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Biomedical subjects

T P Wong

Publications and source records attributed to T P Wong.

At least 19 recordsLinked to original sources

Transcatheter embolisation of visceral pseudoaneurysms--technical difficulties and modification of embolisation technique.

We report 13 successful emergency embolisations for 12 pseudoaneurysms performed in 10 patients. For five pseudoaneurysms the embolisation technique was modified according to number of supplying vessels, flow rate of pseudoaneurysms, vascular anatomy and whether there was clinical evidence of re-bleeding or not. Apart from traditional embolisation technique, modified embolisation techniques are also useful for endovascular therapy of pseudoaneurysms.

Adult↗

Arterial embolisation in intractable primary post-partum haemorrhage: case series.

OBJECTIVE: To evaluate the efficacy and safety of arterial embolisation in the management of intractable primary post-partum haemorrhage. DESIGN. Retrospective case series. SETTING: Regional hospital, Hong Kong. PATIENTS: Nine patients aged 28 to 39 years who were treated for severe primary post-partum haemorrhage between October 2000 and January 2003. INTERVENTION: Emergency transcatheter arterial embolisation. MAIN OUTCOME MEASURES: Clinical outcome and complications. RESULTS: All nine arterial embolisations successfully arrested the haemorrhage. The main cause of primary post-partum haemorrhage was uterine atony. No serious complication arose, although one patient experienced slight numbness of the right leg. Normal menstruation resumed in all patients, except for the one who had had a hysterectomy as initial treatment. One patient became pregnant 1 year after embolisation. Patients were followed up for 10 months. CONCLUSION: In our experience, arterial embolisation is safe and efficacious, and is the treatment of choice for patients with intractable primary post-partum haemorrhage.

Adult↗

Activation of PI3-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons.

Hippocampal CA1 homosynaptic long-term potentiation (LTP) is expressed specifically at activated synapses. Increased insertion of postsynaptic alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) appears to be crucial for CA1 LTP. However, the mechanism underlying AMPAR insertion during LTP remains largely unknown. We now report that phosphatidylinositol 3-kinase (PI3K) is complexed with AMPARs at synapses and activated by selective stimulation of synaptic N-methyl-D-aspartate (NMDA) receptors. Activation of the AMPAR-associated PI3K is required for the increased cell surface expression of AMPARs and LTP. Thus, our results strongly suggest that the AMPAR-PI3K complex may constitute a critical molecular signal responsible for AMPAR insertion at activated CA1 synapses during LTP, and consequently, this lipid kinase may serve to determine the polarity of NMDA receptor-dependent synaptic plasticity.

Androstadienes↗

The impact of Abeta-plaques on cortical cholinergic and non-cholinergic presynaptic boutons in alzheimer's disease-like transgenic mice.

A previous study in our laboratory, involving early stage, amyloid pathology in 8-month-old transgenic mice, demonstrated a selective loss of cholinergic terminals in the cerebral and hippocampal cortices of doubly transgenic (APP(K670N,M671L)+PSl(M146L)) mice, an up-regulation in the single mutant APP(K670N,M671L) mice and no detectable change in the PSl(M146L) transgenics [J Neurosci 19 (1999) 2706]. The present study investigates the impact of amyloid plaques on synaptophysin and vesicular acetylcholine transporter (VAChT) immunoreactive bouton numbers in the frontal cortex of the three transgenic mouse models previously described. When compared as a whole, the frontal cortices of transgenic and control mice show no observable differences in the densities of synaptophysin-immunoreactive boutons. An individual comparison of layer V of the frontal cortex, however, shows a significant increase in density in transgenic models. Analysis of the cholinergic system alone shows significant alterations in the VAChT-immunoreactive bouton densities as evidenced by an increased density in the single (APP(K670N,M671L)) transgenics and a decreased density in the doubly transgenics (APP(K670N,M671L)+PSl(M146L)). In investigating the impact of plaque proximity on bouton density at early stages of the amyloid pathology in our doubly (APP(K670N,M671L)+PSl(M146L)) transgenic mouse line, we observed that plaque proximity reduced cholinergic pre-synaptic bouton density by 40%, and yet increased synaptophysin-immunoreactive pre-synaptic bouton density by 9.5%. Distance from plaques (up to 60 microm) seemed to have no effect on bouton density; however a significant inverse relationship was visible between plaque size and cholinergic pre-synaptic bouton density. Finally, the number of cholinergic dystrophic neurites surrounding the truly amyloid, Thioflavin-S(+) plaque core, was disproportionately large with respect to the incidence of cholinergic boutons within the total pre-synaptic bouton population. Confocal and electron microscopic observations confirmed the preferential infiltration of dystrophic cholinergic boutons into fibrillar amyloid aggregates. We therefore hypothesize that extracellular Abeta aggregation preferentially affects cholinergic terminations prior to progression onto other neurotransmitter systems. This is supported by the observable presence of non-cholinergic sprouting, which may be representative of impending neuritic degeneration.

Acetylcholine↗

Emergency embolization of spontaneous ruptured hepatocellular carcinoma: correlation between survival and Child-Pugh classification.

From February 1994 to April 2000, 29 emergency gelfoam embolizations for spontaneous ruptured hepatocellular carcinoma (HCC) performed in 28 patients were retrospectively reviewed. There were 11 patients in Child's A, 11 in Child's B and six in Child's C classification of cirrhosis. The duration of the procedure, artery embolized and complications were reviewed, and the Child-Pugh classification of each patient was correlated with their mean survival period. Embolization was done in 12 right hepatic arteries, two left hepatic arteries and 15 proper hepatic arteries. In one patient, the left hepatic artery was embolized initially but the proper hepatic artery was also embolized because another subcapsular liver tumour was found after reviewing the preangiogram CT scan. The entire procedure took 40-170 min (mean = 86 min) with no periprocedural complication. Following embolization, the mean survival period for Child's A class was 218.3 days, Child's B class was 83.4 days and Child's C class was 11.0 days. Transcatheter embolization is an effective treatment to arrest bleeding in spontaneous ruptured HCC. Patients with Child's A class cirrhosis have the longest survival. Selective embolization of either the right or the left hepatic artery alone carries the potential risk of missing multifocal HCC that might not be easily appreciated during angiography.

Adult↗

The recovery of some components of the renin angiotensin system in the rat pancreas after chronic exposure to hypoxic condition.

Previous studies have shown that the expression of the major components from a local pancreatic renin-angiotensin system (RAS) was upregulated after chronic exposure to oxygen deprivation (10% oxygen). In the present study, the reversibility of expression for the pancreatic RAS affected by chronic hypoxia was investigated in the pancreas. Rats were first subject to hypoxia for one Month and they were then returned to normoxic conditions for a varying period of time (1, 2, 3 and 4 weeks). The degree of recovery in the expression of RAS components was analyzed with standard curve-quantitative competitive-reverse transcription-polymerase chain reaction (SC-QC-RT-PCR), Western blot analysis and a specific assay for angiotensin-converting enzyme (ACE) activity. Results from SC-QC-RT-PCR showed that the upregulated expression of angiotensin II type 1 (AT(1)) receptor mRNA following chronic hypoxia could be completely restored to the control level after the rats were returned to the normoxic condition for 3 weeks. The reversibility of mRNA expression for angiotensin II type 2 (AT(2)) receptor and angiotensinogen was observed after the return to normoxic conditions for 2 and 3 weeks respectively when compared with that of their respective controls. Results from Western blot analysis further confirmed that the expression of AT(1) receptor protein was also reversible after return to normoxic conditions for 4 weeks. In addition, the activation of ACE activity returned to its normal level in a time-dependent manner. These data indicate that the upregulation of a local pancreatic RAS affected by chronic hypoxia could be recoverable. The significance of its reversibility and adaptability following chronic hypoxia may be of physiological relevance to the pancreas.

Angiotensin II↗

Androgen dependent expression of AT1 receptor and its regulation of anion secretion in rat epididymis.

Our previous studies have provided solid evidence for the presence of an intrinsic angiotensin-generating system in the rat epididymis, which plays an important role in the regulation of the anion and thus fluid secretion by the epididymal epithelium. In the present study, the effect of androgen on the expression of AT(1)receptor and its subsequent regulation of anion secretion by the epididymis were investigated using Western blotting, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in vitro electrophysiological approaches. Results from Western blotting analysis showed that the expression of AT(1)receptor protein was almost abolished by castration whereas its expression was completely restored to the control level when the castrated rats were hormonally replaced with testosterone. Efferent duct ligation, however, appeared not to affect the expression of AT(1)receptor protein by the epididymis. Results from RT-PCR showed that mRNA expression of AT(1)receptor was consistent with that observed in protein expression. Results from short-circuit current (I(SC)) showed that castration almost abolished the angiotensin II-induced I(SC). However, efferent duct ligation did not affect the angiotensin II-induced I(SC), which was completely blocked in the presence of losartan, a specific antagonist of the AT(1)receptor. These data indicate that the expression of epididymal AT(1)receptor is predominantly influenced by testicular androgens but not by testicular factors. This androgen-dependent expression of AT(1)receptor could have a role in the control of AT(1)receptor-mediated anion secretion and thus fluid secretion by the rat epididymis.

Androgens↗

Aging causes a preferential loss of cholinergic innervation of characterized neocortical pyramidal neurons.

Aging is known to markedly affect the number and structural characteristics of both pre- and post-synaptic sites in the cerebral cortex. There is evidence that lamina V pyramidal neurons, and their basilar dendrites in particular, are affected by age-related decline. Furthermore, layer V is the area where the greatest overall age- related losses in the total population of synaptic boutons and of cholinergic boutons are observed. Since both pyramidal neurons and cortical cholinergic input are characteristically compromised in aging, we investigated whether aging altered the pattern of cholinergic boutons in apposition to the soma, proximal and distal basal dendrites of intracellularly labeled lamina V large pyramidal neurons in the parietal cortex of young and aged rats. We observed a significant age-related decrease in the population of both total and cholinergic boutons apposed to proximal and distal dendrites of layer V large pyramidal neurons. However, the age-related decreases of cholinergic presynaptic boutons were higher than those in the total bouton population apposed to the pyramidal neurons. The average decrease in cholinergic boutons in aged rats was 3.7-fold more pronounced than the diminution in the overall number of presynaptic boutons. Our results add important new evidence in support of the concept that the age-related learning and memory deficits are attributable, at least partially, to a decline in the functional integrity of the forebrain cholinergic systems.

Aging↗

Cholinergic nerve terminals establish classical synapses in the rat cerebral cortex: synaptic pattern and age-related atrophy.

This study addresses the issue of whether cholinergic varicosities in the cerebral cortex establish 'classical synapses' or whether they communicate with their targets non-synaptically by 'volume transmission'. Most recent studies in the neocortex have suggested that acetylcholine acts non-synaptically, however in the present study we provide ultrastructural evidence that suggests synaptic mechanisms prevail. This conclusion is based upon our ultrastructural observations that cholinergic boutons--as revealed by immunoreactivity for the specific cholinergic market, vesicular acetylcholine transporter--establish a high percentage of classical synapses in layer V of the rat parietal cortex. Furthermore, the combination of this approach with the intracellular labeling of large pyramidal neurons on slice preparations revealed significant incidences of cholinergic contacts abutting preferentially on dendritic shafts. Finally, we have gathered information suggesting that cholinergic boutons undergo atrophy with aging which could be related to the well-known cholinergic and cognitive decline. These results illustrate that the cholinergic terminations in the neocortex establish proper synaptic connections and that they experience important age-dependent atrophy.

Acetylcholine↗

Transit dose of an Ir-192 high dose rate brachytherapy stepping source.

Clinical dosimetry for high dose rate (HDR) brachytherapy with a single stepping source generally neglects the transit dose. This study investigates the effects of the transit dose in the target volume of an HDR brachytherapy stepping source. A video method was used to analyse the entrance, exit and the interdwell transit speed of the source for different path lengths and step sizes ranging from 2.5 mm to 995 mm. The transit speed was found to vary with the step size and path length. For the travelled distances of 2.5, 5.0, 10.0, 230 and 995 mm, the average transit speeds were 54, 72, 233, 385 and 467 mm s(-1) respectively. The results also show that the manufacturer has attempted to compensate for the effects of interdwell transit dose by reducing the actual dwell time of the source. A well-type chamber was used to determine the dose differences between two sets of measurements, one being the stationary dose only and the other being the sum of stationary and transit doses. Single catheters of active lengths of 20 and 40 mm, different dwell times of 0.5, 1, 2 and 5 s and different step sizes of 2.5, 5 and 10 mm were used in the measurements with the well-type chamber. Most of the measured dose differences between stationary and stationary plus interdwell source movement were within 2%. The additional dose due to the source transit can be as high as 24.9% for the case of 0.5 s dwell time, 10 mm step size and 20 mm active length. The dose difference is mainly due to the entrance and exit source movement but not the interdwell movement.

Biophysical Phenomena↗

Loss of presynaptic and postsynaptic structures is accompanied by compensatory increase in action potential-dependent synaptic input to layer V neocortical pyramidal neurons in aged rats.

Reduction in both presynaptic and postsynaptic structures in the aging neocortex may significantly affect functional synaptic properties in this area. To directly address this issue, we combined whole-cell patch-clamp recording of spontaneously occurring postsynaptic currents (PSCs) with morphological analysis of layer V pyramidal neurons in the parietal cortex of young adult (1- to 2-month-old) and aged (28- to 37-month-old) BN x F344 F(1) hybrid rats. Analysis of spontaneous PSCs was used to contrast functional properties of basal synaptic input with structural alterations in the dendritic tree of pyramidal neurons and density of terminals in contact with these cells. We observed significant changes in a number of morphological parameters of pyramidal neurons in aged rats. These include smaller cell body size and fewer basal dendritic branches (but not of oblique dendrites and dendritic tufts) and spines. Ultrastructural analysis also revealed a lower density of presynaptic terminals per unit length of postsynaptic membrane of labeled pyramidal neurons in the aged brain. This reduction in both presynaptic and postsynaptic elements was paralleled by a significant decrease in frequency of tetrodotoxin-insensitive miniature (action potential-independent) PSCs (mPSCs). The frequency of excitatory and inhibitory mPSCs was reduced to the same extent. In contrast, no significant change was observed in the frequency of spontaneous PSCs recorded in absence of tetrodotoxin (sPSCs), indicating an increase in action potential-dependent (frequency(sPSCs) - frequency(mPSCs)) input to pyramidal neurons in the aged group. This functional compensation may explain the lack of drastic loss of spontaneous neuronal activity in normal aging.

Action Potentials↗

Testicular hormonal regulation of the renin-angiotensin system in the rat epididymis.

Evidence for the existence of an intrinsic angiotensin system based on locally formed angiotensinogen as a precursor for angiotensin production has been demonstrated in the rat epididymis. The data strongly support the presence of an epididymal renin-angiotensin system (RAS) which may be important for epididymal and sperm functions. In the present study, the effects of castration and testicular hormonal replacement on the expression of RAS components from the rat epididymis are investigated at the gene and protein levels. Results from northern blot and western blot analyses consistently showed that the expression of angiotensinogen mRNA and protein was apparently abolished by castration whereas their expression was completely restored to control levels when the castrated rats were hormonally replaced with either testosterone alone or with combined testosterone and estradiol. Northern blot did not detect any signal for angiotensinogen mRNA while western blot could detect a weak signal for angiotensinogen protein when the castrated rats were replaced with estradiol alone. Renin could be detected neither in control, castrated nor hormonally replaced rats. Moreover, the expression of angiotensin II receptor, type I (AT1) was almost abolished by castration as demonstrated by northern blot and reverse transcription-polymerase chain reaction. These data indicate that the expression of RAS by the rat epididymis at the levels of its precursor angiotensinogen and its receptor AT1, is subject to the regulation of testicular hormones and its expression appears to be predominantly testosterone-dependent.

Angiotensinogen↗

Angiotensinogen expression by rat epididymis: evidence for an intrinsic, angiotensin-generating system.

Previous studies have suggested the presence of an intrinsic renin-angiotensin system (RAS) in the rat epididymis with functions in epididymal activity and sperm maturation. In the present study, the localization and expression of angiotensinogen, the component of the RAS which is indispensable for intracellular angiotensin generation, were investigated by immunochemistry, hybridization histochemistry and by reverse-transcriptase polymerase chain reaction (RT-PCR). Western blot analysis of protein from the epididymis confirmed the presence of angiotensinogen with the expected molecular mass of about 60 kDa, in agreement with results from other tissues. Immunocytochemistry showed the regional localization of immunoreactivity for angiotensinogen in the rat epididymis. In situ hybridization histochemistry further demonstrated the expression of angiotensinogen mRNA by the epididymal epithelium in a region-specific manner along the length of the rat epididymis. RT-PCR confirmed that the rat epididymis expresses angiotensinogen mRNA. On the other hand, mRNA of renin was not detected in the rat epididymis using Northern blot and RT-PCR analyses. The present study strongly supports the existence of an intrinsic, angiotensin-generating system based on locally formed angiotensinogen as a precursor for angiotensin production. This epididymal RAS may have paracrine or autocrine roles in mediating the epididymal and sperm functions.

Angiotensinogen↗

Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes.

Cholinergic deficits are one of the most consistent neuropathological landmarks in Alzheimer's disease (AD). We have examined transgenic mouse models (PS1M146L, APPK670N,M671L) and a doubly transgenic line (APPK670N,M671L + PS1M146L) that overexpress mutated AD-related genes [presenilin-1 (PS1) and the amyloid precursor protein (APP)] to investigate the effect of AD-related gene overexpression and/or amyloidosis on cholinergic parameters. The size of the basal forebrain cholinergic neurons and the pattern of cholinergic synapses in the hippocampus and cerebral cortex were revealed by immunohistochemical staining for choline acetyltransferase and the vesicular acetylcholine transporter, respectively. At the time point studied (8 months), no apparent changes in either the size or density of cholinergic synapses were found in the PS1M146L mutant relative to the nontransgenic controls. However, the APPK670N,M671L mutant showed a significant elevation in the density of cholinergic synapses in the frontal and parietal cortices. Most importantly, the double mutant (APPK670N,M671L + PS1M146L), which had extensive amyloidosis, demonstrated a prominent diminution in the density of cholinergic synapses in the frontal cortex and a reduction in the size of these synapses in the frontal cortex and hippocampus. Nonetheless, no significant changes in the size of basal forebrain cholinergic neurons were observed in these three mutants. This study shows a novel role of APP and a synergistic effect of APP and PS1 that correlates with amyloid load on the reorganization of the cholinergic network in the cerebral cortex and hippocampus at the time point studied.

Acetylcholine↗

Rod-type cyclic nucleotide-gated cation channel is expressed in vascular endothelium and vascular smooth muscle cells.

OBJECTIVES: Ca(++)-permeable nonselective cation channels mediate the entry of extracellular Ca++ in vascular endothelium. They are also partly responsible for Ca++ entry in vascular smooth muscle cells (SMCs). The molecular identities of these channels have not been identified. The aim of this study is to examine whether rod-type nucleotide-gated nonselective cation (CNG1) channel, a channel which has been molecularly cloned, is related to the nonselective channels in vascular cells. METHODS: We used RT-PCR, molecular cloning, northern Blot and in situ hybridization to examine the expression of CNG1 mRNA in a variety of guinea pig and rat blood vessels with different diameters and in cultured vascular endothelial cells and vascular smooth muscle cells. RESULTS: We have cloned a 402-bp partial cDNA of CNG1 channel from guinea pig mesenteric arteries. RT-PCR and southern blot results indicate that the CNG1 mRNA is expressed in both cultured vascular endothelial and cultured vascular SMCs. Northern blot revealed the transcripts of approximately 3.2 kb, approximately 5.0 kb, and approximately 1.8 kb in cultured endothelial cells. In situ hybridization yielded strong labeling in endothelium layer of aorta, medium-sized mesenteric arteries, and small mesenteric arteries. CONCLUSION: Our findings suggest a potential role of CNG protein for Ca++ entry in vascular endothelium and vascular smooth muscles. The high expression of CNG1 mRNA in the endothelium of medium-sized arteries and small-sized arteries implicates a possible involvement of CNG1 protein in the regulation of blood supply to different regions and in the regulation of arterial blood pressure.

Amino Acid Sequence↗

Expression and localization of the renin-angiotensin system in the rat pancreas.

The possibility of an intrinsic renin-angiotensin system (RAS) in the pancreas has been raised by previous studies in which immunohistochemical examination showed the presence of angiotensin II and its receptor subtypes, type 1 (AT1) and type 2 (AT2). In the present study, gene expression of several key RAS components was investigated by reverse-transcription PCR. mRNA expression for angiotensinogen, renin and angiotensin II receptor subtypes, AT1a, AT1b and AT2 was shown. The presence of angiotensinogen protein, the mandatory component for an intrinsic RAS, was demonstrated by Western blotting and localized by immunohistochemistry to the epithelia and endothelia of pancreatic ducts and blood vessels respectively. Immunoblot analysis detected a predominant protein band of about 60 kDa in the pancreas. This was consistent with the predicted value for angiotensinogen as reported in other tissues. Together with previous findings, the present study shows that the rat pancreas expresses the major RAS component genes, notably angiotensinogen and renin, required for intracellular formation of angiotensin II. The data support the notion of an intrinsic RAS in the rat pancreas which may play a role in the regulation of pancreatic functions.

Angiotensin II↗

Expression of sperm Ca2+-activated K+ channels in Xenopus oocytes and their modulation by extracellular ATP.

Ionic fluxes across the sperm membrane have been shown to be important in the initiating process of sperm activation and gamete interaction; however, electrophysiological investigation of the ion channels involved has been precluded by the small size of the sperm, especially in mammalian species. In the present study sperm ion channels were expressed in Xenopus oocytes by injection of RNAs of spermatogenic cells isolated from the rat testes. The RNA-injected oocytes responded to ATP, a factor known to regulate sperm activation, with the activation of an outwardly rectifying whole-cell current which was dependent on K+ concentrations and inhibitable by K+ channel blockers, charybdotoxin (CTX) and tetraethylammonium (TEA). The ATP-induced current could be mimicked by a Ca2+ ionophore but suppressed by a Ca2+ chelator applied intracellularly, indicating a Ca2+ dependence of the current. Single-channel measurements on RNA-injected oocytes revealed channels of large conductance which could be blocked by CTX and TEA. Co-injection of germ cell RNAs with the antisense RNA for a mouse gene encoding slowpoke 'Maxi' Ca2+-activated K+ channels resulted in significant reduction of the ATP- and ionomycin-induced current. The expression of the 'Maxi' Ca2+-activated K+ channels in sperm collected from the rat epididymis was also confirmed by Western blot analysis. These results suggest that sperm possess Ca2+-activated K+ channels which may be involved in the process of sperm activation.

Amino Acid Sequence↗