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Biomedical subjects

K Gao

Publications and source records attributed to K Gao.

At least 19 recordsLinked to original sources

Immunogenicity and immune modulation of osteogenic differentiated mesenchymal stem cells from Banna minipig inbred line.

Mesenchymal stem cells (MSCs) represent a good choice for cell transplantation due to their multilineage differentiation ability and low immunogenicity. Our previous in vitro studies indicated that undifferentiated swine MSCs show low immunogenicity suppressing the proliferative responses of human peripheral blood lymphocyte to several antigens. In this study, we investigated the immunogenicity and immune modulation ability of osteogenic differentiated MSCs. SLA class I (P1, P14) was detectable by reverse-transcriptase polymerase chain reaction on both differentiated and undifferentiated MSCs. SLA class II (SLA-DRA, SLA-DQA) was only detectable on differentiated MSCs mixed lymphocyte reaction assays demonstrated that both differentiated and undifferentiated MSCs failed to stimulate proliferative responses by human peripheral blood lymphocytes (hPBLs). Furthermore, as undifferentiated MSCs, osteogenic differentiated MSCs also suppressed hPBL proliferation to phytohemaglutinin.

Animals↗

Measures of health-related quality of life and functional status in survivors of oral cavity cancer who have had defects reconstructed with radial forearm free flaps.

The aim of this study was to evaluate (by postal questionnaire) quality of life and function in patients who have had resections of oral cancer and reconstruction by radial forearm flaps. Between October 1987 and December 2002, 258 patients had reconstructions by radial forearm flaps after resection of tumours in the oral cavity. Of these, 139 surviving patients were identified from the database and were sent questionnaires comprising five sections: Functional Assessment of Cancer Therapy-General (FACT-G) and -Head and Neck (FACT-HN); University of Washington Quality of Life Scale (UWQoL); Performance Status Scale for Head and Neck Cancer (PSS-HN); and the final section addressed dental rehabilitation and morbidity at the donor site. Sixty-three questionnaires (45%) were returned. In 17 (27%), parts of the questionnaire were incomplete. The median UWQoL score was 623/900, FACT-G was 92/108, FACT-HN was 31/48, and PSS-HN showed that eating in public, understandability of speech and normality of diet were 75/100, 75/100 and 50/100, respectively. The effect of stage and site on quality of life and function did not reach statistical significance. The effect of radiotherapy on speech (p=0.036) and diet (p=0.007) was significant. Patients who worried about their cancer returning had a lower UWQoL score (p=0.016). Ninety percent regarded their arm as disfigured, but 81% felt comfortable wearing short-sleeved shirts. Sensation and function of the hand were reported as normal in 87 and 92%, respectively. We conclude that patients who have had oral cancer have a persistent reduction in quality of life and function long after completion of treatment. The effects can be assessed by postal questionnaire, but the low rate of return (45%) and difficulties with completion reduce the quality of the data. Quality of life and function are essential components of improvements in outcome.

Adult↗

Clinical outcome and technical aspects of 263 radial forearm free flaps used in reconstruction of the oral cavity.

BACKGROUND: The aim of this study was to report the applications, complications, and limitations of the radial forearm flap when used for reconstruction after excision of cancers in the mouth. PATIENTS AND METHODS: We reviewed records in our database from October 1987 to December 2002; a total of 505 patients had surgical defects of the head and neck reconstructed with a radial forearm flap: 258 patients had oral cancers, of whom 173 were men and 85 women, median age was 70 years. Five patients had two reconstructions (total 263), of which 247 were fasciocutaneous and 16 osseofasciocutaneous flaps. Mucosal squamous carcinoma accounted for 97% of the primary cancers. RESULTS: There were nine failures of the flap (3.4%) and four episodes of partial necrosis. Four patients (2%) died within 30 days of operation. Orocutaneous fistulas appeared in nine patients (3.4%), 10 patients had wound infections, and nine had haematomas. The nine failed flaps were replaced by a second free flap in one patient, a pectoralis major flap in three, a buccinator myomucosal flap in one, a skin graft in one, and the remaining three defects healed by secondary intention. There was one failure and one partial failure among the 16 osseofasciocutaneous flaps.

Adult↗

Lamotrigine and antiepileptic drugs as mood stabilizers in bipolar disorder.

OBJECTIVE: To review the clinical trials literature on the use of antiepileptic drugs (AED) as mood stabilizers and to suggest an evidence-based approach when utilizing these agents in bipolar disorder. METHOD: The literature is reviewed and subdivided into the following sections: carbamazepine and oxcarbazepine, valproate, lamotrigine, gabapentin and other AED, and discussion. RESULTS: Data exist to support the use of carbamazepine and valproate - and to a lesser extent, oxcarbazepine - in the management of acute manic episodes associated with bipolar I disorder. Lamotrigine, gabapentin, and other AED have not demonstrated consistent anti-manic effects. Clinical trials data favor lamotrigine over all other AED in the treatment of acute bipolar I depression and in rapid cycling bipolar disorder (particularly type II), although the absence of an active comparator in these lamotrigine trials must be noted. Lamotrigine, carbamazepine, and valproate all have evidence supporting their roles as potential long-term mood stabilizers to prevent bipolar relapse, with lamotrigine having a stronger effect in the prevention of depression. CONCLUSION: The AED are a heterogeneous group of medications with differential spectrum of efficacy in the treatment of bipolar disorder.

Acute Disease↗

Management of the neck in patients with T1 and T2 cancer in the mouth.

UNLABELLED: Our aim in this retrospective study was to evaluate the extent of control of metastatic disease in the neck and the survival of patients with T1 and T2 oral cancer. METHODS: All 171 patients with T1 and T2 squamous cell carcinoma (SCC) in the mouth were identified from our computerised database. All had had primary tumours resected and 21 patients with palpable neck nodes had therapeutic neck dissections. Among 150 patients with no palpable nodes, 75 had elective neck dissections, and 75 were observed. The decision to do an elective neck dissection was based on clinical criteria and was not randomised. RESULTS: Cervical nodes contained metastases in 17 of 21 patients who had therapeutic, and 27 of 75 who had elective, neck dissections. Neck metastases developed subsequently in 15 of 75 patients in the observed group, and 9 of these were salvaged by therapeutic neck dissection. The 5-year disease free survival was 19/21 after therapeutic dissection, 72/75 after elective dissection, and 69/75 in the observed group. Patients with cervical nodal metastases had significantly reduced 5-year survival compared with those without (63% and 91%, P = 0.003).

Adult↗

Virtual screening and rational drug design method using structure generation system based on 3D-QSAR and docking.

An efficient virtual and rational drug design method is presented. It combines virtual bioactive compound generation with 3D-QSAR model and docking. Using this method, it is possible to generate a lot of highly diverse molecules and find virtual active lead compounds. The method was validated by the study of a set of anti-tumor drugs. With the constraints of pharmacophore obtained by DISCO implemented in SYBYL 6.8, 97 virtual bioactive compounds were generated, and their anti-tumor activities were predicted by CoMFA. Eight structures with high activity were selected and screened by the 3D-QSAR model. The most active generated structure was further investigated by modifying its structure in order to increase the activity. A comparative docking study with telomeric receptor was carried out, and the results showed that the generated structures could form more stable complexes with receptor than the reference compound selected from experimental data. This investigation showed that the proposed method was a feasible way for rational drug design with high screening efficiency.

Colchicine↗

Docking study of cistanoside C to telomeric DNA fragment.

Experiments show that the natural products phenyl propanoid glycosides (PPGs) extracted from the plant Pedicularis spicata are capable of repairing DNA damaged by oxygen radicals. Based on kinetic measurements and experiments on tumor cells, a theoretical study of the interaction between PPG molecule Cistanoside C and telomeric DNA fragment has been carried out. The docking calculations performed using JUMNA software showed that the Cistanoside C could be docked into the minor groove of telomeric DNA and form complexes with the geometry suitable for an electron transfer between guanine radical and the ligand. Such complexes can be formed without major distortions of DNA structure and are further stabilized by the interaction with the saccharide side-groups.

Catechols↗

Physiological and anatomic evidence for functional subclasses of serotonergic raphe magnus cells.

Serotonergic cells in the medullary nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis (NRMC) project to the spinal cord where they are likely to modulate nociceptive transmission. Previous studies have suggested that these cells are physiologically and anatomically heterogeneous. In the present investigation, we examined whether subclasses of serotonergic RM and NRMC cells can be delineated based on their response to a visceral stimulus, and whether any such subclasses are morphologically distinct. Most RM and NRMC serotonergic cells tested (81 of 116) responded to retraction of the descending aorta into a polyethylene tube (the snare stimulus) with 57% of all cells tested excited and 13% inhibited. Responses of serotonergic cells to the snare outlasted the stimulus, were not reflective of evoked cardiovascular changes, and were observed in sino-aortic deafferented rats, evidence that the snare stimulus does not influence serotonergic cell discharge through activation of baroreceptors. Because serotonergic cells responsive to the snare were also responsive to mechanical brushing within the retroperitoneum, the snare is likely to change serotonergic cell discharge by means of the activation of mechanosensitive visceral afferents. Intracellular labeling of physiologically characterized serotonergic RM and NRMC cells showed that cells that were responsive to the snare stimulus had simpler axonal collateralization patterns than cells that were unresponsive to the snare stimulus. This association between morphological and physiological properties provides additional evidence that subpopulations of serotonergic cells exist and serve varied physiological functions.

Action Potentials↗

Human immunodeficiency virus type 1 integrase: arrangement of protein domains in active cDNA complexes.

Early steps of retroviral replication involve reverse transcription of the viral RNA genome and integration of the resulting cDNA copy into a chromosome of the host cell. The viral-encoded integrase protein carries out the initial DNA breaking and joining reactions that mediate integration. The organization of the active integrase-DNA complex is unknown, though integrase is known to act as a multimer, and high resolution structures of the isolated integrase domains have been determined. Here we use site-specific cross-linking based on disulfide bond formation to map integrase-DNA contacts in active complexes. We establish that the DNA-binding C-terminal domain of one integrase monomer acts with the central catalytic domain from another monomer at each viral cDNA end. These data allow detailed modeling of an integrase tetramer in which pairs of trans interactions link integrase dimers bound to substrate DNA. We also detected a conformational change in integrase- DNA complexes accompanying cleavage of the viral cDNA terminus.

Amino Acid Substitution↗

The discharge of a subset of serotonergic raphe magnus cells is influenced by baroreceptor input.

In order to determine whether serotonergic cells in the medullary raphe magnus (RM) receive baroreceptor input, cells were tested for their responses to descending aortic occlusion, aortic nerve stimulation, or systemic phenylephrine administration in the lightly anesthetized rat. Serotonergic cells were identified physiologically by a quantitative analysis of their slow and steady discharge. Greater than 40% of the serotonergic RM cells tested responded to brief occlusion of the descending aorta at the level of the coeliac arteries, a stimulus that elevated blood pressure by about 30 mmHg. Similarly, about 40% of the serotonergic RM cells responded to stimulation of the aortic nerve, a nerve that contains primarily baroreceptor afferents from the aortic arch. Greater than 70% of RM serotonergic cells responded to phenylephrine administration which elevated blood pressure by an average of 50 mmHg. Serotonergic cell responses to all methods of baroreceptor activation were small in magnitude and were largely restricted in time to the stimulus duration. The results indicate that a subset of serotonergic cells in RM are influenced by baroreceptor activity.

Animals↗

Polyphosphorylation and non-enzymatic template-directed ligation of oligonucleotides.

Oligonucleotide 5'-polyphosphates are formed under potentially prebiotic conditions from oligonucleotide 5'-phosphates and sodium trimetaphosphate. Oligonucleotides activated as polyphosphates undergo template-directed ligation. We believe that these reactions could have produced longer oligonucleotide products from shorter substrates under prebiotic conditions.

Electrophoresis, Polyacrylamide Gel↗

Eremophilenolides from Ligularia fischeri.

The chemical investigation of Ligularia fischeri afforded three new eremophilenolides which were identified as 6 beta-methoxy-8 beta-hydroxy-eremophil-7(11)-en-12,8 alpha-olide, ligufischerin, and 6-oxo-8 beta-hydroxy-eremophil-7(11)-en-12,8 alpha-olide by 1D- and 2D-NMR spectra. In addition, six known eremophilenolides were also obtained.

Asteraceae↗

Aquaticol, a bis-sesquiterpene and iridoid glucosides from Veronica anagallis-aquatica.

Aquaticol, an unusual bis-sesquiterpene was isolated from the medicinal plant Veronica anagallis-aquatica, in addition to 11 known compounds, aucubin, geniposidic acid, mussaenoside, catalposide, verproside, amphicoside, catalpol, boschnaloside, shanzhiside methyl ester, sitosterol and beta-stigmast-4-en-6 beta-ol-3-one. The structure of aquaticol was determined by spectroscopic means and by X-ray crystallographic analysis.

Molecular Structure↗

Serotonergic Raphe magnus cells that respond to noxious tail heat are not ON or OFF cells.

Pharmacological studies have suggested that serotonergic cells in RM contribute to both the inhibition and facilitation of spinal nociceptive transmission. Physiological studies in the medullary nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis have identified putative nociceptive-inhibitory OFF cells and nociceptive-facilitatory neurons ON cells by their responses to noxious thermal stimulation. The present study was designed to determine 1) whether any serotonergic RM cells respond to noxious thermal stimulation and 2) whether noxious heat-responsive serotonergic cells should be classified as ON or OFF cells. Serotonergic cells (n = 150) were identified by physiological criteria in anesthetized rats; 30 of 32 cells tested contained serotonin immunoreactivity. Noxious tail heat elicited a neuronal response in less than a quarter of the serotonergic cells. Most serotonergic cells that responded to tail heat were excited (n = 25), while a small minority of the cells tested were inhibited (n = 8). The tail heat-evoked responses of serotonergic cells were small in magnitude, averaging five to eight spikes in 10 s. Excitatory responses rarely persisted for more than 10 s, while inhibitory responses rarely persisted for more than 20 s. The tail heat-evoked responses of serotonergic cells were compared to those of non-serotonergic cells (n = 186). Non-serotonergic cells that responded to noxious tail heat had significantly greater response magnitudes, averaging 75-95 spikes in 10 s, than heat-responsive serotonergic cells. In addition, most heat-responsive non-serotonergic cells responded for at least 30 s after stimulus onset. These results demonstrate that the tail heat-evoked responses of serotonergic RM cells are qualitatively and quantitatively distinct from those of non-serotonergic ON and OFF cells. It is therefore unlikely that serotonergic RM cells, even the subpopulation that responds to noxious tail heat, share a physiological function with ON and OFF cells.

Animals↗

Influence of idazoxan on analgesia, tolerance, and physical dependence of morphine in mice and rats in vivo.

AIM: To study the influence of idazoxan (Ida), an antagonist of imidazoline receptors (I-R), on analgesia, tolerance, and physical dependence of morphine. METHODS: The effects of Ida on pain threshold and morphine analgesia were observed in mouse acetic acid writhing test and 55 degrees C hot plate test. The effect of Ida on morphine tolerance and physical dependence were observed in mouse tolerant model and in mice and rat models. RESULTS: Ida (3-9 mg/kg) significantly decreased the pain threshold by 120% in acetic acid writhing test and by 39% in 55 degrees C hot plate test of mice, respectively. It inhibited the analgesic effect of morphine in a dose-dependent manner. Ida promoted the development of tolerance to morphine in mice and induced the abstinence syndrome in morphine-dependent mice and rats similar to naloxone. CONCLUSION: I-R and its endogenous ligand agmatine might participate in the pain threshold and influence morphine analgesia as well as negatively regulate tolerance to and physical dependence on morphine.

Adrenergic alpha-Antagonists↗

[Experimental study on decoctum Agrimonia pilosa Ledeb-induced apoptosis in HL-60 cells in vitro].

In this study, MTT assay, cell morphology and flow cytometry were used to explore Agrimonia pilosa Ledeb on HL-60 cells in vitro. The data suggested that Agrimonia pilosa Ledeb had the effects of growth inhibition in HL-60 cells. After treated with decoctum Agrimonia pilosa Ledeb, cells underwent apoptosis with typical morphological feature. DNA histograms by flow cytometric analysis displayed distinct apoptotic peak.

Agrimonia↗