Artificial intelligences in urological practice: the key to success?
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Aged↗
Biomedical subjects
T Cai
Publications and source records attributed to T Cai.
Joint inferences on vaccine efficacy against infection and disease with application to the first HIV vaccine efficacy trial.
In many clinical trials, subjects are followed for two stages of outcomes, and it is of interest to compare the incidence of each outcome between two randomized groups. The outcome of the first stage may influence the outcome of the second stage. Moreover, the relative risks of the two outcomes may be linked, with the time-dependent profile of relative risk for the second outcome functionally dependent on that of the first. For example, during exposure to HIV, virologic and host factors simultaneously impact the probability of infection and the subsequent viral trajectories, and the efficacy of a tested vaccine to prevent infection and to prevent viral failure may work in concert. We address this problem by modeling the relationship between the stage two hazard function and covariates via Cox's proportional hazards model (Cox, 1972), with the stage one log-hazard ratio theta(*) at the first event time Tl, included as a covariate. With theta(*) estimated using three methods, 1) nonparametric kernel smoothing; 2) locally parametric penalized splines; and 3) fully parametric cubic linear splines, we subsequently develop inference procedures for the regression parameter in the stage two Cox model based on each of the estimator of theta(*). The inferential procedures are studied in simulations and are illustrated with application to data from the world's first preventive HIV vaccine efficacy trial.
AIDS Vaccines↗
Predicting clustered dental implant survival using frailty methods.
The purpose of this study was to predict future implant survival using information on risk factors and on the survival status of an individual's existing implant(s). We considered a retrospective cohort study with 677 individuals having 2349 implants placed. We proposed to predict the survival probabilities using the Cox proportional hazards frailty model, with three important risk factors: smoking status, timing of placement, and implant staging. For a non-smoking individual with 2 implants placed, an immediate implant and in one stage, the marginal probability that 1 implant would survive 12 months was 85.8% (95%CI: 77%, 91.7%), and the predicted joint probability of surviving for 12 months was 75.1% (95%CI: 62.1%, 84.7%). If 1 implant was placed earlier and had survived for 12 months, then the second implant had an 87.5% (95%CI: 80.3%, 92.4%) chance of surviving 12 months. Such conditional and joint predictions can assist in clinical decision-making for individuals.
Cluster Analysis↗
The IA-2 interactome.
AIMS/HYPOTHESIS: Islet antigen-2 (IA-2), a major autoantigen in type 1 diabetes, is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase (PTP) family. IA-2 is located in dense-core secretory vesicles and is involved in the regulation of insulin secretion. The present experiments were initiated to identify those proteins that interact with IA-2 (i.e. the IA-2 interactome) as a first step towards elucidating the mechanism(s) by which IA-2 influences insulin secretion and serves as an autoantigen. MATERIALS AND METHODS: To determine the proteins with which IA-2 interacts, a yeast two-hybrid system was used to screen a human foetal library, and deletion mutants were used to determine the binding sites. Positive interactions were confirmed by immunoprecipitation pull-down experiments using cell lysate from transfected mammalian cell lines. RESULTS: Six new interacting proteins were identified by this approach: mitogen-activated protein kinase-activating death domain (MADD), the MADD isoform IG20, PTPrho, PTPsigma, sorting nexin 19 (SNX19) and cyclophilin A. Using a series of IA-2 deletion mutants, we identified the regions on the IA-2 molecule to which five of the interacting proteins bound. Amino acids 744-979 of IA-2 were required for the maximum binding of MADD, IG20 and SNX19, whereas amino acids 602-907 of IA-2 were required for the maximum binding of PTPrho and PTPsigma. Pull-down experiments with cell lysate from transfected mammalian cells confirmed the binding of the interacting proteins to IA-2. CONCLUSIONS/INTERPRETATION: The IA-2 interactome based on, pull-down experiments, currently consists of 12 proteins. The identification of these interacting proteins provides clues as to how IA-2 exerts its biological functions.
Animals↗
Quality of life after radical treatment of prostate cancer: validation of the Italian version of the University of California-Los Angeles Prostate Cancer Index.
OBJECTIVES: To validate an Italian version of the University of California-Los Angeles Prostate Cancer Index (UCLA-PCI). METHODS: Men with prostate cancer treated with radical retropubic prostatectomy (RRP) or external beam radiation (EBR) were retrospectively selected. Each subject was asked to complete the UCLA-PCI short form and the 36-item short-form health survey (SF-36) questionnaires (principal sample); a subgroup completed both questionnaires twice (retest sample). A linguistic translation and validation was performed. Psychometric properties were analyzed. RESULTS: A total of 595 men were included in the study: 394 from the Department of Urology (treated with RRP) and 201 from the Department of Radiotherapy (treated with EBR). Of these, 75 patients (50 from the RRP group and 25 from the EBR group) were selected as the retest cohort. Internal consistency reliability of the SF-36 and UCLA-PCI for the primary sample of the surgery and radiotherapy populations ranged from 0.82 to 0.94; the mean values of sexual function were superior in the principal urology group, whereas the principal radiotherapy group demonstrated superior mean values of urinary function and urinary bother. A strong correlation between urinary function and sexual and bowel function, and between urinary function and all bother scales, was reported only for patients treated with RRP. The expected correlation between sexual function and sexual bother was reported for the EBR group but not for the RRP group. CONCLUSIONS: Our study demonstrated the excellent psychometric properties of the Italian version of the UCLA-PCI; the Italian version of the UCLA-PCI questionnaire will allow cross-cultural comparative studies in men with prostate cancer.
Aged↗
Giant stone in enterocystoplasty.
A giant stone in enterocystoplasty is a very rare condition; only 5 cases have been reported in the literature. A 50-year-old female with an enterocystoplasty due to congenital myelomeningocele presented at our institution for an asymptomatic 10-cm bladder stone, incidentally detected during an imaging procedure for uterine fibroma. The patient was treated with a laparoscopic hysterectomy with bilateral annexectomy, neocystotomy and stone removal under general anesthesia. The case report and an accurate literature review are reported. The incidence, risk factors, pathophysiology and treatment options are analyzed.
Anastomosis, Surgical↗
Frailty approach for the analysis of clustered failure time observations in dental research.
Because dental implant failure patterns tend to cluster within subjects, we hypothesized that the risk of implant failure varies among subjects. To address this hypothesis in the setting of clustered, correlated observations, we considered a retrospective cohort study where we identified a cohort having at least one implant placed. The cohort was composed of 677 patients who had 2349 implants placed. To test the hypothesis, we applied an innovative analytic method, i.e., the Cox proportional hazards model with frailty, to account for correlation within subjects and the heterogeneity of risk, i.e., frailty, among subjects for implant failure. Consistent with our hypothesis, risk for implant failure among subjects varied to a statistically significantly degree (p=0.041). In addition, the risk for implant failure is significantly associated with several factors, including tobacco use, implant length, immediate implant placement, staging, well size, and proximity of adjacent implants or teeth.
Analysis of Variance↗
Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.
Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.
Carcinoma, Hepatocellular↗
The IA-2 gene family: homologs in Caenorhabditis elegans, Drosophila and zebrafish.
AIMS/HYPOTHESIS: IA-2 and IA-2beta are major autoantigens in Type I (insulin-dependent) diabetes mellitus and are expressed in neuroendocrine tissues including the brain and pancreatic islets of Langerhans. Based on sequence analysis, IA-2 and IA-2beta are transmembrane protein tyrosine phosphatases but lack phosphatase activity because of critical amino acid substitutions in the catalytic domain. We studied the evolutionary conservation of IA-2 and IA-2beta genes and searched for homologs in non-mammalian vertebrates and invertebrates. METHODS: IA-2 from various species was identified from EST sequences or cloned from cDNA libraries or both. Expression in tissues was determined by transfection and in situ hybridization. RESULTS: We identified homologs of IA-2 in C. elegans, Drosophila, and zebrafish which showed 46, 58 and 82 % identity and 60, 65 and 87 % similarity, respectively, to the amino acids of the intracellular domain of human IA-2. Further studies showed that IA-2 was expressed in the neural tissues of the three species. Comparison of the genomic structure of the intracellular domain of human IA-2 with that of human IA-2beta showed that they were nearly identical and comparison of the intron-exon boundaries of Drosophila IA-2 with human IA-2 and IA-2beta showed a high degree of relatedness. CONCLUSION/INTERPRETATION: Based on these findings and sequence analysis of IA-2 homologs in mammals, we conclude that there is an IA-2 gene family which is a part of the larger protein tyrosine phosphatase superfamily. The IA-2 and IA-2beta genes represent two distinct subgroups within the IA-2 family which originated over 500 million years ago, long before the development of the pancreatic islets of Langerhans.
Amino Acid Sequence↗
Characterization of ribonuclease MRP function.
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Endoribonucleases↗
Structural components of the nuclear body in nuclei of Allium cepa cells.
Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared as a spherical structure about 0.3 to 0.8 microm in diameter. They possibly were formed in nucleolus and subsequently released, and entered into nucleoplasm. Observation through cytochemical staining method at the ultrastructural level confirmed that nuclear bodies consisted of ribonucleoproteins (RNPs) and silver-stainable proteins. Immunocytochemical results revealed that nuclear bodies contained no DNA and ribosomal gene transcription factor (UBF). Based on these data, we suggested that nuclear bodies are not related to the ribosome or other gene transcription activities, instead they may act as subnuclear structures for RNPs transport from nucleolus to cytoplasm, and may also be involved in splicing of pre-mRNAs.
Cell Nucleolus↗
A de novo complex chromosomal rearrangement with a translocation 7;9 and 8q insertion in a male carrier with no infertility.
A de novo complex chromosomal rearrangement (CCR) involving chromosomes 7, 8 and 9 in a male carrier was ascertained through his healthy wife's recurrent spontaneous abortions. Six pregnancies over eight years resulted in four spontaneous abortions and two livebirths who died perinatally due to abnormal vital signs. Cytogenetic analyses utilizing high resolution chromosome banding technique showed a deletion of band in a der(7) chromosome and an extra band inserting at 8q21.2. Another extra band was also observed at the band 9p24, but it could not be karyotypically determined. Fluorescent in-situ hybridization using chromosome 7 and 8 specific microdissected library as probes confirmed the insertion of a segment from the translocated chromosome 7 into a chromosome 8, and additionally revealed a translocation between chromosomes 7 and 9. The karyotype of the CCR carrier was determined as 46,XY,t(7;9)(q22;p24),ins(8;7)(q21.2;q22q32).ish der(9)(wcp7+);ins(8;7)(wcp8+,wcp7+). Comparing with previously reported male CCR carriers with our case, we conclude that male CCR carriers may not always present with infertility or subfertility phenotypes. This may suggest that rare transmission of male carriers could result from abnormal chromosomal rearrangements during meiosis and gametogenesis in addition to frequent infertility.
Abortion, Habitual↗
Personality profiles and the prediction of categorical personality disorders.
Personality disorders (PDs) are usually construed as psychiatric categories characterized by a unique configuration of traits and behaviors. To generate clinical hypotheses from normal personality trait scores, profile agreement statistics can be calculated using a prototypical personality profile for each PD. Multimethod data from 1,909 psychiatric patients in the People's Republic of China were used to examine the accuracy of such hypotheses in the Interpretive Report of the Revised NEO Personality Inventory. Profile agreement indices from both self-reports and spouse ratings were significantly related to PD symptom scores derived from questionnaires and clinical interviews. However, accuracy of diagnostic classification was only modest to moderate, probably because PDs are not discrete categorical entities. Together with other literature, these data suggest that the current categorical system should be replaced by a more comprehensive system of personality traits and personality-related problems.
Adolescent↗
A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies and interacts with neurofibromatosis type 2 gene product schwannomin.
We report the identification of a full-length novel beta-spectrin II gene (betaSpIIsigma2) in human brain. The betaSpIIsigma2 gene has 32 exons encoding an actin-binding domain, followed by 17-spectrin repeats, and a short COOH-terminal regulatory region that lacks the Pleckstrin homology (PH) domain. Pair-wise sequence analysis showed an additional 36 and 28 amino acids located at the NH2 and COOH-terminal regions of betaSpIIsigma2, respectively. Northern-blot analysis showed an abundant expression of betaSpIIsigma2 transcripts in brain, lung, and kidney. Western-blot analysis confirmed the predicted approximately 225 kD molecular size of betaSpIIsigma2 protein in these same tissues. In brain, immunofluorescent staining revealed that betaSpIIsigma2 was enriched in cerebellar neurons, with specific enrichment in Purkinje cell bodies, but not in dendrites. Of considerable interest, neurofibromatosis type 2 (NF2) gene product schwannomin was found to co-immunoprecipitate with betaSpIIsigma2 in cultured Purkinje cells. These results suggest that betaSpIIsigma2 may play an important role in the assembly of the specialized plasma membrane domain of Purkinje neurons and that schwannomin may be involved in actin-cytoskeleton organization by interacting with betaSpIIsigma2.
Amino Acid Sequence↗
Analysis of the coding and promoter regions of the autoantigen IA-2 in subjects with and without autoantibodies to IA-2.
Despite extensive studies on HLA polymorphism, there have been few, if any, studies on allelic forms or mutations in proteins that serve as autoantigens. The present experiments were designed to look for alterations in the coding and promoter regions of the autoantigen IA-2 in type one (insulin-dependent) diabetic patients with autoantibodies to IA-2 as compared with siblings without diabetes or autoantibodies to IA-2. Genomic DNA was used as a template and was amplified by polymerase chain reaction, with pairs of primers encompassing the promoter region and the 23 exons of the coding region of IA-2. A total of nine nucleotide changes were found in the coding region of the six type 1 diabetic patients; four were silent and five were missense changes, but all occurred in the extracellular domain of IA-2 to which autoantibodies are not directed. Few, if any, changes were found in the 5' upstream (-706 to +135) promoter region. The results of the experiments support the null hypothesis that differences among individuals in the nucleotide and amino acid sequences of the promoter and coding regions of IA-2, respectively, do not account for why some individuals develop autoantibodies to IA-2 and others do not.
Amino Acid Sequence↗
All-trans-retinoic acid increased the expression of integrin alpha5beta1 and induced "anoikis" in SMMC-7721 hepatocarcinoma cell.
It is extensively shown that integrin can regulate various cellular functions, including apoptosis, probably by contributing to signal transduction processes through interaction with extracellular matrix (ECM) proteins. In the present study, DNA flow cytometric analysis demonstrated that SMMC-7721 hepatocarcinoma cells treated with 80 microM all-trans-retinoic acid (atRA) showed an increased expression of the integrin alpha5beta1, which was associated with the growth inhibition of the cells. We found that atRA treated cells showed obvious apoptosis. Then, it was postulated that the enhanced content of integrin alpha5beta1 in the absence of ligation with fibronectin (Fn) would stop transducing survival signals, and lead to decreased cell growth and apoptosis. To elucidate this hypothesis, we cultured the atRA treated cell in L-poly-lysine-coated and Fn-coated flask, respectively. The results indicated that Fn binding prevented the cells from apoptosis induced by atRA, in contrast to L-poly-lysine binding. When the transfectant with enhanced expression of integrin alpha5beta1 at the same level of atRA treated cell was cultured in L-poly-lysine-coated flask, apoptosis was triggered. However, apoptotic cell was not detected when those cells were cultured in Fn-coated flask. Meanwhile, culturing the transfectant in the antibody (against integrin alpha5 subunit)-coated flask induced 18.33% of the cells into apoptosis, which is far more than the control group. Our study suggests that increased expression of integrin alpha5beta1 on the surface of SMMC 7721 hepatocarcinoma cell treated by atRA, when unbound to Fn, would stop transducing survival signals to lead to "anoikis", and can be reverted by the interaction of integrin alpha5beta1 with Fn.
Anoikis↗
[Detection of cytomegalovirus infection in recipients of renal transplantation].
OBJECTIVE: To investigate infection of cytomegalovirus (CMV) in recipients of renal transplantation (RT). METHODS: 167 recipients of RT were screened for the occurrence of CMV infection by using ELISA to test anti-CMV IgG, IgM from serum samples, using immunohistochemistry method to test CMV antigen expression and nest PCR to amplify CMV DNA from blood samples. RESULTS: Of these samples, 165 and 3 came out positive of IgG and IgM with the positive rate being 98.8% and 1.8% respectively. 79 samples resulted in antigen expression (47.3%) with the average antigen index being (3.2, 3.1)/5, 104 WBC. Besides, 85 samples were found to be positive by nest-PCR with the positive rate being 50.9%. CONCLUSIONS: The results indicate that the infection of RT so the detection CMV is common in recipients of RT. So detection of CMV-antibody, CMV antigen and CMV DNA after renal transplantation is very important in early diagnosis of CMV infection.
Adolescent↗
TGF-beta 1 modulated the expression of alpha 5 beta 1 integrin and integrin-mediated signaling in human hepatocarcinoma cells.
Integrins are a family of cell surface adhesion molecules which mediate cell adhesion and initiate signaling pathways that regulate cell spreading, migration, differentiation, and proliferation. TGF-beta is a multifunctional factor that induces a wide variety of cellular processes. In this study, we show that, TGF-beta 1 treatment enhanced the amount of alpha 5 beta 1 integrin on cell surface, the mRNA level of alpha 5 subunit, and subsequently stimulated cell adhesion onto a fibronectin (Fn) and laminin (Ln) matrix in SMMC-7721 cells. TGF-beta 1 could also promote cell migration. Furthermore, our results showed that TGF-beta1 treatment stimulated the tyrosine phosphorylation level of FAK, which can be activated by the ligation and clustering of integrins. PTEN can directly dephosphorylate FAK, and the results that TGF-beta 1 could down-regulate PTEN at protein level suggested that TGF-beta 1 might stimulate FAK phosphorylation through increasing integrin signaling and reducing dephosphorylation of FAK. These studies indicated that TGF-beta 1 and integrin-mediated signaling act synergistically to enhance cell adhesion and migration and affect downstream signaling molecules of hepatocarcinoma cells.
Carcinoma, Hepatocellular↗