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S L Lin

Publications and source records attributed to S L Lin.

At least 109 records · Page 6Linked to original sources
PubMed1994

Shape complementarity at protein-protein interfaces.

A matching algorithm using surface complementarity between receptor and ligand protein molecules is outlined. The molecular surfaces are represented by "critical points," describing holes and knobs. Holes (maxima of a shape function) are matched with knobs (minima). This simple and appealing surface representation has been previously described by Connolly [(1986) Biopolymers, Vol. 25, pp. 1229-1247]. However, attempts to implement this description in a docking scheme have been unsuccessful (e.g., Connolly, ibid.). In order to decrease the combinatorial complexity, and to make the execution time affordable, four critical hole/knob point matches were sought. This approach failed since some bound interfaces are relatively flat and do not possess four critical point matches. On the otherhand, matchings of fewer critical points require a very time-consuming, full conformational (grid) space search [Wang, (1991) Journal of Computational Chemistry, Vol. 12, pp. 746-750]. Here we show that despite the initial failure of this approach, with a simple and straightforward modification in the matching algorithm, this surface representation works well. Out of the 16 protein-protein complexes we have tried, 15 were successfully docked, including two immunoglobulins. The entire molecular surfaces were considered, with absolutely no additional information regarding the binding sites. The whole process is completely automated, with no manual intervention, either in the input atomic coordinate data, or in the matching. We have been able to reach this level of performance with the hole/knob surface description by using pairs of critical points along with their surface normals in the calculation of the transformation matrix. The success of this approach suggests that future docking methods should use geometric docking as the first screening filter.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1994

Three-dimensional, sequence order-independent structural comparison of a serine protease against the crystallographic database reveals active site similarities: potential implications to evolution and to protein folding.

We have recently developed a fast approach to comparisons of 3-dimensional structures. Our method is unique, treating protein structures as collections of unconnected points (atoms) in space. It is completely independent of the amino acid sequence order. It is unconstrained by insertions, deletions, and chain directionality. It matches single, isolated amino acids between 2 different structures strictly by their spatial positioning regardless of their relative sequential position in the amino acid chain. It automatically detects a recurring 3D motif in protein molecules. No predefinition of the motif is required. The motif can be either in the interior of the proteins or on their surfaces. In this work, we describe an enhancement over our previously developed technique, which considerably reduces the complexity of the algorithm. This results in an extremely fast technique. A typical pairwise comparison of 2 protein molecules requires less than 3 s on a workstation. We have scanned the structural database with dozens of probes, successfully detecting structures that are similar to the probe. To illustrate the power of this method, we compare the structure of a trypsin-like serine protease against the structural database. Besides detecting homologous trypsin-like proteases, we automatically obtain 3D, sequence order-independent, active-site similarities with subtilisin-like and sulfhydryl proteases. These similarities equivalence isolated residues, not conserving the linear order of the amino acids in the chains. The active-site similarities are well known and have been detected by manually inspecting the structures in a time-consuming, laborious procedure. This is the first time such equivalences are obtained automatically from the comparison of full structures. The far-reaching advantages and the implications of our novel algorithm to studies of protein folding, to evolution, and to searches for pharmacophoric patterns are discussed.

Amino Acid Sequence↗
PubMed1994

Molecular surface representations by sparse critical points.

We have defined a molecular surface representation that describes precisely and concisely the complete molecular surface. The representation consists of a limited number of critical points disposed at key locations over the surface. These points adequately represent the shape and the important characteristics of the surface, despite the fact that they are modest in number. We expect the representation to be useful in areas such as molecular recognition and visualization. In particular, using this representation, we are able to achieve accurate and efficient protein-protein and protein-small molecule docking.

Chymotrypsin↗
PubMed1994

Effects of copper concentration on mineral nutrient uptake and copper accumulation in protein of copper-tolerant and nontolerant Lotus purshianus L.

One copper-tolerant and one copper-sensitive inbred line of Lotus purshianus L. derived from a copper mine waste site in Northern California and one inbred line of the same species derived from a pasture next to the mine waste were examined for the effects of excessive copper concentrations on mineral nutrient uptake and accumulation of copper in protein fractions. Plants were grown from seeds for a period of 24 days in a modified Hoagland nutrient solution culture supplemented with 3, 6, and 10 microM copper as copper sulfate. The basal nutrient solution without copper amendment was used as the control treatment. The uptake of Cu found in the roots was 100 times or more than that in the leaves. The root tissue copper concentrations reached a plateau under 6 microM copper treatment. The leaf tissue copper concentrations increased with the increase of copper concentration in the solution culture. No difference in pattern of copper uptake was detected between the copper-tolerant and nontolerant plants. The effects of excessive copper concentrations caused reduction of Ca uptake in the leaf tissue and P uptake in both the root and leaf tissues, and no difference was found between the copper-tolerant and nontolerant plants. Increased tissue copper concentration caused greater reduction of Fe, Mn, and Zn uptake in the nontolerant plants than in the tolerant plants; this difference may be important for the growth of the tolerant plants under conditions of excessive copper concentrations. Protein extracted from the roots and leaves of both the copper tolerant and nontolerant plants was subjected to Sephadex G-75 column separation. Two major peaks of protein fractions were detected. Under low (normal level) copper concentration treatment, the copper-tolerant and nontolerant plants had similar Cu/protein ratios. However, under high copper concentration challenged conditions the copper-tolerant plant had a considerably greater Cu/protein ratio (peak II protein) than the nontolerant plants. The amino acid composition of the copper-rich protein fraction (peak II) extracted from both the tolerant and nontolerant plants demonstrated a high asparate (about 25%) content. The contents of glutamate, cystine, and glycine were about 11, 2.5, and 10%, respectively, and the rest of the amino acids were in a range of 2 to 6%. This pattern of amino acid composition is different from the amino acid composition of the phytochelatin metallothionein-like proteins found in copper-tolerant plants which are very high in cysteine.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1994

Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy.

OBJECTIVES: This study attempted to evaluate the long-term efficacy of enalapril versus hydralazine therapy on left ventricular volume, mass and function as well as on the renin-angiotensin system in chronic asymptomatic aortic regurgitation. BACKGROUND: We tested the hypothesis that early administration of a vasodilator drug might be able to reduce left ventricular dilation and mass expansion. Because the renin-angiotensin system may be activated in chronic aortic regurgitation, early enalapril therapy might be beneficial. METHODS: Between 1990 and 1993, 76 asymptomatic nonrheumatic patients with mild to severe chronic aortic regurgitation were enrolled in a randomized, double-blind trial comparing enalapril with hydralazine. All patients underwent serial noninvasive studies. Seventy patients completed the 12-month follow-up. RESULTS: At 1 year, patients receiving enalapril had a significant reduction in left ventricular end-diastolic and end-systolic volume indexes (124 +/- 15 vs. 108 +/- 17 ml/m2, p < 0.01; 50 +/- 12 vs. 40 +/- 14 ml/m2, p < 0.01, respectively) and mass index (131 +/- 16 vs. 113 +/- 19 g/m2, p < 0.01), whereas hydralazine therapy showed no significant changes. Both regimens not only had a significant reduction in left ventricular mean wall stress but also had a mild increase in exercise duration. Only enalapril therapy achieved a significant inhibition of the renin-angiotensin system, in contrast to hydralazine therapy. Moreover, the multiple r2 value from the analysis for end-diastolic volume index using the two variables of age and treatment drugs was 72.1% (p < 0.01). CONCLUSIONS: Both regimens decrease left ventricular mean wall stress. Enalapril therapy achieves significant left ventricular mass regression, left ventricular end-diastolic and end-systolic volume index reduction and renin-angiotensin system suppression. These findings suggest that early unloading enalapril therapy has the potential to favorably influence the natural history of chronic aortic regurgitation.

Aged↗
PubMed1994

A possible relation between pressure loading and thickened leaflets of the aortic valve: a model simulation.

A much smaller percentage of thickened leaflets of the aortic valve have been found in the right or left coronary leaflet than in the noncoronary leaflet. This study investigated the pressure loading transferring to the leaflets of the aortic valve and their effects on the valvular thickening. A simple ascending aorta model was established, and a simulation was made. The pressure loading in the coronary and noncoronary leaflets then were estimated. The simulation results showed that 5.8% to 17.% percentage of pressure loading to the coronary leaflet may be decreased by the coronary perfusion in diastole. The coronary arteries play an important role on pressures in the sinuses of Valsalva. The smaller pressure loading transferring to the coronary leaflet than that to the noncoronary leaflet is one reasonable explanation related to the thickened leaflets of the aortic valve.

Aorta↗
PubMed1993

Different pressure gradients can be produced in a fixed stenosis--an in vitro study.

An in vitro study was conducted, using a stenotic model to demonstrate that different pressure gradients can be produced by the same degree of valvular stenosis. This model is comprised of two cylindric chambers with a diaphragm in the center which had a small central hole. An injector was connected to one end of the prestenotic chamber to produce a steady pulsed flow. A rubber tube was connected to the other end of the poststenotic chamber and led upward to a large reservoir which provided a constant afterload pressure. Two pressure transducers were attached to the two connecting tubes, both linked with two pigtail catheters which were accommodated in the chambers just before and after the stenotic diaphragm. Two sets of injection volumes (20 and 30 ml) and multiple injections with different flow rates (5, 10, 15,...49 ml/s) were administered and resulting pressures measured by the two transducers were recorded. Results showed that different pressure gradients could be produced using the same injection volume, the same afterload, and the same degree of stenosis. The greater the flow rate, the higher the pressure gradient. Good correlation existed between the pressure gradient and the injection flow rate (r = 0.95 and 0.97 for the study groups receiving 20 and 30 ml injection volumes, respectively; p < 0.001 in all comparisons). Thus, a higher pressure gradient may not necessarily indicate a severe degree of valvular stenosis. Evaluation of a stenotic lesion should not be made from the degree of pressure gradient alone--other hemodynamic conditions should also be taken into account.

Blood Flow Velocity↗
PubMed1993

A biometric study of ocular changes during accommodation.

We performed a biometric study that used A-mode ultrasonography on 106 subjects during ocular accommodation. The subjects were divided into two groups; group 1 included 76 subjects and group 2 included 30 subjects. In group 1, we measured the anterior chamber depth, lens thickness, and axial length in the right eye while the left eye, wearing corrective spectacles, focused at distances of 6 m, 33 cm, and 33 cm with an additional correction of +3.0 diopters to offset any accommodative effect. In group 2, we measured the anterior chamber depth, lens thickness, and axial length in the right eye while the left eye focused at distances of 6 m, 33 cm, and 12.5 cm. Similar to the left eyes in group 1, the left eyes in group 2 wore corrective spectacles during all procedures. During accommodation, decreased anterior chamber depth and thickening of the lens were noted in all cases. In group 1, axial length significantly increased an average of 0.06 +/- 0.01 mm (P < .0005) while the left eye focused at a distance of 33 cm. There were no significant changes with the additional +3.0 diopters (P < .05). In group 2, axial length significantly increased an average of 0.05 +/- 0.01 mm (P < .0005) when the left eye focused at a distance of 33 cm, and there was further significant elongation of 0.05 +/- 0.01 mm when the left eye focused at a distance of 12.5 cm. Collectively, these results suggest that axial length increases along with changes in the lens and anterior chamber depth during ocular accommodation.

Accommodation, Ocular↗
PubMed1993

Comparison of sublingual captopril, nifedipine and prazosin in hypertensive emergencies during hemodialysis.

Hypertensive emergencies in hemodialysis require immediate therapy, usually by parenteral drug administration; however, sublingual medications may have potential in this special condition. Sublingual captopril (25 mg), nifedipine (10 mg) and prazosin (2 mg) were prescribed to determine the effectiveness and safety of each medication in the treatment of hypertensive emergencies during hemodialysis. Blood pressure and heart rate were measured continuously up to 120 min postdose. The response rates were 83% for captopril, 90% for nifedipine and 11% for prazosin. The significant hypotensive effects of both sublingual captopril and nifedipine occurred at 10 min and continued up to 120 min. The reduction of systolic blood pressure occurred earlier in nifedipine than captopril (10 vs. 15 min). No significant difference in heart rate between them was noted. There were no side effects in the captopril group but flushing, tachycardia and headache were observed in 4 patients of the nifedipine group. We concluded that sublingual captopril and nifedipine were effective but captopril seemed to have less side effects than nifedipine and may be an excellent alternative to sublingual nifedipine in the urgent treatment of hypertensive emergencies in hemodialysis. Prazosin was not recommended because of its low response rate.

Administration, Sublingual↗
PubMed1993

Primary nasal melanoma with exclusive liver metastasis: a case report.

A 50-year-old male presented with a nasal mass causing obstruction and bleeding. The initial biopsy indicated a malignant lymphoma but the subsequent biopsy diagnosed an undifferentiated carcinoma. However, histopathological study and immunohistochemical study, made a final diagnosis of nasal melanoma. Six months after the diagnosis, the patient developed exclusive liver metastasis. He responded to 1 course of intensive chemotherapy with 200 mg/m2 cisplatin and 5000 mg/m2 dacarbazine for 6 months. For patients with nasal cavity malignancy, the possibility of primary melanoma should be considered. Combination chemotherapy with intensive dose of cisplatin and dacarbazine may be a viable treatment regimen for nasal melanoma with liver metastasis.

Humans↗
PubMed1993

Mitral regurgitation after double balloon or Inoue balloon mitral valvuloplasty.

We performed serial color Doppler echocardiographic studies prospectively before and after double balloon or Inoue balloon mitral valvuloplasty in 44 patients (mean age 45 +/- 13, range 20-74) with pure rheumatic mitral stenosis (by angiography) selected in a case-control manner to compare the incidence and severity of mitral regurgitation. After balloon dilation, mitral valve area increased from 0.9 +/- 0.2 to 1.5 +/- 0.4 cm2 (p < 0.001) in the double balloon group and from 0.9 +/- 0.3 to 1.5 +/- 0.3 cm2 (p < 0.001) in the Inoue balloon group. Twenty-four hours after balloon dilation, 3 patients in the double balloon group and 12 patients in the Inoue balloon group developed moderate to severe mitral regurgitation (p < 0.05). The severity of mitral regurgitation tended to persist or progress during follow-up in both groups, although improvement could also be observed. Two patients with severe mitral regurgitation in the Inoue balloon group underwent mitral valve replacement during follow-up. In conclusion, double balloon and Inoue balloon techniques are both effective in relieving significant mitral stenosis. However, Inoue balloon technique may be associated with slightly higher frequency of mitral regurgitation.

Adult↗
PubMed1992

A monoclonal antibody against a novel 20-kDa protein induces cell adhesion and cytoskeleton-dependent morphologic changes.

A new murine IgA mAb (JKT.M1), developed against Jurkat T cells chronically infected with HIV IIIB induces in vitro homotypic aggregation in several hemopoietic cell lines. The JKT.M1 Ag is expressed on a wide variety of cell types including human lymphocytes, monocytes, platelets, RBC, human umbilical vein endothelial cells, many T cell lines, myelomonocytic cell lines, and a primate kidney cell line. The JKT.M1 Ag shows differential expression on myelomonocytic cells; it is present on K562 and HL60 cell lines, which represent precursors of E and monocytes, respectively, but is not expressed on the surface of U937 and THP-1 cell lines, which appear to represent intermediate cell types of the monocytic cell lineage. However, the JKT.M1 Ag is expressed on mature peripheral blood monocytes and the MonoMac cell line. Immunoprecipitation from cell lysates (Jurkat, SupT1, PBMC, MonoMac) with the JKT.M1 mAb yields a 20-kDa Ag with few if any carbohydrate residues as determined by N-glycanase and neuraminidase treatments. The pI appears acidic by two-dimensional gel analysis, and the nonreduced form migrates more slowly than the reduced form when analyzed by SDS-PAGE suggesting the presence of intramolecular disulfide bridge(s). JKT.M1 mAb-induced cell adhesion is shown to be divalent cation- and temperature-dependent. The adhesion induced by JKT.M1 mAb is inhibited by 20 microM cytochalasin B and also by 2 mM 2-deoxyglucose plus 10 mM sodium azide suggesting that cytoskeletal changes and metabolic energy are required. Aggregation induced by JKT.M1 appears to be independent of CD43, CD44, and VLA4 (CD29/CD49d), mAb against which have also been shown to induce homotypic cell adhesion. Anti-CD18 mAb have been shown to inhibit homotypic aggregation in other studies but failed to do so in the present study. Thus JKT.M1-induced adhesion also appears to be independent of CD18, the beta-chain of leukocyte integrins. However, like mAb against LFA-1, immobilized JKT.M1 stimulates a T cell line to undergo dramatic morphologic changes which could be enhanced by the addition of phorbol ester. These data suggest that the novel 20-kDa molecule recognized by the JKT.M1 mAb may trigger cell adhesion through a previously undescribed mechanism.

Animals↗
PubMed1992

Left ventricular opacification after peripheral venous injection of a modified albumin solution.

The usefulness of a modified albumin solution was assessed in 8 dogs after peripheral venous and inferior vena cava injections. The contrast agent is a mixed solution made of glucose, albumin and glycerin, with sonicated microbubble diameter of 5.0 +/- 2.3 microns. Multiple injections (8 ml each) of this contrast agent (total 80 injections) into peripheral vein and inferior cava were performed. The blood pressure from femoral artery was measured before, during and after injections. Two-dimensional echocardiograms were recorded in a modified long axis view on videotapes for play back analysis. The pulmonary transit time and left ventricular contrast persistent time was determined for each injection. The videodensity of the region of interest (ROI) at the center of right ventricle and left ventricle was measured. The background videodensity of both ventricles was evaluated. The videodensity over the ROI of both ventricles with peak contrast enhancement was measured in all frames for 3 consecutive cardiac cycles. The peak videodensity of right and left ventricle subtracting the background videodensity of each ventricles was further calculated respectively. The injections caused no change in blood pressure or heart rate. All injections produced right ventricular contrast echo. As much as 85% of peripheral venous and 82.5% of inferior vena cava injections resulted in left ventricular contrast which was 0.68 and 0.65 as bright as that produced in the right ventricle. Pulmonary transit time and left ventricle contrast persistent time of peripheral venous injection was 4.05 +/- 0.53 and 13.67 +/- 4.28 seconds respectively. No difference of these data (3.93 +/- 0.47 and 11.65 +/- 4.66 seconds) from those produced by inferior vena cava injections were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1992

The value of transesophageal echocardiography in the diagnosis of cardiac metastasis.

To assess the diagnostic value of transesophageal two-dimensional echocardiography (TEE) as compared with transthoracic echocardiography (TTE), TTE and TEE were performed in eight consecutive patients (age range from 20 to 76 years, six male and two female) with clinical evidence of malignant tumors arising from the liver (n = 1), lung (n = 3), larynx (n = 1), osteogenic sarcoma (n = 1), lymphoma (n = 1), and yolk sac tumor in the anterior mediastinum (n = 1). In one case, the gastroscope could not be inserted because of tumor compression of the esophagus. Transesophageal echocardiography provided superior imaging in the detection of intracavitary metastatic lesions. In the case of right ventricular outflow tract tumor and greater vessel involvement, TTE may provide more imaging than TEE due to a blind area in this region by the transesophageal approach. In conclusion, TEE is complementary to TTE in the diagnosis of metastatic cardiac tumor.

Adult↗
PubMed1992

Usefulness of transesophageal echocardiography for the detection of left atrial thrombi in patients with rheumatic heart disease.

Transesophageal (TEE) and transthoracic (TTE) echocardiograms were performed in 110 patients with rheumatic heart disease to evaluate the usefulness of these methods for the detection of left atrial thrombi. TEE was better than TTE for detecting left atrial thrombi (21 vs 9). The thrombi not detected by TTE were in the left atrial appendage in ten and over the left atrial posterior wall in two. Patients with left atrial thrombi had significantly smaller mitral valve area (P less than 0.01) and greater left atrial dimension (P less than 0.05) than those without. All patients with left atrial thrombi had atrial fibrillation. Thirty-one patients underwent surgical intervention and 13 were found to have left atrial thrombi. TEE detected left atrial thrombi in all 13 patients with a sensitivity of 100%, specificity of 100%, and accuracy of 100%, while TTE detected left atrial thrombi in only nine of these 13 patients with a sensitivity of 69.2%, specificity of 100%, and accuracy of 87.1%. Thus, TEE is superior to TTE for the detection of left atrial thrombi, especially for those thrombi located in the left atrial appendage and along the left atrial posterior wall.

Adult↗
PubMed1992

Optimization character of inspiratory neural drive.

A previous optimal chemical-mechanical model (C.-S. Poon. J. Appl. Physiol. 62: 2447-2459, 1987) suggested that the normal ventilatory responses to CO2 and exercise inputs and mechanical loading can be predicted by the minimization of a controller objective function consisting of the total chemical and mechanical costs of breathing. In this study the model was generalized to include a description of the inspiratory neuromuscular drive as the control output. With a mechanical work rate index for both inspiration and expiration, the general optimization model accurately reproduced the observed responses in the waveshape of inspiratory drive, breathing pattern, and total ventilation under differing conditions of CO2 inhalation, exercise, and inspiratory/expiratory mechanical loads. The simulation results are in general agreement with a wide range of respiratory phenomena, including exercise hyperpnea, CO2 chemoreflex, and post-inspiratory (postinflow) inspiratory activity, as well as respiratory neural compensations for mechanical loading, respiratory muscle fatigue, and muscle weakness.

Animals↗