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Biomedical subjects

W L Huang

Publications and source records attributed to W L Huang.

At least 19 recordsLinked to original sources
PubMed2006

Spinal cord compression and dorsal root injury cause up-regulation of activating transcription factor-3 in large-diameter dorsal root ganglion neurons.

Spinal cord injury causes damage to ascending and descending tracts, as well as to local circuits, but relatively little is known about the effect of such injury on sensory neurons located within adjoining ganglia. We have therefore used immunocytochemistry for activating transcription factor-3 (ATF3), a sensitive marker of axonal damage, in order to examine the effects of spinal cord injury in rats on dorsal root ganglion (DRG) neurons. A 50-g static compression injury applied to the dorsal surface of the T12 thoracic spinal cord led to an up-regulation of ATF3 that was maximal at 1 day and affected 12-14% of DRG neurons in ganglia caudal to the injury (T13-L3). A similar response was seen after a T12 hemisection that transected the dorsal columns except that compression injury, but not hemisection, also evoked ATF3 expression in ganglia just rostral to the injury (T10, T11). ATF3 was up-regulated exclusively in DRG neurons that were of large diameter and immunoreactive for heavy neurofilament. Small-diameter cells, including the population that binds the lectin Grifffonia simplicifolia IB4, did not express ATF3 immunoreactivity. A similar pattern of ATF3 expression was induced by dorsal rhizotomy. The data show for the first time that ATF3 is up-regulated after spinal cord and dorsal root injury, but that this up-regulation is confined to the large-diameter cell population.

Activating Transcription Factor 3↗
PubMed2005

Hypoxia-induced apoptosis in adult rat dorsal root ganglion neurons in vitro.

Following spinal root injury, dorsal root ganglia suffer mechanical trauma and compromised blood supply. Little is known about the consequences for neuronal survival. Here we used cyanide treatment in vitro to examine effects of moderate hypoxia on adult rat dorsal root ganglion cells identified by GAP-43 immunostaining. 400 microM-4 mM cyanide caused sustained increases in intracellular Ca2+. Cyanide at 2 mM led to a significant increase in apoptosis, detected using TUNEL labelling and confirmed by ultrastructural analysis, and a further increase when cultures were left overnight in fresh medium. Our study shows that dorsal root ganglion neurons die by apoptosis following hypoxia and that cell death increases over time. Cyanide response provides a simple assay for testing neuroprotective agents and examining underlying mechanisms.

Animals↗
PubMed2003

Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue.

We have attempted to extend a previously described rat model of focal oligodendrocyte progenitor cell (OPC) depletion, using 40 Gy X-irradiation (Chari and Blakemore [2002] Glia 37:307-313), to the adult mouse spinal cord, to examine the ability of OPCs present in adjacent normal areas to colonise areas of progenitor depletion. In contrast to rat, OPCs in the mouse spinal cord appeared to be a comparatively radiation-resistant population, as 30-35% of OPCs survived in X-irradiated tissue (whereas <1% of OPCs survive in X-irradiated rat spinal cord). The numbers of surviving OPCs remained constant with time indicating that this population was incapable of regenerating itself in response to OPC loss. Additionally, these OPCs did not contribute to remyelination of axons when demyelinating lesions were placed in X-irradiated tissue, suggesting that the surviving cells are functionally impaired. Importantly, the length of the OPC-depleted area did not diminish with time, as would be expected if progressive repopulation of OPC-depleted areas by OPCs from normal areas was occurring. Our findings therefore raise the possibility that the presence of a residual dysfunctional OPC population may inhibit colonisation of such areas by normal OPCs.

Animals↗
PubMed2001

Genetic analysis of recent Taiwanese isolates of a variant of coxsackievirus A24.

Epidemics of acute hemorrhagic conjunctivitis (AHC) caused by a variant of coxsackievirus A24 (CA24v) reappeared in Taiwan in 1990 and 1994, following the first two epidemics of 1985--86 and 1988--89. To analyze the genetic diversity of recent CA24v in Taiwan, 7 Taiwanese strains isolated during the 1990--94 period were studied together with one Japanese and two Thai strains isolated in 1993. A fragment of 674 nucleotides between the carboxy terminal 3A and the amino terminal 3D polymerase, including the entire 3C protease (3C(pro)), was amplified by a reverse transcription-polymerase chain reaction (RT-PCR) and the nucleotide sequences were determined. In the 549 nucleotides (183 amino acids) of the entire 3C(pro), we found nucleotide differences at 80 positions between 10 strains and the prototype strain, EH24/70, one of the earliest strains of CA24v. Most of the nucleotide changes were synonymous substitutions and only nine amino acid changes were found. The nucleotide sequence homologies among 71 strains worldwide were 88-100%. These 71 nucleotide sequences were then analyzed by Neighbor-joining method and phylogenetically separated into three distinct genotypes. Genotype I consisted of early strains isolated in 1970--71 from Singapore and Hong Kong. Genotype II included isolates from Singapore and Thailand obtained in 1975. Genotype III comprised strains from the eastern hemisphere isolated in 1985--94 from Japan, Taiwan, China, Hong Kong, Thailand, Singapore, Pakistan and Ghana. They were further divided chronologically into six clusters. The recent isolates from Taiwan obtained in 1985/1986, 1988/1989 and 1990--94 were classified into genotype III Clusters 1, 5, and 6 respectively. The evolutionary rate was re-estimated to be 3 x 10(- 3) 30 years after the emergence of the virus.

Amino Acid Sequence↗
PubMed2001

Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep.

Glucocorticoids regulate oligodendrocyte maturation and the myelin biosynthetic pathways. Synthetic glucocorticoids, the corticosteroids have been successfully used in clinical practice as a single course to enhance lung maturation and reduce mortality and morbidity in preterm infants with no long-term neurologic or cognitive side effects. However, a trend has arisen to use repeated courses despite an absence of safety data from clinical trials. We examined the effects of clinically appropriate, maternally administrated, repeated courses of corticosteroids on myelination of the corpus callosum using sheep as a large animal model. The corpus callosum is a major white matter tract that undergoes protracted myelination, underpins higher order cognitive processing and developmental damage to which is associated with, for example, cerebral palsy, mental retardation and attention deficit hyperactivity disorder. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104,111,118 and 124 days gestation, stages equivalent to the third trimester in humans. Lambs were delivered at 145 days (term), perfused and the corpus callosum examined light and electron microscopically. Total axon numbers were unaffected (P>0.05). However, myelination was significantly delayed. Myelinated axons were 5.7% in the experimental group and 9.2% in controls (P<0.05); conversely, unmyelinated axons were 88.3 and 83.7% (P<0.05). Myelinated axon diameter and myelin sheath thickness were also reduced (0.68 vs. 0.94 and 0.11 vs. 0.14 microm, P<0.05). Our data suggest that repeated prenatal corticosteroid administration delays myelination of the corpus callosum and that further safety data are needed to evaluate clinical practice.

Agenesis of Corpus Callosum↗
PubMed2001

Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep.

Glucocorticoids are powerful regulators of cell differentiation and maturation. Their synthetic counterparts, the corticosteroids, are used widely in obstetric practice to enhance fetal lung maturation in cases of threatened preterm birth. Here we examined the effects of repeated corticosteroid administration on astrocyte and capillary tight junction development in the fetal sheep brain, selecting the corpus callosum for analysis. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation. Lambs were delivered at term, terminally anaesthetized and transcardially perfused. Transverse semi-thin sections of the corpus callosum were cut and immuno-stained with antibody against glial fibrillary acidic protein (GFAP). Ultra-thin sections were examined in the electron microscope. The percentage area of GFAP staining was reduced in the corticosteroid-treated group compared to control (5.2 vs. 8.7%, P<0.05). The expression of GFAP in peri-capillary and parenchymal astrocytes was also reduced compared to control (peri-capillary: 3.0 vs. 9.5 microm2; parenchymal: 14.6 vs. 29.4 microm2, P<0.05). Furthermore, capillary tight junction maturation was delayed compared to control. Immature 'type II' junctions were more common in the corticosteroid-treated group (63 vs. 22%, P<0.05), whereas more mature 'type III' junctions were less common (27 vs. 65%, P<0.05). Our data suggest that repeated corticosteroids delay both astrocyte and capillary tight junction maturation. The implications for clinical practice are as yet unknown.

Animals↗
PubMed1999

Effect of corticosteroids on brain growth in fetal sheep.

OBJECTIVE: To compare the effects of single and repeated courses of corticosteroids on brain growth in fetal sheep. METHODS: Pregnant sheep were given intramuscular betamethasone (0.5 mg/kg) at 104 days' gestation followed at 111, 118, and 124 days by equivalent volumes of sterile normal saline (n = 12) or betamethasone (n = 12). Controls received equivalent volumes of sterile normal saline at all four intervals (n = 12). Lambs were delivered at 125 (preterm) or 145 (term) days. After perfusion, we measured weights (grams) for whole brain, cerebrum, cerebellum, and brain stem, volumes (milliliters) for whole brain and cerebrum, and maximum cerebral anterior-posterior length, width, and depth (centimeters). RESULTS: In the single-injection group at preterm, there were no significant differences (P = .070) in whole-brain weight between the corticosteroid-treated animals (38.0 +/- 1.81 g) and controls (42.5 +/- 1.65 g). Cerebral length and depth were significantly reduced in the corticosteroid group (P < .05); other measures were not significantly different. At term, whole-brain weight was significantly lower (47.5 +/- 1.70 g; P = .022) compared with controls (53.4 +/- 1.73 g). All other measures were significantly reduced (P < .05) except cerebral and brain-stem weights and cerebral length. In the group that received repeated injections at preterm, whole-brain weight was significantly reduced (35.5 +/- 1.65 g; P = .005) compared with controls (42.5 +/- 1.65 g). All other measures were significantly reduced (P < .05) except cerebellar and brain-stem weights. At term, whole-brain weight was also significantly reduced (42.4 +/- 1.52 g; P = .001) compared with controls (53.4 +/- 1.73 g) as were all other measures (P < .05). CONCLUSION: Administration of single and repeated courses of corticosteroids to pregnant sheep retarded fetal brain growth.

Animals↗
PubMed1999

Effect of exogenous corticosteroids on the developing central nervous system: a review.

Corticosteroid therapy is used in a variety of developmental clinical settings. Prenatally, maternal administration of corticosteroids is used primarily in the prevention of respiratory distress syndrome. Postnatally, corticosteroids are used to treat a variety of infant diseases such as autoimmune hemolytic anemia and hypoglycemia. Treatment regimes often involve repeated administration, on a weekly basis prenatally and daily postnatally, despite an absence of safety data from randomized clinical trials. A large number of animal studies, the majority of which used rodents, have shown that both repeated prenatal or neonatal administration of exogenous corticosteroids has a wide range of detrimental effects on the structure and function of the developing central nervous system (CNS). None of these studies included long-term follow-up. Despite the reported detrimental effects on CNS development, a number of animal studies have shown that pretreatment with corticosteroids nevertheless protect the brain from hypoxia-ischemic injury; however, clinically such treatment is no longer favored. Studies using large animal models and with long-term follow-up should be undertaken to establish the relative risks and benefits of the repeated application of exogenous corticosteroids.

Adrenal Cortex Hormones↗
PubMed1998

Reversal of tumor multidrug resistance by 2-phenyl-3-(3',5'-dimorpholinomethyl-4'-hydroxy)-benzoyl-indole (HWL-12).

AIM: To explore the reversal of multidrug resistance (MDR) by indole derivative HWL-12. METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry. RESULTS: HWL-12 10 mumol.L-1 markedly increased Fura-2 accumulation and was 17.2-fold reversal of MDR in MCF-7/ADR cells. The cellular Dox accumulation in MDR cells was increased in the presence of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox accumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca2+ (addition of egtazic acid). CONCLUSION: HWL-12 has a potent MDR reversal action which was associated with the increase of cellular Dox accumulation in MDR cells and not related with calcium ion concentration.

Breast Neoplasms↗
PubMed1997

Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2.

DNA vaccines encoding a viral protein have been shown to induce antiviral immune responses and provide protection against subsequent viral challenge. In this study, we show that the efficacy of a DNA vaccine can be greatly improved by simultaneous expression of interleukin-2 (IL-2). Plasmid vectors encoding the major (S) or middle (pre-S2 plus S) envelope proteins of hepatitis B virus (HBV) were constructed and compared for their potential to induce hepatitis B surface antigen (HBsAg)-specific immune responses with a vector encoding the middle envelope and IL-2 fusion protein or with a bicistronic vector separately encoding the middle envelope protein and IL-2. Following transfection of cells in culture with these HBV plasmid vectors, we found that the encoded major protein was secreted while the middle protein and the fusion protein were retained on the cell membrane. Despite differences in localization of the encoded antigens, plasmids encoding the major or middle proteins gave similar antibody and T-cell proliferative responses in the vaccinated animals. The use of plasmids coexpressing IL-2 and the envelope protein in the fusion or nonfusion context resulted in enhanced humoral and cellular immune responses. In addition, the vaccine efficacy in terms of dosage used in immunization was increased at least 100-fold by coexpression of IL-2. We also found that DNA vaccines coexpressing IL-2 help overcome major histocompatibility complex-linked nonresponsiveness to HBsAg vaccination. The immune responses elicited by HBV DNA vaccines were also modulated by coexpression of IL-2. When restimulated with antigen in vitro, splenocytes from mice that received plasmids coexpressing IL-2 and the envelope protein produced much stronger T helper 1 (Th1)-like responses than did those from mice that had been given injections of plasmids encoding the envelope protein alone. Coexpression of IL-2 also increased the Th2-like responses, although the increment was much less significant.

Animals↗
PubMed1997

[Synthesis and bioactivity of some 3,4-diacyloxybenzopyrans].

Considerable attention is now being given to the potassium channel openers of benzopyrans as potential therapeutical agents for hypertension. In order to search for novel antihypertensive with high efficacy and low toxicity, integrating structural features of cromakalim and praeruptorin C, twenty-four compounds of 3,4-diacyloxybenzopyrans were designed and synthesized. Some of them exhibited hypotensive activity in Sprague Dawley rats.

Animals↗
PubMed1995

Expression of the Epstein-Barr virus DNA polymerase in Escherichia coli for use as antigen for the diagnosis of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) encoded DNA polymerase (POL) was cloned and over-expressed in Escherichia coli. Western blot analysis confirmed the presence of antibody to this POL protein in sera from nasopharyngeal carcinoma (NPC) patients. By Western blot analysis, moderate to high concentration of IgG POL-specific antibodies were present in 43 of 48 NPC sera and only 4 of 48 healthy, seropositive controls. The POL-specific IgG antibodies appear as early as stage I of NPC, suggesting that the recombinant POL protein can be a useful diagnostic marker for early diagnosis of the disease. It was also found that human sera containing high titer of cytomegalovirus (CMV) antibodies or herpes simplex virus type 1 (HSV-1) antibodies did not cross-react with the recombinant EBV POL, despite the homology shared by DNA polymerase proteins of these viruses.

Amino Acid Sequence↗
PubMed1995

Prominent proliferative response of peripheral blood mononuclear cells to a recombinant non-structural (NS3) protein of hepatitis C virus in patients with chronic hepatitis C.

The proliferative response of peripheral blood mononuclear cells (PBMC) to a recombinant non-structural (NS3) protein of hepatitis C virus (HCV) was studied in 41 patients with chronic hepatitis C. Of them, 28 had chronic persistent hepatitis (CPH) and 13 chronic active hepatitis (CAH). The positive proliferation rate of PBMC to the recombinant NS3 protein, T9Ag, was 66% in the 41 patients (77% in CAH versus 61% in CPH; P > 0.05) when stimulation index (SI) = 4 was set as the cut-off value. However, mean SI of CAH patients was significantly higher than that of CPH patients (8.3 +/- 5.2 versus 5.1 +/- 3.6; P < 0.05). Six other chronic hepatitis patients who were repeatedly negative for anti-HCV antibody but positive for serum HCV RNA also had an SI of > or = 4.0. The frequency of cellular immune response to the T9Ag is among the highest results obtained by using HCV antigens tested so far. Our studies thus indicate that NS3 is an immunologically important region of HCV for T cells. Moreover, the proliferative response to T9Ag may help to establish hepatitis C etiology in chronic hepatitis patients who are seronegative with currently available anti-HCV assays.

Adult↗
PubMed1995

A molecular study of ocular herpes simplex infection in Kaohsiung, Taiwan. Part I: Cleavage pattern analysis.

In order to investigate the relationship between genotypes of herpes simplex virus (HSV) and its clinical pictures in herpes simplex virus keratoconjunctivitis (HSK), fifty nine strains of HSV isolates, collected in the Kaohsiung Medical College Hospital during January 1981 to July 1991, and F strain (ATCC VR-73), a standard HSV-1, were studied. The viruses were isolated from HSK patients. All 59 strains were identified as HSV-1 using immunofluorescence monoclonal antibody method. The HSV DNAs were extracted and digested by restriction enzymes, BamH I, Kpn I and Sal I, followed by electrophoresis, and photographing. Six kinds of DNA cleavage patterns were found in Taiwan. The majority were E subtype (56.4%) then A subtype (27.3%), D subtype (7.3%), F subtype (5.4%), G subtype (1.8%) and H subtype (1.8%). Subtypes B and C were not found in this study. The cleavage patterns of two recurrent cases belonged to E and A subtypes. The identical cleavage patterns of two bilateral infections all belonged to the E subtype.

Animals↗
PubMed1995

[The re-evaluation of the prevalence of trachoma in primary school children in Kaohsiung City].

For years, trachoma screening has been a routine part of the health examination program for all primary school children. In order to ascertain the current prevalence of trachoma in primary school children, we used clinical examination, immunofluorescein-monoclonal antibody and McCoy cell culture technique to examine 771 children from 5 primary schools in Kaohsiung City. Using the results of the McCoy cell culture as a judgement standard, we found that 118 children (15.3%) had chlamydia trachomatis infections. The infection rates of children were statistically insignificant for sex, grade and location of school of children. Among the 118 infected children, most had none or mild (96.6%) conjunctival inflammation. Only 3 children (0.4%) had conjunctival cicatrization complications. These results showed that the repeated reinfections among these children were quite few. The McCoy cell culture was used to test the result of clinical diagnosis made by the senior ophthalmologists. The sensitivity of the clinical diagnosis was 50% and the predictive positive rate was 26.6%. It revealed that the diagnosis of trachoma made by clinical observation only was unreliable. The results of immunofluorescein-monoclonal antibody test showed that 120 children (15.6%) had trachomatous infections. Its sensitivity was 68.4%, and specificity was 91.7%. It revealed that more care should be taken in quality control of laboratory techniques. From these results, we conclude: 1) the trachomatous infections of primary school children in Kaohsiung City are not serious; the repeated infections among

Child↗
PubMed1995

Swyer-James syndrome associated with Noonan syndrome: report of a case.

A 28-year-old man with Noonan syndrome associated with unilateral hyperlucent lung is reported. He had the typical craniofacial appearance and short stature of Noonan syndrome; he had mild mental retardation, atrophic testis, mild funnel chest and kyphosis. cardiovascular abnormalities included asymmetric hypertrophic cardiomyopathy and a significantly different caliber of the left and right pulmonary arteries. The unilateral hyperlucent lung was shown to result from acquired nondestructive emphysema caused by nonvalvular obstruction of the bronchi (Swyer-James syndrome or Macleod's syndrome). To the authors' knowledge, this is the first reported case of Noonan syndrome associated with Swyer-James syndrome.

Adult↗