Biomedical subjects

Rui Li

Publications and source records attributed to Rui Li.

At least 55 records · Page 3Linked to original sources

PubMed2006

Comprehensive analysis of 19q12 amplicon in human gastric cancers.

Amplification at 19q12 has been observed in multiple tumor types, while cyclin E1 (CCNE1) has been considered to be the key oncogene within this amplicon. We have previously applied cDNA microarray analysis to systematically characterize gene expression patterns of gastric tumor and nontumor samples. We identified a cluster of five tightly coregulated genes all located at chromosome 19q12, including CCNE1. We found that the 19q12 gene cluster is highly expressed in gastric tumors compared to nontumor gastric samples. Array based comparative genomic hybridization and real-time PCR was used to define the boundary of the 19q12 amplicon to a region of approximately 200 kb. Interestingly, we found that in some cases amplification at 19q12 was not associated with DNA copy number gain at CCNE1, suggesting that some other genes within the 19q12 amplicon may also have important function during gastric tumorigenesis. We found high expression of the 19q12 gene cluster to be statistically correlated with the cell proliferation gene signature. Using the SAM software, we identified a set of 577 genes whose expression levels positively correlated with the 19q12 gene cluster. GO term analysis revealed that this genelist is enriched with genes involved in cell cycle regulation and cell proliferation. In conclusion, expression array analysis combined with array comparative genomic hybridization and real-time PCR provides a new and powerful tool to identify clusters of genes which may be regulated by genomic DNA aberrations. In addition, our study indicates that amplification at 19q12 is associated with cell proliferation in vivo.

Adenocarcinoma↗

PubMed2006

Amphetamine-induced displacement of [18F] fallypride in striatum and extrastriatal regions in humans.

This study examined D-amphetamine (D-AMPH)-induced displacements of [18F] fallypride in striatal and extrastriatal regions and the correlations of these displacements with cognition, affect, and sensation-seeking behavior. In all, 14 normal subjects, six females and eight males (ages 21-32, mean age 25.9 years), underwent positron emission tomography (PET) with [18F]fallypride before and 3 h after a 0.43 mg/kg oral dose of D-AMPH. Levels of dopamine (DA) D2 receptor density were calculated with the reference region method of Lammerstma. Percent displacements in striatal and extrastriatal regions were calculated for the caudate, putamen, ventral striatum, medial thalamus, amygdala, substantia nigra, and temporal cortex. Correlations of changes in cognition, affect, and sensation seeking with parametric images of D-AMPH-induced DA release were computed. Significant displacements were seen in the caudate, putamen, ventral striatum substantia nigra, and temporal cortex with a trend level change in the amygdala. Greatest displacements were seen in striatal subdivisions-5.6% in caudate, 11.2% in putamen, 7.2% in ventral striatum, and 6.6% in substantia nigra. Lesser decrements were seen in amygdala-4.4%, temporal cortex-3.7%, and thalamus-2.8%. Significant clusters of correlations of regional DA release with cognition and sensation-seeking behavior were observed. The current study demonstrates that [18F]fallypride PET studies using oral D-AMPH (0.43 mg/kg) can be used to study D-AMPH-induced DA release in the striatal and extrastriatal regions in humans, and their relationship with cognition and sensation-seeking behavior.

Administration, Oral↗

PubMed2006

Lesions of an avian forebrain nucleus prevent changes in protein kinase C levels associated with deafening-induced vocal plasticity in adult songbirds.

We investigated the participation of protein kinase C (PKC) in the regulation of vocal plasticity in songbirds. Deafening of adult Bengalese finches causes initial song alteration, followed by stabilization. In parallel, the expression of PKC beta1 increases transiently 2 weeks after deafening, and then decreases gradually in the robust nucleus of the arcopallium (RA) of Bengalese finches, similar to the pattern observed during developmental song learning. First, we showed that in adult zebra finches, whose songs change more gradually after auditory deprivation than those of Bengalese finches, PKC in RA also increased to an equal degree 2 weeks after deafening, despite the species difference. Second, double-labeling with an anterograde tracer and PKC immunofluorescence revealed that PKC immunoreactivity in RA was detected on the synaptic terminals from a high premotor vocal nucleus (HVC), but not from the lateral magnocellular nucleus of the anterior nidopallium (LMAN). To determine what causes deafening-induced PKC increases, we blocked signals from LMAN, the final output nucleus to RA in the anterior forebrain pathway (AFP), by a unilateral LMAN lesion prior to auditory deprivation of adult Bengalese finches. The PKC immunoreactivity increased in RA of the intact hemisphere; however, in RA on the lesioned side, it was less intense than that of the unlesioned side. Thus, the deafening-induced PKC expression was suppressed by lesioning of LMAN. These results suggest that an output signal from the AFP via LMAN induces the increase in PKC activity on HVC-RA synapses that may regulate song plasticity.

Analysis of Variance↗

PubMed2006

Treatment of Streptococcus mutans with antisense oligodeoxyribonucleotides to gtfB mRNA inhibits GtfB expression and function.

We examined the effects of phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODN) targeted to mRNA transcribed from gtfB, which encodes synthesis of water-insoluble glucans in Streptococcus mutans. Treatment of S. mutans with 10 muM antisense PS-ODNs inhibited gtfB mRNA transcription, GtfB expression and water-insoluble glucan synthesis. The architecture of biofilms formed by antisense PS-ODNs-treated S. mutans showed reduced biomass, more dispersed distribution with enlarged interspaces and fewer layers of attached cells. PS-ODN treatment had no effect on the growth of S. mutans. Our results indicated that it might be feasible to use antisense PS-ODN as a novel agent in caries prevention.

Adjuvants, Pharmaceutic↗

PubMed2006

Sex differences in amphetamine-induced displacement of [(18)F]fallypride in striatal and extrastriatal regions: a PET study.

OBJECTIVE: The authors examined gender differences in d-amphetamine-induced displacements of [(18)F]fallypride in the striatal and extrastriatal brain regions and the correlations of these displacements with cognition and sensation seeking. METHOD: Six women and seven men underwent positron emission tomography (PET) with [(18)F]fallypride before and after an oral dose of d-amphetamine. Percent displacements were calculated using regions of interest and parametric images of dopamine 2 (D(2)) receptor binding potential. RESULTS: Parametric images of dopamine release suggest that the female subjects had greater dopamine release than the male subjects in the right globus pallidus and right inferior frontal gyrus. Gender differences were observed in correlations of changes in cognition and sensation seeking with regional dopamine release. CONCLUSION: Findings revealed a greater dopamine release in women as well as gender differences in the relationship between regional dopamine release and sensation seeking and cognition.

Administration, Oral↗

PubMed2006

Respiratory syncytial virus infection reversed anti-asthma effect of neonatal Bacillus Calmette-Guerin vaccination in BALB/c mice.

Bacillus Calmette-Guerin (BCG) vaccination can protect animals from asthma, but the effect of BCG on childhood asthma prevention is controversial in humans. To verify the hypothesis that the BCG anti-asthma effect in childhood might be reversed by a respiratory virus infection, newborn BALB/c mice were divided into five groups. Control and ovalbumin (OVA) groups were mock vaccinated and mock infected. The BCG/OVA group was BCG vaccinated and mock infected. The respiratory syncytial virus (RSV)/OVA group was mock vaccinated and RSV infected. The BCG/RSV/OVA group was BCG vaccinated and RSV infected. Except for the control group, all groups underwent OVA sensitization and challenge. Airway hyperresponsiveness (AHR) was measured after challenge and cells in bronchoalveolar lavage fluid (BALF) were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lung sections were scored. Mice with neonatal BCG vaccination (BCG/OVA group) were significantly protected from BALF eosinophilia, AHR to methacholine, peribronchiolitis, alveolitis, and peribronchial eosinophilia in comparison with the OVA, RSV/OVA, and BCG/RSV/OVA groups. AHR in the OVA group was greater than in the BCG/OVA group but lower than in the RSV/OVA and BCG/RSV/OVA groups. No significant differences in BALF eosinophilia, AHR, and lung inflammation were found between the RSV/OVA and BCG/RSV/OVA groups. The impact of BCG vaccination on anti-asthma in mice was not dependent on interferon-gamma, IL-4, and IL-10 levels. The results suggested that RSV infection can reverse the anti-asthma effect of neonatal BCG vaccination in BALB/c mice.

Animals↗

PubMed2006

[Clinical evaluation of four cytokines in serum and prostatic fluid in chronic abacterial prostatitis].

OBJECTIVE: To investigate the relationship between four cytokines in serum and prostatic fluid and chronic abacterial prostatitis (CAP). METHODS: The levels of interleukin-2 (IL-2), IL-4, IL-8, tumor necrosis factor-alpha (TNF-alpha) were detected in 86 patients with CAP [CAP I (n = 60), WBC > or = 10/HP; CAP II (n = 26, WBC < 10/HP)], and 20 healthy males as control by ELISA. RESULTS: IL-2, IL-8 and TNF-alpha in serum and prostatic fluid, and IL-4 in serum in patients with CAP I were markedly higher than those in the control, respectively (P < 0.05 or P < 0.01). No significant difference was observed in IL-4 level in prostatic fluid among CAP I, CAP II and control groups respectively (P > 0.05), and in IL-2, IL4, TNF-alpha in serum and prostatic fluid between CAP II group and the control (P > 0.05). IL-8 was correlated with WBC number in prostatic fluid (r = 0.62, P < 0.05). CONCLUSION: IL-2, IL-8, TNF-alpha may play roles in the process of pathogenesis of CAP, and they have applicable value in the diagnosis and typing of CAP.

Adult↗

PubMed2006

[The effects of glutathione S-transferase (GSTT1 and GSTM1) genes polymorphisms on treatment efficacy and prognosis of acute myeloid leukemia].

OBJECTIVE: To investigate the impact of GSTT1 and GSTM1 genotypes on response, drug side effects and prognosis of acute myeloid leukemia (AML). METHODS: GSTT1 and GSTM1 genotypes were analysed in 180 AML patients with PCR. Complete remission (CR) rate, drug side-effects, overall survival, relapse-free survival and relapse rate were compared in groups with or without GSTT1 and GSTM1 genes. RESULTS: (1) The CR rate (96.9%) in GSTT1 and GSTM1 genes double-present patients was significantly higher than that in patients of GSTT1 null or GSTM1 null (CR rate 78.0%) (P = 0.013). The risk of failure to achieve CR in patients with GSTT1 null/GSTM1 null is 8.736 times higher than that in patients with GSTT1 and GSTM1 genes double-present (odds ratio OR was 8.736, 95% CI was 1.146 - 66.574). The CR rate (88.4%) in GSTT1 present patients was also significantly higher than that in patients of GSTT1 null (CR rate 74.7%) (P = 0.021, OR = 2.572, 95% CI 1.136 - 5.826). (2) There was no significant relationship between GSTT1/GSTM1 genotypes and the lasting time of neutrophilic granulocyte (ANC) < 0.5 x 10(9)/L and PLT < 20 x 10(9)/L. The risk of ALT abnormality in patients with GSTM1 null is 2.593 times higher than that in patients with GSTM1 present (P = 0.016, 95% CI 1.176 - 5.717). (3) Overall survival and relapse-free survival of GSTT1 and GSTM1 double-present patients were significantly better than those in patients of GSTT1 null/GSTM1 null (mean overall survival was 68.4 months vs 38.5 months, P = 0.028, and mean relapse-free survival was 73.5 months vs 34.9 months, P = 0.014, respectively). Relapse-free survival in GSTT1 null patients was significantly shorter than that in patients with GSTT1 present (26.7 months vs 64.3 months, P = 0.038), but there was no significant difference of overall survival between the two groups. The relapse rate of double-present patients was significantly lower than that of GSTT1 null/GSTM1 null patients (13.3% vs 35.6%, P = 0.019). CONCLUSION: GSTT1 and GSTM1 genotypes were apparently related with response, drug side effects and prognosis of patients with AML. GSTT1 and GSTM1 genotype might be useful in selecting appropriate chemotherapy regimens for patients with AML.

Adolescent↗

PubMed2006

Epigallocatechin gallate protects dopaminergic neurons against 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity by inhibiting microglial cell activation.

OBJECTIVE: To observe whether the dopaminergic neuroprotective effect of (-)-epigallocatechin gallate (EGCG) is associated with its inhibition of microglial cell activation in vivo. METHODS: The effects of EGCG at different doses on dopaminergic neuronal survival were tested in a methyl-4-phenyl-pyridinium (MPP+)-induced dopaminergic neuronal injury model in the primary mesencephalic cell cultures. With unbiased stereological method, tyrosine hydroxylase-immunoreactive (TH-ir) cells were counted in the A8, A9 and A10 regions of the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice. The effect of EGCG on microglial activation in the SN was also investigated. RESULTS: Pretreatment with EGCG (1 to 100 micromol/L) significantly attenuated MPP+-induced TH-ir cell loss by 22.2% to 80.5% in the mesencephalic cell cultures. In MPTP-treated C57BL/6 mice, EGCG at a low concentration (1 mg/kg) provided significant protection against MPTP-induced TH-ir cell loss by 50.9% in the whole nigral area and by 71.7% in the A9 region. EGCG at 5 mg/kg showed more prominent protective effect than at 1 or 10 mg/kg. EGCG pretreatment significantly inhibited microglial activation and CD11b expression induced by MPTP. CONCLUSION: EGCG exerts potent dopaminergic neuroprotective activity by means of microglial inhibition, which shed light on the potential use of EGCG in treatment of Parkinson's disease.

Animals↗

PubMed2006

[An experimental study on mechanical properties of fiber layers in anulus fibrosus of lumbar interverbral disc 4,5].

We tested the mechanical properties of fiber layers in adult anulus fibrosus of lumbar interverbral disc 4,5. Aulus fibrosus of lumbar interverbral disc was delaminated by using microsurgical technique. 8 testing points were taken in each layer according to the fibers going and 5 testing specimens were taken from each testing point. The length was 15-20mm, the width 1-2mm, and the thickness 0. 1-0. 5mm. By using tension test,the relationship curves of stress and strain were tested, the fitting curves and equations were obtained, and then the elastic modulus, damage strain and damage stress were obtained. Therefore we knew the parameters and equations of mechanical properties of each testing point. We got the result that the elastic modulus of each testing point, along the radius from outside to inside, decreased with the increase of layers. The damage stress decreased linearly from outside to inside. The damage strains of the outside 9 layers increased slightly with the increase of layers, and the others were almost constants, i. e. 0.34 +/- 0.14. We get the conclusion that analus fibrosus of intervertebral disc has special mechanical properties corresponding with its functions, which is in a close relationship with lumbar vertebral diseases.

Adult↗

PubMed2006

[Combined effects of neonatal Bacillus Calmette-Guerin vaccination and respiratory syncytial infection on experimental asthma in mice].

OBJECTIVE: Neonatal Bacillus Calmette-Guerin (BCG) vaccination could decrease asthma prevalence in human according to "hygiene hypothesis". The authors proposed a hypothesis that effect of BCG vaccination on inhibiting asthma in human might be reversed by respiratory virus infection. The objective of this study was to observe combined effects of neonatal BCG vaccination and respiratory syncytial virus (RSV) infection on experimental asthma in mice. METHODS: Neonatal BALB/c mice were divided into five groups. Control and ovalbumin (OVA) groups were mock-vaccinated at birth and mock-infected at 3 weeks of age. BCG + OVA group was BCG-vaccinated and mock-infected. RSV + OVA group was mock-vaccinated and RSV-infected. BCG + RSV + OVA group was BCG-vaccinated and RSV-infected. Except for control group, all the other groups underwent ovalbumin (OVA) sensitization and challenge. Airway responsiveness to inhaled methacholine was measured and bronchoalveolar lavage (BAL) was performed after the last challege. Cells in BAL fluid (BALF) were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lungs was scored by staining with hematoxylin and eosin. RESULTS: (1) The numbers of total white cells, lymphocytes, monocytes, neutrophils, and eosinophils in the BALF from all OVA-sensitized/challenged groups were significantly greater than those in control (P < 0.01), and BCG + OVA group had significantly lower total white cells, lymphocytes and eosinophils as compared with other OVA-sensitized/challenged groups (P < 0.05 or 0.01). (2) All OVA-sensitized/challenged groups had significantly lower IFNgamma (P < 0.05) and higher IL-4 (P < 0.05) level in BALF as compared with control, but there was no significant difference among all OVA sensitized/challenged groups. There was no significant difference in IL-10 level between all experimental groups. (3) All OVA-sensitized/challenged groups showed significantly higher serum OVA-specific IgE titers than control (P < 0.05 or 0.01), but no significant difference was found among all OVA sensitized/challenged groups. (4) RSV + OVA and BCG + RSV + OVA groups displayed the highest airway resistance and subsequently in order as follows: OVA group, BCG + OVA group and control group in severity of airway hyperreactivity (AHR), but no significant difference was found between RSV + OVA and BCG + RSV + OVA groups. (5) Histological score of peribronchiolitis, perivasculitis, alveolitis, and peribronchial eosinophilia in all OVA-sensitized/challenged groups was significantly higher than that in control. BCG + OVA group had significantly milder peribronchiolitis and peribronchial eosinophilia than the other OVA-sensitized/challenged groups (P < 0.05) and significantly milder alveolitis than OVA and BCG + RSV + OVA groups (P < 0.05). CONCLUSION: Neonatal BCG vaccination decreased asthmatic inflammation and AHR and RSV infection could reverse anti-asthma effect of neonatal BCG vaccination in OVA-sensitized/challenged mouse model.

Animals↗

PubMed2006

[3D-data acquisition of partially edentulous cast using grating projection method].

OBJECTIVE: A method for 3D-data acquisition of partially edentulous cast was introduced to lay the foundation for reconstructing 3D digital model of a partially edentulous cast and studying computer aided design (CAD) to a removable partial denture framework. METHODS: Using projection system controlled by a computer, four frames of sinusoidal fringe pattern at pi/2 intervals were projected onto the surface of partially edentulous cast consecutively within 0.4 second. Deformed fringe patterns modulated by the surface height of the cast were recorded by a digital camera. The phase value with the height information was demodulated with phase-shifting method. The transition from the unwrapped phase to the height of the points on the cast was performed with triangulation method. The multiview 3D data was integrated automatically to obtain the complete 3D profile data and the 3D digital model of the partially edentulous cast was reconstructed. RESULTS: Dense and complete points-cloud data was achieved without scanning blind zone basically. The anatomic structure of reconstructed 3D digital model was sharp and clear. CONCLUSION: As an alternative for acquiring 3D data of partially edentulous cast, this method presented here with high precision and high speed meets the need for the subsequent 3D design to removable partial denture framework.

Computer-Aided Design↗

PubMed2006

[Study of genes involved in chronic myeloid leukemia with t (3; 21) (q26; q22) in blastic crisis].

OBJECTIVE: To explore genes involved in chronic myeloid leukemia (CML) with t (3; 21) (q26; q22) chromosome translocation in blastic crisis. METHODS: A case of CML patient with t (3; 21) (q26; q22) in blastic crisis was reported. AML1 and bcr/abl genes were detected by FISH in interphase and metaphase cells. Genes involved in t (3; 21) (q26; q22) were analysed by RT-PCR and sequencing. RESULTS: AML1 gene hybridization signal was detected in der (3) and der (21) chromosomes. AML1-Evi1, AML1-MDS1-Evi1, AML1-EAP fusion transcripts and Evi1 gene were detected in mRNA level, but no AML1-Evi1 fusion transcript. The mRNA expression level of AML1-MDS1-Evi1 fusion gene was 1.58 and 1.54 times higher than that of AML1-MDS1 and AML1-EAP, respectively. The mRNA expression level of Evi1 gene of the patient was 2.71 times higher than that of HEL cell line. CONCLUSION: t (3; 21) (q26; q22) resulted in the AML1-MDS1-Evi1, AML1-MDS1, AML1-EAP fusion transcripts, and Evi1 gene was also activated by the translocation. These secondary aberrations should be the molecular basis of CML patient with t (3; 21) (q26; q22) in blastic crisis.

Adult↗

PubMed2006

[Epidemiological feature of metabolic syndrome in Shanghai residents aged 15 - 74 years].

OBJECTIVE: To assess the prevalence of the metabolic syndrome in Shanghai residents. METHODS: A cross-sectional study was conducted in Shanghai with a representative sample of 14,327 Chinese adults from 15 to 74 years of age. The sample was randomly selected using stratified cluster sampling. The criteria of International Diabetes Federation (IDF), the US National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines and the China Diabetes Society (CDS), respectively, were applied for diagnosis. RESULTS: Diagnosed by using the IDF criterion, the crude prevalence of metabolic syndrome was 17.51%, and the age and gender-adjusted prevalence was 12.81% (95% CI: 12.26 - 13.36). The prevalence of the metabolic syndrome was higher in females than in males (14.79% and 10.93%, respectively), and higher in urban residents than in rural ones (13.71% and 10.72%, respectively). The age-specific prevalence of the metabolic syndrome increased in both male and female residents and the prevalence of metabolic syndrome in females 45 years of age or elder was significantly increased. The prevalence of having at least 3 parameters of metabolic syndrome was 22.28%. According to the ATP III guideline, the crude and age-adjusted prevalence of metabolic syndrome was 12.03% and 8.62%, respectively. Based on the criterion of CDS, they were 13.98% and 10.41%. CONCLUSION: There is a high prevalence of metabolic syndrome in Shanghai residents. Metabolic syndrome has become a noteworthy public health problem. It suggests that community-integrated control of metabolic syndrome should have its priority.

Adolescent↗

PubMed2006

[Determination in vitro of rat plasma protein binding rate of sinomenine by using microdialysis method].

AIM: To determine in vitro the rat plasma protein binding rate by using microdialysis method. METHODS: The binding rate was determined by using microdialysis probe as sampling tools and zero-net flux method as calibrating method. The regression equation was made by the difference of concentrations between the dialysis sample and the perfusate. The x-intercept of regression equation was the free drug concentration (Cf). The plasma protein binding rate was calculated by using the following equation: f = ( C0 - Cf)/C0. RESULT: The binding rate was kept relatively stable in the studied concentration range. CONCLUSION: It is feasible that the plasma protein binding rate can be determined by using microdialysis method.

Animals↗

PubMed2006

[Clinical characteristics and immunophenotype of aged patients with acute leukemia].

In order to analyze the clinical characteristics and biological features of acute leukemia in elderly, 104 acute leukemia patients in elderly were retrospectively analyzed and compared with 71 acute leukemia patients below 60 years old. The results showed that: (1) the proportion of AML in the aged group (73%) was higher than that in the young group (54.9%), and the difference was statistically significant (P < 0.05), but AML (M3) was absent in the aged group; (2) the median of bone marrow blast cell in the aged group was significantly lower than that in the young group (P < 0.05); (3) in AML, the frequently of CD14 expression was higher in the aged group (18.8%) than that in the young group (2.6%), while the expression frequencies of CD15 (37.5%), CD117 (62.5%), and CD38 (59.4%) were respectively lower in the aged group than that in the young group which were (69.2%) for CD15, (89.7%) for CD17, and (84.6%) for CD38 respectively, and the difference was also statistically significant (P < 0.05). (4) CD19 was most frequently expressed in ALL of the aged group and the positive rate was 100%; (5) there was no significant difference in expression of special lineage antigens and overlapping lineage antigens between the aged group and the young group (P > 0.05); (6) the expression frequency of unfavorable karyotypes in the aged group was higher than that in the young group, and the difference was statistically very significant (P < 0.01); (7) the complete remission rate (CR rate) in the aged group was 42.9%, 2-year survival rate in the aged group was 5.4%, and treatment-related mortality rate in the aged group was 26.8%, while the CR rate in the young group was 76.6%, the difference was statistically significant (P < 0.05). It is concluded that the expression frequency of CD14 associated with unfavorable prognosis is higher in the aged group than that in the young group, while the expression frequency of CD15 associated with favorable prognosis is lower in the aged group than that in the young group. The expression frequency of unfavorable karyotypes in the aged group is higher than that in the young group. The CR rate of acute leukemia in elderly is low, thus the patients in elderly often have unfavorable prognosis.

Adult↗

PubMed2005

Additional food folate derived exclusively from natural sources improves folate status in young women with the MTHFR 677 CC or TT genotype.

The effectiveness of additional food folate in improving folate status in humans is uncertain particularly in people with the common genetic variant (677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene. To examine the effect of a doubling of food folate consumption on folate status response variables, women (n=32; 18-46 years) with the MTHFR 677 CC or TT genotype consumed either 400 (n=15; 7 CC and 8 TT) or 800 (n=17; 8 CC and 9 TT) microg/day of dietary folate equivalents (DFE) derived exclusively from naturally occurring food folate for 12 weeks. A repeated measures two-factor ANOVA was used to examine the effect of the dietary treatment, the MTHFR C677T genotype and their interactions on serum folate, RBC folate and plasma total homocysteine (tHcy) during the last 3 weeks of the study. Consumption of 800 microg DFE/day resulted in serum folate concentrations that were 67% (P=.005) higher than consumption of 400 microg DFE/day (18.6+/-2.9 vs. 31.0+/-2.7 nmol/L, respectively) and RBC folate concentrations that were 33% (P=.001) higher (1172+/-75 vs. 1559+/-70 nmol/L, respectively). Serum folate (P=.065) and RBC folate (P=.022) concentrations were lower and plasma tHcy was higher (P=.039) in women with the MTHFR 677 TT genotype relative to the CC genotype. However, no genotype by dietary treatment interaction was detected. These data suggest that a doubling of food folate intake will lead to marked improvements in folate status in women with the MTHFR 677 CC or TT genotype.

Adolescent↗

PubMed2005

Interleukin-7-dependent expansion and persistence of melanoma-specific T cells in lymphodepleted mice lead to tumor regression and editing.

Active-specific immunotherapy with dendritic cells loaded with peptide derived from the melanoma antigen, gp100, failed to mediate regression of established B16F10 melanoma in normal mice. Dendritic cell vaccination induced activation and subsequent deletion of adoptively transferred naive CD8+ T-cell receptor transgenic (pmel-1) T cells specific for gp100 in normal mice. In lymphodepleted mice, dendritic cell vaccination produced greater T-cell expansion, long-term persistence of memory T cells, and tumor regression. Most tumors that persisted in the presence of functional memory T cells had either lost or exhibited reduced expression of MHC class I or gp100 proteins. In contrast to other naive T cells, pmel-1 T cells adoptively transferred to lymphodepleted mice exhibited faster proliferation and a more differentiated phenotype after exposure to peptide-pulsed dendritic cells. Proliferation and persistence of pmel-1 T cells was highly dependent on interleukin-7 (IL-7) in irradiated mice, and IL-15 when IL-7 was neutralized, two critical homeostatic cytokines produced in response to the irradiation-induced lymphodepletion.

Animals↗