Assessment of the Appearance and Toxin Production Potential of Invasive Nostocalean Cyanobacteria Using Quantitative Gene Analysis in Nakdong River, Korea.

Invasive nostocalean cyanobacteria (INC) were first reported in tropical regions and are now globally spreading rapidly due to climate change, appearing in temperate regions. INC require continuous monitoring for water resource management because of their high toxin production potential. However, it is difficult to analyze INC under a microscope because of their morphological similarity to nostocalean cyanobacteria such as the genus Aphanizomenon. This study calculates the gene copy number per cell for each target gene through quantitative gene analysis on the basis of genus-specific primers of genera Cylindrospermopsis, Sphaerospermopsis, and Cuspidothrix, and the toxin primers of anatoxin-a, saxitoxin, and cylindrospermopsin. In addition, quantitative gene analysis was performed at eight sites in the Nakdong River to assess the appearance of INC and their toxin production potential. Genera Cylindrospermopsis and Sphaerospermopsis did not exceed 100 cells mL-1 at the maximum, with a low likelihood of related toxin occurrence. The genus Cuspidothrix showed the highest cell density (1759 cells mL-1) among the INC. Nakdong River has potential for the occurrence of anatoxin-a through biosynthesis by genus Cuspidothrix because the appearance of this genus coincided with that of the anatoxin-a synthesis gene (anaF) and the detection of the toxin by ELISA.

Development of Genus-Specific PCR Primers for Molecular Monitoring of Invasive Nostocalean Cyanobacteria.

The geographical range of invasive cyanobacteria with high toxigenic potential is widening because of eutrophication and global warming, thus, monitoring their appearance is necessary for safe water quality control. Most invasive cyanobacteria are nostocalean species, and their accurate identification by classical morphological methods may be problematic. In this study, we developed polymerase chain reaction (PCR) primers to selectively identify five invasive cyanobacterial genera, namely, Chrysosporum, Cuspidothrix, Cylindrospermopsis, Raphidiopsis, and Sphaerospermopsis, using genetic markers such as rbcLX, rpoB, rpoC1, and cpcBA, and determined the amplification conditions for each pair of primers. The primer performances were verified on single or mixed nostocalean cyanobacterial isolates. The five primers allowed selective identification of all the target genera. In field samples collected during summer, when cyanobacteria flourished in the Nakdong River, the respective PCR product was observed in all samples where the target genus was detected by microscopic analysis. Besides, weak bands corresponding to Sphaerospermopsis and Raphidiopsis were observed in some samples in which these genera were not detected by microscopy, suggesting that the cell densities were below the detection limit of the microscopic method used. Thus, the genus-specific primers developed in this study enable molecular monitoring to supplement the current microscopy-based monitoring.

Deciphering the key factors determining spatio-temporal heterogeneity of cyanobacterial bloom dynamics in the Nakdong River with consecutive large weirs.

Following the construction of eight large weirs in a 200-km section of the Nakdong River, which is a major water source for the region, harmful cyanobacterial blooms have been occurring annually, causing severe problems with water quality. The present study investigated the community structure of harmful cyanobacteria and identified temporal and spatial patterns in harmful cyanobacterial blooms and their dynamic relationships with physicochemical, hydrological, and meteorological variables in the eight weir sections for 6 years from 2013 to 2018. The dominant harmful cyanobacteria in the eight weir sections were Aphanizomenon and Microcystis spp. There was a successional phenomenon wherein Aphanizomenon spp. first bloomed in spring, and then Microcystis spp. bloomed as water temperatures increased. Additionally, the initiation and duration of the blooms of both genera were affected by the timing and volume of heavy rainfall that caused flushing of cyanobacterial biomass, resulting in direct reduction of cyanobacterial growth in all sections. The harmful cyanobacteria of upstream weirs did not affect the biomass of downstream weirs in terms of either growth initiation or time taken to reach peak biomass, despite being physically connected. Owing to the long retention time during the dry season, similar to what occurs in separate reservoirs, the water quality of each weir section, particularly regarding nutrient characteristics and retention time, were the major factors determining the harmful cyanobacterial abundance, resulting in heterogeneous spatial distribution of harmful cyanobacterial blooms in the Nakdong River.

Invasion and toxin production by exotic nostocalean cyanobacteria (Cuspidothrix, Cylindrospermopsis, and Sphaerospermopsis) in the Nakdong River, Korea.

The extent and frequency of harmful cyanobacterial blooms are increasing, owing to the climate change caused by global warming, and some harmful filamentous cyanobacteria that were first reported in the tropics are spreading to temperate regions, such as North America, Europe, and Northeast Asia. Although these exotic invasive cyanobacteria have a high toxigenic potential, they are not targeted in management plans in many countries. This study analyzed the occurrence of and potential toxin and off-flavor secondary metabolite production by invasive nostocalean cyanobacteria in the Nakdong River in Korea, which is a temperate region. The occurrence of four species belonging to three genera of cyanobacteria was confirmed in the Nakdong River. The quantities of cyanobacteria in the Nakdong River were mostly low, fewer than 1,000 cells mL-1. Twenty-four strains belonging to four species in three genera of cyanobacteria were isolated from the Nakdong River. Analysis revealed no off-flavor secondary metabolite production by any of the isolates, and those belonging to Cylindrospermopsis raciborskii, Sphaerospermopsis aphanizomenoides, and S. reniformis were identified as nontoxic strains. However, anatoxin-a production was observed in two of the eleven isolates of Cuspidothrix issatschenkoi. Given the sites and the timing of its occurrence, C. issatschenkoi had the highest potential for toxin production among the invasive nostocalean cyanobacteria appearing in the Nakdong River.

Effects of Weir Construction on Phytoplankton Assemblages and Water Quality in a Large River System.

Flow regulation is one of the most common anthropogenic factors affecting rivers worldwide. In Korea, 16 weirs were constructed along four major rivers from 2009 to 2012. This study aimed to elucidate initial changes in physical, chemical, and biological variables after the construction of consecutive weirs on the Nakdong River, a major large river system. Water quality variables and phytoplankton cell densities were investigated at eight representative sites and compared with the data recorded before the weir construction. There were spatial and temporal changes in the hydraulic retention time (HRT), total phosphorus (TP), and chlorophyll a concentrations among the eight weir sections. HRT increased after the weir construction, while TP and chlorophyll a tended to decrease from the middle to lower section of the Nakdong River. Furthermore, differences were observed in the phytoplankton community composition between 2006⁻2007 and 2013. There was a marginal decrease in the duration of centric diatom (Stephanodiscus hantzschii) blooms after weir construction. However, Microcystis aeruginosa proliferated more extensively during summer and autumn than it did before the weir construction. Our results suggest that changes in hydrological factors, in response to consecutive weir construction, may contribute to greater physical, chemical, and ecological variability.

Molecular Verification of Bloom-forming Aphanizomenon flos-aquae and Their Secondary Metabolites in the Nakdong River.

Aphanizomenon spp. have formed harmful cyanobacterial blooms in the Nakdong River during spring, autumn, and now in winter, and the expansion of blooming period and area, associated with the global warming is predicted. The genus Aphanizomenon has been described to produce harmful secondary metabolites such as off-flavors and cyanotoxins. Therefore, the production of harmful secondary metabolites from the Aphanizomenon blooms in the Nakdong River needs to be monitored to minimize the risk to both water quality and public health. Here, we sampled the cyanobacterial blooms in the Nakdong River and isolated ten Aphanizomenon strains, morphologically classified as Aphanizomenon flos-aquae Ralfs ex Bornet et Flahault 1888. Phylogenetic analysis using 16S rRNA and internal transcribed spacer (ITS) region nucleotide sequences confirmed this classification. We further verified the harmful secondary metabolites-producing potential of A. flos-aquae isolates and water samples containing cyanobacterial blooms using PCR with specific primer sets for genes involved in biosynthesis of off-flavor metabolites (geosmin) and toxins (microcystins, saxitoxins and cylindrospermopsins). It was confirmed that these metabolite biosynthesis genes were not identified in all isolates and water samples containing only Aphanizomenon spp. Thus, it is likely that there is a low potential for the production of off-flavor metabolites and cyanotoxins in Aphanizomenon blooms in the Nakdong River.

A Telerehabilitation Approach for Chronic Aphasia Following Stroke.

BACKGROUND: Intensive speech therapy improves language function in patients with chronic aphasia, although treatment in the acute phase is more effective than in the chronic phase. Unfortunately, most patients with stroke go untreated due to socioeconomic problems. This study was performed to develop and test a speech therapy-based telerehabilitation program (iAphasia), suitable for use on a mobile device platform, which would expand access to therapy to patients who frequently go untreated. SUBJECTS AND METHODS: We enrolled 8 patients with chronic poststroke aphasia to receive therapy via our iPad(®) (Apple, Cupertino, CA)-based telespeech therapy program, iAphasia. Participants received 4 weeks of telespeech therapy using iAphasia, which generates six domains with six levels of difficulty. We compared pre- and posttreatment scores on the Korean version of the Western Aphasia Battery (K-WAB) to evaluate effectiveness. Additionally, a 1-month follow-up assessment was performed. RESULTS: We investigated user satisfaction using a questionnaire to assess the feasibility of iAphasia. After the 4-week treatment, language function as measured by the K-WAB improved significantly. The improvement was persistent at the 1-month follow-up visit. The degree of improvement was strongly associated with usage time, regardless of participants' age and severity of aphasia. Overall, satisfaction with iAphasia was rated high. CONCLUSIONS: The results from this study suggest it to be an effective and feasible treatment method for chronic aphasia, although follow-up studies with more subjects and a control group are needed for a more thorough assessment.

A Telescreening Tool to Detect Aphasia in Patients with Stroke.

BACKGROUND: Early identification of patients with stroke-induced aphasia is essential because it is a significant disability affecting daily life and is linked to poor functional outcome after stroke. However, most patients with stroke are unable to undergo aphasia evaluation and detection and therefore remain undiagnosed. The purpose of this study is to develop a valid, reliable mobile aphasia screening test (MAST) for patients in remote locations. MATERIALS AND METHODS: To accomplish this, we enrolled patients with (n=30) and without (n=30) stroke-induced aphasia. A MAST, which adopted the Korean version of the shortened version of the Frenchay Aphasia Screening Test (K-FAST), was designed as an iPad(®) (Apple, Cupertino, CA) application. To validate the MAST, we compared its performance with that of the Korean version of the Western Aphasia Battery (K-WAB) and conventional shortened FAST paper version (K-FAST). We analyzed interrater and internal reliability, using Cronbach's alpha coefficient, and assessed the diagnostic sensitivity, specificity, and power. RESULTS: There was significant correlation between K-FAST and MAST (intraclass correlation coefficient [ICC]=0.995, p<0.001). MAST also had a high correlation with K-WAB (ICC=0.752, p<0.001). Interrater reliability was very high (ICC=0.999, p<0.001). The test had high sensitivity (90.0%) and specificity (73.3%) with an accuracy of 0.930 (95% confidence interval=0.853-1.000). The MAST is a valid and reliable tool for detecting aphasia in patients with stroke. CONCLUSIONS: This telescreening test may overcome the limitations of test administration and may be a convenient and cost-effective alternative to the existing aphasia screening tests for patients with stroke.

Identification of key factors influencing primary productivity in two river-type reservoirs by using principal component regression analysis.

To understand the factors controlling algal production in two lakes located on the Han River in South Korea, Lake Cheongpyeong and Lake Paldang, a principal component regression model study was conducted using environmental monitoring and primary productivity data. Although the two lakes were geographically close and located along the same river system, the main factors controlling primary productivity in each lake were different: hydraulic retention time and light conditions predominantly influenced algal productivity in Lake Cheongpyeong, while hydraulic retention time, chlorophyll a-specific productivity, and zooplankton grazing rate were most important in Lake Paldang. This investigation confirmed the utility of principal component regression analysis using environmental monitoring data for predicting complex biological processes such as primary productivity; in addition, the study also increased the understanding of explicit interactions between environmental variables. The findings obtained in this research will be useful for the adaptive management of water reservoirs. The results will also aid in the development of management strategies for water resources, thereby improving total environmental conservation.

Role of the posterior temporal lobe during language tasks: a virtual lesion study using repetitive transcranial magnetic stimulation.

Functional brain imaging studies have suggested that the superior temporal gyrus (STG) and the middle temporal gyrus (MTG) are involved in phonological and lexical-semantic processing, respectively. However, the precise role of the posterior temporal lobe is not fully understood. To clarify the functional relevance of the left posterior STG and MTG during language processing, we used neuronavigation-guided repetitive transcranial magnetic stimulation (rTMS). The reaction times and error rates for 12 healthy volunteers performing auditory repetition and lexical-semantic decision tasks were compared before and during rTMS stimulation. We applied 1 Hz rTMS over the left posterior STG or MTG or sham stimulation for 10 min in a random order. Stimulation of the left posterior MTG significantly slowed the response time for the lexical-semantic decision task from 478.9±56.5 to 583.1±80.0 ms. However, stimulation over the left posterior STG or MTG did not affect the response time or the error rate for the auditory repetition task. Our results suggest that the left posterior MTG might be involved in lexical decision making. Neuronavigation-guided rTMS virtual lesion studies could help determine the functional roles of specific brain areas in language processing, and our findings provide new evidence supporting the use of neuromodulation through rTMS for patients with aphasia.

Upper extremity rehabilitation of stroke: facilitation of corticospinal excitability using virtual mirror paradigm.

BACKGROUND: Several experimental studies in stroke patients suggest that mirror therapy and various virtual reality programs facilitate motor rehabilitation. However, the underlying mechanisms for these therapeutic effects have not been previously described. OBJECTIVES: We attempted to delineate the changes in corticospinal excitability when individuals were asked to exercise their upper extremity using a real mirror and virtual mirror. Moreover, we attempted to delineate the role of visual modulation within the virtual environment that affected corticospinal excitability in healthy subjects and stroke patients. METHODS: A total of 18 healthy subjects and 18 hemiplegic patients were enrolled into the study. Motor evoked potential (MEP)s from transcranial magnetic stimulation were recorded in the flexor carpi radialis of the non-dominant or affected upper extremity using three different conditions: (A) relaxation; (B) real mirror; and (C) virtual mirror. Moreover, we compared the MEPs from the virtual mirror paradigm using continuous visual feedback or intermittent visual feedback. RESULTS: The rates of amplitude increment and latency decrement of MEPs in both groups were higher during the virtual mirror task than during the real mirror. In healthy subjects and stroke patients, the virtual mirror task with intermittent visual feedback significantly facilitated corticospinal excitability of MEPs compared with continuous visual feedback. CONCLUSION: Corticospinal excitability was facilitated to a greater extent in the virtual mirror paradigm than in the real mirror and in intermittent visual feedback than in the continuous visual feedback, in both groups. This provides neurophysiological evidence supporting the application of the virtual mirror paradigm using various visual modulation technologies to upper extremity rehabilitation in stroke patients.

Extracellular HIV-1 Tat upregulates TNF-α dependent MCP-1/CCL2 production via activation of ERK1/2 pathway in rat hippocampal slice cultures: inhibition by resveratrol, a polyphenolic phytostilbene.

Human immunodeficiency virus-1 (HIV-1) associated dementia (HAD) has been attributed to an encephalitis resulting from intense infiltration of monocytes. Evidence suggests that the viral protein Tat, which is released actively from HIV-1 infected cells, can contribute significantly to this process. Therefore, the principal objective of this study was to evaluate the potential molecular basis for the role of extracellular HIV-1 Tat in the induction of monocyte chemotactic protein-1 (MCP-1/CCL2) in the hippocampus, which is primarily linked to cognitive function and most commonly damaged in HAD. We also attempted to identify the mechanism by which resveratrol (trans-3,5,4'-trihydroxystilbene) modulates MCP-1 release in hippocampal tissues exposed to Tat. An ex vivo study using rat hippocampal slices demonstrated a time- and dose-dependent increase in MCP-1 production from Tat-treated hippocampal tissues. This increase was accompanied by the activation of the MEK/ERK pathway and TNF-α production. Tat-induced MCP-1 release was abrogated by inhibitors of tyrosine kinases (TK), herbimycin A or genistein, a finding that supports the MAPK signaling mechanism. The inhibition of the ERK1/2 pathway with SL327 induced a near-complete abolition of the observed Tat-induced effects. Furthermore, anti-TNF-α antibodies suppressed Tat-induced MCP-1 release. Resveratrol, to a level similar to that of SL327, downregulated Tat-induced proinflammatory responses via the inactivation of ERK1/2. These results indicate that the activation of the ERK1/2 pathway and TK are critical factors in the production of TNF-α and MCP-1 in the Tat-exposed hippocampus. Additionally, the inhibition of Tat-induced production of MCP-1 and TNF-α via the inactivation of the ERK1/2 pathway may represent the anti-inflammatory mechanism of resveratrol in the hippocampus.

Facilitation of corticospinal excitability according to motor imagery and mirror therapy in healthy subjects and stroke patients.

OBJECTIVE: To delineate the changes in corticospinal excitability when individuals are asked to exercise their hand using observation, motor imagery, voluntary exercise, and exercise with a mirror. METHOD: The participants consisted of 30 healthy subjects and 30 stroke patients. In healthy subjects, the amplitudes and latencies of motor evoked potential (MEP) were obtained using seven conditions: (A) rest; (B) imagery; (C) observation and imagery of the hand activity of other individuals; (D) observation and imagery of own ipsilateral hand activity; (E) observation and imagery of the hand activity of another individual with a mirror; (F) observation and imagery of own symmetric ipsilateral hand activity (thumb abduction) with a mirror; and (G) observation and imagery of own asymmetric ipsilateral hand activity (little finger abduction) with a mirror. In stroke patients, MEPs were obtained in the A, C, D, E, F conditions. RESULTS: In both groups, increment of the percentage MEP amplitude (at rest) and latency decrement of MEPs were significantly higher during the observation of the activity of the hand of another individual with a mirror and during symmetric ipsilateral hand activity on their own hand with a mirror than they were without a mirror. In healthy subjects, the increment of percentage MEP amplitude and latency decrement were significantly higher during the observation of the symmetric ipsilateral hand activity with a mirror compared to the observation of the activity of the asymmetric ipsilateral hand with a mirror of their own hand. CONCLUSION: In both groups, corticospinal excitability was facilitated by viewing the mirror image of the activity of the ipsilateral hand. These findings provide neurophysiological evidence supporting the application of various mirror imagery programs during stroke rehabilitation.

Comparison of Escherichia coli uropathogenic genes (kps, usp and ireA) and enteroaggregative genes (aggR and aap) via multiplex polymerase chain reaction from suprapubic urine specimens of young children with fever.

OBJECTIVE: Escherichia coli is the most frequently identified microbiological agent in childhood urinary tract infections (UTIs). However, the pathogenic role of this organism in young children remains to be clearly elucidated. So far, no studies have been conducted in which multiplex polymerase chain reaction (PCR) has been applied to determine the association between childhood UTIs and E. coli and urovirulent genes. MATERIAL AND METHODS: Altogether, 330 suprapubic urine specimens from febrile young children were cultured. In 33 of the cases, E. coli was identified; among these cases, 18 had a UTI (>10(4)-10(5) cfu/ml), four had a suspected UTI (>10(2)-10(3) cfu/ml) and 11 did not have UTIs (10(2) cfu/ml). Using multiplex PCR, three uropathogenic E. coli (UPEC) genes and two enteroaggregative E. coli (EAEC) genes were detected. RESULTS: In the UTI-UPEC cases, the kps gene was detected in 18 of 22 cases (82%) and the usp gene in 16 of 22 cases (73%). Among the 18 cases of children with UTIs characterized by 10(4)-10(5) E. coli cfu/ml, urinary tract abnormalities were identified via dimercaptosuccinic acid scans in seven of 18 cases (39%) and via voiding cystourethrograms in four of the 18 cases (22%). CONCLUSIONS: The UPEC kps and usp genes were clearly associated with childhood UTIs, and may also be associated with kidney or urinary tract dysfunctions in young children. Escherichia coli colony count numbers in excess of 10(4)-10(5) cfu/ml in the suprapubic urine were considered to be strong evidence of UTI in infants.

Expressed sequence tags of Trichinella spiralis muscle stage larvae.

In order to obtain greater insight into the relevant genomic expression patterns of Trichinella spiralis, 992 expressed sequence tags (ESTs) were collected from a cDNA library of T. spiralis muscle stage larvae and assembled into 60 clusters and 385 singletons. Of them, 445 (44.7%) ESTs were annotated to their homologous genes, and small fractions were matched to known genes of nematodes. The annotated ESTs were classified into 25 eukaryotic orthologous groups (KOG). Cytochrome C oxidase (34 clones) was found to be most frequent species.

Human eosinophils show chemotaxis to lymphoid chemokines and exhibit antigen-presenting-cell-like properties upon stimulation with IFN-gamma, IL-3 and GM-CSF.

BACKGROUND: Eosinophils are multifunctional leukocytes. Under physiological conditions, they circulate in the blood and through the tissues to serve their functions. In certain inflammatory states, they enter the T-cell areas of lymph nodes (LNs) that drain the inflamed tissue and communicate with T cells in LNs, but the underlying mechanism that regulates their trafficking to LNs is not yet fully explored. Here, we report that a human eosinophilic leukemia cell line, EoL-1, and human peripheral blood (PB) eosinophils become reactive to the lymphoid chemokines CCL21 and CCL25 upon stimulation. METHODS: EoL-1 cells were differentiated with dibutyryl cyclic AMP (dEoL-1) and subsequently pulsed with IFN-gamma, IL-3 and GM-CSF. The eosinophil fraction was purified from normal human adult PB and incubated for 1 day with the same cytokine combination. RESULTS: Upon cytokine stimulation, dEoL-1 cells expressed chemokine receptors CCR7, CCR9 and CCR3 and developed chemotactic responsiveness to CCL21, CCL25 and CCL11, which bind to the respective receptors. Human PB eosinophils also showed chemotactic responsiveness to CCL21 and CCL25 upon stimulation with IFN-gamma, IL-3 and GM-CSF. In addition, the cytokine-stimulated dEoL-1 cells expressed costimulatory molecules, including CD40, CD80, CD86 and HLA-DR, and also expressed a tolerogenic and Th2-polarizing enzyme, indoleamine 2,3-dioxygenase. CONCLUSIONS: These in vitro observations raise the possibility that eosinophils may utilize lymphoid chemokines to enter LNs and serve antigen-presenting functions in the LN under certain inflammatory conditions.

Questionable role of human herpesviruses in the pathogenesis of Kikuchi disease.

CONTEXT: Kikuchi disease is a self-limiting febrile lymphadenopathy characterized by a patchy area of apoptosis. Kikuchi disease is thought to be caused by a virus, but this has not been clearly demonstrated. Human herpesviruses 6 and 7 (HHV-6 and HHV-7) are lymphotropic viruses that can induce apoptosis in infected lymphocytes. Recently, HHV-8 was reported to be a possible etiologic agent of Kikuchi disease. OBJECTIVE: To investigate the incidence of HHV-6, HHV-7, and HHV-8 infection in patients with Kikuchi disease. DESIGN: Seventy archival tissue specimens (from 50 Kikuchi disease cases and 20 control cases) were tested for the presence of HHV-6 and HHV-7 using a nested polymerase chain reaction, and for the presence of HHV-8 using single-step polymerase chain reaction. Immunohistochemistry for HHV-8 expression was carried out in those cases in which HHV-8 was detected using polymerase chain reaction. RESULTS: Of the 50 cases with Kikuchi disease, 21 (42%) were HHV-6 positive and 32 (64%) were HHV-7 positive. Eight (40%) of the 20 control cases were HHV-6 positive and 9 (45%) were HHV-7 positive. Both HHV-6 and HHV-7 were detected in 15 (30%) of the cases with Kikuchi disease and in 3 (15%) of the control cases. Three (6%) of the 50 cases of Kikuchi disease were HHV-8 positive but revealed no positive cells on immunohistochemical analysis for HHV-8. Human herpesvirus 8 was not expressed in any of the control cases. CONCLUSIONS: There was no association between the presence of HHV-6 or HHV-7 and Kikuchi disease. Because the HHV-8 genome but not protein was detected in a small proportion of the cases of Kikuchi disease, its potential causative role in this disease should be determined by further studies.

Pim-1 induced polyploidy but did not affect megakaryocytic differentiation of K562 cells and CD34+ cells from cord blood.

In a previous study, we determined the gene expression profile of both megakaryocytic and non-megakaryocytic lineage cells via serial analysis of gene expression and microarray methods, and demonstrated that Pim-1 was expressed more abundantly in megakaryocytic lineage cells. In this study, we knocked down Pim-1 in K562 cells, as well as in CD34+ cells from cord blood, via RNA interference, in order to analyze the effects of Pim-1 expression on the megakaryocytic differentiation of these cells. We then additionally overexpressed the Pim-1 genes in K562 cells, and conducted a comparison of these effects with those of RNAi cells on the course of megakaryocytic differentiation. The results of this study revealed that Pim-1 knockdown exerted no effects on commitment or differentiation toward megakaryocytic lineage, as evidenced by the detected CD41+ or CD61+ cells, or on the number of megakaryocytic colony forming units. However, Pim-1 knockdown was found to elicit a reduction in CD41+ cells with >4n DNA content, and a concomitant increase in the fraction of cells achieving a ploidy of >4n in the Pim-1 overexpressing population of K562 cells. Collectively, the findings of these studies indicate that the expression of Pim-1 expression is both necessary and sufficient for polyploidization, but is not critical to cytoplasmic differentiation on megakaryopoiesis.

Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without hyperpyrexia.

Serum cytokine profiles in patients with Plasmodium vivax malaria who presented with and without hyperpyrexia were compared by a retrospective review of the medical records of the consecutive patients seen at the military hospitals near the demilitarized zone in the Republic of Korea from April 2000 through October 2001. Of 162 male patients studied, 120 (86.4%) presented with hyperpyrexia (i.e., an axillary temperature > or = 40 degrees C). The mean +/- SEM ages of the patients with and without hyperpyrexia were 21.5 +/- 0.14 and 21.9 +/- 0.39 years, respectively (P = 0.33). The mean +/- SEM concentrations of serum interleukin (IL)-6 (379.7 +/- 44.1 pg/mL versus 105.4 +/- 26.8 pg/mL; P = 0.002), IL-10 (583.4 +/- 58.2 pg/mL versus 142.4 +/- 39.7 pg/mL; P = 0.0001), and interferon-gamma (312.6 +/- 33.9 pg/mL versus 112.9 +/- 27.1 pg/mL; P = 0.0001) were significantly higher in patients with hyperpyrexia compared with those without hyperpyrexia. The mean +/- SEM concentrations of serum tumor necrosis factor-alpha were 155.5 +/- 54.5 pg/mL and 109.9 +/- 29.3 pg/mL (P = 0.27) in patients who presented with and without hyperpyrexia, respectively. Further studies are needed to examine whether serum concentrations of these cytokines also parallel their concentrations at the tissue sites of their production and action.

Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without hepatic dysfunction.

The aim of this study was to compare the serum cytokine profiles of Plasmodium vivax malaria patients who presented with and without hepatic dysfunction. This is a retrospective analysis of 74 consecutive cases of P. vivax malaria seen at 3 military hospitals near the Demilitarized Zone in South Korea from 1999 to 2000. All patients studied were adult active duty servicemen. On admission, the mean (+/- SEM) age of the patients who presented with (n = 36) and without hepatic dysfunction (n = 38) was 21.6 +/- 0.24 and 22.5 +/- 0.44 years, respectively (P = 0.72). On admission, there was no significant difference between the 2 patient populations in terms of mean temperature, haemoglobin level, haematocrit, total white blood cell count, platelet count, parasite index, and serum concentration of transforming growth factor-beta. Plasmodium vivax malaria patients who presented with hepatic dysfunction had significantly higher mean serum concentrations of soluble Fas ligand, interleukin (IL)-l, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma than those without hepatic dysfunction, suggesting the involvement of these cytokines in the development of hepatic dysfunction. The mean serum concentration of IL-12 was significantly lower in patients with hepatic dysfunction. The mean body temperature was not significantly different between the 2 patient populations.