Biomedical subjects

Yong Choi

Publications and source records attributed to Yong Choi.

53 records · Page 3Linked to original sources

PubMed2004

Clinical significance of thyroid visualization on technegas ventilation scintigraphy.

BACKGROUND: We investigated the clinical significance of thyroid visualization on technegas (TcG) ventilation scintigraphy (TcGS) based on the hypothesis that this visualization may be correlated with thyroid disease with high radioactive thyroid uptake (RATU). METHODS: From a total of 1022 consecutive patients undergoing TcG/99mTc macroaggregated albumin ventilation/perfusion (V/Q) scintigraphy to exclude pulmonary embolism, 114 who underwent in vitro thyroid function tests (TFTs) within 2 weeks of the lung scintigraphy were included in the retrospective study. In addition, in 10 patients in whom high RATU was noted on [99mTc]pertechnetate thyroid scintigraphy, TcGS was performed prospectively. The degree of thyroid activity in each patient was graded on a scale of 0 to 2 (grade 0 = no or faint uptake; grade 1 = mild uptake, but less than the lung; and grade 2 = strong uptake, similar to, or more than, the lung). RESULTS: Thyroid uptake was observed on TcGS in 17.5% of the patient group (20/114; 10 with grade 1, 10 with grade 2). Serum T3, T4 and TSH values differed significantly, depending on the grade of thyroid activity. All patients showing grade 2 thyroid uptake were clinically diagnosed as having Graves' disease. None of the 94 patients with grade 0 on TcGS had evidence of hyperthyroidism, although four patients had hypothyroidism. In the prospective group, all patients showed any visualization of the thyroid on TcGS (3 with grade 1, 7 with grade 2). The final diagnoses for these patients were Graves' disease in six, Hashimoto's thyroiditis in three and post-partum thyroiditis in one. CONCLUSION: Thyroid visualization during TcGS appears to be correlated with thyroid disease with high RATU. Such a finding may also deserve further evaluation for additional irregularities in thyroid function.

Administration, Inhalation↗

PubMed2004

Synthesis and evaluation of 5,7-dihydro-3-[2-[1-(4-[18F]-fluorobenzyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one for in vivo mapping of acetylcholinesterase.

OBJECTIVES: Acetylcholinesterase (AChE) is an important cholinergic marker for the diagnosis of Alzheimer's disease (AD). A recent study has demonstrated that C-labelled 5,7-dihydro-7-methyl-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one (CP-126,998) shows promising results. The demethylated form of this ligand (CP-118,954) is a more potent and selective inhibitor than CP-126,998. In this study, therefore, CP-118,954 was labelled with F and evaluated for the in vivo mapping of AChE. METHODS: The 4-fluoro (1). and 2-fluoro (2). derivatives of CP-118,954 were synthesized from 4-methyl-3-nitroanisole in 11 steps. Their in vitro binding affinities to AChE were measured using Ellman's method. The preparation of [F]-1 was carried out by reductive alkylation of the piperidine precursor with 4-[F]-fluorobenzaldehyde, followed by high-performance liquid chromatography (HPLC) purification. In vitro autoradiography was performed by incubating rat brain coronal slices with [F]-1. Tissue distribution studies were performed in mouse brain and the data were expressed as the percentage of the injected dose per gram of tissue (%ID x g). RESULTS: Two fluorine-substituted AChE inhibitors were synthesized and their in vitro binding data showed that the 4-fluoro and 2-fluoro derivatives (1 and 2) had similar or superior binding affinity to that of the unsubstituted ligand, CP-118,954. The F-labelled ligand was synthesized in 20-35% radiochemical yield (EOS) and with high effective specific activity (36-42 GBq x micromol). Autoradiography showed high uptake of [F]-1 in the striatum and this striatal uptake was completely inhibited by the unlabelled ligand 1. Tissue distribution studies demonstrated that high radioactivity was accumulated in the striatum, an AChE-rich region. CONCLUSIONS: This study demonstrates that [F]-1 may hold promise as a radioligand for the in vivo mapping of AChE.

Acetylcholinesterase↗

PubMed2004

Adult pancreas generates multipotent stem cells and pancreatic and nonpancreatic progeny.

Strategies designed to produce functional cells from stem cells or from mature cells hold great promise for treatment of different cell-degenerative diseases. Type 1 and type 2 diabetes are examples of such diseases. Although different in origin, both involve inadequate cell mass of insulin-producing beta cells, the most abundant cell type of pancreatic islets of Langerhans. Practical realization of such strategies is highly dependent on the elucidation of physiological mechanisms responsible for generation of new beta cells in the pancreas, which at this time are poorly defined. The in vitro differentiation systems allowing generation of new beta cells provide a valuable experimental tool for studying these mechanisms. Few such systems are currently available. In this work, we present an in vitro differentiation system, derived from adult mouse pancreas, capable of generating insulin-producing beta-like cells, which self-organize into islet-like cell clusters (ILCCs) during the course of the culture. Surprisingly, we found that along with the ILCCs, multiple cell types with phenotypic characteristics of embryonic central nervous system and neural crest are also generated. Moreover, several embryonic stem cell-specific genes are induced during the course of these cultures. These results suggest that the adult pancreas may contain cells competent to give rise to new endocrine and neural cells.

Animals↗

PubMed2004

Augmented 18F-FDG uptake in activated monocytes occurs during the priming process and involves tyrosine kinases and protein kinase C.

UNLABELLED: Activated monocytes with a high (18)F-FDG accumulation can affect the results of clinical PET studies. To better understand the mechanisms regulating monocytic (18)F-FDG uptake, we investigated the effect of priming and respiratory-burst generation and further evaluated the role of potential protein kinase pathways. METHODS: Purified human monocytes were primed with interferon-gamma (IFN-gamma), and respiratory burst was generated by stimulation of primed cells with phorbol-12-myristate-13-acetate (PMA). Oxygen-intermediate generation was assessed by luminescence measurements after the addition of lucigenin. (18)F-FDG uptake after 30 min of incubation was measured for unprimed control cells, primed cells, and PMA-stimulated cells. The role of protein kinases was investigated using respective inhibitors. RESULTS: PMA stimulation of primed monocytes dramatically increased oxygen-intermediate generation, leading to a 42.2 +/- 1.1 fold higher level of cumulative luminescence compared with unprimed control cells, whereas IFN-gamma priming alone resulted in low luminescence levels (13.9% +/- 4.6% of PMA-stimulated cells). In contrast, priming alone was sufficient to augment monocytic (18)F-FDG uptake to 273.3% +/- 16.7% of control levels (P < 0.001), and it was not further increased by PMA stimulation. The tyrosine kinase inhibitor, genistein, and the specific protein kinase C inhibitor, staurosporine, completely abolished the priming-induced enhancement of (18)F-FDG uptake and lowered uptake to control levels. Under the same conditions, wortmannin, a phosphatidylinositol 3 kinase (PI3 kinase)-specific inhibitor, and cycloheximide, a protein synthesis inhibitor, were associated with only minor reductions in the enhanced-uptake effect of priming. CONCLUSION: IFN-gamma priming alone, without stimulation of respiratory-burst activity, is sufficient to induce maximal augmentation of (18)F-FDG uptake in monocytes. Furthermore, this metabolic effect appears to involve tyrosine kinases and the protein kinase C pathway but is independent of the PI3 kinase pathway.

Cells, Cultured↗

PubMed2004

18F-FDG PET in patients with esophageal squamous cell carcinoma undergoing curative surgery: prognostic implications.

UNLABELLED: We investigated whether the standardized uptake value (SUV) of the primary tumor, the tumor length measured on a PET image, the number of (18)F-FDG PET-positive nodes, and the PET stage were independent prognostic predictors over other clinical variables in patients with esophageal squamous cell carcinoma who were undergoing curative surgery. METHODS: Sixty-nine patients with newly diagnosed esophageal squamous cell carcinoma who underwent preoperative (18)F-FDG PET and curative esophagectomy were included. The events for survival analysis were defined as recurrence or metastasis and cancer-related death. The disease-free and overall survival rates of each variable were estimated by the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate independent prognostic variables for multivariate survival analysis. RESULTS: Using univariate survival analysis, the presence of adjuvant therapy, pathologic stage, number of CT-positive nodes (0, 1, > or =2), tumor length on PET (cutoff: 3 cm, 5 cm), number of PET-positive nodes (0, 1, 2, > or =3), and PET stage (N0 M0, N1 M0, M1) were significant prognostic predictors for disease-free survival. However, only the number of PET-positive nodes was an independent significant prognostic predictor for disease-free survival in multivariate analysis (hazard ratio = 1.87, P < 0.001). In univariate survival analysis, the sex, presence of adjuvant therapy, clinical and pathologic stages, number of CT-positive nodes, maximum SUV of the primary tumor (cutoff: 6.3, 13.7), tumor length on PET, number of PET-positive nodes, and PET stage were significant prognostic predictors for overall survival. In contrast, the clinical stage (hazard ratio = 0.53, P < 0.05), pathologic stage (hazard ratio = 3.14, P < 0.005), tumor length by PET (hazard ratio = 2.74, P = 0.01), and number of PET-positive nodes (hazard ratio = 1.71, P < 0.05) were independent significant prognostic predictors for overall survival in multivariate analysis. CONCLUSION: In addition to the pathologic stage, (18)F-FDG PET provides noninvasively independent prognostic information using the number of positive lymph nodes and the tumor length on the PET image in preoperative esophageal squamous cell carcinoma. A revised TNM classification system for esophageal carcinoma may consider tumor length and the number of positive lymph nodes as important prognostic factors.

Adult↗

PubMed2003

Prognostic value of cardiac autonomic neuropathy independent and incremental to perfusion defects in patients with diabetes and suspected coronary artery disease.

We investigated the prognostic value of cardiac autonomic neuropathy (CAN) in relation to perfusion defects in 146 diabetic patients with suspected coronary artery disease. Perfusion defects and CAN were significant univariate predictors of death (p=0.05 and p<0.001, respectively) and cardiac events (p<0.001 and p<0.002, respectively). However, CAN remained a significant predictor of death and cardiac events after adjustment for perfusion defects (both p<0.02), and provided prognostic information incremental to that offered by perfusion defects alone (p<0.003 and p<0.006, respectively).

Age Factors↗

PubMed2003

Preferential killing of PTEN-null myelomas by PI3K inhibitors through Akt pathway.

We recently reported that internal deletion of PTEN tumor suppressor gene in OPM2 and Delta47 myeloma lines led to high Akt activation. Re-expression of PTEN induced strong apoptosis and growth inhibition. To understand the biologic importance of the phosphatidylinositol 3 kinase (PI3K)/Akt activation affected by PTEN deletion, we analysed apoptosis and growth inhibition by applying PI3K inhibitors to myeloma lines and by expressing Akt constructs. The PI3K inhibitors preferentially suppressed PTEN-null myeloma growth to those expressing PTEN, indicating that PI3K activation is more critical for growth and survival of those lines with PTEN mutations than others expressing a functional PTEN gene. Since PTEN-null myeloma lines exhibited much stronger Akt activation than PTEN-expressing cells in response to insulin-like growth factor I stimulation, we determined whether Akt could be responsible for PI3K-mediated cell survival and growth of PTEN-null myeloma lines. Expression of an active Akt, but not its kinase dead mutant, reversed wortmannin- and dexamethasone-induced apoptosis and growth inhibition in PTEN-null myeloma lines, suggesting that Akt lies downstream of PI3K for PTEN-null myeloma survival and dexamethasone resistance. In summary, we have provided evidence that PTEN-null myeloma cells are stringently dependent on the PI3K/Akt activation for cell survival. These results may provide a basis to treat myeloma patients with PI3K and Akt inhibitors.

Androstadienes↗

PubMed2003

Acute leukemia: an association with atypical hemolytic uremic syndrome.

A 5-year-old boy was admitted for anemia, thrombocytopenia, and azotemia. Bone marrow examination demonstrated only erythroid hyperplasia, and he was diagnosed with an atypical form of hemolytic uremic syndrome (HUS). He was treated with daily prednisolone, and hematological profiles and renal function normalized 1 month later. However, heavy proteinuria persisted, and renal biopsy findings were consistent with HUS. Four months later, pancytopenia developed with recurrence of azotemia, and a second bone marrow examination revealed acute lymphoblastic leukemia (ALL). The remission of proteinuria with no recurrences of HUS after antileukemic treatment suggests that the HUS was associated with the ALL.

Bone Marrow↗

PubMed2003

Synthesis of radioiodine-labeled 2-phenylethyl 1-thio-beta-D-galactopyranoside for imaging of LacZ gene expression.

A potent inhibitor of beta-galactosidase (EC 3.2.1.23), 2-phenylethyl 1-thio-beta-D-galactopyranoside (PETG), was radioiodinated for noninvasive imaging of LacZ gene expression. In order to introduce radioiodine to the phenyl ring of PETG, 2-(4-bromophenyl)ethanethiol was prepared and attached to the C-1 position of beta-D-galactose pentaacetate under conditions that resulted in the exclusive formation of the beta anomer. The bromo group of PETG was converted to the tributylstannyl group where radioiododemetallation was carried out. Radioiodine-labeled PETG tetraacetate was purified by HPLC, which can be used as a prodrug for biological evaluation or hydrolyzed to 2-(4-[123I/125I]iodophenyl)ethyl 1-thio-beta-D-galactopyranoside ([123I/125I]7) under basic conditions. The resulting radioiodine-labeled PETG was obtained in overall 62% radiochemical yield (decay-corrected) and with specific activity of 46-74 GBq/micromol.

Diagnostic Imaging↗

PubMed2003

ATP6B1 gene mutations associated with distal renal tubular acidosis and deafness in a child.

A large proportion of autosomal recessive distal renal tubular acidosis (RTA) is associated with mutations in the ATP6B1 gene encoding the B1 subunit of H+-ATPase. H+-ATPase is one of the key membrane transporters for net acid excretion in the alpha-intercalated cells of the medullary collecting duct. Sensorineural hearing loss frequently accompanies this type of distal RTA. Mutational analysis of the ATP6B1 gene in a 9-year-old Korean boy with distal RTA and sensorineural hearing loss found 2 heterozygous missense point mutations. Although a single case report, this is the second report documenting ATP6B1 mutations in recessive distal RTA with sensorineural hearing loss after the original report by Karet et al and confirms the novelty of these mutations.

Acidosis, Renal Tubular↗

PubMed2003

Serotonin transporters in the midbrain of Parkinson's disease patients: a study with 123I-beta-CIT SPECT.

UNLABELLED: In Parkinson's disease (PD), both neuropathologic and biochemical studies suggest that serotonin (5-hydroxytryptamine [5-HT]) neurons are affected by the disease process. The integrity of 5-HT transporters was assessed in PD patients with SPECT using 2beta-carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane ((123)I-beta-CIT), which binds with high affinity to both dopamine (DA) and 5-HT transporters. METHODS: Forty-five PD patients at relatively early stages (mean Hoehn-Yahr stage, 2.0 +/- 0.7; range, 1-3) and 7 age-matched healthy control subjects had 15 scans over a 24-h period after injection of (123)I-beta-CIT using a 3-head SPECT system. In the midbrain, the 5-HT transporter parameter k(3)/k(4) was estimated by 3 noninvasive methods: pseudoequilibrium ratio (R(PE)) method, area ratio (R(A)) method, and a modified graphic method that derives the ratio of ligand distribution volumes (R(V)). Striatal V(3)", the DA transporter parameter that is equivalent to k(3)/k(4), was measured using the images acquired at 24 h after tracer injection. All measures were derived using the cerebellum as the reference region. RESULTS: In control subjects, the (123)I-beta-CIT activity in the midbrain reached a peak at 91 +/- 21 min after injection and then washed out at a slow rate (1.1%/h +/- 0.5%/h). The peak specific uptake in the midbrain occurred at 315 +/- 46 min. In PD patients, the temporal patterns of the midbrain and cerebellar activity were not significantly different from those in control subjects. None of midbrain R(PE), R(A), and R(V) was significantly different between control subjects and PD patients, whereas striatal V(3)" was bilaterally reduced in all patients, being 32% lower than that of the control subjects (P = 0.002). In PD patients, none of the midbrain outcome measures was significantly correlated with either striatal V(3)" or motor or nonmotor symptom ratings, including the Hoehn-Yahr stage and the Unified Parkinson's Disease Rating Scale scores. When the studies of 7 PD patients with depression were analyzed separately, none of the midbrain outcome measures in these patients either was different significantly from control values or correlated with the Hamilton Depression Rating Scale score. CONCLUSION: These results suggest that DA and 5-HT transporters are differentially affected in PD, and 5-HT transporters in the midbrain region may not be affected in relatively early stages of PD. Alternatively, 5-HT transporters in the remaining neurons may be upregulated, thus raising the midbrain 5-HT transporter density to almost normal levels.

Adult↗

PubMed2002

Decreased tumor blood flow as measured by positron emission tomography in cancer patients treated with interleukin-1 and carboplatin on a phase I trial.

BACKGROUND: Positron emission tomography (PET) scanning can be used to measure blood flow. When interleukin-1alpha (IL-1) is given in a murine model, it induces acute hemorrhagic necrosis, tumor vascular injury and decreased tumor blood flow, and when given prior to carboplatin, there is enhanced antitumor activity compared to either agent alone. METHODS: In a phase I trial of IL-1 and carboplatin, eligible patients with metastatic disease to the lung had PET scanning performed with (15)O water to assess tumor blood flow before and after IL-1 administration. Doses of IL-1 were 0.03, 0.06, 0.10, 0.15, 0.20 and 0.30 micro g/kg given i.v. over 2 h. At 4 h after IL-1 initiation, carboplatin was administered as a 30-min i.v. infusion at a dose of 400 mg/m(2). Treatment was repeated every 28 days. Other measured parameters included granulocyte kinetics, integrin expression on circulating WBC, and carboplatin pharmacokinetics. Of 16 patients, 11 (8 evaluable) underwent PET scanning before and at 2, 4 and 24 h after IL-1 initiation. RESULTS: Mean measured pretreatment tumor blood flow was 1.82 ml/min per g. At 2, 4 and 24 h it was 1.35, 1.67 and 1.62 ml/min per g respectively. Tumor blood flow was significantly decreased ( P<0.008) at 2 h after IL-1 initiation. In four patients, liver blood flow was measured at the same time-points as tumor blood flow. Liver blood flow was discordant with the tumor blood flow measures, showing no statistically significant change. IL-1 also caused a decreased WBC at 2 h after initiation ( n=14, P=0.025). In addition, polymorphonuclear leukocyte (PMN) and monocyte surface expression of CD11b at 2 h was increased when measured by mean fluorescence intensity flow cytometry (PMN P=0.0269, monocytes P=0.0420). No consistent effect of IL-1 on either carboplatin AUC or platelet nadir was demonstrated. CONCLUSIONS: We conclude that IL-1 has measurable effects on tumor blood flow and causes a significant decrease in blood flow as measured by PET scanning with (15)O water at 2 h after initiation. This decrease is temporally associated with a significant leukopenia and an increased expression of the adhesion integrin CD11b on the circulating cell surface (PMN and monocytes). These results suggest that IL-1 causes decreased tumor blood flow in vivo in human cancer patients, an effect that was temporally related to cytokine-induced peripheral blood cellular changes. Furthermore, our findings suggest that PET scanning may be useful to assess the effect of a systemic antineoplastic agent on tumor blood flow in cancer patients.

Adult↗

PubMed2002

PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells.

Expression of PTEN tumor suppressor gene has been known to dephosphorylate the phosphatidylinositol 3' kinase (PI3K) products on the 3 prime inositol ring, resulting in reduced Akt activation. Loss of PTEN expression in OPM2 and delta47 human myeloma lines led to high Akt activity toward insulin-like growth factor I (IGF-I). In contrast, mouse plasma cell tumor (PCT) lines, expressing wild type PTEN, did not respond to IGF-I for Akt activation. We demonstrated here that endogenous PTEN played a negative role in controlling Akt activity in both mouse PCT and NIH3T3 fibroblast lines by using anti-sense oligonucleotides against PTEN. To determine the role of src-homology 2-containing inositol 5' phosphatase (SHIP) in regulating the PI3K/Akt pathway, we manipulated its expression by down-regulation and overexpression in myeloma, PCT and NIH3T3 lines and analysed Akt activation. Our results showed that SHIP, unlike PTEN, did not affect Akt activity in all systems analysed, despite its ability to dephosphorylate a PI3K product. Although SHIP2 expression resulted in suppression of interleukin-6-mediated mitogen-activated protein kinase activation, expression of SHIP and SHIP2 in a PTEN-null myeloma line did not suppress Akt activity. Biologically, expression of only PTEN, but not SHIP and SHIP2, resulted in growth inhibition and increased apoptosis in OPM2 myeloma line. Together, our results have established the role of PTEN, but not SHIP and SHIP2, in negatively regulating the PI3K/Akt cascade and in myeloma leukemogenesis.

3T3 Cells↗

PubMed2002

Reduction of plasma homocysteine by folic acid in children with chronic renal failure.

Hyperhomocysteinemia is a well-known independent risk factor for cardiovascular disease and is a prevalent abnormality in chronic renal failure. However, studies on this abnormality in children with chronic renal failure, before renal replacement therapy, are scarce. In this study, we measured the plasma homocysteine levels of 27 children (mean age 8.9+/-4.8 years) with predialytic chronic renal failure, and analyzed the effect of folic acid supplementation (1 mg daily for 4 weeks) on the homocysteine levels in 14 of these children. The baseline homocysteine concentration of the patients (12.5+/-6.0 micro mol/l) was higher than that of the control group (5.9+/-1.8 micro mol/l, P<0.001), and correlated positively with age and negatively with folic acid concentration. Folic acid and vitamin B(12) concentrations were not below normal in any patient. The homocysteine concentration was decreased from 13.2+/-6.6 micro mol/l (pretreatment) to 9.3+/-4.2 micro mol/l by folic acid supplementation in the 14 patients. Folic acid supplementation also lowered the prevalence of hyperhomocysteinemia from 64.3% to 42.9%. According to these results, we recommend that folic acid supplementation be started in children with chronic renal failure early in the disease course.

Adolescent↗

PubMed2002

Glucocorticoid diminishes vascular endothelial growth factor and exacerbates proteinuria in rats with mesangial proliferative glomerulonephritis.

Glucocorticoids are widely prescribed for renal diseases. It is believed that glucocorticoids attenuate immune-mediated renal diseases by suppressing the cell-mediated immune system. However, there is evidence that glucocorticoids influence the expression of such growth factors as vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and connective tissue growth factor (CTGF), which are known to influence the development or progression of renal diseases. Therefore, we undertook this study to determine whether glucocorticoids regulate proteinuria or extracellular matrix (ECM) production by altering these growth factors. Mesangial proliferative glomerulonephritis was induced in rats by intravenous injection of monoclonal antibody (OX-7), and dexamethasone (20 mg/kg) was administered intraperitoneally from the third to seventh disease day. Glomerular expression of VEGF, TGF-beta1, and CTGF, the amount of urinary protein, and glomerular ECM were measured on the seventh disease day. The nephritic group showed proteinuria and greater VEGF, TGF-beta1, and ECM production. Dexamethasone aggravated proteinuria (protein, 0.4 +/- 0.1 mg/mg creatinine in the NC group, 6.3 +/- 2.0 mg/mg creatinine in the DC group, and 21.1 +/- 1.9 mg/mg creatinine in the D-Dex group; P < 0.05) and diminished VEGF release (22 +/- 3 pg/mg total protein in the NC group, 292 +/- 26 pg/mg total protein in the DC group, and 198 +/- 23 pg/mg total protein in the D-Dex group; P < 0.05). Expression of TGF-beta1, CTGF, and ECM was not altered significantly by dexamethasone treatment. We found that glucocorticoid diminishes VEGF release and at the same time exacerbates proteinuria in rats with this type of glomerulonephritis.

Animals↗

PubMedDate not supplied

8-cyclopentadienyltricarbonyl 99mtc 8-oxooctanoic acid: a novel radiotracer for evaluation of medium chain fatty acid metabolism in the liver.

8-Cyclopentadienyltricarbonyl 99mTc 8-oxooctanoic acid (99mTc-CpTTOA; 1a) was synthesized for evaluation of medium chain fatty acid metabolism in the liver. 99mTc-CpTTOA was prepared in high radiochemical yield (50-63%) by a double ligand transfer reaction of methyl 8-ferrocenyl-8-oxooctanoate and Na99mTcO4 in the presence of CrCl3 and Cr(CO)6, followed by hydrolysis. This radiotracer was shown to be stable (>90% at 6 h) when incubated with human serum. Aqueous extraction of the radioactivity from the liver and blood samples of mice suggested that 99mTc-CpTTOA was mainly metabolized via beta-oxidation in the liver, and the radioactivity was retained longer in CCl4-treated mice than in control mice, possibly due to impaired beta-oxidation in the former. Planar images of rats injected with 99mTc-CpTTOA showed accumulation of the radioactivity in the liver, kidneys, and bladder with rapid hepatic clearance as a function of time. Analysis of the metabolites from the liver and urine samples of rats further supported that 99mTc-CpTTOA was metabolized to 4-cyclopentadienyltricarbonyl 99mTc 4-oxobutanoic acid (99mTc-CpTTBA; 1c) via beta-oxidation. The results suggested that this radiotracer might be of valuable use in the evaluation of fatty acid metabolism in the liver.

Animals↗

PubMedDate not supplied

The effect of disodium cromoglycate, budesonide, and cyclosporin A on interleukin-4, interleukin-5, and interleukin-13 secretions in Der p I-stimulated T cells from house dust mite-sensitive atopic and nonatopic individuals.

Disodium cromoglycate (DSCG), budesonide, and cyclosporin A (CsA) were the well-known immunomodulators for the allergic and immunologic diseases clinically. In this study, we evaluated the characteristics of inhibition on cytokine synthesis of Der p I-stimulated T cells by the same inhibiting concentrations of DSCG, budesonide, and CsA in house-dust mite antigen (Der p I)-specific atopic and nonatopic healthy individuals. Seven house dust mite allergen specific patients were recruited for this study. Seven healthy volunteers were included on the basis of negative allergic manifestations and low serum immunoglobulin E values. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of recombinant interleukin (rIL)-2 with or without budesonide, DSCG, CsA, and Der p I for 48 hours. Cells were stained with anti-CD4 fluorescein isothiocyanate-conjugated monoclonal antibody, and then anti-human IL-4 phycoerythrin, IL-5, or IL-13 monoclonal antibody, respectively, was added to both blocked and stained samples. Incubation of PBMC from atopics with each immunomodulator and Der p I resulted in the reduction of IL-4 secretion compared with Der p I alone stimulation. However, IL-4 secretion in PBMC from nonatopics was not reduced with DSCG and Der p I stimulation. IL-4, IL-5, and IL-13 secretions of PBMC from atopics were significantly decreased after incubation with each immunomodulator and Der p I, compared with after incubation with Der p I alone. These results might be considered to show either that DSCG has a selective inhibiting effect on cytokine production in T cells from atopics or is a weak inhibitor of cytokine secretions compared with budesonide and CsA at even strength for the inhibition of lymphocyte proliferation in normal, healthy individuals.

Adolescent↗