PubMed Health⌕ Search

Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 19 recordsLinked to original sources
PubMed2006

DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis.

To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer (HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription-polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P=0.009), N stage (P=0.047), overall stage (P=0.011), tumor depth (P=0.009) and extracapsular spread in lymph nodes (P=0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57-21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30-48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.

Animals↗
PubMed2006

A role for the immunomodulatory molecules CD200 and CD200R in regulating bone formation.

Altered osteoprotogerin (OPG) and OPG ligand (RANKL) ratios are known to regulate bone metabolism. We investigated whether CD200:CD200R interaction would alter OPG:RANKL ratios, and thus modulate bone differentiation in cultures derived from neonatal calvariae, a source of osteoblast precursors (OBp), or bone marrow-derived myeloid cells as a source of osteoclast precursors (OCp). We characterized cells in cultures using real-time PCR to measure expression of a number of mRNAs characteristic of cells differentiating towards the osteoblast or osteoclast lineage, and enumerated bone nodule formation and osteoclasts directly. CD200Fc or anti-CD200 mAbs were included as modulating agents. In addition, calvariae from transgenic mice overexpressing CD200 under control of a doxycycline-inducible promoter were used as a source of OBp endogenously overexpressing CD200. Our data show that increased endogenous expression of CD200 on OBp, or addition of CD200Fc into cultures, led to increased OPG:RANKL ratios and increased bone nodule growth, while anti-CD200 abolished this effect.

Animals↗
PubMed2006

Immunodetection of GLUT1, p63 and phospho-histone H1 in invasive head and neck squamous carcinoma: correlation of immunohistochemical staining patterns with keratinization.

Immunodetection of GLUT1, p63 and phospho-histone H1 in invasive head and neck squamous carcinoma: correlation of immunohistochemical staining patterns with keratinizationAims : To examine invasive head and neck squamous carcinomas for expression of GLUT1, a glucose transporter and marker of increased glucose uptake, glycolytic metabolism and response to tissue hypoxia; p63, a p53 homologue that is a marker of the undifferentiated proliferative basaloid phenotype; and phospho-histone H1, a marker of activation of the cell cycle-promoting cyclin-dependent kinases 1 and 2. Methods : Routinely processed slides from 34 invasive squamous carcinomas, including 25 with intraepithelial components, were immunostained with anti-GLUT1 (Chemicon), anti-p63 (4A4, Santa Cruz), and antiphospho-histone H1 (monoclonal 12D11). Results : In keratinizing carcinomas, all three markers were most commonly immunodetected peripherally, with loss of expression in central keratinized zones. In contrast, in non-keratinizing carcinomas, p63 and phospho-histone H1 expression was most commonly observed throughout tumour nests and anti-GLUT1 stained in a pattern suggestive of hypoxia-induced expression ('antistromal' staining), in which cells at the tumour-stromal interface were GLUT1- and cells in central, perinecrotic zones showed progressive induction of GLUT1. Intraepithelial components also displayed basal and 'antibasal' GLUT1 staining patterns, homologous to the pro- and antistromal patterns in invasive carcinoma; basal patterns in intraepithelial lesions appeared to be more predictive of keratinizing invasive carcinoma and antibasal intraepithelial staining more predictive of non-keratinizing poorly differentiated carcinomas. Conclusions : Keratinizing and non-keratinizing squamous carcinomas differ in expression patterns of GLUT1, p63 and phospho-histone H1. In the former, all three markers were typically suppressed in conjunction with keratinization; in the latter, GLUT1 expression was more likely to occur in a hypoxia-inducible pattern and expression of p63 and phospho-histone H1 was unsuppressed. GLUT1 expression patterns in intraepithelial lesions may be predictive of the differentiation status of the associated invasive carcinoma.

Biomarkers, Tumor↗
PubMed2006

Intrauterine lignocaine as an anaesthetic during endometrial sampling: a randomised double-blind controlled trial.

OBJECTIVE: To evaluate the effectiveness of intrauterine lignocaine as an anaesthetic during endometrial sampling. DESIGN: Prospective, randomised, double-blind, placebo-controlled trial. SETTING: Outpatient gynaecological minor operation unit in a public hospital. POPULATION: Two hundred premenopausal women scheduled for endometrial sampling because of abnormal uterine bleeding. METHODS: Transcervical intrauterine instillation of 5 mL of 2% lignocaine or 5 mL of normal saline before performing endometrial sampling with vacuum aspirator. MAIN OUTCOME MEASURES: Evaluation of pain associated with the procedure using a visual analogue scale. RESULTS: The use of intrauterine lignocaine reduced pain during suction curettage in endometrial sampling. CONCLUSIONS: Transcervical instillation of lignocaine reduced pain during endometrial sampling.

Adult↗
PubMed2005

Strange-quark contributions to parity-violating asymmetries in the forward g0 electron-proton scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.

Journal Article↗
PubMed2005

Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials.

BACKGROUND: Plasma and serum biomarkers of angiogenesis and activated endothelial cells were evaluated to assess biological activity of PTK787/ZK 222584 (PTK/ZK), a novel oral angiogenesis inhibitor targeting all known vascular endothelial growth factor (VEGF) receptor tyrosine kinases. PATIENTS AND METHODS: Patients with colorectal cancer (CRC) (n=63) were enrolled into two phase I/II dose escalation trials of PTK/ZK in 28-day cycles until discontinuation. Patients with stable disease for > or =2 months were categorized as 'non-progressors'. Plasma markers of angiogenesis, VEGF-A and basic fibroblast growth factor (bFGF), and the serum markers of activated endothelial cells, sTIE-2 and sE-Selectin, were assessed at baseline, and pre-dose on days 1, 8, 15, 22 and 28 of every cycle, with additional assessments 10 h post-dose on days 1 and 15. The percentage change from baseline was subsequently correlated with AUC and C(max) of PTK/ZK on day 1, cycle 1 and clinical outcome. RESULTS: A dose-dependent increase in plasma VEGF-A and bFGF was observed in the first cycle of PTK/ZK treatment. The correlation of change in plasma VEGF-A with AUC and C(max) was characterized by an E(max) model, suggesting that a change of > or =150% from baseline VEGF-A correlated with non-progressive disease. Change from baseline plasma VEGF-A within the first cycle of treatment was significantly correlated with clinical outcome by logistic regression analysis (P=0.027). CONCLUSIONS: In patients with CRC treated with PTK/ZK, changes in plasma VEGF-A and bFGF demonstrate biological activity of PTK/ZK, may help to establish optimal dose and correlate with outcome.

Aged↗
PubMed2005

A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate.

Migraine is a common disabling condition likely to be associated with dysfunction of brain pathways involved in pain and other sensory modalities. A cardinal, indeed signature, feature of the disorder that led to its name is that the pain may be lateralized. H(2)15O-labelled PET was used to study 24 migraineurs and eight healthy controls. The migraineurs were divided into three groups according to the site of their headache: right, left or bilateral. In each group, a migraine was induced using a glyceryl trinitrate (GTN) infusion. The subjects were scanned at predefined points: pre-infusion, during GTN, during migraine and post-migraine. SPM99 software was used to analyse the data. Significant brainstem activation was seen in the dorsal lateral pons (P < 0.05 after small volume correction) during the migraine state versus the pain-free state when comparing migraineurs with controls. When each group was analysed separately, to investigate laterality, it was found that the dorsal pontine activation was ipsilateral in the right-sided and left-sided groups and bilateral in the bilateral headache group with a left-sided preponderance. Consistent with previous work, the activation persisted after pain was controlled by sumatriptan. These results suggest that lateralization of pain in migraine is due to lateralized brain dysfunction.

Adult↗
PubMed2005

Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1.

Histone deacetylases (HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21Cip1/WAF1 expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.

Apoptosis↗
PubMed2004

Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison.

OBJECTIVE: To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD. METHODS: A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived. RESULTS: The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001). CONCLUSION: This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.

Caudate Nucleus↗
PubMed2004

Analysis of strain difference in behavior to Cholecystokinin (CCK) receptor mediated drugs in PVG hooded and Sprague-Dawley rats using elevated plus-maze test apparatus.

This study investigated the behavioral mechanisms underlying the anxiogenic, or anxiolytic mediated effects of CCK(2) receptor mediated agonist (CCK-4) and antagonist drugs (LY225910, LY288513, CR2945) in PVG hooded and Sprague-Dawley (SD) rats using the elevated plus maze test apparatus. In addition, the effects of a CCK(1) antagonist (CR1409) were investigated for its possible mediation in anxiety behavior between PVG hooded and SD rats. PVG hooded rats treated with CCK-4, decreased the time spent in the open arm and increased the time spent in the closed arm and correspondingly showed increase in the number of entries in the open arms while the number of entries in closed arm was insignificant, whereas SD rats decreased the time spent in the closed arm, while other parameters remained insignificant. PVG hooded rats administered with various CCK(2) antagonists (LY225910, LY288513, and CR2945) significantly increased the time spent in the open arm and correspondingly decreased the time spent in the closed arm, while the number of entries in the open or closed arm was insignificant, in contrast, SD rats failed to show any reliable significance. PVG hooded rats administered with the CCK(1) antagonist (CR1409), failed to show any reliable significance, in contrast, SD rats significantly increased the time spent in the open arm. The strain differences observed in this study suggests that CCK plays mainly as a neuromodulator, in which the various CCK(2) antagonists may not affect baseline anxiety state, but instead they modulate heightened states of anxiety through differential effects of CCK(1)/CCK(2) receptors.

Animals↗
PubMed2004

The CCK2 agonist BC264 reverses freezing behavior habituation in PVG hooded rats on repeated exposures to a cat.

Our previous studies (NeuroReport 12 (2001) 2717) showed that PVG hooded and not Sprague-Dawley (SD) rats exhibit remarkable freezing behavior on exposure to a cat in the cat freezing test apparatus. In the present study, we further examined the differences between these two strains of rats in response to repeated daily exposure to a cat in the cat freezing test apparatus. Freezing behavior habituation was observed in both PVG hooded (days 5-7) and SD rats (days 3-7). A selective CCK(2) agonist (BC264, 0.3 microg/kg, i.p.) on day 8 reversed habituated freezing behavior and locomotor activity in PVG hooded rats, but not in SD rats. These results suggest that CCK2 receptors mediate habituation to an anxiety-inducing stimulus in PVG hooded rats and further suggest that differential expression of these CCK2 receptors underlies this strain difference.

Animals↗
PubMed2004

Distinct regions of periaqueductal gray (PAG) are involved in freezing behavior in hooded PVG rats on the cat-freezing test apparatus.

The periaqueductal gray (PAG) is considered to be an exit relay for defensive responses. Studies have shown that the ventrolateral periaqueductal gray (vlPAG) plays a role in the expression of freezing behavior whereas dorsolateral periaqueductal gray (dlPAG) is involved on both freezing and active forms of defensive behaviors. To further elucidate this theory, lesioned vlPAG and dlPAG rats were exposed to a cat in the cat-freezing test apparatus. Subsequently, a 7-day repeated exposure to a cat was done on the vlPAG and dlPAG lesioned rats. Results showed that the vlPAG lesioned rats demonstrated significant decrease in freezing behavior and corresponding increase in locomotor activity, while the dlPAG lesioned rats failed to show any significance. Subsequent repeated exposure of the vlPAG lesioned rats to a cat for 7 days showed a gradual decrease in freezing behavior with significance shown at days 5, 6 and 7 while the dlPAG lesioned rats failed to show any changes. These results suggest that vlPAG regulates freezing behavior in hooded PVG rats.

Animals↗
PubMed2004

Effectiveness of bupropion as an aid to stopping smoking before elective surgery: a randomised controlled trial.

Smoking is a risk factor for complications during and after surgery, but most smokers are unable to quit before elective surgery. We tested the efficacy of bupropion in improving smoking cessation rates in this setting by enrolling 47 patients from the elective surgery waiting list in a double-blind randomised controlled trial. Patients receiving bupropion had a lower daily cigarette consumption at the time of hospital admission, median (IQR) cigarettes per day: 6 (2-7) vs. 15 (9-20), p = 0.046. They also had a reduction in end-expired carbon monoxide (p = 0.004), a known contaminant of cigarette smoke, and increased arterial oxygen saturation on pulse oximetry (p = 0.011). They were more likely to have stopped smoking at the 3-week visit (p = 0.036), but not at the 6-week visit (p = 0.25) or at the time of hospital admission for surgery (p > 0.99). This study found that smokers waiting for elective surgery are more likely to reduce or stop smoking when treated with bupropion.

Adult↗
PubMed2004

Could nursery rhymes cause violent behaviour? A comparison with television viewing.

AIMS: To assess the rates of violence in nursery rhymes compared to pre-watershed television viewing. METHODS: Data regarding television viewing habits, and the amount of violence on British television, were obtained from Ofcom. A compilation of nursery rhymes was examined for episodes of violence by three of the researchers. Each nursery rhyme was analysed by number and type of episode. They were then recited to the fourth researcher whose reactions were scrutinised. RESULTS: There were 1045 violent scenes on pre-watershed television over two weeks, of which 61% showed the act and the result; 51% of programmes contained violence. The 25 nursery rhymes had 20 episodes of violence, with 41% of rhymes being violent in some way; 30% mentioned the act and the result, with 50% only the act. Episodes of law breaking and animal abuse were also identified. Television has 4.8 violent scenes per hour and nursery rhymes have 52.2 violent scenes per hour. Analysis of the reactions of the fourth researcher were inconclusive. CONCLUSIONS: Although we do not advocate exposure for anyone to violent scenes or stimuli, childhood violence is not a new phenomenon. Whether visual violence and imagined violence have the same effect is likely to depend on the age of the child and the effectiveness of the storyteller. Re-interpretation of the ancient problem of childhood and youth violence through modern eyes is difficult, and laying the blame solely on television viewing is simplistic and may divert attention from vastly more complex societal problems.

Child↗
PubMed2004

Changes in population attitudes about where smoking should not be allowed: California versus the rest of the USA.

BACKGROUND: The decade long California Tobacco Control Program is unique to the nation in its duration, emphasis, and level of funding. Programme emphasis is on changing social norms about smoking as a means to discourage smoking and thus reduce the harmful health effects of tobacco to the population. METHODS: Data from the 1992-93, 1995-96, and 1998-99 Tobacco Use Supplements to the national Current Population Survey (n > 175 000 each period) were used to examine changes in norms regarding where smoking should "not be allowed at all" in both California and in the rest of the USA. Venues queried were restaurants, hospitals, work areas, bars, indoor sports venues, and indoor shopping malls. RESULTS: There were substantial increases in the percentages of the adult population (18+ years) stating that smoking should not be allowed in the venues queried in California by 1998-99 compared to 1992-93; only modest increases were observed in the rest of the USA. In fact, for most venues, the percentages for the rest of the USA were lower in 1998-99 than in California in 1992-93. Further, the percentage increase over this period in respondents stating that smoking should not be allowed in four or more of the six venues was 30% in California and 23% in the rest of the USA. The most dramatic percentage increase in California occurred among current smokers (93%). CONCLUSIONS: A strong, comprehensive tobacco control programme such as California's can influence population norms, including those of smokers, with respect to where smoking should not be allowed.

Adult↗
PubMed2004

Intraoperative patient warming using radiant warming or forced-air warming during long operations.

Forced-air warming is the most commonly used and effective method of active warming. A new radiant warming device (Suntouch, Fisher and Paykel) may provide an alternative when the skin surface available for warming is limited. We conducted a randomized controlled trial to compare the efficacy of the Suntouch radiant warmer and forced-air warming. With ethics committee approval 60 surgical patients having procedures anticipated to be more than two hours in duration were recruited. Patients were randomized to either radiant warming or forced-air warming. All intravenous fluids were warmed but prewarming was not used. The final intraoperative core temperatures (degrees C) for the radiant warming and forced-air warming groups were 36.0 +/- 0.5 and 36.4 +/- 0.6 (P=0.002) respectively. No other patient variables were significantly different. The Suntouch is not as effective as the forced air warming for intraoperative warming during long surgical procedures. The device may be useful when forced-air warming is not possible.

Body Temperature↗