PubMed Health⌕ Search

Biomedical subjects

S Yee

Publications and source records attributed to S Yee.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of a stereotactic frame for repositioning of the rat brain in serial positron emission tomography imaging studies.

For serial imaging studies of the rat brain with positron emission tomography (PET), reproducible positioning of the head can facilitate spatial alignment of images and quantitative analysis. To achieve this aim, we constructed a plastic head frame and tested the positioning reproducibility on a high-resolution small-animal PET scanner, microPET. Two sets of ear bars, with tapers of either 18 degrees (sharp) or 45 degrees (blunt), were evaluated for their relative precision in securing the animal to the frame. For sequential positioning of an animal, average distances from the mean position of 0.51 mm (SD 0.41 mm) and 0.91 mm (SD 0.48 mm) were measured with the sharp and blunt ear bars, respectively. These results show that a rat brain can be reproducibly positioned using the frame, with a variation of position less than the spatial resolution of modern animal PET scanners. Brain regions of interest defined on one scan and copied across subsequent scans of a frame-repositioned animal resulted in an average coefficient of variation of 5.4% (SD 2.7%) using the sharp ear bars and 6.8% (SD 2.5%) using the blunt ear bars. This methodology has the potential to improve quantitative assessment for serial PET studies.

Animals↗
PubMed2000

Isolation of a novel protein tyrosine phosphatase inhibitor, 2-methyl-fervenulone, and its precursors from Streptomyces.

High-throughput screening identified an extract from Streptomyces sp. IM 2096 with inhibitory activity toward several protein tyrosine phosphatases (PTPs). Four 1,2,4-triazine compounds 2096A-D (1-4) were isolated from this extract and their structures elucidated by interpretation of spectroscopic data and confirmed by degradation and synthesis. The novel glycocyamidine derivatives 1 and 2 are diastereomers and may interconvert. Both are inactive in the PTP inhibition assay. Compounds 1 and 2 are unstable and partially decompose to 3 and glycocyamidine (5) at room temperature. Compound 3, known as MSD-92 or 2-methyl-fervenulone, is a broad-specificity PTP inhibitor with comparable potency to vanadate. The imidazo[4, 5-e]-1,2,4-triazine (4), inactive in the PTP-inhibition assay, may be a degradation product of 3.

Enzyme Inhibitors↗
PubMed2000

The expression of Myf5 in the developing mouse embryo is controlled by discrete and dispersed enhancers specific for particular populations of skeletal muscle precursors.

The development of skeletal muscle in vertebrate embryos is controlled by a transcriptional cascade that includes the four myogenic regulatory factors Myf5, Myogenin, MRF4 and MyoD. In the mouse embryo, Myf5 is the first of these factors to be expressed and mutational analyses suggest that this protein acts early in the process of commitment to the skeletal muscle fate. We have therefore analysed the regulation of Myf5 gene expression using transgenic technology and find that its control is markedly different from that of the other two myogenic regulatory factor genes previously analysed, Myogenin and MyoD. We show that Myf5 is regulated through a number of distinct and discrete enhancers, dispersed throughout 14 kb spanning the MRF4/Myf5 locus, each of which drives reporter gene expression in a particular subset of skeletal muscle precursors. This region includes four separate enhancers controlling expression in the epaxial muscle precursors of the body, some hypaxial precursors of the body, some facial muscles and the central nervous system. These elements separately or together are unable to drive expression in the cells that migrate to the limb buds and in some other muscle subsets and to correctly maintain expression at late times. We suggest that this complex mechanism of control has evolved because different inductive signals operate in each population of muscle precursors and thus distinct enhancers, and cognate transcription factors, are required to interpret them.

Animals↗
PubMed1999

Oxidative stress, brain white matter damage and intrauterine asphyxia in fetal lambs.

In order to examine the role of oxidative stress in asphyxia-induced perinatal brain damage, near-term fetal lambs were subjected to umbilical cord occlusion for approximately 60min until fetal arterial pH diminished to less than 6.9 and base excess to less than -20 meq/l. The levels of superoxide, hydrogen peroxide, glutathione (GSH) and thiobarbiturate-reactive substances (TBARS) within brain grey and white matter were determined at 72h to correlate with morphological changes. Although the topography and extent of brain damage varied somewhat from case to case, ranging from focal infarction in grey or white matter to subtle and patchy alterations of white matter, the telencephalic white matter appeared to bear the brunt of damage as compared to other regions. The parietal white matter, in particular was often the seat of early pathological changes that could be seen in isolation. These white matter changes were accompanied by significant increases in hydrogen peroxide and TBARS levels as compared to those in grey matter. In another set of experiments, 8 different brain regions were assayed for TBARS, GSH and superoxide dismutase (SOD). A highly significant rise in the levels of TBARS was again noted in the parietal and frontal white matter. SOD levels were higher in the frontal and parietal white matter, basal ganglia and cerebellum. Cerebral cortical and hippocampal neurons were relatively unaffected until accompanied by more severe damage to grey and white matter at other sites. These results suggest that the developing telencephalic white matter appears to be most vulnerable to the effects of intrauterine fetal asphyxia and that oxidative stress may be a major contributing factor in the pathogenesis of perinatal hypoxic-ischemic encephalopathy.

Animals↗
PubMed1998

Proton resonance assignments and ligand exchange kinetics in high-spin and mixed-spin myoglobin complexes using two-dimensional exchange spectroscopy.

The task of assigning resonances in proton nuclear magnetic resonance spectra of paramagnetic heme proteins can be an arduous process, but with the development of multi-dimensional NMR methods the situation has improved. It is demonstrated here that two-dimensional exchange spectroscopic experiments can be used to obtain to assignment correlations for the heme protons of methydroxy-, metthiocyano-, metaquo-, and metimidazole-myoglobin forms. All the assignments are unambiguous and straightforward when the temperature and mixing times are adjusted to minimize nuclear Overhauser cross-peaks from each complex. Moreover, saturation transfer experiments allow the study of ligand binding kinetics. The exchange rates between metaquo- and metimidazole- (or methyl substituted imidazole) myoglobin complexes are estimated. The differences between the exchange rates reflect differences in the hydrophobic and steric interactions between the ligands and the protein moiety.

Animals↗
PubMed1998

Functional oral-motor skills: Do they change with age?

Dysphagia, a difficulty eating or drinking, appears to increase with age and is a concern for our growing elderly population. Mastication, tongue mobility, and lip closure are skills of the oral phase of ingestion, and have been shown to deteriorate with age. However, it is not clear whether these changes affect functional feeding. It is also unclear whether dysphagia is the result of the aging process itself, or whether it is secondary to disease. Therefore, the purpose of this study was to identify changes during the oral phase of ingestion in a group of healthy seniors. Functional feeding skills and oral praxis abilities were measured in 79 healthy adults aged 60-97 years. The Modified Functional Feeding Assessment (FFAm) subscale of the Multidisciplinary Feeding Profile (MFP) and the Oral Praxis Subtest (OPS) of the Southern California Sensory Integration Test were administered respectively. An interview followed to obtain information on denture wear, use of hearing aids and glasses, and types of foods avoided. Seniors maintained functional feeding skills throughout the four decades studied. These skills were not age-dependent, but depended on whether or not subjects wore full dentures. Even though all of the seniors maintained functional feeding skills, more seniors in the younger group (7th decade 60%, 8th decade 67%) had difficulty with a variety of food textures such as soft, hard, fibrous, and some with tough skins, than the older group (9th decade 40%, 10th decade 44%). Oral praxis abilities were correlated significantly with age, but not with hearing aid use. Overall, healthy seniors maintained their functional feeding and oral praxis skills. Good health and natural dentition appear to be excellent indicators for functional feeding ability.

Aged↗
PubMed1998

A Comparison of Oral Ondansetron and Intravenous Granisetron for the Prevention of Nausea and Emesis Associated with Cisplatin-Based Chemotherapy.

PURPOSE: To compare the efficacy and safety of oral ondansetron with i.v. granisetron each given as a single dose prior to administration of highly emetogenic cisplatin chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed malignancies were randomized to receive a single 24 mg ondansetron hydrochloride tablet plus a 50 ml i.v. infusion of normal saline, or a single 10 µg/kg (50 ml) i.v. infusion of granisetron plus a placebo tablet in this multicenter, double-blind, parallel-group trial. Study drug was administered 30 min prior to a single i.v. infusion of cisplatin (50-75 mg/m&sup2;), given over a period of </= 3 h. Concurrent administration of corticosteroids was not allowed. Efficacy measurements included the number of emetic episodes, need for rescue medication, and patient assessments of nausea and appetite. Complete response (CR) was defined as no emetic episodes, rescue, or withdrawal; major response was defined as one or two episodes. Safety was evaluated by monitoring adverse events and changes in laboratory parameters. RESULTS: A total of 371 patients entered the study and received study drug, of whom 184 received ondansetron and 187 received granisetron. For all parameters tested, a single 24 mg oral ondansetron tablet was at least as effective as i.v. granisetron. CR was achieved in 58% of ondansetron-treated patients and 51% of granisetron-treated patients (95% confidence interval on the difference: -4% to 17%). Subjective assessments revealed no difference with regard to complete control of nausea, appetite, or satisfaction with antiemetic therapy. Both drugs were well tolerated; the most common adverse event was headache. CONCLUSION: A single 24 mg oral dose of ondansetron is at least as safe and effective as a single i.v. infusion of 10 µg/kg of granisetron in preventing nausea and vomiting induced by highly emetogenic cisplatin chemotherapy.

Journal Article↗
PubMed1997

In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man--fact or myth.

PURPOSE: To evaluate and optimize the use of Caco-2 cell monolayers to predict the in vivo absorption of a broad range of compounds in man. METHODS: Caco-2 cells are derived from human adenocarcinoma colon cells and spontaneously differentiate when grown on porous polyethylene terephthalate membranes (PETP) in a 12 well format to form monolayers of polarized cells possessing function similar to intestinal enterocytes. Transport experiments were conducted using 21 day cultured cells in a shaking water bath at 37 degrees C. Radiolabeled mannitol was used to determine monolayer integrity. Apparent permeability coefficient (Papp) was calculated from the appearance of drug in the receiver side. RESULTS: A strong correlation was observed between in vivo human absorption and in vitro Papp for a variety of compounds (R = 0.95, N = 35). For compounds that are substrates of p-glycoprotein (Pgp), use of a Pgp inhibitor resulted in a better estimate of absorption in humans. The results of this study suggest that the overall ranking of compounds with Papp < 1 x 10(-6) cm/sec, between 1-10 x 10(-5) cm/ sec, and > 10 x 10(-6) cm/sec can be classified as poorly (0-20%), moderately (20-70%) and well (70-100%) absorbed compounds, respectively. CONCLUSIONS: These data suggest that Caco-2 cells developed under the culturing and transport conditions defined herein can be used to predict in vivo human absorption of compounds regardless of transport mechanism, viz., transcellular, paracellular and carrier-mediated.

Biological Transport↗
PubMed1996

The effects of glutathione glycoside in methyl mercury poisoning.

The use of glutathione glycoside (GSH-glyc), a compound newly synthesized in our laboratory, was highly effective in raising cellular GSH levels both in vitro and in vivo. Based on mass spectrometry and 1H NMR data, the structure of GSH-glyc was determined to be that of an S-glycoside. Rapid GSH uptake was observed by confocal microscopy in both A549 cells and mouse astrocytes following incubation with GSH-glyc. Intraperitoneal (i.p.) and per oral administration of GSH-glyc in C57BL/6J mice raised GSH concentrations in brain and liver to significantly higher levels than normal. Methyl mercury (MeHg) poisoning of mice with multiple doses of methylmercuric chloride (MMC) induced severe toxic effects associated with marked depletion of brain and liver GSH progressing to death in all animals, whereas the animals primed with GSH-glyc and given MMC and GSH-glyc concurrently were devoid of toxic signs. We suggest, on the basis of D-[3H]glucose and [2- 3H]deoxyglucose uptake studies, that the transport of GSH-glyc across the blood-brain barrier may occur through one of the glucose transport pathways. Although the precise mechanism by which GSH-glyc protects against MeHg poisoning is not clear, it is probable that any one of a number of factors, including conjugation of MeHg, scavenging of free radicals, restoration of reactive thiol groups, and enhancement of MeHg efflux, may have been instrumental. GSH-glyc is a nontoxic compound that can be used to transport GSH into cells, including those of brain and liver, and may prove to be useful for prophylaxis and therapy of tissue injury induced by various neurotoxic compounds, particularly when the capacity to synthesize or regenerate GSH has been compromised.

Animals↗
PubMed1996

Oxidative stress in neurotoxic effects of methylmercury poisoning.

The effects of methylmercuric chloride (MMC) on the rate of oxygen uptake were determined in purified cultures of oligodendrocytes, astrocytes, and cerebral cortical and cerebellar granular neurons obtained from embryonic and neonatal rat brains. Rapid and profound inhibition of oxygen uptake took place in all cell types following MMC exposure. However, the sensitivity of cellular respiration to the toxic effects of MMC appeared to parallel the normal oxygen demands of the cell type. To assess the effects of MMC on mitochondrial electron transport chain (ETC) activity, complex-specific electron donating substrates were used to stimulate the mitochondria obtained from both control and MMC-injected rat brains. Significant increases in reactive oxygen species (ROS) and thiobarbituric acid-reactive substances (TBARS), and a reduction in glutathione levels were observed in the MMC group following stimulation of complex III, but not with stimulation of either complex I or II, suggesting that MMC induces alterations in electron transport in the ubiquinol: cytochrome c oxidoreductase region. The rapidity of oxygen uptake inhibition by MMC in cultured CNS cells and the demonstration of MMC effects on specific enzyme complexes in the mitochondrial ETC strongly support the contention that mitochondria may be the earliest target of MeHg neurotoxicity, and that the mitochondrial ETC is the most likely site where excess ROS are generated in the brain to induce oxidative stress in MeHg poisoning.

Animals↗
PubMed1995

Variable-temperature study of the heme-reorientation process in equine myoglobin.

The redistribution of the initially-formed myoglobin heme-insertion isomers from the initially formed 50/50 mixture to the equilibrium ratio of 90/10 has long been assumed to occur by one of two mechanisms, both of which require the rupture of the heme iron-protein bond (La Mar, G.N., Toi, H. and Krishnamoorthi, K. (1984) J. Am. Chem. Soc. 106, 6395-6401). In this study we compared the use of nuclear magnetic resonance and optical spectroscopic techniques as methods for studying the reorientation of heme within myoglobin. We found that kinetics determinations of the heme insertion isomer redistribution process in Mb by optical spectroscopy are quantitatively compatible with the results obtained by nuclear magnetic resonance spectroscopy. A variable-temperature analysis for horse myoglobin using the optical method at pH 8.4 +/- 0.1 yielded the following activation energy parameters: delta H++ = 31 kcal/mol, delta S++ = 34 cal/mol per K, and delta G++21 degrees C = 21 kcal/mol. The value of delta G++ expected for complete dissociation of the heme from myoglobin can be estimated, from its dissociation constant and insertion rate, to be on the order of 23-27 kcal/mol under the same conditions as our determination. Therefore, although the mechanism for heme reorientation in Mb is likely non-dissociative, it has an activation energy which is not far from the lower bound expected for a complete-dissociation/recombination mechanism. Our measured entropy of activation is not especially large, perhaps owing to a large contribution by the solvent.

Animals↗
PubMed1994

Infection after insertion of alloplastic orbital floor implants.

Ten patients developed infections after alloplastic implantation (nine silicone, one gelatin film [Gelfilm] implant) for orbital floor fracture repair. Infection resulted from the following: (1) dental surgery, (2) upper respiratory infection, (3) inferior extrusion of a retained implant into the maxillary sinus with a fistulous tract into the inferior conjunctival fornix, (4) rhinoplasty, (5) snorting cocaine and other drugs, (6) postoperative infection after orbital floor repair, and (7) medial implant migration resulting in chronic dacryocystitis. In all ten patients, implants were removed because of orbital abscess, recurrent infection, or chronic low-grade infections. Microbiologic culture of removed implants disclosed Staphylococcus aureus, S. epidermidis, Serratia marcescens, and Pseudomonas aeruginosa as the offending organisms. The main complication of infection included severe cicatricial ectropion of the lower eyelid in three patients. The final globe position was not adversely affected by implant removal performed from five months to 20 years after insertion. Guidelines for prevention and management of orbital implant infections based on these ten patients are presented.

Adolescent↗
PubMed1994

Inhibition of cisplatin toxicity without decreasing antitumor efficacy. Use of a dithiocarbamate.

OBJECTIVE: To demonstrate whether a dithiocarbamate derivative, N-methyl-D-glucaminedithiocarbamate, could prevent anorexia and weight loss and enhance survival without decreasing the antitumor efficacy of high-dose cisplatin therapy. DESIGN: One hundred forty-two mice were randomized into groups receiving cisplatin, 5 mg/kg per day, 7.5 mg/kg per day, or 10 mg/kg per day for three days with or without N-methyl-D-glucaminedithiocarbamate, 1000 mg/kg per day. Weight loss and morbidity were examined between groups. Antitumor efficacy of cisplatin combined with N-methyl-D-glucaminedithiocarbamate was examined using a subcutaneous melanoma model. SETTING: Institutional laboratory. MAIN OUTCOME MEASURES: N-methyl-D-glucaminedithiocarbamate intervention would decrease morbidity, weight loss, and increase survival without decreasing the antitumor efficacy of cisplatin. RESULTS: Weight loss and morbidity were significantly reduced when N-methyl-D-glucaminedithiocarbamate was coadministered with cisplatin (P < .05) at all doses of cisplatin. The antitumor efficacy of high-dose cisplatin therapy (7.5 mg/kg per day and 10 mg/kg per day) was not significantly decreased (P > .05) at all doses of cisplatin. CONCLUSION: As N-methyl-D-glucaminedithiocarbamate seems to limit morbidity and mortality of high-dose cisplatin administration without decreasing its antitumor efficacy, this drug deserves further investigation in the treatment of cancer.

Animals↗
PubMed1994

Methylmercury poisoning induces oxidative stress in the mouse brain.

C57BL/6J mice were intoxicated by injection of 2.5 mg/kg body wt of methylmercuric chloride (MMC) daily for 3, 7, and 14 days, and the relative concentrations of superoxide and hydrogen peroxide and the specific activity of superoxide dismutase (SOD) were determined in various cellular fractions of the brain. High brain levels of Hg were associated with significantly increased amounts of superoxide and hydrogen peroxide by Days 3, 7, and 14 and with markedly reduced SOD activity by Days 7 and 14. Such a rise in the levels of reactive oxygen species indicates the induction of oxidative stress within brain tissue. This suggests that suppression of antioxidant activity, including that of SOD and glutathione, together with disturbances in the mitochondrial electron transport chain, may contribute to the induction of oxidative stress in the mouse brain following MMC poisoning.

Animals↗
PubMed1994

Repeated haloperidol increases both calmodulin and a calmodulin-binding protein in rat striatum.

Repeated treatment with the antipsychotic drug, haloperidol, leads to an increased behavioral sensitivity to dopamine agonists exhibited upon withdrawal from the drug. An increase in the particulate content of the endogenous Ca(2+)-binding protein, calmodulin, has been demonstrated after repeated treatment of rats with haloperidol. In this study, the anatomical specificity of the effect of repeated haloperidol treatment on the content and subcellular localization of calmodulin was investigated. Responsivity of calmodulin localization to dopaminergic input following drug treatment was assessed by determining the subcellular localization of calmodulin following an in vivo amphetamine challenge before sacrifice. Male, Sprague-Dawley rats were treated with 0.5 mg/kg haloperidol (s.c.) for 3 weeks and withdrawn from the drug for 4 days. Repeated haloperidol increased calmodulin content only in the striatum but altered the subcellular distribution of calmodulin in rat limbic forebrain and frontal cortex. In the latter areas, the soluble calmodulin was increased while the particulate calmodulin was decreased. There was no change in calmodulin in either hippocampus or cerebellum in response to drug treatment. Challenge with the dopamine mimetic, amphetamine, before sacrifice was effective in redistributing calmodulin only in striatum from rats that had been treated repeatedly with haloperidol, demonstrating an increased sensitivity of the translocation process. In order to determine whether a change in a calmodulin-binding protein would accompany the drug-induced increase in calmodulin, striatal calmodulin-binding proteins were examined using a biotinylated calmodulin overlay technique. Repeated haloperidol treatment enhanced calmodulin binding to a 150 kDa protein in striatal membranes. The 150 kDa protein exhibited the same gel mobility and subcellular distribution as myosin light chain kinase immunoreactivity. There was an increase in myosin light chain kinase immunoreactivity in striatal membranes after repeated haloperidol that was apparent in animals withdrawn either 4 or 10 days from haloperidol treatment. Therefore, repeated haloperidol could increase the rat striatal content of calmodulin and potentially that of the calmodulin-binding protein, myosin light chain kinase. Increases in striatal calmodulin and myosin light chain kinase may signal a greatly enhanced sensitivity of actin-myosin interactions after repeated haloperidol that could contribute to haloperidol-induced neurochemical or morphological changes involved in drug-induced synaptic plasticity.

Amphetamine↗
PubMed1994

Sinusitis in bone marrow transplantation.

Bone marrow transplantation has become a beneficial and curative technique used in treatment of patients with different hematologic conditions. It has become widely used at our institution for hematologic malignancies and certain resistant solid tumors. However, this treatment can result in immunosuppression, with an increased chance of infection. The purpose of this study was to review the causes of infections and determine the number of patients diagnosed with sinusitis. In the retrospective study, we evaluated the cases of bone marrow transplant patients for incidence and cause of fever. Sixty-eight percent of patients had fever after transplant; of these, 59% had fever of unknown origin. Only 1% of the patients with fever were diagnosed with sinusitis. In the evaluation of fever, sinusitis was not usually suspected and therefore was not included in the differential diagnosis. With such a high percentage of fever of unknown origin in this growing patient population, appropriate pretreatment evaluation of each case to rule out sinusitis should be considered.

Bone Marrow Transplantation↗