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Biomedical subjects

L Lang

Publications and source records attributed to L Lang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Evaluation of human transferrin radiolabeled with N-succinimidyl 4-[fluorine-18](fluoromethyl) benzoate.

UNLABELLED: Iron metabolism plays a key role in cell proliferation and survival in rapidly growing cancer cells. Uptake is mediated by the carrier protein transferrin. The increased need for iron has been used as a method to target tumors and there is well-documented evidence that certain tumors can be imaged with tracers such as 67Ga, that mimic transferrin-mediated iron uptake. To obtain a tracer that would be better able to quantitate transferrin kinetics and indirectly evaluate iron metabolism, we have labeled human transferrin with the positron emitter, 18F, with a one-step high-specific activity method developed in our laboratory. METHODS: We measured the binding affinities of [18F]diferric (holo-) and iron-free (apo-) transferrin on two human cell lines. We also compared cellular uptake of [18F]holo-transferrin and [67Ga]citrate in various conditions, and washout of label incorporated into cells. RESULTS: The binding affinity of [18F]holo-transferrin was found to be the same as that reported for [125I]holo-transferrin. In our hands there was no significant difference in binding affinity between diferric holo-transferrin and iron-free apo-transferrin. [18F]holo-transferrin uptake rapidly reaches a steady-state equilibrium between the intracellular and extracellular environment, while gallium accumulation linearly increases with time. [18F]holo-transferrin is rapidly recycled out of the cell with similar kinetics to those reported for [125I]holo-transferrin. CONCLUSION: [18F]holo-transferrin displays the properties of native transferrin and appears suitable for quantitative evaluation of transferrin kinetics in vivo.

Benzoates↗
PubMed1995

Biodistribution of 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragments in nude mice with interleukin 2 alpha receptor-positive tumor xenografts.

We evaluated the biodistribution, pharmacokinetics, and generation of catabolites of an 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragment (dsFv) in tumor-bearing nude mice. This dsFv is genetically engineered from a murine monoclonal antibody that recognizes the alpha subunit of the interleukin 2 (IL-2 alpha) receptor. Labeling was performed with 18F using N-succinimidyl 4-([18F]fluoromethyl)benzoate or with 125I using the Iodo-Gen method. The immunoreactivities of the radiolabeled anti-Tac dsFv were > 82%. The biodistribution was evaluated (at 15, 45, and 90 min and 6 h) in athymic nude mice (approximately five/group) bearing s.c. tumor xenografts. Cell line A431 served as the IL-2 receptor-negative control tumor, whereas the ATAC4 cell line served as our IL-2 receptor-positive tumor. Animals received injections of 18F-labeled anti-Tac dsFv (0.7-1.4 megabecquerels/1.5-3 micrograms) and 125I-labeled anti-Tac dsFv (0.1-0.4 megabecquerels/0.9-1 microgram). Blood clearance for both preparations was rapid, with < 10% retained in the blood by 15 min. Maximum accumulation in ATAC4 tumors occurred between 45 and 90 min and peaked at a mean of 4.2% injected dose/g (18F) and 5.6% of injected dose/g (125I). At 6 h, the ATAC4 tumors contained 11 times more 18F and 3 times more 125I than did the A431 tumors. The ATAC4 tumor:blood ratios for the 18F and 125I were > 12:1 and > 1.4:1 at 6 h, respectively, whereas the ratios for the antigen-negative A431 tumor were less than 1. The kidneys were the major route of elimination. Catabolites appeared quickly and were identified as [125I]iodide and predominantly N-epsilon-[18F]4-fluoromethylbenzoyl(alpha-N-acetyl) lysine. This is the first study to evaluate the biodistribution of an 18F-labeled Fv fragment in vitro and in vivo. In vivo, the dsFv was taken up rapidly by the kidneys, producing lysine-containing catabolites for 18F-labeled dsFv and [125I]iodide for 125I-labeled dsFv.

Animals↗
PubMed1994

One-step synthesis of 18F labeled [18F]-N-succinimidyl 4-(fluoromethyl)benzoate for protein labeling.

[18F]-N-succinimidyl 4-(fluoromethyl)benzoate (1) has been prepared from N-succinimidyl-4-[(4-nitrobenzensulfonyl)oxymethyl]benzoate (2) in one step using Kryptofix 2.2.2/[18F-]. The effect of solvents, potassium salts and temperatures were studied to determine optimum labeling condition. The best results were obtained using carbonate as the counter ion and acetone as the solvent at room temperature. Overall radiochemical yields of approximately 18% (EOS) for the synthesis of 1 were obtained in 30-35 min, including HPLC purification. Proteins were labeled with 1 with labeling yields of 50-70% in 15 min.

Benzoates↗
PubMed1994

[The anti-HCV assay in viral hepatitis and hepatoma and the relationship between HCV infection and blood transfusion].

Two hundred cases of various kinds of viral hepatitis and hepatocellular carcinoma were tested for serum anti-HCV. The positive rates of anti-HVC in patients with severe hepatitis and patients with cirrhosis were 42.86% and 46.15%, respectively. They were significantly higher than those in patients with other kinds of hepatitis (P < 0.05). The positive rate of anti-HCV was 67.5% in patients with posttransfusion hepatitis, 20.47% in healthy blood donors. In posttransfusion hepatitis B it was only 2.5%. Our results demonstrated that blood transfusion played an important role in transmitting HCV. Our findings also indicated that dual infection of HBV and HCV was important in the course of chronic hepatitis, cirrhosis and severe hepatitis. 50% of the anti-HCV positive patients with chronic hepatitis had slightly elevated serum alanine aminotransferase level. This showed that liver damage caused by HCV may be a chronic course.

Adult↗
PubMed1991

Metabolic rate, not percent dehydration, predicts rectal temperature in marathon runners.

This study was designed to determine the factors predicting the post-race rectal temperature in marathon runners. Post-race rectal temperatures of 30 recreational runners (maximum oxygen consumption (VO2max) = 58.3 +/- 5.9 ml O2.kg-1.min-1; mean +/- SD) who completed a 42.2 km marathon at 75.8% (+/- 9.3%) VO2max were measured and related to their levels of dehydration (percent mass loss), their running velocities (km.h-1), and their estimated absolute metabolic rates (1 O2.min-1) for different segments of the 42.2 km race. The influence of certain anthropometric variables was also determined. Percent mass loss during the race (2.5 +/- 1.4%), post-race rectal temperatures (38.9 +/- 0.6 degrees C), and rates of sweat loss (1.0 +/- 0.3 1.h-1) were low. There was no statistical relationship between percent mass loss and post-race rectal temperature. Post-race rectal temperatures were significantly related to the metabolic rates for the full 42.2 km and for the last 21.1 and 6 km of the race, and to the average running velocity for the last 6 km (P less than 0.05 and P less than 0.01). Average sweat rates were related to metabolic rates for 42.2 km and for the last 6 km of the race (P less than 0.05) but were unrelated to running velocity. We conclude that metabolic rate sustained during the latter section of the race, and not the level of dehydration, is the principal determinant of the post-race rectal temperature in marathon runners.

Adult↗
PubMed1987

Nosocomial infections in a neurosurgery department.

A three month prospective survey of nosocomial infections in a Neurosurgery Department was carried out. Results showed that the overall nosocomial infection rate was 6.7 per 100 patient discharges with the rate of infected patients being 4.6 per 100 discharges. Patients in intensive care had two times the risk of acquiring a nosocomial infection then patients in non-intensive care. Both respiratory tract and urinary tract infections accounted for the majority (89.1%) of the nosocomial infections. 69.7% of lower respiratory tract infections were associated with the use of endotracheal tube and/or ventilatory assistance. Similarly, 87.5% of urinary tract infections were associated with the use of indwelling catheters. It is hoped that preventive measures introduced or reemphasized just before and after the study will serve to further lower the nosocomial infection rate in the Neurosurgery Department.

Cross Infection↗
PubMed1986

Glycoprotein phosphorylation in simple eucaryotic organisms. Identification of UDP-GlcNAc:glycoprotein N-acetylglucosamine-1-phosphotransferase activity and analysis of substrate specificity.

UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase activity has been identified in both Acanthamoeba castellani and Dictyostelium discoideum. Each of these activities exhibits a different in vitro specificity toward various purified glycoproteins. The N-acetylglucosaminyl-phosphotransferase of A. castellani is very similar to the mammalian enzyme in that it phosphorylates the lysosomal enzymes cathepsin D and uteroferrin much more efficiently than nonlysosomal glycoproteins and appears to recognize a determinant on the protein portion of these good acceptors. In contrast the D. discoideum enzyme cannot utilize cathepsin D as a good substrate and, although it phosphorylates uteroferrin efficiently, it does not recognize the protein portion of this acceptor. The oligosaccharide of uteroferrin appears to assume a different conformation than the oligosaccharides of other glycoproteins and glycopeptides, as evidenced by its enhanced sensitivity to mannosidase digestion. This conformation, presumably induced by some interaction with the underlying protein, may be responsible for the specific phosphorylation of uteroferrin by the N-acetylglucosaminylphosphotransferase of D. discoideum.

Acid Phosphatase↗
PubMed1986

Phosphorylation of the oligosaccharide of uteroferrin by UDP-GlcNAc:glycoprotein N-acetylglucosamine-1-phosphotransferases from rat liver, Acanthamoeba castellani, and Dictyostelium discoideum requires alpha 1,2-linked mannose residues.

We have investigated the oligosaccharide requirements of the UDP-GlcNAc:glycoprotein N-acetylglucosamine-1-phosphotransferases from rat liver, Acanthamoeba castellani, and Dictyostelium discoideum. Uteroferrin, an acid hydrolase, was phosphorylated by the three N-acetylglucosaminylphosphotransferases, and the phosphorylated oligosaccharides were isolated and analyzed by ion suppression high performance liquid chromatography. In all three cases, the phosphorylated species contained 6 or more mannose residues. Phosphorylation of the Man5GlcNAc2 oligosaccharide could not be detected even though this was the major species on the native uteroferrin. The Man5GlcNAc2 oligosaccharides lack alpha 1,2-linked mannose residues, whereas the larger oligosaccharides contain 1 or more mannose residues in this linkage. Treatment of intact uteroferrin with an alpha 1,2-specific mannosidase-generated molecules whose oligosaccharides consisted almost entirely of species with 5 mannose residues. The N-acetylglucosaminylphosphotransferases could no longer phosphorylate such molecules. These data indicate that at least 1 alpha 1,2-linked mannose residue must be present on uteroferrin's oligosaccharide for phosphorylation to occur.

Acid Phosphatase↗