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Biomedical subjects

S He

Publications and source records attributed to S He.

At least 91 records · Page 5Linked to original sources

Spatial and temporal properties of light adaptation in the rod system.

Little is known about the mechanism that regulates the sensitivity of rod system at its normal operating light levels. Two experiments are reported in this paper. First, we searched for nonlinear distortion products in rod vision that could be generated from any local adaptation process, using a sensitive experimental procedure that has demonstrated local adaptation in cone vision. No local adaptation was evident in the rod system, even at near saturating light levels. Second, to investigate the dynamics of light adaptation in the rod system we presented a uniform flickering background, sinusoidally modulated in time, and measured increment thresholds for brief test flashes that were superimposed on this background at different times during the sinusoidal flicker cycle. At frequencies less than 5-6 Hz, the rod increment threshold follows the background modulation, with a slight phase advance. When the background is modulated faster than 5-6 Hz, the increment threshold remains the same regardless of when the test flash occurred during the background cycle. Thus the rod system sensitivity, unlike that of the cone system, can only change slowly, and is set by a space-integrated signal rather than independently for different rods.

Adaptation, Ocular↗

Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate.

New injectable, in situ crosslinkable biodegradable polymer composites were investigated consisting of poly(propylene fumarate) (PPF), poly(ethylene glycol)-dimethacrylate (PEG-DMA), and beta-tricalcium phosphate (beta-TCP). We examined the effects of the PEG-DMA/PPF double-bond ratio and beta-TCP content on the crosslinking characteristics of the composites including the maximum crosslinking temperature and the gel point, as well as the properties of the crosslinked composites such as the compressive strength and modulus, and the water-holding capacity. The maximum crosslinking temperature was constant averaging 39.7 degrees C for the composite formulations tested. The gel points varied from 8.0 +/- 1.0 to 12.6 +/- 2.5 min and were not affected by the relative amounts of PEG-DMA. The compressive strength at yield of PEG-DMA/PPF composites without beta-TCP increased from 5.9 +/- 1.0 to 11.2 +/- 2.2 MPa as the double-bond ratio of PEG-DMA/PPF increased from 0.38 to 1.88. An increase in compressive modulus was also observed from 30.2 +/- 3.5 to 58.4 +/- 6.2 MPa for the same range of the PEG-DMA/PPF double-bond ratio. Also, the addition of beta-TCP (33 wt%) enhanced the mechanical properties of all composites. The equilibrium water content of networks without beta-TCP increased from 21.7 +/- 0.2 to 30.6 +/- 0.2% for a double-bond ratio of PEG-DMA/PPF ranging from 0.38 to 1.88. However, the mechanical properties of the swollen composites under compression were smaller than the dry ones. These data demonstrate the feasibility of fabricating injectable biodegradable polymer composites with engineered mechanical properties for orthopedic tissue engineering.

Acrylates↗

Modulation of coupling between retinal horizontal cells by retinoic acid and endogenous dopamine.

The regulation of electrical coupling between retinal neurons appears to be an important component of the neuronal mechanism of light adaptation, which enables the retina to operate efficiently over a broad range of light intensities. The information about the ambient light conditions has to be transmitted to the neuronal network of the retina and previous evidence has indicated that dopamine is an important neurochemical signal. In addition, recent studies suggest that another important chemical signal is retinoic acid, which is a light-correlated byproduct of the phototransduction cycle. This review summarizes the latest findings about the effects of dopamine and retinoic acid on gap junctional coupling in the retinas of mouse, rabbit and fish.

Animals↗

Effects of phase aberration on high frame rate imaging.

A high frame-rate (HFR) imaging method (about 3750 frames/s for imaging of biological soft tissues at a depth of 200 mm) has been developed recently with limited diffraction beams. This method uses the fast Fourier transform (FFT) and inverse fast Fourier transform (IFFT) to construct images, and can be implemented with simple and inexpensive hardware, compared to the conventional delay-and-sum method where a digital beam former is usually used. In this paper, phase aberration effects are studied for both the high frame rate and the conventional methods by adding random phase shifts to echo signals obtained from an experiment. In the study, two broadband linear arrays were used to construct images of an ATS 539 tissue-equivalent phantom that has a frequency-dependent attenuation of about 0.5 dB/MHz/cm. The first array has 48 elements, a central frequency of 2.25 MHz, an aperture of 18.288 mm, and a width of 12.192 mm in elevation. The second has 64 elements, a central frequency of 2.5 MHz, and a dimension of 38.4 mm x 10 mm. The-6dB pulse-echo bandwidth of both arrays is about 40% of their center frequencies. Radiofrequency (RF) signals were digitized at 20 mega samples/s at a 12-bit resolution to construct images. Results show that phase aberration has about the same effect on both methods in terms of image resolution and contrast, although the high frame-rate method can be implemented with a simpler system.

Image Processing, Computer-Assisted↗

Multilayer neural networks for solving a class of partial differential equations.

In this paper, training the derivative of a feedforward neural network with the extended backpropagation algorithm is presented. The method is used to solve a class of first-order partial differential equations for input-to-state linearizable or approximate linearizable systems. The solution of the differential equation, together with the Lie derivatives, yields a change of coordinates. A feedback control law is then designed to keep the system in a desired behavior. The examination of the proposed method, through simulations, exhibits the advantages of it. They include easily and quickly finding approximate solutions for complicated first-order partial differential equations. Therefore, the work presented here can benefit the design of the class of nonlinear control systems, where the nontrivial solutions of the partial differential equations are difficult to find.

Algorithms↗

Receptive field microstructure and dendritic geometry of retinal ganglion cells.

We studied the fine spatial structure of the receptive fields of retinal ganglion cells and its relationship to the dendritic geometry of these cells. Cells from which recordings had been made were microinjected with Lucifer yellow, so that responses generated at precise locations within the receptive field center could be directly compared with that cell's dendritic structure. While many cells with small receptive fields had domeshaped sensitivity profiles, the majority of large receptive fields were composed of multiple regions of high sensitivity. The density of dendritic branches at any one location did not predict the regions of high sensitivity. Instead, the interactions between a ganglion cell's dendritic tree and the local mosaic of bipolar cell axons seem to define the fine structure of the receptive field center.

Action Potentials↗

Utilization of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold in the design of potent inhibitors of serine proteases: SAR studies using carboxylates.

A series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds has been synthesized and the inhibitory profile of these compounds toward human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3) was then determined. Most of the compounds were found to be potent, time-dependent inhibitors of elastase, with some of the compounds exhibiting k(inact)/K1 values as high as 4,928,300 M(-1) s(-1). The inhibitory potency of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide platform was found to be influenced by both the pKa and the inherent structure of the leaving group. Proper selection of the primary specificity group (R(I)) was found to lead to selective inhibition of HLE over Cat G, however, those compounds that inhibited HLE also inhibited PR 3, albeit less efficiently. The predictable mode of binding of these compounds suggests that, among closely-related serine proteases, highly selective inhibitors of a particular serine protease can be fashioned by exploiting subtle differences in their S' subsites. This study has also demonstrated that the degradative action of elastase on elastin can be abrogated in the presence of inhibitor 17.

Cyclic S-Oxides↗

Potent inhibition of serine proteases by heterocyclic sulfide derivatives of 1,2,5-thiadiazolidin-3-one 1,1 dioxide.

The existence of subtle differences in the Sn' subsites of closely-related (chymo)trypsin-like serine proteases, and the fact that the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold docks to the active site of (chymo)trypsin-like enzymes in a substrate-like fashion, suggested that the introduction of recognition elements that can potentially interact with the Sn' subsites of these proteases might provide an effective means for optimizing enzyme potency and selectivity. Accordingly, a series of heterocyclic sulfide derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I) was synthesized and the inhibitory activity and selectivity of these compounds toward human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G (Cat G) were then determined. Compounds with P1 = isobutyl were found to be potent, time-dependent inhibitors of HLE and, to a lesser extent PR 3, while those with P1 = benzyl inactivated Cat G rapidly and irreversibly. This study has demonstrated that 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based heterocyclic sulfides are effective inhibitors of (chymo)trypsin-like serine proteases.

Cathepsin G↗

Effects of scanning and reconstruction parameters on image quality in electron-beam CT angiography: coronary artery phantom study.

RATIONALE AND OBJECTIVES: This study compared the image quality obtained with different scanning and reconstruction parameters for electron-beam computed tomographic (CT) angiography and sought optimal methods for visualizing the coronary artery lumen. MATERIALS AND METHODS: Electron-beam CT angiography with contrast material enhancement was used to image 35 branches of fresh postmortem swine coronary arteries. Different collimation widths, fields of view (FOVs), reconstruction kernels, and algorithms were employed to reconstruct the acquired raw data into CT angiographic images. Image quality was compared and analyzed. RESULTS: The contrast-to-noise ratios (C/Ns) for 1.5-, 2-, and 3-mm section thickness were 28.4 +/- 15.2, 31.9 +/- 9.3, and 33.8 +/- 14.5, respectively (P < .05). The lengths of visualized coronary artery lumina were significantly longer for 1.5-mm scanning (71.6 mm +/- 4.3) than for 2-mm (58.3 mm +/- 5.5) and 3-mm scanning (59.0 mm +/- 8.0) (P < .01). The C/Ns for 12.7-, 18.0-, and 26.0-cm FOV reconstruction were 32.8 +/- 9.9, 28.9 +/- 8.2, and 27.1 +/- 8.2, respectively (not significant), and the visualized luminal lengths were 76.1 mm +/- 12.5, 71.7 mm +/- 14.6, and 65.4 mm +/- 13.1, respectively (not significant). The highest C/N (48.2 +/- 13.3) was achieved with smooth kernels and a cone-beam algorithm, and the lowest (14.7 +/- 3.4) with very sharp kernels and a normal algorithm. Cone-beam algorithm images had significantly higher C/Ns than did normal algorithm images (P < .001), and they demonstrated longer coronary artery lumina (P < .01). CONCLUSION: Collimation width, FOV, reconstruction kernels, and algorithms are important in the processing of high-quality electron-beam coronary angiograms. A 1.5-mm collimation width, 12.7-cm FOV, cone-beam reconstruction algorithm, and very sharp kernels should help in obtaining the best image quality and depicting the longest segments of coronary artery lumen.

Algorithms↗

Differential mechanism-based labeling and unequivocal activity assignment of the two active sites of intestinal lactase/phlorizin hydrolase.

Milk lactose is hydrolysed to galactose and glucose in the small intestine of mammals by the lactase/phlorizin hydrolase complex (LPH; EC 3.2.1.108/62). The two enzymatic activities, lactase and phlorizin hydrolase, are located in the same polypeptide chain. According to sequence homology, mature LPH contains two different regions (III and IV), each of them homologous to family 1 glycosidases and each with a putative active site. There has been some discrepancy with regard to the assignment of enzymatic activity to the two active sites. Here we show differential reactivity of the two active sites with mechanism-based glycosidase inhibitors. When LPH is treated with 2',4'-dinitrophenyl 2-deoxy-2-fluoro-beta-D-glucopyranoside (1) and 2', 4'-dinitrophenyl-2-deoxy-2-fluoro-beta-D-galactopyranoside (2), known mechanism-based inhibitors of glycosidases, it is observed that compound 1 preferentially inactivates the phlorizin hydrolase activity whereas compound 2 is selective for the lactase active site. On the other hand, glycals (D-glucal and D-galactal) competitively inhibit lactase activity but not phlorizin hydrolase activity. This allows labeling of the phlorizin site with compound 1 by protection with a glycal. By differential labeling of each active site using 1 and 2 followed by proteolysis and MS analysis of the labeled fragments, we confirm that the phlorizin hydrolysis occurs mainly at the active site located at region III of LPH and that the active site located at region IV is responsible for the lactase activity. This assignment is coincident with that proposed from the results of recent active-site mutagenesis studies [Zecca, L., Mesonero, J.E., Stutz, A., Poiree, J.C., Giudicelli, J., Cursio, R., Gloor, S.M. & Semenza, G. (1998) FEBS Lett. 435, 225-228] and opposite to that based on data from early affinity labeling with conduritol B epoxide [Wacker, W., Keller, P., Falchetto, R., Legler, G. & Semenza, G. (1992) J. Biol. Chem. 267, 18744-18752].

Amino Acid Sequence↗

Magnetostatic image current and its application to an analytic identification of a current dipole inside a conducting sphere.

The image solution for the static magnetic field outside a conducting sphere with an internal current dipole is considered. The image current, which is a linear distribution of magnetic dipoles on the line segment between the dipole point and the center of the sphere, is derived by using the fact that the induced current does not have any contribution to the radial component of the magnetic field outside the sphere. The image is then used to obtain some explicit formulas for identifying the location and tangential moment of the primary current dipole. This explicit identification method is also tested with a real model for a patient's brain.

Brain↗

An optimization approach to multi-dimensional time domain acoustic inverse problems.

An optimization approach to a multi-dimensional acoustic inverse problem in the time domain is considered. The density and/or the sound speed are reconstructed by minimizing an objective functional. By introducing dual functions and using the Gauss divergence theorem, the gradient of the objective functional is found as an explicit expression. The parameters are then reconstructed by an iterative algorithm (the conjugate gradient method). The reconstruction algorithm is tested with noisy data, and these tests indicate that the algorithm is stable and robust. The computation time for the reconstruction is greatly improved when the analytic gradient is used.

Acoustics↗

Transfusion-acquired, autochthonous human babesiosis in Japan: isolation of Babesia microti-like parasites with hu-RBC-SCID mice.

We have isolated piroplasms from a patient who developed the first case of human babesiosis in Japan by using NOD/shi-scid mice whose circulating erythrocytes (RBCs) had been replaced with human RBCs (hu-RBC-SCID mice). Following inoculation of the patient's blood specimen into hu-RBC-SCID mice, parasites proliferated within the human RBCs in the mice, resulting in a high level of parasitemia. Parasite DNA was prepared from blood samples of the patient and the mice, and the nuclear small-subunit rRNA gene (rDNA) was amplified and sequenced. Both DNA samples gave rise to identical sequences which showed the highest degree of homology (99.2%) with the Babesia microti rDNA. Because the patient had received a blood transfusion before the onset of babesiosis, we investigated the eight donors who were involved. Their archived blood samples were analyzed for specific antibody and parasite DNA; only a single donor was found to be positive by both tests, and the parasite rDNA sequence from the donor coincided with that derived from the patient. The donor's serum exhibited a high antibody titer against the isolate from the patient, whereas it exhibited only a weak cross-reaction against B. microti strains isolated in the United States. We conclude that the first Japanese babesiosis case occurred due to a blood transfusion and that the etiological agent is an indigenous Japanese parasite which may be a geographical variant of B. microti. Our results also demonstrated the usefulness of hu-RBC-SCID mice for isolation of parasites from humans and for maintenance of the parasite infectivity for human RBCs.

Animals↗

Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and caucasoid adults and children.

Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus. Cohorts evaluated included 44 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17(Gag) and p24(Gag) sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However, there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17(Gag) peptide residues 16 to 30 (38 versus 12%; P < 0.01), while p24(Gag) peptide residues 41 to 60 contained the dominant Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005). Within this 20-mer p24(Gag), an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design.

Adult↗

E2F is required to prevent inappropriate S-phase entry of mammalian cells.

E2F is a family of transcription factors that regulates the cell cycle. It is widely accepted that E2F-mediated transactivation of a set of genes is the critical activity that governs cellular progression through G(1) into S phase. In contrast to this hypothesis, we demonstrate that E2F actually suppresses the onset of S phase in two cell types when the cells are arrested by gamma irradiation. Our findings indicate that in these cells, the critical event triggering progression from G(0)/G(1) arrest into S phase is the release of E2F-mediated transrepression of cell cycle genes, not transactivation by E2F. Furthermore, our data suggest that E2F-mediated transactivation is not necessary for the G(1)/S-phase transition in these cells.

Animals↗

Evaluation of electron beam tomographic coronary arteriography with three-dimensional reconstruction in healthy subjects.

In this study, the authors evaluated the performance characteristics of contrast-enhanced electron-beam tomography (EBT) with three-dimensional reconstruction in defining the coronary artery lumen in healthy subjects. Thirty patients with normal coronary angiograms by selective coronary arteriography (SCA) underwent contrast-enhanced EBT examination. Measured parameters included degree of luminal enhancement, intravascular contrast-to-noise ratio (CNR), and diameter and length of visualized lumen. Ventricular cavity, aortic blood pool, and coronary artery attenuation were found to be significantly different before and after intravenous injection of contrast material (p < 0.001). CNR decreased from proximal to distal segments within each vessel (p < 0.001), with a peak of 11.2 +/- 2.3 occurring in the proximal left anterior descending coronary artery (LAD) to a low of 4.8 +/- 2.0 in the distal left circumflex (LCX). Luminal diameters visualized by EBT had no significant difference with that of SCA (p > 0.05). Therefore, EBT angiography with three-dimensional reconstruction allows for noninvasive coronary arteriography revealing long segments of the major coronary arteries in normal subjects.

Adult↗

Searching for mechanisms of retinal direction selectivity.

A classic example of a complicated neurocomputation carried out by a relatively simple neuronal circuitry is that some mammalian retinal ganglion cells respond selectively to direction of motion. Search for the mechanisms of direction selectivity in the mammalian retina started some 35 years ago. It has been shown that direction selectivity is caused by an asymmetrical inhibition induced by GABA acting on GABAA receptors. However, the physical circuitry underlining this computation is still not clear. A few recent breakthroughs provide important evidence for the sites where the computation takes place.

Animals↗