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Biomedical subjects

C L Yu

Publications and source records attributed to C L Yu.

At least 127 records · Page 7Linked to original sources

Modulation of lymphocyte proliferation by enzymes that degrade amino acids.

In a previous study we demonstrated thirteen amino acids to be essential and two to be partially essential for lymphocyte proliferation. Arginine is one of the essential amino acids, and the highly purified arginase strongly inhibited lymphocyte proliferation. The modulation of lymphocyte growth by various amino acid-degrading enzymes was studied. Peripheral lymphocytes were cultured in RPMI 1640 with or without amino acid-degrading enzyme for 72 h. A total of 17 commercial L-amino acid-degrading enzymes were studied. At 10 micrograms/ml, both lysine decarboxylase and asparaginase completely inhibited lymphocyte proliferation, arginase resulted in 78% inhibition and tyrosinase 57% inhibition. Other enzymes inhibited less than 20% lymphocyte proliferation; they included alanine dehydrogenase, arginine decarboxylase, aspartase, glutamic decarboxylase, glutamic dehydrogenase, glutaminase, histidase, histidine decarboxylase, leucine dehydrogenase, phenylalanine decarboxylase, phenylalanine hydroxylase, tryptophanase, and tyrosine decarboxylase. All four enzymes that strongly inhibited lymphocyte proliferation degraded amino acids that are essential for lymphocyte growth.

Arginase↗

Characterization of murine liver-derived inhibitory protein.

Murine liver-derived inhibitory protein (LIP) capable of inhibiting human lymphocyte proliferation was highly purified from liver extract. Its molecular weight determined by gel filtration and SDS-PAGE was 105,000 and 38,400 respectively. LIP moved electrophoretically at the gamma-globulin region. Its activity in inhibiting lymphocyte proliferation was temperature-stable up to 60 degrees C, and pH-stable between 4 and 11. It was not cytotoxic to lymphocytes as shown in 51Cr-release experiments. The purified LIP possessed arginase activity.

Animals↗

Serum stimulation of NIH 3T3 cells induces the production of lipids able to inhibit GTPase-activating protein activity.

Quiescent NIH 3T3 cells were stimulated with serum prior to the extraction of total cellular lipids. These lipids were fractionated on thin-layer chromatography plates, and individual fractions were tested for the ability to inhibit GTPase-activating protein (GAP) activity. Two separate GAP inhibitory lipids were produced. One behaved similarly to arachidonic acid during silica gel chromatography, whereas the other was related to a phosphoinositide. Further study of the arachidonic acid-related material indicated that it was produced between 1 and 5 min after serum addition but was never observed in high-density, contact-inhibited cultures. The identity of these lipids is under investigation. The possibility raised by these results, that a metabolite of arachidonic acid is involved in mitogenic signaling, was supported by the finding that several lipoxygenase products of arachidonic acid efficiently inhibited GAP activity. These results provide further support for the hypothesis that lipids, GAP, and ras activity function together in the control of cellular proliferation.

Animals↗

Evidence that an immunosuppressive protein from murine liver is arginase.

A protein (mLIP) with strong inhibitory activity on PHA-induced lymphocyte proliferation was purified to homogeneity from murine liver. Both the arginase activity and the inhibitory activity were found superimposed on the same peak during gel filtration. The arginase activity of mLIP was identified by determining the arginine degradation products, urea (by alpha-diketone-urea complex formation) and ornithine (by HPLC). The inhibitory activity of mLIP was neutralized by adding more arginine to the culture medium. The mutual action between mLIP and arginine was found to be dose-related. Furthermore, the inhibition and arginase activities were simultaneously absorbed by anti-mLIP affinity column and both reappeared in the acid-eluate. These results indicate that the murine liver-derived inhibitory protein is the liver L-arginase itself.

Animals↗

[Protective effects of total saponins of semen Ziziphi spinosae on cultured rat myocardial cells].

The effects of total saponins of Semen Ziziphi spinosae (ZS) were observed on cultured neonatal rat myocardial cells injured by deprivation of oxygen and glucose (DOG) or treatment with chlorpromazine (CPZ) and mitomycin C (MMC). The increases of lactate dehydrogenase release from damaged myocardial cells induced by DOG, CPZ and MMC were attenuated by ZS (33 micrograms/ml) except 11 micrograms/ml which showed no effect on MMC (24 h) and CPZ (9 h)-induced injuries. These data suggest that ZS is an effective protective drug for myocardial cells.

Animals↗

Intrathecal morphine's effect on somatosensory impulses transmission-studied with posterior tibial nerve SSEP.

In order to investigate neurotoxic potential of spinally injected morphine solution, somatosensory evoked potential (SSEP) was utilized to detect the change of electrophysiologic activity of spinal neurons after long term application of intrathecal morphine. Eight patients received intrathecal morphine injection regularly after CHEMO-PORT implantation were studied with posterior tibial nerve SSEP. Patients received SSEP examination just before and right after first episode of morphine injection and were followed up at 30 minutes, 60 minutes, 2 hours, 8 hours, and the 7th day and the third month of regularly injection. The results showed that there were no definite change of latencies and amplitudes of impulses generated by lumbar spinal cord (N22) and cortex (P40). We therefore suggest that electrophysiologic activities of spinal cord and cortex are not affected by chronic intrathecal morphine injection. Possible mechanism and proposed pathway of morphine's action were also discussed.

Evoked Potentials, Somatosensory↗

[Influences of 3,4,5-trihydroxystibene-3-beta-mono-D-glucoside on beat rate and injury of cultured newborn rat myocardial cells].

3,4,5-Trihydroxystibene-3-beta-mono-D-glucoside (PD) from Polygonum cuspidatum 0.05-0.45 mmol/L increased beat rate of myocardial cells from 100% to 112-220%. This action of PD 0.15 mmol/L was agonized by nisoldipine 0.1, propranolol 10 and phentolamine 1 mumol/L. PD (0.05, 0.15 mmol/L) decreased the lactate dehydrogenase (LDH) amount liberated by myocardial cells, from 98 +/- 11 IU/ml of deprivation of oxygen and glucose (DOG) to 55 +/- 16, 68 +/- 14 IU/ml (P less than 0.01) 6 h after injury of DOG; 77 +/- 9, 80 +/- 6 IU/ml (P less than 0.01) 9 h after injury of DOG. PD 0.15 mmol/L decreased the LDH amount liberated by myocardial cells, from 311 +/- 34 to 231 +/- 42 IU/ml (P less than 0.05) 9 h after injury of chlorpromazine (CPZ). It is suggested that PD can protect myocardial cells injured by DOG and CPZ.

Animals↗

[Effects of nicardipine on beating rates of cultured myocardial cells].

Nicardipine (Nic) 15 nmol/L had no effects on beating rates of cultured myocardial cells. Nic 75 and 150 nmol/L depressed the beating rates significantly. Rapid standstills occurred earlier and more in 150 nmol/L group than in 75 nmol/L. Both isoproterenol and CaCl2 restored the beating depressed by Nic. However, only CaCl2 prevented the standstill. These results suggest that nicardipine may compete with calcium in excitation-contraction coupling.

Animals↗

[Median nerve somatosensory evoked potential monitoring during carotid endarterectomy-report of one case].

Carotid endarterectomy was performed on a 64 y/o female patient who had been suffering from multiple transient ischemic attacks caused by the stenosis of right common carotid artery at its bifurcation. Median nerve somatosensory evoked potential (SSEP) was utilized for monitoring cerebral function during and after operation. Latency, amplitude and central conduction time (CCT) of bilateral N13 (CV2) and N20 (C3', C4') were measured as an aid for management of anesthesia, surgical procedure and postoperative care. The results showed SSEP which is sensitive for detection of cerebral ischemia and could help the surgeon and anesthesiologist maintaining optimal cerebral perfusion, but yields little information about postoperative hyperperfusion state. Besides evaluating the efficacy of SSEP, we discussed the problems encountered during the SSEP monitoring.

Carotid Arteries↗

The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids.

Bacterially synthesized c-Ha-ras protein (Ras) was incubated with guanosine triphosphatase (GTPase) activating (GA) protein in the presence of various phospholipids. The stimulation of Ras GTPase activity by GA protein was inhibited in some cases. Among the lipids most active in blocking GA protein activity were lipids that show altered metabolism during mitogenic stimulation. These included phosphatidic acid (containing arachidonic acid), phosphatidylinositol phosphates, and arachidonic acid. Other lipids, including phosphatidic acid with long, saturated side chains, diacylglycerols, and many other common phospholipids, were unable to alter GA protein activity. The interaction of lipids with GA protein might be important in the regulation of Ras activity during mitogenic stimulation.

Animals↗

Alteration of mitogenic responses of mononuclear cells by anti-ds DNA antibodies resembling immune disorders in patients with systemic lupus erythematosus.

Anti-double-stranded DNA antibodies (anti-DNA) purified from pooled active SLE sera by lambda phage DNA-affinity chromatography was found to affect phytohemagglutinin (PHA) and pokeweek mitogen (PWM)-induced responses of normal mononuclear cells. Anti-DNA at a concentration of 0.25 mg/ml (equivalent to 21 units/ml of DNA binding activity) significantly suppressed the PHA-induced [3H]thymidine incorporation of mononuclear cells in 3 days of culture but had no effect on 5-day and 7-day cultures. In contrast, a biphasic effect of anti-DNA on PWM response was found such that early phase (3-day culture) was inhibited whereas late phase (from 5 days to 9 days of culture) was enhanced by the antibodies. Anti-DNA also increased the immunoglobulin synthesis by PWM-stimulated B cells. The inhibition of PHA response in 3-day culture by anti-DNA is not due to changes in T cell subpopulations. Because interleukin 1 (10 units/ml) could restore the PHA response, it appears that anti-DNA suppressed the IL-1 production by monocyte/macrophage. The biphasic effect of anti-DNA on PWM response is the result of monocyte impairment and B cell stimulation by the antibodies. In the early phase (on day 3) the inhibition would seem to be due to impairment of accessory cell function by anti-DNA, though in late phase (after day 5) the anti-DNA may stimulate B lymphocytes to incorporate more thymidine in the presence of PWM. These biological effects of anti-DNA in vitro resemble the in vivo immunologic disorders in patients with SLE, in that impaired cell-mediated immunity and B cell hyperactivity are frequently observed.

Antibodies, Antinuclear↗

Defective helper T cell function in IgM rheumatoid factor synthesis in patients with ankylosing spondylitis.

Despite chronic inflammation and the presence of hypergammaglobulinemia, rheumatoid factor (RF) is rarely found in the blood of patients with ankylosing spondylitis (AS). We used ELISA to compare spontaneous and pokeweed mitogen (PWM)-induced IgG, IgM and IgM rheumatoid factor (IgM-RF) production in normals and in patients with rheumatoid arthritis (RA) and AS. The IgG and IgM synthesis in these three groups did not differ. However, the IgM-RF level in PWM-induced mononuclear cell cultured supernatants of AS was significantly decreased, compared with normal and RA patients. Furthermore, mixing experiments by co-culture of normal T or B cells with patient's B or T cells in the presence of PWM revealed a deficiency of the helper T cell function in patients with AS. These results illustrate the cellular mechanism of the seronegativity of the rheumatoid factor in patients with ankylosing spondylitis.

Arthritis, Rheumatoid↗

Defective phagocytosis, decreased tumour necrosis factor-alpha production, and lymphocyte hyporesponsiveness predispose patients with systemic lupus erythematosus to infections.

Twenty-three patients with systemic lupus erythematosus (SLE) were studied in order to understand the mechanism of increased susceptibility to infection in SLE patients. We found that phagocytosis by polymorphonuclear leucocytes (PMN) was significantly defective in untreated (24.2 +/- 3.1%) and immunosuppressant-treated SLE patients (30.0 +/- 3.6%) compared with normals (47.9 +/- 0.6%), while the generation of superoxide anion radicals was normal. The defective phagocytosis in SLE could be increased by human recombinant tumour necrosis factor alpha (TNF-alpha). However, the percentages of phagocytosis in SLE before and after TNF-alpha stimulation were 56.6% and 60.7% of the normal values. This indicates that certain populations of PMN in SLE are not only defective as regards phagocytosis but also unresponsive to TNF-alpha stimulation. In an ELISA, TNF-alpha production by phorbol myristate acetate (PMA)-stimulated mononuclear cells from SLE patients was significantly decreased (181.4 +/- 22.7 pg/ml vs. 533.0 +/- 81.9 pg/ml, p = 0.002). In addition, the percentage of phytohaemagglutinin (PHA)-stimulated mononuclear cells in S phase in the cell cycle was deficient in patients with SLE (17.2 +/- 1.8% vs. 29.7 +/- 2.9%, p less than 0.001). These results lead us to propose that defective PMN in spontaneous and TNF-alpha-induced phagocytosis, decreased production of TNF-alpha, and lymphocyte hyporesponsiveness predispose patients with SLE to infections.

Adolescent↗

[Effect of nisoldipine on cultured myocardial cells of neonatal rats].

Nisoldipine 1.5 nmol/L, 0.75, and 1.5 mumol/L depressed the beat rates of myocardial cells. The effects were negatively correlated with dosages. Nisoldipine depressed the beat rates increased by calcium chloride 0.15 mmol/L or isoprenaline 1.5 mumol/L and atropine 20 nmol/L. Conversely, the above drugs reversed the beat rates depressed by nisoldipine. Therefore, the acting nisoldipine may be antagonistic to calcium chloride, isoprenaline and atropine. In addition, nisoldipine 10 nmol/L may significantly aggravated the damage to myocardial cells induced by mitomycin C 5 micrograms/ml in which elevated lactate dehydrogenase appeared.

Animals↗

[Effect of oxymatrine on beating of cultured myocardial cells in vitro].

Oxymatrine (OM), extracted from Sophora alopecuroides L, increased the contractility of the left heart atrium and decreased the spontaneous beating rate of right atrium of rabbit as described in our previous paper. The effect of OM on the beating rate of cultured rat myocardial cells was observed in the present study by a method of recording photoelectric energy transformation. OM 50 mumol/L decreased the beating rate of the myocytes by 50 +/- 27% 15 min after administration and also antagonized the positive chronotropic effect of isoproterenol 1.5 mumol/L, while the negative chronotropic effect of OM was completely abolished by prazosin. However, OM 250 mumol/L accelerated the beating rate of myocytes, which was cancelled by propranolol. These results suggest that OM has biphasic effects on cultured rat myocytes: slowing rate by alpha-adrenoceptor stimulation with 50 mumol/L concentration and accelerating rate by beta-adrenoceptor stimulation with 250 mumol/L concentration.

Alkaloids↗

Cellular ras activity and phospholipid metabolism.

Cellular ras activity has been neutralized in 3T3 cells by microinjection of a specific anti-ras monoclonal antibody. The injected antibody efficiently inhibited proliferation in cells treated with a phorbol ester and a calcium ionophore, or with prostaglandin F2 alpha. These treatments were designed to imitate the action of phospholipase C or of phospholipase A2. In addition, the highly efficient mitogenic potential of phosphatidic acid was inhibited by the injected antibody even more efficiently than was serum-induced proliferation. The close reliance of phospholipid-induced mitogenesis upon ras activity suggests that ras proteins are unlikely to function to control the action of a phospholipase.

Animals↗