Search PubMed⌕ Search

Biomedical subjects

A Huang

Publications and source records attributed to A Huang.

232 records · Page 13Linked to original sources
PubMed1978

Cellular and molecular studies on globin gene expression.

Globin gene expression has been studied with the use of a combination of cell and molecular biology techniques. With a somatic cell hybrid between mouse erythroleukemia (MEL) and human erythroid cells, human and mouse globin genes can be coexpressed in the same hybrid cell. Somatic cell hybridization between MEL cells and nonerythroid cells (e.g., human fibroblasts) results in hybrid cells that cannot be induced to produce hemoglobin of any type. Molecular hybridization of cellular DNA and RNA with globin cDNA indicates that the globin genes are present but that no globin mRNA is in the nonexpressing hybrid cell. This finding demonstrates that the loss of globin gene expression in the hybrid cell occurs at the level of transcription or mRNA processing. The nucleus of the nonerythroid cell is not necessary for the extinction of globin gene expression, since cybrids formed from MEL cells with enucleated nonerythroid cells also result in cells which cannot be induced to synthesize hemoglobin even after 40 or more generations. These data suggest that the cytoplasm of cells contains diffusible regulatory molecules which influence globin gene expression. In our attempt to develop an intracellular assay to test for regulatory molecules, we studied the procedure microinjection with red blood cell (RBC) ghosts. Rabbit globin mRNA (with hemin) was loaded into RBC's and then, by Sendai virus-mediated fusion, into Chinese hamster ovary (CHO) cells growing in culture; these microinjected CHO cells synthesized hemoglobin. Since this microinjection procedure appears to be effective in inserting both proteins and nucleic acids into intact cells, it should be possible to develop modifications for inserting aliquots of fractionated cytoplasm into growing cells. The procedure might then be useful as an assay for putative genetic regulatory molecules.

Animals↗
PubMed1976

Effects of nitrogen mustard and splenectomy on mouse bone marrow colony formation in vitro.

Improved tolerance of splenectomized patients with Hodgkin's disease (HD) to radiotherapy and chemotherapy has been reported. The present study was undertaken to determine the effects of splenectomy and nitrogen mustard (NM) on colony-forming cells (CFC's) of bone marrow cells obtained from CF1 male mice by in bitro agar-gel technique. Splenectomized mice were given NM intraperitoneally on day 11. On day 15, they were sacrificed and the bone marrow was cultured with a source of colony-stimulating factor (CSF). Spleen extract was prepared by grinding spleens from CF1 mice. On the eighth day of incubation, significantly higher numbers of CFC's were found in splenectomized animals at 1% confidence level (F Test) compared with the nonsplenectomized animals. Both splenectomized and non-splenectomized mice had a greater colony response after NM (at 5% confidence level) than saline-treated controls. Maximum numbers of colonies were obtained in the nustard-treated asplenic animals. Splenic extract, as well as extracts from other organs, when added to the culture plates resulted in inhibition of colony formation. The significance of in vitro inhibition after addition of organ extract is uncertain.

Animals↗
PubMed1975

Fatal paralytic ileus complicating phenothiazine therapy.

The occurrence of fatal paralytic ileus with peritonitis in a patient receiving phenothiazines and an antiparkinsonian agent is described. Although sporadic reports of this complication have appeared, it has not been emphasized in the literature. Only by being alert to this problem can one hope to achieve earlier diagnosis and begin prompt and appropriate treatment.

Adult↗
PubMedDate not supplied

Adverse events associated with prescription drug cost-sharing among poor and elderly persons.

CONTEXT: Rising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada. Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups. OBJECTIVES: To determine (1) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and (2) rates of emergency department (ED) visits and serious adverse events associated with reductions in drug use before and after policy implementation. DESIGN AND SETTING: Interrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996. Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events. PARTICIPANTS: A random sample of 93 950 elderly persons and 55 333 adult welfare medication recipients. MAIN OUTCOME MEASURES: Mean daily number of essential and less essential drugs used per month, ED visits, and serious adverse events (hospitalization, nursing home admission, and mortality) before and after policy introduction. RESULTS: After cost-sharing was introduced, use of essential drugs decreased by 9.12% (95% confidence interval [CI], 8.7%-9.6%) in elderly persons and by 14.42% (95% CI, 13.3%-15.6%) in welfare recipients; use of less essential drugs decreased by 15.14% (95% CI, 14.4%-15.9%) and 22.39% (95% CI, 20.9%-23.9%), respectively. The rate (per 10 000 person-months) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons (a net increase of 6.8 [95% CI, 5.6-8.0]) and from 14.7 to 27.6 in welfare recipients (a net increase of 12.9 [95% CI, 10.2-15.5]). Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 (95% CI, 8.5-19.9) per 10 000 person-months in elderly persons (prepolicy control cohort, 32.9; postpolicy cohort, 47.1) and by 54.2 (95% CI, 33.5-74.8) among welfare recipients (prepolicy control cohort, 69.6; postpolicy cohort, 123.8). These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs. Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits. CONCLUSIONS: In our study, increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions.

Adult↗
PubMedDate not supplied

Fluoride profiles in dental calculus from Japanese, Chinese and British residents.

Whether the fluoride concentrations and profiles differ in human dental calculus obtained from different countries was investigated. A total of 203 dental calculus deposits on 203 permanent teeth from residents (mean age, 52.1 years) of Nagoya (Japan), Shanghai (China), Leeds (Great Britain) and the Wuhan mountainous area (China, fluoridated area) were analysed. An abrasive microsampling procedure was used to examine fluoride distribution. There were five types of fluoride profiles in dental calculus in each area/country (designated types L, J, U, T, W). In supragingival calculus, type L (highest in the outermost layers) and type J (highest in the innermost layers) both had significantly higher values than type U (high in the surface and innermost layers) but were relatively identical. In subgingival calculus, type W (high in the outermost, mid and innermost layers) was characteristics. Calculus from the Wuhan mountainous area (fluoridated) had the highest fluoride concentration, followed by Leeds (non-fluoridated), and Nagoya and Shanghai (non-fluoridated) calculus had the lowest. Fluoride concentrations in supragingival calculus were higher in teeth extracted because of periodontal diseases than dental caries. It is concluded that fluoride concentrations and distribution in dental calculus differ from country to country, probably due to different fluoride environments.

Adult↗
PubMedDate not supplied

Strand invasion by oligonucleotide--nuclease conjugates.

Conjugates consisting of staphylococcal nuclease crosslinked to oligonucleotides hybridize to supercoiled duplex DNA by Watson--Crick base-pairing. Here we describe this strand invasion. Affinity cleavage by these conjugates provides a probe for the local topology of the DNA duplex and is most efficient at a target DNA sequence known to form a cruciform. Additional supercoiling of the substrate DNA increases selective cleavage at other sequences. Hybridization of the conjugate to duplex DNA is temperature dependent and is stable over time. Affinity cleavage is not substantially inhibited by a 200-fold excess of the analogous unmodified oligonucleotide, demonstrating that hybridization of the unmodified oligonucleotide must be less favored and that the nuclease is involved in substrate binding. Surprisingly, affinity cleavage is also not effectively inhibited by complementary oligonucleotides unless they contain an extended 5'-sequence capable of separate interactions with the nuclease domain of the conjugate. These results suggest that the oligonucleotide-nuclease conjugate prefers to hybridize to target sequences which will allow interactions with both the oligonucleotide and the nuclease domains. Affinity cleavage by oligonucleotide-nuclease conjugates provides general insights for the design of oligonucleotides and their conjugates for strand invasion and affords a convenient competition assay for their hybridization.

Amino Acid Sequence↗
PubMedDate not supplied

Invasive aspergillus rhinosinusitis in patients with acute leukemia.

Invasive aspergillus rhinosinusitis is a potentially lethal complication of chemotherapy-induced neutropenia in patients with acute leukemia. The majority of cases are caused by Aspergillus flavus. The infection is difficult to diagnose early but should be suspected when a neutropenic patient develops persistent fever without a known source, symptoms of rhinitis or sinusitis, cutaneous findings over the nose or sinuses, symptoms and signs of orbital or cavernous sinus disease, or an ulcerating lesion of the hard palate or gingiva. Careful anterior rhinoscopy followed by computed tomography of the sinus helps establish the diagnosis, which should be confirmed by histologic study and culture of biopsied material. Early treatment with aggressive surgery, high-dose amphotericin B and 5-fluorocytosine, and possibly white blood cell transfusions may produce a cure if the patient's bone marrow recovers. Newer antifungal agents offer promise for prophylaxis and treatment of this infection.

Acute Disease↗
PubMedDate not supplied

17beta-estradiol restores endothelial nitric oxide release to shear stress in arterioles of male hypertensive rats.

BACKGROUND: Endothelial nitric oxide (NO)-mediated responses are impaired in arterioles of male spontaneously hypertensive rats (SHR), but they are still present in female SHR. We hypothesized that in vitro incubation of arterioles of male SHR with estrogen will restore NO-mediated responses by upregulation of endothelial NO synthase. METHODS AND RESULTS: Responses to increases in perfusate flow (from 0 to 25 microL/min) and to the calcium ionophore A23187 (5 x 10(-8) to 10(-6) mol/L), norepinephrine (NE; 10(-7) to 3 x 10(-7) mol/L), sodium nitroprusside (SNP; 10(-8) to 10(-6) mol/L), and adenosine (ADO; 10(-6) to 5 x 10(-5) mol/L) were studied in cannulated and pressurized gracilis muscle arterioles ( approximately 75 microm in diameter) isolated from 12-week-old male SHR before and after incubation with 10(-9) mol/L 17beta-estradiol (17beta-E(2)) for 16 to 18 hours. After incubation with 17beta-E(2), basal diameter of arterioles was significantly increased (by approximately 10%), and flow-induced dilation was significantly enhanced (79.8+/-2.9 versus 103.7+/-3.7 microm at 25 microL/min), resulting in a lowered shear stress (62.0+/-9.1 versus 32.5+/-4.2 dyne/cm(2)). Also, vasoconstrictions to A23187 were reversed to dilations (-18.7+/-2.2 versus 18.8+/-1.7 microm), and constrictions to NE were significantly attenuated (-30.7+/-3.0 versus -21.2+/-2.8 microm). These alterations were eliminated by ICI 182,780 (10(-7) mol/L), an estrogen receptor antagonist; 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (10(-5) mol/L), a transcription inhibitor; or N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L), an inhibitor of NO synthase, whereas they were not affected by aminoguanidine (5 x 10(-5) mol/L), a specific inhibitor of inducible NO synthase. Arteriolar responses were not altered by incubation with 17alpha-estradiol. CONCLUSIONS: Estrogen, via a receptor-mediated pathway, upregulates endothelial NO synthase gene expression, leading to increased NO production, and restores the regulation of wall shear stress in arterioles of male SHR.

Adenosine↗
PubMedDate not supplied

The Office of the Future Project: the integration of new technology into office practice. Academic detailing through the super highway. Quebec Research Group on Medication Use in the Elderly.

Effective management of drug therapy in the elderly is a challenge for primary-care physicians. There are 20,400 drugs approved for marketing in Canada. Most elderly patients will fill 33 prescriptions per year and take 5 different medications. To be a safe prescriber in the 1990s, physicians need to be aware that 33,000 drug interactions, 6,500 drug-disease contraindications, and 3,500 drug-allergy contraindications have been documented. Inappropriate prescribing is a problem in the elderly. At least one inappropriate prescription is given to 12% to 46% of seniors, and 25% of drug-related hospital admissions are due to prescribing errors. Half of all physicians will write at least one inappropriate prescription for an elderly patient each year, and one quarter of inappropriate prescriptions will be created by the presence of multiple prescribing physicians. Academic detailing is the most effective approach to improve physician prescribing. However, it is an expensive intervention that must be limited to a small number of drugs and conditions, and it must be continued to retain its effectiveness. Furthermore, it fails to address the problems created by multiple prescribers. In this project, we developed a prototype of the future office practice. Physicians are equipped with personal computers and expert prescribing-system software. This electronic academic detailer reviews all current medications for a patient, identifies therapeutic duplications, generates alerts for 50 prescribing problems that have been identified as clinically relevant by a Canadian expert panel, suggests suitable alternatives, and reviews all new prescriptions for potential problems. Information on all prescriptions received by the physicians' elderly patients is downloaded weekly from the provincial prescription claims database, so that the primary physician is able to coordinate and manage all drugs prescribed to their patients by all physicians. The effectiveness of this intervention is being evaluated in a randomized controlled trial of 110 physicians and approximately 16,000 elderly patients in Montreal. We will test whether the intervention reduces the rate of inappropriate prescribing, as well as the rate of drug-related injuries and hospitalizations among patients treated by physicians in the experimental group.

Aged↗