PubMed Health⌕ Search

Biomedical subjects

S M Han

Publications and source records attributed to S M Han.

At least 37 records · Page 2Linked to original sources
PubMed1997

Loss of heterozygosity of the retinoblastoma and p53 genes in primary cervical carcinomas with human papillomavirus infection.

OBJECTIVE: Paired DNA samples from 55 primary uterine cervical carcinomas and normal bloods were studied for chromosomal allelic loss (loss of heterozygosity; LOH) of the retinoblastoma (Rb) and p53 gene loci by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism analysis. All the study samples contained at least one of the oncogenic human papillomavirus (HPV) type 16 and/or 18 sequences. And the relationships between allelic losses of these genes and conventional clinicopathological parameters were evaluated. METHODS: In order to detect LOH of the Rb gene in cervical cancers, we analyzed four polymorphic intronic sites (intron 1, 17, 20, and 25) of the Rb gene and one additional microsatellite near the Rb locus (D13S118). For detection of the LOH in p53, three intragenic polymorphisms (exon 1, exon 4, intron 6) and one microsatellite distal to the p53 gene (D17S5) were examined. RESULTS: By analyzing this system, we could increase the heterozygosity of the Rb and p53 loci up to 0.91 and 1, respectively. The observed allelic loss rates of the Rb and p53 loci in informative cases were 14% (7/50) and 5.5% (3/55), respectively. The patients with LOH at the D13S118 locus also had the allelic loss of the Rb gene, whereas only one of the four patients with LOH at the D17S5 locus showed a concomittant allelic loss of the p53 gene. The frequency of cervical cancer with one LOH at the Rb or p53 loci was 20% (11/55). No shifted bands were observed in the PCR-single-strand conformation polymorphism analysis of the p53 gene. The LOH of the Rb or p53 gene was not significantly associated with other parameters including clinical stage, histological type, degree of differentiation, status of HPV infection, and p53 gene mutation. CONCLUSION: Concerning the results above, we conclude that the allelic imbalance of the Rb or p53 gene itself is not implicated as a major contributing factor in the malignant transformation or the tumor progression in HPV-positive uterine cervical cancers.

Adult↗
PubMed1997

A comparison between the patella and the calcaneus using ultrasound velocity and attenuation as predictors of bone mineral density.

The bone mineral density (BMD), ultrasound velocity (UV) and attenuation were examined in sixteen matched sets of human patellae and calcanei. For the sixteen calcanei, BMD was strongly correlated with all ultrasound parameters. Calcaneal UV appeared to be inferior to attenuation in the ability to predict BMD. For the sixteen patellae, the average UV was found to be greater in the superior/inferior direction than in the anterior/posterior and medial/lateral directions. It was found that patella BMD was significantly correlated with each of three directional ultrasound velocities. The relationship between BMD and ultrasound attenuation parameters was not significant in the patella. A comparative study of the two different bone sets demonstrated that the BMDs of the patella and calcaneus were significantly correlated with each other. Ultrasound velocity of calcaneus, measured in the medial/lateral direction, was not significantly associated with any of three directional ultrasound velocities in the patella. Similarly, ultrasound attenuation parameters of calcaneus were not significantly correlated with those of patella. The present study also demonstrated evidence that when predicting BMDs at their respective sites using ultrasound, the calcaneus appeared to be superior to the patella.

Aged↗
PubMed1996

Determination of SB 216469-S during tablet production using near-infrared reflectance spectroscopy.

A near-infrared method was developed for analyzing SB 216469-S tablets at various stages of tablet processing, particularly after (i) high shear granulation, (ii) lubrication, (iii) core tablet compression, and (iv) aqueous film coating. Tablets with three different drug concentrations ranging from 1.5% (w/w) to 6.0% (w/w) were examined along with a placebo. Similarly, moisture levels during the granulation drying process were measured, along with the thickness of the tablet coating. Tablet identification inside blister packaging for clinical supplies was also demonstrated.

Chemistry, Pharmaceutical↗
PubMed1995

Functional consequences of directed mutations in human papillomavirus E6 proteins: abrogation of p53-mediated cell cycle arrest correlates with p53 binding and degradation in vitro.

Clinical and epidemiological studies have implicated the involvement of human papillomavirus (HPV) infection in cervical tumorigenesis. We have previously shown that expression of high-risk (HPV16) E6 can abrogate an important cell cycle checkpoint mediated by p53. Sublethal DNA damage causes p53 accumulation and G1 arrest in normal cells, but not in cells with mutant or absent p53, or in cells that express HPV16-E6. To investigate the functional consequences of low-risk (HPV11) E6 expression and to evaluate regions of E6 believed to mediate interaction with p53, we generated several E6 expression constructs, including HPV11-E6, and fourdifferent E6 mutants. HPV16E6 deltaD and HPV16E6 deltaB had short deletions of nucleotides encoding amino acids previously implicated in p53 degradation and binding, respectively. HPV16E6HL and HPV11E6LH had the putative p53 binding domain exchanged between the high- and the low-risk types. Unlike HPV16-E6, HPV11-E6 and the mutant E6 proteins were not able to bind or degrade p53 in in vitro assays. When expressed in RKO cells, HPV11-E6 or the mutant E6 proteins did not prevent p53 accumulation or interfere with p53-dependent WAF1/CIP1 mRNA expression, allowing p53-mediated G, cell cycle arrest after DNA damage. These findings demonstrate that low-risk and high-risk E6 proteins differ in their effects on p53-mediated cell cycle control and that rather subtle mutations of high-risk E6 can alter its ability to abrogate this important cellular response.

Cell Cycle↗
PubMed1993

Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage.

Infection with certain types of human papillomaviruses (HPV) is highly associated with carcinomas of the human uterine cervix. However, HPV infection alone does not appear to be sufficient for the process of malignant transformation, suggesting the requirement of additional cellular events. After DNA damage, normal mammalian cells exhibit G1 cell-cycle arrest and inhibition of replicative DNA synthesis. This mechanism, which requires wild-type p53, presumably allows cells to undertake DNA repair and avoid the fixation of mutations. We directly tested whether the normal response of cervical epithelial cells to DNA damage may be undermined by interactions between the E6 protein expressed by oncogenic HPV types and wild-type p53. We treated primary keratinocytes with the DNA-damaging agent actinomycin D and demonstrated inhibition of replicative DNA synthesis and a significant increase in p53 protein levels. In contrast, inhibition of DNA synthesis and increases in p53 protein did not occur after actinomycin D treatment of keratinocytes immortalized with HPV16 E6/E7 or in cervical carcinoma cell lines containing HPV16, HPV18, or mutant p53 alone. To test the effects of E6 alone on the cellular response to DNA damage, HPV16 E6 was expressed in the carcinoma cell line RKO, resulting in undetectable baseline levels of p53 protein and loss of the G1 arrest that normally occurs in these cells after DNA damage. These findings demonstrate that oncogenic E6 can disrupt an important cellular response to DNA damage mediated by p53 and may contribute to the subsequent accumulation of genetic changes associated with cervical tumorigenesis.

Cell Cycle↗
PubMed1993

p53 gene mutations and MDM2 amplification are uncommon in primary carcinomas of the uterine cervix.

The p53 gene is the most frequently altered gene known thus far in a wide variety of human cancers. Inactivation of p53, either through mutation or through interaction with the human papillomavirus (HPV) E6 oncoprotein, is a characteristic feature of all cervical carcinoma cell lines that have been studied. These findings suggest that p53 inactivation is required for cervical carcinoma development and that HPV infection and p53 mutation may be mutually exclusive. We have studied the p53 gene in 35 primary cervical carcinomas. DNA sequence and single strand conformational polymorphism analyses were used to evaluate p53 in 27 squamous carcinomas (25 HPV-positive) and eight adenocarcinomas (four HPV-positive). A missense mutation of p53 was observed in one HPV 16-positive squamous carcinoma, demonstrating that p53 mutations can occur in combination with HPV infection. The HPV-negative tumors all lacked p53 gene mutations. The absence of p53 mutations in HPV-negative cases prompted an assessment of tumors for MDM2 gene amplification. The MDM2 gene encodes a p53 binding protein and has been found to be amplified in some human tumors lacking p53 mutations. MDM2 amplification was not identified in any of the tumors we examined, including four HPV-negative cases. Our findings show that HPV infection and p53 gene mutation are not mutually exclusive and suggest that many HPV-negative carcinomas may arise via a pathway independent of p53 inactivation.

Adenocarcinoma↗
PubMed1988

Use of hydroxypropyl- and hydroxyethyl-derivatized beta-cyclodextrins for the thin-layer chromatographic separation of enantiomers and diastereomers.

Partially substituted hydroxypropyl-beta-cyclodextrin and hydroxyethyl-beta-cyclodextrin proved to be effective chiral mobile phase additives (CMAs) for the thin-layer chromatographic (TLC) resolution of racemic benzyl-2-oxazolidinone, 5-(4-methyl-phenyl)-5-phenylhydantoin, mephenytoin and several dansyl and beta-naphthylamide amino acids. Several diastereomeric compounds including steroid epimers and alkaloids were separated as well. The derivatized beta-cyclodextrins tended to be much more soluble in water and hydro-organic solvents than native beta-cyclodextrin. Their chromatographic selectivity also was somewhat different. The use of CMAs in TLC is a potentially useful and powerful method that has not been considered adequately. The relative lack of chiral stationary phases available in planar format makes the use of CMAs particularly attractive.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1988

Planar chromatographic separation of enantiomers and diastereomers with cyclodextrin mobile phase additives.

A variety of racemic compounds were resolved using reversed-phase thin-layer chromatography (TLC) with mobile phases containing highly concentration solutions of beta-cyclodextrin (beta-CD). These include the drugs labetalol and mephenytoin, metallocenes, crown ethers, methyl-p-toluenesulfinate, nornicotine derivaties and several dansyl and beta-naphthylamide substituted amino acids. It was possible to resolve some racemates that could not be separated on beta-CD bonded phase liquid chromatography (LC) columns with this technique. Likewise there were some compounds that could be resolved with the LC approach that failed to separate with the present TLC method. In cases of racemates that could be resolved by either approach, it was found that the retention order was exactly opposite for the two methods. Enantiomeric resolution is highly dependent on mobile phase composition. In particular, the type and amount of organic modifier as well as the concentration of beta-CD affect the observed resolution. Possible reasons for the chromatographic behavior are discussed. Several diastereoisomeric compounds were separated as well, including steroid epimers and pharmaceutical compounds.

Amino Acids↗
PubMed1987

Quantitative analytical aspects of reversed-phase liquid chromatography with slurry-packed capillary columns.

Conditions for reproducible packing of fused-silica liquid chromatography capillary columns were demonstrated. The plate height vs. velocity curves were determined for successively prepared columns. In addition, the values of separation impedance were calculated. Several liquid chromatography systems were evaluated in conjunction with the slurry-packed capillaries for the retention and peak area reproducibility.

Chromatography, Liquid↗
PubMed1987

Separation of optical isomers of scopolamine, cocaine, homatropine, and atropine.

Different drug stereoisomers can have different physiological and therapeutic effects. Difficulties in separating optical isomers often make it impractical to market stereochemically pure products or to monitor isomeric contamination. This is not thought to be a problem with drugs isolated from biological sources (the alkaloids, for example). However, small amounts of isomeric impurities also exist in many biological systems. More importantly the isolation and purification process can cause partial or complete racimization in some cases. Great care must be taken in the handling of some drugs and an efficient, sensitive means to monitor racimization is important. Liquid chromatographic separation on a chiral beta-cyclodextrin bonded phase can be an effective technique in many cases. Its use in separating optical isomers of dl-scopolamine, dl-hyoscyamine, dl-homatropine, and dl-cocaine is discussed.

Atropine↗