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Biomedical subjects

V Wong

Publications and source records attributed to V Wong.

At least 19 recordsLinked to original sources

Follicular stem cell carcinoma: histologic, immunohistochemical, ultrastructural, and clinical characterization in 30 dogs.

Diagnostic records of 30 primary and one metastatic follicular stem cell carcinomas in 30 dogs were reviewed. Neoplastic cells had a clear cytoplasm and formed lobules and nests surrounded by a basement membrane. Trichoepitheliomatous and apocrine differentiations were noted in 22 of 30 (73%) and 21 of 30 (70%) primary tumors, respectively. Glycogen was present in 20 of 20 (100%) tumors tested, suggesting tricholemmal differentiation. Antibodies against AE1/AE3 cytokeratin, vimentin, and melanA/MART1 stained 29 of 30 (97%), 29 of 30 (97%), and 12 of 27 (44%) primary tumors, respectively. Small amounts of melanin were identified in 14 primary tumors, either on the hematoxylin and eosin-stained section (n = 6), or on the Fontana-stained section (n = 8 of 14). Ultrastructural features of neoplastic cells included cell junction complexes, swollen mitochondria, neuroendocrine-like granules, and intracytoplasmic non-membrane-bound accumulation of proteinaceous material. Features of this neoplasm are consistent with a follicular stem cell origin. Follow-up information was available for eight dogs. Metastases developed in the draining lymph node at the time of excision of the primary tumor (n = 1) or subsequently (n = 3).

Animals↗

Hypoxia-induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit.

We examined the effects of hypoxia on the release of serotonin (5-HT) from intact neuroepithelial body cells (NEB), presumed airway chemoreceptors, in rabbit lung slices, using amperometry with carbon fibre microelectrodes. Under normoxia (P(O2) ~155 mmHg; 1 mmHg approximately 133 Pa), most NEB cells did not exhibit detectable secretory activity; however, hypoxia elicited a dose-dependent (P(O2) range 95-18 mmHg), tetrodotoxin (TTX)-sensitive stimulation of spike-like exocytotic events, indicative of vesicular amine release. High extracellular K(+) (50 mM) induced a secretory response similar to that elicited by severe hypoxia. Exocytosis was stimulated in normoxic NEB cells after exposure to tetraethylammonium (20 mM) or 4-aminopyridine (2 mM). Hypoxia-induced secretion was abolished by the non-specific Ca(2+) channel blocker Cd(2+) (100 microM). Secretion was also largely inhibited by the L-type Ca(2+) channel blocker nifedipine (2 microM), but not by the N-type Ca(2+) channel blocker omega-conotoxin GVIA (1 microM). The 5-HT(3) receptor blocker ICS 205 930 also inhibited secretion from NEB cells under hypoxia. These results suggest that hypoxia stimulates 5-HT secretion from intact NEBs via inhibition of K(+) channels, augmentation of Na(+)-dependent action potentials and calcium entry through L-type Ca(2+) channels, as well as by positive feedback activation of 5-HT(3) autoreceptors.

Animals↗

Epidemiological study of multiple sclerosis in Hong Kong Chinese: questionnaire survey.

OBJECTIVE: To study the epidemiology of multiple sclerosis in Hong Kong Chinese. DESIGN: Cross-sectional questionnaire survey. SETTING: Neurology and paediatric neurology departments in Hong Kong from January through June 1999. PARTICIPANTS: All confirmed multiple sclerosis patients. MAIN OUTCOME MEASURES: Demographic data, investigation results, Kurtzke's Expanded Disability Status Scale during the last follow-up visit, number of relapses between 1997 and 1998, and treatments used/currently in use. RESULTS: Fifty-three Chinese multiple sclerosis patients were identified. The prevalence was thus estimated to be 0.77 per 100,000 population. This low prevalence was also noted in other multiple sclerosis studies from South-East Asia (range, 0.8-4 per 100,000 population). The female to male ratio among the Chinese multiple sclerosis sufferers was 9.6:1, a figure somewhat higher than that reported in the other studies from South-East Asia (range, 3.2-6.6:1). The Chinese multiple sclerosis patients in this study also had a high spinal cord involvement (66%) and a low presence of cerebrospinal fluid oligoclonal banding (40%). These findings were different from those in Caucasian multiple sclerosis patients. CONCLUSION: Multiple sclerosis in Hong Kong Chinese has a low prevalence, a high female to male ratio, and a low cerebrospinal fluid oligoclonal banding presence.

Adult↗

2,4-Thiazolidinediones as potent and selective human beta3 agonists.

Methylsulfonamide substituted 2,4-thiazolidinedione 22c is a potent (EC50=0.01 microM, IA=1.19) and selective (more than 110-fold over beta1 and beta2 agonist activity) beta3 agonist. This compound has also been proven to be active and selective in an in vivo mode.

Adrenergic beta-3 Receptor Agonists↗

Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity.

Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the findings that CNTF acts via receptors that are not only related to leptin receptors, but also similarly distributed within hypothalamic nuclei involved in feeding. However, although CNTF mimics the ability of leptin to cause fat loss in mice that are obese because of genetic deficiency of leptin (ob/ob mice), CNTF is also effective in diet-induced obesity models that are more representative of human obesity, and which are resistant to leptin. This discordance again raised the possibility that CNTF might be acting via nonleptin pathways, perhaps more analogous to those activated by cachectic cytokines. Arguing strongly against this possibility, we now show that CNTF can activate hypothalamic leptin-like pathways in diet-induced obesity models unresponsive to leptin, that CNTF improves prediabetic parameters in these models, and that CNTF acts very differently than the prototypical cachectic cytokine, IL-1. Further analyses of hypothalamic signaling reveals that CNTF can suppress food intake without triggering hunger signals or associated stress responses that are otherwise associated with food deprivation; thus, unlike forced dieting, cessation of CNTF treatment does not result in binge overeating and immediate rebound weight gain.

Adipose Tissue↗

Genetic imbalances in pT2 breast cancers of southern Chinese women.

While much information has been reported on the genetic alterations in breast cancers of Caucasians, little is known about the Oriental populations where breast cancers currently rank the second most common neoplasm. As a first step toward understanding the underlying genetics changes in this population, we used comparative genomic hybridization (CGH) to the genome-wide analysis of forty pT2 tumors from patients of a racially homogenous population in southern China. A complex pattern of genetic alterations emerged with the commonest chromosomal gains identified on 1q (58%), 8q (55%), 11q13 (25%), 16p (28%), 17q (53%) and 20q (35%), and frequent losses on 8p (38%), 11q (28%), 13q (30%) and 18q (25%). When breast cancers with and without lymph-node metastasis were compared, a higher copy gain of 10p was identified in the node-positive group (P=.036). An overall increase in the average number of genetic aberrations was also identified in the late onset group (>45 years)(P=.042) with a higher incidence of genetic losses noted (P=.035). In particular, losses on 16q were detected in 30% of the late onset patients but none in the early onsets (P=0.049). In this study, we have illustrated the pattern of genetic changes in breast tumors of southern Chinese females. While frequent 1q, 8q, 17q and 20q gains, and common 8p and 13q deletions detected were consistent to those aberrations reported from the Caucasian populations, the difference in genetic changes associated in lymph-node metastasis and age of onset identified should provide the basis for additional investigations into the underlying tumorigenesis in the Oriental population.

Adult↗

How does alteration of hepatic blood flow affect liver perfusion and radiofrequency-induced thermal lesion size in rabbit liver?

The purpose of this study was to test the hypothesis that decreasing liver perfusion in rabbits results in an increase in thermal lesion size and that these effects can be accurately monitored using magnetic resonance imaging (MRI). We additionally tested the hypothesis that the increase in thermal lesion size would depend on the particular vessel or vessels occluded (hepatic artery, portal vein, or both). Using an Institutional Animal Care and Use Committee approved protocol, 20 New Zealand white rabbits were randomly assigned to four treatment groups (five in each group): control and ligation of portal vein (PV), hepatic artery (HA), or both PV and HA (HAPV). Surgical ligation of the appropriate vessel was performed under general anesthesia. Immediately after ligation, the rabbits were placed in a 0.2-T open MR system, and an 18-G copper radiofrequency (RF) electrode with a 2-cm exposed tip was inserted into the liver. RF was applied for 10 minutes with the tip temperature maintained at 90 degrees +/- 2 degrees C. Before and after ablation, perfusion data were obtained for 90 seconds using 30 3-second sequential single oblique-slice fast imaging with steady-state progression (FISP) acquisitions after injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) via the inferior vena cava. Postablation scanning included axial and oblique turbo spin-echo (TSE) T2-weighted (T2w), STIR, and Gd-enhanced T1w sequences. Lesion size was determined perpendicular to the RF electrode using software calipers on the imager. The rabbits were sacrificed after completion of the post-therapy scans, and their livers were harvested for histologic analysis. The liver showed a mean increase in signal amplitude (SA) of 76% 24 seconds after Gd contrast injection in the control group. After contrast injection, the SA increased to a mean of only 66% in the group with ligated hepatic arteries, with no difference in the time to peak compared with the control group. No significant SA increase over baseline could be found in the groups with ligated PV or ligated PV and HA. T2-weighted images demonstrated the highest lesion-to-liver contrast-to-noise ratios (CNRs; mean -5.5) on postprocedure images, followed by STIR images (mean -2.2) in the control group. The lesions were poorly delineated on the Gd-enhanced images. Average maximum lesion sizes (mean +/- 95% confidence interval) were 22 +/- 4.3 mm after ligation of PV, 22 +/- 2.6 mm after ligation of both PV and HA, 14 +/- 2.0 mm after ligation of HA, and 13 +/- 1.9 mm in the control group. We accept the hypothesis that the diameter of the region of coagulation necrosis achieved by standardized RF ablation in the liver increases with reduced organ perfusion and that this effect can be accurately monitored using MRI. The major factor influencing the size of the coagulation area is the portal venous flow. Occlusion of the hepatic artery alone does not significantly increase lesion size. T2w sequences are best suited for postprocedure imaging due to the high lesion-to-liver CNR in rabbits with normal hepatic perfusion. J. Magn. Reson. Imaging 2001;13:57-63.

Animals↗

Effect of vaginally administered fumagillin on the morphology of implantation stage endometrium in the rhesus monkey.

Intravaginal administration of an anti-angiogenic agent, fumagillin, during blastocyst implantation, inhibits pregnancy establishment in a dose-related manner in the rhesus monkey. In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (group 1; n = 5) and test agent (fumagillin, 4 mg/animal; group 2; n = 6) on cycle day 20, and endometrial tissue samples were collected on cycle day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17beta, progesterone and chorionic gonadotrophin in peripheral circulation were determined. From serum profiles of hormones, two monkeys in group 1, and one animal in group 2 appeared pregnant. Endometrial morphology revealed histologic evidence of pregnancy in three of six fumagillin-treated animals, while other three fumagillin-treated animals showed degenerative changes in glands and venules along with marked extravasation. It is possible that the function of corpus luteum was affected by fumagillin treatment resulting in inadequate progesterone production (p <0.05), and consequent inadequate endometrial secretory preparation and receptivity, as revealed from decline in apical movement of vacuoles (p <0.05) and increase (p <0.05) in extravasation of red cells and leukocytes.

Administration, Intravaginal↗

Effect of vaginally administered (Ala(8,13,18))-magainin II amide on the morphology of implantation stage endometrium in the rhesus monkey (Macaca mulatta).

Intravaginal administration of an anti-microbial agent, (Ala(8,13,18))-magainin II amide, during blastocyst implantation inhibits pregnancy establishment in a dose-related manner in the rhesus monkey (Macaca mulatta). In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (Group 1; n = 5) and test agent (magainin, 0.5 mg/animal; Group 2; n = 6) on cycle day 20. Endometrial tissue samples were collected on Cycle Day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17beta, progesterone, and chorionic gonadotrophin in peripheral circulation were determined, which revealed that two monkeys in Group 1 were pregnant while no animals were pregnant in Group 2. Endometrial morphology, however, revealed histologic evidence of pregnancy in three out of the six magainin-treated animals. It appears that intra-vaginal administration of magainin II amide had a marginal effect on the implantation stage endometrium and the initiation of the implantation process in the rhesus monkey.

Administration, Intravaginal↗

West syndrome--The University of Hong Kong experience (1970-2000).

OBJECTIVE: To study the clinical pattern of West syndrome (WS) in a university based hospital. METHODOLOGY: The database of children seen in the Epilepsy Clinic of Queen Mary Hospital and Duchess of Kent Children's Hospital during a 30-year period (1970-2000) was reviewed. RESULTS: A total of 105 cases had WS (1.9%). The number of new cases of WS admitted per year ranged from one to eight. The range of annual incidence of WS to newly diagnosed epilepsy was 0.8-4.8%. The etiology included idiopathic (N=19, 18%), cryptogenic (N=23; 22%), symptomatic (N=56; 53.3%) and unknown (N=7; 5.7%). Adrenocorticotropic hormone (ACTH) and/or prednisone were given to 42 children (40%). Most were effective in controlling WS on an all-or-none fashion. Seizure outcome included 12 with remission, persistent in the same form in two and persisting but changed to another form in the rest. Neurological outcome at the last follow up in 2000 December included multiple disabilities (N=16), cerebral palsy (N=22), mental retardation (N=94) and Lennox-Gastaut syndrome (N=13). We analysed the following risk factors in relation to poor outcome: age of onset, age of presentation, time lag before treatment, etiology, family history of epilepsy and hormonal treatment. Only etiology of WS has a positive correlation with poor outcome (P<0.0005). CONCLUSIONS: WS is an uncommon epileptic syndrome. The majority had poor outcome, especially those with causes identified. Infantile spasm is a specific epileptic phenomenon in a maturational stage of a child when heterogeneous disorders can present with the same clinical epileptic and electroencephalographic phenomenon.

Anticonvulsants↗

Neurologic complications due to catheterization.

In our university cardiac center, the incidence of a cohort of children with acute neurologic complications resulting from cardiac catheterization performed for acyanotic or cyanotic congenital heart disease is 0.38% (14 children of a total of 3,648 catheterization procedures). Neurologic complications consisted of convulsion (n = 10), stroke (n = 6), intracranial hemorrhage (n = 2), extrapyramidal features (n = 1), paraplegia (n = 1), visual impairment (n = 1), hearing impairment (n = 1), and brachial plexus injury (n = 1). The main risk factors included prolonged duration of catheterization procedure and interventional manipulation in addition to cardiac catheterization. The possible mechanisms causing brain injury included cerebral embolism from local clots and hypoxia resulting from complications during the procedure. Other complications included intracranial hemorrhage secondary to anticoagulation and peripheral plexopathy because of prolonged fixed posture during anesthesia. The prognosis for the majority of patients with stroke is good. Neurologic sequelae, such as global developmental delay or epilepsy, occurred in those with hypoxic-ischemic encephalopathy.

Acute Disease↗

Traditional Chinese medicine (tongue acupuncture) in children with drooling problems.

Tongue acupuncture is an innovative technique in traditional Chinese medicine. We have demonstrated that specific tongue acupoints are related to various functional domains. This study aimed to assess the efficacy of tongue acupuncture in children with neurologic disability who had severe drooling problems. We conducted an intent-to-treat study in a cohort of 10 children. A continuous course of tongue acupuncture was performed daily to five acupoints in the tongue for a total of 30 sessions. Standardized outcome measures of drooling were evaluated by a blinded assessor to study the efficacy at baseline and after a course of treatment. Statistically significant improvement was noted in the following outcome measures: (1) mean visual analog scale (VAS) decreased from 6.6 (pre-TAC) to 4.67 (post-TAC) (P = 0.002); (2) mean drooling quotient (DQ) decreased from 14.016% (pre-TAC) to 8.335% (post-TAC) (P = 0.0078); and (3) mean drooling score (DS) decreased from 7.4 (pre-TAC) to 4.4 (post-TAC) (P = 0.002). This study demonstrated the efficacy of tongue acupuncture as an adjunctive or alternative treatment for patients with drooling problems and can be integrated as part of the oromotor stimulation program, drooling program, and behavioral modification program before subjecting the patient to invasive surgical procedures on the salivary glands.

Acupuncture Therapy↗

Ultrasonographic measurement of subarachnoid space in normal infants and children.

This study was undertaken to evaluate the sonographic measurement of subarachnoid spaces in normal children and its relationship with age and to define a normal range in a Chinese population and to differentiate normal variant findings from pathologic dilatation. The subarachnoid spaces in 278 normal term neonates, infants, and children were studied with real-time ultrasound using a 7.5-MHz vector transducer. The craniocortical width, sinocortical width, and interhemispheric width were measured in the coronal plane at the level of the foramen of Monro, on either side of the hemispheres. Correlation of sonographic measurements with age was made. The mean widths were plotted against age. A correlation with age was found in all three spaces, with an increasing trend with age until 28 weeks of gestation. Thereafter, a decreasing trend was noted. The normal upper limit of subarachnoid spaces for children is proposed to be the values on the ninety-fifth percentile of the regression curve. Correlation of measurement with age must be considered to decide whether an increase in subarachnoid space is pathologic or not.

Cephalometry↗

Novel (4-piperidin-1-yl)-phenyl sulfonamides as potent and selective human beta(3) agonists.

A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta(3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta(3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta(3) agonists with low affinities for beta(1)- and beta(2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta(3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta(3) agonist (EC(50)=0.004 microM, IA=1.0) with > 500-fold selectivity over beta(1)- and beta(2)-ARs.

Adrenergic beta-3 Receptor Agonists↗

High-quality, cost-effective strategy for detection of autoantibodies to extractable nuclear antigens.

We evaluated methods for the detection of autoantibodies to extractable nuclear antigens (ENAs) to determine the strategy that yielded the most cost effective and clinically meaningful result. We prospectively compared counterimmunoelectrophoresis (CIEP) with and without serum prediffusion (SPD) and found that SPD significantly improved the quality of precipitation lines. This resulted in a decreased requirement for repeat testing and, consequently, was associated with a significant decrease in reagent costs and specimen turnaround time. We also retrospectively compared reactivity by CIEP, CIEP plus SPD, enzyme-linked immunosorbent assay (ELISA), and line immunoassay (LIA) of 52 serum samples that were previously determined to be positive for ENAs, and we correlated the results with clinical diagnoses. There was significant agreement among CIEP, CIEP plus SPD, ELISA, and LIA for the detection of anti-SS-A, anti-SS-B and anti-RNP. In general, CIEP, CIEP plus SPD, and LIA correlated better with the clinical diagnoses than ELISA, even though ELISA detected anti-ENAs more often than the other methods. CIEP plus SPD is therefore the most cost effective method for the identification of clinically meaningful ENAs. Based on our experience, we now screen for ENAs by CIEP, and positive samples are then typed by CIEP plus SPD. Samples that are difficult to interpret are then further assessed by an alternative method.

Antigens, Nuclear↗

Neuroepithelial bodies in mammalian lung express functional serotonin type 3 receptor.

Serotonin (5-HT) type 3 receptor (5-HT(3)-R) is a ligand-gated ion channel found primarily in the central and peripheral nervous system. We report expression and functional characterization of 5-HT(3)-R in pulmonary neuroepithelial body (NEB) cells. Using nonisotopic in situ hybridization, we demonstrate expression of 5-HT(3)-R mRNA in NEB cells in the lungs of different mammals (hamster, rabbit, mouse, and human). Dual immunocytochemistry (for 5-HT and 5-HT(3)-R) and confocal microscopy localized 5-HT(3)-R on NEB cell plasma membrane from rabbit. The electrophysiological characteristics of 5-HT(3)-R in NEB cells were studied in fresh slices of neonatal hamster lung using the whole cell patch-clamp technique. Application of the 5-HT (5-150 microM) and 5-HT(3)-R agonist 2-methyl-5-HT (5-150 microM) induced inward currents in a concentration-dependent manner. The 5-HT-induced current was blocked (76.5 +/- 5.9%) by the specific 5-HT(3)-R antagonist ICS-205-930 (50 microM), whereas katanserin and p-4-iodo-N-(2-[4-(methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinylbenzamide had minimal effects. Forskolin had no effect on desensitization and amplitude of the 5-HT-induced current. The reduction of Ca(2+) and Mg(2+) in the extracellular solution enhanced the amplitude of the 5-HT-induced current because of slower desensitization. Our studies suggest that 5-HT(3)-R in NEB cells may function as an autoreceptor and may potentially be involved in modulation of hypoxia signaling.

Aminopyridines↗

Molecular genetic study of a childhood form of spinal muscular atrophy.

Molecular genetic studies were performed in 28 cases of childhood-onset spinal muscular atrophy (24 unrelated families). This consisted of type 1 (severe) (n = 5), type 2 (intermediate form) (n = 8), and type 3 (mild) (n = 15). Deletion of exons 7 and 8 of the SMNt gene was found in 100%, 100%, and 93%, respectively, in type 1, 2, and 3 spinal muscular atrophy. Deletion of exons 5 and 6 of the NAIP gene was found in 3 of 5 (60%) of type 1 and none of the type 2 and 3 cases. None of the 32 asymptomatic relatives had homozygous deletions in the SMNt and NAIP genes. Thus, the role of the NAIP gene needs to be specifically defined in spinal muscular atrophy. In a suspected case of spinal muscular atrophy, deletion of the SMNt gene is a useful laboratory marker for confirmation of the diagnosis.

Adolescent↗

Acute gastroenteritis-related encephalopathy.

We studied the incidence of convulsions in 1936 children with acute gastroenteritis. Sixty-eight children had convulsions (3.5%), which were categorized into three groups: (1) bacterial (n = 13; 19%), (2) Rotavirus (n = 30, 44%), and (3) no organism (n = 25; 37%). Only group 2 versus group 3 had a significant association with encephalopathy (P < .002). The relative risk was estimated to determine the risk of encephalopathy: Rotavirus versus no organism isolated (relative risk = 2.308), Rotavirus versus bacterial (relative risk = 1.846), and bacterial versus no organism (relative risk = 1.25). None developed epilepsy. Thus, acute gastroenteritis-related encephalopathy is a benign condition with single or recurrent seizures during an episode of acute gastroenteritis and an excellent prognosis. The underlying mechanism for provoking seizure is unknown. One should be reassured of a good outcome in the majority of children with recurrent episodes of afebrile/febrile seizures during an episode of acute gastroenteritis.

Acute Disease↗