Vibrio vulnificus peritonitis after eating raw sea fish in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD).
Explore the source record for details and available documents.
Food Contamination↗
Biomedical subjects
Dong Wook Kim
Publications and source records attributed to Dong Wook Kim.
A new class of SN2 reactions catalyzed by protic solvents: Facile fluorination for isotopic labeling of diagnostic molecules.
Aprotic solvents are usually preferred for the SN2 reactions, because nucleophilicity and hence SN2 reactivity are severely retarded by the influence of the partial positive charge of protic solvents. In this work, we introduce a remarkable effect of using tertiary alcohols as a reaction medium for nucleophilic fluorination with alkali metal fluorides. In this novel synthetic method, the nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts (such as alkenes, alcohols, or ethers) compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with [18F]fluorine (t1/2 = 110 min) for positron emission tomographic (PET) imaging, and it is illustrated by the synthesis of four [18F]fluoride-radiolabeled molecular imaging probes-[18F]FDG, [18F]FLT, [18F]FP-CIT, and [18F]FMISO-in high yield and purity and in shorter times compared to conventional syntheses.
Alcohols↗
An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.
Phosphorylation of histone H3 at Ser10 increases chromatin accessibility to transcription factor NF-kappaB on a subset of genes involved in immune responses. Here we report that a bacterial pathogen abrogated phosphorylation of histone H3 to 'shape' the transcriptional responses of infected host cells. We identify the Shigella flexneri protein effector OspF as a dually specific phosphatase that dephosphorylated mitogen-activated protein kinases in the nucleus, thus preventing histone H3 phosphorylation at Ser10 in a gene-specific way. That activity of OspF enabled shigella to block the activation of a subset of NF-kappaB-responsive genes, leading to compromised recruitment of polymorphonuclear leukocytes to infected tissues. S. flexneri has thus evolved the capacity to precisely modulate host cell epigenetic 'information' as a strategy for repressing innate immunity.
Bacterial Outer Membrane Proteins↗
Functional conservation of a root hair cell-specific cis-element in angiosperms with different root hair distribution patterns.
Vascular plants develop distinctive root hair distribution patterns in the root epidermis, depending on the taxon. The three patterns, random (Type 1), asymmetrical cell division (Type 2), and positionally cued (Type 3), are controlled by different upstream fate-determining factors that mediate expression of root hair cell-specific genes for hair morphogenesis. Here, we address whether these root hair genes possess a common transcriptional regulatory module (cis-element) determining cell-type specificity despite differences in the final root hair pattern. We identified Arabidopsis thaliana expansinA7 (At EXPA7) orthologous (and paralogous) genes from diverse angiosperm species with different hair distribution patterns. The promoters of these genes contain conserved root hair-specific cis-elements (RHEs) that were functionally verified in the Type-3 Arabidopsis root. The promoter of At EXPA7 (Type-3 pattern) also showed hair cell-specific expression in the Type 2 rice (Oryza sativa) root. Root hair-specific genes other than EXPAs also carry functionally homologous RHEs in their promoters. The RHE core consensus was established by a multiple alignment of functionally characterized RHEs from different species and by high-resolution analysis of At EXPA7 RHE1. Our results suggest that this regulatory module of root hair-specific genes has been conserved across angiosperms despite the divergence of upstream fate-determining machinery.
Arabidopsis Proteins↗
An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases.
CONTEXT: The oncogenic RET/PTC tyrosine kinase causes papillary thyroid cancer (PTC). The use of inhibitors specific for RET/PTC may be useful for targeted therapy of PTC. OBJECTIVE: The objective of the study was to evaluate the efficacies of the recently developed kinase inhibitors SU11248, SU5416, and SU6668 in inhibition of RET/PTC. DESIGN: SU11248, SU5416, and SU6668 were synthesized, and their inhibitory potencies were evaluated using an in vitro RET/PTC kinase assay. The inhibitory effects of the compounds on RET/PTC were evaluated by quantifying the autophosphorylation of RET/PTC, signal transducer and activator of transcription (STAT)-3 activation, and the morphological reversal of RET/PTC-transformed cells. RESULTS: An in vitro kinase assay revealed that SU5416, SU6668, and SU11248 inhibited phosphorylation of the synthetic tyrosine kinase substrate peptide E4Y by RET/PTC3 in a dose-dependent manner with IC(50) of approximately 944 nm for SU5416, 562 nm for SU6668, and 224 nm for SU11248. Thus, SU11248 effectively inhibits the kinase activity of RET/PTC3. RET/PTC-mediated Y705 phosphorylation of STAT3 was inhibited by addition of SU11248, and the inhibitory effects of SU11248 on the tyrosine phosphorylation and transcriptional activation of STAT3 were very closely correlated with decreased autophosphorylation of RET/PTC. SU11248 caused a complete morphological reversion of transformed NIH-RET/PTC3 cells and inhibited the growth of TPC-1 cells that have an endogenous RET/PTC1. CONCLUSION: SU11248 is a highly effective tyrosine kinase inhibitor of the RET/PTC oncogenic kinase.
Administration, Oral↗
Ketogenic diet for treatment of infantile spasms.
This study sought to evaluate the efficacy, tolerability, and safety of a ketogenic diet (KD) in the treatment of infantile spasms (IS), incorporating a revised protocol based on our previous experience with KD. We undertook a retrospective analysis of 43 children who suffered from catastrophic IS and tried KD from June 1995 to May 2004 in two Korean epilepsy centers. Outcome measures included seizure frequency, electroencephalograms (EEGs), adverse reactions, and neurological development. Overall, the diet achieved the seizure-free state in 53.5% (23/43) of patients and a greater than 90% reduction of seizure frequency in 62.8% (27/43) of patients. The seizure outcomes were highly concordant with improvements in EEG findings and development. In addition, KD could be maintained more safely and more comfortably because of our revised protocol that included an initial non-fasting diet, a short-term trial of 8 months, a more protein-rich diet with a lipid to non-lipid ratio of 3:1, and liquid ketogenic milk. Most complications were transient and KD was well tolerated in most cases. KD can be an effective alternative therapy for catastrophic IS, and additional benefits may be derived from constant revision of the diet in the future.
Child, Preschool↗
Fluorine-substituted cyclofenil derivatives as estrogen receptor ligands: synthesis and structure-affinity relationship study of potential positron emission tomography agents for imaging estrogen receptors in breast cancer.
In a search for estrogen receptor (ER) ligands to be radiolabeled with fluorine-18 for imaging of ER-positive breast tumors with positron emission tomography (PET), we investigated cyclofenil analogues substituted at the C3 or C4 position of the cyclohexyl group. McMurry coupling of 4,4'-dihydroxybenzophenone with various ketones produced key cyclofenil intermediates, from which C3 and C4 substituents containing alkyl and various oxygen or fluorine-substituted alkyl groups were elaborated. Binding assays to both ERalpha and ERbeta revealed that the C3 site is more tolerant of steric bulk and polar groups than the C4 site, consistent with a computational model of the ERalpha ligand binding pocket. Fluorine substitution is tolerated very well at some sites, giving some compounds having affinities comparable to or higher than that of estradiol. These fluoro and fluoroalkyl cyclofenils merit further consideration as fluorine-18 labeled ER ligands for PET imaging of ERs in breast tumors.
Binding Sites↗
Lack of association between C3435T nucleotide MDR1 genetic polymorphism and multidrug-resistant epilepsy.
The variability of P-glycoprotein expression in individuals is linked to a C3435T polymorphism of the multidrug-resistance 1 (MDR1) gene, and the CC genotype at the C3435T polymorphism was reported to be associated with multidrug resistance in epilepsy patients. Since population frequencies of polymorphic genes depend on ethnic specificity, we investigated functional significance of the C3435T polymorphism of the MDR1 gene in Korean epilepsy patients. One hundred and eight patients with drug-responsive epilepsy, 63 patients with drug-resistant epilepsy, and 219 control migraine subjects were studied, but the analysis for C3435T allele showed no significant association between the CC genotype and the multidrug-resistant epilepsy. We suggest that influence of the C3435T polymorphism in the multidrug-resistant epilepsy may not be significant in Korean populations and further investigations in various ethnic populations would be necessary to clarify the effect of C3435T polymorphism on the mutidrug resistance in epilepsy patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Increased nitric oxide caused by the ketogenic diet reduces the onset time of kainic acid-induced seizures in ICR mice.
Although the antiepileptic effects of the ketogenic diet (KD) are well documented, the mechanisms underlying this action remain obscure. Nitric oxide (NO) has long been thought to play a role in regulating seizures. However, the effects of the KD on endogenous NO production have not been characterized. Therefore, the present study was designed to examine the effect of the KD on endogenous NO production, as well as the precise role of NO in kainic acid (KA)-induced seizures, in male ICR mice. We first found that preadministration of the KD for 4 weeks increased endogenous NO generation in the hippocampus. We also demonstrated that the increase in NO induced by the KD resulted from increased neuronal NO synthase (nNOS) activity and exerted an antiepileptic effect on KA-induced seizures, based on the results of experiments using NOS-knockout mice and two NOS inhibitors, N-omega-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). These data suggest that the antiepileptic effects of the KD might be mediated, at least in part, by increased NO levels in the hippocampus.
3-Hydroxybutyric Acid↗
Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy.
The tumor microenvironment, in particular, the tumor vasculature, as an important target for the cytotoxic effects of radiation therapy is an established paradigm for cancer therapy. We review the evidence that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated in endothelial cells exposed to ionizing radiation (IR) and is a molecular target for the development of novel radiation sensitizing agents. On the basis of this premise, several promising preclinical studies that targeted the inhibition of the PI3K/Akt activation as a potential method of sensitizing the tumor vasculature to the cytotoxic effects of IR have been conducted. An innovative strategy to guide cytotoxic therapy in tumors treated with radiation and PI3K/Akt inhibitors is presented. The evidence supports a need for further investigation of combined-modality therapy that involves radiation therapy and inhibitors of PI3K/Akt pathway as a promising strategy for improving the treatment of patients with cancer.
Angiogenesis Inhibitors↗
Appearance of intrathymic parathyroid adenomas on pinhole sestamibi parathyroid imaging.
OBJECTIVES: Ectopic inferior parathyroid adenomas (PAs) are frequently located in the anterior mediastinum, quite often in the thymus gland. Correct preoperative localization is particularly helpful for surgical planning. Clinical follow up has shown that most intrathymic adenomas were visualized on pinhole views and located closer to the thyroid than expected. We reviewed the typical appearance of intrathymic PA on pinhole views. METHODS: We retrospectively reviewed sestamibi pinhole parathyroid imaging performed on 163 patients with primary hyperparathyroidism and final diagnoses established by surgery, histology, intraoperative PTH monitoring, and clinical follow up. Studies showing focal increased activity in the lower pole region of the thyroid were selected and divided into 2 groups, group A (foci that are visually not separable from the thyroid) and group B (foci that are completely separated from the thyroid), and correlated with the final diagnoses. RESULTS: Of the 163 patients, 102 had 103 clearly abnormal foci in the lower pole region (bilateral lower pole foci in one study). There were 93 foci in group A and 10 foci in group B. Of the 93 foci in group A, there were 80 normally situated inferior PA, 6 descended superior PA, 3 intrathyroidal PA, one hyperplastic parathyroid gland, one thyroid adenoma, one unidentified, and one intrathymic PA. Of the 10 foci in group B, 3 were eutopic inferior PA and 7 were intrathymic PA. CONCLUSION: Focal increased activity completely separated from the lower pole of thyroid (regardless of the distance of separation) on sestamibi pinhole images indicates a high probability of intrathymic parathyroid adenoma.
Adenoma↗
Multilocus sequence typing (MLST) analysis of Vibrio cholerae O1 El Tor isolates from Mozambique that harbour the classical CTX prophage.
Vibrio cholerae O1 isolates belonging to the Ogawa serotype, El Tor biotype, harbouring the classical CTX prophage were first isolated in Mozambique in 2004. Multilocus sequence typing (MLST) analysis using nine genetic loci showed that the Mozambique isolates have the same sequence type (ST) as O1 El Tor N16961, a representative of the current seventh cholera pandemic. Analysis of the CTX prophage in the Mozambique isolates indicated that there is one type of rstR in these isolates: the classical CTX prophage. It was also found that the ctxB-rstR-rstA-rstB-phs-cep fragment was PCR-amplified from these isolates, which indicates the presence of a tandem repeat of the classical CTX prophage in the genome of the Mozambique isolates. The possible origin of these isolates and the presence of the tandem repeat of the classical prophage in them implicate the presence of the classical CTX phage.
Bacterial Proteins↗
Isolation of Salmonella enterica subspecies enterica serovar Paratyphi B dT+, or Salmonella Java, from Indonesia and alteration of the d-tartrate fermentation phenotype by disrupting the ORF STM 3356.
Salmonella enterica subspecies enterica serovar Paratyphi B [O1,4,(5),12 : Hb : 1,2] can cause either an enteric fever (paratyphoid fever) or self-limiting gastroenteritis in humans. The d-tartrate non-fermenting variant S. enterica subsp. enterica serovar Paratyphi B dT- (S. Paratyphi B) is the causative agent of paratyphoid fever, and the d-tartrate fermenting variant S. enterica subsp. enterica serovar Paratyphi B dT+ (S. Paratyphi B dT+; formerly called Salmonella Java) causes gastroenteritis. S. Java is currently recognized as an emerging problem worldwide. Twelve dT+ S. Java isolates were collected in Indonesia between 2000 and 2002. One-third of them contained Salmonella genomic island 1 (SGI1), which gives the multidrug-resistant phenotype to the bacteria. In this study, a PCR-based method to detect a single nucleotide difference responsible for the inability to ferment d-tartrate, reported elsewhere, was validated. The d-tartrate fermenting phenotype of S. Java was converted to the non-fermenting phenotype by the disruption of the ORF STM 3356, and the d-tartrate non-fermenting phenotype of the ORF STM 3356-disrupted strain and the dT- reference strain was changed to the dT+ phenotype by complementing ORF STM 3356 in trans. The results show that the dT+ phenotype requires a functional product encoded by STM 3356, and support the use of the PCR-based discrimination method for S. Paratyphi B and S. Java as the standard differentiation method.
Anti-Bacterial Agents↗
Clinical characteristics and outcomes of posttransplant lymphoproliferative disorders following allogeneic hematopoietic stem cell transplantation in Korea.
Between 1995 and 2003, seven cases of posttransplant lymphoproliferative disorder (PTLD) were identified among 1,116 patients who received allogeneic hematopoietic stem cell transplantations (HSCT) at Catholic HSCT Center (overall incidence 0.6%). Five (71.4%) patients had episodes of acute graft-versus-host-disease (GVHD) and were treated with steroids. Cervical lymphadenopathy was observed in most cases (71.4%), but clinical symptoms varied depending on the involved sites. Pathologic findings varied: 1 case of plasmacytic hyperplasia, 3 of polymorphic PTLD, 2 of diffuse large B-cell lymphoma, 1 of large T-cell lymphoma, which proved to be associated with Epstein-Barr virus (EBV). The proportion of EBV-negative PTLD was 33.3%. Five patients demonstrated a good response to treatment (treatment response rate 71.4%). The overall mortality was 42.8%, and one death was directly attributable to PTLD. The incidence of PTLD is expected to increase, based on the rising use of grafts from alternative donors and recent clinical features of PTLD manifested by a disseminated and fulminant nature. It is necessary to have a high level of suspicion when monitoring patients and readily adopt prompt and effective cellular immunotherapy for PTLD.
Adolescent↗
Ketogenic diet decreases the level of proenkephalin mRNA induced by kainic acid in the mouse hippocampus.
The ketogenic diet (KD) has been used to control medically refractory epilepsy in children for more than 80 years. Despite the clinical efficacy of the KD, its underlying bases are still obscure. Previous work from our laboratory has established that the KD has an antiepileptic and neuroprotective effect in the kainic acid (KA)-induced seizure model. The neuronal excitation caused by KA leads to increases in the expression of a variety of genes, including immediate-early genes and opioid peptides derived from proenkephalin (PENK) and prodynorphin (PDYN). In particular, the up-regulated PENK gene that is induced by KA in the hippocampal dentate granule cells has proconvulsant properties. PENK is regulated by the c-jun amino-terminal kinase (JNK) signaling pathway, the crucial role of which is involved in the regulation of transcription factors, such as Jun and Fos. In the present study, we examined the effect of the KD on the increase of PENK, Fos, Jun, AP-1 DNA-binding activity and JNK gene expression induced by KA in the mouse hippocampus. Using in situ hybridization and northern blot analysis, we found that the KD significantly decreases the level of PENK gene expression induced by KA of the granular cells in the hippocampus. In addition, we have also found that KD diminished KA-induced AP-1 DNA-binding activity, Fos and Jun expression, and phoshorylated form of the three types of JNKs. These results suggest that the KD suppresses KA-induced activation of JNK signaling pathways, followed by a decrease of PENK gene expression in the hippocampus, thereby resulting in antiepileptic effects.
Animals↗
Response to combined modality therapy correlates with survival in locally advanced non-small-cell lung cancer.
PURPOSE: Although concurrent chemoradiotherapy can now achieve demonstrated long-term survival in patients with locally advanced non-small-cell lung cancer (LANSCLC), it is difficult to predict which patients will benefit most from this therapeutic approach. Studies have suggested that local control, and the response to therapy, may be linked to improved survival; however, detailed analysis of the impact of tumor response to chemoradiotherapy on survival has not been thoroughly reported. Therefore, we sought to determine the impact of the response rate on survival for patients who were treated with combined modality therapy for LANSCLC. METHODS AND MATERIALS: We reviewed the data from 116 patients enrolled between 1994 and 1997 in three trials investigating paclitaxel-based concurrent chemoradiotherapy for LANSCLC. Tumor size measurements were assessed immediately before and 2 months after completion of combined modality therapy to determine the response and to calculate the percentage of decrease in tumor size. RESULTS: Patients with a response (complete or partial) had an improved 4-year overall survival rate compared with patients with no response (stable or progressive disease; 21.1% vs. 3.3%, p <0.0001) in the 109 assessable patients. Progression-free survival also improved significantly with response. An analysis of the percentage of decrease in tumor size vs. survival was performed (n = 74) using Cox proportion model analysis. After combined modality therapy, a 20%, 40%, 60%, 80%, and 100% decrease in tumor size conferred a 39%, 63%, 78%, 86%, and 92% reduction in risk of death compared with a 0% decrease in tumor size (p <0.0001). CONCLUSION: The response by conventional response criteria correlated strongly with improved overall survival and progression-free survival and an increasing percentage of decrease in tumor size resulted in a reduction in the risk of death. Additional investigation of the degree of response as a factor predictive of improved therapeutic efficacy, translating into improved survival, is warranted.
Analysis of Variance↗
Lymphoscintigraphy and triangulated body marking for morbidity reduction during sentinel node biopsy in breast cancer.
Current trends in patient care include the desire for minimizing invasiveness of procedures and interventions. This aim is reflected in the increasing utilization of sentinel lymph node biopsy, which results in a lower level of morbidity in breast cancer staging, in comparison to extensive conventional axillary dissection. Optimized lymphoscintigraphy with triangulated body marking is a clinical option that can further reduce morbidity, more than when a hand held gamma probe alone is utilized. Unfortunately it is often either overlooked or not fully understood, and thus not utilized. This results in the unnecessary loss of an opportunity to further reduce morbidity. Optimized lymphoscintigraphy and triangulated body marking provides a detailed 3 dimensional map of the number and location of the sentinel nodes, available before the first incision is made. The number, location, relevance based on time/sequence of appearance of the nodes, all can influence 1) where the incision is made, 2) how extensive the dissection is, and 3) how many nodes are removed. In addition, complex patterns can arise from injections. These include prominent lymphatic channels, pseudo-sentinel nodes, echelon and reverse echelon nodes and even contamination, which are much more difficult to access with the probe only. With the detailed information provided by optimized lymphoscintigraphy and triangulated body marking, the surgeon can approach the axilla in a more enlightened fashion, in contrast to when the less informed probe only method is used. This allows for better planning, resulting in the best cosmetic effect and less trauma to the tissues, further reducing morbidity while maintaining adequate sampling of the sentinel node(s).
Journal Article↗
Using the intraoperative hand held probe without lymphoscintigraphy or using only dye correlates with higher sensory morbidity following sentinel lymph node biopsy in breast cancer: a review of the literature.
BACKGROUND: There are no studies that have directly investigated the incremental reduction in sensory morbidity that lymphoscintigraphy images (LS) and triangulated body marking or other skin marking techniques provide during sentinel lymph node biopsy (SLNB) compared to using only the probe without LS and skin marking or using only dye. However, an indirect assessment of this potential for additional sensory morbidity reduction is possible by extracting morbidity data from studies comparing the morbidity of SLNB to that of axillary lymph node dissection. METHODS: A literature search yielded 13 articles that had data on sensory morbidity at specific time points on pain, numbness or paresthesia from SLNB that used radiotracer and probe or used only dye as a primary method of finding the sentinel node (SN). Of these, 10 utilized LS, while 3 did not utilize LS. By matching the data in studies not employing LS to the studies that did, comparisons regarding the percentage of patients experiencing pain, numbness/paresthesia after SLNB could be reasonably attempted at a cutoff of 9 months. RESULTS: In the 7 studies reporting on pain after 9 months (> 9 months) that used LS (1347 patients), 13.8% of patients reported these symptoms, while in the one study that did not use LS (143 patients), 28.7% of patients reported these symptoms at > 9 months (P < 0.0001). In the 6 studies reporting on numbness and/or paresthesia at > 9 months that used LS (601 patients), 12.5% of patients reported these symptoms, while in the 3 studies that did not use LS (229 patients), 23.1% of patients reported these symptoms at > 9 months (P = 0.0002). Similar trends were also noted for all these symptoms at < or = 9 months. CONCLUSION: Because of variations in techniques and time of assessing morbidity, direct comparisons between studies are difficult. Nevertheless at a minimum, a clear trend is present: having the LS images and skin markings to assist during SLNB appears to yield more favorable morbidity outcomes for the patients compared to performing SLNB with only the probe or performing SLNB with dye alone. These results are extremely pertinent, as the main reason for performing SLNB itself in the first place is to achieve reduced morbidity.
Journal Article↗