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Biomedical subjects

J C Yang

Publications and source records attributed to J C Yang.

At least 199 records · Page 11Linked to original sources
PubMed1987

Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin 2.

The systemic administration of high-dose recombinant IL 2 mediated significant reductions of established 3-day pulmonary micrometastases from both weakly immunogenic and nonimmunogenic sarcomas. However, when treatment with IL 2 was delayed for 10 days after the injection of tumor cells in an attempt to treat grossly visible pulmonary macrometastases, only those established from weakly immunogenic sarcomas remained susceptible. Established 10-day pulmonary nodules from the nonimmunogenic sarcomas became refractory to IL 2 therapy. We utilized selective depletion of lymphocyte subsets in vivo by the systemic administration of specific monoclonal antibodies to cells bearing either the L3T4 or Lyt-2 marker or a heteroantiserum to cells bearing the ASGM-1 glycosphingolipid to identify lymphocytes involved in IL 2-induced tumor regression. Cells with potent lymphokine-activated killer (LAK) activity against fresh tumor targets in vitro were identified in the lungs of IL 2-treated mice. By flow cytometry analysis, the majority of these effector cells were Thy-1+, L3T4-, Lyt-2-, ASGM-1+. Depletion in vivo of ASGM-1+ cells before the onset of IL 2 administration eliminated the successful therapy of 3-day pulmonary metastases from nonimmunogenic sarcomas, with concurrent elimination of LAK cell activity in the lungs. In mice with 3-day pulmonary metastases from weakly immunogenic sarcomas, both Lyt-2+ cells and ASGM-1+ cells were involved in IL 2-mediated tumor regression, but Lyt-2+ cells appeared to be the more potent mediator in the response. Lyt-2+ cells were also involved in the elimination of grossly visible 10-day macrometastases from these weakly immunogenic tumors. Depletion of L3T4+ cells had no effect on tumor regression. Thus, although LAK effectors derived from ASGM-1+ precursors can eliminate pulmonary micrometastases regardless of tumor immunogenicity, Lyt-2+ cells are predominant effectors in the elimination of both pulmonary micro- and macrometastases from weakly immunogenic sarcomas.

Animals↗
PubMed1987

Peritoneal accumulation of infused stroma-free hemoglobin. Potential toxicity of an oxygen-carrying substitute.

The efficacy of stroma-free hemoglobin (SFH) as an oxygen-carrying red blood cell substitute in shock and trauma remains inconclusive. A major problem is the retention of sufficient intravascular persistence. The sites and mechanisms for clearance of SFH or its chemically modified variants are not well characterized. Capillary leakage has been reported. Any significant leak into the peritoneal cavity may be toxic, especially if bacteria are present. The present study quantitates peritoneal accumulation of SFH and chemically modified adenosine triphosphate (ATP)-SFH following a 50% exchange transfusion in rats. m-Dansyl cadaverine, an endocytotic blocking agent, was studied for its ability to alter accumulation of hemoglobin in the peritoneum. Differences in renal clearance corresponded to differences in vascular halflife of SFH (90 minutes) and ATP-SFH (210 minutes). Peritoneal leakage was not related to vascular persistence. We found that MDC significantly decreases the peritoneal accumulation of ATP-SFH but not that of SFH. We also noted that MDC neither inhibits nor alters renal clearance of either hemoglobin variant. Total peritoneal leakage is, at most, 4% of infused SFH at four hours. Molecular size and charge might be factors important in hemoglobin transport from the vasculature to the peritoneum.

Adenosine Triphosphate↗
PubMed1987

Bioavailability studies of theophylline ethylcellulose microcapsules prepared by using ethylene-vinyl acetate copolymer as a coacervation-inducing agent.

The bioavailability of theophylline microcapsules prepared by using ethylene-vinyl acetate (EVA) copolymer as a coacervation-inducing agent was studied in rats. The dissolution rate of the microcapsules was determined by the rotating-basket and rotating-bottle methods. The higher the concentration of EVA copolymer used, the more sustained was the release of theophylline from the microcapsules. The mean maximum serum levels (Cmax) and time to maximum serum levels (tmax) were not significantly different for theophylline microcapsules prepared by a lower concentration of EVA copolymer (0 and 0.83%, respectively), compared with those for theophylline powder; whereas a significant difference was found when the higher concentration of EVA copolymer was used (greater than 1.7%). With regards to the area-under-the-curve (AUC) value, there was no significant difference between the theophylline powder and theophylline microcapsules. The elimination kinetics and the corresponding half-life (t1/2) were significantly different when the concentration of EVA copolymer was greater than 3.3%. From the above results, it is evident that theophylline microcapsules prepared by using 3.3 and 5.0% EVA copolymer as the coacervation-inducing agent may act as sustained-release dosage forms. The correlation between the dissolution rate in vitro and the bioavailability in rats for theophylline microcapsules was investigated. The mean Cmax and tmax correlated well with the time taken to release 75% of the drug in vitro (t 75%); however, the mean AUC showed no valid correlation with t 75%. This implies that the dissolution rate correlated better with the rate of absorption (Cmax, tmax) than with the extent of absorption (AUC).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Loss of control biomechanics of the human arm-elbow system.

An experimental study was conducted to determine whether external disturbance oscillations, such as those that could be created by hand held tools, alter the dynamic response characteristics of the human arm-muscle system. A special arm-test frame was used to induce external sinusoidal torque oscillations of various amplitudes and frequencies, while the reaction force and angular displacement were monitored. Two different output variable frequency responses were determined using input/output cross-spectrum analysis. The angular displacement of the test frame and a component of hand reaction force were the output variables used, while the test frame torque was the input. Test results from one subject are presented in this paper. Changes in the magnitude and phase angle of the frequency responses were observed for different frequencies of the disturbance torque. These changes indicate that the stability margin and response amplitude of the human arm-muscle system do change as a function of the frequency and amplitude of external disturbance oscillations. This suggests that at certain operating frequencies hand held tools can induce large reaction amplitudes or even loss of control.

Arm↗
PubMed1987

Transcholecystic endoscopic choledocholithotripsy: successful management of retained common bile duct stone.

Removal of large common bile duct stones has been a continuing challenge. The feasibility and efficacy of transcholecystic endoscopic choledocholithotripsy in a high-risk patient are demonstrated in this report. The procedure requires an established cholecystostomy track, catheter dilatation of the cystic duct, and the application of electrohydraulic shock waves to the calculus. The use of a choledochofiberscope permits the passage of the electrohydraulic probe and minimizes complications by direct monitoring. Stone fragments are removed by basket retrieval. This procedure in conjunction with minicholecystostomy may obviate the need for surgery in selected high-risk patients with combined gallbladder and common bile duct stones.

Cholelithiasis↗
PubMed1987

In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2.

A method was described for the generation of cells from tumor-bearing mice; these cells were capable of exhibiting significant antitumor reactivity when adoptively transferred into tumor-bearing hosts. Tumor cell suspensions from a variety of tumors were able to be separated using enzymatic techniques and they were cultured in medium containing recombinant interleukin-2. Activated infiltrating lymphocytes within these tumors expanded; and, by 6-8 days after initiation of culture, lymphocytes predominated and were able to grow to large numbers. The adoptive transfer of these tumor-infiltrating lymphocytes (TILs) made possible mediation of the reduction of established 3-day pulmonary micrometastases from 5 of 7 tumors tested, including two 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, one 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon carcinoma, and the B16 melanoma, all in C57BL/6 mice, as well as the 1660 bladder carcinoma in BALB/c mice. Approximately 2-4 X 10(6) transferred cells were capable of totally eliminating 3-day established metastases. These cells were thus 50 to 100 times more effective than lymphokine-activated killer cells in reducing established metastases; however, they could not be generated from all tumors. The concomitant administration of recombinant interleukin-2 enhanced, by approximately fivefold, the in vivo activity of these cells. The specificity of action of TILs in vivo was different from that determined by classic amputation rechallenge experiments. The tumor-infiltrating lymphocytes that developed this antitumor reactivity appeared to be Thy-1+ and did not bear the asialo GM1 antigen. The potent antitumor effect of these TILs, when transferred in vivo to tumor-bearing hosts, raises the possibility of utilizing similar approaches for the isolation and therapeutic use of lymphocytes with antitumor reactivity from human tumors.

Animals↗
PubMed1986

Inclusion complexation of warfarin with cyclodextrins to improve some pharmaceutical characteristics.

Inclusion complexation of warfarin and alpha- or beta-cyclodextrins in water and in the solid phase were studied by a solubility method, a membrane permeation study, thin-layer chromatography, a dissolution study, IR spectroscopy and differential scanning calorimetry. The solubility of warfarin increased with the addition of cyclodextrins. The apparent stability constants of the alpha- and beta-cyclodextrin complexes are 10.29 M-1 and 148.88 M-1, respectively. The greater the stability constant of the inclusion complex the lesser the permeability of warfarin. Solid complexes of warfarin and alpha- or beta-cyclodextrins were obtained by freeze-drying. Clear differences in IR absorption spectra and DSC thermograms were observed between the inclusion complexes and physical mixtures. The dissolution rate of the freeze-dried warfarin-cyclodextrin complexes was increased about 1200-fold and 550-fold for alpha- and beta-cyclodextrins, respectively. The dissolution rate of warfarin was significantly improved by complex formation.

Calorimetry, Differential Scanning↗
PubMed1986

Murine lymphokine-activated killer (LAK) cells: phenotypic characterization of the precursor and effector cells.

Murine and human lymphocytes incubated in recombinant interleukin 2 (RIL 2) generate a population of cytotoxic cells (lymphokine-activated killer cells [LAK]), which are able to lyse a wide array of fresh tumor cells but do not lyse fresh normal cells. Intravenous administration of these cells with the concomitant administration of RIL 2 can eliminate established pulmonary and hepatic metastases in mice. To characterize the cell that has in vitro LAK activity, we subdivided murine lymphocytes by lysing select subpopulations with the use of complement and antibodies against lymphocyte surface markers or by fluorescence-activated cell sorting. Thy-1.2-negative splenocytes were found to generate near normal amounts of LAK activity after RIL 2 incubation. Small and inconsistent LAK cell activity was generated from Thy-1.2-positive splenocytes. Ia-positive and surface immunoglobulin-positive splenocytes had little or no LAK precursor capability and did not appear to be necessary for LAK activation. Treatment of splenocytes with anti-asialo GM1 (anti-ASGM1) heterosera and complement markedly decreased their ability to generate LAK activity. At the effector stage, cytotoxic cells were of the Thy-1.2-positive, Ia-negative phenotype. Ia-depleted cells were separated into subpopulations bearing or not bearing the gamma Fc receptor (gamma FcR). The majority of cytotoxicity resided in gamma FcR-positive cells. Thus the precursors of murine LAK cells are "null" lymphocytes bearing neither T nor B cell surface markers but develop the Thy-1.2 cell surface marker in vitro, in association with the development of lytic activity for fresh tumor cells after stimulation by RIL 2.

Animals↗
PubMed1986

Colvalent linkage of phospholipid to myelin basic protein: identification of phosphatidylinositol bisphosphate as the attached phospholipid.

Evidence presented demonstrates a covalent attachment of a phospholipid to bovine myelin basic protein. Partial characterization of the phospholipid moiety was performed on myelin basic protein obtained from 32P-phosphorylated whole myelin that was first delipidated by two ether/ethanol (3:2 v/v) extractions, ether extraction, and acetone extraction and then purified by preparative sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The myelin basic protein was precipitated with aqueous acetone and treated with proteases. Treatment with carboxypeptidase Y or trypsin for several hours released a lipophilic fragment, which was purified by reverse-phase high-performance liquid chromatography to yield two "lipopeptides". Such lipopeptides were obtained from both the major and minor myelin basic proteins of rat and bovine brain. Treatment with either mild base or phospholipase C removes the lipophilic character of the peptide fragment. The lipophilic fragment is a substrate for phospholipase D, but it does not comigrate on thin-layer chromatography with any 32P-labeled lipid obtained from myelin incubated with [gamma-32P]ATP. Polyphosphoinositides were shown to be released by mild acid treatment of myelin basic protein that had been extracted with organic solvent and then purified by SDS-polyacrylamide gel electrophoresis. Along with the fact that inositol monophosphate was identified in the partial acid hydrolysate of the lipopeptide, we have concluded that polyphosphoinositide (phosphatidylinositol 4-phosphate and/or phosphatidylinositol 4,5-bisphosphate) was the original phospholipid portion of the lipopeptide.

Animals↗
PubMed1986

Covalent linkage of phospholipid to myelin basic protein: identification of serine-54 as the site of attachment.

The peptide portion of the lipopeptide isolated from bovine myelin basic protein contained glycine, lysine, and serine in a 2:1:1 molar ratio as determined by amino acid analysis. The N-terminus of the peptide was determined to be glycine. The tetrapeptide Gly53-Ser-Gly-Lys56 was the only segment of myelin basic protein that matched the above two characteristics. This tetrapeptide is highly conserved among the myelin basic proteins sequenced so far. After the selective degradation of the lipopeptide, phosphoserine was identified in the acid hydrolysate, thus indicating that Ser-54 of myelin basic protein in bovine brain is the site of attachment of polyphosphoinositide. Interestingly, serine-54 of myelin basic protein can be phosphorylated by the endogenous protein kinase myelin. However, myelin basic protein phosphorylated by the catalytic subunit of an exogenous soluble protein kinase failed to produce radioactively labeled lipopeptide. Hence the endogenous enzymes of myelin are thought to be involved in the formation of the covalent linkage between polyphosphoinositide and myelin basic protein. The conservation in sequence suggests a possible important structural role for the "phospholipidation" of myelin basic protein.

Amino Acids↗
PubMed1986

Multidimensional scaling reveals two dimensions of thermal pain.

The Individual Differences Scaling (INDSCAL) model of multidimensional scaling was used to explore the dimensions of thermal pain. The observers made 66 similarity judgments to all pairs of 12 different thermal stimulus intensities ranging from zero to noxious. Analysis of the data revealed a two-dimensional group stimulus space. The major dimension ordered the stimuli with respect to their intensity. This quantitative, strength-of-sensation dimension may be interpreted as indicating how weak or strong a stimulus feels, apart from any secondary qualities of warmth or pain. The second dimension was related to the qualitative aspects of the stimuli. This bipolar dimension contained two attributes: a pain attribute ranging from just detectable warmth to painful, and a warm-hot attribute running from just detectable warmth to hot. This study demonstrates the utility of the INDSCAL approach to the understanding of pain and offers a new technique for answering the age-old question concerning the number and qualities of the dimensions underlying the pain experience.

Adult↗
PubMed1986

Altered pain and visual sensitivity in humans: the effects of acute and chronic stress.

In the runner study, as measured by tourniquet ischemic pain, exercise stress produced hypoalgesia 20 minutes post-run, followed by hyperalgesia and euphoria at 30 minutes. The hypoalgesia and euphoria were reversed by naloxone. Exercise stress also produced a decrease in P(A), suggesting hypoalgesia to the thermal cutaneous stimulation. However, this analgesia was not naloxone reversible. Nor did exercise stress produce analgesia to cold-pressor pain. In the acupuncture study, noxious electrical stimulation of classical acupuncture sites failed to produce analgesia either during or after stimulation. However, expectation did produce a change in the pain report criterion, but only in the acupunctured arm. Noxious electrical stimulation (TENS) of the median nerve produced no analgesia outside of the related segmental area, that is, acute electrical pain did not produce generalized hypoalgesia. Thus, the effects of the stress produced by noxious electrical stimulation differ from that produced by exercise. In contrast to the results of the acute pain studies, chronic clinical pain, which combines mental stress and pain stress, produced strong hypoalgesia and anesthesia. Again, in contrast to the acute experimental pain studies, the emotional stress of mental illness produces hypoalgesia, but not anesthesia. Finally, the somatosensory system is not the only the sensory system affected by stress. Cold-pressor pain decreases visual sensitivity both during and for a few minutes following stimulation, and does not interfere with short-term (supra-digit span) memory.

Acupuncture Therapy↗