Biomedical subjects

Y Tan

Publications and source records attributed to Y Tan.

At least 37 records · Page 2Linked to original sources

PubMed2001

Synergy between methionine stress and chemotherapy in the treatment of brain tumor xenografts in athymic mice.

This study describes a novel approach to the treatment of brain tumors with the combination of recombinant L-methionine-alpha-deamino-gamma-lyase and chemotherapeutic regimens that are currently used against such tumors. The growth of Daoy, SWB77, and D-54 xenografts in athymic mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of a MET- and choline-free diet and recombinant L-methionine-alpha-deamino-gamma-lyase. The treated tumor-bearing mice were rescued from the toxic effects of MET withdrawal with daily i.p. homocystine. This regimen suppressed plasma MET to levels below 5 microM for several days, with no treatment-related deaths. MET depletion for 10-12 days induced mitotic and cell cycle arrest, apoptotic death, and widespread necrosis in tumors but did not prevent tumor regrowth after cessation of the regimen. However, when a single dose of 35 mg/m(2) of N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), which was otherwise ineffective as a single therapy in any of the tumors tested, was given at the end of the MET depletion regimen, a more than 80-day growth delay was observed for Daoy and D-54, whereas the growth of SWB77 was delayed by 20 days. MET-depleting regimens also trebled the efficacy of temozolomide (TMZ) against SWB77 when TMZ was given to animals as a single dose of 180 mg/m(2) at the end of a 10-day period of MET depletion. The enhanced responses of both Daoy and SWB77 to DNA alkylating agents such as BCNU and TMZ could be attributed to the down-regulation of O(6)-methylguanine-DNA methyltransferase activity. However, the synergy of MET depletion and BCNU observed with D-54 tumors, which do not express measurable O(6)-methylguanine-DNA methyltransferase protein, is probably mediated by a different mechanism. MET depletion specifically sensitizes tumors to alkylating agents and does not significantly lower the toxicity of either BCNU or TMZ for the host. In this regard, the combination approach of MET depletion and genotoxic chemotherapy demonstrates significant promise for clinical evaluation.

Animals↗

PubMed2001

Induction of hepatitis B virus-specific cytotoxic T lymphocytes response in vivo by filamentous phage display vaccine.

The ability of inducing MHC class I restricted cytotoxic T lymphocytes response in vivo via recombinant filamentous phage was investigated. The recombinant filamentous phage particles that displayed the Hepatitis B virus epitope S(28--39) were injected into BALB/c (H-2d) mice without adjuvants. A MHC class I restricted HBs specific CTL response was found 8 days after injection. The potentiality of using the recombinant filamentous phage as anti-virus vaccine was discussed.

Animals↗

PubMed2001

Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid.

Potentiation of the cytotoxic activity of 5-fluorouracil (FUra) by folinic acid (5-HCO-H4folate) is due to elevation of the methylene tetrahydrofolate (CH2-H4folate) level, which increases the stability of the ternary complex of thymidylate synthase (TS), fluorodeoxyuridine monophosphate, and CH2-H4folate that inactivates the TS. Methionine deprivation results in the production of tetrahydrofolate (H4folate) and, subsequently, CH2-H4folate from methyl tetrahydrofolate, as a consequence of the induction of methionine synthesis. We hypothesized that the efficacy of FUra could be augmented by the combination of high-concentration 5-HCO-H4folate and recombinant methioninase (rMETase), a methionine-cleaving enzyme. Studies in vitro were performed with the cell line CCRF-CEM. Cytotoxic synergism of FUra + rMETase and FUra + 5-HCO-H4folate + rMETase was demonstrated with the combination index throughout a broad concentration range of FUra and rMETase. A subcytotoxic concentration of rMETase reduced the IC50 of FUra by a factor of 3.6, and by a factor of 7.5, in the absence and in the presence of 5-HCO-H4folate, respectively. 5-HCO-H4folate increased the intracellular concentrations of CH2-H4folate and H4folate from their baseline levels. Concentrations of folates were not changed by exposure to rMETase. Levels of free TS in cells treated with FUra + 5-HCO-H4folate and with FUra + rMETase were lower than those in cells exposed to FUra alone. The decrease of TS was still more pronounced in cells treated with FUra + 5-HCO-H4folate + rMETase. The synergism described in this study will be a basis for further exploration of combinations of fluoropyrimidines, folates, and rMETase.

Antimetabolites, Antineoplastic↗

PubMed2001

Retention of the Alzheimer's amyloid precursor fragment C99 in the endoplasmic reticulum prevents formation of amyloid beta-peptide.

gamma-Secretase is a membrane-associated endoprotease that catalyzes the final step in the processing of Alzheimer's beta-amyloid precursor protein (APP), resulting in the release of amyloid beta-peptide (Abeta). The molecular identity of gamma-secretase remains in question, although recent studies have implicated the presenilins, which are membrane-spanning proteins localized predominantly in the endoplasmic reticulum (ER). Based on these observations, we have tested the hypothesis that gamma-secretase cleavage of the membrane-anchored C-terminal stump of APP (i.e. C99) occurs in the ER compartment. When recombinant C99 was expressed in 293 cells, it was localized mainly in the Golgi apparatus and gave rise to abundant amounts of Abeta. Co-expression of C99 with mutant forms of presenilin-1 (PS1) found in familial Alzheimer's disease resulted in a characteristic elevation of the Abeta(42)/Abeta(40) ratio, indicating that the N-terminal exodomain of APP is not required for mutant PS1 to influence the site of gamma-secretase cleavage. Biogenesis of both Abeta(40) and Abeta(42) was almost completely eliminated when C99 was prevented from leaving the ER by addition of a di-lysine retention motif (KKQN) or by co-expression with a dominant-negative mutant of the Rab1B GTPase. These findings indicate that the ER is not a major intracellular site for gamma-secretase cleavage of C99. Thus, by inference, PS1 localized in this compartment does not appear to be active as gamma-secretase. The results suggest that presenilins may acquire the characteristics of gamma-secretase after leaving the ER, possibly by assembling with other proteins in peripheral membranes.

Alzheimer Disease↗

PubMed2001

[Effect of activation of p-MAPK on activating c-fos and c-jun proteins in breast cancer].

OBJECTIVE: This paper was to investigate the relationship between expression of p-MAPK and oncogenesis of breast cancer. METHODS: Immunohistochemical technique was used to detect the expression of p-MAPK and c-fos and c-jun proteins in 68 cases of breast cancers, 42 cases of pericarcinomatous tissues and 7 cases of normal breast tissues. RESULTS: Positive stainings of p-MAPK, c-fos, and c-jun were localized in cancer cell nuclei. The positive rates of p-MAPK, c-fos, and c-jun were 86.8% (59/68), 82.4% (56/68), and 77.9% (53/68), respectively, which were much higher than that in pericarcinomatous tissues (P < 0.01). Of some cases, p-MAPK positive staining was also found in the nuclei of the fibroblastic and angioendothelial cells of cancer stroma. CONCLUSION: Activated or overexpressive MAPK activates the immediately-early oncogenes(c-fos, c-jun), which might play an important role in carcinogenesis of breast cancer and be an early event of oncogenesis of breast cancer.

Adult↗

PubMed2001

A new photochromic 8pi-system based on an azaheptatriene-tetrahydroazepinoisoquinoline electrocyclization.

A new photochromic family of tetrahydroazepinoisoquinolines (THAI) 4a-i has been prepared. It undergoes light-induced ring opening from spiro compounds 4 to betaines 3 that decolorize in a very fast cyclizing reaction. Depending on substitution of the precursors 1 and 6, the photochromic styryltetrahydroindolizines (THI) 5k-q are formed in a periselective way. The conformation and configuration of the new photochromic THAI 4 and THI 5 were investigated by NMR and the structure of both compounds was proven by X-ray analysis. The photochromic properties were studied by laser flash photolysis, which afforded the lifetime of the colored form 3 and 3' in the micro- or nanosecond range.

Journal Article↗

PubMed2001

An integrated physical map of 8q22-q24: use in positional cloning and deletion analysis of Langer-Giedion syndrome.

We have developed an integrated map for a 35-cM area of human chromosome 8 surrounding the Langer-Giedion syndrome deletion region. This map spans from approximately 8q22 to 8q24 and includes 10 hybrid cell intervals, 89 polymorphic STSs, 118 ESTs, and 37 known genes or inferred gene homologies. The map locations of 25 genes including osteoprotegerin, syndecan-2, and autotaxin have been refined from the general locations previously reported. In addition, the map has been used to indicate the location of nine deletions in patients with Langer-Giedion syndrome and trichorhinophalangeal syndrome type I to demonstrate the potential usefulness of the map in the analysis of these complex syndromes. The map will also be of interest to anyone trying to clone positionally disease genes in this region, such as Cohen syndrome (8q22-q23), Klip-Feil syndrome (8q22.2), hereditary spastic paraplegia (8q24), and benign adult familial myoclonic epilepsy (8q23.3-q24.1).

Child↗

PubMed2001

Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity.

A major hurdle to lipoplex-based systemic gene delivery is acute inflammatory toxicity. In this study, a safe, simple, and effective alternative to lipoplex administration, specifically, sequential injection of cationic liposome and plasmid DNA, was evaluated. When plasmid DNA was injected into the tail vein of mice 2-5 min after the injection of cationic liposomes, 50-80% lower levels of proinflammatory cytokines, including TNF-alpha, IL-12, and IFN-gamma, were observed compared to lipoplex injection. The sequential injection technique yielded a two- to fivefold higher level of transgene expression in the lung and was more effective in repeated dosing than lipoplex. Other types of lipoplex-associated toxicities, such as neutropenia, lymphopenia, thrombocytopenia, and complement depletion, were also significantly reduced with sequential injection. The reduction in cytokine release was observed with several different liposome formulations and appeared to be a general phenomenon.

Animals↗

PubMed2001

Molecular characterization of the klebicin B plasmid of Klebsiella pneumoniae.

The nucleotide sequence of a bacteriocin-encoding plasmid isolated from Klebsiella pneumoniae (pKlebB-K17/80) has been determined. The encoded klebicin B protein is similar in sequence to the DNase pyocins and colicins, suggesting that klebicin B functions as a nonspecific endonuclease. The klebicin gene cluster, as well as the plasmid backbone, is a chimera, with regions similar to those of pore-former colicins, nuclease pyocins and colicins as well as noncolicinogenic plasmids. Similarities between pKlebB plasmid maintenance functions and those of the colicin E1 plasmid suggest that pKlebB is a member of the ColE1 plasmid replication family.

Amino Acid Sequence↗

PubMed2001

A study of a new TSM bio-mimetic sensor using a molecularly imprinted polymer coating and its application for the determination of nicotine in human serum and urine.

A new bio-mimetic quartz crystal thickness-shear-mode (TSM) sensor, using an imprinted polymer coating as the sensitive material, has been fabricated and applied to the determination of nicotine (NIC) in human serum and urine. The molecularly imprinted polymer (MIP) was synthesized using NIC as the template molecule and methacrylic acid (MAA) as the functional monomer. The sensor showed high selectivity and a sensitive response to NIC in aqueous system. The linear response range of the sensor was between 5.0 x 10(-8) and 1.0 x 10(-4) M with a detection limit of 2.5 x 10(-8) M. The viscoelasticity of the coating in the air and in liquid has been studied by the impedance spectrum. The MIP sensor was stable and exhibited effective reproducibility. Satisfactory results were achieved in the detection of the real samples.

Biosensing Techniques↗

PubMed2001

A piezoelectric biomimetic sensor for aminopyrine with a molecularly imprinted polymer coating.

A molecularly imprinted polymer for aminopyrine was synthesized using methacrylic acid as functional monomer. The polymer was employed as the recognition element of a piezoelectric bulk acoustic wave biomimetic sensor for aminopyrine. Influencing factors were investigated in detail and optimized. This sensor exhibited high selectivity and sensitivity to aminopyrine. The response range of the sensor was between 5.0 x 10(-8) and 1.0 x 10(-4) M with a detection limit of 2.5 x 10(-8) M in the aqueous system. Scatchard analysis with UV spectrophotometry showed that the same class of binding sites was formed in the molecularly imprinted polymer in the studied concentration range, and the dissociation constant and the apparent maximum number of these binding sites were estimated to be 2.29 mM and 165.0 mumol g-1 dry polymer, respectively. Impedance analysis was employed to verify the imprinting effect and lack of variation in the viscoelasticity of the polymer coating during detection.

Aminopyrine↗

PubMed2001

Detection of oligoclonal immunoglobulins in the cerebrospinal fluid by immunofixation electrophoresis.

Many disorders of the central nervous system are associated with increased concentration of cerebrospinal fluid protein due to either an increase in the permeability of blood-brain barrier or the synthesis of immunoglobulins within the central nervous system. Immunofixation electrophoresis was used to detect the immunoglobulins in sera and cerebrospinal fluid in patients with different central nervous system disorders. A strong oligoclonal band, or a single weak monoclonal band, observed in the cerebrospinal fluid but not in the serum, indicates the endogenous immunoglobulin synthesis. In 17 cases of non-infectious central nervous system diseases, we diagnosed one case of progressive multifocal leukoencephalopathy, one case of multiple sclerosis, one case of Guillain-Barre syndrome, and one case of epilepsy. A weak band was observed in both serum and cerebrospinal fluid samples in two cases of cerebral trauma. Out of 25 cases of infectious central nervous system diseases, two cases of nervous system syphilis were positive only in cerebrospinal fluid samples, and 23 cases were negative in both samples. Compared with the standard immunofixation, the application of an enzyme-labeled antibody can significantly increase the sensitivity of the method.

Adult↗

PubMed2001

Adenovirus-mediated increase of HNF-3 levels stimulates expression of transthyretin and sonic hedgehog, which is associated with F9 cell differentiation toward the visceral endoderm lineage.

Retinoic acid-induced differentiation of mouse F9 embryonal carcinoma cells toward the visceral endoderm lineage is accompanied by increased expression of the Forkhead Box (Fox) transcription factors hepatocyte nuclear factor 3a (HNF-3alpha) and HNF-3beta, suggesting that they play a crucial role in visceral endoderm development. Retinoic acid stimulation results in a cascade of HNF-3 induction in which HNF-3alpha is a primary target for retinoic acid action and its increase is required for subsequent induction of HNF-3beta expression. Increased expression of HNF-3beta precedes activation of its known target genes, including transthyretin (TTR), Sonic hedgehog (Shh), HNF-1alpha, HNF-1beta, and HNF-4alpha. In order to examine whether increased HNF-3 expression is sufficient to induce expression of its downstream target genes without retinoic acid stimulation, we have used adenovirus-based expression vectors to increase HNF-3 protein levels in F9 cells. We demonstrate that adenovirus-mediated increase of HNF-3alpha levels in F9 cells is sufficient to induce activation of endogenous HNF-3beta levels followed by increased TTR and Shh expression. Furthermore, we show that elevated HNF-3beta levels stimulate expression of endogenous TTR and Shh without retinoic acid stimulation. Moreover, ectopic HNF-3 levels in undifferentiated F9 cells are insufficient to induce HNF-3alpha, HNF-1alpha, HNF-1beta, and HNF-4alpha expression, suggesting that their transcriptional activation required other regulatory proteins induced by the retinoic acid differentiation program. Finally, our studies demonstrate the utility of cell infections with adenovirus expressing distinct transcription factors to identify endogenous target genes, which are assembled with the appropriate nucleosome structure.

Adenoviridae↗

PubMed2001

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance.

AIM: To study the effect of phosphorylation of MAPK and Stat3 and the expression of c-fos and c-jun proteins on hepatocellular carcinogenesis and their clinical significance. METHODS: SP immunohistochemistry was used to detect the expression of p42/44(MAPK), p-Stat3, c-fos and c-jun proteins in 55 hepatocellular carcinomas (HCC) and their surrounding liver tissues. RESULTS: The positive rates and expression levels of p42/44(MAPK), p-Stat3, c-fos and c-jun proteins in HCCs were significantly higher than those in pericarcinomatous liver tissues (PCLT). A positive correlation was observed between the expression of p42/44(MAPK) and c-fos proteins,and between p-Stat3 and c-jun but there was no significant correlation between p42/44(MAPK) and p-Stat3 in HCCs and their surrounding liver tissues. CONCLUSION: The abnormalities of Ras/Raf/MAPK and JAKs/Stat3 cascade reaction may contribute to malignant transformation of hepatocytes. Hepatocytes which are positive for p42/44(MAPK), c-fos or c-jun proteins may be potential malignant pre-cancerous cells. Activation of MAPK and Stat3 proteins may be an early event in hepatocellular carcinogenesis.

Adult↗

PubMed2001

[Malformed macrocephalous sperm with polytails and chromosomal aberrance].

OBJECTIVE: To investigate the relationship between sperm anomalies and chromosomal aberrance and to further understand the pathological changes of anomalous spermatozoa. METHODS: Light and electronic (SEM or TEM) microscopes were used for morphological analysis. Fluorescence in situ hybridization(FISH) with chromosome X-, Y-specific probes were used for aneuploidy detection in sperms of the patient. RESULTS: Ninety eight point seven five per cent of the Papanicolaou stained sperms were observed to be abnormal; 100% of the sperm heads were abnormal, measured under oil objective (1000 times); 60.25% of the sperms had two or more tails (the maximum being eight tails). SEM and TEM demonstrated that the heads contained a large amount of cytoplasmic structure, the surfaces of heads were uneven, the nuclei were of much irregular shape; besides aberrance in quantity, anomalies occurred with centromeres, mitochondria and flagella in the tails. The results of FISH showed that the aneuploidy rate of sex chromosomes was 61.41% which was parallel to the rate of polytails. CONCLUSION: Even though the chromosomes in somatic cells are normal, the chromosomes in anomalous sperms may be abnormal.

Adult↗

PubMed2001

[Study of a familial insertional translocation involving chromosomes 1 and 7 by using fluorescence in situ hybridization].

OBJECTIVE: To determine the karyotype of a case with a history of spontaneous abortion and terminal deletion by using of conventional G-banding method and search the cause of insertional translocation of chromosomal terminal region. METHODS: Fluorescence in situ hybridization (FISH) technique was performed to analyze the case by using whole chromosome 7 painting probe and subterminal probe of 7q36-->qter which was generated by chromosome microdissection technique. RESULTS: The case was a carrier with a very rare insertional translocation involving chromosomes 1 and 7. The region of chromosome 7q36-->qter was not inserted into chromosome 1. The abnormal chromosome was inherited from her mother. CONCLUSION: The present authors provided an experiment evidence that in this case the chromosome insertional translocation including the terminal region was still a three breakage rearrangement and the terminal deletion found by cytogenetics should be an interstitial deletion. Combining with chromosome microdissection, FISH technique is a powerful diagnostic method for detecting the chromosome structural abnormality.

Adult↗

PubMed2001

Identification of pelvic lymph nodes with chlorophyllin after injection into the uterine cervix: an experimental and clinical study.

We investigated the value of staining retroperitoneal lymph nodes with chlorophyllin in normal dogs and in women with malignant uterine tumors undergoing lymphadenectomy. In dogs, after 0.3% chlorophyllin (sodium copper chlorophyllin) was injected into the canine uterus, the concentration of dye in the bloodstream was measured with a spectrophotometer and sections of stained retroperitoneal lymph nodes were examined using light and electron microscopy. The highest blood levels were detected at 4 hrs and nearly all of the chlorophyllin was gone from the bloodstream by 18 hrs but was retained in nodal macrophages for at least 4 days. No morphological changes were found in the excised lymph nodes. Twenty-four patients with cervical carcinoma and 20 patients with endometrial carcinoma undergoing radical hysterectomy and lymphadenectomy were divided into a lymphatic coloration group (23 patients) and a non-coloration (control) group (21 patients). In the lymphatic coloration group (0.3% chlorophyllin) was injected into the cervix 5 days before elective lymphadenectomy. There were no complications attributed to injection of the chlorophyllin. The number of dissected lymph nodes in the coloration group were greater than the control group (p<0.01) and the time of operation was shorter (p<0.01). These results suggest that chlorophyllin is safe and facilitates identification of retroperitoneal lymph nodes, allows more complete nodal excision and shortens the time of operation in patients undergoing radical hysterectomy with lymphadenectomy.

Adult↗

PubMed2001

[No evidence for association between the alpha 2-macroglobulin polymorphism and Alzheimer's disease in the Han Chinese].

OBJECTIVE: To determine the effect of the pentanucleotide deletion polymorphism adjacent to a consensus splice site in intron 17 of alpha 2-macroglobulin(A2M) gene on the development of late-onset Alzheimer's disease (LOAD) in the Han Chinese in Guangzhou area. METHODS: A2M and apolipoprotein E genotypes were examined by polymerase chain reaction(PCR) and restriction fragment length polymorphism (RFLP) techniques in the patients(32 men and 65 women) with LOAD and age-matched healthy elderly Chinese subjects (57 men and 54 women). RESULTS: The A2M gene deletion allele frequency was 2.6% in the cases with LOAD and 2.7% in the controls. In the LOAD cases, the frequency of apoE-epsilon4 increased significantly (Z=3.32, P<0.01). ApoE-epsilon4 was associated with LOAD (RR=2.67, chi(2)=10.71, P<0.01) while the A2M deletion polymorphism was not associated with LOAD even the samples were stratified according to the presence of the apoE-epsilon4 allele. CONCLUSION: The above data demonstrate that there is no evidence for the association of A2M polymorphism with the development of LOAD in the Han Chinese population in Gaungzhou.

Alzheimer Disease↗