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Biomedical subjects

L Jia

Publications and source records attributed to L Jia.

At least 55 records · Page 3Linked to original sources

Slit2 is a repellent for retinal ganglion cell axons.

We set out to isolate inhibitory guidance cues that affect retinal ganglion cell (RGC) axons in vitro and that could potentially be involved in RGC pathfinding decisions. Here we describe the biochemical purification of an RGC growth cone collapsing factor from bovine brain membranes and its identification as Slit2. Recombinant human Slit2 collapses and repels RGC growth cones from all quadrants of the chick retina. In the developing mouse visual system, slit2 is expressed in the eye, in the optic stalk, and in the ventral diencephalon. Slit2 expression is strong in anterior ventral diencephalic structures but is absent from the ventral midline where the optic chiasm forms. The putative receptors for Slits, robo1 and robo2, are expressed in the inner retinal layer in which RGCs are located. A comparison of the expression patterns of Slit2 and retinal axon trajectories suggests that slit2 acts as a short range repellent for retinal ganglion cell axons.

Animals↗

Antiangiogenic effects of S-nitrosocaptopril crystals as a nitric oxide donor.

Angiogenesis is the formation of new capillaries from preexisting vessels by migration and proliferation of endothelial cells, which produce a cellular signaling messenger, nitric oxide (NO). The purpose of the present study was to examine the effects of exogenous NO donors on angiogenesis by using a novel crystalline NO donor, S-nitrosocaptopril. The characteristic X-ray diffraction pattern of S-nitrosocaptopril was demonstrated for the first time. On primary capillary endothelial cells pretreated with vascular endothelium growth factor (VEGF), S-nitrosocaptopril (1-500 microM), but not captopril, produced a dose-dependent inhibition of endothelial proliferation. On chick embryos of entire living eggs, gelatin sponges adsorbed with VEGF were implanted on the embryo chorioallantoic membrane to promote vascular growth activity within the sponges. Addition of S-nitrosocaptopril crystals (0.1 mg) to the gelatin sponges markedly reduced vascular density around the sponges, whereas captopril did not inhibit neovascularization. The vascular hemoglobin content surrounding each of the gelatin sponges was determined as a confirmatory test. S-nitrosocaptopril, but not captopril, significantly decreased the hemoglobin content of the embryo tissues immediately surrounding the gelatin sponges. In conclusion, S-nitrosocaptopril exerts an inhibitory effect on angiogenesis. This newly discovered function of S-nitrosocaptopril appears to be governed by distinct structural NO moiety.

Angiotensin-Converting Enzyme Inhibitors↗

Central cord injury complicating acute cervical disc herniation in trauma.

STUDY DESIGN: A retrospective study on 24 patients with acute central cervical cord injury caused by traumatic disc herniation. OBJECTIVES: To determine the correlation of disc herniation with central cord injury and to evaluate the role of anterior cervical decompression and interbody fusion in management of this injury. SUMMARY OF BACKGROUND DATA: Acute cervical disc herniation has been documented as a causative factor in spinal cord injury but has been infrequently reported with central cord syndrome. METHODS: Between 1989 and 1994, 24 patients with acute cervical disc herniation and central cord syndrome were studied. These patients underwent anterior decompression and fusion, and were followed for 2 to 7 years, with an average follow-up period of 3 years and 8 months. The degree of disc herniation and neurologic scores were rated. RESULTS: During follow-up period, the American Spinal Injury Association motor score in 24 patients was increased to 86.46 +/- 10.22 from 47.79 +/- 19.66. The age of the patients was very negatively correlated with recovery rate (P < 0.01), but no correlation was observed between severity of cord compression and neurologic scores (P > 0.05). Postoperative neurologic improvement in patients with fracture or dislocation was very significantly slower (P < 0.01) than in those without these injuries. CONCLUSIONS: Far more common than previously expected, acute disc herniation in cervical spine injury is the one of principal cause for central cord syndrome. Magnetic resonance imaging assessment and surgical intervention are required.

Acute Disease↗

Os odontoideum: etiology, diagnosis, and management.

BACKGROUND: There have been few reports of os odontoideum since the initial description. METHODS: Forty-four patients with os odontoideum treated during the period 1980 through 1996 were reviewed. There were 33 males and 11 females. Their ages ranged from 7 to 56 years, with an average of 24.6 years. Five patients with no symptoms were treated conservatively. Thirty-nine patients underwent operative treatment including nine posterior atlantoaxial fusions and 33 occipitocervical fusions. RESULTS: The patients were followed up for one to 16 years, with an average of 6.5 years. Five patients treated conservatively have remained stable. All 39 treated patients achieved solid arthrodesis. The results were satisfactory. CONCLUSIONS: We conclude that fusion is indicated if atlantoaxial instability or clinical symptoms are significant, and that occipitocervical fusion should be considered in the operative management of os odontoideum if atlantoaxial arthrodesis is impossible.

Adolescent↗

Constitutive levels of cAMP-dependent protein kinase activity determine sensitivity of human multidrug-resistant leukaemic cell lines to growth inhibition and apoptosis by forskolin and tumour necrosis factor alpha.

The cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) signal pathway regulates cell proliferation, differentiation and cell death. It may also regulate the multidrug resistance (MDR) phenotype in leukaemic cells. These data showed that MDR1+ K/Dau600 cells exhibited a higher basal level of PKA activity than MDR- parental cells. The significance of this on tumour necrosis factor alpha (TNFalpha)-induced apoptosis and cytostasis was investigated further. In comparison with MDR1- parental cells, K/Dau600 cells had a higher expression of PKA regulatory subunit RIalpha and nuclear catalytic subunit PKAcalpha. They were also more susceptible to inhibition of proliferation and induction of apoptosis by TNFalpha and/or forskolin, but this could be attenuated by H89. An increase in cAMP was associated with the apoptosis in the K/Dau600 cell line. Forskolin inactivated NF-kappaB in K/Dau600 cells but not in K562 cl. 6 cells, whereas TNF activated NF-kappaB in K562 cl.6 cells but not in K/Dau600 cells. 8-Cl-cAMP exhibited similar inhibitory effects on the proliferation of all of the cell lines used via its metabolite 8-Cl-adenosine, which indicates that these effects were independent of residual PKA or cAMP. Therefore, the differential sensitivity to apoptosis and/or growth inhibition could be mediated via cAMP, partly through PKA via NF-kappaB and partly by PKA-independent pathways.

8-Bromo Cyclic Adenosine Monophosphate↗

Effect of intragastric pH on control of peptic ulcer bleeding.

BACKGROUND: We have performed series studies to investigate the effect of intragastric pH on control of peptic ulcer bleeding. In laboratory and animal studies, both platelet aggregation and gastric mucosal bleeding time were shown to be extremely sensitive to different pH levels. Platelet aggregation decreased significantly at pH > or = 6.8 and gastric mucosal bleeding time fell significantly at pH > or = 6.4. In a prospective clinical trial, primed infusions of different dosages of omeprazole (8 or 4 mg/h) after a bolus (40 mg) produced consistently high intragastric pH values in patients with bleeding duodenal ulcer. These results were not significantly different from that obtained from omeprazole 40 mg bolus treatment every 12 h (P > 0.05). However, primed injection with cimetidine (800 mg/12 h) was less effective (P < 0.05). METHODS: In a retrospective analysis, 303 patients with bleeding peptic ulcer who were treated with cimetidine and 326 patients who were treated with omeprazole were compared. RESULTS: The emergency surgery (4.91%) and mortality rates (1.84%) in the omeprazole group were not significantly different (P > 0.05) from those (7.28 and 1.99%) in the cimetidine group. However, the standardized emergency surgery rate of the omeprazole group (3.28%) was significantly lower than that (9.28%) of the cimetidine group (P < 0.05). CONCLUSION: We conclude that increased intragastric pH to at least 6.4 with omeprazole is helpful in controlling peptic ulcer bleeding. Chinese patients require a lower dose of omeprazole than their Western counterparts to control ulcer bleeding.

Adolescent↗

A skeletal gene database.

Systematic organization of documented data coupled with ready accessibility is of great value to research. Catalogs and databases are created specifically to meet this purpose. The Skeletal Gene Database evolves as part of the Skeletal Genome Anatomy Project (SGAP), an ongoing multi-institute collaborative effort, to study the functional genome of bone and other skeletal tissues. The primary objective of the Skeletal Gene Database is to create a contemporary list of skeletal-related genes, offering the following information for each gene: gene name, protein name, cellular function, disease(s) caused by mutation of the corresponding gene, chromosomal location, LocusLink number, gene size, exon/intron numbers, messenger RNA (mRNA) coding region size, protein size/molecular weight, Online Mendelian Inheritance in Man (OMIM) number of the gene, UniGene assignment, and PubMed reference. The database includes genes already known and published in the literature as well as novel genes not yet characterized but known to be expressed in skeletal tissue. It will be posted on the web for easy access and swift referencing. The data will be updated in tempo with current and future research, thereby providing an invaluable service to the scientific community interested in obtaining information on bone-related genes.

Bone and Bones↗

Patterns of intraocular pressure elevation after aqueous humor outflow obstruction in rats.

PURPOSE: To determine the diural intraocular pressure (IOP) response of Brown Norway rat eyes after sclerosis of the aqueous humor outflow pathways and its relationship to optic nerve damage. METHODS: Hypertonic saline was injected into a single episcleral vein in 17 animals and awake IOP measured in both the light and dark phases of the circadian cycle for 34 days. Mean IOP for light and dark phases during the experimental period were compared with the respective pressures of the uninjected fellow eyes. Optic nerve cross sections from each nerve were graded for injury by five independent masked observers. RESULTS: For fellow eyes, mean light- and dark-phase IOP was 21 +/- 1 and 31 +/- 1 mm Hg, respectively. For four experimental eyes, mean IOPs for both phases were not altered. Six eyes demonstrated significant mean IOP elevations only during the dark phase. Of these, five showed persistent, large circadian oscillations, and four had partial optic nerve lesions. The remaining seven eyes experienced significant IOP elevations during both phases, and all had extensive optic nerve damage. CONCLUSIONS: Episcleral vein injection of hypertonic saline is more likely to increase IOP during the dark phase than the light. This is consistent with aqueous outflow obstruction superimposed on a circadian rhythm of aqueous humor production. Because these periodic IOP elevations produced optic nerve lesions, both light- and dark-phase IOP determinations are necessary for accurate correlation of IOP history to optic nerve damage in animals housed in a light- dark environment.

Animals↗

Effect of general anesthetics on IOP in rats with experimental aqueous outflow obstruction.

PURPOSE: To determine the effect of several common general anesthetics on intraocular pressure (IOP) after experimental aqueous outflow obstruction in the rat. METHODS: A single episcleral vein injection of hypertonic saline was used to sclerose aqueous humor outflow pathways and produce elevated IOP in Brown Norway rats. Animals were housed in either standard lighting or a constant low-level light environment. Awake IOPs were determined using a TonoPen (Mentor, Norwell, MA) immediately before induction of anesthesia by either isoflurane, ketamine, or a mixture of injectable anesthetics (xylazine, ketamine, and acepromazine). For each anesthetic, IOPs were measured immediately after adequate sedation (time 0) and at 5-minute intervals, up to 20 minutes. RESULTS; Awake IOPs ranged from 18 to 52 mm Hg. All anesthetics resulted in a statistically significant (P: < 0.01) reduction in measured IOP at every duration of anesthesia when compared with the corresponding awake IOP. With increasing duration of anesthesia, measured IOP decreased approximately linearly for both the anesthetic mixture and isoflurane. However, with ketamine, IOP declined to 48% +/- 11% (standard lighting) and 60% +/- 7% (constant light) of awake levels at 5 minutes of anesthesia, where it remained stable. In fellow eyes, the SD of the mean IOP in animals under anesthesia was always greater than the corresponding SD of the awake mean. Anesthesia's effects in normal eyes and eyes with elevated IOP were indistinguishable. CONCLUSIONS: All anesthetics resulted in rapid and substantial decreases in IOP in all eyes and increased the interanimal variability in IOPs. Measurement of IOP in awake animals provides the most accurate documentation of pressure histories for rat glaucoma model studies.

Acepromazine↗

[Functional status of p53 and chemosensitivity of colon cancer cell lines].

OBJECTIVE: To study the functional status of tumor suppressor gene p53 in relation to chemotherapeutic sensitivity in colon cancer cell lines. METHODS: With the use of functional assay (FASAY) of p53, the existing p53 status (wt, mt) of 6 colon cancer cell lines was determined. The difference in chemotherapeutic sensitivity of colon cancer cells with wild-type p53 was compared with those with mutated type p53 by MTT method, followed by cytometic analysis of cell cycle. RESULTS: The chemotherapeutic sensitivity of Lovo and LS 174T cancer cell lines with wild-type p53 was 5-10 times higher than that of 4 other cell lines with mutated p53. Selective apoptosis and cell cycle arrest in G1 phase occurred when treated with adriamycin. CONCLUSION: The functional status of p53 in human colon cancer cell lines directly affects their sensitivity to chemotherapeutic agents.

Antibiotics, Antineoplastic↗

[Anterior corpectomy combined with cervical spine locking plate for treatment of multilevel cervical spondylotic myelopathy].

OBJECTIVE: To study the value of cervical spine locking plate (CSLP) combined with anterior corpectomy in treating multilevel cervical spondylotic myelopathy (CSM). METHODS: In 55 CSM patients, 36 were male and 19 female, aged on average 51.5 years. The duration of illness was 13 months on average. Pathological segments in 47 patients included two functional segments and in 8 three functional segments. All patients were treated with anterior corpectomy and self-iliac bone graft and CSLP fixation. RESULTS: 51 patients were followed up for 26 months on average. All grafting bones got solid fusion in 12 to 16 weeks postoperatively. Intervertebral spaces were restored after operation. The physiological curve of the cervical spine was good. The effective rate of operation was 94.1% (48/51) and the excellent rate 78.4% (40/51). The JOA score rose from 8.3 points before operation to 14.1 points after operation. CONCLUSIONS: Anterior corpectomy and osteosynthesis of multilevel cervical spondylotic myelopathy are indicated for CSLP fixation. CSLP in the treatment of cervical spine instability is prospective.

Aged↗

[Remodelling of the spinal canal after thoracolumbar burst fractures: significance of nonoperative management].

OBJECTIVES: To determine the phenomenon of remodelling of the spinal canal after thoracolumbar burst fracture and to investigate the efficacy of nonoperative management. METHODS: A total of 31 patients with thoracolumbar burst fractures, including 7 untreated, 16 treated nonoperatively, and 8 treated operatively, were retrospectively analysed and followed up for 3 to 7 year. The initial and final degrees of neurological deficit and stenotic ratio of the spinal canal were recorded. RESULTS: The stenotic ratio significantly decreased (P < 0.01) from the discharge (range: 12.3% to 74.5%, average: 26.2%) to the final follow-up (range: 5.4% to 46.5%, average: 19.2%), but there were no differences (P > 0.05) of stenotic ratio improvement among the patients untreated, and treated nonoperatively and operatively, or among the patients with different degree of neurological deficit. CONCLUSIONS: Significant remodelling of the spinal canal develops after thoracolumbar burst fractures. Nonoperative management may be taken into account for treatment of neurological intact patients with thoracolumbar burst fractures.

Adult↗

Subcellular distribution and redistribution of Bcl-2 family proteins in human leukemia cells undergoing apoptosis.

It has been suggested that the ratio of Bcl-2 family proapoptotic proteins to antiapoptotic proteins determines the sensitivity of leukemic cells to apoptosis. However, it is believed that Bcl-2 family proteins exert their function on apoptosis only when they target to the mitochondrial outer membrane. The vinblastine-resistant T-lymphoblastic leukemic cell line CEM/VLB100 has increased sensitivity to tumor necrosis factor-alpha (TNF-alpha)-induced cytochrome c release, mitochondrial respiratory inhibition, and consequently apoptosis, compared with parental CEM cells. However, there was no difference between the two cell lines in the expression of Bcl-2 family proteins Bcl-2, Bcl-XL, Bcl-XS, Bad, and Bax at the whole cell level, as analyzed by Western blotting. Bcl-2 mainly located to mitochondria and light membrane as a membrane-bound protein, whereas Bcl-XL was located in both mitochondria and cytosol. Similar levels of both Bcl-2 and Bcl-XL were present in the resting mitochondria of the two cell lines. Although the proapoptotic proteins Bcl-XS, Bad, and Bax were mainly located in the cytosol, CEM/VLB100 mitochondria expressed higher levels of these proapoptotic proteins. Subcellular redistribution of the Bcl-2 family proteins was detected in a cell-free system by both Western blotting and flow cytometry after exposure to TNF-alpha. The levels of Bcl-2 family proteins were not altered at the whole cell level by TNF-alpha. However, after exposure to TNF-alpha, Bax, Bad, and Bcl-XS translocated from the cytosol to the mitochondria of both cell lines. An increase in Bcl-2 levels was observed in CEM mitochondria, which showed resistance to TNF-alpha-induced cytochrome c release. By contrast, decreased mitochondrial Bcl-2 was observed in CEM/VLB100 cells, which released cytochrome c from the mitochondria and underwent apoptosis as detected by fluorescence microscopy. We conclude that mitochondrial levels of Bcl-2 family proteins may determine the sensitivity of leukemic cells to apoptosis and that, furthermore, these levels may change rapidly after exposure of cells to toxic stimuli.

Antineoplastic Agents, Phytogenic↗

Hepatitis B virus X protein inhibits nucleotide excision repair.

Human hepatitis B virus (HBV) is a major risk factor of human hepatocellular carcinoma. Both in vivo and in vitro studies have shown that HBV X protein (HBx) can bind to the p53 tumor-suppressor protein and interfere with the role that p53 plays in the cellular response to DNA damage. Our previous work has shown that HBx protein inhibits p53 sequence-specific transcriptional activation, p53-mediated apoptosis and p53 binding to the TFIIH transcription-nucleotide excision repair (NER) factors, including XPB and XPD. To investigate whether HBx interferes with the NER pathway, we utilized cell-proliferation and colony-formation assays to determine if cells expressing HBx are more sensitive to UVC-induced DNA damage. NER was also measured by a plasmid host cell re-activation assay using a vector containing a luciferase reporter gene. UV-irradiated plasmids were transfected into a human RKO colon carcinoma cell line that contains wild-type (wt) p53 as well as its derivatives, either mutant p53-143ala (RKO-143ala) or human papillomavirus E6 (RKO-E6, a wt p53 protein that is rapidly degraded and non-functional). We found that cells expressing HBx are more sensitive to UVC-induced killing. Moreover, expression of HBx resulted in a reduction of NER efficiency in RKO cells to 52 +/- 2% (compared with control), RKO-143a1a cells to 46 +/- 3% and RKO-E6 cells to 60 +/- 3%. Similar results were also obtained with a HepG2 hepatoblastoma cell line carrying wt p53. In addition, we found that HBx bound directly to either XPB or XPD DNA helicase in vitro. Thus, our data indicate that HBx may interfere with the NER pathway through both p53-dependent and p53-independent mechanisms. Because HBx binds to TFIIH-associated proteins, we propose that HBx may interfere with the NER pathway also through binding to and altering the activities of helicases necessary for NER and, thereby, increase the mutation rate induced by chemical carcinogens, such as aflatoxin B1, during human liver carcinogenesis.

Apoptosis↗

Dual actions of S-nitrosylated derivative of vasoactive intestinal peptide as a vasoactive intestinal peptide-like mediator and a nitric oxide carrier.

Vasoactive intestinal peptide (VIP) has been postulated as a non-adrenergic non-cholinergic (NANC) transmitter in the relaxation of vascular and non-vascular systems. In order to synergize the vasoactivities of VIP with nitric oxide (NO), we synthesized a S-nitrosylated derivative of VIP, VIP-Gly-Cys-NO (VIPGC-NO). On aortic rings, VIPGC-NO exhibited a dose-dependent vasorelaxation similar to S-nitrosoglutathione (GSNO), and both induced complete vasorelaxation at 1 microM, whereas, VIP at 1 microM only produced 19% relaxation. The degree of vasorelaxation was proportional to the increases in cyclic GMP with no significant enhancement in cyclic AMP (cAMP) level. On precontracted tracheal rings, VIP, VIPGC-NO, VIPGC and GSNO produced relaxation with EC50 of 74+/-5, 32+/-6, 59+/-9, and 251+/-32 nM, respectively, which was consistent with increases in cyclic GMP (cGMP). A marked increase in cAMP was observed from the tracheal rings pretreated with VIP, VIPGC-NO and its parent VIP-Gly-Cys (VIPGC) as well as isoproterenol. Propranolol only blocked the airway relaxation induced by isoproterenol, but did not antagonize the relaxation induced by VIP, VIPGC and VIPGC-NO. On rabbit sphincter of Oddi, VIP, VIPGC-NO and VIPGC inhibited both basic and acetylcholine-induced contraction frequency and amplitude, whereas, GSNO was less potent than VIP and its derivatives over a range of 2 log units in this respect. On rat gastric fundus, these compounds inhibited contraction amplitude and frequency induced with 5-hydroxytryptamine (5-HT) in the order of inhibitory potency VIP > VIPGC-NO > VIPGC > isoproterenol > GSNO. Our data suggest that: (1) NO is selective in relaxing vascular smooth muscle via the cGMP pathway, whereas VIP is selective in relaxing non-vascular smooth muscles via the activation of both cGMP and cAMP pathways; (2) VIPGC-NO preserves the intrinsic function of VIP but acquires NO-like vasoactivities.

Animals↗

Membrane supports as the stationary phase in high-performance immunoaffinity chromatography.

The membrane with a composite of cellulose grafted with acrylic polymers formed by polymerizing a glycidyl methacrylate in the presence of dispersed cellulose fiber was prepared as the stationary phase; the column (40 x 4 mm i.d.) which was compatible with the HPLC instrument was packed with pieces of the cut membrane. Protein A and human IgG were immobilized on the membrane stationary phase. The column based on the membrane support provided us good reproducibility, high efficiency, and low back pressure. High-performance immunoaffinity chromatographic analysis of human IgG in serum and polyclonal antibody to human IgG raised in goat was performed within 2.5 min. The fast-speed immunoaffinity analysis was developed by increasing the flow rate of the mobile phase and decreasing the duration time for the switch of the mobile phase; an operation for immunoaffinity analysis of human IgG could be finished within 30 s.

Cellulose↗

Immobilized iminodiacetic acid (IDA)-type Cu2+ -chelating membrane affinity chromatography for purification of bovine liver catalase.

A metal ion chelating membrane medium based on iminodiacetate-substituted modified short cotton cellulose was examined for the purification of bovine liver catalase (BLC). The effect of buffer pH, chelator surface density, initial concentration of crude enzyme and flow rate on BLC binding efficiency to the copper ion chelating membrane adsorbent were examined. Under the chromatographic conditions chosen, 67.7% recovery of BLC was attained with an overall 4.2-fold increase in specific activity in a single step. After performance of BLC purification, the chelating membrane adsorbent can be easily regenerated by imidazole or EDTA buffer with higher reviving effectiveness with the latter.

Animals↗

Protein A tangential flow affinity membrane cartridge for extracorporeal immunoadsorption therapy.

Tangential flow affinity membrane cartridge (TFAMC) is a new model of immunoadsorption therapy for hemoperfusion. Recombinant Protein A was immobilized on the membrane cartridge through Schiff base formation for extracorporeal IgG and immune complex removal from blood. Flow characteristics, immunoadsorption capacity and biocompatibility of protein A TFAMC were studied. The results showed that the pressure drop increased with the increasing flow rate of water, plasma and blood, demonstrating reliable strength of membrane at high flow rate. The adsorption capacities of protein A TFAMC for IgG from human plasma and blood were measured. The cartridge with 139 mg protein A immobilized on the matrix (6 mg protein A/g dry matrix) adsorbed 553 mg IgG (23.8 mg IgG/g dry matrix) from human plasma and 499.4 mg IgG (21.5 mg IgG/g dry matrix) from human blood, respectively. The circulation time had a major influence on IgG adsorption capacity, but the flow rate had little influence. Experiments in vitro and in vivo confirmed that protein A TFAMC mainly adsorbed IgG and little of other plasma proteins, and that blood cell damage was negligible. The extracorporeal circulation system is safe and reliable.

Animals↗