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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.

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.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.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%).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.

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.

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.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.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.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.

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.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.There was significant correlation between K-FAST and MAST (intraclass correlation coefficient [ICC]=0.995, p0.001). MAST also had a high correlation with K-WAB (ICC=0.752, p0.001). Interrater reliability was very high (ICC=0.999, p0.001). 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.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.

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.

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 temperatureor = 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.

Part of the neurodegenerative cascade in AIDS dementia may involve overexpression of matrix metalloproteinases (MMPs). Here, we examined the possible effect of HIV-1 gp41, which has been shown as a key determinant associated with pathogenesis of AIDS dementia, on the activity of MMPs using human neuronal and glial cell lines. Zymographic analysis revealed that treatment with the gp41 peptide (aa 583-599) for 24 h markedly elevated the activity of MMP with Mr 66 kDa in the cultured media of glioblastoma cell line T98G in a concentration-dependent manner as well as of neuroblastoma cell line SK-N-SH despite of lower magnitude of the activity. In contrast, the immediately adjacent gp41 peptide (aa 598-613) as well as the reverse peptide (aa 598-583) had a little effect. Recombinant gp41 protein containing extracellular domain also elicited a similar effect, although with a lesser extent. This 66 kDa MMP was confirmed as gelatinase A (MMP-2) based on the results of its activity dependent on Ca2+ and inhibited in the presence of 1,10-phenanthroline or EDTA, as well as its specific immunoreactivity on the Western blot. N-acetyl cysteine (NAC) downregulated this gp41 peptide-induced MMP-2 activity in T98G. The soluble form of amyloid precursor protein (sAPP), which is synthesized in the Escherichia coli system, also inhibited the MMP-2 activity in vitro. Taken together, these results implicate that high production of HIV-1 gp41 or its metabolites containing aa 583-599 within central nervous system (CNS) could result in the increased activity of MMP-2 and that the extracellular deficiency of reducing agent or decreased level of sAPP within CNS could exacerbate this gp41-induced MMP-2 activity.

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.

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-γ, 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-γ, 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.

Thrombopoietin (TPO) is widely used for ex vivo expansion of hematopoietic stem cells. Previously, we have reported that TPO induces a characteristic pattern of apoptosis, and the TPO-induced apoptosis is closely associated with megakaryocyte (MK) differentiation. In the present study, several cytokines, flt3-ligand, stem cell factor (SCF), interleukin-3 (IL-3), IL-6, IL-11, leukemia inhibitory factor, G-CSF, and erythropoietin, which are known to affect megakaryocytopoiesis, have been evaluated to elucidate their effects on the TPO-induced apoptosis. Measurement of apoptosis by flow cytometry revealed that only SCF absolutely reduced the TPO-induced apoptosis in MK fractions, particularly in the late phase of ex vivo expansion. Platelet production was demonstrated by electron microscopy in a later phase when SCF was added. Simultaneous measurement of DNA contents with immunophenotyping demonstrated a significant increase in polyploidization in the CD41+ cell fraction when cultured with SCF. These results suggested that SCF not only inhibited premature senescence but also enhanced maturation of the differentiating cells of MK lineage during ex vivo expansion using TPO.

To elucidate the pathogenic mechanisms involved in neurodegeneration in AIDS patients with cognitive deficits, we have examined the toxic effect of the lentivirus lytic peptide 1 (LLP-1) corresponding to the carboxyl terminus of HIV-1 transmembrane glycoprotein gp41 on human neuronal and glial cell lines. LLP-1 induced a significant lactate dehydrogenase (LDH, a marker of cell death) release from these cells in a concentration- and time-dependent manner, while the noncytolytic LLP-1 analog 2 had little effect. Application of LLP-1 to SH-SY5Y, a well-characterized human neuronal cell line, caused the decline of intracellular glutathione (GSH) content that appeared to occur before a significant LDH release. Furthermore, LLP-1 elicited a significant loss of mitochondrial function as measured by mitochondrial transmembrane potential (MTP). Among the reducing agents and antioxidants tested, GSH and a GSH prodrug N-acetylcysteine (NAC) provided protection against LLP-1-induced neuronal cell death, evidently by restoring the intracellular GSH levels and blocking the disruption of mitochondrial integrity. Thus, gp41-derived LLP-1 may be a potential neurotoxic agent capable of causing the intracellular GSH depletion and disturbing the mitochondrial function, possibly contributing to the neurodegenerative cascade as seen in HIV-1-associated dementia. Our data indicate that restoring both GSH concentration and mitochondrial function may hold promise as possible therapeutic strategies for slowing disease progression of dementia in AIDS patients.

Salmonella penetrates the basement membrane of intestinal epithelial cells into deeper tissues, in which process extracellular matrix proteases should be required. Hypothesizing that the proteases might be provided by host cells, we investigated the changes of expression of urokinase type plasminogen activator(u-PA), plasminogen activator inhibitor-1(PAI-1), and collagenases in epithelial cells(Caco-2) infected with Salmonella typhimurium. The change of mRNA levels, amount of the enzyme secretion and functional activity were analyzed by Northern blot, ELISA, and Zymography. The mRNA level of u-PA was elevated by Salmonella infection itself without any exogenous transcription regulators. u-PA was actively secreted into the medium and was enzymatically active. The synthesis and secretion of PAI-1 was increased over time from 2 hrs post infection(pi) to 8 hrs pi. Zymographic assay revealed that the secretion of collagenases (type IV, type V and interstitial collagenase) were also increased. Taken together, S. typhimurium infection might induce accumulation of pericellular proteolytic activity and consequently degrade the extracellular matrix surrounding the infected cells. These in turn might enable Salmonella to invade into deeper tissues.