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Biomedical subjects

L Y Chang

Publications and source records attributed to L Y Chang.

At least 73 records · Page 4Linked to original sources
PubMed1995

Bronchiolarized metaplasia and interstitial fibrosis in rat lungs chronically exposed to high ambient levels of ozone.

The cellular and tissue changes in the lungs of rats were studied using electron microscopy following 20 months exposure to a range of ozone levels from 0.12 to 1.0 ppm. Male and female Fischer 344 rats were exposed and morphometric methods were used to determine the volume, surface area, and cellular changes observed in bronchiole-alveolar duct regions following chronic ozone exposure. No major gender-related effects were observed in response to chronic inhalation of ozone nor were significant effects of ozone exposure found in either terminal bronchioles or the proximal alveolar regions in animals chronically exposed to 0.12 ppm ozone. The proximal alveolar regions of animals exposed for 20 months to 0.5 and 1.0 ppm ozone were significantly altered with exposure. The high-dose, long-term exposure to ozone resulted in a pronounced increase in volume of both the interstitium and epithelium in the proximal alveolar regions. The thickening of the epithelium was due to a change in tissue type from the normal squamous epithelium to a cuboidal epithelium similar, but not identical, to that found in terminal bronchioles. This bronchiolar epithelial metaplasia of proximal alveolar ducts, which was dose related, was composed of differentiated ciliated and Clara cells similar to those found in terminal bronchioles. In addition, unique cells which contained morphologic features of many different cell types were observed. These cells, which may represent stem cells or differentiated but transformed cells, were found associated with the bronchiolar metaplasia of alveolar ducts. In conjunction with the epithelial changes, cellular and matrix components in the interstitium were increased with chronic exposure to 0.5 and 1.0 ppm ozone. All matrix components were increased including collagen, elastin, and basement membrane, as well as other acellular spaces which did not contain identifiable structures. The total volume of interstitial fibroblasts was also increased in the high-dose exposure group. Alveolar macrophages were increased only in the 1.0 ppm exposed animals. The cell and tissue changes in the terminal bronchioles were less pronounced indicating a relative resistance of this tissue to ozone and mainly consisted of a change in cell type from ciliated to Clara cells in the 1.0 ppm exposed animals. The relative resistance of bronchiolar tissue to high concentration ozone exposure and the extensive bronchiolar epithelial metaplasia may be an adaptive mechanism following chronic ozone exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Catalase and glutathione reductase protection of human alveolar macrophages during oxidant exposure in vitro.

Because alveolar macrophages generate and release reactive oxygen metabolites but also contain antioxidative enzymes, they have the potential of either damaging or protecting tissues. We investigated the relative role of the hydrogen peroxide (H2O2)-scavenging antioxidative enzymes in H2O2 disposal and cell protection using freshly isolated (5 h ex vivo) and overnight (24 h ex vivo) cultured human alveolar macrophages. Cell protection was assessed on the basis of maintenance of cellular high-energy phosphates, leakage of intact nucleotides into the extracellular medium, and appearance of the nucleotide catabolic products xanthine, hypoxanthine, and uric acid. To investigate the relative importance of catalase and the glutathione redox cycle, the experiments were conducted in cells pretreated with amino-triazole (ATZ) to inactivate catalase or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione reductase. Catalase, glutathione peroxidase, and glutathione reductase activities did not change significantly during overnight culture of the cells. Both freshly isolated and cultured cells consumed exogenous H2O2 mainly by the catalase-dependent pathway. When the cells were exposed to H2O2 (100 microM), catalase and the glutathione redox cycle equally participated in maintaining cellular high-energy nucleotides. However, when cultured cells were exposed to formylated peptide (FMLP) (10(-7) M), the glutathione redox cycle was responsible for the maintenance of high-energy nucleotides. Furthermore, in both exposures, the glutathione redox cycle was more important in maintaining cell membrane integrity and preventing nucleotide leakage from the cells. Immunocytochemical labeling showed that catalase was primarily localized in the peroxisomal compartment of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1995

Umbilical venous line related pericardial effusion in a premature neonate: report of a case.

Cardiac tamponade occurs very rarely, but is life-threatening in the newborn. This paper reports a premature newborn who developed profound shock 25 hours after undergoing umbilical venous catheterization. Echocardiography taken later, showed marked pericardial effusion. An umbilical venous catheter was located in the left atrium. Immediate pericardiocentesis was performed, 11 mL of a clear straw-colored fluid was removed and the umbilical venous catheter was withdrawn into the inferior vena cava. The heart rate and blood pressure recovered immediately. Analysis of the pericardial fluid showed a high glucose level of 2,451 mg/dL. There was no pericardial effusion reaccumulation thereafter. Rapid diagnosis and treatment of pericardial effusion are mandatory to prevent subsequent morbidity and mortality when disastrous episodes, such as in the present case, occur.

Cardiac Tamponade↗
PubMed1995

Immunocytochemical localization of the sites of superoxide dismutase induction by hyperoxia in rat lungs.

BACKGROUND: Rats exposed to 85% O2 can survive subsequent exposures to 100% O2. The development of this tolerance to oxygen toxicity is associated with an increase in total pulmonary content of both CuZn and Mn superoxide dismutases (SOD). It is not known, however, in which cells increases in these antioxidant enzymes occur. We carried out an electron microscopic immunocytochemical study to define the distribution of CuZnSOD and MnSOD and their sites of induction in rat lungs. EXPERIMENTAL DESIGN: The lungs of rats exposed to either air or 85% O2 were fixed by instillation of fixative 7 and 14 days after the exposures were started. Cryoultrathin sections were prepared from randomly selected, frozen tissue blocks and were immunolabeled for either CuZnSOD or MnSOD. The labeling densities of the two enzymes in the major alveolar parenchymal cells (type I and type II epithelial cells, interstitial fibroblasts, and endothelial cells), were evaluated. RESULTS: All of the alveolar septal cells studied displayed similar concentrations of CuZnSOD. After 7 or 14 days of exposure to 85% O2, the total lung content of CuZnSOD was increased because of cell hyperplasia and hypertrophy, but the intracellular concentrations of CuZnSOD did not increase. MnSOD was present in the mitochondria of all lung cells in control rat lungs but was highest in alveolar type II epithelial cells. Exposure to 85% O2 increased the concentration of MnSOD in the mitochondria of interstitial fibroblasts by 197 and 139% after O2 exposure of 7 days and 14 days, respectively. A significant induction of MnSOD also occurred in the mitochondria of alveolar type II cells after 7 days of hyperoxia exposure. Biochemical analyses showed that a significant fraction of the hyperoxia-induced MnSOD was in the form of an enzymatically inactive protein. CONCLUSIONS: Hyperoxia induced total lung CuZnSOD in proportion to lung cell hypertrophy and hyperplasia. Total lung MnSOD was increased in association with specific inductions of MnSOD protein expression in the mitochondria of type II alveolar epithelial cells and interstitial fibroblasts. Hyperoxia appeared to result in inactivation and accumulation of the inactive MnSOD as well as induction of enzymatically active MnSOD. The ability of fibroblasts and alveolar type II cells to replace inactive MnSOD or to augment active MnSOD in the mitochondria appears to play important roles in the development of tolerance to hyperoxia by rats.

Animals↗
PubMed1995

Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part VIII: Morphometric analysis of structural alterations in alveolar regions.

Morphometric techniques were used to examine cellular and tissue changes occurring in male and female rat lungs exposed to ozone for a prolonged time. F344/N rats were exposed to 0.0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone for six hours per day, five days per week, for 20 months. Changes in cell volume, cell surface ratios, and cellular characteristics were studied in the terminal bronchioles and in the proximal alveolar regions of the lungs. Animals exposed for 20 months to 0.5 or 1.0 ppm ozone demonstrated dramatic increases in the volume of interstitium and epithelium along the alveolar ducts. The thickening of the epithelium was caused by an epithelial metaplasia in which the normal squamous epithelium was modified to a cuboidal epithelium similar, but not identical, to the type found in terminal bronchioles. This bronchiolar epithelial metaplasia was directly related to dose of ozone, and was characterized by differentiated ciliated cells and Clara cells similar to those found in terminal bronchioles; undifferentiated cuboidal cells also were found in the animals exposed to 0.5 and 1.0 ppm ozone. A mild fibrotic response was seen in the animals exposed to 1.0 ppm ozone, with increases in both the interstitial matrix and cellular interstitium. The individual components of the interstitial matrix, including collagen, elastin, basement membrane, and acellular spaces, all were increased. The increase in cellular interstitium was due to an increase in the volume of interstitial fibroblasts. A slight inflammatory response, identified by an increase in alveolar macrophages, was observed in the animals exposed to 1.0 ppm. The terminal bronchioles were less affected than the proximal alveolar region by the ozone exposures, which may indicate a resistance of this tissue to ozone damage. The changes in the terminal bronchioles mainly consisted of a shift in cell type from ciliated to Clara cells in the animals exposed to 1.0 ppm ozone. The bronchiolar epithelial metaplasia observed in the proximal alveolar ducts may indicate that a protective mechanism develops in response to prolonged exposure to high concentrations of ozone.

Analysis of Variance↗
PubMed1994

Superoxide and peroxynitrite in atherosclerosis.

The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-), yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of .NO reaction with O2-. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of beta very low density lipoprotein with ONOO- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O2- with .NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting .NO stimulation of vascular smooth muscle guanylate cyclase activity.

Acetylcholine↗
PubMed1994

Tenascin-C in rat lung: distribution, ontogeny and role in branching morphogenesis.

Extracellular matrix is important to organogenesis and may function by modifying cellular adhesion, motility, proliferation, and differentiation. Tenascin-C (TN-C) is a matrix molecule reported to bind some cell lines and to inhibit adhesion of some cell types to fibronectin. This report describes the ontogeny and possible functions of TN-C expression in fetal and newborn rat lung. There was a moderate concentration of TN-C protein at the epithelial-mesenchymal interface during fetal lung development in the period of branching morphogenesis. There was a remarkable accumulation of TN-C during the first postnatal week when alveolarization peaked, followed by a decline to barely detectable levels after the third postnatal week when alveolarization was essentially completed. Loss of TN-C protein followed quickly the loss of TN-C mRNA, suggesting a rapid turnover of TN-C in the extracellular matrix. By light microscopy, immunoreactive TN-C was present in early postnatal lung at the epithelial-mesenchymal interface and was distributed throughout lung mesenchyme. Electron microscopic immunocytochemistry showed TN-C was not a part of the basal lamina and that its lung localization was punctate and different from the uniform distribution of laminin. Antiserum to TN-C significantly inhibited branching morphogenesis of fetal lung explants but did not block their growth. Three bacterially expressed segments of TN-C comprising different fibronectin type III domains inhibited branching morphogenesis as effectively as did antiserum, but an expression protein of the carboxyterminal fibrinogen-like segment had no effect. We conclude that TN-C is expressed in a spatio-temporal pattern consistent with a role in lung development and our in vitro studies indicated a functional role for TN-C during lung branching morphogenesis.

Age Factors↗
PubMed1994

Reverse dorsometacarpal flap in digits and web-space reconstruction.

Skin defects in some areas of the digits are difficult to reconstruct, such as the ulnar aspect of the little or ring finger, radial aspect of the index, dorsal or volar aspect of fingers with proximal interphalangeal or metacarpophalangeal joint involvement, and proximal phalanx of the thumb. Moderate or severe contracture of the web space and multiple finger injuries without an available cross-finger flap are also a challenge to reconstructive surgeons. The reverse dorsometacarpal flap presents an option for reconstruction because of these difficulties. It is reliable and versatile in design. The donor site can be closed primarily provided the flap is less than 2 cm wide.

Adult↗
PubMed1994

Quantitative immunocytochemical analysis of Mn SOD in alveolar type II cells of the hyperoxic rat.

We have analyzed the magnitude and uniformity of the expression of manganese superoxide dismutase (Mn SOD) protein in alveolar type II cells of rats exposed to hyperoxia using quantitative colloidal gold immunocytochemistry and morphometric techniques. Sprague-Dawley rats were exposed continuously to normal air or to 85% oxygen for 7 and 14 days. The lungs were fixed by intratracheal instillation of a paraformaldehyde-glutaraldehyde fixative. Lung samples were dehydrated in ethanol and embedded in LR-White. Thin sections for electron microscopy were labeled with anti-rat Mn SOD rabbit antiserum followed by protein-A gold. The labeling density (gold particles/micron 2) over subcellular compartments was determined, and relative organelle volumes were measured using a random point overlay. The results confirm that alveolar type II cells are a locus of Mn SOD response in the lungs of hyperoxic rats and contribute to this response through a combination of changes: an increase of Mn SOD concentration in the mitochondrial matrix, an increase of mitochondrial volume per cell, and type II cell hyperplasia.

Animals↗
PubMed1994

Persistent hyperinsulinemic hypoglycemia due to nesidiodysplasia in a neonate.

A large, one-hour-old female baby was noted to have hypoglycemia immediately after birth. Although early feeding and then intravenous glucose infusion with a dose gradually increased to 30 mg/kg/min were given, the baby still had recurrent hypoglycemia 14 days after birth. High serum insulin/glucose ratios (> 2.5) were noted twice during hypoglycemic episodes. At the same time, the baby's serum growth hormone, thyroid hormone and cortisol levels were within normal ranges. Hyperinsulinism due to nesidiodysplasia was diagnosed and a near-total pancreatectomy was performed at the age of 14 days. After the operation, euglycemia was achieved and there was no episode of hypoglycemia even after fasting for eight hours. Our experience confirms that surgery is the treatment of choice for patients, including neonates, with hyperinsulinemic hypoglycemia.

Female↗
PubMed1994

Immunocytochemical localization of extracellular superoxide dismutase in human lung.

BACKGROUND: Extracellular superoxide dismutase (EC-SOD) is a principal enzymatic scavenger of the superoxide anion in extracellular spaces. It is thought to be important as a defense against superoxide-mediated damage to both cell surfaces and extracellular matrix proteins. EC-SOD may also be important in regulating intercellular signalling by extracellular superoxide. EC-SOD is believed to be mainly located in the extracellular matrix of tissues. However, the specific localization of EC-SOD is unknown. Knowledge of the distribution of EC-SOD is an essential step in defining its functions. EXPERIMENTAL DESIGN: Using light microscopic immunohistochemistry, electron microscopic immunocytochemistry and an EC-SOD affinity-purified polyclonal rabbit antibody to human recombinant EC-SOD, we evaluated the distribution of EC-SOD in human lungs. RESULTS: These studies revealed that in the lung EC-SOD is primarily located in the extracellular matrix. Specifically, EC-SOD is found in areas containing high amounts of type I collagen and other unidentified matrix elements, but was not seen in areas rich in elastin or cartilage. In the lung, EC-SOD is predominantly located around larger vessels and airways, and, to a lesser degree, in the extracellular matrix around alveolar and capillary regions. Some EC-SOD was found in bronchiolar epithelial cell junctions and around the surface of vascular and airway smooth muscle cells. No labeling was seen on endothelial cell surfaces of capillaries, small muscular, or large elastic vessels in the lung. Labeling for EC-SOD was limited to the extracellular spaces, consistent with it being a secreted protein, with the exception of a small amount of intracellular labeling seen in bronchial epithelial cells and type II cells. CONCLUSIONS: The labeling distribution of EC-SOD in human lungs was defined using immunohistochemistry and immunocytochemical techniques. The findings suggest that EC-SOD is not diffusely located throughout the lung, but has a specific distribution in the extracellular matrix. These findings on the distribution of EC-SOD suggest that specific roles for EC-SOD may include the protection of matrix elements such as collagen from oxidative stress and that it may also function in the regulation of intercellular signals that are modulated by reactive oxygen species.

Adult↗
PubMed1993

Sequence of a cDNA encoding the beta 4 subunit of murine integrin.

A cDNA coding for the beta 4 subunit of murine integrin (m beta 4) has been cloned and sequenced using mRNA from a murine lung carcinoma as the template. The 5' sequence contains two AUG codons, the second of which initiates synthesis of the mature protein. The cDNA sequence has an open reading frame coding for 1748 amino acids (aa), including a signal peptide, cysteine-rich region, serine- and threonine-rich region, transmembrane domain, and a cytoplasmic domain of over 1000 aa. Overall, the deduced m beta 4 aa sequence has 88% identity with the human beta 4 subunit (h beta 4) sequence deduced from the sequence of placental mRNA. Reverse transcriptase-polymerase chain reaction using primers flanking splice sites for two variant forms of h beta 4 transcripts provided evidence for alternate splicing of RNA in the murine spleen and to a lesser extent in the skin, uterus, and thymus but was found at only one of the two alternative sites. Five potential glycosylation sites present in the extracellular domain of h beta 4 are conserved in m beta 4. One tyrosine in the terminal region of the cytoplasmic domain (position 1600) is conserved between m beta 4 and h beta 4 and has the consensus sequence for tyrosine phosphorylation. Finally, a genomic restriction map of m beta 4 shows that the gene is about 40 kb in length. No restriction-fragment length polymorphisms were detected between BALB/c liver and BALB/c lung carcinoma DNA.

Alternative Splicing↗
PubMed1993

Immunoglobulin M antibodies against hepatitis C virus antigens: significance and applications.

The immunoglobulin M antibody against hepatitis C viral capsid (core) antigen has been found to be a possible marker for acute infection in post-transfusion hepatitis C. We extended this observation to a sporadic hepatitis C. In addition, a modified recombinant immunoblot assay (RIBA) that contained three HCV antigens (capsid, NS3 and NS5) in one strip was developed and used to study the antibody response among patients. This allowed a simultaneous comparison of either immunoglobulin M or G specific to individual HCV antigen and yielded more information. The assay was found useful in the diagnosis of acute hepatitis C in clinically uncertain cases.

Antigens, Viral↗
PubMed1993

Distribution of CuZn superoxide dismutase in rat liver.

Morphological and cell fractionation approaches were used to establish unambiguously the distribution of CuZn superoxide dismutase (CuZn SOD) in rat hepatocytes. Immunocytochemical observations revealed a primarily cytoplasmic localization of the enzyme. While only trace amounts were found in cell organelles like mitochondria and peroxisomes, lysosomes were labelled stronger than the cytoplasm. The presence of CuZn SOD in lysosomes was also identified in cell fractions of normal and Triton WR-1339-treated rats. Microscopic studies showed that the distribution of CuZn SOD was not affected by Triton, but the Triton treatment induced an apparent increase in the number and size of lysosomes with electron lucent contents which corresponded with a shift of lysosomes to low buoyant density fractions. The majority of CuZn SOD originally present in the mixed mitochondrial-peroxisomal-lysosomal fractions of the normal liver comigrated with the main peak of the lysosomal marker, beta-hexosaminidase, after Triton treatment. The peroxisomal marker, catalase, did not migrate with the CuZn SOD/beta-hexosaminidase-rich fractions in livers from Triton-treated animals. These results confirm earlier observations in rat liver cells, showing that CuZn SOD, a primarily cytosolic enzyme, accumulates in lysosomes. It is not present in significant amounts in rat hepatocyte peroxisomes.

Animals↗
PubMed1993

Distribution of manganese superoxide dismutase mRNA in normal and hyperoxic rat lung.

Aerobic metabolism requires a continuous oxygen supply, which in turn can form partially reduced species (free radicals) that damage cellular components. To prevent this, organisms have elaborate free radical-scavenging defenses that include the superoxide dismutases. The lungs are unique in their role as an oxygen-gathering system, making these defenses critical to lung integrity. Manganese superoxide dismutase (Mn-SOD) levels increase in rats exposed to sublethal doses of hyperoxia and correlate with the development of tolerance to higher levels of hyperoxia. Although pulmonary Mn-SOD protein and mRNA levels both change with hyperoxia, the timing and levels differ dramatically. Lung heterogeneity makes extrapolation of data from whole tissue homogenates or cultures difficult. In this study, in situ hybridization of Mn-SOD in the lungs of adult rats exposed to air or to 85% O2 for 3 days was performed. In animals exposed to either air or 85% O2, Mn-SOD transcripts were present in arterioles, the septal tips of alveolar ducts, alveolar type II cells, and mesothelial cells. Hyperoxic lung had an intense, continuous labeling of the pleura that was distinctly greater than the intermittent labeling of the pleura found in control animals. The high level of expression of Mn-SOD mRNA in alveolar duct septal tips in both control and O2-exposed animals may be secondary to increased aerobic activity in these regions, which contain collagen and elastin and are important stress-bearing elements in the lung. Alveolar type II cells are metabolically active secretory cells and thus may experience increased endogenously generated oxidative stress. Pleural effusions are common after hyperoxic exposures, suggesting damage to the mesothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Intercellular adhesion molecule-1 expression on the alveolar epithelium and its modification by hyperoxia.

The distribution of intercellular adhesion molecule-1 (ICAM-1) on alveolar epithelial cells and the effects of exposure to 100% O2 on ICAM-1 expression in mouse lungs were studied by EM immunocytochemistry and immunoblot analysis. Cryoultrathin sections from mouse lungs exposed to air or 100% O2 for 84 h were labeled with a monoclonal rat anti-mouse ICAM-1 antibody. In the normal lung, abundant ICAM-1 expression was found on the alveolar surface of type I epithelial cells. Furthermore, ICAM-1 is highly concentrated on the surfaces near cell junctions. ICAM-1 was also found on the capillary surface of endothelial cells and alveolar surface of type II cells at densities considerably lower than that found on type I epithelial cells. After exposure to O2, the labeling density of ICAM-1 on the central surface of type I epithelial cells was not changed significantly. However, the gradient of ICAM-1 on the surfaces near cell junctions was nearly abolished. ICAM-1 labeling on the capillary surface of endothelial cells remained low. ICAM-1 was also markedly induced on the alveolar surface of type II epithelial cells after hyperoxic exposure. These results show that ICAM-1 is expressed primarily on type I epithelial cell surfaces near cell junctions. Exposure to hyperoxia causes a dramatic change in the distribution pattern of ICAM-1 on alveolar type I epithelial cells and induces expression of ICAM-1 on alveolar type II epithelial cells. These hyperoxia-induced changes may influence the associated neutrophil invasion/retention in the alveolar air spaces or alveolar walls.

Analysis of Variance↗