Search PubMed⌕ Search

Biomedical subjects

C S Han

Publications and source records attributed to C S Han.

At least 19 recordsLinked to original sources

Production of medium-chain-length polyhydroxyalkanoates by high-cell-density cultivation of Pseudomonas putida under phosphorus limitation.

High-cell-density fed-batch cultures of Pseudomonas putida were carried out for the production of medium-chain-length polyhydroxyalkanoates (PHAs) using oleic acid as a carbon source. By employing an optimal feeding strategy without the limitation of any nutrient, a high cell concentration of 173 g/L was achieved, but the PHA concentration and PHA content were only 32.3 g/L and 18.7 wt%, respectively. To increase the PHA concentration and content, phosphorus limitation was applied during fed-bath culture by reducing the initial KH(2)PO(4) concentration. When the initial KH(2)PO(4) concentration was reduced to 4 g/L, cell concentration, PHA concentration, and PHA content obtained in 38 h were 141 g/L, 72. 6 g/L, and 51.4 wt%, respectively, resulting in a high productivity of 1.91 g PHA/L per hour.

Bioreactors↗

Construction of a BAC contig map of chromosome 16q by two-dimensional overgo hybridization.

We have used sequence-based markers from an integrated YAC STS-content/somatic cell hybrid breakpoint physical map and radiation hybrid maps of human chromosome 16 to construct a new sequence-ready BAC map of the long arm of this chromosome. The integrated physical map was generated previously in our laboratory and contains 1150 STSs, providing a marker on average every 78 kb on the euchromatic arms of chromosome 16. The other two maps used for this effort were the radiation hybrid maps of chromosome 16 from Whitehead Institute and Stanford University. To create large sequenceable targets of this chromosome, we used a systematic approach to screen high-density BAC filters with probes generated from overlapping oligonucleotides (overgos). We first identified all available sequences in the three maps. These include sequences from genes, ESTs, STSs, and cosmid end sequences. We then used BLASTto identify 36-bp unique fragments of DNA for overgo probes. A total of 906 overgos were selected from the long arm of chromosome 16. Hybridizations occurred in three stages: (1) superpool hybridizations against the 12x coverage human BAC library (RPCI-11); (2) two-dimensional hybridizations against rearrayed positive BACs identified in the superpool hybridizations; and (3) pooled tertiary hybridizations for those overgos that had ambiguous positives remaining after the two-dimensional hybridization. For the superpool hybridizations, up to 236 overgos have been pooled in a single hybridization against the 12x BAC library. A total of 5187 positive BACs from chromosome 16q were identified as a result of five superpool hybridizations. These positive clones were rearrayed on membranes and hybridized with 161 two-dimensional subpools of overgos to determine which BAC clones were positive for individual overgos. An additional 46 tertiary hybridizations were required to resolve ambiguous overgo-BAC relationships. Thus, after a total of 212 hybridizations, we have constructed an initial probe-content BAC map of chromosome 16q consisting of 828 overgo markers and 3363 BACs providing >85% coverage of the long arm of this chromosome. The map has been confirmed by the fingerprinting data and BAC end PCR screening.

Chromosomes, Bacterial↗

The top3(+) gene is essential in Schizosaccharomyces pombe and the lethality associated with its loss is caused by Rad12 helicase activity.

The topoisomerase III gene ( top3 (+)) from Schizosaccharomyces pombe was isolated and a targeted gene disruption ( top3 :: kan (R)) was used to make a diploid strain heterozygous for top3 (+). The diploid was sporulated and the top3 :: kan (R)spores went through four to eight cell divisions before arresting as elongated, predominantly binucleated cells with incompletely segregated chromosomes. This demonstrates that top3 (+)is essential for vegetative growth in fission yeast. The aberrant chromosomal segregation seen in top3 :: kan (R)cells is unlike the 'cut' phenotype seen in mitosis-defective mutants and so we refer to this phenotype as 'torn'. A deletion mutant, rad12-hd ( rad12 is a homolog of Saccharomyces cerevisiae SGS1), partially suppressed the lethality of top3 mutants. A point mutant, rad12-K547I, which presumably eliminates helicase activity, also suppresses the lethality of top3 mutants, demonstrating that the lethality seen in top3 (-)cells is most likely caused by the helicase activity of Rad12. This double mutant grows very slowly and has much lower viability compared to rad12-hd top3 :: kan (R)cells, implying that the helicase activity of Rad12 is not the only cause of top3 (-)lethality. The low viability of rad12 (-) top3 (-)mutants compared with rad12 single mutants suggests that Top3 also functions independently of Rad12.

Amino Acid Sequence↗

Langerhans' cell histiocytosis of the spine. Analysis of twenty-three cases.

STUDY DESIGN: Retrospective review of clinical and radiologic data in four major tertiary referral centers. OBJECTIVES: To report clinical and roentgenographic findings, to evaluate the results of various treatment methods, and to propose a protocol for management. SUMMARY OF BACKGROUND DATA: Langerhans' cell histiocytosis of the spine is a rare condition, and therefore, appropriate management is still controversial. METHODS: Clinical and roentgenographic findings of 38 vertebral lesions of 23 children, with average follow-up of 5.4 years, were investigated. This is the most extensive report apparent in the literature to date. The results of treatment were assessed clinically and radiologically. Anterior vertebral body height was measured sequentially to evaluate reconstitution of the vertebral body. RESULTS: The last follow-up examination demonstrated no clinical evidence of disease in all patients, regardless of treatment method. Neurologic deficits developed in four patients, but they completely disappeared. Satisfactory restoration of height was demonstrated in all except five vertebrae: one that had collapsed maximally when the patient was more than 15 years of age and four that had been fused anteriorly or posteriorly. Unsatisfactory results were also seen in a patient with progressive scoliosis and in one with an irregular endplate with disc space narrowing. Both of these complications developed after curettage. CONCLUSIONS: For treatment of single or dual spinal lesions, observation with or without bracing seems to be sufficient. In patients with multifocal lesions, chemotherapy produces good results. For treatment of neurologic deficit, low-dose radiotherapy is favored. Patients who underwent surgery--especially curettage and anterior fusion--had the worst outcome.

Adolescent↗

Primary alveolar soft part sarcoma of bone.

AIMS: Alveolar soft part sarcoma is a distinct, rare soft tissue tumour occurring primarily within the skeletal muscles or musculofascial planes in young adults. Primary involvement of bone is extremely rare. We report on six patients with alveolar soft part sarcoma occurring primarily in bone. METHODS AND RESULTS: Thorough clinical and radiographic examinations were done to rule out any other primary site. The patients were four women and two men aged 17-35 years (mean, 24.5 years). The primary site of the tumour was the femur in three patients, the ilium in one and the fibula in two. In one of the patients with fibular involvement, the tibia was also involved by direct extension. Of the long bone lesions, three were centred in the metaphysis and one in the diaphysis. Radiographically, all of the lesions demonstrated an osteolytic pattern of bone destruction with ill-defined margins and a wide zone of transition between the lesion and adjacent normal bone. Microscopically, all tumours showed the typical histological pattern of alveolar soft part sarcoma. Diastase-resistant, periodic acid-Schiff-positive crystalline structures were identified within the cytoplasm and confirmed ultrastructurally. Immunohistochemically, a keratin stain was negative in all cases; there was positive staining for MyoD1 in the cytoplasm but not the nuclei. Distant metastasis developed in four patients; one died. CONCLUSION: Alveolar soft part sarcoma arising in bone is extraordinarily rare but should be considered in the differential diagnosis of metastatic hypernephroma in a young patient.

Adolescent↗

Trophoblast interferons.

The mechanisms responsible for prevention of corpus luteum regression during early pregnancy are diverse and appear to have arisen in concert with the evolutionary divergence of placental structure. That used by the sub-order Ruminantia is unique and involves the production of a Type I interferon (IFN), IFN-tau (tau). Although IFN-tau resembles other Type I IFNs (such as IFN-alpha, -beta, and -omega) in structure as well as in many of its biological properties, it is not virally inducible and is instead produced constitutively by embryonic trophectoderm during the period immediately prior to implantation. The transcription factor Ets-2 is a component of the regulatory mechanism involved in transcription of IFN-tau. These genes probably arose as the result of a duplication of an IFN-omega gene, 36 million years ago, at about the time the Ruminantia sub-order emerged. They have duplicated extensively since then and there may be 10 or more genes in some present-day species. The expression of different IFN-tau is unequal and they differ in biological potency. The rapid evolution of IFN-tau genes possibly reflects the placenta as a site of considerable genetic experimentation.

Animals↗

Activation of NF-kappaB mediates the PMA-induced differentiation of K562 cells.

The role of NF-kappaB during the PMA-induced megakaryocytic differentiation of K562 cells was investigated using K562 cells transfected with each or both subunits of NF-kappaB. The NF-kappaB subunit-transfected cells have shown much higher sensitivity to PMA-induced differentiation than their parental cells. This result was consistent with the findings that PMA-stimulated activities of NF-kappaB were markedly increased in the NF-kappaB subunit-transfected cells in comparison with their parental cells and PMA-induced differentiation was enhanced by pretreatment with IkappaB-alpha antisense oligonucleotide in the NF-kappaB subunit-transfected cells. Meanwhile, there were basically no difference in the basal and PMA-stimulated MAP kinase activities among the parental and NF-kappaB subunit-transfected cells, respectively. However, PMA-induced differentiation was blocked by pretreatment with PD98059, a specific inhibitor of MEK, in both parental and NF-kappaB-transfected cells. Therefore, these results suggest that during the PMA-induced megakaryocytic differentiation of K562 cells, NF-kappaB works downstream of MAP kinase, or that activation of both NF-kappaB and MAP kinase pathways is involved.

Calcium-Calmodulin-Dependent Protein Kinases↗

Co-administration of sertraline and haloperidol.

Along with recent increased interest in the selective serotonin reuptake inhibitors, a number of studies has been undertaken to observe interactions with different drugs. When selective serotonin reuptake inhibitor was administered together with antipsychotics to schizophrenics showing depressive or obsessive symptoms and negative symptoms, meaningful results were observed. The objective of our research was to identify the changes in the concentration of plasma haloperidol when sertraline was administered to patients who already were being treated with haloperidol. Sixteen patients who did not respond to the traditional antipsychotics after 2 weeks of treatment with a certain dosage of haloperidol were administered with 50 mg of sertraline for a period of 2 weeks. The concentration changes between plasma haloperidol and the reduced haloperidol were observed using high-powered liquid chromatography equipped with a UV detector. There was a significant increase (P < 0.01) in the concentration of haloperidol, the change being from 8.52 +/- 4.22 to 10.91 +/- 5.38 ng/mL. However, the change in the concentration of reduced haloperidol was from 7.41 +/- 7.93 to 5.22 +/- 6.10 ng/mL, showing a significant decrease. The concentrations of total plasma haloperidol showed no significant changes at all. In comparing the ratio of the reduced haloperidol and the haloperidol, the reduction ratio was down to 0.39 +/- 0.27 from 0.94 +/- 0.65 showing a significant decrease. There seems to be few studies done on interactions using serotonergic drugs together with antipsychotics in spite of their clinically applicable possibility. According to similar studies done in the past, co-administering of such drugs not only increases the plasma concentration of antipsychotics, but it also results in clinical improvement of negative symptoms and aggravation of extrapyramidal symptoms. Changes in clinical symptoms and adverse effects were not observed in our study. However, we think these observations need to be included in upcoming larger scale studies.

Adult↗

Fission yeast rad12+ regulates cell cycle checkpoint control and is homologous to the Bloom's syndrome disease gene.

The human BLM gene is a member of the Escherichia coli recQ helicase family, which includes the Saccharomyces cerevisiae SGS1 and human WRN genes. Defects in BLM are responsible for the human disease Bloom's syndrome, which is characterized in part by genomic instability and a high incidence of cancer. Here we describe the cloning of rad12+, which is the fission yeast homolog of BLM and is identical to the recently reported rhq1+ gene. We showed that rad12 null cells are sensitive to DNA damage induced by UV light and gamma radiation, as well as to the DNA synthesis inhibitor hydroxyurea. Overexpression of the wild-type rad12+ gene also leads to sensitivity to these agents and to defects associated with the loss of the S-phase and G2-phase checkpoint control. We showed genetically and biochemically that rad12+ acts upstream from rad9+, one of the fission yeast G2 checkpoint control genes, in regulating exit from the S-phase checkpoint. The physical chromosome segregation defects seen in rad12 null cells combined with the checkpoint regulation defect seen in the rad12+ overproducer implicate rad12+ as a key coupler of chromosomal integrity with cell cycle progression.

Adenosine Triphosphatases↗

Molecular cloning of ovine and bovine type I interferon receptor subunits from uteri, and endometrial expression of messenger ribonucleic acid for ovine receptors during the estrous cycle and pregnancy.

Interferon-tau (IFN-tau), a type I IFN structurally related to IFN-alpha, is regarded as the major antiluteolytic factor secreted by the conceptus of ruminant ungulate species before definitive trophoblast attachment and implantation. It mediates its effects by acting on the uterine endometrium, where it blunts the normal pulsatile production of PGF2alpha, presumably as a result of its binding to type I IFN receptors. In this study, we describe the complementary DNAs for the two known subunits, IFNAR1 and IFNAR2, of this receptor isolated from bovine and ovine endometrial complementary DNA libraries by homology cloning. Although there is extensive inferred amino acid sequence similarity between bovine and ovine IFNAR1 (92% identity) and between bovine and ovine IFNAR2 (88% identity), they have diverged extensively from the human receptor subunits (approximately 67% and approximately 58% identity, respectively). Despite these differences in primary structure, the respective subunits from all three species are organized similarly in their extracellular and cytoplasmic regions, and the bovine and ovine subunits have each retained a number of polypeptide motifs implicated in signal transduction. These uterine receptors also appear not to be splice variants. The cloned ovine IFNAR1 subunit, for example, possesses the expected four extracellular SD100 domains of full-length bovine and huIFNAR1, and only the homologs of the so-called long form (huIFNAR2c) of human IFNAR2 have so far been identified. RT-PCR procedures indicate that the messenger RNA for both subunits are found, not only in endometrium, but in all other tissues examined except those ofpreimplantation conceptuses, which presumably cannot respond to the IFN-tau they produce. Quantitative RNase protection assays of ovine endometrial RNA show that the expression of neither subunit changes greatly during the estrous cycle or pregnancy. These data suggest that the type I IFN receptor, which is expressed by the endometrium and binds IFN-tau, is probably not a structurally unusual form.

Amino Acid Sequence↗

Varicella zoster infection after bone marrow transplantation: incidence, risk factors and complications.

The cellular immunoincompetence which follows bone marrow transplantation (BMT) allows both primary and reactivation infection with herpes viruses. We report the overall incidence and timing of varicella zoster virus (VZV) infections after BMT, including the clinical course, complications and associated clinical risk features. Of 1186 patients undergoing BMT through 1989, 216 patients developed VZV infection between 4 days and 10.8 years after BMT; 86% of them within the first 18 months. Of all patients transplanted, 15 +/- 3% by 6 months and 52 +/- 14% by 5 years had developed VZV infection. Dermatomal zoster represented 62% of the infections, while 32% had complicated VZV infection--CNS, disseminated or visceral zoster. All serious infections occurred within 7 months of BMT but only two patients died, both from VZV pneumonitis. Allogeneic and autologous recipients had a similar incidence of VZV infection. VZV seropositive patients had more frequent, earlier and often more complicated or disseminated infections. Age > or = 10 years and radiation in the pre-transplant conditioning were significantly and independently associated with higher rates of VZV infection within a multivariate regression model. Using this model, we could define clinical risk groups with distinctly different hazards of VZV infection: age > 10 years, radiation pre-BMT and VZV seropositive patients had a 44% incidence by 3 years versus age < 10 years, no radiation and VZV seronegative had a 0% incidence by 3 years. Acyclovir assigned for prophylaxis of CMV or HSV infection had no effect on the timing or incidence of VZV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

Vascularized bone transfer.

We evaluated the results of reconstruction of a skeletal defect with use of a vascularized bone graft from the iliac crest or fibula in 160 patients who had been managed consecutively between 1979 and 1989. The indications for the procedure were a skeletal defect including non-union, resulting from resection of a tumor; traumatic bone loss; osteomyelitis; or a congenital anomaly. The average duration of follow-up was forty-two months (range, twelve to 112 months). For the entire series, the rate of union after the primary procedure was 61 per cent and the over-all rate at the latest follow-up examination (including the patients who had a secondary procedure) was 81 per cent. In a subgroup of seventy-six patients who had union after the primary procedure and did not have additional treatment, the average interval until union was six months and the average interval until full activity was sixteen months. The results were more favorable for the patients who had had reconstruction for resection of a tumor (of sixty-nine patients, fifty-six had union), for a congenital anomaly (of six patients, five had union), or for a non-union without infection (of twenty-five patients, twenty-three had union). The results were less satisfactory for patients who had had the reconstruction for bone loss due to osteomyelitis (of sixty patients, forty-six had union). Our data suggest that vascularized bone transfer for the reconstruction of large skeletal defects is a valuable procedure in appropriately selected patients.

Adolescent↗

Giant cell tumor of the scapula associated with secondary aneurysmal bone cyst.

Giant cell tumors are distinctive neoplasms characterized by a profusion of multinucleate giant cells scattered throughout a stroma of mononuclear cells. Most giant cell tumors are found at the epiphyses of long bones, especially around the knee joint. Flat bone involvement is rare. However, a case of giant cell tumor with secondary aneurysmal bone cyst was encountered at the scapula of a 25-year-old man. Since the occurrence of a giant cell tumor with secondary aneurysmal bone cyst on flat bones (i.e., the scapula) is extremely rare, the above-mentioned case is worthy of reporting.

Adult↗

Ascorbic acid: an endogenous inhibitor of isolated Na+,K+-ATPase.

During attempts to isolate and identify an endogenous ligand for the glycoside binding sites on Na+,K+-ATPase, bovine adrenal glands were found to contain a potent inhibitor of isolated Na+,K+-ATPase. The inhibitory principle was extracted from adrenal cortex, following homogenization in NaHCO3 solution and separation on a Sephadex G-10 column. The active principle was recovered from a fraction which eluted from the column after the 3H2O peak. The extract inhibited isolated Na+,K+-ATPase and the specific [3H]ouabain binding reaction. Sensitivity of the enzyme to the inhibitory action of the extract was species and tissue dependent; however, the pattern and the magnitude of the sensitivity were different from those of the digitalis glycosides. Moreover, the inhibitory principle failed to inhibit sodium pump activity, estimated from ouabain inhibitable 86Rb+ uptake by guinea pig brain slices. The activity of the extract to inhibit isolated Na+,K+-ATPase was stable under acidic condition but was lost rapidly at neutral pH, and could be eliminated by EDTA. In an acidic medium, the inhibitory principle had an absorption maximum at 244 nm which shifted to 264 nm and decayed rapidly at neutral pH. By using mass spectrometry, the principle was identified to be ascorbic acid, which has been shown previously to inhibit isolated Na+,K+-ATPase under appropriate conditions. Because ascorbic acid was incapable of inhibiting the sodium pump in intact cells, this inhibitor of the isolated enzyme does not appear to be the endogenous ligand which regulates sodium pump activity in vivo.

Adrenal Glands↗