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Biomedical subjects

L Gao

Publications and source records attributed to L Gao.

At least 163 records · Page 9Linked to original sources

beta-MHC transgene expression in suspended and mechanically overloaded/suspended soleus muscle of transgenic mice.

Non-weight-bearing (NWB) activity [space flight and hindlimb suspension (HS)] results in the loss of soleus muscle mass, a slow-to-fast fiber-type conversion, and decreased beta-myosin heavy chain (beta-MHC) protein and mRNA expression. To identify beta-MHC promoter sequences required for decreased beta-MHC expression in response to HS, we have modified an existing noninvasive hindlimb unweighting model to accommodate the use of (transgenic) mice. After 2 wk of HS, body and muscle (soleus > gastrocnemius > plantaris) weights were decreased as was the proportion of histochemically classified type I fibers in HS soleus muscle. Northern blot analysis revealed decreases in endogenous mRNA representing beta-MHC, slow myosin light chain 1 and 2, and cardiac/slow troponin C, whereas those representing skeletal troponin C, muscle creatine kinase, and glyceraldehyde-3-phosphate dehydrogenase increased. Protein extracts prepared from HS soleus (SS) muscle of mice harboring transgenes comprised of 5.6 or 0.6 kilobase of wild type (wt) mouse beta-MHC promoter (beta 5.6 wt, beta 0.6wt) and those carrying the simultaneous mutation (mut) of the MCAT, C-rich, and beta e3 subregions (beta 5.6mut3, beta 0.6mut3) revealed decreases in chloramphenicol acetyltransferase (CAT) specific activity relative to respective controls. Decreased CAT mRNA was observed for transgene beta 5.6mut3, line 85. Two weeks of the simultaneous imposition of mechanical overload (synergist ablation) and HS (MOV/HS) countermanded the loss in absolute and normalized SS weight but did not decrease beta 0.6wt transgene expression. These transgenic results demonstrate that regulatory sequences within a 600-base pair beta-MHC promoter are sufficient to direct decreased transcription of beta-MHC transgenes after 2 wk of HS.

Animals↗

[Volume loading experiment in dogs with large area infarction of right and left ventricles].

In order to study volume loading effect on large area myocardial infarction (MI) in right and left ventricles, large area MI in both ventricles and cardiogenic shock in 12 dogs were induced by occluding coronary arteries. Left ventricular systolic pressure (LVSP) and +/- dp/dt max. dropped markedly by 54%, 51% and 47% respectively, whereas right ventricular systolic pressure (RVSP) and +/- dp/dt max. fell by 9%, 25% and 27% respectively. The condition was obviously worse by rapid volume loading (dextran, 30 ml/kg, i.v. in 20 min.) in group I (n = 6), leading to increased retrograde beat of right ventricle, further decrease of +/- dp/dt max. in both ventricles, significant increase of right atrial pressure (RAP) and left ventricular and diastolic pressure (LEVDP) (2.9 +/- 0.2 kPa, P < 0.01 and 5.0 +/- 0.3 kPa, P < 0.001, respectively), and even ventricular fibrillation. Shock was reversed by combined treatment of dopamine (10 micrograms/kg.min) and glyceryl trinitrate (1 microgram/kg.min) in group II (n = 6) in 30 min, showing evident increase of arterial pressure, cardiac output, LVSP and +/- dp/dt max. without rise in RAP and LVEDP.

Animals↗

[Relationship between obese gene expressive product and obesity].

In order to study the relationship between obese protein and obesity. A radioimmunoassay for human plasma obese protein (OP) was established using human OP (57-92) and its specific antiserum. We observed the distribution and the characteristics. Of OP in normal human and mouse tissue and changes of plasma OP in obese patients. We also observed the tissue distribution after intravenous injection of 125I-labeled OP fragments (116-167) and (93-105) in rats. The results were as follows. The contents of OP were much higher in brain tissue than those in abdominal adipose tissue; levels of OP in liver and in skeletal muscle tissue were zero; the contents of abdominal adipose tissue were higher in female mice than those in male mice; the contents of plasma OP in normal human beings were 194.3 +/- 17.7 ng/L, while those in mice were 2257.8 +/- 171.9 ng/L. It was also found that the administered OP fragments were widely distributed in various tissue and organs including the brain. Kidney was the richest in the OP fragments; liver and lung ranked second. The half time of the OP fragments in plasma clearance was about 4.5 min. The contents of OP in obese adults and in obese children were much lower than those in normal control group. There was significant negative correlation between OP levels and body mass index, serum concentration of glucose, cholesterol and triglycerides. So the present study indicates the important relationship between the changes of OP contents and the pathogenesis of obesity.

Adipose Tissue↗

[Alterations of MDM2 and p53 genes in bone tumors].

OBJECTIVE: To determine the frequency of MDM2 and p53 genes and their possible role in the pathogenesis and development in bone tumors. METHODS: Digoxigenin labeling in situ hybridization technique was used to investigate the expression of MDM2 and p53 in 38 cases of bone tumors, including 12 osteosarcomas, 10 chondrosarcomas, 14 giant cell tumors of bone and 2 chondroblastomas. The relationship between MDM2 and p53 expressions was analyzed. RESULTS: The positive rates for MDM2 in osteosarcoma, chondrosarcoma and giant cell tumor of bone were 41.7%, 50.0% and 35.7%, while those for p53 were 58.3%, 40.0% and 21.4%, respectively. The two cases of chondroblastoma showed both MDM2 and p53 overexpression. There was a striking association between MDM2 and p53 overexpressions. CONCLUSION: MDM2 and p53 alterations are frequent events in bone tumors and may be involved in tumorigenesis or tumor progression in bone tumors.

Bone Neoplasms↗

[Oculocardiac reflex in senile cataract operation].

OBJECTIVE: To determine the incidence of the oculocardiac reflex and to identify which steps in the process in senile cataract operation are more important in eliciting the reflex. METHODS: Dynamic electrocardiogram was recorded with a 24 hour Holter's monitoring at the time of following steps: preoperation, retrobulbar anesthesia, softening of eyeball, superior rectus suture, corneoscleral incision, delivery of the nucleus and posterior chamber lens implantation. Oculocardiac reflex was defined as at least a 10% decrease in heart rate below relative baseline. RESULTS: 14 times of oculocardiac reflex occurred in 10 of 30 patients (33.3%). All maneuvers except for superior rectus fixation triggered the reflex in our group. In addition, premature beat was noted in 5 patients. CONCLUSION: Our patients indicate that cataract extraction may result in abnormalities in both heart rate and rhythm. The definition of the oculocardiac reflex may be too conservative and requires redefinition.

Aged↗

[Advance in medical robot].

In this paper, we describe the basic divisions of medical robot, and at the same time their applications filed and developing trend are also been given. Finally some views of the development of medical robot in China are presented.

Microsurgery↗

[Resonance Raman spectra of transition metal Mn(III), Fe(III), Rh(III), Pd(II) porphyrin complexes].

The resonance Raman spectra of Mn(III), Rh(III), Fe(III), Pd(II) protoporphyrin IX-dimethylester (PP) and tetra-phenylporphyrin (TPP) complexes were reported. The difference of their structure-sensitive band frequency was a result of the interaction of different metal ions' outer d electrons with the electrons of the porphyrin ring. As well the effects of different porphyrin rings and their substituts on the structure-sensitive bands were discussed in this paper.

Iron↗

[Simultaneous spectrophotometric determination of three-component mixture by two partial least squares methods].

Two partial least squares methods, classical partial least squares (PLS) and partial least squares based on a kernel algorithm (KPLS), were studied for simultaneous determination of a three-component mixture. Three programs called SPGRAFA, SPGRPLS and SPGRKPLS were designed to perform the calculations. Eight error functions were calculated for deducing the number of factors. Because the size of the kernal matrix was much smaller than the original data matrix, the KPLS applied to calculating the matrix with many wavelengths and fewer number of samples. Experimental results showed both methods to be successful even there was overlap of spectra and agreed well.

English Abstract↗

Lack of germ-line mutations of CDK4, p16(INK4A), and p15(INK4B) in families with glioma.

Gliomas are tumors of the central nervous system that may be inherited in some patients. The gene(s) responsible for the clustering of gliomas in families have not yet been identified. Molecular studies of sporadic high-grade gliomas have revealed mutations or deletions of the genes encoding the protein kinase inhibitors p16(INK4A) and p15(INK4B) in a large proportion of tumors. Moreover, those tumors without deletions frequently display gene amplification and/or over-expression of mRNA encoding the protein kinase cdk4. We hypothesized that germ-line mutations in the p16(INK4A), p15(INK4B), or CDK4 genes might contribute to some cases of familial gliomas. To address this issue, we analyzed 36 kindreds with a predisposition to glial tumors. Genomic DNA from index members of these families was screened by PCR-single-strand conformational polymorphism analysis. We did not detect any functional mutations in the p16(INK4A), p15(INK4B), or CDK4 genes, although two individuals did have a previously described A140T polymorphism in p16(INK4A). Thus, despite the association between the sporadic forms of high-grade glioma and abnormalities of p16(INK4A), p15(INK4B), or CDK4, we found no evidence that germ-line mutations in the coding region of these three genes predispose to inherited glial tumors.

Adult↗

Targeting of antihapten antibodies to activated T cells via an IL-2-hapten conjugate prolongs cardiac graft survival.

Antihapten antibodies binding to ligand-hapten conjugates are able to mediate complement mediated lysis in vitro. Based on this observation we propose a new in vivo immunotherapy using molecules that combine a low molecular weight hapten binding to antibodies preexisting in serum and a cell specific ligand. The ligand-hapten conjugates are potential cytotoxic drugs which may (1) be specific for a given target cell, (2) be nonimmunogenic, (3) be of low molecular weight, (4) form soluble complexes with preexisting antibodies resulting in prolonged half life of the drug, and (5) induce a potent antibody mediated rejection of target cells. These novel compounds could be useful for the elimination of certain cell subsets involved in allograft rejection, cancers, infectious diseases, etc., without some of the pitfalls of conventional immunotherapies. The feasibility of this approach was demonstrated in an animal model using a compound consisting of one interleukin 2 and one fluorescein molecule (IL-2-FITC). BALB/c mice (H2d) previously immunized and expressing anti-FITC antibodies were transplanted with a fully mismatched C57BL/6 (H2b) heterotopic heart allograft. Untreated controls rejected their graft by day 9 (MSD = 9 +/- 0.7). Mice with preexisting anti-FITC antibodies treated with IL-2-FITC maintained their grafts for 38.7 +/- 7.1 days (P < 0.02). No prolongation of graft survival was observed in immunized animals that were treated with IL-2 alone (MSD = 10 +/- 1.4). Nonimmunized animals treated with IL-2-FITC rejected their grafts on day 9.4 +/- 1.1. This demonstrates that IL-2-FITC therapy specifically prolonged graft survival in animals with circulating anti-FITC antibodies. The data suggest that a ligand/hapten pair can redirect preexisting antihapten antibodies toward target cells in vivo. Such compounds may be developed for human use as alternatives to polyclonal or monoclonal antibody therapy.

Animals↗

Mucosal or targeted lymph node immunization of macaques with a particulate SIVp27 protein elicits virus-specific CTL in the genito-rectal mucosa and draining lymph nodes.

The major routes of HIV transmission are through the rectal and cervico-vaginal mucosa. To prevent dissemination of HIV to the regional lymph nodes (LNs), an effective vaccine may need to stimulate CTL in the rectal or genital tract and the draining LNs. We report that mucosal immunization by the recto-oral and vagino-oral route or s.c. immunization targeting the iliac LNs with a particulate SIVp27:Ty-VLP vaccine elicits SIVgag-specific CTL in the regional LNs as well as in the spleen and PBMC. Targeted LN immunization with this vaccine elicited MHC class I-restricted CD8+ CTL responses, and the highest frequency of CTL was found in the iliac LNs. Moreover, SIVgag-specific CTL activity was detected in short term T cell lines established in mononuclear cells eluted from the rectal and cervico-vaginal mucosa. The relative frequency of CTL in short term cell lines prepared from the rectal mucosa (21/113 or 18.6%) was similar to that obtained from the cervico-vaginal mucosa (16/79 or 20.3%). Examination of the relative frequency of CTL to the T cell epitopes residing within SIVp27 showed a higher frequency in iliac LN cells to peptide aa 41-70 than in that to peptide aa 121-150, and this was significant after both recto-oral (chi-squared 6.500, p < 0.02) and vagino-oral (chi-squared = 10.391, p < 0.01) immunization. In contrast, the relative frequency of CTL in PBMC to peptide aa 41-70 (15.5%) was comparable to that elicited by peptide aa 121-150 (17.6%). This study provides novel evidence that mucosal or targeted LN immunization can generate anti-SIV CTL in the rectal and genital mucosa, in the draining LNs, and in the central lymphoid system.

Animals↗

Molecular cloning of cDNA for rat brain GD3-synthase.

The complete nucleotide sequence of the cDNA coding for rat GD3-synthase was determined for the first time using PCR and the rapid amplification of cDNA ends (RACE) procedures. The deduced amino acid sequence consists of 359 residues. The protein contains a potential transmembrane domain with a short N-terminus and such highly conserved regions as the sialylmotifs. An antisense oligonucleotide derived from the rat GD3-synthase cDNA was applied to the cultures of rat cerebellar neurons and results showed a decrease in the synthesis of ganglioside GD3, indicating that the expression of GD3-synthase was modulated by the antisense sequence.

Amino Acid Sequence↗

Association of a 14-3-3 protein with CMP-NeuAc:GM1 alpha 2,3-sialyltransferase.

CMP-NeuAc:GM1 alpha 2,3-sialyltransferase (ST-IV) was purified to homogeneity from rat brain. Microsequencing of the tryptic peptides derived from the purified enzyme revealed two amino acid sequences homologous to the 14-3-3 proteins. A polyclonal antibody was raised against purified ST-IV. A 33 kDa protein was co-immunoprecipitated from rat brain extracts with the anti-(ST-IV) antibody as detected by Western blot analysis. This protein was identified as a subtype of 14-3-3 family by an anti-(14-3-3) antibody. Screening of a rat brain lambda gt11 library using the anti-(ST-IV) antibody resulted in the identification of a cDNA clone coding for the subtype of 14-3-3 protein. These results indicate an association of the 14-3-3 protein with the sialyltransferase. Since the 14-3-3 protein has PKC inhibitor activities and the activity of sialyltransferases is, at least in part, regulated by PKC, the association of the 14-3-3 protein with ST-IV may indicate a role for this protein in the post-translational regulation of the sialyltransferase activity through the processes of phosphorylation and dephosphorylation.

14-3-3 Proteins↗

Imaging of the elastic properties of tissue--a review.

Recently, a number of methods have been developed that make it possible to image the elastic properties of soft tissues. Because certain types of tissues such as malignant lesions, for example, have elastic properties that are markedly different from surrounding tissues, elasticity imaging could provide a significant adjunct to current diagnostic ultrasonic methods. Further, elasticity imaging techniques could be used to augment the study of tissues that change their elastic properties, such as skeletal and cardiac muscle. In this paper, we survey some of the previous work done in the related field of biomechanics, and we review measurement techniques from the 1950s to the 1980s. Different approaches to elastic imaging and signal processing are then discussed and a lexicography for elastic imaging is introduced. It is hoped that this nomenclature will provide a meaningful categorization of various approaches and will make evident the inherent parameters displayed and conditions applied in deriving the resulting images. Key assumptions and signal processing approaches are also reviewed. Finally, directions for future work are suggested.

Animals↗

Redirecting circulating antibodies via ligand-hapten conjugates eliminates target cells in vivo.

The elimination of cell populations in vivo often relies on reagents that are self-limiting, are difficult to design and produce or contain highly toxic components. Here we describe a novel immunotherapy using molecules that combine a cell-specific ligand and a hapten binding to preexisting antibodies in serum. The F(ab')2 fragment of a polyclonal anti-thymocyte globulin (ATG) preparation was used as a T-cell-specific ligand, and fluorescein isothiocyanate (FITC), as the hapten. Clearance of ligand-hapten conjugates from the circulation through formation of immune complexes was prevented through controlled synthesis of conjugates so that they contained one F(ab')2 fragment and one FITC molecule. Administration of a single dose of F(ab')2 or F(ab')2ATG-FITC into naive mice had no effect on the number of circulating T cells. In contrast, injection of F(ab')2ATG-FITC into mice with circulating anti-FITC antibodies resulted in the elimination of peripheral T cells. The reduction in cell numbers was equivalent to that obtained with a corresponding dose of intact ATG. Experiments in thymectomized mice demonstrated that the reduction of circulating T cells was due to target-cell elimination and not to immunomodulation or cellular sequestration. The adaptability of the model to other sources of effector antibodies and more useful ligands is discussed.

Animals↗

Automatic liver segmentation technique for three-dimensional visualization of CT data.

PURPOSE: To develop a system for automatic segmentation of the liver from computed tomographic (CT) scans of the abdomen for three-dimensional volume-rendering displays. MATERIALS AND METHODS: An automated liver segmentation system was developed, which combined domain knowledge with analysis of a global histogram, morphologic operators, and the parametrically deformable contour model. Boundaries of the thresholded liver volume were modified section-by-section by exploiting information from adjacent sections. These boundaries were refined by optimization of the parametrically deformable contour model. Volume-rendered images were created by using the boundaries to exclude tissues outside the liver. The system was tested on CT data sets from 10 cases of potentially resectable hepatic neoplasm. RESULTS: Of the 401 sections in the 10 cases, 53 sections (13.2%) required user modifications during segmentation. The utility of the three-dimensional-rendered images with use of these liver boundaries was judged by a radiologist as being comparable to that of three-dimensional images created with manual editing. Twenty-eight of the sections were deemed imperfect by the radiologist and might need further modifications. CONCLUSION: An effective technique for automatic segmentation of the liver from CT images has been developed. This technique promises to save time and simplify the creation of three-dimensional liver images by minimizing operator intervention.

Humans↗

Beta-MHC and SMLC1 transgene induction in overloaded skeletal muscle of transgenic mice.

The hypertrophic responses of white fast-twitch muscle to mechanical overload has been investigated using transgenic mice. After 7 wk of overload, endogenous beta-myosin heavy chain (MHC) and slow myosin light chain 1 and 2 (SMLC1, SMLC2) protein were increased in the overloaded plantaris (OP) muscle compared with sham-operated control plantaris (CP)muscle. Concurrently, the levels of endogenous beta-MHC, SMLC1, SMLC2, and cardiac/slow troponin C (CTnC) mRNA transcripts were significantly increased in OP muscles, whereas skeletal troponin C (sTnC) mRNA transcript levels decreased. As an initial attempt to locate DNA sequence(s) that governs beta-MHC induction in response to mechanical overload, multiple independent transgenic lines harboring four different human beta-MHC transgenes (beta 1286, beta 988, beta 450, beta 141) were generated. Except for transgene beta 141, muscle-specific expression and induction (3- to 22-fold) in OP muscles were observed by measuring chloramphenicol acetyltransferase activity (CAT assay). Induction of a SMLC1 transgene (3920SMLC1) in OP muscles was also observed. Collectively, these in vivo data provide evidence that 1) a mechanical overload inducible element(s) is located between nucleotides -450 and +120 of the human beta-MHC transgene, 2) 3,900 bp of 5' sequence is sufficient to confer mechanical overload induction of a SMLC1 transgene, and 3) the increased expression of slow/type I isomyosin (beta-MHC, SMLC1, SMLC2) in response to mechanical overload is regulated, in part, transcriptionally.

Animals↗