Search PubMed⌕ Search

Biomedical subjects

S L Lin

Publications and source records attributed to S L Lin.

At least 73 records · Page 4Linked to original sources

CROC-1 encodes a protein which mediates transcriptional activation of the human FOS promoter.

The cloning of signal transducing molecules capable of activating the human FOS proto-oncogene promoter was achieved by co-transfecting a modified human FOS promoter-driven polyomavirus large T antigen gene (P(f)LAG-8) with a human brain cDNA library, incorporated into a replication-competent mammalian retroviral expression vector whose replication occurs in the presence of T antigen. In murine cells, transcriptional activation of the P(f)LAG-8 promoter by a biologically active, cDNA-encoded signalling molecule resulted in plasmid replication. Replicated plasmids, following selective cleavage of unreplicated plasmids by Dpn1, were recovered by transformation into competent bacteria. Successive P(f)LAG-8/cDNA library co-transfections, using library plasmids resulting from prior transfections, ultimately resulted in the identification of individual plasmids capable of transcriptionally activating the FOS promoter. DNA sequencing revealed the first plasmid, denoted CROC-1, to contain a 1.8-kb cDNA encoding a 16.5-kDa nuclear protein possessing a bipartite structure comprised an amino-terminal acidic domain and a carboxy-terminal basic domain, and displaying partial homology to the HMG domain of the TAF(II)250 transcription cofactor. Co-transfection of CROC-1 with various FOS/CAT reporter genes revealed that the human FOS promoter region spanning -56 to - 105, encompassing two identical 8-bp DR enhancer sequences, was necessary for CROC-1-mediated transcriptional activation. Results suggest that CROC-1 participates in intracellular signalling pathways involved in induction of the human FOS promoter.

3T3 Cells↗

Protein binding versus protein folding: the role of hydrophilic bridges in protein associations.

The role of hydrophilic bridges between charged, or polar, atoms in protein associations has been examined from two perspectives. First, statistical analysis has been carried out on 21 data sets to determine the relationship between the binding free energy and the structure of the protein complexes. We find that the number of hydrophilic bridges across the binding interface shows a strong positive correlation with the free energy; second, the electrostatic contribution of salt bridges to binding has been assessed by a continuum electrostatics calculation. In contrast to protein folding, we find that salt bridges across the binding interface can significantly stabilize complexes in some cases. The different contributions of hydrophilic bridges to folding and to binding arise from the different environments to which the involved hydrophilic groups are exposed before and after the bridges are formed. These groups are more solvated in a denatured protein before folding than on the surface of the combining proteins before binding. After binding, they are buried in an environment whose residual composition can be much more hydrophilic than the one after folding. As a result, the desolvation cost of a hydrophilic pair is lower, and the favorable interactions between the hydrophilic pair and its surrounding residues are generally stronger in binding than in folding. These results complement our recent finding that while hydrophobic effect in protein-protein interfaces is significant, it is not as strong as that observed in the interior of monomers. Taken together, these studies suggest that while the types of forces in protein-protein interaction and in protein folding are similar, their relative contributions differ. Hence, association of protein monomers which do not undergo significant conformational change upon binding differs from protein folding, implying that conclusions (e.g. statistics, energetics) drawn from investigating folding may not apply directly to binding, and vice versa.

Binding Sites↗

Studies of protein-protein interfaces: a statistical analysis of the hydrophobic effect.

Data sets of 362 structurally nonredundant protein-protein interfaces and of 57 symmetry-related oligomeric interfaces have been used to explore whether the hydrophobic effect that guides protein folding is also the main driving force for protein-protein associations. The buried nonpolar surface area has been used to measure the hydrophobic effect. Our analysis indicates that, although the hydrophobic effect plays a dominant role in protein-protein binding, it is not as strong as that observed in the interior of protein monomers. Comparison of interiors of the monomers with those of the interfaces reveals that, in general, the hydrophobic amino acids are more frequent in the interior of the monomers than in the interior of the protein-protein interfaces. On the other hand, a higher proportion of charged and polar residues are buried at the interfaces, suggesting that hydrogen bonds and ion pairs contribute more to the stability of protein binding than to that of protein folding. Moreover, comparison of the interior of the interfaces to protein surfaces indicates that the interfaces are poorer in polar/charged than the surfaces and are richer in hydrophobic residues. The interior of the interfaces appears to constitute a compromise between the stabilization contributed by the hydrophobic effect on the one hand and avoiding patches on the protein surfaces that are too hydrophobic on the other. Such patches would be unfavorable for the unassociated monomers in solution. We conclude that, although the types of interactions are similar between protein-protein interfaces and single-chain proteins overall, the contribution of the hydrophobic effect to protein-protein associations is not as strong as to protein folding. This implies that packing patterns and interatom, or interresidue, pairwise potential functions, derived from monomers, are not ideally suited to predicting and assessing ligand associations or design. These would perform adequately only in cases where the hydrophobic effect at the binding site is substantial.

Amino Acids↗

Incidence of NIDDM and the effects of gender, obesity and hyperinsulinaemia in Taiwan.

Our aim is to determine non-insulin-dependent diabetes mellitus (NIDDM) incidence in Taiwan and examine its relation to obesity and hyperinsulinaemia in Chinese men and women. A total of 995 men and 1195 women aged 35-74 years free from diabetes in two townships in Taiwan were followed up with a second examination. At baseline general and metabolic data were recorded, and detailed anthropometric parameters and plasma glucose and insulin were assessed. World Health Organisation (WHO) criteria of fasting glucose 7.8 mmol/l or greater was utilized for defining diabetes. The age-standardized incidence rate based on the United States population in 1970 was 9.3/1000 (CI 5.8-12.8) in men and 9.3/1000 (CI 6.2-12.4) in women and the based on the WHO population in 1976 was 8.9/1000 (CI .5-12.3) in men and 8.9/1000 (CI 5.9-11.9) in women for the Chinese who had a mean BMI slightly greater than 24 (kg/m2). The predictability of the plasma glucose level was greater than that of the insulin level and the obesity indices. NIDDM incidence increased approximately threefold with each 0.67 mmol/l increase in plasma glucose level in men and women. The present study demonstrated the essential relationship of not only BMI but also central obesity indices (such as subscapular and waist circumference) to the incidence of NIDDM among men and women and a stronger relationship between NIDDM incidence and obesity in women than in men. The predictive effects of obesity indices and fasting plasma insulin values on NIDDM risk were independent of each other in men. Obesity and hyperinsulinaemia each without the presence of the other can lead to an increased risk of NIDDM. In women the NIDDM incidence increased more than additively in those with both obesity and hyperinsulinaemia compared to those with single obesity or hyperinsulinaemia. A slightly higher incidence of NIDDM in Taiwan than in western countries was found. The importance of obesity is indicated for predicting NIDDM in the community. Hyperinsulinaemia was found to play a significant role in predicting NIDDM incidence independent of obesity in men and synergistically with obesity in women.

Adult↗

Three-dimensional model of sensory rhodopsin I reveals important restraints between the protein and the chromophore.

A structural model is constructed for the integral membrane protein, sensory rhodopsin I (SRI), the phototaxis receptor of the archaeon Halobacterium salinarium. The model is built on the template of the homologous bacteriorhodopsin (BR). The modeling procedure includes sequence alignment, a side chain rotamer search and simulated annealing by restricted molecular dynamics. The structure is in general agreement with previous results from mutagenesis experiments, chromophore substitution and room and cryogenic temperature spectroscopy. In particular, a residue near the beta-ionone ring of the retinylidene chromophore is found to be critical in maintaining the proper isomeric conformation of the chromophore; a layer of residues lying on the cytoplasmic side of the chromophore pocket is found to modulate the restraints around the C13 region of the chromophore, affecting the isomerizations around its 13 = 14 bond that are important to the protein's activity. The restraints in these regions are more stringent in SRI than in BR. The tightened restraints are chiefly due to van der Waals interactions, where the attractive and repulsive components play separable roles. Aromatic residues account for a majority of the restrictive interactions. It is hypothesized that the enhanced barriers due to these restrictions regulate the progress of SRI's photocycle, so that it can couple with the phototaxis reaction chain in the bacterium. A possibility is also suggested that conformational changes of the protein provide the signal recognized by the transducer.

Amino Acid Sequence↗

Factors related to detection of blood flow by color Doppler ultrasonography in intussusception.

Color Doppler ultrasonography was performed in 125 patients with 134 intussusceptions. Color flow was present in 121 cases of intussusception (group A) and was absent in 13 cases (group B). Young age and duration of symptoms greater than 48 hr were significantly related to the nonvisualization of blood flow detected by color Doppler sonography (P < 0.05). The successful rate of air reduction was significantly higher in group A than in group B (109 of 121 versus 4 of 13). Color Doppler ultrasonography is useful to predict the reducibility of an intussuscepted intestine. The nonvisualization of blood flow by this method is not a contraindication for air reduction.

Adolescent↗

Transitional cell and uncommon urothelial carcinoma of renal pelvis/ureter and bladder: low incidence of human papilloma virus.

BACKGROUND: Recently, it has been proposed that human papilloma virus (HPV) infection may play a role in the carcinogenesis of bladder urothelial malignancy. However, there is still controversy about the prevalence of HPV in such malignancies. With similar techniques of in situ hybridization (ISH) or polymerase chain reaction (PCR), either high or rare frequency have been detected. To evaluate the prevalence of HPV in the urothelial malignancies based on presentations here, 118 cases of urothelial malignancies were analysed, including those of the renal pelvis and ureter which have rarely been reported before. METHODS: Non-isotopic ISH technique was used to detect HPV on paraffin sections, including 51 bladder transitional cell carcinoma (TCC), 48 renal pelvic/ureter TCC, 5 bladder adenocarcinoma, 3 bladder small cell carcinoma, 2 bladder undifferentiated carcinoma, 1 multiple synchronous pelvic and ureteric squamous cell carcinoma (SCC) and 8 bladder SCC. An FITC-labelled probe of wide spectrum HPV was used for screening, and probes of HPV 6/11, 16, 18, 31, 33 were used for typing. RESULTS: By the technique of ISH, wide spectrum HPV was detected in only three of the eight cases of bladder SCC. Of the three positive cases, two were subsequently shown to be uterine cervical SCC with bladder invasion. Therefore, HPV was positive in only one case of primary bladder SCC, occurring in a patient with systemic lupus erythematosus under steroid and cyclophosphamide therapy. Further subtyping was negative for HPV 6/11, 16, 18, 31, and 33. The result indicated that the positive staining by wide spectrum probe was caused by types 30, 35, 45, 51, and/or 52. HPV was not detected in any of the 51 bladder TCC, 48 renal pelvic/ ureter TCC, 5 bladder adenocarcinoma, 3 bladder small cell carcinoma, and 2 bladder undifferentiated carcinoma. CONCLUSIONS: The results are in agreement with the majority of recent reports which suggest that HPV is unlikely to be involved in the etiology of urothelial malignancies; however, it seems probable that immunosuppressed patients are at greater risk for HPV-associated bladder SCC.

Adenocarcinoma↗

The relation between thickened aortic valve and coronary artery disease.

BACKGROUND: The relationship between the site of aortic valve thickening and ipsilateral coronary artery stenosis has not been reported previously. This study was undertaken to test the hypothesis that left-sided coronary cusp thickening may be associated with a left-sided coronary artery stenosis, and also as would be in the right-sided relationship. METHODS: Two-dimensional echocardiography and cardiac catheterization were used to evaluate 420 consecutive patients. One hundred and six patients who had echocardiographic evidence of a single aortic valve thickening were studied to determine whether there was a relation between the coronary artery stenosis and the aortic valve thickening at the same side. Thickened aortic valve was defined as an aortic valve thickness to aortic wall thickness ratio > or = 1.0. Coronary artery disease (CAD) was defined as a > 50% luminal diameter narrowing of the left main coronary artery or a > 70% luminal diameter narrowing of the coronary artery other than the left main coronary artery. RESULTS: Patients with a thickened aortic valve had a greater incidence of CAD (89/132, 67.4%) than those without (141/288, 49.0%) (p < 0.05). In patients with thickened aortic valves, the incidence of CAD was 45.5% in the fifth decade, 60% in the sixth decade, 69.6% in the seventh decade and 74.1% in the eighth decade. Progressive increase of the incidence of CAD was not found in patients without a thickened aortic valve. In the 106 cases with a single aortic valve thickening, 30 patients (28.3%) had a left coronary cusp thickening; 12 of them (40%) had a left-sided coronary artery stenosis, 3 patients (10%) had right coronary artery stenosis and 7 patients (23.3%) had no coronary artery stenosis. In the 34 patients with right coronary cusp thickening, the stenosis occurred at the left coronary artery in 13 patients (38.2%), at the right coronary artery in 3 patients (8.8%) and with normal coronary artery in 5 patients (14.7%). This finding did not support the relationship between thickened aortic valve and coronary artery disease at the same side (chi 2 = 0.06, p = 0.96). CONCLUSIONS: There was a significantly greater incidence of CAD in patients with a thickened aortic valve than in those without. The incidence of CAD in patients with thickened aortic valves increased with age. There was no direct relationship observed between the site of aortic valve thickening and ipsilateral coronary artery stenosis.

Adult↗

Salmonella typhimurium brain abscess in a six-month-old infant: a case report and review of the literature.

We report the case of a six-month-old male infant with brain abscess caused by Salmonella typhimurium. Upon admission, he was suffering from fever, diarrhea, drowsiness and convulsion. Salmonella meningitis was identified by CSF examination. Following failure of antibiotic therapy to control his fever, brain computerized tomography (CT) was ordered 5 days later and revealed a brain abscess. He received surgical excision of the abscess and recovered completely after receiving ceftriaxone therapy for 8 weeks. The case of our patient, together with 11 cases of Salmonella brain abscess from the English literature are reviewed. There was a male preponderance among these patients (male: female = 2.67 : 1) and the majority were less than one year old. Salmonella typhimurium, typhi, and enteritidis occurred most frequently. Fever, seizure, signs and symptoms of increased intracranial pressure and change in mental status were the most common clinical features. Purulent meningitis was a major predisposing factor. Successful treatment was associated with early identification, prompt surgical intervention, high dose, long-term antibiotic therapy, and close follow-up for possible recurrence and to determine the presence of neurological sequelae.

Anti-Bacterial Agents↗

Minimally-invasive early prenatal diagnosis using fluorescence in situ hybridization on samples from uterine lavage.

A two-phase study was undertaken to examine the efficiency of using transcervical cells (TCCs) collected by uterine lavage and fluorescence in situ hybridization (FISH) for early prenatal diagnosis of fetal chromosome aneuploidy. Uterine lavage was performed in 50 women scheduled for elective termination of pregnancy (TOP, n = 35) or chorionic villus sampling (CVS, n = 15) between 6 and 11 weeks of gestation. TCCS were dissociated by trypsin and collagenase, and interphase FISH was carried out for chromosomes X, Y, 13/21, and 18. The phase I study comprised 36 women. The FISH results were compared with the cytogenetic analysis from long-term culture of villus samples collected at TOP or CVS. Among the 36 samples, 15 had a normal male karyotype and 21 had a normal female karyotype. FISH on TCCs correctly identified 13 out of the 15 pregnancies with a male fetus. In phase II, uterine lavage was performed on 14 women. The samples were first tested for the presence of trophoblasts with an anti-trophoblast antibody, GB25, by immunohistochemical staining. Among 12 GB25-positive samples, the FISH results corresponded to the fetal karyotype. One of the GB25-positive samples had five signals for the chromosome 13/21 probe. The cytogenetic analysis confirmed that the fetus had a karyotype of 47, XX, +21. In the GB25-negative samples, FISH failed to identify one male pregnancy. Follow-up was carried out on 13 ongoing pregnancies and no maternal or fetal complications were discovered. This study demonstrates that fetal chromosome numeration can be carried out using FISH on uterine lavage samples in early pregnancy. However, a specific fetal cell marker, such as specific anti-trophoblast antibody, is necessary to avoid a false-negative result.

Adult↗

Predicting the outcome of hemodialysis arteriovenous fistulae using duplex ultrasonography.

Duplex ultrasonography is a reliable method for assessing the anatomic features and blood flow rate of a vascular access point of hemodialysis. We assessed the value of measurement of cross-sectional area and blood flow rate of the major outflow veins using duplex ultrasonography in predicting the outcome of fistulae. Radiocephalic arteriovenous fistulae were created in 126 consecutive end-stage renal failure patients (55 men, 71 women; aged 20-83 yr) and examined using duplex ultrasonography in the second week following surgery. Examinations were repeated in 45 of the 126 fistulae in the third week. The outcome of new fistulae was classified as success or failure. The failure group fistulae were further classified as delayed maturation or primary failure. The cross-sectional area (12.1 +/- 3.5 vs 6.9 +/- 2.4 mm2) and blood flow rate (825.6 +/- 424.3 vs 303.7 +/- 114.5 mL/min) were significantly lower in the failure group, but there was no difference between the subgroups of primary failure and delayed maturation. Receiver-operating characteristic plots were generated for cross-sectional area and blood flow rate. The best cut-off point for distinguishing successful outcome from failure was 8.5 mm2 for cross-sectional area (sensitivity 0.823, specificity 0.867, positive predictive value 0.952, negative predictive value 0.605) and 425 mL/min for blood flow rate (sensitivity 0.813, specificity 0.933, positive predictive value 0.975, negative predictive value 0.609). Our findings show the cross-sectional area and blood flow rate, as measured using duplex ultrasonography, are useful in predicting the outcome of vascular access points of hemodialysis.

Adult↗

A dataset of protein-protein interfaces generated with a sequence-order-independent comparison technique.

While there are a number of structurally non-redundant datasets of protein monomers, there is none of protein-protein interfaces. Yet, the availability of such a dataset is expected to provide an added insight into a number of investigations. First and foremost among these is analyzing the interfaces to obtain their prevailing architectures, the forces that account for the protein-protein associations and their packing considerations. Their comparisons with those of the monomers are likely to shed additional light on protein-protein recognition on the one hand and on the folding of the polypeptide chain on the other. Docking simulations are also expected to benefit from the existence of such a dataset. A major stumbling block to the generation of a dataset of interfaces has been that the interface is composed of at least two chains. Furthermore, in the interfaces, each of the chains might be represented by non-contiguous pieces. Their order in the interfaces being compared might be different as well. This discontinuity stems from the definition of an interface. An interface consists of interacting residues between the chains, and those that are in their vicinity in the supporting scaffold, within a certain distance threshold. This necessarily yields unordered fragments, as well as isolated residues. Our novel, efficient, sequence-order-independent structural comparison technique is ideally suited to handle the task of the generation of a library of structurally non-redundant protein-protein interfaces. As it is computer-vision based, it views atoms as collections of points in space, disregarding their chain connectivity. In this work, 351 interface-families are created. Comparisons of the interfaces, and separately, of the chains which contribute to them, yield some interesting cases. In one of the cases, while two interfaces are similar, the structure of only one of the two chains is similar between the two complexes. The structure of the second chain of the first complex differs from that of the second chain of the second complex. Here the structure of the cleft in the first chain dictates the specific binding interactions. In another case, while the interfaces in the two complexes are similar, both chains composing them differ between the complexes. Lastly, the chains composing the complexes are similar, but the interfaces are dissimilar, providing a set of data for investigations of the favorable orientations of protein-protein associations.

Algorithms↗

Diagnostic value of C-reactive protein in children with perforated appendicitis.

UNLABELLED: The diagnostic value of serum C-reactive protein (CRP) levels in children with perforated appendicitis was prospectively studied in 78 consecutive patients with histologically confirmed appendicitis. The patients were divided into two groups: group A included 56 patients with perforated appendicitis and group B consisted of 22 patients with simple appendicitis. Serum CRP level and leucocyte count were assayed in all and abdominal ultrasonography was performed in 75. The mean age group A patient was significantly lower than that of group B patients (7.5 vs. 10.4 years, P < 0.001). Group A patients had a significantly higher mean serum CRP levels than group B patients (92 vs. 31 mg/l, P < 0.001), while the mean leucocyte count was comparable in the two groups. Of 75 examined patients, 73 (97%) had a pre-operative sonographic diagnosis of appendicitis. CONCLUSION: Perforation is a common complication in children with appendicitis, especially in those of young age and with prolonged pain duration. Greatly increased serum CRP levels (> or = 50 mg/l) and abdominal ultrasonography are important diagnostic aids in such patients.

Adolescent↗

Molecular recognition via face center representation of a molecular surface.

While docking methodologies are now frequently being developed, a careful examination of the molecular surface representation, which necessarily is employed by them, is largely overlooked. There are two important aspects here that need to be addressed: how the surface representation quantifies surface complementarity, and whether a minimal representation is employed. Although complementarity is an accepted concept regarding molecular recognition, its quantification for computation is not trivial, and requires verification. A minimal representation is important because docking searches a conformation space whose extent and/or dimensionality grows quickly with the size of surface representation, making it especially costly with big molecules, imperfect interfaces, and changes of conformation that occur in binding. It is essential for a methodology to establish that it employs an accurate, concise molecular surface representation. Here we employ the face center representation of molecular surface, developed by Lin et al., to investigate the complementarity of molecular interface. We study a wide variety of complexes: protein/small ligand, oligomeric chain-chain interfaces, proteinase/protein inhibitors, antibody/antigen, NMR structures, and complexes built from unbound, separately solved structures. The complementarity is examined at different levels of reduction, and hence roughness, of the surface representation, from one that describes subatomic details to a very sparse one that captures only the prominent features on the surface. Our simulation of molecular recognition indicates that in all cases, quality interface complementarity is obtained. We show that the representation is powerful in monitoring the complementarity either in its entirety, or in selected subsets that maintain a fraction of the face centers, and is capable of supporting molecular docking at high fidelity and efficiency. Furthermore, we also demonstrate that the presence of explicit hydrogens in molecular structures may not benefit docking, and that the different classes of protein complexes may hold slightly different degrees of interface complementarity.

Antigen-Antibody Complex↗

Protein-protein interfaces: architectures and interactions in protein-protein interfaces and in protein cores. Their similarities and differences.

Protein structures generally consist of favorable folding motifs formed by specific arrangements of secondary structure elements. Similar architectures can be adopted by different amino acids sequences, although the details of the structures vary. It has long been known that despite the sequence variability, there is a striking preferential conservation of the hydrophobic character of the amino acids at the buried positions of these folding motifs. Differences in the sizes of the side-chains are accommodated by movements of the secondary structure elements with respect to each other, leading to compact packing. Scanning protein-protein interfaces reveals that similar architectures are also observed at and around their interacting surfaces, with preservation of the hydrophobic character, although not to the same extent. The general forces that determine the origin of the native structures of proteins have been investigated intensively. The major non-bonded forces operating on a protein chain as it folds into a three-dimensional structure are likely to be packing, the hydrophobic effect, and electrostatic interactions. While the substantial hydrophobic forces lead to a compact conformation, they are also nonspecific and cannot serve as a guide to a conformationally unique structure. For the general folding problem, it thus appears that packing is a prime candidate for determining a particular fold. Specific hydrogen-bonding patterns and salt-bridges have also been proposed to play a role. Inspection of protein-protein interfaces reveals that the hallmarks governing single chain protein structures also determine their interactions, suggesting that similar principles underlie protein folding and protein-protein associations. This review focuses on some aspects of protein-protein interfaces, particularly on the architectures and their interactions. These are compared with those present in protein monomers. This task is facilitated by the recently compiled, non-redundant structural dataset of protein-protein interfaces derived from the crystallographic database. In particular, although current view holds that protein-protein interfaces and interactions are similar to those found in the conformations of single-chain proteins, this review brings forth the differences as well. Not only is it logical that such differences would exist, it is these differences that further illuminate protein folding on the one hand and protein-protein recognition on the other. These are also particularly important in considering inhibitor (ligand) design.

Amino Acids↗

Interphase fluorescence in situ hybridization in a Turner syndrome variant with IsoXq. A case report.

BACKGROUND: Performing fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells has been known to produce rapid diagnoses of major chromosomal aberrations. However, if the aberration involves a structural chromosomal anomaly, the FISH result may be not only uninformative but misleading. CASE: FISH with alpha-satellite probes of chromosomes X and Y was performed on the uncultured amniocytes of a prenatal amniotic fluid specimen. Eighty-five percent of the hybridized interphase nuclei displayed two signals when probing with X; no significant hybridization was found when probing with Y. This FISH result was interpreted as normal, disomic for chromosome X. Cytogenetic analysis later, however, disclosed the fetal karyotype to be 46,X,i(Xq). CONCLUSION: Interphase FISH with an alpha-satellite probe (or probe made of repeat centromeric sequences) may be useful in the detection of a numerical anomaly of a chromosome but not of a structural anomaly within the chromosome itself.

Amniotic Fluid↗