Growth factor-induced activation of MSK2 leads to phosphorylation of H3K9me2S10 and corresponding changes in gene expression.

Extracellular signals are transmitted through kinase cascades to modulate gene expression, but it remains unclear how epigenetic changes regulate this response. Here, we provide evidence that growth factor-stimulated changes in the transcript levels of many responsive genes are accompanied by increases in histone phosphorylation levels, specifically at histone H3 serine-10 when the adjacent lysine-9 is dimethylated (H3K9me2S10). Imaging and proteomic approaches show that epidermal growth factor (EGF) stimulation results in H3K9me2S10 phosphorylation, which occurs in genomic regions enriched for regulatory enhancers of EGF-responsive genes. We also demonstrate that the EGF-induced increase in H3K9me2S10ph is dependent on the nuclear kinase MSK2, and this subset of EGF-induced genes is dependent on MSK2 for transcription. Together, our work indicates that growth factor-induced changes in chromatin state can mediate the activation of downstream genes.

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

Breast cancer detection from MR images through an auto-probing discrete Fourier transform system.

A computer-aided detection auto-probing (CADAP) system is presented for detecting breast lesions using dynamic contrast enhanced magnetic resonance imaging, through a spatial-based discrete Fourier transform. The stand-alone CADAP system reduces noise, refines region of interest (ROI) automatically, and detects the breast lesion with minimal false positive detection. The lesions are then classified and colourised according to their characteristics, whether benign, suspicious or malignant. To enhance the visualisation, the entire analysed ROI is constructed into a 3-D image, so that the user can diagnose based on multiple views on the ROI. The proposed method has been applied to 101 sets of digital images, and the results compared with the biopsy results done by radiologists. The proposed scheme is able to identify breast cancer regions accurately and efficiently.

Mandatory temperature monitoring in schools during SARS.

During the SARS outbreak, temperature monitoring was mandatory for all Singapore schoolchildren. None of the Singapore children with SARS were detected through school temperature screening. However, temperature monitoring procedures have a powerful psychological effect of reassuring parents and the public that schools are safe during a SARS outbreak.

Idiopathic pulmonary haemosiderosis--a case report.

Idiopathic pulmonary haemosiderosis (IPH) is a disorder characterised by the triad of haemoptysis, diffuse parenchymal infiltrates on chest roentgenogram and iron-deficiency anaemia. It is a diagnosis of exclusion and the prognosis is bleak despite the varied management options. We report a case of IPH occurring in a child who presented at four months of age with cough, wheeze, haemoptysis and pallor and whose symptoms are currently controlled with high-dose inhaled budesonide and low-dose oral prednisolone.

The XHex homeobox gene is expressed during development of the vascular endothelium: overexpression leads to an increase in vascular endothelial cell number.

The Hex/Prh homeobox gene is expressed in a subset of adult blood cell types and may play a role in the differentiation of the myeloid and B-cell lineages. In a search for homeobox genes involved in cardiovascular development, we have independently isolated a Xenopus laevis cDNA which appears to be the amphibian orthologue of Hex/Prh. Based on high sequence similarity in a number of regions, particularly the critical homeobox, we have named this gene XHex. This developmentally regulated gene is first expressed in the dorsal endomesoderm of the gastrula stage embryo. This tissue goes on to contribute to the structures of the embryonic liver and XHex continues to be expressed in the liver throughout development. From the tailbud stage, XHex is expressed in vascular endothelial cells throughout the developing vascular network. Vascular expression of XHex is transient and commences slightly after expression of the receptor tyrosine kinase gene, flk-1, which is known to be essential for vascular development. This observation raises the possibility that XHex is one of the transcription factors that responds to the VEGF/Flk-1 signal transduction pathway leading to differentiation of vascular endothelial cells. XHex is unique amongst homeobox genes in displaying expression in the endothelial layer throughout the developing vasculature. Overexpression of XHex sequences in the frog embryo causes disruption to developing vascular structures and an increase in the number of vascular endothelial cells, suggesting a possible role in regulation of cell proliferation.

Ectopic Cushing's syndrome in a young female with atypical [corrected] bronchial carcinoid tumour.

A 17-year-old female with a large mass in the left thorax presenting with ectopic Cushing's syndrome is described. Biochemical evaluation revealed a corticotropin(ACTH)-dependent hypercortisol state. Surgical resection of the tumour resulted in clinical remission and correction of hypercortisolism and normal plasma ACTH levels. The histology was that of an atypical carcinoid. Bronchial carcinoid tumour is an extremely uncommon but well recognised cause of ectopic Cushing's syndrome. These patients may pose diagnostic dilemma in distinguishing form those with Cushing's disease because of the similarity in the clinical, biochemical and radiologic findings.

Xbap, a vertebrate gene related to bagpipe, is expressed in developing craniofacial structures and in anterior gut muscle.

The Drosophila bagpipe (bap) gene is involved in the specification of the musculature of the embryonic midgut. We report the isolation and characterization of a Xenopus sequence, Xbap, which is closely related to bap. Xbap is also expressed in the developing musculature of the midgut, suggesting that this developmental role of bagpipe is evolutionarily conserved. However, a second, novel role in development is suggested by the observation that Xbap is also expressed in a region of the developing facial cartilage. Using a combination of cartilage staining and comparison to the goosecoid head expression pattern, we show that Xbap expression marks the precursors to the basihyobranchial, palatoquadrate, and possibly Meckel's cartilages. This vertebrate bagpipe sequence therefore is expressed in both mesodermally and neural crest-derived tissues.

Paraganglioma with pulmonary metastases: a case report.

Distant metastases due to paraganglioma are a rare occurrence. We report a case of paraganglioma with pulmonary metastases and review the literature on paragangliomas. A 29-year-old female presented with cervical lymphadenopathy, excision biopsy of which confirmed the diagnosis of paraganglioma. She subsequently underwent tumour embolisation and received a course of radiotherapy. Seven years later, she was investigated for multiple pulmonary nodules noted on her chest roentgenogram. Histology of the wedge excision of the lung showed metastatic paraganglioma. Increased catecholamine production was documented; this was however not associated with symptoms of catecholamine excess. Reports concerning the treatment of paragangliomas with pulmonary metastases are few, given their rarity.

Case of pulmonary alveolar proteinosis treated by sequential whole-lung lavages and a review of the condition.

We report our first local case of pulmonary alveolar proteinosis that required symptomatic therapy with whole lung lavage. This is a rare condition associated with the accumulation of phospholipid material in the alveoli. The presentation is usually insidious and the symptomatology varies from vague complaints to severe crippling dyspnoea. The diagnosis is often delayed and usually made after the exclusion of other conditions. While there is no definitive treatment apart from lung transplant, whole-lung lavage is a safe, repeatable procedure which offers the best prospect for symptomatic, physiological and radiological improvement in severe cases.

A Metamorphic Inducer in the Opisthobranch Haminaea callidegenita: Partial Purification and Biological Activity.

Larvae of Haminaea callidegenita (Mollusca: Cephalaspidea) were induced to metamorphose by a compound found in the gelatinous matrix composing most of the egg mass. A functionally similar compound isolated from adult tissue also induced metamorphosis in H. callidegenita larvae. Opisthobranchs are frequently induced to metamorphose by a specific prey item or a substrate characteristic of the adult habitat, but this is the first known instance of metamorphosis occurring in response to a compound produced by adult conspecifics. The inducer was purified from egg mass jelly (EMJ) by high pressure liquid chromatography (HPLC) and was found to be smaller than 1000 Da, polar, non-proteinaceous, and very stable. We isolated a compound of identical activity from egg masses produced by four other opisthobranch species, suggesting that the same or chemically similar compounds are intrinsic to opisthobranch egg masses. However, only H. callidegenita larvae metamorphosed in response to EMJ. Competent larvae of five other mollusc species did not respond to the partially purified EMJ inducer but did respond to a specific substrate associated with each species. The presence of the inducer within the egg mass causes an unusual developmental pattern in H. callidegenita, a poecilogonous species that produces both swimming veliger and crawling juvenile offspring.

Marden-Walker syndrome in two siblings.

Two siblings are reported who have features of the Marden-Walker syndrome. They have congenital joint contractures, camptodactyly, talipes equinovarus, abnormal facies, global delay in developmental milestones, hypotonia and failure to thrive. About 20 cases have been reported in the world literature. A summary of some of the cases is presented. This syndrome appears to be an autosomal recessive trait in some families.

PaO2, SaO2 and what constitutes adequate oxygenation in the premature newborn.

3 neonates admitted into our intensive care unit had their arterial blood gases analyzed. A total of 64, 67 and 73 arterial blood samples were analyzed for the 3 neonates respectively. The relationship between PaO2 and the corresponding SaO2 were plotted in an oxygen hemoglobin dissociation curve. PaO2 of 50mmHg corresponded to SaO2 of 80%, 84% and 92% for the 3 babies respectively, reflecting the fact that SaO2 can differ considerably. PaO2 of 50mmHg or SaO2 of 87% by themselves are inadequate as indicators of lower limit of arterial oxygenation. Indeed a consideration of other factors such as oxygen consumption, cardiac output, hemoglobin concentration are integral to this issue. PaO2 of 70mmHg corresponded to SaO2 of 92%, 93% and 97% respectively. However, at the upper limit of arterial oxygenation, the oxygen hemoglobin dissociation curve flattens out and PaO2 is a more sensitive indicator of the upper limit of arterial oxygenation as compared to SaO2.

Isolation of Neurons of a Nudibranch Veliger.

A technique was developed to dissociate and culture identified sensory neurons and interneurons from the anterolateral propodial ganglia of metamorphically competent veligers of the nudibranch, Onchidoris bilamellata. Receptor cells have been represented as receiving an environmental cue that initiates the settlement response. The ganglionic cells, along with other cell-types from the propodial region housing the ganglia, were excised with a large-bore micropipette, and dissociated by mild trypsin incubation and trituration. Cells and tissues were plated in poly-L-lysine-coated plastic culture dishes containing modified Aplysia medium and survived for up to four days. The different cell-types possess diagnostic features, so they can be recognized under culture conditions. Sensory cells were bipolar in profile, with one end of the cell being thickened, representing the receptor apparatus. Interneurons are unipolar or bipolar in shape, and bear thin neurites. Other cell-types, including myocytes, ciliated epidermal cells, nonciliated epidermal cells, and gland cells were identified. Identifications of living cells were corroborated through electron microscopical analysis.

The importance of septic work-up in the febrile neonate.

71 febrile neonates admitted to the Paediatric and Neonatal Department in 1988 and 1989 were studied. Septic work ups were done for 84% of patients & 80% had lumbar puncture. These infants were subdivided into 5 groups in order to identify the significance of the various stages of septic work up. It was found that 48% of patients with significant infections were only diagnosed after some stage of septic work up. 14% had meningitis and diagnosed only after CSF examination. Only in 13% of patients the diagnosis could be made confidently without a septic work up confirming that the diagnosis of infection in the neonate is difficult and often missed without a septic work up. Clinical impression by paediatricians reduced the number of patients requiring unnecessary investigations and receiving empiric therapy. We recommend maintaining our present cautious policy of admitting neonates with pyrexia.

Kinetics of Fertilization in the Sea Urchin Strongylocentrotus franciscanus: Interaction of Gamete Dilution, Age, and Contact Time.

Determining fertilization success of free spawning organisms in the field requires knowledge of how eggs and sperm interact under varying encounter frequencies and durations. In the laboratory, we investigated the relative influence of sperm concentration, egg concentration, sperm-egg contact time, and sperm age on fertilization in the sea urchin Strongylocentrotus franciscanus. Our results indicated that sperm concentration, sperm-egg contact time, sperm age, and individual variability were sequentially the most important factors influencing fertilization success. Egg concentration was not significant over the range tested. A theoretical model of fertilization (Vogel-Czihak-Chang-Wolf model) was used to estimate the two rate constants of fertilization kinetics: the rate constant of sperm-egg encounter and rate constant of fertilization. This model explained 91% of the variation in fertilization success, provided estimates of the rate constants involved in fertilization, and indicated the proportion (3%) of sperm-egg contacts that result in fertilization. Estimates of sperm swimming velocity and egg diameter were used to independently calculate the rate of sperm-egg encounter and confirm the predictions of the model. This model also predicts the non-significant effect of egg concentration on fertilization success found empirically.

Reliability of the Dinamap non-invasive monitor in the measurement of blood pressure of ill Asian newborns.

Four hundred thirty-one paired sets of readings of systolic and diastolic blood pressure and 438 paired sets of readings of mean arterial BP from 49 ill newborns, including 21 very low birth weight infants, were analyzed for the extent and pattern of agreement and the linear relationship between the Dinamap oscillometric monitor and the direct intraarterial blood pressure readings. Agreement between the two methods was measured by the intraclass correlation, whereas the linear relationship was assessed by the product-moment correlation. The intraclass correlations for systolic, diastolic and mean blood pressures were 0.696, 0.766, and 0.781, respectively. The product-moment correlations for systolic, diastolic and mean blood pressures were 0.706, 0.768, and 0.786, respectively. BP measurements by the Dinamap monitor showed reasonably close agreement to those obtained by the intraarterial mean arterial pressure ranges above 40 mmHg. For mean arterial pressure of 40 mmHg and lower, BP readings by the Dinamap monitor tended to be higher than those obtained by the intraarterial method. These findings appeared to be consistent regardless of the birth weight of the newborn.

Sindrome utero-mano-pie (o génito-mano-pie) / Hand-foot-uterus syndrome (or genital-hand-foot-genital syndrome)

Se presenta un caso de síndrome útero-mano-pie. Los dermatoglifos se encuentran alterados así como los huesos de las manos y pie. Presenta útero doble y septum vaginal