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Biomedical subjects

L Y Chang

Publications and source records attributed to L Y Chang.

At least 19 recordsLinked to original sources
PubMed2002

Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy.

AIM: The mechanism of pulmonary oedema, a life-threatening manifestation of enterovirus 71 (EV71) encephalitis, is unclear. Our aim was to assess the relationship of proinflammatory cytokines to EV71-related pulmonary oedema. METHODS: Proinflammatory responses in 33 EV71 patients with various complications and 21 normal healthy children were measured using an enzyme-linked immunosorbent assay. RESULTS: EV71 patients with both encephalitis and pulmonary oedema were found to have much higher levels of blood interleukin-6 (IL-6) (947 +/- 1239 vs 4.9 +/- 3.1 pg/ml, p = 0.0003), tumour necrosis factor-alpha (TNF-alpha) (22.4 +/- 29.5 vs 5.3 +/- 1.0 pg/ml, p = 0.0035), interleukin Ibeta (IL-1beta) (48.4 +/- 85.2 vs 4.9 +/- 10.1 pg/ml, p = 0.01), white blood cell count (28.3 +/- 7.6 vs 15.5 +/- 6.8 10(9)/L, p > or = 0.0001) and blood glucose (501 +/- 186 vs 165 +/- 117 mg/dL, p = 0.0009) than patients with EV71 encephalitis alone. In fact, the cytokine levels in patients with encephalitis only or in those without complications were not significantly different from the levels found in normal children. The sensitivity, specificity, positive and negative predictive values of IL-6 > 70 pg/ml for EV71 encephalitis with pulmonary oedema were all 100%. CONCLUSION: Patients with EV71-related encephalitis combined with pulmonary oedema were found to have significantly elevated levels of proinflammatory cytokines and the best predictor for this complicated condition was found to be the level of serum IL-6.

Analysis of Variance↗
PubMed2001

DGT as an in situ tool for measuring radiocesium in natural waters.

The application of diffusive gradients in thin-films (DGT) samplers for the measurement of cesium radionuclides in solution, using an ammonium molybdophosphate (AMP) binding agent, was tested under both laboratory and field conditions. In the former they proved able to reproduce known 134Cs concentrations (60 Bq L(-1)) with a high degree of accuracy and precision over periods up to approximately 1 d, in freshwaters over a wide range of pH and temperature, and in saline water. In field trials in a freshwater lake receiving nuclear power station discharges, mean concentrations of 137CS (47-61 mBq L(-1)) were measured over periods from 5 d to 1 month. These agreed, within error, with mean concentrations determined from grab samples but rigorous field validation of long-term (month) deployments of DGT devices proved impossible using conventional sampling procedures, due to loss of 137Cs to container walls. Identified limitations of the DGT technique included probable AMP degradation over longer periods and calibration problems if large changes in temperature and concentration occurred together. Potential limitations due to biofilm growth were considered not to be significant. Despite the limitations, the technique appears to measure concentrations accurately for deployment times of 1 month or less. It has several advantages over traditional sampling methods for monitoring radionuclides in the solution/dissolved phase, including its simplicity, provision of time-averaged mean concentrations, and automatic in-situ concentration onto a medium with ideal counting geometry for gamma spectrometry.

Cesium Radioisotopes↗
PubMed2001

Normotopic and heterotopic cortical representations of mystacial vibrissae in rats with subcortical band heterotopia.

The tish rat is a neurological mutant exhibiting bilateral cortical heterotopia similar to those found in certain epileptic patients. Previous work has shown that thalamocortical fibers originating in the ventroposteromedial nucleus, which in normal animals segregate as 'barrel' representations for individual whiskers, terminate in both normotopic and heterotopic areas of the tish cortex (Schottler et al., 1998). Thalamocortical innervation terminates as barrels in layer IV and diffusely in layer VI of the normotopic area. Discrete patches of terminals are also observed in the underlying heterotopic area suggesting that representations of individual vibrissa may be present in the heterotopic somatosensory areas. The present study examines this issue by investigating the organization of the vibrissal somatosensory system in the tish cortex. Staining for cytochrome oxidase or Nissl substance reveals a normal complement of vibrissal barrels in the normotopic area of the tish cortex. Dense patches of cytochrome oxidase staining are also found in the underlying lateral portions of the heterotopic area (i.e. the same area that is innervated by the ventroposteromedial nucleus). Injections of retrograde tracers into vibrissal areas of either the normotopic or heterotopic area produce topographically organized labeling of neurons restricted to one or a small number of barreloids within the ventroposteromedial nucleus of the thalamus. Physical stimulation of a single whisker (D3 or E3) elicits enhanced uptake of [(14)C]2-deoxyglucose in restricted zones of both the normotopic and heterotopic areas, demonstrating that single whisker stimulation can increase functional activity in both normotopic and heterotopic neurons. These findings indicate that the barrels are intact in the normotopic area and are most consistent with the hypothesis that at least some of the individual vibrissae are 'dually' represented in normotopic and heterotopic positions in the primary somatosensory areas of the tish cortex.

Animals↗
PubMed2001

A 60-kilodalton immunodominant glycoprotein is essential for cell wall integrity and the maintenance of cell shape in Streptococcus mutans.

We have demonstrated previously by Western blotting that in naturally sensitized humans, the serum or salivary antibody response to Streptococcus mutans was directed predominantly to a protein antigen with a size of approximately 60-kDa. To identify this immunodominant antigen, specific serum antibodies were eluted from immunoblots and five positive clones with inserts ranging in length from 3 to 8 kb from identical chromosomal loci were obtained by screening a genomic expression library of Streptococcus mutans GS-5. Amino acid sequencing established the identity of this immunodominant antigen, a 60-kDa immunodominant glycoprotein (IDG-60), to be a cell wall-associated general stress protein GSP-781, which was originally predicted to have a molecular mass of approximately 45 kDa based on the derived nucleotide sequence. Discrepancy in the molecular mass was also observed in recombinant his-tagged IDG-60 (rIDG-60) expressed from Escherichia coli. Glycosylation, consisting of sialic acid, mannose galactose, and N-acetylgalactosamine, was detected by lectin binding to IDG-60 in cell wall extracts from S. mutans and rIDG-60 expressed in vivo or translated in vitro. Despite the presence of multiple Asn or Ser or Thr glycosylation sites, IDG-60 was resistant to the effect of N-glycosidase F and multiple O-glycosidase molecules but not to beta-galactosidase. Insertional inactivation of the gene encoding IDG-60, sagA, resulted in a retarded growth rate, destabilization of the cell wall, and pleiomorphic cell shape with multifold ingrowth of cell wall. In addition, distinct from the parental GS-5 strain, the isogenic mutant GS-51 was unable to survive the challenge of low pH and high osmotic pressure or high temperature. Expression of the wild-type gene in trans within GS-51 from plasmid pDL277 complemented the growth defect and restored normal cell shape. These results suggested that IDG-60 is essential for maintaining the integrity of the cell wall and the uniformity of cell shape, both of which are indispensable for bacteria survival under stress conditions.

Adult↗
PubMed2001

Glutamine protects mitochondrial structure and function in oxygen toxicity.

Glutamine is an important mitochondrial substrate implicated in the protection of cells from oxidant injury, but the mechanisms of its action are incompletely understood. Human pulmonary epithelial-like (A549) cells were exposed to 95% O2 for 4 days in the absence and presence of glutamine. Cell proliferation in normoxia was dependent on glutamine, and glutamine deprivation markedly accelerated cell death in hyperoxia. Glutamine significantly increased cellular ATP levels in normoxia and prevented the loss of ATP in hyperoxia seen in glutamine-deprived cells. Mitochondrial membrane potential as assessed by flow cytometry with chloromethyltetramethylrosamine was increased by glutamine in hyperoxia-exposed A549 cells, and a glutamine dose-dependent increase in mitochondrial membrane potential was detected. Glutamine-supplemented, hyperoxia-exposed cells had a higher O2 consumption rate and GSH content. Electron and fluorescence microscopy revealed that, in hyperoxia, glutamine protected cellular structures, especially mitochondria, from damage. In hyperoxia, activity of the tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase was partially protected by its indirect substrate, glutamine, indicating a mechanism of mitochondrial protection.

Adenosine Triphosphate↗
PubMed2001

Attenuation of bleomycin-induced pulmonary fibrosis by a catalytic antioxidant metalloporphyrin.

Oxidative stress plays an important role in the development of fibrotic responses in the lung. However, it is not clear whether inhibiting oxidative stress with antioxidants can attenuate fibrotic processes in the lung. The objective of these studies was to test whether the catalytic antioxidant porphyrin manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) could protect mice against bleomycin-induced lung fibrosis. A 10 mg/kg intraperitoneal dose of MnTBAP was established as safe and had a serum and lung half-life of 9.5 h in mice. Based on this data, four groups of mice were given one dose of bleomycin (3.2 U/kg, intratracheal) or saline and MnTBAP (5 mg/kg, intraperitoneal) or saline twice daily for 14 d. Lung fibrosis was assessed by measuring (1) lung hydroxyproline content as an index of collagen accumulation, (2) airway dysfunction by whole body plethysmography, and (3) histopathology. Bleomycin produced a 20% loss in body weight that was only 10% in the bleomycin/MnTBAP group. Bleomycin produced a twofold increase in hydroxyproline content that was decreased 23% by MnTBAP. Bleomycin produced a twofold increase in airway dysfunction that was also attenuated 30% by MnTBAP. Histopathologic analysis of the lungs of mice treated with bleomycin demonstrated a severe fibrotic response that was attenuated 28% by MnTBAP. Future studies on the oxidant mechanisms that MnTBAP is affecting in this bleomycin model of lung fibrosis may shed light on potential new therapeutic approaches for treating interstitial lung diseases.

Animals↗
PubMed2001

Duration of enterovirus shedding in stool.

Excretion of enterovirus (EV) may persist for months after an EV infection; the exact duration of excretion, however, is not yet known. Twelve children who were infected with EV between September 1998 and June 1999 were enrolled into this study. The patients included 4 boys and 8 girls, aged from 1 month to 5 years. Six patients were asked to join this virus isolation program, and the other 6 were followed-up regularly. Only 2 of the patients were infected with EV 71. To delineate the duration of EV shedding in each case, throat swabs for virus isolation were performed every 1 or 2 weeks for at least 1 month, and stools were analyzed for at least 2 months following the same schedule. After the infection, EV was identifiable in the throat in 4 patients for 1 to 2 weeks. Excretion of EV through stool was evidenced for up to 7 weeks in 6 patients, 8 weeks in 3, and 11 weeks in 1. In the 2 patients who failed to show up for follow-up visits from the 7th week, excretion of EV through stool was recorded for at least 7 weeks. Different serotypes of EV could be isolated from the same patient who was not experiencing febrile illness in 2 instances in a series of virus cultures. Coexistence of vaccine poliovirus and non-polio EV, both isolated from stool, was evidenced in 2 patients. Results from this study suggest that EV may not be identified from the throat 2 weeks after the infection, but its excretion through stool can persist for up to 11 weeks. This study also demonstrated that subclinical EV coinfection could occur, and that live vaccine poliovirus did not interfere with the invasion of other non-polio EV.

Child, Preschool↗
PubMed2001

Characteristics of group A streptococcal bacteremia with comparison between children and adults.

This retrospective study aimed to compare the characteristics of group A streptococcal bacteremia in children and adults. A total of 76 (12 children and 64 adults) patients with group A streptococcal bacteremia treated from October 1995 through September 2000 at the Linko Chang Gung Memorial Hospital were included. The mean age was 47.6 years (range, 12 days-90 years). Forty-four (57.9%) patients had predisposing medical conditions. Malignant cancer (23.7%) and diabetes (22.4%) were the 2 most common conditions, which occurred only in adults. Two (16.7%) children had chickenpox associated with secondary group A streptococcal bacteremia. Skin and soft tissue infection (60.5%) was the most common clinical manifestation. The mortality rate related to group A streptococcal bacteremia was 25%. Twelve patients met the criteria of streptococcal toxic shock syndrome and 6 (50%) were children (p<0.05). Despite immediate and aggressive treatment, mortality due to streptococcal toxic shock syndrome was 66.7%. The incidence of streptococcal toxic shock syndrome was much higher in children (50%) than in adults (9.4%). Early diagnosis of invasive group A streptococcal infections and streptococcal toxic shock syndrome requires awareness of the presentations and a high level of suspicion. For fulminant group A streptococcal infection, a combination of a beta-lactam antibiotic plus clindamycin and/or adjuvant therapy with intravenous immunoglobulin is recommended.

Adolescent↗
PubMed2001

Deep neck infections in children.

From December 1989 through 1998, a total of 68 children with deep neck infection were enrolled into this study. The mean age was 5.9 years (range, 1 month-15.8 years). Infections in the retropharyngeal space (36.7%) were most common, followed by parapharyngeal space (30.8%), peritonsillar space (20.6%), and submandibular space (11.9%). Fever, neck pain, and swelling were the most frequent symptoms. The most common pathogens were viridans streptococci (41%, 16/39) and Staphylococcus aureus (26%, 10/39). Other isolates included Prevotella spp., Veillonella spp., Klebsiella pneumoniae, Escherichia coli, Morganella spp., and Enterobacter spp. Mixed infection was found in 46% (18/39) of patients. The mean duration of hospitalization was 12.4 days (range, 2-45 days). Complete resolution was achieved in 61 (89.7%) children. Complications occurred in 7 patients, including recurrence, mediastinal spread, bacteremia, and suppurative thyroiditis; the patient with mediastinal spread plus bacteremia died. Five patients had congenital cyst and 4 of them had complications or recurrence/relapse. In conclusion, infections in the retropharyngeal space and polymicrobial infections were most common in deep neck infection of Taiwan children.

Anti-Bacterial Agents↗
PubMed2000

Functional complementation by wheat eIF2alpha in the yeast GCN2-mediated pathway.

Translational control by specific eIF2alpha phosphorylation on serine 51 has been characterized in all eukaryotes with the significant exception of plants. In order to evaluate the capability of plant eIF2alpha to functionally control translation, the wild type (51S) and a nonphosphorylatable mutant (51A) of wheat eIF2alpha were expressed in a yeast genetic system. Expression of either wheat protein did not handicap growth under conditions that repress the eIF2alpha phosphorylation pathway. However, under conditions that induce specific eIF2alpha phosphorylation only strains expressing wheat 51S were able to grow between 2 and 4 days. Growth was dependent upon activity of yeast eIF2alpha kinase GCN2 and resulted in the increased translation of GCN4. The association between plant eIF2alpha and yeast eIF2B is supported by their specific coimmunoprecipitation from transgenic yeast cells. These data support the similarity among eukaryotic translational initiation processes and strengthen the concept that plants may contain an eIF2alpha phosphorylation pathway.

DNA-Binding Proteins↗
PubMed2000

Expression of capsid [correction of caspid] protein VP1 for use as antigen for the diagnosis of enterovirus 71 infection.

To produce enterovirus 71 antigen for diagnostic purposes, the gene encoding the entire capsid protein VP1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR), cloned and expressed in Escherichia coli as a poly-histidine fusion protein. Western blotting experiments with sera from patients with enterovirus 71 infection indicated that immunoglobulin G (IgG) and IgM antibodies bound to a single polypeptide VP1. According to these results, IgM anti-VP1 appeared in sera of patients with a symptomatic enterovirus 71 acute infection, whereas IgG anti-VP1 was present in sera of past infection. This finding suggests that detecting IgG and IgM immune responses against linear epitopes of recombinant VP1 is an effective means of determining the different phases of enterovirus 71 infection. In addition, sera containing coxsackie virus 16 (CA16) antibodies did not cross-react with the recombinant VP1 of enterovirus 71, despite the homology between VP1 proteins of both viruses. Comparison with reference PCR and neutralization assays showed these antibody tests to be appropriate for the serodiagnosis of enterovirus 71 infection.

Antibodies, Viral↗
PubMed2000

Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998.

A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. Enterovirus 71 was implicated as the cause of this outbreak. In order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of VP1 that is important for serotypic specificity, and the 5'-non-coding region (5'-NCR) that is important for replication efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5'-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97-100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide homology was 90-91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.

5' Untranslated Regions↗
PubMed2000

Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in Taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies.

We report a fatal case of enterovirus type 71 (EV 71) infection in an 8-year-old girl during a summer outbreak of hand, foot, and mouth disease in 1998 in Taiwan. The clinical course was rapidly progressive, with manifestations of hand, foot, and mouth disease, aseptic meningitis, encephalomyelitis, and pulmonary edema. The patient died 24 hours after admission. Postmortem study revealed extensive inflammation in the meninges and central nervous system and marked pulmonary edema with focal hemorrhage. Brain stem and spinal cord were most severely involved. The inflammatory infiltrates consisted largely of neutrophils involving primarily the gray matter with perivascular lymphocytic cuffing, and neuronophagia. The lungs and heart showed no evidence of inflammation. EV 71 was isolated from the fresh brain tissues and identified by immunofluorescence method with type-specific EV 71 monoclonal antibody. It was also confirmed by neutralization test and reverse-transcriptase polymerase chain reaction with sequence analysis. The present case was the first example in which EV 71 was demonstrated to be the causative agent of fatal encephalomyelitis during its epidemic in Taiwan.

Antigens, Viral↗
PubMed2000

Factors associated with intestinal perforation in children's non-typhi Salmonella toxic megacolon.

BACKGROUND: To evaluate the risk factors for intestinal perforation in children with toxic megacolon caused by non-typhi Salmonella infection. METHODS: During an 11-year period we reviewed the records of children treated for non-typhi Salmonella infection. All of the subjects had positive stool culture for non-typhi Salmonella and were treated with intravenous ceftriaxone during hospitalization. Clinical data reviewed included demographic features, clinical manifestations, laboratory findings, radiologic findings, microbiology, therapeutic effect of hydration and rectal tube placement and the operative findings. Patients with toxic megacolon were defined as those having toxic appearance, diarrhea, high fever (>39 degrees C) and marked colon dilatation with maximal diameter > 1.5 times the width of the vertebra body of the first lumbar spine (L1-VB). To define the risk factors for patients with toxic megacolon complicated by intestinal perforation, patients were divided into two groups for analysis: P group, those complicated with intestinal perforation; and NP group, those without intestinal perforation. Differences in age, sex, severity of diarrhea, duration of fever, hemogram and its differential, culture, stool analysis, serum C-reactive protein (CRP), electrolytes, maximal colon diameter, medical therapy and timing of rectal tube insertion between the two groups were analyzed. Statistical analyses were conducted with chi square tests and multiple logistic regression. RESULTS: A total of 75 patients (P group, 27 patients; NP group, 48 patients) ages 4 months to 6 years were evaluated. With chi square analysis 7 variables were found to be significantly associated with intestinal perforation: age >1 year; fever >5 days; ratio of immature to total neutrophils >20%; serum CRP >200 mg/l; colon diameter >2.5 times the width of L1-VB; inadequate early hydration; and delay in rectal tube insertion. With multivariate analysis age >1 year, serum CRP >200 mg/l and colon diameter >2.5 times of width of L1-VB, inadequate early hydration and delay in rectal tube insertion were the most significant factors associated with intestinal perforation. CONCLUSION: Identification of patients with toxic megacolon associated with non-typhi Salmonella infection at risk for further intestinal perforation is possible. Early effective fluid resuscitation and rectal tube insertion may be helpful to prevent the occurrence of intestinal perforation.

Child↗
PubMed1999

Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease.

BACKGROUND: In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. METHODS: We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. FINDINGS: Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 [95% CI 2.6-60.1], p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p=0.003). INTERPRETATION: EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.

Adolescent↗
PubMed1999

A mechanism of paraquat toxicity involving nitric oxide synthase.

Paraquat (PQ) is a well described pneumotoxicant that produces toxicity by redox cycling with cellular diaphorases, thereby elevating intracellular levels of superoxide (O-(2)). NO synthase (NOS) has been shown to participate in PQ-induced lung injury. Current theory holds that NO reacts with O-(2) generated by PQ to produce the toxin peroxynitrite. We asked whether NOS might alternatively function as a PQ diaphorase and reexamined the question of whether NO/O-(2) reactions were toxic or protective. Here, we show that: (i) neuronal NOS has PQ diaphorase activity that inversely correlates with NO formation; (ii) PQ-induced endothelial cell toxicity is attenuated by inhibitors of NOS that prevent NADPH oxidation, but is not attenuated by those that do not; (iii) PQ inhibits endothelium-derived, but not NO-induced, relaxations of aortic rings; and (iv) PQ-induced cytotoxicity is potentiated in cytokine-activated macrophages in a manner that correlates with its ability to block NO formation. These data indicate that NOS is a PQ diaphorase and that toxicity of such redox-active compounds involves a loss of NO-related activity.

Animals↗