Morphological characterisation of glial and neuronal tau pathology in globular glial tauopathy (Types II and III).

AIMS: Globular glial tauopathy (GGT) is a new category within the 4-repeat tauopathies that is characterised neuropathologically by tau-positive globular glial inclusions (GGIs), namely, globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). Occurrence of tau-positive neuronal cytoplasmic inclusions (NCIs) is also a feature. GGT is classified into three pathological subtypes (Types I, II and III). We studied the tau pathology in 6 cases of GGT (Type II, n = 3; Type III, n = 3), with special reference to GAIs and NCIs. METHODS: Neuropathological examinations were conducted, along with immunohistochemistry, morphometry and three-dimensional imaging, and biochemical and genetic analysis of tau. RESULTS: The cortical GAIs in Type II and those in Type III were distinguishable from each other. In the motor cortex, GAIs were much more numerous in Type III than in Type II. Prominent occurrence of perikaryal globular structures was a feature of GAIs in Type III. By contrast, prominent occurrence of radiating process-like structures was a feature of GAIs in Type II. Overall, the GAIs were significantly smaller in Type III than in Type II. NCIs were divisible into three subgroups in terms of shape: diffuse granular, thick cord-like, and round/horseshoe-shaped structures. In all cases, NCIs were a feature of the upper and lower motor neurons. Interestingly, the round/horseshoe-shaped NCIs were observed only in Type III cases. CONCLUSIONS: These findings, which characterised GAIs and NCIs, indicated that Type II and Type III constitute two distinct pathological subtypes, and also further strengthen the concept of GGT as a distinct entity.

Genetic and phenotypic profile of 112 patients with X-linked Charcot-Marie-Tooth disease type 1.

BACKGROUND AND PURPOSE: X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), caused by mutations in gap junction protein beta 1 (GJB1), is characterized by various central nervous system symptoms and gender differences of clinical severity. The aim of this study was to identify the frequency and mutation spectrum of CMTX1 patients in Japan and to demonstrate their phenotypic diversities. METHODS: Using three high-throughput sequencing systems, targeted gene panel sequencing on 1483 unrelated index patients with suspected Charcot-Marie-Tooth (CMT) disease was performed. The peripheral and central nervous system involvements of all patients with GJB1 variants were assessed retrospectively and a detailed gender comparison was conducted with the CMT examination score. RESULTS: Twenty-three novel and 36 described GJB1 variants were identified from 88 pedigrees, in which 34 female and 78 male patients were enrolled. Mean age at onset of the male patients was much younger than the females, 21.56 ± 17.63 years vs. 35.53 ± 23.72 years (P = 0.007). Male patients presented with more severe phenotypes in every examination item, but statistical differences were observed only in motor dysfunctions of the lower extremities and vibration sensation. No significant sensory difference was identified between genders, either clinically or electrophysiologically. Central nervous system dysfunctions were found in 15 patients from 12 pedigrees. Therein, six patients developed stroke-like phenotypes, with dysarthria as the leading symptom. CONCLUSIONS: A relatively lower frequency of CMTX1 (5.9%) was demonstrated and a broad mutation spectrum of GJB1 was described. Detailed clinical differences between genders and various central nervous system symptoms were also illustrated, even in the same pedigree.

Structural basis of the redox switches in the NAD+-reducing soluble [NiFe]-hydrogenase.

NAD+ (oxidized form of NAD:nicotinamide adenine dinucleotide)-reducing soluble [NiFe]-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD+):quinone oxidoreductase (complex I), but the geometrical arrangements of the subunits and Fe-S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules. The oxidized active site includes a six-coordinate Ni, which is unprecedented for hydrogenases, whose coordination geometry would prevent O2 from approaching. In the reduced state showing the normal active site structure without a physiological electron acceptor, the flavin mononucleotide cofactor is dissociated, which may be caused by the oxidation state change of nearby Fe-S clusters and may suppress production of reactive oxygen species.

Clinical and mutational spectrum of Charcot-Marie-Tooth disease type 2Z caused by MORC2 variants in Japan.

BACKGROUND AND PURPOSE: The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot-Marie-Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan. METHODS: We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next-generation sequencing, and samples from 434 mutation-negative patients were subjected to whole-exome sequencing. We extracted MORC2 variants from these whole-exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines. RESULTS: We identified MORC2 variants in 13 patients. As the second most common causative gene of CMT type 2 after MFN2, MORC2 variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length-dependent polyneuropathy, and electrophysiological studies revealed sensory-dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys. CONCLUSIONS: Our study is the largest report of patients harboring MORC2 variants. We revealed a clinical and mutational spectrum of Japanese patients with MORC2 variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.

Clinical and mutational spectrum of Japanese patients with Charcot-Marie-Tooth disease caused by GDAP1 variants.

BACKGROUND: Mutations in GDAP1 are responsible for heterogeneous clinical and electrophysiological phenotypes of Charcot-Marie-Tooth disease (CMT), with autosomal dominant or recessive inheritance pattern. The aim of this study is to identify the clinical and mutational spectrum of CMT patients with GDAP1 variants in Japan. MATERIALS AND METHODS: From April 2007 to October 2014, using three state-of-art technologies, we conducted gene panel sequencing in a cohort of 1,030 patients with inherited peripheral neuropathies (IPNs), and 398 mutation-negative cases were further analyzed with whole-exome sequencing. RESULTS: We identified GDAP1 variants from 10 patients clinically diagnosed with CMT. The most frequent recessive variant in our cohort (5/10), c.740C>T (p.A247V), was verified to be associated with a founder event. We also detected three novel likely pathogenic variants: c.928C>T (p.R310W) and c.546delA (p.E183Kfs*23) in Case 2 and c.376G>A (p.E126K) in Case 8. Nerve conduction study or sural nerve biopsy of all 10 patients indicated axonal type peripheral neuropathy. CONCLUSION: We identified GDAP1 variants in approximately 1% of our cohort with IPNs, and established a founder mutation in half of these patients. Our study originally described the mutational spectrum and clinical features of GDAP1-related CMT patients in Japan.

Immunosuppression Modification by Everolimus With Minimization of Calcineurin Inhibitors Recovers Kidney Graft Function Even in Patients With Very Late Conversion and Also With Poor Graft Function.

BACKGROUND: Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects. METHODS: Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed. The average posttransplant period at conversion was 7.4 years and no less than 3 years. Conversion of immunosuppression was accomplished by reducing CNI by 40% in dose and beginning EVR at 1 or 1.5 mg. Changes in graft function were examined, and adverse effects were evaluated. RESULTS: Significant improvement in graft function was observed quickly after EVR administration, and it had persisted for 1 year after conversion as a 7% increase in estimated glomerular filtration rate. No obvious acute rejection was observed. Further analyses concerning "timing of EVR conversion" and "graft function at conversion" were performed. Graft function was significantly improved even in patients with late conversion at 2 to 10 years. The estimated glomerular filtration rate was significantly improved even in patients with poor function. CONCLUSIONS: We concluded that this modification to the immunosuppressive regimen, as expected, reduced CNI nephrotoxicity. Our results showed that even patients with very late conversion or poor graft function also benefited from EVR conversion with CNI minimization.

Identification and functional activity of a staphylocoagulase type XI variant originating from staphylococcal food poisoning isolates.

UNLABELLED: Staphylocoagulase, an extracellular protein secreted by Staphylococcus aureus, has been used as an epidemiological marker. At least 12 serotypes and 24 genotypes subdivided on the basis of nucleotide sequence have been reported to date. In this study, we identified a novel staphylocoagulase nucleotide sequence, coa310, from staphylococcal food poisoning isolates that had the ability to coagulate plasma, but could not be typed using the conventional method. The protein encoded by coa310 contained the six fundamental conserved domains of staphylocoagulase. The full-length nucleotide sequence of coa310 shared the highest similarity (77·5%) with that of staphylocoagulase-type (SCT) XIa. The sequence of the D1 region, which would be responsible for the determination of SCT, shared the highest similarity (91·8%) with that of SCT XIa. These results suggest that coa310 is a novel variant of SCT XI. Moreover, we demonstrated that coa310 encodes a functioning coagulase, by confirming the coagulating activity of the recombinant protein expressed from coa310. This is the first study to directly demonstrate that Coa310, a putative SCT XI, has coagulating activity. These findings may be useful for the improvement of the staphylocoagulase-typing method, including serotyping and genotyping. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to identify a novel variant of staphylocoagulase type XI based on its nucleotide sequence and to demonstrate coagulating activity in the variant using a recombinant protein. Elucidation of the variety of staphylocoagulases will provide suggestions for further improvement of the staphylocoagulase-typing method and contribute to our understanding of the epidemiologic characterization of Staphylococcus aureus.

FoxO1 signaling plays a pivotal role in the cardiac telomere biology responses to calorie restriction.

This study examined whether the forkhead transcription factors of O group 1 (FoxO1) might be involved in telomere biology during calorie restriction (CR). We used FoxO1-knockout heterozygous mice (FoxO1(+/-)) and wild-type mice (WT) as a control. Both WT and FoxO1(+/-) were subjected to ad libitum (AL) feeding or 30% CR compared to AL for 20 weeks from 15 weeks of age. The heart-to-body weight ratio, blood glucose, and serum lipid profiles were not different among all groups of mice at the end of the study. Telomere size was significantly lower in the FoxO1(+/-)-AL than the WT-AL, and telomere attrition was not observed in either WT-CR or FoxO1(+/-)-CR. Telomerase activity was elevated in the heart and liver of WT-CR, but not in those of FoxO1(+/-)-CR. The phosphorylation of Akt was inhibited and Sirt 1 was activated in heart tissues of WT-CR and FoxO1(+/-)-CR. However, the ratio of conjugated to cytosolic light chain 3 increased and the level of p62 decreased in WT-CR, but not in FoxO1(+/-)-CR. A marker of oxidative DNA damage, 8-OhdG, was significantly lower in WT-CR only. The level of MnSOD and eNOS increased, and the level of cleaved caspase-3 decreased in WT-CR, but not FoxO1(+/-)-CR. Echocardiography showed that the left ventricular end-diastolic and systolic dimensions were significantly lower in WT-CR or FoxO1(+/-)-CR than WT-AL or FoxO1(+/-)-AL, respectively. The present studies suggest that FoxO1 plays beneficial roles by inducing genes involved in telomerase activity, as well as anti-oxidant, autophagic, and anti-apoptotic genes under conditions of CR, and suggest that FoxO1 signaling may be an important mediator of metabolic equilibrium during CR.

Forced expression of PDX-1 gene makes hepatoma cells to acquire glucose-responsive insulin secretion while maintaining hepatic characteristic.

Evidence shows that forced expression of the PDX1 gene converts hepatoma cells, mouse liver epithelial cells (MLECs) and HepaRG cells, into insulin—producing cells, β—cells, or islets of Langerhans. However, no reports have investigated the characteristics of mouse or human hepatocytes introduced with the PDX1 gene over prolonged observation periods. In this study, we immunohistologically and molecularly investigated the alternative processes induced by PDX1 gene introduction in mouse and human hepatocytes over prolonged observation periods using immunocytochemistry, immunofluorescence, polymerase chain reaction (PCR), Western blotting, and flow cytometry (FCM) analysis. Immunocytochemical and immunofluorescent observations showed that MLECs and HepaRG cells on 2 and 21 days after introduction of the PDX1 gene comprised cells double—positive for insulin and albumin. Additionally, they showed MAFA expression and glucose—responsive insulin secretion with glucokinase expression. However mouse embryonic fibroblasts introduced with PDX1—GFP could not acquire glucose—responsive insulin secretion and glucokinase expression. Subsequently, we hypothesized that the number of albumin—positive MLECs and HepaRG cells would decrease after introduction of PDX1 due to the conversion of MLECs and HepaRG cells into insulin—producing cells. However, FCM analysis indicated that the number of albumin—positive MLECs and HepaRG cells was not altered by the introduction of PDX1. We thought that MLECs and HepaRG cells introduced with the PDX1 gene could acquire a functional insulin secretory capacity without conversion to β—cells, or islets of Langerhans, and the acquisition could need glucokinase expression.

Associations between abdominal visceral fat and surrogate measures of obesity in Japanese men with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: There are ethnic differences in the distribution of abdominal obesity associated with metabolic disorders. In Japan, the appropriate reference values for abdominal obesity have not been established in individuals with spinal cord injury (SCI), although there are a number of studies in Western countries. This study evaluates the associations between visceral fat area (VFA), waist circumference (WC) and body mass index (BMI), to examine cutoffs and estimate the error for WC and BMI equivalent to 100 cm(2) VFA in Japanese men with SCI. SETTING: National Rehabilitation Center for Persons with Disabilities, Japan. METHODS: Seventy-four men (aged 45.6 (s.d. 14.3) years) participated in the study. VFA was quantified using computed tomography at the level of the umbilicus, and associations were determined using nonlinear regression analysis. The error of the estimates from the regression equation was assessed using a Bland-Altman plot. RESULTS: The mean VFA was 101.2 (s.d. 53.0) cm(2) and 32 subjects had a VFA ⩾100 cm(2). The cutoffs for a VFA of 100 cm(2) were WC, 81.3 cm and BMI, 22.5 kg m(-2). The relationship between the estimated and actual values showed that the error increased as VFA increased, which resulted in a negative proportional bias. CONCLUSION: The suggested cutoff for Japanese men with SCI is a VFA of 100 cm(2), which is lower than that in the healthy able-bodied population for both WC and BMI. Further investigation is needed to determine the reference value for estimating SCI-specific VF accumulation.

Wearable blood flowmeter appcessory with low-power laser Doppler signal processing for daily-life healthcare monitoring.

A new appcessory for monitoring peripheral blood flow in daily life consists of a wearable laser Doppler sensor device and a cooperating smart phone application. Bluetooth Low Energy connects them wirelessly. The sensor device features ultralight weight of 15 g and an intermittent signal processing technique that reduces power consumption to only 7 mW at measurement intervals of 0.1 s. These features enable more than 24-h continuous monitoring of peripheral blood flow in daily life, which can provide valuable vital-sign information for healthcare services.

Variable alteration of regional tissue oxygen pressure in rat hippocampus by acute swimming exercise.

UNLABELLED: One of the events in the brain is an increasing cerebral blood flow during exercise. The tissue oxygen level may be increased because blood flow correlates with tissue oxygen level. However, it is little known whether the tissue oxygen pressure in hippocampal region (Hip-pO2) will be affected by exercise. AIMS: The aim of this study is to examine Hip-pO2 levels in the hippocampus and its changes during exercise. MAIN METHODS: We applied improved Clark-type electrodes to measure Hip-pO2 level in the hippocampus of rats that were subjected to three groups, 2h swimming without weights (low intensity, n=6), 2h swimming with a 5 g weight (moderate intensity, n=6), and 2h swimming with a 10 g weight (high intensity, n=6). KEY FINDINGS: Exercise affected the Hip-pO2 level, the responses varied with the exercise intensity and duration. Interestingly during and after the Low intensity swimming the Hip-pO2 level showed long lasting enhancement (10-20% above resting level). But the moderate and high intensity swimming increased Hip-pO2 level at the start of the swimming (50%, P<0.05 and slightly above resting level, respectively, at 10 min of 2h swimming) and then began to decrease (at 120 min and 10 min of 2h swimming, respectively), and suppressed the Hip-pO2 levels during post exercise resting period (2h) (85-95% of resting level, NS and 60-70% of resting level P<0.05, respectively). SIGNIFICANCE: We propose that exercise-induced hippocampal hyper/hypo oxygen condition may participate in beneficial exercise effects on brain function.

Facilitative effect of serotonin(1A) receptor agonists on cognition in patients with schizophrenia.

Disturbances of cognitive function are considered to largely affect the outcome in patients with schizophrenia. There is much attention to the role of psychotropic compounds acting on serotonin (5-HT) receptors in ameliorating cognitive deficits of the disease. Among the 5-HT receptor subtypes, the 5-HT(1A) receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence. The neural network underlying the ability of 5-HT(1A) agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and gamma-aminobutyric acid neurons. Recent advances of electrophysiological measures, such as event-related potentials, have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs or related compounds acting directly or indirectly on 5-HT(1A) receptors. These considerations are expected to promote the development of novel therapeutics for the betterment of functional outcome in people suffering from schizophrenia.

Efficacy and safety of bipolar electrode grasping forceps for laparoscopic myomectomy in uterine cervical myoma.

INTRODUCTION: Myomectomy for cervical myoma is problematic because cervical myomas are very close to neighboring structures, such as the ureters, uterine artery, bladder and rectum. There are a few reports on laparoscopic myomectomy for cervical myomas to avoid blood loss, such as occlusion of iliac arteries and clipping of the uterine artery. We evaluated the efficacy and safety of bipolar electrode grasping forceps for laparoscopic myomectomy in uterine cervical myoma. METHODS: From November 2006 to May 2009, eight women with uterine cervical myoma underwent laparoscopic myomectomy. We employed electrode grasping forceps with a combination of two tenaculums for separating and securing hemostatsis. RESULTS: Seven of eight cases were successfully treated by laparoscopic myomectomy, but one patient, with a large 900-g myoma was converted to the laparotomy as a result of blood loss (1800 mL). Among the other seven cases, the average weight of the myoma was 132 g (range, 16-310 g) and the operating time was 176 min. (range, 125-255 min). No complications occurred. Of the four cases who wanted to become pregnant postoperatively, two became pregnant and delivered by Caesarean section. CONCLUSION: These findings indicate that bipolar electrode grasping forceps using two tenaculums for traction of the myoma are useful for laparoscopic myomectomy in cervical myomas.

The correlation between the telomeric parameters and the clinical laboratory data in the patients with brain infarct and metabolic disorders.

OBJECTIVE: To elucidate the correlation between the telomere length and subtelomeric methylated status in peripheral leukocytes and the laboratory data of inpatients with brain infarction and metabolic disorders. This is the first report describing a link between routine clinical laboratory data and genomic aging. DESIGN: Cross-sectional population-based study. SETTING: Chronic disease ward of Kyushu University Hospital at Beppu in Japan. PARTICIPANTS: Inpatients with brain infarction and metabolic disorders. MEASUREMENTS: The laboratory data of male patients were collected and the telomeric parameters in their peripheral leukocytes were determined by a Southern blot analysis with methylation-sensitive and insensitive isoschizomers. Any correlations between the laboratory data and the telomeric parameters were assessed. RESULTS: The patients revealed a significant correlation among the fasting blood sugar, HbA1c, serum creatinine and urea nitrogen levels with the mean telomere length, expression of long telomeres ( > 9.4 kb), or the subtelomeric hypermethylation status of long telomeres. CONCLUSION: Our results suggested that the hyperglycemia and renal function of patients with metabolic disorders correlated positively with the aging-associated telomeric changes.

Enhanced growth inhibition of metastatic lung tumors by intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes in mice.

Interleukin 12 (IL-12) is a proinflammatory cytokine with antitumor activity. All-trans-retinoic acid (ATRA) exerts antitumor effects by regulating a variety of gene expressions, including tumor necrosis factor receptor 1 (TNFR1), increases the number of TNFR1 and potentiates TNF-alpha-induced apoptosis in cancer cells. In this study, ATRA-incorporated cationic liposome (ATRA-cationic liposome)/IL-12 plasmid DNA (pDNA) complexes were prepared to improve therapeutic efficacy of cationic liposome/IL-12 pDNA complexes in a mouse model of metastatic lung tumor after intravenous injection. IL-12 production in lungs by ATRA-cationic liposome/IL-12 pDNA complexes was comparable with that by cationic liposome/IL-12 pDNA complexes. The number of metastatic tumor cells (colon26/Luc) was quantitatively evaluated by measuring luciferase activity. ATRA-cationic liposome/IL-12 pDNA complexes reduced the number of colon26/Luc cells and tumor nodules in lungs. ATRA-cationic liposome/IL-12 pDNA complexes significantly prolonged the survival time of mice, whereas cationic liposome/IL-12 pDNA only slightly prolonged it. ATRA-cationic liposome/IL-12 pDNA complexes increased the TNFR1 mRNA upregulation and the number of apoptotic cells in the lung. Moreover, reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were observed in mice treated with ATRA-cationic liposome/IL-12 pDNA complexes. These results suggest that intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes is an effective method for the treatment of lung metastasis in mice.

Detailed images of asteroid 25143 Itokawa from Hayabusa.

Rendezvous of the Japanese spacecraft Hayabusa with the near-Earth asteroid 25143 Itokawa took place during the interval September through November 2005. The onboard camera imaged the solid surface of this tiny asteroid (535 meters by 294 meters by 209 meters) with a spatial resolution of 70 centimeters per pixel, revealing diverse surface morphologies. Unlike previously explored asteroids, the surface of Itokawa reveals both rough and smooth terrains. Craters generally show unclear morphologies. Numerous boulders on Itokawa's surface suggest a rubble-pile structure.

Suppression of TNFalpha production in LPS induced liver failure in mice after intravenous injection of cationic liposomes/NFkappaB decoy complex.

NFkappaB decoy, double stranded oligonucleotides containing NFkappaB binding sequences, inhibits NFkappaB-mediated production of inflammatory cytokines, and therefore NFkappaB decoy has been applied to several diseases. However, naked NFkappaB decoy, which is quickly cleared from the circulation in mice after intravenous injection, is readily absorbed into the systemic circulation. In order to deliver enough NFkappaB decoy for a therapeutic effect, it is necessary to develop a carrier, which enables much more NFkappaKB decoy to transfer to the target cells. In this study, using N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride (DOTMA)/cholesterol (1 :1) liposomes, the therapeutic effect of NFkappaB decoy was investigated in an LPS induced acute hepatitis model mice. The mean diameter of the cationic liposomes/NFkappaB decoy complex was about 70.9 nm and the zeta potential of complex was about 37.4 mV. Tissue distribution was determined by measuring the radioactivity of a cationic liposomes/ [32P] NFkappaB decoy complex after intravenous injection. The cationic liposomes/[32P] NFkappaB decoy complex was rapidly accumulated in the lung and gradually moved to the liver. The therapeutic effect was determined by the serum concentration of TNFalpha in LPS treated mice. The production of TNFalpha was significantly inhibited by cationic liposomes/NFkappaB decoy complex but not by cationic liposomes/random decoy complex or naked NFkappaB decoy. These results suggested that NFkappaB decoy therapy could be achieved using cationic liposomes. This information is of great value for the design of NFkappaB decoy carrier systems.

Cardiorespiratory responses during passive walking-like exercise in quadriplegics.

STUDY DESIGN: Cross-sectional and comparative investigation using quadriplegics (QP) and nondisabled subjects (ND). OBJECTIVE: To evaluate cardiorespiratory responses during passive walking-like exercise (PWE) in QP. SETTING: National Rehabilitation Center for Persons with Disabilities in Japan. METHOD: The subjects were seven male QP with complete lesion (age: 27.0 +/- 5.4, injured level: C6-C7) and six male ND (age: 26.3 +/- 4.5). Cardiorespiratory responses were measured until voluntary fatigue during PWE, the rhythmical activity of paralyzed lower limbs synchronized with arm movements. RESULTS: There were no significant differences in oxygen consumption (VO(2)), pulmonary ventilation (VE), heart rate (HR) and oxygen pulse (O(2) pulse) between QP and ND during PWE. ND showed increased ventilatory equivalent for oxygen (VE/VO(2) ratio) during exercise, while QP showed a significantly greater respiratory rate (RR) during exercise than ND (P < 0.05). CONCLUSION: PWE elicited an increase in VO(2) with workload increment in QP similar to ND. However, higher RR suggested the intrinsic dysfunction of RR control during submaximal exercise in QP. From these results, it was thought that respiratory response would be the restriction factor of efficient oxygen transportation during PWE in QP.

A new congenital form of X-linked autophagic vacuolar myopathy.

In a new family with X-linked congenital autophagic vacuolar myopathy (AVM), seven affected boys presented with congenital hypotonia, dyspnea, and dysphagia with delayed motor milestones. Muscle pathology revealed autophagic vacuoles with sarcolemmal features, multilayered basal lamina with marked sarcolemmal deposition of C5-9 membrane attack complex and calcium, histologically indistinguishable from childhood-onset X-linked myopathy with excessive autophagy (XMEA). Haplotype analysis suggests that this new AVM and XMEA may be allelic despite different clinical presentations.