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Biomedical subjects

Y C Wu

Publications and source records attributed to Y C Wu.

At least 19 recordsLinked to original sources

NUC-1, a caenorhabditis elegans DNase II homolog, functions in an intermediate step of DNA degradation during apoptosis.

One hallmark of apoptosis is the degradation of chromosomal DNA. We cloned the Caenorhabditis elegans gene nuc-1, which is involved in the degradation of the DNA of apoptotic cells, and found that nuc-1 encodes a homolog of mammalian DNase II. We used the TUNEL technique to assay DNA degradation in nuc-1 and other mutants defective in programmed cell death and discovered that TUNEL labels apoptotic cells only during a transient intermediate stage. Mutations in nuc-1 allowed the generation of TUNEL-reactive DNA but blocked the conversion of TUNEL-reactive DNA to a subsequent TUNEL-unreactive state. Completion of DNA degradation did not occur in the absence of cell-corpse engulfment. Our data suggest that the process of degradation of the DNA of a cell corpse occurs in at least three distinct steps and requires activities provided by both the dying and the engulfing cell.

Animals↗

Analysis of programmed cell death in the nematode Caenorhabditis elegans.

The nematode Caenorhabditis elegans has been shown to be an excellent model organism with which to study the mechanisms of programmed cell death because of its powerful genetics and the ability to study cell death with single-cell resolution. In this chapter, we describe methods that are commonly used to examine various aspects of programmed cell death in C. elegans. These methods, in combination with genetic analyses, have helped identify and characterize many components of the C. elegans cell death pathway, illuminating the mechanisms by which these components affect programmed cell death.

Animals↗

ent-kaurane diterpenoids from Annona glabra.

Three new kaurane diterpenoids, annoglabasin C (16alpha-acetoxy-ent-kauran-19-oic acid-17-methyl ester) (1), annoglabasin D (16alpha-acetoxy-ent-kauran-19-al-17-methyl ester) (2), and annoglabasin E (16alpha-hydro-19-ol-ent-kauran-17-oic acid) (3), and a new norkaurane diterpenoid, annoglabasin F (16alpha-acetoxy-19-nor-ent-kauran-4alpha-ol-17-methyl ester) (4), along with 13 known kaurane derivatives were isolated from the stems of Annona glabra. 16alpha-Methoxy-ent-kauran-19-oic acid (5) and 16alpha-hydro-ent-kauran-17,19-dimethyl ester (6) were obtained for the first time as natural products. The structures of compounds 1-6 were characterized by spectral analysis.

Diterpenes↗

Aristolactams and dioxoaporphines from Fissistigma balansae and Fissistigma oldhamii.

Investigation of extracts of Fissistigma balansae and Fissistigma oldhamii resulted in the isolation of 11 aristolactams-stigmalactam (1), piperolactam A (2), piperolactam C (3), aristolactam AII (4), aristolactam AIIIa (5), aristolactam BII (6), aristolactam BIII (7), aristolactam FII (8), goniothalactam (9), enterocarpam I (10), and velutinam (11)-as well as two dioxoaporphines, noraristolodione (12) and norcepharadione B (13). The new compound 1 was identified by spectral data interpretation. Compounds 1-13 were subjected to antiplatelet aggregation testing.

Animals↗

Tupichigenin A, a new steroidal sapogenin from Tupistra chinensis.

From the underground parts of Tupistra chinensis, a novel polyhydroxylated spirostanol sapogenin, tupichigenin A [(20S, 22R)-spirost-25(27)-ene-1beta,2beta,3beta,5beta- tetraol] (1), was isolated and determined structurally on the basis of spectroscopic methods. Also isolated was the known steroidal sapogenin (20S, 22R)-spirost-25(27)-ene-1beta,2beta,3beta,4beta, 5beta, 7alpha-hexaol-6-one (2).

China↗

New alkaloids from Annona purpurea.

Three new alkaloids, promucosine (1), romucosine F (2), and romucosine G (3), along with 28 known compounds, were isolated from the MeOH extract of stems of Annona purpurea. The structures of 1-3 were determined on the basis of spectral data and chemical evidence.

Alkaloids↗

Combining radiation therapy with interleukin-3 gene immunotherapy.

The goal of this study was to explore immunological strategies to increase local and systemic tumor control in patients receiving radiation therapy. In previous studies, interleukin-3 (IL-3) gene expression within murine tumors was shown to increase their response to irradiation through immune mechanisms. In this study, the efficacy of systemically administered IL-3 gene-transduced irradiated tumor cell vaccines was tested for their ability to augment radiation responses against established immunogenic (FSAR) and nonimmunogenic (FSAN) tumors. Vaccines of irradiated FSAR/FSAN or FSAN-JmIL-3/FSAR-JmIL-3 cells were given intraperitoneally just before and after local irradiation of parental tumors with diameters of 8 mm, as well as in two booster doses. The IL-3 gene-transduced tumor cell vaccines were more effective than the parental vaccines at delaying tumor growth after irradiation, although no complete cures resulted. Responses were largely specific to the tumor type, indicating that tumor-specific immunity was enhanced by IL-3 vaccine administration. When the experiment was repeated in the C3H/HeJ mice, which are deficient in tumor necrosis factor-alpha production, the vaccines were still effective, but less so than in C3H/HeN mice. Systemic IL-3 vaccine treatment increased intratumoral levels of intercellular adhesion molecule-1, Mac-1, EB22/5.3, tumor necrosis factor-alpha, and IL-1 mRNA in irradiated tumors, indicating that cellular infiltration was part of the response. The study demonstrates that local radiation therapy can enhance the efficacy of genetically altered vaccine-based immunotherapy for cancer by decreasing tumor burden. At the same time, tumor cell vaccines may improve the cure rate of local radiation therapy by eliminating residual cancer cells. Although less effective than intratumoral gene expression, administration of IL-3 gene-transduced tumor cell vaccines is clinically a more feasible strategy that may be useful in situations in which the tumor load is small.

Animals↗

A novel mutation in the hepatocyte nuclear factor-1alpha/MODY3 gene in Chinese subjects with early-onset Type 2 diabetes mellitus in Taiwan.

AIMS: The goal of this study was to determine the frequency of mutation in hepatic nuclear factor (HNF)-1alpha, a gene recently implicated as causing maturity-onset diabetes of the young (MODY) and to analyse the respective clinical presentations in an ethnically Chinese population. METHODS: Fifteen unrelated subjects (nine females and six males) aged less than 35 years who had early-onset diabetes were analysed to test the possibility that mutation of the HNF-1alpha gene was responsible for this disorder. Genomic DNA extraction, polymerase chain reaction and DNA sequence analysis were performed accordingly. RESULTS: One patient with MODY had a novel missense mutation in exon 3 of the HNF-1alpha gene (Y218C) in a region of the protein that corresponds to a predicted DNA binding domain. CONCLUSIONS: A Y218C mutation in HNF-1alpha gene was identified in one family in Taiwan.

Adolescent↗

Mechanisms for the formation of glycoxidation products in end-stage renal disease.

BACKGROUND: Advanced glycation end products (AGEs) accumulate on tissue and plasma proteins in patients with renal failure far in excess of normal aging or diabetes. The aim of these studies was to elucidate the nature of the precursors and the pathways that lead to an accelerated formation of two structurally identified AGEs [pentosidine and Nepsilon(carboxymethyl)lysine (CML)] in the uremic milieu. METHODS: Serum levels of the glycoxidation products, pentosidine and CML, were quantitated by high-performance liquid chromatography in uremic patients treated by dialysis. The formation of early glycation products (as furosine) and late glycoxidation products was modeled in uremic serum and in spent peritoneal dialysate. RESULTS: Clinical factors that affect circulating levels of AGEs included dialysis clearance and dialyzer membrane pore size, but not the presence or absence of diabetes. Both pentosidine and CML form at an accelerated rate in serum from uremic patients. Chelating agents most effectively slow the formation in vitro. In uremic fluids, the primary mechanism of formation of pentosidine is through the Amadori pathway. The primary mechanism of formation of CML is through metal-chelated autoxidation of reducing sugars generating reactive carbonyl precursors. In uremic serum, the presence of an unidentified reactive low molecular weight precursor accelerates the formation of pentosidine. CONCLUSIONS: The formation of the two glycoxidation products, pentosidine and CML, proceeds by different pathways and is enhanced by different precursors in the uremic milieu. The formation of both AGEs is markedly enhanced by metal-catalyzed reactions, evidence for the presence of increased metal-ion mediated oxidant stress in uremia.

Adult↗

Thoracoscopic removal of intrathoracic neurogenic tumors: a combined Chinese experience.

OBJECTIVE: To review the surgical and clinical results of minimally invasive resection of intrathoracic neurogenic tumors using a video-assisted thoracoscopic technique. SUMMARY BACKGROUND DATA: Thoracoscopy has emerged as a possible means for diagnosing and managing various intrathoracic disorders. Benign intrathoracic tumors often are ideal lesions for resection using a video-assisted technique. The authors report on their combined experience with the thoracoscopic resection of 143 intrathoracic neurogenic tumors. METHODS: Between March 1992 and February 1999, 143 patients with intrathoracic neurogenic tumors were diagnosed and underwent resection using video-assisted thoracoscopic techniques in three teaching centers. Case selection, surgical technique, and clinical results were reviewed. RESULTS: The average age of the patients was 40.8 years; 57.3% were male. Thirty-eight patients (27%) had symptoms attributable to the masses. Seventy-two masses were neurofibromas, 33 were neurilemmomas, 7 were paragangliomas, and 31 were ganglioneuromas. All but seven tumors were located in the posterior mediastinum. The masses were on average 3.5 cm in greatest diameter. The mean surgical time was 40 minutes, and the average hospital stay was 4.1 days. There were no major postoperative complications or recurrences to date. Nine patients reported paresthesias over the chest wall during a mean follow-up of 29 months. CONCLUSIONS: Resection of intrathoracic neurogenic tumors using a thoracoscopic technique based on standard surgical indications would seem to be appropriate. Most of these masses are benign and readily removed. For dumbbell tumors, a combined thoracic and neurosurgical approach is mandatory.

Adult↗

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↗

Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial.

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) is reduced after subarachnoid hemorrhage (SAH), and symptomatic vasospasm is a major cause of morbidity and mortality. Volume expansion has been reported to increase CBF after SAH, but CBF values in hypervolemic (HV) and normovolemic (NV) subjects have never been directly compared. METHODS: On the day after aneurysm clipping, we randomly assigned 82 patients to receive HV or NV fluid management until SAH day 14. In addition to 80 mL/h of isotonic crystalloid, 250 mL of 5% albumin solution was given every 2 hours to maintain normal (NV group, n=41) or elevated (HV group, n=41) cardiac filling pressures. CBF ((133)xenon clearance) was measured before randomization and approximately every 3 days thereafter (mean, 4.5 studies per patient). RESULTS: HV patients received significantly more fluid and had higher pulmonary artery diastolic and central venous pressures than NV patients, but there was no effect on net fluid balance or on blood volume measured on the third postoperative day. There was no difference in mean global CBF during the treatment period between HV and NV patients (P=0.55, random-effects model). Symptomatic vasospasm occurred in 20% of patients in each group and was associated with reduced minimum regional CBF values (P=0.04). However, there was also no difference in minimum regional CBF between the 2 treatment groups. CONCLUSIONS: HV therapy resulted in increased cardiac filling pressures and fluid intake but did not increase CBF or blood volume compared with NV therapy. Although careful fluid management to avoid hypovolemia may reduce the risk of delayed cerebral ischemia after SAH, prophylactic HV therapy is unlikely to confer an additional benefit.

Adult↗

A novel agarofuran sesquiterpene, celahin D from Celastrus hindsii Benth.

A novel agarofuran sesquiterpene polyol ester, 1beta,2beta,6alpha,15beta-tetracetoxy-8 beta,9alpha-dibenzoyloxy-beta- dihydroagarofuran (celahin D) (1), two known analogues of 1,1beta-acetoxy-8beta,9alpha-dibenzoyloxy-4al pha6alpha-dihydroxy-2beta(alphamethylbutanoyloxy)-beta-++ +dihydroagarofuran (2) and beta-acetoxy-8beta,9alpha-dibenzoyloxy-6alpha-hy droxy-2beta(alpha -methylbutanoyloxy)-beta-dihydroagarofuran (3), and a known cytotoxic sesquiterpene pyridine alkaloid, emarginatine E (4) were isolated from the stems of Celastrus hindsii Benth. Three known triterpenes, loranthol (5), lupenone (6) and friedelinol (7) were also obtained from the titled plant. Structural elucidation of compound 1 was established by 2D NMR spectra.

Magnetic Resonance Spectroscopy↗

Spirostanol sapogenins from the underground parts of Tupistra chinensis.

Chemical examination of the underground parts of Tupistra chinensis led to the isolation of two new 5beta-spirostane type steroidal sapogenins, tupichigenin B (1) and C (2), together with two known steroidal sapogenins, ranmogenin A (3) and delta25(27)-pentrogenin (4). The structures of 1 and 2 were established as spirost-25(27)-ene-1beta,3beta,4beta,5beta,6b eta-pentaol and 1beta,2beta,3beta,4beta,5beta-pentahydroxyspi rost-25(27)-en-6-one, respectively, on the basis of detailed analysis of their physical and spectral data.

China↗

Vertical alignment axis for transtibial prostheses: a simplified alignment method.

BACKGROUND AND PURPOSE: To evaluate a simplified method of alignment for fitting a transtibial prosthesis known as the vertical alignment axis method. METHODS: We measured the relationship between the vertical projection of the prosthetic socket center (geometric center of the cross section of the transtibial prosthetic socket at the level of the patella tendon bar) and the alignment reference center (junction of the middle and posterior thirds of the longitudinal axis of the shoe) in 36 dynamically aligned transtibial prostheses. The prostheses were fabricated by students, and the fit (proper vs improper) was assessed by the faculty. RESULTS: The faculty members found 26 of the 36 prostheses to be properly fitted. The vertical projections of the socket centers of the properly-fitted prostheses were concentrated within a small area of the shoe tracing (a mean value of 1.3 mm medially and 6.4 mm anteriorly from the alignment reference center). Conversely, in the improperly-fitted prostheses, the vertical projections of the socket center were scattered well away from the alignment reference center; the mediolateral deviation was significantly greater for improperly-fitted prostheses than for those that were properly fitted (p < 0.001). CONCLUSIONS: These results demonstrate the usefulness of the vertical alignment axis procedure. This procedure may help clinicians to better understand the alignment of transtibial prostheses and gait deviations associated with improper prosthesis fit.

Adult↗

Clinical significance of serum soluble interleukin 2 receptor-alpha in esophageal squamous cell carcinoma.

Although the serum level of soluble interleukin-2 receptor alpha (sIL-2Ralpha) has been shown to correlate with progression and prognosis of several cancers, data to support its clinical significance to esophageal squamous cell carcinoma (ESCC) are limited. This study was conducted to assess the prognostic value and source of sIL-2Ralpha in patients with ESCC. From January 1986 to June 1997, 125 patients with histopathologically confirmed ESCC were enrolled for study. Ninety-three patients underwent en bloc esophagectomy, and 32 patients with unresectable tumor underwent palliative surgery. Four (4.3%; 4 of 93) patients died of surgical complications. Serum levels of sIL-2Ralpha were measured by ELISA. Expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma in the pathological section was determined, respectively, by immunohistochemistry (IHC) and in situ hybridization (ISH). Compared with the healthy control group (1020 +/-476 pg/ml, n = 103), ESCC patients tended to have significantly higher serum sIL-2Ralpha concentrations (1424 +/- 798 pg/ml, n = 121). The sIL-2Ralpha level was correlated with age, Tumor-Node-Metastasis classification, tumor stage, reading score of the IHC staining, and survival but not with the pathological grade or lymphovascular invasion. Prognosis was worse for patients with high sIL-2Ralpha levels (> or =1500 pg/ml) than for those with low serum sIL-2Ralpha levels (< 1500 pg/ml; P = 0.0209). It can be used as an independent prognostic factor of ESCC. In the pathological sections, expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma was detected in 17 (18.1%), 83 (89.2%), and 83 (89.2%) cases, respectively, by IHC, and the message of IL-2Ralpha was identified in tumor cells by ISH in 30.1% (28 of 93) of the cases. Serum concentrations of sIL-2Ralpha are frequently elevated in ESCC patients and are correlated with disease progression and survival. These data indicate that, in addition to activated T cells, cancer cells could be an important source of sIL-2Ralpha in ESCC patients.

Aged↗

Association of HLA-te22 antigen with anti-nuclear antibodies in Chinese patients with erosive oral lichen planus.

The purpose of this study was to determine the frequencies of the presence of serum anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA) in 76 patients with oral lichen planus (OLP), in 77 patients with other oral mucosal diseases, and in 41 healthy control subjects. HLA phenotypes in some of the patients with OLP and recurrent aphthous ulcers (RAU) were determined to show whether there was an association of HLA antigens with the presence of autoantibodies. Indirect immunofluorescence techniques with mouse liver or stomach as the substrate were used to detect the serum ANA or SMA, respectively. The B lymphocytes isolated from peripheral blood were used for HLA typing by means of a standard microcytotoxicity assay. We found that the positive rate of serum ANA in patients with OLP (29%, p < 0.01), especially in patients with erosive OLP (34%, p < 0.001), was significantly higher than that in the normal control subjects (5%). The frequency of serum SMA in patients with OLP (20%, p < 0.01), in patients with RAU (17%, p < 0.01), or in patients with oral squamous cell carcinomas (41%, p < 0.001) was also significantly higher than that in normal control individuals (0%). In the erosive OLP group, the HLA-Te22 antigen occurred more frequently in patients with positive ANA (75%, p < 0.05) than in those with negative ANA (25%). We conclude that there is an association of HLA-Te22 antigen with ANA in Chinese patients with erosive OLP.

Adolescent↗