Concurrent outbreak of PMWS and PDNS in a herd of pigs in Korea.
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Animals↗
Biomedical subjects
J Kim
Publications and source records attributed to J Kim.
A case of biphenotypic blast crisis of unclassified myeloproliferative disorder.
We report a first case of biphenotypic blast crisis of unclassified myeloproliferative disorder (MPD). A 20-year-old patient presented with fever, splenomegaly, marked leukocytosis (603 x 10(3)/ micro l), and blasts in the peripheral blood. Since Ph chromosome and bcr-abl gene rearrangement were absent, the diagnosis of an unclassified MPD in the blast crisis phase was established. Immunophenotyping confirmed a biphenotypic crisis of myeloid and T-lymphoid antigens. The patient went into a complete remission after chemotherapy, but marked granulocytic hyperplasia (M:E ratio of 5.7) and 90% cellularity remained. Blast crisis recurred during subsequent intensification chemotherapy and the patient did not go into a complete remission regardless of the intense chemotherapy. The blast crisis transformed from unclassified MPD had a grave prognosis as it responded poorly to chemotherapy. This unique blast crisis is distinguishable from the blast crisis of chronic myelogenous leukemia.
Adult↗
Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours.
Only about half of patients with a poor-prognosis non-seminomatous germ-cell tumours can achieve a cure. The aim of this phase II study was to assess the efficacy and toxicity of a dose-dense alternating chemotherapy regimen in this subset of patients. High volume non-seminomatous germ-cell tumours was defined as follows: at least two sites of non pulmonary metastases, an extragonadal primary tumour, a serum human chorionic gonadotropin level higher than 10 000 mIU x ml(-1), or a alpha-foetoprotein level higher than 2000 mIU ml(-1). Patients who fulfilled these criteria were treated with the so-called BOP-CISCA-POMB-ACE regimen (bleomycin, vincristine, and cisplatin; cisplatin, cyclophosphamide, and doxorubicin; cisplatin, vincristine, methotrexate, and bleomycin; etoposide, dactinomycin, and cyclophosphamide) plus granulocyte colony-stimulating factor. A total of 58 patients were enrolled. Patients were retrospectively classified according to the International Germ-Cell Cancer Consensus Group classification; 38 patients (66%) had poor-prognosis disease and 19 patients (33%) had intermediate-prognosis. Patients received a median of 2.5 courses (range 0.25 to five courses) of the BOP-CISCA-POMB-ACE regimen. Forty-two patients (72.4%) had a complete response to therapy. With a median follow-up time of 31 months, the 3-year progression-free survival rate was 71% (95% confidence interval, 60 to 84%) and the 3-year overall survival rate was 73% (95% confidence interval: 62 to 86%). The 3-year PFS rates were 83% (95% confidence interval: 68 to 100%) in the intermediate-prognosis group and 65% (95% confidence interval: 51 to 82%) in the poor-prognosis group. Early side effects included mainly grade 4 haematologic toxicity (neutropaenia in 79% of patients, thrombocytopaenia in 69%, anaemia in 22%), grade 4 stomatitis (19%), and four early deaths (7% of patients), at least partially related to toxicity. The dose-dense BOP-CISCA-POMB-ACE regimen is highly active in patients with non-seminomatous germ-cell tumours classified as intermediate-prognosis or poor-prognosis according to the International Germ-Cell Cancer Consensus Group. Because outcomes with this regimen compare favourably with outcome after standard therapy, dose-dense chemotherapy should be further investigated in this subset of patients.
Adolescent↗
Prevalence of Brachyspira pilosicoli in Korean pigs, determined using a nested PCR.
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Animals↗
Genotypic prevalence of the fimbrial adhesins (F4, F5, F6, F41 and F18) and toxins (LT, STa, STb and STx2e) in Escherichia coli isolated from postweaning pigs with diarrhoea or oedema disease in Korea.
A PCR was used to determine the genotypic prevalence of five fimbrial adhesins (F4, F5, F6, F41 and F18), two heat-stable enterotoxins (STa and STb), the heat-labile enterotoxin (LT), and the shiga toxin 2e (Stx2e) in 230 isolates of Escherichia coli from postweaning pigs with diarrhoea or oedema disease. Ninety-four (40.9 per cent) of the isolates carried genes for at least one of the fimbrial adhesins or toxins. Genes for the F18 fimbrial adhesin were detected in 18.3 per cent, and genes for F4, F6, F5 and F41 were detected in 10.0 per cent, 4.3 per cent, 1.7 per cent and 0.8 per cent of the isolates, respectively. Genes for STa, STb and LT were detected in 25.7 per cent, 15.2 per cent and 8.7 per cent of the isolates, respectively. Genes for Stx2e were detected in 36 (15.6 per cent) of the isolates, and among them 24 also contained the gene for F18ab and four also contained the gene for F18ac.
Adhesins, Escherichia coli↗
Codon-improved Cre recombinase (iCre) expression in the mouse.
By applying the mammalian codon usage to Cre recombinase, we improved Cre expression, as determined by immunoblot and functional analysis, in three different mammalian cell lines. The improved Cre (iCre) gene was also designed to reduce the high CpG content of the prokaryotic coding sequence, thereby reducing the chances of epigenetic silencing in mammals. Transgenic iCre expressing mice were obtained with good frequency, and in these mice loxP-mediated DNA recombination was observed in all cells expressing iCre. Moreover, iCre fused to two estrogen receptor hormone binding domains for temporal control of Cre activity could also be expressed in transgenic mice. However, Cre induction after administration of tamoxifen yielded only low Cre activity. Thus, whereas efficient activation of Cre fusion proteins in the brain needs further improvements, our studies indicate that iCre should facilitate genetic experiments in the mouse.
Animals↗
Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.
Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.
Algorithms↗
Self-assembled "nanocubicle" as a carrier for peroral insulin delivery.
AIMS/HYPOTHESIS: A patient with (insulin-dependent) diabetes mellitus receives at least one subcutaneous insulin injection a day to maintain low serum glucose concentrations. Since patients' compliance with such dosage regimens is too low, the development of an oral formula is clearly attractive. We present the development of a liquid formula that can be easily dispersed in water to produce particles named "nanocubicles" which efficiently encapsulate insulin. METHODS: Fasted streptozotocin-induced diabetic rats were administered orally with particles encapsulating insulin, and particles without insulin or soluble insulin in water. Groups of rats were also injected soluble insulin in PBS for control. Blood glucose concentration and insulin concentration were measured 1, 2, 3, 4 and 6 h after the administration of the insulin formulas. RESULTS: In vitro experiments show that the particles can be taken up by the Caco-2 cells at a high ratio. The serum glucose concentration was controlled for more than 6 h after oral insulin administration but returned to the basal concentration in 3 h when 1 IU/kg of insulin was injected intravenously. CONCLUSION/INTERPRETATION: Our biocompatible and stable oral insulin formulation is easy to prepare and produces reproducible hypoglycaemic effects, therefore we anticipate clinical acceptance and utilization of this form of insulin therapy.
Administration, Oral↗
Selected pesticide residues in house dust from farmers' homes in central New York State, USA.
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Agriculture↗
IL-4 increases Simian immunodeficiency virus replication despite enhanced SIV immune responses in infected rhesus macaques.
It is widely believed that a Th1 type CD4 response is critical for enhancement of CD8 immunity and for controlling HIV-1 infection. Th2 type responses, such as what might be seen in a chronic parasitic infection, would sacrifice cellular immunity and thus benefit the virus at the expense of the host. However, there has been little direct examination of the hypothesis in a primate model system. Accordingly, the simian immunodeficiency virus (SIV) infected rhesus macaque model was used to investigate the impact of immunisation with SIV expressing DNA constructs and co-injection with IL-4 on the SIV specific immunological responses, lymphocyte cell counts, as well as the impact on viral load. IL-4 is a Th2 type cytokine, which enhances antibody production and inhibits a CD4 Th1 phenotype. Rhesus macaques were infected with 10 AID50 of SIVmac239 and treated with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) 9 weeks post-infection. During PMPA treatment, animals were immunised with plasmids that expressed the SIV proteins, env, rev, gag and pol. In addition, they were immunised with a construct that encoded the gene for IL-4. IL-4 co-immunisation increased the neutralizing antibody titres in this group. Importantly, the viral loads in animals vaccinated with IL-4 expressing plasmid increased during the immunisation regimens despite the higher neutralizing antibody titres. In addition, neutralizing antibodies did not correlate with viral set point prior to PMPA treatment, however, there was a correlation between viral loads and antibody titres following the treatment with PMPA. Antibody titres decreased following the suppression of viral load. Importantly, vaccination in the absence of IL-4 protected CD4 levels without increasing viral load. The data support the hypothesis that inappropriate immune bias toward a Th2 pathway would ultimately enhance disease progression.
Animals↗
Postsynaptic action mechanism of somatostatin on the membrane excitability in spinal substantia gelatinosa neurons of juvenile rats.
We used tight-seal, whole-cell recording in juvenile rat spinal slices to investigate the action of somatostatin on substantia gelatinosa neurons. Bath application of somatostatin caused a robust and repeatable hyperpolarization or outward current in substantia gelatinosa neurons. Somatostatin inhibited spontaneous action potentials in subpopulation of substantia gelatinosa neurons. The amplitude of dorsal root-evoked excitatory postsynaptic currents and the frequency of spontaneous excitatory postsynaptic currents were not affected by somatostatin. The current induced by somatostatin developed almost instantaneously and did not show any time-dependent inactivation. The current-voltage relationship exhibited inward rectification. The conductance of somatostatin-sensitive current increased with the concentration of external K(+). The reversal potentials in different external K(+) concentrations were close to the K(+) equilibrium potentials. The effect of somatostatin was dose-dependent, with an EC(50) of 113 nM. The somatostatin-sensitive current was blocked by low concentration of extracellular Ba(2+) but not by glibenclamide, an inhibitor of ATP-sensitive K(+) channels. Hyperpolarization-activated cation current in a subpopulation of substantia gelatinosa neurons was not affected by somatostatin. In neurons recorded with an internal solution containing GTPgammaS, somatostatin induced outward current and hyperpolarization that did not reverse on washing. When the spontaneous induction of outward current with GTPgammaS was greatest, somatostatin did not induce any outward currents. Furthermore, intracellular dialysis of GDPbetaS, a G-protein antagonist, abolished the effect of somatostatin. In addition, SST-sensitive neurons were fewer in slices incubated with pertussis toxin than in adjacent control slices incubated without pertussis toxin. These results suggest that somatostatin decreases the postsynaptic membrane excitability of substantia gelatinosa neurons by a pertussis toxin-sensitive G-protein-mediated activation of an inwardly rectifying K(+) conductance.
Age Factors↗
Inclusion of Vpr accessory gene in a plasmid vaccine cocktail markedly reduces Nef vaccine effectiveness in vivo resulting in CD4 cell loss and increased viral loads in rhesus macaques.
We compared the immunogenicity of plasmid vaccines containing multiple human immunodeficiency virus (HIV) antigens and found that covaccination with plasmids expressing HIV-1 14 kDa vpr gene product profoundly reduces antigen-specific CD8-mediated cytotoxic T-cell activity (CTL). Interestingly, Th1 type responses against codelivered antigens (pGag-Pol, pNef, etc.) encoded by the plasmid vaccines were suppressed. This suggested that vpr might compromise CD8 T-cell immunity in vivo during infection. A pilot primate vaccine study was designed to test the hypothesis to compare the following groups: unvaccinated controls, animals vaccinated without simean immunodeficiency virus (SIV)-Nef antigen plasmid, and animals covaccinated with the identical plasmid antigen and a plasmid construct encoding SIV Vpr/Vpx. Animals were subsequently challenged intrarectally with pathogenic SIVmac251 after the final vaccination of a multiple immunization protocol. Control animals were all infected and exhibited high viral loads and rapid CD4+ T-cell loss. In contrast, the Nef plasmid-vaccinated animals were also infected but exhibited preservation of CD4+ T-cells and a multilog reduction in viral load compared with controls. Animals covaccinated multiple times with the Nef vaccine and pVpr/Vpx plasmid suffered rapid and profound loss of CD4+ T-cells. These results have important implications for the design of multicomponent and particle vaccines for HIV-1 as well as for our understanding of HIV/SIV pathogenesis in vivo.
Animals↗
Melasma: histopathological characteristics in 56 Korean patients.
BACKGROUND: Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun-exposed areas of the skin. Its histopathological characteristics are not fully understood. OBJECTIVES: To characterize the histopathological features of facial melasma skin in comparison with adjacent normal skin. METHODS: Biopsies were taken from both melasma lesional skin and adjacent perilesional normal skin in 56 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana-Masson, diastase-resistant periodic acid-Schiff, Masson trichrome and Verhoeff-van Gieson stains, and immunostaining for melanocytes. Data on the changes in number of melanocytes and melanin contents of the epidermis were analysed by a computer-assisted image analysis program. The ultrastructure of the skin was also examined. RESULTS: The amount of melanin was significantly increased in all epidermal layers in melasma skin. The staining intensity and number of epidermal melanocytes increased in melasma lesions. Lesional skin showed more prominent solar elastosis compared with normal skin. Melanosomes increased in number and were more widely dispersed in the keratinocytes of the lesional skin. Lesional melanocytes had many more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in their cytoplasm. A dihydroxyphenylalanine reaction was apparent in the cisternae and vesicles of the trans-Golgi network in melanocytes from lesional skin. CONCLUSIONS: Melasma is characterized by epidermal hyperpigmentation, possibly caused both by an increased number of melanocytes and by an increased activity of melanogenic enzymes overlying dermal changes caused by solar radiation.
Adult↗
Increased expression of alpha-melanocyte-stimulating hormone in the lesional skin of melasma.
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Adult↗
Anti-microbial susceptibility for east1 + Escherichia coli isolated from diarrheic pigs in Korea.
The in vitro susceptibilities of 128 isolates of east1 + Escherichia coli from pre-weaned and post-weaned pigs with diarrhoea were tested with nine commonly used anti-microbial agents by an agar dilution minimal inhibitory concentration (MIC) procedure according to National Committee for Clinical Laboratory Standards guidelines. For the isolates from preweaned and post-weaned pigs, most of them were susceptible to low concentrations (MIC90) of tetracycline (4 and 2 microg/ml), ceftiofur (2 and 2 microg/ml), and colistin (4 and 2 microg/ml). Marked resistance was found in others.
Animals↗
Double in situ hybridization for simultaneous detection and differentiation of porcine circovirus 1 and 2 in pigs with postweaning multisystemic wasting syndrome.
Double in situ hybridization using a digoxigenin-labelled porcine circovirus 1 (PCV1) and biotinylated PCV2 probe, was developed for the simultaneous detection and differentiation of PCV1 and PCV2 in formalin-fixed, paraffin-embedded tissues from pigs with postweaning multisystemic wasting syndrome. The combination of an alkaline phosphatase conjugated antidigoxigenin system with alkaline phosphatase conjugated streptavidin-biotin system allowed identification of PCV1 and/or PCV2. No evidence of cross-reaction was observed. Positive cells exhibited a red or dark brown reaction product for PCV1 and PCV2, respectively. Both PCV DNAs were observed mainly in the cytoplasm but occasionally in the nucleus. Co-localization of hybridization signal for both PCV1 and PCV2 was present in macrophages and multinucleated giant cells of the lymph node and spleen. This double-labelling technique for the differentiation between PCV1 and PCV2 is suitable for pathogenesis studies and diagnostic applications.
Animals↗
Usefulness of silicone plate for sellar floor reconstruction.
During the transsphenoidal approach (TSA), the proper sellar floor reconstruction plays an important role in the surgical results. The authors have evaluated the usefulness of a silicone as a substitute for bone splint in sellar floor reconstruction. Silicone plates were used in 10 patients who had 7 pituitary adenomas, 2 Rathke's cleft cysts, and 1 metastatic tumor. Among the ten cases, seven underwent standard TSAs and three received extended TSAs. The silicone plate was cut to a size slightly larger than that of bone window, inserted with a three-pronged fork, and then adjusted precisely. In nine patients, complications that related to surgical repair did not occur. A postoperative cerebrospinal fluid (CSF) rhinorrhea occurred in one pituitary macroadenoma, and no infection was observed in any case. From the authors' experience, advantages of the silicone plate are its simplicity to shape for any size of defects, and the easy detectability of the previous bone window at reoperation.
Adult↗
Geometry of gene expression dynamics.
MOTIVATION: A gene expression trajectory moves through a high dimensional space where each axis represents the mRNA abundance of a different gene. Genome wide gene expression has a dynamic structure, especially in studies of development and temporal response. Both visualization and analyses of such data require an explicit attention to the temporal structure. RESULTS: Using three cell cycle trajectories from Saccharomyces cerevisiae to illustrate, we present several techniques which reveal the geometry of the data. We import phase-delay time plots from chaotic systems theory as a dynamic data visualization device and show how these plots capture important aspects of the trajectories. We construct an objective function to find an optimal two-dimensional projection of the cell cycle, demonstrate that the system returns to this plane after three different initial perturbations, and explore the conditions under which this geometric approach outperforms standard approaches such as singular value decomposition and Fourier analysis. Finally, we show how a geometric analysis can isolate distinct parts of the trajectories, in this case the initial perturbation versus the cell cycle. CONTACT: junhyong.kim@yale.edu
Algorithms↗