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Biomedical subjects

W M Lee

Publications and source records attributed to W M Lee.

At least 19 recordsLinked to original sources

Ovariectomy during the luteal phase influences secretion of prolactin, growth hormone, and insulin-like growth factor-I in the bitch.

A decline in circulating progesterone concentration plays an important role in the ethiopathogenesis of pseudopregnancy in the bitch. Because growth hormone (GH) and prolactin (PRL) are essential for normal mammogenesis and the secretion of these hormones is influenced by changes in the circulating progesterone concentration, the purpose of this study was to investigate the effects of mid-luteal phase ovariectomy on the 6-h pulsatile plasma profiles of GH and PRL and the basal plasma concentrations of GH, PRL, and insulin-like growth factor-I (IGF-I) in six beagle bitches. Ovariectomy was followed by only mild or covert signs of pseudopregnancy. The sharp decrease of the plasma progesterone concentration was accompanied by decreased basal plasma concentrations of GH and IGF-I and a rise in basal plasma PRL concentration. GH and PRL were secreted in a pulsatile fashion both prior to and after ovariectomy. The mean basal plasma GH concentration was significantly higher before ovariectomy than on days 1 and 7 after ovariectomy. The mean area under the curve above the zero level (AUC(0)) for GH was significantly higher before than at 7 days after ovariectomy. The mean area under the curve above basal level (AUC(b)) and the frequency of GH pulses at 7 days after ovariectomy were significantly higher than before and 1 day after ovariectomy. Both the mean basal plasma PRL concentration and the mean AUC(0) for PRL increased after ovariectomy. In conclusion, ovariectomy of bitches in the mid-luteal phase stops progesterone-induced GH release from the mammary gland, as evidenced by the lowering of basal plasma GH levels, the recurrence of GH pulsatility, and the lowering of circulating IGF-I levels. The sudden lowering of plasma progesterone concentration is probably a primary cause of a prolonged increase in PRL secretion. These observations underscore the importance of similar, albeit less abrupt, hormonal changes in the cyclical physiological alterations in the mammary gland and in the development of pseudopregnancy.

Animals↗

Brief report: no evidence for parvovirus B19 or hepatitis E virus as a cause of acute liver failure.

Viral hepatitis A and B are known to cause acute liver failure. While nearly 20% of acute liver failure cases are of indeterminate etiology, screening for other viruses has not been uniformly performed. We looked for evidence for parvovirus B19 and hepatitis E virus in sera from U.S. acute liver failure patients. For B19, 78 patients' sera, including 34 with indeterminate etiology, were evaluated by DNA dot-blot hybridization, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay for immunoglobin G and M antibodies; none showed evidence for infection.

Antibodies, Viral↗

Regulation of acetyl-CoA carboxylase.

Acetyl-CoA carboxylase (ACC) catalyses the formation of malonyl-CoA, an essential substrate for fatty acid synthesis in lipogenic tissues and a key regulatory molecule in muscle, brain and other tissues. ACC contributes importantly to the overall control of energy metabolism and has provided an important model to explore mechanisms of enzyme control and hormone action. Mammalian ACCs are multifunctional dimeric proteins (530-560 kDa) with the potential to further polymerize and engage in multiprotein complexes. The enzymatic properties of ACC are complex, especially considering the two active sites, essential catalytic biotin, the three-substrate reaction and effects of allosteric ligands. The expression of the two major isoforms and splice variants of mammalian ACC is tissue-specific and responsive to hormones and nutritional status. Key regulatory elements and cognate transcription factors are still being defined. ACC specific activity is also rapidly modulated, being increased in response to insulin and decreased following exposure of cells to catabolic hormones or environmental stress. The acute control of ACC activity is the product of integrated changes in substrate supply, allosteric ligands, the phosphorylation of multiple serine residues and interactions with other proteins. This review traces the path and implications of studies initiated with Dick Denton in Bristol in the late 1970s, through to current proteomic and other approaches that have been consistently challenging and immensely rewarding.

Acetyl-CoA Carboxylase↗

Effects of dexamethasone on peripheral blood mononuclear cell phenotype in weanling piglets.

The aim of this study was to evaluate the effect of dexamethasone treatment on the immune system of weanling piglets. Piglets were administered dexamethasone (DEX; 1mg/kg, IM) every 12h for 2 consecutive days (short-term experiment) or DEX (1mg/kg, IM) daily for 2 weeks (long-term experiment). The relative percentage of CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) was significantly decreased (P<0.05) in both short- and long-term DEX-treated groups compared to their control groups. The percentage of IgM(+) cells in PBMCs of the long-term DEX-treated group was greatly increased (P<0.05) in comparison to the control group. The results of this study indicate that short-term DEX-treatment increases leucocyte function; however, long-term DEX-treatment depresses leucocyte function, especially that of CD8(+) T cells.

Animals↗

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States.

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.

Adult↗

Iatrogenic bilateral pneumothorax arising from acupuncture: a case report.

Acupuncture is often regarded as innocuous. However, its complication can be serious and deadly if unattended. We report a case of iatrogenic bilateral pneumothorax after acupuncture therapy. Setting up a government regulatory body and using needles with safety design can prevent further inadvertent incidences from occurring.

Acupuncture Therapy↗

Embryotrophic factor-3 from human oviductal cells enhances proliferation, suppresses apoptosis and stimulates the expression of the beta1 subunit of sodium-potassium ATPase in mouse embryos.

BACKGROUND: Embrytrophic factor-3 (ETF-3) from human oviductal cells enhanced the development of mouse preimplantation embryos. This report studied the embryotrophic mechanisms of the molecule. METHODS AND RESULTS: Mouse embryos were incubated with ETF-3 for 24 h at different stages of development. ETF-3 treatment between 96 and 120 h post-HCG increased the cell count of blastocysts, whilst treatment between 72 and 96 h post-HCG enhanced the expansion and hatching of the blastocysts. ETF-3 increased the cell number of the embryos by suppressing apoptosis and increasing proliferation as determined by TUNEL and bromodeoxyuridine uptake assays, respectively. Real-time quantitative PCR showed that the in vivo developed and ETF-3-treated blastocysts had a significantly higher mRNA copy number of Na/K-ATPase-beta1, but not of hepsin, than that of blastocysts cultured in medium alone. The former gene was associated with cavitation of blastocysts while the latter was related to hatching of blastocyst. The beneficial effect of ETF-3 on blastocyst hatching was also seen when ETF-3-supplemented commercially available sequential culture medium for human embryo culture was used to culture mouse embryos. CONCLUSIONS: ETF-3 improves embryo development by enhancing proliferation, suppressing apoptosis and stimulating expression of genes related to blastocyst cavitation. Supplementating human embryo culture medium with ETF-3 may improve the success rate in clinical assisted reproduction.

Animals↗

Optical vortex beam shaping by use of highly efficient irregular spiral phase plates for optical micromanipulation.

Optical dark traps such as Laguerre-Gaussian beams, modulated optical vortices, and high-order Bessel beams have been used in the micromanipulation of microparticles. Such optical traps are highly versatile, as they are able to trap both high- and low-index microparticles as well as to set them into rotation by use of the orbital angular momentum of light. Holography has been widely used to modulate the shape of an optical vortex for new optical traps. We show that, by designing the shape of a spiral phase plate and using electron-beam lithography for fabrication, one can modulate the amplitude and the phase of an optical vortex with respect to the specific shape of the spiral phase plate as required. Furthermore, to the best of our knowledge this is the first report of transferring orbital angular momentum from a spiral phase plate to an absorptive microparticle in an experiment. Hence, with this technique, optical dark traps can easily be designed and fabricated.

Journal Article↗

Assessment of the performance characteristics of a prototype 12-element capacitive contact flexible microstrip applicator (CFMA-12) for superficial hyperthermia.

The electrical performance of the CFMA-12 operating at 433 MHz is assessed under laboratory conditions using a RF network analyser. From measurements of the scattering parameters of the CFMA-12 on both a multi-layered muscle- and fat/muscle-equivalent phantom, the optimal water bolus thickness, at which the transfer of the energy to the phantom configuration is maximal, is determined to be approximately 1 cm. The SAR distribution of the CFMA-12 in a multi-layered muscle-equivalent phantom is characterized using Schottky diode sheets and a TVS-600 IR camera. From the SAR measurements using the Schottky diode sheets it is shown that the contribution of the E(x) component to the SAR (SAR(x)) is maximal 7% of the contribution of the E(y)component to the SAR (SAR(y)) at different layers in both phantom configurations. The complete SAR distribution (SAR(tot)) at different depths is measured using the power pulse technique. From these measurements, it can be seen that SAR(y)at a depth of 0 cm in the muscle-equivalent phantom represents up to 80% of SAR(tot). At 1 and 2 cm depth, SAR(y) is up to 95% of SAR(tot). Therefore, in homogeneous muscle-equivalent phantoms, E(y) is the largest E-field component and measurement of SAR(y) distribution is sufficient to characterize SAR-steering performance of the CFMA-12. SAR steering measurements at 1 cm depth in the muscle-equivalent phantom show that the SAR maximum varies by 40% (1 SD) around the average value of 38.8 W kg(-1) (range 10-65 W kg(-1)) between single antenna elements. The effective fieldsize (E(50)) varies by 14% (1 SD) around the average value of 19.1 cm(2).

Absorption↗

J/psi polarization in 800-GeV p-Cu interactions.

We present measurements of the polarization of the J/psi produced in 800-GeV proton interactions with a copper target. Polarization of the J/psi is sensitive to the ccmacr; production and hadronization processes. A longitudinal polarization is observed at large x(F), while at small x(F) the state is produced essentially unpolarized or slightly transversely polarized. No significant variation of the polarization is observed versus p(T).

Journal Article↗

Dynamic optical manipulation with a higher-order fractional bessel beam generated from a spatial light modulator.

Higher-order Bessel beams have been demonstrated to have the ability to trap and rotate low- and high-index particles simultaneously [Phys. Rev. A 66, 063402 (2002)]. The rotation and trapping is caused by the presence of orbital angular momentum arising from its azimuthal phase variation (that changes at integer multiples of 2pi) and the concentric rings of the Bessel mode. We demonstrate for the first time to our knowledge a branch from the family of higher-order Bessel beams that has fractional azimuthal variation at its beam axis. This new family of laser beams has the ability to perform dynamic optical manipulation with dynamic control of a spatial light modulator. Furthermore, we take the opportunity to explore the propagation characteristics of higher-order Bessel beams for which the azimuthal phase changes at noninteger multiples of 2pi.

Journal Article↗

Pulsatile secretion pattern of growth hormone in dogs with pituitary-dependent hyperadrenocorticism.

The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (+/-S.E.M.) basal GH level in dogs with PDH (0.7+/-0.1 microg/l) and the control dogs (0.6+/-0.1 microg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6+/-0.6 microg/l per 6 h) was significantly lower than that in the control dogs (7.3+/-1.0 microg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6+/-0.1 microg/l per 6 h) was significantly lower than that in the control dogs (3.7+/-1.0 microg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0-7 pulses/6 h) was significantly lower (P = 0.04) than that (5 pulses/6 h, range 3-9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.

Adrenal Cortex Hormones↗

Embryotrophic factor-3 from human oviductal cells affects the messenger RNA expression of mouse blastocyst.

Our previous results showed that embryotrophic factor-3 (ETF-3) from human oviductal cells increased the size and hatching rate of mouse blastocysts in vitro. The present study investigated the production of ETF-3 by an immortalized human oviductal cell line (OE-E6/E7) and the effects of ETF-3 on the mRNA expression of mouse embryos. The ETF-3 was purified from primary oviductal cell conditioned media using sequential liquid chromatographic systems, and antiserum against ETF-3 was raised. The ETF-3-supplemented Chatot-Ziomek-Bavister medium was used to culture Day 1 MF1 x BALB/c mouse embryos for 4 days. The ETF-3 treatment significantly enhanced the mouse embryo blastulation and hatching rate. The antiserum, at concentrations of 0.03-3%, abolished the embryotrophic effect of ETF-3. Positive ETF-3 immunoreactivity was detected in the primary oviductal cells, OE-E6/E7, and blastocysts derived from ETF-3 treatment. Vero cells (African Green Monkey kidney cell line), fibroblasts, and embryos cultured in control medium did not possess ETF-3 immunoreactivity. The mRNA expression patterns of the treated embryos were studied at the blastocyst stage by mRNA differential display reverse transcription-polymerase chain reaction (DDRT-PCR). The DDRT-PCR showed that some of the mRNAs were differentially expressed after ETF-3 treatment. Twelve of the differentially expressed mRNAs that had high homology with cDNA sequences in the GenBank were selected for further characterization. The differential expression of seven of these mRNAs (ezrin, heat shock 70-kDa protein, cytochrome c oxidase subunit VIIa-L precursor, proteinase-activated receptor 2, eukaryotic translation initiation factor 2beta, cullin 1, and proliferating cell nuclear antigen) was confirmed by semiquantitative RT-PCR. In conclusion, immortalized oviductal cells produce ETF-3, which influences mRNA expression of mouse blastocyst.

Animals↗

A randomized trial of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon.

BACKGROUND: Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C-infected patients. The use of high-dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved. AIM: To compare the efficacy and safety of re-treatment with an induction regimen of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy. METHODS: Previous virological non-responders to standard dose interferon (3-5 MU three times weekly for > or = 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha-2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000-1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy. RESULTS: End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow-up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06). CONCLUSIONS: In this small pilot study, a 36-week high-dose induction interferon monotherapy protocol did not yield sustained responses in previous non-responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High-dose interferon with ribavirin appears to be a therapeutic option for non-responders to conventional interferon monotherapy.

Adult↗

Influence of acute and chronic alcohol intake on the clinical course and outcome in acetaminophen overdose.

BACKGROUND: Animal studies on acetaminophen toxicity suggest that chronic alcohol intake affects the outcome adversely, whereas acute alcohol intake seems protective. Few clinical data are available. METHODS: We studied 209 consecutive patients with single-dose acetaminophen overdose. The combined influence of independent variables (gender, age, dose, delay to antidote treatment, chronic and acute alcohol intake and nomogram risk group) on dependent variables (death, development of hepatic encephalopathy and biochemical liver markers) was studied using multiple or logistic regression analysis. RESULTS: Fifty-seven (27.3%) patients had chronic alcohol intake and 45 (21.5%) patients had acute alcohol intake. Forty-four (21.1%) patients developed hepatic coma and 20 (43.5%) of these patients died. Chronic alcohol intake was significantly and independently associated with the development of hepatic coma, with a lower prothrombin index, lower platelet count, higher creatinine and higher bilirubin. The relative risks for hepatic coma and death were 5.3 (95% confidence interval, 2.2-12.4) and 1.4 (95% confidence interval, 0.5-3.9), respectively, in the chronic alcohol intake group compared with the no chronic alcohol intake group. Acute alcohol intake was not significantly associated with any of the dependent variables studied. CONCLUSIONS: Chronic alcohol intake enhances acetaminophen hepatotoxicity, whereas acute alcohol intake does not affect the clinical course.

Acetaminophen↗

Quantitative T1rho magnetic resonance imaging of RIF-1 tumors in vivo: detection of early response to cyclophosphamide therapy.

This study compares two potential magnetic resonance imaging (MRI) indices for noninvasive early detection of tumor response to chemotherapy: the spin-lattice relaxation in the rotating frame (T1rho) and the transverse relaxation time (T2). Measurements of these relaxation parameters were performed on a s.c. murine radiation-induced fibrosarcoma (RIF-1) model before and after cyclophosphamide treatment. The number of pixels exhibiting T1rho values longer than controls in viable regions of the tumor increased significantly as early as 18 h after drug administration and remained elevated up to 36 h after treatment (P < 0.005). Although a trend of increasing T2s relative to controls was noted in viable regions of the tumor 36 h after treatment, the changes were not statistically significant. Histological examination indicated a decrease in mitotic index that paralleled the changes in T1rho. We conclude that T1rho measurements may be useful for noninvasive monitoring of early response of tumors to chemotherapy.

Animals↗

Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations.

Noninvasive monitoring of antiangiogenic therapy was performed by serial power Doppler ultrasound imaging of murine tumors treated with recombinant interleukin 12, the results of which were correlated with assessments of tumor vascularity by microscopy. Growth of established K1735 tumors, but not of IFN-gamma-unresponsive K1735.N23 variants, was suppressed by treatment. Serial Doppler imaging of K1735 tumor vascularity during treatment revealed a progressive change from a diffuse perfusion pattern to a more punctate distribution. Quantitative analysis of the images revealed that color-weighted fractional average, representing overall tumor perfusion, consistently decreased in these tumors, primarily because of a decrease in fractional tumor cross-sectional area carrying blood flow. In contrast, these parameters increased in nonresponsive tumors during treatment. Confocal microscopy of thick tumor sections revealed a reduction in the density and arborization of vessels labeled in vivo by fluorochrome-conjugated lectin with effective treatment. Immunohistological examination of thin tumor sections confirmed the preferential loss of small vessels with successful therapy. Similar changes in tumor vascular anatomy and perfusion were also observed during recombinant interleukin 12 treatment of two other responsive murine tumor types. These results indicate that power Doppler ultrasound is a sensitive, noninvasive method for reporting functional consequences of therapy-induced vascular anatomical changes that can be used to serially monitor tumor perfusion and efficacy of antivascular therapy in clinical trials.

Animals↗

Observation of polarization in bottomonium production at square root of s = 38.8 GeV.

We present a measurement of the polarization observed for bottomonium states produced in p-Cu collisions at square root of s = 38.8 GeV. The angular distribution of the decay dimuons of the Upsilon(1S) state shows no polarization at small values of the fractional longitudinal momentum x(F) and transverse momentum p(T) but significant positive transverse production polarization for either p(T)>1.8 GeV/c or for x(F)>0.35. The Upsilon(2S+3S) (unresolved) states show a large transverse production polarization at all values of x(F) and p(T) measured. These observations challenge NRQCD calculations of the polarization expected in the hadronic production of bottomonium states.

Journal Article↗