PubMed Health⌕ Search

Biomedical subjects

C S Chiang

Publications and source records attributed to C S Chiang.

At least 37 records · Page 2Linked to original sources

Comparison of virus culture and the polymerase chain reaction for diagnosis of mucocutaneous herpes simplex virus infection.

BACKGROUND AND OBJECTIVES: The diagnosis of mucocutaneous herpes simplex virus (HSV) is hampered by suboptimal sensitivity of virus culture and atypical clinical morphology. GOALS: To compare the diagnostic usefulness of the polymerase chain reaction (PCR) and virus culture. STUDY DESIGN: Consecutive samples from 246 patients at an urban sexually transmitted diseases clinic were tested for HSV by both PCR and virus culture. RESULTS: Only 59% of HSV-positive samples were correctly diagnosed by the clinician; 11% had an atypical appearance. HSV-positive lesions were more often vesiculoulcerative or crusted than HSV-negative lesions, and of shorter median duration. Thirty-one samples were PCR positive and virus culture negative; these were often from crusted or older lesions. However, PCR was negative in 27 instances in which HSV was diagnosed clinically, of which 2 were vesicular and 15 ulcerative. CONCLUSIONS: HSV PCR is more rapid and sensitive than virus culture for diagnosis of mucocutaneous lesions. The data suggesting that PCR may be suboptimally sensitive need to be further investigated.

Female↗

Macrophage/microglial-mediated primary demyelination and motor disease induced by the central nervous system production of interleukin-3 in transgenic mice.

Activated macrophage/microglia may mediate tissue injury in a variety of CNS disorders. To examine this, transgenic mice were developed in which the expression of a macrophage/microglia activation cytokine, interleukin-3 (IL-3), was targeted to astrocytes using a murine glial fibrillary acidic protein fusion gene. Transgenic mice with low levels of IL-3 expression developed from 5 mo of age, a progressive motor disorder characterized at onset by impaired rota-rod performance. In symptomatic transgenic mice, multi-focal, plaque-like white matter lesions were present in cerebellum and brain stem. Lesions showed extensive primary demyelination and remyelination in association with the accumulation of large numbers of proliferating and activated foamy macrophage/microglial cells. Many of these cells also contained intracisternal crystalline pole-like inclusions similar to those seen in human patients with multiple sclerosis. Mast cells were also identified while lymphocytes were rarely, if at all present. Thus, chronic CNS production of low levels of IL-3 promotes the recruitment, proliferation and activation of macrophage/microglial cells in white matter regions with consequent primary demyelination and motor disease. This transgenic model exhibits many of the features of human inflammatory demyelinating diseases including multiple sclerosis and HIV leukoencephalopathy.

Animals↗

Previous heat shock treatment attenuates bicuculline-induced convulsions in rats.

Exposure to elevated temperature provokes a sequence of events (heat shock response) in all living organisms. Through this response, heat shock proteins (HSPs) are induced and protect the cells against subsequent injury. We investigated the effect of heat treatment on bicuculline-induced convulsions, and analyzed a possible role of HSPs. Screw electrodes were implanted in the brain of mature male Wistar rats for electroencephalogram (EEG) recording. Experimental rats were subjected to whole-body hyperthermia at 41-42 degrees C for 15 min. Fifteen hours later, bicuculline was injected intraperitoneally to induce convulsions in both experimental and control groups. The heated rats showed a significant attenuation of the convulsive response, in terms of both spike discharges in EEG and clinical seizures. Further-more, induction of HSP72 was detected in the brain of heat-treated rats by immunoblotting, appearing at 4 h and reaching a maximal level 16-24 h after the heat shock. We conclude that the previous heat treatment stabilized neuronal excitability, most probably through the induction of HSP72.

Animals↗

CHL1 encodes a component of the low-affinity nitrate uptake system in Arabidopsis and shows cell type-specific expression in roots.

The Arabidopsis CHL1 (AtNRT1) gene confers sensitivity to the herbicide chlorate and encodes a nitrate-regulated nitrate transporter. However, how CHL1 participates in nitrate uptake in plants is not yet clear. In this study, we examined the in vivo function of CHL1 with in vivo uptake measurements and in situ hybridization experiments. Under most conditions tested, the amount of nitrate uptake by a chl1 deletion mutant was found to be significantly less than that of the wild type. This uptake deficiency was reversed when a CHL1 cDNA clone driven by the cauliflower mosaic virus 35S promoter was expressed in transgenic chl1 plants. Furthermore, tissue-specific expression patterns showed that near the root tip, CHL1 mRNA is found primarily in the epidermis, but further from the root tip, the mRNA is found in the cortex or endodermis. These results are consistent with the involvement of CHL1 in nitrate uptake at different stages of root cell development. A functional analysis in Xenopus oocytes indicated that CHL1 is a low-affinity nitrate transporter with a K(m) value of approximately 8.5 mM for nitrate. This finding is consistent with the chlorate resistance phenotype of chl1 mutants. However, these results do not fit the current model of a single, constitutive component for the low-affinity uptake system. To reconcile this discrepancy and the complex uptake behavior observed, we propose a "two-gene" model for the low-affinity nitrate uptake system of Arabidopsis.

Animals↗

Asymmetric corneal toricity and pseudokeratoconus in videokeratography.

BACKGROUND: The diagnosis of asymmetric corneal toricity in video- keratography is based on the occurrence of an asymmetric bow tie pattern in the corneal map, which is usually attributed to corneal radial asymmetry but can be an artifact produced by misalignment of the videokeratograph with the corneal apex. METHODS: This study determined whether asymmetric bow tie patterns in 16 subjects (ages 24 to 40 years with corneal toricity of 0.37 to 1.50D) could be converted to symmetric bow tie patterns by changing the alignment of the videokeratograph so that it was directed at the corneal apex. RESULTS: In changing from regular to apex alignment the corneal map became more symmetric in 11 eyes, had no change in 3 eyes and increased in 2 eyes. No radius change could be measured centrally, but there were significant changes of greater than 1.00D in the peripheral corneal radii of 8 eyes. CONCLUSIONS: An asymmetric or angled bow tie appearance of a corneal map suggests a decentered apex rather than corneal asymmetry and may lead to a misdiagnosis of the type or magnitude of corneal toricity, keratoconus or other corneal irregularities.

Adult↗

Isolation and sequence determination of the cDNA encoding DNA polymerase delta from Drosophila melanogaster.

The cDNA encoding the catalytic subunit of Drosophila melanogaster (Dm) DNA polymerase delta (Pol delta) was isolated by a combination of PCR amplification and cDNA library screening. The cDNA is 3457 nucleotides in length and contains an open reading frame (ORF) that encodes a protein of 1092 amino acids (124,799 Da). The ORF contains the sequence that was determined for a peptide from the purified catalytic subunit of Dm Pol delta. Polyclonal antibodies raised against Dm Pol delta specifically recognize a protein of the expected size when the cDNA is expressed in either Escherichia coli or insect cells. Comparison of the deduced aa sequence with other Pol delta sequences demonstrates that Pol delta is one of the most highly conserved of the DNA polymerases.

Amino Acid Sequence↗

Induction of acute phase gene expression by brain irradiation.

PURPOSE: To investigate the in vivo acute phase molecular response of the brain to ionizing radiation. METHODS AND MATERIALS: C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-gamma), tumor necrosis factors (TNF-alpha and TNF-beta), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), alpha 1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. RESULTS: Levels of TNF-alpha, IL-1 beta, ICAM-1, EB22/5.3 and to a lesser extent IL-1 alpha and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. CONCLUSIONS: The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances.

Animals↗

Location of the major corneal reference points.

INTRODUCTION: The two principal applications of corneal topography are those pertaining to corneal shape, such as contract lens posterior surface design, and those pertaining to corneal power, such as predicting power changes after refractive surgery. Corneal topography measurements for these applications have advantages when related to two major reference points, the corneal apex for shape and the corneal sighting center for power. METHOD: Instantaneous corneal power, toricity, and axis were measured by videokeratography in 20 right eyes using the standard instrument alignment and alignments at each of the 2 major reference points. RESULTS: In comparing the central corneal measurements by videokeratography using the standard alignment to alignment at the corneal sighting center, there were minimal differences of less than 0.50 D for central power, toricity, and axis. In comparing the results for regular alignment to apex alignment there were significant differences for power (greater than 0.50 D) in 5 eyes, toricity in 3 eyes, and axis shifts of greater than 10 degrees in 5 eyes. In comparing the results for the corneal sighting center to apex alignments there were significant differences for power in 4 eyes, toricity in 2 eyes, and axis in 5 eyes. Changes of greater than 1.00 D occurred in the corneal periphery. CONCLUSIONS: In comparing standard videokeratograph alignment to alignment at the corneal sighting center, there were statistically insignificant differences in videokeratography results for corneal power, toricity, and axis. Significantly larger differences were found in comparing standard alignment and alignment at the corneal apex, especially for measurements in the corneal periphery.

Adult↗

Modification of tumor microenvironment by cytokine gene transfer.

The tumor microenvironment is determined by the interactions between host and tumor cells, a process in which cytokines play a major role. We have used retroviral vectors to insert and express cytokine genes in tumor cells so as to induce predictable changes in the host cells that infiltrate tumors. This frequently caused changes in tumor cell phenotype through autocrine/intracrine pathways. We reasoned that cytokine-induced alterations in tumor cell phenotype and/or in infiltrating host cells might alter the in vitro and in vivo cellular response to irradiation. In the present paper we document some of the effects of expression of interleukin-6 (IL-6) and IL-7 genes in tumor cells in this regard. The studies support the hypothesis that cytokines may play a role in determining both intrinsic tumor radioresponsiveness and the tumor microenvironment and in these ways may influence in vivo tumor irradiation responses. Possible cytokine gene-mediated approaches to radiotherapy cancer are discussed.

Animals↗

Superior vena cava syndrome in lung cancer: an analysis of 54 cases.

Traditionally, superior vena cava syndrome (SVCS) has been recognized as an oncologic emergency, and with clinical suspicion of the syndrome, tissue diagnosis was often delayed due to possible complications in diagnostic procedures and immediately threatening of life. Previously, local radiotherapy was regarded as the best immediate strategy for management of the condition. We have analyzed 54 lung cancer patients with SVCS in the past 6 years. Our results show that dyspnea (34 cases, 63%) and facial swelling (29 cases, 54%) are the two most common symptoms. The most frequent physical finding was venous distension of the neck (35 cases, 65%). The chest X-ray findings also showed a large ratio of superior mediastinal widening (26 cases, 48%). Fine needle aspiration of palpable lymph node (20 cases, 37%) and trans-thoracic needle aspiration guided by ultrasound (US) (8 cases, 14%) made diagnosis of at least half of the cases possible (28 cases, 51%). Both of these procedures are safer and easier than other invasive methods of examination. Of the 54 patients, small cell carcinoma constituted the majority of the cases (23 cases, 43%) and, with combination chemotherapy, there was a good response rate and a longer survival time (7.4 months) as compared to that of non-small cell carcinoma (3.7 months) treated by radiotherapy. We conclude that lung cancer with SVCS could be quickly and safely diagnosed by needle aspiration of the palpable lymph node or trans-thoracic needle aspiration guided by US, and that with combination chemotherapy the SVCS in small cell carcinoma can be effectively relieved.

Adult↗

Expression of the inducible nitric oxide synthase. Correlation with neuropathology and clinical features in mice with lymphocytic choriomeningitis.

Nitric oxide (NO) synthesized by the cytokine-inducible enzyme, nitric oxide synthase (iNOS), is thought to be a key mediator in the host immune response to infection, in which it may have protective, as well as injurious, actions. We sought evidence for a role of NO in the pathogenesis of lymphocytic choriomeningitis by examining the cerebral expression of the iNOS gene in mice after intracranial inoculation of lymphocytic choriomeningitis virus. In euthymic, but not athymic, mice, elevated expression of iNOS mRNA was observed in the brain by day 5 and increased further to high levels by day 6 postinfection. Of the peripheral organs, only the spleen showed significant increases in iNOS mRNA at day 3 postinfection. In situ hybridization revealed that iNOS RNA expression was restricted to cells within the inflammatory infiltrates and in proximity to areas of lymphocytic choriomeningitis virus infection in the brain. Immunostaining for iNOS protein identified numerous positive cells within the inflammatory infiltrates present in the meninges and choroid plexus. Phenotypic analysis revealed the majority of the iNOS containing cells to be Mac-1 positive. T lymphocytes that belonged to the CD8+ and CD4+ subsets were negative for iNOS expression. The kinetics and distribution of cerebral iNOS expression in lymphocytic choriomeningitis are consistent with a major role for the iNOS/NO pathway in the pathogenesis of this immune-mediated neurologic disease.

Amino Acid Oxidoreductases↗

Reactive gliosis as a consequence of interleukin-6 expression in the brain: studies in transgenic mice.

Gliosis is a characteristic pathologic state in many CNS disorders. Cytokines are considered to be effectors of gliosis. In order to explore the role of IL-6 in gliosis, the temporal and spatial expression of the IL-6 gene and its consequent effects on the brain were studied in a GFAP-IL6 transgenic mouse model. In GFAP-IL6 mice, IL-6 transgene expression was detectable in the brain at 1 week postnatally and increased to maximal levels by 3 months of age before declining at 8 and 12 months. Enhanced glial fibrillary acidic protein (GFAP) (marker for astrocytes) and Mac-I (marker for microglia) mRNA expression were first prominent at 1 month, increased to maximum levels by 3 months and remained significantly elevated through 12 months of age. Western blot analysis revealed that the enhanced GFAP mRNA expression in these transgenic mice was accompanied by increased GFAP protein levels. Immunostaining for Mac-I demonstrated that in addition to an increased staining intensity, the number of cells expressing the microglial/macrophage marker was also apparently increased, particularly in the cerebellum and brain stem. Concurrent with IL-6 transgene mRNA expression and reactive gliosis, upregulation of IL-1 alpha/beta, TNF alpha, ICAM-1 and EB22/5.3 (acute-phase reactant) but not inducible nitric oxide synthase gene expression was also observed. EB22/5.3 mRNA expression was most prominent and increased progressively with age. Expression of the IL-6, GFAP and EB22/5.3 RNAs was found to have similar distribution in the brain being found predominantly in the cerebellum, brain stem and sub-cortical regions. In conclusion, the constitutive expression of IL-6 in the brain induced the development of a pronounced and lifelong reactive gliosis affecting both astrocytes and microglia. The altered state of these cells may contribute to the functional and structural CNS impairment exhibited by the GFAP-IL6 mice. Finally, in these mice, expression of the EB22/5.3 gene correlated closely with the progression of neuropathy indicating that this acute-phase response gene was a good marker for and may be involved in the pathogenesis of CNS injury mediated by the expression of IL-6.

Amino Acid Oxidoreductases↗

Neopterin, soluble interleukin-2 receptor and adenosine deaminase levels in pleural effusions.

We evaluated soluble interleukin-2 receptors (sIL-2R), neopterin and adenosine deaminase (ADA) in pleural effusions from 93 patients with tuberculosis, malignancies, uremia, pneumonia and other kinds of pleurisy. There were significantly elevated ADA (102.7 +/- 47 U/l) and sIL-2R (8,238 +/- 4,117 U/ml) values in tuberculous (TB) pleural fluids as compared with other non-TB pleural fluids (p < 0.005). The neopterin levels in pleural fluid were significantly lower in the cancer group (17.3 +/- 7.8 nmol/l; p < 0.005) and most strikingly elevated (309.4 +/- 112.2 nmol/l; p < 0.0001) in patients with uremic pleural effusions. Using cut-off values of 60 U/l in ADA and 5,000 U/l in sIL-2R, 92.0 and 86.9% of pleural effusions were TB in origin. Eighty-four percent of patients with malignant pleural effusions had neopterin levels less than 25 nmol/l.

Adenosine Deaminase↗

G2/M-phase arrest and release in ataxia telangiectasia and normal cells after exposure to ionizing radiation.

Cells from patients with ataxia telangiectasia (AT) are abnormal in their response to irradiation as judged by clonogenic survival and accumulation in G2 phase. The relationship of the results of these two assays, however, is still a matter of controversy. Flow cytometry was used to measure the distribution of cells in the phases of the cell cycle after 2 Gy irradiation in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) and SV40-transformed fibroblasts. AT cells showed increased and prolonged accumulation in G2/M phase regardless of the cell type (lymphoblastoid or fibroblast) or complementation group (A, C or D). To test the hypothesis that prolonged accumulation of AT cells in G2 phase after irradiation was not simply a reflection of their radiosensitivity, we gave iso-survival radiation doses to SV40-transformed fibroblasts of two AT and one control cell lines. The two AT cell lines exited from the G2/M-phase block more slowly than control cells after each dose tested. This implies that prolonged accumulation in G2/M phase in AT cells is not directly related to radiosensitivity as measured by clonogenic survival, but that factors involved in the exit from G2 phase after irradiation may be abnormally regulated. We found that G2-phase arrest of AT cells did not necessarily result in a fatal consequence in the first cell cycle after irradiation. Furthermore, G2-phase arrest did not lead to detectable DNA fragmentation characteristic of apoptosis as judged by gel electrophoresis.

Ataxia Telangiectasia↗

Interleukin-3 in gene therapy of cancer.

Retroviral Jzen vectors were used to introduce cytokine genes into cell lines established from a "moderately immunogenic" FSAR and a "non-immunogenic" FSAN murine fibrosarcoma. The effects of cytokine gene expression on tumour behaviour and host responses have been studied in vitro and in vivo. In this paper we report that, in comparison to other cytokines, interleukin-3 (IL-3) was surprisingly effective at enhancing the immunogenicity of irradiated tumour cell vaccines as seen by the development of protective immunity to parental tumour growth. Protection was tumour-specific and spleen cells from immunized mice could adoptively transfer immunity causing established parental tumours to regress in SCID mice. IL-3 acted through paracrine and endocrine pathways to induce largely a granulocyte infiltrate into tumours and through an autocrine pathway to increase major histocompatibility complex class I expression on both tumour types and CD44 expression on one. IL-3 gene transfer is worth further investigation as a method for enhancing the efficacy of tumour cell vaccines, but our study emphasizes that cytokine gene transduction can lead to stimulation of autocrine as well as paracrine pathways and both might be important in the generation of specific anti-tumour responses. These effects need to be carefully considered if cytokine gene transfer is to be effectively used in cancer immunotherapy.

Animals↗