Biomedical subjects

Y Shen

Publications and source records attributed to Y Shen.

At least 19 recordsLinked to original sources

PubMed2007

Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy.

IgA nephropathy (IgAN) is a polygenic disorder and the precise role of genetic factors remains elusive. Increasing evidences have implicated the aberrant galactosylation of IgA1 molecules in the pathogenesis of IgAN. The galactosyltransferase, core 1 beta3-Gal-T, and its chaperone, Cosmc, play important roles in beta1,3 glycosylation of IgA1 molecule. A case-control association study was performed to investigate the association between single-nucleotide polymorphisms (SNPs) of C1GALT1 and C1GALT1C1 genes and the susceptibility to IgAN. A total of 1164 subjects were enrolled, including 670 IgAN patients and 494 geographically matched healthy controls. Five SNPs, -734C/T, -465A/G, -330G/T, -292C/-, and 1365G/A in C1GALT1 were selected as tagging SNPs. The D allele and DD genotype of -292C/- in IgAN patients were significantly lower than in the controls (P<0.01). The frequency of haplotype YATIG (Y=C or T) was significantly lower in patients than in controls (0.0719 vs 0.1168, P=2.775 x 10(-4), odds ratio (OR)=0.70). The haplotype YAGDA (0.1236 vs 0.0791, P=3.815 x 10(-3), OR=1.77) and YATDG (0.0840 vs 0.0298, P=1.258 x 10(-5), OR=3.03) were significantly higher in patients than in controls. The present study suggested that the polymorphisms of C1GALT1 gene were associated with the genetic susceptibility to IgAN in Chinese population.

Adolescent↗

PubMed2007

Is the dementia rate increasing in Beijing? Prevalence and incidence of dementia 10 years later in an urban elderly population.

OBJECTIVE: To examine the time trend of dementia morbidity over the past decade in Beijing, China. METHOD: In 1997, 1593 community-dwelling elderly aged 60+ years were examined and followed-up over 2-years to identify incident dementia. A similar cohort study of dementia conducted in the same district 10 years prior was used as historical comparison to examine the time trend of dementia incidence. RESULTS: Forty prevalent dementia cases were identified at the initial examination for a prevalence of 2.51% (95% CI: 1.74-3.28) and 25 incident cases were identified at the follow-up visit for an incidence of 0.90% (0.55-1.25) among residents aged 60+ years. Alzheimer's dementia (AD) was the most common type of dementia in both prevalent and incident cases. CONCLUSION: The prevalence and incidence rates of dementia in Beijing were slightly higher than those 10 years ago, which was partly because of population aging. AD became the most common subtype of dementia.

Aged↗

PubMed2006

'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737.

ABT-737 is a subnanomolar inhibitor of the antiapoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w. Although ABT-737 triggers extensive cell death in many small-cell lung carcinoma (SCLC) cell lines, some of the SCLC cell lines and the majority of the cancer cell lines derived from other solid tumors were found to be resistant to ABT-737. To better understand the mechanism of resistance to ABT-737, we screened a short interfering RNA library consisting of short interfering RNA against 4000 'druggable' targets in an SCLC-derived cell line, NCI-H196. By comparing the knockdowns with phenotypes, all of the three top 'hits' from the screen were found to result from off-target gene silencing. Interestingly, the three off-target siRNAs were found to knock down an antiapoptotic Bcl-2 family protein Mcl-1 owing to the complementation between their seed regions with the 3' untranslated region (3' UTR) of Mcl-1. Furthermore, reducing the level of Mcl-1 using siRNAs or the small-molecule compounds Bay43-9006 and Seliciclib was sufficient to overcome the resistance to ABT-737 in the resistant SCLC cell line and cancer cell lines derived from other solid tumors. These results provide further evidence that Mcl-1 is the major factor that causes resistance to ABT-737 in cancer cells derived from diverse solid tumors, and the combination of Mcl-1 downregulating agents with ABT-737 could be potent therapeutic regimens for patient with ABT-737-resistant SCLC and many other types of solid tumors.

3' Untranslated Regions↗

PubMed2006

Poly(ADP-ribose) polymerase-1 plays a role in suppressing mammary tumourigenesis in mice.

The DNA strand break-binding molecule, poly(ADP-ribose) polymerase-1 (PARP-1), plays a role in DNA repair, chromosomal stability, transcription and cell death. Accumulating evidence suggests that dysfunction of PARP-1 contributes to tumorigenesis. Here, we report that PARP-1 deficiency causes mammary carcinoma formation in female mice, and that the introduction of Trp53 mutations accelerates the onset and shortens the latency of mammary tumorigenesis. We show that PARP-1 deficiency results in chromosomal aneuploidy and centrosome amplification, which are substantiated by the inactivation of Trp53 in primary mammary epithelial (PME) cells. In addition, PARP-1 deficiency compromises p53 activation and impairs BRCA1 recruitment to the sites of DNA damage in PME cells. PARP-1 complementation partly rescues the defective DNA damage response mediated by p53 and BRCA1. The present study thus identifies a role of PARP-1 in suppressing mammary tumorigenesis in vivo and suggests that dysfunction of PARP-1 may be a risk factor for breast cancer in humans.

Animals↗

PubMed2006

Common polymorphisms in the CACNA1H gene associated with childhood absence epilepsy in Chinese Han population.

Variants with a relatively high frequency in the CACNA1H gene have previously been identified in cases of childhood absence epilepsy (CAE) in the Chinese Han population most of which are located in exons 6 to 12. In present study we attempted to further investigate whether the CACNA1H gene is associated with CAE. Exons 6 to 12 of CACNA1H gene were sequenced in samples of 100 CAE trios recruited consecutively, and 191 normal human controls. Single nucleotide polymorphisms (SNPs) were studied in both single locus and haplotype analyses in 218 CAE trios, of which 118 trios were selected from our previous research. Case-control comparisons and the transmission disequilibrium test (TDT) both supported a coding SNP (cSNP) rs9934839 (R603R) in exon 9 as being close related to CAE. The carriers of the G allele of rs9934839 had a 3-fold higher risk of CAE than non-carriers. Moreover, another cSNP rs8044363 was predicted to be connected directly with CAE in a Bayesian network. In addition, two haplotypes consisting of five cSNPs in the region of CACNA1H were statistically associated with CAE. Our research provides new evidence to further support the hypothesis that CACNA1H may be an important susceptibility gene for CAE in the Chinese Han population.

Asian People↗

PubMed2006

A novel mitochondrial DNA missense mutation at G3421A in a family with maternally inherited diabetes and deafness.

OBJECTIVE: Mutations in mtDNA are thought to be responsible for the pathogenesis of maternally inherited diabetes. Here, we report a family with maternally inherited diabetes and deafness whose members did not harbour the mtDNA A3243G mutation, the most frequent point mutation in mitochondrial diabetic patients. This study aimed to investigate a possible other mtDNA mutation and its prevalence in type 2 diabetic patients. METHODS: Height, body weight, waistline, and hip circumference were measured and serum biochemical marks determined in all members of the family. In addition, a 75 g oral glucose tolerance test and electric listening test were conducted in these members. Genomic DNA was prepared from peripheral leukocytes. Direct sequencing of PCR products was used to detect the mtDNA mutation in this family. The prevalence of mtDNA G3421A nucleotide substitutions was investigated by restriction fragment length polymorphism analysis in 1350 unrelated type 2 diabetic patients recruited by random cluster sampling from the central city area of Shanghai, China. RESULTS: (1) A new missense homoplasmic mutation of mtDNA G3421A was found in a maternally inherited diabetic family and existed neither in 1350 unrelated type 2 diabetic patients nor in 50 non-diabetic individuals. (2) The mode of mutation and diabetes transmission was typical maternal inheritance in this family. (3) All diabetic family members were found to have an onset at 35-42 years of age, accompanied by deafness of varying degrees. CONCLUSION: mtDNA G3421A (Val39Ile) found in a family with maternally inherited diabetes and deafness is a novel missense mutation. Whether this is a diabetogenic mutation and its effect on mitochondrial function needs to be further studied.

Adolescent↗

PubMed2006

High prevalence of albuminuria in population-based patients diagnosed with type 2 diabetes in the Shanghai downtown.

OBJECTIVE: The prevalence of albuminuria and the risk factors associated with albuminuria were evaluated among the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown. We also evaluated the variability of urinary albumin-to-creatinine ratio (ACR) among the three measurements and the relationship between diabetic retinopathy (DR) and albuminuria. METHODS: The 1039 Chinese patients diagnosed with type 2 diabetes aged over 30 were investigated by randomized cluster sampling in the Shanghai downtown and 1018 patients were analyzed in this study. Body mass measurements including height, weight, waist circumference and hip circumference, resting blood pressure, fasting blood measures, urinary ACR and the digitally stored fundus images were investigated. The prevalence of albuminuria was calculated and the risk factors associated with albuminuria were evaluated by stepwise logistic regression. The concordance of urinary ACR was evaluated by observed agreement. The relationship between albuminuria and DR was also evaluated. RESULTS: (1) The mean age of all patients was 66.10+/-11.54 years and the duration of diabetes was 7.89+/-7.16 years. (2) The prevalence of albuminuria was 49.6% among the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown, 41.4% with microalbuminuria and 8.2% with macroalbuminuria. (3) Microalbuminuria was significantly associated with systolic blood pressure, gender and waist circumference. Macroalbuminuria was significantly associated with systolic blood pressure and duration of diabetes. (4) Observed agreement among the three urinary ACR measurement for albuminuria staging was 73.3% (first versus second), 64.5% (first versus third) and 77.5% (second versus third). Observed agreement in the albuminuria staging between the single urinary ACR measurement and all three urinary ACR measurements was 85.8% (first versus all three), 87.6% (second versus all three) and 81.9% (third versus all three). (5) The percentage of DR in the macroalbuminuric group (59.2%) was significantly higher than that in the normalbuminuria group (16.1%) and microalbuminuria group (24.6%). (6) The macroalbuminuric patients with DR had significantly increased fasting blood glucose and HbA1c compared with the macroalbuminuric patients without DR. CONCLUSION: The prevalence of microalbuminuria observed in the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown reached up to 41.4% though the observations in our study might be representative of the diabetic patients of the Shanghai downtown. We agreed that at least two of the three urinary collections were done in a 3- to 6-month period because of the day-to-day variability in albumin excretion. The percentage of DR among the patients with macroalbuminuria was 59.2%, and the macroalbuminuric patients with the significantly high plasma glucose and DR were prone to diagnose DN.

Adult↗

PubMed2006

Extent and pattern of DNA methylation alteration in rice lines derived from introgressive hybridization of rice and Zizania latifolia Griseb.

We have reported previously that introgression by Zizania latifolia resulted in extensive DNA methylation changes in the recipient rice genome, as detected by a set of pre-selected DNA segments. In this study, using the methylation-sensitive amplified polymorphism (MSAP) method, we globally assessed the extent and pattern of cytosine methylation alterations in three typical introgression lines relative to their rice parent at approximately 2,700 unbiased genomic loci each representing a recognition site cleaved by one or both of the isoschizomers, HpaII/MspI. Based on differential digestion by the isoschizomers, it is estimated that 15.9% of CCGG sites are either fully methylated at the internal Cs and/or hemi-methylated at the external Cs in the rice parental cultivar Matsumae. In comparison, a statistically significant increase in the overall level of both methylation types was detected in all three studied introgression lines (19.2, 18.6, 19.6%, respectively). Based on comparisons of MSAP profiles between the isoschizomers within the rice parent and between parent and the introgression lines, four major groups of MSAP banding patterns are recognized, which can be further divided into various subgroups as a result of inheritance of, or variation in, parental methylation patterns. The altered methylation patterns include hyper- and hypomethylation changes, as well as inter-conversion of hemi- to full-methylation, or vice versa, at the relevant CCGG site(s). Most alterations revealed by MSAP in low-copy loci can be validated by DNA gel blot analysis. The changed methylation patterns are uniform among randomly selected individuals for a given introgression line within or among selfed generations. Sequencing on 31 isolated fragments that showed different changing patterns in the introgression line(s) allowed their mapping onto variable regions on one or more of the 12 rice chromosomes. These segments include protein-coding genes, transposon/retrotransposons and sequences with no homology. Possible causes for the introgression-induced methylation changes and their implications for genome evolution and crop breeding are discussed.

Cytosine↗

PubMed2006

Herpes simplex virus 1 (HSV-1) for cancer treatment.

Cancer remains a serious threat to human health, causing over 500 000 deaths each year in US alone, exceeded only by heart diseases. Many new technologies are being developed to fight cancer, among which are gene therapies and oncolytic virotherapies. Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus with many favorable properties both as a delivery vector for cancer therapeutic genes and as a backbone for oncolytic viruses. Herpes simplex virus type 1 is highly infectious, so HSV-1 vectors are efficient vehicles for the delivery of exogenous genetic materials to cells. The inherent cytotoxicity of this virus, if harnessed and made to be selective by genetic manipulations, makes this virus a good candidate for developing viral oncolytic approach. Furthermore, its large genome size, ability to infect cells with a high degree of efficiency, and the presence of an inherent replication controlling mechanism, the thymidine kinase gene, add to its potential capabilities. This review briefly summarizes the biology of HSV-1, examines various strategies that have been used to genetically modify the virus, and discusses preclinical as well as clinical results of the HSV-1-derived vectors in cancer treatment.

Genetic Vectors↗

PubMed2006

Effect of transpiration on Pb uptake by lettuce and on water soluble low molecular weight organic acids in rhizosphere.

The effect of transpiration (high and low) on Pb uptake by leaf lettuce and on water soluble low molecular weight organic acids (LMWOAs) in rhizosphere has been studied. After two weeks of growth the plants were cultured in greenhouse for more four weeks and two days. Pb(NO(3))(2) solutions of different concentrations (100, 200, and 300 mg l(-1) of Pb) were then added to the quartz sand pots of different plants and studies were initiated. Blank experiments (without treating the quartz sand pots with Pb(NO(3))(2) solutions) were also run in parallel. No significant differences in the growth of the plants with the concentrations of added Pb(NO(3))(2) solutions were observed by both low and high transpirations at the end of the 0, 3rd, and 10th days of studies. The total evaporation of the volatiles during 10 days did not depend on the concentration of Pb(2+) but with high transpiration the rate of evaporation was significantly higher than with low transpiration. Uptake of Pb by shoots and roots of the plants was found to be proportional to the concentration of various Pb(NO(3))(2) solutions added and more accumulation was observed in roots than in shoots at the end of 3rd and 10th days. High transpiration created more Pb uptake than low transpiration did. One volatile acid, propionic acid and nine non-volatile acids, lactic, glycolic, oxalic, succinic, fumaric, oxalacetic, D-tartaric, trans-aconitic, and citric acids in rhizosphere quartz sands were identified and quantified by gas chromatography (GC) analysis. D-Tartaric and citric acids were major among the non-volatile acids. The amount of LMWOAs in rhizosphere quartz sands increased with the higher amount of Pb uptake and also with the duration of studies. The total quantities of the LMWOAs in the rhizosphere quartz sands were significantly higher under high transpiration with 300 mg l(-1) Pb solution addition at the end of 10th day. The present study shows prominent correlation between transpiration and uptake of heavy metal and interesting correlation between Pb contaminated level and quantity of water soluble LMWOAs in rhizosphere quartz sands. The latter thus deserves of further studies.

Adsorption↗

PubMed2006

White matter damage on diffusion tensor imaging correlates with age-related cognitive decline.

BACKGROUND: Damage to white matter tracts, resulting in "cerebral disconnection," may underlie age-related cognitive decline. METHODS: Using diffusion tensor MRI (DTI) to investigate white matter damage, and magnetic resonance spectroscopy (MRS) to look at its underlying pathologic basis, the authors investigated the relationship between white matter structure and cognition in 106 healthy middle-aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD) values, whole brain white matter histograms, and regions of interest placed in the white matter of the centrum semiovale were analyzed. Correlations with executive function, working memory, and information-processing speed were performed. RESULTS: There was a progressive reduction in FA and increase in diffusivity with age in both region of interest (r = 0.551, p < 0.001), and whole brain histograms (r = 0.625, p < 0.001). DTI values correlated with performance in all three cognitive domains. After controlling for age, DTI parameters correlated with working memory but not with the other two cognitive domains. MRS studies found a correlation of N-acetyl aspartate, a neuronal marker, with DTI parameters (r = 0.253, p < 0.05). CONCLUSION: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.

Aged↗

PubMed2006

Ulinastatin attenuates lung ischemia-reperfusion injury in rats by inhibiting tumor necrosis factor alpha.

UNLABELLED: Ischemia-reperfusion (I/R) injury may influence graft function following transplantation. Ulinastatin, a urinary trypsin inhibitor has been shown to attenuate I/R injury in various organs such as intestine, heart, and kidney in animals. The present experiment was designed to evaluate the effect of pretreatment with ulinastatin on I/R-induced lung injury. METHODS: After establishing a constant left lung warm ischemia-reperfusion model in rats, 45 animals were randomly divided into three experimental groups: sham group (n = 15), IR group (n = 15), and ulinastatin (5000 U/kg pre-ischemia) + IR group (n = 15). The lung injury was evaluated by tissue myeloperoxidase activity, with simultaneous estimation of the serum concentration of TNFalpha. RESULTS: The ulinastatin-pretreated animals exhibited markedly decreased lung tissue myeloperoxidase activity (P < .05). Blood gas analysis demonstrated, that the treated animals had significantly ameliorated pulmonary oxygenation (P < .05). The serum concentration of TNF-alpha in the ulinastatin-pretreated group was markedly decreased compared with that of the I/R group (P < .05). CONCLUSIONS: Ulinastatin attenuated I/R-induced lung injury. This function is partly related to the capacity of the agent to inhibit myeloperoxidase activity in lung tissue and decrease systemic expression to TNF-alpha.

Animals↗

PubMed2006

Light retardance by human oocyte spindle is positively related to pronuclear score after ICSI.

Disturbed spindle assembly increases risks of chromosome mal-segregation. Non-invasive polarization microscopy (PolScope) was employed in two centres to assess spindle integrity for the first time quantitatively in human oocytes from consenting patients undergoing intracytoplasmic sperm injection (ICSI) with respect to pronuclear (PN) score after fertilization. In one centre oocytes were selected before ICSI, in another selection was after ICSI according to PN score. In both centres, mean retardance of light by birefringent spindles in oocytes forming a pre-embryo with good PN score after ICSI was significantly higher compared with spindles in oocytes developing into a lower PN score pre-embryo with limited developmental potential (P < 0.001). Transfers involving oocytes with high retardance and at least one good PN score embryo resulted more frequently in a conception than transfers from oocytes with spindles of lower mean retardance and lower PN score embryos. There was a trend for an inverse relationship between age and magnitude of retardance in a small oocyte cohort. The study suggests that quantitative evaluation of mean retardance of light by the oocyte spindle predicts oocyte health, is related to PN score of the embryo and may be especially useful to assess oocyte quality in countries with legal restrictions to select after fertilization.

Adult↗

PubMed2006

Association of TPH1 with suicidal behaviour and psychiatric disorders in the Chinese population.

Tryptophan hydroxylase (TPH), the rate limiting enzyme in serotonin biosynthesis, is one of the most important regulating factors in the serotonergic system. Recently, polymorphisms of the TPH gene have been identified as being associated with suicide, but the evidence is inconsistent. To investigate the role in suicide of one of the isoforms, TPH1, we examined the association of five single nucleotide polymorphisms (SNPs) in the promoter region and in intron 7 of the TPH1 gene based on a sample from the Chinese population of 810 subjects, of whom 329 had made no suicide attempts (NSA), 297 had made suicide attempts (SA), and 184 were healthy subjects (HS). In this study, we observed statistically significant differences between NSA and HS subjects in allele distributions on one marker, -6526A (p = 0.0329; odds ratio (OR) 1.36; 95% confidence interval (CI) 1.01 to 1.81). No significant difference in genotype distribution or allele frequencies of other polymorphisms was found between the suicide victims and the controls. The overall haplotype frequency was significantly different between cases and healthy controls (p = 0.000024 NSA v HS; p < 0.000001, SA v HS; p < 0.000001, cases v HS). We found the haplotype TCAAA of -7180/-7065/-6526/218/779 to be strongly associated with suicidal behaviour and psychiatric disorders (p = 0.00243; OR = 1.62; 95% CI 1.17 to 2.24 and p = 0.018; OR = 1.41; 95% CI 1.05 to 1.91), which suggests an association of TPH1 with suicidal behaviour and indicates that TPH1 may play a significant role in the aetiology of psychiatric disorders in the Han Chinese population.

Alleles↗

PubMed2006

AUNX1, a novel locus responsible for X linked recessive auditory and peripheral neuropathy, maps to Xq23-27.3.

BACKGROUND: We report here the genetic characterisation of a large five generation Chinese family with the phenotypic features of auditory neuropathy and progressive peripheral sensory neuropathy, and the genetic feature of X linked recessive inheritance. Disease onset was at adolescence (at an average age of 13 years for six affected subjects). The degree of hearing impairment varied from mild to severe, with decreased otoacoustic emissions; auditory brainstem responses were lacking from onset. METHODS: Two-point and multipoint model based linkage analysis using the MILNK and LINKMAP programs of the FASTLINK software package produced maximum two-point and multipoint LOD scores of 2.41 and 2.41, respectively. RESULTS: These findings define a novel X linked auditory neuropathy locus/region (AUNX1, Xq23-q27.3). This region is 42.09 cM long and contains a 28.07 Mb region with flanking markers DXS1220 and DXS8084, according to the Rutgers Combined Linkage-Physical Map, build 35. However, mutation screen of the candidate gene SLC6A14 within the region did not identify the causative genetic determinant for this large Chinese family.

China↗

PubMed2005

High magnitude of light retardation by the zona pellucida is associated with conception cycles.

BACKGROUND: Failures in expression of zona proteins correlate to subfertility in animals. Low expression of the zona proteins by the growing human oocyte may indicate reduced developmental potential. Therefore, we non-invasively analysed the thickness and the structure of the zona pellucida (ZP) of human oocytes with respect to embryo fate after ICSI. METHODS: Retardance magnitude and thickness of the inner, middle and outer layers of the ZP were quantitatively analysed by a Polscope in 166 oocytes selected for transfer after ICSI (63 patients; 32.8 +/- 4.4 years) on the basis of pronuclear score at day 1. Blastomere number was determined at day 2. Data were compared between conception cycles (CC; 65 oocytes/23 patients) and non-conception cycles (NCC; 101 oocytes/40 patients) and with respect to maternal age. RESULTS: The thickness was slightly elevated (P < 0.001), and the mean magnitude of light retardance was nearly 30% higher (P < 0.001) in the inner layer of the zona pellucida of oocytes contributing to CC compared to NCC. Embryos in the CC group tended to develop faster. CONCLUSIONS: The magnitude of light retardance by the zona pellucida inner layer appears to present a unique non-invasive marker for oocyte developmental potential.

Adult↗

PubMed2005

Effect of water-soluble fraction of cigarette smoke on human aortic endothelial cells--a proteomic approach.

Proteomic analysis is an important investigative tool used to systematically explore cellular proteins that are responsive to adverse environmental challenges. Tobacco smoking is the second major cause of death in the world. In this study, we utilized two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) technologies to explore protein changes in human aortic endothelial cells (HAECs) in response to cigarette smoke extracts (CSE). Among 389 individual proteins resolved using 2-DE, 43 had a 2- to 3-fold change in levels as measured by spot intensity and 32 had more than a 3-fold change. Sixteen of the 32 spots with sufficient amount of proteins were excised for identification by performing matrix-assisted laser desorption/ionization (MALDI)-MS analysis. Using a peptide mass fingerprinting (PMF) to search the nrNCBI database, we identified all these 16 proteins, which were either increased (n = 9) or decreased (n = 7) after CSE treatment. All these proteins have known functions, however, none have been reported to be altered after CSE treatment. The findings from our study suggest that utilizing a systemic investigative tool, such as the proteomic approach using 2-DE, may play an important role in discovering novel molecular mechanisms for cigarette smoking-induced pathological changes. Further investigation following the systemic discoveries must be further examined as they may potentially lead to new therapeutic approaches to smoking-induced diseases - a health issue affecting everyone in the world.

Aorta↗

PubMed2005

Having a higher blast percentage in circulation than bone marrow: clinical implications in myelodysplastic syndrome and acute lymphoid and myeloid leukemias.

Determining the percentage of peripheral blood (PB) and bone marrow (BM) blasts is important for diagnosing and classifying acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Although most patients with acute leukemia or MDS have a higher percentage of BM blasts than PB blasts, the relative proportion is reversed in some patients. We explored the clinical relevance of this phenomenon in MDS (n = 446), AML (n = 1314), and acute lymphoblastic leukemia (ALL) (n = 385). Among patients with MDS or ALL, but not AML, having a higher blast percentage in PB than in BM was associated with significantly shorter survival. In multivariate analyses, these associations were independent of other relevant predictors, including cytogenetic status. Our findings suggest that MDS and ALL patients who have a higher percentage of PB blasts than BM blasts have more aggressive disease. These data also suggest that MDS classification schemes should take into account the percentage of blasts in PB differently from the percentage of blasts in BM.

Acute Disease↗