Biomedical subjects
Publications and source records attributed to W Y Lin.
The authors describe a case of suppressed normal thyroid tissue in a patient with autonomous toxic nodule, which was visualized by a Tc-99m MIBI thyroid scan without thyrotropin (TSH) stimulation. The findings suggest that Tc-99m MIBI can be a substitute for conventional thyroid imaging using I-131 to visualize suppressed normal thyroid tissue without TSH stimulation and its side effects.
The origin of the fluorescence changes observed in stopped-flow experiments of the hydrolysis of three 5-(dimethylamino)naphthalene-1-sulfonyl-(dansyl) peptide substrates by porcine kidney cytosol leucine aminopeptidase has been investigated. The substrates used all have the potential to accept energy from aromatic residues of the enzyme via resonance energy transfer when they are bound as enzyme-substrate complexes, indicating that fluorescence changes due to the buildup and decay of such intermediates are possible. However, the fluorescence of these substrates differs from that of the products, and direct excitation of their dansyl groups during hydrolysis can also be responsible for the observed fluorescence changes due to changes in the concentrations of free substrate and product. The dansyl fluorescence changes observed with excitation wavelengths near 280 nm are not accompanied by quenching of the enzyme fluorescence, as would be expected if there were enzyme-to-substrate energy transfer. The magnitude of the maximal fluorescence change at a fixed concentration of substrate is also independent of the enzyme concentration. Furthermore, the excitation profile for the fluorescence changes shows that they arise from direct excitation of the dansyl group. Thus, there is no energy transfer in these reactions, and the fluorescence changes observed arise from direct excitation of the dansyl group and reflect the instantaneous concentration of substrate. This behavior contrasts sharply with that for the reaction of carboxypeptidase A with dansyl-Gly-Tyr, which has been studied as a positive control for an energy-transfer system.(ABSTRACT TRUNCATED AT 250 WORDS)
Stopped-flow fluorescence experiments have been carried out at 23 degrees C to study the hydrolysis of Leu-Gly-NHNH-Dns [Dns = 5-(dimethylamino)naphthalene-1-sulfonyl] and Leu-Gly-NH(CH2)2NH-Dns by porcine kidney cytosol leucine aminopeptidase (LAP). Experiments have been performed with LAP species containing Mg(II), Mn(II), Ni(II), Cu(II), Zn(II), and no metal ion at the regulatory metal binding site. The fluorescence changes observed on hydrolysis of these dansyl substrates by LAP arise from changes in the concentration of substrate. Several kinetic relationships have been developed that allow the steady-state kinetic parameters for these reactions to be determined from the stopped-flow fluorescence traces. When any of the five metal ions are bound at the regulatory site, kcat and KM are both raised to approximately the same extent with the result that the maximum increase observed for kcat/KM is only approximately twofold. The effects of these metal ions on kcat, KM, and kcat/KM observed for these substrates differ markedly from those for less physiologically relevant substrates, such as Leu-p-nitroanilide, that do not have amino acids on both sides of the scissile bond. This suggests that earlier conclusions regarding the effect of the regulatory metal ion on the activity of LAP may have been misleading and casts doubt as to whether the term "regulatory site" has validity in the context of LAP-catalyzed reactions under physiological conditions.
Stopped-flow fluorescence experiments have been carried out to study the steady-state kinetics of hydrolysis of Leu-Gly-NHNH-Dns [Dns = 5-(dimethylamino)naphthalene-1-sulfonyl] by porcine kidney cytosol leucine aminopeptidase (LAP) in 50% v/v methanol/buffer solution at ambient temperature and the pre-steady-state kinetics of this reaction in the -35 to 0 degrees C temperature range. Experiments have been carried out on LAP species containing Mg(II), Mn(II), Cu(II), Ni(II), Zn(II), and no metal ion at the regulatory metal binding site. At ambient temperatures, the stopped-flow fluorescence changes observed on hydrolysis of the substrate have been used to measure the steady-state kinetic parameters kcat and KM. The results show that 50% v/v methanol lowers the values of kcat from 2- to 12-fold compared to the reactions in the absence of methanol for all of the metallo-LAP, but that the values of KM are essentially unaffected. The pre-steady-state reactions carried out under nonturnover conditions at -35 degrees C reveal a new relaxation for LAP species with Ni(II), Cu(II), and Zn(II) in the regulatory site. The value of kobsd for this relaxation reaches a plateau at high substrate concentrations, and the magnitude of its fluorescence change at a fixed concentration of substrate is proportional to the enzyme concentration. Thus, this relaxation corresponds to the production and decay of a new enzyme-substrate intermediate not observed at higher temperatures whose fluorescence differs from that of the succeeding intermediate that is normally seen above -26 degrees C.
The effect of Cu(II), Ni(II), Zn(II), Mg(II), and Mn(II) on the fluorescence of porcine kidney cytosol leucine aminopeptidase and three of its dansyl(Dns) peptide substrates, Leu-Gly-NHNH-Dns, Leu-Gly-NH(CH2)2NH-Dns, and Leu-Gly-NH(CH2)6NH-Dns, has been investigated. These five metal ions were chosen for study because each binds to the regulatory metal binding site of leucine aminopeptidase. Since the binding is relatively weak, kinetic studies of the different metalloderivatives of the enzyme are normally carried out in the presence of large molar excesses of these metal ions that can potentially affect both the enzyme and substrate. The fluorescence of all of the dansyl-peptides, as well as several other dansyl species, is quenched by Ni(II) and Cu(II), but not by Mg(II), Mn(II), or Zn(II). The absorption spectra of these dansyl substrates are also perturbed by Ni(II) and Cu(II). The rate at which maximal quenching for some dansyl species is attained after mixing with Ni(II) and Cu(II) is slow and the quenching is reversed on addition of EDTA. These results indicate that the quenching is the result of complex formation between the fluorophores and these metal ions. The association constants for the metal complexes have been determined from Stern-Volmer plots. In addition to complex formation, Ni(II) and Cu(II) cause the degradation of Leu-Gly-NHNH-Dns through a two step mechanism involving loss of dansic acid. Ni(II) and Cu(II) also partially quench the fluorescence of leucine aminopeptidase through contact with its surface accessible Trp residues. These observations indicate that care must be taken in stopped flow fluorescence studies of reactions between this enzyme and its dansyl substrates to avoid adverse effects brought about by Ni(II) and Cu(II).
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Esophageal motility was studied in 24 patients with mixed connective tissue disease (MCTD) and 20 control subjects by the solid phase radionuclide esophageal transit study. A computer routine modified from Klein and Russel was used. Total mean transit time, regional mean transit time, residual fraction after first swallow, and retrograde index increased significantly in MCTD patients compared with normal control subjects. An abnormal total mean transit time occurred in 84% (20 of 24) of the patients with MCTD. Our results confirmed that delayed esophageal transit is common in patients with MCTD.
PURPOSE: Irradiation of the arterial wall with beta particles has been shown to be effective in inhibiting neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA). In this study, we describe the use of 188W/188Re generators to obtain 188Re (half-life 16.9 h, maximal beta energy of 2.12 MeV) as a new candidate radioisotope for endovascular irradiation. We have evaluated two [188Re]-compounds as candidates for use as solution-based radiation sources that would allow conventional liquid-filled balloon inflation for delivery of radiation to the vessel wall. While balloon rupture at nominal inflation pressures is a very rare event, (<1 per 10,000 at high pressure), radioisotope release could potentially result in significant dose to radiation-sensitive organs. We have thus evaluated the biodistribution, dosimetry, and kinetics of excretion in rats of two 188Re-labeled compounds that are proposed for intravascular therapy. MATERIALS AND METHODS: Rhenium-188 was obtained as [188Re]-sodium perrhenate by saline elution of an alumina-based 188W/188Re generator system (>500 mCi). High specific volume solutions of the [188Re]-sodium perrhenate (>50 mCi/ml) were obtained by post-elution concentration of the generator bolus by passage through a tandem silver cation/anion column system. Rhenium-188-labeled benzoylthioacetyltriglycine (MAG3) was prepared by stannous ion reduction of [188Re]-perrhenate in the presence of the benzyl-MAG3 substrate, and was characterized as a single radioactive component. Rhenium-188-perrhenate and [188Re]-MAG3 were administered to separate groups of Fischer rats, which were sacrificed at various times and the tissue distribution of 88Re determined in the major organs. Excretory products were also collected daily from separate groups of rats for each agent over 7 days. The effects of perchlorate and iodide preblocking and postdisplacement of thyroid uptake of [188Re]-perrhenate were also evaluated. RESULTS: Organ uptake values were modest for both agents [<0.25 % injected dose(ID)/gram of tissue at 6 h] for all organs evaluated except for the thyroid, with the intestines and intestinal contents showing the highest uptake values (0.72-1.97 %ID/gram). Whereas thyroid uptake of 188Re after injection of [188Re]-MAG3 was low (0.16 %ID/gram), uptake after injection of [188Re]-perrhenate was higher and could be blocked by pretreatment with perchlorate (intravenous [IV]) or displaced by perchlorate posttreatment. Also, oral or IV iodide pre- or postadministration could also significantly block or displace thyroid uptake of [188Re]-perrhenate. Both [188Re] agents were excreted primarily via the urinary bladder. The excretion half-life of [188Re]-perrhenate was about 7 h; in contrast, the [188Re]-MAG3 complex showed 50% excretion in less than 2 h. The large intestines received the most significant adsorbed dose, with values of 2.0 cGy/ mCi for [188Re]-perrhenate and 4.6 x 10(-3) cGy/mCi for [188Re]-MAG3. CONCLUSIONS: Rhenium-188-MAG3 shows more rapid urinary bladder excretion in rats than perrhenate and both agents show low organ uptake. Thyroid uptake of free [188Re]-perrhenate can be blocked or displaced with oral perchlorate administration. For the projected use of [188Re]-MAG3 for balloon inflation required for irradiation of the arterial wall, calculated organ dose values are within acceptable limits in the unlikely event of low pressure balloon rupture. Rhenium-188-MAG3 in solution is thus a new candidate for balloon dilation providing uniform endovascular irradiation following PTCA for restenosis therapy.
BACKGROUND: Intravascular brachytherapy is an effective method for inhibiting coronary restenosis after percutaneous transluminal coronary angioplasty. A new concept for preventing restenosis is the use of a liquid-filled balloon containing a beta-ray-emitting radioisotope. Generator-produced rhenium-188 (Re-188) is a good candidate for intravascular brachytherapy. However, in the unlikely event of balloon rupture, release of Re-188 perrhenate may cause a high radiation dose to the thyroid and stomach. In this study, we compared the biodistributions of three Re-188 preparations (Re-188 perrhenate, Re-188 pentetic acid [DTPA], and Re-188 MAG3) to assess the radiation dose to organs in a rat model that mimicked balloon rupture. METHODS AND RESULTS: After injection of Re-188 preparations intravenously, rats were killed at 10 minutes, 30 minutes, 60 minutes, 2 hours, and 6 hours (n = 5/group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter. In addition, urine excretion and thyroid gland uptake were evaluated in rats (n = 5/group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed all 3 agents were excreted primarily via urine. In the Re-188 MAG3 group, 82% was excreted within 1 hour, but in the Re-188 perrhenate group, only 28% was excreted. The biodistribution data for these agents revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA and Re-188 MAG3 groups. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for all 3 agents. The thyroid radiation values were 0.163, 0.0167, and 0.00728 mGy/MBq for Re-188 perrhenate, Re-188 DTPA, and Re-188 MAG3, respectively. The stomach radiation values were 0.127 mGy/MBq for Re-188 perrhenate, 0.013 mGy/MBq for Re-188 DTPA, and 0.0104 mGy/MBq for Re-188 MAG3. CONCLUSIONS: In the event of balloon rupture, the release of Re-188 MAG3 or Re-188 DTPA results in lower radiation doses than release of Re-188 perrhenate, especially to the thyroid gland and the stomach.
BACKGROUND/AIMS: The purpose of this study is to evaluate the efficacy of technetium-99m labeled red blood cell liver single photon emission computed tomography (RBC liver SPET) in evaluating the diagnostic ability for differentiating the nature of a solitary liver tumor detected with ultrasonography in hepatitis B carrier patients. METHODOLOGY: One hundred and one hepatitis B carrier patients (56 males, 45 females, aged 13-70 years) with a solitary solid liver mass found on ultrasonography were included in this study. The final diagnosis was made after liver biopsy, aspiration with cytology and/or autopsy in 27 patients and after follow-up with both clinical and ultrasonography findings in 74 patients. RESULTS: Hemangioma was found in 79 patients, hepatocellular carcinoma in 14, focal nodular hyperplasia in 5, fatty liver in 2, and metastasis in 1. The diagnostic sensitivity of RBC liver SPET for hemangioma, with a hyperechoic, hypoechoic, or isoechoic ultrasonography pattern, was between 75-80%, while the specificity for all patterns was 100%. For mixed-echoic lesions, the sensitivity was 100%, but the specificity was only 50%. Two false-positives were noted; both were mixed-echoic lesions. CONCLUSIONS: RBC liver SPET is useful for differentiating hemangioma from other liver tumors in hepatitis B carrier patients with a various sonographic patterns, especially for those who had a mixed-echoic sonographic liver mass.