Search PubMed⌕ Search

Biomedical subjects

L Hu

Publications and source records attributed to L Hu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Samarium(0) and 1,1'-dioctyl-4,4'-bipyridinium dibromide: a novel electron-transfer system for the chemoselective reduction of aromatic nitro groups.

A mild and efficient electron-transfer method was developed for the chemoselective reduction of aromatic nitro groups using samarium(0) metal in the presence of a catalytic amount of 1,1'-dioctyl-4,4'-bipyridinium dibromide. This method was found to give the product aromatic amine in 79-99% yield with selectivity over a number of other functional and protecting groups such as alkene, azide, benzyl ether, nitrile, amide, halide, p-toluenesulfonamide, t-Boc, tert-butyldiphenylsilyl ether, and aliphatic nitro groups. Our results also indicate that samarium(0) plays an important role in the reduction process and that 1,1'-dioctyl-4,4'-bipyridinium dibromide acts as an electron-transfer catalyst and is essential in the activation of samarium(0) metal. The major active reducing agent responsible for the reduction is believed to be the radical cation species formed from 1,1'-dioctyl-4,4'-bipyridinium dibromide.

Journal Article↗
PubMed2001

Conformational origin of the aggregation of recombinant human factor VIII.

Aggregation of proteins is a major problem in their use as drugs and is also involved in a variety of pathological diseases. In this study, biophysical techniques were employed to investigate aggregate formation in the pharmaceutically important protein, recombinant human factor VIII (rhFVIII). Recombinant human factor VIII incubated in solution at 37 degrees C formed soluble aggregates as detected by molecular sieve chromatography and dynamic light scattering. This resulted in a corresponding loss of biological activity. Fluorescence and CD spectra of the thermally stressed rhFVIII samples did not, however, suggest significant differences in protein conformation. To identify conformational changes in rhFVIII that may be involved in rhFVIII aggregation, temperature and solutes were used to perturb the native structure of rhFVIII. Far-UV CD and FTIR studies of rhFVIII as a function of temperature revealed conformational changes corresponding to an increase in intermolecular beta-sheet content beginning at approximately 45 degrees C with significant aggregation observed above 60 degrees C. Fluorescence and DSC studies of rhFVIII also indicated conformational changes initiating between 45 and 50 degrees C. An increase in the exposure of hydrophobic surfaces was observed beginning at approximately 40 degrees C, as monitored by increased binding of the fluorescent probe, bis-anilinonaphthalene sulfonic acid (bis-ANS). Perturbation by various solutes produced several transitions prior to extensive unfolding of rhFVIII. In all cases, a common transition, characterized by an increase in the wavelength of the fluorescence emission maximum of rhFVIII from approximately 330 to 335 nm, was observed during thermal and solute perturbation of factor VIII. Moreover, this transition was correlated with an increased association of factor VIII upon incubation at 37 degrees C in the presence of various solutes. These results suggest that association of rhFVIII in solution was initiated by a small transition in the tertiary structure of the protein which produced a nucleating species that led to the formation of inactive soluble aggregates.

1-Propanol↗
PubMed2001

Transforming growth factor beta in experimentally detached retina and periretinal membranes.

This study was undertaken to determine whether experimental retinal detachment produces changes in retinal localization of three isoforms of transforming growth factor beta (TGF-beta) and the type II receptor for this protein. Neural retinas of young adult cats were detached from the pigment epithelium. Survival times varied from 3 to 28 days to study the temporal course of TGF-beta localization during retinal degeneration. ELISA assay for TGF-beta1 and -beta2 was performed on samples of fluid from the vitreous chamber to determine whether active or inactive TGF-beta was present. Confocal microscopy was used to localize TGF-beta1, -beta2 and -beta3 and the type II TGF-beta receptor at the various detachment durations. Following experimental retinal detachment the levels of TGF-beta2 increased in the vitreous chamber but no changes in TGF-beta1 were detected. Levels were increased 3 days post-detachment and continued throughout the 28 day period studied. The most prominent changes in immunolocalization occurred in the TGF-beta1 and -beta2 isoforms. Increased immunolabeling was seen in Müller cells and ganglion cell bodies. Hypertrophied Müller cell processes formed periretinal membranes that were heavily labeled by the TGF-beta2 antibody. Some increased immunostaining for TGF-beta3 was observed in the ganglion cell bodies. Labeling for the TGF-beta type II receptor was seen in Müller cells, ganglion cells and the inner and outer plexiform layers in both normal and detached retinas. Changes in localization of the receptor after detachment paralleled the changes seen in TGF-beta protein localization. These results demonstrate that retinal detachment induces the synthesis and secretion of TGF-beta2. Growth factor and receptor immunolabeling were increased in Müller cells suggesting that this isoform is involved in the retinal gliotic response and may contribute to the development of proliferative vitreoretinopathy.

Animals↗
PubMed2001

New glycosphingolipid containing an unusual sphingoid base from the basidiomycete Polyporus ellisii.

A new 9-methyl-sphinga-4,8-dienine-containing glucocerebroside (1), together with two additional known analogs, cerebrosides B and D, was isolated from the chloroform-soluble lipid fraction of the ethanol and chloroform/methanol extract of the fruiting bodies of the basidiomycete Polyporus ellisii Berk. and characterized. The structure and relative stereochemistry of the new compound were identified as (2S,3R,4E,8E-1-(beta-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxyheptadecanoyl]amino-9-methyl-4,8-octadecadiene by means of spectroscopic (1H,13C, and two-dimensional nuclear magnetic resonance; mass spectrometry) and chemical methods.

Alkanes↗
PubMed2001

Role of abnormal nitric oxide systems in salt-sensitive hypertension.

A large percentage of human hypertensive patients are salt sensitive, referring to the dependence of hypertension on sodium intake, but the cause of the salt sensitivity is not known. Although several mechanisms may contribute to salt-sensitive hypertension, the nitric oxide (NO) system appears to play a major role. Studies in humans and Dahl salt-sensitive (S) rats indicate that NO production is decreased during hypertension. Intravenous L-arginine infusion in Dahl S rats increases NO production and prevents salt-sensitive hypertension. In the Dahl salt-resistant (R) rat, NO production by both inducible NO synthase (iNOS) and neuronal NOS (nNOS) help to prevent salt-sensitive hypertension. Experimental evidence is summarized, indicating that the Dahl S rat has a deficient production of NO by nNOS, although NO production by iNOS appears to moderately decrease salt sensitivity. Other evidence about the importance of NO in salt-sensitive hypertension is reviewed, including the role of the renal NO system.

Animals↗
PubMed2001

Campylobacter jejuni--microtubule-dependent invasion.

Campylobacter jejuni is the leading bacterial cause of food-borne illness worldwide and a major cause of Guillain-Barré paralysis. Recent molecular and cellular studies of one well-characterized C. jejuni strain have begun to unravel the details of an unusual microtubule-dependent (actin-filament-independent) gut-invasion mechanism, through which at least some C. jejuni initiate disease. Although responsible for causing a human dysenteric syndrome remarkably similar to that triggered by Shigella spp., current evidence suggests that C. jejuni use some markedly different molecular mechanisms of pathogenesis compared with shigellae.

Campylobacter Infections↗
PubMed2001

Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP.

Dentinogenesis imperfecta 1 (DGI1, MIM 125490) is an autosomal dominant dental disease characterized by abnormal dentin production and mineralization. The DGI1 locus was recently refined to a 2-Mb interval on 4q21 (ref. 1). Here we study three Chinese families carrying DGI1. We find that the affected individuals of two families also presented with progressive sensorineural high-frequency hearing loss (gene DFNA39). We identified three disease-specific mutations within the dentin sialophosphoprotein gene (DSPP) in these three families. We detected a G-->A transition at the donor-splicing site of intron 3 in one family without DFNA39, a mutation predicted to result in the skipping of exon 3. In two other families affected with both DGI1 and DFNA39, however, we identified two independent nucleotide transversions in exons 2 and 3 of DSPP, respectively, that cause missense mutations of two adjacent amino-acid residues in the predicted transmembrane region of the protein. Moreover, transcripts of DSPP previously reported to be expressed specifically in teeth are also detected in the inner ear of mice. We have thus demonstrated for the first time that distinct mutations in DSPP are responsible for the clinical manifestations of DGI1 with or without DFNA39.

Asian People↗
PubMed2001

Sequence verification as quality-control step for production of cDNA microarrays.

To generate cDNA arrays in our core laboratory, we amplified about 2300 PCR products from a human, sequence-verified cDNA clone library. As a quality-control step, we sequenced the PCR products immediately before printing. The sequence information was used to search the GenBank database to confirm the identities. Although these clones were previously sequence verified by the company, we found that only 79% of the clones matched the original database after handling. Our experience strongly indicates the necessity to sequence verify the clones at the final stage before printing on microarray slides and to modify the gene list accordingly.

Gene Library↗
PubMed2001

Comparative evaluation of laser-based microarray scanners.

Laboratories use different laser-based scanners to scan microarray images. To assess whether results from different scanners are comparable, and thus whether data from different laboratories can be compared, we scanned the same microarray slide with three commercial scanners that use different imaging techniques. After the acquisition of the microarray images produced by the three scanners, the images were quantified using a single imaging software package and protocol. The results were compared, and we found that the data obtained from the three scanners were comparable and that the variations caused by the use of different instruments were negligible, in spite of the fact that the scanners were based on different optical imaging techniques.

Carbocyanines↗
PubMed2001

Thrombin induces increased expression and secretion of VEGF from human FS4 fibroblasts, DU145 prostate cells and CHRF megakaryocytes.

Angiogenesis is required for tumor growth and metastasis. It has recently been suggested that thrombin is a potent promoter of angiogenesis. We therefore examined the possibility that thrombin could be inducing the expression of vascular endothelial growth factor (VEGF), which promotes endothelial growth. Primary human FS4 fibroblasts as well as tumor cell lines: prostate DU145 and megakaryocyte CHRF were incubated with thrombin (0.25-1 unit/ml) for 1-8 hrs and then examined for mRNA by Northern Analysis. Enhanced mRNA (approximately 3-4 fold over base line) was noted at 2-4 hrs, with 0.5 u/ml thrombin. The effect was specific for thrombin activity on its PAR-1 receptor, since equal units of hirudin completely inhibited the response and the thrombin effect could be mimicked with the 14 mer thrombin receptor activation peptide (TRAP). Upregulation of mRNA was associated with enhanced VEGF protein synthesis and secretion as assayed by immunoblot. Enhanced expression of VEGF mRNA was not secondary to enhanced transcription (nuclear run on experiments), but due to an >3 fold stabilization of mRNA (Actinomycin D chase experiment). Enhanced VEGF mRNA stabilization is promoted by the PI3Kinase and serine/threonine kinase pathways, since thrombin-induced mRNA expression is inhibited by Wortmanin and H7. No effect was noted with the MAPKinase inhibitor, PD98059. Thus, thrombin-induced tumorigenesis and metastasis is associated with enhanced VEGF protein synthesis and secretion via the stabilization of VEGF mRNA promoted by the PI3Kinase and serine/threonine kinase pathways. This could help explain how thrombin promotes angiogenesis.

Adenocarcinoma↗
PubMed2001

Regeneration of nNOS-containing nerve fibers in rat corpus cavernosum.

OBJECTIVE: To investigate the effect of cavernous nerve injury on the nNOS-containing nerve fibers in corpus cavernosum. METHODS: Thirty-three male Sprague Dawley (SD) rats were randomly divided into 3 groups: sham-operated controls (n = 5) underwent pelvic exploration without transection of the cavernous nerve; unilateral injury group (n = 14) had their cavernous nerve cut on one side; and bilateral injury group (n = 14) underwent neurotomy on both sides. Corpora cavernosa were harvested at the 3rd week and 6th month after surgery. nNOS-positive nerve fibers were examined with streptavidin-peroxidase immunohistochemistry techniques (SP method). RESULTS: After bilateral ablation, the nNOS-positive nerve fibers were significantly decreased at the 3rd week (17 +/- 4) and remained so at the 6th month (16 +/- 4). For the unilateral injury group, the nNOS-positive nerve fibers were similarly decreased on the side of the neurotomy at the 3rd week (18 +/- 6), but by the 6th month, the number increased significantly (61 +/- 9) and approximated the level on the contralateral side (81 +/- 13). CONCLUSION: Following unilateral cavernous nerve ablation in rats, nNOS-containing nerve fibers regenerate 6 months after surgery. This regeneration process does not occur in animals with bilateral cavernous nerve injury, suggesting that during radical pelvic surgery, the cavernous nerve has to be preserved at least on one side in order to maintain the capacity for penile erection.

Animals↗
PubMed2001

[Angiotensin II in rostral ventrolateral medulla mediates amino acids release from spinally projecting nerve terminals in the spinal cord].

Microdialysis in the intermediolateral column (IML) was employed to examine amino acids release induced by angiotensin II (ANG II) applied into the rostral ventrolateral medulla (RVLM). Microinjection of ANG II (100 pmol, n = 11) into the RVLM significantly increased (P < 0.01) the release of aspartate (from 4.75 +/- 1.01 to 8.90 +/- 2.28 pmol/20 microliters) and glutamate (from 18.99 +/- 8.64 to 73.88 +/- 29.26 pmol/20 microliters) in the spinal cord. The increase of glutamate release was significantly attenuated (P < 0.05) by pretreatment with losartan (10 nmol, n = 8) at the same RVLM site. Immunofluorescence double labeling combined with confocal microscopic observation demonstrated that 62%-91% of the glutamatergic neurons in the RVLM were double-labeled with AT1 receptors, supporting the view that ANG II-induced glutamate release in the spinal cord may arise from the AT1 receptor-containing glutamatergic spinally projecting neurons in the RVLM.

Angiotensin II↗
PubMed2001

[Invasive rhinocerebral aspergillosis occurred during myelosuppressive phase after chemotherapy: a case report and literature review].

OBJECTIVE: To report a case of invasive rhinocerebral aspergillosis (IRA) during myelosuppressive phase after chemotherapy and the treatment outcome. METHODS: A patient with acute non-lymphoblastic leukemia (M(2a)) occurred IRA during myelosuppressive phase after chemotherapy and was treated with amphotericin B (AmB, including AmB-L), garlicin, 5-flucytosine (5-FC), fluconazole, itraconazole, ketoconazole, econazole and griseofulvin with twice of cerebrotomy lesion resections and cerebral decompressions. RESULTS: Though the survival time of this patient is a little longer than the others, she finally died of uncontrolled infection. CONCLUSION: For most of the IRA, there remains no effective treatment. The best treatment is AmB in combination with surgical excision.

Adult↗
PubMed2001

[The influences upon the passive tensile of the masticatory muscles and ligaments by Herbst appliance under various bite reconstruction--a three dimensional finite element analysis].

OBJECTIVE: This study aimed to provide some biomechanical references for the clinical use and improvement of Herbst appliance. METHODS: The three-dimensional model of the 'Temporomandibular joint mandible Herbst appliance system' was set up by SUPER SAP software (version 9.3). On this model, the passive tensile in the masticatory muscles and ligaments were analyzed under various bit reconstruction designed according to specified advanced displacement and vertical bite opening. RESULTS: When Herbst appliance drove the mandible forward, there was not any tensile in the medial, lateral pterygoid and the collateral ligament, while the temporalis, the deep paret of masseter, the stylomandibular ligament, and the sphenomandibular ligament were passively drawn. Under various bite reconstruction, the passive tensile in the medial temporalis, the posterior temporalis, the stylomandibular ligament and the sphenomandibular ligament increased with the amount of the advancement of the mandible; The passive tensile in the posterior temporalis and the deep part of masseter increased with the amount of vertical bite opening of the mandible. CONCLUSION: The StL, SpL, PT and AT played an important role in functional reconstruction of mandible by Herbst. All five group of bite reconstruction (3-7 mm advancement, 4-2 mm vertical bite opening of the mandible) designed by this study can be selected in clinic according to the patient's capability of adaptation, the extent of malocclusion and the potential and direction of growth.

Finite Element Analysis↗
PubMed2001

[The influences of the stress distribution on the condylar cartilage surface by Herbst appliance under various bite reconstruction--a three dimensional finite element analysis].

OBJECTIVE: The distribution of stress on the surface of condylar cartilage was investigated. METHODS: Three-dimensional model of the 'Temporomandibular joint mandible Herbst appliance system' was set up by SUPER SAP software (version 9.3). On this model, various bite reconstruction was simulated according to specified advanced displacement and vertical bite opening. The distribution of maximum and minimum principal stress on the surface of condylar cartilage were computerized and analyzed. RESULTS: When Herbst appliance drove the mandible forward, the anterior condyle surface was compressed while the posterior surface was drawn. The trend of stress on the same point on the condyle surface was consistent in various reconstruction conditions, but the trend of stress on various point were different in same reconstruction conditions. CONCLUSION: All five groups of bite reconstruction (3-7 mm advancement, 4-2 mm vertical bite opening of the mandible) designed by this study can be selected in clinic according to the patient's capability of adaptation, the extent of malocclusion and the potential and direction of growth.

Cartilage, Articular↗
PubMed2000

EphB receptors interact with NMDA receptors and regulate excitatory synapse formation.

EphB receptor tyrosine kinases are enriched at synapses, suggesting that these receptors play a role in synapse formation or function. We find that EphrinB binding to EphB induces a direct interaction of EphB with NMDA-type glutamate receptors. This interaction occurs at the cell surface and is mediated by the extracellular regions of the two receptors, but does not require the kinase activity of EphB. The kinase activity of EphB may be important for subsequent steps in synapse formation, as perturbation of EphB tyrosine kinase activity affects the number of synaptic specializations that form in cultured neurons. These findings indicate that EphrinB activation of EphB promotes an association of EphB with NMDA receptors that may be critical for synapse development or function.

Animals↗
PubMed2000

An alternative interpretation of nanobacteria-induced biomineralization.

The reported isolation of nanobacteria from human kidney stones raises the intriguing possibility that these microorganisms are etiological agents of pathological extraskeletal calcification [Kajander, E. O. & Ciftçioglu, N. (1998) Proc. Natl. Acad. Sci. USA 95, 8274-8279]. Nanobacteria were previously isolated from FBS after prolonged incubation in DMEM. These bacteria initiated biomineralization of the culture medium and were identified in calcified particles and biofilms by nucleic acid stains, 16S rDNA sequencing, electron microscopy, and the demonstration of a transferable biomineralization activity. We have now identified putative nanobacteria, not only from FBS, but also from human saliva and dental plaque after the incubation of 0.45-microm membrane-filtered samples in DMEM. Although biomineralization in our "cultures" was transferable to fresh DMEM, molecular examination of decalcified biofilms failed to detect nucleic acid or protein that would be expected from growth of a living entity. In addition, biomineralization was not inhibited by sodium azide. Furthermore, the 16S rDNA sequences previously ascribed to Nanobacterium sanguineum and Nanobacterium sp. were found to be indistinguishable from those of an environmental microorganism, Phyllobacterium mysinacearum, that has been previously detected as a contaminant in PCR. Thus, these data do not provide plausible support for the existence of a previously undiscovered bacterial genus. Instead, we provide evidence that biomineralization previously attributed to nanobacteria may be initiated by nonliving macromolecules and transferred on "subculture" by self-propagating microcrystalline apatite.

Bacteria↗