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Biomedical subjects

Y S Chan

Publications and source records attributed to Y S Chan.

At least 73 records · Page 4Linked to original sources

Hyperbaric oxygen in the treatment of diabetic foot infection.

BACKGROUND: Although hyperbaric oxygen therapy to treat diabetic foot lesions has been approved for insurance reimbursement in Taiwan, its clinical application has not yet been well accepted. This study evaluated multiple healing predictive factors in patients with diabetic foot infections to determine the usefulness of adjunctive hyperbaric oxygen in the treatment of such patients. METHODS: From March 1995 to May 1996, we treated 31 diabetic patients presenting with infected foot lesions with a regimen of adequate metabolic control, frequent wound debridement and hyperbaric oxygen therapy. Age, gender, leukocyte count, total lymphocyte count, hemoglobin, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), glycosylated hemoglobin Alc (HbAlc), albumin, ankle-brachial index, types of bacterial cultures and number of debridements were compared between successful and failed treatments. Independent t-test and Fisher's exact test were used to identify the prognostic factors associated with outcome of treatment. RESULTS: The mean age of the patients was 63.0 +/- 9.7 years (range 43 to 81). The mean number of hyperbaric oxygen therapies was 35.3 +/- 21.8 treatments (range 5 to 83). Of the 31 patients, 6 received below knee amputation, and 25 had their foot preserved or achieved a lower level of amputation. Elevated leukocyte count and low ankle-brachial index were significantly related to poor outcome. CONCLUSIONS: In the treatment of diabetic foot infection, adjunctive hyperbaric oxygen therapy seems to be a useful tool to enhance wound healing provided that there are preserved circulation and controlled infection.

Adult↗

Spatiotemporal characteristics of central otolith neurons.

PURPOSE: To review the spatiotemporal behaviours of central otolith neurons in decerebrate animals. DATA SOURCES: Laboratory of Neurophysiology, Department of Physiology, Faculty of Medicine, The University of Hong Kong. DATA EXTRACTION: Results of key research findings from 1992 to 1997. RESULTS: With constant velocity colckwise (CW) and counterclockwise (CCW) off-vertical axis rotations as stimuli to the otolith organs, neurons in the vestibular nuclei and medullary reticular formation showed characteristic spatiotemporal behavious. One-dimensional neurons showed symmetric and stable bidirectional response sensitivities (delta) to change in velocity while two-dimensional neurons showed asymmetric and variable delta to velocity. This CW-CCW asymmetry to bidirectional rotations may provide directional coding in the modulation of neural signals. Vestibular nuclear neurons also displayed distinct spontaneous discharge patterns at the stationary and earth-horizontal position, indicating that one- and two-dimensional neurons belong to physiologically distinct etities. These spatiotemporal behavious of the vestibular nuclear neurons were also shown to be precisely controlled by imputs from the vestibulocerebellum and/or bilateral otoliths. In both the vestibular nucleus and the reticular formation, the best response orientations of one-dimensional neurons and the orientations of the maximum response vector of two-dimensional neurons were found to point in all directions close to the horizontal plane, indicating that all head orientations on this plane are encoded across an ensemble of neurons. CONCLUSION: Otolith-evoked behaviours of the one-dimensional and two-dimensional neurons constitute an important element for the recognition of the direction and orientation of head motion in space.

Animals↗

Spontaneous activity of otolith-related vestibular nuclear neurons in the decerebrate rat.

The discharge properties of lateral and descending vestibular neurons responsive to constant velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions, were studied at the stationary and earth-horizontal position of decerebrate adult rats. From the coefficient of variation (CV), the spontaneous activities of OVAR-responsive neurons were classified into regular and irregular patterns. Of the neurons (n = 36) that showed symmetric and stable bidirectional response sensitivity (delta defined as CW gain over CCW gain) to OVAR (10 degrees tilt), some exhibited progressive phase shift with velocity (1.75-15 degrees/s) while others exhibited stable response phase. Most neurons of the former group (93% or 12/13) showed regular discharge pattern while only 22% (n = 5/23) of the latter group showed such a pattern. Though the phase-stable neurons showed a significantly higher average CV than the phase-shifted neurons, there was no significant difference between the mean spontaneous firing rates of these neurons. The neurons (n = 17) that showed asymmetric and variable delta to OVAR velocity can also be grouped-those that exhibited a greater gain with rotations directed towards the side of recording (I neurons) showed irregular discharge pattern while those that exhibited a greater gain with rotations directed towards the side contralateral to recording (C neurons) showed regular discharge pattern. The I and C neurons also exhibited significant difference in mean firing rates. The relationship between the response characteristics of the OVAR-responsive neurons and their spontaneous activity at the stationary and earth-horizontal position is discussed.

Action Potentials↗

Response of medial medullary reticular neurons to otolith stimulation during bidirectional off-vertical axis rotation of the cat.

In decerebrate cats, the extracellular activities of neurons in the medial medullary reticular formation were studied during constant velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions (at 10 degrees tilt). Spontaneously active neurons demonstrated sinusoidal position-dependent discharge modulations to OVAR which selectively stimulates the otoliths. Two features of neuronal responses to bidirectional OVAR were identified. Within the velocity spectrum tested (1.75-15 degrees/s), some neurons showed symmetric bidirectional response sensitivity (delta value) to CW and CCW rotations. The spread of the delta values of each of these neurons with velocity was small. This group of reticular neurons were described as exhibiting symmetric and velocity-stable bidirectional response sensitivity. The mathematically derived gain tuning ratios of these neurons were within the range of narrowly spatiotemporal-tuned neurons. Another group of reticular neurons, however, showed asymmetric bidirectional response sensitivity to CW and CCW rotations; a few of these neurons were responsive only to OVAR of one direction but not to both. For each of this second group of neurons, the spread of the delta values with velocity was large. These reticular neurons were described as exhibiting asymmetric and velocity-variable bidirectional response sensitivity. The gain tuning ratios of these latter neurons were found to be within the range of broadly spatiotemporal-tuned neurons. Single neurons of both groups displayed orientational tuning. Both the best response orientations of neurons that showed symmetric and velocity-stable bidirectional response sensitivity and the preferred orientations of neurons that showed asymmetric and velocity-variable bidirectional response sensitivity were found to point in all directions on the rotary plane. The response dynamics of the former group of neurons was also examined. All showed flat response gain across the entire velocity range. Some showed a flat response lead while others showed a progressive shift from small response lead at low velocity to phase close to zero at higher velocities. The functional significance of these medial medullary reticular neurons to the direction and orientation of head tilt is discussed.

Animals↗

Effects of kainic acid administered to the caudal ventrolateral medulla on arterial blood pressure in the spontaneously hypertensive and normotensive Wistar-Kyoto rats.

To compare the inhibitory influence of the caudal ventrolateral medulla (CVLM) on rostral ventrolateral medulla (RVLM) between spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats, we studied the blood pressure responses to administration of kainic acid, an excitotoxic agent, to CVLM. Unilateral or bilateral administration of kainic acid led to an initial reduction in blood pressure in both types of rats. In SH rats, this was followed by a gradual and sustained pressor response. This biphasic response in arterial blood pressure was observed in only one-third of the WKY rats. The elevation in blood pressure was significantly greater in SH than in WKY rats. The finding suggests that the tonic inhibitory influence from CVLM to RVLM may be greater in SH than in WKY rats.

Animals↗

Identification of plant cytoskeletal, cell cycle-related and polarity-related proteins using Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe has been used to identify Arabidopsis thaliana proteins that may play a role in cell shape maintenance or cell cycle regulation. An Arabidopsis thaliana cDNA library was constructed in pREP5N vector under the control of the inducible nmt1 promoter and transformed into S. pombe. Expression of the A. thaliana sequences was induced and clones showing severe morphological changes were identified and analysed. Comparison of the sequences of the inserts with the sequence data bases revealed that several cDNAs encode proteins known to play a role in function of the cytoskeleton, the cell cycle and establishment of cell polarity. These include alpha-1, alpha-2, alpha-6 and beta-6 tubulins, myosin heavy chain-like protein, ubiquitin conjugating enzymes UBC9 (E2), 26S protease subunits, Ranbinding protein, myb protein, PRL1 gene product and rho protein. Approximately 30% of the clones encode novel sequences. The results suggest that S. pombe phenotypic screening can be used to identify plant proteins involved in cell shape maintenance and regulation during cell cycle and development.

Actin Depolymerizing Factors↗

Apolipoprotein E genotype and Alzheimer's disease in Hong Kong elderly Chinese.

We studied the apolipoprotein E (apoE) allele frequencies in 65 Chinese patients with late-onset Alzheimer's disease (AD) and 82 age- and sex-matched controls. The apoE epsilon 4 allele frequency was significantly higher in the AD group than in the control group (0.169 versus, p < 0.01). There were five homozygotes for epsilon 4 in the AD group but none among the controls. The odds ratio for AD was 1.6 for epsilon 4 heterozygotes. The age at onset was lower in the presence of the epsilon 4 allele and higher with the epsilon 2 allele, although neither of these differences reached statistical significance. The association between apoE alleles and AD previously reported in Caucasian populations was also present in this reports of lower prevalence of AD compared with the prevalence of multi-infarct dementia.

Aged↗

Concordant childhood acute lymphoblastic leukemia in monozygotic twins.

Two 4-year-old monozygotic Chinese, female twins developed concordant childhood acute lymphoblastic leukemia (ALL) within an interval of about 2 weeks. Based on morphology and cytochemistry findings of the bone marrow blast cells, a diagnosis of ALL, L1 was made. Immunophenotyping showed the blast cells of both twins expressed similar antigens, i.e. HLA-DR, CD10, CD13, CD19, CD22 and CD34. Identical blood group, same HLA (human leucocyte antigen) genotype, sex and similar appearance suggest that the twins are monozygotic. Since the bone marrow leukemic cells of both twins were identical in morphology and expressed the same antigens with almost similar percentages of positivity, it is likely that the blast cells were derived from the same single clone. Based on the single clone hypothesis, the leukemogenic event must have arisen in utero in one twin and the cells from the abnormal clone then spread to the other twin via shared placental anastomoses.

Child, Preschool↗

Correlation of a missense mutation in the human Secretor alpha 1,2-fucosyltransferase gene with the Lewis(a+b+) phenotype: a potential molecular basis for the weak Secretor allele (Sew).

A missense mutation (A385 to T), predicting an Ile129 to Phe substitution, in the human Secretor alpha 1,2-fucosyltransferase gene was present in double dose in Lewis(a+b+) individuals, but not in Lewis(a-b+) individuals. Co-segregation of the Lewis(a+b+) phenotype with homozygosity for the mutation was also verified. These results yield a potential molecular basis for the weak Secretor allele (Sew) accounting for the Lewis(a+b+) phenotype.

Alleles↗

Properties of otolith-related vestibular nuclear neurons in response to bidirectional off-vertical axis rotation of the rat.

In decerebrate rats, the responses of tilt-sensitive neurons in the lateral and descending vestibular nuclei were studied during constant velocity 10 degrees off-vertical axis rotations (OVAR) in the clockwise (VW) and counterclockwise (CCW) directions. Seventy three otolith-related units showed a sinusoidal position-dependent discharge modulation to OVAR of both directions; 20 of these showed clipped firing rates in parts of a 360 degree OVAR cycle. With increase in the velocity of rotation (1.75-15 degrees/s), one group of units (n = 36) showed a stable ratio of bidirectional response sensitivity and symmetric response magnitudes to CW and CCW rotations. These units showed gain tuning ratios similar to those of narrowly spatiotemporal-tuned neurons. The other group of OVAR responsive units (n = 13) exhibited velocity-variable and asymmetric bidirectional response sensitivities. Their gain tuning ratios were similar to those of broadly spatiotemporal-tuned neurons. For units with velocity-stable and symmetric bidirectional response sensitivity as well as gain tuning ratio of the narrowly spatiotemporal-tuned neurons, their response gains remained stable with velocity. Some showed stable response phase lead or lag with velocity increase while others showed progressive shifts from response lead of 13 degrees to response lag of -25 degrees. The best response orientations of these units with velocity-stable and symmetric bidirectional response sensitivity were found to point in all directions on the place of rotation. The functional significance of these tilt- and OVAR-sensitive central otolith neurons is discussed.

Animals↗

Discordant regulation of SCL/TAL-1 mRNA and protein during erythroid differentiation.

The SCL/TAL1 gene was originally identified by virtue of its rearrangement and transcriptional activation in patients with T cell acute lymphoblastic leukaemia. It encodes a helix-loop-helix transcription factor, is not normally expressed in T cells, but is expressed in erythroid, mast, megakaryocytic and progenitor cells. Over-expression of sense and antisense constructs have implicated SCL as a positive regulator of erythroid differentiation. In addition we have previously shown that SCL mRNA levels undergo biphasic modulation during induced erythroid differentiation of murine erythroleukaemia (MEL) cells with a transient early fall followed by a late rise. In this paper we have studied expression of the SCL protein during erythroid differentiation and also the molecular basis for the raised SCL mRNA levels that accompany erythroid differentiation. We have generated an anti-SCL antiserum and used it to demonstrate that an early transient fall in SCL protein does not occur during induced differentiation of MEL cells. Furthermore SCL protein levels underwent a late fall in three different models of erythroid differentiation and in two models of myeloid differentiation. The fall in SCL protein levels during induced erythroid differentiation contrasted with the concomitant marked rise in SCL mRNA levels. These observations have significant implications for the mechanism by which SCL may regulate erythropoiesis. In addition we have demonstrated that the stability of SCL mRNA was only marginally enhanced during erythroid differentiation of MEL cells, whereas the activity of a luciferase reporter construct driven by the SCL promoter was increased 11- to 17-fold. Up-regulation of transcription therefore accounted for most of the increase in SCL mRNA levels during erythroid differentiation.

Animals↗

Role of dorsal motor nucleus of vagus in gastric function and mucosal damage induced by ethanol in rats.

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.

Animals↗

Elevated spontaneous activity of phenylephrine-excited neurons in the caudal ventrolateral medulla of spontaneously hypertensive rats.

1. The caudal ventrolateral medulla (CVLM) of pentobarbital-anaesthetized spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats was identified by the depressor response with microinjection of glutamate. 2. The mean firing rate of the spontaneously active phenylephrine-excited CVLM neurons was significantly greater in SHR than in WKY. The pattern of neuronal firing in terms of coefficient of variation and skewness of the interspike interval histogram was similar in both types of rats. 3. Administration to CVLM of kainic acid, an excitotoxic agent, led to a biphasic blood pressure response--a transient reduction followed by a gradual and sustained elevation. The elevation in blood pressure was significantly greater in SHR than in WKY. 4. These findings suggest that the barosensitive CVLM neurons are more active and the tonic inhibitory influence from CVLM to rostral ventrolateral medulla (RVLM) is greater in SHR than in WKY. It is therefore not likely that the elevated spontaneous activity of the RVLM cardiovascular neurons in SHR is due to a smaller inhibitory influence from CVLM.

Adrenergic alpha-Agonists↗

Neuronal responses in the y group nucleus of unilaterally labyrinthectomized cats during off-vertical axis rotations.

In cats which were decerebrated and unilaterally labyrinthectomized on the day of the experiment, the responses of neurons in the y group nucleus on the lesioned side were studied during constant velocity off-vertical axis rotations, which selectively stimulated the remaining intact otolith receptors. During 360 degrees rotations, neurons exhibited position-dependent modulation in discharge rate, thus showing that the y group neurons receive signals of head positional changes from the contralateral otoliths. Most y group neurons had their best response orientations within +/- 45 degrees of the head-up and head-down positions (i.e. antero-posterior or pitch direction) in the plane of rotation studied. This implies that the spatial coding property of these otolith neurons enables them to be particularly catered for small head tilts about the sagittal plane of the animal.

Animals↗

Structure of the gene encoding the murine SCL protein.

We have determined the molecular structure of the gene encoding the murine SCL protein (helix-loop-helix transcription factor). The gene consists of seven exons spanning approx. 20 kb. The intron/exon structure, coding region sequences and sequences present at the splice junctions were highly conserved between mouse and human. The 5' flanking sequence contains CCAAT and TATA consensus motifs with several putative binding sites for SP-1, AP-1 and GATA-1. Multiple mRNA transcripts were generated by alternate exon usage. The transcripts differed primarily in the 5' untranslated region (UTR), but potentially also encode a smaller SCL protein. Despite the high degree of conservation between species, the heptamer/nonamer signal sequences in the 5' region of the human SCL gene (the frequent site of SCL disruption in human leukemia) were poorly represented in the murine sequence. In keeping with this, structural abnormalities of murine SCL were uncommon in murine leukemias that express the SCL transcript.

Animals↗

Effects of [Sar1, Ile8]-angiotensin II on rostral ventrolateral medulla neurons and blood pressure in spontaneously hypertensive rats.

The present study was an attempt to determine the influence of brain angiotensin II, the activity of which is known to be higher in spontaneously hypertensive rat, on the spontaneous activity of the cardiovascular neurons in the rostral ventrolateral medulla of the spontaneously hypertensive rat. Both the spontaneous activity of the spinal projecting rostral ventrolateral medulla cardiovascular neurons and the arterial blood pressure were simultaneously measured in the pentobarbital-anesthetized spontaneously hypertensive rat and its normotensive control, the Wistar Kyoto rat, following microinjection to rostral ventrolateral medulla of an angiotensin II antagonist, [Sar1, Ile8]-angiotensin II (sarile). A microinjection method was developed that enabled us to perform extracellular recording of the rostral ventrolateral medulla cardiovascular neurons during the microinjection of drug to the vicinity of the neuron. It was found that sarile reduced both the arterial blood pressure and firing rate of some rostral ventrolateral medulla cardiovascular neurons dose-dependently. The effects of sarile were significantly greater in spontaneously hypertensive rat than in the Wistar Kyoto rat. The present findings indicate that the rostral ventrolateral medulla cardiovascular neurons of spontaneously hypertensive rat exhibit an augmented sensitivity to endogenous brain angiotensin II. Such an increase in sensitivity to brain angiotensin II in the spontaneously hypertensive rat may contribute to the enhanced spontaneous activities of rostral ventrolateral medulla cardiovascular neurons, as in the sarile responsive single discharge units, even in the resting or prestimulation state. This interaction of brain angiotensin II and rostral ventrolateral medulla cardiovascular neurons is likely to be contributory to the genesis of hypertension in this strain of rats.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Partially transformed T3T3 cells express high levels of mutant p53 in the 'wild-type' immunoreactive form with defective oligomerization.

High levels of wild-type p53 suppress transformed growth of many cell lines and yet murine T3T3 cells shown partially transformed growth despite high endogenous levels of phenotypically 'wild-type' p53. On sequencing T3T3 p53 was found to encode missense mutations at codons 230 and 287 and, although endogenous T3T3 p53 is 'wild type', the protein adopted the mutant phenotype when expressed in vitro. Size fractionation of T3T3 cell lysate indicated monomeric p53 possibly in complex with a low molecular weight protein. When expressed in vitro T3T3 p53 formed dimers and higher order structures. Thus T3T3 cells appear (i) to drive endogenous mutant p53 to adopt conformational epitopes characteristic of the 'wild-type' protein, and (ii) to interfere with normal assembly of p53 quaternary structure. Phosphopeptide mapping of p53 from 3T3x cells, T3T3 cells and SV3T3 cells indicated reduced amino terminal phosphorylation of the mutant p53 phenotype. Alternative splicing of p53 was also detected in 3T3x cells; similar splicing occurs in wild-type p53 (Han & Kulesz-Martin, 1992; Nucl. Acids Res., 20, 1979-1981) and a possible regulatory function is discussed.

3T3 Cells↗