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Biomedical subjects

E Cheung

Publications and source records attributed to E Cheung.

At least 19 recordsLinked to original sources
PubMed2001

Effect of histological damage on long-term kidney transplant outcome.

BACKGROUND: Chronic renal allograft failure remains a major challenge to overcome. Factors such as donor quality, delayed graft function (DGF), acute rejection, and immunosuppression are known to affect long-term outcome, but their relationship to histological damage to graft outcome is unclear. METHODS: Protocol kidney biopsies (n=112) obtained at 3 months after transplantation yielded 102 with adequate tissue. Histology was scored by the Banff schema, and compared with implantation biopsies (n=91), repeat 12-month histology (n=39), decline in serum creatinine and serial isotopic glomerular filtration rate, onset of chronic allograft nephropathy (CAN), and actuarial graft survival censored for death with a functioning graft. RESULTS: At a median follow-up of 9.3 years, 20 patients had graft failure and 26 died with a functioning graft. Banff chronic nephropathy was present in 24% of 3-month biopsies, and was predicted by microvascular disease in the donor, cold ischemia, DGF, and acute vascular rejection (P<0.001). Acute glomerulitis at 3 months correlated with segmental glomerulosclerosis at 12 months, subsequent recurrent glomerulonephritis, and graft failure (P<0.01). Subclinical rejection at 3 months occurred in 29% of biopsies, correlated with prior acute rejection and HLA mismatch, and led to chronic histological damage by 12 months (r=0.25-0.67, P<0.05-0.001). Subclinical rejection, arteriolar hyalinosis, and tubulitis present at 3 months had resolved by 12 months. The 10-year survival rates for Banff chronic nephropathy were 90.4% for grade 0, 81.0% grade 1, and 57.9% for grades 2 or greater (P<0.01). Early tubulointerstitial damage at 3 months profoundly influenced graft survival beyond 10 years. CAN was predicted by kidney ischemia, 3-month chronic intimal vascular thickening, tubular injury, proteinuria, and late rejection. Chronic fibrointimal thickening of the small arteries and chronic interstitial fibrosis at 3 months independently predicted graft loss and decline in renal function (P<0.05-0.001). CONCLUSIONS: Early transplant damage occurs in the tubulointerstitial compartment from preexisting donor kidney injury and discrete events such as vascular rejection and DGF. Subsequent chronic damage and graft failure reflect accumulated previous injury and chronic interstitial fibrosis, vascular impairment, subclinical rejection, and injury from late rejection. CAN may be conceptualized as the sequelae of incremental and cumulative damage to the transplanted kidney. The duration of graft survival is dependent and predicted by the quality of the transplanted donor kidney combined with the intensity, frequency, and irreversibility of these damaging insults.

Adult↗
PubMed2001

Specific down-regulation of an engineered human cyclin D1 promoter by a novel DNA-binding ligand in intact cells.

Cyclin D1 is expressed at abnormally high levels in many cancers and has been specifically implicated in the development of breast cancer. In this report we have extensively analyzed the cyclin D1 promoter in a variety of cancer cell lines that overexpress the protein and identified two critical regulatory elements (CREs), a previously identified CRE at -52 and a novel site at -30. In vivo footprinting experiments demonstrated factors binding at both sites. We have used a novel DNA-binding ligand, GL020924, to target the site at -30 (-30-21) of the cyclin D1 promoter in MCF7 breast cancer cells. A binding site for this novel molecule was constructed by mutating 2 bp of the wild-type cyclin D1 promoter at the -30-21 site. Treatment with GL020924 specifically inhibited expression of the targeted cyclin D1 promoter construct in MCF7 cells in a concentration-dependent manner, thus validating the -30-21 site as a target for minor groove-binding ligands. In addition, this result validates our approach to regulating the expression of genes implicated in disease by targeting small DNA-binding ligands to key regulatory elements in the promoters of those genes.

Binding Sites↗
PubMed2001

DNA binding by the ETS-domain transcription factor PEA3 is regulated by intramolecular and intermolecular protein.protein interactions.

The control of DNA binding by eukaryotic transcription factors represents an important regulatory mechanism. Many transcription factors are controlled by cis-acting autoinhibitory modules that are thought to act by blocking promiscuous DNA binding in the absence of appropriate regulatory cues. Here, we have investigated the determinants and regulation of the autoinhibitory mechanism employed by the ETS-domain transcription factor, PEA3. DNA binding is inhibited by a module composed of a combination of two short motifs located on either side of the ETS DNA-binding domain. A second type of protein, Ids, can act in trans to mimic the effect of these cis-acting inhibitory motifs and reduce DNA binding by PEA3. By using a one-hybrid screen, we identified the basic helix-loop-helix-leucine zipper transcription factor USF-1 as an interaction partner for PEA3. PEA3 and USF-1 form DNA complexes in a cooperative manner. Moreover, the formation of ternary PEA3.USF-1.DNA complexes requires parts of the same motifs in PEA3 that form the autoinhibitory module. Thus the binding of USF-1 to PEA3 acts as a switch that modifies the autoinhibitory motifs in PEA3 to first relieve their inhibitory action, and second, promote ternary nucleoprotein complex assembly.

Amino Acid Sequence↗
PubMed2000

Enantio- and diastereodifferentiating cis,trans-photoisomerization of 2beta,3beta-diphenylcyclopropane-1alpha-carboxylic acid derivatives in organized media.

[reaction: see text] Four methods of asymmetric induction in the cis, trans-photoisomerization of 2beta, 3beta-diphenylcyclopropane-1alpha-carboxylic acid derivatives were studied. Best results (ca. 80% de) were obtained by irradiation of chiral esters, amides, and salts in NaY and LiY zeolites and in the pure crystalline state.

Journal Article↗
PubMed2000

Compliance of the respiratory system in newborn and adult rats after gestation in hypoxia.

We hypothesized that hypoxia during gestation modifies the compliance of the respiratory system of newborn and adult rats. Pregnant rats were placed in a hypobaric chamber at an inspired oxygen pressure of 86 mmHg (equivalent to 12% O2 in normobaria) from day 4 of gestation until day 2 post-partum. Three-day-old rat pups were smaller than controls, with higher hematocrit; the lungs were also small, with less protein and DNA content. The pressure (x-axis)-volume (y-axis) curve of the respiratory system was displaced to the right of the control curve, and the compliance of the respiratory system, measured on the inflation or deflation limb of the pressure-volume curve, was decreased by approximately 20-25%, depending upon the normalization procedure (per body mass or per dry lung weight). In 50-day-old rats exposed to hypoxia during gestation, body weight, hematocrit, lung mass and DNA content were normal; the compliance of the respiratory system, measured at ventilation frequencies between 20 cpm and 100 cpm, was higher than in controls by approximately 20%. It is concluded that the effects of prenatal hypoxia on the compliance of the respiratory system can vary with age. In the rat the process of alveolar formation initiates postnatally. Hence, in the newborn the effects of the prenatal hypoxia on the compliance of the respiratory system are likely to be dominated by the hypoxic pulmonary hypoplasia and hypertension, which decrease the compliance of the respiratory system. In the adult, the effects of the decreased alveolar formation are the prevailing ones, increasing the compliance of the respiratory system.

Age Factors↗
PubMed2000

Competition between cyclization, cleavage, and reverse hydrogen transfer in 1,4-hydroxybiradicals: crystal structure--solid state reactivity correlations

[reaction: see text] To provide experimental evidence on the relationship between stucture and reactivity in 1,4-hydroxybiradical intermediates, the Norrish type II photochemistry of a homologous series of spirobenzoyladamantane derivatives was investigated in the crystalline state and the outcome correlated with the structures of the compounds as determined by X-ray crystallography. The results provide an unusually detailed and compelling picture of the geometric factors responsible for the partitioning of these reactive intermediates among cleavage, cyclization, and reverse hydrogen transfer.

Journal Article↗
PubMed2000

Pharmacokinetic analysis of pegylated megakaryocyte growth and development factor in humans.

Phase I studies with pegylated megakaryocyte growth and development factor (PEG-rHuMGDF), a c-Mpl ligand that stimulates megakaryopoiesis, have demonstrated that PEG-rHuMGDF is biologically active alone and causes a dose-related enhancement of platelet recovery when administered after chemotherapy. Here we report the dose-ranging pharmacokinetics of PEG-rHuMGDF. Pre-injection blood samples were drawn daily for pharmacokinetic studies on 43 patients. An ELISA, established using PEG-rHuMGDF as the standard, was able to quantitate Mpl ligand at concentrations > 0.02 ng/mL. Over the dose range 0.03 to 5.0 microg/kg/day, subcutaneous administration produced linear increases in steady-state serum levels. Maximum levels of PEG-rHuMGDF attained after 5.0 microg/kg/day were 5.88 to 10.9 ng/mL. After discontinuation of PEG-rHuMGDF, concentrations of Mpl ligand returned to baseline within 5 days. The pharmacokinetics were best described by a one-compartment model with first-order absorption, an absorption delay, and non linear clearance over the first 48 hours. The mean terminal half-life was 33.3 + 16.7 hours, and the average apparent at steady state was 27.7 + 14.0 mL/h/kg; both were independent of administered dose. The apparent clearance of PEG-rHuMGDF was not predicted by platelet count. Administration of chemotherapy and Filgrastim did not alter the pharmacokinetics of PEG-rHuMGDF.

Antineoplastic Agents↗
PubMed1999

DNA-binding activity of the transcription factor upstream stimulatory factor 1 (USF-1) is regulated by cyclin-dependent phosphorylation.

The ubiquitous transcription factor upstream stimulatory factor (USF) 1 is a member of the bzHLH (leucine zipper-basic-helix-loop-helix) family, which is structurally related to the Myc family of proteins. It plays a role in the regulation of many genes, including the cyclin B1 gene, which is active during the G2/M and M phases of the cell cycle and may also play a role in the regulation of cellular proliferation. We show that the affinity of recombinant USF-1 for DNA is greatly increased by treatment with active cyclin A2-p34(cdc2) or cyclin B1-p34(cdc2) complexes and that its interaction with DNA is dependent on p34(cdc2)-mediated phosphorylation. We have localized the phosphorylation site(s) to a region that lies outside the minimal DNA-binding domain but overlaps with the previously identified USF-specific region. Deletion studies of USF-1 suggest that amino acids 143-197 regulate DNA-binding activity in a phosphorylation-dependent manner.

Animals↗
PubMed1999

The prolonged hematologic effects of a single injection of PEG-rHuMGDF in normal and thrombocytopenic mice.

A single injection of > or =10 microg/kg PEG-rHuMGDF in mice causes a dose-dependent increase in circulating platelets beginning on day 3 and peaking on days 5-6. The mean platelet volume and platelet distribution width at doses > or =100 microg/kg initially increase in a dose-dependent fashion and later decrease. However, the mean platelet volume does not change when platelets are incubated with PEG-rHuMGDF in vitro. The number of marrow megakaryocytes increases in a dose-dependent fashion as early as day 1 and peaks on day 3. Marrow megakaryocyte colony-forming units (CFU-Meg) do not increase on days 1-3 at a dose of 100 microg/kg (a dose that increases platelet numbers two- to threefold and may be clinically relevant), but the relative frequency of high ploidy megakaryocytes and the proportion of large marrow megakaryocytes (29-50 microm in diameter) increases. After a dose of 1,000 microg/kg the percentage of megakaryocytes in mitosis peaks at 24-48 hours and the percentage of megakaryocytes incorporating BrdU is maximal at 48 hours, the relatively delayed peak of BrdU incorporation most likely representing endomitosis. The relative frequency of type II and III megakaryocytes peaks on days 3 and 4, respectively. Pharmacokinetic analysis of PEG-rHuMGDF shows peak serum concentrations at 2-4 hours and a terminal half-life of 11.4+/-2.5 hours. A single injection of PEG-rHuMGDF ameliorates carboplatin-induced megakaryocytopenia and thrombocytopenia in a dose-response dependent fashion. In conclusion, a single injection of PEG-rHuMGDF increases megakaryocyte and platelet production in normal and myelo-suppressed mice.

Acetylcholinesterase↗
PubMed1998

Lack of effect of RPE65 removal on the enzymatic processing of all-trans-retinol into 11-cis-retinol in vitro.

RPE65 is a major membrane associated protein found in the vertebrate retinal pigment epithelium (RPE). Various studies have shown this protein to be essential for visual function, possibly at the level of the processing of retinoids. The pigment epithelium is the anatomical site in which the visual chromophore 11-cis retinal is generated. The two critical RPE enzymes in the isomerization pathway are lecithin retinol acyl transferase (LRAT) and isomerohydrolase, which processes all-trans-retinyl esters into 11-cis-retinol. Both enzymes are membrane bound. It is shown here that RPE65 can be largely extracted (90-95%) from RPE membranes by 1 M KCl by itself, or with added detergent CHAPS. The almost quantitative extraction of RPE65 from RPE membranes has little or no effect on in vitro LRAT and isomerohydrolase activities in quantitative enzymatic assays using RPE membranes, suggesting that RPE65 may not have an important role to play in the enzymatic processing of all-trans-retinol into 11-cis-retinol in vitro.

Acyltransferases↗
PubMed1998

Antiulcer drug prescribing in hospital successfully influenced by "immediate concurrent feedback".

OBJECTIVE: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage. METHODS: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals. RESULTS: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals. CONCLUSION: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

Administration, Oral↗
PubMed1997

Prevention of thrombocytopenia and neutropenia in a nonhuman primate model of marrow suppressive chemotherapy by combining pegylated recombinant human megakaryocyte growth and development factor and recombinant human granulocyte colony-stimulating factor.

This report examines the effects on hematopoietic regeneration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) (2.5 micrograms/ kg/d) alone and in combination with recombinant human granulocyte colony stimulating factor (rHu-GCSF) (10 micrograms/ kg/d) for 21 days in rhesus macaques receiving intense marrow suppression produced by single bolus injections of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia (platelet count < 100 x 10(9)/L) was observed between days 12 and 25 (nadir 39 +/- 20 x 10(9)/L on day 17), and neutropenia (absolute neutrophil count < 1 x 10(9)/L) occurred between days 8 and 30 (nadir 0.167 +/- 0.120 x 10(9)/L on day 15). PEG-rHuMGDF (2.5 micrograms/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.9 +/- 0.2 ng/mL and increased the platelet count twofold over basal prechemotherapy levels (856 +/- 594 x 10(9)/L v baseline of 416 +/- 88 x 10(9)/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was not significantly altered (neutrophil count 0.224 +/- 0.112 x 10(9)/L v 0.167 +/- 0.120 x 10(9)/L; P > .3). rHu-GCSF (10 micrograms/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.4 +/- 1.1 ng/mL, and reduced the time for the postchemotherapy neutrophil count to attain 1 x 10(9)/L from 22 days to 4 days (P = .005). The postchemotherapy neutropenic nadir was 0.554 +/- 0.490 x 10(9)neutrophils/L (P = .3 v hepsulfam-only control of 0.167 +/- 0.120 x 10(9)/L). However, thrombocytopenia of < 100 x 10(9) platelets/L was not shortened (persisted from day 12 to day 25), or less severe (nadir of 56 +/- 32 x 10(9) platelets/L on day 14; P = .7 compared with untreated hepsulfam animals). The concurrent administration of rHu-GCSF (10 micrograms/kg/d) and PEG-rHuMGDF (2.5 micrograms/kg/d) in four animals resulted in postchemotherapy peripheral platelet counts of 127 +/- 85 x 10(9)/L (P = .03 compared with 39 +/- 20 x 10(9)/L for untreated hepsulfam alone, and P = .02 compared with 856 +/- 594 x 10(9)/L for PEG-rHuMGDF alone), and shortened the period of neutropenia < 1 x 10(9)/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing PEG-rHuMGDF to 10 micrograms/kg/d and maintaining the 21-day schedule of coadministration with rHu-GCSF (10 micrograms/kg/d) in another four animals produced postchemotherapy platelet counts of 509 +/- 459 x 10(9)/L (P < 10(-4) compared with untreated hepsulfam alone, and P = .04 compared with 2.5 micrograms/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of either agent. The administration of PEG-rHuMGDF (2.5 micrograms/kg/d) from day 1 through day 22 and rHu-GCSF (10 micrograms/kg/d) from day 8 through day 22 in six animals produced peak postchemotherapy platelet counts of 747 +/- 317 x 10(9)/L(P < 10(-4) compared with untreated hepsulfam alone, and P = .7 compared with PEG-rHuMGDF alone), and maintained the neutrophil count > 3.5 x 10(9)/L (P = .008 v rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow suppression. This improvement in platelet and neutrophil responses by delaying the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of optimizing the dose and schedule of cytokine combinations after severe myelosuppressive chemotherap

Alkylating Agents↗
PubMed1997

Ablation of human nail by pulsed lasers.

BACKGROUND AND OBJECTIVE: The hard and resistant structure of the nail plate forms a natural barrier that limits the penetration of topical drugs. To overcome this barrier, the use of pulsed laser systems has been suggested. The purpose of this study was to evaluate the effect of four laser systems on nail plate ablation rates, ablation efficiencies, and subsequent craters morphology. STUDY DESIGN/MATERIAL AND METHODS: Solid state Er:YAG (2.94 microns, 250 microseconds), a Ho:YSGG (2.08 microns, 250 microseconds), a XeC1 Excimer (308 nm, 15 ns), and a novel solid-state ultrashort pulse laser (1.05 microns, 350 fs) were used. Ablation rates, surface morphology, and extent of collateral damage were evaluated using light and electron microscopy. RESULTS: Best ablation efficiencies were demonstrated with the ultrashort pulsed laser (1 micron/mJ), whereas maximum material removal per pulse was obtained with the Er:YAG laser (80 microns/ pulse). Scanning electron microscopy showed cracking damage with both Ho:YSGG and Er:YAG. XeC1 and the ultrashort pulse system left tissue surfaces free of cracks or thermal damage. CONCLUSION: With its minimal acoustical and mechanical impact, high efficiency, and negligible collateral damage, the ultrashort pulse laser at 3 J/cm2 was found to be the optimal laser system for nail ablation.

Humans↗
PubMed1997

Purification, crystallization, and preliminary X-ray studies of 10-formyltetrahydrofolate synthetase from Clostridia acidici-urici.

The monofunctional enzyme 10-formyltetrahydrofolate synthetase (THFS), which is responsible for the recruitment of single carbon units from the formate pool into a variety of folate-dependent biosynthetic pathways, has been subcloned, purified, and crystallized. The crystals belong to space group P2(1), with unit cell dimensions a = 102.4 A, b = 116.5 A, c = 115.8 A, and beta = 103.5. The crystal unit cell and diffraction is consistent with an asymmetric unit consisting of the enzyme tetramer, and a specific volume of the unit cell of 2.7 A3/ Da. The crystals diffract to at least 2.3 A resolution after flash-cooling, when using a rotating anode x-ray source and an RAXIS image plate detector.

Bacterial Proteins↗
PubMed1997

Purification, crystallization, and preliminary x-ray studies of a bifunctional 5,10-methenyl/methylene-tetrahydrofolate cyclohydrolase/dehydrogenase from Escherichia coli.

A bifunctional enzyme that catalyzes the conversion of formyltetrahydrofolate to methylene-tetrahydrofolate (5,10-methenyltetrahydrofolate cyclohydrolase and 5,10-methylene tetrahydrofolate dehydrogenase), has been subcloned from a cDNA library, purified to homogeneity, and crystallized. The crystals belong to space group I222, with unit cell dimensions of a = 64.5 A, b = 84.9 A, c = 146.1 A. The crystal unit cell and diffraction is consistent with an asymmetric unit consisting of the enzyme monomer, and a specific volume of the unit cell of 3.2 A3/Da. The crystals diffract to at least 2.8 A resolution after flash-cooling, when using a rotating anode x-ray source and an RAXIS image plate detector. A 2.56 A resolution native data set has been collected at beamline X12-C at the NSLS.

Aminohydrolases↗
PubMed1996

Dose-response effects of pegylated human megakaryocyte growth and development factor on platelet production and function in nonhuman primates.

Thrombopoietin (TPO) is the physiologic Mpl-ligand regulating platelet production. Pegylated human recombinant megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated polypeptide Mpl-ligand derivitized with poly-(ethylene glycol), induces megakaryocyte endoreduplication and proliferation in vitro and in vivo. In the present study, the dose-response effects of PEG-rHuMGDF on pharmacokinetics, megakaryocytopoiesis, platelet production, and platelet function were characterized for dosing 0.05, 0.10, 0.50, or 2.5 micrograms/kg/d in 22 baboons for 28 days. Daily subcutaneous injections of PEG-rHuMGDF produced linear log-dose responses in (1) steady-state trough plasma levels of PEG-HuMGDF (P < 10(-3)); (2) marrow megakaryocyte volume (P < 10(-3)), ploidy (P < 10(-4)), and number (P < .01); and (3) peripheral platelet concentrations (P < 10(-4)) and platelet mass turnover (P < 10(-3)). Platelet morphology, life span, and recovery were normal, and peripheral leukocyte, neutrophil, and erythrocyte counts were not significantly affected by PEG-rHuMGDF (P > .1 in all cases). PEG-rHuMGDF at 0.5 micrograms/kg/d produced similar blood concentrations of Mpl-ligand and platelets as 10 times the dose of rHu-MGDF (5.0 micrograms/kg/d), reflecting the extended plasma half-life achieved through pegylation. Whereas PEG-rHuMGDF did not induce platelet aggregation in vitro, platelet aggregatory responsiveness induced by thrombin receptor agonist peptide (TRAP1-6) and collagen was transiently enhanced ex vivo during the initial few days of PEG-rHuMGDF administration. However, adenosine diphosphate (ADP)-induced platelet aggregation was not enhanced ex vivo by PEG-rHuMGDF therapy. 111In-platelet deposition on segments of homologous endarterectomized aorta (EA) and vascular graft (VG) interposed in arteriovenous femoral shunts increased in direct proportion to the circulating platelet concentration (P < 10(-4) for both EA and VG); 125l-fibrin accumulation was not affected by PEG-rHuMGDF-induced increases in peripheral platelet counts. Changes in platelet production and function produced by PEG-rHuMGDF returned to baseline within 2 weeks after discontinuing treatment. Thus, in nonhuman primates, PEG-rHuMGDF increases platelet production in a linear log-dose-dependent manner by stimulating megakaryocyte endoreduplication and new megakaryocyte formation from marrow hematopoietic progenitors. These findings suggest that appropriate dosing of PEG-rHuMGDF therapy during periods of chemotherapy-induced marrow suppression may maintain hemostatic concentrations of peripheral platelets without increasing the risk of thrombosis.

Adenosine Diphosphate↗
PubMed1996

Organization and characterization of the two yeast ribosomal protein YL19 genes.

A second copy of the Saccharomyces cerevisiae ribosomal protein YL19 gene was isolated through the use of the RPL19A gene as a probe. The nucleotide sequence of the gene, RPL19B, was determined. RPL19B contains an intron of 384 nucleotides located near its 5'-end. The coding regions of the two yeast genes, RPL19A and RPL19B, differ in only 34 nucleotides, none of which lead to changes in the amino-acid sequences of the predicted protein of 189 amino acids. RPL19B is also closely linked to a mitochondrial ADP/ATP carrier protein gene AAC2. Yeast cells containing disruption of either RPL19A or RPL19B formed smaller colonies than wild-type strains; however, simultaneous deletion of both genes is lethal.

Amino Acid Sequence↗