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R Han

Publications and source records attributed to R Han.

At least 91 records · Page 5Linked to original sources
PubMed1995

Dependence of the phosphorylation of alkaline phosphatase by phosphate monoesters on the pKa of the leaving group.

The hydrolysis and transphosphorylation reactions of a series of phosphate monoesters, ROPO3(2)-(R = 2,4-dinitrophenyl, 4-nitrophenyl, phenyl, glucose-1, glycerol-1, methyl, ethyl, and dodecyl), catalyzed by Escherichia coli alkaline phosphatase and a mutant enzyme, Ser102Cys, have been studied at alkaline pH using the rates of change in the 31P NMR signals of substrate, the hydrolysis product (inorganic phosphate), and the transphosphorylation product (O-Tris phosphate) as the assay. The kcat at pH 8.0 for the wild-type enzyme is approximately 30 s-1 and is independent of the nature of the R group, when the pKa of the leaving group is < 10. Under these conditions the rate of phosphorylation is much faster than dissociation of inorganic phosphate, 15-60 s-1. If the pKa of the leaving group is between 10 and 15, phosphorylation and dissociation of the product phosphate both contribute to the rate limit. If the pKa of the leaving group is > 15, phosphorylation is rate limiting. A Bronsted plot of log kcat vs pKa of the leaving group for those substrates for which phosphorylation is rate limiting yields a beta lg of approximately -0.6. In contrast to the wild-type enzyme, the log kcat values for the S102C mutant enzyme catalyzing the hydrolysis of phosphate esters are linearly dependent on the pKa's of the leaving group throughout the range of pKa from 4 to 16. Phosphorylation of C102 is the rate controlling step, and kcat is independent of the Tris concentration as predicted for rate limiting phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1995

Novel oral medication delivery system for famotidine.

A famotidine wafer that rapidly disperses on the tongue without water is a novel alternative to other histamine2 (H2)-antagonist dosage forms. Benefits associated with such a dosage form include convenience and potentially improved compliance for patients who dislike or have difficulty taking tablets and capsules. This report describes the research of three studies on the famotidine wafer dosage form. In the first trial, the bioequivalence and tolerability of the new 40-mg famotidine wafer and the marketed 40-mg famotidine tablet were studied in a 2-period crossover study (n = 18). The two formulations were bioequivalent as assessed by area under the plasma concentration versus time curve and maximum plasma concentration of famotidine. The plasma concentration of famotidine associated with 50% inhibition of pentagastrin stimulated gastric acid secretion (EC50; 10 ng/mL) was attained on average within 0.5 hours post-dose for the wafer and tablet. In a second trial, the tolerability of the famotidine 20-mg and 40-mg wafers or placebo given twice daily (bid) for 14 days were evaluated (n = 192). Both wafer strengths were well and equally tolerated. In a third trial of 450 subjects, the 40-mg wafer was preferred over tablets by 75% of the subjects, when they were asked to consider the method of administration and flavor. When used as an alternative to tablets and other conventional dosage forms, the wafers have the potential therapeutic benefit of improved compliance. It is concluded that similar systemic exposure, excellent tolerability, palatability, and preference make the famotidine wafer a clinically acceptable and convenient dosage from for patients on H2-antagonist therapy.

Administration, Oral↗
PubMed1995

Diagnostic approach to reflex sympathetic dystrophy after fracture: radiography or bone scintigraphy?

The aim of this paper was to compare the value of bone scintigraphy and radiography in the early diagnosis of post-fracture reflex sympathetic dystrophy (RSD). Thirty-seven adult patients with post-fracture RSD (28 in the first and nine in the second clinical stage of RSD), as well as seven patients with fracture but without RSD (control group), were investigated by radiography and bone scintigraphy. All of them were immobilized (duration of immobilization: 4-22 weeks). In 21 persons three phase bone scintigraphy was performed. The best distinction between the control group and the RSD patients was achieved by delayed bone scintigrams. The sensitivity (97%), positive predictive value (97%) and accuracy (95%) of delayed bone scintigraphy were very high compared to the values for radiography, which were 73%, 90% and 70% respectively. Bone scintigraphy also displayed higher specificity (86%) and negative predictive value (86%) than radiography (57% and 29% respectively). In the first clinical stage the difference between the accuracy of bone scintigraphy (97%) and radiography (63%) was greater than for the whole group. In the second stage of RSD the accuracy of bone scintigraphy (86%) and radiography (81%) was similar. Three-phase bone scintigraphy is not necessary for the diagnosis of post-fracture RSD: it is sufficient to perform delayed bone scintigraphy. It is concluded that bone scintigraphy is to be preferred to radiography for the early diagnosis of post-fracture RSD in the first clinical stage. In the second stage the diagnostic capabilities of bone scintigraphy and radiography are more comparable.

Adult↗
PubMed1995

Differential expression of collagen-binding receptors in fetal rat lung cells.

Interactions of cells with molecules of the extracellular matrix (ECM) are mediated via specific cell surface receptors. Because collagen is an important ECM component in the developing lung, we investigated the expression of collagen receptors by distal fetal lung epithelial cells and fibroblasts. Cell attachment experiments revealed that fibroblasts but not epithelial cells adhered to various types of collagen. With the use of subunit-specific antibodies, we demonstrated the presence of the collagen integrins alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 at the fibroblast surface but only the integrin alpha 3 beta 1 on epithelial cells. Affinity chromatography on collagen-Sepharose identified only alpha 1 beta 1 and alpha 2 beta 1 as collagen-binding integrins in extracts of 125I surface-labeled fibroblasts. No collagen-binding receptors were detected in extracts of surface-iodinated epithelial cells. Message for alpha 1- and alpha 2-integrin was readily demonstrated for fibroblasts, but both mRNAs were hardly detectable in epithelial cells. In contrast, epithelial cells expressed significantly greater alpha 3 mRNA levels than fibroblasts. These data demonstrate that alpha 1 beta 1- and alpha 2 beta 1-integrins function as collagen-binding receptors in fetal lung fibroblasts. Distal fetal lung epithelial cells do not express the alpha 1 beta 1- and alpha 2 beta 1-integrins and do not adhere to collagen. The alpha 3 beta 1-integrin, which is expressed by both cell types, does not function as a collagen receptor.

Animals↗
PubMed1995

Effect of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo(a)pyrene.

Glycyrrhetinic acid (GA) is an active component of Glycyrrhiza uraleusis fisch. In this study, GA was found to inhibit ear edema and ornithine decarboxylase (ODC) activity induced by croton oil in mice. GA could also protect rapid DNA damage and decrease the unscheduled DNA synthesis induced by benzo(a)pyrene. The results demonstrate that GA has a potential cancer chemopreventive activity.

Animals↗
PubMed1995

Meta-[131I]iodobenzylguanidine in the scintigraphic evaluation of neural crest tumors.

Since February 1990, 74 patients (116 studies) underwent scintigraphy with meta-[131I]iodobenzylguanidine ([131I]MIBG). Eighteen patients had pheochromocytomas, 2 paragangliomas, 2 malignant insulinomas, 1 carcinoid, 2 medullary thyroid carcinoma and 49 children had neuroblastomas. Scintigraphy was performed following a thyroid blockade, at 24 and 48 hours after i.v. injection of 0.5 mCi/1.7 m2 [131I]MIBG. Grade of heart intensity (GHI) uptake and the intensity of salivary gland visualization (SGI) were estimated semiquantitatively, according to the method of Nakajo et al. Sensitivity in the primary pheochromocytomas was 93.9%; sensitivity and specificity in the primary neuroblastomas were 93.7% and 100% respectively; in the secondary neuroblastomas they were 100%, and 100%. Metastases in 2 malignant insulinomas and in 1 case of medullary thyroid carcinoma were also demonstrated. Only one false negative (in pheochromocytoma) and one false positive (Conn's syndrome) result was obtained. Mean values and range of MIBG uptake measured according to Shulkin's procedure were: for pheochromocytoma 3.95% (0.1-15), primary neuroblastoma 0.7% (0.05-1.92%), and neuroblastoma metastases 0.12% (0.002-0.83%). Assessment of [131I]MIBG uptake seems to be helpful in the follow-up of some neural crest tumors and is essential as a prelude to [131I]MIBG therapy.

3-Iodobenzylguanidine↗
PubMed1994

Bladder irrigation specimens assayed by fluorescence in situ hybridization to interphase nuclei.

Bladder irrigation specimens provide a sampling of the entire bladder urothelium and are the most practical sample for longitudinally monitoring patients. This study presents cross-sectional fluorescence in situ hybridization (FISH) analyses with correlated DNA cytometry data on 76 patients monitored for recurrent bladder tumors. FISH probes complementary to centromeric satellite sequences for chromosomes 1, 7, 9, 11, 15, and 17 were used. Aberrations in copy number were observed for chromosomes 1, 7, 11, and 17 principally in patients with aneuploid tumors. Monosomy of chromosome 9 was observed in 39% of the diploid and 31% of the specimens with high hyperdiploid fraction. Significantly, 24% of patients with a history of bladder cancer but with no clinical evidence of disease exhibited monosomy of chromosome 9. This suggests a persistent and significantly large population of abnormal cells in the absence of clinical evidence of disease. Loss of chromosome 9 relative to DNA ploidy was observed in 24% of patients with no evidence of disease, in 59% of patients with tumor, and in 79% of patients with histologically confirmed transitional cell carcinoma, grades 1-3. Loss of chromosome 15 was also observed in a large percentage of patients. Loss of chromosome 15 was observed in 41% of specimens from patients in whom no tumor was seen, in 38% of specimens from patients with tumor, and in 67% of specimens from patients with histologically confirmed transitional cell carcinoma. Results of this study document the use of bladder irrigation specimens as a specimen source for FISH analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Highlight on the studies of anticancer drugs derived from plants in China.

Recent progress on the study of anticancer drugs originating from plants in China is reviewed in this paper. Guided by the experience of traditional Chinese medicine, several new drugs have been found. Indirubin from Indigofera tinctoria is useful for the treatment of chronic myelocytic leukemia. Irisquinone from Iris latea pallasii and 10-hydroxy camptothecin from Camptotheca accuminata have exhibited definite activity on rodent tumors. Recent studies indicate that ginsenoside Rh2 is an inducer of cell differentiation in melanoma B-16 cells in vitro. Pharmacological studies have demonstrated that curcumin from Curcuma longa is an antimutagen as well as an antipromotor for cancer. Daidzein and acetyl boswellic acid have been shown to be effective inducers of cell differentiation in HL-60 cells. Guided by the chemotaxonomic principle of plants, harringtonine and homoharringtonine isolated from Cephalotaxus hainanesis have exhibited significant antileukemia activity and are widely used in clinics in China. Taxol from Taxus chinensis has been shown to be an important new anticancer drug with unique chemical structure and mechanism of action. The continuous search for new anticancer drugs from plants will be a fruitful frontier in cancer treatment and chemoprevention.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Analysis of the nucleotide sequence variation of the antigen-binding domain of DR alpha and DQ alpha molecules as related to the evolution of papillomavirus-induced warts in rabbits.

We previously found that regression of skin warts induced by the Shope cottontail rabbit papillomavirus in New Zealand White rabbits, as well as malignant conversion of persistent warts, are linked to a restriction fragment length polymorphism of the major histocompatibility complex class II DR alpha and DQ alpha genes. To find out whether this immunogenetic control could be connected with the antigen binding and presentation function of the alpha 1 domain of class II molecules, we have sequenced the exon 2 of the four DR alpha EcoRI and six of the seven DQ alpha PvuII restriction fragment length polymorphism alleles identified, and deduced the encoded amino acid sequences. We found no amino acid polymorphism among DR alpha alleles, indicating that the alpha 1 domain of the DR alpha chain does not condition wart regression or cancer development. In contrast, 27 of the 82 amino acids of the DQ alpha 1 domain were found variable, defining five amino acid sequence alleles. The restriction fragment length polymorphism allele linked to regression and another allele not linked to regression share the same alpha 1 domain, indicating that wart regression is rather conditioned by a closely linked gene. The most divergent DQ alpha 1 allele, however, was that associated with a higher risk of cancer. Alignment of rabbit and human DQ alpha exon 2 alleles disclosed that amino acid charge variations occur at positions assumed to be important for peptide binding in humans. By modulating the affinity for tumor-specific antigenic peptides, such transitions could affect immune surveillance and, thus, condition the risk for progression to carcinoma of papillomavirus-associated lesions.

Alleles↗
PubMed1994

Ontogeny and regulation of platelet-derived growth factor gene expression in distal fetal rat lung epithelial cells.

Using flow cytometry, thymidine uptake into DNA, and expression of two growth-related genes, histone 3 and c-myc, we found an increase in the proportion of distal lung epithelial cells in the G0/G1 phase of the cell cycle with advancing gestation. Since our previous studies had demonstrated that platelet-derived growth factor (PDGF) is essential for the progression of these cells from the G0/G1 to the S phase of cell cycle, we investigated the gene and protein expression of PDGF-related genes (PDGF-A, PDGF-B, alpha-receptor, and beta-receptor) in distal fetal lung epithelial cells. The cells transcribed all the PDGF-related genes and translated the PDGF-A and PDGF-B mRNAs into protein, as demonstrated by immunocytochemistry and immunoprecipitation. To explore an autocrine role for PDGF in distal fetal lung epithelial cells, intervention studies using PDGF-A and -B chain-specific antisense oligodeoxynucleotides (ODN) were carried out. Antisense PDGF-B ODN, but not antisense PDGF-A ODN, significantly reduced the DNA synthesis of these cells. The inhibitory effect of antisense PDGF-B ODN on DNA synthesis was reversed by the addition of exogenous PDGF-BB, which supports an autocrine role in the DNA synthesis of these cells. We also examined the expression of PDGF genes in distal fetal lung epithelial cells during late gestation. PDGF-A chain and beta-receptor gene expressions declined with advancing gestation, whereas expression of message for PDGF-B chain and alpha-receptor increased. The increases in message for PDGF-B chain and alpha-receptor with advancing gestation were due to a greater rate of transcription, whereas the developmental decrease of PDGF-A chain and beta-receptor mRNAs was caused by a decrease in RNA stability. Taken together with the ODN data, these results suggest that the G0/G1 cell cycle arrest of distal lung epithelial cells during late fetal gestation is due to a decrease in PDGF beta-receptor expression by the cells.

Animals↗
PubMed1994

[Comparison of the sensitivity of retinoic acid sensitive and resistant HL-60 cell lines to several anti-leukemia drugs].

By using MTT and trypan blue exclusion assay, the sensitivity of retinoic acid sensitive HL-60 and resistant HL-60/RA cell to six anti-leukemia drugs such as RA, Ara-c, harringtonine was compared. It was found that all five drugs except RA exhibited an approximately equivalent IC50 to HL-60 and HL-60/RA cells. The results suggest that tumor cells may not develop resistance to differentiation inducer and cytotoxic anti-tumor agent parallel. It also suggests that it is reasonable to use a combination of differentiation and cytotoxic anti-leukemia agents concomitantly or sequentially.

Antineoplastic Agents↗
PubMed1994

[Chronological characteristics of retinoic acid-induced HL-60 cell differentiation].

HL-60 cells can be induced to differentiate into mature granulocytic cells in a continuous exposure to all-trans retinoic acid (RA) for at least 96 h. In this study, RA was removed after being exposed to HL-60 cells for 12-96h. Then the cells were reincubated in a fresh medium without drug for additional 48-144h and their differentiation markers such as NBT reduction, morphological changes and cytokinetic characteristics were studied. The results demonstrated that once exposed continuously to 1.0 mumol/L RA for at least 48h, the HL-60 cells would proceed to terminal differentiation: about 60-90 percent of the cells became NBT positive, 40-80 percent of cells exhibited decreased nucleus/cytoplasm ratio and marked reduction in the number of nucleoli and displayed matured granulocytic morphology. Cytokinetic studies demonstrated 48-85 percent of cells arrested in G1 phase, which is typical for differentiated cells. However, if the cells were exposed to RA for less than 48h, they would not show differentiation phenotype. These results indicate that 48h exposure is critical for HL-60 cell differentiation induced by RA, and the cell differentiation induced by RA is irreversible and RA-independent.

Cell Differentiation↗
PubMed1994

[Effect of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo (a) pyrene].

Glycyrrhetinic acid (GA) is an active component of Glycyrrhiza uralensis Fisch. In this study, the effects of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo (alpha) pyrene were studied. Mouse ear edema was visible obviously at the 6th h after topical application of single dose croton oil. A topical application of croton oil on the back of ICR mice for 5 h, induced elevation of ornithine decarboxylase (ODC) activity in epidermal. The administration of glycyrrhetinic acid (50-200 mg.kg-1.d-1) to animals for 3 days exhibited 20%-80% inhibition of epidermal ornithine decarboxylase activity in a dose-dependent manner. Benzo (alpha) pyrene obviously caused DNA damage and unscheduled DNA synthesis mediated by S9 fraction in Chinese hamster lung cell line. Glycyrrhetinic acid was found to protect the rapid DNA damage induced by benzo (alpha) pyrene. At concentration of 5 micrograms.ml-1, glycyrrhetinic acid exhibited 70% protection. At 20 micrograms.ml-1, this action was more potent and approached to 80%. The addition of hydroxyurea 10 mmol.L-1 suppressed DNA replicative synthesis to 84.04% and benzo (alpha) pyrene stimulated the DNA repair synthesis (6-fold). Glycyrrhetinic acid (20 micrograms.ml-1 and 50 micrograms.ml-1 significantly decreased the stimulation of DNA repair synthesis induced by benzo (alpha) pyrene. This suggests that glycyrrhetinic acid has effective anti-initiating and anti-promoting activities and could be used for cancer chemopreventive purpose.

Animals↗
PubMed1994

[Induction of apoptosis by harringtonine and homoharringtonine in HL-60 cells].

Harringtonine (HT) and homoharringtonine (HHT) are two alkaloids isolated from the bark of the evergreen tree Cephalotaxus hainanensis Li in the 1970s. They were found to have activity against murine leukemia, Lewis lung carcinoma and B16 melanoma, and used as anti-leukemia drugs clinically. Apoptosis is an active process of programmed cell suicide and now is believed to be an important target for tumor chemotherapy. In this report, the apoptosis inducing effect of HT and HHT in HL-60 cells were observed. The experiments demonstrated that 2 x 10(-7) mol.L-1 of HT and 10(-7) mol.L-1 of HHT could induce apoptosis in HL-60 cells when the cells were exposed to HT and HHT for 4 h. In agarose gel electrophoresis, DNA extracted from HL-60 cells treated with HT and HHT showed a typical internucleosomal DNA degradation, i.e., DNA ladder and parallel morphological changes as nuclear chromosome segmentation and condensation as well as cytoplasma vacuolation. This effect of HT and HHT was shown to appear in a concentration- and time-dependent manner. The efficacy of HT and HHT in inducing apoptosis of HL-60 cells was found to parallel with their cytotoxic activity in HL-60 cells. These results suggest that the mechanism of antitumor action of HT and HHT is related to their apoptosis inducing activity.

Antineoplastic Agents, Phytogenic↗
PubMed1994

[A study on chemoprevention of retinamide II from cervical precancerous lesions].

The patients with cervical precancerous lesions were double-blindly randomized into two groups. The one was treated with retinamide II (RII) suppository intravaginally and the other with placebo, once daily for 50 days as a course. The results showed precancerous lesions in 68.57% of the patients disappeared, with an overall effective rate of 74.29% after two-course treatment with RII. Its long-term curative effect approximated to that with laser beam radiation and electrocautery (P > 0.05), and differed significantly (P < 0.01) from that with common antiphlogistic. So, RII can be used as a major measure in prevention and treatment for cervical cancer in high-incidence areas in our country.

Administration, Intravaginal↗
PubMed1994

[Inhibitory effect of a third generation retinoid R8923 and all-trans retinoic acid on two-stage chemical carcinogenesis of BALB/3T3-A31 cells in vitro].

The inhibitory effect of a third generation retinoid R8923 and all-trans retinoic acid (RA) on malignant transformation of Balb/3T3-A31 cells induced by 3-methylcholanthrene (3-MCA) and 12-0-tetradecanoyl phorbol-13-acetate(TPA) was studied in paper. Malignant transformation of Balb/3T3-A31 cells was evaluated by scoring transformation foci and soft agar assay. Actively growing Balb/3T3-A31 cells (1.5 x 10(4) cells per 60-mm-diameter glass dish) were cultured in 5ml of Eagle's Minimum Essential Medium supplemented with 10 percent fetal bovine serum. Twenty-four hours after plating, the cells were treated with 3-MCA (2 micrograms/ml) for 72 hours. TPA was added into the medium at a concentration of 100 ng/ml for 2 weeks. Thirty-six days after cell plating, the transformation foci were counted and the soft agar assay of the cells isolated from each glass dish was performed. Results showed that there were 16.0 +/- 1.58 transformation foci/dish and the colony forming efficiency in soft agar assay was 138.6 +/- 14.47/10(3) cells in 3-MCA and TPA treated dishes (control group). When the cells were exposed to R8923 or RA (at a concentration of 10(-6) M), the transformation foci were 11.2 +/- 0.84 /dish and 9.2 +/- 1.10/dish respectively, and the corresponding colony forming efficiency values were 66.1 +/- 7.68/10(3) cells and 64.8 +/- 4.46/10(3) cells. They were significantly lower than that of the control group. These results demonstrated that R8923 and RA could effectively inhibit 3-MCA and TPA induced malignant transformation of Balb/3T3-A31 cells and suggested that R8923 is a potential drug for cancer chemoprevention.

3T3 Cells↗