Electron-impact-ionization cross section for the hydrogen atom.
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Journal Article↗
Biomedical subjects
W Hu
Publications and source records attributed to W Hu.
Use of cultured human neuroblastoma cells in rapid discovery of the voltage-gated potassium-channel blockers.
Depolarization of human neuroblastoma cells by high concentrations of extracellular potassium ions, leads to the activation of the voltage-gated potassium channels. The activity of such potassium channels can be effectively and rapidly monitored by tracking the efflux of 86Rb from pre-loaded target cells in response to the depolarizing stimulus. The inclusion of compounds with unknown activity in the assay medium, can result in the identification of novel blockers of the voltage-gated potassium channels. Since this functional assay is performed in 96-well microtitre plates, it represents a rapid and high-volume primary screening method for the detection and identification of the voltage-gated potassium-channel blockers, which may have therapeutic utility in several indications including memory degeneration and cardiac arrhythmias.
4-Aminopyridine↗
Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis.
Clonal expansion of T cell specificities in the synovial fluid of patients has been taken as evidence for a local stimulation of T cells. By studying the T cell receptor (TCR) repertoire of CD4+ T cells in the synovial and peripheral blood compartments of patients with early rheumatoid arthritis (RA), we have identified clonally expanded CD4+ populations. Expanded clonotypes were present in the peripheral blood and the synovial fluid but were not preferentially accumulated in the joint. Dominant single clonotypes could not be isolated from CD4+ cells of HLA-DRB1*04+ normal individuals. Clonal expansion involved several distinct clonotypes with a preference for V beta 3+, V beta 14+, and V beta 17+CD4+ T cells. A fraction of clonally related T cells expressed IL-2 receptors, indicating recent activation. The frequencies of clonally expanded V beta 17+CD4+ T cells fluctuated widely over a period of one year. Independent variations in the frequencies of two distinct clonotypes in the same patient indicated that different mechanisms, and not stimulation by a single arthritogenic antigen, were involved in clonal proliferation. These data support the concept that RA patients have a grossly imbalanced TCR repertoire. Clonal expansion may result from intrinsic defects in T cell generation and regulation. The dominance of expanded clonotypes in the periphery emphasizes the systemic nature of RA and suggests that T cell proliferation occurs outside of the joint.
Amino Acid Sequence↗
[Anterior interosseous flap].
An anatomical study which was carried out on 44 upper limbs of fresh cadavers has enabled us to describe a new flap based on the superior perforating branch of the anterior interosseous artery: "the anterior interosseous flap". The anterior interosseous artery participates in the vascularization of the dorsal aspect of the distal two-third of the forearm by providing two perforating branches, "the superior and the inferior perforating branches". The superior perforating branch of the anterior interosseous artery, pedicle of the flap, perforates the interosseous membrane 10 +/- 2 cm above the radio-carpal joint and runs in the septum between the extensor pollicis longus and brevis muscles accompanied by two venae comitantes. The calibre of the artery at its origin varies from 0.9 to 1.5 mm. During its course, the artery gives 5 to 7 septocutaneous branches to reach the overlying skin in the posterior aspect of the distal two-thirds of the forearm. It also gives 3 to 5 osseous branches spreading over the dorsal aspect of the distal third of the radius and several muscle branches to the abductor pollicis longus, extensor pollicis longus and brevis, extensor indicis and extensor digitorum muscles. The inferior perforating branch of the anterior interosseous artery generally perforates the interosseous membrane 4 to 5 cm above the radio-carpal joint. After giving a medial branch which anastomoses with the posterior interosseous artery (in 42 out of 44 cases) the inferior perforating branch of the anterior interosseous artery always runs distally to join the dorsal vascular network of the wrist which is rich enough to produce a retrograde arterial blood flow. This flap can be used as an island flap (with a retrograde or a direct blood flow) or a free flap. The surgical procedure of the retrograde island flap consists in raising the cutaneous or compound flap based on the superior perforating branch, division of the interosseous membrane and ligature of the anterior interosseous trunk proximally. The flap is vascularized by a retrograde blood flow through the dorsal (or volar or both) vascular network of the wrist. Theoretically, the most distal point of rotation of the flap is located at the level of the luno-capitate joint and the pedicle is long enough to allow the most distal point of the flap to reach the DIP joint of the finger.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
[The "extreme" brachial flap: a distal pedicled use of an external brachial flap. Preliminary report].
The authors present a new application of the procedure they called the "reverse flow YV pedicle extension" which allows a very distal pedicled mobilisation of the lateral arm flap. Until now, only the distally based lateral arm flap and the ulnar recurrent fascicutaneous island flap could to be transferred distally but reached only the proximal third of the forearm. In our experience these flaps did not seem to be very reliable. Lengthening of the lateral arm flap pedicle using the lateral triceps artery (branch arising from the profunda brachii artery) allows the lateral arm flap to be transferred beyond the distal third of the forearm. This so-called "extreme" lateral arm flap has advantages and disadvantages which are discussed in this paper. We consider cutaneous or osteocutaneous reconstructions of the forearm to be the best indication for this flap. Our first clinical case is reported.
Accidents, Traffic↗
[Reverse flow YV pedicle extension: a method of doubling the arc of rotation of a flap under certain conditions].
The authors present a new surgical procedure which allows the transfer of pedicled flaps distally to the origin of their vascular pedicle. They call this procedure the "reverse-flow YV pedicle extension of a flap". The idea is to raise a flap distally on a branch of a Y-like vascular bifurcation. The section of the trunk of the bifurcation turns the Y-into a V-vascular pattern, which allows distal mobilisation of the flap on the remaining branch of the V. The distal range of transposition of the flap can reach twice the length of one bifurcation of the flap. The arterial blood supply is provided by reverse-flow through the attached remaining branch of the V. Venous drainage is ensured as in a distally based pedicled flap. Up until now, the authors have performed six different applications of this procedure: arterial lengthening of a latissimus dorsi flap pedicled on the circumflex scapular artery for coverage of the vertex (a venous anastomosis is required in this case; lengthening of the submental vein in very distal transfers of a submental flap; lengthening of an arteriovenous pedicle: transfer of the anterior interosseous flap which can reach the PIP joint of long digits, transfer of an amputated digit on to the adjacent stump, distal transfer of a medial plantar flap allowing it to reach the tip of the toes, transfer of the lateral arm flap on to the triceps branch of the profunda brachii artery. This flap can reach the metacarpal area of the hand. This procedure seems to very usefully replace microsurgical techniques in many circumstances in which, until now, they would have been necessary. Further applications will be discussed.
Female↗
Rapidly-frozen polypeptide samples for characterization of high definition dynamics by solid-state NMR spectroscopy.
A method is described for defining anisotropic local dynamics in polypeptides by solid-state NMR. To avoid conformational heterogeneity introduced by large hexagonal ice crystals in low temperature hydrated samples, a fast-freezing technique is used for sample preparation. For a demonstration of this approach, the backbone librational motions of the gramicidin A channel conformation are studied in hydrated DMPC bilayers. The static 15N chemical shift tensor is characterized at 123 K for the Ala3 site. The temperature dependence of this tensor yields a determination of the librational amplitude and anisotropy of the motionally sampled space. This amplitude represents the sum of nanosecond and picosecond time-frame motions, both of which have a significant amplitude.
Alanine↗
High-resolution conformation of gramicidin A in a lipid bilayer by solid-state NMR.
Solid-state nuclear magnetic resonance spectroscopy of uniformly aligned preparations of gramicidin A in lipid bilayers has been used to elucidate a high-resolution dimeric structure of the cation channel conformation solely on the basis of the amino acid sequence and 144 orientational constraints. This initial structure defines the helical pitch as single-stranded, fixes the number of residues per turn at six to seven, specifies the helix sense as right-handed, and identifies the hydrogen bonds. Refinement of this initial structure yields reasonable hydrogen-bonding distances with only minimal changes in the torsion angles.
Amino Acid Sequence↗
Thermalization and spectral distortions of the cosmic background radiation.
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Journal Article↗
Restrictions in the repertoire of allospecific T cells. Contribution of the alpha-helical sequence polymorphism of HLA-DR molecules.
We have studied the molecular diversity of the allogeneic TCR repertoire specific for the HLA-DR4 variant, DRB1*0404, by analyzing the V beta gene segment usage of CD4+ T cell clones from nine different donors and comparing the V beta repertoire in allospecific and unselected T cell populations. To investigate the forces shaping the repertoire of the alloreactive T cell response we compared the diversity of TCR specificities utilized in very similar and in disparate responder/stimulator combinations. Six of the responders shared the HLA-DRB1*0401 allele, which differs from the HLA-DRB1*0404 allele by only two amino acid substitutions at positions 71 and 86 of the HLA-DR beta 1 chain; three responders expressed HLA-DRB1 alleles with extensive polymorphisms compared with the stimulator HLA-DRB1 allele. In all nine responders, TCR specificities recruited to recognize HLA-DRB1*0404 were strongly biased toward the dominant usage of one to three V beta elements. Despite some degree of heterogeneity between different responders, the overall pattern was very similar with a hierarchy of TCR V beta elements expressed by HLA-DRB1*0404 specific T cells. A core group of V beta elements (V beta 6, 5, 2, 13.2, 18, and 7) was preferentially used, whereas other V beta elements including V beta 3, 4, and 8 were infrequently used or not used at all. Sequencing of the VDJ beta region from selected T cell clones showed no junctional bias associated with the preferential V beta gene segment usage. Surprisingly, the T cell diversity in focused and in complex alloreactive responses were equally biased. The finding that HLA-DR4+ and DR4- donors exhibited a similar bias supports the interpretation that the alpha-helical HLA-DR structure of the stimulator cell has a dominant contribution in shaping the alloreactive repertoire.
Amino Acid Sequence↗
Tryptophans in membrane proteins: indole ring orientations and functional implications in the gramicidin channel.
Orientational constraints generated from solid-state NMR of uniformly aligned gramicidin A in hydrated lipid bilayers have been used to determine the indole ring orientations for the four tryptophans of the gramicidin A monomer with respect to the bilayer normal and the channel axis. 15N epsilon 1 labeled tryptophan has been incorporated into gramicidin at positions 9, 11, 13, and 15. The chemical shift tensor orientation has been oriented with respect to the N-H bond via doubly labeled sample in which the 15N epsilon 1-1H has been exchanged for 2H. By observation of the dipolar coupled 15N chemical shift powder pattern of the amino acid, sigma cc has been shown to be perpendicular to the plane of the ring and that sigma aa makes an angle of 25 degrees with respect to the N-H bond. The indole ring orientations were obtained from a consideration of both the chemical shift and the 15N-1H dipolar interaction. These four rings have very similar orientations with respect to the bilayer normal as given by the range of angles between the bilayer and ring normals (64-67 degrees). Furthermore, the N-H bond orientations with respect to the bilayer normal varies by only 10 degrees among the four sites. This orientational analysis has been based on an assumption that large amplitude librational motions in the hydrated bilayer samples are not averaging the nuclear spin interactions. This assumption was verified by analyzing the 2H quadrupole spectra of d5-Trp11-labeled gramicidin A in oriented preparations. The orientations predicted for the five C-H bonds in the indole ring from the 15N data agreed (root-mean-square deviation of 3.7 degrees) with the observed orientations from quadrupole splittings of the C-D bonds in the ring. From the orientation of the indole rings with respect to the bilayer normal and a polypeptide backbone conformation, the four typtophans of the gramicidin monomer are oriented with respect to the backbone of the channel conformation. The similarity among the indole orientations with respect to the bilayer normal is therefore consistent with the electrophysiological results that the individual replacement of the indole rings with phenyl rings results in a incremental decrease in the conductance of the channels formed. The indole orientations with respect to the backbone as defined by the side-chain torsion angles is not uniquely determined but yields a discrete set of possible values.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Thermalization constraints and spectral distortions for massive unstable relic particles.
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Journal Article↗
Detection and enumeration of circulating tumour cells in colorectal cancer.
Immunocytochemistry was used in parallel with conventional cytology to detect circulating malignant epithelial cells in 42 patients undergoing resection for colorectal cancer. Preoperative peripheral and peroperative mesenteric venous blood samples were taken. Tumour cells were isolated on a density gradient and cytospins prepared. Slides were stained by conventional cytology (May-Grünwald-Giemsa) and by an indirect immunoperoxidase technique with the anticytokeratin antibody KG8.13. Using conventional cytology, definite morphological evidence of malignancy was observed in three patients and suspicious features in a further seven. Immunocytochemistry confirmed these findings in all three of the malignant but in only one of the suspicious cases. Counts of immunostained cytospins showed the concentration of tumour cells in blood samples from these four patients to be in the range 0-954 cells/ml. This study supports the use of immunological markers to detect and enumerate malignant cells. This method provides a powerful tool to investigate one aspect of the metastatic process.
Adult↗
Orientational constraints as three-dimensional structural constraints from chemical shift anisotropy: the polypeptide backbone of gramicidin A in a lipid bilayer.
Chemical shifts observed from samples that are uniformly aligned with respect to the magnetic field can be used as very high-resolution structural constraints. This constraint takes the form of an orientational constraint rather than the more familiar distance constraint. The accuracy of these constraints is dependent upon the quality of the tensor characterization. Both tensor element magnitudes and tensor orientations with respect to the molecular frame need to be considered. Here these constraints have been used to evaluate models for the channel conformation of gramicidin A. Of the three models used, the one experimentally derived model of gramicidin in sodium dodecyl sulfate micelles fits the data least well.
Amino Acid Sequence↗
2H NMR determination of the global correlation time of the gramicidin channel in a lipid bilayer.
A detailed experimental description of molecular dynamics requires an accurate description of the global correlation time. For the gramicidin cation-selective channel the local dynamics of the polypeptide backbone are thought to play a very significant role in the functional process of this channel which occurs on the 10-100-ns time scale. By solid-state NMR spectroscopy an experimental description of the local dynamics including a description of the axis about which the motions occur, the amplitude of the motions, whether they are diffusional or discontinuous and the frequency of the motions is possible. Initial interpretations of the NMR data for this polypeptide backbone in fully hydrated lipid bilayers suggests that the time scale for the local motions is the same as the kinetic time scale (North and Cross, 1993). Here the global correlation time is found from d4-Ala3 and d4-Ala5-gramicidin A powder pattern spectra to be 36 microseconds at 309 K. This surprisingly long correlation time may reflect the high viscosity of the peptide environment or possibly the higher molecular weight of a peptide-lipid aggregate. Furthermore, this reassessment of the global correlation time supports the initial interpretation of relaxation data for the local motions.
Biophysical Phenomena↗
Energy distribution of secondary electrons in electron-impact ionization of hydrogenic and heliumlike ions.
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Journal Article↗
Partial agonist effect of the platelet-activating factor receptor antagonists, WEB 2086 and WEB 2170, in the rat perfused heart.
1. WEB 2086 and WEB 2170 are potent platelet-activating factor (PAF) receptor antagonists and have been used widely as pharmacological tools to investigate the actions of PAF in a variety of biological systems. 2. Low concentrations of WEB 2086 and WEB 2170 blocked the vasoconstrictor action of PAF in the rat perfused heart. In this study, we observed that moderate concentrations of WEB 2086 and WEB 2170 increased the perfusion pressure in rat isolated hearts under constant flow perfusion. The vasoconstrictor actions of WEB 2086 and WEB 2170 were not observed with a structurally different PAF receptor antagonist, FR-900452. 3. To determine whether this vasoconstrictor action of WEB 2086 involved non-specific effects or was via the activation of PAF receptors, hearts were pretreated with 1000 pmol PAF or 50 microM FR-900452. These pretreatments attenuated the vasoconstrictor action of 1 microM WEB 2086, suggesting that the action of WEB 2086 may be mediated via PAF receptors. Pretreatment with the leukotriene receptor antagonist (L-649,923, 5 microM) and the leukotriene synthesis inhibitor (MK-886, 10 microM) that are known to block the vasoconstrictor action of PAF receptor activation also attenuated the vasoconstrictor action of WEB 2086. Pretreatment with PAF or MK-886 attenuated the vasoconstrictor action of 0.5 microM WEB 2170. 4. When PAF receptors were activated by PAF in the perfused heart, significant amounts of leukotriene C4 and leukotriene C4/D4/E4 were detected in the coronary effluent. However, no significant amount of these leukotrienes was detected in the coronary effluent when hearts were perfused with 1 microM WEB 2086 or 0.5 microM WEB 2170. 5. In summary, our results indicate that WEB 2086 and WEB 2170 possess partial agonist effects in the rat perfused heart where they produced vasoconstriction via the activation of PAF receptor. This action could be attenuated by PAF pretreatment or a PAF receptor antagonist. The vasoconstrictor action of WEB 2086 and WEB 2170 involved the production of leukotrienes. But unlike the vasoconstrictor action of PAF, no significant amount of leukotrienes was detected in the effluent suggesting that the vasoconstrictor action of WEB 2086 and WEB 2170 may be explained on the basis of intracellularly or locally produced leukotrienes.
Animals↗
A flow dialysis cell for on-line measurement of glucose in fermentation broth.
A plate flow dialysis cell, employing an acetate cellulose ultrafiltration membrane, was designed and tested for applicability to on-line sampling in fermentation. The glucose contained in effluents of both sample stream channel (Channel A) and carrier stream channel (Channel B) was determined with an enzyme electrode flow injection analysis system. Glucose penetration rate was defined as Rp, Rp = Gb/(Ga + Gb), here Ga and Gb are glucose concentrations of effluent of channel A and B respectively. A higher penetration rate was obtained when using phosphate buffer (0.01M) as carrier solution instead of using distilled water. Operating pressure differences, temperature and residential time affected glucose penetration. Under the condition of 0.02MPa pressure differences and 0.23 min of residential time (12.8ml/L), Rp was about 12% in the range of 10-70mM with CV < 4%. When sample stream was yeast broth, the glucose penetration rate Rp was stable for at least 48 hr. Good relationship was observed between on-line and off-line sampling for glucose determination in yeast fermentation, the correlation coefficient r was 0.985.
Culture Media↗