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Biomedical subjects

L Jia

Publications and source records attributed to L Jia.

At least 73 records · Page 4Linked to original sources

Physicochemistry, pharmacokinetics, and pharmacodynamics of S-nitrosocaptopril crystals, a new nitric oxide donor.

S-nitrosocaptopril (CapNO) has been proposed as a compound possessing capacities of both a nitric oxide (NO) donor and an inhibitor of angiotensin converting enzyme (ACE). In the present study, we characterized the physicochemical, pharmacokinetic, and pharmacological properties of the crystalline CapNO. The novel stable crystals are in a red flake form. Spectroscopic analyses of CapNO revealed its UV/visible lambda(max) and the corresponding extinction coefficients, and characteristic infrared frequencies for the N=O and S-N stretch. The NMR signals corresponding to the protons attached to the carbon (C-S) and the carbon itself were remarkably shifted downfield upon S-nitrosylation. Mass and HPLC analyses, solubility, and melting point of CapNO were determined. Simultaneous on-line analyses of pharmacodynamic and pharmacokinetic profiles of CapNO in catheterized awake rats of spontaneous hypertension (SHR) showed acute decreases in mean arterial pressure (MAP), concomitant with the corresponding increases in plasma levels of CapNO after po or iv administration. The pharmacokinetic parameters for CapNO, i.e., t(1/2), T(max), C(max), V(d), AUC, and oral bioavailability were analyzed to understand the dose-dependent potency and effective period of CapNO. The highest concentrations of oral CapNO distributed in tissues were found in kidney, liver, lung, and small intestine. CapNO was excreted predominantly via urine, and second via feces in the detectable forms of thiols and nitrogen oxide although a small portion of CapNO was found in bile. The results provide the evidence of in vivo cleavage of the S-N bond and biotransformation of CapNO.

Animals↗

Transferrin receptor overexpression enhances transferrin responsiveness and the metastatic growth of a rat mammary adenocarcinoma cell line.

We previously found that breast cancer cell transferrin receptor expression and proliferative response to transferrin often correlated with metastatic capability. To further explore this, we transfected mammary tumor cells with a cDNA coding for the transferrin receptor and examined the effects of its overexpression on various cellular properties. A human transferrin receptor expression plasmid was made by excising the cDNA for the receptor from pcDTR1 and ligating it into the multiple cloning site of pcDNAINeo. The resulting construct was transfected into the poorly metastatic rat MTLn2 line that expresses low endogenous levels of rat transferrin receptor, and transfection-induced receptor expression was ascertained using antibodies specific for the human protein. Approximately 50% of the initial geneticin-resistant transfected MTLn2 cells overexpressed human transferrin receptor protein. High expressors were further isolated by four sequential FACS sorts. The final cell population expressed approximately 3-7 times more cell surface transferrin receptor than did vector transfected controls. Both lines proliferated at the same rate in normal (medium plus 5% FBS) culture conditions. However, in serum-free conditions, the transferrin receptor overexpressor cells displayed a pronounced proliferative response to transferrin whereas the control line did not. When injected into the mammary fat pads of female nude mice, cells from both lines formed micrometastases to the lung that were specifically visualized by immunohistochemical staining of rat cytokeratin 17. This revealed that the transferrin receptor transfected line formed larger lesions of this nature than did cells from the vector transfected controls. When injected into the tail vein of female nude mice, the transferrin receptor overexpressors likewise formed gross lung metastases of remarkably greater size than did the vector only transfectants. Overexpression of cell surface human transferrin receptor on MTLn2 cells appeared to affect their in vitro growth response to transferrin and their ability to grow at a secondary site in vivo.

Adenocarcinoma↗

Pgp-positive leukaemic cells have increased mtDNA but no increased rate of proliferation.

Cells of solid tumours tend to rely on glycolysis for energy. On the other hand, increased glycolysis in solid tumour cells expressing the multidrug resistance protein MDR-1 has been associated with increased malignancy in tumours. We have previously shown that cells of the MDR-1-positive CEM/VLB100 leukaemic cell line have increased mitochondrial electron transport chain (mtETC) activity compared with parental CEM cells. In the present study we used infrared (IR) spectroscopy to demonstrate that the mitochondrial DNA (mtDNA) content in the CEM/VLB100 cell line was significantly increased compared to that in the parental CEM cells. The increase in mtDNA was not accompanied by an increase in mitochondrial protein as both lipid and protein levels were decreased in CEM/VLB100 mitochondria. The ATP content was similar in these two cell lines. However, the ATP-dependent membrane efflux pump function in CEM/VLB100 cells was significantly reduced when mitochondrial ATP synthesis was inhibited by oligomycin, a specific inhibitor of mitochondrial F0F1-ATPase. Proliferation of CEM/VLB100 cells was significantly decreased compared to parental CEM cells, and was independent of p53 expression. Thus, we conclude that: (1) IR spectroscopy is a potential powerful technique for detecting mtDNA, protein and lipid contents simultaneously; (2) leukaemic cells mainly rely on mtDNA for energy; (3) increased expression of an ATP-dependent membrane efflux pump such as Pgp may up-regulate ATP generation and mtDNA content. These metabolic perturbations may exist merely to serve the efflux pump and do not result in an increase in leukaemic cell proliferation. In addition, the associated reduction in mitochondrial lipid and protein may contribute to sensitize the cells to cytochrome c release.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[A large-scale study on the safety and epidemiological efficacy of Japanese encephalitis (JE) live vaccine (SA14-14-2) in the JE endemic areas].

OBJECTIVE: To measure the safety and epidemiological efficacy of Japanese encephalitis live vaccine(SA14-14-2). METHODS: Guoyang and Mengcheng counties in Anhui Province, were chosen as observed spots where high incidence of JE was noticed in China. 1-6 years old children in two counties were inoculated with vaccine manufactured by Chengdu Biological Products Institute in the beginning of 1992. All children of 1-6 years old received one primary dose of live vaccine and the children at one or two years old were respectively given one dose for primary or booster vaccination in 1993-1996. Side effects of live vaccine had been under surveillance for five years for its safety JE cases during the epidemic season (Jun to October), were diagnosed clinically and serologically. RESULTS: Data on the safety and efficacy of the JE live vaccine(SA14-14-2) are listed as follows:1) During 1992-1996, a total number, of 335,941 children at 1-6 year old were vaccinated. No vaccine-associated encephalitis, meningitis or other serious adverse events were observed. 2) The incidence of JE case has greatly declined since the beginning of large-scale vaccination. The average JE morbidity dcreased from 11.34/100,000 in 1987-1991 to 2.74/100,000 in 1992-1996(P < 0.005). 3) The incidence of JE case in 1-6 years old in that period reduced as well. The average JE morbidity decreased from 56.24/100,000 to 13.83/100,000 in Guoyang and from 44.57/100,000 to 16.94/100,000 in Mengcheng counties respectively(P < 0.005). Most of the JE cases (94%) occurred in the unvaccinated children including all the 18 death cases. 4) Serum antibody response to immunization were measured by plaque reduction neutralization test. Neutralizing antibody seroconversion after one single vaccination were 83.87%-94.74%. CONCLUSION: The results further confirmed that JE live vaccine is safe for children and effective for prevention from JE disease in JE endemic areas.

Antibodies, Viral↗

[Radiculopathy after cervical laminectomy].

OBJECTIVE: To investigate radiculopathy after multilevel laminectomy in patients with cervical compression myelopathy and underlying mechanism. METHODS: We retrospectively reviewed 287 consecutive patients with cervical compression myelopathy treated by multilevel cervical laminectomy and identified 37 patients (12.9%) with postoperative radiculopathy. There were 27 men and 10 women, with an average age of 56 years at time of surgery. The diagnosis was either cervical spondylosis (25 patients) or ossification of the posterior longitudinal ligament (12 patients). RESULTS: Radiculopathy was observed from 4 hours to 6 days after surgery. The most frequent patterns of paralysis were C(5) and C(6) root involvements of the motor-dominant type. All patients showed complete recovery in 2 weeks to 3 years (average, 5.4 months). Follow up results showed that the recovery rate was negatively related to the duration of complete recovery of postoperative radiculopathy (r = -0.832, P < 0.01) and the patients with spondylotic myelopathy had a significantly better clinical recovery rate than those with ossification of the posterior longitudinal ligament (t = 2.960, P < 0.01). CONCLUSIONS: Postoperative radiculopathy is complicated with posterior cervical decompression and associated with tethering effect upon the nerve root. More logical procedures for prevention of postoperative radiculopathy are decompression through an anterior decompressive procedure in conjunction with a spinal fusion, which may achieve stabilization and directly remove all of the anterior spinal cord compression at multiple levels.

Adult↗

[The relationship between cartilage end-plate calcification and disc degeneration: an experimental study].

OBJECTIVE: To study the relationship between cartilage end-plate calcification and intervertebral disc degeneration. METHODS: An experimental model of cervical disc degeneration in rabbits was established by resection of cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from cervical vertebrae. Mechanical instability in the cervical spine elicited by this surgical intervention accelerated the process of intervertebral disc degeneration. The degrees of intervertebral disc degeneration were graded morphologically. The thickness of the calcified layer and the uncalcified layer of the cartilage end-plate was measured in each degenerated cervical disc. RESULTS: A positive correlation existed between the thickness of the calcified layer of the cartilage end-plate and the degree of the cervical disc degeneration (r = 0.92). CONCLUSION: The calcification of the cartilage end-plate could initiate and promote intervertebral disc degeneration.

Animals↗

[Prevalence of blindness among adults aged 50 years or above in Shunyi county of Beijing].

OBJECTIVE: To estimate the prevalence of blindness among older adults aged >or= 50 years in Shunyi county of Beijing, China. METHODS: Cluster sampling was used in randomly selecting individuals aged >or= 50 years in 28 villages in Shunyi county in fall, 1996. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. RESULTS: 5,555 individuals were enumerated. The response rate was 91.5%. In this population, the prevalence of blindness was 1.7% defined as pinhole visual acuity < 0.05 in both eyes; or 2.8% were blind, defined as presenting visual acuity < 6/60 in both eyes. Blindness was associated with older age and female gender. The principal cause of blindness in eyes was cataract. CONCLUSIONS: The prevalence of blindness was decreased 35.8% after ten year active eye-care program in the survey area. However, cataract blindness continues as a significant problem among elderly, especially females, in this population sample of rural area.

Age Factors↗

[Effect of gui xin tong on sorbitol and nerve conduction velocity in diabetic rats].

OBJECTIVE: To investigate the effect of Gui Xin Tong(GXT) on sorbitol and nerve conduction velocity in diabetic rats. METHOD: The model rats suffering from diabetes were induced by STZ, and blood sugar levels above 16 mmol/L were chosen for observation. The rats were divided into GXT group, AG group and control group. The nerve conduction velocity, aldose reductase activity and sorbitol in STZ induced diabetic rats were investigated. RESULT: Compared with the control group GXT could increase the sciatic nerve conduction velocity significantly (P < 0.05), decrease the RBC and sciatic nerve, aldose reductase activity, and RBC-sorbitol content. CONCLUSION: GXT has the effect of improving nerve conduction velocity significantly and reducing aldose reductase activity and sorbitol

Aldehyde Reductase↗

[Protein A tangential flow membrane chromatographic column used for immunoadsorption therapy].

Tangential flow membrane chromatographic column is a new model of immunoadsorption therapy from blood. The results showed that the structure of the column and the flowing channel had a little damages for blood cells. The relation of flow-rate and backpressure with water, plasma and blood individually as the fluid flowing through the column has been studied. It was observed that backpressures increased with fluid viscosity, when flow-rate of blood was 120 mL/min and the backpressure reached 0.093 MPa; The adsorption capacity of protein A of the column for IgG from human plasma has been measured. When plasma and blood individually circulated through the column for 1 h, the column 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 great influence on IgG adsorption capacity; but the circulation rate had a little influence on IgG adsorption capacity. The result of extracoporeal blood perfusion for dog showed that the Protein A column has good blood biocompatibility.

Chromatography↗

[Hydrophobic membrane chromatography for fast purification of biological macromolecules].

Cellulose membrane bonded with four commonly used hydrophobic groups, octyl, butyl, phenyl and polyethylene glycol was first investigated for their binding and purification characteristics of protein and enzyme with octyl- and phenyl-Sepharose CL-4 B as controls. Hydrophobic membranes bound BSA effectively by hydrophobic interaction in high salt solution. Their binding capacities were not notably affected by significantly increasing the flow mass rate or decreasing the mass concentration of protein solution, but were much lower than those of octyl- and phenyl-Sepharose CL-4B. 11.8 fold of purification with an approximately 100% recovery of bovine liver catalase was achieved by step gradient elution on the phenyl cellulose membrane cartridge in a single step in only ten mins or a little more. Increase of the flow mass rate had no effect on the purification of catalase, however, the processing time was shortened greatly. Hydrophobic membrane chromatography here reported exibits a potential of fast processing of the protein solution in large volume with low mass concentration of the target protein, such as genetic engineering culture solution.

Animals↗

The effects of S-nitrosocaptopril on renal filtration and blood pressure in rats.

The present investigation was performed to evaluate the effects of S-nitrosocaptopril, a novel vasodilator possessing the capacities of both an angiotensin converting enzyme inhibitor and an NO donor, on blood pressure and renal function in rats. S-nitrosocaptopril produced acute reductions in mean arterial pressure after both oral dosing (5, 10, 50 mg/kg) to chronically-catheterized awake rats and intravenous administrations (0.125, 1.25, 12.5 mg/kg) to anesthetized rats. The hypotensive magnitude and duration of S-nitrosocaptopril were dose-dependent. Acute pressure-associated reductions in the glomerular filtration rate and urine flow were observed only at high concentration of S-nitrosocaptopril (12.5 mg/kg, i.v.) in both awake and anesthetized rats. These decreases were transient, followed by an overshoot of glomerular filtration rate and urine flow above basal values. In contrast, captopril (i.v.) did not produce any significant acute effects on mean blood pressure and glomerular filtration rate in either awake or anesthetized rats. In rats with acute hypertension induced by NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg, i.v.), S-nitrosocaptopril (0.125 mg/kg, i.v.) significantly abolished the hypertensive effects. In contrast, the hypertension was not affected by captopril. In two-kidney one-clipped Goldblatt hypertensive rats, oral administration of S-nitrosocaptopril (25 mg/kg, b.i.d.) for 10 days significantly reduced systolic blood pressure and preserved glomerular filtration rate. The oral antihypertensive effect of S-nitrosocaptopril was more potent than captopril (P < 0.05). In conclusion, these findings indicate that: (1) S-nitrosocaptopril provides both acute and chronic anti-hypertensive effects orally and intravenously, whereas captopril has only moderate chronic oral effects; and (2) S-nitrosocaptopril preferentially decreases blood pressure without markedly affecting glomerular filtration rate.

Administration, Oral↗

Visual acuity and quality of life outcomes in patients with cataract in Shunyi County, China.

PURPOSE: To measure visual acuity and vision-related quality of life in individuals in rural China operated on for cataract. METHODS: Five thousand fifty-two persons age 50 years and older, 90.9% (5,052/5,555) of a randomly selected population in Shunyi County, were examined in the fall of 1996. Visual functioning and quality of life questionnaires were administered to those with presenting visual acuity less than 6/60 in either eye and to those who were aphakic or pseudophakic. RESULTS: Of the 87 individuals operated on for cataract, 12% (10/87) had presenting visual acuity of 6/18 or more in both eyes, and 24.1% (21/87) had less than 6/60. Twenty-five percent (29/116) of the 116 eyes operated on for cataract had presenting visual acuity of 6/18 or more, and 44.8% (52/116) had less than 6/60. Aphakic cases without glasses and uncorrectable aphakia attributable to surgical complications were common. In a multivariate regression model, including time period of surgery, hospital type, and surgical procedure, only pseudophakia was associated with better outcomes (P = .05). On a scale from 0 (maximum problems) to 100 (no problems), the mean visual functioning score (+/-SD) for the operated-on population was 61.9 +/- 30.0, and 71.0 +/- 31.8 for the quality of life questionnaire. These scores were comparable to those of the unoperated-on population with moderate bilateral blindness (<6/60 to > or =3/60 in the better eye). Visual functioning and quality of life scores were closely correlated with visual acuity in operated-on (r = 0.64 and r = 0.61, respectively) and unoperated-on populations (r = 0.68 and r = 0.59, respectively). CONCLUSIONS: Both clinical and patient-reported cataract surgery outcomes are below what should be achievable. Improvement in outcomes must be given greater emphasis if the potential of cataract surgery in restoring sight is to be realized.

Aged↗

Prevalence of blindness and cataract surgery in Shunyi County, China.

PURPOSE: To estimate the prevalence of blindness and cataract surgery among older adults in rural China. METHODS: Cluster sampling was used in randomly selecting men and women aged 50 years or older for visual acuity testing and an eye examination in 28 villages in Shunyi County. The survey, which was carried out in the fall of 1996, was preceded by a pilot study in which operational methods were refined and quality assurance evaluations carried out. RESULTS: Of 5,555 enumerated subjects > or =50 years of age, 91.5% (5,084/5,555) were examined and 90.9% (5,052/5,555) were tested for visual acuity. In this population, 2.8% (139/5,052) were blind, defined as presenting visual acuity less than 6/60 in both eyes. Blindness was associated with older age and female sex. Cataract was the principal cause of blindness in at least one eye in 48.2% (67/139) of blind people. The ratio of those blind from cataract who were operated on to the those who could have been operated on, cataract surgical coverage, was estimated to be 47.8% (54/113). Cataract surgery was associated with younger age but not sex or education. CONCLUSIONS: Blindness, particularly blindness related to cataract, continues to be a significant problem among the elderly, especially women, in this population-based sample of rural Chinese. Despite an active eye-care program in Shunyi County, only half of those who might benefit from cataract surgery are receiving it.

Age Distribution↗

Promoter recognition by a cyanobacterial RNA polymerase: in vitro studies with the Calothrix sp. PCC 7601 transcriptional factors RcaA and RcaD.

To study the transcriptional apparatus and the mechanisms that control gene expression in cyanobacteria, the RNA polymerase was purified from the filamentous Calothrix sp. PCC 7601 and used in in vitro transcription assays. Conditions required for specific transcription initiation to occur were analyzed with the eleven Calothrix PCC 7601 genes for which the 5' ends have been mapped. Most of the transcripts directly obtained did not have the expected size, providing a test for looking at specific transcription factors. Addition of RcaA, a protein that binds to the promoter region of the phycobiliprotein cpeBA operon, restored accurate initiation of transcription in the in vitro system for three phycobiliprotein promoters. RcaA thus is a transcription factor that allows to mimick in vivo transcription. In parallel, the functional properties of the Escherichia coli and cyanobacterial RNA polymerases were compared. The enteric enzyme could not precisely initiate transcription at the promoter of a phycobiliprotein gene and, reciprocally, the cyanobacterial RNA polymerase could initiate transcription at PlacUV5, but not from wild-type Plac promoters. The different behaviours of the enzymes are discussed in the light of the structural differences that exist between subunits of the RNA polymerases.

Binding Sites↗

Solitary bone cyst in the odontoid process and body of the axis. A case report and review of literature.

A four-year-old boy presented with a solitary bone cyst in the odontoid process and body of the axis. Plain radiographs showed a radiolucent lesion with extreme thinning of the cortex and MRI demonstrated a high signal intensity in the interlesional matrix. The cystic component extended into the body of the axis through a defect in the epiphyseal plate. At operation, the cavity of the cyst was found to contain serosanguineous fluid, and histological examination showed that it was lined by a thin layer of connective tissue. The cyst may have originated from a defect in the epiphyseal plate.

Bone Cysts↗

Radiculopathy after laminectomy for cervical compression myelopathy.

Postoperative radiculopathy is a complication of posterior cervical decompression associated with tethering of the nerve root. We reviewed retrospectively 287 consecutive patients with cervical compression myelopathy who had been treated by multilevel cervical laminectomy and identified 37 (12.9%) with postoperative radiculopathy. There were 27 men and ten women with a mean age of 56 years at the time of operation. The diagnosis was either cervical spondylosis (25 patients) or ossification of the posterior longitudinal ligament (12 patients). Radiculopathy was observed from four hours to six days after surgery. The most frequent pattern of paralysis was involvement of the C5 and C6 roots of the motor-dominant type. The mean time for recovery was 5.4 months (two weeks to three years). The results at follow-up showed that the rate of motor recovery was negatively related to the duration of complete recovery of postoperative radiculopathy (gamma=-0.832, p < 0.01) and that patients with spondylotic myelopathy had a significantly better rate of clinical recovery than those with ossification of the posterior longitudinal ligament (t=2.960, p < 0.01). Postoperative radiculopathy may be prevented by carrying out an anterior decompression in conjunction with spinal fusion, which will achieve stabilisation and directly remove compression of the cord at multiple levels.

Adult↗