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Biomedical subjects

F Jiang

Publications and source records attributed to F Jiang.

138 records · Page 8Linked to original sources

Modified polyvinyl alcohol-benzoporphyrin derivative conjugates as phototoxic agents.

Photosensitizing and biodistribution characteristics of a photosensitizer (benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight = 10,000) were tested in vitro and in vivo. Modified PVA was loaded with BPD at molar ratios 1:12, 1:25, 1:50, 1:75 and 1:100. Most of the work was carried out with a conjugate having a 1:25 molar ratio. In vitro photosensitization was tested using A549 (human lung carcinoma), A432 (human epidermoid carcinoma) and P815 (mastocytoma of DBA/2 mice) cell lines. Photosensitization of M1 (rhabdomyosarcoma of DBA/2 mice) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated 3H-BPD and 3 h later light activation of tumor cells was carried out in vitro. Biodistribution studies were carried out using M1 tumor-bearing DBA/2 mice and 3H-BPD either free or conjugated to M-PVA. The results of these studies showed that the conjugation of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing activity of the photosensitizer molecules and at the same time gained new characteristics, advantageous for photodynamic treatment, especially in vivo. In vitro M-PVA-BPD conjugates were at least as efficient in photosensitization of tumor cells as an equivalent number of free BPD molecules, both in the presence and in the absence of serum. Although the biodistribution was in general comparable to free BPD, the conjugate (1:25) reached slightly higher levels in the blood, kidney, lung and spleen, and lower levels in the liver, brain, skin and muscle in comparison with free BPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of ethanol on glucose utilization by cultured mammalian embryos.

We have previously observed correlations between placental glucose transfer and growth of fetuses of ethanol (EtOH)-fed and control rats. In the present study, whole mammalian embryos were used to define the interaction of glucose supply and the effects of EtOH on growth and differentiation. Rat embryos were cultured in 75% normal rat serum from day 9.5 to day 11.5 of gestation. EtOH produced dose-dependent reductions of embryo protein content (mean +/- SEM = 212 +/- 5, 171 +/- 11, 141 +/- 16, and 113 +/- 9 micrograms/embryo in the presence of 0, 25, 50, and 100 mM EtoH, respectively). Somite number was 25.7 +/- 0.3, 23.4 +/- 0.7, 21.8 +/- 0.7, and 21.1 +/- 0.4 under the same conditions. Exposure to ethanol during the first 24 hr in culture decreased embryo protein content to the same extent as exposure for the entire 48-hr culture period. After 46 hr in culture, control and ethanol-exposed embryos were incubated with 14C-glucose for 2 hr. Ethanol produced dose-dependent reductions of CO2 production, anabolic utilization, lactate release, and total glucose utilization. Glucose supplementation (300 mg/dl) significantly increased embryo protein content and each of these glucose utilization parameters. When glucose utilization was expressed relative to embryo protein content, incorporation of the label into embryonic tissues was significantly reduced by ethanol and increased by glucose supplementation. Embryo protein content correlated closely (r = 0.871, p less than 0.0001) with anabolic glucose utilization. Thus, ethanol directly affects embryo glucose utilization, both as an energy source and as a synthetic substrate, in addition to its effects on placental glucose transfer.

Animals↗

Visual functions and trace element metabolism in tobacco-toxic optic neuropathy.

Visual functions and nutrition metabolic characteristics were studied in 8 subjects (16 eyes) with tobacco-toxic optic neuropathy (TTON). Their visual functions tested by psychophysical and electrophysiologic methods showed that 1: 1. central vision diminished in 16 eyes, 2. dyschromatopsias were found in 14 tested eyes, 3. bilateral symmetrical central or cecocentral scotomas were the visual field characteristics in all cases, 4. PVEP were severe abnormal in 3 spatial frequencies in all cases and 56.3% of 15' checkboard PVEP showed flat responses, which indicated the impairment of optic nerve dominated by the central field. However, the preserved visual responses could be obtained by FVEP test in 14 tested eyes even though their visual acuity were between the range of 0.02-0.2 and flat PVEP responses. The II and III wave latencies of primary stage were more prolonged than those of control group (P < 0.01), which further indicated the preferential demyelination corresponding to the papillomacular bundles, 5. ERG showed slightly attenuated amplitudes in 5 of 8 tested eyes, which indicated the secondary and mild retinal lesion. On the other hand, TTON occurred on a background of long-term, heavy smoking, drinking, emaciation and malnutrition bodies with low serum zinc level.

Adult↗

Electron spin echo envelope modulation studies of the Cu(II)-substituted derivative of isopenicillin N synthase: a structural and spectroscopic model.

Electron spin echo envelope modulation spectroscopy (ESEEM) was used to study the active site structure of isopenicillin N synthase (IPNS) from Cephalosporium acremonium with Cu(II) as a spectroscopic probe. Fourier transform of the stimulated electron spin-echo envelope for the Cu(II)-substituted enzyme, Cu(II)IPNS, revealed two nearly magnetically equivalent, equatorially coordinated His imidazoles. The superhyperfine coupling constant, Aiso, for the remote 14N of each imidazole was 1.65 MHz. The binding of substrate to the enzyme altered the magnetic coupling so that Aiso is 1.30 MHz for one nitrogen and 2.16 MHz for the other. From a comparison of the ESEEM of Cu(II)IPNS in D2O and H2O, it is suggested that water is a ligand of Cu(II) and this is displaced upon the addition of substrate.

Acremonium↗

"Soft docking": matching of molecular surface cubes.

Molecular recognition is achieved through the complementarity of molecular surface structures and energetics with, most commonly, associated minor conformational changes. This complementarity can take many forms: charge-charge interaction, hydrogen bonding, van der Waals' interaction, and the size and shape of surfaces. We describe a method that exploits these features to predict the sites of interactions between two cognate molecules given their three-dimensional structures. We have developed a "cube representation" of molecular surface and volume which enables us not only to design a simple algorithm for a six-dimensional search but also to allow implicitly the effects of the conformational changes caused by complex formation. The present molecular docking procedure may be divided into two stages. The first is the selection of a population of complexes by geometric "soft docking", in which surface structures of two interacting molecules are matched with each other, allowing minor conformational changes implicitly, on the basis of complementarity in size and shape, close packing, and the absence of steric hindrance. The second is a screening process to identify a subpopulation with many favorable energetic interactions between the buried surface areas. Once the size of the subpopulation is small, one may further screen to find the correct complex based on other criteria or constraints obtained from biochemical, genetic, and theoretical studies, including visual inspection. We have tested the present method in two ways. First is a control test in which we docked the components of a molecular complex of known crystal structure available in the Protein Data Bank (PDB). Two molecular complexes were used: (1) a ternary complex of dihydrofolate reductase, NADPH and methotrexate (3DFR in PDB) and (2) a binary complex of trypsin and trypsin inhibitor (2PTC in PDB). The components of each complex were taken apart at an arbitrary relative orientation and then docked together again. The results show that the geometric docking alone is sufficient to determine the correct docking solutions in these ideal cases, and that the cube representation of the molecules does not degrade the docking process in the search for the correct solution. The second is the more realistic experiment in which we docked the crystal structures of uncomplexed molecules and then compared the structures of docked complexes with the crystal structures of the corresponding complexes. This is to test the capability of our method in accommodating the effects of the conformational changes in the binding sites of the molecules in docking.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Antibody Complex↗

Correlation of gene structure and psychophysical measurement in red-green color vision deficiency in Chinese.

PURPOSE: To study the correlation of genotype for X-linked red-green gene array with color vision phenotype in 58 subjects with red-green color vision deficiency. METHODS: The molecular structure of red and green pigment genes on 58 X chromosomes was studied exon-by-exon by using heteroduplex-SSCP analysis and sequencing. The color vision of these subjects was determined by a Neitz anomaloscope. RESULTS: Variations in the red and green pigment genes were detected in 43 subjects and a hybrid gene was found in 27 subjects. About 50% of the fusion sites occurred at intron 2-3. All 3 anomalous trichromats with intron 4 fusion were mild type but another 3 with intron 2-3 fusion were severe type. No subjects with mild type of color vision defects had a fusion site at intron 2-3 or its upstream. Three subjects with complete deletion of the green pigment gene manifested deuteranomaly. CONCLUSIONS: Protans can be differentiated from deutans on the basis of genotype. It is still difficult to establish a clear correlation of different anomalous trichromats with genotype. The fusion site of a hybrid gene affects the phenotype to some degree. Intron 2-3 is the common place for gene crossover.

Blotting, Southern↗

The role of protein kinase Calpha in U-87 glioma invasion.

To investigate the hypothesis that protein kinase Calpha (PKCalpha) is functional glial tumor cell invasion, stable PKCalpha sense and antisense transfected U-87 cell lines were established and PKCalpha expression characterized by Western blot and PKC activity assays. Invasion assays including barrier migration (Koochekpour et al., Extracellular matrix proteins inhibit proliferation, upregulate migration and induce morphological changes in human glioma lines. Eur. J. Cancer, 1995, 31, 375-380; Merzak et al., CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res., 1994, 54, 3988-3992; Merzak et al., Cell surface gangliosides are involved in the control of human glioma cell invasion in vitro. Neurosci. Lett., 1994, 177, 11-16), and spheroid confrontation were used to study the relationship between PKCalpha expression and invasiveness. PKCalpha overexpressing clones show increased barrier migration (1.5x) relative to the control transfected clones. PKCalpha inhibited clones exhibited reduced invasiveness, to < 50%. In coculture with PKCalpha overexpressing clones, the remaining normal fetal rat brain aggregate volume was significantly decreased (up to 200%) but 90% of the initial brain volume was left in PKCalpha inhibited clone in the rat brain aggregate tumor spheroid confrontation. This effect was not associated with significant growth inhibition. We conclude that expression of PKCalpha in glioma-derived cell lines appears to be central to glioma invasion in vitro.

Animals↗

A case report of frosted branch angiitis and its visual electrophysiology.

We reported a 5-years old boy with frosted branch angiitis in both eyes. The visual acuities of the two eyes were suddenly lost to 5/50. The fluorescein angiography, electroretinograms (ERGs) and pattern evoked potentials (PVEPs) had been tested at the acute and the recovery stage of the disease. At the onset of the disease, fluorescein angiography showed obvious dye leakage from dilated retinal veins. The PVEPs and whole field ERGs including rod, maximum, OPs and cone responses were seriously decreased and prolonged, indicating that the visual pathway's and retinal functions were greatly damaged. The patient had an excellent response to systemic prednisone. One month after the treatment, the visual acuities recovered to 60/50 in both eyes. The fluorescein angiography showed that leakage from blood vessels was diminished, but the lesions at macula and optic disc were persisted a longer time even to the end of treatment. Through 6 months medication, nearly all of the electrophysiological abnormalities had been resolved.

Administration, Oral↗

Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor-alpha in human aortic smooth muscle and embryonic kidney cells.

NADPH oxidases are important sources of vascular superoxide, which has been linked to the pathogenesis of atherosclerosis. Previously we demonstrated that the Nox4 subunit of NADPH oxidase is a critical catalytic component for superoxide production in quiescent vascular smooth muscle cells. In this study we sought to determine the role of Nox4 in superoxide production in human aortic smooth muscle cells (AoSMC) and embryonic kidney (HEK293) cells under proinflammatory conditions. Incubation with tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml) for 12 h increased superoxide production in both cell types, whereas angiotensin II, platelet-derived growth factor or interleukin-1beta had little effects. Superoxide production was completely abolished by the NADPH oxidase inhibitors diphenyline iodonium and apocynin, but not by inhibitors of xanthine oxidase, nitric oxide synthase or mitochondrial electron transport. TNF-alpha upregulated the expression of Nox4 in AoSMC at both message and protein levels, while Nox1 and Nox2 were unchanged. In contrast, upregulation of Nox2 appeared to mediate the enhanced superoxide production by TNF-alpha in HEK293 cells. We suggest that Nox4 may be involved in increased superoxide generation in vascular smooth muscle cells under proinflammatory conditions.

Angiotensin II↗

A study of the purine derivative AIT-082 in G93A SOD1 transgenic mice.

AIT-082 is a purine derivative with neuroprotective and neurotrophic activity that is desirable in a candidate therapy for Amyotrophic Lateral Sclerosis. Consequently, we investigated the effect of AIT-082 in a transgenic mouse model of ALS. AIT-082 (0, 1, 3, 10, 30, 60, 100 mg/kg) was given to TgN(SOD1-G93A)1Gur transgenic mice from age 30 days until death. The age at onset of clinical signs of disease and the age at death were recorded for each animal. Disease progression was measured by the weekly average distance run in a running wheel. Analysis was made by the Kaplan Meier method with log rank statistics, log rank for trend and Cox regression. Neuropathological study of the brain, spinal cord, muscles and other organs was undertaken at death. In a second experiment we studied the effect of AIT-082 (30 mg/kg) at the onset of disease and during survival of transgenic G93A SOD1 mice, beginning dosing at different ages (20, 30, 40, 60, 80 days). Disease onset was mildly earlier (i.e. worse) at 1 and 10 mg/kg AIT-082 and mildly delayed at 30 mg/kg. This improvement did not reach the usual statistical significance. There was no difference in the age at death for any treatment dose. There was no difference in the neuropathology of treated and untreated G93A mice. However, there was an early improvement in the running wheel function at all tested doses. Using Cox regression, after adjustment for sex, the mice in the running wheels had slightly delayed onset of disease without change in survival and, after adjustment for exercise, the female mice had slightly improved survival. Consequently, AIT-082 would not be an attractive candidate for ALS clinical trials as monotherapy and justification for its use in combination therapy would require additional laboratory support. There was dissociation between the endpoints of disease progression (as judged by running wheel performance) and disease onset and survival. AIT-082 improved early running wheel performance yet led to accelerated late decline and had no impact on survival. It is possible that the drug facilitates early sprouting that leads to accelerated late decline.

Aminobenzoates↗

Risk factors for anatomical success and visual outcome in patients undergoing silicone oil removal.

PURPOSE: To define risk factors for anatomical success and visual outcome in patients undergoing removal of silicone oil. METHODS: This retrospective study included patients who had silicone oil removed at this hospital between 1996 and 2000. All were followed for at least six months. Patients with recurrent retinal detachment after silicone oil removal were compared with patients without this complication. We also compared patients whose vision improved or stabilized with patients whose vision deteriorated. Risk factors for anatomical success and visual outcome were identified. RESULTS: We analysed 94 eyes of 92 patients with silicone oil removal. Nineteen eyes (20%) had recurrent retinal detachment, and in 30 eyes (32%), the vision deteriorated after removal of the oil. Initial vision less than ambulatory vision, initial pathology of giant retinal tears and recurrent retinal detachment, postoperative hypotony and postoperative epiretinal membrane occurred more frequently in eyes with than without recurrent retinal detachment. Pre- and postoperative hypotony, postoperative epiretinal membranes and postoperative recurrent retinal detachment were also more frequent in eyes with deteriorated vision. CONCLUSIONS: When treating giant retinal tears or recurrent retinal detachments with silicone oil tamponade, surgeons and their patients need to be aware of the higher possibility of unfavorable results, particularly when the initial vision is less than ambulatory vision. The presence of risk factors before and after silicone oil removal should remind surgeons of the higher risk profile of this particular surgery.

Adolescent↗