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Biomedical subjects

L Gao

Publications and source records attributed to L Gao.

At least 181 records · Page 10Linked to original sources
PubMed1996

Induction of beta-MHC transgene in overloaded skeletal muscle is not eliminated by mutation of conserved elements.

Mechanical overload leads to hypertrophy, increased type I fiber composition, and beta-myosin heavy chain (beta-MHC) induction in the fast-twitch plantaris muscle. To better understand the mechanism(s) involved in beta-MHC induction, we have examined inducible expression of transgenes carrying the simultaneous mutation of three DNA regulatory subregions [muscle CAT (MCAT), C-rich, and beta e3] in the context of either 5,600-base pair (bp; beta 5.6mut3) or 600-bp (beta 0.6mut3) beta-MHC promoter in overloaded plantaris muscles of transgenic mice. Protein extract from mechanically overloaded plantaris muscle of mice, harboring either mutant transgene beta 5.6mut3 or beta 0.6mut3, showed an unexpected 2.8- to 4.5-fold increase in chloramphenicol acetyltransferase (CAT) specific activity relative to their respective controls. Similar results were obtained with wild-type (wt) beta-MHC transgenes (beta 5.6wt, beta 0.6wt). Histochemical staining for both myofibrillar ATPase and CAT activity and CAT immunohistochemistry revealed a striking increase in type I fibers and that CAT expression was restricted to these fibers in overloaded plantaris muscle of beta 5.6mut3 transgenic mice. Our transgenic data suggest that beta-MHC transgenes, and perhaps the endogenous beta-MHC gene, are induced by mechanical overload via a mechanism(s) that does not exclusively require the MCAT, C-rich, or beta e3 subregions.

Animals↗
PubMed1996

Muscle-specific and inducible expression of 293-base pair beta-myosin heavy chain promoter in transgenic mice.

The DNA regulatory element(s) involved in beta-myosin heavy chain (beta-MHC) induction by the physiological stimulus of mechanical overload have not been identified as yet. To delineate regulatory sequences that are required for mechanical overload induction of the beta-MHC gene, transgenic mouse lines were generated that harbor transgenes containing serial deletions of the human beta-MHC promoter to nucleotides -293 (beta 293), -201 (beta 201), and -141 (beta 141) from the transcription start site (+1). Mechanically overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endogenous beta-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltransferase specific activity) revealed that only transgene beta 293 expression was muscle specific in both fetal and adult mice and was induced in the plantaris (10- to 27-fold) and soleus (2- to 2.5-fold) muscles by mechanical overload. Histochemical staining for myosin adenosinetriphosphatase activity revealed a fiber-type transition of type II to type I in the overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous beta-MHC gene in response to developmental signals and to the physiological signals generated by mechanical overload in fast- and slow-twitch muscles.

Adenosine Triphosphatases↗
PubMed1996

Sex ratio at birth in China: features and influences.

The gradual increase in the sex ratio at birth (SRB) that has been recorded in China since 1980 is examined, and an attempt is made to identify the reasons for this increase. The author concludes that "such demographic variables as child-bearing age, parity and the sex of children have not determined the rising SRB since the 1980s in China. Rather, the traditional bias towards giving birth and reporting male offspring was responsible for the high SRB score and for the disparities in SRB between different socio-economic groups." The extent to which the birth of female babies is not reported is assessed, as is the extent of sex-selective abortion.

Abortion, Induced↗
PubMed1996

Cardiovascular effects of injection of argipressin into lateral septal nuclei in rats.

AIM: To determine whether argipressin (Arg) plays a role in central neural control of cardiovascular function by acting on the lateral septal nuclei (LSN). METHODS: Measuring mean arterial blood pressure (MAP) and heart rate (HR) responses followed microinjection of Arg into the LSN of rats anesthetized with urethane. RESULTS: Arg (100, 200, and 400 ng) injected into the LSN produced a dose-dependent hypertension and tachycardia. Maximal changes of MAP were 0.9 +/- 0.6, 2.3 +/- 1.3, 4.0 +/- 1.4 kPa, respectively; maximal changes of HR were 12 +/- 27, 50 +/- 33, and 89 +/- 27 bpm, respectively. Pretreatment of the LSN with a vasopressin 1 type antagonist d (CH2)5Tyr(Me) Arg abolished the MAP and HR responses produced by injection of Arg. Peripheral alpha-adrenergic blockade with phentolamine blocked the hypertension responses to injection of Arg into the LSN. CONCLUSION: Arg acts in the region of the LSN to exert a central action on the cardiovascular system that is mediates by stimulation of sympathetic outflow.

Animals↗
PubMed1996

Investigation on inhibition of biological effects of endothelin.

The effects of a series of substances on the biological function of endothelin (ET) are reported. The substances used are: synthetic inhibitors of endothelium derived relaxing factors (EDRFs), inhibitor of big-endothelin converting enzyme phosphoramidon, antiserum of endothelin, antagonists of endothelin A receptor BQ123 and JKC301, and two Chinese anti-snake venom herb medicines Lobelia radicans Thumb and Taris polyphylla Smith var. chinensis (Franch) Hara. The results showed that inhibiting the production of nitric oxide (NO) could stimulate ET release from vascular endothelium, elevate plasma ET and increase blood pressure. These changes could be reversed by L-arginine (L-Arg), the substrate of nitric oxide synthase (NOS). The amount of ET released by arterial endothelium could be increased or inhibited by inhibiting or stimulating the synthesis of prostacyclin (PGI2). The plasma ET level and blood pressure in both SHR and WKY rats could be decreased by giving phosphoramidon (PhR). The above results indicate that the biological effects of ET could be antagonized by inhibiting the synthesis or release of ET, decreasing the level of plasma ET, blocking the binding of ET with its receptor and using some Chinese anti-snake venom herb medicines.

Animals↗
PubMed1996

Both L- and D-isomers of allotrap 2702 prolong cardiac allograft survival in mice.

BACKGROUND: Peptides derived from a conserved region of the human leukocyte antigen class I heavy chain (a.a. 75-84) have been shown to have immunomodulatory activity. The peptide 07.75-84, derived from HLA-B7, prolonged Lewis 1.W cardiac allograft survival in Lewis 1.A recipients. In combination with cyclosporine A, permanent heart allograft acceptance was induced in the Lewis to ACI donor/recipient combination. In mice, 2702.75-84, derived from HLA-B2702, prolonged the survival of C57B1/6 skin allograft in CBA recipients. In vitro, 2702.75-84 inhibited NK and cytotoxic T cells. To further evaluate the immunomodulatory activity of both L- and D-isoforms of 2702.75-84, we studied their effects in a mouse cardiac allograft model. METHODS: Peptides consisting of L- and D-amino acids were synthesized and administered to CBA (H-2k) recipients of a C57B1/6 (H-2b) cardiac allografts. In addition to peptide monotherapy, combinations of peptide with cyclosporine A and azathioprine were evaluated. Graft survival was monitored by palpation. Breakdown products of 2702.75-84 were identified by a combination of high-performance liquid chromatography and mass spectrometry. RESULTS: Daily administration of 2702.75-84 to CBA (H-2k) recipients of a C57B1/6 (H-2b) cardiac allograft prolonged graft survival to 11.4 +/- 2.6 days compared with 7.5 +/- 1.2 days in untreated control animals (n = 8; p = 0.0003, Mann-Whitney U Test). Other major histocompatibility complex class I-derived peptides including HLA-G.75-84, HLA-07.75-84, HLA-2705.75-84, H-2Kk.75-84, H-2Dk.75-84, H-Kb.75-84, and H-2Db.75-84 had no effect. In combination with a subtherapeutic dose of cyclosporine A (days 0 to 4), 2702.75-84 prolonged graft survival to at least 70 days (five of eight grafts still beating, p = 0.0002) compared with a median graft survival of 14 days in animals that received cyclosporine A monotherapy. Like other peptides consisting of L-amino acids, 2702.75-84 is subject to degradation by serum proteases. Breakdown products of 2702.75-84 were identified by a combination of high-performance liquid chromatography and mass spectrometry. These compounds were found to be inactive when tested in vivo. In contrast to peptides consisting of L-amino acids, peptides consisting of D-amino acids are resistant to proteolytic degradation. When D2702.75-84 was administered to graft recipients at 5 to 10 mg/kg/day (days 0 to 10), graft survival was prolonged to more than 50 days (5 of 13 grafts still beating, p = 0.0001). In combination with azathioprine, administration of D2702.75-84 induced graft acceptance (> 100 days) in 100% of animals (all grafts still beating). CONCLUSIONS: This study shows that administration of 2702.75-84 consisting of L- or D-amino acids will prolong graft survival in mice. In addition, the data suggest that the D2702 isomer is more potent than the L-isomer in vivo and may allow reduced dosage or frequency of administration.

Adjuvants, Immunologic↗
PubMed1996

[High homology between antigen of HFRSV with anti-idiotype antibody against HFRSY].

OBJECTIVE: To detect the structural characterization of genes of the anti-idiotype antibody and the antigen. METHODS: The hybridoma (C8) secreted the anti-idiotype human McAb against hemorrhagic fever virus (HFRSV). The variable region genes of heavy and light chain of the anti-Id huMcAb were cloned. The homology was analysed between the variable region genes and the genes of HFRSV. RESULTS: The 45-55 amino acids of VH and 58-68 amino acids of VL were highly homologic to the 447-457 amino acids of G2 protein in Hantaan virus. And the homologeneous regions were similar in secondary structure of the three proteins. CONCLUSION: There is a molecular basis in the anti-idiotype antibody imaging antigen.

Antibodies, Anti-Idiotypic↗
PubMed1996

[The prospect of prevention and treatment of Cor pulmonale on a 20-year follow-up of 40 middle to old aged cases of COPD and Cor pulmonale].

OBJECTIVE: To study the outcome of current therapy for COPD and Cor pulmonale by long-term follow-up of COPD patients. METHOD: Forty cases of middle to old aged COPD and Cor pulmonale patients were followed up for a period of 20 years. RESULTS: The pulmonary function of all the patients reduced significantly more than healthy elderly, while no difference was noted in blood gas analysis. 23 patients with advanced COPD developed cor pulmonale, so that the number of cases with cor pulmonale increased significantly from 7 to 30. By the end of follow-up 19 cases survived (48%), 21 cases (Cor pulmonale 19, COPD 2) died (53%). CONCLUSIONS: In view of the high mortality of cor pulmonale and the tremendous treatment cost, it was considered that the prospect for cor pulmonale management should be put on treating COPD to avoid development of Cor pulmonale. The keys of treating COPD are stop of smoking, protection from cold, early treatment of respiratory infection and further establishment of pulmonary rehabilitation work.

Aged↗
PubMed1996

[The expression of bcl-2, P53 and c-erbB-2 onco-proteins in breast cancer and their clinicopathological significance].

In order to study the interrelation between bcl-2, P53 and c-erbB-2 protein, their expression in 145 breast carcinomas were observed by immunohistochemical LSAB method. 19 cases were negative, 12 were positive for the three oncoproteins. 19 cases were positive for c-erbB-2 only. 20 positive for P53 only and 20 positive for bcl-2 only. 26 cases were positive for both P53 and c-erbB-2, 17 for both c-erbB-2 and bcl-2, 12 for both P53 and bcl-2. Strong inverse correlation was found between the expression of P53 and bcl-2 (P < 0.001). The P53 expression or the expression of both P53 and c-erbB-2 correlated with low histological grade, while the bcl-2 expression correlated with high histological grade (P < 0.05). The necrosis in tumors with only bcl-2 expression was less than those with c-erbB-2 or both c-erbB-2 and P53 expression (P < 0.02). Mitosis count was lower in tumors with only bcl-2 expression than those with expression of both c-erbB-2 and P53 (P < 0.05). The expression of c-erbB-2 and P53 proteins are associated with poor prognosis (P < 0.02, P < 0.05) but not affected by bcl-2. The results suggest that bcl-2, P53 and c-erbB-2 are involved in tumorigenesis and development of breast carcinoma with different biological effects.

Adult↗
PubMed1996

[Specific binding of human bone morphogenetic protein (2A) with mouse osteoblastic cells].

Human bone morphogenetic protein 2A (hBMP2A) cDNA terminal S67 nucleotides were cloned and expressed in a phage display vector pCSM21. Human BMP2A C-terminal peptide displayed on the surface of the phage can bind specifically to the surface of mouse osteoblastic cell (MC3T3) membrane. ELISA assay showed a positive signal of the binding by using antibody against M13 phage gene 8 protein. After labeling with 3HTdR, the counts of the binding groups were 3 to 10 times higher than the control groups. It suggests that the surface of MC3T3 cells exist the receptor for hBMP2A.

Animals↗
PubMed1995

Tumor-associated E6 protein of human papillomavirus type 16 contains an unusual H-2Kb-restricted cytotoxic T cell epitope.

We previously showed that CTL from H-2b mice immunized against the E6 protein of human papilloma virus (HPV) type 16 recognized a 10-mer peptide corresponding to amino acids 131 to 140. We show in this study that the minimal epitope, 130 to 137, is a 8-mer peptide presented by H-2Kb class I molecules. At position P8, the 130 to 137 peptide contains a hydrophobic methionine anchor residue, but P3 and P5 do not contain the typical anchor residues that are frequently found in Kb-bound peptides. Analysis with alanine-substituted peptides indicates that the tryptophan at P3 acts as an alternative anchor mediating Kb binding, while an arginine at P2 is a TCR contact residue. Synthetic 9-mer peptides corresponding to residues 130 to 138 are as efficiently recognized by CTL as 130 to 137 peptides. Analysis of extracts of E6-expressing cells suggests that Ag processing may produce multiple peptides containing the minimal 130 to 137 epitope. In vitro binding studies indicate that Kb binding of peptide 130 to 137 is approximately five orders of magnitude less efficient than Kb binding of previously identified CTL epitopes. In contrast, the E6 protein contains another potential CTL epitope in the region of amino acids 41 to 50. A synthetic peptide spanning this region binds very strongly to Kb and is capable of stimulating a strong peptide-specific CTL response. In the context of the whole protein, however, this epitope remains cryptic.

Amino Acid Sequence↗
PubMed1995

A synthetic dimeric HLA class I peptide inhibits T cell activity in vitro and prolongs allogeneic heart graft survival in a mouse model.

A peptide derived from the alpha 1 domain of the human HLA class I heavy chain (amino acids 75-84; B2702.75-84) has been shown to inhibit human cytotoxic T and NK cell activity in a non-allele-restricted manner. In vivo, this peptide prolonged skin allograft survival in a murine model. Here we demonstrate prolongation of heart allograft survival in mice and extend the characterization of the immunomodulatory activity of B2702.75-84. Similar to what has been observed with retrovirus-derived peptides, the inhibitory capability of this peptide was increased when bound to a carrier protein. An increased immunomodulatory activity was also observed with the dimeric peptide B2702.84-75-75-84 or the multimeric B2702.75-84.MAP. This peptide not only inhibited cytotoxic T and NK cells but also anti-CD3-induced T cell proliferation as well as a mixed lymphocyte reaction (MLR). Flow cytometric analysis of T cells harvested from anti-CD3-stimulated spleen cell culture in the presence of B2702.84-75-75-84 showed decreased expression of activation markers (CD25, ICAM-1, Pgp-1, CD69) compared with untreated control cultures. The superior activity of B2702.84-75-75-84 could also be demonstrated in vivo. Administration of B2702.84-75-75-84 prolonged the survival of B6 (H2b) hearts in CBA (H2k) recipients to 15 +/- 2.7 (P = 0.0002 vs. control) days compared with 11.4 +/- 2.6 (P = 0.01) days in B2702.75-84 treated animals and 7.5 +/- 1.1 days in untreated controls. Administration of control peptides had no significant effect on allograft survival. In combination with a subtherapeutic dose of cyclosporine, B2702.75-84 induced long-term graft survival in 60% of recipients.

Amino Acid Sequence↗
PubMed1995

Mouse aggrecan, a large cartilage proteoglycan: protein sequence, gene structure and promoter sequence.

Seven genomic clones for mouse aggrecan core protein have been isolated including 3 kb of 5'- and 7 kb of 3'-flanking sequences. All exon sequences and their intron boundary sequences in these clones were identified and mapped by DNA sequencing. The gene spans at least 61 kb and contains 18 exons. Exon 1 encodes 5'-untranslated sequence and exon 2 contains a translation start codon, methionine. The coding sequence is 6545 bp for a 2132-amino-acid protein with calculated M(r) = 259,131 including an 18-amino-acid signal peptide. There is a strong correlation between structural domains and exons. Notably, the chondroitin sulphate domain consisting of 1161 amino acids is encoded by a single exon of 3.6 kb. Although link protein has similar structural domains and subdomains, the sequence identity and the organization of exons encoding the subdomains B and B' of G1 and G2 domains revealed a strong similarity of mouse aggrecan to both human versican and rat neurocan. Primer extension analysis identified four transcription start sites which are close together. The promoter sequence showed high G/C content (65%) and contained several consensus binding motifs for transcription factors including Sp-1 and the glucocorticoid receptor. There are stretches of sequences similar to the promoter region of both the type-II collagen and link protein genes. These sequences may be important for cartilage gene expression.

Aggrecans↗
PubMed1995

Cytokine mRNA profiles in mouse orthotopic liver transplantation. Graft rejection is associated with augmented TH1 function.

Although mouse liver allografts are spontaneously accepted without immunosuppression in many strain combinations, rejection can be induced by presensitization with a donor skin graft two weeks prior to transplantation. In this study, the semiquantitative reverse transcription polymerase chain reaction (RTPCR) was used to assess the involvement of T helper (TH) cell subsets in liver allograft acceptance by determining cytokine mRNA in the graft and spleen of recipients with (A) spontaneously accepting allografts (B) rejecting liver allografts after previous skin sensitization, and (C) syngeneic controls. Spontaneously accepted liver allografts showed upregulation of TH1 (IL-2, IFN-gamma) and TH2 (IL-4, IL-10) intragraft cytokine mRNA, which peaked at day 6 and tapered off thereafter, when compared with levels in syngeneic grafts, but both IFN-gamma and IL-10 mRNA persisted up to day 30. This cytokine mRNA profile correlated with the transient intragraft inflammation associated with spontaneously resolving rejection. Presensitized recipients that rejected their grafts revealed marked upregulation of TH1 (IL-2 and IFN-gamma) and TH2 (IL-4, IL-6) intragraft cytokine mRNAs compared with spontaneously accepting recipients, although IL-10 mRNA levels showed no differences between the two groups. The most striking difference was seen in IFN-gamma levels, which correlated well with the preferential deposition of IgG2a antibody isotype in the rejecting compared with the spontaneously accepting liver allograft recipients. These results suggested an association between liver allograft rejection and enhanced TH1 cytokine immune response. The ability to reject liver allografts by the adoptive transfer of splenocytes, but not serum, from a sensitized mouse ruled out preformed antibodies alone as a cause of rejection. However, spleen cytokine mRNA profiles showed no differences or trends in TH1 or TH2 expression in spontaneously accepting versus rejecting recipients, which suggested that the spleen is not a major site of alloreactive immune expansion. These data suggest that spontaneous acceptance of mouse liver allografts is associated with an insufficient intragraft TH1 cytokine response, the cause of which is currently under investigation.

Animals↗