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Biomedical subjects

A Yuan

Publications and source records attributed to A Yuan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Quantification of iodine-131 in tumors using a threshold based on image contrast.

Accurate and reproducible quantification of tumor radioactivity by imaging requires definition of a region of interest (ROI) for the tumor. The use of a threshold for creating the tumor ROI based on tumor-to-background image contrast (image contrast) was examined. Quantification of iodine-131 in spheres in a phantom that simulated tumors in patients was investigated using planar imaging and geometric-mean and effective-point-source methods. Thresholds that provided the least quantitative error for spheres with different diameters (1-5 cm) and locations (0-11 cm deep in the body), 131I concentrations (0.037-3.2 MBq/ml), and sphere-to-background concentration ratios (1:0, 14:1 and 7:1) were investigated. The correlation between threshold and sphere image contrast was examined. The phantom study showed that an appropriate threshold value for quantification of tumor radioactivity could be determined using image contrast for a single view, provided that image contrast was >/=1.5. The error of quantification was less than 10% for spheres with high image contrast (>/=1.5) but was greater than 17% for spheres with low image contrast (<1.5). When image contrast-dependent thresholds were applied to patient studies, 131I concentrations determined by imaging were in good agreement with the concentrations determined by counting biopsy samples. Additionally, reproducibility was improved when compared with a visual boundary method. It is concluded that accurate and reproducible quantification of radioactivity in tumors is achievable using thresholds based on image contrast if image contrast is greater than or equal to 1.5. Optimal thresholds for quantification of tumor radioactivity were similar if image contrast was similar despite differing tumor diameters, locations and 131I concentrations. Under certain circumstances, the effective-point-source method was preferable to the geometric-mean method.

Humans↗
PubMed1998

[Treatment of 34 cases of chronic aplastic anemia using prepared Rehmannia polysaccharide associated with stanozolol].

OBJECTIVE: To investigate the effect and side effect of prepared Rehmannia polysaccharide (PRP) associated with stanozolol in treating chronic aplastic anemia (CAA). METHODS: Thirty-four cases of CAA were treated by PRP liquid associated with stanozolol, course of 3 week treatment, and control group (17 cases of CAA) was treated by stanozolol alone. RESULTS: Effective rate was 85.3% in treatment group, and that of control group was 58.8%, there was significant difference between them (P < 0.05). Symptom remission of treatment group was earlier than that of control group, symptom scoring between two groups, the difference was highly significant (P < 0.01). Blood cell had a distinct elevation after treatment with PRP associated with stanozolol, and had a significant difference in comparing with pre-treatment in treatment group (P < 0.01). Side effect of PRP was not found during treatment of CAA. CONCLUSIONS: PRP associated with stanozolol to treat CAA has an additional effect, it can accelerate symptom remission without any additional side effect.

Adolescent↗
PubMed1997

Impact of splenomegaly on therapeutic response and I-131-LYM-1 dosimetry in patients with B-lymphocytic malignancies.

BACKGROUND: Patients with B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) frequently have splenomegaly, which has been reported to cause poor tumor targeting of radiolabeled antibodies. Consequently, patients with splenomegaly have been ineligible for some trials of radioimmunotherapy because of the assumption that they would not benefit. METHODS: Forty-nine patients with NHL and five with CLL received an initial dose of 131I-Lym-1 ranging from 740-8140 MBq. Six patients had prior splenectomy. The remaining 48 patients had spleen volumes ranging from 140-2830 ml determined using x-ray computed tomography. Medical Internal Radiation Dose Committee formalism was used to determine dosimetry, and spleen volume was used to adjust the S value for the spleen of each patient. RESULTS: Spleen radiation dose decreased as spleen volume increased, although there was a positive correlation (r = 0.75) between spleen volume and spleen cumulated activity. There was no clear relationship between spleen volume and tumor radiation dose, although tumor radiation doses were low in five patients whose spleen volumes were greater than or equal to 970 ml. There was no apparent relationship between spleen volume and therapeutic response to 131I-Lym-1. Two of five patients whose spleen volumes were greater than or equal to 970 ml responded despite low tumor radiation doses, whereas two of six patients with prior splenectomy did not respond. CONCLUSIONS: The results of this study provide no clear evidence that patients with splenomegaly should be excluded from radioimmunotherapy trials because of the assumption that they will not benefit. Splenomegaly was associated with decreased radiation dose to the spleen, and to tumors only for extraordinarily large spleens.

Humans↗
PubMed1997

Imaging for improved prediction of myelotoxicity after radioimmunotherapy.

BACKGROUND: The severity of myelotoxicity after radioimmunotherapy has been predicted from body and blood radiation doses to marrow. However, marrow radiation can be increased substantially if the marrow or skeleton contains the malignancy targeted by the radiolabeled monoclonal antibodies. A study of 29 patients treated with iodine-131 (131I)-Lym-1 showed that radiation doses to marrow from body and blood had little correlation with myelotoxicity. The purpose of the present study was to assess the significance of marrow targeting and other factors for prediction of myelotoxicity. METHODS: Injected radioactivity and nontargeted radiation doses to marrow were compared with peripheral blood cell counts after the first therapy dose of 131I-Lym-1 in 16 heavily pretreated patients with non-Hodgkin's lymphoma (NHL). Bone marrow biopsy, targeted marrow radiation doses, marrow image uptake scores, age, Karnofsky performance score (KPS), previous chemotherapy, and tumor burden were also compared with blood counts. RESULTS: Myelotoxicity was not predicted well by injected radioactivity, total body radiation, or body and blood radiation doses contributed to marrow (P > 0.1). Biopsy-proven bone marrow lymphoma also failed to predict myelotoxicity (P > 0.1). Thrombocytopenia and leukopenia were predicted well by targeted radiation dose to marrow (P < 0.05) obtained by 131I imaging. Similarly, marrow image scores predicted decreases in platelets and white blood cells (WBCs; P < 0.05). Prediction of myelotoxicity using marrow radiation dose methods was slightly improved when serum lactic dehydrogenase (LDH), age, KPS, and prior chemotherapy were included in the analysis (P < or = 0.01). CONCLUSIONS: Prediction of myelotoxicity was improved in this group of patients by assessment of the targeting component of marrow radiation and was better predicted and obtained more easily by semiquantitative marrow image scores. Further improvement in prediction was slight when other factors were considered.

Bone Marrow↗
PubMed1997

Axonal transport and distribution of cyclophilin A in chicken neurones.

In the course of pulse-label studies on the axonal transport of the small, basic, actin-binding proteins--actin depolymerizing factor, cofilin and profilin--in chicken motor neurones, we observed a heavily labelled protein of M(r) 18 kDa and pI 8.2 on fluorographs of two-dimensional polyacrylamide gels. On the basis of its M(r), pI and amino acid composition, we tentatively identified it by database searching as cyclophilin A and subsequently confirmed its identity by immunostaining. Like actin and its associated proteins, cyclophilin A was transported in slow component b of axonal transport, but unlike these proteins, cyclophilin A did not copurify with actin on DNase I. It was not found amongst labelled proteins transported by fast axonal transported by fast axonal transport. Immunostaining of chicken dorsal root ganglion cells revealed that it accumulated in neurites at points of branching, varicosities and growth cones. Our results raise the possibility that cyclophilin A is important in maintaining the native folding of actin and associated proteins during transit in axons and assembly in growth cones.

Amino Acids↗
PubMed1997

Resolution of an early RecA-recombination intermediate by a junction-specific endonuclease.

The nucleoprotein filament formed on a circular single strand by Escherichia coli RecA protein in vitro can pair with homologous duplex DNA even when the latter lacks a free homologous end, but subsequent progression of the reaction through strand exchange requires an end in at least one strand of the duplex DNA. We purified from E. coli an endonuclease activity that cleaves the outgoing strand of duplex DNA at the junction of homologous and heterologous sequences in three-stranded RecA-recombination intermediates. This endonuclease activity also cleaves specifically at the junctions of duplex and single-stranded regions in synthetic double-stranded oligonucleotides whose central portion consists of unpaired heterologous sequences. These activities are consistent with a role in recombination and repair of DNA.

Base Sequence↗
PubMed1997

Ortho-substituted benzofused macrocyclic lactams as zinc metalloprotease inhibitors.

The design and preparation of ortho-substituted benzofused macrocyclic lactams are described. The benzofused macrocyclic lactams were designed as neutral endopeptidase 24.11 (NEP) inhibitors. Docking studies were carried out in a model of thermolysin (TLN) using the MACROMODEL and QXP modeling programs to select suitable ring sizes. These studies predicted that the 11-, 12-, and 13-membered ring macrocyclic lactams would be active in both enzymes TLN and NEP. Good predictability of experimental results, within this series, of binding to thermolysin and to a lesser extent to NEP was observed. A visual comparison, docked at the active site of TLN, is presented for thiorphan, a 10-membered ring macrocycle and an 11-membered ring benzofused macrocyclic lactam. Potent inhibition of both NEP and thermolysin was obtained. The 11-membered ring macrocycle 25a is the most potent inhibitor from this series of compounds (TLN IC50 = 68 nM; NEP IC50 = 0.9 nM). The effects of prodrug 44b administered at 10 mg/kg po on plasma atrial natriuretic peptide (ANP) levels in conscious rats was greater than 200% over a 4 h period.

Animals↗
PubMed1997

Meta-substituted benzofused macrocyclic lactams as zinc metalloprotease inhibitors.

The design, synthesis, and biochemical profile of meta-substituted benzofused macrocyclic lactams are described. The meta-substituted benzofused macrocyclic lactams were designed to have a degree of flexibility allowing the amide bond to occupy two completely different conformations while maintaining sufficient rigidity to allow for strong interaction between enzyme and inhibitor. Using TFIT, a novel molecular superimposition program, it was shown that the meta analogs could be readily superimposed onto our ACE inhibitor template whereas no low-energy superimpositions of the ortho-substituted macrocycles could be found. The macrocycles were prepared by tethering aldehyde 1 derived from S-glutamic acid or S-aspartic acid to a meta-substituted phosphonium bromide 2. Homologation to a monocarboxylic acid methyl ester malonate followed by deprotection and cyclization gave the macrocyclic frame. Further manipulation gave the desired compounds. Unlike the ortho-substituted benzofused macrocyclic lactams described in the previous paper which are selective NEP inhibitors, the meta-substituted compounds are dual inhibitors of both NEP and ACE. The most potent member of this new series, compound 16a, inhibited both enzymes with an IC50 = 8 nM in NEP and 4 nM in ACE.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Reproducibility of operator processing for radiation dosimetry.

Reproducibility of operator processing for radiation dose and biological half-life was assessed for radioimmunotherapy. Mean coefficient of variation for intra-operator consecutive processing and for inter-operator processing was less than 15% for all tissues. The mean coefficient of variation for intraoperator processing over 2 wk or inter-operator processing comparing an experienced and less experienced operator was generally greater, and particularly so for tumors. Satisfactory reproducibility was achievable using visual determination of regions of interests after 80 h of training.

Breast Neoplasms↗
PubMed1997

Practical determination of organ S values for individual patients for therapy.

Radiation dose calculations using S values of a reference man can introduce substantial errors for individuals patients. We found that all non target sources can be included in the remainder of the body estimate for therapeutic radionuclides. A practical method to derive organ S values based on MIRD data and the mass of the organ and total body of individual patients is proposed.

Humans↗
PubMed1997

Prediction of myelotoxicity using radiation doses to marrow from body, blood and marrow sources.

UNLABELLED: Bone marrow is generally the dose-limiting organ in radioimmunotherapy (RIT). Although radiation doses to marrow estimated from tracer doses have been shown to be comparable to those from therapy doses of radionuclide, the correlation of marrow radiation dose and myelotoxicity has not been well documented. The purpose of this study was to evaluate the relationship between radiation dose to marrow and subsequent changes in peripheral blood cell counts. METHODS: Radiation doses to marrow from three sources, body, blood and marrow targeting, were compared with changes in blood counts after the first therapy dose of (131)I-Lym-1 in 16 patients. Doses of (131)I-Lym-1 ranged from 1.1-8.2 GBq (29-222 mCi). Cumulated radioactivity in the body and marrow were obtained using sequential, quantitative images of the body and lumbar vertebrae, respectively, and that in blood using activity in blood samples. The individual and sum of radiation doses from penetrating radiations in the body, and nonpenetrating radiations in the blood and marrow, were compared with blood counts. RESULTS: In this group of patients, median radiation doses were 15.1, 15.4 and 42.1 cGy from body, blood and marrow targeting, respectively. Linear regression of radiation doses from body and blood versus fractional decreases in blood counts produced correlation coefficients of 0.38, 0.06, 0.22 and less than 0.01 for platelets, granulocytes, white blood cells (WBCs) and hematocrit, respectively. Linear regression of targeted marrow radiation doses versus fractional decreases in blood counts produced correlation coefficients 0.61, 0.31, 0.54 and 0.20 for platelets, granulocytes, WBCs and hematocrit. The closest association was found between radiation dose to marrow from marrow targeting and change in platelet count (r = 0.61). CONCLUSION: In patients, such as those with non-Hodgkin's lymphoma (NHL), likely to have marrow targeting, prediction of myelotoxicity by conventional body and blood contributions to marrow is substantially improved by the use of radiation dose to marrow estimated from images.

Blood↗
PubMed1997

Prediction of myelotoxicity using semi-quantitative marrow image scores.

UNLABELLED: Marrow radiation with resultant myelosuppression is usually dose-limiting in radioimmunotherapy (RIT). This study evaluated the relationship between a semiquantitative score of radiolabeled antibody marrow uptake obtained by imaging and subsequent decrease in peripheral blood cell counts in a patient population in whom marrow malignancy is common. METHODS: Semiquantitative scores were assigned to lumbar marrow images of 18 patients acquired 0, 6, 24 and 48 hr after the first therapy dose of 131I-Lym-1. Scores were adjusted for injected dose (GBq) and body surface area (m2), and correlated with post-therapy blood counts. A well-defined scale, where 0 and 4 represented least to highest marrow uptake when compared to background, was used to assign marrow image scores. Injected doses of 131I-Lym-1 ranged from 1.1-8.2 GBq (29-222 mCi). RESULTS: Linear regression of summed marrow scores (0-24 hr after injection) versus decrease in cell counts produced correlation coefficients of 0.76, 0.44, 0.58 and 0.46 for platelets, granulocytes, white blood cells (WBC) and hematocrit, respectively. Scores for individual and other combinations of images obtained immediately up to 24 hr after injection were also predictive.

Blood Cell Count↗
PubMed1996

A Markov model for the assembly of heterochromatic regions in position effect variegation.

Here we give a mathematical model for the assembly of heterochromatic regions at the heterochromatin-euchromatin interface in position effect variegation. This probabilistic model predicts the proportions of cells in which a gene is active in cells with one and two variegating chromosomes. The association of heterochromatic proteins to form remodeled chromatin following DNA replication is mainly described by accumulation independent conditional probabilities. These probabilities are conditional on the boundary of the sites to which the proteins can bind; they give the relative attractiveness of the sites to a protein complex chosen at random from a pool of available complexes. The number of complexes available is assumed to be limited and rates of reaction are implicitly modeled by the conditional probabilities. In general, these conditional probabilities are not known, however, they can be experimentally determined. By comparing double variegation situations to single variegation, this model shows that there may be an effect on the expression of reporter genes located near the interfaces due to different sites competing for heterochromatic proteins. In addition, this model suggests that in some cases the attractiveness of sites may change in the presence of other chemical species. Consequently, the model distinguishes between two sorts of data obtained from competition experiments using position effect variegation. The two sorts of data differ as to whether there is a change in the attractiveness of sites in addition to an effect from different sites competing for the same constituents of heterochromatin. Subject to the fact that some of its parameters are not known precisely, this model replicates data from several experiments and can give predictions in other cases.

Animals↗
PubMed1996

Slow axonal transport of soluble actin with actin depolymerizing factor, cofilin, and profilin suggests actin moves in an unassembled form.

We examined the axonal transport of actin and its monomer binding proteins, actin depolymerizing factor, cofilin, and profilin, in the chicken sciatic nerve following injection of [35S]methionine into the lumbar spinal cord. At intervals up to 20 days after injection, nerves were cut into 1-cm segments and separated into Triton X-100-soluble and particulate fractions. Actin and its binding proteins were then isolated by affinity chromatography on DNase I-Sepharose and by one- and two-dimensional polyacrylamide gel electrophoresis. Fluorographic analysis showed that the specific activity of soluble actin was two to three times that of its particulate form and that soluble actin, cofilin, actin depolymerizing factor, and profilin were transported at similar rates in slow component b of axonal flow. Our data strongly support the view that the mobile form of actin in slow transport is soluble and that a substantial amount of this actin may travel as a complex with actin depolymerizing factor, cofilin, and profilin. Along labeled nerves the specific activity of the unphosphorylated form of actin depolymerizing factor, which binds actin, was not significantly different from that of its "inactive" phosphorylated form. This constancy in specific activity suggests that continuous inactivation and reactivation of actin depolymerizing factor occur during transport, which could contribute to the exchange of soluble actin with the filamentous actin pool.

Actin Depolymerizing Factors↗
PubMed1996

Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy.

UNLABELLED: Copper-67 (67Cu) is an attractive radionuclide for radioimmuno-therapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. METHODS: A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. RESULTS: As the amount of 64Cu increased, the full width at tenth maximum of the line spread function increased, although there was no significant change in full width at half maximum. The number of scatter counts from 64Cu increased as the amount of 64Cu or the size of the source region of interest increased. When 64Cu was 25% of the total activity, less than 10% of the total 67Cu photopeak counts detected with a scintillation camera were attributable to 64Cu. Although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was five times greater than that from 64Cu, the marrow dose (CGy/GBq) from 67Cu was only three times greater than that from 64Cu. Therefore, the therapeutic index was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25% of the total activity, there was less than a 10% decrease in the therapeutic index. CONCLUSION: The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 64Cu. The 25% radioimpurity of 64Cu causes less than 10% deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration.

Bone Marrow↗
PubMed1996

Prediction of radiation doses from therapy using tracer studies with iodine-131-labeled antibodies.

UNLABELLED: Tracer pharmacokinetic studies are often used in treatment planning for radionuclide therapy including radioimmunotherapy. This study evaluates the validity of using tracer studies to predict radiation doses from therapy with the same radiolabeled antibody. METHODS: Quantitative imaging and blood radioactivity were used to obtain the pharmacokinetics and radiation doses that were delivered to the total body, blood, marrow, lungs, liver, kidneys, thyroid, spleen and tumors. Tracer and therapy data for eight patients with lymphoma and one patient with breast cancer were compared using linear regression statistics. Doses of 131I-labeled antibody for the tracer studies ranged from 0.1 to 0.4 GBq (2 to 10 mCi), and therapy doses ranged from 0.7 to 5.6 GBq (20 to 150 mCi). RESULTS: Radiation doses to tissues and, in particular, the bone marrow and tumors were reliably predicted from tracer studies. In this group of patients, median dose to marrow from marrow targeting, total body and blood was 9.2 cGy/GBq for tracer studies and 7.6 cGy/GBq for therapy studies with a median difference of 0.5 cGy/GBq. Median dose to tumors was 81.1 cGy/GBq for tracer studies and 70.3 cGy/GBq for therapy studies with a median difference of 5.9 cGy/GBq. CONCLUSION: In these patients, tracer studies were predictive of the radiation doses from therapy for total body, major organs and tumors. The radiation doses to marrow and tumors, which are the usual determinants of the therapeutic index, correlated well between tracer and therapy studies (r > or = 0.95).

Antibodies, Monoclonal↗
PubMed1996

[A study on the changes of DCC and MCC genes in colorectal carcinoma and adenoma].

Both deleted in colorectal carcinoma (DCC) and mutated in colorectal carcinomas (MCC) genes are newly found tumour suppresser genes in colorectal carcinomas. In this study mutations of DCC gene and loss of heterozygosity (LOH) of MCC gene were detected with Southern blot and PCR methods respectively. The study consisted of 30 cases of colorectal adenoma (10 with mild, 10 with moderate and 10 with severe dysplasia) and 33 cases of colorectal carcinomas (13 highly, 10 moderately and 10 poorly differentiated, meanwhile 9 in Dukes A, 10 in B and 14 in C stage). Their paired normal colorectal mucosa served as control. The results were as follows: mutation of DCC was not found in any specimen with normal mucosa or with adenoma of mild and moderate dysplaaia, while it was found in one if those with severe dysplasia. Mutation of DCC was, however, found in 7 of the 33 specimens with carcinoma and there was a correlation between the positive rate and the differentiation or staging of the carcinoma. LOH of MCC was not found in normal mucosa, but it was found in 2/10, 3/10 and 4/10 of the adenoma specimens with mild, moderate and severe dysplasia respectively. 18/33 of the carcinoma specimens was found to have LOH of MCC and there was also a correlation between the positive rate and the differentiation or staging of the carcinoma. These results suggest that the frequency of multiple gene changes increase with poor differentiation and increased staging of colorectal carcinoma.

Adenoma↗