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Biomedical subjects

S Feng

Publications and source records attributed to S Feng.

At least 19 recordsLinked to original sources

STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-kappaB p65.

We recently demonstrated that STAT5 can induce a variety of biological functions in mouse IL-3-dependent Ba/F3 cells; STAT5-induced expression of pim-1, p21(WAF/Cip1), and suppressor of cytokine signaling-1/STAT-induced STAT inhibitor-1/Janus kinase binding protein is responsible for induction of proliferation, differentiation, and apoptosis, respectively. In the present study, using a constitutively active STAT5A (STAT5A1*6), we show that STAT5 induces macrophage differentiation of mouse leukemic M1 cells through a distinct mechanism, autocrine production of IL-6. The supernatant of STAT5A1*6-transduced cells contained sufficient concentrations of IL-6 to induce macrophage differentiation of parental M1 cells, and STAT3 was phosphorylated on their tyrosine residues in these cells. Treatment of the cells with anti-IL-6 blocking Abs profoundly inhibited the differentiation. We also found that the STAT5A1*6 transactivated the IL-6 promoter, which was mediated by the enhanced binding of NF-kappaB p65 (RelA) to the promoter region of IL-6. These findings indicate that STAT5A cooperates with Rel/NF-kappaB to induce production of IL-6, thereby inducing macrophage differentiation of M1 cells in an autocrine manner. In summary, we have shown a novel mechanism by which STAT5 induces its pleiotropic functions. Cytokines

Animals↗

Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal relationship with hepatitis C virus allograft hepatitis, and impact on mortality.

BACKGROUND: Recent studies suggest an association between diabetes mellitus and hepatitis C virus (HCV) infection. Our aim was to determine (1) the prevalence and determinants of new onset posttransplant diabetes mellitus (PTDM) in HCV (+) liver transplant (OLT) recipients, (2) the temporal relationship between recurrent allograft hepatitis and the onset of PTDM, and (3) the effects of antiviral therapy on glycemic control. METHODS: Between January of 1991 and December of 1998, of 185 OLTs performed in 176 adult patients, 47 HCV (+) cases and 111 HCV (-) controls were analyzed. We reviewed and analyzed the demographics, etiology of liver failure, pretransplant alcohol abuse, prevalence of diabetes mellitus, and clinical characteristics of both groups. In HCV (+) patients, the development of recurrent allograft hepatitis and its therapy were also studied in detail. RESULTS: The prevalence of pretransplant diabetes was similar in the two groups, whereas the prevalence of PTDM was significantly higher in HCV (+) than in HCV (-) patients (64% vs. 28%, P=0.0001). By multivariate analysis, HCV infection (hazard ratio 2.5, P=0.001) and methylprednisolone boluses (hazard ratio 1.09 per bolus, P=0.02) were found to be independent risk factors for the development of PTDM. Development of PTDM was found to be an independent risk factor for mortality (hazard ratio 3.67, P<0.0001). The cumulative mortality in HCV (+) PTDM (+) versus HCV (+) PTDM (-) patients was 56% vs. 14% (P=0.001). In HCV (+) patients with PTDM, we could identify two groups based on the temporal relationship between the allograft hepatitis and the onset of PTDM: 13 patients developed PTDM either before or in the absence of hepatitis (group A), and 12 concurrently with the diagnosis of hepatitis (group B). In gr. B, 11 of 12 patients received antiviral therapy. Normalization of liver function tests with improvement in viremia was achieved in 4 of 11 patients, who also demonstrated a marked improvement in their glycemic control. CONCLUSION: We found a high prevalence of PTDM in HCV (+) recipients. PTDM after OLT was associated with significantly increased mortality. HCV infection and methylprednisolone boluses were found to be independent risk factors for the development of PTDM. In approximately half of the HCV (+) patients with PTDM, the onset of PTDM was related to the recurrence of allograft hepatitis. Improvement in glycemic control was achieved in the patients who responded to antiviral therapy.

Antiviral Agents↗

Five unique compounds: xyloketals from mangrove fungus Xylaria sp. from the South China Sea coast.

Five unique metabolites, xyloketals A (1), B (2), C (3), D (4), and E (5), and the known 6 were isolated from mangrove fungus Xylaria sp. (no. 2508), obtained from the South China Sea. The structures of these compounds were elucidated by spectroscopic and X-ray diffraction experiments. Xyloketal A is a ketal compound with a C(3) symmetry and xyloketals B-E are its analogues. It was found that xytoketal C slowly rearranged to xytoketal B in DMSO-d(6)() solution at room temperature. Xyloketal A exhibited the activity of inhibiting acetylcholine esterase.

Acetylcholinesterase↗

Paternal population history of East Asia: sources, patterns, and microevolutionary processes.

Asia has served as a focal point for human migration during much of the Late Pleistocene and Holocene. Clarification of East Asia's role as a source and/or transit point for human dispersals requires that this region's own settlement history be understood. To this end, we examined variation at 52 polymorphic sites on the nonrecombining portion of the Y chromosome (NRY) in 1,383 unrelated males, representing 25 populations from southern East Asia (SEAS), northern East Asia (NEAS), and central Asia (CAS). The polymorphisms defined 45 global haplogroups, 28 of which were present in these three regions. Although heterozygosity levels were similar in all three regions, the average pairwise difference among haplogroups was noticeably smaller in SEAS. Multidimensional scaling analysis indicated a general separation of SEAS versus NEAS and CAS populations, and analysis of molecular variance produced very different values of Phi(ST) in NEAS and SEAS populations. In spatial autocorrelation analyses, the overall correlogram exhibited a clinal pattern; however, the NEAS populations showed evidence of both isolation by distance and ancient clines, whereas there was no evidence of structure in SEAS populations. Nested cladistic analysis demonstrated that population history events and ongoing demographic processes both contributed to the contrasting patterns of NRY variation in NEAS and SEAS. We conclude that the peopling of East Asia was more complex than earlier models had proposed-that is, a multilayered, multidirectional, and multidisciplinary framework is necessary. For instance, in addition to the previously recognized genetic and dental dispersal signals from SEAS to NEAS populations, CAS has made a significant contribution to the contemporary gene pool of NEAS, and the Sino-Tibetan expansion has left traces of a genetic trail from northern to southern China.

Animals↗

Oscillatory electroosmosis-enhanced intra/inter-particle liquid transport and its primary applications in the preparative electrochromatography of proteins.

The concept of generating an oscillatory electroosmotic flux inside the porous particle to enhance the intra-particle mass transport was presented and a new kind of electrochromatography carried out in a five-compartment electrolyzer were developed. The adsorbent was packed in the central compartment, while the neighboring compartments were used as the elution compartments and the electrode compartments, respectively. Chromatographic separations of human serum albumin on Blue Sepharose Fast Flow, bovine serum albumin (BSA) on DEAE-Sepharose Fast Flow, and BSA on hydroxyapatite were carried out, respectively. The adsorption isotherms were shown to be independent of electric field, while the increase in the electric field strength resulted in a linear increase in the magnitude of electroosmotic flux and the improvement of the breakthrough behavior in all cases. The experiment results have demonstrated the effectiveness of the oscillatory electroosmosis in enhancing intra- and inter-particle mass transport and its high potential to large-scale chromatography.

Adsorption↗

Infection of mice with the agent of human granulocytic ehrlichiosis after different routes of inoculation.

Population kinetics of the agent of human granulocytic ehrlichiosis (aoHGE) were examined after needle and tickborne inoculation of C3H mice. Blood, skin, lung, spleen, liver, kidney, brain, lymph node, and bone marrow samples were analyzed by using real-time polymerase chain reaction (PCR) at various intervals after inoculation, using a p44 gene target. The highest number of copies of the p44 gene target occurred in blood and bone marrow samples, emphasizing aoHGE leukocytotropism. Numbers of copies of the p44 gene target in other tissues reflected vascular perfusion rather than replication. Needle-inoculated infected mice had earlier dissemination, but kinetics of infection in both groups were parallel, with declining rates of infection by day 20 and recovery in some mice on days 20-60 after inoculation. On the basis of an aoHGE lysate ELISA, mice seroconverted by day 10 after inoculation. Therefore, real-time PCR is useful for quantitative studies with the aoHGE in experimental infections, and results showed that needle inoculation can be used to study the aoHGE infection because of its similarity to tickborne inoculation.

Animals↗

Glycoprotein Ib/IX/V binding to the membrane skeleton maintains shear-induced platelet aggregation.

The extracellular domain of glycoprotein (Gp) Ibalpha serves as the von Willebrand factor (vWf) receptor that triggers shear stress-dependent platelet aggregation. Its intracellular domain associates with actin-binding protein-280 (filamin 1a) that binds directly to filamentous actin, thereby linking the membrane skeleton to GpIbalpha. We examined the functional significance of GpIbalpha interactions with actin during platelet aggregation in response to 120 dyn/cm(2) shear stress. Lysates of resting and sheared platelets were centrifuged at approximately 13,000xg for 15 min, and GpIbalpha was immunoprecipitated from the lysate supernatant. GpIbalpha and coimmunoprecipitated proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotted with antibodies specific for GpIbalpha and actin. We observed a significant increase in the amounts of actin coimmunoprecipitating with GpIbalpha as platelets aggregated in response to shear stress. Actin/GpIbalpha interactions reached a maximum after 90 s of shear stress. Monoclonal antibody (mAb) blockade of vWf binding to GpIbalpha inhibited shear stress-induced platelet aggregation and actin associating with GpIbalpha. Pretreatment of platelets with cytochalasin D resulted in the inhibition of actin binding to GpIbalpha in sheared platelets and in an increase in the rate and magnitude of platelet disaggregation. These data indicate that shear stress causes changes in the association between GpIbalpha and the actin-based membrane skeleton. The increased interaction between GpIbalpha and the actin-based membrane skeleton results from shear-induced vWf binding to GpIbalpha and is mechanoprotective in that it maintains shear-induced aggregation of activated platelets.

Actins↗

Higher-order transverse modes of ultrashort isodiffracting pulses.

We present a family of space-time nonseparable analytic solutions describing spatiotemporal dynamics of isodiffracting single-cycle and few-cycle pulses with Hermite-Gaussian and Laguerre-Gaussian transverse profiles. These solutions are space-time localized wave packets propagating in free space. The transverse field profile acts as a spatially dependent filter, modifying the pulse spectrum and removing certain frequencies. The consequences of those effects in the time domain are the distortions of pulse envelope and temporal wave form and the creation of "dark pulses" at certain transverse positions. In addition, due to the space-time coupling, the instantaneous transverse field pattern changes inside the pulse, as well as with propagation distance. These higher-order mode solutions can be used to analyze reflected or scattered terahertz pulses, and to understand the wave-form distortions of terahertz signals in applications. They are also capable of modeling pulsed fields of phase locking of both transverse and longitudinal modes in total mode-locked lasers.

Journal Article↗

Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers.

Paclitaxel (Taxol) is an antineoplastic drug effective for various cancers especially ovarian and breast cancer. Due to its high hydrophobicity, however, an adjuvant such as Cremophor EL has to be used in its clinical administration, which causes serious side-effects. Nanospheres of biodegradable polymers could be an ideal solution. This study investigates the effects of various emulsifiers on the physical/chemical properties and release kinetics of paclitaxel loaded nanospheres fabricated by the solvent extraction/evaporation technique. It is shown that phospholipids could be a novel type of emulsifiers. The nanospheres manufactured with various emulsifiers were characterized by laser light scattering for their size and size distribution; scanning electron microscopy (SEM) and atomic force microscopy (AFM) for their surface morphology; zeta potential analyser for their surface charge; and, most importantly, X-ray photoelectron spectroscopy (XPS) for their surface chemistry. The encapsulation efficiency and in vitro release profile were measured by high performance liquid chromatography (HPLC). It is found that dipalmitoyl-phosphatidylcholine (DPPC) can provide more complete coating on the surface of the products which thus results in a higher emulsifying efficiency compared with polyvinyl alcohol (PVA). Our result shows that the chain length and unsaturation of the lipids have a significant influence on the emulsifying efficiency. Phospholipids with short and saturated chains have excellent emulsifying effects.

Antineoplastic Agents, Phytogenic↗

Phosphatidylinositol 4,5-bisphosphate induces actin stress-fiber formation and inhibits membrane ruffling in CV1 cells.

Phosphatidylinositol 4,5 bisphosphate (PIP(2)) is widely implicated in cytoskeleton regulation, but the mechanisms by which PIP(2) effect cytoskeletal changes are not defined. We used recombinant adenovirus to infect CV1 cells with the mouse type I phosphatidylinositol phosphate 5-kinase alpha (PIP5KI), and identified the players that modulate the cytoskeleton in response to PIP(2) signaling. PIP5KI overexpression increased PIP(2) and reduced phosphatidylinositol 4 phosphate (PI4P) levels. It promoted robust stress-fiber formation in CV1 cells and blocked PDGF-induced membrane ruffling and nucleated actin assembly. Y-27632, a Rho-dependent serine/threonine protein kinase (ROCK) inhibitor, blocked stress-fiber formation and inhibited PIP(2) and PI4P synthesis in cells. However, Y-27632 had no effect on PIP(2) synthesis in lysates, although it inhibited PI4P synthesis. Thus, ROCK may regulate PIP(2) synthesis by controlling PI4P availability. PIP5KI overexpression decreased gelsolin, profilin, and capping protein binding to actin and increased that of ezrin. These changes can potentially account for the increased stress fiber and nonruffling phenotype. Our results establish the physiological role of PIP(2) in cytoskeletal regulation, clarify the relation between Rho, ROCK, and PIP(2) in the activation of stress-fiber formation, and identify the key players that modulate the actin cytoskeleton in response to PIP(2).

ADP Ribose Transferases↗

New materials in hydrothermal synthesis.

In this Account we describe the hydrothermal synthesis of some new materials including microporous crystals, ionic conductors, complex oxides and fluorides, low-dimensional aluminophosphates, inorganic-organic hybrid materials, and particularly condensed materials such as diamond and inorganic helical chains. Hydrothermal synthesis in biology and environment sciences is also introduced. The increasing interest in hydrothemal synthesis derives from its advantages in terms of high reactivity of reactants, easy control of solution or interface reactions, formation of metastable and unique condensed phases, less air pollution, and low energy consumption.

Crystallization↗

RAPD-PCR typing of Acinetobacter isolates from activated sludge systems designed to remove phosphorus microbiologically.

AIMS: This study investigated whether there were differences in RAPD fingerprints between already described genomic species of Acinetobacter and those from activated sludge systems. Whether plant-specific populations of acinetobacters exist was also examined. METHODS AND RESULTS: Fifty-two isolates of Acinetobacter from four biological phosphorus removal (EBPR) systems of different configurations, and the known genomic species, were characterized using RAPD-PCR, and fragments separated on agarose gels. Patterns were analysed using Gel Pro software and data analysed numerically. RAPD-PCR produced patterns suggesting that many environmental isolates differ from known genomic species. In two cases, strains from individual plants clustered closely enough together to imply that there may be plant-specific populations of acinetobacters. CONCLUSION: The data suggest that current understanding of the taxonomic status of Acinetobacter may need modifying to accommodate non-clinical isolates, as many of the clusters emerging after numerical analysis of RAPD-PCR fragments from activated sludge isolates were quite separate from the clusters containing the already described genomic species. Some evidence was also obtained from the clusters generated to support a view that particular populations of Acinetobacter may occur in individual activated sludge plants. SIGNIFICANCE AND IMPACT OF THE STUDY: These data suggest that the current understanding of the systematics of Acinetobacter, based as it is almost exclusively on clinical isolates, may need drastic revision to accommodate environmental strains. They also suggest that a re-examination of the importance and role of Acinetobacter in the activated sludge process may be appropriate.

Acinetobacter↗

Identification and quantitation of 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid, a major metabolite of delta9-tetrahydrocannabivarin.

After incubation of delta9-tetrahydrocannabivarin with human hepatocytes, a major metabolic product was detected by gas chromatography-mass spectrometry that showed identical retention time and mass spectrum to the synthetic 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (11-nor-delta9-THCV-9-COOH). Analysis of human urine specimens from marijuana users and plasma samples from Marinol users showed that 11-nor-delta9-THCV-9-COOH was only present in urine specimens of marijuana users. These results supported the conclusion that identification of 11-nor-delta9-THCV-9-COOH in a donor's urine specimen indicates the use or ingestion of cannabis-related product(s) and would not explain the sole use of Marinol.

Chromatography, High Pressure Liquid↗

Delta9-tetrahydrocannabivarin as a marker for the ingestion of marijuana versus Marinol: results of a clinical study.

Delta9-tetrahydrocannabinol (THC), the main psychologically active ingredient of the cannabis plant (marijuana), has been prepared synthetically and used as the bulk active ingredient of Marinol, which was approved by the FDA for the control of nausea and vomiting in cancer patients receiving chemotherapy and as an appetite stimulant for AIDS patients. Because the natural and the synthetic THC are identical in all respects, it is impossible to determine the source of the urinary metabolite of THC, 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), in a urine specimen provided in a drug-testing program. Over the last few years there has been a need to determine whether a marijuana positive drug test is the result of the ingestion of marijuana (or a related product) or whether it results from the sole use of Marinol. We have previously proposed the use of delta9-tetrahydrocannabivarin (THCV, the C3 homologue of THC) as a marker for the ingestion of marijuana (or a related product) because THCV is a natural component of most cannabis products along with THC and does not exist in Marinol. We have also reported that THCV is metabolized by human hepatocytes to 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (THCV-COOH); therefore, the presence of the latter in a urine specimen would indicate that the donor must have used marijuana or a related product (with or without Marinol). In this study, we provide clinical data showing that THCV-COOH is detected in urine specimens collected from human subjects only after the ingestion of marijuana and not after the ingestion of Marinol (whether the latter is ingested orally or by smoking). Four subjects (male and female) participated in the study in a three-session, within-subject, crossover design. The sessions were conducted at one-week intervals. Each subject received, in separate sessions and in randomized order, an oral dose of Marinol (15 mg), a smoked dose of THC (16.88 mg) in a placebo marijuana cigarette, or a smoked dose of marijuana (2.11% THC and 0.12% THCV). Urine samples were collected and vital signs were monitored every 2 h for a 6-h period following drug administration. Subjects were then transported home, were given sample collection containers and logbooks, and were instructed to record at home the volume and time of every urine collection for 24 h, and once a day for the remainder of a week (6 days). Subjects were also instructed to freeze the urine samples until the next session. All urine samples were analyzed by GC-MS for THC-COOH and THCV-COOH using solid-phase extraction and derivatization procedure on RapidTrace and TBDMS as the derivative. The method had a limit of detection of 1.0 ng/mL and 1.0 ng/mL for THCV-COOH and THC-COOH, respectively.

Administration, Oral↗

Hydrolysis of conjugated metabolites of buprenorphine. I. The quantitative enzymatic hydrolysis of buprenorphine-3-beta-D-glucuronide in human urine.

Buprenorphine, which is a powerful analgesic, a substitution drug for opioids widely used in Europe, and a promising new drug currently undergoing clinical trials in the treatment of opioid dependence in the U.S., is excreted in human urine mainly as glucuronide conjugates. In gas chromatographic-mass spectrometric analysis, the urine specimens must be first hydrolyzed to release buprenorphine from its glucuronide conjugates. In order to evaluate the existing hydrolysis methods and to find the optimal hydrolysis conditions, buprenorphine-3-beta-D-glucuronide (B3G) was synthesized. Urine fortified with synthetic B3G was hydrolyzed using acid, base, and beta-glucuronidases from different source species, including Helix pomatia, Escherichia coli, and Patella vulgata. Glusulase, a preparation containing both beta-glucuronidase (H. pomatia) and sulfatase, was also tested. Whereas both acidic and basic hydrolysis were ineffective, quantitative hydrolysis could be achieved by using beta-glucuronidases under appropriate conditions. However, we found that there was a marked difference in the reactivity of these enzymes (E. coli > H. pomatia >> P. vulgata). The optimal incubation conditions for enzymatic hydrolysis of B3G were 2 h at 37 degrees C for E coli and 4 h at 60 degrees C or 16 h at 37 degrees C for H. pomatia. Using 1000 Fishman units of either of these two enzymes, effective hydrolysis could be achieved even when the B3G concentration was as high as 2000 ng/mL. Glusulase was equally effective toward B3G if the fortified urine samples were incubated with 25 microL of this enzyme for 1 h at 60 degrees C.

Animals↗