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Biomedical subjects

S Hu

Publications and source records attributed to S Hu.

At least 253 records · Page 14Linked to original sources
PubMed1997

Effects of spatial frequency of a vertically striped rotating drum on vection-induced motion sickness.

PURPOSE: The present study investigated the effects of differential spatial frequencies of a vertically striped, horizontally rotating drum on the observer's frequency of eye nystagmus, perceived velocity of self-motion, and symptoms of motion sickness. METHODS AND RESULTS: Two experiments were conducted. In Experiment 1, each of 10 subjects viewed 1 min of an optokinetic rotating drum at the speed of 10 rpm covered with 6, 12, 24, 48, and 96 pairs of black and white stripes, presented in counterbalanced order. The results indicated that subjects perceived significantly stronger circular vection (p < 0.05) and generated significantly higher frequencies of eye nystagmus (p < 0.05) when they were viewing 24 pairs of black and white stripes than when they were viewing any of the other combinations of 6, 12, 48, or 96 black and white stripes. In Experiment 2, 100 highly susceptible subjects viewed 16 min of an optokinetic rotating drum covered with one of the five different numbers of black and white stripe pairs: 6, 12, 24, 48, and 96. The results indicated that subjects in the group viewing 24 moving contrasts perceived significantly stronger circular vection (p < 0.001), reported significantly more severe symptoms of motion sickness (p < 0.001), and showed significantly greater ratios of EGG 4-9 cycles per minute spectral intensity between drum rotation and baseline periods (p < 0.004) than those in the groups of viewing 6, or 96 moving contrasts. CONCLUSION: These results demonstrated that the severity of vection-induced motion sickness is affected by differential spatial frequencies of the stripes of the rotating drum and may be affected by number of horizontal eye movements.

Adolescent↗
PubMed1997

Activation of mu opioid receptors inhibits microglial cell chemotaxis.

Opiates modulate many macrophage functions. Microglia, the resident macrophages of the brain, migrate to sites of inflammation within the CNS. Using primer sets designed to span the entire open reading frame of the human brain mu opioid receptor (MOR), we found that microglial cells constitutively expressed MOR mRNA. The cDNA sequences of the MOR open reading frame in microglia were identical to those of human brain tissue. Using enriched human fetal microglial cell cultures, we found that morphine potently inhibited the directed migration (chemotaxis) of microglial cells toward C5a in a dose-dependent manner with an IC50 value of 1 fM morphine. We also found that DAMGO, a selective MOR ligand, dose-dependently suppressed microglial cell chemotaxis with an IC50 value of 1 nM, which was significantly attenuated by 10 nM beta-funaltrexamine. Taken together, these findings suggest that activation of constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the brain.

Base Sequence↗
PubMed1997

Immunomodulatory role of opioids in the central nervous system.

Endogenous opioid peptides play a variety of roles in the central nervous system (CNS) from development to immune modulation. These functions are mediated mostly via specific opioid receptors uniquely localized in different brain regions and cells. Exogenous opioids can influence and modulate neuronal and glial cell function via an opioid receptor mediated mechanism, leading to either protection or damage of the brain. Mechanisms underlying CNS opioid effects may be mediated via immune mediators, such as cytokines, beta-chemokines, and free radicals (i.e. reactive oxygen intermediates (ROI) and nitric oxide (NO)) produced by activated glial cells (microglia and astrocytes). In the pathogenesis of HIV-1 infection in drug addicts, opiates such as morphine have been postulated to promote the progression of this virus and the development of secondary opportunistic infections. Kappa opioid receptor (KOR) ligands, on the other hand, may play a neuroprotective role. Differences in species, age, sex, cell culture system, stimuli, opioid administration route, concentrations used, strain of infectious agents, and treatment regimes have contributed to many conflicting results in the field of opioid research. More studies are needed to delineate how opioids exert their effects on glial cells as well as neurons with the goal of finding new therapeutic approaches for neurodegenerative diseases, such as AIDS dementia.

Adjuvants, Immunologic↗
PubMed1997

Color Doppler imaging diagnosis of intra-ocular tumor.

OBJECTIVE: To demonstrate the color Doppler imaging (CDI) of intra-ocular tumors and its importance in the diagnosis of these tumors. METHODS: Ninety-two patients with intra-ocular tumors (105 eyes) were examined by using CDI to observe the vasculature of these tumors, and using SAS soft ware to analyze the results. RESULTS: Blood flow signal was found in retinoblastoma, melanoma of choroid, angioma of choroid, angioma of optic disc, Coats' disease, persistent hyperplastic primary vitreous (PHPV) and metastatic tumors of choroid, but not found in choroid osteoma and melanocytoma of optic disc. The blood flow decreases in central retinal artery in choroidal melanoma and also in ophthalmic artery, central retinal artery and posterior ciliary artery in angioma of choroid (P < 0.01). It was found that blood velocity is much faster in choroidal melanoma than in choroidal angioma (P < 0.05). CONCLUSIONS: CDI is very important and helpful in the diagnosis of intra-ocular tumors.

Adolescent↗
PubMed1997

Inhibition of vascular smooth muscle cell proliferation by introduction of retinoblastoma gene via a recombinant adenovirus vector.

OBJECTIVE: To investigate the vascular smooth muscle cell (SMC) growth suppression by recombinant adenovirus vector expressing a retinoblastoma (Rb) protein and to explore a gene therapy approach for vascular proliferative disorders including atherosclerosis and artery restenosis. METHODS: A replication-deficient adenovirus vector encoding a wild-type Rb and AdCMVRb, was constructed and transfected into cultured rabbit aortic SMC. The efficiency of gene transfection and expression was detected by immunochemical staining and polymerase chain reaction. The role of Rb in regulating vascular SMC proliferation was observed by cell-counting, [3H] thymidine incorporation, and flow cytometry. RESULTS: Wild-type Rb gene transfected effectively into the cultured SMC with AdCMVRb can suppress growth factor-stimulated cell proliferation through regulation of DNA synthesis and cell cycle progression. CONCLUSION: The results demonstrate the potential of adenovirus-mediated Rb gene therapy for atherosclerosis and artery restenosis after balloon angioplasty.

Adenoviruses, Human↗
PubMed1997

[The relationship between concentration of growth hormone in serum and microangiopathy in patients with diabetes mellitus].

OBJECTIVE: To study the relationship between growth hormone (GH) and microangiopathy in patients with diabetes mellitus in order to elucidate pathogenesis on microangiopathy in diabetics. METHODS: GH and insulin (INS) were detected by rdioimmunoassay, and blood sugar (BS) was detected by oxydase method. RESULTS: 138 NIDDM diabetics were examined. The concentration of serum GH in diabetics without microangiopathy (2.3 +/- 1.2 micrograms/L) was higher than in normal people (1.0 +/- 1.2 micrograms/L) and GH in diabetics with microangiopathy (5.74 +/- 1.94 micrograms/L) was higher than in diabetics without microangiopathy. The differences were significant (P < 0.01). As the history of diabetes went on, the level of GH in serum increased, and the incidence of microangiopathy increased too. The correlation of GH in serum with BS was parallel. The correlation of GH in serum with INS was not apparent. 27 ID-DM diabetics were examined, their level of GH in serum (6.8 +/- 3.4 micrograms/L) was higher than that of NIDDM diabetics (4.6 +/- 1.8 micrograms/L). They were all patients with microangiopathy. CONCLUSION: The rise of GH in serum may be an important pathogeny that causes microangiopathy in diabetics.

Adult↗
PubMed1997

[The effect of wuto granules on the levels of excitatory amino acids in extracellullar fluid of rat hippocampus following cerebral ischemia].

We observed the changes of excitatory amino acids (EAA) in extracellular fluid (ECLF) in rat hippocampus in case of cerebral ischemia after giving Wuto Granule compring the test groups with the control groups by microdialysis method. Results showed that there was no effect on EAA in extrcellular fluid by the drug before cerebral ischemia, but there existed staistical singnifcant changes of EAA in extracellular fluid one hour after cerebral ischemia comparing the test groups Glu and Asp with the control groups (P < 0.01). We found that there is a decrease of release of release of EAA in ECLF in case of ischemia by Wuto Granule. It could be deduced that Wuto Granule can penetrate the brain-blood barrier and this can protect the brain incse of ischemia. The application of intracerebral micrdialysis has provided a new method for the research work of pharmacology.

Animals↗
PubMed1997

[A preliminary evaluation on transcranial Dopplor ultrasonic scanning for differentiation of symptoms and signs in patients with ganyang shangkangzheng].

Intracranial main artery of Ganyang Shangkangzheng and its related syndrome were determined by Transcranial Doppler (TCD) Ultrasonography. The results showed that the blood flow speed in the mid-cerebral artery of 32 cases with Ganyang Shangkangzheng was obviously higher than that of the healthy group, Ganhuo Shangyan group and Gan-shenyinxu group, similar change was found in three kinds of parameters in the blood flow speed. Therefore, the results suggest that TCD in determinating the blood flow speed of middle cerebral artery can be thought as one of the diagnostic assays in differentiation of symptom and sign of Ganyang Shangkangzheng.

Adult↗
PubMed1996

On the mechanism of the differential effects of NS004 and NS1608 in smooth muscle cells from guinea pig bladder.

Our recent study revealed that the reported BK(Ca) channel openers NS004 (5-trifluoromethyl-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-2H-benzimidazo le-2-one) and its analog NS1608 (N-(3-(trifluoromethyl)phenyl)-N'-(2-hydroxy-5-chlorophenyl)urea) produced a differential pattern of action on the BK(Ca) channel in porcine coronary arterial cells (Hu, S., H.S. Kim and C.A. Fink, 1995, Differential effects of the BK(Ca) channel openers NS004 and NS1608 in porcine coronary arterial cells, Eur. J. Pharmacol. 294, 357). In this study, using the patch-clamp method on the smooth muscle cells from guinea pig bladder detrusor, the activity profile of NS004 and NS1608 on the whole-cell BK(Ca) current (I(BK)) was examined and found to be similar to that in coronary arterial cells. NS004 did not significantly modify I(BK) at concentrations below 5 microM, but robustly augmented I(BK) at concentrations greater than 20 microM. With a minimum effective concentration of 0.5 microM, NS1608 caused potentiation of I(BK) with a bell-shaped concentration-response relationship. The activation was maximized between 5-10 microM and substantially attenuated at higher concentrations. The behavior of single BK(Ca) channels in the presence of NS004 and NS1608 was scrutinized to elucidate the mechanism underlying their distinct patterns of action. The channel open-state probability (NPo) was increased by NS004 at 0.5, 5 and 50 microM to a respective 1.75 +/- 0.38, 4.05 +/- 0.90, and 15.01 +/- 3.66 fold (n = 7) of the control by increasing the open time and the frequency of opening while having no effect on the single BK(Ca) channel conductance. NS1608 at 0.5 and 5 microM increased NPo to 1.69 +/- 0.43 and 18.03 +/- 6.64 fold of the control (n = 4), respectively. NS1608 at higher concentrations repeatedly blocked channel openings as evidenced by the highly flickering open state, though the overall open time and frequency of opening remained high. The diminished activation of I(BK) by 50 microM NS1608 manifested therefore a net result of these two opposing actions on the single channels. Thus, the two structurally related BK(Ca) channel openers interact distinctly with the channel gating components.

Animals↗
PubMed1996

Artificial neural networks aided deconvolving overlapped peaks in chromatograms.

A novel method for deconvolving overlapped peaks in chromatograms is proposed. The basic idea of this method consists of finding a set of parameters which characterize the shape of the overlapped peaks and using a multi-layered perceptron network for quantitatively correlating the parameters with the percentage area of an individual peak. The proposed method performs very well with high accuracy and less computing time compared to other conventional methods.

Chromatography↗
PubMed1996

In vitro and in vivo evaluation of an endothelin inhibitor reveals novel K+ channel opening activity.

A low molecular weight endothelin (ET-1) inhibitor (Ex. 127, European Patent Application 404 525 A2, Takeda Chemical Ind., 1991), CGS 26061, was synthesized and evaluated to determine its mechanism of action. CGS 26061 (10 microM) failed to inhibit binding of [125I]ET-1 in porcine thoracic aorta and was without effect on ET-1-induced [3H]inositol phosphate accumulation in A7r5 cells. However, CGS 26061 relaxed porcine coronary arterial rings precontracted with ET-1. In addition, contractions to PGF2 alpha and low K+ (20 mM) but not high K+ were attenuated, suggesting that CGS 26061 (1, 10 microM) is a potassium channel opener. Patch-clamp experiments confirmed the K+ channel activity (0.1-10 microM). The originally re ported inhibition of ET-1-induced pressor responses by Ex. 127 (CGS 26061) was not replicated in the anesthetized dog or conscious rat nor was it shown to be antihypertensive in SHR. These data have identified CGS 26061 as a novel K+ channel opener with a unique cardiovascular profile.

Animals↗
PubMed1996

ErbB receptor activation, cell morphology changes, and apoptosis induced by anti-Her2 monoclonal antibodies.

A panel of mAbs were generated against the purified soluble form of erbB2/Her2 receptor, corresponding to the extracellular region of the receptor, and examined for their ability to mimic the receptor ligand. Some of the mAbs strongly induced tyrosine phosphorylation of 180-185 kDa proteins, including not only Her2 but also Her3 and Her4 receptors, when they were expressed on the surface of breast cancer cells. These mAbs do not cross-react with Her3 or Her4 as demonstrated by competition study. Receptor phosphorylation was also observed with the cell lines transfected with Her2 or a chimeric receptor consisting of the extracellular domain of Her2 and the transmembrane and cytoplasmic domains of epidermal growth factor receptor. Selected mAbs were tested for their ability to change cell morphology, and one specific mAb, mAb74, induced cell morphology changes and apoptosis.

Animals↗
PubMed1996

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

Microglial cells, the resident macrophages of the brain, play an important role in the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1), and recent studies suggest that opioid peptides regulate the function of macrophages from somatic tissues. We report herein the presence of kappa opioid receptors (KORs) in human fetal microglia and inhibition of HIV-1 expression in acutely infected microglial cell cultures treated with KOR ligands. Using reverse transcriptase-polymerase chain reaction and sequencing analyses, we found that mRNA for the KOR was constitutively expressed in microglia and determined that the nucleotide sequence of the open reading frame was identical to that of the human brain KOR gene. The expression of KOR in microglial cells was confirmed by membrane binding of [3H]U69,593, a kappa-selective ligand, and by indirect immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593 resulted in a dose-dependent inhibition of expression of the monocytotropic HIV-1 SF162 strain. This antiviral effect of the kappa ligands was blocked by the specific KOR antagonist, nor-binaltrophimine. These findings suggest that kappa opioid agonists have immunomodulatory activity in the brain, and that these compounds could have potential in the treatment of HIV-1-associated encephalopathy.

Analgesics↗
PubMed1996

Minibody: A novel engineered anti-carcinoembryonic antigen antibody fragment (single-chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts.

A novel engineered antibody fragment (VL-VH-CH3, or "minibody") with bivalent binding to carcinoembryonic antigen (CEA) was produced by genetic fusion of a T84.66 (anti-CEA) single-chain antibody (scFv) to the human IgG1 CH3 domain. Two designs for the connecting peptide were evaluated. In the T84.66/212 LD minibody, a two-amino acid linker (generated by fusion of restriction sites) was used to join VH and CH3. In the T84.66/212 Flex minibody, the human IgG1 hinge plus an additional 10 residues were used as the connecting peptide. Size exclusion chromatography of purified minibodies demonstrated that both proteins had assembled into Mr80,000 dimers as expected. Furthermore, analysis by SDS-PAGE under nonreducing conditions was consistent with disulfide bond formation in the hinge of the T84.66 Flex minibody. Purified minibodies retained high affinity for CEA (KA, 2 x 10(9) M(-1)) and demonstrated bivalent binding to antigen. Tumor targeting properties were evaluated in vivo using athymic mice bearing LS174T human colon carcinoma xenografts. 123I-labeled T84.66 minibodies demonstrated rapid, high tumor uptake, reaching 17% injected dose/gram (%ID/g) for the LD minibody and 33%ID/g for the Flex minibody at 6 h following injection. Radioiodinated minibody also cleared rapidly from the circulation, yielding high tumor:blood uptake ratios: 44.5 at 24 h for the LD minibody and 64.9 at 48 h for the Flex minibody. Rapid localization by the T84.66/212 Flex minibody allowed imaging of xenografts at 4 and 19 h after administration.

Animals↗
PubMed1996

GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF.

We report the expression cloning and characterization of GDNFR-alpha, a novel glycosylphosphatidylinositol-linked cell surface receptor for glial cell line-derived neurotrophic factor (GDNF). GDNFR-alpha binds GDNF specifically and mediates activation of the Ret protein-tyrosine kinase (PTK). Treatment of Neuro-2a cells expressing GDNFR-alpha with GDNF rapidly stimulates Ret autophosphorylation. Ret is also activated by treatment with a combination of GDNF and soluble GDNFR-alpha in cells lacking GDNFR-alpha, and this effect is blocked by a soluble Ret-Fc fusion protein. Ret activation by GDNF was also observed in cultured embryonic rat spinal cord motor neurons, a cell type that responds to GDNF in vivo. A model for the stepwise formation of a GDNF signal-transducing complex including GDNF, GDNFR-alpha, and the Ret PTK is proposed.

Amino Acid Sequence↗
PubMed1996

The Drosophila melanogaster similar bHLH-PAS gene encodes a protein related to human hypoxia-inducible factor 1 alpha and Drosophila single-minded.

The Drosophila melanogaster (Dm) similar (sima) gene was isolated using a low-stringency hybridization screen employing a Dm single-minded gene basic helix-loop-helix (bHLH) DNA probe. sima is a member of the bHLH-PAS gene family and the conceptual protein shares a number of structural features, including a bHLH domain, PAS domain, and homopolymeric amino acid stretches. Sima is most closely related to the human hypoxia-inducible factor 1 alpha bHLH-PAS protein. In situ hybridization experiments reveal that sima is transcribed in most or all cells throughout embryogenesis. It has been cytologically mapped to position 99D on the third chromosome, and is not closely linked to other known bHLH-PAS genes.

Amino Acid Sequence↗
PubMed1996

Arylacetamide-derived fluorescent probes: synthesis, biological evaluation, and direct fluorescent labeling of kappa opioid receptors in mouse microglial cells.

Fluorescein isothiocyanate isomer I (FITC-I) conjugates of 2-(3,4-dichlorophenyl)-N-methyl-N-[1-(3- or 4-aminophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (10 and 14) were prepared either without or with an intervening mono-, di-, or tetraglycyl linker. The 3-substituted fluorescent probes (2-5) were found to retain potent agonist activity in smooth muscle preparations as well as high kappa receptor affinity and selectivity in receptor binding assays. The 4-substituted series (6-9) were substantially less potent than the corresponding 3-substituted compounds. Flow cytometric analysis demonstrated high levels of direct kappa-specific staining of mouse microglial cells by the fluorescent probe 5 containing a tetraglycyl linker, as indicated by a 41% decrease in percent cells positively labeled and a 61% decrease in mean fluorescence intensity in the presence of the kappa-selective antagonist, norbinaltorphimine (norBNI). In similar studies, the probe 2 without a linker exhibited only nonspecific binding. This is the first report of direct, selective staining of kappa opioid receptors by a fluorescent nonpeptide opioid ligand. The results of the present study illustrate the importance of introducing hydrophilic linkers to reduce nonspecific binding of fluorescent probes for opioid receptors.

Acetamides↗