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Biomedical subjects

L Chow

Publications and source records attributed to L Chow.

At least 19 recordsLinked to original sources

Scleroderma renal crisis sine scleroderma during pregnancy.

Renal crisis is a serious complication of systemic sclerosis. Its occurrence prior to the development of skin sclerosis is exceedingly rare. We report a patient who developed acute renal failure during pregnancy. Renal biopsy showed features compatible with scleroderma renal crisis but typical cutaneous changes were only evident 2 months after the renal episode. The relationship between pregnancy, scleroderma activity and renal crisis is discussed.

Adult↗

Syphilitic myelitis with diffuse spinal cord abnormality on MR imaging.

Syphilitic myelitis is a very rare manifestation of neurosyphilis. The MRI appearance of syphilitic myelitis is not well documented and only a few cases have been reported. We present a 52-year-old woman with acute onset of paraplegia. Magnetic resonance imaging of the spine showed diffuse high signal intensity in the whole spinal cord on T2-weighted images. Focal enhancement was observed in the dorsal aspect of the thoracic cord on T1-weighted gadolinium-enhanced images. To our knowledge, diffuse spinal cord abnormality in syphilitic myelitis has not been reported in the international literature. Disappearance of the diffuse high-signal lesions with residual focal enhancement was noted after antibiotic therapy. The patient suffered significant neurological deficit despite improvement in the MR images. In this article we present the imaging findings and review the literature of this rare condition.

China↗

Antibody to the nonstructural protein NS1 of Japanese encephalitis virus: potential application of mAb-based indirect ELISA to differentiate infection from vaccination.

An indirect enzyme-linked immunosorbent assay (ELISA) was developed to detect and differentiate the antibody responses to Japanese encephalitis (JE) virus nonstructural protein NS1 between infected and vaccinated individuals. The results showed that all convalescent sera from JE patients contained NS1-specific IgG antibodies, while 65 and 40% of these sera showed detectable NS1-specific IgM and IgA antibodies, respectively. Specificity analysis showed that NS1-specific IgM and IgA antibodies from JE patients do not cross-react to dengue virus NS1 glycoprotein, while IgG antibodies from 10% of JE patients showed significant cross-reaction to dengue virus NS1 glycoprotein. To differentiate infection from vaccination, the immune sera from 24 children vaccinated with inactivated JE vaccine were analyzed. The data showed that none of these immune sera had detectable NS1-specific IgG antibodies. The results demonstrated the potential application of JE NS1-specific indirect ELISA to differentiate infection from vaccination.

Adult↗

Structural characterization of the 60-kDa bermuda grass pollen isoallergens, a covalent flavoprotein.

Our studies suggest a tripartite structure for the 60-kDa allergen of Bermuda grass pollen (BG60) including a short N-terminal segment, a FAD-binding domain, and a C-terminal domain. The lower molecular weight isoallergens lack the N-terminal segment. The higher protease susceptibility and the lower melting temperature of approximately 20 degrees C of the lower molecular weight isoforms suggest that the N-terminal segment is essential for a compact structure. Database screening reveals that the protease-digested peptide sequences (approximately 180 residues in total) share 40% identity with the plant berberine bridge enzymes. In particular, a 24-residue peptide sequence displays high similarity to a conserved FAD-binding motif. The spectroscopic and SDS-PAGE analyses suggest that the cofactor FAD is covalently linked to the central domain. Therefore, we conclude that BG60 is identified as the first flavinylated allergen.

Allergens↗

Effect of elevated concentration of alkaline phosphatase on cardiac troponin I assays.

Troponin I is the regulatory subunit of troponin complex associated with the actin thin filament within muscle cells. Cardiac troponin I (cTnI) is a good marker for diagnosis of myocardial damage. Several immunoassays are available for determination of cTnI in serum. The Stratus cTnI fluorometric enzyme immunoassay (Dade International) uses alkaline phosphatase (ALP) substrate. The microparticle enzyme immunoassay (MEIA) for cTnI (Abbott Laboratories) also uses ALP conjugate. On the other hand, the chemiluminescent assay (CLIA) for cTnI (Bayer Diagnostics) does not use ALP. ALP activity may frequently be elevated in serum of patients being evaluated for suspected myocardial infarction. Therefore, we studied the potential interference of ALP in cTnI assays. Serum pools were prepared from patients, and various concentrations of ALP solution were added to different aliquots. The cTnI concentrations were measured by the Stratus, MEIA, and CLIA assays. We observed no interference of ALP in the MEIA and CLIA assay for cTnI. On the other hand, we observed significant positive interference of ALP when cTnI concentrations were measured using the Stratus.

Alkaline Phosphatase↗

Uncommon hand tumours.

This paper presented clinical examples of some rare or uncommon presentations of tumours of the hand, including glomus tumour, intraosseous dermoid, fibrolipoma of the radial nerve, blastomycotic cyst and synovial sarcoma. Each lesion is illustrated by review of case histories, radiological and pathological features.

Adult↗

Membrane perturbation and the mechanism of lipid-mediated transfer of DNA into cells.

Mixtures of cationic lipids and unsaturated phosphatidylethanolamine are used extensively for the intracellular delivery of plasmids and antisense oligodeoxynucleotides (ODN) in vitro. However, the mechanism by which cytoplasmic delivery of these large molecules is achieved remains unclear. The common hypothesis is that phosphatidylethanolamine promotes fusion of lipid/DNA particles with endosomal membranes, but this is inconsistent with several reports that have failed to correlate the fusogenic activity of a wide variety of lipid/DNA particles, measured by lipid mixing techniques, with their transfection activity. To address this issue further we have conducted a detailed analysis of the lipid mixing and DNA transfer activity of two, physically similar but functionally different, lipid/DNA particles composed of equimolar dioleyldimethylammonium chloride (DODAC) and dioleoylphosphatidylethanolamine (DOPE) or dioleoylphosphatidylcholine (DOPC). In combination with DODAC both phospholipids form almost identical lipid/DNA particles, they are endocytosed by cells to the same extent and each undergoes equivalent lipid mixing with cell membranes after uptake. Despite this, DNA transfer is 10- to 100-fold more extensive for lipid/DNA particles containing DOPE. We conclude that lipid mixing between lipid-based delivery systems and endosomal membranes must occur for DNA transfer to occur. However, the potency of different lipid/DNA particles correlates better with the ability of the exogenous lipid to disrupt membrane integrity.

Animals↗

Dengue NS1-specific antibody responses: isotype distribution and serotyping in patients with Dengue fever and Dengue hemorrhagic fever.

To understand the antibody responses to dengue (DEN) nonstructural 1 (NS1) glycoprotein and their roles in protective immunity or pathogenesis of dengue fever (DF) and dengue hemorrhagic fever (DHF), we have analyzed the NS1-speccific IgM, IgA and IgG antibodies from patients with DF and DHF. An isotype-specific, indirect enzyme-linked immunosorbent assay (ELISA) was established by coating a NS1-specific monoclonal antibody (MAb), D2/8-1, to capture soluble NS1 antigens secreted in the culture supernatants of Vero cells infected with DEN virus. We observed strong anti-NS1 antibody responses in all of the convalescent sera of patients with DF and DHF. Similar NS1-specific isotypic and serotypic antibody responses were found in the sera from DF and DHF patients. The results showed that all DEN infections induced significant NS1-specific IgG, whereas 75% and 60% of primary DF patients vs. 40% and 90% of secondary DF patients produced IgM and IgA antibodies, respectively. Specificity analysis showed that DEN NS1-specific IgG and IgA antibodies cross-react strongly to Japanese encephalitis (JE) virus NS1 glycoprotein, whereas DEN NS1-specific IgM antibodies do not cross-react to JE virus NS1 glycoprotein at all. The serotype specificity of NS1-specific IgM, IgA and IgG were found to be 80%, 67% and 75% for primary infections, and 50%, 22% and 30% for secondary infections in positive samples of DF patients. Similar pattern was found in DHF patients. The results showed that all of the DF and DHF patients produced significant NS1-specific antibodies. We did not observe direct correlation between the anti-NS1 antibody responses and DHF because sera from patients with DF and DHF showed similar anti-NS1 antibody responses.

Antibodies, Monoclonal↗

Efficient diagnosis of dengue infections using patients' peripheral blood leukocytes and serum/plasma.

OBJECTIVE: Dengue fever has been one of the most important health problems in Taiwan since a large outbreak during 1987 and 1988. It is critically necessary to have a diagnostic approach that can detect early infections in an outbreak or even find infections existing in silent transmission of the disease. METHODS: To develop an efficient diagnostic protocol, 105 plasma/serum and 35 peripheral blood leukocyte (PBL) specimens from the 1994 outbreak in southern Taiwan were collected for assessment by various diagnostic techniques in this study. RESULTS: In acute blood samples, dengue viruses were isolated from 19.4% (14/72) and 33.3% (14/42) of reported and confirmed cases, respectively. Viral RNA in serum/plasma was detected from 20.0% (12/60) of acute samples, which was significantly higher than that from convalescent samples (3/44; 6.8%). However, viral RNA in PBLs, detected by reverse transcription polymerase chain reaction (PBL-RT-PCR), could be observed in 73.2% (19/26) and 66.7% (6/9) of acute and convalescent samples, respectively. The persistence of dengue viruses in PBLs was also evidenced by the presence of viral antigens in 42.9% (4/7) of confirmed convalescent samples by the immunofluorescence antibody test. In addition, IgM antibodies were detected in 43.8% (46/105) of reported cases and 85.2% (46/54) of confirmed cases by the IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). CONCLUSIONS: Although IgM antibody detection achieved the highest detection rate among techniques assessed in this study, no individual test can actually reach full efficiency for early diagnosis of dengue infections. Here, we propose a protocol which applies MAC-ELISA and PBL-RT-PCR in sequence, by which 22 confirmed cases were definitely proved as dengue positive. High levels of both sensitivity and specificity were shown in this protocol.

Antibodies, Viral↗

Performance evaluation of a new chemiluminescent cardiac troponin I assay.

Cardiac troponin I is a marker for diagnosis of myocardial damage. Several immunoassays are currently available for determination of concentrations of troponin I in serum. We evaluated a chemiluminescent assay for troponin I using ACS:180 automated analyzer (Bayer Diagnostics). We compared our results with two other immunoassays using the OPUS Magnum (OPUS troponin I assay, Dade Behring) and AxSYM (microparticle enzyme immunoassay, Abbott) analyzers. The within-run and between-run CVs were less than 5% for all three levels of controls. The chemiluminescent assay for troponin I was linear up to a serum troponin I concentration of 50 ng/mL and the detection limit was 0.1 ng/mL of troponin. A good correlation between troponin I concentration measured by the chemiluminescent assay (y axis) and the microparticle enzyme immunoassay (MEIA) (x axis) was observed, although the concentrations of troponin I in individual specimens were approximately four times higher, when measured by the MEIA assay, than those measured by chemiluminescent assay. The correlation coefficient was 0.98 with the regression equation y = 0.22x + 1.125. We also observed a good correlation in troponin I concentrations obtained by the chemiluminescent assay (y axis) and OPUS troponin I assay (x axis). The correlation coefficient was 0.96 and the regression equation was y = 0.79x - 0.52. The correlation coefficient was 0.93 when we compared troponin I concentrations obtained by the OPUS assay (x axis) with the corresponding concentrations obtained by the MEIA assay (y axis). The corresponding regression equation was y = 0.25x + 3.5. We conclude that the chemiluminescent troponin I assay showed good analytical performance.

Humans↗

Two novel mutations of the FMO3 gene in a proband with trimethylaminuria.

The mammalian flavin-containing monooxygenases catalyze the NADPH-dependent N-oxygenation of nucleophilic nitrogen-, sulfur-, and phosphorus-containing chemicals, drugs, and xenobiotics, including trimethylamine. The FMO3 gene encodes the dominant catalytically active isoform present in human liver. We have identified two missense mutations in the coding region of the gene in a proband with trimethylaminuria (TMA): M66I and R492W. Whereas two mutations (P153L, E305X) accounted for TMA in our eight unrelated previously documented Australian families of British origin, the present report is the first evidence of compound heterozygosity for two rare mutations in a proband with this disorder. This suggests that other rarer alleles, also causing TMA, will be found in the same populations.

Adult↗

Effect of heating human sera at a temperature necessary to deactivate human immunodeficiency virus on measurement of free phenytoin, free valproic acid, and free carbamazepine concentrations.

Minimizing the risk for infection to laboratory staff from a contaminated blood sample is a major safety goal in the clinical laboratory. One dangerous pathogen, the human immunodeficiency virus (HIV), can be deactivated by heating sera at 56 degrees C for 30 minutes. The authors previously reported that if serum was subjected to those conditions, the concentrations of the nine most commonly monitored drugs were not altered, whereas phenytoin and carbamazepine concentrations were reduced slightly. Monitoring free phenytoin, free valproic acid, and free carbamazepine concentrations is strongly recommended for patients with uremia, liver disease, and hypoalbuminemia. Because drug protein binding can be affected by temperature, the authors investigated the effect on free drug concentrations of sera heated to levels necessary for deactivation of the HIV virus. They measured total and free drug concentrations in serum pools prepared from patients receiving phenytoin, valproic acid, and carbamazepine. Serum pools were heated at 56 degrees C for 30 minutes and then brought to room temperature. The total and free drug concentrations were measured immediately after heating and then at 20- and 45-minute intervals. The concentrations of free phenytoin and free valproic acid were significantly higher after heat treatment. However, after equilibration of sera at room temperature for 20 minutes, the free concentrations of phenytoin were comparable to preheating values, although total phenytoin concentrations (Serum Separator Tubes) were reduced slightly. In contrast, free valproic acid concentrations did not return to the original levels even after 45 minutes. Free carbamazepine concentrations did not change even immediately after heating. However, total carbamazepine concentrations were reduced slightly when sera were heated in serum separator tubes (SST Tubes).

Anticonvulsants↗

Assessment of chemosensitivity in patients with osteogenic sarcoma using the doxorubicin binding assay.

BACKGROUND AND OBJECTIVES: Assessment of chemosensitivity in patients with osteosarcoma may help identify those with resistance to chemotherapy. In this study, we investigated the clinical value of the doxorubicin binding assay in its ability to identify patients with drug resistance. METHODS: We tested tumor tissue samples obtained at biopsy of 24 patients with high-grade osteosarcoma aged 9-61 years (mean 19.2) for sensitivity to doxorubicin, using the doxorubicin binding assay. Tumor excision was performed in these patients after neoadjuvant chemotherapy. Chemotherapy response was judged on the basis of tumor necrosis achieved and was compared with doxorubicin sensitivity in each of these patients. RESULTS: Doxorubicin sensitivity was good in 15 and poor in 9 of 24 patients studied. In patients with good sensitivity (n = 15), 9 (60%) exhibited a good response to chemotherapy while response was poor in 6. In patients with poor sensitivity (n = 9), response to chemotherapy was poor in all 9 (100%) patients and 7 (77.8%) of these patients developed metastatic disease within a mean period of 5.2 months, resulting in two deaths. The results were statistically significant at P = 0.0193. CONCLUSIONS: Doxorubicin binding assay may be useful in identifying patients with inherent resistance to chemotherapy. As the outcome of patients showing resistance to doxorubicin is poor, innovative strategies may need to be developed for this group of patients.

Adolescent↗

The nuclear receptor transcription factor, retinoid-related orphan receptor beta, regulates retinal progenitor proliferation.

We examined the role of retinoid-related orphan receptor (ROR)beta, a member of the nuclear receptor family of transcription factors, in retinal neurogenesis. In situ hybridization studies showed that RORbeta is expressed in retinal progenitor cells in the embryonic rat retina. Further studies demonstrated that RORbeta colocalizes with Chx10, a transcription factor thought to influence retinal progenitor proliferation (Burmeister, M., Novak, J., Liang, M-Y., Basu, S., Ploder, L., Hawes, N.L. Vidgen, D., Hoover, F., Goldman, D. , Kalnins, V.I., Roderick, T.H., Taylor, B.A., Hankin, M.H. and McInnes, R.R., 1996. Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nature Genetics 12, 376-383). Northern analysis reveals that RORbeta expression is dramatically decreased in the ocular retardationJ mutant, which possesses a defect in the Chx10 gene. Overexpression of RORbeta in retinal progenitors by biolistic transfection results in an increase in the number of large cell clones. These data support a role for RORbeta in regulating retinal progenitor proliferation, possibly via the Chx10 gene.

Animals↗