Biomedical subjects

J Peng

Publications and source records attributed to J Peng.

At least 19 recordsLinked to original sources

PubMed2006

Rh proteins vs Amt proteins: an organismal and phylogenetic perspective on CO2 and NH3 gas channels.

Rh (Rhesus) proteins are homologues of ammonium transport (Amt) proteins. Physiological and structural evidence shows that Amt proteins are gas channels for NH(3), but the substrate of Rh proteins, be it CO2 as shown in green alga, or NH3/NH4+ as shown in mammalian cells, remains disputed. We assembled a large dataset generated of Rh and Amt to explore how Rh originated from and evolved independently of Amt relatives. Analysis of this rich data implies that Rh was split from Amt first to emerge in archaeal species. The Rh ancestor underwent divergence and duplication along speciation, leading to neofunctionalization and subfunctionalization of the Rh family. The characteristic organismal distribution of Rh vs. Amt reflects their early separation and subsequent independent evolution: they coexist in microbes and invertebrates but do not in fungi, vascular plants or vertebrates. Rh gene-duplication was prominent in vertebrates: while epithelial RhBG/RhCG displayed strong purifying selection, erythroid Rh30 and RhAG experienced different episodes of positive selection in each of which adaptive evolution occurred at certain time points and in a few codon sites. Mammalian Rh30 and RhAG were subject to particularly strong positive selection in some codon sites in the lineage from rodents to human. The grounds of this adaptive evolution may be driven by the necessity to increase the surface/volume ratio of biconcave erythrocytes for facilitative gas diffusion. Altogether, these results are consistent with Rh proteins not being the orthologue of Amt proteins but having gained the function for CO2/HCO3- transport, with important roles in systemic pH regulation.

Amino Acid Sequence↗

PubMed2006

Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes.

AIMS: To explore the contribution of islet autoimmunity and genetic mutations in Chinese patients initially thought to have Type 1B diabetes. METHODS: A group of 33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the absence of autoantibodies to glutamic acid decarboxylase (GAD), IA-2, insulin, thyroid globulin or thyroid peroxidase, or high-risk HLA-DQ haplotypes. The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes. Mutations of HNF-1alpha (MODY3) and neuroD1/beta2 (MODY6) genes were screened using the single-strand conformation polymorphism (SSCP) technique and sequencing. Mitochondrial DNA mutations were analysed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Within the cohort, we found one patient with a novel mutation, R321H (CGC-->CAC) in exon 5 of the HNF-1alpha gene, one with ND1 mt3316 G-->A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/beta2 gene, and two patients with autoantibodies to SOX13. CONCLUSIONS: Some of the Chinese patients originally thought to have Type 1B diabetes do have other evidence of islet autoimmunity and genetic mutations involved in the underlying aetiology. This suggests that more rigorous screening for these conditions is needed before classifying subjects as having Type 1B diabetes.

Adolescent↗

PubMed2006

QTL mapping under ascertainment.

Mapping quantitative trait loci (QTL) using ascertained sibships is discussed. It is shown that under the standard normality assumption of variance components analysis the efficient scores are unchanged by ascertainment, and two different schemes of ascertainment correction suggested in the literature are asymptotically equivalent. The use of conditional maximum likelihood estimators derived under the normality assumption to estimate nuisance parameters is shown to result in only a small loss of power compared to the case of known parameters, even when the distribution of phenotypes is non-normal and/or the ascertainment criterion is ill defined.

Chromosome Mapping↗

PubMed2005

Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-gamma ligands induces apoptosis on human myeloid leukemia cells in vitro.

The present study was undertaken to investigate the mechanisms of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligand-induced apoptosis on human myeloid leukemia K562 and HL-60 cell lines. The results revealed that both 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) have significant anti-proliferation- and apoptosis-inducing effects on these two kinds of leukemia cells. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly using Wright's and Hoechst 33258 staining. Reverse transcription-PCR and western blot analyses demonstrated that both survivin and bcl-2 expression were downregulated markedly, while bax expression was upregulated concurrently when apoptosis occurred. We therefore conclude that 15d-PGJ2 and TGZ have significant apoptosis effects on K562 and HL-60 cells in vitro, and that upregulation of bax as well as downregulation of survivin and bcl-2 expression may be the important apoptosis-inducing mechanisms. The results suggest that PPAR-gamma ligands may serve as potential therapeutic agents for both acute and chronic myeloid leukemia.

Antineoplastic Agents↗

PubMed2005

Muscle atrophy in titin M-line deficient mice.

We investigated the response to deletion of the titin M-line region in striated muscle, using a titin knockout model and a range of techniques that include histology, in situ hybridization, electron microscopy, and 2D gel analysis. We found that the loss of titin's kinase domain and binding sites for myomesin and MURF-1 causes structural changes in the sarcomere that proceed from the M-line to the Z-disc and ultimately result in disassembly of the sarcomere. Disassembly goes along with central localization of nuclei (a hallmark for muscular dystrophy), up-regulation of heat-shock proteins, and induction of proteasome activity. While fiber type composition does not change in soleus and extensor digitorum longus muscle, fiber size is reduced. Animals die from complications of muscle atrophy at five weeks of age. In addition to the structural importance of the titin M-line region in any striated muscle, our data show how differences in M-line composition between heart and skeletal muscle affect sarcomere stability and function.

Animals↗

PubMed2005

[Ovarian cancer: incidence and mortality in France].

OBJECTIVES: To describe the ovarian cancer incidence and mortality trends in France from 1980 to 2000. MATERIALS AND METHODS: Incidence data were obtained from 9 French departments covered by cancer registries which systematically record all cancers, of which those of the ovary. Mortality data has been provided by INSERM bureau in charge of the analysis of death certificates. RESULTS: With 4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer still shows a poor prognosis. Age adjusted incidence and mortality rates are almost stable over the study period at an annual rate of 9 by 100000 for incidence and 5.5 by 100000 for mortality. However the risk of developing this cancer and the risk of dying from it, steadily decreased for the cohort born in 1930 to 1950, and the beginning of this reduction corresponds exactly to the beginning of oral contraception. We present comparisons between departments and analyze the border-line tumors in parallel with invasive cancers. CONCLUSION: The cancer of the ovary represents only a small part of female cancers (3.8%) in France and its incidence is stable over time, but its prognosis is very bad.

Adolescent↗

PubMed2005

Therapeutic management of laryngeal cancer. Results of a study of 356 patients from the Cancer Registry of the Somme, France.

CONCLUSIONS: The global survival rate was low compared to those reported in the literature, in which the analyzed populations were selected according to the tumor stage or treatment. This study should be prolonged and should also involve other cancer registries in France in order to increase the number of patients and to analyze tumors of comparable stage and therapeutic management. OBJECTIVE: To analyze the survival rate of a non-selected laryngeal cancer population from the Cancer Registry of the Somme, a French region. MATERIAL AND METHODS: A total of 356 patients were included in a retrospective study covering the period 1987-1997. Survival and prognostic factors were analyzed. Statistical analysis was performed using the Kaplan-Meier method, the Cox model and the chi2 test. RESULTS: The 5-year global survival rate was 42% for males and 55% for females. Tumor localization, T, N and M stages and surgery were found to be significant prognostic factors. Sex and age were not statistically significant factors. For stage I tumors, surgery alone gave better results than radiotherapy alone in terms of global survival. No difference occurred in terms of local recurrence. A similar comparison was not possible for stage II-IV tumors owing to the small number of cases.

Adult↗

PubMed2005

Oridonin-induced apoptosis in leukemia K562 cells and its mechanism.

Oridonin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Recently oridonin has been reported to have anti- tumor effects in a large variety of malignant diseases. In this study, we investigated the apoptotic inducing effect of oridonin in leukemia K562 cells and its mechanism. Cell growth inhibition was measured using a microculture tetrazolium assay, apoptosis was measured by flow cytometry and electron microscopy as well as by DNA fragmentation analysis. Telomerase activity was measured by TRAP-enzyme- linked immunosorbent assay, and the expression of Bcl-2 and Bax proteins was detected by western blot analysis. The results showed that oridonin could inhibit the proliferation and induce apoptosis on leukemia K562 cells remarkably. Telomerase activity as well as Bcl-2 expression was down- regulated, while Bax expression was up-regulated concurrently, when apoptosis ocurred. We therefore conclude that oridonin demonstrated anti-proliferative and apoptosis-inducing effects on K562 cells in vitro, and that changes in bcl-2 and bax protein levels as well as telomerase activity may play an important role in its mechanism of action.

Antineoplastic Agents↗

PubMed2005

Performance of a combined eco-system of ponds and constructed wetlands for wastewater reclamation and reuse.

An on-site study on the operational performance of a combined eco-system of ponds and SF constructed wetland for municipal wastewater treatment and reclamation/reuse in Donging City, Shandong, China was carried out from January 2001 through October 2003. The removal efficiencies for various main parameters were: TSS 84.8 +/- 7.3%, BOD5 87.2 +/- 5.3%, CODCr 70.2 +/- 18.6%, TP 52.3 +/- 23.1%, and NH(3)-N 54.8 +/- 23.9% with effluent concentration of TSS 9.12 +/- 5.12 mg/l, BOD5 6.44 +/- 4.58 mg/l, CODCr, 42.8 +/- 6.7 mg/l, TP 0.94 +/- 0.27 mg/l and NH(3)-N 7.95 +/- 2.36 mg/l. In addition, the removal efficiencies for faecal coliforms and total bacteria were > 99.97% and > 99.998% respectively, which well meet Chinese National standards for effluent quality of municipal wastewater treatment plants. The composition of TSS was closely related to CODCr and BOD5 variations, and nitrification-denitrification is the major mechanism of nitrogen removal both in ponds and in wetlands. In addition, sedimentation also played an important role in the removal of TSS, nitrogen, phosphorus and BOD5. The removal efficiencies of various parameters, the number of species and biomass of biological community in the system increased gradually with the ecological maturation.

Ammonia↗

PubMed2004

[Gynecological and breast cancer in the department of Somme].

BACKGROUND: Breast and gynecological tumors are the most common cancers in women. The aim of this study was to show the epidemiologic features of gynecological and breast cancers in the French administrative district of La Somme. METHODS: This study focused on the 1982-1999 period. Incidence, mortality and survival rates were calculated. RESULTS: In 1997-1999, the world standardized breast incidence and mortality rates were 81.6 and 20.2 per 100,000 females per year. Breast and genital tract cancers accounted for 47% of all cancers in women. The incidence and mortality of uterine cervix cancers showed a clear decline over the past 10 years, whereas the trend of breast cancers was dominated by continuing increase. However, mortality was stable for breast cancers. Five year relative survival rates were respectively 80% for breast cancers, and 68%, 76%, 38%, for uterine cervix, uterine body and ovary cancers respectively. Incidence and mortality rates in Somme were in the middle risk range of other cancer French registries. CONCLUSION: The results of this study indicate that genital tract and breast cancers constitute a serious public health problem pointing out the importance of screening activities in the Somme area.

Adult↗

PubMed2004

Bone mass density and risk of breast cancer and survival in older women.

STUDY OBJECTIVE: Older women with high bone mineral density (BMD) have an increased risk of breast cancer but it is not well known whether this association is associated with the stage of the tumor. The objective of the study is to determine if older women with high BMD are likely to develop a more aggressive form of breast cancer, as defined by mortality. PATIENTS: We prospectively studied 1504 women who were 75 years of age or older at the entry in the study (range, 75-90 years), between 1992 and 1994. BMD was measured by dual-photon X-ray absorptiometry at three skeletal sites (trochanter, Ward's triangle, femoral neck). The women were followed for a mean of 7 years for the occurrence of breast cancer. Cox proportional-hazards models were used to obtain estimates of the relative risk of breast cancer and relative risk of death according to the BMD. MAIN RESULTS: Forty-five incident breast cancer cases were identified. In multivariate analyses of the risk of breast cancer for women in the highest tertile of BMD was greater than for women in the lowest tertile. Indeed, the women with a trochanter BMD in the highest tertile were at 2.3-fold increased risk compared with women in the lowest tertile. The women with highest tertile BMD measured at the Ward's triangle and at the femoral neck were respectively at 2.2-and 3.3-fold increased risk compared with women at the lowest risk. The 7-year survival rates were markedly less favorable for women in the second and third tertile of the three skeletal sites compared with the lowest tertile. The risk of death was greater for women in the highest tertile of BMD than for women in the lowest tertile at every skeletal site. CONCLUSION: Elderly women with high BMD have an increased risk of breast cancer, especially advanced cancer, compared with women with low BMD.

Absorptiometry, Photon↗

PubMed2004

Deletion of arginine codon 229 in the Rhce gene alters e and f but not c antigen expression.

BACKGROUND: Rh CcEe antigens occur as ce, Ce, cE, or CE alleles in the RBC membrane. Their epitope structures and the location of their cis interacting products remain to be defined. MATERIALS AND METHODS: A rare blood sample from a white male whose parents are first cousins was identified. Hemagglutination was performed using standard methods. RH structure and genotype was assessed by Southern blots. Rh transcripts were obtained by gene-specific RT-PCR and sequenced. The mutation was verified by genomic PCR assays. RESULTS: The donor's RBCs typed D+C-c+E-e-f(Rh6)- with a normal c dose, suggesting the Dc- phenotype. Further tests revealed a weak and qualitatively altered e expression. Southern blots indicated a genotype of Dce/dce without other gross changes. RT-PCR detected a triplet deletion (Delta685AGA687) in the Rhce gene that specifies codon 229 for arginine (Arg229). Sequencing of the region around the mutated exon 5 confirmed the donor to be homozygous for the AGA deletion. DISCUSSION: Arg229 is invariant on external loop 4 and close to the Ala226Pro change specific for e/E polymorphism. The qualitative and quantitative alteration of e antigen defines Arg229 as a crucial component for e/E epitope presentation. Given a normal dose of c antigen, the disruption of f (Rh6) by Arg229 deletion suggests that external loop 4 is a major structural element contributing to the expression of RHCE cis interacting antigenic products.

Amino Acid Sequence↗

PubMed2004

RH locus contraction in a novel Dc-/D-- genotype resulting from separate genetic recombination events.

BACKGROUND: The rare phenotypes Dc- and D-- lack the expression of E/e and CcEe antigens, respectively; their cotransmission in a single family has not been reported. STUDY DESIGN AND METHODS: Six members of a Chinese family with two exhibiting the Dc- phenotype were studied using standard serologic methods. Rh genotypes were analyzed by Southern blot, and RH loci, by exon PCR. Rh transcripts were characterized by gene-specific RT-PCR and sequencing. RESULTS: Although Rh typing detected two members as Dc- homozygotes, RFLP analysis and exon PCR showed them to be Dc- heterozygotes with a partial deletion of RHCE. cDNA sequencing showed the expression in the family of normal RHD and RHCe as well as hybrid transcripts, RHD(1-9)/RHCE(10) and RHCE(1-3)/RHD(4-10). Thus, the Dc- members had the genotype of Dc-/ D-- and expressed both hybrid genes that were inherited from their parents, respectively. DISCUSSION: This is the first demonstration in a family that the Dc- and D-- complexes neither are linked with a normal RHD or RHCE gene. The segregation of these two different hybrid genes with single break points suggests their independent genetic origin and provides molecular insights into the dynamic nature of genomic rearrangements leading to RH locus contraction.

Adult↗

PubMed2004

Influence of abnormal screens on delays and prognostic indicators of screen-detected breast carcinoma.

BACKGROUND: Delay to diagnosis following an abnormal screening result is associated with morbidity such as anxiety, but its effect on prognosis is unknown. METHODS: Using data from the Somme area breast cancer screening programme (France), we identified 29,511 women aged 50-69 years who underwent screening between 1996 and 2000. We prospectively followed women with an abnormal screening result until completion of the assessment process and evaluated the effect of delay to notification, diagnosis and treatment on prognostic indicators. RESULTS: Women with high-suspicion screens (n=976) compared with those with intermediate-suspicion screens (n=1008) were investigated more promptly, presented larger tumours (62% vs 42%, p=0.03), and were more likely to be lymph node positive (36% vs 17%, p=0.02). Compared with a delay to diagnosis </=1 month, the odds ratio for tumour size greater than 10 mm was 1.4 (95% confidence interval[CI], 0.90-1.90) for a delay of 1 to </=6 months, and 1.8 (95% CI, 1.02-2.85) for a delay >6 months. Similarly, a 1.4-fold and 2-fold increased risk of lymph node involvement was observed for delays of >3 to </=6 months and >6 months, respectively, compared with the reference interval. CONCLUSION: The authors' findings suggest that women with high-suspicion mammograms were investigated more promptly, and that delays to diagnosis of asymptomatic breast carcinoma >6 months were associated with progression of the cancer measured by tumour size >10 mm and lymph node metastasis.

Aged↗

PubMed2003

Efficient multipoint mapping: making use of dominant repulsion-phase markers.

The paper is devoted to the problem of multipoint gene ordering with a particular focus on "dominance" complication that acts differently in conditions of coupling-phase and repulsion-phase markers. To solve the problem we split the dataset into two complementary subsets each containing shared codominant markers and dominant markers in the coupling-phase only. Multilocus ordering in the proposed algorithm is based on pairwise recombination frequencies and using the well-known travelling salesman problem (TSP) formalization. To obtain accurate results, we developed a multiphase algorithm that includes synchronized-marker ordering of two subsets assisted by re-sampling-based map verification, combining the resulting maps into an integrated map followed by verification of the integrated map. A new synchronized Evolution-Strategy discrete optimization algorithm was developed here for the proposed multilocus ordering approach in which common codominant markers facilitate stabilization of the marker order of the two complementary maps. High performance of the employed algorithm allows systematic treatment for the problem of verification of the obtained multilocus orders, based on computing-intensive bootstrap and jackknife technologies for detection and removing unreliable marker scores. The efficiency of the proposed algorithm was demonstrated on simulated and real data.

Algorithms↗

PubMed2003

[Systemic embolism after reversion to sinusal rhythm of persistent atrial flutter].

BACKGROUND: The incidence of embolism in atrial flutter has been underestimated in the routine clinical practice. PATIENTS AND METHODS: In this study the incidence of thromboembolic events after restoration of sinus rhythm (by catheter ablation or cardioversion) was compared in two groups of consecutive patients, with a different anticoagulation protocol. A total of 169 patients were evaluated. A first retrospective analysis of 79 non anticoagulated patients (group I). A second prospective group of 90 patients who were treated with an anticoagulation protocol (group II) similar to that for patients with atrial fibrillation. All had typical atrial flutter of at least one month's duration before the procedure. RESULTS: The mean age of patients in group I was 61 12 years and the mean left ventricular ejection fraction was 57 6%. Patients in group II had a mean age of 61 10 years and the mean left ventricular ejection fraction was 56 9%. No differences were observed regarding prevalence of structural cardiopathy, arterial hypertension, diabetes mellitus, left ventricular dysfunction, atrial size or atrial fibrillation between the two groups of patients. Four patients in the retrospective analysis (5%) had an embolic event associated with the procedure, compared with 0 (0%) in the group of patients treated with the anticoagulation protocol. The efficient anticoagulation was associated with a lower risk of thromboembolic events (p < 0.05). CONCLUSIONS: The incidence of embolic events after reversion to sinusal rhythm of persistent atrial flutter can be decreased. These patients should follow the same recommendations of anticoagulation that apply for patients with persistent atrial fibrillation that are going to be reverted to sinus rhythm.

Anticoagulants↗

PubMed2003

Involvement of vanilloid receptors in heat stress-induced delayed protection against myocardial ischemia-reperfusion injury.

Sprague-Dawley rats were pretreated with whole body hyperthermia (rectal 42 degrees C) for 15 min, 24 h before the experiments, and then the left main coronary artery of rat hearts was subjected to a 60 min occlusion followed by 3 h reperfusion. Myocardium injury degree was evaluated by measurement of infarct size and serum creatine kinase (CK) activity. Plasma concentrations of calcitonin gene-related peptide (CGRP), and the expression of alpha- and beta-CGRP mRNA in dorsal root ganglia were determined by radioimmunoassay and semi-quantitative reverse-transcription polymerase chain reaction, respectively. Hyperthermia treatment significantly reduced infarct size and CK release concomitantly with a dramatic increase in plasma concentrations of CGRP and the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, which was completely abolished by pretreatment with capsazepine (38 mg/kg, s.c.), a competitive vanilloid receptor 1 antagonist. These results suggests that vanilloid receptor 1 on capsaicin-sensitive sensory nerves plays an important role in the modulation of the delayed cardioprotection induced by heat stress in rats.

Animals↗

PubMed2003

Evaluation of an algorithm to identify incident breast cancer cases using DRGs data.

Hospital databases have the potential to be inexpensive, timely and nationally representative sources of information about cancer. This study examines the utility of the French hospital database adapted from the Diagnosis Related Group (DRG) classification and named 'Programme de médicalisation des systèmes d'information (PMSI)', as an independent source to identify incident cancer cases. From the 19 679 women hospitalized and treated in 1998 in the public hospitals of the Somme area in France, we identified those diagnosed with breast cancer in the PMSI database. These women were matched with women in the cancer registry of the Somme area who had been diagnosed with breast cancer in 1998. An algorithm was used to identify cancer-related diagnoses and procedures reported to PMSI. The sensitivity, specificity and positive predictive value (PPV) of the PMSI database were calculated using the cancer registry as a gold standard. The PMSI database had 85% sensitivity, 99.9% specificity and 97% PPV for women hospitalized with breast cancer as a principal diagnosis. The sensitivity was higher by 9% for hospitalization with breast cancer as a secondary diagnosis but had a lower PPV (78%). In conclusion, the PMSI database seems to offer an interesting potential to assess breast cancer incidence, because of its high sensitivity, in particular when secondary diagnosis was considered, and its very high specificity and PPV. However, these preliminary results need to be confirmed by other studies in France before such databases are used, particularly in areas without cancer registries.

Algorithms↗