Biomedical subjects

M Han

Publications and source records attributed to M Han.

At least 37 records · Page 2Linked to original sources

PubMed2001

Does capsular incision at radical retropubic prostatectomy affect disease-free survival in otherwise organ-confined prostate cancer?

OBJECTIVES: To evaluate the influence of isolated, histologically identified capsular incision (CI) (exposure of benign or malignant glands to the inked surgical margin in the setting of organ-confined disease) on disease progression after anatomic radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. METHODS: Between March 1993 and September 1999, 4747 men underwent RRP at the Johns Hopkins Hospital; 107 men (2.3%) were diagnosed with CI in otherwise organ-confined disease; 92 (86%) had at least 6 months (mean 30) of follow-up. We matched these CI cases (based on surgeon, age, clinical stage, final pathologic Gleason grade, and preoperative serum prostate-specific antigen level) one-for-one with controls in three additional pathologically defined groups and compared the freedom from disease progression (prostate-specific antigen level greater than 0.2 ng/mL and/or local palpable recurrence) after RRP. RESULTS: The actuarial 3-year likelihood of freedom from disease progression was 87.8% for the CI group, 96.4% for men with organ-confined disease (P = 0.10), 91.3% for men with extraprostatic extension and negative surgical margins (P = 0.99), and 73.9% for men with positive surgical margins resulting from extraprostatic extension (P <0.01). No statistically significant difference was found in the actuarial likelihood of freedom from disease progression between men with CI into benign glands (n = 22) and men with CI into tumor (n = 70) (P = 0.93). CONCLUSIONS: No statistically significant difference was found in the likelihood of early recurrence between patients with isolated CI and other specimen-confined disease. Patients with isolated CI have a significantly lower likelihood of early recurrence than patients with positive surgical margins due to extraprostatic extension, regardless of whether the CI is into benign glands or tumor. Long-term follow-up is necessary to confirm these findings.

Adult↗

PubMed2001

Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience.

In a large series of 2404 men with a mean follow-up of 6.3 plus or minus 4.2 years (range, 1-17) after anatomic RRP for clinically localized prostate cancer, 412 men (17%) have recurred. A detectable PSA was the only evidence of recurrence in 9.7%, whereas 1.7% and 5.8% had local recurrence and distant metastasis, respectively. The overall actuarial 5-, 10-, and 15-year recurrence-free survival rates for these men were 84%, 74%, and 66%, respectively. As demonstrated in the authors' previous reports, the actuarial likelihood of a postoperative recurrence increased with advancing clinical stage, Gleason-score, preoperative PSA level, and pathologic stage. Subdivision of men with Gleason 7 tumors resulted in better stratification. There was a similar actuarial likelihood of postoperative recurrence for men with Gleason 4 + 3 and Gleason score 8 to 10 disease. The actuarial rate of recurrence of tumor for men with Gleason 3 + 4 disease was statistically different from the rate for men with Gleason score 6 or Gleason 4 + 3 disease. The overall actuarial metastasis-free survival rates at 5, 10, and 15 years were 96%, 90%, and 82%, respectively. The overall actuarial cancer-specific survival rates at 5, 10, and 15 years were 99%, 96%, and 90%, respectively. This study provides long-term outcome of patients with clinically localized cancer who underwent RRP between 1982 and 1999. Recognizing that this long-term study includes many patients with more advanced disease diagnosed before the PSA era, caution must be exercised in comparing these results with the outcomes for cohorts of patients treated since 1989. Anatomic RRP is an effective way to manage clinically localized prostate cancer. Excellent long-term results can be obtained with RRP for early stage disease. The proportion of men with early stage prostate cancer will continue to increase with wide use of serum PSA testing and digital rectal examination.

Adenocarcinoma↗

PubMed2001

Improvement of generalization ability for identifying dynamical systems by using universal learning networks.

This paper studies how the generalization ability of models of dynamical systems can be improved by taking advantage of the second order derivatives of the outputs with respect to the external inputs. The proposed method can be regarded as a direct implementation of the well-known regularization technique using the higher order derivatives of the Universal Learning Networks (ULNs). ULNs consist of a number of interconnected nodes where the nodes may have any continuously differentiable nonlinear functions in them and each pair of nodes can be connected by multiple branches with arbitrary time delays. A generalized learning algorithm has been derived for the ULNs, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. First, the method for computing the second order derivatives of ULNs is discussed. Then, a new method for implementing the regularization term is presented. Finally, simulation studies on identification of a nonlinear dynamical system with noises are carried out to demonstrate the effectiveness of the proposed method. Simulation results show that the proposed method can improve the generalization ability of neural networks significantly, especially in terms that (1) the robust network can be obtained even when the branches of trained ULNs are destructed, and (2) the obtained performance does not depend on the initial parameter values.

Computer Simulation↗

PubMed2001

Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation.

BACKGROUND: Arrestins are responsible for the desensitization of many sequence-divergent G protein-coupled receptors. They compete with G proteins for binding to activated phosphorylated receptors, initiate receptor internalization, and activate additional signaling pathways. RESULTS: In order to understand the structural basis for receptor binding and arrestin's function as an adaptor molecule, we determined the X-ray crystal structure of two truncated forms of bovine beta-arrestin in its cytosolic inactive state to 1.9 A. Mutational analysis and chimera studies identify the regions in beta-arrestin responsible for receptor binding specificity. beta-arrestin demonstrates high structural homology with the previously solved visual arrestin. All key structural elements responsible for arrestin's mechanism of activation are conserved. CONCLUSIONS: Based on structural analysis and mutagenesis data, we propose a previously unappreciated part in beta-arrestin's mode of action by which a cationic amphipathic helix may function as a reversible membrane anchor. This novel activation mechanism would facilitate the formation of a high-affinity complex between beta-arrestin and an activated receptor regardless of its specific subtype. Like the interaction between beta-arrestin's polar core and the phosphorylated receptor, such a general activation mechanism would contribute to beta-arrestin's versatility as a regulator of many receptors.

Amino Acid Sequence↗

PubMed2001

Functional genomics of plant photosynthesis in the fast lane using Chlamydomonas reinhardtii.

Oxygenic photosynthesis by algae and plants supports much of life on Earth. Several model organisms are used to study this vital process, but the unicellular green alga Chlamydomonas reinhardtii offers significant advantages for the genetic dissection of photosynthesis. Recent experiments with Chlamydomonas have substantially advanced our understanding of several aspects of photosynthesis, including chloroplast biogenesis, structure-function relationships in photosynthetic complexes, and environmental regulation. Chlamydomonas is therefore the organism of choice for elucidating detailed functions of the hundreds of genes involved in plant photosynthesis.

Animals↗

PubMed2001

A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy.

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration.

Amino Acid Sequence↗

PubMed2001

Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules.

Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots (zinc sulfide-capped cadmium selenide nanocrystals) into polymeric microbeads at precisely controlled ratios. Their novel optical properties (e.g., size-tunable emission and simultaneous excitation) render these highly luminescent quantum dots (QDs) ideal fluorophores for wavelength-and-intensity multiplexing. The use of 10 intensity levels and 6 colors could theoretically code one million nucleic acid or protein sequences. Imaging and spectroscopic measurements indicate that the QD-tagged beads are highly uniform and reproducible, yielding bead identification accuracies as high as 99.99% under favorable conditions. DNA hybridization studies demonstrate that the coding and target signals can be simultaneously read at the single-bead level. This spectral coding technology is expected to open new opportunities in gene expression studies, high-throughput screening, and medical diagnostics.

Biotechnology↗

PubMed2001

Cytoplasmic dynein light intermediate chain is required for discrete aspects of mitosis in Caenorhabditis elegans.

We describe phenotypic characterization of dli-1, the Caenorhabditis elegans homolog of cytoplasmic dynein light intermediate chain (LIC), a subunit of the cytoplasmic dynein motor complex. Animals homozygous for loss-of-function mutations in dli-1 exhibit stochastic failed divisions in late larval cell lineages, resulting in zygotic sterility. dli-1 is required for dynein function during mitosis. Depletion of the dli-1 gene product through RNA-mediated gene interference (RNAi) reveals an early embryonic requirement. One-cell dli-1(RNAi) embryos exhibit failed cell division attempts, resulting from a variety of mitotic defects. Specifically, pronuclear migration, centrosome separation, and centrosome association with the male pronuclear envelope are defective in dli-1(RNAi) embryos. Meiotic spindle formation, however, is not affected in these embryos. DLI-1, like its vertebrate homologs, contains a putative nucleotide-binding domain similar to those found in the ATP-binding cassette transporter family of ATPases as well as other nucleotide-binding and -hydrolyzing proteins. Amino acid substitutions in a conserved lysine residue, known to be required for nucleotide binding, confers complete rescue in a dli-1 mutant background, indicating this is not an essential domain for DLI-1 function.

Alleles↗

PubMed2001

Rhodopsin: structural basis of molecular physiology.

The crystal structure of rod cell visual pigment rhodopsin was recently solved at 2.8-A resolution. A critical evaluation of a decade of structure-function studies is now possible. It is also possible to begin to explain the structural basis for several unique physiological properties of the vertebrate visual system, including extremely low dark noise levels as well as high gain and color detection. The ligand-binding pocket of rhodopsin is remarkably compact, and several apparent chromophore-protein interactions were not predicted from extensive mutagenesis or spectroscopic studies. The transmembrane helices are interrupted or kinked at multiple sites. An extensive network of interhelical interactions stabilizes the ground state of the receptor. The helix movement model of receptor activation, which might apply to all G protein-coupled receptors (GPCRs) of the rhodopsin family, is supported by several structural elements that suggest how light-induced conformational changes in the ligand-binding pocket are transmitted to the cytoplasmic surface. The cytoplasmic domain of the receptor is remarkable for a carboxy-terminal helical domain extending from the seventh transmembrane segment parallel to the bilayer surface. Thus the cytoplasmic surface appears to be approximately the right size to bind to the transducin heterotrimer in a one-to-one complex. Future high-resolution structural studies of rhodopsin and other GPCRs will form a basis to elucidate the detailed molecular mechanism of GPCR-mediated signal transduction.

Amino Acid Sequence↗

PubMed2001

Role of C. elegans lin-40 MTA in vulval fate specification and morphogenesis.

Vulval differentiation in Caenorhabditis elegans involves several fundamental cellular events, including cell fusion, division and migration. We have characterized the role of the lin-40 (also known as egr-1) gene in these cellular processes. LIN-40 is homologous to the metastasis-associated factor 1 (MTA1) in mammals, which has been identified as a component of the nucleosome remodeling and histone deacetylation (NuRD) complex that functions as a transcriptional co-repressor. We show here that lin-40 negatively regulates vulval fate specification at least partly by promoting cell fusion between the vulval precursor cells and the hypodermal syncytium at an early larval stage. This inhibitory function of lin-40 might be carried out by downregulating lin-39 Hox expression. We also show that lin-40 is specifically required for cell divisions along the transverse orientation during vulval morphogenesis.

Animals↗

PubMed2001

unc-83 encodes a novel component of the nuclear envelope and is essential for proper nuclear migration.

Nuclear migration plays an essential role in the growth and development of a wide variety of eukaryotes. Mutations in unc-84, which encodes a conserved component of the nuclear envelope, have been shown to disrupt nuclear migration in two C. elegans tissues. We show that mutations in unc-83 disrupt nuclear migration in a similar manner in migrating P cells, hyp7 precursors and the intestinal primordium, but have no obvious defects in the association of centrosomes with nuclei or the structure of the nuclear lamina of migrating nuclei. We also show that unc-83 encodes a novel transmembrane protein. We identified three unc-83 transcripts that are expressed in a tissue-specific manner. Antibodies against UNC-83 co-localized to the nuclear envelope with lamin and UNC-84. Unlike UNC-84, UNC-83 localized to only specific nuclei, many of which were migratory. UNC-83 failed to localize to the nuclear envelope in unc-84 mutants with lesions in the conserved SUN domain of UNC-84, and UNC-83 interacted with the SUN domain of UNC-84 in vitro, suggesting that these two proteins function together during nuclear migration. We favor a model in which UNC-84 directly recruits UNC-83 to the nuclear envelope where they help transfer force between the cytoskeleton and the nucleus.

Active Transport, Cell Nucleus↗

PubMed2001

Isolated local recurrence is rare after radical prostatectomy in men with Gleason 7 prostate cancer and positive surgical margins: therapeutic implications.

PURPOSE: We determined whether the high biochemical failure rate in men with Gleason score 7 disease and positive surgical margins after radical retropubic prostatectomy is secondary to distant metastasis or to local tumor recurrence that could be eliminated by immediate adjuvant radiation therapy. MATERIALS AND METHODS: Between 1982 and 1997, 112 men with Gleason score 7 disease and positive surgical margins but no seminal vesicle or lymph node involvement underwent radical retropubic prostatectomy without immediate adjuvant radiation or hormonal therapy. Median followup was 8 years (range 1 to 16) and 45 men (40%) were followed 10 years or more. Kaplan-Meier actuarial survival estimates were used to determine the actuarial 5 and 10-year post-prostatectomy, and 5-year post-radiation recurrence rates. RESULTS: The actuarial 5 and 10-year post-prostatectomy biochemical, local and distant recurrence rates were 40% and 52%, 6% and 6%, and 7% and 16%, respectively. For 20 men who received radiation therapy for isolated prostate specific antigen elevation actuarial 5-year post-radiation biochemical recurrence-free rate was 34%. For 5 men who received radiation therapy for local recurrence actuarial 5-year post-radiation biochemical recurrence-free rate was 20%. CONCLUSIONS: Isolated clinical local recurrence is rare during long-term followup of men with Gleason score 7 disease and positive surgical margins at radical prostatectomy. Radiation therapy given at prostate specific antigen elevation poorly controlled the disease. Because patients with biochemical failure rarely had local recurrence at long-term followup, they most likely harbored subclinical distant metastasis. These data suggest that immediate adjuvant radiation therapy will not have a major impact on outcome because most men with Gleason score 7 disease and positive surgical margins in whom treatment fails most likely had distant metastasis at surgery. To improve the outcome in cases of Gleason score 7 disease and positive surgical margins a systemic approach to adjuvant therapy is necessary.

Aged↗

PubMed2001

Collision efficiency factor of bubble and particle (alpha bp) in DAF: theory and experimental verification.

The collision efficiency factor of bubble and particle (alpha bp) in dissolved air flotation (DAF) can be calculated theoretically by trajectory analysis, which takes into account both hydrodynamics and interparticle forces. To determine the theoretically optimum particle size for any given bubble size, a collision efficiency diagram for DAF was developed where collision efficiency is contoured on a plane of particle and bubble sizes for different conditions of particle zeta potential. A set of experiments tested the validity of the suggested collision efficiency diagram, and examined whether pretreatment is important and why slight coagulant overdosing and shorter flocculation times are generally preferred in DAF, both current accepted practice. Batch DAF reactors were used and kaolin samples were prepared from jar tests using different alum dosages and flocculation times. The particle size distribution, particle zeta potential, and turbidity removal in each experiment were measured, as were bubble size and zeta potential. The results agreed well with the predictions of the collision efficiency diagram and explained current practices. A collision efficiency diagram identifies the pretreatment goal, i.e., tailoring of the optimum characteristics required of particles (zeta potential and size) under existing operational bubble characteristic.

Air↗

PubMed2001

[Detection of TORCH genom in the cardiac tissue of congenital heart disease].

OBJECTIVE: To explore relationships of TORCH (cytomegalovirus/CMV, toxoplasma/TOX, rubella virus/RV, herpes simplex virus-2 HSV2) infection with congenital heart disease (CHD). METHODS: We conducted comparison to detection TORCH pathogenic gene in 42 cases of CHD and 38 controls by polymerase chain reaction (PCR). RESULTS: 1. The positive rate of CMV, HSV2 and TOX in 66 cases of CHD were 26.2%, 4.7% and 16.7%, respectively, while those of 38 cases in control groups were 21.1%, 2.6% and 2.6%, respectively. The infection condition of TOX was significantly different (P = 0.0378), while those of CMV and HSV were not statistically different (P > 0.05) between CHD and control groups. 2. 7 of 30(23.3%) were positive for RV-RNA, compared with control group which were all negative, it was significantly higher (P = 0.0328). CONCLUSION: This is the first report of the presence of TORCH genes in CHD cardiac tissue by PCR. It might lay the foundation for studying the relationship of TORCH infection with CHD in molecular level.

Animals↗

PubMed2001

Era specific biochemical recurrence-free survival following radical prostatectomy for clinically localized prostate cancer.

PURPOSE: We retrospectively reviewed a large series of men with clinically localized prostate cancer who underwent surgery to define the extent of stage migration and its influence on biochemical recurrence in 3 different eras of prostate cancer management. MATERIALS AND METHODS: A total of 2,370 men were treated with radical prostatectomy from 1982 to 1998. We analyzed the freedom from biochemical (prostate specific antigen) progression after radical prostatectomy. We compared the distribution of pathological stage by the year of surgery. We then compared the biochemical recurrence-free survival rate according to the different eras that reflect a change in prostate cancer management. RESULTS: There was a significant downward stage migration of prostate cancer and an increasing proportion of men who presented with organ confined disease in recent years. The actuarial biochemical recurrence-free rate was significantly different for patients who underwent surgery between 1982 and 1988, compared with those between 1989 and 1998 (p <0.001). These changes may have reflected the benefits of early detection with prostate specific antigen and digital rectal examination, better preoperative selection of patients for surgery as well as the effect of lead time. CONCLUSIONS: Widespread early detection programs for prostate cancer resulted in downward stage migration in men presenting with prostate cancer at our institution during the last 18 years. Also, we have demonstrated a biochemical recurrence-free survival advantage, probably secondary to an improved therapeutic outcome as well as lead time bias, in men who underwent surgery between 1989 and 1998, compared with those between 1982 and 1988. When trying to compare the efficacy of different treatment modalities for prostate cancer, the era in which patients underwent therapy is an important factor to be considered.

Adult↗

PubMed2001

Detection of human herpesvirus 8 DNA in acute leukemia patients.

OBJECTIVE: To determine the prevalence of human herpesvirus 8 (HHV-8) DNA in acute leukemia (AL) patients. METHODS: The presence of HHV-8 DNA sequences in peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) from 50 AL patients was examined using polymerase chain reaction (PCR). Nine human hematopoietic cell lines and PBMC from 30 normal donors were also included. RESULTS: HHV-8 DNA sequences were detected in one case of acute myelogenous leukemia (AML). The specimens from the bone marrow aspirate, peripheral blood and serum of this patient were all positive. None of the normal donors and human hematopoietic cell lines showed evidence of HHV-8 DNA. CONCLUSION: The results suggest that the prevalence of HHV-8 is low in AL in China.

Acute Disease↗

PubMed2001

[Dynamic monitoring of Ph positive cells during early post-transplant period in chronic granulocytic leukemia by interphase FISH].

OBJECTIVE: To assess the effectiveness of transplantation and observe the kinetics of residual leukemic cells during early post-transplantation period in chronic granulocytic leukemia (CGL). METHODS: Ten normal controls, seven untreated CGL patients and eleven CGL patients after allogeneic bone marrow transplantation (allo-BMT) or peripheral blood stem cell transplantation (PBSCT) were studied by interphase fluorescence in situ hybridization (I-FISH) with the FITC fluorescein labeled BCR probe. Conventional cytogenetic analysis (CCA) and reverse transcriptase-polymerase chain reaction (RT-PCR) were also employed. RESULTS: The normal cutoff was defined as less than 6.68% (x +/- 3s) from the analysis of normal controls. The reproduciblity of FISH method was confirmed by serial dilutions by mixing Ph positive cells and normal cells. Forty specimens from 11 CGL patients at 1 week to 6 years post-BMT were investigated after PBSCT and the results showed that (1) FISH and RT-PCR could accurately evaluate Ph (+) cells during early transplantation period (within one month), but RT-PCR was more sensitive in six months after BMT. (2) Residual Ph (+) cells tended to be linear decreasing with the time after transplantation and fell in normal range in most samples three months later. The mean time of normaligation was 57 days (20 to 170 days). (3) One case relapsed and received a second transplantation. FISH presented more precise data for predicting relapse as compared to CCA and RT-PCR. CONCLUSIONS: I-FISH as a useful tool can not only offer more precise assessment of residual leukemic cells compared with CCA and RT-PCR, but also provide dynamic monitoring during early post-BMT period to evaluate the transplantation outcome and predict relapse.

Adult↗

PubMed2001

[Study on analysis of trace phenol in small amount of aqueous sample by liquid-liquid micro-extraction and gas chromatography].

A method for the liquid-liquid micro-extraction and gas chromatographic analysis of trace phenol in small amount of aqueous sample has been developed. The influences of acid and salts on recovery rate of phenol were examined. And, the influences of injection speeds and the conditions of silica wool in injection port on the quantitation precision were tested. With a direct injection port, an FID and a DB-1 capillary column of wide bore, a detection limit of 1 microgram.L-1 can be obtained employing 8 mL water sample, 160 microL ethyl acetate and 3.5 g ammonium sulfate. The added recoveries were in the range of 95.0%-98.5%. The relative standard deviations were in the range of 2.8%-3.3%. This method is simple, convenient, rapid, accurate and practical.

Chromatography, Gas↗