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1.  Intra-Arterial Chemotherapy for Malignant Gliomas: a Critical Analysis 
Interventional Neuroradiology  2011;17(3):286-295.
Summary
Intra-arterial (IA) chemotherapy for malignant gliomas including glioblastoma multiforme was initiated decades ago, with many preclinical and clinical studies having been performed since then. Although novel endovascular devices and techniques such as microcatheter or balloon assistance have been introduced into clinical practice, the question remains whether IA therapy is safe and superior to other drug delivery modalities such as intravenous (IV) or oral treatment regimens. This review focuses on IA delivery and surveys the available literature to assess the advantages and disadvantages of IA chemotherapy for treatment of malignant gliomas. In addition, we introduce our hypothesis of using IA delivery to selectively target cancer stem cells residing in the perivascular stem cell niche.
PMCID: PMC3396041  PMID: 22005689
glioblastoma multiforme, blood brain barrier, perivascular niche, superselective intra-arterial cerebral infusion, selective intra-arterial niche disruption
3.  Reversed halo sign on thin-section CT in a patient with non-specific interstitial pneumonia 
The British Journal of Radiology  2011;84(1001):e103-e105.
We present a case of non-specific interstitial pneumonia (NSIP) with reversed halo sign on thin-section CT. A 52-year-old female presented with a cough and New York Heart Association (NYHA) class 2 dyspnoea of 4 months duration. A chest radiograph showed poorly defined, patchy ground-glass opacities in both lungs. Thin-section CT demonstrated the reversed halo sign, which is a central ground-glass opacity surrounded by crescent or ring-shaped areas of consolidation in multifocal areas. Multifocal patchy ground-glass opacity and consolidation and enlarged paratracheal, hilar and subcarinal lymph nodes were also shown. Video-assisted thoracic surgical (VATS) lung biopsy was performed, and histopathology revealed cellular NSIP.
doi:10.1259/bjr/43867123
PMCID: PMC3473648  PMID: 21511742
4.  Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation 
Journal of neurochemistry  2006;97(5):1467-1480.
Because of their ability to proliferate and to differentiate into diverse cell types, embryonic stem (ES) cells are a potential source of cells for transplantation therapy of various diseases, including Parkinson’s disease. A critical issue for this potential therapy is the elimination of undifferentiated cells that, even in low numbers, could result in teratoma formation in the host brain. We hypothesize that an efficient solution would consist of purifying the desired cell types, such as neural precursors, prior to transplantation. To test this hypothesis, we differentiated sox1-green fluorescent protein (GFP) knock-in ES cells in vitro, purified neural precursor cells by fluorescence-activated cell sorting (FACS), and characterized the purified cells in vitro as well as in vivo. Immunocytofluorescence and RT-PCR analyses showed that this genetic purification procedure efficiently removed undifferentiated pluripotent stem cells. Furthermore, when differentiated into mature neurons in vitro, the purified GFP+ cell population generated enriched neuronal populations, whereas the GFP− population generated much fewer neurons. When treated with dopaminergic inducing signals such as sonic hedgehog (SHH) and fibroblast growth factor-8 (FGF8), FACS-purified neural precursor cells responded to these molecules and generated dopaminergic neurons as well as other neural subtypes. When transplanted, the GFP+ cell population generated well contained grafts containing dopaminergic neurons, whereas the GFP− population generated significantly larger grafts (about 20-fold) and frequent tumor-related deaths in the transplanted animals. Taken together, our results demonstrate that genetic purification of neural precursor cells using FACS isolation can effectively remove unwanted proliferating cell types and avoid tumor formation after transplantation.
doi:10.1111/j.1471-4159.2006.03841.x
PMCID: PMC2610439  PMID: 16696855
embryonic stem cell; fluorescence-activated cell sorting; neural precursors; sox1; transplantation
5.  EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells 
British Journal of Cancer  2001;84(6):844-850.
Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 μM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day−1mouse−1starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF. © 2001 Cancer Research Campaign http://www.bjcancer.com
doi:10.1054/bjoc.2000.1691
PMCID: PMC2363808  PMID: 11259102
epigallocatechin gallate (EGCG); vascular endothelial growth factor (VEGF); colon carcinoma; Erk-1; Erk-2; angiogenesis
6.  A case of localized persistent interstitial pulmonary emphysema. 
Journal of Korean Medical Science  2001;16(2):225-228.
Interstitial pulmonary emphysema is a well-documented complication of assisted mechanical ventilation in premature infants with respiratory distress syndrome. Localized persistent interstitial pulmonary emphysema (LPIPE) confined to a single lobe was incidentally presented in a 4-day-old female infant. This patient was a normal full-term baby with no respiratory distress symptom and no experience of assisted mechanical ventilation. Chest radiograph showed radiolucent area in right lower lobe zone, which needed differential diagnosis from other congenital lesions such as congenital cystic adenomatoid malformation and congenital lobar emphysema. CT scan showed irregular-shaped air cystic spaces and pathologically, cystic walls primarily consisted of compressed lung parenchyma and loose connective tissue intermittently lined by multinucleated foreign body giant cells.
PMCID: PMC3054734  PMID: 11306752
7.  Interaction of Bacillus subtilis purine repressor with DNA. 
Journal of Bacteriology  1997;179(23):7394-7402.
A purine repressor (PurR) mediates adenine nucleotide-dependent regulation of transcription initiation of the Bacillus subtilis pur operon. This repressor has been purified for the first time, and binding to control site DNA was characterized. PurR binds in vitro to four operons. Apparent Kd values for binding were 7 nM for the pur operon, 8 nM for purA, 13 nM for purR, and 44 nM for the pyr operon. In each case, DNase I footprints exhibited a pattern of protected and hypersensitive sites that extended over more than 60 bp. A GAAC-N24-GTTC sequence in the pur operon was necessary but not sufficient for the PurR-DNA interaction. However, this motif, which is conserved in the four binding sites, was not required for binding of PurR to purA. Thus, the common DNA recognition element for binding of PurR to the four operons is not known. Multiple PurR-pur operon DNA complexes having a binding stoichiometry that was either approximately two or six repressor molecules per DNA fragment were detected. The results of a torsional constraint experiment suggest that control site DNA forms one right-handed turn around PurR.
PMCID: PMC179690  PMID: 9393704
8.  Cross-resistance of the diamondback moth indicates altered interactions with domain II of Bacillus thuringiensis toxins. 
We compared responses to six insecticidal crystal proteins from Bacillus thuringiensis by a Cry1A-resistant strain (NO-QA) and a susceptible strain (LAB-P) of the diamondback moth, Plutella xylostella. The resistant strain showed > 100-fold cross-resistance to Cry1J and to H04, a hybrid with domains I and II of Cry1Ab and domain III or Cry1C. Cross-resistance was sixfold to Cry1Bb and threefold to Cry1D. The potency of Cry1I did not differ significantly between the resistant and susceptible strains. Cry2B did not kill resistant or susceptible larvae. By combining these new data with previously published results, we classified responses to 14 insecticidal crystal proteins by strains NO-QA and LAB-P. NO-QA showed high levels of resistance to Cry1Aa, Cry1Ab, and Cry1Ac and high levels of cross-resistance to Cry1F, Cry1J, and H04. Cross-resistance was low or nil to Cry1Ba, Cry1Bb, Cry1C, Cry1D, Cry1I, and Cry2A. Cry1E and Cry2B showed little or no toxicity to susceptible or resistant larvae. In dendrograms based on levels of amino acid sequence similarity among proteins, Cry1F and Cry1J clustered together with Cry1A proteins for domain II, but not for domain I or III. High levels of cross-resistance to Cry1Ab-Cry1C hybrid H04 show that although Cry1C is toxic to NO-QA, domain III or Cry1C is not sufficient to restore toxicity when it is combined with domains I and II of Cry1Ab. Thus, diamondback moth strain NO-QA cross-resistance extends beyond the Cry1A family of proteins to at least two other families that exhibit high levels of amino sequence similarity with Cry1A in domain II (Cry1F and Cry1J) and to a protein that is identical to Cry1Ab in domain II (H04). The results of this study imply that resistance to Cry1A alters interactions between the insect and domain II.
PMCID: PMC168069  PMID: 8702276
9.  Expression of low density lipoprotein receptors in lymphoblasts induced by anti-CD3 antibody in patients with hypercholesterolemia. 
Journal of Korean Medical Science  1995;10(5):318-323.
Familial hypercholesterolemia(FH) is a disease based on defects of low-density lipoprotein receptors(LDL-R). To interrupt and control the natural course of this disease, early identification of these patients is important. The routine lipid profile tests for hypercholesterolemia can not differentiate objectively FH from secondary hypercholesterolemia. The exact diagnosis of FH heterozygotes is especially essential because it is easier to develop premature coronary heart diseases compared with secondary hyper-cholesterolemia. A simplified rapid and precise method for the mass screening of FH patients and the differentiation between FH heterozygote and secondary hyperlipidemia was needed. For the test, lymphocytes were used as target cells in LDL-R assay. After a 5 day culture with anti-CD3 Ab as a mitogen, indirect immunofluorescence stain and flow cytometric analysis were applied. The results were as follows; 74 +/- 9% of the stimulated lymphoblasts from normal controls expressed LDL-R activity. Cultured, but unstimulated, lymphocytes of normal controls showed 27 +/- 8% positivity and total cultured lymphocytes showed positivity of 46 +/- 11% positivity. Lymphoblasts, unstimulated lymphocytes, and total cultured lymphocytes from hyper-cholesterolemia without FH showed 74 +/- 10%, 25 +/- 10% and 50 +/- 17%, respectively, which showed no significant differences from normal control groups. FH Heterozygotes showed LDL-R positivity, 21 +/- 11% in lymphoblasts, 11 +/- 6% in unstimulated lymphocytes and 18 +/- 7% in total cultured lymphocytes. These data imply that adequately stimulated lymphocytes might be used for detecting defects in LDL-R and used to differentiate FH from secondary hypercholesterolemia.
PMCID: PMC3054148  PMID: 8750056
10.  Distribution of cryV-type insecticidal protein genes in Bacillus thuringiensis and cloning of cryV-type genes from Bacillus thuringiensis subsp. kurstaki and Bacillus thuringiensis subsp. entomocidus. 
DNA dot blot hybridizations with a cryV-specific probe and a cryI-specific probe were performed to screen 24 Bacillus thuringiensis strains for their cryV-type (lepidopteran- and coleopteran-specific) and cryI-type (lepidopteran-specific) insecticidal crystal protein gene contents, respectively. The cryV-specific probe hybridized to 12 of the B. thuringiensis strains examined. Most of the cryV-positive strains also hybridized to the cryI-specific probe, indicating that the cryV genes are closely related to cryI genes. Two cryV-type genes, cryV1 and cryV465, were cloned from B. thuringiensis subsp. kurstaki HD-1 and B. thuringiensis subsp. entomocidus BP465, respectively, and their nucleotide sequences were determined. The CryV1 protein was toxic to Plutella xylostella and Bombyx mori, whereas the CryV465 protein was toxic only to Plutella xylostella.
PMCID: PMC167511  PMID: 7793960
11.  Bone marrow pathology of culture proven typhoid fever. 
The authors analysed bone marrow findings of sixteen cases of culture proven typhoid fever to reveal the pathologic changes according to the disease stage. The most frequent finding was chronic granulomatous inflammation (eight cases). Infection (bacteria) associated hemophagocytic syndrome (four cases), reactive marrow (two cases), and non specific findings (two cases) were also encountered. Granulocytic hyperplasia with hemophagocytosis appeared at the early stage and was followed by infection (bacteria) associated hemophagocytosis and granuloma in proliferative stage. In lysis (late) stage, granulomatous inflammation was noted. However, resolution of granulomatous inflammation was not distinct. Some nuclear debris and phagocytosis were remarkable in well-formed granulomas. Thrombocytopenia was the most remarkable peripheral blood finding at the time of biopsy. Anemia, leukopenia, and pancytopenia were also observed in descending order.
PMCID: PMC3053902  PMID: 8068220

Results 1-11 (11)