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Biomedical subjects

M J Li

Publications and source records attributed to M J Li.

49 records · Page 3Linked to original sources

[Synthesis and radiosensitizing activity of benzimidazoles].

In search for effective radiosensitizer with low neurotoxicity, benzimidazole compounds were synthesized. Reaction of 2-nitrobenzimidazole with ethyl chloroformate yielded ethyl alpha-(2-nitrobenzimidazolyl-1)-formate(1) or ethyl alpha-(2-hydroxybenzimidazolyl-1)-formate(2), depending upon the solvents used. Reaction of 2-nitrobenzimidazole with 1,2-epoxy-3-chloropropane gave a cyclized compound which was confirmed to be benzimidazo(1,2b)-5'-chloromethyl-oxazolidine(3). In attempt to increase hydrophilicity, 1-substituted 2(3'-pyridyl)-5-nitrobenzimidazoles were prepared by reaction of 2-(3'-pyridyl)-5(6)-nitrobenzimidazole(4) with alkyl epoxides or ethyl chloroacetate. Some of the compounds synthesized were tested for radiosensitizing activity in Ehrlich ascites carcinoma-bearing mice. Preliminary results showed that some compounds have radiosensitizing activity. The radiosensitizing enhancement ratio (SER) of compounds 3, 5 and 6 were found to be 1.50, 1.52 and 1.65 respectively.

Animals↗

A unique human mutant B-lymphoblastoid cell line (ataxia telangiectasia) which exhibits increased sister-chromatid exchange retaining hypersensitivity to neocarzinostatin and bleomycin.

Chromosome aberrations and sister-chromatid exchanges (SCEs) were examined in 4 ataxia telangiectasia (AT)-derived B-lymphoblastoid cell lines (B-LCLs) (AT-S, AT-SHI, AT-SHI B13A and AsHa) following treatments with neocarzinostatin (NCS) and bleomycin. All of these cell lines exhibited extremely high frequencies of chromosome aberrations with the NCS and bleomycin treatments. Among them, AsHa, a mutant B-LCL originating from an AT patient, showed high frequencies of SCEs under high bromodeoxyuridine (BrdU) concentrations retaining hypersensitivity to NCS and bleomycin with regard to chromosome aberrations. A clear BrdU dose-dependent increase in SCEs (9.85 SCEs/cell at 40 micrograms/ml, 36.65 SCEs/cell at 100 micrograms/ml on average) in this mutant was observed. When AsHa mutant cells were treated with NCS (0.02 microgram/ml) and/or bleomycin (5.0 micrograms/ml) under 40 micrograms/ml BrdU (minimum BrdU concentration for sister-chromatid differential staining), SCE levels increased from 9.85 (baseline level) to 21.1 with NCS and 20.5 with bleomycin, in a dose-dependent manner. These observations indicate that AsHa is a unique AT-derived mutant cell clone with a high SCE character retaining the original hypersensitivity to bleomycin and NCS.

Antibiotics, Antineoplastic↗

Bromodeoxyuridine (BrdU) template and thymidine pool effects on high frequencies of sister-chromatid exchange (SCE) in Bloom syndrome cells and a mutant cell line (AsHa) originated from ataxia telangiectasia.

The effect of bromodeoxyuridine (BrdU)-substituted DNA template and thymidine (dT) pool on excess sister-chromatid exchanges (SCEs) was studied in Bloom syndrome (BS) cells and an ataxia telangiectasia (AT)-derived mutant cell line (AsHa). When BS endomitotic cells were labeled with low and high (or high and low) BrdU concentrations during S1 and S2, only the BrdU concentration during S1 phase affected the observed SCE. In BS cells about a 10-fold increase in SCEs occurs during or following replication on a BrdU-substituted template (high-high and high-low BrdU labeling) relative to the normal DNA template. SCEs decreased to about half in AsHa cells labeled with various BrdU doses (40, 60, 80 and 100 micrograms/ml) during only S1, compared with those labeled during S1 and S2. Co-cultivation of AsHa and BS cells resulted in a significant reduction in SCE level from 70 to 13-17 in BS cells, lowered the BrdU concentrations necessary for sister-chromatid differential (SCD) staining from 40 to 10 micrograms/ml with normal SCE level and resulted in decreased level of SCEs at high BrdU concentrations (80-100 micrograms/ml) (12-14 SCE) in AsHa cells, compared with the originally increased SCE level (36.65 SCE at 100 micrograms/ml) without co-culture. However, co-cultivation between AsHa and normal cells lowered the BrdU dose necessary for SCD staining from 40 to 30 micrograms/ml; the dT pool possibly balanced at this level, which is clearly higher than that at co-cultivation between AsHa and BS cells. The reason for the very high BrdU doses needed to achieve SCD would seem to be that AsHa cells have high levels of thymidylate (TMP) synthetase, which maintain a large endogenous thymidine pool. This has been confirmed by direct measurement. These findings strongly support that excess and decreased dT pools are closely related to the condition necessary for high SCE induction.

Ataxia Telangiectasia↗

[Study on DNA content and nucleus/cytoplasm ratio of esophageal epithelium during malignant change].

DNA content and nucleus/cytoplasm ratio were assayed in the paracancerous mucosa from 37 cases of esophageal carcinoma by microspectrophotometry (Leitz MPV3). The histopathological diagnosis was made at the same area. In normal epithelium and simple hyperplasia, the relative DNA content was within the range of 2C-4C; cells with DNA content of 4C or greater than 4C were found mostly in invasive carcinoma. There were two different types of DNA content histogram observed in atypical hyperplasia and carcinoma in situ. One type was similar to simple hyperplasia and the other type was similar to invasive carcinoma. These results indicated that two different malignant features might be obtained under the same histopathological diagnosis. The nucleus/cytoplasm ratio in simple hyperplasia was close to that of normal mucosa. In atypical hyperplasia and carcinoma in situ, especially in the middle and superficial layers of the epithelium, the nucleus/cytoplasm ratio increased markedly, which indicated that the cells in these layers were poorly differentiated.

Cell Nucleus↗

[Nuclear DNA content in nasopharyngeal carcinoma (NPC) cells].

Cancer cell nuclear DNA content of 40 biopsy imprints of NPC was measured by Leitz MPV3 microspectrophotometer using scanning method. The pathological diagnosis and histological classification were done on the same specimens. By morphology, the poorly differentiated squamous carcinoma (34 cases) could be divided into four subtypes: ordinary nucleus type (14), spindle nucleus type (5), large and pleomorphic nucleus types (12 and 3). The first two types revealed a bimodal peak DNA histogram (2C and 4C) and slightly scattering toward the right to the 8C region in some nuclear DNA. The large nucleus type showed the bimodal peaks with a broad 4C and many nuclear DNA located in the 4C-8C range. The pleomorphic nucleus type appeared as multiple low peaks diffusing between 2C-12C. The vesicular nucleus cell carcinoma (3 cases) had a double peak DNA histogram similar to the ordinary nucleus type. The undifferentiated cell carcinoma (1 case) showed a broad unimodal peak DNA, ranging from 2C to 6C. The well differentiated squamous carcinoma (2 cases) had a double peak DNA, which was close to the normal diploid pattern but each peak was relative wide and a few DNA value located beyond the 4C region. The results indicate that DNA values showing a predominance of double peak histogram and diploid pattern imply the low grade malignancies in its biological behavior. In contrast, those showing the aneuploid and multiploid patterns in the majority of cancer cells point to the high grade malignancies. Hence, the supplementary DNA measurement of NPC cells can judge exactly the malignant degree of the tumor and provide evidence for prognosis.

Carcinoma, Squamous Cell↗

Diagnosis of congenital hypothyroidism from human anagen scalp hair by infrared microspectroscopy.

A highly efficient Fourier transform infrared (FT-IR) microscopy was used to determine the biophysical structure of anagen scalp hair roots of neonates suffering from congenital hypothyroidism (CH) due to ectopic thyroid. The present results indicate that the lower composition near 1,053 cm(-1) (also assigned to the aromatic iodide stretching band) in the infrared (IR) spectra of the hair roots for CH patients was directly associated with the lower serum level of T4 and fT4, and the elevated TSH levels determined by RIA method. This strongly implies the lower evidence of the aromatic iodide stretching band in the IR spectra of hair roots. These findings suggest that FT-IR microscopy has the potential to become a good diagnostic tool and that hair can be useful as a genetic marker.

Cell Cycle↗

In vitro degradation and dissolution behaviours of microspheres prepared by three low molecular weight polyesters.

Three low-molecular weight polyesters, poly(L-lactic acid) (PLA), copoly(lactic acid/glycolic acid) (PLGA) and poly(delta-valerolactone) (PV), were used to prepare water-soluble sodium diclofenac-loaded microspheres by using the oil-in-oil (o/o) emulsification-solvent evaporation method. Their micromeritic and physicochemical properties, and degradation and dissolution behaviours were determined in vitro. The results indicate that high encapsulation efficiency and better monodispersity might be achieved by the o/o emulsification-solvent evaporation method, depending on the amount of drug loading used. The slower evaporation of organic solvent from the system during microencapsulation seemed to modify the crystallinity of drug and polyester in the microspheres, determined by powder x-ray diffractometry and differential scanning calorimetry. The in vitro degradation rate of all the microspheres in pH7.4 phosphate buffer solution showed first-order kinetics and ranked in the order of PLGA > PLA > PV microspheres. Furthermore, the first-order release rate was also found in all the microspheres after an initial drug burst and ranked in the order of PLGA> PLA > PV microspheres, too. The relationship between degradation and dissolution behaviours of these microspheres is discussed.

Biodegradation, Environmental↗

Changes in the skin moisture contents, skin color, and skin protein conformational structures of sprague-dawley rats after ultraviolet B irradiation.

The influence of ultraviolet B (UVB) irradiation on the skin moisture contents, skin color, and protein secondary structure in the skin of alive Sprague-Dawley (SD) rats was investigated. The UVB irradiation source emitted 725 +/- 10 microW/cm(2) of UVB range with a peak at 302 nm during the exposure course of 6 h/day for 3 successive days. The moisture content of SD rat's skin first decreased with the UVB irradiation, then returned to normal level on days 1 and 2, and, finally, decreased significantly with the increase of UVB irradiation on day 3. After the 6-hour irradiation on days 1 and 2, the moisture contents of the irradiated skin of SD rat returned to normal values, suggesting repairability of the irradiated skin of SD rat during the following 18 hour period without irradiation. By increasing frequency and duration of UVB irradiation, the skin color parameters exhibited a lower L* value, a greater a* value, and a higher DeltaE value, indicating that the skin color darkened and reddened. The slight modification of protein secondary structure of the skin of SD rats after repeated UVB irradiation was evidenced. However, the infrared spectrum during the initial course of irradiation, from day 1 to day 3, exhibited a similar pattern. Thus, the alive SD rat's skin was repairable during the 18-hour period without irradiation.

Animals↗