Biomedical subjects

S He

Publications and source records attributed to S He.

At least 37 records · Page 2Linked to original sources

PubMed2001

The activation of synovial mast cells: modulation of histamine release by tryptase and chymase and their inhibitors.

Mast cells have been implicated as having pivotal roles in arthritis, but little is known of the processes leading to the activation of synovial mast cells or their potential for pharmacological control. We have investigated the ability of tryptase and chymase, and inhibitors of these major mast cell proteases to modulate the activation of mast cells from human synovial tissue. The tryptase inhibitor drug N-(1-hydroxy-2-naphthoyl)-L-arginyl-L-prolinamide hydrochloride (APC366) inhibited immunoglobulin E (IgE)-dependent histamine release in a dose-dependent manner, with about 70% inhibition being achieved at a dose of 300 microM. Histamine release stimulated by calcium ionophore A23187 was also inhibited by this compound. The chymase inhibitor chymostatin inhibited IgE-dependent histamine release by approximately 60% at 1 microg/ml. Tryptase at concentrations of 3.0 microg/ml and greater stimulated histamine release from synovial cells, which was dependent on catalytic activity, whereas chymase had little effect on these cells. The activation of mast cells by tryptase may represent an amplification process in the synovium. The mast cell stabilising properties of inhibitors of tryptase and chymase could be of therapeutic value in arthritis.

Calcimycin↗

PubMed2001

Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection.

Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201-restricted CTL response is directed towards the epitope SLYNTVATL ("SL9") in p17 Gag (residues 77-85). This epitope is targeted by 75% of HLA-A*0201-positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide-major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201-positive subjects with acute HIV-1 infection (P = 2 x 10(-6)), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201-positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates.

Acute Disease↗

PubMed2001

1,2,5-Thiadiazolidin-3-one 1,1 dioxide: a powerful scaffold for probing the S' subsites of (chymo)trypsin-like serine proteases.

The 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I) embodies a motif that allows it to dock to the active site of (chymo)trypsin-like proteases in a predictable and substrate-like fashion. Consequently, inhibitors derived from this heterocyclic scaffold interact with both the S and S' subsites of an enzyme. Exploitation of binding interactions with both the S and S' subsites of a target enzyme may lead to compounds with greatly enhanced enzyme selectivity and inhibitory potency. This preliminary report describes the use of a series of compounds having the heterocyclic scaffold linked to various amino acids to probe the S' subsites of human leukocyte elastase (HLE), proteinase 3 (PR 3), and cathepsin G (Cat G). For comparative purposes, a series of compounds derived from a related scaffold, isothiazolidin-3-one 1,1 dioxide (II), was also generated. Several of the compounds were found to be highly potent and selective time-dependent inhibitors of HLE, PR 3, and Cat G.

Cathepsin G↗

PubMed2001

Fast method for the localisation of current dipoles in the human brain.

A fast algorithm for localising multiple current dipoles in the human brain by measuring the external magnetic field is presented. A genetic algorithm is used first for rough estimate of locations. To speed up the global optimisation algorithm, an explicit solution for a spherical head model is used for the rough estimation. This rough estimate is then used as a start for a fine search using a gradient-based algorithm, in which a boundary element solution for a realistic brain-shaped head model is used. Numerical simulation indicates that the present algorithm converges three-four times faster than an algorithm using a brain-shaped head model in all the steps.

Algorithms↗

PubMed2001

Visual motion and the human brain: what has neuroimaging told us?

Recently, neuroimaging techniques have been applied to the study of human motion perception, complementing established techniques such as psychophysics, neurophysiology and neuropsychology. Because vision, particularly motion perception, has been studied relatively extensively, it provides an interesting case study to examine the contributions and limitations of neuroimaging to cognitive neuroscience. We suggest that in the domain of motion perception neuroimaging has: (1) revealed an extensive network of motion areas throughout the human brain, in addition to the well-studied motion complex (MT+); (2) verified and extended findings from other techniques; (3) suggested extensive top-down influences on motion perception; and (4) allowed experimenters to examine the neural correlates of awareness. We discuss these contributions, along with limitations and future directions for the neuroimaging of motion.

Attention↗

PubMed2001

Filling-in at the natural blind spot contributes to binocular rivalry.

The human natural blind spot is usually filled in based on the contextual information. When two sufficiently different images are presented to the two eyes, observers typically perceive an alternation between the two images (binocular rivalry). Both the filling-in process and binocular rivalry have been the subject of considerable research. This study investigates whether filled information in one eye's natural blind spot can contribute to binocular rivalry. A radial grating (D=12 degrees ) was presented to one eye, centered on the natural blind spot. Observers perceived a complete figure in monocular view; the blind spot area was filled-in based on the surrounding information. Simultaneously, a circular grating smaller than the blind spot (D=4 degrees ), was presented to the fellow eye in the region corresponding to the other eye's blind spot. The amount of rivalry as indexed by how often the smaller circular grating remained visible was measured. The results suggest that the filled information in the area of the blind spot does contribute to the rivalry process.

Humans↗

PubMed2001

Inhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.

A challenge associated with drug design is the development of selective inhibitors of proteases (serine or cysteine) that exhibit the same primary substrate specificity, that is, show a preference for the same P(1) residue. While these proteases have similar active sites, nevertheless there are subtle differences in their S and S' subsites which can be exploited. We describe herein for the first time the use of functionalized sulfonamides as a design and diversity element which, when coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold yields potent, time-dependent inhibitors of the serine proteases human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G(Cat G). Our preliminary findings suggest that (a) appending to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold recognition and diversity elements that interact with both the S and S' subsites of a target protease may result in optimal enzyme selectivity and potency and, (b) functionalized sulfonamides constitute a powerful design and diversity element with low intrinsic chemical reactivity and potentially wide applicability.

Cathepsin G↗

PubMed2001

Medial axis reformation: a new visualization method for CT angiography.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate a new method (medial axis reformation [MAR]) for visualizing three-dimensional vascular data at electron-beam computed tomographic (CT) angiography. MATERIALS AND METHODS: MAR was performed automatically with a personal computer-based workstation. After the region of interest was edited, voxels were divided into groups according to their path lengths. Centroids of groups were connected to form the medial axis. Then, the medial axis was refined with multiscale medial response. Bifurcations were also detected and refined. Finally, curved sections were generated through the branches and laid out onto a single image by using a splitting method. The authors performed MAR during electron-beam CT angiography of coronary arteries, common carotid arteries, and iliac arteries. RESULTS: MAR displayed curved sections of branched vessels on one image, cut through the axis of vessels to show the vessel diameter objectively, and allowed the viewing direction to be altered arbitrarily. CONCLUSION: Results of preliminary applications demonstrate that MAR is a valuable new visualization method for CT angiography.

Adult↗

PubMed2001

Effects of window and threshold levels on the accuracy of three-dimensional rendering techniques in coronary artery electron-beam CT angiography.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the effect of window level and gray-scale threshold on the demonstration of coronary artery lumina at three-dimensional electron-beam computed tomographic (CT) angiography. MATERIALS AND METHODS: Forty-four coronary artery branches in postmortem pigs were evaluated with electron-beam CT angiography, and the findings were compared with those from conventional angiography. Images from electron-beam CT angiography were reconstructed with maximal intensity projection (MIP), multiplanar reformation (MPR), and shaded-surface display (SSD). Four categories of window level and gray-scale threshold were evaluated. RESULTS: Three-dimensional electron-beam CT angiography accurately depicted the luminal diameters of the coronary arteries compared with conventional angiography (r = 0.83-0.90, P < .0001). The length of lumina visualized at electron-beam CT angiography was significantly shorter than that visualized with conventional angiography (P < .001). The use of MPR enabled visualization of longer segments of coronary arteries than did the use of MIP or SSD (P < .05). The higher the window level and gray-scale threshold used, the smaller the coronary luminal diameters measured (P < .05). The most accurate window level and gray-scale threshold (82.6 HU +/- 29.8 and 89.5 HU +/- 29.7, respectively) were found to correspond to the attenuation of the lumina (275.8 HU +/- 58.8). Results of simple linear regression showed a strong correlation between luminal attenuation and window level (r = 0.89, P < .0001) or gray-scale threshold (r = 0.95, P < .0001). CONCLUSION: Electron-beam CT angiography shows promise in the visualization of coronary artery lumina. For accurate display of lumina, a proper window level and gray-scale threshold for three-dimensional rendering techniques should be determined and used on the basis of the attenuation of the target vessel.

Animals↗

PubMed2001

Optimal electrocardiographically triggered phase for reducing motion artifact at electron-beam CT in the coronary artery.

RATIONALE AND OBJECTIVES: The authors performed this study to (a) investigate coronary movement with electron-beam computed tomography (CT) and (b) find the optimal electrocardiographic (ECG) triggering phase for eliminating motion artifact. MATERIALS AND METHODS: One hundred fifty-one patients without arrhythmia were examined with electron-beam CT. First, movie scans were obtained to create displacement and velocity graphs of coronary artery movement. Then, a volume scan with an exposure time of 100 msec was obtained with various ECG trigger settings. RESULTS: Movement patterns of coronary arteries varied with heart rate. Optimal triggering phase was before atrial systole (near 71% of the R-R interval) when heart rate was slower than 68 beats per minute and at ventricular end systole when heart rate was fast. Rate of severe motion artifacts decreased from 43% to 0% when triggering was altered from 80% of the R-R interval to the individual optimal value. Experimental values of the optimal phase at different heart rates were derived, and severe motion artifact was only 3.0% with these values. CONCLUSION: ECG triggering set according to the heart rate enables a great reduction in motion artifacts at electron-beam CT with a 100-msec exposure time. The results may have implications for magnetic resonance imaging of the coronary artery.

Adult↗

PubMed2001

A rapid, simple and sensitive flow cytometric system for detection of Plasmodium falciparum.

We have established a rapid, simple and sensitive flow cytometric system for the detection of Plasmodium falciparum that involves lysing erythrocytes and staining parasites at the same time using a newly developed hemolysing and staining solution containing dodecyl methyl ammonium chloride and acridine orange. In this system, freed parasites of P. falciparum could be plotted separately from erythrocyte ghosts, white blood cells and platelets on the two-dimensional scattergram of forward-angle light scatter and green fluorescence by flow cytometry with an argon laser. It took only 2-3 min per sample to obtain the scattergram and analyze the data, including the time of sample preparation for flow cytometric analysis. Sample preparation with this method does not require any difficult handling procedures. The threshold of parasite detection was almost equal to that of microscopic examination for cultured P. falciparum. The results of drug-susceptibility assays using this system were also almost identical to those obtained using microscopic examination. In this system, parasites at different erythrocytic stages could be easily distinguished. This system must prove useful and practical for basic laboratory studies of P. falciparum including those requiring the differential measurement of parasites at specific erythrocytic stages.

Acridine Orange↗

PubMed2001

Hypercoagulation in surgical postmenopausal women having hormone replacement with overdose estradiol.

A benefit of estradiol replacement preventing coronary heart disease (CHD) after menopause has been suggested by clinical investigations. In the department of gynecology at our hospital, we met by chance eight senior women who were hysterectomized due to different benign gynecological disorders. Acting on their own, they took a daily dose of estradiol valerate as high as 8-50 mg for 3 years, in comparison with 1-2 mg used in routine hormonal replacement therapy. We were interested to assess whether the overdose estrogen disturbs the hemostatic function, thus losing the favorable effect on CHD occurrence. Plasma levels of some procoagulants/anticoagulants were assayed in the eight women with replacement therapy and the results were compared with those of seven age-matched senior women and of 14 young healthy women with normal menstrual cycles. Using a new laboratory method recently developed by us, the overall hemostatic potential, shown as a single parameter (Abs-sum), was also determined. Results showed that high-dose estradiol activated coagulation and depressed fibrinolysis, leading to the net effect of elevated overall hemostatic potential. Thus, the overdose estradiol replacement may not be beneficial in preventing CHD after menopause, or it may even increase the risk due to the hypercoagulable state induced therefrom.

Adult↗

PubMed2001

Evaluation of cardiovascular parameters of a selenium-based antihypertensive using pulsed Doppler ultrasound.

The pharmacology of selenium is of much interest because selenium deficiency has been linked to cardiovascular diseases, cancer, and arthritis, and selenoenzymes are critical cellular antioxidants. We have previously reported that phenyl-2-aminoethylselenide (PAESe) and its derivatives represent a novel class of selenium-based antihypertensive agents that exhibit unique biochemical and pharmacologic properties. We now report on experiments designed to probe the hemodynamic mechanism of action of these compounds in spontaneously hypertensive rats (SHR). A noninvasive pulsed Doppler ultrasound probe was used to measure peak blood flow velocity in the aortic arch from the right second intercostal space. PAESe was found to increase peak aortic blood flow velocity (+44%), heart rate (+16%), and blood flow acceleration (+105%), while decreasing left ventricular ejection time (LVET) (-37%) concomitant with a decrease in mean arterial pressure (-54%). These results were compared with the known vasodilator hydralazine, which had similar effects on mean arterial pressure (MAP) and peak velocity but caused an increase in LVET (+42%) and a decrease in heart rate (-18%). Taken together, our results suggest that PAESe decreases blood pressure via a decrease in peripheral resistance, which overcomes the initial increase in heart rate and acceleration to give a net decrease in MAP.

Animals↗

PubMed2001

Modified clotting properties of fibrinogen in the presence of acetylsalicylic acid in a purified system.

To assess how treatment with acetylsalicylic acid (ASA) alters the fibrin network structure, clotting was initiated in purified fibrinogen incubated with ASA by adding thrombin. Clotting time and maximum absorbance of the fibrin aggregation curve were used to demonstrate the potential of fibrin generation. The results showed that the clotting properties of fibrinogen decreased and that the affinity of plasminogen to fibrin or thrombin inhibition by antithrombin increased if plasminogen or antithrombin, respectively, were present in the reaction system. The effect of ASA varied in a dose dependent manner. It was concluded that ASA may directly or indirectly confer positive or negative effects on the stability of the fibrin clot and that the balance between these effects may be regulated by the ASA dose.

Aspirin↗

PubMed2001

Persistence of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte clones in a subject with rapid disease progression.

We longitudinally measured T-cell receptor transcript frequencies of human immunodeficiency virus type 1 (HIV-1) specific cytotoxic T lymphocytes (CTL) in an individual with rapidly progressive disease and high levels of viremia. CTL clones elicited during acute HIV-1 infection were present at the time of death, despite absent functional CTL responses, arguing against clonal deletion as a mechanism for the decline of CTL responses observed during HIV-1 infection.

Chronic Disease↗

PubMed2001

The alpha(1)- and alpha(2)-isoforms of Na-K-ATPase play different roles in skeletal muscle contractility.

The Na-K-ATPase, which maintains the Na(+) and K(+) gradients across the plasma membrane, can play a major role in modulation of skeletal muscle contractility. Although both alpha(1)- and alpha(2)-isoforms of the Na-K-ATPase are expressed in skeletal muscle, the physiological significance of these isoforms in contractility is not known. Evaluation of the contractile parameters of mouse extensor digitorum longus (EDL) was carried out using gene-targeted mice lacking one copy of either the alpha(1)- or alpha(2)-isoform gene of the Na-K-ATPase. The EDL muscles from heterozygous mice contain approximately one-half of the alpha(1)- or alpha(2)-isoform, respectively, which permits differentiation of the functional roles of these isoforms. EDL from the alpha(1)(+/-) mouse shows lower force compared with wild type, whereas that from the alpha(2)(+/-) mouse shows greater force. The different functional roles of these two isoforms are further demonstrated because inhibition of the alpha(2)-isoform with ouabain increases contractility of alpha(1)(+/-) EDL. These results demonstrate that the Na-K-ATPase alpha(1)- and alpha(2)-isoforms may play different roles in skeletal muscle contraction.

Animals↗

PubMed2001

Scattering of a Hermite-Gaussian beam field by a chiral sphere.

Scattering of a Hermite-Gaussian beam field by a chiral sphere is analyzed. A Hermite-Gaussian beam field is expressed as a superposition of multipole fields at complex-source points. Electromagnetic fields are expanded in terms of the spherical vector wave functions. The unknown expansion coefficients for the scattered field and the internal field are determined by the boundary conditions. As numerical examples, the scattered near fields of the beam incidence are calculated, and the effects of the chirality and the radius of the chiral sphere on the fields are examined. The results for a Gaussian beam incidence are also compared with those of a plane-wave incidence.

Journal Article↗

PubMed2001

[Effect on manganese exposure on blood prolactin and plasma renin activity].

In order to study the adverse effects of manganese on neuro-endocrine and cardiovascular system, radioimmunoassay (RIA) was used to test the blood prolactin concentration and plasma renin activity among manganese-exposed workers. The result showed that the blood prolactin concentration and Plasma renin activity in manganese exposed workers were significantly higher than those of control group. It suggested that manganese exposure might affect the function at tubero-infundibular area and renin-angiotensin aldosterone system.

Adult↗