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Biomedical subjects

Bruce Y Lee

Publications and source records attributed to Bruce Y Lee.

15 recordsLinked to original sources
PubMed2006

Defective carbohydrate metabolism in mice homozygous for the tubby mutation.

Tub is a member of a small gene family, the tubby-like proteins (TULPs), with predominant expression in neurons. Mice carrying a mutation in Tub develop retinal and cochlear degeneration as well as late-onset obesity with insulin resistance. During behavioral and metabolic testing, we found that homozygous C57BL/6J-Tub(tub) mice have a lower respiratory quotient than C57BL/6J controls before the onset of obesity, indicating that tubby homozygotes fail to activate carbohydrate metabolism and instead rely on fat metabolism for energy needs. In concordance with this, tubby mice show higher excretion of ketone bodies and accumulation of glycogen in the liver. Quantitation of liver mRNA levels shows that, during the transition from light to dark period, tubby mice fail to induce glucose-6-phosphate dehydrogenase (G6pdh), the rate-limiting enzyme in the pentose phosphate pathway that normally supplies NADPH for de novo fatty acid synthesis and glutathione reduction. Reduced G6PDH protein levels and enzymatic activity in tubby mice lead accordingly to lower levels of NADPH and reduced glutathione (GSH), respectively. mRNA levels for the lipolytic enzymes acetyl-CoA synthetase and carnitine palmitoyltransferase are increased during the dark cycle and decreased during the light period, and several citric acid cycle genes are dysregulated in tubby mice. Examination of hypothalamic gene expression showed high levels of preproorexin mRNA leading to accumulation of orexin peptide in the lateral hypothalamus. We hypothesize that abnormal hypothalamic orexin expression leads to changes in liver carbohydrate metabolism and may contribute to the moderate obesity observed in tubby mice.

Acetate-CoA Ligase↗
PubMed2006

The impact of a concurrent trauma alert evaluation on time to head computed tomography in patients with suspected stroke.

BACKGROUND: Emergency department (ED) overcrowding threatens quality of care by delaying the time to diagnosis and treatment of patients with time-sensitive diseases, such as acute stroke. OBJECTIVE: The authors hypothesized that the presence of a trauma alert evaluation would impede the time to head computed tomography (hCT) in patients with stroke-like symptoms. METHODS: This was a secondary analysis of prospectively collected data on patients with potential stroke who received an hCT in an urban trauma center ED from January 1, 2004, to November 30, 2004. Structured data collection included historical and examination items, National Institutes of Health (NIH) stroke scale score, laboratory and radiographic results, and final diagnosis. Admitted patients were followed in hospital. Patients who presented within one hour following a trauma evaluation were compared with patients who presented without concurrent trauma for triage time until completion of hCT. Chi-square, t-tests, and 95% confidence intervals (95% CIs) were used for comparisons. RESULTS: The 171 patients enrolled had a mean (+/- standard deviation) age of 60.7 (+/- 7) years; 60% were female; and 58% were African American. Of these, 72 patients had a significant cerebrovascular event (38 [22%] ischemic stroke, 25 [15%] transient ischemic attack, seven [4%] intracranial hemorrhage, one [0.6%] subarachnoid hemorrhage, and one [0.6%] subdural hematoma). The remaining diagnoses included 4.6% migraine, 2.3% seizure, 2.9% syncope, 2.3% Bell's palsy, and 2.9% vertigo. There was no significant difference in time to hCT in patients who presented during a trauma activation and those who did not (99 minutes [interquartile range (IQR) = 24-156] vs. 101 minutes [IQR = 43-151.5]; p = 0.537). In subgroup analysis of patients with a significant cerebrovascular event, times to hCT were also similar (24 minutes [IQR = 12-99] vs. 61 minutes [IQR = 15-126]; p = 0.26). CONCLUSIONS: In the authors' institution, the presence of concurrent trauma evaluation does not delay CT imaging of patients with potential stroke.

Adult↗
PubMed2005

Cerebral blood flow effects of pain and acupuncture: a preliminary single-photon emission computed tomography imaging study.

BACKGROUND: The purpose of this study was to investigate the cerebral blood flow changes associated with the analgesic effect of acupuncture in patients with chronic pain. METHODS: Seven patients presenting with a chronic pain syndrome and 5 healthy controls were included. All single-photon emission computed tomography (SPECT) scans were acquired with a uniform protocol. The patient group was injected with the radioisotope hexamethyl propyleneamine oxime (HMPAO) while experiencing their usual level of pain. A baseline scan was acquired approximately 20 minutes after administration of the HMPAO. The patient then underwent acupuncture therapy with needles placed in points specifically selected to relieve pain. When the pain improved, as determined by a 10-digit score for pain assessment, the patient was reinjected with HMPAO and imaged 20 minutes later for the acupuncture scan. The reference group also had a baseline and acupuncture scan, although the acupuncture itself was performed using a standardized set of needle points. RESULTS: The reference group participants were found to have significant increases in the thalamic and prefrontal cortex activity on the acupuncture scan compared to the baseline. The baseline scans of the pain patients showed significant asymmetric uptake in the thalami compared to controls. This asymmetry reversed or normalized after the acupuncture therapy. Significant correlations were observed between the change of activity in the prefrontal cortex and ipsilateral sensorimotor area. CONCLUSION: The results from these cases show that HMPAO-SPECT is capable of detecting changes in cerebral blood flow associated with pain and that acupuncture analgesia is associated with changes in the activity of the frontal lobes, brain stem, and thalami.

Acupuncture Analgesia↗
PubMed2004

Site-specific phosphorylation of phosducin in intact retina. Dynamics of phosphorylation and effects on G protein beta gamma dimer binding.

Phosducin (Pdc) is a G protein beta gamma dimer (G beta gamma) binding protein, highly expressed in retinal photoreceptor and pineal cells, yet whose physiological role remains elusive. Light controls the phosphorylation of Pdc in a cAMP and Ca(2+)-dependent manner, and phosphorylation in turn regulates the binding of Pdc to G(t)beta gamma or 14-3-3 proteins in vitro. To directly examine the phosphorylation of Pdc in intact retina, we prepared antibodies specific to the three principal phosphorylation sites (Ser-54, Ser-73, and Ser-106) and measured the kinetics of phosphorylation/dephosphorylation during light/dark adaptation and the subsequent effects on G(t)beta gamma binding. Ser-54 phosphorylation increased slowly (t((1/2)) approximately 90 min) during dark adaptation to approximately 70% phosphorylated and decreased rapidly (t((1/2)) approximately 2 min) during light adaptation to less than 20% phosphorylated. Ser-73 phosphorylation increased much faster during dark adaptation (t((1/2)) approximately 3 min) to approximately 50% phosphorylated and decreased more slowly during light adaptation (t((1/2)) approximately 9 min) to less than 20% phosphorylated. The Ca(2+) chelator BAPTA-AM blocked Ser-54 phosphorylation during dark adaptation but had no effect on Ser-73 phosphorylation. In contrast, Ser-106 was not phosphorylated in either the light or dark. Importantly, G beta gamma binding to Pdc was enhanced by Ca(2+) chelation and the binding kinetics closely paralleled those of Ser-54 dephosphorylation, indicating that Ser-54 phosphorylation controls G(t)beta gamma binding in vivo. These results suggest a pivotal role of Ser-54 and Ser-73 phosphorylation in determining the interactions of Pdc with its binding partners, G(t)beta gamma and 14-3-3 protein, which may regulate the light-dependent translocation of the photoreceptor G protein.

14-3-3 Proteins↗
PubMed2004

FDG-PET findings in patients with suspected encephalitis.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) may be used to establish a diagnosis of encephalitis, yet prior descriptions are mainly limited to small case reports. We explore the role of FDG-PET in the diagnostic evaluation of encephalitis. METHODS: Brain FDG-PET was acquired in a consecutive case series of 10 cases of suspected encephalitis over a 5-year-period. Cases with positive Lyme serology were excluded. Two expert reviewers graded the FDG-PET studies in blinded fashion with respect to the clinical history. Retrospective review of the clinical history and examination, laboratory findings, electroencephalogram (EEG), and magnetic resonance imaging (MRI) studies was performed. A diagnosis of encephalitis was based on a combination of the clinical and diagnostic examination findings in each case. RESULTS: Encephalitis was diagnosed in 6 of 10 cases. FDG-PET hypermetabolism was demonstrated in 5 cases of encephalitis, most frequently involving the medial temporal lobes. Multifocal hypometabolism was noted in at least 2 regions in all 6 cases of encephalitis, with at least 4 regions of hypometabolism noted in 5 of 6 cases. Nonencephalitis cases revealed hypermetabolism in only 1 of 4 cases, ascribed to status epilepticus. Hypometabolism was evident in all nonencephalitis cases. CONCLUSION: Encephalitis frequently manifests as FDG-PET hypermetabolism, but focal hypometabolism can also be observed. Seizure activity must be excluded as a possible cause of hypermetabolism in patients suspected of having encephalitis. Because other conditions that can cause hypometabolism may mimic encephalitis clinically, FDG-PET is more likely to serve as an adjunct to lumbar puncture, EEG, and clinical findings rather than a primary diagnostic tool in the management of patients suspected of having encephalitis.

Adolescent↗
PubMed2002

Ubiquitylation of the transducin betagamma subunit complex. Regulation by phosducin.

G proteins (Galphabetagamma) are essential signaling molecules, which dissociate into Galpha and Gbetagamma upon activation by heptahelical membrane receptors. We have identified the betagamma subunit complex of the photoreceptor-specific G protein, transducin (T), as a target of the ubiquitin-proteasome pathway. Ubiquitylated species of the transducin gamma-subunit (Tgamma) but not the alpha- or beta-subunits were assembled de novo in bovine photoreceptor preparations. In addition, Tgamma was exclusively ubiquitylated when Tbetagamma was dissociated from Talpha. Ubiquitylation of Tbetagamma on Tgamma was selectively catalyzed by human ubiquitin-conjugating enzymes UbcH5 and UbcH7 and was coincident with degradation of the entire Tbetagamma subunit complex in vitro by a mechanism requiring ATP and the proteasome. We also show that Tbetagamma association with phosducin, a photoreceptor-specific protein of unknown physiological function, blocks Tbetagamma ubiquitylation and subsequent degradation. Phosphorylation of phosducin by Ca(2+)/calmodulin-dependent protein kinase II, which inhibits phosducin-Tbetagamma complex formation, completely restored Tbetagamma ubiquitylation and degradation. We conclude that Tbetagamma is a substrate of the ubiquitin-proteasome pathway and suggest that phosducin serves to protect Tbetagamma following the light-dependent dissociation of Talphabetagamma.

Animals↗