52 results about "Alpha-fetoprotein" patented technology

The invention relates to the technical field of biological medicine, in particular to a T cell receptor targeting AFP peptide, a preparation method of the T cell receptor and a companion diagnostic kit. A T cell receptor targeting an AFP peptide is provided, the sequence of the AFP peptide is FMNKFIYEI, and the T cell receptor comprises a TCR [alpha] chain variable domain and a TCR [beta] chain variable domain. Corresponding nucleic acid molecules, vectors and host cells, and methods of making T cell receptors are provided. Further provided is a companion diagnostic kit containing the cell receptor. The invention provides a better choice for concomitant diagnosis and treatment products of cells of alpha fetoprotein (AFP).

The invention provides a detection method of an end face integrated reflection type SPR optical fiber biosensor manufactured based on a 2PP technology. An experiment system mainly comprises a single-mode optical fiber, an optical fiber coupler, an SPR probe, a tungsten lamp light source, a sample pool, a spectrum analyzer and a computer. The method is characterized in that a volcanic three-dimensional microstructure is directly constructed on the end face of a single-mode fiber through a 2PP technology, a metal film with the thickness of about 50nm is deposited on the inner wall of the volcanic three-dimensional microstructure, and a stable and efficient SPR excitation structure is formed; the structural parameters are subjected to FDTD simulation optimization design, and have the characteristics of high quality factor and high sensitivity. The sensor can be used for AFP detection, the sensitivity reaches 0.684 nm / (ng / mL) within the linear range of 0-10 ng / mL, the normal and risk early warning concentration interval of human serum AFP is covered, and the sensor has good biological suitability and early hepatocellular carcinoma screening capacity; in addition, the probe structure is small in size, detection can be completed only by a few microliters of liquid to be detected, and the probe is suitable for a microfluidic platform with an extremely low sample size or a clinical sampling scene. Compared with the prior art, the device has the advantages of high structural integration, high sensitivity, low sample consumption, convenience in manufacturing, stability, reliability and the like.

The invention belongs to the technical field of optical fiber sensing, and provides an optical fiber microstructure biosensor for detecting alpha fetoprotein and a preparation method thereof, and the method comprises the following steps: step 1, synthesizing a gold nanorod; 2, selecting a single-mode optical fiber for real-time monitoring, removing a coating layer, placing the single-mode optical fiber in a fusion splicer, drawing to obtain a micro-conical optical fiber, enabling CO2 laser to act on a conical waist area of the micro-conical optical fiber to manufacture a cone, taking out the optical fiber, and cooling and curing to obtain an optical fiber microstructure sensor; step 3, immersing a sensing area of the optical fiber microstructure sensor into NaOH, washing and drying, and immersing the sensing area into an MPTMS-ethanol solution; washing is carried out, and then the sensing area is immersed in a GNRs-PEG-COOH solution; washing and drying, immersing the sensing area in an EDC / NHS mixed solution for soaking, washing and drying, and putting the sensing area in an mAb solution for soaking; and washing and drying to obtain the optical fiber microstructure biosensor.

The invention relates to the technical field of biological medicine, in particular to a T cell receptor targeting AFP peptide, a preparation method of the T cell receptor and a companion diagnostic kit. A T cell receptor targeting an AFP peptide is provided, the sequence of the AFP peptide is FMNKFIYEI, and the T cell receptor comprises a TCR [alpha] chain variable domain and a TCR [beta] chain variable domain. Corresponding nucleic acid molecules, vectors and host cells, and methods of making T cell receptors are provided. Further provided is a companion diagnostic kit containing the cell receptor. The invention provides a better choice for concomitant diagnosis and treatment products of cells of alpha fetoprotein (AFP).

The invention belongs to the technical field of medical diagnosis, and discloses a marker for evaluating the curative effect of treating hepatocellular carcinoma by combining TACE with Czodili monoclonal antibody and bevacizumab, and a construction method and application of an FAAP prognostic scoring model. The invention develops and verifies an FAAP prognostic scoring system, and a novel composite model integrates four indexes of fibrin degradation product / cholinesterase ratio * 1000 (FCR), aspartate aminotransferase (AST), alpha fetoprotein (AFP) and portal vein tumor thrombus (PVTT), and is used for predicting the survival condition of uHCC patients subjected to TACE-Czodimab-bevacizumab triple therapy. The tool has an instant clinical value, can optimize patient selection, guides adaptive treatment upgrading, and provides a standardized curative effect evaluation basis for a clinical test for exploring a TACE-immunotherapy-anti-angiogenesis combined scheme.

The invention relates to the technical field of albumin oligopeptides, in particular to a preparation method of albumin oligopeptides and application of the albumin oligopeptides in promotion of postoperative patient recovery. The albumin oligopeptide provided by the invention can be taken before, during or after an operation, not only can quickly promote postoperative recovery and reduce the content of total bilirubin and direct bilirubin of a patient, but also can reduce the activity of glutamic oxalacetic transaminase and glutamic-pyruvic transaminase, and also can reduce the activity of carbohydrate antigen 199 and the content of alpha fetoprotein. In addition, by taking the albumin oligopeptide, the bitter throat dryness can be improved, nausea and vomiting symptoms can be eliminated, and the albumin oligopeptide has the effect of promoting postoperative liver function recovery of obstructive jaundice.

The invention belongs to the technical field of biomedical detection, and particularly discloses a nucleic acid aptamer for specifically recognizing serum alpha fetoprotein and application of the nucleic acid aptamer. The nucleotide sequence of the nucleic acid aptamer comprises a sequence as shown in SEQ ID No.1, or has more than 90% of homology with the sequence as shown in SEQ ID No.1, or one or more nucleotides are deleted or added in the sequence as shown in SEQ ID No.1. The nucleic acid aptamer can realize specific efficient recognition of AFP protein, also shows extremely high selectivity in a complex serum sample environment, eliminates non-specific adsorption interference of homologous protein and other serum interference protein, greatly reduces the false positive rate, and improves the accuracy and specificity of clinical detection. And the material constructed by directionally functionalizing the aptamer on the surface of the magnetic nano-carrier has rapid magnetic response performance, separation and enrichment of target protein can be realized within seconds, and the clinical diagnosis time is greatly shortened.

A clinical decision support device, comprising: a parameter acquisition module, configured to acquire measured values for markers in a biomarker combination of a subject, wherein the biomarker combination at least comprises an alpha fetoprotein, an abnormal prothrombin, γ-glutamyltransferase, and an albumin; a risk assessment module, configured to input the measured values for the markers in the biomarker combination into a calculation model to obtain an output of the calculation model as a liver cancer risk prediction result of the subject; and an output module, configured to output the liver cancer risk prediction result of the subject. Also disclosed are a sample analysis system and a method for assessing a liver cancer risk of a subject, capable of better assessing a liver cancer risk of a subject.

The present invention relates to the field of biomedical technologies, and particularly to a T cell receptor targeting an AFP peptide, a preparation method thereof, and an accompanying diagnostic kit. A T cell receptor targeting an AFP peptide is provided, the sequence of the AFP peptide is FMNKFIYEI, and the T cell receptor comprises a variable domain of the TCRα chain and a variable domain of the TCRβ chain. Corresponding nucleic acid molecules, vectors, and host cells are provided, as well as a method for preparing the T cell receptor. An accompanying diagnostic kit containing the cell receptor is further provided. The present invention provides a better choice for products for the accompanying diagnosis and treatment of cells of alpha-fetoprotein (AFP).

The invention provides a photoelectrochemical aptamer sensor for detecting alpha fetoprotein and a preparation method of the photoelectrochemical aptamer sensor, and relates to the technical field of sensors. According to the invention, a solvothermal method and a chemical reduction method are combined to gradually load BiPO4 nanosheets and Ag NPs onto TiO2NRA, so that the Ag / BiPO4 / TiO2NRA ternary composite material is obtained. Through the synergistic effect of a Type II type n-n heterojunction formed by TiO2NRA and BiPO4 and the surface plasma resonance (SPR) effect of Ag, the utilization rate of a photoelectric material to visible light is increased, and the photoelectric property of the photoelectric material is improved, so that the sensitivity of a photoelectrochemical biosensor is improved, and the detection range of alpha fetoprotein to be detected is expanded. In addition, a Type II type n-n heterojunction constructed by BiPO4 and TiO2NRA improves the transfer rate of electrons, the SPR effect of metal Ag is combined with the Type II type n-n heterojunction structure, a visible light source is utilized to a great extent, the photoelectric property of the photoelectrochemical aptamer sensor is improved, the sensitivity of the alpha fetoprotein photoelectrochemical aptamer sensor is further improved, and the detection limit is lower.

The invention discloses a rare earth nanoprobe, a preparation method and application thereof, and belongs to the technical field of biomedical detection.According to the technology, the rare earth nanoprobe with the high fluorescence quantum yield is synthesized, specific recognition of tumor markers is achieved through the aptamer technology, and the detection sensitivity and selectivity are remarkably improved. The fluorescence signal amplification effect of the rare earth nanoprobe and the modern fluorescence detection technology are innovatively combined, so that simultaneous detection of multiple tumor markers such as carcino-embryonic antigen (CEA), prostate specific antigen (PSA) and alpha fetoprotein (AFP) becomes possible. According to the method, the detection limit reaches the pg / mL level, the operation is simple and convenient, the cost is low, and the feasibility of clinical application is greatly improved. Besides, through multiple detection design, the detection efficiency and accuracy are further improved, an effective tool is provided for early diagnosis, curative effect monitoring and prognosis evaluation of tumors, and wide clinical application prospects and market potential are shown.

The invention provides a living cell surface double-tumor marker in-situ detection method based on a closed bipolar electrode (cBPE) array and an electrochemiluminescence (ECL) technology. The living cell surface double-tumor marker in-situ detection method is used for synchronously quantifying carcino-embryonic antigen (CEA) and alpha-fetoprotein (AFP). According to the system, the high specific surface area, the ordered porous structure and the rich surface amino active sites of a covalent organic framework (COF) material are utilized, and the excellent conductivity and biocompatibility of gold nanoparticles (Au NPs) are combined, so that the bifunctional signal probe COF (at) Au (at) MBApt is constructed. The probe can simultaneously load a large number of signal molecule methylene blue (MB) and is coupled with a targeting aptamer (Apt), so that high-capacity labeling and specific recognition of a target marker are realized.

The application relates to a preparation method and application of a ternary heterojunction composite photoelectrochemical immunosensor, and belongs to the technical field of photoelectrochemical biosensors, and particularly relates to a preparation method and application of a photoelectrochemical immunosensor for detecting alpha-fetoprotein by adopting a BiPO4 / BiOBr / CdS composite material. The method is characterized in that a ternary heterojunction is assembled on an FTO modified electrode to fix a capture antibody, and the accurate determination of alpha-fetoprotein is realized through a photocurrent signal response. The BiPO4 / BiOBr heterojunction expands the forbidden band width and expands the light absorption range; due to the sensitization of CDs, the absorption of visible light is enhanced, so that the photocurrent signal is increased. The method has the advantages of good stability, strong specificity, high sensitivity, good reproducibility and the like, is good for the rapid detection of alpha-fetoprotein, solves the existing technical difficulties, and provides a feasible method for the detection of tumor markers.

The invention relates to the technical field of detection, in particular to a microfiltration device for alpha fetoprotein heteroplasmon detection, a limiting baffle ring is arranged at the top of a supporting head in a microfiltration head component, corresponding limiting is provided for placement of a filter membrane, and the filter membrane is in contact with the inner side wall of the limiting baffle ring, so that a gap is prevented from being generated, and the detection accuracy of alpha fetoprotein heteroplasmon detection is improved. The working efficiency of filtering and adsorbing the alpha fetoprotein heterogeneous is improved, and the positive effect is achieved on the accuracy of subsequent detection work; an auxiliary assembly is further arranged in the supporting head part, so that the filter membrane can be better taken out, and the phenomenon that the filter membrane is easily damaged when the filter membrane is clamped by tweezers from the middle part of the filter membrane is avoided; in addition, an auxiliary pressing ring in the arranged volume cup assembly also has an extrusion limiting effect on the filter membrane, namely the problem that the filter membrane shakes when liquid is poured in is avoided, and the working stability of the filter membrane is improved; and the method has positive significance in improving the detection and filtering work efficiency of the alpha fetoprotein variant.

The application belongs to the field of biosensors, and provides a construction method and application of an electrochemical biosensor for quantifying AFP-L3% (AFP-L3 / AFP), and the specific process is as follows: Au@UiO-66 nanocomposites are obtained by using a hydrothermal method and an immersion reduction method, TCEP can open S-S in alpha-fetoprotein to obtain sulfydryl (-SH) and connect to Au@UiO-66, in-situ synthesis of AFP aptamer-copper clusters (Apt-CuNCs) is carried out by using DNA as a template, Apt-CuNCs are used to recognize total AFP, the content of total AFP is determined by using the generated Cu electrochemical signal, then, the Apt-CuNCs are subjected to enzymatic cleavage and stripping by using exonuclease I, alpha-fetoprotein heterogeneity (AFP-L3) is labeled by using lentil agglutinin (LCA) functionalized silver nanoparticles LCA@AgNPs, the content of AFP-L3 is determined by using the generated Ag electrochemical signal, and AFP-L3% can be calculated by combining the data of the two, and the electrochemical biosensor constructed by the method can be used for determining AFP-L3% in human serum.

A system for generating a hepatocellular carcinoma (HCC) report for a subject based on blood-based molecular profiling is provided. The system includes a sample preparation module configured to process a blood sample by isolating both plasma and serum fractions. A nucleic acid extraction module extracts a microRNA (miRNA) profile from the plasma fraction, and a real-time PCR module detects and quantifies the expression levels of a predefined panel of miRNAs, including miR-361-5p, miR-130a-3p, miR-27a-3p, miR-30d-5p, and miR-193a-5p. The expression levels of the predefined panel of miRNAs are used by a trained machine learning classifier to generate a HCC risk classification categorizing the subject into one of HCC risk levels. An alpha-fetoprotein (AFP) level detected and quantified from the serum fraction may also be used in combination with the miRNA expression levels in the HCC risk classification for enhanced prediction accuracy.

The invention relates to the technical field of biological detection, and discloses a reagent composition for liver cancer detection, a kit and application. The reagent composition provided by the invention comprises a combination of primers and probes for detecting the methylation states of the FAM109B gene, the RIMS2 gene, the SNX31 gene, the FAR1 gene and the FLJ26850 gene, so that the methylation state of a specific target sequence in the liver cancer characteristic gene can be detected, and the detection sensitivity and specificity of the liver cancer are at a relatively high level. The reagent composition provided by the invention can be used for noninvasive liver cancer screening, and during liver cancer screening, compared with conventional liver ultrasound and alpha fetoprotein combined detection, the detection sensitivity is greatly improved, the early screening accuracy of liver cancer is improved, and the misdiagnosis rate and missed diagnosis rate are greatly reduced.

As demonstrated herein, soluble human FcRn binds to AFP with affinities greater than observed with albumin, and is able to interfere with FcRn-mediated protection of and functional associations with IgG. Accordingly, provided herein, in some aspects, are compositions and methods to inhibit FcRn and AFP interactions in diseases or disorders where elevated AFP levels are associated with immunosuppression. Also provided herein, in some aspects, are compositions and methods to enhance or potentiate FcRn and AFP interactions in diseases or disorders with decreased AFP levels or diseases or disorders where increasing AFP levels increasing with immunosuppression.

The invention belongs to the technical field of alpha fetoprotein visual quantitative analysis, and particularly relates to a visual quantitative analysis method for alpha fetoprotein in saliva, a double-recognition multiple-quenching molecular imprinting and electrochemical luminescence microscope is constructed, and MI-ECLM takes self-developed SECLM as a signal output device and comprises a molecular imprinting polymer and a double-mechanism quencher; preparing a saliva sample and performing pretreatment; the pretreated saliva sample is placed on an MI-ECLM sensor, and an optical image is obtained through electrochemical luminescence imaging; and analyzing the optical image to realize visual quantitative detection of alpha fetoprotein in saliva.

The invention discloses an intelligent prediction system and method for early recurrence risk after liver cancer thermal ablation, and aims to solve the technical problem that prediction is not timely and inaccurate due to the fact that an existing prediction model ignores intraoperative dynamic information. According to the method, dynamic time sequence data such as tissue impedance and power in the thermal ablation process are collected in real time, and preoperative static data such as tumor size and alpha fetoprotein level are combined, so that a double-branch fusion prediction model is constructed. The model comprises a time sequence processing branch used for learning dynamic data time dependence and a static processing branch used for extracting static data features. By fusing the features of the two branches, the model can output a probability value representing the postoperative early recurrence risk. According to the method and the system, instant accurate risk stratification after operation is realized, and further, intraoperative intervention can be guided through real-time feedback, so that the early recurrence risk is actively reduced, and the prognosis of a patient is improved.

The invention discloses a method for detecting early hepatocellular carcinoma and a reagent set used by the method. The detection method comprises the following steps: performing biomarker identification of a group of methylated genes with difference in a computing system; performing, in a computing system, a quantitative measurement of the degree of methylation from the selected plurality of biomarkers in the group using a quantitative methylation-specific polymerase chain reaction; executing a formula calculation in the calculation system according to the methylation degree of the selected biomarker to obtain an M score of the selected biomarker; and performing a risk level assessment of hepatocellular carcinoma using the resulting M fraction or a combination of M fraction and serum alpha fetoprotein in a computing system.

The invention relates to the technical field of medical imaging omics analysis, and discloses an early-stage liver cancer postoperative recurrence prediction model and method based on imaging omics phenotypes, and the method comprises the following steps: data collection and preprocessing, feature screening and standardization, model construction, model verification and risk layering. The data acquisition and preprocessing is to obtain preoperative enhanced CT image data and clinical information of an early-stage hepatocellular carcinoma (HCC) patient meeting the agralan standard, and the clinical information comprises serum alpha fetoprotein (AFP) level and tumor number. According to the image omics phenotype-based early liver cancer postoperative recurrence prediction model and method, pre-operation and post-operation dual models are constructed by integrating pre-operation enhanced CT image omics characteristics (including first-order statistics, texture and wavelet characteristics), clinical parameters (such as serum alpha fetoprotein and tumor number) and post-operation pathological variables (such as microvascular invasion and satellite nodules).

The present invention discloses a photoelectrochemical detection device and application based on radiation modulation, belonging to the technical field of photoelectrochemical sensing and biological detection; a detection device applicable to the detection of alpha-fetoprotein, comprising a photoelectrochemical biosensor and a photoelectrochemical test device; the photoelectrochemical biosensor includes an ATA thin film electrode; the ATA thin film electrode includes an FTO substrate; a Au film layer is provided on the upper surface of the FTO substrate, and a TiO2 film layer is provided on the upper surface of the Au film layer; a AuNPs layer is deposited on the TiO2 film layer; the photoelectrochemical test device includes an optical chopper connected to a lock-in amplifier; the lock-in amplifier is connected to a low-pass filter; the optical chopper is arranged between the light source and the photoelectrochemical biosensor; the photoelectrochemical biosensor is connected to the low-pass filter through an electrochemical workstation; the present invention uses lock-in amplification combined with the ATA thin film electrode to enable the detection of the analyte to have a lower detection limit and a larger detection range.

This invention provides a nanocomposite material, its preparation method, and its application in a sandwich-structured enhanced immunosensor, belonging to the field of biosensor technology. This invention synthesizes a Ru@SiO2-NH2-Au nanocomposite material using a chemical oxidation method, constructs a Fe3O4@SiO2-NH2 composite carrier as a sensing platform, and successfully achieves ultrasensitive ECL immunosensor detection. The separation and enrichment of Fe3O4 during the sensing process improves detection efficiency. The -NH2 functional groups modified on the SiO2 surface provide active sites for the immobilization of the nanocomposite material and the specific recognition and binding of alpha-fetoprotein (AFP), achieving a highly efficient "carrier-functional material-target biomarker" interaction. This ECL immunosensor can detect AFP with high sensitivity, exhibiting a linear relationship within the range of 97.0% to 103.6%, with a detection limit of 1.28 × 10⁻⁶. ‑13 mg·mL ‑1 This provides a valuable reference for the future development of other AFP sensors.

This invention relates to the field of biodetection technology, and discloses a reagent composition, kit, and uses for liver cancer detection. The reagent composition provided by this invention includes a detection... FAM109B Gene, RIMS2 Gene, SNX31 Gene, FAR1 Genes and FLJ26850 The combination of primers and probes for gene methylation status enables the detection of methylation status of specific target sequences in the aforementioned liver cancer characteristic genes, achieving high sensitivity and specificity for liver cancer detection. The reagent composition of this invention allows for non-invasive liver cancer screening, and compared to conventional liver ultrasound and alpha-fetoprotein (AFP) testing, it significantly improves detection sensitivity, increases the accuracy of early liver cancer screening, and substantially reduces the rates of misdiagnosis and missed diagnosis.

The present invention relates to a composition for diagnosing, detecting, or monitoring a liver cancer disease, comprising nucleic acid affinity ligands and / or peptide affinity ligands for a group of biomarkers comprising at least Prolactin, Alpha Fetoprotein (AFP) and Interleukin-6 (IL-6) and, optionally, further comprising one or more of Squamous Cell Carcinoma Antigen (SCC), Metallopeptidase Inhibitor 1 (TIMP-1) and CYFRA 21-1. The present invention further envisages corresponding methods for diagnosing, detecting or monitoring a cancer disease in a subject, as well as a computer-implemented method for the analysis of a sample of a subject, a computer-implemented method for providing a trained machine learning model, the use of affinity ligands for detecting, diagnosing, or monitoring a liver cancer disease, in particular early forms of liver cancer.

The present invention relates to using genes that express specific alterations for hepatocellular carcinoma as biomarkers for detecting and diagnosing hepatocellular carcinoma cells. As biomarkers of the present invention, hyaluronan-mediated motility receptor (HMMR), neurexophilin 4 (NXPH4), paired-like homeodomain 1 (PITX1), thrombospondin 4 (THBS4), or ubiquitin-conjugating enzyme E2T (UBE2T) specifically alter their expression for hepatocellular carcinoma. Therefore, they have the following effects: they can be used as hepatocellular carcinoma-specific markers, and if they are used separately alone, or in combination with alpha-fetoprotein, or in other combinations, hepatocellular carcinoma can be diagnosed more specifically and accurately.

The invention belongs to the technical field of liver disease diagnosis, and particularly relates to a biomarker for auxiliary diagnosis of liver diseases and application, the biomarker comprises serum phosphatidylcholine, and further comprises any one or two of alpha fetoprotein and chitosanase 3-like protein 1. As a newly discovered liver disease diagnosis index, the PC provided by the invention has the highest predictive ability in hepatitis and higher predictive ability in liver cirrhosis and liver cancer, can improve the predictive ability of other indexes on liver diseases, and has very high clinical value.

The present invention relates to in vitro diagnostic reagents, and in particular to a composition for determining alpha-fetoprotein heterogeneities and its application. The composition comprises a first reagent group for capturing alpha-fetoprotein heterogeneities and a second reagent group for separating and determining alpha-fetoprotein heterogeneities in the same reaction system; the first reagent group comprises a lectin magnetic bead reagent and a sample diluent; the second reagent group comprises an AFP capture magnetic bead reagent, a signal-labeled AFP detection antibody reagent, and an eluent; or the second reagent group comprises a streptavidin magnetic bead reagent, a biotin-labeled AFP capture antibody reagent, a signal-labeled AFP detection antibody reagent, and an eluent; or, the first reagent group comprises a lectin magnetic bead reagent and a streptavidin magnetic bead reagent; the second reagent group comprises a biotin-labeled AFP capture antibody reagent, a signal-labeled AFP detection antibody reagent, and an eluent. The composition has strong specificity, high sensitivity, and strong instrument versatility, and can greatly improve the detection efficiency of AFP-L3.

The invention relates to the technical field of detection, in particular to a microfiltration device for alpha fetoprotein heteroplasmon detection, a limiting baffle ring is arranged at the top of a supporting head in a microfiltration head component, corresponding limiting is provided for placement of a filter membrane, and the filter membrane is in contact with the inner side wall of the limiting baffle ring, so that a gap is prevented from being generated, and the detection accuracy of alpha fetoprotein heteroplasmon detection is improved. The working efficiency of filtering and adsorbing the alpha fetoprotein heterogeneous is improved, and the positive effect is achieved on the accuracy of subsequent detection work; an auxiliary assembly is further arranged in the supporting head part, so that the filter membrane can be better taken out, and the phenomenon that the filter membrane is easily damaged when the filter membrane is clamped by tweezers from the middle part of the filter membrane is avoided; in addition, an auxiliary pressing ring in the arranged volume cup assembly also has an extrusion limiting effect on the filter membrane, namely the problem that the filter membrane shakes when liquid is poured in is avoided, and the working stability of the filter membrane is improved; and the method has positive significance in improving the detection and filtering work efficiency of the alpha fetoprotein variant.