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Biomedical subjects

Y Chan

Publications and source records attributed to Y Chan.

At least 19 recordsLinked to original sources

Heterogeneous responses of aquaporin-4 in oedema formation in a replicated severe traumatic brain injury model in rats.

Aquaporin-4 (AQP4) is the most abundant water channel in the rat brain. In this study, the distribution pattern and mRNA expression levels of AQP4 were examined in a severe traumatic brain injury model by immunohistochemistry and reverse transcription-polymerase chain reaction. Oedema formation and blood-brain barrier (BBB) integrity were assessed by wet-dry weight measurements and immunostaining of endogenous IgG respectively. In the oedematous contusional cortex with impaired BBB integrity, negative immunostaining of AQP4 and down-regulation of its mRNA level were identified (P<0.05) at 1 day post-injury, while in other oedematous regions of the injured brain where BBB was intact, there was no significant change in the AQP4 expression level. This heterogeneous pattern of AQP4 responses can be interpreted as follows: focal brain injury (such as a contusion) with impaired BBB resulting in vasogenic oedema is associated with reduction of AQP4 expression, whereas, in cytotoxic oedema, associated with diffuse brain injury with intact BBB, changes in AQP4 expression are not significant. This study provides basic information for investigating new treatments for traumatic brain oedema.

Animals↗

Detection of an intense resonance at 2.4 ppm in 1H MR spectra of patients with severe late-delayed, radiation-induced brain injuries.

Proton MRS and MRI were used to monitor the progression of severe cerebral radiation injuries in 10 patients over a period of 18 months. An unknown resonance (Px) in the 2.37-2.40 ppm region was consistently detected in the affected temporal lobes of four patients. The detection of Px was only confined to spectra with lactate (Lac) and in patients with the highest severity grading of radiation injury. The incidence of Px in Lac-positive spectra was 42.8% (15/35) and in lesions with highest injury grading was 46.8% (15/32). Lesions with Px had significantly higher Lac/creatine (Cr) ratios and more extensive mass effect changes when compared to lesions without Px. The probable identity of Px was examined in the context of anaerobic glycolysis producing pyruvate (2.37 ppm) and the model of metabolic changes in brain abscess formation implicating succinate (2.40 ppm).

Adult↗

Magnetic resonance imaging of the fetus in congenital intrathoracic disorders: preliminary observations.

BACKGROUND AND OBJECTIVE: Advances in magnetic resonance imaging (MRI) provide high-quality images of the intrathoracic organs. We studied the ability of MRI to define spatial relationships of the fetal lungs and measured lung volume in two cases of congenital diaphragmatic hernia (CDH), one of severe oligohydramnios secondary to bilateral cystic renal dysplasia and one case of prenatal chylothorax. PATIENTS AND METHODS: We performed pelvic MRI using single-shot fast spin echo (SSFSE) pulse sequence in four pregnant women referred because of abnormal prenatal ultrasound (US) findings associated with pulmonary hypoplasia. RESULTS: The exact anatomic position of the contents of the hernia in CDH, including the position of the liver, was better defined with MRI. Pleural effusions were identified as well as the renal abnormality in the case of oligohydramnios. Lung volume was measured and the degree of pulmonary hypoplasia was quantified in every case. Lung-to-thorax ratio was calculated in the case of fetal chylothorax. CONCLUSION: Ongoing work suggests that MRI can provide additional detailed quantitative information in prenatal disorders associated with fetal lung compression and resulting hypoplasia. Correlation of fetal lung volume with postnatal management and outcome may affect prognosis in these cases.

Chylothorax↗

Reflected shock experiments on the equation-of-state properties of liquid deuterium at 100-600 GPa (1-6 mbar)

New laser-driven shock experiments have been used to study the equation-of-state (EOS) properties of liquid deuterium. Reflected shocks are utilized to increase the shock pressure and to enhance the sensitivity to differences in compressibility. The results of these experiments differ substantially from the predictions of the Sesame EOS. EOS models showing large dissociation effects with much greater compressibility (up to a factor of 2) agree with the data. By use of independent techniques, this experiment offers the first confirmation of an earlier observation of enhanced compressibility in liquid deuterium.

Journal Article↗

Maternal uniparental disomy of chromosome 16 and body stalk anomaly.

We report on a fetus with placental trisomy 16, maternal uniparental disomy (UPD), and body stalk anomaly. Body stalk anomaly is a rare, fatal developmental abnormality consisting of a defective abdominal wall with abdominal organs in a sac outside the abdominal cavity covered by amnion adherent to the placenta with absence or severe shortness of the umbilical cord. Trisomy 16 was identified in the placenta in all cells. Amniocentesis was karyotypically normal. Parental origin studies showed maternal UPD for chromosome 16 in post-termination fetal tissue. The cause of the body stalk anomaly is not clearly defined. There are no other reports of placental karyotype or UPD investigations with body stalk anomaly. To our knowledge, this is the first report of placental trisomy 16, UPD in fetus, and body stalk anomaly, suggesting placental insufficiency or imprinting effects as cause of this anomaly. Am. J. Med. Genet. 94:284-286, 2000.

Abdominal Muscles↗

The impact of acute hyponatraemia on severe traumatic brain injury in rats.

The effect of experimental acute hyponatraemia on severe traumatic brain injury (TBI) was studied in a modified impact-acceleration model. The cortical contusional volume was quantified by image analysis on serial sections, injured axons were visualized and quantified by beta-Amyloid Precursor Protein (beta-APP) immunohistochemical staining. Regional brain water content was estimated by the wet-dry weight method. The experiment was conducted in Group I (injury only) and Group II (injury followed by acute hyponatraemia). Comparison between the two groups showed that acute hyponatraemia significantly increased contusional volume (3.24 +/- 0.70 mm3 vs. 1.80 +/- 0.65 mm3, P = 0.009) and the number of injured axons (128.7 +/- 44.3 vs. 41.7 +/- 50.1, P = 0.04) in the right thalamus & basal ganglia region. Water content of the brain stem region was also significantly increased by acute hyponatraemia (73.71 +/- 0.14% vs. 72.28 +/- 0.93%, P = 0.004). These results suggest that acute hyponatraemia potentiates secondary brain damage in severe TBI by augmentation of both focal contusion and diffuse axonal injury. The injured brain stem region is more susceptible to edema formation induced by experimental acute hyponatraemia.

Amyloid beta-Protein Precursor↗

Comparative avian phylogeography of Cameroon and equatorial Guinea mountains: implications for conservation.

We illustrate the use of Faith's 'Phylogenetic Diversity' measure to compare the phylogeographic structure of two bird species with patterns of avian endemism across six mountains in Cameroon and Equatorial Guinea. The Mountain Greenbul and Cameroon Blue-headed Sunbird showed phylogeographic patterns that together defined three biogeographic regions: Bioko, Mt. Cameroon, and the northern mountains of Cameroon. In contrast, the distributions of endemic species were largely a function of geographical distance, with close mountains sharing more endemic species than distant mountains. Moreover, for both species, populations on Mt. Cameroon were distinctive with respect to the ecologically relevant character bill size. Our results, while preliminary, illustrate the utility of a comparative approach for identifying geographical regions that harbour evolutionarily distinct populations and caution against using only the distributional patterns of endemics to prioritize regions for conservation. Results show that patterns of endemism may not be concordant with patterns of phylogenetic diversity nor morphological variation in a character important in fitness. While incorporation of additional species from unrelated taxa will be necessary to draw definitive conclusions about evolutionarily distinct regions, our preliminary results suggest a conservation approach for the Afromontane region of the Gulf of Guinea that would: (i) emphasize protection of both Bioko and Mt. Cameroon, thereby maximizing preservation of within-species phylogenetic and morphologic diversity; (ii) emphasize protection within the northern mountains to further conserve intraspecific phylogenetic diversity and maximize protection of endemic species.

Animals↗

Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction.

BACKGROUND: Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi (SO) basal pressure (SO stenosis). AIM: To evaluate the effects of sphincterotomy in patients randomised on the basis of results from endoscopic biliary manometry. METHODS: Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retrograde cholangiography, transient increases in liver enzymes after episodes of pain, or positive responses to challenge with morphine/neostigmine. The manometric record was categorised as SO stenosis, SO dyskinesia, or normal, after which the patient was randomised in each category to sphincterotomy or to a sham procedure in a prospective double blind study. Symptoms were assessed at intervals of three months for 24 months by an independent observer, and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months. RESULTS: In the SO stenosis group, symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure (p = 0.041). When manometric records were categorised as dyskinesia or normal, results from sphincterotomy and sham procedures did not differ. Complications were rare, but included mild pancreatitis in seven patients (14 episodes) and a collection in the right upper quadrant, presumably related to a minor perforation. At three months, the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter. CONCLUSION: In patients with presumed SO dysfunction, endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis.

Adult↗

Integration of FGF and TWIST in calvarial bone and suture development.

Mutations in the FGFR1-FGFR3 and TWIST genes are known to cause craniosynostosis, the former by constitutive activation and the latter by haploinsufficiency. Although clinically achieving the same end result, the premature fusion of the calvarial bones, it is not known whether these genes lie in the same or independent pathways during calvarial bone development and later in suture closure. We have previously shown that Fgfr2c is expressed at the osteogenic fronts of the developing calvarial bones and that, when FGF is applied via beads to the osteogenic fronts, suture closure is accelerated (Kim, H.-J., Rice, D. P. C., Kettunen, P. J. and Thesleff, I. (1998) Development 125, 1241-1251). In order to investigate further the role of FGF signalling during mouse calvarial bone and suture development, we have performed detailed expression analysis of the splicing variants of Fgfr1-Fgfr3 and Fgfr4, as well as their potential ligand Fgf2. The IIIc splice variants of Fgfr1-Fgfr3 as well as the IIIb variant of Fgfr2 being expressed by differentiating osteoblasts at the osteogenic fronts (E15). In comparison to Fgf9, Fgf2 showed a more restricted expression pattern being primarily expressed in the sutural mesenchyme between the osteogenic fronts. We also carried out a detailed expression analysis of the helix-loop-helix factors (HLH) Twist and Id1 during calvaria and suture development (E10-P6). Twist and Id1 were expressed by early preosteoblasts, in patterns that overlapped those of the FGF ligands, but as these cells differentiated their expression dramatically decreased. Signalling pathways were further studied in vitro, in E15 mouse calvarial explants. Beads soaked in FGF2 induced Twist and inhibited Bsp, a marker of functioning osteoblasts. Meanwhile, BMP2 upregulated Id1. Id1 is a dominant negative HLH thought to inhibit basic HLH such as Twist. In Drosophila, the FGF receptor FR1 is known to be downstream of Twist. We demonstrated that in Twist(+/)(-) mice, FGFR2 protein expression was altered. We propose a model of osteoblast differentiation integrating Twist and FGF in the same pathway, in which FGF acts both at early and late stages. Disruption of this pathway may lead to craniosynostosis.

Acrocephalosyndactylia↗

Deferoxamine-induced bone dysplasia in the distal femur and patella of pediatric patients and young adults: MR imaging appearance.

OBJECTIVE: We investigated the MR imaging appearance of deferoxamine-induced bone dysplasia in the distal femur and patella in patients with thalassemia major. MATERIALS AND METHODS: Thirty-five patients with homozygous ss-thalassemia major who were undergoing regular transfusions and chelation therapy underwent coronal T1-weighted MR imaging of the femur, including the femoral head and the distal femoral epiphysis. Additional coronal fat-saturated dual-echo and sagittal T1-weighted images of the distal femur and patella were obtained in 11 patients who were suspected of having distal femoral lesions on the basis of the coronal T1-weighted images of the entire femur. RESULTS: No dysplastic change was detected in the proximal femur on coronal T1-weighted images. In 22 distal femurs of 11 patients, the following abnormalities were detected on MR imaging: blurred physeal-metaphyseal junction (n = 22), distal metaphyseal areas of hyperintensity (n = 21), physeal widening (n = 18), metadiaphyseal lesions (n = 11), epiphyseal lesions (n = 10), and patellar lesions (n = 2). Physeal widening and distal metaphyseal hyperintense areas were all more pronounced peripherally. Of the 21 distal metaphyseal hyperintensities, lateral abnormalities were larger than medial abnormalities in 16. Of the 18 distal femurs in which physeal widening was detected, the lateral widening was more marked than the medial widening in 12. Patients with MR imaging evidence of bone dysplasia have a significantly (p = 0.003) greater height reduction than patients without such evidence of bone dysplasia. CONCLUSION: Deferoxamine-induced bone dysplasia in the distal femur and patella is represented by a spectrum of morphologic changes in the epiphysis, physis, metaphysis, and metadiaphysis on MR imaging.

Adolescent↗

Characterization of the human endothelial nitric-oxide synthase promoter.

Understanding transcription initiation of the endothelial nitric-oxide synthase (eNOS) gene appears pivotal to gaining a comprehensive view of NO biology in the blood vessel wall. The present study therefore focused upon a detailed dissection of the functionally important cis-DNA elements and the multiprotein complexes implicated in the cooperative control of constitutive expression of the human eNOS gene in vascular endothelium. Two tightly clustered cis-regulatory regions were identified in the proximal enhancer of the TATA-less eNOS promoter using deletion analysis and linker-scanning mutagenesis: positive regulatory domains I (-104/-95 relative to transcription initiation) and II (-144/-115). Analysis of trans-factor binding and functional expression studies revealed a surprising degree of cooperativity and complexity. The nucleoprotein complexes that form upon these regions in endothelial cells contained Ets family members, Sp1, variants of Sp3, MAZ, and YY1. Functional domain studies in Drosophila Schneider cells and endothelial cells revealed examples of positive and negative protein-protein cooperativity involving Sp1, variants of Sp3, Ets-1, Elf-1, and MAZ. Therefore, multiprotein complexes are formed on the activator recognition sites within this 50-base pair region of the human eNOS promoter in vascular endothelium.

Animals↗

Math-Fact Retrieval as the Cognitive Mechanism Underlying Gender Differences in Math Test Performance.

Males from select populations receive better scores on standardized math achievement tests than females. The research reported in this article evaluates the hypothesis that the reason for these differences is that males are faster at retrieving basic math facts. Studies 1-3 demonstrate that math-fact retrieval predicts performance on math achievement tests with students in grades 5-8 and in college. Studies 4-6 show that males and females in grades 2-8 and in college have different patterns of math-fact retrieval performance and that males at the high positive end of the retrieval distribution are faster than comparable females. Study 5 also demonstrates that math-fact retrieval varies in three populations (Anglo-American, Chinese-American, Hong Kong Chinese) and that speed of retrieval improves with practice. Studies 7-9 tested the hypothesis that males are faster than females on retrieval tasks in general. Study 7 showed that there were no gender differences on simple retrieval tasks, and Studies 8 and 9 showed that females were slightly faster than males on verbal-processing tasks. The General Discussion indicates that the math-fact retrieval hypothesis is consistent with previous research. It also relates the math-fact retrieval hypothesis to theories of cognitive performance and introduces the practice and engagement hypothesis. This hypothesis explains the origin of gender differences in math and reading and relates those differences to the existing literature on gender differences in academic performance. The article concludes with a description of needed future research and a discussion of the educational implications of the math-fact retrieval hypothesis. Copyright 1999 Academic Press.

Journal Article↗

Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo.

Alpha-actinins belong to a family of actin-binding and crosslinking proteins and are expressed in many different cell types. Multiple isoforms of alpha-actinin are found in humans and are encoded by at least four distinct genes. Human skeletal muscle contains two sarcomeric isoforms, alpha-actinin-2 and -3. Previous studies have shown that the alpha-actinins function as anti-parallel homodimers but the question of heterodimer formation between two different isoforms expressed in the same cell type has not been explored. To address this issue, we expressed both alpha-actinin-2 and -3 in vitro and were able to detect their interaction by both blot overlay and co-immunoprecipitation methods. We were also able to demonstrate the presence of heterodimers in vivo in human skeletal muscle and in COS-1 cells transiently transfected with both isoforms. Our results clearly demonstrate the potential for alpha-actinin isoforms to form heterodimers which might have unique functional characteristics.

Actinin↗