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Biomedical subjects

P Fan

Publications and source records attributed to P Fan.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effects of ammonium ions on synaptic transmission and on responses to quisqualate and N-methyl-D-aspartate in hippocampal CA1 pyramidal neurons in vitro.

Effects of NH4Cl on CA1 pyramidal neurons and synaptic transmission were investigated with intracellular recording in fully submerged rat hippocampal slices. Superfusion with 1-4 mM NH4Cl reversibly depolarized the membrane by 15.1 +/- 1.4 mV, reduced the amplitude and broadened the duration of action potentials due to a slower rate of repolarization, without significant change in membrane conductance. When membrane potential was returned to control level by the injection of a steady outward current, action potential amplitude recovered but repolarization remained slow. The extent of depolarization was not dependent on the concentration of NH4Cl between 1 and 4 mM. NH4Cl greatly depressed orthodromic transmission evoked by the stimulation of Schaffer collateral/commissural fibers several minutes after depolarizing the CA1 neuron. Interruption of transmission began with a decrease in excitatory postsynaptic potential (EPSP) amplitude and eventually EPSPs were almost eliminated. When NH4Cl was removed, it took 2-3 min for membrane potential and 10-15 min for transmission to recover. Inward currents induced by bath application of quisqualate acting on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were also depressed. In contrast, NH4Cl enhanced N-methyl-D-aspartate (NMDA)-induced currents. This potentiation disappeared in the absence of added Mg2+. A reduction in quisqualate-induced responses provided a possible explanation for the inhibition of excitatory transmission by NH4Cl.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Backbone dynamics of (Pro-Hyp-Gly)10 and a designed collagen-like triple-helical peptide by 15N NMR relaxation and hydrogen-exchange measurements.

The backbone dynamics of specific residues in two collagen-like triple-helical peptides with (X-Y-Gly)n sequences have been investigated using two-dimensional inverse-detected 15N NMR relaxation measurements and hydrogen-exchange experiments. One peptide, (POG)10, has the highest possible imino acid content and is considered to be a very stable prototype of a triple helix. The second peptide, (POG)3ITGARGLAGPOG(POG)3 (denoted T3-785), models an imino acid poor region of type III collagen and contains 12 residues from near the unique collagenase cleavage site. 15N relaxation parameters and hydrogen-exchange data were obtained for a glycine residue in the center of (POG)10 and for the tripeptide unit Gly-Leu-Ala in the middle of T3-785. Analysis of the relaxation data of the rodlike triple-helical peptides required the assumption of anisotropic overall motion, and the model-free approach of Lipari and Szabo (1982) was used to derive overall motional parameters and the order parameter, S2, that describes the amplitudes of the internal motion. First the mobilities of the Gly, Leu, and Ala residues in peptide T3-785 were compared. Both hydrogen-exchange methods and relaxation measurements indicated that the residue in the Y position (Ala) is more mobile than residues in the Gly and X positions (Leu). The slower exchange rates of Gly and Leu compared to that of Ala are consistent with the two-hydrogen-bonded model for the triple helix. Then the backbone mobilities of the central Gly residue were compared for the two peptides (POG)10 and T3-785. In this case, 15N relaxation measurements give different results from hydrogen exchange. The glycine residues in the trimer form of both T3-785 and (POG)10 have high values for the order parameter (near 0.85), suggesting similar small-amplitude internal motions and rigid backbones in both peptides. In contrast to the similar values of the order parameters, hydrogen-exchange data indicate that the central Gly exchanges at a faster rate in the trimer form of T3-785 than in (POG)10. These results suggest that a Gly in the imino acid rich environment of (POG)10 is dynamically different from a Gly in the imino acid poor environment of T3-785 and that the difference lies in the slower motion related to stability, rather than the faster motion on the picosecond time scale. This sequence-dependent difference in dynamical properties may have important consequences for recognition processes in collagen.

Amino Acid Sequence↗
PubMed1993

Two-dimensional NMR assignments and conformation of (Pro-Hyp-Gly)10 and a designed collagen triple-helical peptide.

Homonuclear and heteronuclear 2D NMR methods are used to study two triple-helical peptides. One peptide, (POG)10, is considered to be the most stable prototype of a triple helix. The second peptide, (POG)3ITGARGLAGPOG(POG)3 (denoted T3-785), was designed to model an imino acid poor region of collagen and contains 12 residues from near the unique collagenase cleavage site in type III collagen. Both peptides associated as trimers, with melting temperatures of 60 degrees C for (POG)10 and 25 degrees C for the T3-785 peptide. Sequence-specific assignments were made for a tripeptide unit POG in (POG)10, and 80% of the POG triplets are found to be in an equivalent environment. In T3-785, with nonrepeating X-Y-Gly units incorporated in the sequence, the three chains of the homotrimer can be distinguished from one another by NMR. The solution conformation of (POG)10 is very similar to the model derived from X-ray fiber diffraction data, although the peptide contains less ordered regions at the peptide ends. In the trimer from of T3-785, the central residues of the three chains are closely packed, and the data are consistent with a triple-helical model with a one-residue stagger of three parallel chains. For T3-785, in contrast to (POG)10, there are also resonances from a less ordered form, which are probably due to the presence of a small amount of monomer. The similarity of the backbone conformations of T3-785 and (POG)10 suggests that an alternative conformation is not present in the imino acid poor region.

Amino Acid Sequence↗
PubMed1993

Structural characterization of monellin in the alcohol-denatured state by NMR: evidence for beta-sheet to alpha-helix conversion.

Two-dimensional 1H NMR spectroscopy and hydrogen exchange methods have been used to characterize the alcohol-denatured state of monellin. Monellin is a sweet tasting protein composed of two chains. In the native state, the A-chain consists entirely of beta-structure, and the B-chain contains both alpha- and beta-structure. Upon addition of either 50% ethanol or 50% trifluoroethanol (TFE), the native structure of monellin is disrupted resulting in an alcohol-denatured state with properties different from those of the random coil state. In the alcohol-denatured state, the far-UV circular dichroism (CD) spectrum displays a higher helical content relative to the native state and the intensity of the near-UV CD signal is completely lost. One-dimensional NMR studies show that there are approximately 14 amide protons protected from exchange with solvent in the alcohol-denatured state and that large portions of the protein exchange at a rate that is comparable to the exchange rate of the protein in urea. Utilizing hydrogen exchange trapping techniques, the slowly exchanging residues are identified at pH 2.0 in 50% ethanol and 50% TFE (A10-A15, A18, A19, A21, A24, and A39) and are found to be clustered on one region of the A-chain. Preliminary 2D NMR assignments show that in the alcohol-denatured state the A-chain of monellin undergoes structural reorganization, with one strand of the native state beta-sheet on the A-chain (residues A17-A30) becoming an alpha-helix in the alcohol-denatured state. The secondary structure of the A-chain in the alcohol-denatured state is different from the native state structure, although the slowly exchanging residues are similar.

Amino Acid Sequence↗
PubMed1993

Comparison of various agents in contrast enhancement of color Doppler flow images: an in vitro study.

The commercially manufactured contrast agents, Echovist and Albunex, were compared with sonicated conventional agents, indocyanine green, 29% renografin-60, 0.9% normal saline and 25% mannitol in their ability to enhance color Doppler flow signals. In a pneumatically regulated pulsatile flow system, a glycerine, saline (0.9%) and sand (5 microns particle size) solution was imaged using a 2.5 MHz phased-array transducer. Four different flow velocities (0.40, 0.35, 0.30 and 0.25 m/s) as measured by color Doppler guided pulse Doppler were utilized. All color Doppler settings were kept constant throughout the study. Utilizing a power injector, four different volumes (1.0, 1.5, 2.0 and 2.5 mL) of each contrast agent were injected into the flow medium at various transducer angles (20, 30, 40 and 60 degrees) and various distances from the transducer (3.38, 5.5, 6.76 cm). For Echovist and Albunex, several concentrations varying from 2% to 100% were used. Keeping instrument settings constant, color flow areas obtained before and after each contrast injection were planimeterized and the percent increase in the color flow area computed and compared. At full (100%) concentration, 20 degrees transducer angle and a flow velocity of 0.40 m/s, the maximum increase in the color flow area was 568%, 251%, 180%, 110%, 71%, and 38% for Echovist, Albunex, sonicated indocyanine green, renografin, normal saline and mannitol, respectively. However, a significant reduction in the degree of color flow enhancement was observed, with decreases in the concentration of these agents, and increases in the Doppler beam incident angle or distance from the transducer. Increasing the flow velocity of the medium into which contrast was injected did not produce significant changes in the contrast enhancement effect for all agents except Echovist. Increasing the injection volume significantly increased the color flow area for sonicated agents but not for Echovist or Albunex. This preliminary in vitro study shows that the commercially manufactured contrast agents, Echovist and Albunex, are much superior to sonicated conventional contrast agents in the enhancement of color Doppler flow signals. Of the sonicated agents, indocyanine green had the best enhancement capability.

Blood Flow Velocity↗
PubMed1993

Structure-function studies of the C-terminal alpha-helix of human interleukin-2 by site-directed mutagenesis.

By using oligonucleotide-mediated site-directed mutagenesis, we obtained three human interleukin-2 analogs with substitution of Pro in the C-terminal amphiphilic alpha-helix, 125Pro-IL-2, 127Pro-IL-2 and 125Pro-127Pro-IL-2. The bioactivities of all these analogs were decreased. The extent of the decrease in bioactivity coincided with the degrees of secondary and tertiary structure destroyed, as evaluated by circular dichroism and intrinsic fluorescence analysis. The results suggested that the integrity of the hydrophobic face in the C terminal alpha-helix is crucial for the structure and function of interleukin-2.

Base Sequence↗
PubMed1993

Influence of left ventricular assist on valvular regurgitation.

BACKGROUND: The effects of mechanical left ventricular assist on the nonassisted right ventricle have not been fully elucidated. Current information indicates that the right ventricle benefits from a lower left atrial pressure; however, ventricular septal shifting and increased venous return caused by left ventricular assist impair right ventricular function. Acute intraoperative alterations in mitral and tricuspid valve regurgitation (MR and TR, respectively) may occur as a result of mechanical left ventricular assist but have not yet been documented. METHODS AND RESULTS: Eight patients undergoing implantation of a left ventricular assist device (LVAD) as a bridge to transplantation were studied during surgery by transesophageal echocardiography. MR was present in seven of eight patients, and TR was present in eight of eight patients before LVAD implant (mean MR jet area, 10.6 +/- 2.4 cm2, mean TR jet area, 4.8 +/- 1.0 cm2). Immediately after LVAD placement, MR was still present in seven of eight patients, and TR was present in eight of eight patients (mean MR jet area, 4.2 +/- 0.9 cm2; mean TR jet area, 8.4 +/- 1.9 cm2) (P < .05 preimplant versus postimplant jet area). These changes in MR and TR were associated with a decrease in left ventricular end-systolic dimension (62 +/- 4 versus 48 +/- 3 mm) and an increase in right ventricular end-systolic dimension (31 +/- 4 versus 40 +/- 5 mm) (P < .05 preimplant versus postimplant end-systolic dimension). No patients developed progressive right ventricular failure during 70 to 279 days of LVAD support. CONCLUSIONS: Mechanical left ventricular assist causes an acute decrease in preexisting MR. However, left ventricular assist may acutely worsen TR, presumably by shifting the ventricular septum leftward and increasing venous return to the right ventricle.

Cardiomyopathy, Dilated↗
PubMed1992

Application of echocardiographic color flow Doppler mitral regurgitation to the diagnosis of acute cardiac transplantation rejection.

Numerous noninvasive techniques have been examined for the detection of acute rejection following cardiac transplantation, but none has proven sufficiently sensitive to replace the endomyocardial biopsy. A prospective study was performed in 92 heart transplant patients in order to test the hypothesis that mitral regurgitant ratio by two-dimensional echocardiography with Doppler flow mapping could detect moderate or severe acute allograft rejection. There were 82 rejection episodes identified, of which 40% were associated with mitral regurgitation by echo-Doppler at the beginning of the episode. With augmentation of immunosuppression during a rejection episode, there was a progressive fall in the degree of mitral incompetence (P = 0.03). The sensitivity of color Doppler studies in identifying rejection was low (60% of all rejection episodes had no associated mitral incompetence at the beginning of the episode), but the likelihood of rejection progressively increased with higher degrees of mitral regurgitation (P less than 0.01), approaching 60% when the echo-Doppler regurgitant ratio exceeded 15%. Echo-Doppler studies do not provide sufficient sensitivity to be useful as a screening technique for acute cardiac rejection, but high or increasing echocardiographic mitral regurgitant ratio is predictive of acute rejection and should indicate prompt endomyocardial biopsy.

Adolescent↗
PubMed1992

Three-dimensional and four-dimensional transesophageal echocardiographic imaging of the heart and aorta in humans using a computed tomographic imaging probe.

We evaluated the clinical applicability of a prototype tomographic transesophageal echocardiographic (TEE) system, which not only provides conventional TEE images but also three-dimensional tissue reconstruction and four-dimensional display capabilities. The probe was used in 16 patients in the echocardiographic laboratory, intensive care unit, and the operating room. The instrument is a 5-MHz, 64-element, phased array unit mounted on a sliding carriage within a casing. After appropriate probe placement within the esophagus, the probe is straightened, a balloon surrounding the probe is inflated, and data acquisition begun with ECG and respiration gating. With computer controlled transducer movement at 1-mm increments, a complete cardiac cycle is recorded at each tomographic level. These are processed using a dedicated four-dimensional software, and displayed as a dynamic three-dimensional tissue image of the heart. We were able to see the dynamic motion of the ventricles and all the valves in the four-dimensional format. In addition to four-dimensional display, we were able to cut and visualize the heart in dynamic mode in any desired plane and also in multiple planes. Patients tolerated the procedure well. We conclude that this tomographic four-dimensional approach, which does not require tedious off-line processing, can easily be performed in patients and has a strong clinical potential.

Aorta↗
PubMed1990

Neurochemical and electrophysiological studies on the inhibitory effect of ammonium ions on synaptic transmission in slices of rat hippocampus: evidence for a postsynaptic action.

To elucidate the mechanisms involved in the inhibition of synaptic transmission by ammonium ions, the effects of NH4Cl on glutamate release and on synaptic transmission from Schaffer collaterals to CA1 pyramidal cells were measured in fully submerged slices of rat hippocampus. The large, Ca(2+)-dependent release of glutamate evoked by electrical-field stimulation or by 56 mM K+ was not reduced by 5 mM NH4Cl. In contrast, 5 mM NH4Cl decreased the smaller, field stimulation-induced release of glutamate observed in the presence of low concentrations of Ca2+ (0.1 mM), as well as the spontaneous release of glutamate both in normal and low Ca2+. Unlike the Ca(2+)-dependent release of glutamate, synaptic transmission was reversibly depressed even by 1 mM NH4 Cl. Firing of CA1 pyramidal cells evoked by iontophoretically applied glutamate was significantly inhibited by 2 or 5 mM NH4Cl. This depression was increased in the presence of 25 microM bicuculline. Results suggest that ammonium ions do not depress the Ca(2+)-dependent release of glutamate originating from synaptic vesicles, which is involved in synaptic transmission. Rather, ammonium ions inhibit synaptic transmission by a postsynaptic action, a conclusion strengthened by the inhibitory effect of NH4Cl on glutamate-induced firing. However, NH4Cl may inhibit the formation of cytoplasmic glutamate, the source of spontaneous and Ca(2+)-independent release.

Amino Acids↗
PubMed1990

A fluorescence study of the binding of Hoechst 33258 and DAPI to halogenated DNAs.

We have studied the time-resolved and the steady-state fluorescence of the DNA groove binders 4',6-diamidino-2-phenylindole (DAPI) and Hoechst 33258 with the double stranded DNAs poly(dA-dU) and poly(dI-dC) and their halogenated analogs, poly(dA-I5dU) and poly(dI-Br5dC). These studies were prompted by earlier observations that steady-state fluorescence of Hoechst 33258 is quenched on binding to halogenated DNAs (presumably due to an intermolecular heavy atom effect involving the halogen atom in the major groove), and recent studies which clearly point to a binding-site in the minor groove of DNA. Measurements of the time resolved fluorescence decay demonstrate that the fluorescence of Hoechst 33258 is quenched on binding to the halogenated DNAs, in agreement with previous observations. However, quenching studies carried out using the free halogenated bases IdUrd and BrdCyd in solution yielded bimolecular rate constants more than one order of magnitude larger than those expected for an intermolecular heavy atom effect. Moreover, the quenching of the Hoechst 33258 fluorescence was accompanied by an accelerated photochemical destruction of Hoechst 33258. We therefore conclude that the fluorescence quenching observed with halogenated DNAs is probably due to a photochemical reaction involving Hoechst 33258, rather than direct contact of Hoechst 33258 with the halogen substituents in the major groove of the DNA. The fluorescence decay measurements however, do provide clear evidence for at least two different modes of binding. Taking into account the alternating sequences used in this study and the possibility of two different conformations for bound dye, at least four different modes of binding are plausible. Our present data do not allow us to distinguish between these alternatives. The time-resolved fluorescence decays and fluorescence quantum yields of DAPI are not affected by the presence of the heavy atom substituents in the DNA major groove. Based on this observation and earlier reports that DAPI binds in one of the DNA grooves, we conclude that the high affinity sites for DAPI on DNA are located in the minor groove.

Benzimidazoles↗
PubMed1990

[Effects of high carbohydrate and high fat diet on plasma apolipoproteins AI, AII, B100, CI, CII, CIII and E in normal and hypertriglyceridemic humans].

Effects of high carbohydrate (CHO) and high fat diet on plasma apolipoproteins (apo) AI, AII, B100, CI, CII, CIII and E were assessed in 10 healthy subjects and 10 patients with endogenous hypertriglyceridemia. High CHO diet consisted of 80% CHO, 5% fat and 15% protein of total calories, and high fat diet consisted of 40% CHO, 45% fat and 15% protein. After 5 days normal diet (60% of total calories from CHO, 25% from from fat and 15% from protein), the subjects studied received sequentially high CHO diet and normal diet for 5 days and high fat diet and normal diet for 5 days. Fasting blood samples were drawn on days 1, 3, and 5 of high CHO and high fat diet period, and 5 days after taking normal diet. Results showed that fasting plasma apo AI slightly decreased (P less than 0.01) on day 3 of the high CHO diet period and slightly increased (P less than 0.01) on day 3 of the high fat diet period, plasma apo AII increased after intake of high CHO diet, but no changes were observed after the subjects were placed on high fat diet. Fasting plasma apo B100 decreased (P less than 0.001) in hypertriglyceridemics on the 3rd day of the high CHO diet, but no differences were noted in normal subjects on the same diet. On the 3rd day of the high fat diet period, apo B100 increased (P less than 0.01) in normal subjects, but no changes were found in hypertriglyceridemics. Apo CII and CIII levels declined during the high CHO diet period but increased in normal subjects after intake of high fat died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Effect of high carbohydrate and high fat diets on plasma glucose, insulin and lipids in normal and hypertriglyceridemic subjects].

The fasting plasma glucose, insulin and lipids response to high-carbohydrate-low-fat diets and low-carbohydrate-high-fat diets in normal subjects and patients with endogenous hypertriglyceridemia was observed. The normal, high carbohydrate and high fat diets consisted of 60%, 80% and 40% carbohydrate, 25%, 5% and 45% fat and 15% protein of total calorie respectively. The fasting plasma glucose levels increased (P less than 0.01) on day 1, insulin increased on day 3 (P less than 0.01 and P less than 0.05) and TG levels increased on days 3 and 5 after taking high carbohydrate diets both in the normal and hypertriglyceridemic groups. The fasting plasma TC and HDL-C decreased on high carbohydrate diets mainly in the hypertriglyceridemic group. The fasting plasma glucose slightly decreased on day 5, TG decreased on day 1 (P less than 0.05) and TC increased on day 1 and 3 (P less than 0.01) after taking high fat diets, but no differences were observed in insulin levels. Fasting plasma HDL-C levels in the normal group remained unchanged, but significantly decreased 3 days after taking high fat diets in the hypertriglyceridemic group (P less than 0.001). Our results indicate that high carbohydrate intake may be an important cause of hypertriglyceridemia in our country. This diet may cause a slight increase in the blood glucose level, which in turn stimulates an increase in plasma lipids and decrease in HDL-C, which is associated with an increase in the incident of coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Can two-dimensional echocardiography and Doppler color flow mapping identify the need for tricuspid valve repair?

Tricuspid regurgitation severity was assessed preoperatively with Doppler color flow mapping and these assessments were compared with surgical findings in 90 patients undergoing mitral or aortic valve replacement, or both. Group I (n = 52) required tricuspid valve annuloplasty because tricuspid regurgitation was judged intraoperatively to be severe; in Group II (n = 38), tricuspid valve annuloplasty was not performed because tricuspid regurgitation was judged intraoperatively not to be severe. With use of the apical four chamber and parasternal short-axis imaging planes, the severity of tricuspid regurgitation by Doppler color flow mapping was assessed by comparing the maximal area of tricuspid regurgitant signals with the right atrial area taken in the same frame in which the maximal tricuspid regurgitant signals were noted. This ratio was found to be greater than or equal to 34% (mean 50.2 +/- 11.8%) in 50 (96%) of 52 patients in Group I and less than 34% (mean 27.5 +/- 6.9%) in 36 (95%) of 38 patients in Group II (p less than 0.001). The maximal diastolic tricuspid anulus diameter measured with the same two-dimensional imaging planes was greater than or equal to mm/m2 body surface area (mean 26.7 +/- 5.2 mm/m2) in 46 patients (88%) in Group I and less than 21 mm/m2 (mean 17.8 +/- 2.5 mm/m2) in 36 patients (95%) in Group II (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1989

Doppler color flow mapping in the evaluation of prosthetic mitral and aortic valve function.

Doppler color flow mapping and color-guided conventional Doppler studies were performed on 119 patients with 126 prosthetic valves (mitral alone in 60, aortic alone in 52 and both mitral and aortic in 7 patients) within 2 weeks of the catheterization study or surgery, or both. The mean pressure gradients derived by color-guided continuous wave Doppler ultrasound correlated well with those obtained at catheterization for both the tissue and mechanical mitral and aortic prostheses (r = 0.85 to 0.87). For the effective prosthetic orifice areas, better correlation with catheterization results were obtained with the tissue mitral (r = 0.94) and tissue aortic (r = 0.87) prostheses than with the mechanical mitral (r = 0.79) and mechanical aortic (r = 0.76) prostheses. The maximal width of the color flow signals at their origin from the tissue mitral prostheses also correlated well with the effective prosthetic orifice area at catheterization (r = 0.81). Doppler color flow mapping identified prosthetic valvular regurgitation with a sensitivity and specificity of 89% and 100%, respectively, for the mitral and 92% and 83% for the aortic prostheses. There was complete agreement between the Doppler color flow mapping and angiographic grading of the severity of prosthetic valvular regurgitation in 90% of mitral and 73.5% of the aortic regurgitant prostheses with under- or overestimation by greater than 1 grade in only two cases. Valvular and paravalvular regurgitation was correctly categorized by Doppler color flow mapping in relation to the surgical findings in 94% of the mitral and 80.5% of the aortic prostheses.

Adult↗
PubMed1989

[Serum lipids and apolipoproteins AI, B100, CI and CII in patients with apoplexy].

Serum triglycerides, cholesterol, HDL-cholesterol and apolipoproteins (apo) AI, B100. CI and CII were determined and analyzed in 72 apoplectic patients and 64 age-matched normal subjects. Significantly increased triglycerides, low HDL-C and slightly decreased cholesterol levels were found in the apoplectics. Apo AI was slightly decreased and apo B100 slightly increased in the apoplectics compared with normal subjects. Apo CI and CII levels were significantly decreased in the apoplectics. The results are discussed.

Adult↗