Biomedical subjects
Publications and source records attributed to Y Lai.
Microchannels are fabricated into conventional single-mode fibers by femtosecond laser processing and chemical etching. Fabrication limitations imposed by the fiber geometry are highlighted and resolved through a simple technique without compromising fabrication flexibility. A microfluidic fiber device consisting of a 4 microm wide microchannel that intersects the fiber core for refractive index sensing is further demonstrated.
A femtosecond laser inscription technique is proposed for the fabrication of a fiber grating laser directly into a nonphotosensitive gain fiber. A distributed Bragg reflector fiber grating laser is realized in a conventional, untreated Er:Yb-codoped fiber as an illustration. Robust, single-mode, single-polarization laser operation at temperatures in excess of 600 degrees C is further achieved without compromising performance. A nonlinear, thermally induced wavelength shift is also observed at elevated temperatures.
Beta-cell replacement is the only way to restore euglycaemia in patients with type-1 diabetes. Pancreatic tissue, processed for subsequent clinical islet transplantation, is exposed to ischaemia causing injury and death in a large number of islets before and after transplantation. In this review we summarize what is known on the sources of environmental stress for pancreatic islets, such as insufficient oxygen supply during pancreas procurement and in culture prior to intraportal transplantation, nutritional and oxygen deprivation during the isolation process, and the consequences of hyperglycaemia. An increasingly recognized role in the modulation of beta-cell function and these environmental stress factors plays the vascular network of the pancreatic islets. Islet revascularization by angiogenesis is relevant for the survival of the graft subsequent to transplantation. Potential strategies offered by therapeutic induction of revascularization to ameliorate the detrimental impact of these factors on the quality of islet transplants are discussed.
OBJECTIVE: The present study aims to accurately estimate the in vivo brain-to-skull conductivity ratio by means of cortical imaging technique. Simultaneous extra- and intra-cranial potential recordings induced by subdural current stimulation were analyzed to get the estimation. METHODS: The effective brain-to-skull conductivity ratio was estimated in vivo for 5 epilepsy patients. The estimation was performed using multi-channel simultaneously recorded scalp and cortical electrical potentials during subdural electrical stimulation. The cortical imaging technique was used to compute the inverse cortical potential distribution from the scalp recorded potentials using a 3-shell head volume conductor model. The brain-to-skull conductivity ratio, which leads to the most consistent cortical potential estimates with respect to the direct intra-cranial measurements, is considered to be the effective brain-to-skull conductivity ratio. RESULTS: The present estimation provided consistent results in 5 human subjects studied. The in vivo effective brain-to-skull conductivity ratio ranged from 18 to 34 in the 5 epilepsy patients. CONCLUSIONS: The effective brain-to-skull conductivity ratio can be estimated from simultaneous intra- and extra-cranial potential recordings and the averaged value/standard deviation is 25+/-7. SIGNIFICANCE: The present results provide important experimental data on the brain-to-skull conductivity ratio, which is of significance for accurate brain source localization using piece-wise homogeneous head models.
The cytoskeleton plays important roles in cell function and is therefore implicated in the pathogenesis of many human liver diseases, including malignant tumors. The stability of cytokeratin proteins during tumor transformation in human hepatocellular carcinoma has been studied with a molecular approach previously. The results demonstrate that the cytokeratin is modulated in human hepatocellular carcinoma. Besides this, three low molecular weight cytokeratin molecules (named HCC CK) are found. This indicates that these HCC CKs have undergone modulation from the human hepatocyte cytokeratin 18. We also checked the cytokeratin profile of the human hepatoma cell line PLC/PRF/5 with the same methods to ensure the HCC CK molecules are produced by modulation but not protein degradation. The stability of cytokeratin molecules was studied by a different approach. The cytokeratin compositions of human liver cells (Chang cell line) were analysed under the effects of microtubule-disrupting drug (colchicine) by SDS-PAGE, Western blot, immunoprecipitation using a commercially available monoclonal anti-cytokeratin 18 antibody and immunofluorescent staining. Within 1 h of treatment, the microtubule began to collapse and the filamentous structure was shortening. The microtubule had almost collapsed and became fragmented to form a lattice-like network after 24 h of treatment. The cytokeratin was modulated after long-term (24 h) treatment of colchicine, and the molecular weight became 14 kD and the antigenicity was lost. The stability of cytokeratin molecules was related to the intact microtubule network, after disruption of the microtubule the cytokeratin would be modulated. The intact microtubule network was a stabilizing factor of cytokeratin 18 in human liver cells.
Previous studies have indicated a correlation between local variation in wall shear stress in arterial blood flow and atheroma development. The purpose of this study was to analyze the hemodynamics in vascular segments from morphologically realistic three-dimensional (3D) reconstruction, and to compare the computed wall shear stress in a compliant vascular segment model and the corresponding rigid walled model. Cross-sectional images of the segments of femoral and carotid arteries in five Yucatan miniswine were obtained using intravascular ultrasound (IVUS) imaging and the segment geometry was reconstructed at different times in the cardiac cycle. The actual measured wall motion from the reconstruction was employed to specify the moving boundaries for simulation of physiological distensibility. Velocity profiles and wall shear stress were computed using unsteady computational fluid dynamics analysis. The computed results revealed that the maximum wall shear stress in the compliant model was approximately 4-17 percent less than that in the rigid model if the wall motion is larger than 10 percent. Our analysis demonstrates that inaccuracies due to inflow velocity profile can be minimized by the extension of the model upstream. The phase angle between the diameter change and wall shear is affected by the local changes in geometry of the arteries. These simulations can be potentially used to analyze the effect of regional wall motion changes in the presence of atherosclerotic lesions on the local fluid dynamics and to correlate the same with subsequent growth of the lesions.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: To evaluate the effect of intraoperative local arterial infusion chemotherapy for gastric cancer. METHODS: The effects of intraoperative local arterial infusion chemotherapy in 40 patients with gastric cancer were assessed. Twenty-four patients with gastric cancers who underwent the intraoperative systemic chemotherapy were taken as controls. The removed specimens were examined microscopically to show the degeneration and necrosis of the tumour cell. RESULTS: After the treatment of the tumour cells, all of the cases in the study group showed various degrees of degeneration and necrosis. The immediate effective rate was 95% for the the study group but only 41.67% for the control group (P < 0.05). CONCLUSION: Intraoperative local arterial infusion chemotherapy for gastric cancer has good immediate effect and little side effect; it prevents the intraoperative iatrogenic metastases and implantation and decreases the postoperative recurrence of gastric cancer.
A DNA repair synthesis assay monitoring nucleotide excision repair (NER) was established in cell-free extracts of unicellular alga Chlorella pyrenoidosa using cisplatin- or mitomycin C-damaged plasmid DNA as the repair substrate. The algal extracts promoted a damage-dependent increase in 32P-dATP incorporation after normalization against an internal control. To identify the proteins responsible for NER, a biotin-labeled duplex 27 mer (2 µg) irradiated with or without UV (27 kJ m(-2)) was immobilized on streptavidin-conjugated agarose beads and incubated with C. pyrenoidosa extracts (50 µg) to pull down repair proteins. The extracts post incubation with beads carrying unirradiated 27 mer promoted an eightfold increase in repair synthesis in plasmid DNA (1 µg) damaged by 16.8 pmol of cisplatin. The extracts obtained after affinity adsorption with UV-damaged DNA ligand, however, failed to repair plasmid DNA treated with cisplatin, reflecting that some proteins crucial to NER had been sequestered by the damaged 27 mer. A polypeptide approximately 70-72 kDa in molecular mass was found to bind much more strongly to the damaged DNA than to the control DNA after analyzing the proteins bound to the beads by SDS-PAGE, and this polypeptide is believed to play a role in NER in C. pyrenoidosa.
The detection of T(H)1-type and T(H)2-type cells directly in situ would be of great value in the study of T(H) development and function in vivo. Transgenic mice expressing human Thy1 and mouse Thy1.1 under the control of the murine IFN-gamma and IL-4 promoters, respectively, have been generated. The hThy1(+) cells represent (with some temporal lag) most of the IFN-gamma-producing CD4(+) T-cells, while the mThy1.1(+) cells represent only a percentage of IL-4 secreting cells. This may be due to mono-allelic expression of the IFN-gamma and IL-4 genes. Since permeabilization is not required for the detection of the transgenic surface markers, these transgenic mice can facilitate the detection of T(H)1-type and T(H)2-type cells by flow cytometry with surface immunofluorescent staining. These surface markers should permit isolation of viable cells according to their T(H) type for adoptive transfer experiments, and may serve as a model system for tracing the development of T(H)1 and T(H)2-type cells in vivo.
The phosphorylation state of the proteins, regulated by phosphatases and kinases, plays an important role in signal transduction and long-term changes in neuronal excitability. In neurons, cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and calcineurin (CN) are attached to a scaffold protein, A kinase anchoring protein (AKAP), thought to anchor these three enzymes to specific sites of action. However, the localization of AKAP, and the predicted sites of linked phosphatase and kinase activities, are still unknown at the fine structural level. In the present study, we investigated the distribution of AKAP79 in the hippocampus from postmortem human brains and lobectomy samples from patients with intractable epilepsy, using preembedding immunoperoxidase and immunogold histochemical methods. AKAP79 was found in the CA1, presubicular and subicular regions, mostly in pyramidal cell dendrites, whereas pyramidal cells in the CA3, CA2 regions and dentate granule cells were negative both in postmortem and in surgical samples. In some epileptic cases, the dentate molecular layer and hilar interneurons also became immunoreactive. At the subcellular level, AKAP79 immunoreactivity was present in postsynaptic profiles near, but not attached to, the postsynaptic density of asymmetrical (presumed excitatory) synapses. We conclude that the spatial selectivity for the action of certain kinases and phosphatases regulating various ligand- and voltage-gated channels may be ensured by the selective presence of their anchoring protein, AKAP79, at the majority of glutamatergic synapses in the CA1, but not in the CA2/CA3 regions, suggesting profound differences in signal transduction and long-term synaptic plasticity between these regions of the human hippocampus.
Explore the source record for details and available documents.
Since endotheliocyte strains of guinea-pig and inbred strains of guinea-pig are not easily obtained, it is impossible to ensure the consistence of antigenicity between endotheliocytes and donor organs when endotheliocytes are used as an inductor in the research of immunological tolerance. So it is necessary to establish the guinea-pig endotheliocyte-donor model. One side of common carotid arteries was removed and reversed. After collagenase digestion, culture of endotheliocytes was performed. And the survival time of guinea-pig was observed. Cultured cells were confirmed as endotheliocytes by the study of morphology, immunohistochemistry and electron microscopy. The two-month-survival of guinea-pigs was 92% (103/112). The establishment of guinea-pig endotheliocyte-donor model can provide the foundation for the research of guinea-pig endotheliocyte and immunological tolerance.
OBJECTIVE: To evaluate the relationship between the expression of multidrug resistance gene (mdr1) or multidrug resistance-associated protein gene (MRP) and the prognosis in patients with acute leukemia (AL). METHODS: The expression of mdr1 and MRP were measured in 55 patients with AL by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The mdr1 and MRP gene expression levels in the relapsed AL and the blastic phase of CML group (0.735 +/- 0.249, 1.157 +/- 0.447) were significantly higher than those in the untreated group (0.408 +/- 0.186, 0.465 +/- 0.253) (P < 0.01). The complete remission (CR) rate in high mdr1 and MRP expression group was significantly lower than that in low mdr1 and MRP expression group (P < 0.01) in a follow up of 40 AL patients. CONCLUSION: Increased expression of mdr1 and MRP gene might be an important factor for predicting drug resistance, relapse and unfavorable prognosis in AL patients.
Targeting of protein kinases and phosphatases provides additional specificity to substrate selectivity in cellular signaling. In the case of the Ca2+/calmodulin-dependent protein phosphatase calcineurin, AKAP79 has been shown to bind calcineurin and inhibit its activity in vitro (Coghlan, V., Perrino, B. A., Howard, M., Langeberg, L. K., Hicks, J. B., Gallatin, W. M., and Scott, J. D. (1995) Science 267, 108-111). In the present study, we characterized the binding regions on calcineurin A (CnA) and AKAP79 that are important for this interaction. Residues 30-98 and 311-336 on CnA, and residues 108-280 on AKAP79 were found to be important for binding. The binding of CnA by AKAP79 does not require the calcineurin B subunit, and occurs in a region distinct from where the immunosuppressant-immunophilin complex bind. AKAP79 also bound to CnA in cells transfected with AKAP79 and CnA. To determine the function of AKAP79-calcineurin interaction in intact cells, we measured the dephosphorylation and subsequent activation of NFAT, a transcription factor that is a substrate for calcineurin. Overexpression of AKAP79 inhibited NFAT dephosphorylation, resulting in a decrease in NFAT activation. These results demonstrated that AKAP79 can bind to and inhibit calcineurin activity in vivo, suggesting a physiological role for AKAP79-calcineurin interaction in NFAT-mediated signaling.
To find index for early diagnosis of antemortem wound, the authors used the ICS analysis in a quantitive study of 5-hydroxytryptamine(5-HT) levels on rat's incised-skin antemortem wound in comparison with the postmortem wound inficted at various intervals. The results showed that the 5-HT increased significantly at 5 min, reached a peak at 15 min and decreased at 60 min on antemortem wounds. The 5-HT levels of antemortem groups were prominently high (more than 40%, P < 0.05) as compared with those of postmortem group and the levels of 5-HT on the wounds of postmortem groups were higher (35.77%, P < 0.05) than those of controls as well. The authors suggest that in the cases where the levels of 5-HT are as high as 40% on the edges of the injured skin, the injury should be considered an antemortem wound.
Ca2+ influx through skeletal muscle Ca2+ channels and the force of contraction are increased in response to beta-adrenergic stimulation and high-frequency electrical stimulation. These effects are thought to be mediated by cAMP-dependent phosphorylation of the skeletal muscle Ca2+ channel. Modulation of the cloned skeletal muscle Ca2+ channel by cAMP-dependent phosphorylation and by depolarizing prepulses was reconstituted by transient expression in tsA-201 cells and compared to modulation of the native skeletal muscle Ca2+ channel as expressed in mouse 129CB3 skeletal muscle cells. The heterologously expressed Ca2+ channel consisting of alpha1, alpha2delta, and beta subunits gave currents that were similar in time course, current density, and dihydropyridine sensitivity to the native Ca2+ channel. cAMP-dependent protein kinase (PKA) stimulation by Sp-5,6-DCl-cBIMPS (cBIMPS) increased currents through both native and expressed channels two- to fourfold. Tail currents after depolarizations to potentials between -20 and +80 mV increased in amplitude and decayed more slowly as either the duration or potential of the depolarization was increased. The time- and voltage-dependent slowing of channel deactivation required the activity of PKA, because it was enhanced by cBIMPS and reduced or eliminated by the peptide PKA inhibitor PKI (5-24) amide. This voltage-dependent modulation of the cloned skeletal muscle Ca2+ channel by PKA also required anchoring of PKA by A-Kinase Anchoring Proteins because it was blocked by peptide Ht 31, which disrupts such anchoring. The results show that the skeletal muscle Ca2+ channel expressed in heterologous cells is modulated by PKA at rest and during depolarization and that this modulation requires anchored protein kinase, as it does in native skeletal muscle cells.