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Biomedical subjects

J Fang

Publications and source records attributed to J Fang.

At least 55 records · Page 3Linked to original sources

Chemical modifications of the (1-->3)-alpha-D-glucan from spores of Ganoderma lucidum and investigation of their physicochemical properties and immunological activity.

A linear (1-->3)-alpha-D-glucan was isolated from the spores of Ganoderma lucidum (Fr.) Karst. Six different functionalized derivatives of the (1-->3)-alpha-D-glucan-aminopropylated, hydroxyethylated, sulfated, carboxymethylated, carboxymethylated and sulfated, and benzylamidated-carboxymethylated-with varying degrees of substitution were synthesized. The structural features and physicochemical properties of all derivatives were investigated by means of chemical and spectral analyses, and their effects on lymphocyte proliferation and antibody production were tested in vitro and in vivo. In general, the structural and physicochemical properties, and lymphocyte proliferation activity of all samples varied with the functionalized groups and the degree of substitution. The results of immunological assays indicated that some modified derivatives had potent stimulating effects on lymphocyte proliferation and antibody production and the introduction of carboxymethyl group with low degree of substitution (DS<0.28) was the best choice on the improvement of the immunostimulating activity.

Adjuvants, Immunologic↗

Self-assembled bismuth nanocrystallites.

Using a high-temperature organic solution reduction method, highly crystalline and single domain bismuth nanoparticles have been synthesized and self-assembled.

Journal Article↗

HIF-1alpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis.

The switch to the angiogenic phenotype represents a critical checkpoint during tumor progression. The acquisition of new capillary vessels provides newly vascularized tumor nodules with a distinct biological advantage over their avascular counterparts by conferring upon them the ability to expand and develop both locally and metastatically. To identify the molecules and mechanisms underlying this rate-limiting step in successful tumorigenesis, we have developed an in vivo tumor model that reproducibly recapitulates the angiogenic switch. Using this model, we have analyzed vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hypoxia-inducible factor-1alpha (HIF-1alpha) expression and activity in both avascular and vascular growth phases of the tumor. A significantly higher level of VEGF protein was detected in avascular tumor nodules compared with vascular nodules. As avascular tumors became vascularized, VEGF levels decreased approximately 10-fold. In contrast, bFGF levels were not elevated in avascular nodules but rather were detected at levels approximately 2 times higher in vascular nodules compared with the avascular tumor nodules. Given that VEGF is transcriptionally regulated by HIF-1alpha, immunohistochemical studies of chondrosarcoma nodules were conducted and revealed that the nuclear translocation of HIF-1alpha was detected exclusively in avascular tumor nodules. This study implicates HIF-1alpha-mediated up-regulation of VEGF but not bFGF in the switch to the angiogenic phenotype during tumorigenesis.

Animals↗

Changes in forest biomass carbon storage in China between 1949 and 1998.

The location and mechanisms responsible for the carbon sink in northern mid-latitude lands are uncertain. Here, we used an improved estimation method of forest biomass and a 50-year national forest resource inventory in China to estimate changes in the storage of living biomass between 1949 and 1998. Our results suggest that Chinese forests released about 0.68 petagram of carbon between 1949 and 1980, for an annual emission rate of 0.022 petagram of carbon. Carbon storage increased significantly after the late 1970s from 4.38 to 4.75 petagram of carbon by 1998, for a mean accumulation rate of 0.021 petagram of carbon per year, mainly due to forest expansion and regrowth. Since the mid-1970s, planted forests (afforestation and reforestation) have sequestered 0.45 petagram of carbon, and their average carbon density increased from 15.3 to 31.1 megagrams per hectare, while natural forests have lost an additional 0.14 petagram of carbon, suggesting that carbon sequestration through forest management practices addressed in the Kyoto Protocol could help offset industrial carbon dioxide emissions.

Biomass↗

Structural and immunological studies of a major polysaccharide from spores of Ganoderma lucidum (Fr.) Karst.

A polysaccharide isolated from spores of the fungus, Ganoderma lucidum, was found to be a complex glucan. On the basis of compositional and methylation analyses, periodate oxidation, Smith degradation, 1D and 2D NMR, and ESIMS experiments of the native polysaccharide and its degraded products, the polysaccharide was shown to have a backbone of beta-(1-->3)-linked D-glucopyranosyl residues, with branches of mono-, di- and oligosaccharide side chains substituting at the C-6 of the glucosyl residues in the main chain. Conformational analysis in aqueous solution and immunological activities of the native and degraded glucans were also investigated. The results suggested that the degree of substitution on the main chain and the length of side chains may be very important factors in determining the conformation and the biological activities of beta-(1-->3)-linked glucans.

Animals↗

Sleep modifies glutamate decarboxylase mRNA within the barrel cortex of rats after a mystacial whisker trim.

STUDY OBJECTIVES: Determine the effects of time of day and sleep deprivation on glutamate decarboxylase 67,000 MW (GAD67) mRNA during cortical synaptic reorganization induced by a unilateral trimming of the mystacial vibrissae in rats. DESIGN: Two experiments were conducted--One measured GAD67 mRNA in the barrel cortex at 3 or 6 h after a unilateral whisker cut at either light or dark onset; the other measured GAD67 mRNA after a unilateral whisker cut at light onset with or without sleep deprivation. SETTING: University-based Research Laboratory. PARTICIPANTS: Sprague-Dawley rats (250-350 g). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The reverse transcriptase polymerase chain reaction was used to measure the time of day changes in GAD67 mRNA after a unilateral whisker cut. GAD67 mRNA decreased in the barrel cortex at 3 and 6 h after a whisker trim at dark onset when the rats were mainly awake. No changes were observed in GAD67 mRNA levels after a whisker cut at light onset, a time when the rats mainly sleep. In situ hybridization for GAD67 mRNA supported these findings; no changes in GAD mRNA occurred in layer 4 of the barrel cortex that received input from the mystacial whiskers that were trimmed at light onset. However, when the rats were sleep-deprived, GAD67 mRNA increased in the barrel cortex receiving input from the lip hairs surrounding the trimmed mystacial whiskers. CONCLUSIONS: These data imply that sleep modifies GAD67 mRNA expression and that this effect is dependent upon the nature of the ongoing synaptic reorganization. They support the notion that sleep serves a synaptic function.

Animals↗

Deficiency of growth hormone-releasing hormone signaling is associated with sleep alterations in the dwarf rat.

The somatotropic axis, and particularly growth hormone-releasing hormone (GHRH), is implicated in the regulation of sleep-wake activity. To evaluate sleep in chronic somatotropic deficiency, sleep-wake activity was studied in dwarf (dw/dw) rats that are known to have a defective GHRH signaling mechanism in the pituitary and in normal Lewis rats, the parental strain of the dw/dw rats. In addition, expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and in the pituitary was also determined by means of reverse transcription-PCR, and GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and pituitary GHRH-R mRNA levels were decreased in the dw/dw rats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content in dw/dw rats was also less than that found in Lewis rats. The dw/dw rats had less spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4 hr of sleep deprivation, rebound increases in NREMS and REMS were normal in the dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in the dw/dw rats were only one-half of the response in the Lewis rats. The results are compared with sleep findings previously obtained in GHRH-deficient transgenic mice. The alterations in NREMS are attributed to the defect in GHRH signaling, whereas the decreases in REMS might result from the growth hormone deficiency in the dw/dw rat.

Animals↗

Sleep deprivation but not a whisker trim increases nerve growth factor within barrel cortical neurons.

Sleep is hypothesized to influence activity-driven changes in the brain microcircuitry. A change in the barrel cortex following the removal of the mystacial whiskers in rats is a model for synaptic plasticity. This model was combined with sleep deprivation and immunoreactivity for nerve growth factor (NGF) was determined. Sleep deprivation for 6 h after light onset significantly increased the number of NGF-immunoreactive pyramidal neurons in layer V of the barrel cortex. However, unilateral trimming of mystacial whiskers did not affect NGF immunoreactivity in the contralateral or ipsilateral barrel cortices when rats were allowed to sleep. If the rats received a unilateral whisker cut at light onset, and subsequently were deprived of sleep, increases in the NGF-immunoreactive neurons were only observed in the barrel cortex on the side that received input from the remaining intact whiskers. In contrast, NGF immunoreactivity on the side contralateral to the cut whiskers decreased in sleep-deprived animals to levels below those observed in the control animals that were allowed to sleep. These results suggest that NGF expression is influenced by the interaction of sleep, afferent input and the nature of ongoing synaptic reorganization. Further, results are consistent with the hypothesis that growth factors, such as NGF, form part of the mechanism responsible for sleep regulation and that they also form one facet of sleep-related synaptic plasticity.

Animals↗

Structures of bovine glutamate dehydrogenase complexes elucidate the mechanism of purine regulation.

Glutamate dehydrogenase is found in all organisms and catalyses the oxidative deamination of l-glutamate to 2-oxoglutarate. However, only animal GDH utilizes both NAD(H) or NADP(H) with comparable efficacy and exhibits a complex pattern of allosteric inhibition by a wide variety of small molecules. The major allosteric inhibitors are GTP and NADH and the two main allosteric activators are ADP and NAD(+). The structures presented here have refined and modified the previous structural model of allosteric regulation inferred from the original boGDH.NADH.GLU.GTP complex. The boGDH.NAD(+).alpha-KG complex structure clearly demonstrates that the second coenzyme-binding site lies directly under the "pivot helix" of the NAD(+) binding domain. In this complex, phosphates are observed to occupy the inhibitory GTP site and may be responsible for the previously observed structural stabilization by polyanions. The boGDH.NADPH.GLU.GTP complex shows the location of the additional phosphate on the active site coenzyme molecule and the GTP molecule bound to the GTP inhibitory site. As expected, since NADPH does not bind well to the second coenzyme site, no evidence of a bound molecule is observed at the second coenzyme site under the pivot helix. Therefore, these results suggest that the inhibitory GTP site is as previously identified. However, ADP, NAD(+), and NADH all bind under the pivot helix, but a second GTP molecule does not. Kinetic analysis of a hyperinsulinism/hyperammonemia mutant strongly suggests that ATP can inhibit the reaction by binding to the GTP site. Finally, the fact that NADH, NAD(+), and ADP all bind to the same site requires a re-analysis of the previous models for NADH inhibition.

Adenosine Diphosphate↗

The cloning of a rat peptidoglycan recognition protein (PGRP) and its induction in brain by sleep deprivation.

Peptidoglycan recognition protein (PGRP) binds to peptidoglycan (PG) or live bacteria and is upregulated by PG. PGRP is a ubiquitous protein involved in innate immunity. Tag7, a novel cytokine, is also induced by bacterial products; tag7 is apoptotic to murine L929 cells in a NF-kappaB-independent manner. Both of these genes are expressed in brain, lymphatic and haematopoietic tissues. We provide evidence that murine PGRP and tag7 encode identical transcripts and have structural relationships to lysozymes. Further, we have cloned the cDNA of rat PGRP and analyzed its expression in brains of sleep-deprived and control rats. The mRNA levels of PGRP/tag7 were measured by RT-PCR and compared to the housekeeping gene porphobilinogen deaminase (PBD). PGRP was constitutively expressed in rat brain. PGRP mRNA was increased by 43% and 17% in the brainstem and hypothalamus, respectively, in sleep-deprived rats compared to controls. The upregulation of PGRP expression by sleep deprivation suggests a role for PGRP in a homeostatic regulation of sleep.

Amino Acid Sequence↗

Seasonal changes of reproductive behavior and fecal steroid concentrations in Père David's deer.

From July 1997 to September 1997 and from March 1998 to July 1998, we studied reproductive behaviors of Père David's deer in Dafeng, China. During the field behavioral observations, we collected fresh voided fecal samples from the Père David's stags and hinds periodically and kept those samples under -20 degrees C until laboratory analysis. We analyzed the fecal testosterone, estradiol, and progesterone concentrations in those samples using radioimmunoassay. During this study, we also recorded 17 types of male reproductive behaviors and nine types of female reproductive behaviors. Reproductive behaviors and the fecal steroid concentrations showed overt seasonal fluctuations. There were statistically significant correlations between some male reproductive behaviors, such as anogenital sniffing, urine sniffing, urine spraying, wallowing, bellowing, antler adorning, Antler swags mud, chasing, herding hinds, chin resting, mounting and copulating, with the fecal testosterone concentrations. These results suggested that seasonal reproductive behaviors in stags are strongly associated with circulating testosterone. We also found that some female reproductive behaviors fluctuate corresponding with changes in fecal estrogen concentrations. Although there was no direct evidence to confirm the correlations between female reproductive behaviors and fecal estrogen in our experiment, we could not rule out that reproductive activities of hinds were largely related to ovarian estrogen secretion, and estrogen is necessary for inducing female reproductive behaviors.

Acclimatization↗

Changes in serum leptin levels during r-hGH treatment in growth hormone-deficient children.

To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebuttal children with growth hormone deficiency 1, 3 and 6 months before and after the treatment with recombinant human growth hormone (r-hGH). For comparison, 34 normal prepubertal children were also investigated. Relationship between leptin levels and body mass index (BMI) was observed at the same time. Our results showed that serum leptin level in normal prepubertal children was 1.22 +/- 0.34 ng/ml; the pretreatment serum leptin levels in GHD children was 3.08 +/- 2.41 ng/ml, which was significantly different from those 1, 3 and 6 months after GH treatment (i.e. 1.64 +/- 1.37 ng/ml, 1.57 +/- 1.40 ng/ml and 1.35 +/- 0.89 ng/ml respectively) (all P < 0.001). Our results suggested that r-hGH has a suppressive effect on leptin expression.

Adolescent↗

Polymorphism in ornamental and common carp strains (Cyprinus carpio L.) as revealed by AFLP analysis and a new set of microsatellite markers.

Forty-seven new microsatellite markers were generated and applied, together with the AFLP (Amplified Fragment Length Polymorphism) technique using two different enzyme combinations, to the genetic analysis of two carp species, Cyprinus carpio L. and Ctenopharyngodon idella. The extent of polymorphism and the genetic relationships between nine carp populations were studied. The incidence of microsatellites containing CA and CT motifs was estimated to be one every 17.4 and one every 126.3 kb, respectively, and their average allele numbers were four and five, respectively. Across populations, the average proportion of individuals that were heterozygous for microsatellite markers was 44.2% and the average allele number was 4.02. The EcoRI/TaqI combination generated more analyzable AFLP bands than the EcoRI/MseI pair, making the former preferable for the analysis of carp populations. The proportion of polymorphic AFLP bands within populations ranged from 6.7% in grass carp to 59.9% in Kohaku strain (Koi) of the ornamental carp. The fixation index (FST) for microsatellites in these populations was estimated to be 0.37, and for AFLP markers the value was 0.39. Genetic distance matrices derived from microsatellites and from two AFLP analyses were positively correlated. Grass carp showed fewer AFLP bands than other populations and was genotyped by only half of the microsatellite markers. These findings agree with genetic distance estimates in suggesting that the grass carp is phylogenetically quite remote from all the other populations examined.

Animals↗

Effects of bisphenol A on energy balance and accumulation in brown adipose tissue in rats.

Some environmental contaminants have the potential to affect humans or animals by mimicking the effects of hormones. Bisphenol A (BPA) is a weak estrogen agonist when tested using in vitro or in vivo bioassays. In addition to the well documented effects of estrogens on reproductive functions, ovarian hormones also have salient effects on mammalian energy balance and feeding behavior. In this study, we investigated the effects of BPA on body weight and food intake of ovariectomized adult female rats. Treatment with doses of 4 or 5 mg/day for 15 days resulted in a significant reduction of body weight gain with no reduction in food intake. A dose of 1 mg/day did not affect feeding or weight gain. BPA was detected in the blood, brain and adipose tissues of the BPA-treated animals but not in the vehicle control group. There was a preferential concentration of BPA in brown adipose tissue. These results indicate that BPA can affect energy balance and that brown adipose tissue may be a primary tissue into which BPA accumulates in mammals.

Adipose Tissue↗

Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging.

OBJECTIVES: To evaluate the relationship between low prostate-specific antigen (PSA) levels that are considered normal and the long-term risk of prostate cancer. METHODS: The relative risk of, and cumulative probability of freedom from, prostate cancer by PSA level and age decade was evaluated in male participants of a longitudinal aging study, the Baltimore Longitudinal Study of Aging (National Institute on Aging). The relative risk was estimated from a Cox proportional hazards regression model for men aged 40 to 49.9 (n = 351) and 50 to 59.9 (n = 445). The disease-free probability was determined by Kaplan-Meier survival analysis. RESULTS: The relative risk of prostate cancer for men aged 40 to 49.9 was 3.75 (range 1.6 to 8.6) when the PSA level was at or greater than the median (0.60 ng/mL) compared with men with PSA levels less than the median. This risk was similar for men aged 50 to 59.9 when comparing those with PSA levels greater than and less than the median (0.71 ng/mL). At 25 years, the cumulative probability of freedom from prostate cancer for men aged 40 to 49.9 was 89.6% (range 81% to 97%) and 71.6% (range 60% to 83%) when the PSA level was less than and greater than the median, respectively. The 25-year disease-free probability for men aged 50 to 59.9 was 83.6% (range 76% to 91%) and 58.9% (range 48% to 70%) when the PSA level was less than and greater than the median, respectively. CONCLUSIONS: The association between the baseline serum PSA level and the subsequent risk of prostate cancer suggests that the biologic events that predispose to prostate cancer begin early in middle age. Men who have baseline PSA levels that are "normal" but reflect a higher risk of prostate cancer may be the most appropriate candidates for future prevention trials. Those men with the lowest risk of prostate cancer on the basis of the baseline PSA measurements are unlikely to benefit from frequent PSA surveillance in an effort to detect prostate cancer early.

Adult↗