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Biomedical subjects

Z Yu

Publications and source records attributed to Z Yu.

At least 325 records · Page 18Linked to original sources
PubMed1994

Peptide-antibody conjugates for tumour therapy: a MHC-class-II-restricted tetanus toxin peptide coupled to an anti-Ig light chain antibody can induce cytotoxic lysis of a human B-cell lymphoma by specific CD4 T cells.

Anti-idiotype antibody therapy of B-cell lymphomas, despite numerous promising experimental and clinical studies, has so far met with limited success. Tailor-made monoclonal anti-idiotype antibodies have been injected into a large series of lymphoma patients, with a few impressive complete tumour remissions but a large majority of negative responses. The results presented here suggest that, by coupling to antilymphoma idiotype antibodies a few molecules of the tetanus toxin universal epitope peptide P2 (830-843), one could markedly increase the efficiency of this therapy. We show that after 2-hr incubation with conjugates consisting of the tetanus toxin peptide P2 coupled by an S-S bridge to monoclonal antibodies directed to the lambda light chain of human immunoglobulin, human B-lymphoma cells can be specifically lysed by a CD4 T-lymphocyte clone specific for the P2 peptide. Antibody without peptide did not induce B-cell killing by the CD4 T-lymphocyte clone. The free cysteine-peptide was also able to induce lysis of the B-lymphoma target by the T-lymphocyte clone, but at a molar concentration 500 to 1000 times higher than that of the coupled peptide. Proliferation assays confirmed that the antibody-peptide conjugate was antigenically active at a much lower concentration than the free peptide. They also showed that antibody-peptide conjugates required an intact processing function of the B cell for peptide presentation, which could be selectively inhibited by leupeptin and chloroquine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Pharmacokinetics of SDZ 64-412, a novel antiasthmatic agent, following intravenous, oral, and inhalation dosing in the rat.

The pharmacokinetics of SDZ 64-412, an antiasthmatic agent, were investigated following intravenous, oral, and inhalation dosing in rats. 14C-SDZ 64-412 was administered intravenously (2.75 mg kg-1) and orally (5.5 mg kg-1, 110 mg kg-1), whereas non-radiolabeled drug (5.04 mg kg-1) was administered using nose-only inhalation chambers. Radioactivity and parent drug concentrations in blood, lung, and excreta were determined at designated times post-dose. SDZ 64-412 was rapidly and extensively (approximately 80%) absorbed following both oral doses, although absorption appeared to be prolonged with increasing dose. The absorbed drug was shown to undergo extensive and saturable first-pass metabolism. The bioavailability of the parent drug, calculated by dose-normalized AUC and deconvolution methods, was only 10-15% from the low dose, but increased to approximately 40% following the high dose. Following inhalation dosing, SDZ 64-412 concentrations in blood and lungs increased rapidly, and did not decline immediately after termination of dosing. The inhalation dose yielded a bioavailability of approximately 40%, and AUC of the drug in lungs was approximately 25 times greater than in blood. In general, SDZ 64-412 was extensively distributed and rapidly eliminated from the systemic circulation. Biliary excretion was the predominant route of radioactivity excretion. The present findings suggest that inhalation administration provides a viable means of delivery of SDZ 64-412.

Administration, Inhalation↗
PubMed1994

Luting cement-metal surface physicochemical interactions on film thickness.

Low film thickness is critical to the clinical success of cemented castings. This study investigated the effect of luting agent-metal physico-chemical surface interactions on film thicknesses of representative luting agents. Control group luting agents were placed between two glass plates, as described by American Dental Association specifications 8, 61, and 66, and test group luting agents were positioned between glass and metal plates. The materials selected were zinc phosphate cement, polycarboxylate cement, glass ionomer cement, glass ionomer-composite resin hybrid cement and a resinous cement, with a type III gold alloy, a noble metal ceramic alloy, and a base metal ceramic alloy. A two-way analysis of variance and follow-up tests were done. The effects of the type of metal surface, type of cement, and their statistical interaction significantly affected film thickness (p < 0.0001). The type of cement had a greater affect on film thickness than the type of metal. A glass ionomer cement produced lower overall film thicknesses than other cement types, and a noble metal ceramic alloy created lower overall film thicknesses than other types of metal. American Dental Association specifications for cement film thickness did not accurately reflect normal cement use.

American Dental Association↗
PubMed1994

In vivo microleakage of luting cements for cast crowns.

Standardized tooth preparations were completed on previously intact human molars in vivo, and castings were made with a precious metal ceramic alloy by conventional techniques. The castings were randomly assigned to the following luting agents: zinc phosphate, composite resin-glass ionomer hybrid, and a composite resin-glass ionomer hybrid with a dentinal bonding agent and were cemented in a standardized manner to periodontally compromised molars. After 6 months the teeth were carefully extracted, stained, embedded, and sectioned, and the in vivo microleakage was measured. ANOVA disclosed significant differences between groups, and a multiple comparisons test revealed that the zinc phosphate group leaked significantly more than other cement groups.

Adult↗
PubMed1994

An ultra-sensitive electrochemical enzyme immunoassay for thyroid stimulating hormone in human serum.

A sensitive heterogeneous electrochemical enzyme immunoassay has been developed for thyroid stimulating hormone (TSH) by modifying a commercially available two-site immunoenzymometric assay. p-Aminophenyl phosphate (PAPP) was used as the substrate of alkaline phosphatase, and hydrolysed to p-aminophenol (PAP). The amount of PAP produced from the assay was proportional to the amount of TSH in the sample. Detection of PAP was done by oxidative amperometry in a flow injection system. The working electrode was a glassy carbon electrode whose potential was held at +325 mV (vs Ag/AgCl). The amperometric detection of PAP required only 1 microliter of sample (the range of linearity: 50.0 fmol-100 pmol PAP, the limit of detection: 10.9 fmol PAP). Intra-assay precision over the assay range of linearity (0.02-60 mIU l-1 or 0.02-60 pIU TSH) showed a maximum RSD of 8.0%, and a low detection limit of 0.01 mIU l-1 or 0.01 pIU TSH. The study also indicates that this two-site electrochemical enzyme immunoassay correlates well with the Bio-Rad's immunoradiometric assay currently used in our medical center (r = 0.992, slope = 1.53, n = 43) and a highly sensitive immunochemiluminometric assay in the Nichols Institute (r = 0.986, slope = 0.499, n = 23).

Electricity↗
PubMed1994

Pharmacokinetics of intranasally-administered dihydroergotamine in the rat.

Intranasal dosing of dihydroergotamine (DHE) allows convenient self-administration and provides an alternate route of administration for the treatment of migraine in addition to the existing parenteral dosage forms. In this study, the pharmacokinetics of 3H-DHE were investigated following intravenous and intranasal dosing (0.343 mg DHE/animal) in the rat. Intranasal administration of DHE resulted in rapid absorption. The extent of absorption of the radiolabeled dose was approximately 45%-60%. Absolute bioavailability of the parent drug was 35%-40%, as determined by deconvolution and by the ratios of AUC0-infinity following intranasal and intravenous dosing. Due to the limited capacity of the nostrils, approximately half of the intranasal dose was swallowed into the gastrointestinal tract. Biliary excretion was found to be the predominant pathway of radioactivity excretion following both routes of administration. The results from this study suggest that intranasal administration provides a viable means of delivering DHE into the systemic circulation.

Administration, Intranasal↗
PubMed1994

Effect of current magnitude and drug concentration on iontophoretic delivery of octreotide acetate (Sandostatin) in the rabbit.

The effect of current magnitude and drug concentration on transdermal iontophoretic delivery of octreotide acetate (Sandostatin) was examined in the rabbit. Plasma samples were collected over 24 hours and octreotide concentrations were determined by a radioimmunoassay. Without an electrical current, negligible plasma concentrations of octreotide were obtained. Following initiation of iontophoresis, plasma concentrations of octreotide increased rapidly, although did not sustain at a plateau level during the dosing period. Octreotide concentrations declined rapidly after removal of the device. Increasing the electrical current from 50 microA/cm2 to 150 microA/cm2 yielded a proportional increase in the delivery. Increasing the drug concentration in the device from 2.5 mg/mL to 5 mg/mL resulted in approximately proportional increase in plasma octreotide concentrations; however, further increase in plasma concentrations was not observed for drug concentrations beyond 5 mg/mL. Iontophoretic delivery at the conditions which yielded the highest octreotide concentrations in this study (5 mg/mL solution at 150 microA/cm2 for 8 hours) yielded an apparent bioavailability (which represents an underestimate of the absolute bioavailability determined when the patches are run to exhaustion) of approximately 8%.

Amino Acid Sequence↗
PubMed1994

Saturated molecular map of the rice genome based on an interspecific backcross population.

A molecular map has been constructed for the rice genome comprised of 726 markers (mainly restriction fragment length polymorphisms; RFLPs). The mapping population was derived from a backcross between cultivated rice, Oryza sativa, and its wild African relative, Oryza longistaminata. The very high level of polymorphism between these species, combined with the use of polymerase chain reaction-amplified cDNA libraries, contributed to mapping efficiency. A subset of the probes used in this study was previously used to construct an RFLP map derived from an inter subspecific cross, providing a basis for comparison of the two maps and of the relative mapping efficiencies in the two crosses. In addition to the previously described PstI genomic rice library, three cDNA libraries from rice (Oryza), oat (Avena) and barley (Hordeum) were used in this mapping project. Levels of polymorphism detected by each and the frequency of identifying heterologous sequences for use in rice mapping are discussed. Though strong reproductive barriers isolate O. sativa from O. longistaminata, the percentage of markers showing distorted segregation in this backcross population was not significantly different than that observed in an intraspecific F2 population previously used for mapping. The map contains 1491 cM with an average interval size of 4.0 cM on the framework map, and 2.0 cM overall. A total of 238 markers from the previously described PstI genomic rice library, 250 markers from a cDNA library of rice (Oryza), 112 cDNA markers from oat (Avena), and 20 cDNA markers from a barley (Hordeum) library, two genomic clones from maize (Zea), 11 microsatellite markers, three telomere markers, eleven isozymes, 26 cloned genes, six RAPD, and 47 mutant phenotypes were used in this mapping project. Applications of a molecular map for plant improvement are discussed.

Avena↗
PubMed1994

Lysis of porcine trophoblast cells by endometrial natural killer-like effector cells in vitro does not require interleukin-2.

Cells with cytotoxic activity against the cell line K562 and expressing perforin have been demonstrated in endometrial cells isolated from pigs early in pregnancy. This study was designed to determine whether porcine trophoblast cells were susceptible to these endometrial effector cells in vitro. Pregnant gilts (n = 8) were slaughtered between Days 17 and 20 of gestation. Immediately after slaughter, both the endometrial effector cells and trophoblast cells were isolated enzymatically from each animal. Enzymatically dispersed endometrial cells were further fractionated by size at unit gravity, whereas trophoblast cells were enriched by discontinuous density centrifugation on Percoll. Cytolytic activity was evaluated against Na2 51CrO4-labeled trophoblast and K562 cells. Comparison was made between freshly prepared and interleukin-2 (IL-2)-stimulated effector cells. The effect of prostaglandin E2 (PGE2) was tested by including it directly in the 51Cr-release assay. The results indicated that porcine trophoblast cells, like K562 cells, could be recognized and directly lysed by endometrial effector cells. Preculture of effector cells with IL-2 was not required for target lysis but enhanced their cytolytic activity against both trophoblast and K562 targets. In contrast, PGE2 exhibited highly suppressive effects on the cytotoxic activity of both freshly isolated and IL-2-stimulated endometrial effector cells. Conjugate assays demonstrated the binding of trophoblast and K562 targets by effector cells of similar morphology. Cold-target inhibition assays suggested that the effectors in porcine endometrial cell preparations that killed trophoblast and K562 cells were the same NK cell-like population.

Animals↗
PubMed1994

Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture, and ryanodine binding.

To study the mechanisms of cardiac dysfunction in experimental diabetes, adult rat cardiomyocyte shortening (measured with a video edge-detector system), the sarcoplasmic reticulum (SR) Ca2+ content [assessed by rapid-cooling contracture (RCC) and caffeine contracture (CC)] was examined. Ryanodine binding to the SR Ca(2+)-release channel of myocardium homogenate was also studied. Myocytes from diabetic rats showed depressed shortening (44% decrease compared with controls), reduced maximum rates of shortening and relengthening (58 and 56% decrease, respectively), and prolonged time to peak shortening (47% increase). RCCs and CCs from diabetic cells were 68 and 75% of the control values, respectively. Most of these cardiomyocyte abnormalities were corrected by daily insulin treatment in the diabetic rats. Ryanodine binding parameters indicated that the number of high-affinity binding sites was decreased in diabetic hearts. These data suggest that changes in contractile parameters as measured in diabetic myocytes are in good agreement with data obtained from intact heart or cardiac tissue preparations. Decreased SR Ca2+ content and reduced ryanodine binding sites indicate that the SR functions of storage and release of Ca2+ were depressed. This consequently may cause depressed contraction in diabetic hearts.

Animals↗
PubMed1994

Depressed [Ca2+]i responses to isoproterenol and cAMP in isolated cardiomyocytes from experimental diabetic rats.

Experimentally, diabetic rat hearts are characterized by diminished responses to beta-adrenergic stimulation. Among the aberrant responses are diminished beta-adrenoceptor number and depressed contractile protein activity. In this study, intracellular Ca2+ concentration ([Ca2+]i) was determined by microfluorescence in response to beta-adrenergic stimulation to understand the basis for the changes in the beta-adrenergic pathway in diabetic myocardium. In quiescent myocytes, isoproterenol caused a decrease in [Ca2+]i, which was blocked by timolol and thapsigargin. This suggests that the beta-agonist-induced [Ca2+]i changes are mediated, in part, by sarcoplasmic reticulum Ca-adenosinetriphosphatase. Diabetic myocytes showed a blunted response to isoproterenol, which was reversed by insulin treatment. In electrically stimulated myocytes, isoproterenol and 8-bromo-adenosine 3',5'-cyclic monophosphate (cAMP) increased [Ca2+]i and contraction in a concentration-dependent manner. Electrically stimulated diabetic myocytes demonstrated a depressed maximum [Ca2+]i response to isoproterenol and 8-bromo-cAMP without a change in sensitivity. These data suggest that in addition to alterations in beta-adrenoceptor function there are postreceptor defects in diabetic myocardium that may impair the regulation of [Ca2+]i in diabetic myocardium.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

[Serological investigation on intrafamilial transmission of HCV infection].

To clarify the intrafamilial transmission of HCV infection, the antibody to HCV was assayed in 124 serum samples from the family members of 60 HCV-Ab (+) index cases (group C), and compared with that from 83 family members of 40 HCV-Ab (-) index patients with hepatitis B (group B), Nine of 124, including 2 parents, 6 spouse and 1 granddaughter, were positive for anti-HCV. The prevalence of anti-HCV was 7.3% (9/124) in total, and 1.85% (2/108) in the subjects who had no history of blood donation. None of 83 was positive for anti-HCV in group B. On the other hand, the prevalence of HBV infection was 25.33% in the group of HCV infection only, and 40.91% in the group with HBV/HCV double-infection or HBV infection. It indicates that the risk of HBV intrafamilial transmission is higher than that of HCV, and the risk of transmission of HCV from mother to infant may be lower than that of sexual transmission.

Adolescent↗
PubMed1994

Diminished luminal release of esophageal epidermal growth factor in patients with reflux esophagitis.

OBJECTIVES: It has recently been demonstrated that human esophageal mucosa, containing numerous submucosal mucous glands, has the ability to elaborate significant amounts of esophageal epidermal growth factor (eEGF). Because of its role in the maintenance of the integrity of the esophageal mucosa, we elected to study the rate of secretion of eEGF in patients with reflux esophagitis (RE), compared with controls, using our newly developed esophageal perfusion model. METHODS: Fourteen healthy asymptomatic volunteers and 14 patients with endoscopically confirmed esophagitis underwent esophageal perfusion with saline, HCl (0.01 M, pH 2.1) HCl/pepsin (0.5 mg/ml of HCl), and ending NaCl solution during four consecutive 8-min perfusion periods. All perfusates were assayed for EGF by RIA (Amersham). Results are expressed as mean +/- SEM. Student's t test was used for statistical analysis. RESULTS: The basal rate of luminal EGF release in patients with RE was 3.78 +/- 0.29 ng/min. This value significantly declined (2.27 +/- 0.27 ng/min; p < 0.001) during mucosal exposure to HCl but was significantly enhanced when the HCl perfusing solution was supplemented with pepsin (4.20 +/- 0.29; p < 0.001 vs. HCl). Introduction of saline during the last perfusion period maintained a rate of luminal EGF release similar to that observed during the initial esophageal perfusion with saline. Luminal release of EGF in patients with RE was significantly lower, compared with corresponding values recorded in controls during perfusion with saline (3.78 +/- 0.29 vs. 14.1 +/- 1.25 ng/min; p < 0.00001), with HCl (2.27 +/- 0.27 vs. 5.95 ng/min; p < 0.0001), with HCl/pepsin solution (4.2 +/- 0.29 vs. 11.7 +/- 1.88 ng/min; p < 0.0001), and during the final perfusion period with saline (3.73 +/- 0.25 vs. 15.1 +/- 1.1 ng/min; p < 0.00001). Therefore, the rate of luminal EGF release in controls was 4-fold, 3-fold, 3-fold, and 4-fold higher than that of patients with RE during perfusion with initial saline, HCl, HCl/pepsin and final saline, respectively. CONCLUSIONS: 1) Decreased esophageal EGF in patients with RE may facilitate the development or delay the healing of mucosal injury. 2) Depletion of EGF from the mucus layer covering the epithelium under the impact of refluxed luminal acid/pepsin may be considered as one of the potential underlying mechanisms leading to damage of the esophageal mucosa during gastroesophageal reflux episodes.

Epidermal Growth Factor↗
PubMed1994

[Atrial specific granules are an intracellular calcium store].

In order to elucidate whether the secretion of atrial natriuretic peptide (ANP) is correlated to the release of calcium (Ca) from the atrial specific granules (ASG), it is necessary to explore whether the ASG contain highly concentrated Ca and how the high Ca is maintained in the ASG. The present study was designed to determine Ca in the ASG with the quantitative electron microscope X-ray microanalysis and Ca(2+)-ATPase with electron microscopic (EM) cytochemical technique. The ultrathin cryosections of rapid frozen fresh rat auricles were used for measuring Ca concentration with a JEM-1200EX electron microscope equipped with a Link AN 10,000 energy dispersive X-ray spectroscope. The measurement showed that the Ca concentration in the ASG was quite high, being 81 +/- 15 mmol/kg (n = 10), comparable with that found in the sarcoplasmic reticulum. With the Ca(2+)-ATPase EM cytochemical technique, the reaction products proved to be deposited on the membrane of the ASG. It was postulated that the Ca(2+)-ATPase on the membrane of ASG pumped Ca2+ out of the cytosol into the ASG and thus maintained a high Ca concentration inside the ASG. Therefore, the ASG might be considered to be a Ca store in atrial cardiocytes.

Animals↗