Biomedical subjects

M Han

Publications and source records attributed to M Han.

At least 19 recordsLinked to original sources

PubMed2006

Specific interaction between the initiator protein (Rep) and origin of plasmid ColE2-P9.

The replication initiator protein (Rep) of plasmid ColE2-P9 (ColE2) is multifunctional. We are interested in how Rep binds to the origin (Ori) to perform various functions. We used the wild type and variants of Rep to study the Rep-Ori interaction by both in vitro and in vivo approaches, including biochemical analyses of protein-DNA interactions and an in vivo replication assay. We identified three regions (I, II, and III) of Rep, located in the C-terminal half, and three corresponding binding sites (I, II, and III) in Ori which are important for Rep-Ori interaction. We showed that region I, containing a putative helix-turn-helix motif, is necessary and sufficient for specific Ori recognition, interacting with site I of the origin DNA from the major groove. Region II interacts with site II of the origin DNA, from the adjacent minor groove in the left half of Ori, and region III interacts with site III, next to the template sequence for primer synthesis, which is one and one-half turn apart from site I on the opposite surface of the origin DNA. A putative linker region located between the two DNA binding domains (regions II and III) was identified, which might provide Rep an extended conformation suitable for binding to the two separate sites in Ori. Based on the results presented in this paper, we propose a model for Rep-Ori interaction in which Rep binds to Ori as a monomer.

Amino Acid Sequence↗

PubMed2006

Sebum output as a factor contributing to the size of facial pores.

BACKGROUND: Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, genetic predisposition, ageing, chronic ultraviolet light exposure, comedogenic xenobiotics, acne and seborrhoea. This study was an attempt to determine the factors related to enlarged pores. OBJECTIVES: To assess the relationship of sebum output, age, sex, hormonal factors and severity of acne with pore size. METHODS: A prospective, randomized, controlled study was designed. A total of 60 volunteers, 30 males and 30 females, were recruited for this study. Magnified images of pores were taken using a dermoscopic video camera and measured using an image analysis program. The sebum output level was measured with a Sebumeter. RESULTS: Using multiple linear regression analysis, increased pore size was significantly associated with increased sebum output level, sex and age. Among the variables, sebum output level correlated most with the pore size followed by male sex. In comparing male and female participants, males had higher correlation between the sebum output level and the pore size (male: r = 0.47, female: r = 0.38). Thus, additional factors seem to influence pore size in females. Pore size was significantly increased during the ovulation phase (P = 0.008), but severity of acne was not significantly associated with the pore size. CONCLUSIONS: Enlarged pore sizes are associated with increased sebum output level, age and male sex. In female patients, additional hormonal factors, such as those of the menstrual cycle, affect the pore size.

Acne Vulgaris↗

PubMed2005

PI3K/Akt-dependent regulation of the transcription factor myocyte enhancer factor-2 in insulin-like growth factor-1- and membrane depolarization-mediated survival of cerebellar granule neurons.

Survival signals such as insulin-like growth factor-1 (IGF-1) or membrane depolarization convey their neuronal protective effects through the activation of signaling networks and nuclear factors. In cerebellar granule neurons, IGF-1 mediates survival primarily through the PI3K/Akt pathway. The function of the transcription factor myocyte enhancer factor-2 (MEF2) is required for mediating membrane depolarization-dependent neuronal survival. However, whether PI3K/Akt regulates MEF2 and the role of MEF2 in IGF-1-mediated survival of neurons are unknown. In addition, the contribution of the PI3K/Akt pathway in membrane depolarization-induced neuronal survival remains undefined. We show here that the PI3K/Akt pathway promotes the survival of cerebellar granule neurons derived from Long-Evans rats following IGF-1 stimulation or membrane depolarization through regulation of MEF2 activity. IGF-1 stimulated the gene transactivation activity of MEF2 and its DNA binding potential. Moreover, regulation of MEF2 function by IGF-1 was dependent on the activity of the PI3K/Akt signaling pathway. Blocking MEF2 function reduced IGF-1-induced survival of cerebellar granule neurons. Membrane depolarization stimulated phosphorylation of Akt in cerebellar granule neurons. Blocking of the PI3K/Akt pathway with either a pharmacological inhibitor of PI3K, LY294002, or dominant negative mutants of PI3K and Akt inhibited the membrane depolarization-induced increase in MEF2 transactivation as well as its DNA binding activity and reduced neuronal survival. Together, these findings provide clear evidence to support an important role of the PI3K/Akt pathway in the regulation of nuclear survival factor MEF2 upon either IGF-1 stimulation or membrane depolarization, thus placing MEF2 as a novel downstream effector of the PI3K/Akt pathway in neurons.

Action Potentials↗

PubMed2005

Blood-based biomarkers for detecting mild osteoarthritis in the human knee.

OBJECTIVE: This study was designed to test the utility of a blood-based approach to identify mild osteoarthritis (OA) of the knee. METHODS: Blood samples were drawn from 161 subjects, including 85 subjects with arthroscopically diagnosed mild OA of the knee and 76 controls. Following RNA isolation, an in-house custom cDNA microarray was used to screen for differentially expressed genes. A subset of selected genes was then tested using real-time RT-PCR. Logistic regression analysis was used to evaluate linear combinations of the biomarkers and receiver operating characteristic curve analysis was used to assess the discriminatory power of the combinations. RESULTS: Genes differentially expressed (3543 genes) between mild knee OA and control samples were identified through microarray analysis. Subsequent real-time RT-PCR verification identified six genes significantly down-regulated in mild OA: heat shock 90kDa protein 1, alpha; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein; interleukin 13 receptor, alpha 1; laminin, gamma 1; platelet factor 4 (also known as chemokine (C-X-C motif) ligand 4) and tumor necrosis factor, alpha-induced protein 6. Logistic regression analysis identified linear combinations of nine genes--the above six genes, early growth response 1; alpha glucosidase II alpha subunit; and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian)--as discriminatory between subjects with mild OA and controls, with a sensitivity of 86% and specificity of 83% in a training set of 78 samples. The optimal biomarker combinations were then evaluated using a blind test set (67 subjects) which showed 72% sensitivity and 66% specificity. CONCLUSIONS: Linear combinations of blood RNA biomarkers offer a substantial improvement over currently available diagnostic tools for mild OA. Blood-derived RNA biomarkers may be of significant clinical value for the diagnosis of early, asymptomatic OA of the knee.

Adult↗

PubMed2004

Dynamic profile calculation of deposition resolution by high-energy electrons in electron-beam-induced deposition.

The effect of the accelerating voltage of incident electrons on the resolution of electron-beam-induced deposition was investigated by a dynamic Monte Carlo profile simulator which includes the electron scattering in the already grown deposit structure. By simulating the deposition at two different accelerating voltages of 20 and 200 kV with an idealistic zero-diameter incident probe on a bulk substrate, it was revealed that the smaller size structures were attainable by 200 keV than by 20 keV. The effect of the substrate was also argued by comparing the above results with the simulation results obtained for a point-like starting substrate. Surprisingly, the shapes of the deposits grown on bulk substrates were reproduced well by the simulations starting from point-like substrates indicating the small effect of the substrate on the shape of deposits.

Journal Article↗

PubMed2004

Application of transmission electron microscopes to nanometre-sized fabrication by means of electron beam-induced deposition.

Electron beam-induced deposition was carried out using a scanning transmission electron microscope with a field emission gun to fabricate nanometre-sized structures. A small amount of a metal-organic gas was introduced near the substrate in the microscope chamber, and focused electron beams were irradiated. Two- and three-dimensional structures were fabricated by scanning the beam position. The minimum line width of the freestanding structures was 8 nm at a constant gas flux used. This line width of 8 nm is considered to be achieved by employing a high accelerating voltage, which leads to a small probe size, and the optimum scanning speed.

Imaging, Three-Dimensional↗

PubMed2003

NXY-059, a nitrone with free radical trapping properties inhibits release of cytochrome c after focal cerebral ischemia.

Recent studies have demonstrated that disodium 2,4-disulfophenyl-N-tert-butylnitrone (NXY-059), a novel nitrone with free radical trapping properties, has a considerable neuroprotective effect against cerebral ischemic injury. The mechanisms of its action have not been fully defined. In order to evaluate whether NXY-059 exerts its protective effects by inhibiting the release of cytochrome c, a key initiator of programmed cell death pathway, we have studied the effects of NXY-059 on reducing infarct volume and on inhibiting cytochrome c release from the mitochondria after transient focal cerebral ischemia. Wistar rats were subjected to 2 hr of middle cerebral artery occlusion and perfusion-fixed after 4, 6, 12, and 24 hr of reperfusion. NXY-059 (30 mg/kg) was i.v. injected 1 hr after reperfusion and followed immediately by 30 mg/kg/hr continuous i.v. infusion for the entire reperfusion period. The results showed that NXY-059 reduced infarct volume from 37.2% to 12.5% (p<0.0001). Immunocytochemistry demonstrated that the release of cytochrome c increased at 6 hr, peaked at 12 and 24 hr of reperfusion. NXY-059 treatment prevented ischemia-induced cytochrome c release. NXY-059 may reduce ischemic brain damage through suppressing the cell death pathway that is initiated by cytochrome c release.

Animals↗

PubMed2002

Novel pathway to the growth of diamond on cubic beta-SiC(001).

By carrying out first-principles calculations on diamond-forming processes, we predict a method for the heteroepitaxial growth of diamond on cubic beta-SiC(001). In the method, we used two processes: (i) the preformation of an sp(3)-like surface configuration of beta-SiC(001) by the adsorption of group-V surfactants; (ii) the successive growth of diamond by the segregation of the surfactants onto a surface and the desorption of surface hydrogen. Analyzing the segregation energies, we found that the atomic size effect plays a crucial role in the surfactant-mediated growth of diamond on beta-SiC(001).

Journal Article↗

PubMed2002

Simultaneous removal of cadmium and turbidity in contaminated soil-washing water by DAF and electroflotation.

The removal of cadmium and turbidity from contaminated soil-washing water was studied by dissolved air flotation (DAF) and electroflotation at laboratory scale by using sodium lauryl sulfate (SLS) as an anionic surfactant, and calcium hydroxide (Ca(OH)2) as a coagulant. Using DAF, and in the presence of SLS or Ca(OH)2, the maximum recovery rate of cadmium obtained at a stoichiometric cadmium to collector and coagulant ratio of 1:4.5 was 51.1% and 80.8%, while the removal rate of turbidity was 18.4% and 19.2%. However, satisfactory cadmium and turbidity removal was not obtained by DAF. Much more significant removal of cadmium (100%, not detected in the residual) and turbidity (95.7%) was obtained by electroflotation using an aluminium metal plate as electrode, which generated hydroxide and aluminum ion. As a consequence, electroflotation is considered an effective method to separate cadmium and turbidity from contaminated soil-washing water. The electroflotation process may have practical applications for the removal of other hazardous metals from contaminated soil-washing water.

Air↗

PubMed2001

Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells.

Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70(-/-), XRCC4(-/-), and DNA-PKcs(-/-) cells, with the increase being particularly striking in Ku70(-/-) cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.

Animals↗

PubMed2001

C. elegans Rb, NuRD, and Ras regulate lin-39-mediated cell fusion during vulval fate specification.

The tumor suppressor Rb and the NuRD (nucleosome remodeling and histone deacetylation) complex have been implicated in transcriptional repression during cell cycle progression and cell fate specification. The Rb/E2F complex physically interacts with and thus recruits the NuRD complex to actively repress transcription. Caenorhabditis elegans counterparts of Rb, E2F/DP, and some NuRD complex components appear to function in a common class B synthetic Multivulva (synMuv) pathway to antagonize RTK/Ras signaling during vulval fate specification. Therefore, it has been suggested that they function together in a single complex to repress vulva-specific gene transcription. However, little is known about the in vivo interactions between these class B synMuv genes and their relationships with other pathways in specific cellular processes during vulval development. We show that C. elegans Rb/E2F and NuRD complexes antagonize Ras activity by controlling a lin-39 Hox-mediated cell fusion event that regulates the competence of vulval cells. Interestingly, Rb/E2F and NuRD complexes exhibit very different genetic properties. While the NuRD complex negatively regulates lin-39 Hox activity, likely by downregulating its expression, RB/E2F appears to play dual roles in regulating lin-39: a negative role in controlling its activity and a previously uncharacterized positive role in regulating its expression.

Animals↗

PubMed2001

A RHO GTPase-mediated pathway is required during P cell migration in Caenorhabditis elegans.

The Rho family of guanine triphosphate hydrolases controls various cellular processes, including cell migration. We describe here the demonstration of a role for a RhoA GTPase homologue during cell migration in Caenorhabditis elegans. We show that eliminating or reducing rho-1 gene function by using a dominant-negative transgene or dsRNA interference results in a severe defect in migration of hypodermal P cells to a ventral position. Biochemical and genetic data also suggest that unc-73, which encodes a Trio-like guanine nucleotide exchange factor, may act as an activator of rho-1 in the migration process. Mutations in let-502 ROCK, a homologue of a RhoA effector in mammals, also cause defects in P cell migration, suggesting that it may be one of several effectors acting downstream of rho-1 during P cell migration. Finally, we provide evidence to support the idea that other small Rac subfamily small GTPases act redundantly and in parallel to RHO-1 in this specific cell migration event.

Animals↗

PubMed2001

Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila.

In Drosophila, the amidated neuropeptide pigment dispersing factor (PDF) is expressed by the ventral subset of lateral pacemaker neurons and is required for circadian locomotor rhythms. Residual rhythmicity in pdf mutants likely reflects the activity of other neurotransmitters. We asked whether other neuropeptides contribute to such auxiliary mechanisms. We used the gal4/UAS system to create mosaics for the neuropeptide amidating enzyme PHM; amidation is a highly specific and widespread modification of secretory peptides in Drosophila. Three different gal4 drivers restricted PHM expression to different numbers of peptidergic neurons. These mosaics displayed aberrant locomotor rhythms to degrees that paralleled the apparent complexity of the spatial patterns. Certain PHM mosaics were less rhythmic than pdf mutants and as severe as per mutants. Additional gal4 elements were added to the weakly rhythmic PHM mosaics. Although adding pdf-gal4 provided only partial improvement, adding the widely expressed tim-gal4 largely restored rhythmicity. These results indicate that, in Drosophila, peptide amidation is required for neuropeptide regulation of behavior. They also support the hypothesis that multiple amidated neuropeptides, acting upstream, downstream, or in parallel to PDF, help organize daily locomotor rhythms.

Amides↗

PubMed2001

Evaluation of artificial neural networks for the prediction of pathologic stage in prostate carcinoma.

BACKGROUND: Currently, the standard for predicting pathologic stage from information available at the time of prostate biopsy is the "Partin nomograms" that were derived using logistic regression analysis. The authors retrospectively reviewed a large series of men with clinically localized prostate carcinoma who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy. They then utilized pathologic and clinical data at the time of prostate biopsy to develop and test an artificial neural network (ANN) to predict the final pathologic stage for this group of men. They then compared the results of ANN with the previous nomograms. METHODS: Five thousand seven hundred forty-four men were treated at the authors' institution from 1985 to 1998. An ANN was developed using two randomly selected training and validation sets for predicting pathologic stage. Input variables included age, preoperative serum prostate specific antigen level, clinical TNM (tumor, lymph node, and metastasis) classification, and Gleason score from the biopsy specimen. Outcomes included organ confinement and lymph node involvement status. RESULTS: The ANN was slightly superior to the nomograms in predicting pathologic stage, such as organ confinement and lymph node involvement status. CONCLUSIONS: In predicting organ confinement and lymph node involvement status, ANN was more accurate and had a larger area under ROC than the nomograms based on the logistic regression method. Artificial neural network models can be developed and used to better predict final pathologic stage when preoperative pathologic and clinical features are known.

Adult↗

PubMed2001

Artificial neural network model for the assessment of lymph node spread in patients with clinically localized prostate cancer.

OBJECTIVES: To develop an artificial neural network (ANN) model to predict lymph node (LN) spread in men with clinically localized prostate cancer and to describe a clinically useful method for interpreting the ANN's output scores. METHODS: A simple, feed-forward ANN was trained and validated using clinical and pathologic data from two institutions (n = 6135 and n = 319). The clinical stage, biopsy Gleason sum, and prostate-specific antigen level were the input parameters and the presence or absence of LN spread was the output parameter. Patients with similar ANN outputs were grouped and assumed to be part of a cohort. The prevalence of LN spread for each of these patient cohorts was plotted against the range of ANN outputs to create a risk curve. RESULTS: The area under the receiver operating characteristic curve for the first and second validation data sets was 0.81 and 0.77, respectively. At an ANN output cutoff of 0.3, the sensitivity achieved for each validation set was 63.8% and 44.4%; the specificity was 81.5% and 81.3%; the positive predictive value was 13.6% and 6.5%; and the negative predictive value was 98.0% and 98.1%, respectively. The risk curve showed a nearly linear increase (best fit R(2) = 0.972) in the prevalence of LN spread with increases in raw ANN output. CONCLUSIONS: The ANN's performance on the two validation data sets suggests a role for ANNs in the accurate clinical staging of patients with prostate cancer. The risk curve provides a clinically useful tool that can be used to give patients a realistic assessment of their risk of LN spread.

False Negative Reactions↗

PubMed2001

Serum acid phosphatase level and biochemical recurrence following radical prostatectomy for men with clinically localized prostate cancer.

OBJECTIVES: Serum acid phosphatase (ACP) was once used as the marker for advanced prostate cancer. However, with the development of assays for prostate-specific antigen (PSA), a more sensitive and specific tumor marker, the use of ACP has diminished. We investigated the prognostic value of preoperative serum ACP in predicting prognosis for men with localized prostate cancer following radical retropubic prostatectomy (RRP). METHODS: Of 2293 men treated from 1982 to 1998, 1681 men had a preoperative ACP measurement using an enzymatic assay. We analyzed the actuarial freedom from biochemical (PSA) progression following RRP according to ACP levels. We used multivariate logistic regression and proportional hazards models to determine the independent prognostic value of ACP level with respect of pathologic stage and biochemical recurrence. RESULTS: ACP was not an independent predictor of organ confinement or lymph node involvement in the multivariate logistic regression models using preoperative variables. However, in the proportional hazards model, ACP was an independent predictor of tumor recurrence following RRP, and there was a statistically significant improvement in biochemical recurrence-free survival for men with lower levels of ACP (P <0.001). Furthermore, the normalized hazard ratios of ACP and PSA for predicting biochemical recurrence were similar. CONCLUSIONS: Stratification of men according to their preoperative ACP levels was predictive of patient outcome after RRP. Proportional hazards modeling using preoperative variables demonstrated that the serum ACP level is an independent predictor of tumor recurrence following RRP.

Acid Phosphatase↗

PubMed2001

Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy.

OBJECTIVES: To develop a model that will identify a contemporary cohort of patients at high risk of early prostate cancer recurrence (greater than 50% at 36 months) after radical retropubic prostatectomy for clinically localized disease. Data from this model will provide important information for patient selection and the design of prospective randomized trials of adjuvant therapies. METHODS: Proportional hazards regression analysis was applied to two patient cohorts to develop and cross-validate a multifactorial predictive model to identify men with the highest risk of early prostate cancer recurrence. The model and validation cohorts contained 904 and 901 men, respectively, who underwent radical retropubic prostatectomy at Johns Hopkins Hospital. This model was then externally validated using a cohort of patients from the Mayo Clinic. RESULTS: A model for weighted risk of recurrence was developed: R(W)'=lymph node involvement (0/1)x1.43+surgical margin status (0/1)x1.15+modified Gleason score (0 to 4)x0.71+seminal vesicle involvement (0/1)x0.51. Men with an R(W)' greater than 2.84 (9%) demonstrated a 50% biochemical recurrence rate (prostrate-specific antigen level greater than 0.2 ng/mL) at 3 years and thus were placed in the high-risk group. Kaplan-Meier analyses of biochemical recurrence-free survival demonstrated rapid deviation of the curves based on the R(W)'. This model was cross-validated in the second group of patients and performed with similar results. Furthermore, similar trends were apparent when the model was externally validated on patients treated at the Mayo Clinic. CONCLUSIONS: We have developed a multivariate Cox proportional hazards model that successfully stratifies patients on the basis of their risk of early prostate cancer recurrence.

Adult↗

PubMed2001

Verrucous carcinoma of the renal pelvis.

We report a case of a verrucous carcinoma of the renal pelvis after a long history of a renal pelvis stone. Only 1 case of verrucous carcinoma of the renal pelvis has been previously reported, and ours is the first case not associated with a horseshoe kidney.

Carcinoma, Verrucous↗