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J R Sun

Publications and source records attributed to J R Sun.

At least 19 recordsLinked to original sources
PubMed2001

An indicator cell assay for detection of human cytomegalovirus based on enhanced green fluorescent protein.

An indicator cell line (ML-UL54-EGFP) for the detection of human cytomegalovirus (HCMV) by a simple and direct method was developed. The stable line was constructed by introducing into mink lung cells an expression cassette that contains the enhanced green fluorescent protein (EGFP) reporter gene under the control of an HCMV-inducible promoter. The promoter was from the upstream region of the HCMV UL54 (pol) gene, an early gene promoter that is activated in the early phase of HCMV infection. Following infection with HCMV for 48 h, the stable line expressed well detectable level of the EGFP as observed under a fluorescence microscope. The sensitivity of the indicator cell assay is at least comparable with that of a plaque assay as assessed with a panel of HCMV strains. There were no detectable fluorescent cells after inoculations with several viruses other than HCMV, indicating high specificity. Analysis with flow cytometry revealed that the induced fluorescence from the infected cells was proportional to the titer of HCMV inoculated, making it possible to quantify HCMV infectious particles. In summary, the EGFP-based indicator cell line is of potential use for rapid detection and quantification of HCMV in clinical specimens.

Animals↗
PubMed2001

Molecular pathways that modify tumor radiation response.

Aberrant expression of signal transduction molecules in pathways controlling cell survival, proliferation, death, or differentiation are a common feature of all tumors. The identification of the molecules that are involved allows the development of novel tumor-specific strategies. Not surprisingly, targeting these pathways often also results in radiosensitization. The efficacy of such directed therapies may, however, be limited by the heterogeneity and the multiple mutations that are associated with the cancerous state. A more robust alternative may be to target global mechanisms of cellular control. The ubiquitin/proteasome degradation pathway is one candidate for such therapeutic intervention. This pathway is the main posttranscriptional mechanism that controls levels of many short-lived proteins involved in regulation of cell cycle progression, DNA transcription, DNA repair, and apoptosis. Many of these proteins are involved in various malignancies and/or radiation responses. In recent years, proteasome inhibitors have gained interest as a promising new group of antitumor drugs. PS-341, a reversible inhibitor of proteasome chymotryptic activity, is currently being tested in phase I clinical trials. In this study, we show that proteasome inhibition by PS-341 can alter cellular radiosensitivity in vitro and in vivo, in addition to having direct antitumor effects.

Animals↗
PubMed2001

[Altered behaviour and expression of Fos in rats born in hypergravity and their re-adaptation to the normal gravity].

Changes in behaviour relevant to the vestibular system were studied in Long-Evans rats which were fertilized, born and housed in 2 acceleration of gravity for 4 months and thereafter exposed to 1 acceleration of gravity, and expression of Fos protein in the brain stem was examined. Data from the hypergravity rats were compared respectively with those from the rotation group and the labyrinthectomized group. Static and locomotion modes of the hypergravity rats were changed, tension of extensor was enhanced and the abilities in locomotion equalization and orientation in swimming and air-righting response were reduced. The adaptation process varied with different behaviours. The time for recovery of the ability of orientating in swimming was the longest, taking more than 1 month. The Fos protein expression provides a useful tool for mapping brain functional activities after sensory stimulation, showing a low basal level in normal and labyrinthectomized groups. The hypergravity rats, on the other hand, exhibited more Fos-positive cells in the superior colliculus, inferior colliculus, periaqueductal gray, raphe dorsal nucleus and solitary nucleus. In contrast, the inferior olivary nuclei, locus coeruleus and vestibular nuclei were not strongly labeled. These spatial patterns of Fos expression suggest that a decrease in gravity-inertial force may activate a neural pathway different from the vestibulo-olivar pathways activated by an increase in gravity-inertial force.

Adaptation, Physiological↗
PubMed1998

[Enhancement of GAP-43 mRNA expression in the rat medial vestibular nucleus by labyrinthectomy].

Vestibular compensation is the most extensively investigated model for neuroplasticity. Growth-associated protein (GAP-43) mRNA plays a significant role in nerve regeneration and synaptic remodeling. Using in situ hybridization with DIG (digoxigenin)-labeled GAP-43 cDNA probe, changes of GAP-43 mRNA expression in the medial vestibular nucleus in the labyrinthectomized rats at 5, 12, 20 and 30th day after operation were investigated. The results clearly demonstrated that labyrinthectomy increased GAP-43 mRNA expression to different extents and amplitudes in bilateral medial vestibular nuclei. This finding suggests that upregulation of GAP-43 mRNA expression is related to regenerative sprouting, synaptic remodeling and neuroplasticity in vestibular compensation.

Adaptation, Physiological↗
PubMed1998

[Vestibular compensation: a privileged model for the study on plasticity of central nervous system].

Vestibular compensation is now considered as a privileged model for the study of the underlying mechanisms of restitution and substitution of functions after nervous system lesions. This model is ubiquitously suited for the research of plasticity of central nervous system and recuperation of functions. This review focuses on the latest progress of the research on vestibular compensation in the aspects of electrophysiology, biochemistry and molecular neurobiology as well as the expression of growth-associated protein (GAP-43), and the pharmacological effects of extract of Ginkgo biloba(EGb 761) during the course of vestibular compensation are specially discussed.

Adaptation, Physiological↗
PubMed1997

Induction of c-fos and junB mRNA following in vivo brain irradiation.

Although radiotherapy is a front line treatment for brain tumors, little is known about the in vivo molecular responses of brain to irradiation. In this study, expression of c-fos, c-jun and junB immediate-early genes were followed in mouse brain after irradiation. C-fos and junB, but not c-jun, mRNA was induced within 15 min in unanesthetized irradiated mice. Induction was transient and lasted < 4 h. The response was dose-dependent with increases in c-fos and junB mRNA levels after dose of > or = 2 and 7 Gy, respectively. Anesthesia of mice with pentobarbitol delayed the increases in mRNA expression and the response was attenuated. Pre-treatment of mice with dexamethasone, in a schedule which suppressed acute-phase gene expression after brain irradiation, did not significantly change c-fos and junB induction. Our results show that c-fos and junB responses occur in the brain in response to irradiation and that they can be modified by pentobarbital treatment but suggest that there is no direct correlation between the level of mRNA expression and later expression of cytokines or other acute-phase response genes.

Animals↗
PubMed1997

Delayed molecular responses to brain irradiation.

The chance of life-threatening complications occurring late after brain irradiation limits the efficacy of this form of cancer therapy. The molecular and cellular events that trigger radiation-induced brain damage are still unknown, but since they have the potential to serve as valuable targets for therapeutic intervention they are worth delineating. In this murine study, the effect of irradiation on the expression of molecules which are known to contribute to brain damage in other model systems was examined. Expression of genes encoding cytokines (TNF-alpha/beta, IL-1 alpha/beta, IL-2, IL-3, IL-4, IL-5, IL-6 and IFN-gamma), cytokine receptors (TNF-Rp55 and p75, IL-1R- p60 and p80, IFN-gamma R, and IL-6R), the cell adhesion molecule (ICAM-1), inducible nitric oxide synthetase (iNOS), anti-chymotrypsin (EB22/5.3), and the gliotic marker (GFAP) was evaluated over a 6-month period using a sensitive RNase protection assay (RPA). We had previously demonstrated that within 24 h of brain irradiation there is an acute transitory molecular response involving TNF-alpha, IL-1, ICAM-1, EB22/5.3 and GFAP. This study shows re-elevation of TNF-alpha, EB22/5.3 and GFAP mRNA levels at 2-3 months, but only TNF-alpha mRNA was overexpressed at 6 months. These time points are when neurological abnormalities are seen after higher doses. The data suggest that TNF-alpha may be involved in late brain responses to irradiation and could contribute to clinical symptoms.

Animals↗
PubMed1997

[Changes and compensation in the locomotor pattern of unilateral vestibular neurectomized cats].

In the present study the locomotor activity of unilateral vestibular neurectomized cats while crossing over a rotating beam along its longitudinal axis at different speeds was investigated. The kinematics of the body movement was recorded by means of a motion analysis system, with an optical automatic TV-image processor (E. L. I. T. E system) allowing a computer reconstruction of the 3 dimensional motion. Analysis was focused on the locomotion pattern as defined by several parameters including step length, step frequency and velocity, and an estimate of the height of the body gravity center. The results obtained with non-rotating beam showed that unilateral vestibular neurectomy induced significant changes in locomotor activity of the lesioned cats. Animals crossed over the beam with very slow locomotion speed and they typically exhibited a strong reduction in step length associated with a decrease in frequency. In addition, the gravity center of the walking cats was lower than the normal. The analysis performed with the rotating beam revealed different strategies of compensation, with cats moving either faster or slower as compared to their preoperative performance. Such strategies in locomotion speed regulation avoided falling from the rotating beam. Recovery to a nearly normal locomotor pattern was observed thereafter with a time delay comparable to that found in other behavioral studies dealing with the vestibular compensation process in the cat.

Adaptation, Physiological↗
PubMed1997

[Effect of norepinephrine on the thermosensitive neurons in preoptic area of hypothalamus tissue slices in cold acclimatized rats].

In this work, single unit firing activities were recorded in the preoptic anterior hypothalamus (POAH) brain slices of cold acclimatized and room-temperature housed rats (CR and RR) and the effects of NE on the neuronal discharges were observed. The neurons of POAH in CR became much more sensitive to NE than that in RR (the threshold concentration of NE of CR became significantly lowered). In comparison with RR, the percentage of warm sensitive neurons that could be excited by NE was decreased and some of them even showed inhibitory responses. On the other hand, the percentage of cold sensitive neurons that could be inhibited by NE was decreased and some of them even showed excitatory responses. The percentage of thermo-insensitive neurons that could be either excited or inhibited by NE were increased.

Acclimatization↗
PubMed1996

[Adaptive changes of preoptic thermosensitive neurons in hypothalamic tissue slices of rats after long-term exposure to cold environmental temperature].

In the present work, thermosensitivity and spontaneous firing rate of 86 preoptic neurons in hypothalamic tissue slices from 20 cold acclimated rats (CR, at 5 +/- 1 degrees C for more than 3 weeks) and 127 neurons from 35 warm acclimated rats (WR, at 20 +/- 3 degrees C for the same period) were recorded and compared. The results showed that: (1) The percentage of cold-sensitive neurons in CR were higher than that in WR, the critical temperature and the lowest temperature of the spontaneous firing activity of cold-sensitive neurons in CR were also lower than that in WR. (2) Thermosensitivity and critical temperature of the warm-sensitive neurons in CR were remarkably decreased, and spontaneous firing rate under 37 degrees C was increased. (3) Spontaneous firing rate (37 degrees C) of temperature insensitive neurons in CR were conspicuously increased and the lowest temperature extended downward. These profound changes in response to long-term cold exposure suggested that plasticity of preoptic neurons was involved in the thermoregulation in cold adaptation.

Adaptation, Physiological↗
PubMed1995

Induction of acute phase gene expression by brain irradiation.

PURPOSE: To investigate the in vivo acute phase molecular response of the brain to ionizing radiation. METHODS AND MATERIALS: C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-gamma), tumor necrosis factors (TNF-alpha and TNF-beta), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), alpha 1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. RESULTS: Levels of TNF-alpha, IL-1 beta, ICAM-1, EB22/5.3 and to a lesser extent IL-1 alpha and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. CONCLUSIONS: The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances.

Animals↗
PubMed1993

Lack of differential radiosensitization of hypoxic cells in a mouse tumor at low radiation doses per fraction by cisplatin.

Korbelik and Skov (Radiat. Res. 119, 145-156, 1989) have reported that cis-diamminedichloroplatinum (II) (cisplatin) shows substantial preferential radiosensitization of hypoxic cells in vitro at low radiation doses (1-4 Gy), and that the interaction seen with low doses of radiation is greatly diminished at high radiation doses. If such an interaction occurred with fractionated irradiation in vivo, it would be extremely important to radiation therapy, since the sensitizer enhancement ratios achievable in the low-dose region are higher than those achievable with current hypoxic cell radiosensitizers. We have tested this possibility in an experimental mouse tumor using fractionated irradiation under conditions in which the response of the tumor was determined by either its aerobic or its hypoxic cells. RIF-1 tumors were irradiated with 10 fractions of 1-4 Gy every 12 h with cisplatin given either as 12 mg/kg once before the first radiation dose or as 1.2 mg/kg at various times prior to each radiation dose. The tumors were irradiated with or without a clamp applied 2-3 min before each radiation dose. The effectiveness of the treatments was assayed by regrowth delay. Cisplatin caused a similar regrowth delay when used alone in both clamped and nonclamped tumors and produced a similar additive or supra-additive interaction when used with the 10 fractionated radiation schedule whether the tumors were hypoxic or aerobic. Our data suggest that cisplatin does not show any preferential radiosensitization of hypoxic cells with low-dose multifraction irradiation in this tumor, although a clear schedule-dependent interaction between the drug and radiation was seen for both aerobic and hypoxic tumors.

Animals↗
PubMed1991

scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair.

C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B cell-mediated immunity, apparently as a result of defective V(D)J joining of the immunoglobulin and T-cell receptor gene elements. In the present studies, we have defined the tissue, cellular, and molecular basis of another characteristic of these mice: their hypersensitivity to ionizing radiation. Bone marrow stem cells, intestinal crypt cells, and epithelial skin cells from scid mice are 2- to 3-fold more sensitive when irradiated in situ than are congenic BALB/c or C.B-17 controls. Two independently isolated embryo fibroblastic scid mouse cell lines display similar hypersensitivities to gamma-rays. In addition, these cell lines are sensitive to cell killing by bleomycin, which also produces DNA strand breaks, but not by the DNA crosslinking agent mitomycin C or UV irradiation. Measurement of the rejoining of gamma-ray-induced DNA double-strand breaks by pulsed-field gel electrophoresis indicates that these animals are defective in this repair system. This suggests that the gamma-ray sensitivity of the scid mouse fibroblasts could be the result of reduced repair of DNA double-strand breaks. Therefore, a common factor may participate in both the repair of DNA double-strand breaks as well as V(D)J rejoining during lymphocyte development. This murine autosomal recessive mutation should prove extremely useful in fundamental studies of radiation-induced DNA damage and repair.

Animals↗
PubMed1989

Enhancement of the antitumor effect of flavone acetic acid by the bioreductive cytotoxic drug SR 4233 in a murine carcinoma.

Flavone acetic acid (FAA, NSC 347512) is a new anticancer drug currently undergoing clinical investigation. Although the precise mechanism for its broad spectrum of activity against transplanted murine solid tumors is unknown, it has been reported that FAA reduces tumor blood flow and produces hemorrhagic necrosis. We have confirmed this finding with the murine transplanted carcinoma SCCVII: 200 mg/kg FAA reduced tumor blood flow to 20-30% of normal for 1-2 days as determined by rubidium 86 extraction. In an attempt to exploit the tumor hypoxia produced by FAA, we have combined it with the novel bioreductive drug SR 4233, a benzotriazine dioxide with high selective toxicity for hypoxic cells. Marked enhancement of the antitumor effect of FAA (200 mg/kg) was observed when it was combined with SR 4233 (0.1 and 0.2 mmol/kg). This was seen using tumor cell survival, regrowth delay, and histological endpoints, with the best results obtained when the two agents were injected simultaneously. These data suggest that targeting bioreductive cytotoxic agents to tumors by producing tumor hypoxia may be a valid way of increasing the tumor cell killing of these agents.

Animals↗
PubMed1989

Establishment, characteristics, and utilization of a new in vivo-in vitro system.

Radiotherapy and chemotherapy are two important methods for malignant tumor treatment. To research radiobiological response in therapy, we have established a better experimental method in contrast to the traditional ones such as TCD50, regrowth delay, cell survival curve, etc, all with their limitations. A new mouse tumor in vivo-in vitro system LA795 Vv-Vt has been developed for studies on radiobiology. Such a system could be used to study the in vivo response of a solid tumor by the in vitro cloning assay. For the purpose of increasing the PE in vitro, LA795 Vv-Vt tumor line was purified through culturing the cells as a clonogenic spheroid. The spheroids were then injected into the flank of mouse subcutaneously for tumor growth. The in vivo-in vitro system LA795 Vv-Vt is an excellent model dissecting and analyzing the various factors which affect tumor development and determine the response of tumor to specific agent and regimens.

Animals↗