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Biomedical subjects

H F Lu

Publications and source records attributed to H F Lu.

46 records · Page 3Linked to original sources
PubMed1995

Biphasic transcriptional regulation of the interferon regulatory factor-1 gene by prolactin: involvement of gamma-interferon-activated sequence and Stat-related proteins.

Stimulation of quiescent Nb2 T cells by PRL leads to the rapid transcriptional activation of a T cell activation gene, interferon regulatory factor-1 (IRF-1). IRF-1 is induced twice by PRL in a single cell cycle, first during G1 at 30-60 min and again over early S phase at 10-12 h. By nuclear run-on transcription analysis of IRF-1 promoter-chloramphenicol acetyl transferase (CAT) constructs, the -1.7 kilobase (kb) 5'-flanking IRF-1 DNA was shown to contain elements that mediate both G1 and S phase expression. The -200 bp IRF-1 promoter DNA contains elements that respond to G1 PRL stimulation in a protein synthesis independent manner, suggesting the involvement of pre-existing factors. Further promoter deletion analysis delineated a minimal PRL responsive region between -112 and -205 bp. Within this region is a Gamma Interferon Activated Sequence or GAS, consisting of two inverted GAAA motifs (-123/-113), which confers PRL-inducible expression to a reporter gene, suggesting that GAS can function as a PRL responsive element. Further, GAS exhibits binding with nuclear proteins in a PRL-inducible, cell cycle-dependent manner. One of these proteins appears to be related to the emerging family of Signal Transducer and Activator of Transcription or Stat factors. These studies suggest that the GAS site and Stat-like proteins participate in PRL receptor signal transduction to regulate the biphasic expression of the IRF-1 gene in PRL-stimulated T cells.

Animals↗
PubMed1994

Molecular determinants of bioactivity of the Saccharomyces cerevisiae lipopeptide mating pheromone.

The a-factor of Saccharomyces cerevisiae (YIIKGVF-WDPAC(Farnesyl)-OCH3) is a peptide pheromone in which post-translational modification with a farnesyl isoprenoid and carboxyl methyl group is required for export and bioactivity. Truncated and carboxyl-terminal modified analogs of the a-factor were synthesized in order to determine the effect of such modifications on bioactivity. Bioactivity studies on carboxyl-terminal analogs in which the chirality, the cysteine thioether, and the carboxyl ester were varied in an attempt to study the influence of topology on a-factor activity indicate that the hydrophobicity conferred by the farnesyl moiety and not its specific spatial orientation is a key determinant of a-factor potency. Analyses on truncated a-factors suggest that sequential removal of NH2-terminal residues leads to a gradient of potency loss, with some amino acids exhibiting a slightly greater contribution to bioactivity than others. Random oligonucleotide-targeted mutagenesis of the gene encoding a-factor was coupled to a biological screen to identify altered a-factor peptides which are secreted yet exhibit a loss of a-factor bioactivity. Transformants exhibiting this phenotype were examined to identify codon changes presumably responsible for the altered phenotype, thus indicating residues that may contribute significantly to a-factor bioactivity.

Amino Acid Sequence↗
PubMed1993

S-100 protein remains a practical marker for melanocytic and other tumours.

S-100 protein, extracted from bovine brain, is the first described of the modern generation of marker molecules for melanocytic tumours. Despite the observation that many different types of cells express S-100 protein, detection of the molecule in tumour cells in appropriate clinical and pathological circumstances is a widely used and effective adjunct to the determination that a tumour is melanocytic. Antibodies to S-100 protein are best deployed as part of a package that includes antibodies to other melanoma-associated epitopes (HMB-45, NKI-C3/Beteb), cytokeratins and common leukocyte antigen. Antibodies to S-100 protein may also increase the accuracy of melanoma staging and permit detection of small numbers of metastatic tumour cells that are not detectable by conventional histology. Future applications will probably include the wider use of antibodies to the S-100 protein monomers (alpha and beta) and the detection and quantification of S-100 protein in body fluids and tissues.

Biomarkers, Tumor↗
PubMed1990

Quantitative conversion of the (6-4) photoproduct of TpdC to its Dewar valence isomer upon exposure to simulated sunlight.

It has been found that the (6-4) photoproduct of thymidylyl-(3'----5')-deoxycytidine (TpdC) is converted quantitatively to a further photoproduct upon exposure to Pyrex-filtered medium pressure mercury arc light. Infrared UV, FAB MS, 1H NMR, 13C NMR and 31P NMR spectra were obtained for both the (6-4) product and its photolysis product. 1H NMR assignments were made on the basis of proton decoupling and homonuclear shift correlated experiments and 13C NMR assignments were made on the basis of proton-detected heteronuclear shift correlated experiments. The Dewar pyrimidinone structure was assigned to the photolysis product by analysis of the spectral data in comparison to those of the Dewar photoproduct of TpT and other Dewar pyrimidinones. The (6-4) product of TpdC is the second member of the class of (6-4) photoproducts that has been found to photoisomerize to its Dewar valence isomer upon exposure to wavelengths greater than 280 nm, the first being that of TpT (Taylor and Cohrs, 1987, J. Am. Chem. Soc. 109, 2834-2835). These results further support the proposal that all members of the (6-4) photoproduct class are converted to their Dewar valence isomers upon exposure to sunlight.

Dinucleoside Phosphates↗
PubMedDate not supplied

Micrometastases detected by cytokeratin 19 expression in sentinel lymph nodes of patients with early-stage cervical cancer.

The purpose of this study was to detect micrometastases in sentinel lymph nodes (SLNs) by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) analyses for cytokeratin 19 (CK19) expression in early-stage cervical cancer. One hundred twenty-five SLNs were collected from 46 patients with early-stage cervical cancer. Conventional histopathologic techniques revealed 14 metastatic SLNs from 11 out of 46 patients. CK19 expression was detected by RT-PCR and IHC in all the 125 SLNs. Cervical cancer tissues from nine patients and five pelvic lymph nodes from the patients without tumor were utilized as positive and negative controls, respectively. All the metastastic SLNs on conventional histopathologic techniques were positive by either RT-PCR or IHC analyses, while all the positive controls were positive and all the negative controls were negative as expected. Of 35 patients without metastatic SLNs on conventional histopathologic techniques, the detection rate of micrometastases was 42.85% by RT-PCR and 20% by IHC analyses. RT-PCR and IHC were more sensitive to identify micrometastases in SLNs of patients with early-stage cervical cancer than routine pathology. These findings demonstrated that micrometastasis could be identified by molecular technique such as RT-PCR and IHC analyses for CK19 expression. RT-PCR was more sensitive to detect micrometastases in SLNs than IHC in patients with early-stage cervical cancer. Therefore, molecular assessment of the SLNs may be a valuable tool to complement routine histologic examination of cervical cancer. The importance of micrometastases in SLNs is under close clinical observation to determine whether it can be used as a predicting factor to help us make decision whether to proceed with whole-pelvic lymph node dissection or as a prognostic factor for clinical outcome.

Adenocarcinoma↗
PubMedDate not supplied

Effects of the immunomodulator tilorone on the acetylation of 2-aminofluorene and DNA-2-aminofluorene adducts in the rats.

The present studies were undertaken to determine the effect of tilorone dihydrochloride (a synthetic interferon inducer) on the in vivo acetylation of 2-aminofluorene and DNA-2-aminofluorene adducts. For in vivo examination, pretreatment with tilorone dihydrochloride (50 mg/kg) 48 hr prior to the administration of 2-aminofluorene (50 mg/kg) resulted in a 35% and 29% increase in the fecal and urinary recovery of N-acetyl-2-aminofluorene and a 52% increase in the metabolic clearance of 2-aminofluorene to N-acetyl-2-aminofluorene. Following the exposure of rats to the 2-aminofluorene with or without pretreatment with tilorone dihydrochloride, DNA-2-aminofluorene adducts were determined in liver, bladder, lung and also in circulating leukocytes. The DNA-2-aminofluorene adducts in liver were increased by pretreatment with tilorone dihydrochloride. This is the first demonstration of tilorone-induced increasing in N-acetylation of carcinogens and DNA-carcinogen adducts in vivo.

2-Acetylaminofluorene↗