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Biomedical subjects

L Li

Publications and source records attributed to L Li.

At least 1,567 records · Page 87Linked to original sources

[Tension-stress effect on genesis and growth of the external anal sphincter].

The relationship between the length of the external anal sphincter (EAS) and the anal pressure was observed in 37 guinea pigs. The results showed that if the muscle was stretched from 100% to 300% of its original length, the resting anal pressure was kept relatively steady (steady phase), but the actively contracting pressure was proportionally increased; if from 300% to 370%, a sharp increase of resting anal pressure was developed (accelerating phase), but the actively contracting pressure would gradually decrease to zero; beyond 370%, the resting anal pressure remained unchanged (plateau phase), while in the muscle, the nerve fiber, muscle fiber and blood vessel were damaged and necrotic. However, if the muscle was continously stretched at the accelerating phase of the resting anal pressure for 6 days, the muscle could grow in length at a rate of 2mm/d. In the growth muscle, the muscle cell was hypertrophic, the Schwann's cell in the nerve fiber was generated and the blood vessel became abundant. Both transversely split sarcomere and longitudinally split sarcomere were seen in the muscle cell in electron microscope. This result has surgical importance for treatment of anorectal anomaly.

Anal Canal↗

[Radiolabelling and assay of Chinese agkistrodon acutus venom with carrier-free Na 125I].

Chinese agkistroden acutus venom (CAAV) was radiolabelled with carrier-free Na 125I by the method of Iodogen. The specific activity and radiochemical purity for radiolabelled products were 4236.5 x 10(10) Bq/mmol and 98%, respectively. Each CAAV molecule carried 0.52 125I atom. Physical and chemical characterization of radiolabelled CAAV was similar to unradiolabelled CAAV. Binding analysis showed that 125I-CAAV was bound to platelet in a saturable manner. Binding sites per platelet were 13,255 +/- 6292/platelet. The dissociation constant (Kd) was 3.2 +/- 0.69 x 10(-10) mol/L. These results are similar to binding sites of other snake venom on platelet. The investigation showed that radiolabelled CAAV made by our laboratory was useful for radioligand binding assay.

Agkistrodon↗

[Reports on two species of Pegohylemyia tibetana group in Xiling snow mountain of Dayi county, Sichuan, China (Anthomyiidae, Diptera)].

Male:Body 7mm. in length. Having a pair of bristles on the distal part of cercal plate, a blunt round angle of postgonite, the new species being less related to Pegohylemyia macrospini gera Deng, 1990, but having 4 pairs of large spines on the 5th sternite, a spherical point of postgonite and biconcave surstyli at apex, thus differing from the relative species. Holotype male, paratypes 18 male male, Xiling snow mountain of Dayi county, Sichuan, 17, July 1993, coll. Geng Lin, Deng Anxiao. Male:Body 7mm. in length. Having 4 pairs of spines on the 5th sternite being similar to Pegohylemyia nigribella above, but having legs with yellow color and round apex of surstyli resembling Pegohylemyia setisilva Jin, 1983; however, broadening postgonite and slender surstyli may be distinguished from all yellow leg species in this group. Holotype male:paratypes 63 male male, date and place of collection being the same as the first species above, coll Geng Lin, Li Ling, Deng Anxiao. Holotype and paratypes are kept in author's laboratory.

Animals↗

Effects of osthole on isolated guinea pig heart atria.

AIM: To study the effects of osthole (Ost) on the isolated guinea pig atria and the relationship between Ost effect and Ca2+. METHODS: Contractions of left atria were induced by electric stimulations. The contractile amplitude of left atria pre- and post-treated with Ost was measured according to the cumulative concentration method, the drug being added at 15 min intervals, the pA2 or pD2' were calculated. It were measured that the effects of Ost to the positive staircase and to the post-rest potential enhancement. The contractile responses were recorded via an auto-equiolibration recording instrument. RESULTS: Ost 10-300 mumol.L-1 and Ver 0.1-30 mumol.L-1 decreased the contractile force and inhibited the isoprenaline-induced restoration of contractile response in the left atria rendered inexcitable by KCl 25 mmol.L-1. Ost and Ver antagonized the CaCl2- and isoprenaline-induced positive inotropic response noncompetively, the pD2' values to Ost were 4.41 +/- 0.13 and 4.90 +/- 0.15, to Ver were 6.53 +/- 0.22 and 6.91 +/- 0.17, respectively. Both of them inhibited the contraction of the left atrium and reversed the frequency-contraction response from positive to negative staircase in the higher dosage (500 and 1 mumol.L-1), but they showed only slight inhibitory effect on post-rest potentiation. CONCLUSION: Ost was similar to, but much less potent than Ver in inhibiting the isolated guinea pig atria.

Animals↗

Arabinosyl-2-fluoroadenine augments cisplatin cytotoxicity and inhibits cisplatin-DNA cross-link repair.

Cytotoxicity was increased significantly when arabinosyl-2-fluoroadenine (F-ara-A) was administered in simultaneous combination with cisplatin (CDDP) to human colon tumor cell lines relatively sensitive (LoVo) or resistant (CP2.0) to CDDP. Because the mechanism of action of F-ara-A indicates that it may be an effective inhibitor of DNA repair, we hypothesized that F-ara-A induces cytotoxic augmentation by suppressing cellular repair in CDDP-damaged DNA lesions. To test this, we compared the repair of CDDP-induced DNA interstrand cross-links in the total genome and in ERCC1 gene-specific sequences of LoVo and CP2.0 cells for treatments with CDDP and CDDP plus F-ara-A. We determined the DNA repair by measuring the rate of removal of the cross-links, using two methods, i.e., an ethidium bromide fluorescence binding assay, which detects the DNA lesion in the total genome, and a method combining denaturation/renaturation neutral agarose gel electrophoresis and Southern hybridization to detect gene-specific lesions. When F-ara-A (15 microM) was coadministered with CDDP (15 micrograms/ml for LoVo cells and 30 micrograms/ml for CP2.0 cells) for 4 hr, the initial cross-link index for the total genome was increased 67% (4.5 versus 2.7 with CDDP alone) in LoVo cells and 93% (2.9 versus 1.5 with CDDP alone) in resistant CP2.0 cells. At 10 hr after the treatment, only 5% of the cross-links had been removed in combination-treated LoVo cells, compared with 40% in CDDP-treated LoVo cells; in CP2.0 cells, F-ara-A inhibited the removal of cross-links from 95% to 45%. Similar results were obtained for ERCC1 gene-specific DNA sequences. These data suggest that F-ara-A enhances the accumulation of CDDP-induced cross-links in LoVo and CP2.0 cells by suppressing the repair of such lesions, thereby enhancing the cytotoxicity of CDDP in combination treatment.

Antineoplastic Agents↗

Differential down-regulation of epidermal growth factor receptors expressed in the metastatic variants of human lung cancer adenocarcinoma cell line DMS4C.

The metastatic variants of human lung adenocarcinoma cell line DMS4C were established by selection in vivo. Lung, brain, spleen and liver metastatic tumors derived from intracarotid inoculation of athymic BALB/c mice were collected, and their corresponding variant cell lines established. The epidermal growth factor (EGF) receptor expression of the parental cell line as well as the metastatic variant cell lines were investigated. 125I-labeled EGF binding assays showed that there were two types of EGF receptors in both parental and metastatic variants. Compared to DMS4C, the EGF binding capacities were found to be down-regulated by 70, 79, 85 and 89% for lung, spleen, liver and brain variant, respectively. The dissociation constants of spleen, liver and brain EGF receptors were distinct from that of the parental cell line. The EGF receptor autophosphorylation activity of lung variant was shown to be down-regulated as shown by immune complex kinase assay that corresponded to EGF receptor numbers whereas kinase activities of the liver, spleen and brain variants EGF receptors were completely abolished. However, the 170 kilodalton EGF receptor was shown to be unaltered during metastasis. The results indicated that, during metastasis progression, the proliferation of adenocarcinoma cells may have adopted a different growth regulation that is independent of EGF receptor kinase-modulated autocrine pathway. The result also implies that other oncogene may emerge as the major growth regulator for distant metastasis of adenocarcinoma cancer cells. This work provides a model for understanding tumor metastasis progression of human lung cancer.

Adenocarcinoma↗

Brain activity of a rat reflects apparently the stimulation of acupuncture. A radioautography using 2-deoxyglucose.

To confirm a relationship between the central nervous system and the acupuncture, the response was examined in the rat brain using radioautography with tritiated 2-deoxyglucose, after stimulation of some acupoints. Eight groups, of a total of 27 rats were submitted to acupuncture at 6 different acupoints (Zusanli, Renzhong, Tianshu, Shenmen, Neiguan, Yongquan) and control, with or without electric pulses or with anesthesia respectively, prior to the injection with isotopic deoxyglucose. A hundred twenty cryosections were cut from a freshly frozen brain and exposed on single-coated X-ray films. The results showed that the acupuncture on the four acupoints of Zusanli, Tianshu, Shenmen and Neiguan enhanced the activity of the neocortex, the limbic cortex and the thalamic nuclei in comparison with the control group. The acupoints on Renzhong and Yongquan depressed the activity on the thalamic nuclei and the midbrain. The anesthesia with pentobarbital concealed the most activity on the whole area of the brain, which hardly responded to any stimulation of acupuncture. These results lead to the suggestion that the brain may reflect the signals by the stimulation of acupuncture and change the activity depending upon each acupoint.

Acupuncture Therapy↗

[Different expressions of alpha 2 (IV) and alpha 3 (IV) collagen mRNAs in renal glomeruli of IgA nephropathy].

The levels of extracellular matrix protein mRNAs were increased prior to the appearance of histological glomerulosclerosis in isolated glomeruli from several animal models. Striker studied renal biopsies (Seminar in Nephrology, 13:508,1993). We made a comparable study in human renal biopsies to assess the levels of glomerular alpha 2 (IV) and alpha 3 (IV) collagen gene expressions in renal biopsies. Renal biopsy specimens were obtained from 11 patients (7 IgA nephropathy and 4 mesangial proliferative glomerulonephritis). Glomerular lesion was divided into 5 grades. The amount of collagen type IV in glomerular matrix was evaluated by immunoperoxidase staining using a monoclonal antibody to type IV collagen. For gene expression analysis, glomeruli were dissected out from about 10% of each biopsy specimen. The expressions of alpha 2 (IV) and alpha 3 (IV) collagen mRNAs were analyzed by using in situ reverse transcription coupled with polymerase chain reaction. Each PCR reaction contained an amount of cDNA template equivalent to that obtained from 1/10 of a glomerulus, alpha 2 (IV) and alpha 3 (IV) collagen mRNAs were detected in all specimens. All 3 cases of IgAN with grade III glomerular lesion had a more marked increment of glomerular alpha 2 (IV) collagen cDNA than that of the other 3 IgAN patients with grade II lesion (the intensity of PCR product, grade III 0.54 +/- 0.12, VS grade II 0.25 +/- 0.08, P < 0.05). No discrepancies were detected in the level of glomerular alpha 3 (IV) collagen cDNA and the intensity of collagen IV staining between these two groups of IgAN. Interestingly, in MsPGN patients there was no difference in the expression of glomerular alpha 2 (IV) collagen mRNA between grade II and grade III glomerular lesions. The results suggested that the detection of glomerular alpha 2 (IV) collagen mRNA level in IgAN patients may help to define the pathological classification.

Adolescent↗

[Studies on inhibitive effects of organic selenium on cell damage caused by SiO2].

Changes in potassium content of macrophage in guinea pigs and in membrane protein of erythrocytes in rats caused by quartz dust, and the effects of selenium-protein and selenium-containing polysaccharide of cell membrane on them were determined with atomic absorption spectrometry and electronic spin label. Results showed quartz could significantly decrease potassium content of macrophage with a dose-effect relationship. Potassium content in the exposed group could return to normal level as the control group by adding Se-protein into quartz dust. Rotational correlation times of the membrane protein in erythrocytes could be decreased by quartz dust, and Se-protein and Se-containing polysaccharide could make them normal. It suggested quartz could cause cell permeability significantly increased, cleavage of peptide-chain of membrane protein, degradation and cross-linkage of protein, and cell damage, but organic selenium could decrease cytotoxicity caused by quartz dust and protect cells from the damage.

Animals↗

Inhibitors of the intracellular Ca(2+)-ATPase in cultured mouse keratinocytes reveal components of terminal differentiation that are regulated by distinct intracellular Ca2+ compartments.

Differentiation of mammalian epidermis is associated with spatially and temporally coordinated changes in gene expression as cells migrate from the proliferative basal cell compartment through the nonproliferative spinous and granular cell layers where the terminal phase of maturation is completed. Previous studies have suggested that a gradient of Ca2+ in the epidermis in vivo and increased extracellular Ca2+ in vitro induce differentiation of mammalian epidermal keratinocytes. Chelation of intracellular free Ca2+ prevents this Ca(2+)-induced differentiation, but sites of action for intracellular Ca2+ remain undefined. In this study, thapsigargin (Tg) and cyclopiazonic acid (CPA), inhibitors of the endoplasmic reticulum Ca(2+)-ATPase, were used to evaluate the relative contribution of cytoplasmic and stored Ca2+ to Ca(2+)-induced terminal differentiation of cultured mouse keratinocytes. A sustained increase of both intracellular free Ca2+ (Cai) and ionomycin-sensitive Ca2+ stores is associated with Ca(2+)-induced keratinocyte terminal differentiation. Tg and CPA was used to change this coordinated regulation of free and stored Ca2+. In the absence of extracellular Ca2+, both Tg and CPA transiently increase Cai and deplete intracellular Ca2+ stores; while in the presence of extracellular Ca2+, Tg and CPA stimulate Ca2+ influx and cause a sustained increase in Cai while depleting stored Ca2+. In the presence of extracellular Ca2+, Tg (5 to 20 nM) and CPA (5 to 25 microM) inhibit Ca(2+)-induced morphological changes and stratification and prevent the suppression of DNA synthesis by Ca2+. Tg and CPA also inhibit the expression of mRNA and protein for specific epidermal spinous cell markers, keratins 1 (K1) and 10 (K10), prevent the redistribution of E-cadherin from a diffuse membranous pattern to concentration at cell-cell junctions, and inhibit the activation of a reporter gene regulated by a K1 enhancer element shown previously to be Ca2+ sensitive. These effects of Tg and CPA can be reversed by increasing the extracellular Ca2+ to levels that partially restore Ca2+ stores. In contrast, Tg and CPA enhance the expression of profilaggrin and loricrin mRNA and protein, markers of granular cell differentiation. These divergent actions of Tg and CPA on distinct components of the keratinocyte differentiation program suggest that adequate intracellular Ca2+ stores are important for the expression of spinous cell proteins and inhibition of DNA synthesis, while elevation of Cai stimulates the expression of markers of granular cell differentiation.

Animals↗

Cloning, expression and characterization of a single-chain antibody PS-9 targeted to pancreatic cancer.

Genes encoding single-chain antibodies have been first constructed, which consist of the heavy and light chain variable domains of antibody PS-9 joined together by a flexible peptide linker. The genes were cloned into coat protein g3p genes of pCANTAB5 phagemids, and expressed as fusion proteins on the phage tips. Immunological assay demonstrated that the engineered antibodies specifically bound to cancer cells LS-174-T as well as to pure bovine submaxillary gland mucin. Their specificity and affinity appeared the same as their parent antibodies. Our results supposed that the single-chain antibodies will be a target for the diagnosis and treatment of cancer.

Antibodies, Monoclonal↗

High-level expression of human beta-interferon gene in the silkworm with new constructed BmNPV vector.

Bombyx mori nuclear polyhedrosis virus (BmNPV) and Bombyx mori cells as well as silkworm larvae were used successfully for the production of biologically active recombinant proteins. There are only a few types of BmNPV general vectors. Here a new type of vector plasmid pBm92 was constructed in this experiment. The translational initiation codon ATG of the polyhedrin gene in Pbm92 was changed into ATT, and then five cloning sites of a foreign gene were ligated after the +12 bp site of the polyhedrin gene. Human beta-interferon (HuIFN-beta) gene was cloned into Pbm92 to construct pBmIFN +12; meanwhile we constructed the transfer vector Pbmifn-3 in which HuIFN-beta was cloned after the -3 bp site of the polyhedrin gene. BM-N cells were cotransfected with the two types of transfer vector plasmid DNAs and BmNPV genomic DNA. Recombinant viruses that were screened did not produce polyhedrin inclusion bodies in the virus plaque assay, and were identified by the hybridization of recombinant virus DNA with HuIFN-b gene probe. IFN activity of the culture media of Bm-N cells infected with recombinant virus BmIFN +12 was 2.0 x 10(6) IU/mL, and IFN activity of hemolymph of silkworm larvae infected with BmIFN +12 was 5.0 x 10(7) IU/mL. Expression level of BmIFN +12 was two to four times more than that of BmIFN -3. The rHuIFN-beta produced by BM-N cells and silkworm larvae has an antigenicity identical to that of the native HuIFN-beta.

Animals↗

Clinical application of monoclonal antibody-drug conjugate to immunotargeting chemotherapy of bladder cancer.

Monoclonal antibody-drug conjugate was applied in a clinical trial for patients with bladder cancer. Monoclonal antibody HB7A from a mouse splenocyte immunized against human bladder cancer was used as a drug carrier. The anti-cancer drug adriamycin (ADR) was bound to HB7A through a dextran (DEX) bridge to form the conjugate HB7A-DEX-ADR. The in vitro cytotoxic effect of the conjugate on BIU-87 bladder cancer cells was similar to that of free ADR and the mixture of HB7A and ADR. Seven patients with bladder cancer were given HB7A-DEX-ADR intravenously. The immunoperoxidase studies of the resected specimens showed that HB7A was localized specifically in cancer, and histological studies revealed degenerative and necrotic changes of the tumor cells. Patients receiving the conjugate did not experience serious side effects. This study suggests that immunotargeting chemotherapy with HB7A-DEX-ADR is well tolerated by patients and its cytotoxicity on tumor is substantial.

Aged↗

[Proto-oncogene point mutation of c-Ha-ras in bronchogenic carcinoma].

11 bronchogenic carcinoma and 8 corresponding paracarcinoma specimens were detected for activating point mutation in codon 12 of c-Ha-ras gene by Southern blotting hybridization technique. The c-Ha-ras gene was found to be activated by point mutation in codon 12 in 8 of bronchogenic carcinoma and 1 of paracarcinoma tissues. The mutative and unmutative hybrid band was both discovered in 2 of paracarcinoma tissues. Analysis of clinical and pathological features, we conclude that: (1) The point mutation of c-Ha-ras gene codon 12 is found in 77.8% bronchogenic carcinoma among Chinese; (2) At least in part cases, mutation of c-Ha-ras gene codon 12 is not the "initiation" event, but may be a early-stage event in the pathogenesis; (3) No apparent association between the c-Ha-ras gene codon 12 mutation and pathological types, disease stages and history of smoking is present.

Adenocarcinoma↗

[The effects of zhuling-duotang, hepatitis B vaccine and bacillus Calmette-Guerin on immunoactivities of peripheral blood mononuclear cells: an in vitro research].

"Zhuling-duotang (a polysaccharide preparation of the Chinese traditional herb medicine polyporusum bellatus) and hepatitis B vaccine (HB vaccine)" and "Persantin and bacillus calmeteguerin (BCG)" have been used to treat chronic hepatitis B. To elucidate their therapeutic mechanism, we studied the effects of zhuling-duotang, HB vaccine and BCG on immunoactivities of nomal human peripheral blood mononuclear cells (PBMCs). Cytotoxicity of PBMCs incubated with such drugs against target cells K562, HepG2 or 2.2.15 was detected by using 3H-TdR release assay. IL-2 and IFN-gamma activities of the supernatant were assayed. Immunofluorescent analysis of molecular CD4, CD8, CD16, IL-2R on the surface of PBMCs were done. The results showed that: (1) Zhuling-duotang and BCG could significantly increase the cytotoxicity of PBMCs. They could induce PBMCs to produce IL-2 but not IFN-gamma. They also could stimulate PBMCs to express IL-2R. Zhuling-duotang and BCG did not affect the percentage of CD4+, CD8+, CD16+ cells among PBMCs. (2) HB vaccine did not significantly increase the cytotoxicity of PBMCs. (3) The cytotoxicity of PBMCs induced by Zhuling-duotang combined with HB vaccine was not significantly higher than that of PBMCs induced by Zhuling-duotang alone.

Adjuvants, Immunologic↗

Production of transforming growth factor-beta by cultured rat mesangial cells.

The purpose of this study was to examine whether transforming growth factor-beta (TGF beta) acts as an autocrine cytokine in cultured mesangial cells. Measangial cell conditioned media (CM) were prepared and tested for their effect on mesangial cell proliferation. CM showed a concentration dependent inhibition on mesangial cell proliferation and the activity was enhanced by treating conditioned media with acid. Gel filtration analysis showed peak inhibitory activity to reside in fractions with an estimated molecular weight range of 16-30 KD. The activity was partially blocked by anti-TGF beta antibody, but not nonimmune control IgG. The presence of TGF beta was confirmed using the mink lung epithelial cell assay. Furthermore, the addition of anti-TGF beta antibody directly into culture media significantly enhanced mesangial cell proliferation. These results demonstrate that measangial cell produce both active and latent forms of TGF beta, which functions as an autocrine growth inhibitor for mesangial cells.

Animals↗