Biomedical subjects

M Han

Publications and source records attributed to M Han.

At least 91 records · Page 5Linked to original sources

PubMed1999

Low-density lipoprotein apheresis retards the progression of hyperlipidemic overt diabetic nephropathy.

BACKGROUND: Hyperlipidemia has recently received attention as being involved in the progression of diabetic nephropathy (DN). Low-density lipoprotein apheresis (LDL-A) can remove a large amount of plasma lipid directly from the patients in a short time. METHODS: Fifteen type 2 diabetic patients with overt nephropathy received LDL-A in two different manners: short-term intensive therapy (SIT) for nine patients and long-term intermittent therapy (LIT) for six patients. RESULTS: The changes in the monthly decline rates of reciprocal serum creatinine (1/Cr) were -0.035 +/- 0.020 in the three-month period before SIT, 0.047 +/- 0.041 during and until two weeks after SIT, and -0.035 +/- 0.015 after a period of two weeks from the therapy. The mean duration of LIT in six patients was 8.2 +/- 7.4 months, and the mean monthly decline rates of 1/Cr significantly decreased during the period of LIT as compared with the six-month period before the treatment. CONCLUSION: LDL-A can retard the progression of overt DN, especially when it is performed repeatedly for a long period at two-week intervals.

Aged↗

PubMed1999

Clinical and genetic studies of an autosomal dominant cone-rod dystrophy with features of Stargardt disease.

Cone-rod dystrophy (CORD) and Stargardt disease (STGD) are two hereditary retinal dystrophies with similarities to age-related macular degeneration. Cone-rod dystrophies are a group of degenerative disorders resulting in decreased visual acuity and color vision, attenuated electroretinographic (ERG) responses, and atrophic macular lesions. Autosomal dominant, autosomal recessive, and X-linked forms of cone-rod dystrophy have been reported. Stargardt disease is characterized by reduced visual acuity, atrophic macular changes, prominent 'flavimaculatus flecks' in the pigment epithelium of the posterior retina, and a virtually pathognomic 'dark choroid' pattern on fluorescein angiography. Stargardt disease is classically inherited as an autosomal recessive trait, although numerous families have been described in which features of Stargardt disease are transmitted in an autosomal dominant manner. We have identified a new kindred with autosomal dominant cone-rod dystrophy with features of Stargardt-like disease. Detailed clinical evaluation, genotype analysis, and linkage analysis were performed. Fluorescein angiography revealed a 'dark choroid' pattern in three affected subjects. Electroretinography disclosed markedly reduced scotopic and photopic responses in three affected individuals. Genetic analysis revealed linkage to known loci for cone-rod dystrophy (CORD7) and Stargardt-like disease (STGD3) on chromosome 6q14. A peak lod score of 3.3 was obtained with the marker D6S280 at straight theta =0.010. A physical map was constructed by screening a YAC library with short tandem repeat markers in the region. Screening of a candidate gene, the rho1 subunit of the GABA receptor, failed to reveal any mutations.

Adult↗

PubMed1999

A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4.

Chromosome Mapping↗

PubMed1999

The clinical usefulness of F-18 FDG coincidence PET without attenuation correction and without whole-body scanning mode in pulmonary lesions comparison with CT, MRI, and clinical findings.

PURPOSE: This study was undertaken to assess the clinical usefulness of fluorine-18 flurodeoxyglucose (F-18 FDG) coincidence detection (CoDe) positron emission tomography (PET) of various lung lesions by comparing it with CT, MRI, and clinical findings. MATERIALS AND METHODS: Forty-two patients with pulmonary lesions underwent CoDe PET using a dual-head gamma camera equipped with a 5/8 inch thick NaI (Tl) crystals. The patients were prepared for the study by overnight fasting. Data was acquired at approximately 1 hour after the intravenous injection of 111 to 370 MBq (3 to 10 mCi) of F-18 FDG. A spinal scan of the thorax was performed using a slip ring gantry for 30 minutes. After rebinning, routine tomographic slices were reconstructed without attenuation correction and the images were analyzed visually. RESULTS: Pathologic diagnoses and staging were obtained at surgery in nine patients; in the remaining 33 patients, aspiration cytology was available. CoDe PET detected all 35 pathologically proved malignant lesions. In nine patients who underwent surgery, seven CoDe PET studies corresponded with pathologic staging, whereas in six of the nine patients, CT and MRI corresponded with the pathologic findings. Seven patients also had benign lesions that showed FDG uptake. CONCLUSIONS: F-18 FDG CoDe PET was sensitive in the evaluation of lung lesions but was not specific for malignancy. F-18 FDG CoDe PET was more sensitive than CT and MRI in nodal staging in the limited number of patients studied thus far.

Aged↗

PubMed1999

Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization.

Genetic screens for modifiers of activated Ras phenotypes have identified a novel protein, kinase suppressor of Ras (KSR), which shares significant sequence homology with Raf family protein kinases. Studies using Drosophila melanogaster and Caenorhabditis elegans predict that KSR positively regulates Ras signaling; however, the function of mammalian KSR is not well understood. We show here that two predicted kinase-dead mutants of KSR retain the ability to complement ksr-1 loss-of-function alleles in C. elegans, suggesting that KSR may have physiological, kinase-independent functions. Furthermore, we observe that murine KSR forms a multimolecular signaling complex in human embryonic kidney 293T cells composed of HSP90, HSP70, HSP68, p50(CDC37), MEK1, MEK2, 14-3-3, and several other, unidentified proteins. Treatment of cells with geldanamycin, an inhibitor of HSP90, decreases the half-life of KSR, suggesting that HSPs may serve to stabilize KSR. Both nematode and mammalian KSRs are capable of binding to MEKs, and three-point mutants of KSR, corresponding to C. elegans loss-of-function alleles, are specifically compromised in MEK binding. KSR did not alter MEK activity or activation. However, KSR-MEK binding shifts the apparent molecular mass of MEK from 44 to >700 kDa, and this results in the appearance of MEK in membrane-associated fractions. Together, these results suggest that KSR may act as a scaffolding protein for the Ras-mitogen-activated protein kinase pathway.

14-3-3 Proteins↗

PubMed1999

COG-2, a sox domain protein necessary for establishing a functional vulval-uterine connection in Caenorhabditis elegans.

In screens for mutants defective in vulval morphogenesis, multiple mutants were isolated in which the uterus and the vulva fail to make a proper connection. We describe five alleles that define the gene cog-2, for connection of gonad defective. To form a functional connection between the vulva and the uterus, the anchor cell must fuse with the multinucleate uterine seam cell, derived from uterine cells that adopt a (pi) lineage. In cog-2 mutants, the anchor cell does not fuse to the uterine seam cell and, instead, remains at the apex of the vulva, blocking the connection between the vulval and uterine lumens, resulting in an egg-laying defective phenotype. According to lineage analysis and expression assays for two (pi)-cell-specific markers, induction of the (pi) fate occurs normally in cog-2 mutants. We have cloned cog-2 and shown that it encodes a Sox family transcription factor that is expressed in the (pi) lineage. Thus, it appears that COG-2 is a transcription factor that regulates a late-stage aspect of uterine seam cell differentiation that specifically affects anchor cell-uterine seam cell fusion.

Amino Acid Sequence↗

PubMed1999

UNC-84 localizes to the nuclear envelope and is required for nuclear migration and anchoring during C. elegans development.

Nuclear migrations are essential for metazoan development. Two nuclear migrations that occur during C. elegans development require the function of the unc-84 gene. unc-84 mutants are also defective in the anchoring of nuclei within the hypodermal syncytium and in the migrations of the two distal tip cells of the gonad. Complementation analyses of 17 unc-84 alleles defined two genetically separable functions. Both functions are required for nuclear and distal tip cell migrations, but only one is required for nuclear anchorage. The DNA lesions associated with these 17 mutations indicate that the two genetically defined functions correspond to two distinct regions of the UNC-84 protein. The UNC-84 protein has a predicted transmembrane domain and a C-terminal region with similarity to the S. pombe spindle pole body protein Sad1 and to two predicted mammalian proteins. Analysis of a green fluorescent protein reporter indicated that UNC-84 is widely expressed and localized to the nuclear envelope. We propose that UNC-84 functions to facilitate a nuclear-centrosomal interaction required for nuclear migration and anchorage.

Amino Acid Sequence↗

PubMed1999

A gp330/megalin-related protein is required in the major epidermis of Caenorhabditis elegans for completion of molting.

A genetic analysis of a gp330/megalin-related protein, LRP-1, has been undertaken in Caenorhabditis elegans. Consistent with megalin's being essential for development of mice, likely null mutations reveal that this large member of the low density lipoprotein receptor family is also essential for growth and development of this nematode. The mutations confer a striking defect, an inability to shed and degrade all of the old cuticle at each of the larval molts. The mutations also cause an arrest of growth usually at the molt from the third to the fourth larval stage. Genetic mosaic analysis suggests that the lrp-1 gene functions in the major epidermal syncytium hyp7, a polarized epithelium that secretes cuticle from its apical surface. Staining of whole mounts with specific monoclonal antibodies reveals that the protein is expressed on the apical surface of hyp7. Sterol starvation can phenocopy the lrp-1 mutations, suggesting that LRP-1 is a receptor for sterols that must be endocytosed by hyp7. These observations indicate that LRP-1 is related to megalin not only structurally but also functionally.

Animals↗

PubMed1999

[Evaluation of fat nutrition in the energy intake on low protein diets for patients with chronic renal failure].

Low protein diet has been proven to retard the progression of chronic renal failure. In this diet, the energy intake depends mainly on fats and carbohydrates instead of protein, and precautions should be taken against increasing risks of both lipid nephrotoxicity and atherosclerosis. In order to assess the adequacy of fat nutrition in a low protein diet for patients with chronic renal failure, we evaluated the total amounts of dietary fat intake, dietary individual fatty acid intake and serum individual fatty acid concentrations in 16 patients, whose mean creatinine clearance was 21.3 +/- 12.1 ml/m, serum creatinine 3.8 +/- 2.2 mg/dl and serum urea nitrogen 41.5 +/- 18.6 mg/dl. The percentage ratio of fat intake to total energy intake was 26.7 +/- 5.2%. The ratio of intake of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids was 1:2:1.8, and n-6/n-3 was 8.5 +/- 9.3. These were significant correlations between dietary intake and the serum concentrations in both EPA and the ratio of EPA/AA. Consequently, it might be considered that polyunsaturated fatty acids intake should be lowered and patients with chronic renal failure on a low protein diet should be advised about the proper selection of foods containing animal protein and plant-derived oil. It may be beneficial to recommend the intake of more EPA and lowering the ratio of n-6/n-3 intake might be useful in improving the fat nutrition to adequate levels in these patients.

Aged↗

PubMed1999

Killing effect of interleukin-2 and interferon-alpha activated leukemic bone marrow in remission on K562 leukemic cells.

OBJECTIVE: To evaluate the killing effect of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) activated bone marrow cells on K562 cells. METHODS: Semi-solid colony and 3H-TdR incorporating method were used. RESULTS: Bone marrow from leukemia patients in remission was activated in vitro with IL-2 for 3 days. The activated bone marrow (ABM) displayed killing effects of 0.31-2.30 logs on K562 cells. This killing effect was further increased to 0.30-3.15 logs when IFN-alpha added with IL-2 to the marrow for activation. IL-2 alone or in combination with IFN-alpha showed no inhibition of CFU-GM and K562 cells. Compared with IL-2 or IFN-alpha alone, the combination of the two cytokines could more effectively maintain the killing effect of ABM on leukemic cells. CONCLUSIONS: IFN-alpha can augment the purging effect of IL-2 ABM and combination of the two cytokines can effectively maintain the cytotoxicity of ABM.

Acute Disease↗

PubMed1999

[Acute lymphoblastic leukemia complicated with tumor lysis syndrome--four cases report].

OBJECTIVE: To report four acute lymphoblastic leukemia(ALL) patients who developed tumor lysis syndrome(TLS) after initial chemotherapy. METHODS: The clinical features and blood biochemical changes of four patients with TLS were analysed. RESULTS: TLS was characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. Three cases had renal dysfunction and the other died of acute renal failure. After allopurinol therapy and alkalinization of urine, the blood biochemical parameter became normalization in all the three cases. CONCLUSIONS: TLS can be effectively controlled by early recognition and administration of allopurinol therapy and alkalinization of urine.

Adult↗

PubMed1999

[Comparison of clinical outcome between allogeneic peripheral blood stem cell transplantation and bone marrow transplantation].

OBJECTIVE: To compare the clinical outcome of allogeneic peripheral blood stem cell transplantation(PBSCT) with that of bone marrow transplantation(BMT). METHODS: Twenty-six patients received allo-BMT and 24 received allo-PBSCT in our hospital between August 1991 and September 1998. Conditioning regimens were CY 120 mg/kg plus STBI 9-10 Gy or BU 16 mg/kg or Mel 140-160 mg/m2 plus CY 120 mg/kg. RESULTS: Twenty-three patients of PBSCT and 24 of BMT group engrafted successfully. The median follow-up duration was 352(19-745) days for the PBSCT group and 546(19-2,329) days for the BMT group. Transplant-related death was 4(16.7%) patients in the PBSCT and 7(26.9%) in BMT group (P = 0.38). Three(12.5%) patients in PBSCT and 5(19.2%) in BMT group relapsed(P = 0.27). The 2-year probabilities of disease-free survival(DFS) for PBSCT and BMT group were (67.9 +/- 11.3)% and (57.7 +/- 9.7)%, respectively(P = 0.24). aGVHD occurred in 6(25%) patients in the PBSCT and 6 (23.1%) in the BMT group (P = 0.624), while cGVHD did in 13(56.5%) and 1 (3.85%), respectively (P = 0.0002). CONCLUSION: The clinical outcome of allo-PBSCT is similar to allo-BMT, except for a higher incidence of cGVHD.

Acute Disease↗

PubMed1999

[Pure red cell aplasia after allogeneic peripheral blood stem cell transplantation: a case report and literature review].

OBJECTIVE: To report a case of post-allogeneic peripheral blood stem cell transplantation (allo-PBSCT) pure red cell aplasia(PRCA) and the treatment outcome. METHODS: A patient with acute non-lymphoblastic leukemia(M2a) was treated with allo-PBSCT. His post-PBSCT PRCA was treated with plasmapheresis(2-3 times weekly) and Epo(3,000 U/day, subcutaneously). RESULTS: Reticulocyte count (Ret) recovered to 0.01 at day +131 and hemoglobin reached 110 g/L at day +154. Erythroid cells in the bone marrow recovered to 0.25, and BFU-E and CFU-E within normal range. This normalized hematopoiesis remained for over 5 months after the cessation of Epo. CONCLUSION: Post allo-PBSCT PRCA can be successfully treated with plasma exchange and Epo.

Adult↗

PubMed1999

Investigation of parvovirus B19 in cardiac tissue from patients with congenital heart disease.

OBJECTIVE: To explore the correlation between human parvovirus B19 (HPV-B19) and congenital heart (CHD) and to investigate the teratogenic effect of HPV-B19. METHODS: A case control study was conducted to investigate the embedded autopsy cardiac tissues of 29 cases of CHD and 30 controls without CHD with nest polymerase chain reaction (PCR). Other viruses, including herpes simplex virus (HSV). Toxoplasma gondii (TOX), cytomegalovirus (CMV) and rubella virus (RV) were also studied in 10 cases of each group with corresponding PCR kits. RESULTS: Five of 29 (17.2%) CHD cases were positive for HPV-B19, while all the 30 controls were negative for HPV-B19 (P=0.0237). All cases studied were negative for both HSV and TOX. Three cases in each group were positive for CMV, with presence of HPV-B19 DNA in 2 cases in the CHD group. Only two cases in the CHD group showed positive reaction for RV. CONCLUSIONS: As far as we know, it is the first report of the presence of HPV-B19 in cardiac tissues of CHD patients. The detection rate of HPV-B19 DNA is significantly different between the two groups, inferring that HPV-B19 might be correlated with CHD.

Adolescent↗

PubMed1999

[Effect of replenishing liver and kidney, supplementing qi and activating blood circulation recipe on proliferation and relevant gene expression of vascular smooth muscle cells].

OBJECTIVE: To study the effect of replenishing Liver and Kidney, supplementing Qi and activating blood circulation recipe (TCM) on the proliferation and relevant gene expression of vascular smooth muscle cells (VSMC). METHODS: Using 3H-TdR incorporation to investigate the VSMC proliferation, using Northern blotting and reverse Polymerase Chain Reaction (RT-PCR) to detect the effect of serum with TCM on induced NO synthase (iNOS), endothelin (ET) induced c-jun and proliferation cell nucleus antigen (PCNA) gene expression. RESULTS: The 3H-TdR incorporation value of VSMC treated by serum with TCM was lower than that of control serum (P < 0.05). Rich iNOS mRNA was detected in the VSMC stimulated by serum with TCM. Expressions of c-jun and PCNA gene induced by ET in the VSMC were significantly inhibited by serum with TCM. CONCLUSION: The TCM could significantly inhibit VSMC proliferation.

Animals↗

PubMed1998

SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in C. elegans.

We describe the identification and characterization of a novel gene, sur-8, that positively regulates Ras-mediated signal transduction during C. elegans vulval development. Reduction of sur-8 function suppresses an activated ras mutation and dramatically enhances phenotypes of mpk-1 MAP kinase and ksr-1 mutations, while increase of sur-8 dosage enhances an activated ras mutation. sur-8 appears to act downstream of or in parallel to ras but upstream of raf. sur-8 encodes a conserved protein that is composed predominantly of leucine-rich repeats. The SUR-8 protein interacts directly with Ras but not with the Ras(P34G) mutant protein, suggesting that SUR-8 may mediate its effects through Ras binding. A structural and functional SUR-8 homolog in humans specifically binds K-Ras and N-Ras but not H-Ras in vitro.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Constitutive activation of opsin by mutation of methionine 257 on transmembrane helix 6.

Rhodopsin is a member of the large family of G protein-coupled receptors (GPCR's). Constitutive activity of GPCR's, defined as ligand-independent signaling, has been recognized as an important feature of receptor function and has also been implicated in the molecular pathophysiology of a number of human diseases. Rhodopsin has evolved a unique mechanism to minimize receptor basal activity. The chromophore 11-cis-retinal, which acts as an inverse agonist in rhodopsin, is covalently bound to the receptor to ensure extremely low receptor signaling in the dark. In this study, we replaced Met257 in TM helix 6 of opsin with each of the remaining 19 amino acids. Only mutant opsin M257R failed to be expressed in COS-cell membranes. Each of the remaining 18 mutant opsins, with the exception of M257L, was significantly constitutively active. Two mutants in particular, M257Y and M257N, displayed very high levels of constitutive activity. In addition, the double-site mutants with substitutions of both Met257 and Glu113 in TM helix 3 tended to be much more constitutively active than the sums of the activities of the individual single-site mutants. Based on existing structural models of rhodopsin, we conclude that Met257 may form an important and specific interhelical interaction with a highly conserved NPXXY motif in TM helix 7, which stabilizes the inactive receptor conformation by preventing TM helix 6 movement in the absence of all-trans-retinal. Furthermore, we are able to show that the pharmacological properties of the large number (approximately 50) of mutant opsins that we have characterized to date support the two-state model of GPCR function. These results suggest that rhodopsin and other GPCR's share a common mechanism of receptor activation that involves specific changes in helix-helix interactions.

Amino Acid Sequence↗

PubMed1998

Homology-directed repair is a major double-strand break repair pathway in mammalian cells.

Mammalian cells have been presumed to repair potentially lethal chromosomal double-strand breaks (DSBs) in large part by processes that do not require homology to the break site. This contrasts with Saccharomyces cerevisiae where the major DSB repair pathway is homologous recombination. Recently, it has been determined that DSBs in genomic DNA in mammalian cells can stimulate homologous recombination as much as 3 or 4 orders of magnitude, suggesting that homology-directed repair may play an important role in the repair of chromosomal breaks. To determine whether mammalian cells use recombinational repair at a significant level, we have analyzed the spectrum of repair events at a defined chromosomal break by using direct physical analysis of repair products. When an endonuclease-generated DSB is introduced into one of two direct repeats, homologous repair is found to account for 30-50% of observed repair events. Both noncrossover and deletional homologous repair products are detected, at approximately a 1:3 ratio. These results demonstrate the importance of homologous recombination in the repair of DSBs in mammalian cells. In the remaining observed repair events, DSBs are repaired by nonhomologous processes. The nonhomologous repair events generally result in small deletions or insertions at the break site, although a small fraction of events result in larger chromosomal rearrangements. Interestingly, in two insertions, GT repeats were integrated at one of the broken chromosome ends, suggesting that DSB repair can contribute to the spread of microsatellite sequences in mammalian genomes.

Animals↗