Search PubMed⌕ Search

Biomedical subjects

S Huang

Publications and source records attributed to S Huang.

At least 37 records · Page 2Linked to original sources
PubMed2004

Differential effects of estrogen and raloxifene on messenger RNA and matrix metalloproteinase 2 activity in the rat uterus.

A detailed analysis of the differential effects of estrogen (E) compared to raloxifene (Ral), a selective estrogen receptor modulator (SERM), following estrogen receptor (ER) binding in gynecological tissues was conducted using gene microarrays, Northern blot analysis, and matrix metalloproteinase (MMP) 2 activity studies. We profiled gene expression in the uterus following acute (1 day) and prolonged daily (5 wk) treatment of E and Ral in ovariectomized rats. Estrogen regulated twice as many genes as Ral, largely those associated with catalysis and metabolism, whereas Ral induced genes associated with cell death and negative cell regulation. Follow-up studies confirmed that genes associated with matrix integrity were differentially regulated by Ral and E at various time points in uterine and vaginal tissues. Additional experiments were conducted to determine the levels of MMP2 activity in uterus explants from ovariectomized rats following 2 wk of treatment with E, Ral, or one of two additional SERMs: lasofoxifene, and levormeloxifene. Both E and lasofoxifene stimulated uterine MMP2 activity to a level twofold that of Ral, whereas levormeloxifene elevated MMP2 activity to a level 12-fold that of Ral. These data show that one of the significant differences between E and Ral signaling in the uterus is the regulation of genes and proteins associated with matrix integrity. This may be a potential key difference between the action of SERMs in the uterus of postmenopausal women.

Animals↗
PubMed2004

Complex nested promoters control tissue-specific expression of acetyl-CoA carboxylase genes in wheat.

Cis-acting regulatory elements of the wheat acetyl-CoA carboxylase (ACC) gene family were identified by comparing the promoter activity of 5' end gene fragments fused to a reporter gene in two transient expression systems: wheat protoplasts and epidermal cells of mature embryos. Expression of the plastid and the cytosolic ACC genes is each driven by two nested promoters responsible for the synthesis of two transcript types. The internal promoter is located in an intron removed from transcripts originating at the first promoter. These complex promoters, which are different for the cytosolic and plastid ACC genes, control tissue-specific expression of the enzymatic activity supplying cytosolic, plastid, and mitochondrial pools of malonyl-CoA. The activity of one such complex promoter, driving expression of one of the cytosolic ACC genes, was studied throughout development of transgenic wheat plants carrying a full-length promoter-reporter gene fusion. High activity of the promoter was detected in the coleoptile, in the upper sheath section of the leaf, on the top surface of the ovary, in some sections of the main veins in the lemma and glume, and in abaxial epidermis hair cells of the lemma, glume, and rachis. The findings are consistent with the developmental and environmental requirements for very-long-chain fatty acids and flavonoids, whose synthesis begins with the ACC reaction in the cytosol of these specific cell types.

Acetyl-CoA Carboxylase↗
PubMed2004

mTOR as a target for cancer therapy.

The target of rapamycin, mTOR, acts as a sensor for mitogenic stimuli, such as insulin-like growth factors and cellular nutritional status, regulating cellular growth and division. As many tumors are driven by autocrine or paracrine growth through the type-I insulin-like growth factor receptor, mTOR is potentially an attractive target for molecular-targeted treatment. Further, a rationale for anticipating tumor-selective activity based on transforming events frequently identified in malignant disease is becoming established.

Animals↗
PubMed2004

Fluorescence microscopy of colour-tagged nanoparticles that are undergoing thermal motion.

To bypass limitations of conventional biochemical analysis, single-particle biochemical analysis is used. To improve single-particle biochemical analysis, procedures are needed to keep nanometre-sized particles in focus while the particles are undergoing thermal motion. A simple, inexpensive procedure is developed here for keeping particles in focus during the continuous observing/discriminating/recording of two different particles, both of which are undergoing thermal motion. This procedure concentrates the particles in a plane of solution that is in focus when the cover glass surface is in focus. An essential component of the procedure is the addition of molten, low-melt agarose to the specimen. Motionless binding to glass is inhibited by inclusion of anti-stick additives in the specimen. Both carrier protein (gelatin) and non-ionic detergent (Triton X-100) are anti-stick additives successfully used here. Intact bacteriophages T3 and T7 are used as model particles, in anticipation of the use of the procedures developed here for the analysis of the assembly of bacteriophages. Observing/discriminating/recording of colour-tagged bacteriophages T3 and T7 is achieved at video frame rate with image splitting to discriminate colours.

Acetic Acid↗
PubMed2004

A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women.

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor alpha (ERalpha). RIZ1 has previously been shown to be a specific ERalpha coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704(+/-) of a proline at position 704) to coactivate the ERalpha and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERalpha in a ligand- and dose-dependent manner compared with P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704(+/-)) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704(+/-) group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). We conclude that RIZ1 may be a new candidate gene for involvement in the variation seen in BMD.

Adult↗
PubMed2003

Prospects for spermatogenesis in vitro.

In recent years, extraordinary progress has been made in a broad range of reproductive technologies, including spermatogonial transplantation in the male. However, effective procedures for the complete recapitulation of spermatogenesis in vitro, including meiosis, have remained elusive. Such procedures have the potential to facilitate (1) mechanistic studies of spermatogenesis, (2) directed genetic modification of the male germ line, and (3) treatment of male factor infertility. Early studies demonstrated the importance of germ cell-Sertoli association for germ cell survival in vitro. Recently, evidence for male germ cell survival and progression through meiosis has been reported for the rat, mouse, and man. We demonstrated the expression of spermatid-specific genes (protamine and transition protein 1) by alginate-encapsulate neonatal bull testis cells after 10 weeks in culture, suggesting that meiosis had occurred. Although identifiable germ cells in these cultures were very sparse, some indication of acrosome development was observed. Following round spermatid injection (ROSI) with presumptive spermatids produced in vitro, 50% of blastocysts produced were diploid and 37% were Y-chromosome positive. Improved culture conditions, which promote germ cell survival, differentiation, and proliferation, are essential for in vitro spermatogenesis (IVS) to become a useful technology. Other approaches to male germ cell manipulation and spermatid production are discussed.

Animals↗
PubMed2003

Otoplasty by percutaneous anterior scoring. Another twist to the story: a long-term study of 114 patients.

A large number of techniques have been described for the correction of prominent ears to improve the cosmetic outcome and reduce the complication rates. The procedure favoured by the senior author brings together a number of refinements, notably, percutaneous anterior scoring using a modified green needle, control over the degree of fold created and a simple but effective dressing. 114 consecutive patients underwent the correction of 214 ears, with a mean follow up of 3 years and 11 months (9 months to 9 years and 6 months). The senior author performed 100 of these procedures and supervised a senior trainee for the remainder. The mean patient age was 18 years 3 months (3 to 66 years). 57 males and 57 females. 56 general anaesthetic and 58 local anaesthetic. Post-operative complications were; haemorrhage, one ear (required a dressing change); infection, four ears (treated with antibiotics); hypertrophic scarring, two ears which settled (no keloid); recurrence one ear (repeated surgery); continued prominence six ears (two had repeated surgery). No prominent sutures, no anterior skin necrosis, no visible irregularity of the anterior surface of the cartilage and no haematoma occurred. We feel that the low complication rate is due to maximising the advantages and minimising the disadvantages of the different techniques and refinements. We recommend this technique for the routine correction of prominent ears due to a poorly formed antihelical fold or deep conchal bowl.

Adolescent↗
PubMed2003

Responses by coleoptiles of intact rice seedlings to anoxia: k(+) net uptake from the external solution and translocation from the caryopses.

This study evaluated the effects of anoxia on K(+) uptake and translocation in 3-4-d-old, intact, rice seedlings (Oryza sativa L. cv. Calrose). Rates of net K(+) uptake from the medium over 24 h by coleoptiles of anoxic seedlings were inhibited by 83-91 %, when compared with rates in aerated seedlings. Similar uptake rates, and degree of inhibition due to anoxia, were found for Rb(+) when supplied over 1.5-2 h, starting 22 h after imposing anoxia. The Rb(+) uptake indicated that intact coleoptiles take up ions directly from the external solution. Monovalent cation (K(+) and Rb(+)) net uptake from the solution was inhibited by anoxia to the same degree for the coleoptiles of intact seedlings and for coleoptiles excised, 'aged', and supplied with exogenous glucose. Transport of endogenous K(+) from caryopses to coleoptiles was inhibited less by anoxia than net K(+) uptake from the solution, the inhibition being 55 % rather than 87 %. Despite these inhibitions, osmotic pressures of sap (pi(sap)) expressed from coleoptiles of seedlings exposed to 48 h of anoxia, with or without exogenous K(+), were 0.66 +/- 0.03 MPa; however, the contributions of K(+) to pi(sap) were 23 and 16 %, respectively. After 24 h of anoxia, the K(+) concentrations in the basal 10 mm of the coleoptiles of seedlings with or without exogenous K(+), were similar to those in aerated seedlings with exogenous K(+). In contrast, K(+) concentrations had decreased in aerated seedlings without exogenous K(+), presumably due to 'dilution' by growth; fresh weight gains of the coleoptile being 3.6- to 4.7-fold greater in aerated than in anoxic seedlings. Deposition rates of K(+) along the axes of the coleoptiles were calculated for the anoxic seedlings only, for which we assessed the elongation zone to be only the basal 4 mm. K(+) deposition in the basal 6 mm was similar for seedlings with or without exogenous K(+), at 0.6-0.87 micro mol g(-1) f. wt h(-1). Deposition rates in zones above 6 mm from the base were greater for seedlings with, than without, exogenous K(+); the latter were sometimes negative. We conclude that for the coleoptiles of rice seedlings, anoxia inhibits net K(+) uptake from the external solution to a much larger extent than K(+) translocation from the caryopses. Furthermore, K(+) concentrations in the elongation zone of the coleoptiles of anoxic seedlings were maintained to a remarkable degree, contributing to maintenance of pi(sap) in cells of these elongating tissues.

Biological Transport↗
PubMed2003

Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China.

Severe acute respiratory syndrome (SARS), now known to be caused by a coronavirus, probably originated in Guangdong province in southern China in late 2002. The first major outbreak occurred in Guangzhou, the capital of Guangdong, between January and March 2003. This study reviews the clinical presentation, laboratory findings and response to four different treatment protocols. Case notes and laboratory findings were analysed and outcome measures were collected prospectively. The SARS outbreak in Guangdong province and the outbreak in Guangzhou associated with hospitals in the city are described, documenting clinical and laboratory features in a cohort of 190 patients randomly allocated to four treatment regimens. Patients were infected by close contact in either family or health-care settings, particularly following procedures likely to generate aerosols of respiratory secretions (e.g. administration of nebulized drugs and bronchoscopy). The earliest symptom was a high fever followed, in most patients, by dyspnoea, cough and myalgia, with 24 % of patients complaining of diarrhoea. The most frequent chest X-ray changes were patchy consolidation with progression to bilateral bronchopneumonia over 5-10 days. Thirty-six cases developed adult respiratory distress syndrome (ARDS), of whom 11 died. There was no response to antibiotics. The best response (no deaths) was seen in the group of 60 patients receiving early high-dose steroids and nasal CPAP (continuous airway positive pressure) ventilation; the other three treatment groups had significant mortality. Cross-infection to medical and nursing staff was completely prevented in one hospital by rigid adherence to barrier precautions during contact with infected patients. The use of rapid case identification and quarantine has controlled the outbreak in Guangzhou, in which more than 350 patients have been infected. Early administration of high-dose steroids and CPAP ventilation appears to offer the best supportive treatment with a reduced mortality compared with other treatment regimens.

Adult↗
PubMed2003

Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial.

The aim of the study was to compare the safety and effectiveness of as-needed formoterol with salbutamol in a large international real-life asthma study. Children and adults (n=18,124) were randomised to 6 months as-needed treatment with open-label formoterol 4.5 microg Turbuhaler or salbutamol 200 microg pressurised metered dose inhaler or equivalent. Primary safety variables were asthma-related and nonasthma-related serious adverse events (SAE)s and adverse events (AE)s resulting in discontinuation (DAE)s. The primary efficacy variable was time to first asthma exacerbation. The incidences of AEs, SAEs and DAEs arising from SAEs were not significantly different between treatments. DAEs for nonserious AEs were higher with formoterol. Asthma-related AEs decreased with formoterol (1,098 (12.3%) versus 1,206 (13.5%)), asthma-related SAEs were similar (108 (1.2%) versus 121 (1.4%)) but more asthma-related DAEs occurred in the formoterol group (89 (1.0%) versus 48 (0.5%)). Time to first exacerbation was prolonged (hazard ratio 0.86) and less as-needed and maintenance medication was used with formoterol. Reductions of exacerbations with as-needed formoterol versus salbutamol increased with increasing age and asthma medication level. This real-life study demonstrates that formoterol as-needed has a similar safety profile to salbutamol, and its use as a reliever therapy is associated with fewer asthma symptoms and exacerbations.

Administration, Inhalation↗
PubMed2002

MRI of joint fluid in femoral head osteonecrosis.

OBJECTIVE: To evaluate the relationship between joint fluid, intramedullary pressure (IMP), bone marrow edema, and stages of osteonecrosis of the femoral head (ONFH). MATERIAL AND METHODS: We reviewed the magnetic resonance (MR) images of 28 patients with 40 documented ONFHs. IMP was measured in 16 symptomatic hips. The amount of joint fluid was graded as 0 (no fluid), 1 (fluid <5 mm in width), or 2 (fluid > or = 5 mm in width) adjacent to the entire length of the femoral neck. Associated focal and diffuse bone marrow abnormalities were evaluated. A control group of 29 recruited individuals without symptoms related to hip disease were examined. Follow-up MR images were obtained in four patients (five affected hips) 6-10 months after core decompression. RESULTS: Of the 40 affected hips, the severity of ONFH was divided into stages 0 (n=4), I (n=28), and II (n=8 hips) on MR findings. The correlation of joint fluid to IMP and to the presence of bone marrow edema was poor. The amount of joint fluid correlated significantly with the stage of ONFH. None of the five affected hips showed decreased joint fluid on follow-up MR images. CONCLUSION: The amount of joint fluid correlates well with the stage of ONFH. The amount of joint fluid does not correlate with IMP or bone marrow edema.

Adult↗
PubMed2002

A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma.

A rapid and systematic review of the effectiveness and cost-effectiveness of temozolomide in the treatment of recurrent malignant glioma was commissioned by the NHS HTA Programme on behalf of NICE. The full report has been published elsewhere. This paper summarizes the results for the effectiveness of temozolomide in people with recurrent glioblastoma multiforme and anaplastic astrocytoma. The review was conducted using standard systematic review methodology involving a systematic literature search, quality assessment of included studies with systematic data extraction and data synthesis. One randomized controlled trial and four uncontrolled studies were identified for inclusion. The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from temozolomide may have been in those patients who had not received any prior chemotherapy regimens, however further randomized controlled trials are required to confirm this suggestion. Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life. Overall the evidence-base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide. Large, well-designed randomized controlled trails conducted in a wider patient population are needed.

Antineoplastic Agents, Alkylating↗
PubMed2002

ICP monitoring following bilateral carotid occlusion in GFAP-null mice.

To investigate the possible role of glial fibrillary acidic protein (GFAP) in cerebral ischemia, we have monitored the intracranial pressure (ICP) and local cerebral blood flow (ICBF) following bilateral carotid artery occlusion (BCAO) in GFAP-null mice and their wild type littermates. GFAP-null mice (B6, 129-GfaptmlMes) were obtained from Jackson Laboratories. The ICP and ICBF was continuously monitored during 15 minutes BCAO and reperfusion. The variation of the circle of Willis was also investigated in both GFAP-null and wild type mice. The breakdown of blood brain barrier (BBB) was assessed by immunohistochemical staining against mouse immunogloblins (IgG). A significantly more profound and immediate decrease in ICBF after BCAO was observed in GFAP-null mice (p < 0.04, ANOVA). GFAP-null mice also showed a significant increase (% change) in ICP after reperfusion (p < 0.05, ANOVA). There were no gross differences in the circle of Willis between GFAP-null and wild type mice. No abnormal IgG immuno-reactivity was observed in the forebrain of both animals. These results indicate a high susceptibility to cerebral ischemia in GFAP-null mice and suggest an important role for astrocytes and GFAP in the progress of ischemic brain damage and increased ICP after cerebral ischemia with reperfusion.

Animals↗
PubMed2002

Micrometer-sized short-lived radioactive aerosol particles for convenient use in laboratory measurements.

For calibration and testing of radioactive aerosol measuring equipment such as continuous air monitors and cascade impactors, and other research applications, it is helpful to have a convenient and relatively safe means of producing radioactive aerosol particles of controlled size and activity. We describe a technique for producing such particles in the micrometer-diameter size range using electrostatic deposition of radon decay products onto otherwise nonradioactive powders of different sizes. An electric field focuses radon decay products (primarily 218Po) onto the surface of a powdered substrate that is then suspended by a technique such as pneumatic dry dispersion. Only a modest-activity commercial 222Rn source (e.g., containing as little as 10(5) Bq of 226Ra) is required, and issues of radioactive cleanup and contamination are minimized due to the short half-lives (26.8 min or less) of the decay products. We report representative results using powders of glass beads, iron oxide, and iron and gold metals in the size range of 0.3 to 30 microm. Yields for the deposited radioactivity per unit concentration of 222Rn gas were of the order of 5 x 10(-7) Bq (214Bi) per milligram substrate per Bq m(-3) of 222Rn for an electrostatic collection time of 30 min.

Aerosols↗
PubMed2002

Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells.

Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.

Animals↗
PubMed2001

Regulation of ribosome biogenesis within the nucleolus.

Ribosome biogenesis is both necessary for cellular adaptation, growth, and proliferation as well as a major energetic and biosynthetic demand upon cells. For these reasons, ribosome biogenesis requires precise regulation to balance supply and demand. The complexity of ribosome biogenesis gives rise to many steps and opportunities where regulation could take place. For trans-acting factors involved in ribosome biogenesis in the nucleolus, there may be a dynamic coordination, both spatially and temporally, that regulates their functions from the transcription of rDNA to the assembly and export of preribosomal particles. Here we summarize most of the described regulations on ribosome biogenesis in the nucleolus. However, these may represent only a small fraction of a larger picture. Further studies are required to determine the initial signals, signal transduction pathways utilized, and the specific targets of these regulatory modifications and how these are used to control ribosome biogenesis as a whole.

Biological Transport↗