Multiple nodular adenosis concurrent with primary breast lymphoma: pitfall in PET.
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Adult↗
Biomedical subjects
M Yun
Publications and source records attributed to M Yun.
(18)F-fluorodeoxyglucose positron emission tomography detection of eccrine porocarcinoma.
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Acrospiroma↗
The cerebrovascular response to traditional acupuncture after stroke.
Acupuncture is useful in treating the nausea and vomiting related to chemotherapy, adult postoperative surgery pain and postoperative dental pain. We obtained single-photon emission computed tomography (SPECT) brain perfusion images of six patients with middle cerebral artery occlusion obtained before and after acupuncture and compared the changes in regional cerebral blood flow (rCBF) to those in normal control. Images were obtained before and after acupuncture at six traditional acupoints (LI 4, 10, 11, 15 and 16 and TE5) in the affected arm. The baseline image was subtracted from the postacupuncture image, to produce a subtraction image displaying only voxels with values >2 SD from the mean and those voxels were coregistered to the baseline SPECT or T2-weighted MRI. Similar images were obtained before and after acupuncture of eight normal volunteers. Statistical parametric mapping with a threshold of P =0.001 and a corrected P of 0.05 was performed for group comparison between postacupuncture and baseline SPECT. Focally increased CBF was seen in all patients especially in the hypoperfused zone surrounding the ischaemic lesion, the ipsilateral or contralateral sensorimotor area, or both. Normal subjects showed increased rCBF mainly in the parahippocampal gyrus, premotor area, frontal and temporal areas bilaterally and ipsilateral globus pallidus. Acupuncture stimulation after stroke patients appears to activate perilesional or use-dependent reorganised sites and might be a way of looking at brain reorganisation.
Acupuncture Therapy↗
A structural pathway for activation of the kinesin motor ATPase.
Molecular motors move along actin or microtubules by rapidly hydrolyzing ATP and undergoing changes in filament-binding affinity with steps of the nucleotide hydrolysis cycle. It is generally accepted that motor binding to its filament greatly increases the rate of ATP hydrolysis, but the structural changes in the motor associated with ATPase activation are not known. To identify the conformational changes underlying motor movement on its filament, we solved the crystal structures of three kinesin mutants that decouple nucleotide and microtubule binding by the motor, and block microtubule-activated, but not basal, ATPase activity. Conformational changes in the structures include a disordered loop and helices in the switch I region and a visible switch II loop, which is disordered in wild-type structures. Switch I moved closer to the bound nucleotide in two mutant structures, perturbing water-mediated interactions with the Mg2+. This could weaken Mg2+ binding and accelerate ADP release to activate the motor ATPASE: The structural changes we observe define a signaling pathway within the motor for ATPase activation that is likely to be essential for motor movement on microtubules.
Amino Acid Substitution↗
F-18 FDG uptake in the large arteries: a new observation.
PURPOSE: The cellular components of the atherosclerotic plaque, such as macrophages, exhibits high glucose metabolic activity. The aim of this study was to show the frequency of vascular uptake and possibly to explain the significance of this finding on fluorodeoxyglucose (FDG) positron emission tomographic (PET) scans. METHODS: We evaluated the presence of FDG vascular uptake in 132 consecutive patients undergoing whole-body PET scans and 5 patients who had only lower extremity scans. The presence of vascular FDG uptake was assessed in the abdominal aorta, iliac, and proximal femoral arteries on the 132 whole-body scans, whereas only the femoral and the popliteal arteries were examined on the leg scans. The patients' ages ranged from 20 to 80 years, and they were divided into three age groups: 35 patients were younger than 40 years (group 1; mean age, 32.4 years), 48 patients were 41 to 60 years (group 2; mean age, 50.3 years), and 54 patients were older than 60 years (group 3; mean age, 70.3 years). RESULTS: Fifty percent (69 of 137) of the total population showed vascular FDG uptake in at least one vessel. Thirty-four percent (12 of 35) of group 1, 50% (24 of 48) of group 2, and 61% (33 of 54) of group 3 showed vascular wall uptake (P = 0.017 between groups 1 and 3). In addition, the correlation between the mean age of the age groups and the prevalence of FDG vascular uptake is strong (r = 0.99). CONCLUSIONS: Vascular FDG uptake is present in 50% of the patients examined for this study, with an increased prevalence in older patients. This vascular uptake might be explained by smooth muscle metabolism in the media, subendothelial smooth muscle proliferation from senescence, and the presence of macrophages within the atherosclerotic plaque. The relative contribution of these sources needs further investigation.
Adult↗
A normal variant on Tl-201 and Tc-99m MIBI whole-body imaging: the superior right atrial wall (auricle) and superoanterior right ventricular wall are often seen as mediastinal lesions.
PURPOSE: The authors have often observed on Tl-201 and Tc-99m sestamibi (MIBI) scans in patients with thyroid cancer a small focus of increased uptake in the right midparasternal region (focus A) or sometimes in the lower mid chest at the level of the lower sternum (focus B) just inferomedial to focus A. The objective of this study was to assess the frequency of this finding on Tl-201 MIBI studies, to assess the incidence of true pathologic lesions corresponding to these foci, and to identify their nature. MATERIALS AND METHODS: One hundred ten whole body Tl-201 studies using 4 mCi (148 MBq) and 84 MIBI studies using 20 mCi (740 MBq: first-pass, planar, and SPECT images) were reviewed. The appearance of either focus A or focus B on three orthogonal SPECT images was correlated with an atlas of cross-sectional anatomy and computed tomography. If focus A was seen on the immediate static image (obtained at the end of the first-pass acquisition without moving the patient), this image was coregistered with a selected image from the first-pass study showing the superior vena cava and also with another selected image showing the ascending aorta. RESULTS: Focus A was seen in 40% of Tl-201 scans and in 49% of MIBI scans, whereas focus B was seen in 20% of Tl-201 scans and 39% of MIBI scans. On correlation of the SPECT images with a cross-sectional anatomy atlas, focus A and focus B invariably corresponded to the superior portion of the right auricle and basal superoanterior right ventricular wall, respectively. These myocardial regions are prominent and sometimes appear as discrete foci because they are considerably thicker than other parts of the right atrial and right ventricular muscle, respectively, and because they are seen partly end-on in the anterior projection. CONCLUSIONS: The superior portion of the right auricle and basal superoanterior right ventricular myocardium often appear as isolated foci on whole-body Tl-201 and MIBl scans. Neither focus should be interpreted as a metastatic lesion in patients with possible cancer or as an ectopic parathyroid adenoma in patients with hyperparathyroid disease.
Adolescent↗
Incidental recognition of left subclavian vein obstruction on renal scintigraphy.
In a renal transplant recipient with persistently poor graft function, the flow phase of a renal scan incidentally revealed multiple venous collaterals with focally increased vascular activity near the left lobe of the liver (quadrate lobe). This was initially assumed to represent superior vena cava (SVC) obstruction. A renal biopsy was contemplated to exclude acute rejection because of a nondiagnostic flow phase (loss of a bolus effect). However, because the possibility of venous obstruction at the level of the subclavian and/or brachiocephalic veins (without involving the SVC) also existed, another renal scan was performed, with injection of radiotracer into the contralateral arm. This showed a patent SVC and reasonably preserved renal perfusion consistent with acute tubular necrosis. Subsequently, left subclavian vein obstruction was identified. The graft function improved with conservative management for acute tubular necrosis. These findings illustrate the danger of considering only SVC obstruction when collateral flow patterns and focal hot spots in the liver are present.
Collateral Circulation↗
F-18 FDG positron emission tomography to differentiate diabetic osteoarthropathy from septic arthritis.
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Arthritis, Infectious↗
F-18 FDG uptake in a patient with psoriatic arthritis: imaging correlation with patient symptoms.
The authors describe a patient with psoriatic arthritis in whom an increased level of F-18 fluorodeoxyglucose (F-18 FDG) uptake was seen in the joints of the hands. The areas of increased activity correlated well with the regions of symptoms reported by the patient. This case illustrates the potential use of F-18 FDG positron emission tomography to quantitatively assess the degree of arthritis activity.
Antineoplastic Agents↗
18F-FDG PET in characterizing adrenal lesions detected on CT or MRI.
UNLABELLED: The purpose of this study was to evaluate the ability of (18)F-FDG PET to characterize adrenal lesions in patients with proven or suspected cancers. METHODS: A retrospective analysis was performed on 50 adrenal lesions in 41 patients, whose PET scans were done to evaluate the primary or metastatic disease. CT had shown 50 adrenal lesions in 41 patients and MRI had revealed 13 lesions in 10 patients. There were 34 patients with proven malignancy (28 lung cancer, 3 thyroid cancer, 2 colorectal cancer, and 1 lymphoma) and 7 with lung nodules. Of the 50 lesions, 18 were eventually determined to be malignant either by histopathology (n = 7) or by follow-up (n = 11). The remaining 32 lesions were proven or assumed to be benign by histopathology (n = 4) or clinical follow-up (n = 28). Unlike previously published reports, PET was interpreted as positive if the uptake was equal to or greater than that of the liver. RESULTS: No malignant lesion yielded a negative result on PET. Most lesions (13/18) showed significantly higher FDG uptake than that of the liver. In the remaining 5 lesions (2 metastases from neuroendocrine tumor, 2 early metastases, and 1 necrotic metastasis), FDG uptake was equal to or slightly higher than that of the liver. Of the 32 benign lesions, there were 2 lesions with uptake equal to or slightly higher than that of the liver, 3 with uptake less than the liver but more than the background, and 27 with uptake of the background. MRI identified 3 of the 13 lesions as false-positives but FDG PET correctly identified all 3 as benign. The other 10 adrenal lesions accurately diagnosed by MRI were also characterized by PET. FDG PET for characterization of adrenal lesions showed a sensitivity of 100%, a specificity of 94%, and an accuracy of 96%. CONCLUSION: FDG PET showed excellent diagnostic performance in differentiating adrenal lesions detected on CT or MRI. Because FDG PET has the additional advantage of evaluating the primary lesions as well as metastases, it could be cost-effective and the modality of choice for the characterization of adrenal lesions, especially in patients with malignancy.
Adrenal Gland Diseases↗
Structural basis for the feedback regulation of Escherichia coli pantothenate kinase by coenzyme A.
Pantothenate kinase (PanK) is a key regulatory enzyme in the coenzyme A (CoA) biosynthetic pathway and catalyzes the phosphorylation of pantothenic acid to form phosphopantothenate. CoA is a feedback inhibitor of PanK activity by competitive binding to the ATP site. The structures of the Escherichia coli enzyme, in complex with a nonhydrolyzable analogue of ATP, 5'-adenylimido-diphosphate (AMPPNP), or with CoA, were determined at 2.6 and 2.5 A, respectively. Both structures show that two dimers occupy an asymmetric unit; each subunit has a alpha/beta mononucleotide-binding fold with an extensive antiparallel coiled coil formed by two long helices along the dimerization interface. The two ligands, AMPPNP and CoA, associate with PanK in very different ways, but their phosphate binding sites overlap, explaining the kinetic competition between CoA and ATP. Residues Asp(127), His(177), and Arg(243) are proposed to be involved in catalysis, based on modeling of the pentacoordinate transition state. The more potent inhibition by CoA, compared with the CoA thioesters, is explained by a tight interaction of the CoA thiol group with the side chains of aromatic residues, which is predicted to discriminate against the CoA thioesters. The PanK structure provides the framework for a more detailed understanding of the mechanism of catalysis and feedback regulation of PanK.
Adenosine Triphosphate↗
Structural analysis of glyceraldehyde 3-phosphate dehydrogenase from Escherichia coli: direct evidence of substrate binding and cofactor-induced conformational changes.
The crystal structures of gyceraldehyde 3-phosphate dehydrogenase (GAPDH) from Escherichia coli have been determined in three different enzymatic states, NAD(+)-free, NAD(+)-bound, and hemiacetal intermediate. The NAD(+)-free structure reported here has been determined from monoclinic and tetragonal crystal forms. The conformational changes in GAPDH induced by cofactor binding are limited to the residues that bind the adenine moiety of NAD(+). Glyceraldehyde 3-phosphate (GAP), the substrate of GAPDH, binds to the enzyme with its C3 phosphate in a hydrophilic pocket, called the "new P(i)" site, which is different from the originally proposed binding site for inorganic phosphate. This observed location of the C3 phosphate is consistent with the flip-flop model proposed for the enzyme mechanism [Skarzynski, T., Moody, P. C., and Wonacott, A. J. (1987) J. Mol. Biol. 193, 171-187]. Via incorporation of the new P(i) site in this model, it is now proposed that the C3 phosphate of GAP initially binds at the new P(i) site and then flips to the P(s) site before hydride transfer. A superposition of NAD(+)-bound and hemiacetal intermediate structures reveals an interaction between the hydroxyl oxygen at the hemiacetal C1 of GAP and the nicotinamide ring. This finding suggests that the cofactor NAD(+) may stabilize the transition state oxyanion of the hemiacetal intermediate in support of the flip-flop model for GAP binding.
Animals↗
Refinement of the positive predictive value of gallbladder nonvisualization after morphine administration for acute cholecystitis based on the temporal pattern of common bile duct activity.
UNLABELLED: The authors previously reported two major patterns in the time-activity curve of the common hepatic bile duct (BD) after morphine administration in patients with gallbladder nonvisualization. The first pattern consists of a gradual increase in BD activity (of variable duration) occurring during a simultaneous decrease in liver parenchymal activity (BD increase), representing the physiologic effects of morphine administration. The second pattern consists of a continuous decrease in BD activity that parallels the activity in the liver parenchyma (BD decrease), representing lower or no physiologic effects of morphine administration. The authors hypothesize that gallbladder nonvisualization associated with a continuous decrease in BD activity after morphine administration will have a lower positive predictive value (PPV) for acute cholecystitis than gallbladder nonvisualization associated with an increase in BD activity. METHODS: Thirty-six patients who had morphine-augmented cholescintigraphy were divided into two groups: 19 with BD increase after morphine administration and 17 with BD decrease. RESULTS: Of the 36 patients, 22 had acute cholecystitis. The positive predictive value (PPV) of gallbladder nonvisualization was 61%. All of the remaining 14 had chronic cholecystitis. Of 19 patients with BD increase, 15 had acute cholecystitis (PPV = 79%), whereas only 7 of 17 patients with BD increase (PPV = 41 %) had acute cholecystitis (P = 0.023 by the one-tailed and 0.038 by the two-tailed Fisher exact tests). CONCLUSIONS: Gallbladder nonvisualization after morphine administration with the pattern of BD decrease is not as reliable (intermediate probability in this series) for the diagnosis of acute cholecystitis as is nonvisualization of the gallbladder in patients with a pattern of BD increase (high probability).
Acute Disease↗
Development of a thermo-reversible insulin liquid suppository with bioavailability enhancement.
The purpose of this work is to develop a thermo-reversible insulin liquid suppository, which undergoes a phase transition to bioadhesive gels at body temperature and enhances the bioavailability of insulin. The effects of insulin and sodium salicylate on the physicochemical properties of a liquid suppository composed of poloxamer P 407, P 188 and polycarbophil were investigated. The pharmacodynamic study and quantitative histological assessment of the rectal mucosa of rats were carried out after the dose of insulin-loaded liquid suppositories with different amounts of sodium salicylate into streptozotocin-treated rats. Only thermo-reversible insulin liquid suppository [insulin/P407/P188/polycarbophil/sodium salicylate (100 (IU/g)/15/20/0.2/10%)] showed the optimal physicochemical properties and good safety in rats. It gave significantly lower plasma glucose levels, AUC(0-->4h) (the area below basal glucose level) and C(nadir) (the plasma glucose levels at the nadir) than did the solid and liquid suppositories without sodium salicylate in rats, indicating that the insulin from liquid suppository with sodium salicylate could be well absorbed in rats due to the absorption enhancing effect of sodium salicylate. It is concluded that thermo-reversible insulin liquid suppository [insulin/P 407/P 188/polycarbophil/sodium salicylate (100 (IU/g)/15/20/0.2/10%)], which was easy to administer without any pain during insertion and remained at the administered sites, could have a potential to be developed as a more convenient, safe and effective rectal delivery system of insulin.
Administration, Rectal↗
[Radiofrequency treatment of ethmoidal nerve with allergic rhinitis under nasal endoscopy].
OBJECTIVE: To study the effect of radiofrequency treatment of ethmoidal nerve on allergic rhinitis. METHOD: Eighty-eight cases of allergic rhinitis were treated with ethmoidal nerve radiofrequency under nasal endoscopy. RESULT: It showed marked effectiveness in 73 cases (83.0%), immprovement in 11 cases (12.5%) and failed in 4 cases (4.5%) in one year follow-up. The overall effective rate was 95.5%. CONCLUSION: This result indicated that it is a choice for treating allergic rhinitis to apply ethmoidal nerve radiofrequency under nasal endoscopy.
Adolescent↗
Potent and efficacious thienylamidine-incorporated thrombin inhibitors.
Novel thrombin inhibitors incorporating thienylamidine at the P1 position were designed and synthesized. These compounds are potent, trypsin-selective and efficacious in the rat model of venous thrombosis. The proposed P1 binding mode in the thrombin active site was confirmed by X-ray crystallographic analysis.
Animals↗
Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor.
Systematic variation of the so-called P-pocket moiety of benzamidrazone-based selective thrombin inhibitors led to the discovery of LB30057. It is potent (Ki = 0.38 nM for human thrombin), selective (Ki = 3290 nM for bovine trypsin), and orally bioavailable (58% oral bioavailability in dogs). LB30057 was efficacious in thrombosis animal models.
Animals↗
Structural modification of an orally active thrombin inhibitor, LB30057: replacement of the D-pocket-binding naphthyl moiety.
An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (Ki = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (Ki = 0.045 nM).
Administration, Oral↗