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.     

Regional gene expression in the epithelia of the Xenopus tadpole gut

In recent years much progress has been made in the understanding of the genes and mechanisms involved in specification of the cells of the endoderm, which give rise to the epithelium of the gut and respiratory system. However, little is known about the way in which the gut becomes patterned along its anterior-posterior axis, that is, how boundaries are established between the different epithelia of the gut tube. Here we show that the expression patterns of five genes divide the Xenopus tadpole gut epithelium into at least four regions along this axis in the undifferentiated, 3-day-old gut (stage 41), and that these divisions are maintained until at least 7 days, when cell differentiation is well under way. In addition, the restricted expression patterns of these genes clearly mark the anterior and posterior boundaries of the intestine. Xsox2 is expressed in the anterior gut, spanning the oesophagus and stomach but terminating at the stomach/intestine boundary. Xcad1 and Xcad2, two caudal-type homeobox genes, are expressed in a region with an anterior limit at this boundary and a posterior limit between the colon and proctodeum, therefore covering the whole of the small and large intestines. Intestinal fatty acid binding protein (IFABP) is expressed only in the anterior small intestine, and the even-skipped homeobox gene Xhox3 is expressed in the most posterior part of the gut, the proctodeum.     

The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization

Sulfate plays an essential role during growth, development, bone/cartilage formation, and cellular metabolism. In this study, we have determined the structure of the human Na+-sulfate cotransporter (hNaSi-1) cDNA (Human Genome Nomenclature Committee-approved symbol SLC13A1) and gene (NAS1). hNaSi-1 encodes a protein of 595 amino acids with 13 putative transmembrane domains. hNaSi-1 mRNA expression was exclusive to the human kidney. Expression of hNaSi-1 protein in Xenopus oocytes demonstrated a high-affinity Na+-sulfate cotransporter that was inhibited by selenate, thiosulfate, molybdate, tungstate, citrate, and succinate. Antisense inhibition experiments suggest hNaSi-1 to represent the major Na+-sulfate cotransporter in the human kidney. NAS1 was localized on human chromosome 7, mapped to 7q31-q32, near the sulfate transporter genes, DRA and SUT-1. The NAS1 gene contains 15 exons, spanning over 83 kb in length. Knowledge of the structure, function, and chromosomal localization of hNaSi-1 will permit the screening of NAS1 mutations in humans with disorders in renal sulfate reabsorption and homeostasis.     

Optimization of lambda-carrageenan as a chiral selector in capillary electrophoresis separations

Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, was employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. In order to improve the utility of the chiral selector, the purity and concentration of the lambda-carrageenan and other important capillary electrophoresis method parameters were investigated. The results indicated that the purity and concentration of the lambda-carrageenan, ionic strength of the buffer, and temperature were critical to successful enantioseparation. These new method conditions were then applied to previously investigated beta-blockers (such as propranolol HCl and pindolol) and racemic tryptophan derivatives. These studies were successful in identifying important method conditions for the improved enantioselectivity with lambda-carrageenan.     

One-pot synthesis and biological evaluation of aspergillamides and analogues

A one-pot total synthesis of aspergillamide and analogues by a solution phase Ugi multi component reaction (MCR) is described. The reaction is easily performed in 96-well plates and offers a facile access to diverse aspergillamide analogue compound libraries. The antibiotic and cytotoxic activity of these compounds is measured. Several of them are more potent than the natural product.     

P. carinii induces selective alterations in component expression and biophysical activity of lung surfactant

Studies of Pneumocystis carinii pneumonia (PCP) suggest an important role for the surfactant system in the pathogenesis of the hypoxemic respiratory insufficiency associated with this infection. We hypothesized that PCP induces selective alterations in alveolar surfactant component expression and resultant biophysical properties. PCP was induced by intratracheal inoculation of 2 x 10(5) P. carinii organisms into C.B-17 scid/scid mice. Six weeks after inoculation, large (LA)- and small (SA)-aggregate surfactant fractions were prepared from bronchoalveolar lavage fluids and analyzed for expression of surfactant components and for biophysical activity. Total phospholipid content was significantly reduced in LA surfactant fractions from mice infected with PCP (53 +/- 15% of uninfected mice; P < 0.05). Quantitation of hydrophobic surfactant protein (SP) content demonstrated significant reductions of alveolar SP-B and SP-C protein levels in mice with PCP compared with those in uninfected mice (46 +/- 7 and 19 +/- 6%, respectively; P < 0.05 for both). The reductions in phospholipid, SP-B, and SP-C in LA fractions measured during PCP were associated with an increase in the minimum surface tension of LAs as measured by pulsating bubble surfactometer (13.1 +/- 1.1 vs. 5.4 +/- 1.8 mN/m; P < 0.05). In contrast to decreases in the hydrophobic SPs, SP-D content in the SA fraction was markedly increased (343 +/- 30% of control value; P < 0. 05) and SP-A levels in LA surfactant were maintained (93 +/- 26% of control value) during P. carinii infection. In all cases, the changes in SP content were reflected by commensurate changes in the levels of mRNA. We conclude that PCP induces selective alterations in surfactant component expression, including profound decreases in hydrophobic protein contents and resultant increases in surface tension. These changes, demonstrated in an immunologically relevant animal model, suggest that alterations in surfactant could contribute to the hypoxemic respiratory insufficiency observed in PCP.     

Relation of the size and intracellular sorting of apoB to the formation of VLDL 1 and VLDL 2

In this study, we tested the hypothesis that two separate pathways, the two-step process and an apolipoprotein B (apoB) size-dependent lipidation process, give rise to different lipoproteins. Expression of apoB-100 and C-terminally truncated forms of apoB-100 in McA-RH7777 cells demonstrated that VLDL particles can be assembled by apoB size-dependent linear lipidation, resulting in particles whose density is inversely related to the size of apoB. This lipidation results in a LDL-VLDL 2 particle containing apoB-100. VLDL 1 is assembled by the two-step process by apoB-48 and larger forms of apoB but not to any significant amount by apoB-41. The major amount of intracellular apoB-80 and apoB-100 banded with a mean density of 1.10 g/ml. Its formation was dependent on the sequence between apoB-72 and apoB-90. This dense particle, which is retained in the cell, possibly by chaperones or association with the microsomal membrane, is a precursor of secreted VLDL 1. The intracellular LDL-VLDL 2 particles formed during size-dependent lipidation appear to be the precursors of intracellular VLDL 1. We propose that the dense apoB-100 intracellular particle is converted to LDL-VLDL 2 by size-dependent lipidation. LDL-VLDL 2 is secreted or converted to VLDL 1 by the uptake of the major amount of triglycerides.