Search PubMed⌕ Search

Biomedical subjects

S Huang

Publications and source records attributed to S Huang.

At least 145 records · Page 8Linked to original sources
PubMed2000

Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis.

The distal portion of chromosome 1p is one of the most commonly affected regions in human cancer. In this study of hereditary and sporadic colorectal cancer, a region of frequent deletion was identified at 32.2 centimorgans from 1ptel. Deletion breakpoints clustered in the vicinity of or inside the gene RIZ, which encodes a retinoblastoma protein-interacting zinc finger protein. Sequence analysis revealed frequent frameshift mutations of the RIZ gene. The mutations consisted of 1- or 2-bp deletions of a coding (A)(8) or (A)(9) tract and were confined to microsatellite-unstable colorectal tumors, being present in 9 of 24 (37.5%) primary tumors and in 6 of 11 (54.5%) cell lines; in 2 cell lines the mutation was homozygous/hemizygous. The mutations apparently were selected clonally in tumorigenesis, because similar poly(A) tracts in other genes were not affected. Two alternative products of the gene exist, RIZ1, which contains a PR (PRDI-BF1-RIZ1) domain implicated in tumor suppressor function, and RIZ2, which is lacking this motif. Furthermore, the C-terminal region, which contains the poly(A) tracts, includes a PR-binding motif, possibly mediating interactions with other proteins or with RIZ itself (oligomerization). Four of eleven microsatellite-unstable colorectal cancer cell lines, three of which had frameshifts, showed reduced or absent mRNA expression of RIZ1. In a cell line that is homozygous/hemizygous for the typical frameshift mutation, immunoblotting showed truncated RIZ protein, whereas adenovirus-mediated RIZ1 expression caused G(2)/M arrest and apoptosis. We propose that RIZ is a target of the observed 1p alterations, with impairment of the PR domain-mediated function through either frameshift mutation or genomic deletion.

Apoptosis↗
PubMed2000

The LIM homeobox gene Lhx9 is essential for mouse gonad formation.

During mammalian embryonic development, the ovaries and testes develop from somatic cells of the urogenital ridges as indifferent gonads, harbouring primordial germ cells that have migrated there. After sex determination of the gonads, the testes produce testosterone and anti-Mullerian hormone which mediate male sexual differentiation, and the female developmental pathway ensues in their absence. Here we show that transcripts of the LIM homeobox gene Lhx9 are present in urogenital ridges of mice at embryonic day 9.5; later they localize to the interstitial region as morphological differentiation occurs. In mice lacking Lhx9 function, germ cells migrate normally, but somatic cells of the genital ridge fail to proliferate and a discrete gonad fails to form. In the absence of testosterone and anti-Mullerian hormone, genetically male mice are phenotypically female. The expression of steroidogenic factor 1 (Sf1), a nuclear receptor essential for gonadogenesis, is reduced to minimal levels in the Lhx9-deficient genital ridge, indicating that Lhx9 may lie upstream of Sf1 in a developmental cascade. Unlike mice lacking other genes that mediate early stages of gonadogenesis, Lhx9 mutants do not exhibit additional major developmental defects. Thus, LHX9 mutations may underlie certain forms of isolated gonadal agenesis in humans.

Animals↗
PubMed2000

Differential regulation of the phosphatidylinositol 3-kinase/Akt and p70 S6 kinase pathways by the alpha(1A)-adrenergic receptor in rat-1 fibroblasts.

Phosphatidylinositol (PI) 3-kinase and its downstream effector Akt are thought to be signaling intermediates that link cell surface receptors to p70 S6 kinase. We examined the effect of a G(q)-coupled receptor on PI 3-kinase/Akt signaling and p70 S6 kinase activation using Rat-1 fibroblasts stably expressing the human alpha(1A)-adrenergic receptor. Treatment of the cells with phenylephrine, a specific alpha(1)-adrenergic receptor agonist, activated p70 S6 kinase but did not activate PI 3-kinase or any of the three known isoforms of Akt. Furthermore, phenylephrine blocked the insulin-like growth factor-I (IGF-I)-induced activation of PI 3-kinase and the phosphorylation and activation of Akt-1. The effect of phenylephrine was not confined to signaling pathways that include insulin receptor substrate-1, as the alpha(1)-adrenergic receptor agonist also inhibited the platelet-derived growth factor-induced activation of PI 3-kinase and Akt-1. Although increasing the intracellular Ca(2+) concentration with the ionophore A23187 inhibited the activation of Akt-1 by IGF-I, Ca(2+) does not appear to play a role in the phenylephrine-mediated inhibition of the PI 3-kinase/Akt pathway. The differential ability of phenylephrine and IGF-I to activate Akt-1 resulted in a differential ability to protect cells from UV-induced apoptosis. These results demonstrate that activation of p70 S6 kinase by the alpha(1A)-adrenergic receptor in Rat-1 fibroblasts occurs in the absence of PI 3-kinase/Akt signaling. Furthermore, this receptor negatively regulates the PI 3-kinase/Akt pathway, resulting in enhanced cell death following apoptotic insult.

Animals↗
PubMed2000

Temperature trends over the past five centuries reconstructed from borehole temperatures

For an accurate assessment of the relative roles of natural variability and anthropogenic influence in the Earth's climate, reconstructions of past temperatures from the pre-industrial as well as the industrial period are essential. But instrumental records are typically available for no more than the past 150 years. Therefore reconstructions of pre-industrial climate rely principally on traditional climate proxy records, each with particular strengths and limitations in representing climatic variability. Subsurface temperatures comprise an independent archive of past surface temperature changes that is complementary to both the instrumental record and the climate proxies. Here we use present-day temperatures in 616 boreholes from all continents except Antarctica to reconstruct century-long trends in temperatures over the past 500 years at global, hemispheric and continental scales. The results confirm the unusual warming of the twentieth century revealed by the instrumental record, but suggest that the cumulative change over the past five centuries amounts to about 1 K, exceeding recent estimates from conventional climate proxies. The strength of temperature reconstructions from boreholes lies in the detection of long-term trends, complementary to conventional climate proxies, but to obtain a complete picture of past warming, the differences between the approaches need to be investigated in detail.

Journal Article↗
PubMed2000

The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain.

Transforming growth factor-beta (TGF-beta) family members signal through a unique set of intracellular proteins called Smads. Smad4, previously identified as the tumor suppressor DPC4, is functionally distinct among the Smad family, and is required for the assembly and transcriptional activation of diverse, Smad-DNA complexes. We previously identified a 48-amino acid proline-rich regulatory element within the middle linker domain of this molecule, the Smad4 activation domain (SAD), which is essential for mediating these signaling activities. We now characterize the functional activity of the SAD. Mutants lacking the SAD are still able to form complexes with other Smad family members and associated transcription factors, but cannot activate transcription in these complexes. Furthermore, the SAD itself is able to activate transcription in heterologous reporter assays, identifying it as a proline-rich transcriptional activation domain, and indicating that the SAD is both necessary and sufficient to activate Smad-dependent transcriptional responses. We show that transcriptional activation by the SAD is p300-dependent, and demonstrate that this activity is associated with a physical interaction of the SAD with the amino terminus of p300. These data identify a novel function of the middle linker region of Smad4, and define the role of the SAD as an important locus determining the transcriptional activation of the Smad complex.

Amino Acid Sequence↗
PubMed2000

Review: perinucleolar structures.

Several perinucleolar structures have been described in recent years. This review primarily summarizes recent studies regarding two of these structures, the perinucleolar compartment (PNC) and the Sam68 nuclear body (SNB). A number of studies have explored their ultrastructure and molecular components. Despite their different nuclear localizations, PNCs and SNBs share some common characteristics. They both are enriched with RNA binding proteins and nucleic acids and are predominantly localized to the periphery of the nucleolus. They are observed mostly in transformed cells, although prevalence differs among different cell types and cell lines. Their structural integrity is influenced by the transcriptional state of the cell. However, the functions of both the PNC and the SNB remain unknown. In addition to the PNC and SNB, a perinucleolar structure immunolabeled with an antibody to hnRNP L will be discussed.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Intraoperative loading attenuates nausea and vomiting of tramadol patient-controlled analgesia.

PURPOSE: To evaluate the adverse effect profile of tramadol by patient-controlled analgesia (PCA) with administration of the loading dose either intraoperatively or postoperatively. METHODS: Sixty adult patients scheduled for elective abdominal surgery were enrolled into this prospective, randomized, double blind study. The patients were anesthetized in a similar manner. At the beginning of wound closure, the patients were randomly allocated to receive 5 mg x kg(-1) tramadol (Group 1) or normal saline (Group 2). In the post-anesthesia care unit (PACU), when patients in either group complained of pain, 30 mg x ml(-1) tramadol i.v. were given every three minutes until visual analogue scale (VAS) 3, followed by tramadol PCA with bolus dose of 30 mg and five minute lockout interval. Pain control and adverse effect assessments were done in the PACU and every six hours for 48 hr post drug by an independent observer. RESULTS: The loading dose was 290 +/- 45 mg in Group 1 and 315 +/- 148 mg in Group 2. In PACU, more nausea/vomiting both in terms of incidence (13/30, 43% vs 2/30, 6.6%, P < 0.05) and severity (nausea/vomiting score 2.5 +/- 2.0 vs 0.2 +/- 0.6, P < 0.05) was observed in patients with postoperative loading than in those with intraoperative loading of tramadol. CONCLUSION: Administering the loading dose of tramadol during surgery decreases the nausea/vomiting associated with high dose of tramadol and improves the quality of tramadol PCA in the relief of postoperative pain.

Adult↗
PubMed2000

NADPH-diaphorase activity and nitric oxide synthase activity in the kidney of the clawed frog, Xenopus laevis.

Nitric oxide (NO) may play a central role in controlling renal hemodynamics and renal salt excretion. Thus, several investigations focused on localization and function of nitric oxide synthase (NOS) isoforms in the mammalian kidney. Although studies of amphibians have contributed significantly to the elucidation of renal physiology, NOS has not been investigated in the amphibian kidney. Therefore, we characterized NOS and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase biochemically and, furthermore, visualized putative NO-producing cells in the kidney of the clawed frog, Xenopus laevis. Our results indicate that NADPH-diaphorase activity correlates with NOS activity. Both enzyme activities eluted at 225 mM NaCl on a diethylaminoethanol anion exchange column and had an apparent molecular weight of 235 kDa, as estimated on an S-300 Sephacryl column. In addition, these enzymes were sensitive to Ca2+ and NADPH, but insensitive to calmodulin antagonists (trifluoperazine, W-13) or omission of calmodulin from the reaction medium. The molecular identity of NOS in Xenopus kidney extract was estimated using polymerase chain reaction. Primers to Xenopus neuronal NOS hybridized to a transcript in Xenopus kidney homogenate. NADPH-diaphorase histochemistry revealed staining in the neck segment, distal tubules, collecting segment, and peritoneal funnels. NOS-immunoreactive material was visualized in distal tubules. These results indicate that Xenopus kidney contains at least neuronal NOS, but may contain an additional NOS isoform, which is less calmodulin sensitive.

Animals↗
PubMed2000

Differential basis of strain and rearing effects on open-field behavior in Fawn Hooded and Wistar rats.

Open-field behavior was examined under several conditions in isolation-reared, and socially reared, Fawn Hooded (FH) and Wistar rats. Lighting conditions (red or white light) and complexity (object or no object) were varied: Experiment 1, white light, no object; Experiment 2, red light, no object; Experiment 3, white light, object; Experiment 4, red light, object. The plasma corticosterone (CORT) response to open-field exposure was examined two further experiments. Observation of differences in open-field behavior, resulting from strain or rearing condition, was dependent on both lighting condition and complexity. Differences in exploratory behavior exhibited by isolation-reared rats were best explained by changes in response to novelty, while those in FH, relative to Wistar, rats were primarily due to increased anxiety. Supporting these conclusions, FH rats had enhanced stimulated CORT levels, while isolation rearing was without effect.

Animals↗
PubMed2000

Urinary NMP22 and renal cell carcinoma.

OBJECTIVES: To demonstrate the incidence of positive urinary nuclear matrix protein 22 (NMP22) values associated with renal cell carcinoma (RCC) of the kidney. Currently, urinary NMP22 is used to detect recurrent transitional cell carcinoma of the bladder. METHODS: From May 1997 to March 1998, urinary NMP22 values were obtained from 65 patients who had undergone either computed tomography scanning of the abdomen or renal ultrasound. Of the 65, 32 presented with solid renal masses. These patients underwent radical or partial nephrectomy; subsequent pathologic examination revealed that 30 had RCC. Two patients had oncocytomas. The remaining 33 patients presented with blunt abdominal trauma or abdominal pain or for follow-up for a urologic problem (a kidney stone or benign renal cyst). These patients had no evidence of renal malignancy on imaging and were used as controls. RESULTS: The urinary NMP22 values of patients with RCC were significantly higher than the values found in the control group (13.69 +/- 8.40 U/mL versus 3.03 +/- 2.70 U/mL, P <0.0078). Of the 30 patients with RCC, 12 (40%) had positive urinary NMP22 values of 10 U/mL or above. Chi-square analysis revealed a significant difference between the NMP22 values of the two groups (P <0.005). There were two false-positive NMP22 values in the 35 control patients. CONCLUSIONS: Urinary NMP22 values used to detect transitional cell carcinoma in individuals with previously diagnosed bladder cancer should be more broadly evaluated, since elevations have also been found to occur in RCC of the kidney. This finding may result in an increase in the incidental discovery of RCC. Future, more specific, NMP assays may hold promise for the detection of RCC.

Biomarkers, Tumor↗
PubMed2000

Synthesis, characterization and cytotoxicity of new platinum(IV) axial carboxylate complexes: crystal structure of potential antitumor agent [PtIV(trans-1R,2R-diaminocyclohexane)trans(acetate)2Cl2].

A series of new platinum(IV) complexes of the type [PtIV(DACH)trans(L)2Cl2] (where DACH = trans-1R,2R-diaminocyclohexane, and L = acetate, propionate, butyrate, valerate, hexanoate, or heptanoate) bearing the carboxylate groups in the axial positions have been synthesized and characterized by elemental analysis, IR, and 195Pt NMR spectroscopy. The crystal structure of the analogue [PtIV(DACH)trans(acetate)2Cl2] was determined by single crystal X-ray diffraction method. There were two crystallographically independent molecules, both of which lie on crystallographic two-fold axes. The bond lengths and bond angles of both the molecules were the same within the experimental error. The compound crystallizes in the monoclinic space group C2, with a = 11.180(2) A, b = 14.736(3) A, c = 10.644(2) A, beta = 112.38(3) degrees, Z = 4 and R = 0.0336, based upon a total of 1648 collected reflections. In this complex, the platinum had a slightly distorted octahedron geometry owing to the presence of a geometrically strained five-member ring. The two adjacent corners of the platinum plane were occupied by the two amino nitrogens of DACH, whereas the other two equatorial positions were occupied by two chloride ions. The remaining two axial positions were occupied by the oxygens of acetate ligands. The DACH ring was in a chair configuration. An intricate network of intermolecular hydrogen bonds held the crystal lattice together. These analogues were evaluated in vitro and demonstrated cytotoxic activity against the human ovarian 2008 tumor cell line (IC50 = 0.001-0.06 microM). Structure-activity study revealed that activity was highest for the analogue where L = butyrate.

Antineoplastic Agents↗
PubMed2000

Probing the roles of the only universally conserved leucine residue (Leu122) in the oligomerization and chaperone-like activity of Mycobacterium tuberculosis small heat shock protein Hsp16.3.

To understand the role of the only universally conserved hydrophobic residue among all the members of the sHsp family, this extremely well conserved Leu122 residue in Hsp16.3 was replaced by valine, alanine, asparigine, or aspartate residues. Only very small amounts of the L122D and L122N mutant Hsp16.3 proteins were expressed in the transformed E. coli; however, both the L122V and L122A were readily expressed. The L122V and L122A mutant proteins had similar oligomeric structures to the wild-type protein at room temperature. Examination of the L122A mutant protein by native pore gradient PAGE and CD spectroscopy, however, revealed a smaller oligomeric size and different secondary structure at 37 degrees C. Both L122V and L122A mutant proteins exhibited significantly lowered chaperone activities. Observations reported here suggest a very important role of this only universally conserved Leu residue in both the formation of specific oligomeric structures and the molecular chaperone activities of Hsp16.3.

Bacterial Proteins↗
PubMed2000

The multifocal electroretinogram in age-related maculopathies.

To measure and compare the multifocal electroretinogram in control group and patients with age-related maculopathies, 17 eyes of control subjects, 9 eyes of wet-form ARMD, 8 eyes of dry-form ARMD and 14 eyes of idiopathic macular hole were tested with VERIS Sciences 4.0. The latencies and average response densities of 6 ring retinal regions in control eyes were compared with those in ARMD and macular hole. The amplitude depression and latency prolongation were found in age-related maculopathies. The changes of multifocal ERG were dramatic in wet-form ARMD and moderate in dry-form ARMD and IMH, which were correspondent with the pathological changes of the diseases. Our results suggest that the multifocal electroretinogram can be used to quantity the visual function in age-related maculopathies.

Aged↗
PubMed2000

Induction of melanoma-associated antigen systemic immunity upon intratumoral delivery of interferon-gamma retroviral vector in melanoma patients.

A total of 17 patients with metastatic melanoma were treated with intratumoral interferon-gamma (IFN-gamma) retroviral vector in a phase I clinical trial. A cycle of treatment consisted of five daily injections every 2 weeks. Patients were divided into two treatment arms that involved a single course (one cycle) of treatment (group I; n = 9) and multiple cycles (six cycles) of treatment (group II; n = 8). Patients received intratumoral injections of IFN-gamma (10(7) plaque-forming units/mL administered at 0.3, 0.5, and 1.0 mL per cohort of patients). All patients receiving multiple injections either maintained stable disease (n = 5) or achieved a partial or complete response (n = 3) of the injected lesion, whereas in patients receiving a single cycle of treatment, only one of nine patients had a response. Patients were assessed for immunoglobulin G antibody (Ab) responses to the melanoma-associated antigens (MAA) tyrosinase, gp100, TRP-2, and MAGE-A1 by affinity enzyme-linked immunosorbent assay. Anti-MAGE-A1 and tyrosinase Ab were significantly elevated from baseline (day 0) to week 16 during treatment (P = .005; P = .002, respectively) in patients who received multiple injections. Patients undergoing treatment who had a clinical response (stable disease or better) also had significantly more elevated Ab responses to a greater number of MAA (P = .0004). The induction of systemic Ab responses to multiple MAA also correlated with systemic clinical responses. These studies suggest that multiple anti-MAA Ab responses are associated with clinical responses to IFN-gamma retroviral treatment and may be used as surrogate response markers.

Adolescent↗
PubMed2000

Level of interleukin-8 expression by metastatic human melanoma cells directly correlates with constitutive NF-kappaB activity.

The purpose of this study was to determine whether constitutive NF-kappaB activity regulates the expression level of interleukin-8 (IL-8) in metastatic human melanoma cells. Cultures of metastatic human A375 melanoma cells expressed higher levels of IL-8 mRNA and protein than nonmetastatic A375 human melanoma cells. No discernible differences in IL-8 half-life were found between metastatic and nonmetastatic cells, but cells that overexpressed IL-8 had a higher transcription rate and increased IL-8 promoter activity. Analysis of the IL-8 promoter using deletion mutants revealed that the region within -133 was essential for constitutive IL-8 promoter activity and that mutation of NF-kappaB binding sites eliminated the constitutive IL-8 promoter activity. The activation of constitutive IL-8 transcription directly correlated with the level of constitutive NF-kappaB activity. Transfection of melanoma cells with a dominant-negative mutant IkappaBalpha expression vector (pLXSN-IkappaBalphaM) significantly decreased the level of constitutive NF-kappaB activity and expression of IL-8, demonstrating that constitutive NF-kappaB/relA activities contribute to overexpression of IL-8 in highly metastatic human melanoma cells.

Base Sequence↗
PubMed2000

Functional coupling of Ca(2+) channels to ryanodine receptors at presynaptic terminals. Amplification of exocytosis and plasticity.

Ca(2+)-induced Ca(2+) release (CICR) enhances a variety of cellular Ca(2+) signaling and functions. How CICR affects impulse-evoked transmitter release is unknown. At frog motor nerve terminals, repetitive Ca(2+) entries slowly prime and subsequently activate the mechanism of CICR via ryanodine receptors and asynchronous exocytosis of transmitters. Further Ca(2+) entry inactivates the CICR mechanism and the absence of Ca(2+) entry for >1 min results in its slow depriming. We now report here that the activation of this unique CICR markedly enhances impulse-evoked exocytosis of transmitter. The conditioning nerve stimulation (10-20 Hz, 2-10 min) that primes the CICR mechanism produced the marked enhancement of the amplitude and quantal content of end-plate potentials (EPPs) that decayed double exponentially with time constants of 1.85 and 10 min. The enhancement was blocked by inhibitors of ryanodine receptors and was accompanied by a slight prolongation of the peak times of EPP and the end-plate currents estimated from deconvolution of EPP. The conditioning nerve stimulation also enhanced single impulse- and tetanus-induced rises in intracellular Ca(2+) in the terminals with little change in time course. There was no change in the rate of growth of the amplitudes of EPPs in a short train after the conditioning stimulation. On the other hand, the augmentation and potentiation of EPP were enhanced, and then decreased in parallel with changes in intraterminal Ca(2+) during repetition of tetani. The results suggest that ryanodine receptors exist close to voltage-gated Ca(2+) channels in the presynaptic terminals and amplify the impulse-evoked exocytosis and its plasticity via CICR after Ca(2+)-dependent priming.

Animals↗