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Biomedical subjects

Y Luo

Publications and source records attributed to Y Luo.

At least 37 records · Page 2Linked to original sources

Genetic background regulates semaphorin gene expression and epileptogenesis in mouse brain after kainic acid status epilepticus.

The host response to neural injury, which can include axonal sprouting and synaptic reorganization is likely to be under tight genetic regulatory control at the level of the genome and may be implicated in epileptogenesis. Despite its importance, however, the molecular basis of synaptic reorganization is unclear. We have studied the development of synaptic reorganization, semaphorin gene expression, and epileptogenesis in hippocampus of epileptogenic sensitive (FVB/NJ) and epileptogenic resistant (C57BL/6J) mice (i.e. distinct genetic backgrounds) after kainic acid-induced status epilepticus. Our results support the hypothesis that disruption of transcriptional regulation of axon guidance genes leads to a differential loss of tonic neuropilin-2 dependent activation of semaphorin 3F receptors on hippocampal neurons on distinct genetic backgrounds. This results in rearranged synaptic circuitry and thus promotes epileptogenesis. These findings may define biologic principles underlying the role of semaphorin signaling which may broadly apply to other systems undergoing neural regeneration.

Animals↗

Removal of copper and copper-binding organic ligands during potable water treatment.

The concentrations and chemical speciation of copper before and after potable water treatment have been examined using 3 techniques: a copper ion-selective electrode (Cu-ISE), chemiluminescence (CL) and anodic stripping voltammetry (ASV), together with water quality parameters colour, turbidity and dissolved organic carbon (DOC). As expected, only a small fraction of colour (6.6-11%), turbidity (6.7-14%) and DOC (20%) remained after treatment. The removal of Cu and Cu-binding natural organic matter (NOM) was more variable but still significant: 17-64% of total dissolved Cu and 19-61% of Cu-binding NOM (as determined by ASV) remained after treatment. Labile Cu levels, as measured by CL, were 0-23% after treatment. The Cu-ISE titrations showed significant Cu-binding in raw water in the concentration range 10(-7) to 10(-6) mol l(-1) Cu2+, but very little binding after treatment. The results indicate that conventional water treatment has a significant effect on both total Cu levels and Cu-binding NOM, with implications for Cu2+ speciation and bio-availability, particularly in reticulation systems containing copper pipes.

Copper↗

Congenital facial linear porokeratosis.

We report a unique case of congenital linear porokeratosis with exclusive facial involvement in a 27-year-old Chinese man. No other family member was affected. To our knowledge, this is the first report in the English literature of congenital linear porokeratosis confined to the face.

Adult↗

Pharmacokinetics of dexamethasone with pharmacokinetic/pharmacodynamic model of the effect of dexamethasone on endogenous hydrocortisone and cortisone in the horse.

A compartmental model was used to describe the pharmacokinetics of dexamethasone (DXM) and changes in the plasma concentration of endogenous cortisone (COR) and hydrocortisone (HYD) following intravenous (i.v.) administration of DXM (0.05 mg/kg) in horses. Quantification of DXM, COR and HYD in equine plasma was achieved using liquid chromatography interfaced with triple spray quadrupole quantum tandem mass spectrometry (LC/TSQ-MS/MS). The median alpha (t(1/2alpha)), beta (t(1/2beta)), and gamma (t(1/2gamma)) half-lives were 0.33, 2.2, and 10.7 h respectively. The area under the DXM plasma concentration curve (AUC) was 113.5 ng.h/mL. At 72 h post-DXM administration, the plasma concentration of DXM in all horses was below the level of quantification (100 pg/mL). The baseline plasma concentration of COR was 3.5 +/- 0.69 ng/mL and declined significantly (P < 0.02) to 2.9 +/- 0.86 ng/mL at 1 h. The nadir in COR plasma concentration was 0.65 +/- 0.12 ng/mL at 28.8 +/- 9.0 h, and the DXM plasma concentration was 0.19 +/- 0.13 ng/mL. COR concentration returned to baseline at 96 h. Baseline plasma concentration of HYD was 58.8 +/- 11.7 ng/mL and declined significantly (P < 0.001) to 41.1 +/- 14.9 ng/mL at 1 h following DXM administration but recovered to baseline at 96 h. The sensitivity of LC/TSQ-MS/MS allowed complete description of the pharmacokinetics of DXM and its effect on plasma concentrations of both COR and HYD.

Animals↗

Muscle infarction involving muscles of abdominal and thoracic walls in diabetes.

AIMS: This paper presents two cases of muscle infarction involving four major muscles of the anterior abdominal wall (case 1) and pectoralis major (case 2) in individuals with diabetes. METHODS: Erythrocyte sedimentation rate (ESR) and creatine kinase (CK) were measured and Doppler ultrasound, an open muscle biopsy (case 1) and magnetic resonance imaging (MRI) (case 2) were performed. RESULT: The diagnosis of muscle infarction was made by histological findings and MRI images with hyper-intensive signals on a gadolinium-enhanced T2-weighted sequence, respectively. Both patients were treated with bed rest, immobilization of the involved extremities, analgesia and intensive insulin therapy. In addition, anticoagulant drugs such as low molecular weight heparin sodium and cilostazol, and some traditional Chinese medicines such as ligustrazine and salvia miltiorrhiza were administered. The symptoms of both patients resolved gradually after 3 weeks. However, muscle infarction reoccurred in case 1 on the opposite side of the abdomen and recovered after 40 days. CONCLUSIONS: This is the first report of muscle infarction involving the muscles of anterior abdominal walls and pectoralis major in diabetes. MRI is the best non-invasive technique and T2-weighted imaging is the most valuable method for the diagnosis. In addition to supportive therapy, administration of anticoagulant agents and some Chinese traditional medicine may be useful in symptom relief.

Abdominal Muscles↗

Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke.

OBJECTIVE: To investigate whether the extent of white matter lesions (WML) on fluid attenuated inversion recovery (FLAIR) MRI sequences is an independent risk factor for recurrent stroke, and to document the pattern of acute cerebral infarcts using diffusion weighted imaging (DWI) in patients with different severities of WML. METHODS: In a prospective cohort study, 228 consecutive stroke patients were studied between 1999 and 2001 in a community hospital. The severity of WML was graded as 0 (no WML), 1 (mild), 2 (moderate), or 3 (severe) according to the FLAIR appearances. DWI was used to document the location and size of the infarct. RESULTS: 31 patients had grade 0 WML, 69 had grade 1, 59 had grade 2, and 69 had grade 3. Age was independently associated with WML on logistic regression analysis (p = 0.0001). Acute cerebral infarcts in deep white matter were correlated with increasing severity of WML. On a median follow up of 23.0 months, life table analysis showed that recurrent stroke was related to the severity of WML (recurrence rate 7.8% in grade 0, 9.3% in grade 1, 17.7% in grade 2, 43.7% in grade 3; p = 0.0001). Survival was reduced in patients with severe WML (p = 0.0068). A Cox proportional hazards model showed WML to be predictive of recurrent stroke (p = 0.000, hazard ratio = 4.177 (95% confidence interval, 2.038 to 8.564)) and also for survival (p = 0.040, hazard ratio = 2.021 (1.032 to 3.960)). CONCLUSIONS: Patients with severe leukoaraiosis have increased risk of deep subcortical stroke and a higher risk of recurrent stroke.

Acute Disease↗

Efficient preparation of L-cysteic acid and its esters.

L-Cysteic acid and its esters were prepared in good yields from the oxidation of L-cystine by chlorine in water and in alcohols. When the reaction was carried out in alcohols the corresponding esters were produced.

Alcohols↗

DNA vaccines designed to inhibit tumor growth by suppression of angiogenesis.

The development of new blood vessels, i.e. angiogenesis, is a rate-limiting step in the development of tumors since tumor growth is generally limited to 1-2 mm3 in the absence of a blood supply. Thus, the inhibition of tumor growth by attacking the tumor's vascular supply offers a primary target for antiangiogenic intervention by DNA-based vaccines. Here, we describe two novel orally delivered DNA vaccines which suppress tumor angiogenesis and induce a robust cell-mediated immune response that provides for long-lived protection against melanoma, colon, breast and non-small-cell lung carcinoma in mouse model systems. These vaccines, which are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs, are directed against such targets as vascular endothelial growth factor receptor 2 (FLK-1) and transcription factor Fos-related antigen 1 (Fra-1). Both vaccines break peripheral T cell tolerance against these self-antigens and induce a robust T cell-mediated immune response leading to suppression of tumor angiogenesis and resulting in effective suppression of tumor growth and metastases. Such research efforts may open up new possibilities for the rational design of future DNA vaccines effective for the prevention and treatment of cancer.

Animals↗

Studies on molecular mechanisms of Ginkgo biloba extract.

In the past decade, interest by the general public in the use of herbal dietary supplements has risen exponentially. As throughout history, individuals are now turning to the use of "natural" therapies for the prevention, treatment and cure of almost every ailment and aging malady imaginable. often without substantial proof of safety or efficacy. One of the most popular herbal supplements is Ginkgo biloba extract, taken for its perceived "memory enhancing" properties. Given the inordinate popularity, growing use, and substantial number of pharmaceutical products containing G. biloba, coupled with demands for product safety and "hard evidence," science has followed this trend closely with an ever-expanding body of pharmacological and clinical data on such preparations. Claims that standardized G. biloba extract (EGb 761) can modulate the cellular environment of an organism under both physiological and stress conditions may be attributed to its multivalent or totipotent properties, and can now be substantiated by the availability of modern molecular techniques. As opposed to pharmacologically manufactured or synthetic drugs, which provide a single target for a single receptor as the mechanism of action, EGb 761 is able to up- or down-regulate signaling pathways, gene transcription, cellular metabolism, etc., and thus assist in the regulation of the general physiological status of the cell and/or organism in response to stressors posed by both intracellular and extracellular conditions. Presumably, this is one of the biggest advantages of using natural products for the prevention and treatment of infirmity, as well as the maintenance of health in an organism.

Amyloid beta-Peptides↗

Recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) expressing mouse IL-18 augments Th1 immunity and macrophage cytotoxicity.

Interleukin-18 (IL-18) has been demonstrated to synergize with BCG for induction of a T-helper-type 1 (Th1) immune response. Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a recombinant (r) BCG strain that functionally secretes mouse (m) IL-18. This rBCG-mIL-18 strain significantly increased production of the major Th1 cytokine IFN-gamma in splenocyte cultures, at levels comparable to that elicited by control BCG plus exogenous rIL-18. IFN-gamma production by splenocytes was eliminated by addition of neutralizing anti-IL-18 antibody. Endogenous IL-12 played a favourable role whereas IL-10 played an adverse role in rBCG-mIL-18-induced IFN-gamma production. Enhanced host antimycobacterial immunity was observed in mice infected with rBCG-mIL-18 which showed less splenic enlargement and reduced bacterial load compared to control mice infected with BCG. Further, splenocytes from rBCG-mIL-18-infected mice, in response to BCG antigen, displayed increased production of IFN-gamma and GMCSF, decreased production of IL-10, elevated cellular proliferation and higher differentiation of IFN-gamma-secreting cells. rBCG-mIL-18 also enhanced BCG-induced macrophage cytotoxicity against bladder cancer MBT-2 cells in a dose-dependent manner. Neutralizing all endogenous macrophage-derived cytokines tested (IL-12, IL-18 and TNF-alpha) as well as IFN-gamma severely diminished the rBCG-mIL-18-induced macrophage cytolytic activity, indicating a critical role for these cytokines in this process. Cytokine analysis for supernatants of macrophage-BCG mixture cultures manifested higher levels of IFN-gamma and TNF-alpha in rBCG-mIL-18 cultures than in control BCG cultures. Taken together, this rBCG-mIL-18 strain augments BCG's immunostimulatory property and may serve as a better agent for bladder cancer immunotherapy and antimycobacterial immunization.

Animals↗

Pharmacokinetics and disposition of clenbuterol in the horse.

The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life (t(1/2k)) of 9.2 h, area under the time-concentration curve (AUC) of 12.4 ng.h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution (V(d)) was 1616.0 mL/kg and plasma clearance (Cl) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrations also declined mono-exponentially with a median elimination half-life (t(1/2k)) of 12.9 h, a Cl of 94.0 mL/h/kg and V(d) of 1574.7 mL/kg. Following the last p.o. administration the baseline plasma concentration was 537.5 +/- 268.4 and increased to 1302.6 +/- 925.0 pg/mL at 0.25 h, and declined to 18.9 +/- 7.4 pg/mL at 96 h. CLB was still quantifiable in urine at 288 h following the last administration (210.0 +/- 110 pg/mL). The difference between plasma and urinary concentrations of CLB was 100-fold irrespective of the route of administration. This 100-fold urine/plasma difference should be considered when the presence of CLB in urine is reported by equine forensic laboratories.

Administration, Oral↗

Tissue distribution of clenbuterol in the horse.

Plasma and tissue concentrations of clenbuterol (CLB) were determined following oral (p.o.) administration of 1.6 microg/kg twice daily (b.i.d.) for 2 weeks. Horses were administered the last dose on morning of day 15, killed at 0.25, 24, 48, and 72 h post-administration. At 0.25 h, the highest tissue concentrations of CLB were found in the liver (16.21 ng/g), lung (6.48 ng/g), left ventricle (4.99 ng/g), kidney (3.35 ng/g), bronchi (2.56 ng/g), right ventricle (2.08 ng/g), and eye fluids (1.09 ng/g) all of which were higher than that of plasma (1.10 ng/mL). The elimination half-lives (t(1/2k)) for CLB in tissues ranged from 21.2 to 56.3 h, the longest were in the eye fluids (56.9 h), spleen (21.2 h), cerebrum (27.1 h), cerebellum (21.5) and cecum (23.7 h). The t(1/2k) for plasma was 10.9 h. Tissue/plasma ratios of liver (14.7), lung (5.9), left ventricle (4.6), kidney (3.1), bronchi, (2.3) and right ventricle (1.9) were high at 0.25 h and remained elevated up to 72 h. Accumulation and sustained high concentration of CLB relative to plasma in these tissues contributed to the prolonged elimination and the ability to quantify CLB in plasma and urine for a prolonged period.

Administration, Oral↗

DNA vaccines suppress angiogenesis and protect against growth of breast cancer metastases.

Two novel oral DNA-based vaccines provide immune protection against breast cancer in mouse model systems. These vaccines are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs and are directed against novel targets such as transcription factor Fos-related antigen 1 (Fra-1) and endoglin (CD105). Both vaccines elicit suppression of angiogenesis in the breast tumor vasculature and break peripheral tolerance by eliciting potent cell-mediated protective immunity against these tumor self-antigens resulting in effective suppression of breast tumor growth and metastasis.

Animals↗

Molecular structure of alcohol-water mixtures.

We use x-ray emission spectroscopy to elucidate the molecular structure of liquid methanol, water, and methanol-water solutions. We find that molecules in the pure liquid methanol predominantly persist as hydrogen-bonded chains and rings with six and/or eight molecules of equal abundance. For water-methanol solutions we find evidence of incomplete mixing at the microscopic level. Our results provide a new explanation for a smaller entropy increase in the solution due to water molecules bridging methanol chains to form rings.

Journal Article↗

Changes in life quality following third molar surgery--the immediate postoperative period.

OBJECTIVES: This study describes patients' perceptions of changes in oral health related quality of life (OHQOL) in the early postoperative period following third molar surgery. METHODS: One hundred patients were enrolled in a prospective cohort study of the surgical removal of lower third molars under local anaesthetic. Two specific oral health related quality of life measures, OHIP-14 and OHQoLUK, were administered to the study group prior to surgery. Standardized surgical and analgesic protocols were followed. Patients kept a diary of changes in life quality each postoperative day (POD) for 7 days, completing both OHIP-14 and OHQoLUK daily. RESULTS: Both oral health related quality of life measures identified a significant deterioration in quality of life on POD1 (P<0.01) and this remained evident on POD2 (P<0.01), POD3 (P<0.01), POD4 (P<0.01) and POD5 (P<0.05). By POD6 and POD7 there was no significant difference in quality of life compared with preoperative status (P>0.05). Deterioration in life quality over the study period was associated with postoperative clinical findings (P<0.05): swelling and trismus. CONCLUSION: The study concludes that there is a significant deterioration in oral health related quality of life in the immediate postoperative period following third molar surgery; particularly during the first five days. This is associated with postoperative clinical findings. This has implication for patients deciding on third molar surgery and informed consent.

Attitude to Health↗

Genetic diversity of Actinomyces naeslundii genospecies 2 in mother-child pairs.

Actinomyces naeslundii genospecies 2 (gsp-2) are members of the autochthonous oral flora. Chromosomal DNA fingerprinting (CDF) with SmaI revealed extensive genetic diversity among A. naeslundii gsp-2 strains within individual mothers and children. There was a low prevalence of genotype match among A. naeslundii gsp-2 strains between all mother and child pairs.

Actinomyces↗

Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumour activity.

Intravesical BCG therapy is effective in the treatment of superficial bladder cancer. Both clinical and experimental results suggest a role for cytokines and delayed-type hypersensitivity (DTH) in BCG-induced antitumour immunity. We characterized the modulatory effects of BCG on bladder cytokine expression and determined the relationship between DTH and BCG antitumour activity. The bladders of mice were instilled with BCG through a catheter. Bladder tissue RNA and urine were collected for evaluation of cytokine expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and/or ELISA. IFN-gamma and TNF-alpha, the two major cytokines associated with DTH, were efficiently induced by BCG. IL10, an important down-regulator of DTH, was also induced by BCG. Constitutive levels of IL4 and IL5 were observed, but neither IL4 nor IL5 were modulated by BCG. Similar results were observed in the kinetic analysis of urinary cytokines in patients after intravesical BCG therapy. Production of Th1 (T helper type 1) cytokines (IFN-gamma, IL2 and IL12) preceded that of the Th2 (T helper type 2) cytokine IL10. A tendency toward higher ratios of IFN-gamma versus IL10 for BCG responders also was observed. In animal studies the absence of IL10 abrogated either by antibody inhibition or the use of genetically modified, IL10 deficient (IL10-/-) mice resulted in enhanced DTH responses. Under conditions of enhanced DTH, a significant enhancement in antitumour activity was observed. These data demonstrate that DTH and its associated mononuclear infiltration and cytokine production are important to the antitumour activity of intravesical BCG therapy, and suggest that effects to diminish IL10 production may have therapeutic value.

Animals↗