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Biomedical subjects

S Chiang

Publications and source records attributed to S Chiang.

At least 19 recordsLinked to original sources

Effect of additives on LiMo3Se3 nanowire film chemical sensors.

Here we investigate the effect of lithium iodide and cetyltrimethylammonium (CTA) bromide additives on the ability of LiMo(3)Se(3) nanowire film sensors to bind and detect organic solvents electrically. Both additives decrease the electrical conductivity of the films. Lithium iodide increases the response of the films to both polar and nonpolar analytes. CTA increases the response of the films to nonpolar analytes but reduces the response to polar analytes. Quartz crystal microbalance measurements show that the modified electrical sensitivities of the films are due to altered analyte adsorption abilities of the films. These results show that the Li(+) ions are involved in analyte binding in native LiMo(3)Se(3) films and that a programming of LiMo(3)Se(3) nanowire film sensors is possible by replacing lithium cations with other receptors.

Journal Article↗

Molecular adsorption to LiMo3Se3 nanowire film chemiresistors.

Thin films of metallic nanowire bundles derived from the Chevrel compound LiMo3Se3 undergo reversible increases of their electrical resistance (up to 70%) upon exposure to vapors of organic solvents (Qi, X. B.; Osterloh, F. E. J. Am. Chem. Soc. 2005, 127 (21), 7666-7667). Using quartz crystal microbalance measurements with four analytes, we demonstrate here that the temporal and steady-state resistance changes of the films depend on the time following the adsorption and on the number of molecules that adsorb to the nanowire films at a given pressure. The adsorption ability of the films and the corresponding film resistance increase in the row: hexane < THF < ethanol < DMSO, closely following the polarities of the solvents. On average, approximately 10(5) analyte molecules per LiMo3Se3 unit are required to produce a measurable electrical response. Atomic force microscopy scans on nanowire films reveal that analytes deposit on top of the nanowire bundles and cause the films to swell by approximately 6% in volume. The temporal and steady-state resistance data of the LiMo3Se3 chemiresistors can be explained by assuming that coating of the nanowire bundles with analyte molecules reduces the interwire charge transport in the films.

Journal Article↗

Linking surface stress to surface structure: measurement of atomic strain in a surface alloy using scanning tunneling microscopy.

Annealed submonolayer CoAg/Ru(0001) films form an alloy with a structure that contains droplets of Ag surrounded by Co [G. E. Thayer, V. Ozolins, A. K. Schmid, N. C. Bartelt, M. Asta, J. J. Hoyt, S. Chiang, and R. Q. Hwang, Phys. Rev. Lett. 86, 660 (2001)]. To understand how surface stress contributes to the formation of this structure, we use scanning tunneling microscopy to extract atomic displacements at the boundaries between regions of Co and Ag. Comparing our measurements to Frenkel-Kontorova model calculations, we show how stress due to lattice mismatch contributes to the formation of the alloy droplet structure. In particular, we quantitatively evaluate how competing strain and chemical energy contributions determine surface structure.

Journal Article↗

Role of stress in thin film alloy thermodynamics: competition between alloying and dislocation formation.

Using scanning tunneling microscopy (STM) and first-principles local-spin-density-approximation calculations to study submonolayer films of Co (1-c)Ag (c)/Ru(0001) alloys, we have discovered a novel phase-separation mechanism. When the Ag concentration c exceeds 0.4, the surface phase separates between a dislocated, pure Ag phase and a pseudomorphically strained Co(0.6)Ag (0.4) surface alloy. We attribute the phase separation to the competition between two stress relief mechanisms: surface alloying and dislocation formation. The agreement between STM measurements and our calculated phase diagram supports this interpretation.

Journal Article↗

T-helper-1 and T-helper-2 responses in psychiatric disorders.

The expanding field of psychoneuroimmunology has markedly increased knowledge about the interference of the central nervous system and the immune system. Immunological abnormalities in psychiatric patients have been repeatedly described in the last century. Modern concepts of immunology and the growing knowledge of psychoneuroimmunology may help in understanding the distinct immunological mechanisms in psychiatric disorders. One of these concepts regarding the adaptive immune system is the discrimination between Th1-like cell-mediated and Th2-like antibody-related immune responses. This article systematically describes alterations of Th1- or Th2-specific parameters in the major psychiatric disorders schizophrenia, major depression, and Alzheimer's disease. There are several hints of associations of these two distinct arms of immune response with subgroups of schizophrenia and major depression. The immunological research in Alzheimer's disease has already led to a preclinical model of immunotherapy. Categorization of immune parameters may also help to identify a possible immune-related pathophysiology in psychotic and affective disorders, resulting in specific treatment strategies.

Humans↗

A modified enzyme-linked immunosorbent assay for the detection of avian pneumovirus antibodies.

Avian pneumovirus (APV) infection of turkeys in Minnesota was first confirmed in March 1997. Serum samples (n = 5,194) from 539 submissions to Minnesota Veterinary Diagnostic Laboratory were tested by a modified enzyme-linked immunosorbent assay (ELISA). Of these, 2,528 (48.7%) samples from 269 submissions were positive and 2,666 (51.3%) samples from 270 submissions were negative for APV antibodies. Most positive samples were from Kandiyohi, Stearns, Morrison, and Meeker counties in Minnesota. In addition, 10 samples from South Dakota were positive. The sensitivity and specificity of the ELISA test with anti-chicken and anti-turkey conjugates were compared by testing field and experimental sera. The ELISA test with anti-turkey conjugate was more sensitive than that with anti-chicken conjugate. The ELISA tests with antigens prepared with APV strains isolated from Colorado and Minnesota were also compared. No difference was detectable. Currently, the Minnesota Veterinary Diagnostic Laboratory uses an antigen prepared from the Colorado isolate of APV and a goat anti-turkey conjugate in the ELISA test.

Animals↗

Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan.

Lurtotecan is a clinically active water-soluble camptothecin analogue that has been formulated into a low-clearance unilamellar liposome, NX 211. Comparative studies between free drug and NX 211 have been performed assessing pharmacokinetics in nude mice, tissue distribution in tumor-bearing mice, and antitumor efficacy in xenografts. Compared with lurtotecan, NX 211 demonstrated a significant increase in plasma residence time and a subsequent 1500-fold increase in the plasma area under the drug concentration curve. The volume of distribution was also greatly restricted, suggesting altered tissue distribution. Evaluation of tissues 24 h after administration of either [14C]NX 211 or [14C]lurtotecan to ES-2 tumor-bearing mice demonstrated a 40-fold increase in radiolabeled compound in the tumors of NX 211-treated mice compared with mice treated with lurtotecan. In single-dose efficacy studies, NX 211 produced a consistent 3-fold or greater increase in therapeutic index compared with lurtotecan in both the KB and ES-2 xenograft models. When compared at equitoxic levels in repeat-dose efficacy studies, NX 211 generated durable cures lasting >60 days and a 2-8-fold increase in log10 cell kill, compared with lurtotecan and topotecan, respectively. Together, these data demonstrate that NX 211 has significant therapeutic advantage over lurtotecan and that the improved antitumor activity is consistent with increased exposure and enhanced drug delivery to tumor sites.

Animals↗

Multiple activation steps of the N-formyl peptide receptor.

The human N-formyl peptide receptor (FPR) is representative of a growing family of G protein-coupled receptors (GPCR) that respond to chemokines and chemoattractants. Despite the importance of this receptor class to immune function, relatively little is known about the molecular mechanisms involved in their activation. To reveal steps required for the activation of GPCR receptors, we utilized mutants of the FPR which have previously been shown to be incapable of binding and activating G proteins. For this study, the FPR mutants were expressed in human myeloid U937 cells and characterized for functions in addition to G protein coupling, such as receptor phosphorylation and ligand-induced receptor internalization. The results demonstrated that one of the mutants, R123G, though being unable to activate G protein, was capable of undergoing ligand-induced phosphorylation as well as internalization. Receptor internalization was monitored by following the fate of the ligand as well as by directly monitoring the fate of the receptor. The results with the R123G mutant were in contrast to those obtained for mutants D71A and R309G/E310A/R311G which, though being expressed at the cell surface and binding ligand, were incapable of being phosphorylated or internalized upon agonist stimulation. These results suggest that following ligand binding at least two "steps" are required for full activation of the wild-type FPR. That these observations may be of more general importance in GPCR-mediated signaling is suggested by the highly conserved nature of the mutants studied: D71, R123, and the site represented by amino acids 309-311 are very highly conserved throughout the entire superfamily of G protein-coupled receptors. Models of receptor activation based on the observed results are discussed.

Animals↗

Hair cell formation in cultures of dissociated cells from the vestibular sensory epithelium of the bullfrog.

HYPOTHESIS: Bullfrog vestibular hair cells are capable of regenerating in vitro. BACKGROUND: Recent studies have established that sensory organs in the inner ear of vertebrates continue to produce hair cells after birth. However, the mechanisms responsible for the regulation of this process are not well understood. The current study reports the development of a novel method for the culture of dispersed cells from the bullfrog inner ear. METHODS: New hair cell formation in this in vitro preparation was shown by sequential photomicroscopy. Studies with the selective marker for mitotic activity 5-bromo-2-deoxyuridine (BrdU) were done to estimate the level of cell proliferation and to quantify postmitotic hair cell formation. Finally, confirmation of cell type was obtained by scanning electron microscopy and by the use of specific markers for hair cells. RESULTS: Once the optimal culture conditions were established in the initial experiments, the formation of new hair cells was directly visualized in all unstained live cultures and fixed preparations without exception. Asymmetric division of progenitor cells, with subsequent differentiation of one of the daughter cells into new hair cells, also was documented by photomicroscopy. Approximately 12% of the cells were labeled with BrdU, of which 6% were hair cells, showing that new hair cell formation was subsequent to mitotic division in vitro. The identity of newly formed hair cells was verified as follows: 1) morphologically by scanning electron microscopy; 2) by positive labeling with phalloidin-rhodamine, a marker for actin; and 3) by positive calmodulin immunocytochemistry. CONCLUSIONS: This study reports the development of an in vitro culture preparation in which undifferentiated epithelial cells proliferate to become new hair cells. Evidence is provided of division of hair cell progenitors and subsequent differentiation of the daughter cells as one of the mechanisms involved in new hair cell formation in the culture preparation. This newly developed cell culture technique provides a powerful tool for further study of the process of hair cell formation in the vestibular end organ.

Animals↗

Cervical cancer in young women in Taiwan: prognosis is independent of papillomavirus or tumor cell type.

The objective of this study was to address the hypotheses that younger patients with cervical cancer have a uniquely worse clinical outcome and/or are more likely to have adverse tumor cell types or specific human papillomaviruses (HPV). Cases of stage Ib-IIa cervical cancer among women 35 years of age or younger (82) and over 35 (54) were analyzed and compared with respect to the following: (1) histologic type (squamous vs nonsquamous), (2) human papillomavirus (HPV) type via polymerase chain reaction, and (3) clinical parameters, including tumor size, nodal metastases, and recurrence/persistence. Patients 35 years of age or younger had a survival similar (71.2% vs 72.4%) to that of older women from the same institution. In the younger group, outcome was not correlated with the presence or absence of HPV or HPV type. Nonsquamous carcinomas, including adenocarcinoma and small cell carcinoma, were strongly associated with HPV18, were more prevalent in the younger group, and had a slightly higher risk of recurrence/persistence; however, these differences were not significant and 71% of the recurrences were squamous cell carcinomas. Thus, in young Taiwanese women with stage Ib-IIa cervical cancer, the majority of deaths cannot be attributed to a specific HPV type or unique tumor morphology.

Adult↗

Absolute and comparative subcutaneous bioavailability of ardeparin sodium, a low molecular weight heparin.

Ardeparin sodium (Normiflo, Wyeth-Ayerst) is a low molecular weight heparin undergoing clinical evaluation as an antithrombotic agent. The objective of this study was to evaluate the absolute and comparative bioavailability of ardeparin following subcutaneous administration of three different formulations [two formulations of ardeparin at 10,000 anti-factor Xa (aXa) U/ml, but with different preservatives, and a 20,000 aXa U/ml formulation]. The study was conducted using a randomized 4-period crossover design (three subcutaneous treatments and one intravenous treatment) in 24 healthy subjects, and the pharmacokinetics of ardeparin were characterized by plasma anti-factor IIa (aIIa) and anti-factor Xa (aXa) activities. The mean absolute bioavailability of ardeparin based on aIIa activity ranged from 62% to 64% and the mean absolute bioavailability based on aXa activity ranged from 88% to 97%. Based on bioequivalence testing criteria, the three ardeparin formulations were bioequivalent.

Adult↗

Conformational flexibility and crystallization of tandemly linked type III modules of human fibronectin.

Fibronectin is a large cell adhesion molecule that is composed of several functional domains. The cell-binding domain that binds to cell surface integrins consists of repeated homologous type III modules. In this study, recombinant fragments from the cell-binding domain of human fibronectin that participate in a newly characterized fibronectin-fibronectin interaction with FNIII1 were crystallized. In each case, the crystals had more than one fibronectin fragment in the asymmetric unit. Crystals of FNIII10-11 grew in the space group C2 with a = 117.1 A, b = 38.6 A, c = 80.6 A, beta = 97.2 degrees, and two molecules in the asymmetric unit. These crystals diffracted to 2.5 A resolution. Fragment FNIII8-11 and a shorter fragment, FNIII8-10, crystallized in hexagonal space groups with large unit cells and two to four molecules per asymmetric unit. Even very large crystals of these fragments did not diffract beyond 4 A. The crystal packing for this collection of fibronectin fragments suggests conformational flexibility between linked type III modules. The functional relevance of this flexibility for elongated versus compact models of the cell-binding domain of fibronectin is discussed.

Ammonium Sulfate↗

Pharmacokinetics of the aldose reductase inhibitor tolrestat: studies in healthy young and elderly male and female subjects and in subjects with diabetes.

Tolrestat is an aldose reductase inhibitor undergoing clinical trials in diabetic subjects that may reduce the severity of chronic tissue damage associated with hyperglycemia. These studies were conducted to evaluate the pharmacokinetics of tolrestat in healthy young and elderly male and female subjects and in young and elderly subjects with diabetes. The drug was administered in a multiple-dose regimen, and steady-state parameters were obtained. There were no important gender-related differences, but mean values for apparent oral clearance, renal clearance, and corresponding unbound parameters were significantly lower for the elderly healthy subjects than for the young healthy subjects. The drug is highly bound to plasma proteins, and the unbound fraction (0.75%) did not differ among the subjects. The results from young and elderly diabetic subjects suggest that diabetes per se has no influence on tolrestat disposition but that there is an age-related reduction in apparent oral clearance (30 versus 18 ml/hr/kg) and a corresponding increase in the minimum steady-state plasma concentration (1.2 versus 1.9 micrograms/ml). These data indicate a possible need to reduce the dose of tolrestat in elderly subjects, assuming the same concentration-response relationship.

Administration, Oral↗

The dose proportionality of the pharmacokinetics of ardeparin, a low molecular weight heparin, in healthy volunteers.

Ardeparin is a low molecular weight heparin currently being evaluated as an antithrombotic agent. The objective of this investigation was to assess the effects of dose on the pharmacokinetics of ardeparin after subcutaneous administration. Eighteen healthy subjects received doses of 30 U/kg, 60 U/kg, and 100 U/kg antifactor Xa (aXa) of ardeparin by subcutaneous injection. Plasma antifactor IIa (aIIa) activity levels after the 30- and 60-U/kg doses of ardeparin were too low to reliably characterize the disposition of the drug. However, the pharmacokinetics of ardeparin could be characterized by using pharmacodynamic measurements of plasma aXa activity. The rate of absorption of ardeparin after subcutaneous administration did not change with increasing dose. The volume of distribution (Vd) of ardeparin was small, reflecting minimal distribution outside the intravascular space, and was independent of dose. The total clearance of ardeparin, however, decreased with increasing dose, and half-life (t1/2) was prolonged at the higher doses. Within the observed dose range, a doubling of the ardeparin dose resulted in an area under the plasma aXa activity-versus-time curve (AUC) that was approximately 25% greater than expected on the basis of linear disposition. The differences in AUC and clearance between the three doses suggest that the mechanism of elimination of ardeparin is saturable.

Adult↗

Prenatal diagnosis of omphalocele associated with umbilical cord cyst.

BACKGROUND: To study the cytogenetics, ultrasound findings, biochemical screening, perinatal outcome, and associated abnormalities in cases of omphaloceles associated with umbilical cord cysts. METHODS: From 1988 to 1994, three cases of omphaloceles with umbilical cord cysts were identified at Mackay Memorial Hospital. We compared the clinical data of our three cases with six other cases in the published literature. RESULTS: Two cases of omphaloceles with umbilical cord cysts were affected with trisomy 18. One had bilateral choroid plexus cyst, intrauterine growth retardation, low levels of maternal serum alpha-fetoprotein and free beta-human chorionic gonadotropin, and the other had cleft lip and palate, single umbilical artery and intrauterine growth retardation. An elevated level of maternal serum alpha-fetoprotein was found in the case with normal karyotype. Elevated levels of amniotic fluid alpha-fetoprotein were found in two cases. Rupture of the umbilical cord cyst and disruption of the umbilical cord occurred in one case at delivery. Based on the gross and microscopic examinations, the cord cysts we observed are likely to be pseudocysts. CONCLUSION: The umbilical cord cysts most commonly associated with omphaloceles are pseudocysts and allantoic cysts. Among our three cases and the six other cases published in the literature, four out of these nine cases were trisomy 18. Prenatal diagnosis of omphaloceles or umbilical cord cysts by ultrasound warrants cytogenetic analysis and detailed sonogram to rule out the possible combination of both abnormalities and trisomy 18. If an omphalocele is associated with a large umbilical cord cyst and a normal karyotype, cesarean section is recommended to prevent the dilemma of intrauterine vascular compromise of umbilical blood flow during labor.

Abnormalities, Multiple↗