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Biomedical subjects

K Han

Publications and source records attributed to K Han.

At least 109 records · Page 6Linked to original sources

Oxidation and glucose conjugation of synthetic abietane diterpenes by Cunninghamella sp. II. Novel routes to the family of diterpenes from Tripterygium wilfordii.

Abietane diterpenes from the perennial herb, Tripterygium wilfordii, have been shown to possess antiinflammatory activity. To obtain novel analogues of these diterpenes, two synthetic diterpenes, isotriptophenolide [1] (12,19-dihydroxy-18(4-->3)abeo-abieta-3,8,11,13-tetraen++ +-18-oic acid lactone) and triptophenolide [3] (14,19-dihydroxy-18(4-->3)abeo-abieta-3,8,11,13-tetraen++ +-18-oic acid lactone) were incubated with the filamentous fungi, Cunningbamella echinulata and C. elegans. The structures of the metabolites were then determined by spectroscopic methods. Both species of Cunninghamella glucosidated 1 at C-12 to yield 2. When incubated with triptophenolide [3], C. elegans and C. echinulata produced hydroxylated [6] and glucosylated [7] metabolites. In addition to B-ring hydroxylation, aromatic hydroxylation at ring C was also observed. Both species hydroxylated 3 to yield the dihydrodiol 4 which autooxidized to the quinone 5.

Biotransformation↗

Psychometric characteristics of the MMPI-2 Cook-Medley Hostility scale.

The Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1943) Cook-Medley Hostility scale (Ho) has been studied a great deal because of its relation to coronary disease and mortality. However, little research has been conducted with the Ho scale on the revised MMPI (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). This study examined the psychometric characteristics of the MMPI-2 Ho scale. Only nine of the original 50 Ho items were slightly changed in the revision. Ho scores were highly correlated with MMPI-2 scales CYN, K, TPA, and ASP, supporting the interpretation of Ho as a measure of cynicism. High correlations with other MMPI-2 scales also suggested that Ho is related to general psychopathology and negative affectivity. Male Ho scorers were rated by their spouses as hotheaded, bossy, demanding, and argumentative. For women, Ho scale scores were less strongly associated with ratings of overt hostility. Principal components analysis of Ho revealed four underlying dimensions: Cynicism, Hypersensitivity, Aggressive Responding, and Social Avoidance.

Journal Article↗

[Appropriation of time for professional staff and appropriation of costs for services, education and research at a major teaching hospital].

Cost analysis of hospital graduate medical education (GME) cannot follow standard accounting procedure because most of the services, teaching and research activities involved are performed simultaneously. This paper surveys work time allocation and analyzes the budgetary appropriation of a major teaching hospital in Taiwan, ROC based on answers given in a specially designed questionnaire. Percentages of working time used for services, teaching, research by the 2206 professionals at the hospital were 84.0%, 10.3% and 5.7% respectively; for the 776 physicians the figures were 64.1%, 22.7% and 13.2% respectively; GME represented a 12.22% share of the operation budget. In view of the fact that the IRB (Intern-Resident/Bed) ratio of the hospital reaches a high of 45%, GME investment is apparently insufficient. To obtain a reasonable ratio of teaching activities, hospital physicians expressed the opinion that the GME expenditure rate should be at least 18.95%. The Labor Insurance Plan, currently the biggest of its kind in this country, pays 3% of GME expenses to all hospitals. This payment neglects the different teaching load in different hospitals.

Cost Allocation↗

Prostanoid secretion by rat hepatic sinusoidal endothelial cells and its regulation by exogenous adenosine triphosphate.

We investigated the secretory profiles of prostanoids in two types of nonparenchymal cell from the rat liver, sinusoidal endothelial cells and Kupffer cells, in primary culture both under basal conditions and after stimulation with adenine nucleotides. Prostaglandin (PG) E2 was the main prostanoid secreted by both types of hepatic nonparenchymal cell in the basal and adenosine triphosphate (ATP)-stimulated states. Time- and concentration-dependent effects of ATP-mediated PGE2 secretion were noted in sinusoidal endothelial cells, whereas the profile of the relative potencies of individual nucleotides was consistent with the presence of P2y and P1 purinergic receptors. In Kupffer cells, the regulation of prostanoid secretion by adenine nucleotides was essentially the same as that in sinusoidal endothelial cells except that adenosine did not stimulate prostanoid secretion and that prostanoid secretion differed somewhat; Kupffer cells secreted relatively more PGF2 alpha and less 6-keto-PGF1 alpha than sinusoidal endothelial cells in the presence of ATP, suggesting the presence of only P2y receptors. In summary, PGE2 is the main prostanoid secreted by hepatic nonparenchymal cells and its secretion may be stimulated by adenine nucleotides and adenosine.

Adenine Nucleotides↗

A distributed, scalable, community care network architecture for wide-area electronic patient records: modeling and simulation.

Principal systems issues relative to computerizing patient medical records that are yet to be addressed in the scientific literature include (1) the characteristics of networks, i.e. bandwidth and capacity, and their impact on the performance of the system, (2) the architecture and the underlying algorithm of the system, (3) the location and migration of medical records, (4) scalability of the system, and (5) the nature of the performance variation under heavy and light use of the network. Key parameters that affect performance include the number of patients, doctors, frequency of patient visits, and the number of electronic queries and record entries initiated during a patient-doctor interaction episode. This paper presents AMPReD, a Distributed, Scalable, Community Care Network Architecture that aims to provide Real-Time Access to Geographically-Dispersed Patient Medical Records. The AMPReD model includes stationary hospitals and medical clinics, mobile clinics, migrating doctors as well as patients, the communications network, and the patient medical record database. AMPReD's goals include (1) the accurate modeling of the propagation of medical records and (2) providing real-time access to patient medical records from anywhere in the system. To achieve these goals, an asynchronous, distributed algorithm must be developed that achieves concurrent access of multiple, autonomous databases. AMPReD is modeled and simulated for a representative community care network on a network of workstations configured as a loosely-coupled parallel processor, for different parametric combinations of number of doctors, patients, and number of queries or record entries generated corresponding to every patient-doctor interaction episode. AMPReD defines and obtains key performance measures including the idle times of the doctors, patient waiting times, the access times of queries as functions of their sizes, and the growth of the databases. In addition, AMPReD also measures the deviation of the actual time required for a patient-doctor interaction episode from the scheduled interaction interval, as a function of the network load. For the representative system selected, performance measures indicate that the network, utilizing 1/2T1 links, and the database system poses no bottleneck to the system even where the number of doctors and patients within a 30 minute interval are chosen at 192 and 200 respectively. A T1 is a standard, digital, transmission link that is rated at 1.44Mbits/sec.

Algorithms↗

cAMP, ethanol, and CO2 production with the addition of D-glucose anomer to starved yeast cells.

cAMP, ethanol, and CO2 production in starved yeast cells after the addition of D-glucose anomer was measured and compared over a wide range of anomer concentrations. At 1.0 g/l or higher concentrations, the addition of beta-D-glucose resulted in a higher cAMP peak. beta-D-glucose was more rapidly metabolized to ethanol and CO2 than alpha-D-glucose, although there was no notable difference in the uptake rates of the two anomers. At 0.4 g/l D-glucose anomer, the differences in cAMP and ethanol production rates for the two anomers were not significant. At 0.2 g/l D-glucose anomer or lower concentrations, ethanol production with alpha-D-glucose was higher than that with beta-D-glucose. The uptake rate of alpha-D-glucose was higher than that of beta-D-glucose at this low concentration.

Carbon Dioxide↗

Tyrosinase production in recombinant E. coli containing trp promoter and ubiquitin sequence.

We have successfully expressed the active tyrosinase of Streptomyces antibioticus in Escherichia coli under the control of the trp promoter by fusing the sequence to the ORF438 gene. Because our attempt to connect the polycistronic gene of ORF438 and tyrosinase directly to the trp promoter of E. coli resulted in the expression of functionally inactive tyrosinase, we decided to fuse the COOH-terminus of ubiquitin sequence to the NH2-terminus of ORF438. Ubiquitin fusion has been shown to augment the yield of cloned gene products in E. coli by increasing the stability or translational efficiency of the fusion proteins. As a result, E. coli transformants harboring a plasmid pTRUBF that contains the ubiquitin-fused ORF438 and the tyrosinase gene produced the strong black pigment of melanin. About 300 units of tyrosinase per liter of batch culture were detected when cultivated in M9 medium containing casamino acids, L-tyrosine, and copper supplements. The black pigment, however, was not seen when grown in LB medium, suggesting that the trp promoter is well regulated. When recombinant E. coli cells grown in LB medium were transferred to a tryptophan-deficient minimal medium with phenol, we observed that phenol was removed from the solution, and the color of the medium turned black. This is due to the fact that the tyrosinase has polyphenol oxidase properties. We expect to use this recombinant E. coli for the waste treatment of phenolic compounds.

Base Sequence↗

Role of polymorphonuclear leukocytes in galactosamine hepatitis: mechanism of adherence to hepatic endothelial cells.

To investigate the role of polymorphonuclear leukocytes in galactosamine-induced hepatic injury, we injected rats intraperitoneally with antiserum against rat polymorphonuclear leukocytes to deplete circulating neutrophils, then administered galactosamine plus lipopolysaccharide. Polymorphonuclear leukocytes in the hepatic sinusoids were increased after administration of galactosamine plus lipopolysaccharide, whereas pretreatment with the antiserum decreased the number of circulating leukocytes and reduced the mortality and the severity of hepatic injury. Serum collected 1 hr after galactosamine/lipopolysaccharide treatment enhanced in vitro polymorphonuclear leukocyte adherence to hepatic endothelial cells and induced leukocyte superoxide production. Intercellular adhesion molecule-1 expression on hepatic endothelial cells was also enhanced after stimulation with the serum. Polymorphonuclear leukocyte adhesion was partially inhibited by an antibody against tumor necrosis factor-alpha but not by superoxide dismutase. These results suggest that polymorphonuclear leukocytes play an important role in galactosamine-induced hepatic injury and that the accumulation and activation of leukocytes, as well as the enhanced expression of adhesion molecules on hepatic endothelial cells, can be induced by biologically active mediators such as tumor necrosis factor-alpha. In addition, prostaglandins E1 and E2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury.

Alprostadil↗

Implantation of PNS graft inhibits the induction of neuronal nitric oxide synthase and enhances the survival of spinal motoneurons following root avulsion.

In a spinal root injury model, our previous studies have shown that induction of nitric oxide synthase (NOS) appears only in spinal motoneurons of the root-avulsed segment in which significant motoneuron loss occurs but not in those of the distal root-axotomized segment (root axotomy 5-10 mm from the spinal cord) in which most motoneurons survive the injury. One hypothesis for the different response of motoneurons to root avulsion and distal root axotomy is that neurotrophic factors produced by the remaining peripheral nervous system (PNS) component are available for the distally axotomized motoneurons but are not available following avulsion. This hypothesis is tested in the present study by implantation of a PNS graft following the root avulsion. Results of the present study show that implantation of a PNS graft significantly enhances the survival of motoneurons following avulsion. Expression of NOS due to avulsion injury is completely inhibited in all motoneurons that regrow into the PNS graft. These results indicate that induction of NOS in avulsed motoneurons may result from the deprivation of neurotrophic factors produced by the PNS component, and the survival promoting effects of neurotrophic factors may be achieved by modifying certain cellular molecules such as NOS.

Amino Acid Oxidoreductases↗

Comparison of chromosome aberrations in leiomyoma and leiomyosarcoma using FISH on archival tissues.

Fluorescence in situ hybridization (FISH) with chromosome-specific probes was used to study cytogenetic changes in five cases of leiomyosarcoma (LMS) and nine cases of uterine leiomyoma (LM). Biotinylated DNA probes for the centromeric regions of chromosomes 1, 6, 8, 9, 17, and 18, painting probes for chromosomes 1 and 22, and the cosmid probe for chromosome region 21q22.3 were used on nuclei isolated from paraffin blocks. Four of five LMS cases revealed major chromosomal aberrations, while the only case with minor clonal aberrations was subsequently found not to be a typical LMS. The most common numerical aberrations found in the LMS cases were extra copies of chromosome 8 (three of five cases), loss of chromosome 1 (three of five cases), and loss of chromosome 6 (two of five cases). One of two LMS cases studied with a chromosome 1 painting probe demonstrated translocations of chromosome 1. In contrast to LMS, only five of nine uterine LM cases had abnormal clones, and these were smaller than those in LMS. Two LM cases showed 9% tetrasomy 8 with 17 or 20% monosomy 6, and three other cases had monosomy 6 clones in 18-34% of cells. These results indicate that typical LMS is characterized by multiple chromosomal aberrations affecting most of the cells, whereas borderline LMS and LM have fewer affected chromosomes and less clonal involvement.

Adult↗

Quantifying chromosome changes and lineage involvement in myelodysplastic syndrome (MDS) using fluorescent in situ hybridization (FISH).

A simplified technique for fluorescent in situ hybridization (FISH) was used to investigate the prevalence of chromosomally abnormal clones in 13 cases of myelodysplastic syndrome (MDS). Biotinylated centromeric probes for chromosomes 7, 8, 12 and X, as well as painting probes for chromosomes 7 and 11, were applied to air-dried bone marrow smears stored from 6 to 23 months. Nine of the cases had been previously karyotyped, and five of these demonstrated normal karyotypes which were confirmed by FISH. The remaining four cases showed different chromosome changes. One case of sideroblastic anemia with chronic lymphocytic leukemia showed minor clones with either monosomy 12 (12% of cells) or tetraploidy (15% of cells) by FISH, whereas metaphase cytogenetics had demonstrated trisomy 12 in 20% of cells, with no evidence of tetraploidy. Another case which had been previously karyotyped was found to have a t(7;11) in 90% of cells while only 10% of cells were shown by FISH to contain this translocation. Monosomy 7 was demonstrated by FISH in a case of refractory anemia (RA), while trisomy 8 was found in a case of RA with excess blasts in transformation (RAEB-T), and in both of these cases the aneuploid clone was present in eosinophils as well as in erythroid and granulocytic precursors but not in lymphocytes or histiocytes, thereby demonstrating the value of FISH for identifying the affected cell lineage.

Aged↗

Detection of aneuploidy and possible deletion in paraffin-embedded rhabdomyosarcoma cells with FISH.

Conventional cytogenetic studies of solid tumors are limited by the difficulty of culturing tumor cells, while in situ hybridization using paraffin sections of interphase cells results in too many truncated cells. To solve these problems, fluorescent in situ hybridization (FISH) technique was used on free nuclei isolated from formalin-fixed paraffin-embedded embryonal rhabdomyosarcoma (RMS) tissue using our modification of Hedley's method for isolation of nuclei. Biotinylated DNA probes for the centromeric regions of chromosomes 6, 8, 11, 12, 17, and 18, painting probes for chromosomes 8 and 11, and a cosmid probe for the HER-2/neu oncogene, were used. The centromeric probes worked well, demonstrating two copies of chromosomes 6, 17, and 18, but three copies of chromosome 11 in 52.9% of nuclei. Four copies of chromosome 8 were observed in 57.1% of nuclei and five or more in 17.1%. Chromosome 12 demonstrated 21.8% trisomy and 62.2% tetrasomy. Painting probes for chromosome 11 also worked well and matched the results of the centromeric probes, with no suggestion of structural aberration. However, the results of the painting probe for chromosome 8 yielded fluorescent areas of different sizes, suggesting that some of the extra chromosomes 8 could be deleted. The cosmid probe for the HER-2/neu oncogene also worked well, and revealed two signals in each nucleus without evidence of amplification. This study illustrates the successful use of a new technique for studying chromosomal aberration in paraffin-embedded solid tumors. The importance of this technique is that it has not been previously possible to use painting probes or cosmid probes on paraffin tissue sections. Use of this procedure will broaden the type of retrospective studies that can be performed to include detection of deletions or translocations.

Aged↗

Prediction of common folding structures of homologous RNAs.

We have developed an algorithm and a computer program for simultaneously folding homologous RNA sequences. Given an alignment of M homologous sequences of length N, the program performs phylogenetic comparative analysis and predicts a common secondary structure conserved in the sequences. When the structure is not uniquely determined, it infers multiple structures which appear most plausible. This method is superior to energy minimization methods in the sense that it is not sensitive to point mutation of a sequence. It is also superior to usual phylogenetic comparative methods in that it does not require manual scrutiny for covariation or secondary structures. The most plausible 1-5 structures are produced in O(MN2 + N3) time and O(N2) space, which are the same requirements as those of widely used dynamic programs based on energy minimization for folding a single sequence. This is the first algorithm probably practical both in terms of time and space for finding secondary structures of homologous RNA sequences. The algorithm has been implemented in C on a Sun SparcStation, and has been verified by testing on tRNAs, 5S rRNAs, 16S rRNAs, TAR RNAs of human immunodeficiency virus type 1 (HIV-1), and RRE RNAs of HIV-1. We have also applied the program to cis-acting packaging sequences of HIV-1, for which no generally accepted structures yet exist, and propose potentially stable structures. Simulation of the program with random sequences with the same base composition and the same degree of similarity as the above sequences shows that structures common to homologous sequences are very unlikely to occur by chance in random sequences.

Algorithms↗

Use of fluorescence in situ hybridization for retrospective detection of aneuploidy in multiple myeloma.

In malignancies with a low mitotic index such as multiple myeloma (MM), conventional cytogenetic studies may not be informative. This study's purpose was to assess specific numerical chromosomal aberrations in non-dividing MM cells by fluorescence in situ hybridization (FISH) of DNA chromosome probes on bone marrow smears. Old air-dried bone marrow smears from 18 MM patients were probed with alpha satellite DNA sequences for chromosomes 7, X, and Y, and a whole painting probe for chromosome 11. Plasma cells were identified by their morphologic characteristics so that counts of fluorescent signals in the nuclei of MM cells could be differentiated from those of normal marrow cells. Numerical chromosome aberrations were found in 66.7% of the cases (12 of 18), including 5 cases of trisomy 7, 2 cases of tetraploidy, 2 cases of monosomy X in females, 2 cases of disomy X in males, and 1 case of nullisomy Y. In addition, 2 of the 7 cases probed with chromosome 11 paint demonstrated 3 signals in about 15% of the cells. This study illustrates the advantages of FISH for interphase analysis of chromosome aberrations in slowly dividing cells, as well as the ability to use old slides for retrospective studies.

Adult↗