Biomedical subjects

J Y Hsu

Publications and source records attributed to J Y Hsu.

At least 19 recordsLinked to original sources

PubMed2004

Nanolayer parametric instability in near-field optics.

Parametric decay of electromagnetic waves into two Langmuir oscillations near the quarter critical density is suggested as being attributable to an enhanced electric field and to surface-enhanced Raman scattering in near-field optics. A nanolayer of silver aggregates localizes the wave in the evanescent region to a one-wavelength span and results in a wave-number mismatch as well as in a reduced growth rate. The fastest-growing mode has a growth rate that scales with the square root of the nanolayer's thickness.

Journal Article↗

PubMed2003

Derivation of the density functional theory from the cluster expansion.

The density functional theory is derived from a cluster expansion by truncating the higher-order correlations in one and only one term in the kinetic energy. The formulation allows self-consistent calculation of the exchange correlation effect without imposing additional assumptions to generalize the local density approximation. The pair correlation is described as a two-body collision of bound-state electrons, and modifies the electron- electron interaction energy as well as the kinetic energy. The theory admits excited states, and has no self-interaction energy.

Journal Article↗

PubMed2001

Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.

We have discovered an early mitotic inhibitor, Emi1, which regulates mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Emi1 is a conserved F box protein containing a zinc binding region essential for APC inhibition. Emi1 accumulates before mitosis and is ubiquitylated and destroyed in mitosis, independent of the APC. Emi1 immunodepletion from cycling Xenopus extracts strongly delays cyclin B accumulation and mitotic entry, whereas nondestructible Emi1 stabilizes APC substrates and causes a mitotic block. Emi1 binds the APC activator Cdc20, and Cdc20 can rescue an Emi1-induced block to cyclin B destruction. Our results suggest that Emi1 regulates progression through early mitosis by preventing premature APC activation, and may help explain the well-known delay between cyclin B/Cdc2 activation and cyclin B destruction.

Adenosine Triphosphatases↗

PubMed2001

Reduced 1alpha-hydroxylase activity in human prostate cancer cells correlates with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition.

Evidence from epidemiological, molecular, and genetic studies suggests a role for vitamin D in the development and/or progression of prostate cancer. In experimental models and clinical trials, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was shown to exert antiproliferative, prodifferentiating, and antimetastatic/invasive effects on prostatic epithelial cells. Because the direct clinical application of 1,25(OH)2D3 is limited by the major side effect of hypercalcemia, we investigated the potential therapeutic utility of its less calcemic precursor, 25-hydroxyvitamin D3 [25(OH)D3], which is converted locally within the prostate to 1,25(OH)2D3 by 1alpha-hydroxylase. Quantification of 1alpha-hydroxylase activity in human prostatic epithelial cells by enzyme-substrate reaction analyses revealed a significantly decreased activity in cells derived from adenocarcinomas compared with cells derived from normal tissues or benign prostatic hyperplasia (BPH). In growth assays, we found that 25(OH)D3 inhibited growth of normal or BPH cells similarly to 1,25(OH)2D3. In contrast, in primary cultures of cancer cells and established cell lines, the antiproliferative action of 25(OH)D3 was significantly less pronounced than that of 1,25(OH)2D3. Our results indicate that growth inhibition by 25(OH)D3 depends on endogenous 1alpha-hydroxylase activity, and that this activity is deficient in prostate cancer cells. This finding has ramifications for both the prevention and therapy of prostate cancer with vitamin D compounds.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed2000

Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes.

Phosphorylation of histone H3 at serine 10 occurs during mitosis and meiosis in a wide range of eukaryotes and has been shown to be required for proper chromosome transmission in Tetrahymena. Here we report that Ipl1/aurora kinase and its genetically interacting phosphatase, Glc7/PP1, are responsible for the balance of H3 phosphorylation during mitosis in Saccharomyces cerevisiae and Caenorhabditis elegans. In these models, both enzymes are required for H3 phosphorylation and chromosome segregation, although a causal link between the two processes has not been demonstrated. Deregulation of human aurora kinases has been implicated in oncogenesis as a consequence of chromosome missegregation. Our findings reveal an enzyme system that regulates chromosome dynamics and controls histone phosphorylation that is conserved among diverse eukaryotes.

Animals↗

PubMed2000

E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors.

In human epidermis, functional symbiosis requires homeostatic balance between keratinocytes and melanocytes. Compelling evidence from co-culture studies demonstrated a sophisticated, multileveled regulation of normal melanocytic phenotype orchestrated by undifferentiated, basal-type keratinocytes. Keratinocytes control cell growth and dendricity, as well as expression of melanoma-associated cell surface molecules of normal melanocytes. In contrast, melanoma cells are refractory to the keratinocyte-mediated regulation. The loss of regulatory dominance by keratinocytes occurs in concert with down-regulation of E-cadherin expression in melanoma cells. To investigate the potential role of E-cadherin in melanoma-keratinocyte interaction, we transduced E-cadherin-negative melanoma cells with full-length E-cadherin cDNA using an adenoviral vector. Our results show that functional E-cadherin expression in melanoma cells leads to cell adhesion to keratinocytes rendering them susceptible for keratinocyte-mediated control. In a skin reconstruction model, ectopic E-cadherin expression inhibits invasion of melanoma cells into dermis by down-regulating invasion-related adhesion receptors, MelCAM/MUC18 and beta3 integrin subunit, and by induction of apoptosis. Thus, disruption of the E-cadherin-mediated, normal regulatory control from keratinocytes may represent one of the mechanisms accounting for melanocyte transformation.

Adenoviridae↗

PubMed2000

The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases.

Recently, many new examples of E3 ubiquitin ligases or E3 enzymes have been found to regulate a host of cellular processes. These E3 enzymes direct the formation of multiubiquitin chains on specific protein substrates, and - typically - the subsequent destruction of those proteins. We discuss how the modular architecture of E3 enzymes connects one of two distinct classes of catalytic domains to a wide range of substrate-binding domains. In one catalytic class, a HECT domain transfers ubiquitin directly to substrate bound to a non-catalytic domain. Members of the other catalytic class, found in the SCF, VBC and APC complexes, use a RING finger domain to facilitate ubiquitylation. The separable substrate-recognition domains of E3 enzymes provides a flexible means of linking a conserved ubiquitylation function to potentially thousands of ubiquitylated substrates in eukaryotic cells.

Animals↗

PubMed2000

Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14.

Multiple covalent modifications exist in the amino-terminal tails of core histones, but whether a relationship exists between them is unknown. We examined the relationship between serine 10 phosphorylation and lysine 14 acetylation in histone H3 and have found that, in vitro, several HAT enzymes displayed increased activity on H3 peptides bearing phospho-Ser-10. This augmenting effect of Ser-10 phosphorylation on acetylation by yGcn5 was lost by substitution of alanine for arginine 164 [Gcn5(R164A)], a residue close to Ser-10 in the structure of the ternary tGcn5/CoA/histone H3 complex. Gcn5(R164A) had reduced activity in vivo at a subset of Gcn5-dependent promoters, and, strikingly, transcription of this same subset of genes was also impaired by substitution of serine 10 to alanine in the histone H3 tail. These observations suggest that transcriptional regulation occurs by multiple mechanistically linked covalent modifications of histones.

Acetylation↗

PubMed2000

Diffuse leiomyomatosis of the esophagus.

BACKGROUND: Leiomyomas are rare esophagus neoplasms. They are usually solitary, and the diffuse lesion is extremely rare. CASE REPORT: A 19-year-old male presented with a 3-year history of occasional dysphagia and postprandial regurgitation. The chest radiographs showed a huge mass in the posterior mediastinum. Barium esophagograms showed narrowing of the middle third esophagus with proximal dilatation. The fibroesophagoscopy demonstrated multiple submucosal nodules below a level 22 cm from the incisor and covered with intact mucosa. CT scans of the chest showed a long segment of circumferential soft tissue in the posterior mediastinum which encircled and involved the upper two thirds of the esophagus. An intrathoracic esophagectomy with cervical esophagogastrostomy via the substernal route was performed. Grossly, multiple confluent myomatous nodules circumferentially involved the upper and middle third of the esophagus. Histologic findings showed diffuse leiomyomatosis of the esophagus. CONCLUSION: Esophageal leiomyomatosis should be considered in a young patient with long-standing dysphagia in whom smooth, tapered esophageal narrowing on barium study and circumferential esophageal wall thickening on CT scan are seen. An esophagectomy combined with a reconstruction procedure is indicated.

Adult↗

PubMed1999

Expression and cellular localization of ribonucleotide reductase small subunit M2 protein in hydroxyurea-resistant Leishmania mexicana amazonensis.

We raised a specific antiserum against the recombinant M2 subunit protein of ribonucleotide reductase of Leishmania mexicana amazonensis in rabbit. This antiserum was used to study the expression and cellular location of the M2 protein in wildtype as well as hydroxyurea-resistant variants (HuR) of the parasite. The protein increased with increasing dose of the drug used for selection of resistance. The increase in protein level was accompanied by an increase in the copy numbers of mRNA of the M2 gene in the variants. In contrast to mammalian cells, the M2 protein of Leishmania is located in the nucleus rather than in the cytoplasm. The number of cells expressing M2 protein is also different in mammalian cells versus Leishmania. In mammalian cells, expression of M2 protein is a strictly S-phase-correlated event and in exponentially growing cells only approximately 50% of the cells are in S-phase and only these cells synthesize M2 protein. In L. m. amazonensis, however, almost all exponentially growing cells are positive for M2 protein. This makes it unlikely that M2 protein expression in Leishmania is S-phase dependent. In view of these findings, a fresh look in the future into the regulatory mechanisms of synthesis and the site of action of RNR in L. m. amazonensis is warranted.

Animals↗

PubMed1999

Characterization by pulse-field electrophoresis of a new region of DNA amplification containing the M2 subunit of ribonucleotide reductase in hydroxyurea-resistant Leishmania.

An extrachromosomal circular DNA of of approximately 50-kb size was amplified in the hydroxyurea-resistant variant of Leishmania mexicana amazonensis. The amplicon carried the M2 gene of ribonuleotide reductase as part of the gene encoding resistance to hydroxyurea. The amplicon was unstable. It disappeared rapidly as shown in pulse-field gradient electrophoresis gels after reversion of the cells for 20-80 days. This loss of amplified DNA was accompanied by a rapid loss of resistance to hydroxyurea during the same period. The amplicon was not hybridized to specific probes from any of the four regions of DNA amplification previously reported for Leishmania. This region of amplification thus appears to be a new region of DNA amplification in Leishmania.

Animals↗

PubMed1998

ET-1 expression and growth inhibition of prostate cancer cells: a retinoid target with novel specificity.

Endothelin-1 (ET-1) is not only a potent vasoconstrictor but also serves as an important growth stimulator in various cancers, including breast, cervical, pancreatic, and prostate cancer. This suggests that blockage of ET-1 production may suppress tumor growth and possibly metastasis. We observed that certain synthetic retinoids, and all-trans-retinoic acid can repress LNCaP prostate cancer cell growth in vitro. In addition, these retinoid compounds counteracted exogenous ET-1-induced growth stimulation. Retinoid-dependent growth retardation of LNCaP cells coincided with suppression of ET-1 gene expression to a level undetectable by reverse transcription-PCR. Contrarily, the androgen-insensitive DU145 cells were refractory to retinoid treatment. To investigate the underlying mechanisms of the cell-specific response to retinoids, we transfected ET-1 promoter constructs containing wild-type or mutated AP-1 or GATA-2 site into prostate cancer cells. Distinct regulations of ET-1 promoter activity were found; in LNCaP cells, both binding sites are essential for optimal promoter activation, whereas in DU145 cells, additional promoter sequences and/or transcriptional factors seem to be involved. Furthermore, several anti-AP-1 selective retinoids failed to repress ET-1 promoter activity and to exhibit a cell growth-inhibitory effect on LNCaP cells, suggesting that different retinoid structural configurations are required for the inhibition of an AP-1 complex versus an AP-1/GATA-2 complex.

DNA-Binding Proteins↗

PubMed1998

Adenoviral gene transfer of beta3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma.

Expression of the beta3 subunit of the alphavbeta3 vitronectin receptor on melanoma cells is associated with tumor thickness and the ability to invade and metastasize. To address the role of alphavbeta3 in the complex process of progression from the nontumorigenic radial to the tumorigenic vertical growth phase of primary melanoma, we examined the biological consequences of overexpressing alphavbeta3 in early-stage melanoma cells using an adenoviral vector for gene transfer. Overexpression of functional alphavbeta3 in radial growth phase primary melanoma cells 1) promotes both anchorage-dependent and -independent growth, 2) initiates invasive growth from the epidermis into the dermis in three-dimensional skin reconstructs, 3) prevents apoptosis of invading cells, and 4) increases tumor growth in vivo. Thus, alphavbeta3 serves diverse biological functions during the progression from the nontumorigenic radial growth phase to the tumorigenic and-invasive vertical growth phase primary melanoma.

Adenoviridae↗

PubMed1998

Color Doppler ultrasound pulsatile flow signals of thoracic lesions: comparison of lung cancers and benign lesions.

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p < 0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p < 0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p < 0.01; for PI, all p< or =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p > 0.05 for RI and PI), and even a significant difference from SCC (p < 0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.

Adenocarcinoma↗

PubMed1998

Ultrasound-guided small-bore Elecath tube insertion for the rapid sclerotherapy of malignant pleural effusion.

BACKGROUND: Traditional pleurodesis for malignant pleural effusion is performed by large-bore chest tube insertion with the instillation of sclerosing agents after the compressed lung re-expansion and pleural fluid drainage of 100-150 ml/day. This study was carried out to evaluate the possibility of rapid sclerotherapy for malignant pleural effusions by insertion of a small-bore Elecath tube (12-French) under ultrasound guidance and intrapleural injection of bleomycin 60 IU. METHODS: Twenty-six patients, with 28 cytopathologically proven malignant pleural effusions (two patients had bilateral pleural effusions) and receiving the insertion of the Elecath tube for drainage, were included in our series. This rapid and short-term sclerosing method was performed and completed by intrapleural injection of bleomycin when the pleural effusion had been clearly drained by the small-bore Elecath tube and the compressed lung had fully re-expanded on follow-up chest radiographs. RESULTS: Twenty patients with 22 pleural effusions underwent the intrapleural injection of bleomycin, with the results of pleurodesis being complete response 41% (9/22), partial response 36% (8/22) and failure 23% (5/22). Interestingly, among the 17 successful procedures of pleurodesis (complete response and partial response), 71% (12) procedures could be completed within 2 days (seven within one day and five within 2 days). The remaining unsuccessful procedures carried out on six patients without the injection of bleomycin were due to a non-re-expanded lung (n = 3) and inadequate drainage (n = 3); of these, four patients also received the large-bore chest tube insertion after the removal of the Elecath tube, but the compressed lung still could not re-expand. The complications of the bleomycin injection were fever [77% (17/22)], vomiting [14% (3/22)] and hiccup [5% (1/22)]. CONCLUSION: The method of rapid sclerotherapy for malignant pleural effusions by small-bore Elecath tube is promising, with a success rate achieving 77%, usually within 2 days.

Bleomycin↗

PubMed1998

Preliminary result of phase II study of paclitaxel and cisplatin chemotherapy for advanced non-small-cell lung cancer in Chinese patients.

This phase II study was designed to assess the response rate and toxicity of paclitaxel and cisplatin chemotherapy in Chinese patients with untreated advanced non-small-cell lung cancer (NSCLC). Eligibility requirements included histologically confirmed stage IIIb-IV NSCLC, Eastern Cooperative Oncology Group performance status less than 2, no previous chemotherapy, and adequate bone marrow, renal, and hepatic function. From April 1996 through March 1997, 32 patients were treated. The dose of paclitaxel was 135 mg/m2 as a 3-hour infusion on day 1 and cisplatin 75 mg/m2 on day 2. The regimen was repeated every 3 to 4 weeks for up to 6 to 8 cycles unless there was evidence of tumor progression. The median age was 57 years (range, 31-77 years). Sixty-five percent were men. Sixty-nine percent had adenocarcinoma, and 75% had stage IV disease. One hundred seventy-two cycles were administrated; 18 patients (56%) completed all six cycles. Peripheral neuropathy and myelosuppression were the principle toxicities. Neurotoxicity appeared to be dose limiting and manifested primarily as paresthesia. Grade 2 neurotoxicity was observed in 5% of courses, which was slowly reversible. However, the severity of myelosuppression was generally mild to moderate. No episode of neutropenic fever was noted. Thrombocytopenia remained infrequent throughout the study. Other nonhematologic toxicities were also generally mild. The objective response rate was 50%. In conclusion, this combination of paclitaxel and cisplatin is active in Chinese patients with advanced NSCLC. It merits further investigation in phase III trials.

Adult↗

PubMed1997

Ultrasound-guided fine needle aspiration biopsy in the diagnosis of chronic pulmonary infection.

Fourteen patients, with abnormalities on their chest radiographs found over a period of > or = 4 weeks and diagnosed as chronic pulmonary infections in the follow-up, underwent ultrasound-guided fine-needle aspiration biopsy (US-guided FNAB). Six patients also underwent color Doppler ultrasound examination before needle aspiration biopsy. Nine patients had a confirmed diagnosis [tuberculosis (n = 1), cryptococcosis (n = 3), actinomycosis (n = 2), and aspergillosis (n = 1)] or a suggestive diagnosis [caseating granulomatous inflammation (n = 1) and caseous necrosis (n = 1)] made after US-guided FNAB. The remaining 5 patients were finally diagnosed by US-guided large-bore cutting biopsy (n = 1, tuberculosis) and surgical resection [aspergillosis and organized pneumonia (n = 1), mucormycosis and organized pneumonia (n = 1), penicillium infection and organized pneumonia (n = 1), and cryptococcosis (n = 1)]. In 8 patients receiving gray scale US examination only, complications developed in 2 patients after US-guided FNAB [minimal pneumothorax (n = 1) and hemoptysis (n = 1)]. Of the 6 patients who also underwent color Doppler US examination, 4 had detectable blood vessels within the lesion. Thus, the site for US-guided FNAB was changed in 2 patients to prevent injury to prominent blood vessels. There were no complications observed following color Doppler US examination. We conclude that US-guided FNAB is useful for diagnosing chronic pulmonary infections, and color Doppler US is valuable for preventing injury to blood vessels.

Adult↗

PubMed1997

Importance of sputum differential cell counting in the diagnosis of airway diseases.

We examined the sputum of 114 subjects by noninvasive methods (voluntary coughing or induced cough with hypertonic saline) to determine whether sputum examination could be used to separate patients with episodic wheezing, dyspnea or cough of unknown origin into different diagnostic categories. An increased percentage of sputum eosinophils was seen in 92% (48/52) of asthmatics, 36% (9/25) of patients with chronic obstructive pulmonary disease (COPD) and 28% (7/25) of chronic coughers, but not in any of the 12 patients with congestive heart failure (CHF). Eight patients with combined symptoms of COPD and asthma (mixed COPD subgroup) showed above average diurnal peak expiratory flow variation (10.3 +/- 2.1% vs 2.5 +/- 1.4%, p < 0.05) and an above average percentage of sputum eosinophils (19.8 +/- 9.1 vs 2.1 +/- 3.2, p < 0.01) than those in the pure COPD group. After therapeutic corticosteroid trial, all of the mixed COPD patients and six of the 17 pure COPD patients were steroid responders. Seven of the 25 chronic coughers had sputum eosinophilia, but no asthmatic symptoms. The cough symptoms subsided in five of these seven patients after steroid treatment but not in the other 18 chronic coughers. Further study is indicated to determine if simple eosinophilic bronchitis is an early stage of asthma. In conclusion, sputum differential cell counting is a useful noninvasive diagnostic tool in differentiating diseases with episodic wheezing or chronic cough.

Adolescent↗