Search PubMed⌕ Search

Biomedical subjects

L Y Chang

Publications and source records attributed to L Y Chang.

At least 55 records · Page 3Linked to original sources

Clinical experience of postage stamp autograft with porcine skin onlay dressing in extensive burns.

Fifteen patients with extensive burns (deep second-degree burn > 50%, or third-degree burn > 30% of total body surface area) were treated with postage stamp autograft and meshed porcine skin onlay dressing from 1992 to 1996. All patients received the procedure within 10 days of sustaining the burn, with an average of 6.3 days. The areas chosen for postage stamp autograft were the anterior chest, abdomen, back, buttocks and the proximal part of the extremities. The scalp was the donor site of choice when available. The harvested skin was cut into 0.5-1.0 cm postage-stamp-like squares and applied to the recipient sites separated by a distance of 0.5-2.0 cm. The expansion ratio was from 1:4 to 1:9. Meshed porcine skin was then used for onlay dressing. The average graft area was 26% of the total body surface area. The success rate of the skin grafts was nearly 100% in 14 patients. One patient had a 40% loss due to contamination from adjacent wounds. In conclusion, the postage stamp autograft with porcine skin overlay is an effective way to treat extensive burn wounds in the early stages.

Adolescent↗

Limb-threatening necrotizing alternariosis salvaged by adjunctive hyperbaric oxygen therapy.

We describe, to our knowledge, the first case of limb-threatening necrotizing alternariosis whose limbs were successfully salvaged by adjunctive hyperbaric oxygen therapy (HBO2). This 58-y-old patient was immunocompromised with both diabetes and Cushing's syndrome. She suffered from necrotizing soft tissue infection of both legs caused by Alternaria. It was impossible to halt the progression of the invasive infection with standard anti-fungal treatment and aggressive surgical debridement. After the use of HBO2, the wound was stabilized and eventually healed. Adjunctive HBO2 in this case has demonstrated its role in the treatment of complicating necrotizing soft tissue infection caused by invasive fungal infection. The possible mechanisms may be the potentiation of immune responses and the enhancement of fibroblast proliferation.

Alternaria↗

Anti-intercellular adhesion molecule-1 antibody and intercellular adhesion molecule-1 gene deficiency do not prevent pulmonary neutrophil recruitment in polymicrobial sepsis.

The intercellular adhesion molecule (ICAM)-1 is expressed constitutively in normal lungs and increased in pulmonary inflammation. Whether increased ICAM-1 expression in the lung contributes to neutrophil sequestration during lung inflammation in sepsis is unclear. We tested this hypothesis in mice after systemic sepsis from cecal ligation and puncture (CLP). ICAM-1 expression in mouse CLP lung tissue was found to increase with time. The time course of lung ICAM-1 up-regulation correlated with increases in lung myeloperoxidase (MPO) activity and neutrophil sequestration by light microscopy. The monoclonal IgG2b rat anti-mouse antibody, an anti-ICAM-1 antibody (YN1/1.7), administered intravenously at doses of 3, 10, or 30 mg/kg, however, did not decrease the lung MPO levels compared with nonimmune rat IgG. In support of these findings, lung MPO content in ICAM-1-deficient mice that underwent CLP was significantly higher than similarly treated ICAM-1-sufficient mice. Our results suggest that neutrophil sequestration in the mouse lung after CLP is not dependent on ICAM-1.

Animals↗

Detection of hepatitis B surface gene mutation in carrier children with or without immunoprophylaxis at birth.

To investigate the clinical significance of mutation in hepatitis B virus (HBV) surface gene, DNA sequence analysis of the "a" determinant was performed on sera from 27 carrier children with immunoprophylaxis, their mothers, and 21 carriers without vaccination. A precore mutant (G to A) at nucleotide 1896 was detected in sera from 11 carriers without vaccination. Mutations in the "a" determinant were detected in 6 (22%) of the vaccinated children. Four HBV strains showed a Gly-to-Arg mutation at the 145th codon of the surface gene. Amino acid substitutions at amino acid 133 and 144 were noted in the other 2 children. Only 1 mother had the same predominant strain of mutant virus as her child. These observations indicate that immune pressure exerted by immunoprophylaxis at birth may select for a mutant virus.

Adolescent↗

99Tcm-MDP scintigraphy in high-voltage electrical burn patients.

In high-voltage electrical burn injuries (> 1000 V), it is difficult to identify the site and extent of non-viable deep tissue damage for debridement to avoid further tissue injury from wound infection and the risk of sepsis. This prospective study was designed to evaluate the usefulness of 99Tcm-methylene di-phosphonate (99Tcm-MDP) scintigraphy in detecting the extent of tissue injury and determining the level of amputation required for electrical burn patients. Over a 5 year period, 33 high-voltage electrical burn patients were studied. Blood flow and blood pool studies revealed absent perfusion in 37 limbs, all of which eventually were amputated. In addition to a routine three-phase bone scan, images were obtained at 30-60 min (early images) to evaluate whether soft tissue injury could be detected better at that time. For comparison of the detection rate from the early images and bone (delayed) images, 164 corresponding spot views of both images were reviewed. Eighty-three and 125 tissue necrotic lesions were demonstrated by the early images and bone images respectively. All of the 83 lesions found by the early images were more clearly identified by the bone images. All but one of the 125 lesions underwent surgical debridement or amputation. We concluded that the blood flow and blood pool images correlated well with the level of amputation required. The site and extent of tissue necrotic lesions can be clearly identified on 99Tcm-MDP bone scans. Because the early images were less sensitive in detecting tissue necrosis, we suggest that early imaging is not necessary.

Adolescent↗

Hepatitis B vaccination in preterm infants.

AIM: To investigate the immunogenicity and safety of existing recommendations for hepatitis B vaccination in preterm infants. METHODS: Recombinant hepatitis B vaccine (H-B-VAX II, 5 micrograms per dose) was given to 85 preterm infants divided into two groups, using two different schedules. Forty four group A infants with birthweights of < 2000 g received three doses at 1, 2, and 7 months of age. Forty one group B infants with birthweights of > or = 2000 g received three doses at 0, 1, and 6 months of age. RESULTS: After vaccination, 42 infants from group A (95%) and 37 infants from group B (90%) developed protective levels of antibody. The final seropositive rate and the geometric mean concentration of hepatitis B surface antibody between the two groups were not significantly different. The immune response of preterm infants to hepatitis B vaccines was similar to that of term infants in a previous study. CONCLUSIONS: Preterm infants can be given hepatitis B vaccines using one of the above two different schedules, at a cutoff birthweight of 2000 g.

Antibodies, Viral↗

Extracellular superoxide dismutase is upregulated with inducible nitric oxide synthase after NF-kappa B activation.

Inflammatory cytokines have been shown to upregulate secretion of the antioxidant enzyme extracellular superoxide dismutase (EC-SOD) in dermal fibroblasts and, in other cells, to stimulate production of nitric oxide (.NO). Because superoxide rapidly scavenges .NO, forming the injurious peroxynitrite anion (OONO-), we hypothesize that stimulated cells upregulate EC-SOD expression concurrently with .NO release. To test for coregulation of EC-SOD and .NO within the same cell, the timing of inducible nitric oxide synthase (iNOS) and EC-SOD transcription was measured after exposure of a rate type II pneumocyte analog, the L2 cell line, to a combination of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Upregulation of iNOS and EC-SOD transcription occurred after 6 h of exposure, and transcription of both genes was linked by activation of the transcription factor nuclear factor-kappa B. Both EC-SOD and iNOS were elevated in rat lung homogenates 24 h after intratracheal instillation with IFN-gamma and TNF-alpha. The observation that EC-SOD and iNOS are temporally coregulated after cytokine exposure suggests the possibility of a critical mechanism by which cells might protect .NO and avoid the formation of OONO- during inflammation.

Animals↗

Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II. Morphometric analysis.

Hyperoxia damages lung parenchyma via increased cellular production of reactive oxygen species that exceeds antioxidant defenses. We hypothesized that aerosolized human recombinant manganese superoxide dismutase (rhMnSOD) would augment extracellular antioxidant defenses and attenuate epithelial injury in the lung during hyperoxia in primates. Twenty-four adult male baboons were anesthetized and mechanically ventilated with 100% oxygen for 96 h. The baboons were divided equally into four groups. Oxygen alone and oxygen plus rhMnSOD given at 3 mg . kg-1 . day-1 were compared to assess efficacy of the drug. Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg . kg-1 . day-1 to study dose effects and toxicity. Quantitative morphometry showed protection of alveolar epithelium from hyperoxia by 3 mg . kg-1 . day-1 rhMnSOD (P < 0.05). In addition, interstitial fibroblast volumes were increased in the treatment group (P = 0.06). This effect appeared greater at the two higher doses of the rhMnSOD. The aerosolized drug was localized to the surface of airways and air spaces and macrophages by immunolabeling studies, suggesting efficacy via physicochemical properties that localize it to cell surfaces or by effects on alveolar macrophage function.

Animals↗

Extracellular superoxide dismutase mRNA expressions in the human lung by in situ hybridization.

The extracellular form of superoxide dismutase (EC-SOD), SOD3, is contained in the human lung in relatively high amounts when compared to other organs. It has not been previously shown whether or not EC-SOD is synthesized and secreted by specific lung cells. We examined the expression of EC-SOD mRNA in human lung cells by in situ hybridization using a digoxigenin-labeled EC-SOD cRNA probe. Strong signals of EC-SOD synthesis were found in the epithelium of all airways. Secretory and basal cells, but not ciliated cells, were labeled for EC-SOD mRNA. Expression of EC-SOD mRNA was found in endothelial cells lining both arteries and veins. Many cells in the alveolar septum exhibited strong expression of EC-SOD mRNA. In addition, epithelial cells lining the outer wall of intrapulmonary airways and vessels were heavily labeled for EC-SOD mRNA. The lung parenchymal epithelial cells containing EC-SOD mRNA were identified as alveolar type II cells by colocalization with surfactant protein-A. Human alveolar macrophages were found to contain a substantial amount of EC-SOD mRNA expression. Alveolar type I epithelial cells and capillary endothelial cells did not display detectable signals of EC-SOD mRNA. Smooth muscle cells in muscular arteries were not labeled by the EC-SOD mRNA probe. These results show that airway epithelial cells and alveolar type II cells are the major cell types that synthesize fibroblasts EC-SOD in the human lung. EC-SOD has been shown by immunocytochemistry to be associated with the extracellular matrix around airway epithelium and in the walls of intrapulmonary arterioles. The site of EC-SOD localization, therefore, is closely related to the site of its synthesis.

Adult↗

Seroepidemiological study of measles after the 1992 nationwide MMR revaccination program in Taiwan.

The incidence of measles declined rapidly in Taiwan after the introduction of the measles vaccine into the routine immunization schedule in 1978. However, an epidemic still occurred every 3-5 years until recently. A nationwide measles-mumps-rubella (MMR) revaccination program for school and preschool children has been in place since 1992 to control the indigenous transmission of measles. In order to understand the current immune status after this recent nationwide revaccination program, we determined the presence of measles IgG antibodies by enzyme-linked immunosorbent assay (ELISA) in 1,281 blood samples from healthy persons aged from 2 months to above 30 years collected between 1993 and 1995, and also in another batch of 90 sera samples from children aged 2 years collected before 1992. The results showed that 1) the measles antibody seropositive rate (36.4%) was lowest in children aged 5-7 months and rose to an unexpectedly high level of 85.8% at the age of 12-14 months, 2) the seropositive rate rose further to between 85.9% and 95.1% after 2 years of age and remained high in adults and pregnant women, and 3) the seropositive rate of the 2-year-old children collected before 1992 was 61.4%, which was significantly lower than the rate of the same age group collected after the nationwide MMR revaccination program. We conclude that the national revaccination program has promoted effectively measles immunity in Taiwan. This immunity explains the rarity of reported measles cases since the last epidemic in 1989. This revaccination program should continue and be extended to all preschool children and young adults so that indigenous measles can be eliminated by the year 2000.

Adult↗

Safety and immunogenicity of a conjugated Haemophilus influenzae type B polysaccharide-Neisseria meningitidis outer membrane protein vaccine.

This study was performed to determine the immunogenicity and safety of a conjugate Haemophilus influenzae type b (Hib) vaccine (PedvaxHIB:Merck Sharp & Dohme Inc, West Point, PA, USA) in Taiwanese children. There were two groups in this study. Group A included 56 infants at 2 months of age, who received an initial dose of Hib conjugate vaccine at age 2 months and 4 months. Another booster dose was given between 12 and 15 months of age. Group B included 58 children, aged 11 to 14 months, who were vaccinated at the time of enrollment and 2 months after the first vaccination. The results showed that this Hib conjugate vaccine was highly immunogenic with 100% and 86% of vaccinees in group A developing anti-Hib polyribosylribitol phosphate (PRP) antibody titers above 0.15 microgram/mL and 1 microgram/mL, respectively, after two vaccinations. A slightly better response rate was observed in group B, with 100% and 97% of vaccinees developing antibody titers above 0.15 microgram/mL and 1 microgram/ml, respectively, after two vaccinations. A significant booster effect was seen in group A; the proportion of subjects with antibody titers above 1 microgram/mL increased from 38% to 95%, and the geometric mean titer increased from 0.68 microgram/mL to 11.92 micrograms/mL. Adverse reactions were uncommon. Mild reactions consisted of low-grade fever and local discomfort. We conclude that the Hib conjugate vaccine is highly immunogenic and safe when given to Taiwanese children as young as 2 months of age.

Antibodies, Bacterial↗

Laser desorption mass spectrometry for point mutation detection.

A point mutation can be associated with the pathogenesis of inherited or acquired diseases. Laser desorption mass spectrometry coupled with allele specific polymerase chain reaction (PCR) was first used for point mutation detection. G551D is one of several mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene present in 1-3% of the mutant CFTR alleles in most European populations. In this work, two different approaches were pursued to detect G551D point mutation in the cystic fibrosis gene. The strategy is to amplify the desired region of DNA template by PCR using two primers that overlap one base at the site of the point mutation and which vary in size. If the two primers based on the normal sequence match the target DNA sequence, a normal PCR product will be produced. However, if the alternately sized primers that match the mutant sequence recognize the target DNA, an abnormal PCR product will be produced. Thus, the mass spectrometer can be used to identify patients that are homozygous normal, heterozygous for a mutation or homozygous abnormal at a mutation site. Another approach to identify similar mutations is the use of sequence specific restriction enzymes which respond to changes in the DNA sequence. Mass spectrometry is used to detect the length of the restriction fragments generated by digestion of a PCR generated target fragment.

Cell Line↗

Heparin induces dimerization and confers proliferative activity onto the hepatocyte growth factor antagonists NK1 and NK2.

Hepatocyte growth factor (HGF) is a potent epithelial mitogen whose actions are mediated through its receptor, the proto-oncogene c-Met. Two truncated variants of HGF known as NK1 and NK2 have been reported to be competitive inhibitors of HGF binding to c-Met, and to function as HGF antagonists (Lokker, N.A., and P.J. Godowski. 1993. J. Biol. Chem. 268: 17145-17150; Chan, A.M., J.S. Rubin, D.P. Bottaro, D.W. Hirschfield, M. Chedid, and S.A. Aaronson. 1991. Science (Wash. DC). 254:1382-1387). We show here, however, that NK1 acts as a partial agonist in mink lung cells. Interestingly, NK1, which is an HGF antagonist in hepatocytes in normal conditions, was converted to a partial agonist by adding heparin to the culture medium. The interaction of NK1 and heparin was further studied in BaF3 cells, which express little or no cell surface heparan sulfate proteoglycans. In BaF3 cells transfected with a plasmid encoding human c-Met, heparin and NK1 synergized to stimulate DNA synthesis and cell proliferation. There was no effect of heparin on the IL-3 sensitivity of BaF3-hMet cells, and no effect of NK1 plus heparin in control BaF3 cells, indicating that the response was specific and mediated through c-Met. The naturally occurring HGF splice variant NK2 also stimulated DNA synthesis in mink lung cells and exerted a heparin-dependent effect on BaF3-hMet cells, but not on BaF3-neo cells. The activating effect of heparin was mimicked by a variety of sulfated glycosaminoglycans. Mechanistic studies revealed that heparin increased the binding of NK1 to BaF3-hMet cells, stabilized NK1, and induced dimerization of NK1. Based on these studies, we propose that the normal agonist activity of NK1 and NK2 in mink lung cells is due to an activating interaction with an endogenous glycosaminoglycan. Consistent with that model, a large portion of the NK1 binding to mink lung cells could be blocked by heparin. Moreover, a preparation of glycosaminoglycans from the surface of mink lung cells induced dimerization of NK1. These data show that the activity of NK1 and NK2 can be modulated by heparin and other related glycosaminoglycans to induce proliferation in cells expressing c-Met.

Animals↗

Lung epithelial cell-released nitric oxide protects against PMN-mediated cell injury.

A calcium-independent type II nitric oxide (NO) synthase has been localized in lung epithelial cells; however, the function of NO. released by epithelial cells is unclear. We hypothesized that epithelial-derived NO may affect the interactions between polymorphonuclear neutrophils (PMN) and the alveolar epithelium and studied PMN adhesion and cytotoxicity to lung epithelial cells. A dose- and time-dependent production of NO. by L2 cells can be induced by a mixture of inflammatory mediators (cytomix) containing lipopolysaccharide, tumor necrosis factor-alpha, and interferon-gamma. Increased NO. production by L2 cells was associated with decreased 51Cr release by the epithelial cells after they were incubated with activated PMN. Addition of NG-monomethyl-L-arginine or oxyhemoglobin reversed the protective effects of cytomix, suggesting that increased NO. production by L2 cells was responsible for the decreased 51Cr release. However, PMN adhesion and intercellular adhesion molecule-1, a major adhesion molecule involved in PMN adhesion to epithelium, were increased by cytomix. We conclude that NO. released by lung epithelial cells was involved in protecting epithelial cells from PMN-mediated cytotoxicity. NO.-mediated protection of lung epithelial cells occurred in spite of PMN adhesion being increased, suggesting that reduced adhesion is not required for NO.-mediated inhibition of PMN cytotoxicity.

Animals↗

Contrasting response of lung parenchymal cells to instilled TNF alpha and IFN gamma: the inducibility of specific cell ICAM-1 in vivo.

Induction of intercellular adhesion molecule-1 (ICAM-1) by proinflammatory cytokines during inflammation plays an important role in regulating polymorphonuclear neutrophil (PMN) migration and localization. In this report, we examined the effects of tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) on specific lung cell expression of ICAM-1 in vivo and the accompanying morphological changes. Balb-c mice were treated with phosphate-buffered saline (PBS) alone or with PBS containing 5 micrograms TNF alpha or IFN gamma through intranasal instillation. Twenty-four hours after treatment, their lungs were processed for immunoblot analysis and electron microscope immunocytochemistry. In the normal lung, the ICAM-1 level is high on type I alveolar epithelial cells, medium on arterial and venous endothelial cells, low on type II epithelial cells and capillary endothelium, and not detectable on bronchial epithelium. Topical treatment of the lung with either TNF alpha or IFN gamma induced a 50-60% increase in total lung and alveolar ICAM-1. A dramatic increase of alveolar type II cell surface ICAM-1 was observed (> 20-fold). Both cytokines caused 2-3-fold higher ICAM-1 expression on capillary endothelial cells and a 40% increase of ICAM-1 on alveolar type I cells that was not uniform. However, due to the large total surface area of type I epithelium, type I cells contribute 70-86% of total alveolar septal ICAM-1 and > 90% of alveolar surface ICAM-1 in either treated or normal mouse lungs. Increased ICAM-1 expression was also observed on nonparenchymal endothelial and epithelial cells. Margination and sequestration of PMN in cytokine-treated lungs were observed by histologic examination, measurements of total lung myloperoxidase activity, and number of neutrophils recovered in bronchoalveolar lavage fluid. These results showed that TNF alpha and IFN gamma induce ICAM-1 expression and infiltration of neutrophils in the lung. The response of specific lung cells in terms of induction of ICAM-1 in response to cytokine stimulation varied significantly, particularly between type I and type II epithelial cells.

Administration, Intranasal↗

Influenza B virus infection associated with shock in a two-month-old infant.

Influenza B virus usually causes a mild and self-limiting illness. A 2-month-old infant presented with acute symptoms suggestive of septic shock but recovered after vigorous resuscitation 1 day later. Influenza B was isolated from a throat swab taken from the infant. Bacterial cultures of blood, urine and spinal fluid had no growth. This case illustrates that the clinical signs and symptoms of influenza in infants may be indistinguishable from bacterial sepsis.

Humans↗

Copper, zinc superoxide dismutase in Escherichia coli: periplasmic localization.

Cu,ZnSOD purified from Escherichia coli has been used to raise antibodies in rabbits. The resultant antiserum was found to recognize a single band on Western blots of SDS-polyacrylamide gel electropherograms, and that single band coincided with the position of the Cu,ZnSOD. Ultrathin sections of fixed E. coli were treated with the antibody followed by protein A bearing 10-nm gold particles. Electron microscopy revealed that Cu,ZnSOD was largely localized in the periplasm in polar bays.

Animals↗