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Biomedical subjects

Q Song

Publications and source records attributed to Q Song.

At least 109 records · Page 6Linked to original sources

Coordinating movement at two joints: a principle of linear covariance.

1. Six subjects performed fast, "single-joint" flexions at either the elbow or shoulder over three angular distances in a sagittal plane. Movement endpoints were located to require flexion of only a single, "focal" joint, without any external, mechanical constraint on the other, "nonfocal" joint. Three subjects performed another series of movements between two targets while moving along different paths and in which both joints were flexed. 2. We compared the torque patterns that were produced at the two joints. For single-joint movements, they were both biphasic pulses that accelerated and then decelerated the limb. 3. The torque at the nonfocal joint of a single joint movement was very close to linearly proportional to that at the focal joint throughout the movement. Elbow and shoulder torques differed by a linear scaling constant and went through extrema and zero crossings almost simultaneously. 4. In contrast, during movements in which subjects were explicitly instructed to use a hand path they would not naturally, use the linear interjoint torque scaling rule did not apply. This demonstrated that when we wish to move along a path between two targets that is not produced by linear torque covariation, we are able to modify that rule at will. 5. We speculate that linear, dynamic covariation of the torque patterns across two joints may be an important principle for reducing the number of degrees of freedom that the nervous system must independently control in performing unconstrained limb movements over naturally chosen paths.

Analysis of Variance↗

Coordinating two degrees of freedom during human arm movement: load and speed invariance of relative joint torques.

1. Eight subjects performed three series of pointing tasks with the unconstrained arm. Series one and two required subjects to move between two fixed targets as quickly as possible with different weights attached to the wrist. By specifying initial and final positions of the finger tip, the first series was performed by flexion of both shoulder and elbow and the second by shoulder flexion and elbow extension. The third series required flexion at both joints, and subjects were instructed to vary movement speed. We examined how variations in load or intended speed were associated with changes in the amount and timing of the electromyographic (EMG) activity and the net muscle torque production. 2. EMG and torque patterns at the individual joints varied with load and speed according to most of the same rules we have described for single-joint movements. 1) Movements were produced by biphasic torque pulses and biphasic or triphasic EMG bursts at both joints. 2) The accelerating impulse was proportional to the load when the subject moved "as fast and accurately as possible" or to speed if that was intentionally varied. 3) The area of the EMG bursts of agonist muscles varied with the impulse. 4) The rates of rise of the net muscle torques and of the EMG bursts were proportional to intended speed and insensitive to inertial load. 5) The areas of the antagonist muscle EMG bursts were proportional to intended movement speed but showed less dependence on load, which is unlike what is observed during single-joint movements. 3. Comparisons across joints showed that the impulse produced at the shoulder was proportional to that produced at the elbow as both varied together with load and speed. The torques at the two joints varied in close synchrony, achieving maxima and going through zero almost simultaneously. 4. We hypothesize that "coordination" of the elbow and shoulder is by the planning and generation of synchronized, biphasic muscle torque pulses that remain in near linear proportionality to each other throughout most of the movement. This linear synergy produces movements with the commonly observed kinematic properties and that are preserved over changes in speed and load.

Arm↗

Modulators of crescentic glomerulonephritis.

Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis and is associated with a poor prognosis. An understanding of the mechanisms involved in crescent formation is crucial for the development of new therapies for this disease. This article reviews current ideas on the pathogenesis of glomerular crescent formation and describes methods for modulation of this process. Emphasis is given to the role of the proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha in crescent development and its modulation by cytokine blockade.

Animals↗

High level of circulating human tissue kallikrein induces hypotension in a transgenic mouse model.

We established a unique transgenic mouse model in liver-targeted expression of human tissue kallikrein using a mouse albumin enhancer and promoter. Northern blot analysis and ELISA showed that human tissue kallikrein was predominantly expressed in the liver of transgenic mice and secreted into the circulation at a high level. The transcript was also detected in the kidney, pancreas, salivary gland and heart at a low level by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Systolic blood pressures were measured by the tail-cuff method, all three independent transgenic mouse lines are hypotensive (84.6 +/- 1.0 mmHg, n = 17; 84.5 +/- 1.5 mmHg, n = 9; 83.1 +/- 0.8 mmHg, n = 13, P < 0.01) compared with the control mice (100.9 +/- 0.9 mmHg, n = 17). Administration of aprotinin, a potent tissue kallikrein inhibitor or Hoe 140, a bradykinin receptor antagonist, restored the blood pressure of transgenic mice but had no significant effect on control littermates. These studies show that over-production of tissue kallikrein in the circulation plays a role in blood pressure regulation.

Animals↗

Expression of p53, bcl-2, bax, bcl-x2 and c-myc in radiation-induced apoptosis in Burkitt's lymphoma cells.

Apoptosis, a form of physiological cell death, is a genetically determined program essential for normal development and maintenance of tissues, which has been linked to a variety of gene products. We have examined the susceptibility to radiation-induced apoptosis of cell lines derived from the human B cell tumour, Burkitt's lymphoma (BL), displaying a variety of phenotypic characteristics and expressing genes implicated in apoptosis at different levels. The susceptibility to apoptosis following gamma radiation varied significantly amongst the lines. Cell lines with wild type p53 were susceptible to radiation-induced apoptosis but two of five BL lines with only mutant p53 allele also displayed similar susceptibility. Some BL cell lines that expressed bcl-2 at levels comparable with Epstein-Barr virus (EBV) transformed normal B cells were highly susceptible to gamma radiation-induced apoptosis, whereas others expressing low levels were resistant. When these lines were analysed for bax and bcl-X(L) expression again no correlation was observed with susceptibility or resistance to apoptosis. Two BL cell lines having deregulated expression of c-myc were resistant to the induction of apoptosis while two others which had regulated c-myc expression were susceptible. Thus the status of p53, c-myc, bcl-2, bcl-X(L) and bax is not sufficiently informative in BL lines to predict susceptibility to radiation-induced apoptosis.

Journal Article↗

Protein kinase A inhibitors enhance radiation-induced apoptosis.

In addition to a role for de novo protein synthesis in apoptosis we have previously shown that activation of a protein phosphatase or loss of activity of a kinase is also important in radiation-induced apoptosis in human cells [Baxter, and Lavin (1992): J Immunol 148:149-1954]. We show here that some inhibitors of protein kinases exacerbate radiation-induced apoptosis in the human cell line BM13674. The specific protein kinase A inhibitor isoquinoline sulfonamide (20 microM) gave rise to significantly increased levels of apoptosis at 2-6 h postirradiation compared to values after radiation exposure only. The same concentration of isoquinolinesulfonamide, which was effective in increasing apoptosis, reduced activity markedly. A 66% inhibition of cyclic AMP-dependent protein kinase A activity occurred in unirradiated cells at this concentration of H89 and activity was reduced to 58% in irradiated cells. Calphostin C, a specific inhibitor of protein kinase C, at a concentration of 0.1 microM, which caused 68% inhibition of enzyme activity in irradiated cells, failed to enhance the level of radiation-induced apoptosis. Other kinase inhibitors did not lead to an additional increase in apoptosis over and above that observed after irradiation. The results obtained here provide further support for an important role for modification of existing proteins during radiation-induced apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Multiple phosphorylation of ribosomal protein S6 and specific protein synthesis are required for prothoracicotropic hormone-stimulated ecdysteroid biosynthesis in the prothoracic glands of Manduca sexta.

Prothoracicotropic hormone (PTTH)-stimulated protein phosphorylation leads to ecdysteroidogenesis (molting hormone biosynthesis) in the prothoracic glands of the tobacco hornworm, Manduca sexta. The phosphorylation of 34 and 50 kDa peptides (p34 and p50) paralleled the increase in ecdysteroidogenesis, and the dephosphorylation of p34 and p50 preceded a decrease in ecdysteroidogenesis. Inhibition by rapamycin of p34, but not p50, phosphorylation prevented PTTH-stimulated ecdysteroidogenesis in a dose-dependent manner, suggesting that p34 phosphorylation is requisite for PTTH-stimulated ecdysteroidogenesis. Two proteins whose synthesis was rapidly stimulated by PTTH were p50 and p70. The time-course of PTTH-stimulated synthesis of p50 paralleled that of p34 phosphorylation and that of ecdysteroidogenesis. Rapamycin inhibited PTTH-stimulated synthesis of p50 and p70, suggesting that specific protein synthesis is also required for PTTH-stimulated ecdysteroidogenesis, confirming the results of Rybczynski and Gilbert [(1994) Insect Biochem. Molec. Biol. 24, 175-189], and that p34 phosphorylation may regulate the downstream synthesis of p50 and p70, possible key regulatory proteins leading to ecdysteroidogenesis. Results from two-dimensional (2D)-PAGE analysis of the ribosomal proteins purified from prothoracic glands, demonstrated that p34 is indeed ribosomal S6, and is phosphorylated at up to five sites (P1-5) upon PTTH stimulation. The multiple phosphorylation of S6 was inhibited completely by rapamycin as shown in 2D gel maps, further confirming that p34 is ribosomal protein S6. Temporal analysis of PTTH-stimulated S6 phosphorylation by 2D-PAGE revealed that phosphorylation of S6 at the P1 site was temporally correlated with the initiation of ecdysteroidogenesis, and that multiple phosphorylation at all five sites (P1-5) was correlated with the maximal synthesis of ecdysteroids. Dephosphorylation of S6 was accompanied by a decrease in ecdysteroidogenesis. These data demonstrate that p34 is ribosomal protein S6 and that both the phosphorylation of S6 and specific protein synthesis are required for PTTH-stimulated ecdysteroidogenesis in the prothoracic gland.

Animals↗

Cellular localization of tissue kallikrein and kallistatin mRNAs in human kidney.

The renal kallikrein-kinin system has been implicated in the regulation of blood pressure and sodium/water excretion. The activity of renal kallikrein is controlled by a number of factors in vivo. Kallistatin is a newly identified serine proteinase inhibitor (serpin) which binds to tissue kallikrein and inhibits its enzymatic activity in vitro. To understand the role of kallistatin in modulating tissue kallikrein's function in vivo, we examined the anatomical relationship between human tissue kallikrein and kallistatin in the kidney by in situ hybridization histochemistry. Tissue kallikrein and kallistatin gene transcripts were identified using digoxigenin-labeled riboprobes at the cellular level. Antisense and sense riboprobes corresponding to the 3' region of the human kallikrein and kallistatin mRNAs were synthesized by in vitro transcription and used for hybridization. Using an antisense kallikrein riboprobe, sites of kallikrein synthesis were localized in the distal tubules, collecting ducts and Henle's loops of the kidney. To a lesser degree, juxtaglomerular cells were also stained. Kallistatin mRNA was found at the same sites where kallikrein mRNA was localized. The most intense signals of both kallikrein and kallistatin were seen in the distal tubules and collecting ducts. Hybridization was specific for the target mRNA since sense kallikrein or kallistatin riboprobe did not bind to the sections. Immunoreactive human renal kallikrein and kallistatin levels were measured in the kidney and urine by immunoassays using specific antibodies. Co-localization of kallikrein and kallistatin mRNA in the kidney suggests a potential role of kallistatin in regulating tissue kallikrein's function.

Carrier Proteins↗

Does the common bile duct dilate after cholecystectomy? Sonographic evaluation in 234 patients.

OBJECTIVE: The purpose of this study was to determine whether the common bile duct dilates after cholecystectomy. SUBJECTS AND METHODS: All 234 patients who had cholecystectomy at our hospital between October 1985 and April 1994 were included in this study. The luminal diameter of the proximal segment of the common bile duct was measured on antero-posterior transverse sonograms 4-15 days before cholecystectomy. In all patients, the luminal diameter was measured again on sonograms obtained 7-2160 days after surgery (mean, 393 days; median, 180 days; mode, 360 days). A diameter of 6 mm or less was considered normal. This study contained 197 patients with a normal common bile duct (< or = 6 mm) and 37 patients with a dilated common bile duct (> 6 mm). RESULTS: The mean diameter of the common bile duct measured on sonograms was 5.9 mm before cholecystectomy and 6.1 mm after cholecystectomy. This difference was statistically significant (p < .05). The diameter of the common bile duct increased in 110 patients, decreased in 61 patients, and stayed the same in 63 patients. Of the 234 patients, 197 (84%) had a normal preoperative diameter of the common bile duct, whereas 167 (71%) had a common bile duct with a normal diameter postoperatively. CONCLUSION: The diameters of the common bile duct as measured on sonograms increase slightly after cholecystectomy. Most patients do not have significant compensatory dilatation of the duct after cholecystectomy.

Adult↗

[High yield techniques for bupleurum falcatum L].

The growth of plants may be controlled by clipping the aerial part. This may increase the yield of Bupleurum falcatum. Different methods of cultivation may result in different outputs of crude drugs. Compared with land plotting, deep ploughing and high ridging may increase the root weight of one-year-old plant by 28% and 50% respectively.

Plants, Medicinal↗

Prospective studies on the relationship between the 50 g glucose challenge test and pregnant outcome.

The 50 g oral glucose challenge test (50gGCT) was performed on 622 pregnant women, and 75 g oral glucose tolerance test (75gGTT) was further done on subjects with screening tests value of > or = 7.78 mmol/L. The results showed that there were 16.56% (103/622) women with screening value of > or = 7.78 mmol/L, among whom, 32 were identified as having gestational impaired glucose tolerance (GIGT) and 12, gestational diabetes mellitus (GDM) by confirmatory test of 75gGTT. The sensitivity of 50gGCT was 42.72%(44/103). The incidences of edema-proteinuria-hypertension syndrome (EPH-syndrome), premature rupture of membranes, fetal macrosomia, operative deliveries and perinatal morbidity were higher in women with GIGT/GDM than in women without GIGT/GDM. It suggests that 50gGCT is an ideal method of screening for GDM and should be performed on all pregnant women.

Adult↗

Reorientations in the bacteriorhodopsin photocycle.

Reversible photoinduced reorientations of bacteriorhodopsin have been detected in suspensions of the purple membrane of Halobacterium salinarium. The anisotropy in bacteriorhodopsin during the nanosecond through millisecond stages of the photocycle was measured by time-resolved linear dichroism and transient absorption measurements. From these measurements the anisotropies of the K, L, M, and O intermediates were determined and related to the chromophore orientation with respect to the initially selected orientation. The anisotropies of the K and L states are 0.38 +/- 0.01 and 0.35 +/- 0.01, respectively. Further anisotropy decay after formation of the M intermediate in about 0.5 ms is evidence of orientational motion at this stage in the photocycle. A constant anisotropy with a value of 0.39 +/- 0.02 in the O intermediate demonstrates a recovery of the initial protein orientation with the formation of the O state. These results demonstrate that reorientations in BR are photoinduced and reversible. Similar measurements for L and M were carried out for purple membrane in polyacrylamide gels, where the anisotropies in the L and M states are 0.38 +/- 0.014 and 0.36 +/- 0.01, respectively. These results show that reorientations also occur in BR immobilized in gels. Anisotropy decay in the M state after formation of the M intermediate was not detected in the gels, in contrast to the M intermediate in suspensions. Orientational changes are observed for BR in purple membrane suspensions in the K state, during the K-->L step, in the M state possibly related to an M1-->M2 transition, and in the O state, where an almost complete return to the original orientation occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗

S6 phosphorylation results from prothoracicotropic hormone stimulation of insect prothoracic glands: a role for S6 kinase.

The insect prothoracic glands are the source of steroidal molting hormone precursors and the glands are stimulated by a brain neuropeptide, prothoracicotropic hormone (PTTH). Previous work from this laboratory revealed that PTTH acts via a cascade including Ca2+/calmodulin activation of adenylate cyclase, protein kinase A, and the subsequent phosphorylation of a 34 kDa protein (p34) hypothesized, but not proven, to be the S6 protein of the 40S ribosomal subunit. The immunosuppressive macrolide, rapamycin, is a potent inhibitor of cell proliferation, a signal transduction blocker, and also prevents ribosomal S6 phosphorylation in mammalian systems. We demonstrate here that rapamycin inhibited PTTH-stimulated ecdysteroidogenesis in vitro by the prothoracic glands of the tobacco hornworm, Manduca sexta, with half-maximal inhibition at a concentration of about 5 nM. At concentrations above 5 nM, there was a 75% inhibition of ecdysteroid biosynthesis. Similar results were observed with the calcium ionophore (A23187), a known stimulator of ecdysteroidogenesis. Most importantly, the inhibition of ecdysteroid biosynthesis was accompanied by the specific inhibition of the phosphorylation of p34, indicating that p34 indeed is ribosomal protein S6. In vivo assays revealed that injection of rapamycin into day 6 fifth instar larvae resulted in a decreased hemolymph ecdysteroid titer and a dose-dependent delay in molting and metamorphosis. When S6 kinase (S6K) activity was examined using rapamycin-treated prothoracic glands as the enzyme source and a synthetic peptide (S6-21) or a 40S ribosomal subunit fraction from Manduca tissues as substrate, the date revealed that rapamycin inhibited S6K activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Spermine and polylysine enhanced phosphorylation of calmodulin and tubulin in an insect endocrine gland.

Spermine-stimulated and heparin-inhibited phosphorylation of both exogenous casein and endogenous protein substrates of the prothoracic gland were measured in prothoracic gland cytosolic fractions from fifth instar larvae and early pupae of the tobacco hornworm, Manduca sexta. The results reveal a striking increase in casein kinase II (CKII) activity, i.e. approximately 3-fold above basal level in the presence of 5 mM spermine, with the highest activity exhibited by gland fractions from day 0-2 larvae, newly pupated animals and day 1 pupae. These results were verified by the results from Western blot analysis using a CKII alpha-subunit specific antibody and a 10 a.a. synthetic peptide that is a specific substrate for CKII. Several endogenous proteins were found to be substrates for CKII when assayed in the presence of spermine or polylysine. A 19 kDa peptide was shown to be calmodulin (CaM) by using the purified Manduca brain CaM as an indicator, and was only phosphorylated in the presence of polylysine. A 52 kDa protein was identified as tubulin by immunoprecipitation with a tubulin-specific monoclonal antibody, and was shown to be phosphorylated in the presence of spermine and polylysine. The possible roles of phosphocalmodulin and phosphotubulin are discussed in the context of prothoracic gland function.

Amino Acid Sequence↗

Electrochemical therapy in the treatment of malignant tumours on the body surface.

From November 1988 to May 1991, 113 patients with malignant tumours on their body surface, who were at great operative risk or had refused surgery, underwent local treatment with electrochemical therapy (ECT). After 2.6 years' follow up, total effective rate of the cure was 79.7%. The clinical results were considered satisfactory.

Adolescent↗

Cloning and characterization of a human protein phosphatase 1-encoding cDNA.

While sequence information is available for a number of eukaryotic protein phosphatase 1 (PP1)-encoding genes, the cloning and characterization of a complete human pp1 gene has not been reported. We have used two conserved regions within the pp1 family of genes to synthesize oligodeoxyribonucleotide primers for the amplification of a 438-bp sequence from human mRNA. This DNA fragment was sequenced to verify that it corresponded to a pp1 cDNA and it was used to screen a human cDNA library to isolate a full-length clone. The deduced amino acid (aa) sequence identified a protein of 330 aa in length. Comparison with the rabbit pp1 cDNA sequence showed some nucleotide differences, largely at the third position of the codon, with complete concordance at the aa level. Northern blot analysis revealed an mRNA of approximately 1.6 kb.

Amino Acid Sequence↗

Calyculin A, a potent inhibitor of phosphatases-1 and -2A, prevents apoptosis.

Exposure of the Burkitt's lymphoma cell line BM13674 cells to gamma-radiation or heat results in extensive DNA fragmentation and morphological changes characteristic of apoptosis. When cells were gamma-irradiated in the presence of calyculin A, a potent inhibitor of the catalytic subunit of phosphatases 1 and 2A, apoptosis was prevented. This was shown to be concentration dependent with maximal inhibition occurring at 20nM. Both DNA fragmentation and the morphological features characteristic of apoptosis were prevented by incubation with calyculin A. The concentration required to inhibit apoptosis (20 nM) was considerably less than that reported previously for okadaic acid (500 nM), also an inhibitor of phosphatase activity as well as apoptosis. In addition, while okadaic acid caused a marked condensation of nuclear material in both control and irradiated cells, while preventing apoptosis, no such changes in chromatin were evident in the presence of calyculin A. It is clear from these data and other results with protein synthesis inhibitors that the complete machinery for apoptosis, induced under certain conditions, preexists in the cell, and phosphatase activity plays a key role in this process.

Apoptosis↗

Inhibition of apoptosis in human tumour cells by okadaic acid.

Gamma-radiation, tetrandrine, bistratene A, and cisplatin were all found to induce pronounced morphological changes characteristic of apoptosis and extensive DNA fragmentation in the human BM13674 cell line 8 h after treatment. Apoptosis induced in BM13674 cells by these diverse agents was markedly inhibited by 1 microM okadaic acid, a tumour promoter that inhibits protein phosphatases 1 and 2A. This compound also inhibited the appearance of apoptosis in fresh human leukaemia cells that had been exposed to gamma-radiation. The inhibition of apoptosis was confirmed using fluorescence microscopy and DNA gel electrophoresis. Dephosphorylation of a limited number of proteins was shown to be associated with apoptosis and okadaic acid prevented these dephosphorylations. Previous studies on the BM13674 cell line showed that an inhibitor of protein synthesis failed to prevent apoptosis in these cells. The present data provides further support that posttranslational modification of proteins, in particular, phosphorylation/dephosphorylation status, plays an important role in inhibition/activation of programmed cell death in different human cells after exposure to several cytotoxic agents.

Acetamides↗