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Biomedical subjects

S T Kim

Publications and source records attributed to S T Kim.

At least 109 records · Page 6Linked to original sources
PubMed1994

Characterization of (6-4) photoproduct DNA photolyase.

Pyrimidine (6-4) pyrimidone photoproduct is the second most abundant UV photoproduct in DNA. Recently, it was reported that Drosophila melanogaster cell-free extracts restored the biological activity of (6-4) photo-product-containing DNA in a light-dependent reaction (Todo, T., Takemori, H., Ryo, H., Ihara, M., Matsunaga, T., Nikaido, O., Sato, K., and Nomura, T. (1993) Nature 361, 372-374) concomitant with the loss of (6-4) photoproduct antigenic sites and (6-4) photoproduct-caused alkali-labile sites. In the present study we show that the (6-4) photoproduct but not its Dewar isomer is the substrate for the enzyme, that the enzyme has an action spectrum peak at 400 nm, and that the efficiency of repair per incident photon is very low compared with cyclobutane pyrimidine dimer photolyases. Furthermore, we provide evidence that the (6-4) photoproduct photolyase converts the photoproduct to unmodified bases probably through an oxetane intermediate.

Animals↗
PubMed1994

Hepatic resections for primary liver cancer.

The medical records of 399 patients who underwent hepatic resection between January 1981 and December 1990 were reviewed. Information regarding the results of the hepatic resection in terms of the operative indication, operative procedure, operative morbidity, and mortality was abstracted. As of the end of 1990, a total of 402 hepatic resections had been completed, including those of 319 primary malignancies, 4 secondary malignancies, 2 gallbladder carcinomas, 42 cases of intrahepatic cholelithiasis, and 35 benign masses. Major hepatic resections were performed on 117 patients (29%), of whom 60 (51%) had histologically proven liver cirrhosis. Minor hepatic resections were performed on the remaining 285 patients (71%). Sepsis was the most frequent complication, which manifested primarily as wound infection (71 cases) or intra-abdominal infection (25 cases). Nonfatal hepatic failure occurred in nine patients with cirrhosis and one patient without cirrhosis. There were 38 operative deaths among the 402 hepatic resections, for an overall operative mortality of 9.4%; 25 of those deaths were due to hepatic failure after the operation, accounting for 66% of the total operative mortality. There was an increasing frequency of hepatic resection during the last 5 years. The indication for resection due to hepatocellular carcinoma increased from 87 to 195 cases. The cumulative data show a decrease in the incidence of complications and the operative mortality rate. In the most recent period, nonlethal postoperative complications occurred in 135 of 286 patients (47%). The overall 1-, 3-, and 5-year survival rates for 172 patients, excluding cases of operative mortality, palliative resection, and re-resection, were 71.0%, 39.8%, and 28.3%, respectively.

Adolescent↗
PubMed1994

Pathogenetic mechanisms involved in mesangial interposition in IgA nephropathy.

To investigate the pathogenetic mechanisms of mesangial interposition (MI) in IgA nephropathy, we examined renal biopsy samples from 20 patients with IgA nephropathy. Electron microscopic morphometric analysis showed that cytoplasmic protrusion of mesangial cells (MCs) into endothelial cells (ECs) or capillary lumina, and widening of the lamina rara interna (LRI) were significantly more prominent in glomeruli with MI than in those without. Immunoelectron microscopy revealed that the ratio of positive endothelial staining with a polyclonal antibody against human platelet-derived growth factor (PDGF) BB was significantly higher in capillary loops with MI than in those without. Enhanced capillary staining of fibronectin related to MI was not recognized. These results suggest that MI in IgA nephropathy is caused by factors such as enhancement of cytoplasmic extensibility of the MCs, widening of the LRI and chemotactic influence of PDGF-BB located in the glomerular ECs.

Adult↗
PubMed1994

Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma.

An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which shows almost the same phenotype as CTCL, ie, a helper/inducer T-cell phenotype (CD4-positive, CD8-negative), and usually involves the skin. This article describes differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant physical findings were lymph node, bone marrow and skin involvement, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, in contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was shown. The predominant phenotype of the neoplastic cells in the skin of patients with CTCL was CD3+, CD4+, CD29+, CD45RO+, HLA-DR+, HLA-DQ+, CD7-, L-selectin-, and CD45RA-. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25, and HLA-DR. That is, the predominant neoplastic cell phenotype was helper T-cell, which was CD3+, CD4+, L-selectin+, CD25+, CD45RA+, HLA-DR+, CD29-, and CD45RO- in peripheral blood, and CD3+, CD4+, L-selectin+, CD29+, CD45RO+, HLA-DR+, and CD45RA- in the skin and lymph nodes. Phenotypic heterogeneity of ATL cells and heterogeneity of CD45R isoform expression on ATL cells were evident in different organs. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL. CTCL cells do not share the same phenotype as ATL cells.

Adult↗
PubMed1994

Characteristics of protein removal in hemodiafiltration.

The on-line HDF system with central supply of the dialysis solution has been developed, which enables us to give more patients HDF treatment at the same time. The high quality infusate was made of dialysis solution by consecutive ultrafiltration with three different filters. The technical notes on assuring accurate infusion rates were also made. From the standpoint of preventing dialysis-related amyloidosis, more aggressive methods to eliminate beta 2-m and larger proteins were described. The RR in the plasma level of beta 2-m was excellent, ranging from 0.75 to 0.84 in all patients. The efficient removal favorably diminishes the overload and the uptake of beta 2-m molecules by inflammatory cells. The aggressive removal of larger proteins is shown to relieve some of the local and systemic inflammatory processes. Taken together, it is possible that the release of amyloidogenic metabolites can be suppressed by proper HDF therapy. The proof of the clinical effectiveness of such a strategy awaits a long-term observation and criticism.

Blood Proteins↗
PubMed1993

Midkine that promotes survival of fetal human neurons is produced by fetal human astrocytes in culture.

Midkine (MK), a retinoic acid responsive gene product, is a novel heparin-binding growth factor with an apparent molecular weight of 14-kDa. In fetal human neuron cultures, addition of recombinant human MK (10-100 ng/ml) resulted in a 3-fold increase in the number of surviving neurons under the serum-free culture condition. Production of MK was identified in the conditioned medium of astrocyte-enriched cultures by immunoblotting but not in the medium of neuron-enriched cultures. The level of MK production was not affected by treatment with retinoic acid. These results indicate that in the developing human central nervous system, astrocytes secrete MK that exhibits potent trophic activity to neurons.

Animals↗
PubMed1993

Time-resolved EPR studies with DNA photolyase: excited-state FADH0 abstracts an electron from Trp-306 to generate FADH-, the catalytically active form of the cofactor.

Photolyase repairs UV-induced cyclobutane-pyrimidine dimers in DNA by photoinduced electron transfer. The enzyme isolated from Escherichia coli contains 5,10-methenyltetrahydrofolate, which functions as the light-harvesting chromophore, and fully reduced flavin adenine dinucleotide (FAD), which functions as the redox catalyst. During enzyme preparation, the flavin is oxidized to FADH0, which is catalytically inert. Illumination of the enzyme with 300- to 600-nm light converts the flavin to the fully reduced form in a reaction that involves photooxidation of an amino acid in the apoenzyme. The results of earlier optical studies had indicated that the redox-active amino acid in this photoactivation process was tryptophan. We have now used time-resolved electron paramagnetic resonance (EPR) spectroscopy to investigate the photoactivation reaction. Excitation of the flavin-radical-containing inactive enzyme produces a spin-polarized radical that we identify by 2H and 15N labeling as originating from a tryptophan residue, confirming the inferences from the optical work. These results and Trp-->Phe replacement by site-directed mutagenesis reveal that flavin radical photoreduction is achieved by electron abstraction from Trp-306 by the excited-state FADH0. Analysis of the hyperfine couplings and spin density distribution deduced from the isotopic-labeling results shows that the product of the light-driven redox chemistry is the Trp-306 cation radical. The results strongly suggest that the active form of photolyase contains FADH- and not FADH2.

Amino Acid Sequence↗
PubMed1993

DNA photolyase repairs the trans-syn cyclobutane thymine dimer.

DNA photolyases catalyze the splitting of the cyclobutane ring joining the two dihydropyrimidines of a pyrimidine dimer by a photoinduced electron-transfer reaction. Previous studies concluded that photolyase repairs only the cis-syn form of the eight stereoisomers of the cyclobutane pyrimidine dimer (Pyr[ ]Pyr). In this study we found that Escherichia coli photolyase binds to the trans-syn-I isomer of T[ ]T with about 10(4)-fold lower affinity than the cis-syn isomer but it repairs it relatively efficiently.

Base Sequence↗
PubMed1993

Evidence for lack of DNA photoreactivating enzyme in humans.

Photoreactivating enzyme (DNA photolyase; deoxyribocyclobutadipyrimidine pyrimidine-lyase, EC 4.1.99.3) repairs UV damage to DNA by utilizing the energy of near-UV/visible light to split pyrimidine dimers into monomers. The enzyme is widespread in nature but is absent in certain species in a seemingly unpredictable manner. Its presence in humans has been a source of considerable controversy. To help resolve the issue we used a very specific and sensitive assay to compare photoreactivation activity in human, rattlesnake, yeast, and Escherichia coli cells. Photolyase was easily detectable in E. coli, yeast, and rattlesnake cell-free extracts but none was detected in cell-free extracts from HeLa cells or human white blood cells with an assay capable of detecting 10 molecules per cell. We conclude that humans most likely do not have DNA photolyase.

Base Sequence↗
PubMed1993

The photo repair of pyrimidine dimers by DNA photolyase and model systems.

Pyrimidine dimers are eliminated from DNA by a number of different mechanisms known as DNA repair. Photoreactivation, the reversal of the harmful effects of short wavelength radiation by subsequent exposure to longer wavelengths, is one such mechanism. In photoreactivation, the enzyme DNA photolyase utilises light in order to catalyse the cleavage of the cyclobutane ring of the pyrimidine dimer. The results of recent studies of E. coli DNA photolyase and model systems using techniques such as steady state and flash photolysis, time resolved fluorescence and photo CIDNP are surveyed. A mechanism is proposed for the in vitro reaction of E. coli DNA photolyase which involves photoreduction of the FAD radical cofactor followed by electron donation to the dimer from the excited singlet state of reduced FAD.

DNA↗
PubMed1993

A case of cutaneous B-cell lymphoma with a storiform stromal reaction.

A case of cutaneous B-cell lymphoma is described. The patient was treated only by surgical excision of the skin tumors five times during a period of about two years from February of 1984 to October of 1986. After the last surgical excision, a continuous disease-free period was achieved. Biopsy samples showed dense lymphocytic infiltrations with discrete masses in the dermis and subcutis; one of them showed a storiform pattern. At the time, the infiltrating cells were composed of medium and large lymphoid cells and spindle-shaped cells. The medium and large lymphoid cells were positive for CD20, CD22 and HLA-DR and negative for CD3, CD4, CD5, CD8, CD43, and kappa and lambda light chain. The spindle-shaped cells were negative for CD20, CD43, kappa and lambda light chain, lysozyme, and S-100 protein.

Adult↗
PubMed1993

A case of cutaneous B-cell lymphoma treated successfully with MACOP-B.

A case of cutaneous B-cell lymphoma successfully treated by MACOP-B therapy is described. The patient was a 43-year-old man with reddish tumors measuring 3 to 7 cm in diameter on the right cheek and the post-auricles. Histopathologically, massive infiltrations of medium-sized atypical lymphoid cells were found in the reticular dermis and subcutis. A clear zone beneath the epidermis was also detected. The atypical lymphoid cells were positive for CD19, CD20, CD22 and HLA-DR but negative for CD3, CD4, CD5, CD10, CD43, CD45RO and CDw75. The patient was treated successfully with the MACOP-B protocol from March of 1990 to May of 1990. Since April of 1990, he has been free of disease.

Adult↗
PubMed1993

Cutaneous B-cell lymphoma--a clinical, pathological and immunohistochemical study.

Eleven cases of cutaneous B-cell lymphoma (CBCL) were studied. The ages at presentation ranged from 34 to 79 years (mean = 59.9 years). Six patients were female and five male. Five of the 11 patients had a solitary tumour and the other six had multiple tumours at initial presentation. According to Burg's classification, six cases were at stage I, two stage II, two stage III and one was at stage IV at initial presentation. Abnormalities in laboratory data were rare, except for serum lactic dehydrogenase values. Epidermotropism was not detected, and the area mainly affected by neoplastic cells was the reticular dermis (seven cases) and subcutis (four cases). Biopsy specimens from the patients analysed by immunohistochemical techniques on paraffin or cryostat sections showed CD20 and/or CD22 positivity. Biopsy specimens from two patients which showed CD10 positivity were diffuse large cell types by the working formulation and presented as pre-B-cell lymphoma. At least two groups of CBCL were demonstrable on the basis of prognosis. One was a benign low-grade lymphoma presenting with solitary tumours, mature B-cell markers and intermediate-grade pathology, and the other was a high-grade lymphoma with multiple tumours, pre-B-cell or mature B-cell markers and a poor prognosis.

Adult↗
PubMed1993

Photochemistry, photophysics, and mechanism of pyrimidine dimer repair by DNA photolyase.

DNA photolyases photorepair pyrimidine dimers (Pyr < > Pyr) in DNA as well as RNA and thus reverse the harmful effects of UV-A (320-400 nm) and UV-B (280-320 nm) radiations. Photolyases from various organisms have been found to contain two noncovalently bound cofactors; one is a fully reduced flavin adenine dinucleotide (FADH-) and the other, commonly known as second chromophore, is either methenyltetrahydrofolate (MTHF) or 8-hydroxydeazaflavin (8-HDF). The second chromophore in photolyase is a light-harvesting molecule that absorbs mostly in the near-UV and visible wavelengths (300-500 nm) with its high extinction coefficient. The second chromophore then transfers its excitation energy to the FADH-. Subsequently, the photoexcited FADH- transfers an electron to the Pyr < > Pyr generating a dimer radical anion (Pyr < > Pyr.-) and a neutral flavin radical (FADH.). The Pyr < > Pyr.- is very unstable and undergoes spontaneous splitting followed by a back electron transfer to the FADH.. In addition to the main catalytic cofactor FADH-, a Trp (Trp277 in Escherichia coli) in apophotolyase, independent of other chromophores, also functions as a sensitizer to repair Pyr < > Pyr by direct electron transfer.

Bacteria↗