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BACKGROUND Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha fetoprotein (AFP) are biomarkers for hepatocellular carcinoma (HCC). However, their performance in patients with cirrhosis related to hepatitis C virus (HCV) treated with direct-acting antiviral agents (DAA) is unknown. AIM To evaluate PIVKA-II and AFP as HCC predictors in DAA-treated patients with HCV-related cirrhosis METHODS: In this single centre study, patients with cirrhosis from chronic HCV infection and with a sustained virological response (SVR) to DAA were tested for PIVKA-II and AFP (Fujirebio, Japan) at the start of DAA treatment (baseline), end of treatment (EOT) and at HCC diagnosis. RESULTS We included 400 patients with mean age 65 (24-92); 56% were men. From baseline to EOT, PIVKA-II did not change (35 vs 35 mAU/mL, P = 0.43) while AFP significantly decreased (12 vs 6 ng/mL, P or ≤41 mAU/mL (P or ≤15 ng/mL (P = 0.02). By combining EOT-PIVKA-II and AFP, the 4-year probabilities of HCC were 3% in patients testing negative for both markers, 18% in patients positive for both, and 38% in patients positive for at least one (P

Changes in Gc-globulin (Gc) and in alpha-foetoprotein (AFP) have been shown to be related to outcome in patients with acute liver failure (ALF). Gc is a serum protein that complexes with intravascular actin released during cellular necrosis. AFP, also made by hepatocytes, is associated with hepatocellular growth and regeneration. Previously, low absolute levels or decreases over time in either AFP or Gc portended to be a poor outcome.In a retrospective analysis of the double-blind trial of intravenous N-acetylcysteine (NAC) for ALF not because of acetaminophen, sera on days 1 and 3 or days 2 and 4 following admission were available to measure AFP in 70 patients and Gc in 66 patients. Mann-Whitney U tests were performed on the admission values, the absolute change and the fractional change of AFP and Gc to compare TFS (transplant-free survival) and non-TFS (death or transplantation). Logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate the markers in comparison and in addition to King's College Criteria (KCC).Transplant-free survival patients were characterized by increases in AFP, whereas non-TFS had significantly different (negative) absolute and fractional changes (P .01). The addition of declining AFP levels to KCC improved the area under the curve in predicting non-TFS (AUC70%). Gc globulin values did not differ between TFS and non-TFS in the 2-day intervals studied (P .2).In this comparison of two prognostic markers in patients with non-acetaminophen-induced ALF, rising AFP but not rising Gc levels was associated with TFS.ClinicalTrials.gov number NCT00004467.

Background & aims This study investigates the long-term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving entecavir (ETV) therapy. Methods We enrolled 481 nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months. Results The 8-year cumulative incidences of developing HCC, cirrhotic events and liver-related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis-4 (FIB-4) and alpha-foetoprotein (AFP) levels at 12 months of treatment, and FIB-4 increase from baseline to 12 months were independent factors of HCC. FIB-4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB-4 cut-off values of 3, 3 and 5 as well as AFP cut-offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB-4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8-year incidences of HCC, cirrhotic events and liver-related mortality in the subgroups with low FIB-4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality. Conclusion The combination of FIB-4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy.

Background & Aims We investigated the significance of 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) parameters and alpha-foetoprotein (AFP) levels in patients with locally advanced hepatocellular carcinoma (LA-HCC). Methods We retrospectively analysed data of 228 patients with LA-HCC who underwent pretreatment 18F-FDG PET between January 2003 and December 2013. All patients were treated using liver-directed therapy involving radiotherapy. The maximum standardized uptake values (SUVs) and tumour-to-extratumoural liver SUV ratios were calculated, and pretreatment AFP values were obtained. Results Patients were divided into high and low maximum SUV (SUVmax) groups according to a SUV cut-off of 4.825 determined via receiver-operating characteristic analysis. High AFP level (>550 ng/mL) and high SUVmax were significant predictors of overall and progression-free survival. Better treatment responses and longer median progression-free and overall survival were observed in the low SUVmax group, compared to the high SUVmax group. Similar results were obtained for SUV ratio-based (cut-off value: 2.355) and AFP-based analyses (cut-off value: 550 ng/mL). Three risk groups were identified using the double biomarkers of SUVmax and AFP value as strong prognosticators predictive of survival outcomes. This risk stratification was identified as a prognosticator of survival outcomes, even after subgroup analyses. Furthermore, in high risk group, significantly high extrahepatic failure was shown while in low risk group, significantly low intrahepatic failure. Conclusions Clinical significance of double biomarkers, SUV and AFP, could be translated into risk stratification for LA-HCC. It could be a valuable tool for survival outcome prediction.

Given the interest of many people and families directly or indirectly affected by hereditary tyrosinemia (HT1), I have tried to give my view on the history of the disease from 1965 to 2015 (Fig. 1.1).

Summary Besides structural and physiological data of alpha foetoprotein, this paper points out the optimal conditions for sampling, assays and interpretation of results.

Alpha-foetoprotein (AFP), one of the first protein tumour markers discovered, is widely used today in clinical practice. Its application for the screening and diagnosis of hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a matter of extensive debate. In addition to the studies focused on the role of the AFP in the diagnosis of HCC, in recent years AFP has been used to guide the therapeutic choice in HCC and monitor the treatment. Here, we summarize the latest studies that show the interest of AFP quantification in determining the suitability of liver transplantation or to follow-up on patients receiving the targeted treatment sorafenib. We also highlight the recent studies showing the active role of AFP in tumour progression, and the new modes of regulation of this tumour marker. Among these is the regulation of AFP through tumour proteostasis and the Unfolded Protein Response (UPR). We discuss the implications of this new knowledge in the therapeutic context, in terms of interpreting serum levels of AFP, and the new perspectives offered by AFP for the study of tumour proteostasis.

Liver transplantation (LT) is a validated treatment for selected cirrhotics with hepatocellular cancer (HCC). A retrospective single center study including 137 recipients having proven HCC was done to refine inclusion criteria for LT as well as to look at impact of locoregional treatment (LRT) on outcome. At pre-LT imaging, 42 (30.6%) patients were Milan criteria (MC)-OUT; 28 (20.4%) were University of California San Francisco criteria (UCSFC)-OUT. Pre-LT LRT was performed in 109 (79.6%) patients. Multivariate analysis identified four factors to be independently predictive of recurrence: tumour number >3, AFP level ≥400 ng/ml, microvascular invasion and rejection needing anti-lymphocytic antibodies. When considering pre-transplant variables only, AFP level ≥400 ng/ml (HR = 5.13; P

Un hamartome mesenchymateux (HM) du foie chez une petite fille âgee de sept mois etait associe avec une discrete augmentation du taux serique d'alpha foetoproteine (AFP) (320 pgJL, taux normal < 25 apresl'âge de six mois). L'examen anatomopathologique mettait en evidence un contingent hepatocellulaire abondant a la peripherie de la tumeur. Les hepatocytes tumoraux etaient legerement atypiques et exprimaient l'AFP en immunohistochimie. Chez deux autres petites filles âgees respectivement de 14 mois et deux mois, presentant un HM et un taux augmente d'AFP (320 μg/L et 7500 μg/L, respectivement), le diagnostic preoperatoire d'hepatoblastome a ete pose a tort. L'HM du foie s'accompagnant d'un taux serique augmente d'AFP peut donc simuler un hepatoblastome radiologiquement dans les cas ou les kystes manquent, et un hepatoblastome foetal a l'examen anatomo-pathologique si un prelevement biopsique interesse seulement le contingent hepatocellulaire peripherique de l'HM.

Content: Prelabour rupture of membranes (PROM) complicates overall 10% of gestations which include 7% at term and 3 % preterm gestations. Making an early and accurate diagnosis of PROM is important, to allow gestational age specific obstetric interventions and to optimize perinatal outcome. Objective: To study the efficacy of alpha-foeto protein in cervicovaginal secretions, to diagnose prelabour rupture of membranes. Setting: A tertiary care centre. Materials and Methods: We performed a prospective study on 130 patients who were at ≥ 24 weeks of gestation, who had complaint of leaking per vagina, between September 2011 and August 2013. Alpha-foetoprotein test was perfomed on cervicovaginal secretions which were collected during per-speculum examinations. A diagnosis of prelabour rupture of membranes was made, based on combined clinical diagnosis which was made during hospital stay of the patients prospectively. The efficacy of Alpha-foetoprotein was studied. Stastical Analysis: Chi-square test, Kappa analysis. Results: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Alpha-foetoprotein were 88.9%, 98.5%, 98.3%, 90.1% and 93.8% respectively. Degree of agreement of Alpha-foetoprotein with combined clinical diagnosis was 0.875. Conclusion: Assessment of alpha-foetoprotein levels in cervi-covaginal secretions can be used as a reliable test to diagnose prelabour rupture of membranes when faced with a diagnostic dilemma.

Background & Aims In this study, we investigated the clinical usefulness of AFP and PIVKA-II in subdividing prognostic groups in patients with locally advanced HCC treated locally. Methods Patients who had undergone local treatment for locally advanced HCC between 2001 and 2006 were enrolled. Response to treatment was defined as a reduction in AFP or PIVKA-II by more than 50% from baseline levels at 1 month after the treatment completion. Patients were divided according to their AFP and PIVKA-II response: A↓P↓ [AFP response (+) and PIVKA-II response (+)]; A↓P↑ [AFP response (+) and PIVKA-II response (−)]; A↑P↓ [AFP response (−) and PIVKA-II response (+)]; A↑P↑ [AFP response (−) and PIVKA-II response (−)]. Clinical characteristics and prognosis were compared between groups. Results Patients were subdivided into four groups by the change in the level of the biomarkers AFP and PIVKA-II, and the survival outcomes of each group were distinct. Among patients with an AFP response, further subdivision by PIVKA-II response revealed that those in the A↓P↓ group had a longer median progression-free survival (PFS) and overall survival (OS) compared with those in the A↓P↑ group (PFS: 16.2 vs. 5.1 months, P = 0.009; OS: 26.3 vs. 7.3 months, P = 0.017). Combination of AFP and PIVKA-II response showed a predictive power for PFS and OS comparable to radiological criteria and better than AFP response alone. Conclusions In patients with locally advanced HCC, the use of a combination of two biomarkers, AFP and PIVKA-II, appears useful in predicting treatment outcomes through the subdivision of prognostic groups.

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Elevated serum levels of alpha-fetoprotein, a fetal serum protein, occurs on development of hepatoma or germ cell tumors, mainly yolk sac tumor. Very few cases of endometrial carcinoma associated with elevated serum alpha-fetoprotein have been reported. It is important to be aware of such entities to ensure correct diagnosis and hence patient management. We report a case of a 71 years old lady presenting with postmenopausal bleeding and elevated serum alpha-fetoprotein. Investigations confirmed the patient had an alpha-fetoprotein producing endometrial serous carcinoma. This is the third case of alpha-foetoprotein producing serous carcinoma. We discuss the clinicopathological features of the case and review the literature for previously reported alpha-fetoprotein producing endometrial carcinomas. These cases show aggressive behavior and very poor prognosis.

Serum and urine banks have proved to be useful in the conduct of epidemiological studies. Samples collected as part of a large prospective study can be stored and retrieved later for laboratory analyses, selecting samples from groups of special interest and also from matched controls. The applications of the method are considered under three headings: firstly as a marker of a medical disorder, secondly as a measure of the extent of exposure to a harmful agent and thirdly as a direct measure of a suspected harmful or protective agent. Examples of each are given. Banks of biological samples other than serum or urine, such as hair and nail, are now being formed. The scientific opportunities of these collections are great and it will be of interest to see how they will be used.

Suppression of human α-foetoprotein-producing hepatocellular carcinoma growth in nude mice by an anti α-foetoprotein antibody-daunorubicin conjugate with a poly-L-glutamic acid derivative as intermediate drug carrier

This article reviews the value of the tumour markers alpha-foetoprotein (AFP) and human chorionic gonadotrophin (hCG) in the management of patients with testicular germ-cell tumours, especially non-seminomatous tumours. Recent developments in their use, such as metabolic decay rate analysis, are discussed. Possible new markers for testicular cancer, particularly SP-1 and placental alkaline phosphatase, are reviewed.

1. 1. Porcine α-foetoprotein, APP, was isolated from serum of pig foetuses using preparative electrophoresis and irnmunosorbent techniques. 2. 2. The purity of the isolated AFP was controlled by polyacrylamide gel electrophoresis, electro-immunoassay and by injection of isolated AFP into rabbits. 3. 3. During the preparation of AFP from foetal pig serum an unexpected α 1 -globulin appeared as a contaminating protein. 4. 4. The molecular weight, isoelectric point and sedimentation coefficient were found to be 70,000, 4–61 and 4–56 respectively. No microheterogeneity as regards the physicochemical parameters investigated could be seen. The results were compared with those reported for some other mammals.

This study assessed the reactions of pregnant women who received ultrasound examination during their pregnancy. The subjects included 30 women who were diagnosed to have raised serum alpha foetoprotein (AFP) in a previous bloodtest and ultrasound scanning was therefore performed to further diagnose foetal abnormalities. Another 30 pregnant women receiving routine scanning for dates also served as subjects. The women were interviewed before and immediately after scanning and a questionnaire was sent to them four weeks after the examination. Results indicated that following scanning the subjects rated the procedure to be less distressing or less physically uncomfortable than they had initially expected. Most of them described the experience as ‘wonderful’ and ‘fine’. The follow-up opinion survey further confirmed that the women were satisfied with the procedures. Their responses highlighted the importance of giving feedback and allowing time to talk to the doctors when such an obstetric procedure w...

A technique for quantitative determination of human placental lactogen (HPL) hormone and alpha-foetoprotein (AFP) in serum or plasma in the same rocket immunoelectrophoresis is described. The HPL rockets are stained with Coomassie brilliant blue and the AFP rockets are visualized by auto-radiography or by a spark chamber technique. Sixty-seven HPL-AFP estimates were made on different sera from 21 women with twin pregnancies. Both the HPL and AFP concentrations were higher in serum from twin pregnancies than in serum from single pregnancies. The diagnostic use of the combined HPL-AFP assay, especially in the early diagnosis of twin pregnancies and of neural tube malformations, is discussed.

An analysis of survival time of 57 West European patients with hepatocellular carcinoma was carried out to define which of several possible factors (age, sex, cirrhosis and raised serum alpha-foetoprotein (AFP)) influenced survival. Although survival was significantly longer in younger patients (P less than 0.02) and in patients with normal serum AFP (P less than 0.01), multivariate analysis showed that significant variation in survival time is better explained by the single factor, the presence of cirrhosis, than by AFP level. This does not seem to apply for patients with this tumour in Africa and the Far East, and there may be a fundamental difference in the natural history of the tumour between high- and low-incidence areas.

Summary In the course of immunofluorescence absorption studies it was found that, besides Marek's disease tumour‐associated surface antigen (MATSA), two foetal antigens could be distinguished on MSB‐1 line cells, one of which was chicken foetal red blood cell antigen (chFRBC) and another chicken alpha‐foetoprotein (chAFP). The experiments suggest a lack of homology between the three antigens.

Female rats were maintained on standard laboratory diet, Miller's diet or Miller's diet containing 3'MeDAB. Animals fed standard or Miller's diet did not excrete alpha-foetoprotein (AFP) in their urine. Early appearance of AFP was demonstrated by examining the urine of rats on the 3'MeDAB regimen. The incidence of positive urine samples was high between the 5th and 7th week of the experiment. It thereafter declined, but from the 3rd month it steadily rose and reached a maximum of 80% at about 10 months. Though urinary excretion of AFP was irregular in individual animals, several positive urine samples were obtained from all rats followed for more than a few months. The urine of 90% of hepatoma-bearing rats contained AFP at the time of killing. The incidence of elevated serum AFP levels as determined by immunodiffusion, increased with the duration of the experiment, but was still only 70 percent in rats fed 3'MeDAB for over 34 weeks. The severity of the hepatic alterations, as well as hepatocytic uptake of [3H]thymidine, increased with time. The serum of animals fed the standard diet was negative, whereas AFP was very infrequently detected in the serum of rats given Miller's hypoprotein diet. The results demonstrate that, in a population exposed to hepatocarcinogenic agent, the recurring detection of urinary excretion of AFP is a useful indicator of the high risk of developing hepatomas. Images Fig. 2 Fig. 3 Fig. 5

A method of isolating rabbit alpha-foetoprotein (RAFP) from amniotic fluid, liver extract and foetal and neonatal serum is described. RAFP was purified by a stepwise procedure involving gel filtration, preparative polyacrylamide gel electrophoresis and concanavalin A affinity chromatography. Monomeric and dimeric forms of RAFP were present in purified extracts. Four molecular variants of RAFP have been identified by concanavalin A chromatography and crossed immunoelectrophoresis.

Finnstrom, O., Gothefors, L. and Zetterlund, B. (Departments of Paediatrics, University Hospitals, Linkoping and Umea, Sweden). Studies on maturity in newborn infants. VII. Foetal haemoglobin. Acta Paediatr Scand, 64:404, 1975.–Cord blood from 125 newborns of various gestational ages has been analysed for the ratio foetal haemoglobin to total haemoglobin, using an alkali denaturation method. The quotient, percentage of foetal haemoglobin divided by birth weight correlates well with gestational age. Thus the percentage of foetal haemoglobin in cord blood can be used as a method for estimating maturity in newborn infants. Foetal haemoglobin has been compared with other methods for maturity assessments and seems to give the same precision in estimating gestational age as the best of these, which is the scoring of external characteristics. However, the latter method is considerably less time-consuming and more suitable for routine use.

Two rat alpha-foetoproteins (AFP) of different origin and purified according to two different techniques were labelled with 125I using an identical procedure. After labelling the reactivity of one of these AFPs was not modified whereas that of the other was markedly increased; this in spite of a greater purity made the latter unsuitable for the radioimmunoassay of rat AFP. The observed difference may be due to the technique of purification and brings additional evidence for the necessity of checking the reactivity of tracers.

The relative concentration of AFP in the foetal and neonatal rabbit was studied by immunological methods. A peak foetal concentration of AFP was found between the 24th and 26th days of gestation. AFP could not be detected in newborn serum after the 28th day post-partum. The concentration of AFP between the 20th and 25th days of gestation was found to rise from 327 mg/100 ml to 525 mg/100 ml. The synthesis of AFP in young and adult rabbits was successfully induced (a) during liver regeneration following carbon tetrachloride intoxication in rabbits less than 14 weeks of age, and (b) following the induction of hepatomas by oral administration of N.nitrosodiethylamine. L'ONTOGENIE DE L'ALPHA-FœTOPROTeINE CHEZ LE FETUS DE LAPIN OU LE LAPIN NOUVEAU-NE ET SON INDUCTION EXPERIMENTALE CHEZ LES LAPINS ADULTES La concentration relative de l'AFP chez le fœtus de lapin ou le lapin nouveau-ne a ete etudiee par des methodes immunologiques. On observe une concentration maximale d'AFP chez le fœtus entre le vingt-quatrieme et le vingt-sixieme jour de gestation. On ne decele plus d'AFP dans le serum de lapin nouveau-ne apres le vingt-huitieme jour post-partum. La concentration de l'AFP entre le vingtieme et le vingt-cinquieme jour de gestation est passee de 327 mg/100 ml a 525 mg/100 ml. La synthese de l'AFP chez les lapereaux et les lapins adultes a pu ětre induite a) pendant la regeneration du foie apres intoxication des lapins de moins de 14 semaines par le tetrachlorure de carbone et b) apres l'induction d'hepatomes par administration orale de N. nitrosodiethylamine.

Sections of paraffin-embedded tissue blocks fixed by ethanol/acetic acid were found to be very suitable for immunofluorescent (IF) study of αfp. In paraffin blocks the antigen was preserved for at least 1 year. It was possible to prepare serial sections for routine histological examination and simultaneous IF localization of several antigens practically in the same cells. Antibodies to αfp were obtained by glutaraldehyde immunosorbent technique. Their monospecificity was controlled by IF reaction on the αfp-negative sections and by neutralization with pure αfp. To differentiate αfp localization due to passive serum uptake from specific sites of αfp production or storage, a simultaneous study of αfp and γ-globulin γG distribution was performed. Only the structures containing αfp without γG were regarded as specifically connected with αfp metabolism. These were liver parenchyma cells in foetal and newborn liver and tumour cells in human primary liver carcinoma. Etude par Immunofluorescence de L'a-fcetoproteine (ufp) Dans le Foie et les Tumeurs Hepatiques. I. Technique de Localisation de L'afp Dans les Coupes Tissulaires Nous avons observe que des coupes tissulaires enrobees de paraffine et fixees a l'acide ethanol-acetique conviennent parfaitement a l'etude par immunofluorescence (IF) de l'afp. L'antigene s'est conserve au moins un an dans les blocs de paraffine. Nous avons pu preparer des coupes en serie pour l'examen histologique systematique et pour la localisation simultanee par IF de divers antigenes pratiquement dans les měmes cellules. Nous avons obtenu des anticorps a l'αfp par la methode d'immuno-absorption au glutaraldehyde. Leur monospecificie a ete contrǒlee par reaction d'IF sur les coupes αfp-negatives et par neutralisation au moyen d'αfp pure. Afin de differencier la localisation de l'αfp due a l'incorporation passive de serum des sites specifiques de production ou de stockage de l'αfp, nous avons effectue une etude simultanee de la distribution de l'αfp et de la γ-globuline (γg). Seules les structures contenant de l'αfp mais pas de γg ont ete considerees comme secifiquement liees au metabolisme de l'αfp. II sagissait des cellules parenchymateuses du foie de fαtus et de nouveau-ne et des cellules tumorales de carcinomes primitifs du foie humain.

Carbohydrate antigen 19-9 as a serum marker of hepatocellular carcinoma: Comparison with alpha-foetoprotein

Ten preparations containing various levels of alpha-foetoprotein have been assayed by eight different laboratories in an international collaborative study of the W.H.O. alpha-foetoprotein standard. Included among the preparations, all of which were analyzed by the radioimmunoassay technique, were normal serum, sera from women before and after delivery, sera from teratoblastoma, alcoholic cirrhosis, and primary liver cancer patients, and amniotic fluid. The study establishes the validity of the W.H.O. standard for specimens with a wide range of AFP titer. Results have lower variability when expressed in comparison with the W.H.O. standard than when compared with the local standard used in each laboratory. Within-laboratory variability was some 2·5 times as great using the local standard but both standards show important differences between laboratories; the worst laboratory had more than 10 times greater within-laboratory variance (of the log concentration) than the best after all assays failing a rigorous test of technical validity had already been removed. Agreement between laboratories was better for preparations with more than 45 international units of alpha-foetoprotein/ml such as sera from women in the second half of gestation. For preparations with very low AFP content, such as normal human sera, only one laboratory was capable of providing dose-response curves parallel to that of the standard. A statistical technique (cubic splines) is discussed which allows useful information to be extracted from poor or oddly shaped assay curves. It is also noted, however, that an experienced laboratory worker is often even more effective in recovering results from bad assays.

α-FOETOPROTEiNS (AFP) have been observed in the serum of all mammalian species so far studied1,2. In the rabbit AFP constitutes about 33% of the total serum protein on day 20 of gestation and reaches a peak concentration around days 24 to 26 (ref. 3). This ontogenic pattern is similar to that of the rat where maximum concentration is also reached late in gestation, but differs from the human where a steady decline occurs after the first trimester4,5. Although considerable interest has attached to the reappearance of AFP in the serum of adult animals and human patients with hepatocellular cancer6–9, little attention has been given to the possible role of this protein in normal development. The preliminary experiments reported here were designed to investigate this aspect by selectively neutralising AFP in vivo with specific antibodies.

The maturation of the inhibitory feedback action of oestrogen on FSH secretion in the immature female rat was studied from 5 days of age until after the first ovulation. To study the role of the oestrogen binding alpha-foetoprotein (AFP) which is present in the blood of young animals, the effects of various doses of oestradiol and of the synthetic oestrogen R2858 (11β-methoxy-17-ethynyl-oestradiol), which is not bound by AFP, were compared in ovariectomized rats. A rise in the serum concentration of FSH within 2 days of ovariectomy was first observed in rats ovariectomized at 8 days of age. Between 8 and 28 days of age the rise in FSH after ovariectomy could be prevented by oestrogen injections in such a way that the resulting FSH concentration amounted to 50% of that in ovariectomized control rats. This was achieved with a constant dose of 0·00015 μg R2858/100 g body weight, whereas the dose of oestradiol needed decreased from 0·05 to 0·01 μg/100 g body weight indicating an increased sensitivity to the feedback action of oestradiol. After day 28, sensitivity to the feedback action of both R2858 and oestradiol decreased progressively up to the time of the first ovulation. In contrast to results at earlier ages, none of the doses of either oestrogen was capable of maintaining near-physiological concentrations of FSH after 20 days of age. It is concluded that the apparent increase in sensitivity to the feedback action of oestradiol occurring before 28 days of age reflects the disappearance of AFP from the blood, whereas the subsequent decrease in sensitivity is independent of AFP. Moreover, it is concluded that up to about 20 days of age oestradiol could be, though not necessarily is, the sole ovarian factor involved in regulating FSH secretion, whereas at later ages additional steroids and/or factors must be involved.

Lack of suppressive effect of α-foetoprotein on development of experimental allergic encephalomyelitis in rats

Rat alpha-foetoprotein was separated into nine molecular variants by electrophoresis and affinity chromatography on Ricinus communis agglutinin and concanavalin-A. The nine variants are able to bind oestrone with the same capacity of one binding site per alpha-foetoprotein molecule. The association constants seem to vary with the sialic acid composition of the iso-alpha-foetoprotein.