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Biomedical subjects

A Liu

Publications and source records attributed to A Liu.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1997

Three-dimensional reconstruction of curves from pairs of projection views in the presence of error. I. Algorithms.

We have previously described an approach to 3D intracerebral vascular reconstruction that uses an MRA as a reconstruction base. Additional vessels seen only by angiography are added by segmenting 2D curves from projection angiograms and reconstructing these curves into 3D, building upon the MRA. Intracerebral vascular reconstruction is difficult for at least two reasons. First, 2D curves must be associated on projection images even when the human eye cannot do so. Second, 3D curves must be reconstructed in the presence of errors such as misregistration, image distortion, and misdefinition of 2D curves. This paper is the first of two that address the specific issue of reconstruction of a 3D curve from a given pair of 2D curves in the presence of error. The method explicitly separates what can and cannot be determined from a pair of projection views. It is also capable of recognizing interruptions produced by viewplane errors, of continuing reconstruction beyond such interruptions, and of localizing and estimating the magnitude of the interruptions. These measurements can also be used to estimate the lengths of regional disparities between a pair of 2D curves, leading to a quantitative estimate of the capacity of a pair of 2D curves to combine to create a 3D object (match value). Match values can be used, in turn, as part of the strategy for automatically associating pairs of 2D curves. This paper provides methods for reconstructing a given pair of 2D curves into 3D in the presence of error and for calculating match values. Error analysis is given in the companion report.

Algorithms↗
PubMed1997

Three-dimensional reconstruction of curves from pairs of projection views in the presence of error. II. Analysis of error.

We have previously described an approach to 3D intracerebral vascular reconstruction that uses an MRA as a reconstruction base. Additional vessels seen only by angiography are added by segmenting 2D curves from projection angiograms and reconstructing these curves into 3D, building upon the MRA. This paper is the second of two that discuss the specific problem of reconstructing a 3D curve from a given pair of 2D curves in the presence of error. The method presented is capable of detecting and handling many errors produced by misregistration, image distortion, or misdefinition of 2D curves. The first paper gives an algorithm. The current paper discusses factors affecting the accuracy of a reconstructed curve, with emphasis upon registration error. We analyze the spatial accuracy of a reconstructed point in terms of the relationships between pixel size, relative viewing angle, 3D point location, and registration error. We provide a theoretical framework that, given the known error properties of a registration algorithm, allows optimization of the viewing geometry so as to produce the highest precision of point reconstruction. A major focus is the effect of registration error upon the reconstruction of a curve. We subdivide registration error into two types, one of which produces smoothly continuous point placement errors and the other of which produces pixel pairing errors. We test our ability to reconstruct a 3D curve in the presence of both. Finally, we summarize approaches to other sources of error. We conclude with a list of recommendations to optimize reconstruction accuracy. When projection points are associated by the rules of epipolar geometry, viewplane point displacements should not exceed 1.5-2 mm along the axis perpendicular to epipolar planes.

Biometry↗
PubMed1997

Differential expression of transforming growth factor-beta receptors in rat kidney development.

Transforming growth factor-beta 1 (TGF-beta 1) is strongly expressed during embryogenesis and in sites undergoing intense development and morphogenesis. Two receptor serine/threonine kinases (types I and II) have been identified as signal-transducing TGF-beta receptors. This study was undertaken to further explore the role of the distinct TGF-beta receptors during kidney development. The species-specific sequence information for the two T beta R-I, namely, activin receptor-like kinase-5 (ALK-5) and Tsk7L, in the rat was sought. Two full-length T beta R-I cDNAs were cloned from a neonatal rat kidney and lung libraries, and sequencing revealed that they were the rat homologs of human ALK-5 and murine Tsk7L. Both types I and II TGF-beta receptors are expressed in the kidney as determined by Northern blot analysis. T beta R-II mRNA abundance was significantly greater in the neonatal rat kidney compared with the adult rat kidney. Similarly, ALK-5 mRNA was more highly expressed in the fetal and neonatal rat kidney than the adult rat kidney. In contrast, there was no significant difference in Tsk7L mRNA abundance among the fetal, neonatal, and adult rat kidney. Thus, based on these findings, both T beta R-II and ALK-5 are developmentally regulated in the kidney. Increased expression of T beta R-II and ALK-5 proteins in the developing kidney was confirmed by immunohistochemistry. Interestingly, the two TGF-beta receptors did not entirely colocalize, raising the intriguing possibility that other TGF-beta signaling receptors may be involved.

Activin Receptors, Type I↗
PubMed1997

[Clinical evaluation on parenteral nutrition in neonatal disease].

Thirty cases of neonatal disease were treated with parenteral nutrition (PN) as an adjuvant treatment and compared with the control group (n = 30). The body weight and plasma albumin increased remarkably in the PN group (P < 0.01, P < 0.05). No significant metabolic complication was occurred (P > 0.05). PN proved to be a safe and effective approach for neonatal patients, in which nutritional admixture components were adjusted day by day according to gestational age, body weight, disease course and monitor indexes to match the actual gastric intestinal tract function.

Humans↗
PubMed1997

[A comparative study of lanthanum, cerium and fluoride on the prevention of root surface caries by various procedure].

In order to evaluate the anticaries effects of several trace elements by combined and respective treating procedure, studies on inhibiting demineralization and improving remineralization were carried out with lanthanum, cerium and fluoride in a pH-cycling condition. The analysis of polarized microscope and electron microprobe demonstrated that the lanthanum and fluoride to an acetate buffer solutions had less severe demineralization of root surface than individual lanthanum or fluoride to the solution. The former, furthermore, precipitated a compound membrane which may be F-La(Ce)-Ca containing crystal on the root surface, and showed a better resistibility to acid. A further discussion was made from the viewpoint of crystal physiochemistry.

Adolescent↗
PubMed1997

[Chemical constituents of the leaves of Ginkgo biloba].

Four compounds were isolated from ethyl acetate extract of the leaves of Ginkgo biloba. Compounds II, III, IV were identified as ginkgolides A, B and C respectively, Compound I, which was obtained from the leaves of G. biloba for the first time, was identified as 3,3'-dimethoxy-4,4'-dihydroxy-stilbene by spectroscopic methods.

Diterpenes↗
PubMed1997

[A prospective study on transfusion-related hepatitis C virus infection].

64 cases of blood recipients were followed-up for 6 months to study infection of hepatitis C virus. The infection rate of hepatitis C virus was 18.75% in total, including 8 cases of post-transfusion hepatitis C (PT-HC), 1 case of subclinical PT-HC, and 3 cases of anti-HCV sero conversion only. The time of initial ALT abnormality and anti-HCV sero conversion were 28 to 91 (51.9 +/- 20.9) days and 23 to 76 (42.4 +/- 15.9) days after blood transfusion respectively. There were 2 cases with cytomeglovirus infection and another 5 cases with unknown infectious agent were found in this study.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

Methods for displaying intracerebral vascular anatomy.

We are developing three-dimensional imaging methods to portray vascular anatomy better, including noise-free display of vessels extracted from 3-D data sets, tree-based display, and reconstruction of angiographic data (preliminary work has resulted in the successful reconstruction of aneurysms from angiographic data). Fast, interactive display permits real-time manipulation of viewing orientation.

Computer Systems↗
PubMed1997

Clinical evaluation of indium-111-labeled chimeric anti-CEA monoclonal antibody.

UNLABELLED: Chimeric T84.66 (cT84.66) is a high-affinity (1.16 x 10[11] M[-1]) IgG1 monoclonal antibody (MAb) against carcinoembryonic antigen (CEA). This pilot trial evaluated the tumor-targeting properties, biodistribution, pharmacokinetics and immunogenicity of 111In-labeled cT84.66. METHODS: Patients with CEA-producing metastatic malignancies were administered a single intravenous dose of 5 mCi 111In-diethylenetriaminepentaacetic acid-cT84.66. Serial blood samples, 24-hr urine collections and nuclear images were collected up to 7 days postinfusion. Human antichimeric antibody response was assessed up to 6 mo postinfusion. RESULTS: Imaging of at least one known tumor site was observed in 14 of 15 (93%) patients. Seventy-four lesions were analyzed with an imaging sensitivity rate of 45.1% and a positive predictive value of 94.1%. In one patient, two additional bone metastases developed within 6 mo of antibody administration at sites initially felt to be falsely positive on scan. One patient developed a human antichimeric antibody response predominantly to the murine portion of the antibody. The antibody cleared serum with a median T(1/2alpha) of 6.53 hr and a T(1/2beta) of 90.87 hr. Interpatient variations in serum clearance rates were observed and were secondary to differences in clearance and metabolic rates of antibody-antigen complexes by the liver. One patient demonstrated very rapid clearance of antibody by the liver, which compromised antibody localization to the primary tumor. Antibody uptake in primary and metastatic tumors ranged from 0.5% to 10.5% injected dose/kg, resulting in estimated radiation doses ranging from 0.97 to 21.3 cGy/mCi 90Y. Antibody uptake in regional lymph nodes ranged from 1.3% to 377% injected dose/kg, resulting in estimated radiation doses ranging from 2.0 to 617 cGy/mCi 90Y. CONCLUSION: Chimeric T84.66 demonstrated tumor targeting that was comparable to that of other radiolabeled intact anti-CEA Mabs. Its immunogenicity after single administration was lower than murine Mabs. These properties make cT84.66 or a lower molecular weight derivative attractive for further evaluation as an imaging agent. These same properties also make it appropriate for future evaluation in Phase I therapy trials. Finally, a wide variation in the rate of antibody clearance was observed, with one patient demonstrating very slow clearance, resulting in the highest estimated marrow dose of the group, and one patient demonstrating unusually rapid clearance, resulting in poor antibody localization to tumor. Data from this study suggest that serum CEA levels, antibody-antigen complex clearance and, therefore, antibody clearance are influenced by both the production and clearance rates of CEA. 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↗
PubMed1997

Pharmacokinetic modeling and absorbed dose estimation for chimeric anti-CEA antibody in humans.

UNLABELLED: The objective of this article was to model pharmacokinetic data from clinical diagnostic studies involving the 111In-labeled monoclonal antibody (MAb) chimeric T84.66, against carcinoembryonic antigen. Model-derived results based on the 111In-MAb blood, urine and digital imaging data were used to predict 90Y-MAb absorbed radiation doses and to guide treatment planning for future therapy trials. Fifteen patients with at least one carcinoembryonic antigen-positive lesion were evaluated. We report the kinetic parameter estimates and absorbed 111In-MAb dose and projected 90Y-MAb doses for each patient as well as describe our approach and rationale for modeling an extensive set of pharmacokinetic data. METHODS: The ADAPT II software package was used to create three- and five-compartment models of uptake against time in the patient population. The "best-fit" model was identified using ordinary least squares. Areas under the curve were calculated using the modeled curves and input into MIRDOSE3 to estimate absorbed radiation doses for each patient. RESULTS: A five-compartment model best described the liver, whole body, blood and urine data for a subcohort of nine patients with digital imaging data. A three-compartment model best described the blood and urine data for all 15 clinical patients accrued in the clinical trial. For the subcohort, the largest projected 90Y-MAb doses were delivered to the liver (mean, 24.78 rad/mCi; range, 15.02-37.07 rad/mCi), with red marrow estimates on the order of 3.32 rad/mCi (range, 1.24-5.55) of 90Y. Corresponding estimates for the 111In-MAb were 3.18 (range, 2.09-4.43) and 0.55 (range, 0.34-0.74), respectively. CONCLUSION: The three- and five-compartment models presented here were successfully used to represent the blood, urine and imaging data. This was evidenced by the small standard errors for the kinetic parameter estimates and R2 values close to 1. As planned future therapeutic trials will involve stem cell support to alleviate hematological toxicities, the development of an approach for estimating doses to other major organs is crucial.

Adult↗
PubMed1997

Estimating residence times and their associated errors in patient absorbed-dose calculation.

OBJECTIVE: An approach for estimating organ residence times (tau) and their errors in patient internal emitter radiation dosage calculations has been determined. METHODS: Using a modeling algorithm and its associated parameters, chimeric anti-CEA monoclonal antibody (cT84.66) patient organ uptake data and residence times of source organ activity were calculated. Through the covariance matrix of the model's parameters and subsequent Monte Carlo simulations, errors in organ residence time (gamma tau) also were estimated RESULTS: These relative tau errors were found to be model-dependent; increasing as the number of organs being simultaneously modeled in a set of two patients being considered for 90Y-cT84.66 radioimmunotherapy. CONCLUSION: Use of modeling and Monte Carlo methods provide a general, direct procedure for calculating the degree of accuracy of activity integrals and other mathematical functions of kinetic variables.

Algorithms↗
PubMed1997

[The contents of plasma norepinephrine and epinephrine in patients with five types of Gan syndromes in TCM and its significance for diagnosis].

Plasma norepinephrine (NE) epinephrine (E) concentrations in patients with five types of Gan syndromes and relative syndromes were determined. The healthy individuals served as control. The contents of NE and E in Ganyang Huafeng Zheng (5975.8 +/- 305.6 pmol.L-1, 2227.7 +/- 12.57 pmol.L-1) were significantly increased; Ganxue Xu Zheng (1100.4 +/- 105.5, 451.2 +/- 70.9 pmol.L-1) were decreased, and lower than the normal controls. NE and E contents in both Ganyang Shangkang Zheng (3962.6 +/- 354.4, 1225.6 +/- 163.5 pmol.L-1) and Ganhuo Shangyan Zheng (3398.1 +/- 303.8, 1134.4 +/- 146.9 pmol.L-1) were increased remarkably, but there was no difference between them. Plasma NE, E concentrations can be considered as one of the comprehensive laboratory parameters in diagnosis of the four above mentioned Gan syndromes.

Adolescent↗
PubMed1996

Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development.

The Ikaros gene, an essential regulator of lymphocyte differentiation, encodes, by means of differential splicing, protein isoforms with a distinct number of Kruppel-type zinc fingers organized in two domains. Deletion of the N-terminal zinc finger domain responsible for the sequence-specific DNA binding of the Ikaros proteins results in an early and complete arrest in lymphocyte development in homozygous mutant mice. In sharp contrast, heterozygotes reliably develop T cell leukemias and lymphomas. Here we show that the C-terminal zinc finger domain present in all of the Ikaros wild-type and mutant isoforms is responsible for their stable interactions off DNA and plays a pivotal role in determining their overall activity. Mutations in the C-terminal zinc fingers which ablate Ikaros protein interactions have a dramatic effect on the ability of these proteins to bind DNA and activate transcription. Therefore, interactions between Ikaros isoforms with an intact DNA binding domain are essential for their function. In contrast, interactions between isoforms with and without a DNA binding domain result in Ikaros complexes that do not bind DNA and, as a consequence, cannot activate transcription. Dominant-negative Ikaros isoforms are generated in smaller amounts by the wild-type Ikaros gene but are also produced exclusively by the N-terminally deleted Ikaros locus. Given these data, we propose that interactions between Ikaros isoforms are essential for normal progression through the lymphoid pathways. Mutations in the Ikaros gene that prevent Ikaros protein interactions or which change the relative ratio of DNA to non-DNA binding isoforms have profound effects in both lymphoid specification and homeostasis.

3T3 Cells↗