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Biomedical subjects

M J Suh

Publications and source records attributed to M J Suh.

11 recordsLinked to original sources

Repair activities of 8-oxoguanine DNA glycosylase from Archaeoglobus fulgidus, a hyperthermophilic archaeon.

Oxidative DNA damage is caused by reactive oxygen species formed in cells as by products of aerobic metabolism or of oxidative stress. The 8-oxoguanine (8-oxoG) DNA glycosylase from Archaeoglobus fulgidus (Afogg), which excises an oxidatively-damaged form of guanine, was overproduced in Escherichia coli, purified and characterized. A. fulgidus is a sulfate-reducing archaeon, which grows at between 60 and 95 degrees C, with an optimum growth at 83 degrees C. The Afogg enzyme has both DNA glycosylase and apurinic/apyrimidinic (AP) lyase activities, with the latter proceeding through a Schiff base intermediate. As expected for a protein from a hyperthermophilic organism, the enzyme activity is optimal near pH 8.5 and 60 degrees C, denaturing at 80 degrees C, and is thermally stable at high levels of salt (500mM). The Afogg protein efficiently cleaves oligomers containing 8-oxoG:C and 8-oxoG:G base pairs, and is less effective on oligomers containing 8-oxoG:T and 8-oxoG:A mispairs. While the catalytic action mechanism of Afogg protein is likely similar to the human Ogg1 (hOgg1), the DNA recognition mechanism and the basis for 8-oxoG substrate specificity of Afogg differ from that of hOgg.

Amino Acid Sequence↗

Two interaction modes of the gp41-derived peptides with gp41 and their correlation with antimembrane fusion activity.

Peptides derived from gp41 effectively block the gp41-mediated cell fusion or HIV infection. A 36-mer (naDP178), 51-mer (C51) and 27-mer peptide (C27) from the membrane proximal region of gp41 have been examined their interaction modes with the coiled-coil motif of gp41 presented in thioredoxin (Trx-N) or the bacterially expressed ectodomain of gp41 (Ec-gp41ec). All of these peptides effectively inhibited the gp41-mediated membrane fusion, however, they showed distinct interaction modes with Ec-gp41ec or Trx-N. C51 peptide bound tightly to Trx-N, and it increased the solubility of Ec-gp41ec. naDP178 showed very weak binding affinity to Trx-N, however, it effectively solubilized Ec-gp41ec. In contrast, C27 peptide showed significant binding to Trx-N; however, it did not affect the solubility of Ec-gp41ec. These interaction modes of C-peptides were assumed to be related to their different inhibitory mechanism against gp41-mediated cell fusion.

Amino Acid Motifs↗

Improved photochemotherapy of malignant cells with daunomycin and the KTP laser.

Laser photochemotherapy of malignancies may become an effective palliative treatment for advanced had and neck cancer using light-sensitive, chemotherapeutic drugs activated in tumors via interstitial laser fiberoptics. Previously, it was reported that cultured human P3 squamous cells incubated 2 hours with daunomycin (Dn) exhibited tenfold enhanced cytotoxicity after exposure to argon laser light at 514 nm. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and daunomycin topoisomerase inhibition. In the current study phototoxicity of Dn-sensitized human cancer cells was tested using broad-spectrum white light compared to monochromatic green-wavelength light. Drug uptake and laser energy levels were optimized for maximum synergy. To test light-enhanced chemotherapy in vitro, the kinetics of cell uptake and toxicity of daunomycin was measured at 1, 2, and 5 microg/ml in three human tumor cell lines: P3 squamous-cell carcinoma, M26 melanoma, and TE671 fibrosarcoma. After 2 hr Dn uptake, all cell lines were tested for phototherapy response by exposure to 300- to 900-nm visible light from a xenon lamp or monochromatic 532-nm green light from a KTP laser. When the KTP laser output was varied from 0 to 120 Joules in Dn-sensitized tumor cells, a linear phototherapy response was seen with energy as low as 12 J inducing drug phototoxicity. These results provide evidence that daunomycin cytotoxicity is enhanced when exposed to 532-nm laser illumination in the three tumor types tested and confirm that the response is related to both energy level and drug dose.

Carcinoma, Squamous Cell↗

Anthrapyrazoles and interstitial laser phototherapy for experimental treatment of squamous cell carcinoma.

Interstitial laser therapy (ILT) is an effective palliative treatment for advanced head and neck cancer, but recurrence often is seen at the margin. The objective of the current study was to test combined drug and laser therapy as an experimental approach for improved treatment of human squamous cell carcinoma (SCCA). Human SCCA tumor transplants were grown in nude mice and injected with the photosensitive anthrapyrazole CI-941 before ILT. Intralesional drug injections alone at levels ranging from 60 to 1200 microg/gm of tumor induced a growth delay at the higher doses, but recurrence was seen in all 35 tumors tested. SCCA tumor transplants injected with 240 microg/gm CI-941 followed after 4 hours by ILT with the KTP532 laser led to a complete response rate of 72% (21/29) compared with 45% (13/29) for ILT alone. Laser chemotherapy was a significant improvement compared with ILT when partial and complete responses were combined (P < 0.03). The results provide preclinical evidence that laser chemotherapy may become a useful minimally invasive treatment for advanced squamous cell carcinoma of the head and neck.

Animals↗

Laser and cisplatinum for treatment of human squamous cell carcinoma.

OBJECTIVE: Interstitial laser therapy (ILT) with the neodymium:yttrium-aluminum-garnet (Nd:YAG) (1064 nm) laser via fiberoptics is becoming a more precise, minimally invasive alternative for thermoablation of unresectable or recurrent head and neck neoplasms, but recurrence is often seen at the margin. Combining intratumor chemotherapy with interstitial laser should be most effective using drugs activated by thermal energy. The objective of the current study was to test intratumor cisplatinum (cis-diaminedichloroplatinum [CDDP]) injections given in conjunction with laser therapy as an experimental approach for improved treatment of squamous cell carcinoma (SCC). METHODS: Human SCC tumors were grown as subcutaneous transplants in nude mice and injected with CDDP (0.4 to 1.2 mg/g) in water or in collagen-based gel carrier with epinephrine (epi-gel) followed by ILT via 0.6-mm fiberoptics coupled to an Nd:YAG laser (1064 nm/180 J). RESULTS: Tumors injected with CDDP epi-gel exhibited a partial response with two- to fourfold tumor delay compared with aqueous drug or untreated SCC transplants during 10 weeks' follow-up. Combined drug and laser therapy significantly (P < .01) decreased tumor volume, with recurrence in only 25% of animals tested compared with 78% tumor regrowth after ILT alone. CONCLUSION: These initial results suggest that laser chemotherapy may become an effective treatment for advanced head and neck cancer.

Animals↗

Application of capillary electrophoresis to determination of enzyme activity and other properties of phosphatidylinositol-specific phospholipase C.

This paper describes a method for monitoring enzymatic activity using micellar electrokinetic chromatography (MEKC). MEKC is used to analyze the activity of phosphatidylinositol-specific phospholipase C (PI-PLC) with convenience and precision. PI specific PLC enzyme converts phosphatidylinositol (PI) to diacylglycerol (DAG) and inositol 1,2-cyclic phosphate (IP). The assay system developed is based on monitoring both the breakdown of substrate and the formation of products simultaneously. To obtain the best separation for the substrate PI and product DAG, we investigated changes in concentration of electrolyte buffer and SDS as well as in pH of the electrolyte buffer. Since the structures of the substrate and products are different, the reaction could be monitored easily by MEKC mostly based on hydrophobicity. Under the separation conditions developed, we investigated the enzymatic activity of PI-PLC depending on the concentrations of phosphatidylinositol, various divalent cations and the reaction temperature. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to confirm the molecular masses of the substrate PI and products DAG and IP. The results of this study show that capillary electrophoresis can be widely applied to analyze and characterize many other enzymes since capillary electrophoresis has several advantages as follows, simplicity, speed, no need for radiolabelled substrate, small sample volumes and sufficient accuracy.

Cations, Divalent↗

[A study of factors influencing the state of adaptation of hemiplegic patients].

The purposes of this study are to delineate a profile of the state of a stroke patient's adaptation at 3 months after hospitalization and to explore the relationship between the level of adaptation and the variables which influence the adaptation of hemiplegic patients. To these ends, theoretical framework was derived basically from the stress adaptation model. The basic assumption underlying the level of adaptation is influenced by the presenting focal, contextual and residual stimuli. This group of stimuli is further operationalized and represented by a perception of stress, which is the perceived effect of the disability and by the mediating variables such as sociodemographic factors as an external conditioning variables and perceived social support and hardiness personality characteristics as an internal intervening variables. The dependent variables in this study is the level of physical, psychological and social adaptation and is hypothesized to be a function of the interaction between 3 sets of variables namely, the perceived disability effect, external conditioning variables and internal intervening variables. A total of fourty three subjects from 3 general hospitals in Seoul were observed and interviewed with the aid of 7 structured instruments. The data were collected twice on each subject: first, at the pre-discharge period and at 3 months post-discharge from hospital for the second time. The study was carried out for the period from February to August, 1988. The instruments used for the study include 4 existing scales and 3 scales developed by the researcher for this study. They are: 1) The ADL dependency scale and the scale of the clinical physical functions for the assessment of physical adaptation. 2) the SDS (self report of depression) to measure the level of psychological adaptation. 3) The scale for the amount of social activities for the measurement of the level of social adaptation. 4) The scale for the perceived effect of disability for the measurement of the focal stimuli. 5) The health related hardiness scale and the perceived interpersonal support self evaluation list (ISEL) for the measurement of the hardiness personality character and the perceived social support. The data obtained were analyzed using percentage, one way ANOVA, Pearson coefficients correlation and stepwise multiple regression. The findings provide valuable information about the present level of physical adaptation at 3 months after discharge. The patient revealed a decreased ADL dependency and lowered limitation of physical function as compared with pre-discharge state. Psychologically, the average degree of depression at follow up was within normal range of depression.(ABSTRACT TRUNCATED AT 400 WORDS)

Activities of Daily Living↗

[Study on work stress perceived by clinical nurses].

This study was designed to measure the degree of work stress perceived by clinical nurses working in psychiatric ward, and to identify the factors influencing the difference of work stress. The survey method was used and the subjects of this study consisted of 135 psychiatric nurses from 7 university hospitals and 4 provincial general hospitals. The data were collected from August 1 to 20, 1988. The instrument used for this study was PNOSS (Psychiatric Nurse Occupational Stress Scale) which was developed by Bai (1989). The confidence verification of this instrument was computed and the Cronbach alpha was 0.94050. Data were analysed by t-test and ANOVA on 5% significant level with SPSS program. The results of study were summarized as follow: 1) The degree of perceived stress among psychiatric nurses was considerably high (4.32 out of 6.00). 2) Among the stressors, inadequate staffing (5.04), hospital administration problems (4.7) and the conflict of nurse-patient relationship were identified as the stress factors with high rank of degree of stress. 3) There was significant relationship between the degree of stress and the demographic variables of nurses such as the marital status, educational level, and the motivation of working in psychiatric ward. 4) There was significant relationship between the job-related variables such as the working duration, the motivation of working and nurse's attitude toward the psychiatric patients. 5) The relationship between several stress factors and some of the demographic and the job-related variables were significantly identified.

Demography↗