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Biomedical subjects

R S Liu

Publications and source records attributed to R S Liu.

At least 37 records · Page 2Linked to original sources

Diagnosis and localization of testosterone-producing ovarian tumors: imaging or biochemical evaluation.

OBJECTIVE: In the testosterone-secreting ovarian tumor (TSOT), the role of whole-body positron emission tomography (WBPET) with (fluorine-18)-2-deoxyglucose scanning (FDG) and/or [(11)C]acetate is unclear, although it presents a rationale that these functional tumors would be more active and have increased use of glucose and oxygen consumption than normal tissues. CASE: A 52-year-old woman had a history of steroid cell tumors of the right ovary (IIA) and she received staging surgery including total hysterectomy, salpingo-oophorectomy, and lymph node sampling. Reelevated serum levels of T (5.24 ng/ml) were noted 52 months later. The patient received serial preoperative examinations including WBPET with FDG and acetate, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) to evaluate her recurrence. A suspicious mass on the liver was found on ultrasound, CT, and MRI. The ultrasound-guided biopsy was performed three times, and each of them failed to provide any pathological confirmation. Functional imaging studies showed an abnormal uptake in WBPET using [(11)C]acetate but were negative using FDG. Because of the size of the tumor, the patient's hesitatancy toward an operation, and good previous response to gonadotropin-releasing hormone (GnRH) agonist treatment, the patient received a six-cycle GnRH agonist treatment. Serum T levels returned to normal limits after administration of the first dose of GnRH agonist. At follow-up, serum hormone levels were all within the normal ranges consistent with menopause, but the size of the metastatic tumor was constant. The tumor was then completely excised pathologically proven to be a metastatic TSOT. CONCLUSIONS: Recurrent TSOT might be successfully detected using WBPET with [(11)C]acetate. In addition, GnRH agonist could be tried in patients with TSOT if initial responses were excellent and surgical intervention could not be performed.

Carbon Radioisotopes↗

A longitudinal quantitative MRI study of community-based patients with chronic epilepsy and newly diagnosed seizures: methodology and preliminary findings.

Experimental and human data suggest that progressive cerebral damage may result from the cumulative effect of brief recurrent seizures. Longitudinal studies addressing this fundamental question, however, are lacking. We have addressed this need with a large prospective community-based observational study, which aims to rescan 154 patients with chronic active epilepsy and 90 patients with newly diagnosed seizures, after an interval of 3.5 years. Here, we describe the quantitative magnetic resonance methods used to identify subtle volume changes in hippocampal, cerebellar, and neocortical structures over time and report preliminary findings. Using this methodology, we have previously shown that we can reliably detect individual hippocampal volume (HV) and cerebellar volume (CBV) changes greater than 3.1 and 3.0%, respectively (Lemieux et al, 2000). Analysis of the first 53 subjects (24 patients with chronic active epilepsy, 9 patients with newly diagnosed seizures, and 20 controls) has demonstrated significant HV losses in 4 individuals. Automated and semiautomated calculation has detected significant reductions in CBV, total brain volume, and gray matter volume in 2, 3, and 1 subject, respectively. There were no significant white matter volume losses detected. Data collected from rescanning the entire cohorts will help to provide further information on the relationship between recurrent seizures and secondary brain damage.

Adult↗

Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in melanoma-bearing animals.

UNLABELLED: In this study, the effectiveness of a 188Re labeled sulfur colloid with two particle size ranges was used to evaluate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. METHODS: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10-melanoma-bearing BDF(1) mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10(5) B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (n=16 approximately 18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes (<3 microm:80.4 +/-7.2%, colloid 1) and the other receiving larger particle sizes (<3 microm:12.3+/-1.0%, colloid 2). The animals were checked daily until death and their survival recorded. RESULTS: Colloid 2 showed higher accumulation in almost all tissues, the highest accumulation organ was tumor ( approximately 40%), then spleen ( approximately 20%), stomach ( approximately 15%), diaphragm ( approximately 3%), and liver ( approximately 2%). There was a significant increase in survival time with increasing amount of the larger-particle-size colloid. Administered levels of 16-31 MBq/mouse were most efficacious and with higher amounts the survival times decreased significantly below that of the controls. There was a significant difference in the dose-response curves for the two preparations. Protection factors (1/Relative-risk) of nearly 5 were achieved using the larger colloid size, and nearly 30 using the smaller colloid size. An amount of 16-31 MBq of the colloid 2 was the optimal activity in these studies. On the one hand, the survival data agreed well with the biodistribution data, where higher accumulation was found in tumor with colloid 2. CONCLUSION: Rhenium-188 offers on-site availability, medium half-life, higher beta-particle energy of 2.12 MeV for therapy and emission of 155keV gamma photon suitable for imaging. The present study demonstrated that 188Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals.

Animals↗

The role of dopamine transporter imaging agent [99mTc]TRODAT-1 in hemi-parkinsonism rat brain.

This study aims to investigate the relationship between the determination of dopamine level by high performance liquid chromatography (HPLC) with electrochemical detection (ECD) and the detection of dopamine transporter (DAT) counts using autoradiography with DAT image agent [99mTc]TRODAT-1. For striatal lesions, pretreatment of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle shows that autoradiogaphic labeling of striatum region is reduced to near-background level. Using HPLC with ECD, unilateral 6-OHDA treatment is associated with significant (p < 0. 0002) reductions of dopamine levels. For the striatum of the 6-OHDA-lesioned side, dopamine content and DAT counts are reduced to 97% and 90%, respectively. Thus, our observation indicates a potential of using [99mTc]TRODAT-1 for the evaluation of animal DAT.

Animals↗

Photoisomerization by hula-twist: a fundamental supramolecular photochemical reaction.

The volume-conserving hula-twist cis/trans isomerization process has been incorporated in a general scheme for photoisomerization of polyenes, applicable to small organic molecules as well as to protein-bound polyene chromophores. The main theme is that in solution the conventional one-bond-flip mechanism dominates, while in frozen media (or under other forms of supramolecular constraint) the hula-twist mechanism takes over. Literature examples of photoisomerization obtained under confined conditions have been critically reviewed, the applicability of HT has been examined, and new systems unambiguously testing this volume-conserving process are proposed.

Isomerism↗

Clinical significance of oral urease in diagnosis of Helicobacter pylori infection by [13C]urea breath test.

This study was performed to evaluate the effect of oral flora on [13C]urea breath test in detecting H. pylori infection and find an optimal method and timing for sample collection. Forty-five volunteers were included in this study. The [13C]urea breath test was performed using mouthwash, endoscopic administration, and conventional methods. According to the receiver-operating characteristic curves, the earliest optimal time for discriminating H. pylori-positive and H. pylori-negative patients was at 25 min with the mouthwash method with 78% sensitivity and 82% specificity, at 2 min with the endoscopic administration method with 100% sensitivity and 100% specificity, and at 6 min with the conventional method with 100% sensitivity and 95% specificity. The study shows a significant effect of oral urease on the results of the [13C]urea breath test. The timing of sampling collection can be shortened to 6 min with the conventional method or to 2 min through endoscopic administration.

Adult↗

99Tcm-dimercaptosuccinic acid renal scintigraphy for detection of renal cortical defects in acute pyelonephritis: posterior 180 degrees SPECT versus planar image and 360 degrees SPECT.

To evaluate the usefulness of the posterior 180 degrees acquisition technique for renal defects in acute pyelonephritis (APN), a prospective study was conducted using planar imaging, 360 degrees and posterior 180 degrees renal single photon emission computed tomography (SPECT) with 99Tcm-dimercaptosuccinic acid. Sixty subjects with the suspicion of APN were included. The kidneys were divided into three zones: each was graded as positive, equivocal or negative for renal defects. To evaluate inter-observer variation, each study was read in a double-blind fashion by two nuclear physicians. Renal defects were found in 24 patients (31 kidneys and 47 zones) with posterior 180 degrees SPECT, 23 patients (29 kidneys and 44 zones) with 360 degrees SPECT (McNemar's test, P = 0.375 for zones) and 15 patients (16 kidneys and 24 zones) with planar image (P = 0.001 for zones, vs 180 degrees and 360 degrees SPECT). The proportion of positive agreement for posterior 180 degrees and 360 degrees SPECT between readers for the presence of renal defects was 0.81 and 0.62, respectively, whereas the proportion of negative agreement was 0.92 and 0.87, respectively. Both posterior 180 degrees and 360 degrees SPECTs significantly detected more renal defects than planar imaging. The detectability of renal defects in APN by posterior 180 degrees renal SPECT was equal to 360 degrees SPECT but inter-observer agreement was better.

Adolescent↗

Does inadequate exercise lower the accuracy of myocardial perfusion scintigraphy?

The predictive accuracy of exercise myocardial perfusion scintigraphy (EMPS) in detecting coronary artery disease (CAD) in patients who fail to achieve an adequate level of exercise is not clear. This investigation was carried out in order to compare the sensitivity, specificity and accuracy of EMPS in adequate exercise patients with those in inadequate exercise patients. We have retrospectively compared the results of EMPS with coronary angiography (CAG). One hundred and forty-eight patients with both tests within 6 weeks were included. Adequate exercise was defined as > or = 85% maximally predicted heart rate for age. The overall sensitivity and specificity of EMPS to detect CAD were 92.5% (74/80) and 75%, (51/68), respectively. The sensitivity and specificity in adequate exercise patients were 94.1% (32/34) and 67.6% (23/34), whereas those in inadequate exercise patients were 91.3% (42/46) and 82.4% (28/34). The accuracy was 80.9% (55/68) and 87.5% (70/80), respectively. Patients with inadequate exercise had lower sensitivity but higher specificity of EMPS for detecting CAD, and achieved a higher accuracy than those with adequate exercise.

Adult↗

Optimized protocols in terms of equalizing the true and accidental coincidences of each bed position in static multiple bed position carbon-11 PET studies and a target single bed position study.

Quantitative carbon-11 (11C) positron emission tomography (PET) is gaining more attention in oncological applications. In addition, it was discovered that accidental coincidences (randoms) can play an important role in studies such as partial volume effects correction without needing to use anatomical information. However, because of the short half-life of 11C, a homogeneous multiple bed position 11C image is hard to obtain. This study aimed to determine whether innovative pseudogating, optimized pseudogating and optimized double-up methods could match the true counts and randoms to each bed position and to a target single bed position study. A long cylindrical phantom filled with [11C]acetate was scanned by a dedicated PET scanner using six protocols: whole body, frame-duration-compensated whole body, double-up, optimized double-up, pseudogating, and optimized pseudogating. The differences between the protocols are in the initial activity, frame duration and frame number for each bed position. The parameters for pseudogating were determined according to the theory that true counts and randoms are proportional to the radioactivity and its square, respectively. The results show that the stated goals could only be achieved by pseudogating and optimized pseudogating. We conclude that pseudogating or optimized pseudogating must be applied for a critical quantitative study. However, optimized double-up and double-up methods are good alternatives for semi-quantitative and qualitative studies, respectively.

Algorithms↗

The nature of the delocalized cations in azulenic bacteriorhodopsin analogs.

Depending on the size and shape of their azulenic chromophores, azulenic bacteriorhodopsin (bR) pigment analogs can exist as either an initial pigment P1, a more red-shifted final pigment P2 or an equilibrium mixture of both. The absorption spectra of red-shifted bR analogs exhibit characteristic narrow-band shapes similar to charge fully delocalized cyanine-like dyes. Therefore, all such red-shifted pigments are believed to be highly delocalized, bond-equalized carbocations. We have determined structural requirements that facilitate their formation. To describe fully the red-shift potentials of these retinal analogs, we have introduced a new parameter-percent red-shift (PRS). A large PRS value not only reflects the extent of red-shift, but is also suggestive of extensive delocalization of the positive charge. Relevance of these findings in consideration of the possibility of forming stable O-intermediates is presented. The postulated resonance hybrid-like structures for different cations of the positively charged protonated Schiff base chromophores are in fact structurally distinct species, equilibrating in response to local perturbations within the supramolecular protein environment.

Bacteriorhodopsins↗

Preclinical evaluation of locoregional delivery of radiolabeled iododeoxyuridine and thymidylate synthase inhibitor in a hepatoma model.

UNLABELLED: We report improved incorporation of the radiolabeled-thymidine analog [125I/131I]5-iodo-2'-deoxyuridine ([125I/131I]IdUrd) into DNA by the addition of Thymitaq, a thymidylate synthase inhibitor, as a strategy of molecular radiotherapy for hepatoma treatment. METHODS: The synergistic effect of combination [125I]IdUrd and Thymitaq in clonogenic survival and DNA incorporation was shown on the human hepatoma cell line Hep3B. Radiobiodistribution of intrahepatic arterially injected [125I]IdUrd and Thymitaq was studied in a rat N1S1 hepatoma model. In vivo therapeutic effects of locoregional delivery of both drugs were evaluated in mouse subcutaneous hepatoma and ascitic hepatoma models. RESULTS: In a clonogenic assay, Thymitaq showed a synergistic effect with [125I]IdUrd but not cold IdUrd. Thymitaq had a dose-dependent modulation effect on DNA-[125I]IdUrd incorporation. The biodistribution study indicated a slower clearance rate of [125I]IdUdR in the hepatoma as well as an initially higher uptake of [125I]IdUrd into DNA when the [125I]IdUrd was combined with Thymitaq. In vivo studies showed a superior therapeutic effect of combination Thymitaq and [125I]IdUrd in both subcutaneous and ascites tumor models, but the combination of [131I]IdUrd and [125I]IdUrd may be more effective than Auger electron emitters alone for the treatment of subcutaneous tumor. CONCLUSION: The strategy of locoregional delivery of [125I/131I]IdUrd to a tumor site through an intrahepatic arterial, intratumoral, or intraperitoneal route in combination with Thymitaq is promising and may also have a favorable therapeutic index in vivo.

Animals↗

Evaluation of early-stage Parkinson's disease with 99mTc-TRODAT-1 imaging.

UNLABELLED: Parkinson's disease is a progressive neurodegenerative disorder characterized by a selective loss of dopamine in the striatum. Problems remain in the accurate diagnosis of Parkinson's disease. A 99mTc-labeled tropane derivative that binds to dopamine transporter with high selectivity is [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)] (TRODAT-1). The purpose of this study was to investigate the potential usefulness of 99mTc-TRODAT-1 imaging in the evaluation of patients with early-stage Parkinson's disease. METHODS: Thirty-four patients with early-stage idiopathic Parkinson's disease were recruited. For all patients, the Parkinson's disease was stage 2 or less as assessed by the Hoehn and Yahr scale. Seventeen age-matched healthy volunteers (8 men, 9 women) served as controls. 99mTc-TRODAT-1 was prepared from a lyophilized kit. Brain SPECT imaging was performed between 165 and 195 min after injection, using a double-head camera equipped with fanbeam collimators. Specific uptake in the striatum and its subregions, including the putamen and caudate nucleus, was calculated and compared with that of the other sides and of healthy volunteers. RESULTS: A continuous reduction in specific striatal uptake of 99mTc-TRODAT-1 with increasing disease severity was found in Parkinson's disease patients (control vs. stage I vs. stage II, 1.98 vs. 1.62 vs. 1.22, respectively, P < 0.01). The changes were magnified by measurement of specific putaminal uptake (control vs. stage I vs. stage II, 1.81 vs. 1.27 vs. 0.94, respectively, P < 0.01). The mean values of specific putaminal uptake contralateral to the more affected limbs were significantly decreased compared with the ipsilateral sides in both stage I and stage II groups (1.02 vs. 1.49 for stage I and 0.73 vs. 1.14 for stage II, P < 0.01). Moreover, a significant loss of putaminal uptake ipsilateral to the symptoms was found in the stage I group compared with the healthy volunteers (1.49 vs. 1.81, P < 0.01). The difference became greater when the posterior putaminal uptakes were compared. No remarkable adverse reactions were found in either healthy volunteers or Parkinson's disease patients during or after imaging. CONCLUSION: For clinical practice, 99mTc-TRODAT-1 may serve as a useful imaging agent for the early detection of Parkinson's disease.

Aged↗

The case of medium-dependent dual mechanisms for photoisomerization: one-bond-flip and hula-twist.

This paper critically reviews examples in the literature of photochemical cis-trans isomerization paying particular attention to the medium effect and accompanied conformational changes. A case is made that the Hula-Twist mechanism, postulated in 1985 as a photochemical reaction pathway for a polyene chromophore imbedded in a protein binding cavity such as those of rhodopsin and bacteriorhodopsin, is also a dominant reaction pathway for a diene, or a longer polyene confined in a rigid (relative to isomerization rate) medium. The conventional one-bond-flip process is the preferred reaction pathway in a fluid medium. While defining experiments are proposed, this dual mechanistic approach successfully accounts for all examples in the literature on photoisomerization reactions whether involving conformational changes or not.

Isomerism↗

Total synthesis of (+)-blastmycinone, (-)-litsenolide C1, and related natural trisubstituted lactones via alkynyltungsten compounds.

A general method for total synthesis of natural trisubstituted gamma-lactones is developed on the basis of the chemistry of alkynyltungsten compounds. The key step in this approach involves the cycloalkenation of tungsten-eta1-(3R,4S)-pent-1-yne-3,4-diol with aldehydes to give tungsten-oxacarbenium salts, further leading to 3-alkylidene-4-hydroxy-5-methyl-gamma-lactones upon demetalation. This synthetic sequence proceeds well for alkynylaldehydes and the MOM derivative of tungsten-eta1-(3R,4S)-pent-1-yne-3,4-diol. The resulting butyrolactone products are transformed into natural trisubstituted butyrolactones including (+)-blastmycinone, (+)-blastmycinolactol, (+)-antimycinone, NFX-2, and (+)-isodihydromahubanolide A. By using the same approach based on (R)-ethyl lactate, the natural (-)-litsenolide C1 can be prepared in a few steps.

4-Butyrolactone↗