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Biomedical subjects

P S Huang

Publications and source records attributed to P S Huang.

At least 19 recordsLinked to original sources
PubMed2001

Drug-targeting strategies in cancer therapy.

Genetic changes in cell-cycle, apoptotic, and survival pathways cause tumorigenesis, leading to significant phenotypic changes in transformed cells. These changes in the tumor environment - elevated expression of surface proteases, increased angiogenesis and glucuronidase activity - can be taken advantage of to improve the therapeutic index of existing cancer therapies. Targeting cytotoxics to tumor cells by enzymatic activation is a promising strategy for improving chemotherapeutics.

Antineoplastic Agents↗
PubMed2001

Cryogen spray cooling in conjunction with pulse dye laser treatment of port wine stains of the head and neck.

BACKGROUND: When a cryogen spurt is applied to the skin surface for an appropriately short period of time, the spatial distribution of cooling remains localized in the normal overlying epidermis, while leaving the temperature of deeper port wine stain (PWS) blood vessels unchanged. Furthermore, cooling continues after pulsed laser exposure as cryogen remaining on the surface evaporates and removes heat deposited by light absorption in epidermal melanin. The objective of this study was to evaluate the efficacy and advantages of cryogen spray cooling plus flashlamp-pumping in conjunction with dye laser treatment (CSC-LT) of PWS. METHODS: From 1996 to 2000, a retrospective study was conducted on 63 patients, consisting of 43 women and 20 men, between the ages of 8 and 62 years treated with pulsed dye laser (lambda = 585 nm, tau p = 450 microseconds) over a 4-year period. The duration of cryogen spurts and the delay period between cryogen delivery and laser illumination were controlled. An infrared focal plane array thermodetector measured changes of lesion surface temperature which were recorded. The subject was asked to score discomfort during treatment using a pain scale. The primary efficacy measure was the quantitative assessment of a blanching response score. RESULTS: The ambient skin surface temperature of PWS was 33.31 +/- 1.55 degrees C. The mean pain score for uncooled sites was 39.85 +/- 0.23 compared to 20.18 +/- 0.15 for cooled sites. There was a statistically significant difference in pain elimination between cooled and uncooled sites (p = 0.001). The mean blanching response score of CSC-LT was 3.70. A significant blanching response of PWS when receiving CSC-LT was noted. CONCLUSION: Our clinical studies demonstrate the feasibility of selective epidermal cooling while achieving photothermolysis of blood vessels during pulsed dye laser treatment of PWS.

Adolescent↗
PubMed2000

Development of a binding assay for p53/HDM2 by using homogeneous time-resolved fluorescence.

The p53 tumor suppressor protein is activated and stabilized in response to DNA damage, resulting in cell cycle arrest or apoptosis. HMD2 is a negative regulator of p53. Binding of p53 by HDM2 traffics p53 from the nucleus to the cytoplasm where it is recognized and targeted for ubiquitin-mediated degradation (D. A. Freedman, L. Wu, and A. J. Levine, 1999, Cell. Mol. Life Sci. 55, 96-107). Several reports have suggested that disruption of this complex in normal cells results in p53 signaling (V. Böttger, A. Böttger, A. Sparks, W.-L. Liu, S. F. Howard, and D. P. Lane, 1997, Curr. Biol. 7, 860-869; C. Wasylyk, R. Salvi, M. Argentini, C. Dureuil, I. Delumeau, J. Abecassis, L. Debussche, and B. Wasylyk, 1999, Oncogene 18, 1921-1934). A homogeneous time-resolved fluorescence (HTRF) assay has been developed to monitor p53/HDM2 binding. This assay employs a site-specific biotinylated p53 protein, a GST-fused HDM2 protein, and two fluorophore-conjugated detection reagents, streptavidin-XL665 and europium cryptate-labeled anti-GST antibody ¿Eu(K)-anti-GST. Binding of p53 to HDM2 brings the fluorophores into close proximity, allowing fluorescence resonance energy transfer to occur. Development of this assay and comparison to a traditional ELISA are described in this report. The HTRF assay was then utilized to assess the effect of serine phosphorylation within the p53 N-terminus on HDM2 binding, and to determine the relative affinity of a p73 peptide for HDM2.

Amino Acid Sequence↗
PubMed1999

Blood alcohol concentration among injured drivers in Hualien County.

Vehicle-related injuries are the major cause of death and injuries in Hualien County. Driving under the influence of alcohol plays a major role in such crashes. From December 1997 to May 1998, we determined the blood alcohol concentrations of 750 injured drivers from vehicle crashes, visiting the two emergency rooms of teaching hospitals in Hualien. The objectives of this study were to investigate the incidence of alcohol used in vehicle crashes, to identify the prevalence groups for prevention and to discuss alcohol testing at emergency services. Sixty-four percent were male; 27.5% were aborigines. The mean age was 36.5 +/- 16.5 years. About 54.1% tested positive for blood alcohol concentration (BAC), which ranged from 13 to 611 mg/dL; 38.6% had BAC levels exceeding 50 mg/dL and 21.1% exceeding 200 mg/dL. The mean BAC was 85.9 mg/dL (+/- 118.5). Middle-aged males and aborigines were more likely to drive under the influence of alcohol. We recommend blood alcohol testing to be mandatory at the emergency service and to be used as evidence for prosecution in a court of law. Preventing drunk driving through community programs is imperative, especially in the aboriginal communities.

Adolescent↗
PubMed1997

Oncogene products as therapeutic targets for cancer.

Enormous progress has been made in the last several years in delineating signal transduction pathways associated with cell proliferation and apoptosis. The components of these pathways, which include both oncogenes and tumor suppressors, may provide viable targets for therapeutic intervention for the treatment of cancer and other diseases. This review highlights some of these recent biologic and pharmacologic advances, focusing on the ras pathway and on p53-dependent apoptosis.

Antineoplastic Agents↗
PubMed1995

An SH3 domain is required for the mitogenic activity of microinjected phospholipase C-gamma 1.

Phospholipase activity is elevated in dividing cells. In response to growth factor stimulation, phospholipase C-gamma (PLC-gamma) binds to activated tyrosine kinase receptors via SH2 binding domains, resulting in phosphorylation of PLC-gamma and activation of its enzyme activity. These observations suggest that PLC-gamma participates in the signal transduction pathway employed by growth factors to promote mitogenesis. Consistent with this hypothesis, microinjection of purified bovine PLC-gamma into quiescent fibroblasts has been previously reported to initiate a mitogenic response [Smith et al. (1989) Proc. Natl. Acad. Sci. 86, 3659]. We have reproduced this result using recombinant rat PLC-gamma protein. Surprisingly, however, a catalytically inactive mutant of PLC-gamma, H335Q, also elicited a full mitogenic response. The capacity to induce mitogenesis by microinjection of PLC-gamma was mapped to the 'Z' domain of the protein, which contains PLC-gamma's SH2 and SH3 motifs. Inactivation of the phosphorylated tyrosine binding properties of both SH2 domains had no effect on the mitogenic activity of the Z-domain peptide. However, deletion of the SH3 domain resulted in a complete loss of activity. These results suggest that PLC-gamma's mitogenic properties do not require the enzyme's phospholipase activity, but are instead mediated by a novel pathway for mitogenic stimulation which is dependent upon an intact SH3 domain.

3T3 Cells↗
PubMed1994

Retinoblastoma protein reverses DNA bending by transcription factor E2F.

E2F is a mammalian transcription factor involved in cell cycle regulation. The retinoblastoma gene product, pRB, binds to E2F in a cell cycle-dependent manner and appears to turn E2F from a transcriptional activator into a repressor. We show here that in vitro binding of pRB has three major effects on the DNA binding properties of E2F affinity-purified from HeLa cells; pRB binding increases the half-life of E2F.DNA complexes 10-15-fold, it reduces E2F specific DNA binding in the presence of nonspecific DNA by sequestering E2F, and it partially reverses the DNA bending induced by E2F. Upon specific DNA binding, E2F induces a DNA bend with a flexure angle of 125 degrees. Both full-length pRB105 and the N-terminally truncated pRB60 bind to the E2F.DNA complex with a Kd,app of 150 pM and reduce the apparent DNA bending to less than 80 degrees. DNA footprinting analysis indicates that the nonspecific DNA binding activity of pRB is not involved in this effect. Our biochemical data suggest that transcriptional activation by E2F may involve DNA bending and that the reversal of bending upon binding of pRB may turn E2F into a repressor.

Base Sequence↗
PubMed1993

Transcription factor E2F binds DNA as a heterodimer.

E2F is a mammalian transcription factor that appears to play an important role in cell cycle control. DNA affinity column-purified E2F from HeLa cells reproducibly exhibits multiple protein bands when analyzed by SDS/PAGE. After electrophoretic purification, electroelution, and refolding of the individual protein components, the E2F DNA binding activity of the individual proteins was poor. However, upon mixing the individual components together, a dramatic (100- to 1000-fold) increase in specific DNA binding activity was observed. The five protein bands isolated can be separated into two groups based on apparent molecular mass. Optimal reconstitution of activity requires one of the two proteins found in the group of larger molecular mass (approximately 60 kDa) and one of the three proteins in the smaller-sized group (approximately 50 kDa). The reconstituted heterodimer is identical to authentic affinity-purified E2F by three criteria: DNA-binding specificity, DNA pattern, and binding to the retinoblastoma gene product. A recently cloned protein with E2F-like activity, RBP3/E2F-1, is related to the protein components of the group of larger molecular mass, as determined by Western blot analysis and reconstitution experiments. These data suggest that E2F, like many other transcription factors, binds DNA as an oligomeric complex composed of at least two distinct proteins.

Adenoviruses, Human↗
PubMed1993

Protein domains governing interactions between E2F, the retinoblastoma gene product, and human papillomavirus type 16 E7 protein.

Human papillomaviruses (HPVs) are the etiological agents for genital warts and contribute to the development of cervical cancer in humans. The HPV E7 gene product is expressed in these diseases, and the E7 genes from HPV types 16 and 18 contribute to transformation in mammalian cells. Mutation and deletion analysis of this gene suggests that the transforming activity of the protein product resides in the same domain as that which is directly involved in complex formation with the retinoblastoma gene product (pRB). This domain is one of two conserved regions (designated CRI and CRII) shared by E7 and other viral oncoproteins which bind pRB, including adenovirus E1A protein. Binding of HPV type 16 E7 protein to pRB has previously been shown to affect pRB's ability to bind DNA and to form complexes with other cellular proteins. In the current study, we map the functional interaction between E7 protein and pRB by monitoring the association between a 60-kDa version of the pRB, pRB60, and the cellular transcription factor E2F. We observe that CRII of E7 (amino acids 20 to 29), which completely blocks binding of full-length E7 protein, is necessary but not sufficient to inhibit E2F/pRB60 complex formation. While CRI of E1A (amino acids 37 to 55) appears to be sufficient to compete with E2F for binding to pRB60, the equivalent region of E7 is neither necessary nor sufficient. Only E7 fragments that contained both CRII and at least a portion of the zinc-binding domain (amino acids 60 to 98) inhibited E2F/pRB60 complex formation. These results suggest that pRB60 associates with E7 and E2F through overlapping but distinct domains.

Amino Acid Sequence↗
PubMed1993

[The establishment of genomic DNA libraries for the human malaria parasite Plasmodium falciparum].

The DNA of Plasmodium falciparum has been purified and fragmented with restriction endonuclease BamHI. The fragments have been incorporated in vitro into derivatives of bacteriophage lambda EMBL4 digested with BamHI and Sal I. The recombinant mixture has been ligated and packaged in vitro. The recombinant phages have been identified in E. coli L95 host cell and the libraries have been established in which most of the parasite DNA is represented. The ligation proportion of vector to insert is 3:1. The recombinant phages of 4 x 10(5) have been obtained. By plaque hybridization, we have been able to recover from these libraries specific clones containing repetitive DNA sequences.

Animals↗
PubMed1991

Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product.

The E7 transforming protein of human papilloma virus-16 binds to the retinoblastoma gene product (pRb) through a nine-amino-acid segment of E7 (21-29). This segment of E7 is homologous to the pRb-binding domains of the simian virus 40 large T and adenovirus E1A transforming proteins. Each of these viral transforming proteins bind to the same region of pRb. To isolate cellular proteins that interact with this viral protein-binding domain on pRb, we used recombinant pRb to screen a human complementary DNA expression library. Two cDNAs were isolated that encode retinoblastoma binding proteins (RBP-1 and RBP-2). We report here that these RBP genes exist in separate loci and produce discrete messenger RNAs. The predicted amino-acid sequence of these genes showed no homology to known proteins, but both RBPs contain the pRb binding motif conserved between E7, large T and E1A14. In vitro expression of the RBP cDNAs yielded proteins that specifically bound to pRb. Recombinant E7 protein, the E7 21-29 peptide and the homologous RBP-1 peptide inhibited RBP-pRb binding. Mutations introduced into the putative pRb-binding segment in RBP-1 impaired its binding activity. These studies indicate that the cellular RBP-1, RBP-2 and viral E7 proteins interact with pRb through similar domains.

Amino Acid Sequence↗
PubMed1991

Malignant carcinoid tumor metastatic to the dura mater simulating a meningioma.

A 50-year-old man, transferred from another hospital, was admitted because of adult onset seizures. Nine months earlier, he had undergone an esophagogastrectomy; the lesion was confirmed to be a carcinoid tumor. Laboratory tests, chest x-rays, and electrocardiogram were normal. A second liver and spleen scan was performed. A computed tomographic scan revealed a well-circumscribed homogeneous enhancement of a lesion in the left frontal superficial area. On the 10th day, the patient underwent a left frontal parietal craniotomy. Postoperatively, he manifested no residual neurological deficits and was discharged on the 6th postoperative day. A week later, he was readmitted for treatment of aphasia and right hemiparesis; he was treated and discharged. The patient survived 16 more months. The occurrence of central nervous system metastasis from carcinoid tumor is rare. This tumor resembled, in many respects, a parasagittal meningioma. Radiological findings on the computed tomographic scan were typical of these tumors. This patient was diagnosed as having metastatic disease just 9 months after the diagnosis of the primary tumor and 13 months from the onset of any symptoms. This is a short period of time compared with that reported in other cases.

Brain Neoplasms↗
PubMed1989

Klippel-Feil syndrome in association with a craniocervical dermoid cyst presenting as aseptic meningitis in an adult: case report.

Intracranial tumors associated with Klippel-Feil syndrome usually occur in children, with spinal tumors being more common in adults affected by the syndrome. A rare case of a dermoid cyst at the craniocervical junction presenting as aseptic meningitis in an adult with Klippel-Feil syndrome is described. A review of the literature on tumors associated with this syndrome is also presented.

Adult↗
PubMed1986

[Immunohistochemical and cytochemical analysis of lymphocytes and plasma cells in nasopharyngeal carcinoma].

Cytoplasmic IgA+, IgG+ and IgM+ in plasma cells, present in biopsy tissue of 68 patients with nasopharyngeal carcinoma (NPC) and 40 patients with chronic nasopharyngitis (CN), were studied by immunoperoxidase (PAP) technique. EB virus VCA-IgA serum antibody in all these patients was determined. At the same time, the activity of T lymphocytes of 41 patients (23 with NPC and 18 with CN) was investigated by alpha-naphthyl acetate esterase (ANAE) method. The number of T lymphocytes in NPC was far less than that in CN. This suggests that the impediment or deficiency in cellular immunity may promote the development and growth of tumor. The number of IgA+ plasma cells in NPC was obviously more than that in CN. As the increase in the level of VCA-IgA serum antibody in NPC patients corresponded to the increase in the number of IgA+ plasma cells in the tumor tissue, it was presumed that part of the IgA+ plasma cells might participate in the production and introduction of VCA-IgA antibody. We suggest that the examination of VCA-IgA serum antibody be a reliable screening test for NPC. No significant difference was found in the numbers of IgG+ plasma cells between NPC and CN. IgM+ plasma cells were rare in both.

Antigens, Viral↗