Gonadotrophin-independent puberty in a boy with a beta-HCG-secreting brain tumour

We report on a short-statured boy in whom therapy with recombinant human growth hormone was initiated at the age of 9.7 years for assumed idiopathic growth hormone deficiency. On recombinant human growth hormone, height improved from -1.9 (standard deviation score) to -0.9 within 1 year, and the patient entered puberty spontaneously at 10.7 years. At 11.6 years he showed low morning cortisol and thyroxine levels, but was otherwise well. He showed an inconspicuous growth, and puberty progressed adequately until the age of 13.4 years, when he developed signs of an increased intracranial pressure, and a suprasellar choriocarcinoma was diagnosed. This case confirms the fact that beta chorionic gonadotrophin secreting tumours will not be diagnosed by the characteristic clinical manifestation of gonadotrophin-independent puberty if they occur at a time when normal puberty is expected. Particularly, it raises the question of how often the CNS should be re-evaluated by magnetic resonance imaging in children with growth hormone deficiency and normal initial neuroradiological imaging, when they develop additional hormonal deficiencies but no other clinical symptoms of an intracranial process.     

Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

ABSTRACT: BACKGROUND: The placental syncytiotrophoblast is the major source of maternal plasma corticotropin-releasing hormone (CRH) in the second half of pregnancy. Placental CRH exerts multiple functions in the maternal organism: It induces the adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone, regulates the timing of birth via its actions in the myometrium and inhibits the invasion of extravillous trophoblast cells in vitro. However, the auto- and paracrine actions of CRH on the syncytiotrophoblast itself are unknown. Intrauterine growth restriction (IUGR) is accompanied by an increase in placental CRH, which could be of pathophysiological relevance for the dysregulation in syncytialisation seen in IUGR placentas. METHODS: We aimed to determine the effect of CRH on isolated primary trophoblastic cells in vitro. After CRH stimulation the trophoblast syncytialisation rate was monitored via syncytin-1 gene expression and beta-hCG (beta-human chorionic gonadotropine) ELISA in culture supernatant. The expression of the IUGR marker genes leptin and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) was measured continuously over a period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which are known features of IUGR. RESULTS: CRH did not influence the differentiation of isolated trophoblasts into functional syncytium as determined by beta-hCG secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH treatment significantly increased leptin and 11beta-HSD2 expression, as well as leptin secretion into culture supernatant after 48 h. CONCLUSION: The relevance of CRH for placental physiology is underlined by the present in vitro study. The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might promote fetal nutrient supply and placental corticosteroid metabolism in the phase before labour induction.     

Recurrence following transsphenoidal surgery for acromegaly.

The long-term results of transsphenoidal adenomectomy and the incidence of possible recurrences were studied in 61 patients who had normal basal serum growth hormone (GH) levels 1 week after surgery. The patients were followed up for an average of 6.0 years (range: 1.5-14.0 years) by repeated measurements of GH, oral glucose tolerance testing (OGTT) and at the last follow-up visit also by assaying somatomedin C levels. In 4 of the patients, the basal GH levels had increased to values above 5 ng/ml. In 43 patients, a normal suppression of GH during an oral glucose load was observed shortly after surgery. In only 2 of these cases did a transiently inadequate suppression develop during the follow-up period, although clinical acromegaly did not recur and the somatomedin C levels remained normal. It is concluded that recurrence of active acromegaly is unlikely to occur in patients who achieve a normal glucose-induced suppression of GH levels shortly after adenomectomy. As such, an OGTT provides better prognostic information than basal human GH level measurements and may give a clearer and earlier indication of surgical success.     

Formation of N,N-Dimethylglycine, Acetic Acid, and Butyric Acid from Betaine by Eubacterium limosum

Two bacterial strains that grow anaerobically on betaine were isolated from enrichment cultures and identified as strains of Eubacterium limosum. In a mineral medium supplemented with yeast extract and Casitone, the doubling time of E. limosum strain 11A on betaine was 6 h at 37°C. The molar growth yield amounted to 9 g of dry cell mass per mol. Betaine was fermented in accordance with the following equation: 7 betaine + 2 CO₂ → 7 N,N-dimethylglycine + 1.5 acetate + 1.5 butyrate. E. limosum also grew on methanol and choline. The former was converted to acetate and butyrate, and the latter was converted to N,N-dimethylethanolamine, acetate, and butyrate. The conditions for the quantitative determination of N,N-dimethylglycine by capillary tube isotachophoresis have been determined.     

Suberoylanilide hydroxamic acid (SAHA) has potent anti-glioma properties in vitro, ex vivo and in vivo

Current treatment modalities for malignant gliomas do not allow long-term survival. Here, we identify suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylases (HDAC), as an effective experimental anti-glioma agent. Administration of SAHA to various glioma cell lines obtained from human, rat and mouse inhibited tumour cell growth in a range of 1-10 microm. This anti-glioma property is associated with up-regulation of the cell cycle control protein p21/WAF, as well as the induction of apoptosis. A novel tumour invasion model using slice cultures of rat brain corroborated the anti-glioma properties of SAHA in the organotypic brain environment. In this model, glioma invasion compromised adjacent brain parenchyma, and this tumour-associated cytotoxicity could be inhibited by SAHA. In addition, a 10-fold dose escalation experiment did not challenge the viability of cultured brain slices. In vivo, a single intratumoural injection of SAHA 7 days after orthotopic implantation of glioma cells in syngeneic rats doubled their survival time. These observations identify chromatin-modifying enzymes as possible and promising targets for the pharmacotherapy of malignant gliomas.     

Loss of heterozygosity on chromosome 3, bands q24----qter, in a diploid meningioma.

Cytogenetic analysis of a meningioma from a 46-year-old female patient exhibited as the sole cytogenetic aberration a deletion on the long arm of one chromosome 3 involving bands 3q24----qter. To verify this finding, RFLP analysis was performed with two polymorphic probes, MOX2 and D3S5. The patient was informative for both single copy probes and demonstrated loss of heterozygosity in the region above whereas chromosome 22 displayed no loss of heterozygosity as judged by a proximal and a distal probe.     

Attitudinal reciprocity in food sharing among brown capuchin monkeys

Capuchin monkeys (Cebus apella) share food even if separated by a mesh restraint. Pairs of capuchins were moved into a test chamber in which one of them received apple pieces for 20 min, and the other received carrot pieces for the next 20 min. Previous research had shown a correlation between the rate of food transfer in both directions across female-female dyads. The present study confirmed this result. Reciprocity across dyads can be explained, however, by symmetry in affiliative and tolerant tendencies between two individuals, provided these tendencies determine food sharing. The present study was designed to exclude this symmetry-based explanation by testing each pair (N=16) of adult females on six separate occasions. There existed a significant covariation across tests of sharing in both dyadic directions, a result unexplained by relationship symmetry. Moreover, control procedures (i.e. testing of a food possessor without a partner, or testing of two individuals with the same food or two different foods at the same time) indicated that behaviour during food trials is not fully explained by mutual attraction or aversion. The monkeys take the quality of their own and the partner's food into account, and possessors limit transfers of high-quality foods. Instead of a symmetry-based reciprocity explanation, a mediating role of memory is suggested, and a mirroring of social attitude between partners. Copyright 2000 The Association for the Study of Animal Behaviour.