Biomedical subjects

A Liu

Publications and source records attributed to A Liu.

At least 19 recordsLinked to original sources

PubMed1999

Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness.

OBJECTIVE: The absence of endothelial cells at the luminal surface of a prosthetic vascular graft potentiates thrombosis and neointimal hyperplasia, which are common causes of graft failure in humans. This study tested the hypothesis that pretreatment with chronic in vitro shear stress enhances subsequent endothelial cell retention on vascular grafts implanted in vivo. METHODS: Cultured endothelial cells derived from Fischer 344 rat aorta were seeded onto the luminal surface of 1.5-mm internal diameter polyurethane vascular grafts. The seeded grafts were treated for 3 days with 1 dyne/cm2 shear stress and then for an additional 3 days with 1 or 25 dyne/cm2 shear stress in vitro. The grafts then were implanted as aortic interposition grafts into syngeneic rats in vivo. Grafts that were similarly seeded with endothelial cells but not treated with shear stress and grafts that were not seeded with endothelial cells served as controls. The surgical hemostasis time was monitored. Endothelial cell identity, density, and graft patency rate were evaluated 24 hours after implantation. Endothelial cell identity in vivo was confirmed with cells transduced in vitro with beta-galactosidase complementary DNA in a replication-deficient adenoviral vector. Histologic, scanning electron microscopic, and immunohistochemical analyses were performed 1 week and 3 months after implantation to establish cell identity and to measure neointimal thickness. RESULTS: The pretreatment with 25 dyne/cm2 but not with 0 or 1 dyne/cm2 shear stress resulted in the retention of fully confluent endothelial cell monolayers on the grafts 24 hours after implantation in vivo. Retention of seeded endothelial cells was confirmed by the observation that beta-galactosidase transduced cells were retained as a monolayer 24 hours after implantation in vivo. In the grafts with adherent endothelial cells that were pretreated with shear stress, immediate graft thrombosis was inhibited and surgical hemostasis time was significantly prolonged. Confluent intimal endothelial cell monolayers also were present 1 week and 3 months after implantation. However, 1 week after implantation, macrophage infiltration was observed beneath the luminal cell monolayer. Three months after the implantation in vivo, subendothelial neointimal cells that contained alpha-smooth muscle actin were present. The thickness of this neointima averaged 41 +/- 12 micrometer and 60 +/- 23 micrometer in endothelial cell-seeded grafts that were pretreated with 25 dyne/cm2 shear stress and 1 dyne/cm2 shear stress, respectively, and 158 +/- 46 micrometer in grafts that were not seeded with endothelial cells. CONCLUSION: The effect of chronic shear stress on the enhancement of endothelial cell retention in vitro can be exploited to fully endothelialize synthetic vascular grafts, which reduces immediate in vivo graft thrombosis and subsequent neointimal thickness.

Adenoviridae↗

PubMed1998

The tyrosyl free radical of recombinant ribonucleotide reductase from Mycobacterium tuberculosis is located in a rigid hydrophobic pocket.

The tyrosyl free radical in protein R2-2 of class Ib ribonucleotide reductase (RNR) fromMycobacterium tuberculosis is essential for the enzymatic activity and has an EPR spectrum remarkably similar to that of the tyrosyl radical YD* in PSII. The EPR relaxation properties of the radical suggest a very weak exchange coupling between the two redox centers, the radical and the diferric cluster. The tyrosyl radical gives almost identical EPR spectra in the temperature interval 10-293 K. We conclude that the tyrosyl radical sits in a rigid pocket. Two ring protons and one beta-methylene proton account for the major anisotropic hyperfine interactions. A high-frequency EPR spectrum of the radical showed a resolved gx = 2. 0092, indicating that a hydrogen bond to the phenolic oxygen of the radical is absent. Theoretical modeling studies based on the structural data known for Salmonella typhimurium class Ib RNR protein R2F revealed a hydrophobic wall aligned with the radical harboring residue Y110. The distance between the phenolic oxygen of the radical and the diferric cluster is longer in the two class Ib nrdF R2 proteins than in other characterized class Ia R2 proteins. The tyrosyl radical in protein R2-2 from M. tuberculosis was accessible to direct reduction by dithionite in the absence of a mediator. The radical could be partly regenerated when the system was exposed to O2 after the completion of anaerobic reduction. This indicates that the Fe3+ ions also had become reduced by dithionite.

Bacterial Proteins↗

PubMed1998

Photorefractive materials for nonvolatile volume holographic data storage

Optically gated recording and nonvolatile readout in a digital volume holographic data storage system that uses a pair of mutually incoherent light sources during recording and only one for readout were demonstrated recently. This approach used stoichiometric lithium niobate, which after post-growth processing gave rise to an at least two orders of magnitude improvement in sensitivity over the best materials reported previously. It is also shown that by adding certain dopants (iron and manganese) to near-stoichiometric lithium niobate, the dark storage time and gating efficiency can be increased compared with previous work. The underlying physical mechanisms of gated recording and the effectiveness of the gating process responsible for this manifold improved performance are discussed, and bipolarons and small polarons are identified as the responsible photorefractive species.

Journal Article↗

PubMed1998

New paramagnetic species formed at the expense of the transient tyrosyl radical in mutant protein R2 F208Y of Escherichia coli ribonucleotide reductase.

The highly conserved residue F208 in protein R2 of E. coli ribonucleotide reductase is close to the binuclear iron center, and found to be involved in stabilizing the tyrosyl radical Y122. in wild type R2. Upon the reconstitution reaction of the mutant R2 F208Y with ferrous iron and molecular oxygen, we observed a new EPR singlet signal (g = 2.003) formed concomitantly with decay of the transient tyrosyl radical Y122. (g = 2.005). This new paramagnetic species (denoted Z) was stable for weeks at 4 degrees C and visible by EPR only below 50 K. The EPR singlet could not be saturated by available microwave power, suggesting that Z may be a mainly metal centered species. The maximum amount of the compound Z in the protein purified from cells grown in rich medium was about 0.18 unpaired spin/R2. An identical EPR signal of Z was found also in the double mutant R2 F208Y/Y122F. In the presence of high concentration of sodium ascorbate, the amounts of both the transient Y122. and the new species Z increased considerably in the reconstitution reaction. The results suggest that Z is most likely an oxo-ferryl species possibly in equilibrium with a Y208 ligand radical.

Binding Sites↗

PubMed1998

Simultaneous HLA Class I and Class II antibodies screening with flow cytometry.

A flow cytometric method of simultaneously screening both HLA Class I and Class II panel reactive antibodies (PRA) was developed using a pool of 30 different Class I and 30 different Class II microbeads coated with purified HLA antigens. The antibodies in the serum that react specifically to the coated HLA antigens are detected by using a FITC-conjugated antibody against human IgG. Percent PRA can be determined by the percentage of microbeads that react positively to the serum. There is no cross-reactivity between the Class I and Class II microbeads. A mixture of Class I and Class II microbeads can be distinguished by their different fluorescent properties on the flow cytometry analysis. Thus, both Class I and Class II PRA can be detected from a single tube reaction.

Antibodies↗

PubMed1998

Alteration of limb and brain patterning in early mouse embryos by ultrasound-guided injection of Shh-expressing cells.

A basic limitation of the study of development in the mouse is the inaccessibility of the embryos, which are encased in the maternal uterus. We demonstrate the first use of ultrasound backscatter microscopy for guiding injections of cells and other agents into early stage mouse embryos. Cells were injected into the mouse neural tube cavity as early as 9.5 days post coitus (E9.5), and into the developing limb buds as early as E10.5. Furthermore, a cell-line engineered to express the secreted factor Sonic Hedgehog (Shh) was injected into early developing mouse brains or limbs. The Shh-expressing cells were found to induce ectopic expression of the Shh target genes Patched and Hnf3beta in the dorsal brain, and to alter digit patterning in the anterior limb bud. These results show that gene misexpression studies can be performed in mouse embryos using ultrasound-guided injection of transfected cells or retroviruses. In combination with the many available mouse mutants, this method offers a new approach for analyzing genetic interactions through gain-of-function studies performed in mutant mouse backgrounds.

Animals↗

PubMed1998

Quantitative structure-activity relationships on 5-substituted terbenzimidazoles as topoisomerase I poisons and antitumor agents.

Several 5-substituted terbenzimidazoles were synthesized and evaluated as mammalian topoisomerase I poisons and for cytotoxicity against a human lymphoblastoma cell line, RPMI-8402. No correlation was observed between topoisomerase I poisoning activity and the Hansch pi value or the sigma meta and sigma para values associated with each substituent. These data suggest that electronic effects and relative lipophilicity of substituents at the 5-position of these terbenzimidazoles do not have a significant effect upon intrinsic topoisomerase I poisoning activity. There was, however, a good correlation between the relative pi values for the various substituents evaluated and cytotoxic activity. Experimentally determined log P values did not correlate well with either cytotoxicity or pi values. Capacity factors (log k') as determined by high pressure liquid chromatography did correlate well with the pi values of varied substituents and cytotoxicity. These data indicate that the relative lipophilic activity of substituents at the 5-position of these terbenzimidazoles can strongly influence relative cytotoxic activity.

Antineoplastic Agents↗

PubMed1998

Monte Carlo-assisted voxel source kernel method (MAVSK) for internal beta dosimetry.

A method is described for the determination of patient-specific organ beta doses given a known cumulated internal radioactivity distribution. A voxel source kernel for 90Y analogous to the point source function was simulated. Dose to each organ of interest could then be estimated by convolving the voxel source kernel with the patient's 3-D volume with known radioactivity assigned to each voxel. The dose calculation on eight organs took less than 1 min per patient using a Sun Sparc10 workstation.

Humans↗

PubMed1998

TGF-beta type II receptor in rat renal vascular development: localization to juxtaglomerular cells.

To further define the role of transforming growth factor-beta (TGF-beta) receptors in renal vascular development, detailed immunohistochemical studies of TGF-beta receptor expression were performed from gestational day 15 through adulthood. On gestational day 15, TGF-beta type II receptor immunoreactivity was restricted to perirenal stromal and vascular cells. On gestational day 17 TGF-beta type II receptor immunoreactive stromal cells were observed within the kidney, with the same distribution as stromal alpha-smooth muscle actin and renin immunoreactive cells, and intense stromal TGF-beta type II receptor immunoreactivity continued through postnatal day 5. As vascular development progressed, TGF-beta type II receptor, alpha-smooth muscle actin and renin immunoreactivity became progressively restricted to small renal arteries and arterioles. Expression of TGF-beta type II receptors and renin was very intense in afferent glomerular arterioles during postnatal days 5 to 15, and then became progressively restricted only to juxtaglomerular cells in the mature kidney. TGF-beta type I receptor (ALK-5, ALK-1 and ALK-2) immunoreactivity was not detected in stromal or vascular elements during development or in the mature kidney. Intense TGF-beta type II receptor expression in renal stromal vascular smooth muscle cell precursors and developing blood vessels suggests a role for the TGF-beta type II receptors in the formation of the renal vascular smooth muscle compartment. The continued intense expression in juxtaglomerular cells argues for a role in renin synthesis and/or release. The absence of ALK-5, ALK-1, and ALK-2 in developing vascular smooth muscle and mature juxtaglomerular cells indicates that the canonical view of TGF-beta signaling may not hold in these locations.

Actins↗

PubMed1998

Shear stress and the endothelium.

Shear stress and the endothelium. Vascular endothelial cells (ECs) in vivo are influenced by two distinct hemodynamic forces: cyclical strain due to vessel wall distention by transmural pressure, and shear stress, the frictional force generated by blood flow. Shear stress acts at the apical cell surface to deform cells in the direction of blood flow; wall distention tends to deform cells in all directions. The shear stress response differs, at least partly, from the cyclical strain response, suggesting that cytoskeletal strain alone cannot explain it. Acute shear stress in vitro elicits rapid cytoskeletal remodeling and activates signaling cascades in ECs, with the consequent acute release of nitric oxide and prostacyclin; activation of transcription factors nuclear factor (NF)kappaB, c-fos, c-jun and SP-1; and transcriptional activation of genes, including ICAM-1, MCP-1, tissue factor, platelet-derived growth factor-B (PDGF-B), transforming growth factor (TGF)-beta1, cyclooxygenase-II, and endothelial nitric oxide synthase (eNOS). This response thus shares similarities with EC responses to inflammatory cytokines. In contrast, ECs adapt to chronic shear stress by structural remodeling and flattening to minimize shear stress. Such cells become very adherent to their substratum and show evidence of differentiation. Increased adhesion following chronic shear stress has been exploited to generate vascular grafts with confluent EC monolayers, retained after implantation in vivo, thus overcoming a major obstacle to endothelialization of vascular prostheses.

Animals↗

PubMed1998

Pulmonary embolus in pregnant patients: survey of ventilation-perfusion imaging policies and practices.

PURPOSE: To assess the policies and practices of nuclear medicine facilities as regards ventilation-perfusion (V-P) imaging in pregnant patients suspected of having pulmonary embolus. MATERIALS AND METHODS: Surveys were mailed to physician-directors of 1,000 randomly selected facilities at which nuclear imaging studies are performed. Information gathered included use of V-P imaging in pregnant patients, written policies, informed consent procedures, and modifications of standard protocols. RESULTS: Of the 1,000 surveys mailed, 327 (33%) completed surveys were returned. Of these 327 respondents, 220 (67%) reported that they perform V-P imaging in pregnant patients suspected of having pulmonary embolus. Of these 220 respondents, 115 (52%) routinely obtain informed consent, and 170 (77%) modify their standard V-P imaging protocol for pregnant patients. The most common modification (135 [79%] of 170 respondents) was reduction of the perfusion agent dose. Reported practice patterns for written policies, informed consent, and modifications did not show statistically significant trends among respondents in varying practice settings or geographic locations. CONCLUSION: Most respondents perform V-P imaging in pregnant patients suspected of having pulmonary embolus, with considerable variability in their policies and practices.

Data Collection↗

PubMed1998

Changes in mechanical strength of intramuscular connective tissue during postmortem aging of beef.

We studied changes in mechanical strength during postmortem aging of bovine semitendinosus muscle using intramuscular connective tissue (IMCT) preparations from muscle stored at 4 degrees C. In the preparation, muscle fiber elements were removed, leaving a virtually intact structure of the endomysium and perimysium. The shear-force value of the IMCT preparation remained unchanged up to 10 d postmortem and decreased linearly thereafter. The yield of the perimysial fraction, which was measured as an indicator of mechanical properties of the perimysium, remained almost unchanged up to 14 d postmortem, and decreased gradually thereafter. These results suggest that the mechanical strength of the intramuscular connective tissue changes slowly during postmortem aging of beef; it remains almost unchanged for up to 10 d postmortem and progressively decreases thereafter. Thus, intramuscular connective tissue seems to affect beef tenderization in extended aging.

Animals↗

PubMed1998

Dose escalation trial of indium-111-labeled anti-carcinoembryonic antigen chimeric monoclonal antibody (chimeric T84.66) in presurgical colorectal cancer patients.

UNLABELLED: Chimeric T84.66 (cT84.66) is a high-affinity (1.16x10(11) M(-1)) IgG1 monoclonal antibody against carcinoembryonic antigen (CEA). The purpose of this pilot trial was to evaluate the tumor-targeting properties, biodistribution, pharmacokinetics and immunogenicity of 111In-labeled cT84.66 as a function of administered antibody protein dose. METHODS: Patients with CEA-producing colorectal cancers with localized disease or limited metastatic disease who were scheduled to undergo definitive surgical resection were each administered a single intravenous dose of 5 mg of isothiocyanatobenzyl diethylenetriaminepentaacetic acid-cT84.66, labeled with 5 mCi of 111In. Before receiving the radiolabeled antibody, patients received unlabeled diethylenetriaminepentaacetic acid-cT84.66. The amount of unlabeled antibody was 0, 20 or 100 mg, with five patients at each level. Serial blood samples, 24-hr urine collections and nuclear images were collected until 7 days postinfusion. Human antichimeric antibody response was assessed up to 6 mo postinfusion. RESULTS: Imaging of at least one known tumor site was performed in all 15 patients. Fifty-two lesions were analyzed, with an imaging sensitivity rate of 50.0% and a positive predictive value of 76.9%. The antibody detected tumors that were not detected by conventional means in three patients, resulting in a modification of surgical management. Interpatient variations in serum clearance rates were observed and were secondary to differences in clearance and metabolic rates of antibody and antibody:antigen complexes by the liver. Antibody uptake in primary tumors, metastatic sites and regional metastatic lymph nodes ranged from 0.4% to 134% injected dose/kg, resulting in estimated 90Y-cT84.66 radiation doses ranging from 0.3 to 193 cGy/mCi. Thirteen patients were evaluated 1-6 mo after infusion for human antichimeric antibody, and none developed a response. No major differences in tumor imaging, tumor uptake, pharmacokinetics or organ biodistribution were observed with increasing protein doses, although a trend toward increasing blood uptake and decreasing liver uptake was observed with increasing protein dose. CONCLUSION: Chimeric T84.66 demonstrated tumor targeting comparable to other radiolabeled intact anti-CEA monoclonal antibodies. Its immunogenicity after single administration was lower than murine monoclonal antibodies. These properties make 111In-cT84.66, or a lower molecular weight derivative, attractive for further evaluation as an imaging agent. Yttrium-90 dosimetry estimates predict potentially cytotoxic radiation doses to select tumor sites, which makes 90Y-cT84.66 also appropriate for further evaluation in Phase I radioimmunotherapy trials. Although clinically important changes in biodistribution, pharmacokinetics and tumor targeting with increasing protein doses of 111In-cT84.66 were not demonstrated, the results do suggest that antibody clearance from the blood is driven by hepatic uptake and metabolism, with more rapid blood clearance seen in patients with liver metastases. These patients with rapid clearance and potentially unfavorable biodistribution for imaging and therapy may, therefore, be a more appropriate subset in which to evaluate the role of administering higher protein doses. This underscores the need to further identify, characterize and understand those factors that influence the biodistribution and clearance of radiolabeled anti-CEA antibodies, to allow for better selection of patients for therapy and rational planning of radioimmunotherapy.

Adult↗

PubMed1998

Expression patterns of costimulatory molecules on cells derived from human hematological malignancies.

In order to elucidate the possibility of costimulatory molecules-mediated immuno or immuno-gene therapy for human hematological malignancies, we analyzed 30 hematopoietic cell lines and cells obtained from 48 patients with hematological malignancies for the expression of costimulatory molecules such as CD80 and CD86. The 30 hematopoietic cell lines were composed of 4 cell lines derived from the patients with T-cell acute lymphoblastic leukemia (T-ALL), 3 from Philadelphia chromosome positive ALL (Ph1+ALL), 8 from acute myeloblastic leukemia (AML), 3 from acute promyelocytic leukemia (APL), 8 from chronic myeloid leukemia at blast crisis (CML-BC), 3 from Burkitt's lymphoma and one from follicular cell lymphoma. The expression of CD80 or CD86 was frequent on cell lines derived from the patients with CML-BC or Burkitt's lymphoma, while it was rare on cell lines from T-ALL. Subsequently we analyzed the cells obtained from 48 patients with hematological malignancies, which consisted of 6 samples from patients with ALL, 30 from AML, 2 from CML-BC, 3 from B-cell lymphoma and one from each acute mixed leukemia (AMixL), adult T cell leukemia (ATL), T-cell large granular lymphocytic leukemia (T-LGL leukemia), chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS)-RAEB in T, multiple myeloma (MM) or T-cell lymphoma. Among all the 48 cases, all cases except one case with CLL and two with B cell lymphoma were demonstrated to be negative for CD80 on the neoplastic cells. CD86 and HLA-DR were shown to be expressed in 50% and 88% of total 48 cases respectively. In 30 AML samples, CD86 was positive in 15 cases (50%), which was sharply in contrast with the finding that CD80 was not detected in any AML samples. HLA-DR was expressed in 25 AML samples (83%). We also treated seven human hematopoietic cell lines with IFN-gamma, IL-12 or IL-15 and observed whether these cytokines could induce or enhance the expression of CD40, CD54, CD58 and HLA-DR as well as CD80 and CD86. The present study demonstrated that the expression of CD86 could be upregulated not only by IFN-gamma, but also by IL-12 or IL-15 in some cell lines. These findings suggested the possibility that the absence of CD80 on neoplastic cells may be associated with the lack of efficient anti-tumor immunity in most patients with hematological malignancies and that the immuno or immuno-gene therapy manipulating the expression of costimulatory molecules such as CD80 may be a useful treatment modality for hematological malignancies.

Adult↗

PubMed1997

Induction of allograft nonresponsiveness after intrathymic inoculation with donor class I allopeptides. II. Evidence for persistent chronic rejection despite high levels of donor microchimerism.

We have recently demonstrated that three synthetic peptides corresponding to the donor class I RT1.Aa molecule induce long-term survival of cardiac allografts in the PVG.R8-to-PVG.1U rat strain combination (disparate for one isolated class I, RT1.A, molecule) when presented to the recipient immune system in the thymus. Long-term graft survivors had measurable levels of donor-reactive alloantibodies in their serum. In this study, we examined long-term allografts for the presence of chronic rejection and donor microchimerism to assess whether this regimen of immune modulation establishes true tolerance and whether this tolerance is dependent upon the presence of donor-recipient microchimerism. Histological examination of long-term heart grafts (>100 days) demonstrated chronic rejection, including a mild degree of myocardial infiltration by mononuclear cells, mild to moderate myocardial fibrosis, and various vascular changes ranging from focal intimal thickening to total vascular lumen blockade due to smooth muscle cell proliferation. In contrast, long-term syngeneic hearts transplanted under similar experimental conditions lacked these pathological manifestations. Donor microchimerism was analyzed using the polymerase chain reaction with a pair of oligonucleotides specific for the donor class I RT1.Aa gene and genomic DNA harvested from various tissues from graft recipients. We detected high levels of donor microchimerism in the heart, kidney, liver, skin, bone marrow, thymus, and lymph nodes of long-term graft recipients. Donor microchimerism was also detected in unmanipulated control graft recipients at rejection (7 days) and in intrathymically manipulated recipients that rejected allografts in a delayed fashion (12-82 days). These data clearly demonstrate that intrathymic inoculation of donor class I allopeptides induces long-term graft survival but does not prevent chronic rejection. Allograft rejection occurred despite high levels of donor microchimerism, providing direct evidence that donor-recipient microchimerism is not sufficient for the prevention of acute or chronic rejection in this model.

Animals↗

PubMed1997

Terbenzimidazoles: influence of 2"-, 4-, and 5-substituents on cytotoxicity and relative potency as topoisomerase I poisons.

Terbenzimidazoles poison the nuclear enzyme topoisomerase I and possess significant cytotoxic activity against several human tumor cell lines. The relative pharmacological activity of 4,5- and 5,6-benzoterbenzimidazoles was compared to that of 5-phenylterbenzimidazole (3). 5,6-Benzoterbenzimidazole is inactive as a topoisomerase I poison and did not exhibit significant cytotoxic activity. In contrast, 4,5-benzoterbenzimidazole retained activity as a topoisomerase I poison but exhibited weak cytotoxic activity relative to 3. While 5-(1-naphthyl)terbenzimidazole is less potent than 3 as a topoisomerase I poison and cytotoxic agent, 5-(2-naphthyl)-terbenzimidazole has comparable activity to 3. The presence of a p-methoxy or p-chloro substituent on the phenyl moiety did not dramatically alter the pharmacological activity of 3. Several analogs of 3 were synthesized wherein the 2"-substituent varied from methyl, ethyl, propyl, isopropyl, phenyl to p-methoxyphenyl. Evaluation of the intrinsic activity of these analogs as topoisomerase I poisons indicates that topoisomerase I poisoning was not diminished by the presence of a methyl, ethyl, propyl, and isopropyl substituent at the 2"-position. Among the various 2"-substituted analogs evaluated, only in the case of 2"-(p-methoxyphenyl)-5-phenylterbenzimidazole was a significant decrease in cytotoxicity observed.

Antineoplastic Agents↗

PubMed1997

Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate.

Immune regulation of contact sensitivity to the poison ivy/oak catechol was studied at the level of class II MHC-restricted T cell recognition of hapten:peptide conjugates. In this study we have shown that 1) T cells from C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3-pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized peptides derived from syngeneic cells linked to the same catechol; 2) T cells from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in response to a peptide carrier:PDC conjugate only when it was linked at the 7th, but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity following treatment with a single I-Ak binding peptide carrying PDC covalently bound to a lysine residue at the middle (7th) TCR contact position. Tolerization with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell proliferative responses that correlated with diminished IL-2 secretion. On the basis of these data we propose that it may be sufficient to couple the hapten at a single, well-chosen position on a carrier peptide to target a relevant population of T cells involved in contact sensitivity.

Administration, Topical↗

PubMed1997

Comparison of cerclage techniques using a hose clamp versus monofilament cerclage wire or cable.

To assess the compressive force generated by different techniques of cerclage wiring, the compression produced by 6 different cerclage techniques, including monofilament wires, Dall-Miles cables (Howmedica, Rutherford, NJ), and hose clamps, was measured. Tests were performed on both a polysulfone cylinder model and a cadaver bone model. The hose clamp generated significantly higher compression force than any other cerclage device tested. Doubled wires produced similar compressive force as the cables. As the hose clamp is the least expensive and produces the maximum compression, it may be advantageous in instances in which maximum compression is desirable as a temporary device, but because it is not implantable, it must be replaced by other techniques prior to wound closure. The Dall-Miles cable is expensive and its compressive force can be equaled at lower cost by a doubled wire. The use of a single strand of monofilament wire was the least effective.

Bone Wires↗