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Biomedical subjects

Y L Yan

Publications and source records attributed to Y L Yan.

48 records · Page 3Linked to original sources

Holoprosencephaly and chromosomal anomalies.

Holoprosencephaly is a rare cerebral malformation resulting from failure or incomplete cleavage of the forebrain. The sonographic diagnosis consists of monoventricle, fused thalami and absent cavum septum pellucidi. Chromosomal anomalies, diabetes mellitus, alcohol, autosomal recessive inheritance and toxins have been implicated. We describe seven cases of holoprosencephaly diagnosed in the antenatal and postnatal periods. The chromosomal anomalies included trisomy 13, triploidy, trisomy 13 with an unbalanced 13; 14 translocation and isochromosome of the long arm of 18. The clinicopathological findings and chromosomal anomalies are correlated.

Abortion, Therapeutic↗

Expression of a type II collagen gene in the zebrafish embryonic axis.

To understand the hierarchy of developmental controls underlying axis specification in vertebrate embryos, it is helpful to identify relationships between regulatory molecules and the genes that give axial cells their differentiated phenotypes. This work reports the cloning and expression pattern of one of these differentiation genes, a type II collagen (col2a1) gene from the zebrafish Danio rerio. Along the embryonic axis, col2a1 is expressed dynamically in three rows that are each a single cell wide: the notochord and the rows of cells immediately dorsal and ventral to it--the floor plate of the central nervous system, and the hypochord. In addition, col2a1 is expressed in the pharyngeal arches, the epithelium of the otic capsule, and in the mesenchyme of the neurocranium. Experiments probed the expression pattern of col2a1 relative to that of known or potential regulators of axis development, including axial, sonic hedgehog, twist, and cyclops. The results showed that the spatial and temporal pattern of col2a1 expression in axial mesoderm follows the expression of twist closer than other genes tested. In cyclops embryos, which lack an intact floor plate, col2a1 expression was usually low, but not missing in cells in the ventral spinal cord. Because col2a1 expression reveals abnormalities in the notochord of cyclopsb16 embryos, and less col2a1-expressing mesenchyme accumulates rostral to the notochord in cyclops embryos, the effects of the cyclopsb16 mutation are not confined to the central nervous system.

Animals↗

Second trimester colour Doppler imaging of the uterine artery: reproducibility of the resistance index.

Second trimester assessment of uterine blood flow has been advocated as a predictor of subsequent adverse perinatal outcome. The reproducibility of uterine artery resistance index, as assessed using colour Doppler imaging, was investigated. Two observers, both of whom were experienced in colour Doppler assessment of uterine artery flow velocity waveforms, performed the measurements. One-way analysis of variance was used to evaluate intraobserver variability and the limits of agreement method was used to determine the 95% prediction interval for interobserver differences. The intraobserver standard deviation was small for both observers. The limits of agreement for interobserver differences were wide (-0.24, 0.16), similar in magnitude to those reported by other workers who assessed the uterine vessel using continuous wave Doppler. The poor reproducibility of the resistance index suggests that second trimester Doppler assessment of uterine artery flow velocity waveforms may be better described using other semiquantitative methods such as the presence or absence of a diastolic notch.

Female↗

Alterations of G-protein coupling function in phosphoinositide signalling pathways of rat hippocampus by ischaemic brain injury.

The activation of membrane-associated phospholipase C is rapidly and transiently induced in the central nervous system by a variety of stimuli. Ischaemic brain injury is one of the situations that leads to a dramatic increase in polyphosphoinositide (PPI) turnover. In this study, stimulation of PPI hydrolysis by glutamate (500 microM) was measured in hippocampal slices from rats up to 21 days after an ischaemic insult of 30 min. Ischaemia was induced using the four-vessel occlusion method. PPI hydrolysis elicited by glutamate was significantly increased in the slices prepared from ischaemic rats 24 h after reperfusion, the accumulation of inositol phosphates (InsPs) and inositol 1,4,5-trisphosphate (Insp3) was 614 +/- 74% (n = 8) and 182 +/- 11% (n = 9) of the basal level respectively. This potentiation was also observed 21 days after ischaemia. Hyper-responsiveness to glutamate was also accompanied by an increase in AIF4(-)-stimulated formation of [3H]inositol phosphates. In addition, global ischaemia did not change either high-affinity [3H]glutamate binding in hippocampal membranes or the stimulation of PPI hydrolysis by carbachol or noradrenaline in hippocampal slices. The present results suggest that the increased responsiveness to glutamate is the result, at least in part, of functional changes at the G-protein level, and may contribute to the pathophysiology of ischaemic brain injury or to the regenerative phenomena that accompany ischaemic damage.

Aluminum Compounds↗

Accumulation of glutamate is regulated by calcium and protein kinase C in rat hippocampal slices exposed to ischemic states.

There is now convincing evidence that excessive accumulation of the excitatory amino acid glutamate (Glu) in the extracellular space is toxic to neurons. However, the regulation of the release and uptake of Glu in producing this toxic concentration has not been adequately ascertained. The authors report that in hippocampal slices, the output of Glu significantly increased under in vitro ischemic states. Glu in the extracellular space increased fivefold. Since daurisoline, a drug that blocks N-type Ca2+ channels, or Ca(2+)-free solution potently and effectively lowered this stimulated output, it was hypothesized that the Glu output is mediated by Ca2+ influx in nerve terminals. When the slices were incubated for 30 minutes under ischemic state, daurisoline caused only small alterations in the postischemic accumulation of Glu. However, Glu accumulation was markedly attenuated by H-7, but not by calmidazolium, facilitated by PDB whereas 8-bromo-cAMP was without effect. It appears therefore that during a 30-minute ischemic insult, protein kinase C (PKC) was involved in the Glu accumulation of supernatant. A direct demonstration of this concept was obtained by showing significant increases in PKC activation in presynaptic nerve terminals (from 1.34 +/- 0.1 to 9.34 +/- 0.89 U) following 30 minutes of ischemia. DNQX, a non-NMDA receptor antagonist, potently reduced PKC activities and decreased extra Glu accumulation. Also observed was the inhibition of 1-[3H]-Glu uptake into synaptosomes by PDB. These results provide direct evidence that Ca2+ influx enhances Glu release, which in turn leads to inhibition of its reuptake, and is coupled with PKC activities in presynaptic nerve terminals.

Alkaloids↗

The spatial distribution of spindle microtubules in anaphase 3Y1 cells.

The spatial distribution of the microtubules (MT) in the rat 3Y1 cells in mitosis was investigated by immunoelectron microscopy and computer-graphic reconstruction of serial thin sections. In anaphase the interzone-MT increased in number gradually with advancing phase, while the kinetochore-MT in half-spindles decreased. The interzone-MT overlapped with each other at the equatorial region of the cell, and they formed a specific structure called the 'stem bodies'. The ends of the interzone-MT opposite to the stem bodies often attached to chromosomes but not to the poles. The stem bodies were not labeled with immunogold particles of anti-alpha tubulin. Some of the stem bodies or MT which originate from stem bodies were found just beneath the plasma membrane in the equatorial region where abundant actin filaments appear showing the formation of the contractile ring and subsequently the cleavage furrow begins. On the basis of these observations it is assumed that the interzone-MT is involved both in the separation of chromosomes in anaphase and in the formation of the cleavage furrow in telophase.

Anaphase↗

Structural changes of iliac cancellous bone in postmenopausal women: a scanning electron microscopic study.

The functional state of iliac cancellous bones in healthy postmenopausal women was investigated by scanning electron microscopy (SEM) using a modified organic preparation method. SEM analysis of the location, number, size and phase of the remodeling sites showed that normal iliac cancellous bone of postmenopausal women has high resorbing activity in the early stage of postmenopause in both the region near the cortico-endosteum and the midway region, while in the late stage of postmenopause there is a great difference in resorbing activity between the two regions; namely, the resorbing activity progressively decreases with age, but high resorbing activity is continuously present in the region near the cortico-endosteum. Our results suggest the possibility that at the region near the cortico-endosteum the bone volume loss occurs continuously throughout all the stages of post-menopause, while at the midway region it occurs only in the early stage and not in the late stage of postmenopause.

Aged↗

Pregnanes that bind to the digitalis receptor: synthesis of 14-hydroxy-5 beta,14 beta-pregnane glycosides from digitoxin and digitoxigenin.

The preparation of the mono-, bis-, and trisdigitoxosides of 14-hydroxy-5 beta,14 beta-pregnan-20-one and 14,20 beta-dihydroxy-5 beta,14 beta-pregnane by two routes, based on the conversion of the alpha,beta-unsaturated gamma-lactone in digitoxin to the 20-ketone and 20 beta-alcohol by ozonolysis and zinc-acetic acid treatment followed by lithium tri-tert-butoxyaluminum hydride reduction, are described. Synthesis of the alpha-L-rhamnoside derivatives is described also. Structures were confirmed by 1H and 13C NMR spectra. These derivatives show strong interaction with the cardiac glycoside receptor of heart muscle in an [3H]ouabain radioligand binding assay. Structure-activity relationships which are reported for glycosides and genins show that the alpha-L-rhamnoside derivatives are more potent than the beta-D-digitoxoside or the beta-D-glucoside and that the beta-D-glucosides are more potent than the mono-, bis-, and trisdigitoxosides. Potency is not increased by the addition of the second and third digitoxose units.

Digitalis↗

Vitellogenesis in Drosophila: sequestration of a yolk polypeptide/invertase fusion protein into developing oocytes.

The mechanism of yolk deposition into developing oocytes of Drosophila was investigated by following the fate of a reporter protein fused to a vitellogenin, or yolk polypeptide (YP). Embryos were transformed with a hybrid gene consisting of the promotor and amino terminal 430 codons of the Yp2 gene fused to the cytoplasmic form of the invertase gene from the yeast Saccharomyces cerevisiae. RNA hybridization experiments with established lines of transformed flies showed that the hybrid gene was expressed in female fat bodies and ovaries but not in any male cells. Immunoblotting and endoglycosidase digestion showed that the hybrid protein was secreted from fat body cells via the secretory pathway, transported in hemolymph, and sequestered into developing oocytes. Transfusion experiments with hemolymph and pure invertase showed that sequestration of invertase depended on its attachment to YP. Immunocytochemistry demonstrated that the hybrid protein became localized in yolk granules as oocytes developed. Females homozygous for the fusion gene are generally sterile; their eggs containing the hybrid protein often collapse and their embryos fail to develop, suggesting that the structure of the yolk polypeptides is important for embryonic development. These experiments show that YP2 carries structural information sufficient to direct a reporter protein from fat body cells, through the hemolymph, and into the yolk granules of developing oocytes. This work provides a means of identifying the features of yolk polypeptides that are responsible for their deposition into yolk during oogenesis.

Amino Acid Sequence↗

Sequence homologies among the three yolk polypeptide (Yp) genes in Drosophila melanogaster.

To identify candidates for cis-acting sequences that regulate the sex-, stage-, and cell-specific expression of three coordinately regulated yolk polypeptide genes (Yp) in Drosophila melanogaster, we have mapped the Yp3 transcript, sequenced a 4278 bp DNA fragment containing the Yp3 gene, compared Yp3 region sequences to corresponding parts of Yp1 and Yp2, and compared the predicted amino acid sequence of YP3 to YP1 and YP2. The results showed that the Yps are largely homologous in translated regions, especially in the 3' half of the genes. Untranscribed flanking regions had little homology. A conserved inverted repeat (the H-box) has homology both to vertebrate steroid hormone receptor binding sites and to the ecdysone control region of Drosophila's hsp23. These results identify sequences to mutate in order to define elements that regulate Yp gene expression and govern YP polypeptide function.

Amino Acid Sequence↗