Linkage of human chorionic gonadotrophin and placental lactogen biosynthesis to trophoblast differentiation and tumorigenesis

Normal trophoblast of the human placenta elaborates at least two major protein hormones, chorionic gonadotrophin (hCG) and placental lactogen (hPL). Molar and choriocarcinoma tissues characteristically synthesize large amounts of hCG and hPL. To examine the role of trophoblast differentiation in the expression of the hCG and hPL genes, we studied the cytological distribution of their mRNAs in tissue sections of human hydatidiform mole and choriocarcinoma by in situ hybridization. Histologically, these tissues are in different stages of cellular differentiation. In normal placenta, hCG alpha/beta mRNA can be localized to some cytotrophoblasts and primarily to the syncytium, whereas hPL mRNA appears only in the syncytial layer. In hydatidiform mole, which still retains placental villous morphology, the hPL gene and hCG alpha and beta genes are expressed but are poorly localized because of the admixture of cyto- and syncytiotrophoblasts. By contrast, choriocarcinoma, which is devoid of placental villous pattern but in which the cyto- and syncytiotrophoblast-like components are distinguishable, expresses hCG alpha and beta in the syncytial-like areas but little, if any, hPL. These results suggest that a certain level of trophoblast differentiation, such as villous formation, is associated with hPL expression, while the hCG alpha gene and the hCG beta gene can be expressed in more disorganized tissues which contain cytotrophoblastic elements.     

Characterization of human chorionic gonadotropin in urine of patients with trophoblastic diseases by Western blotting using specific antibodies

Human chorionic gonadotropin (hCG) from urine of patients with trophoblastic diseases was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by Western blotting using specific antibodies. Western blotting using anti-hCG beta carboxy-terminal peptide (CTP) revealed that the molecular weights of the beta subunits of the three molar hCG samples were identical to that of standard hCG beta, but those of choriocarcinoma hCG samples were individually different. In the five choriocarcinoma hCG samples, the beta subunits of three samples were apparently larger than standard hCG beta, while those of two samples were smaller than standard hCG beta but larger than desialylated standard hCG beta. These results suggest that structural changes of carbohydrates of hCG, which may be induced by malignant transformation of the trophoblast, can be observed as differences in molecular weight. In SDS-PAGE under nonreducing conditions. Western blotting using anti-hCG beta-CTP revealed a single band corresponding to hCG beta. Under reducing conditions with dithiothreitol (DTT), however, a second low-molecular-weight material (called here CTP') could be observed with anti-hCG beta-CTP. All five choriocarcinoma hCG samples were much more susceptible than standard hCG to cleavage of CTP' by DTT. We conclude that estimations of molecular weight and susceptibility to DTT reduction of urinary hCG by Western blotting using specific antibodies are useful in the diagnosis of choriocarcinoma.     

Hepatic granuloma: decreasing trend in a high‐incidence area

Background: Hepatic granuloma (HG) has a high reported incidence in Saudi Arabia (14.6%). We aimed to identify the incidence of HG in our centres and review its presenting features and underlying aetiology. Methods: A total of 5531 liver biopsies were screened through a computer database over 13 years. Sixty‐six (1.2%) patients fulfilled our inclusion criteria. The patients were then divided into three groups according to the aetiology. Group 1, tuberculosis (n=26); Group 2, viral hepatitis B and C (n=11); and Group 3, idiopathic (n=9). The demographical data and the clinical and biochemical features of all the groups were analysed. Results: Infections comprised of 72.2% of HG. The incidence of tuberculosis was 42.6%, viral hepatitis 16.3% and idiopathic 14.8%. Fever (47.5%), weight loss (42.6%) and fatigue (45.9%) were commonly found symptoms. Fever and weight loss were significantly more frequently presenting symptoms in Group 1 than in Groups 2 and 3 (P=0.0002, 0.04, 0.001 and 0.02 respectively). The mean bilirubin levels in Group 1 were significantly lower than in Groups 2 and 3 (P=0.04 and 0.03 respectively). The mean albumin levels were significantly lower in Group 3 compared with Group 2 (P=0.002), and Group 1 had lower levels compared with Group 2 (P=0.018). Conclusion: The incidence of HG is much lower than reported previously from this region. Tuberculosis and viral hepatitis are the most common causes and, contrary to previous reports, schistosomiasis is rare. Fever and weight loss distinguished tuberculous HG.     

Clinical utility of human chorionic gonadotropin and alpha-subunit measurements

Sensitive and quantitative radioimmunoassays of serum human chorionic gonadotropin (hCG) levels have expanded the utility of hCG measurements from a simple pregnancy test into a powerful tool applicable in an increasing number of clinical disorders. Proper management of gestational trophoblastic disease depends on reliable and sensitive hCG determinations. Information on the in vivo doubling time of hCG in early pregnancy can be used in more effective diagnosis of early pregnancy disorders such as ectopic pregnancy and spontaneous abortion. Serum hCG is an effective tumor marker in the staging and management of testicular cancer and potentially of nontrophoblastic cancers. Measurement of glycoprotein hormone alpha-subunit levels has clinical application in gestational trophoblastic disease, abnormal pregnancy, and some forms of nontrophoblastic malignancy.     

Duarte (DG) galactosemia: a pilot study of biochemical and neurodevelopmental assessment in children detected by newborn screening

Newborn screening for galactosemia has shown a high prevalence of partial galactose uridyl transferase deficiencies such as Duarte (DG) galactosemia.Study objective: To determine whether (a) there is any clinical impact of DG galactosemia on development (b) there is a relationship between outcome and biochemical parameters in patients who receive no treatment.Study population: Twenty-eight children with DG galactosemia. Group-I—17 children had a lactose restricted diet in the first year of life. Group-II—11 children had a regular diet since birth.Methods: Developmental, physical, and ophthalmologic assessments were completed on both DG groups. RBC gal-1-p and urine galactitol were monitored during the follow-up visits in every child with DG galactosemia. Gal-1-p, urine galactitol, liver function tests, and FSH were tested at the time of study visit.Results: The groups had statistically significant differences on RBC gal-1-p and urine galactitol at the 2 week, 1 month, 6 month, and 1 year time points. There was no statistical difference of gal-1-p or urine galactitol in group-I and -II at the time of study. The groups had statistically significant differences on adaptive scores, but not on language or IQ. None of the DG subjects had abnormal liver function at the time of diagnosis or the study visit. The FSH levels were normal. There were no statistically significant relationships between the first year metabolic values and developmental outcomes.Conclusions: The data presented here indicate that clinical and developmental outcomes in DG galactosemics are good regardless of any diet changes.     

Hepatic inflammatory pseudotumor presenting in an 8-year-old boy: A case report and review of literature

Hepatic inflammatory pseudotumors are uncommon benign lesions. Accurately diagnosing hepatic inflammatory pseudotumor can be very challenging because the clinical presentation and radiological appearances are nonspecific and cannot be certainly distinguished from malignant neoplastic processes. Herein, we present a case of hepatic IPT in an 8-year-old boy who presented to clinic with a 3-mo history of a tender hepatic mass, fever of unknown origin, and 9-kg weight loss. The physical examination was notable for tender hepatomegaly. Laboratory investigations were notable for a normal hepatic profile and elevated erythrocyte sedimentation rate and C-reactive protein. A T2-attenuated magnetic resonance imaging scan of the abdomen showed a 4.7 cm × 4.7 cm × 6.6 cm, contrast-enhancing, hyper-intense, well-defined lesion involving the right hepatic lobe. In view of the unremitting symptoms, tender hepatomegaly, thrombosed right hepatic vein, nonspecific radiological findings, and high suspicion of a deep-seated underlying infection or malignancy, a right hepatic lobectomy was recommended. Microscopically, the hepatic lesion exhibited a mixture of inflammatory cells (histiocytes, plasma cells, mature lymphocytes, and occasional multinucleated giant cells) in a background of dense fibrous tissue. Immunohistochemically, the cells stained negative for SMA, ALK-1, CD-21 and CD-23, diffusely positive for CD-68, and focally positive for IgG4. The final histopathological diagnosis was consistent with hepatic IPT. At the postoperative 4-mo follow-up, the patient was asymptomatic without radiological evidence of recurrence.