Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study.

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.

Outcomes of flexor tendon repairs in zone 2 subzones with early active mobilization.

We report on the outcomes of flexor tendon repair in zone 2 subzones with early active mobilization in 102 fingers in 88 consecutive patients. There were 28, 53, 15, and six fingers with repairs in zones 2A to 2D, respectively. Rupture of the repair occurred in four fingers, all in zone 2B. Excluding those with repair ruptures, the mean total active motion was 230° (range 143°-286°). Evaluated with Tang's criteria, the outcomes were ranked excellent in 39 fingers, good in 46, fair in ten, poor in three, and failure in four. The outcomes in zone 2C were significantly inferior to those in zones 2B and 2D ( p = 0.02). Our results suggest that the tendon laceration in the area covered by the A2 pulley (zone 2C) is the most difficult area to obtain satisfactory active digital motion and tendon repair in zone 2B is the area where the risk of rupture is highest. LEVEL OF EVIDENCE: IV.

Clinical results of releasing the entire A2 pulley after flexor tendon repair in zone 2C.

UNLABELLED: We report the results of complete release of the entire A2 pulley after zone 2C flexor tendon repair followed by early postoperative active mobilization in seven fingers and their comparisons with 33 fingers with partial A2 pulley release. In seven fingers, release of the entire A2 pulley was necessary to allow free gliding of the repairs in five fingers and complete release of both the A2 and C1 pulleys was necessary in two. No bowstringing was clinically evident in any finger. Two fingers required tenolysis. Using Tang's criteria, the function of two digits was ranked as excellent, four good and one fair; there was no failure. The functional return in these seven fingers was similar with that in 33 fingers with partial A2 pulley release; in these patients only one finger required tenolysis. Our results support the suggestion that release of the entire A2 pulley together with the adjacent C1 pulley does not clinically affect finger motion or cause tendon bowstringing, provided that the other pulleys are left intact. LEVEL OF EVIDENCE: IV.

Outcomes of release of the entire A4 pulley after flexor tendon repairs in zone 2A followed by early active mobilization.

We report the outcomes of repair of the flexor digitorum profundus tendon in zone 2a in 22 fingers. The tendon was repaired with a six-strand repair method and the A4 pulley was completely released. Release of the C2 pulley combined with the A4 pulley was necessary in 12 fingers, nine fingers underwent a complete release of the A3, C2, and A4 pulleys, and one finger underwent a release of the C1, A3, C2, and A4 pulleys. The mean total active motion of the three finger joints was 234° at 5 to 12 months of follow-up. No bowstringing was noted in these fingers. The good and excellent recovery of active digital motion was in 20 (91%) out of 22 fingers according to Strickland's criteria or Tang's criteria. Our results suggest that release of the A3, C2, and A4 pulleys makes the repair surgery easier and does not cause tendon bowstringing.

Community-Based Intervention for Prevention of Dementia in Japan.

Population aging is accelerating, with prolonged life expectancy and a decrease in birth rate. As age is a significant risk factor for dementia, we are confronted with an ever-increasing prevalence of mild cognitive impairment (MCI)/dementia. Thus, the Japanese National Center for Geriatrics and Gerontology launched a project to promote community-based research, including the development of an effective screening system for high-risk groups and intervention for dementia prevention. This review introduces the project, the Obu Study of Health Promotion for the Elderly, with the following strategic triad: 1) Identification of the target population by population screening; we regarded patients with MCI as the target population, and developed a screening test battery to identify MCI in a population screening setting. 2) Scientific evaluation of community-based intervention; we developed an interventional method combining exercise and cognitive training ("cognicise"). In practical settings, "cognicise" is programmed into multicomponent exercise intervention, which was reported to have benefits of cognitive improvement and reduction of brain atrophy based on randomized controlled trials. 3) Standardization of the methods of population screening and community-based intervention for evidence-based policy making and widespread implementation. Dementia prevention, or at least delaying the onset of dementia and/or stopping/slowing the progression of dementia, should benefit the whole society as well as individuals. It is our continuing challenge to improve the screening system and community-based intervention for dementia prevention through accumulation of evidence.

Clinical outcomes of early active mobilization following flexor tendon repair using the six-strand technique: short- and long-term evaluations.

We evaluated the factors influencing outcomes of flexor tendon repair in 112 fingers using a six-strand suture with the Yoshizu #1 technique and early postoperative active mobilization in 101 consecutive patients. A total of 32 fingers had injuries in Zone I, 78 in Zone II, and two in Zone III. The mean follow-up period was 6 months; 16 patients (19 fingers) participated in long-term follow-up of 2 to 16 years. The total active motion was 230° SD 29°; it correlated negatively with age. The total active motion was 231° SD 28° after repair of the lacerated flexor digitorum superficialis tendon, and was 205° SD 37° after excision of the flexor digitorum superficialis tendon ends (p = 0.0093). A total of 19 fingers showed no significant increases in total active motion more than 2 years after surgery. The rupture rate was 5.4% in our patients and related to surgeons' level of expertise. Five out of six ruptured tendons were repaired by inexperienced surgeons. Level of Evidence IV.

Evaluation of panoramic radiographs taken at the initial visit at a department of paediatric dentistry.

OBJECTIVES: To examine oral and maxillofacial lesions other than those related to the chief complaint in panoramic radiographs taken at the department of paediatric dentistry at our hospital. METHODS: We retrospectively reviewed all 1092 patients who had visited the department of paediatric dentistry at our hospital and had a panoramic radiograph taken between August 1999 and October 2004. The following information was obtained from the patients' files and panoramic radiographs: gender, age, chief complaints and the presence or absence of lesions. RESULTS: Lesions were observed in 140 of the 1092 panoramic radiographs (12.8%). Among the 140 patients discovered to have lesions in the panoramic radiographs, 66 (47.1%, or 6.05% of the entire group of 1092 patients) had different lesions from those underlying the chief complaint. These 66 patients ages ranged from 3 years to 14 years and the lesions involved 39 (59.1%) missing teeth, 20 (30.3%) mesiodentes, 4 supernumerary teeth, 1 odontoma, 1 radicular cyst and 1 impacted tooth. The missing teeth were observed in the central and lateral incisor, canine, and first and second premolar positions of both jaws, especially in the lower lateral incisor and upper central incisor positions. CONCLUSIONS: We were able to detect incidental lesions at a rate of 6.05% (66 of 1092 patients) and at a relatively early age (mean 6.8 years) in the present study. Early treatment of these lesions could avoid maxillofacial deformity and other complications.

Reactivity of synthetic SAG1 (p30) peptide sequences with RH, S273 and Beverley strain-induced anti-Toxoplasma gondii antibodies.

OBJECTIVES: We compared the reactivity of IgG1 and IgG2a antibodies in mouse sera after infection with virulent RH and low-virulent S273 and Beverley strains of Toxoplasma gondii against RH SAG1 recombinant p30 (rp30) and synthetic SAG1 peptides. METHODS: Infected mouse serum samples were collected 9 days after infection, and the level of total IgG, IgG1 and IgG2a against the RH SAG1 rp30 protein and twenty peptides of the RH SAG1 protein were assessed. The glycosylphosphatidylinositol (GPI) modification site, the hydrophilic-hydrophobic structure, the transmembrane region and the secondary structure of the SAG1 sequence of virulent and low-virulent strains were analyzed using software. RESULTS: The virulent strain-infected mice produced a higher level of IgG1 but a lower IgG2a against the rp30 antigen, while the low-virulent strain-infected mice produced a higher level of IgG2a than the virulent strain. The difference in the secondary structure of SAG1 protein between the virulent and low-virulent strain was largely confined to amino acid positions 291-336, showing mutations and GPI anchor site. CONCLUSION: The difference in the reactivity of IgG against the rp30 antigen and synthetic peptides between virulent and low-virulent strains points to the importance of the primary and secondary structure assumed by antigens in the activation of Th cells and, subsequently, in the induction of IgG and its subclasses.

Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition.

The concentrations of free amino acids in plasma change coordinately and their profiles show distinctive features in various physiological conditions; however, their behavior can not always be explained by the conventional flow-based metabolic pathway network. In this study, we have revealed the interrelatedness of the plasma amino acids and inferred their network structure with threshold-test analysis and multilevel-digraph analysis methods using the plasma samples of rats which are fed diet deficient in single essential amino acid. In the inferred network, we could draw some interesting interrelations between plasma amino acids as follows: 1) Lysine is located at the top control level and has effects on almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in the network, which has direct links to the most number of other amino acids. 3) Threonine and methionine are interrelated to each other and form a loop structure.

A rapid and quantitative detection system for Streptococcus mutans in saliva using monoclonal antibodies.

A new semiquantitative enumeration system was developed to detect Streptococcus mutans in saliva. Using species-specific monoclonal antibodies, the system quickly detected salivary S. mutans in 30 min and classified the results into three levels. In this study, saliva samples collected from 28 young adults aged between 22 and 24 years were subjected to the monoclonal antibody-based detecting system and selective medium-based detecting methods. The results generated from the PCR-confirmed culture method indicated the mean salivary S. mutans counts at level 1, 2 and 3 were 5.7 x 10(4), 1.3 x 10(5) and 3.4 x 10(6) CFU/ml, respectively. The differences between level 3 and 1 and level 3 and 2 were statistically significant (one-way ANOVA; p < 0.01). The results generated from the system were consistent with the data generated from two culture-based commercial products.

Increased susceptibility to apoptosis in CD45(+) myeloma cells accompanied by the increased expression of VDAC1.

Expression of CD45 is quite variable in human myeloma cells and cell lines, such as U266, and CD45(+) U266 proliferates in response to a growth factor, interleukin-6. Here, we show that CD45(+) myeloma cell lines were more sensitive to various apoptotic stimuli, such as oxidative stress and endoplasmic reticulum (ER)-stress, than CD45(-) cells. Reactive oxygen species and calcium ion seemed to be involved in the susceptibility to apoptosis of CD45(+) U266. The activation of the src family kinases associated with CD45 phosphatase played an important role in the augmented apoptosis in CD45(+) U266 by oxidative stress. These results indicate that the CD45-expression renders myeloma cells competent for not only mitogenic but also apoptotic stimuli, resulting in either proliferation or apoptosis of CD45(+) myeloma cells dependently upon the circumstantial stimuli. Furthermore, voltage-dependent anion channel (VDAC) 1 was identified as a gene highly expressed in CD45(+) U266 by cDNA subtraction. The increased expression of VDAC1 seemed to augment the sensitivity to the ER-stress because the VDAC1-transfected U266 was more susceptible to the thapsigargin-induced apoptosis. Thus, CD45 expression accompanied by the increased VDAC1 expression sensitizes myeloma cells to the various extracellular stimuli that trigger apoptosis via the mitochondrial pathways.

Toxoplasma gondii antigens GRA1 (p24) and SAG1 (p30): a comparison of their stimulatory influence on T-cell activation and cytokine expression in in vitro cultures.

The influence of recombinant cell surface SAG1 (rp30) and secretory GRA1 (rp24) antigens (Ag) on T-cell activation and cytokine induction in vitro was compared. T-cell activity and the level of IFN-gamma, IL-10 and IL-12 expression in rp30-immunized T cells were considerably increased in the presence of rp30 Ags. IgG2a and IgG1 antibodies (Ab) were detected in sera of rp24- and rp30-immunized mice, with the secretory rp24 Ag having induced significantly higher titer of IgG1 Ab. In vitro, the greater antigenicity of surface rp30 Ag was notable based on the level of T-cell activation, and cytokine synthesis suggestive of the participation of Th1 cells. Although, IFN-gamma expression by rp24 Ag was lower compared to rp30 Ag, the synthesis of both IgG2a and IgG1 Abs reflects the protective nature of rp24 Ag. We have generated two recombinant Toxoplasma gondii Ags that demonstrated differences in antigenicity in vitro. It would be interesting to evaluate the mechanism(s) of immunity induced by SAG1 (p30) and GRA1 (p24) Ags against infection with T. gondii in vivo.

Salivary flow and its relationship to oral signs and symptoms in patients with dry eyes.

OBJECTIVES: The aim of this study was to investigate oral symptoms and clinical parameters in dry eye patients. Subjective reports of the sensation of a dry mouth, salivary flow rates, and clinical parameters of oral disease related to three different types of dry eye patients were examined. SUBJECTS AND METHODS: There were 224 individuals, including dry eye patients and control subjects. The dry eye patients were classified into three types: patients with Sjögren's syndrome (SS-DE), patients without SS-DE (non-SS-DE), and patients with Stevens-Johnson syndrome (SJS-DE). Salivary flow rates were measured using two kinds of sialometry. Subjective and objective oral symptoms and signs were also examined. RESULTS AND CONCLUSION: Over half of the dry eye patients complained of a dry mouth. The flow rates of their stimulated whole saliva and parotid saliva were significantly lower than those of the control groups (P < 0.05, P < 0.01). The sensation of a dry mouth and changes in oral soft tissues, dental caries, and oral Candida frequently occurred in dry eye patients.

Unresponsiveness to surface antigen 1 modifies cytokine profiles in acute Toxoplasma gondii infection.

Resistance to Toxoplasma gondii involves the development of a highly polarized Th1-type cytokine expression. SAG1 transgenic mice are highly susceptible to T. gondii infection due to their non-reactivity to SAG1 of the protozoan parasite. Here we describe cytokine profiles during the acute phase of T. gondii infection, which are associated with the susceptibility of SAG1 transgenic mice. SAG1 transgenic mice showed a 4.5-fold increase in susceptibility upon inoculation with a sublethal dose of the Beverley strain of T. gondii compared to their wild-type counterparts (mortality: 81 vs. 18%, respectively). When analysis of the most important cytokines involved in the mediation of resistance to infection was carried out, SAG1 transgenic mice exhibited low production levels of IL-12, IFN-gamma and TNF-alpha in sera during the acute phase of T. gondii infection. Antibody and T cells specific for SAG1 were not mounted upon SAG1 stimulation in SAG1 transgenic mice. Moreover, in vitro studies indicated that in SAG1 transgenic mice IFN-gamma and IL-12 production was lower than in their wild-type counterparts, although levels of TNF-alpha increased in SAG1 transgenic mice on day 9 after infection. Low IgG2a levels were detected in SAG1 transgenic mouse sera. Unresponsiveness to SAG1 of T. gondii renders SAG1 transgenic mice unable to develop a strong Th1-based protection against T. gondii infection. These results provide evidence that SAG1 is a pivotal antigen involved in the induction of immune responses towards the development of Th1-protective immunity during T. gondii infection.