PubMed Health⌕ Search

Biomedical subjects

M Han

Publications and source records attributed to M Han.

At least 73 records · Page 4Linked to original sources

Mutations in cye-1, a Caenorhabditis elegans cyclin E homolog, reveal coordination between cell-cycle control and vulval development.

We have identified strong loss-of-function mutations in the C. elegans cyclin E gene, cye-1. Mutations in cye-1 lead to the underproliferation of many postembryonic blast lineages as well as defects in fertility and gut-cell endoreduplication. In addition, cye-1 is required maternally, but not zygotically for embryonic development. Our analysis of vulval development in cye-1 mutants suggests that a timing mechanism may control the onset of vulval cell terminal differentiation: once induced, these cells appear to differentiate after a set amount of time, rather than a specific number of division cycles. cye-1 mutants also show an increase in the percentage of vulval precursor cells (VPCs) that adopt vulval cell fates, indicating that cell-cycle length can play a role in the proper patterning of vulval cells. By analyzing cul-1 mutants, we further demonstrate that vulval cell terminal differentiation can be uncoupled from associated changes in vulval cell division planes.

Amino Acid Sequence↗

Non-steroidal anti-androgens in prostate cancer--current treatment practice.

Adenocarcinoma of the prostate is a common disease that causes significant morbidity and mortality in the adult male population. Hormonal therapy for prostate cancer is considered when a patient fails with initial curative therapy, such as radical prostatectomy or definitive radiation therapy, or if he is found with an advanced disease. Many hormonal agents have been developed to exploit the fact that prostate cancer growth is dependent on androgen. Non-steroidal anti-androgens (NSAAs) block androgen at the cellular level. Numerous clinical trials comparing monotherapy of castration and combination therapy of castration and NSAAs have been performed. At present, the results of the trials with regard to the survival of patients under therapy are conflicting. When the disease recurs in a patient in the middle of combination androgen blockade therapy, androgen withdrawal should be considered. The benefits of NSAA in monotherapy, intermittent or neoadjuvant therapy are not clear at present. Better designed, larger cohort clinical trial may be necessary to clarify the confusion.

Calcium Oxalate↗

Ability of the 1992 and 1997 American Joint Committee on Cancer staging systems for prostate cancer to predict progression-free survival after radical prostatectomy for stage T2 disease.

PURPOSE: In a revised 1997 edition the American Joint Committee on Cancer (AJCC) staging for prostate cancer reduced the subdivision of T2 disease from 3 (T2a, T2b and T2c) to 2 substages by combining single lobe disease (T2a and T2b) into a single stage, now termed T2a. We retrospectively reviewed a large series of men with clinically organ confined prostate cancer who underwent surgery by a single surgeon to determine how this change affected the ability of the staging system to predict outcome. MATERIALS AND METHODS: Of 2, 293 cases treated with radical prostatectomy from 1982 to 1998, 1, 314 were clinically staged to have T2 disease. We analyzed the freedom from biochemical prostate specific antigen (PSA) progression after radical prostatectomy according to the 1992 and 1997 AJCC staging criteria. RESULTS: Overall the actuarial 5 and 10-year biochemical progression-free survival rates for the whole group were 82% and 71%, respectively. The actuarial recurrence-free rate was significantly different for patients with 1992 AJCC T2a (T2a92) versus T2b (T2b92) disease (p <0.0001) but similar for those with 1992 T2b versus T2c (T2c92) disease (p = 0.1165). The actuarial recurrence-free rate was significantly different for patients with 1997 AJCC T2a (T2a97) versus T2b (T2b97) disease (p = 0.0001). However, the overall recurrence-free rate was lower in the T2a97 group compared with the T2a92 group. CONCLUSIONS: The 1992 AJCC staging of T2 prostate cancer yielded a significant difference in the outcome of patients with single lobe disease (T2a92 and T2b92), which is obscured by the 1997 staging criteria. Therefore, we believe that the next revision of the AJCC staging system should revert back to the 1992 AJCC system of subdividing a single lobe disease category into T2a and T2b. Alternatively the committee may want to merge T2b92 and T2c92 stages into a new staging entity, since there was no statistical difference in the outcome of these 2 groups.

Adult↗

Molecular cloning and characterization of the promoter region of the inducible nitric oxide synthase gene of the rat.

To investigate the mechanism by which inducible nitric oxide synthase (iNOS) within vascular smooth muscle cells (VSMC) is expressed following exposure to proinflammatory cytokines, we cloned the promoter region of the rat iNOS gene by a single specific primer PCR cloning strategy. The 5;-flanking region of the rat iNOS gene contains interferon-gamma (IFN-gamma)- and tumor necrosis factor-alpha (TNF-alpha)-responsive elements and an NF-kappaB-binding consensus sequences. The position and alignment of these consensus sequences are distinct from those in the mouse iNOS and human iNOS genes. It was shown that some nuclear factor(s) which bound specifically to the fragment of the rat iNOS gene containing several consensus sequences were produced after VSMC were treated with interleukin 1 (IL-1) and IFN-gamma.

Animals↗

[The localization of parvovirus B19 in cardiac biopsy tissue of congenital heart disease].

OBJECTIVE: To explore the relationship between parvovirus B19 infection and congenital heart disease (CHD), and distribution of parvovirus B 19 gene in cardiac tissue. METHODS: We conducted a case controls study investigating the presence of B19 gene in cardiac biopsy tissue of 37 cases of CHD, 8 cases of rheumatic heart disease (RHD) and 20 cases of non-CHD with nested polymerase chain reaction (Nested PCR) and in situ hybridization (ISH). RESULTS: Among 37 CHD patients, 6 were B19 DNA positive in cardiac tissue (18.92%), while in control group, including 8 RHD patients (autopsy specimens) and 20 non-CHD patients, the B19 gene were all negative, there was a significant difference of B19 gene presence between CHD group and control group (P = 0.0421). ISH of B19 gene in cardiac tissue were positive in 4 CHD patients and all were negative in control group. The B19 gene was found locating in the nucleus of cardiac cell by ISH. CONCLUSIONS: Parvovirus B19 infection correlated with CHD. Since B19 gene was mainly found in the cardiac cell nucleus, maybe it influenced the regulation of gene expression and affected the development of heart with the result of CHD.

Adolescent↗

[Establishment and biological characteristics of a novel erythroleukemia cell line (HIE1)].

OBJECTIVE: To establish a novel leukemia cell line and characterize its biological characteristics. METHOD: The cell line was established by liquid cell culture. The genetic marker was analyzed by R-banding and reverse transcriptase-polymerase chain reaction (RT-PCR), cell morphology by microscopy, electron microscopy and histochemical staining, cell surface antigen by monoclonal antibody, hemoglobin by hyperomethemoglobin measurement and electrophoresis, erythroid differentiation by benzidine-staining, and monocyte-macrophage differentiation by cell morphology and phagocytosis. RESULTS: A novel erythroleukemia cell line (HIE1), with original cell genetic marker (Ph chromosome, bcr/abl fusion gene rearrangement), was established from a CML patient in blast crisis, and has been passaged for over 60 generations. Myelomonocyte marker and hemoglycoprotein A were found on the cell surface. HIE1 cells contained hemoglobin, the same HbA and HbA(2) bands as in normal individuals were displayed by Hb electrophoresis. The benzidine positive HIE1 cells were induced after exposure to 3.6 x 10(-4) mmol/L Ara-C. When HIE1 cells were treated with 100 ng/ml PMA for 3 days, one third of the cells became spindle in shape, and 6.5% of the cells exert phagocytosis. The cells were classified into two types with Wright-staining: one showing light blue cytoplasm and a few of cells with basophilic granules, the other showing dark blue cytoplasm with vacuoles and pseudopods without granules. In addition, POX, SB, CE stains were negative, and AE, PAS, ACP stains positive. Colony formation of the cells was 37%, the cell doubling time was 22 - 24 hrs, and EB virus detection was positive. CONCLUSION: A novel erythroleukemia cell line with bcr/abl fusion gene and characteristics of myelomonocytic and erythroid cells was established.

Cell Differentiation↗

[Treatment of acute lymphoblastic leukemia by autologous stem cell transplantation: an analysis of 30 cases].

OBJECTIVE: To evaluate the clinical outcome of autologous stem cell transplantation (ASCT) in acute lymphoblastic leukemia (ALL) and the affected factors. METHODS: Data of 30 ALL patients received ASCT in our hospital between July 1987 and December 1997 were retrospectively analyzed. Twenty-four of them were in the first complete remission (CR(1)) and six in the second complete remission (CR(2)) or early relapse (ER). Conditioning regimens were CTX 120 mg/kg + single total body irradiation 9 - 10 Gy (sTBI) or Bu 16 mg/kg of Mel 140 - 180 mg/m(2) + Ara-c 2 - 4 g/m(2). RESULTS: All patients reconstituted hematopoiesis. The median follow-up duration was 504 (18-3043) days. Transplant-related mortality was 10%. The probabilities of 3 year disease-free survival (DFS) for ALL in CR(1) and CR(2) were 67.7% +/- 10.3% and 16.7% +/- 15.2%, respectively (P = 0.00547); the 3 year DFS was significantly better with posttransplant treatment than without it (92.3% +/- 7.4% vs 50.0% +/- 17.7%, P = 0.0130). CONCLUSION: Acute lymphoblastic leukemia patients without HLA-matched related donor are recommended for ASCT in CR(1). To reduce relapse and improve the outcome, adoptive immunotherapy or maintenance chemotherapy should be given after ASCT.

Adolescent↗

[The impact of hepatitis B virus infected patients or donors on the outcome of hematopoietic stem cell transplantation].

OBJECTIVE: To investigate the impact of recipients and/or donors infected with hepatitis B on the outcome of hematopoietic stem cells transplantation (HSCT). METHODS: We analyzed retrospectively the transplantation outcome in 26 of 164 hematological diseases patients who and whose donors were infected with hepatitis prior to transplantation. RESULTS: (1) Three of the 26 patients developed VOD after HSCT, the incidence (11.5%) is significant higher than that in patients and donors who did not infected with HBV (P < 0.05). (2) Two of 5 patients transfused hematopoietic stem cells from HBsAg + donors developed hepatitis B. (3) Four patients with allogeneic stem cell transplantation developed hepatic failure (HF) which occurred during cyclosporin (CsA) being tapered off or withdrawal. The incidence of HF in patients and/or donors infected with HBV (15.4%) is obviously higher than that in patients and donors who did not (0.08%, P < 0.01). (4) In 4 patients with HbeAg +, 2 patients died of HF after allogeneic HSCT, the other 2 patients survived after autologous HSCT. CONCLUSION: Donors and recipients infected with hepatitis B are not contraindication of HSCT, but patients with allogeneic HSCT are in danger to develop LF during CsA being tapered off or withdrawal.

Adolescent↗

A PP2A regulatory subunit positively regulates Ras-mediated signaling during Caenorhabditis elegans vulval induction.

We describe evidence that a regulatory B subunit of protein phosphatase 2A (PP2A) positively regulates an RTK-Ras-MAP kinase signaling cascade during Caenorhabditis elegans vulval induction. Although reduction of sur-6 PP2A-B function causes few vulval induction defects in an otherwise wild-type background, sur-6 PP2A-B mutations suppress the Multivulva phenotype of an activated ras mutation and enhance the Vulvaless phenotype of mutations in lin-45 raf, sur-8, or mpk-1. Double mutant analysis suggests that sur-6 PP2A-B acts downstream or in parallel to ras, but likely upstream of raf, and functions with ksr-1 in a common pathway to positively regulate Ras signaling.

Adaptor Proteins, Signal Transducing↗

The ABCR gene in recessive and dominant Stargardt diseases: a genetic pathway in macular degeneration.

Stargardt disease (STGD) is a juvenile-onset macular dystrophy and can be inherited in an autosomal recessive or in an autosomal dominant manner. Genes involved in dominant STDG have been mapped to human chromosomes 13q (STGD2) and 6q (STGD3). Here, we identify a new kindred with dominant STGD and demonstrate genetic linkage to the STGD3 locus. Because of a more severe macular degeneration phenotype of one of the patients in this family, the gene responsible for the recessive STGD1, ABCR, was analyzed for sequence variants in all family members. One allele of the ABCR gene was shown to carry a stop codon-generating mutation (R152X) in three family members, including the one patient who had inherited also the dominant gene. A grandparent of that patient with the same ABCR mutation developed age-related macular degeneration (AMD), consistent with our earlier observation that some variants in the ABCR gene may increase susceptibility to AMD in the heterozygous state. Based on these results, we propose that there is a common genetic pathway in macular degeneration that includes genes for both recessive and dominant STGD.

ATP-Binding Cassette Transporters↗

Invariant or highly conserved TCR alpha are expressed on double-negative (CD3+CD4-CD8-) and CD8+ T cells.

TCR alpha (TCRA) expression was examined in RNA samples from PBMC and isolated populations of CD4+, CD8+, and DN T cells from 15 healthy individuals. The expressed TCR repertoire was surveyed using spectratype analysis, a technique that displays the distribution of complementarity determining region 3 (CDR3) lengths for each TCRAV gene family. The results revealed the presence of unusual populations of double-negative (DN; CD4-CD8-CD3+) T cells that express invariant or conserved TCRAV4A, AV7, AV19, and AV24 chains. Each of the conserved TCRA families was over-represented in >70% of the individuals studied, and all individuals expressed at least one of the over-represented TCRAV families. Over-represented conserved AV4A or AV7 sequences were also present in CD8+ T cells from most donors. The extent of TCRA sequence conservation is unparalleled. TCRAV4A, AV19, and AV24 sequences were invariant, although AV4A and AV19 transcripts contained N region additions. TCRAV24 transcripts derived from the direct juxtaposition of V and J gene segments. TCRAV7 sequences showed some diversity in two amino acids encoded at junctions of V and J gene segments. Although derivation of DN T cells with conserved TCRA chains is puzzling, the wide-spread expression of these unusual cells suggests an important function.

Adult↗

[Antagonism of folic acid on the toxicity of aspirin in yolk sac of rats].

The antagonistic effects of folic acid to aspirin on the development of rat yolk sac and embryos were studied during early organogenesis by using whole embryo culture technique and electron microscopy. The results showed that when treated with aspirin, the diameter of yolk sac and the body length of embryo were much shorter, the frequencies of abnormal embryos were significantly higher, and the yolk sac became thinner than those without treatment. The number of blood islands and capillaries decreased, the differentiation and development of blood vessel were retarded in the treated group. Ultrastructure observation also showed that the numbers of microvilli and capillaries were greatly decreased, and the structure and the numbers of lysosomes, endoplasmic reticula and ribosomes significantly changed in the treated group. When aspirin was added with high folic acid serum, the toxicity on yolk sac decreased or disappeared. The results suggested that the protection of yolk sac would be related to the antagonism of folic acid to aspirin.

Animals↗

A Caenorhabditis elegans homologue of hunchback is required for late stages of development but not early embryonic patterning.

We have cloned a Caenorhabditis elegans homologue of the Drosophila gap gene hunchback (hb) and have designated it hbl-1 (hunchback-like). hbl-1 encodes a predicted 982-amino-acid protein, containing two putative zinc-finger domains similar to those of Drosophila Hunchback. The gene is transcribed embryonically, but unlike the maternally expressed Drosophila hb, its mRNA is not detected in C. elegans oocytes. A hbl-1::gfp reporter is expressed primarily in ectodermal cells during embryonic and larval development. Double-stranded RNA-interference (RNAi) was used to indicate hbl-1 loss-of-function phenotypes. Progeny of hbl-1(RNAi) hermaphrodites exhibit a range of defects; the most severely affected progeny arrest as partially elongated embryos or as hatching, misshapen L1 larvae. Animals that survive to adulthood exhibit variably dumpy (Dpy), uncoordinated (Unc), and egg-laying defective (Egl) phenotypes, as well as defects in vulval morphology (Pvl). Abnormal organization of hypodermal cells and expression of a hypodermal marker in hbl-1(RNAi) animals suggests that most of the phenotypes observed could be due to improper specification of hypodermal cells. The pattern of hbl-1 expression is similar to that reported for the leech hunchback homologue Lzf-2, suggesting that these proteins may have similar biological functions in diverse species with cellular embryos.

Amino Acid Sequence↗

Isolation and mapping of the rabbit DM genes.

Proper peptide presentation by major histocompatibility complex (MHC)-encoded class II antigens is dependent on the products of the MHC DM loci. We identified the rabbit orthologues (RLA-DMA and -DMB) of human HLA-DMA and -DMB and found that they have 76.9% and 78.8% identity with HLA-DMA and -DMB, respectively. Like classical class II MHC genes, RLA-DM genes are more closely related to human HLA-DM genes than to mouse H2-DM. Among the DM family, there is a high degree of variability at the amino terminus of the DMa chains, and length variability in the cytoplasmic tails of both DMalpha and DMbeta. The rabbit DM genes are coexpressed with class II genes in lymphoid tissues, as are the DM genes of other mammals. The RLA-DM locus maps to the class II region of the rabbit MHC, and is flanked by the DP and DOB loci. Despite having some similarities to class II genes of bony fishes, the DM family represents a separate branch of the MHC class II family.

Amino Acid Sequence↗

A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease.

PURPOSE: To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Stargardt disease. METHODS: A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evaluation and fluorescein angiography. Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gene were analyzed by single-stranded confirmation polymorphism analysis, followed by direct sequencing of observed variants, to identify mutations in the ABCR gene. RESULTS: We identified a previously unreported kindred of eight siblings, four of whom had mutations in both of their ABCR alleles. A previously described G-to-C transversion of nucleotide 2588, predicting a Gly863Ala amino acid substitution, and a novel G-to-A transition of nucleotide 161, resulting in a Cys54Tyr substitution, were identified. These mutations co-segregated with the affected members of this family. Three of the siblings demonstrated clinical features characteristic of classic Stargardt disease, with bilateral regions of macular atrophy associated with yellow-white "flavimaculatus" flecks in the posterior pole at the level of the retinal pigment epithelium. The fourth affected sibling showed features of early Stargardt disease, with a beaten-bronze appearance to both maculas, as well as perimacular flecks. In all four affected patients, fluorescein angiography showed a characteristic peripheral dark choroid. CONCLUSIONS: We have identified both a previously described and a novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease. In-depth knowledge of the ABCR mutation spectrum in patients with Stargardt disease will provide for more efficient screening and may provide potential therapies for Stargardt disease and other retinal diseases.

ATP-Binding Cassette Transporters↗

Polymorphism of human CD1 genes.

Human CD1 genes have been reported to be invariant or to show limited polymorphism. Recently, certain functions of CD1 antigens have been described to include the presentation lipid and glycolipid antigens. These observations prompted a thorough survey of the genetic polymorphism in the five human CD1 genes (CD1a-CD1e). Using polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) combined with sequence analyses, exons 2 and 3 from CD1a-CD1e were characterized from a total of 110 unrelated healthy donors. Results showed that all five genes (CD1a-CD1e) are polymorphic in exon 2. Substitutions in CD1b and CD1c are silent, whereas, substitutions in CD1a, CD1d and CD1e result in amino acid replacements in the deduced protein products. CD1a and CD1e polymorphisms are prevalent in the population. The substitutions in CD1a have characteristics that may influence interactions with beta2-microglobulin beta2-m) or accessory molecules. The substitution in CD1e is located in the region predicted to interact with ligands and may differentially impact the ability of CD1e alleles to bind antigen.

Amino Acid Sequence↗