

Science.gov (United States)

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-06-28

To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. GCs promote the development of rat colon. AFP appears to be involved, in

Expression of alpha-amylase in Bacillus licheniformis.

OpenAIRE

Rothstein, D M; Devlin, P E; Cate, R L

1986-01-01

In Bacillus licheniformis, alpha-amylase production varied more than 100-fold depending on the presence or absence of a catabolite-repressing carbon source in the growth medium. alpha-Amylase was produced during the growth phase and not at the onset of the stationary phase. Induction of alpha-amylase correlated with synthesis of mRNA initiating at the promoter of the alpha-amylase gene.

Increased voluntary exercise in mice deficient for tumour necrosis factor-alpha and lymphotoxin-alpha.

NARCIS (Netherlands)

Netea, M.G.; Kullberg, B.J.; Vonk, A.G.; Verschueren, I.; Joosten, L.A.B.; Meer, J.W.M. van der

2007-01-01

BACKGROUND: The endogenous mediators playing a role in the sensing of fatigue and cessation of exercise are yet to be characterized. We hypothesized that proinflammatory cytokines, in particular tumour necrosis factor-alpha (TNFalpha) and lymphotoxin-alpha (LT) transmit signals leading to fatigue.

Measurement and analysis of $\\alpha$ particle induced reactions on yttrium

CERN Document Server

Singh, N L; Chintalapudi, S N

2000-01-01

Excitation functions for /sup 89/Y[( alpha ,3n); ( alpha ,4n); ( alpha , p3n); ( alpha , alpha n); ( alpha , alpha 2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ( alpha , xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ( alpha , alpha xn) type of reactions. To the best of our knowledge, the excitation functions for ( alpha ,4n), ( alpha , p3n), ( alpha , alpha n) and ( alpha , alpha 2n) reactions were measured for the first time. (23 refs).

Measurement and analysis of alpha particle induced reactions on yttrium

Energy Technology Data Exchange (ETDEWEB)

Singh, N.L.; Gadkari, M.S. [Baroda Univ. (India). Dept. of Physics; Chintalapudi, S.N. [IUC-DAEF Calcutta Centre, Calcutta (India)

2000-05-01

Excitation functions for {sup 89}Y[({alpha},3n);({alpha},4n);({alpha},p3n);({alpha},{alpha}n);({alpha},{alpha}2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ({alpha},xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ({alpha},{alpha}xn) type of reactions. To the best of our knowledge, the excitation functions for ({alpha},4n), ({alpha},p3n), ({alpha},{alpha}n) and ({alpha},{alpha}2n) reactions were measured for the first time. (orig.)

Alpha clustering in nuclei

International Nuclear Information System (INIS)

Hodgson, P.E.

1990-01-01

The effects of nucleon clustering in nuclei are described, with reference to both nuclear structure and nuclear reactions, and the advantages of using the cluster formalism to describe a range of phenomena are discussed. It is shown that bound and scattering alpha-particle states can be described in a unified way using an energy-dependent alpha-nucleus potential. (author)

Alpha particle analysis using PEARLS spectrometry

International Nuclear Information System (INIS)

McKlveen, J.W.; Klingler, G.W.; McDowell, W.J.; Case, G.N.

1984-01-01

Alpha particle assay by conventional plate-counting methods is difficult because chemical separation, tracer techniques, and/or self-absorption losses in the final sample may cause either non-reproducible results or create unacceptable errors. PEARLS (Photon-Electron Rejecting Alpha Liquid Scintillation) Spectrometry is an attractive alternative since radionuclides may be extracted into a scintillator in which there would be no self-absorption or geometry problems and in which up to 100% chemical recovery and counting efficiency is possible. Sample preparation may include extraction of the alpha emitter of interest by a specific organic-phase-soluble compound directly into the liquid scintillator. Detection electronics use energy and pulse-shape discrimination to provide discrete alpha spectra and virtual absence of beta and gamma backgrounds. Backgrounds on the order of 0.01 cpm are readily achievable. Accuracy and reproducibility are typically in the 100 +-1% range. Specific procedures have been developed for gross alpha, uranium, plutonium, thorium, and polonium assay. This paper will review liquid scintillation alpha counting methods and reference some of the specific applications. 8 refs., 1 fig

[Alpha-melanocyte-stimulating hormone. From bench to bedside].

Science.gov (United States)

Böhm, M; Luger, T A

2010-06-01

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that is produced by the skin itself from the precursor proopiomelanocortin. It crucially mediates ultraviolet light-induced tanning after binding to melanocortin-1 receptors (MC-1R) expressed on the surface of epidermal melanocytes. The potent pigment-inducing and also cytoprotective actions of alpha-MSH are the rationale for the performance of first phase II clinical trials with Nle4-D-Phe7-alpha-MSH (NDP-alpha-MSH), a subcutaneously administered synthetic and superpotent alpha-MSH analogue, in patients with photodermatoses such as erythropoietic protoporphyria. Since alpha-MSH has shown promising anti-inflammatory and antifibrotic properties in numerous preclinical studies, it will be most interesting to evaluate these effects in further clinical pilot studies with NDP-alpha-MSH. In addition to alpha-MSH analogues, truncated tripeptides such as KDPT which do not bind to MC-1R but have sustained anti-inflammatory properties are currently emerging as another novel therapeutic strategy in dermatology.

Far-Infrared and Millimeter Continuum Studies of K-Giants: Alpha Boo and Alpha Tau

Science.gov (United States)

Cohen, Martin; Carbon, Duane F.; Welch, William J.; Lim, Tanya; Forster, James R.; Goorvitch, David; Thigpen, William (Technical Monitor)

2002-01-01

We have imaged two normal, non-coronal, infrared-bright K-giants, alpha Boo and alpha Tau, in the 1.4-millimeter and 2.8-millimeter continuum using BIMA. These stars have been used as important absolute calibrators for several infrared satellites. Our goals are: (1) to probe the structure of their upper photospheres; (2) to establish whether these stars radiate as simple photospheres or possess long-wavelength chromospheres; and (3) to make a connection between millimeter-wave and far-infrared absolute flux calibrations. To accomplish these goals we also present ISO Long Wavelength Spectrometer (LWS) measurements of both these K-giants. The far-infrared and millimeter continuum radiation is produced in the vicinity of the temperature minimum in a Boo and a Tau, offering a direct test of the model photospheres and chromospheres for these two cool giants. We find that current photospheric models predict fluxes in reasonable agreement with those observed for those wavelengths which sample the upper photosphere, namely less than or equal to 170 micrometers in alpha Tau and less than or equal to 125 micrometers in alpha Boo. It is possible that alpha Tau is still radiative as far as 0.9 - 1.4 millimeters. We detect chromospheric radiation from both stars by 2.8 millimeters (by 1.4 millimeters in alpha Boo), and are able to establish useful bounds on the location of the temperature minimum. An attempt to interpret the chromospheric fluxes using the two-component "bifurcation model" proposed by Wiedemann et al. (1994) appears to lead to a significant contradiction.

A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait.

Science.gov (United States)

Steinberg, M H; Coleman, M B; Adams, J G; Hartmann, R C; Saba, H; Anagnou, N P

1986-02-01

A novel deletion of at least 26 kilobase of DNA, including both alpha-globin genes, the psi alpha- and psi zeta-globin genes, but sparing the functional zeta-gene was found in a 10-year-old black boy with HbH disease and sickle cell trait. This particular deletion has not previously been described in blacks. Its existence makes it likely that the absence of Hb Barts hydrops fetalis in blacks is due to the rarity of the chromosome lacking two alpha-globin genes rather than a result of early embryonic death due to the failure to synthesize embryonic hemoglobins because of deletion of functional zeta-globin genes.

Color image enhancement of medical images using alpha-rooting and zonal alpha-rooting methods on 2D QDFT

Science.gov (United States)

Grigoryan, Artyom M.; John, Aparna; Agaian, Sos S.

2017-03-01

2-D quaternion discrete Fourier transform (2-D QDFT) is the Fourier transform applied to color images when the color images are considered in the quaternion space. The quaternion numbers are four dimensional hyper-complex numbers. Quaternion representation of color image allows us to see the color of the image as a single unit. In quaternion approach of color image enhancement, each color is seen as a vector. This permits us to see the merging effect of the color due to the combination of the primary colors. The color images are used to be processed by applying the respective algorithm onto each channels separately, and then, composing the color image from the processed channels. In this article, the alpha-rooting and zonal alpha-rooting methods are used with the 2-D QDFT. In the alpha-rooting method, the alpha-root of the transformed frequency values of the 2-D QDFT are determined before taking the inverse transform. In the zonal alpha-rooting method, the frequency spectrum of the 2-D QDFT is divided by different zones and the alpha-rooting is applied with different alpha values for different zones. The optimization of the choice of alpha values is done with the genetic algorithm. The visual perception of 3-D medical images is increased by changing the reference gray line.

Magnetofluorescent nanocomposites and quantum dots used for optimal application in magnetic fluorescence-linked immunoassay.

Science.gov (United States)

Tsai, H Y; Li, S Y; Fuh, C Bor

2018-03-01

Magnetofluorescent nanocomposites with optimal magnetic and fluorescent properties were prepared and characterized by combining magnetic nanoparticles (iron oxide@polymethyl methacrylate) with fluorescent nanoparticles (rhodamine 6G@mSiO 2 ). Experimental parameters were optimized to produce nanocomposites with high magnetic susceptibility and fluorescence intensity. The detection of a model biomarker (alpha-fetoprotein) was used to demonstrate the feasibility of applying the magnetofluorescent nanocomposites combined with quantum dots and using magnetic fluorescence-linked immunoassay. The magnetofluorescent nanocomposites enable efficient mixing, fast re-concentration, and nanoparticle quantization for optimal reactions. Biofunctional quantum dots were used to confirm the alpha-fetoprotein (AFP) content in sandwich immunoassay after mixing and washing. The analysis time was only one third that required in ELISA. The detection limit was 0.2 pg mL -1 , and the linear range was 0.68 pg mL -1 -6.8 ng mL -1 . This detection limit is lower, and the linear range is wider than those of ELISA and other methods. The measurements made using the proposed method differed by less than 13% from those obtained using ELISA for four AFP concentrations (0.03, 0.15, 0.75, and 3.75 ng mL -1 ). The proposed method has a considerable potential for biomarker detection in various analytical and biomedical applications. Graphical abstract Magnetofluorescent nanocomposites combined with fluorescent quantum dots were used in magnetic fluorescence-linked immunoassay.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Science.gov (United States)

Yoo, S H; Kwon, J H; Nam, S W; Kim, H Y; Kim, C W; You, C R; Choi, S W; Cho, S H; Han, J-Y; Song, D S; Chang, U I; Yang, J M; Lee, H L; Lee, S W; Han, N I; Kim, S-H; Song, M J; Hwang, S; Sung, P S; Jang, J W; Bae, S H; Choi, J Y; Yoon, S K

2018-04-16

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response. © 2018 John Wiley & Sons Ltd.

Case Study - Alpha

Directory of Open Access Journals (Sweden)

Stephen Leybourne

2016-11-01

Full Text Available This case study was developed from an actual scenario by Dr. Steve Leybourne of Boston University.  The case documents the historical evolution of an organization, and has been used successfully in courses dealing with organizational and cultural change, and the utilization of ‘soft skills’ in project-based management. This is a short case, ideal for classroom use and discussion.  The issues are easily accessible to students, and there is a single wide ranging question that allows for the inclusion of many issues surrounding strategic decision-making, and behavioural and cultural change. Alpha was one of the earlier companies in the USA to invest in large, edge-of-town superstores, with plentiful free vehicle parking, selling food and related household products. Alpha was created in the 1950s as a subsidiary of a major publicly quoted retail group.  It started business by opening a string of very large discount stores in converted industrial and warehouse premises in the south of the United States. In the early days shoppers were offered a limited range of very competitively priced products. When Alpha went public in 1981 it was the fourth largest food retailer in the US, selling an ever-widening range of food and non-food products.  Its success continued to be based on high volume, low margins and good value for money, under the slogan of ‘Alpha Price.’

Ultrastructural studies of human and rabbit alpha-M-globulins.

Science.gov (United States)

Bloth, B; Chesebro, B; Svehag, S E

1968-04-01

Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

Alpha heating in toroidal devices

International Nuclear Information System (INIS)

Miley, G.H.

1978-01-01

Ignition (or near-ignition) by alpha heating is a key objective for the achievement of economic fusion reactors. While good confinement of high-energy alphas appears possible in larger reactors, near-term tokamak-type ignition experiments as well as some concepts for small reactors (e.g., the Field-Reversed Mirror or FRM) potentially face marginal situations. Consequently, there is a strong motivation to develop methods to evaluate alpha losses and heating profiles in some detail. Such studies for a TFTR-size tokamak and for a small FRM are described here

Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Feng,L.; Gell, D.; Zhou, S.; Gu, L.; Kong, Y.; Li, J.; Hu, M.; Yan, N.; Lee, C.; et al.

2005-01-01

Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

Expression and secretion of Bacillus amyloliquefaciens alpha-amylase by using the yeast pheromone alpha-factor promoter and leader sequence in Saccharomyces cerevisiae.

OpenAIRE

Southgate, V J; Steyn, A J; Pretorius, I S; Van Vuuren, H J

1993-01-01

Replacement of the regulatory and secretory signals of the alpha-amylase gene (AMY) from Bacillus amylolique-faciens with the complete yeast pheromone alpha-factor prepro region (MF alpha 1p) resulted in increased levels of extracellular alpha-amylase production in Saccharomyces cerevisiae. However, the removal of the (Glu-Ala)2 peptide from the MF alpha 1 spacer region (Lys-Arg-Glu-Ala-Glu-Ala) yielded decreased levels of extracellular alpha-amylase.

Interactions between an alpha-helix and a beta-sheet. Energetics of alpha/beta packing in proteins.

Science.gov (United States)

Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A

1985-12-05

Conformational energy computations have been carried out to determine the favorable ways of packing a right-handed alpha-helix on a right-twisted antiparallel or parallel beta-sheet. Co-ordinate transformations have been developed to relate the position and orientation of the alpha-helix to the beta-sheet. The packing was investigated for a CH3CO-(L-Ala)16-NHCH3 alpha-helix interacting with five-stranded beta-sheets composed of CH3CO-(L-Val)6-NHCH3 chains. All internal and external variables for both the alpha-helix and the beta-sheet were allowed to change during energy minimization. Four distinct classes of low-energy packing arrangements were found for the alpha-helix interacting with both the parallel and the anti-parallel beta-sheet. The classes differ in the orientation of the axis of the alpha-helix relative to the direction of the strands of the right-twisted beta-sheet. In the class with the most favorable arrangement, the alpha-helix is oriented along the strands of the beta-sheet, as a result of attractive non-bonded side-chain-side-chain interactions along the entire length of the alpha-helix. A class with nearly perpendicular orientation of the helix axis to the strands is also of low energy, because it allows similarly extensive attractive interactions. In the other two classes, the helix is oriented diagonally relative to the strands of the beta-sheet. In one of them, it interacts with the convex surface near the middle of the saddle-shaped twisted beta-sheet. In the other, it is oriented along the concave diagonal of the beta-sheet and, therefore, it interacts only with the corner regions of the sheet, so that this packing is energetically less favorable. The packing arrangements involving an antiparallel and a parallel beta-sheet are generally similar, although the antiparallel beta-sheet has been found to be more flexible. The major features of 163 observed alpha/beta packing arrangements in 37 proteins are accounted for in terms of the computed

Testing hypotheses involving Cronbach's alpha using marginal models

NARCIS (Netherlands)

Kuijpers, R.E.; van der Ark, L.A.; Croon, M.A.

2013-01-01

We discuss the statistical testing of three relevant hypotheses involving Cronbach's alpha: one where alpha equals a particular criterion; a second testing the equality of two alpha coefficients for independent samples; and a third testing the equality of two alpha coefficients for dependent

Alpha/beta separation in liquid scintillation gel samples

International Nuclear Information System (INIS)

Grau Carles, A.; Grau Malonda, A.

1994-01-01

The pulse shape analysis commonly used in liquid scintillation alpha/beta separations is satisfactory for moderate quench levels. However, for gel samples, the alpha particle counting efficiency is never greater than 10%, and an optimum separation of the alpha component cannot be achieved when beta to alpha counting rate ratios are greater than 100. In such cases, it is better to use a spectrum analysis method for alpha/beta separation. ((orig.))

Alpha Channeling in Rotating Plasma with Stationary Waves

International Nuclear Information System (INIS)

Fetterman, A.; Fisch, N.J.

2010-01-01

An extension of the alpha channeling effect to supersonically rotating mirrors shows that the rotation itself can be driven using alpha particle energy. Alpha channeling uses radiofrequency waves to remove alpha particles collisionlessly at low energy. We show that stationary magnetic fields with high n θ can be used for this purpose, and simulations show that a large fraction of the alpha energy can be converted to rotation energy.

Reggeon field theory for alpha (0)>1

CERN Document Server

Amati, Daniele; Le Bellac, M; Marchesini, G

1976-01-01

The asymptotic behaviour of the scattering amplitude is obtained when the pomeron has intercept alpha (0) larger than one. The reggeon field theory is studied by introducing a lattice in impact parameter space. Use is made of a previous result showing that asymptotically the dynamics is controlled at each lattice site ( alpha '=0 case) by a two-level structure. This leads to a non-Hermitean Hamiltonian expressed in terms of spin operators in which the intersite interaction term is proportional to the pomeron slope alpha '. The spectrum of such a system shows a degenerate ground state for alpha (0)> alpha /sub c/>or approximately=1 and a continuum with vanishing excitation gap at alpha (0)= alpha /sub c/. The vacuum does not change structure at the critical value. The criticality is shown by an order parameter which is given by the matrix element of a field operator between the vacuum and its degenerate companion. The nature of this critical phenomenon is better understood by continuously transforming the Hami...

Innovations in Los Alamos alpha box design

International Nuclear Information System (INIS)

Ledbetter, J.M.; Dowler, K.E.; Cook, J.H.

1985-01-01

Destructive examinations of irradiated fuel pins containing plutonium fuel must be performed in shielded hot cells with strict provisions for containing the plutonium. Alpha boxes provide containment for the plutonium, toxic fission products, and other hazardous highly radioactive materials. The alpha box contains windows for viewing and a variety of transfer systems specially designed to allow transfers in and out of the alpha box without spread of the hazardous materials that are contained in the box. Alpha boxes have been in use in the Wing 9 hot cells at Los Alamos National Laboratory for more than 20 years. Features of the newly designed alpha boxes are presented

Training detector as simulator of alpha detector

International Nuclear Information System (INIS)

Tirosh, D.; Duvniz, E.; Assido, H.; Barak, D.; Paran, J.

1997-01-01

Alpha contamination is a common phenomena in radiation research laboratories and other sites. Training staff to properly detect and control alpha contamination, present special problems. In order to train health physics personnel, while using alpha sources, both the trainers and the trainees are inevitably exposed to alpha contamination. This fact of course, comes in conflict with safety principles. In order to overcome these difficulties, a training detector was developed, built and successfully tested. (authors)

Grindability of alpha-case formed on cast titanium.

Science.gov (United States)

Koike, Marie; Jacobson, David; Chan, Kwai S; Okabe, Toru

2009-09-01

The hardened alpha-case (alpha-case) layer inevitably forms on the surface of titanium castings when prepared by investment casting. Because the hardness of the alpha-case is incomparable to that of the interior structure, the perception exists that the alpha-case is difficult to remove during cutting, grinding and polishing. Grindability (ease of grinding) of cast cpTi and cast Ti-6Al-4V was evaluated by grinding cast specimens incrementally using a SiC abrasive wheel. The present study revealed that the presence of the brittle alpha-case with lower fracture toughness is beneficial in grinding titanium. The alpha-case on the ductile cpTi can be ground much easier than its bulk interior structure. In less ductile Ti-6Al-4V, the grinding rate is much higher than that of cpTi, and the alpha-case and its interior structure are at similar levels since the fracture toughness of its alpha-case and the bulk material is not large enough.

Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.

Science.gov (United States)

Lee, Dae-Hee; Lee, Yong J

2008-10-01

Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1alpha accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1alpha accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O(2)) in the presence of 100 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. (c) 2008 Wiley-Liss, Inc.

Functional and genomic analyses of alpha-solenoid proteins.

Science.gov (United States)

Fournier, David; Palidwor, Gareth A; Shcherbinin, Sergey; Szengel, Angelika; Schaefer, Martin H; Perez-Iratxeta, Carol; Andrade-Navarro, Miguel A

2013-01-01

Alpha-solenoids are flexible protein structural domains formed by ensembles of alpha-helical repeats (Armadillo and HEAT repeats among others). While homology can be used to detect many of these repeats, some alpha-solenoids have very little sequence homology to proteins of known structure and we expect that many remain undetected. We previously developed a method for detection of alpha-helical repeats based on a neural network trained on a dataset of protein structures. Here we improved the detection algorithm and updated the training dataset using recently solved structures of alpha-solenoids. Unexpectedly, we identified occurrences of alpha-solenoids in solved protein structures that escaped attention, for example within the core of the catalytic subunit of PI3KC. Our results expand the current set of known alpha-solenoids. Application of our tool to the protein universe allowed us to detect their significant enrichment in proteins interacting with many proteins, confirming that alpha-solenoids are generally involved in protein-protein interactions. We then studied the taxonomic distribution of alpha-solenoids to discuss an evolutionary scenario for the emergence of this type of domain, speculating that alpha-solenoids have emerged in multiple taxa in independent events by convergent evolution. We observe a higher rate of alpha-solenoids in eukaryotic genomes and in some prokaryotic families, such as Cyanobacteria and Planctomycetes, which could be associated to increased cellular complexity. The method is available at http://cbdm.mdc-berlin.de/~ard2/.