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Biomedical subjects

Y C Ma

Publications and source records attributed to Y C Ma.

At least 19 recordsLinked to original sources

Infrared probe of the electronic structure and charge dynamics of Na0.7CoO2.

We present measurements of the optical spectra on Na(0.7)CoO(2) single crystals. The optical conductivity shows two broad interband transition peaks at 1.6 eV and 3.1 eV, and a weak midinfrared peak at 0.4 eV. The intraband response of conducting carriers is different from that of a simple Drude metal. A peak at low but finite frequency is observed, which shifts to higher frequencies with increasing temperature, even though the dc resistivity is metallic. The origin of the interband transitions and the low-frequency charge dynamics have been discussed and compared with other experiments.

Journal Article↗

Low-dose alemtuzumab (Campath) in myeloablative allogeneic stem cell transplantation for CD52-positive malignancies: decreased incidence of acute graft-versus-host-disease with unique pharmacokinetics.

Alemtuzumab is effective in reducing the risk of acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (ASCT). Alemtuzumab may also delay immune reconstitution and reduce graft-versus-leukemia effects. The optimal dose has not been established. We investigated engraftment, acute GVHD incidence and severity, and pharmacokinetics of alemtuzumab associated with the use of low-dose alemtuzumab/cyclophosphamide/total body irradiation and ASCT for patients with aggressive CD52-positive hematologic malignancies. In all, 12 patients were treated. Alemtuzumab 10 mg daily on days -7 to -3 was given intravenously. Tacrolimus and methotrexate were used for GVHD prophylaxis. Alemtuzemab was not detected in any of the 36 sequential serum samples tested between days -1 and +21 of transplant. All patients engrafted rapidly; the median time to an absolute neutrophil count >0.5 x 10(9)/l was 14 days (range 11-17 days), and the median time to a platelet count >20 x 10(9)/l was 16 days (range 6-30 days). By 1 month after transplant, nine patients had 100% donor chimerism, while three had mixed donor chimerism. At 3 months, 11 had achieved 100% donor chimerism. No cases of grade III/IV acute GVHD occurred. At a median follow-up interval of 14.7 months (range 4-24), seven patients remained alive, and five remained free of disease.

Acute Disease↗

Novel regulation and function of Src tyrosine kinase.

Src tyrosine kinase is a critical signal transducer that modulates a wide variety of cellular functions. Misregulation of Src leads to cell transformation and cancer. Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are another group of signaling molecules that transduce signals from cell-surface receptors to generate physiological responses. Recently, it was discovered that G alpha s and G alpha i could directly stimulate Src family tyrosine kinase activity. This novel regulation of Src tyrosine kinase by G proteins provides insights into the adenylyl cyclase-independent signaling mechanisms involved in ligand-induced receptor desensitization, internalization and other physiological processes.

Animals↗

RGS-PX1, a GAP for GalphaS and sorting nexin in vesicular trafficking.

Heterotrimeric GTP-binding proteins (G proteins) control cellular functions by transducing signals from the outside to the inside of cells. Regulator of G protein signaling (RGS) proteins are key modulators of the amplitude and duration of G protein-mediated signaling through their ability to serve as guanosine triphosphatase-activating proteins (GAPs). We have identified RGS-PX1, a Galpha(s)-specific GAP. The RGS domain of RGS-PX1 specifically interacted with Galpha(s), accelerated its GTP hydrolysis, and attenuated Galpha(s)-mediated signaling. RGS-PX1 also contains a Phox (PX) domain that resembles those in sorting nexin (SNX) proteins. Expression of RGS-PX1 delayed lysosomal degradation of the EGF receptor. Because of its bifunctional role as both a GAP and a SNX, RGS-PX1 may link heterotrimeric G protein signaling and vesicular trafficking.

Adrenergic beta-2 Receptor Agonists↗

Urinary thiodiglycolic acid levels for vinyl chloride monomer-exposed polyvinyl chloride workers.

Thiodiglycolic acid (TdGA) is the major metabolite of vinyl chloride monomer (VCM) detected in human urine. Although urinary TdGA has been reported to be associated with ambient VCM exposure, the relationship between urinary TdGA and a low level of air VCM is not clear. Questionnaires were administered to 16 polyvinyl chloride manufacturing workers to obtain a detailed history of occupation and lifestyle. For each worker, personal air monitoring for VCM was performed and a time-weighted average for VCM exposure was calculated. The urinary TdGA levels at the end of a work shift, and at the commencement of the next shift, were also assessed for each worker. Urine analysis revealed that TdGA levels at the beginning of the next shift were higher than those at the end of that shift. Workers experiencing a VCM exposure greater than 5 ppm in air revealed a urinary TdGA level significantly greater than those experiencing a VCM exposure of less than 5 ppm (P < 0.05). The best fit of regression for urinary TdGA on air VCM was Y = 1.06 + 0.57X for urine collected at the commencement of the following work shift, where X is the air VCM concentration and Y is the urinary TdGA concentration (r2 = 0.65, P < 0.01). We conclude that the urinary TdGA level is best detected at the commencement of the next shift and that it can be used as an exposure marker for polyvinyl chloride workers when the air VCM level to which they are exposed is greater than 5 ppm.

Adult↗

Src tyrosine kinase is a novel direct effector of G proteins.

Heterotrimeric G proteins transduce signals from cell surface receptors to modulate the activity of cellular effectors. Src, the product of the first characterized proto-oncogene and the first identified protein tyrosine kinase, plays a critical role in the signal transduction of G protein-coupled receptors. However, the mechanism of biochemical regulation of Src by G proteins is not known. Here we demonstrate that Galphas and Galphai, but neither Galphaq, Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c-Src. Galphas and Galphai similarly modulate Hck, another member of Src-family tyrosine kinases. Galphas and Galphai bind to the catalytic domain and change the conformation of Src, leading to increased accessibility of the active site to substrates. These data demonstrate that the Src family tyrosine kinases are direct effectors of G proteins.

Animals↗

Apoptotic signaling through the beta -adrenergic receptor. A new Gs effector pathway.

Stimulation of beta-adrenergic receptor normally results in signaling by the heterotrimeric G protein G(s), leading to the activation of adenylyl cyclase, production of cAMP, and activation of cAMP-dependent protein kinase (PKA). Here we report that cell death of thymocytes can be induced after stimulation of beta-adrenergic receptor, or by addition of exogenous cAMP. Apoptotic cell death in both cases was observed with the appearance of terminal deoxynucleotidyl transferase-mediated UTP end labeling reactivity and the activation of caspase-3 in S49 T cells. Using thymocytes deficient in either Galpha(s) or PKA, we find that engagement of beta-adrenergic receptors initiated a Galpha(s)-dependent, PKA-independent pathway leading to apoptosis. This alternative pathway involves Src family tyrosine kinase Lck. Furthermore, we show that Lck protein kinase activity can be directly stimulated by purified Galpha(s). Our data reveal a new signaling pathway for Galpha(s), distinct from the classical PKA pathway, that accounts for the apoptotic action of beta-adrenergic receptors.

Animals↗

Identification of the binding site for Gqalpha on its effector Bruton's tyrosine kinase.

Heterotrimeric G proteins and tyrosine kinases are two major cellular signal transducers. Although G proteins are known to activate tyrosine kinases, the activation mechanism is not clear. Here, we demonstrate that G protein Gqalpha binds directly to the nonreceptor Bruton's tyrosine kinase (Btk) to a region composed of a Tec-homology (TH) domain and a sarcoma virus tyrosine kinase (Src)-homology 3 (SH3) domain both in vitro and in vivo. Only active GTP-bound Gqalpha, not inactive GDP-bound Gqalpha, can bind to Btk. Mutations of Btk that disrupt its ability to bind Gqalpha also eliminate Btk stimulation by Gqalpha, suggesting that this interaction is important for Btk activation. Remarkably, the structure of this TH (including a proline-rich sequence) -SH3 fragment of the Btk family of tyrosine kinases shows an intramolecular interaction. Furthermore, the crystal structure of the Src family of tyrosine kinases reveals that the intramolecular interaction of SH3 and its ligand is the major determining factor keeping the kinase inactive. Thus, we propose an activation model that entails binding of Gqalpha to the TH-SH3 region, thereby disrupting the TH-SH3 intramolecular interaction and activating Btk.

Agammaglobulinaemia Tyrosine Kinase↗

Effect of docosahexaenoic acid on the synthesis of phosphatidylserine in rat brain in microsomes and C6 glioma cells.

Docosahexaenoic acid (22:6n-3) is the major polyunsaturated fatty acid (PUFA) in the CNS and accumulates particularly in phosphatidylserine (PS). We have investigated the effect of the 22:6n-3 compositional status on the synthesis of PS. The fatty acid composition of brain microsomes from offspring of rats artificially reared on an n-3-deficient diet showed a dramatic reduction of 22:6n-3 content (1.7 +/- 0.1%) when compared with control animals (15.0 +/- 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n-6) content, which replaced the 22:6n-3 phospholipids with 22:5n-6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The n-3 deficiency did not affect the total amount of polyunsaturated phospholipids in brain microsomes; however, it was associated with a decrease in the total polyunsaturated PS content and with increased levels of 1-stearoyl-2-docosapentanoyl (18:0/22:5n-6) species, particularly in phosphatidylcholine. Incorporation of [3H]serine into PS in rat brain microsomes from n-3-deficient animals was slightly but significantly less than that of the control animals. Similarly, C6 glioma cells cultured for 24 h in 22:6n-3-supplemented media (10-40 microM) showed a significant increase in the synthesis of [3H]PS when compared with unsupplemented cells. Our data show that neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids and suggest that 22:6n-3 may be a modulator of PS synthesis.

Animals↗

[Effect of norepinephrine on the thermosensitive neurons in preoptic area of hypothalamus tissue slices in cold acclimatized rats].

In this work, single unit firing activities were recorded in the preoptic anterior hypothalamus (POAH) brain slices of cold acclimatized and room-temperature housed rats (CR and RR) and the effects of NE on the neuronal discharges were observed. The neurons of POAH in CR became much more sensitive to NE than that in RR (the threshold concentration of NE of CR became significantly lowered). In comparison with RR, the percentage of warm sensitive neurons that could be excited by NE was decreased and some of them even showed inhibitory responses. On the other hand, the percentage of cold sensitive neurons that could be inhibited by NE was decreased and some of them even showed excitatory responses. The percentage of thermo-insensitive neurons that could be either excited or inhibited by NE were increased.

Acclimatization↗

Cloning of a cDNA encoding the small subunit of cytochrome b558 (cybS) of mitochondrial fumarate reductase (complex II) from adult Ascaris suum.

Complex II in the mitochondria of the adult parasitic nematode, Ascaris suum, exhibits high fumarate reductase activity in addition to succinate dehydrogenase activity and plays a key role in the anaerobic energy metabolism of the worm. In this study, the amino acid sequence of the small subunit of cytochrome b558 (cybS) in adult complex II was deduced from the cDNA isolated by immunoscreening an A. suum muscle cDNA library. Histidine residues, which are possible heme axial ligands in cytochrome b558, were found in the second transmembrane segment of the subunit. This is the first report of the primary structure of the small subunit in the two-subunit cytochrome b in mitochondrial complex II from a multicellular eukaryote.

Amino Acid Sequence↗

Specificity of polyunsaturated fatty acid release from rat brain synaptosomes.

Release of specific polyunsaturated fatty acids for cell membranes may have a significant implication in biological function, considering the involvement of various fatty acids in cell signal transduction. In the present study, release of polyunsaturated fatty acids from rat brain synaptosomes by endogenous synaptosomal lipase activity was examined in comparison to that by cobra venom phospholipase A2 (Naja naja naja). Cobra venom phospholipase A2 (Naja naja naja) preferentially hydrolyzed docosahexaenoic acid (22:6n-3) from both synaptosomes and lipid mixtures containing similar classes of lipids commonly found in the brain. Arachidonic acid (20:4n-6) and oleic acid (18:1n-9) were also hydrolyzed; however, monoene species was hydrolyzed slower than were polyenoic species in synaptosomes. Phosphatidylethanolamine was the most preferred phospholipid class for release of 22:6n-3 fatty acid from both lipid mixtures and synaptosomes. In contrast to hydrolysis by cobra venom phospholipase A2, endogenous synaptosomal lipase activity preferentially hydrolyzed 20:4n-6 from rat brain synaptosomes, despite the high abundance of 22:6n-3 in synaptosomal membranes. Preferential release of 20:4n-6 was observed over a wide range of pH values and calcium concentrations. Synaptosomal 22:6 species appeared to be resistant to hydrolysis even after stimulation with various agents such as phorbolmyristate, suggesting that physiological importance of 22:6n-3 in neuronal membranes may not be as the release fatty acid.

Animals↗

Spontaneous rectus sheath hematoma during treatment of pulmonary embolism with warfarin: report of a case.

We present a case of a patient suffering from acute abdomen with a palpable mass on the left lower quadrant of the abdominal wall. The clinical manifestations and plain abdomen gave the misleading diagnosis of a ventral hernia. A review of the patient history revealed the use of anticoagulants for pulmonary embolism, and as a result computed tomography (CT) was performed which provided an accurate diagnosis of rectus sheath hematoma. The probable pathogenesis is discussed.

Aged↗

[Adaptive changes of preoptic thermosensitive neurons in hypothalamic tissue slices of rats after long-term exposure to cold environmental temperature].

In the present work, thermosensitivity and spontaneous firing rate of 86 preoptic neurons in hypothalamic tissue slices from 20 cold acclimated rats (CR, at 5 +/- 1 degrees C for more than 3 weeks) and 127 neurons from 35 warm acclimated rats (WR, at 20 +/- 3 degrees C for the same period) were recorded and compared. The results showed that: (1) The percentage of cold-sensitive neurons in CR were higher than that in WR, the critical temperature and the lowest temperature of the spontaneous firing activity of cold-sensitive neurons in CR were also lower than that in WR. (2) Thermosensitivity and critical temperature of the warm-sensitive neurons in CR were remarkably decreased, and spontaneous firing rate under 37 degrees C was increased. (3) Spontaneous firing rate (37 degrees C) of temperature insensitive neurons in CR were conspicuously increased and the lowest temperature extended downward. These profound changes in response to long-term cold exposure suggested that plasticity of preoptic neurons was involved in the thermoregulation in cold adaptation.

Adaptation, Physiological↗

Development of the on-line high-performance liquid chromatography/thermospray mass spectrometry method for the analysis of phospholipid molecular species in rat brain.

An on-line thermospray liquid chromatography/mass spectrometry method was developed to rapidly analyze phosphoglyceride molecular species in biological fluid. After total lipid extraction, the extract was subjected to the analysis using on-line reversed-phase high-performance liquid chromatography (HPLC) and filament-on thermospray mass spectrometry. Using nonconventional HPLC conditions, partial separation of individual phospholipid class (phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine) and partial separation of molecular species within each class were achieved. In addition, good peak shape was maintained throughout the analysis. By monitoring characteristic fragment ions (diacylglycerol ions) formed in the filament-on thermospray process and according to the retention time, individual molecular species in each phospholipid class can be identified. Using this method, we observed significant differences in the molecular species composition of each phospholipid class in rat whole-brain lipid. Although nonlinear calibration curves were observed for all the diacylglycerol ions monitored, even in the presence of internal standard, semiquantitative and quantitative results still could be obtained for a mixture of phospholipids.

Animals↗

Malignant hemangioendothelioma presenting as omental masses in a child.

Malignant hemangioendothelioma is an uncommon lesion of the omentum in children. Multiple foci of malignant hemangioendothelioma is even more rare in the omentum. In the present case, a computed tomography scan of the abdomen showed multiple enhanced nodular lesions. To our knowledge, this is the first report of this tumor occurring in a child.

Adolescent↗