NF-kB decoy oligodeoxynucleotide preserves disc height in a rabbit anular-puncture model and reduces pain induction in a rat xenograft-radiculopathy model.

While it is known that the degenerated intervertebral disc (IVD) is one of the primary reasons for low-back pain and subsequent need for medical care, there are currently no established effective methods for direct treatment. Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes' expression, among which are inflammatory cytokines, in many tissues including the IVD. NF-κB decoy is an oligodeoxynucleotide containing the NF-κB binding site that entraps NF-κB subunits, resulting in suppression of NF-κB activity. In the present preclinical study, NF-κB decoy was injected into degenerated IVDs using the rabbit anular-puncture model. In terms of distribution, NF-κB decoy persisted in the IVDs up to at least 4 weeks after injection. The remaining amount of NF-κB decoy indicated that it fit a double-exponential-decay equation. Investigation of puncture-caused degeneration of IVDs showed that NF-κB decoy injection recovered, dose-dependently, the reduced disc height that was associated with reparative cell cloning and morphological changes, as assessed through histology. Gene expression, by quantitative real-time polymerase chain reaction (qRT-PCR), showed that NF-κB decoy attenuated inflammatory gene expression, such as that of interleukin-1 and tumor necrosis factor-α, in rabbit degenerated IVDs. NF-κB decoy also reduced the pain response as seen using the "pain sensor" nude rat xenograft-radiculopathy model. This is the first report demonstrating that NF-κB decoy suppresses the inflammatory response in degenerated IVDs and restores IVD disc height loss. Therefore, the intradiscal injection of NF-κB decoy may have the potential as an effective therapeutic strategy for discogenic pain associated with degenerated IVDs.

Filamentous fungi with high paraquat-degrading activity isolated from contaminated agricultural soils in northern Thailand.

The contamination of paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) herbicide from the farming area has become a public concern in many countries. This herbicide harms to human health and negatively effects the soil fertility. Several methods have been introduced for the remediation of paraquat. In this study, 20 isolates of the paraquat-tolerant fungi were isolated from the contaminated soil samples in northern Thailand. We found that isolate PRPY-2 and PFCM-1 exhibited the highest degradation activity of paraquat on synthetic liquid medium. About 80 and 68% of paraquat were removed by PRPY-2 and PFCM-1 respectively after 15 days of cultivation. Based on the morphological characteristic and molecular analysis, the fungal isolate PRPY-2 and PFCM-1 were identified as Aspergillus tamarii and Cunninghamella sp. respectively. The biosorption of paraquat on these fungal mycelia was also investigated. It was found that only 8-10% of paraquat could be detected on their mycelia, while 24-46% of paraquat was degraded by fungal mycelia. This is the first report on paraquat degrading ability by A. tamarii and Cunninghamella sp. It is demonstrated that these filamentous fungi are promising microorganisms available for remediation of paraquat contaminated environment.

Epidemiology of hospitalised paediatric community-acquired pneumonia and bacterial pneumonia following the introduction of 13-valent pneumococcal conjugate vaccine in the national immunisation programme in Japan.

Studies on community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP) related to the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in Asia are scarce. This study aimed to investigate the epidemiological and microbiological determinants of hospitalised CAP and PP after PCV13 was introduced in Japan. This observational hospital-based surveillance study included children aged ⩽15 years, admitted to hospitals in and around Chiba City, Japan. Participants had bacterial pneumonia based on a positive blood or sputum culture for bacterial pathogens. Serotype and antibiotic-susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae isolates from patients with bacterial pneumonia were assessed. The CAP hospitalisation rate per 1000 child-years was 17.7, 14.3 and 9.7 in children aged <5 years and 1.18, 2.64 and 0.69 in children aged 5-15 years in 2008, 2012 and 2018, respectively. There was a 45% and 41% reduction in CAP hospitalisation rates, between the pre-PCV7 and PCV13 periods, respectively. Significant reductions occurred in the proportion of CAP due to PP and PCV13 serotypes. Conversely, no change occurred in the proportion of CAP caused by H. influenzae. The incidence of hospitalised CAP in children aged ⩽15 years was significantly reduced after the introduction of PCV13 in Japan. Continuous surveillance is necessary to detect emerging PP serotypes.

Prognostic significance of genetic biomarkers in isocitrate dehydrogenase-wild-type lower-grade glioma: the need to further stratify this tumor entity - a meta-analysis.

The clinical outcomes of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade glioma (LGG) have been the subject of debate for some time. In this meta-analysis, we aimed to assess the prognostic values of several known genetic markers (e.g. TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. Four electronic databases, including PubMed, Scopus, Web of Science and Virtual Health Library, were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival were calculated using a random-effect model weighted by an inverse variance method. A total of 11 studies were finally selected from 2274 articles for meta-analyses. Several genetic alterations were demonstrated to have a negative impact on prognosis of IDH-wt LGGs, specifically TERT promoter mutation (HR, 1.96; 95% CI, 1.42-2.70), H3F3A mutation (HR, 3.21; 95% CI, 1.86-5.55) and EGFR amplification (HR, 1.67; 95% CI, 1.02-2.74). However, CDKN loss, ATRX mutation and coexisting gain of chromosome 7/loss of chromosome 10 showed no clinical significance in this glioma entity. Our study results demonstrated that IDH-wt LGGs are heterogeneous in clinical outcome and not all tumors have a poor prognosis. The presence of TERT promoter mutation, H3F3A mutation and EGFR amplification showed negative prognostic impacts in this tumor entity. These genetic events can be used to better stratify patient outcomes.

Differential Expression of Claudin 1 and 4 in Basal Cell Carcinoma of the Skin.

Basal cell carcinoma (BCC) is the most common human malignancy. The biological behavior of this entity is remarkably indolent. Claudin plays an important role in tight junctions, regulating paracellular passage of variable substance including growth factors and maintaining the polarity of epithelia. Up- or downregulated claudin expression has been reported in many cancers. Nevertheless, claudin expression in BCC of the skin remains unclear. We therefore examined the status of claudin 1 and 4 expressions in BCC and adjacent normal skin by immunohistochemistry (IHC). Our IHC results demonstrated high claudin 1 expression and low claudin 4 expression in 33 of 34 lower-grade BCCs. In lower-grade BCC, claudin 1 was increased and claudin 4 was decreased compared with the normal skin. Claudin 1 was inclined to be highly expressed in the membrane and cytoplasm of tumour cells in the periphery of tumour nest. Conversely, almost all lower-grade BCCs (33/34) and one of two higher-grade BCC lacked or showed focal positivity for claudin 4. These results imply that the expression pattern is characteristics of lower-risk BCC. Interestingly, one of the two higher-grade BCCs demonstrated the converse expression patterns of claudins, with decreased claudin 1 and increased claudin 4. The combination of immunohistochemical claudin 1 and 4 expression may offer a useful ancillary tool for the pathological diagnosis of BCC. Furthermore, membranous and intracellular claudins may present future therapeutic targets for uncontrollable BCC.

Electro-optic Bdot probe measurement of magnetic fluctuations in plasma.

We propose a combined use of a Pockels electro-optic sensor with a pickup loop coil (Bdot probe) for the measurement of magnetic fluctuations in plasmas. In this method, induced fluctuating voltage on the coil loop is converted into an optical signal by a compact electro-optic sensor in the vicinity of the measurement point and is transferred across optical fiber that is unaffected by electric noise or capacitive load issues. Compared with conventional Bdot probes, the electro-optic Bdot probe (1) is electrically isolated and free from noise pickup caused by the metallic transmission line and (2) can be operated at a higher-frequency range because of the smaller capacitance of the operation circuit, both of which are suitable for many plasma experiments. Conversely, the sensitivity of the current electro-optic Bdot probe arrangement is still significantly lower than that of conventional Bdot probes. A preliminary measurement result with the electro-optic Bdot probe showed the detection of a magnetic fluctuation signal around the cyclotron frequency range in the RT-1 magnetospheric plasma experiment.

Viral level is an indicator of long-term outcome of hepatitis B virus e antigen-negative carriers with persistently normal serum alanine aminotransferase levels.

The association between viral level and the long-term outcomes of hepatitis B virus (HBV) carriers who test negative for hepatitis B virus e antigen (HBeAg) but have persistently normal serum alanine aminotransferase levels (PNALT) remains unclear. We examined hepatocarcinogenesis, hepatitis reactivation, predictive factors and the time course of HBV DNA levels during follow-up in 104 HBeAg-negative Japanese carriers with PNALT. During a mean follow-up period of 6.4 ± 3.4 years, 5 patients (4.8%) had hepatocarcinogenesis and 14 (13.5%) had hepatitis reactivation. At 5 and 10 years, the cumulative rates of hepatocarcinogenesis were 2.4% and 9.9%, while those of hepatitis activation were 13.7% and 15.5%, respectively. An HBV DNA level of ≥5 log10 copies/mL was the sole predictor of hepatocarcinogenesis with a univariate analysis. An HBV DNA level of ≥5 log10 copies/mL and an alanine aminotransferase (ALT) level of >20 to ≤40 IU/L were independent predictors of hepatitis reactivation in a Cox model. Because there was no association between hepatocarcinogenesis and ALT activity, the HBV DNA level was considered an essential predictor. In addition, the baseline HBV DNA level was related to the future level and was not subject to wide fluctuations. Our results showed that an HBV DNA level of ≥5 log10 copies/mL predicts subsequent hepatocarcinogenesis and hepatitis reactivation in HBeAg-negative carriers with PNALT. As the baseline HBV DNA level reflects the future level, appropriate clinical management according to the viral level is expected to decrease future risk.

Neuroendocrine ductal carcinoma in situ of the breast: cytological features in 32 cases.

OBJECTIVE: The purpose of this study was to clarify the cytological features of neuroendocrine ductal carcinoma in situ (NE-DCIS) of the breast. METHODS: We analysed the cytopathological findings in 22 fine needle aspiration (FNA) smears and 17 nipple discharge smears obtained from 32 Japanese patients with NE-DCIS. RESULTS: The background of the FNA smears was clear (59%), mucoid (23%), haemorrhagic (14%) or necrotic (5%). Most of the FNA smears (95%) showed high cellularity. Characteristically, NE-DCIS cells were loosely arranged in three-dimensional solid clusters or singly dispersed. Well-developed vascular cores with or without malignant cells were occasionally recognized. The tumour cells were polygonal or spindle-shaped with a fine granular, abundant cytoplasm. Nuclei with finely granular chromatin were round or oval and often eccentrically located (plasmacytoid appearance). Mitotic figures were infrequent. Nuclear grade was estimated to be low in 86%. Most nipple discharge smears had fairly low cellularity with poorly preserved cell clusters in a markedly haemorrhagic background, although two (12%) were extremely cellular with cytological characteristics similar to those of the FNA smears. Pre-operative cytological malignant diagnoses were made in 42% of FNA smears and 0% of nipple discharge smears. Immunohistochemistry for neuroendocrine markers (chromogranin A and synaptophysin) confirmed the neuroendocrine nature of this tumour in adequate cytological specimens. CONCLUSIONS: NE-DCIS has distinctive cytological features and can therefore be diagnosed as a neuroendocrine tumour in most FNAs and some nipple discharge smears by cytological examination employing immunohistochemical techniques. We emphasize that a breast lesion with these features may be in situ and not invasive, and also that there is a risk of under-diagnosis.

Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies.

OBJECTIVES: To assess whether smoking is a risk factor for developing rheumatoid arthritis (RA). DESIGN: Meta-analysis. DATA SOURCES: were observational studies that examined the association between smoking history and the risk of developing RA identified through Medline and EMBASE (from 1966 to December 2006), relevant books and a reference search. Two authors independently extracted the following: authors' names, publication year, sample size, participant characteristics, odds ratios (OR) or relative risks, adjustment factors, study design and area where the study was conducted. Data syntheses were based upon random effects model. Summarised syntheses effects were expressed by OR. RESULTS: Sixteen studies were selected from among 433 articles. For men, summary OR for ever, current and past smokers were 1.89 (95% CI 1.56 to 2.28), 1.87 (1.49 to 2.34) and 1.76 (1.33 to 2.31), respectively. For rheumatoid factor-positive (RF+) RA, summary OR for ever, current and past smokers were 3.02 (2.35 to 3.88), 3.91 (2.78 to 5.50) and 2.46 (1.74 to 3.47), respectively. Summary OR for 20 or more pack-years of smoking was 2.31 (1.55 to 3.41). For women, summary OR for ever, current and past smokers were 1.27 (1.12 to 1.44), 1.31 (1.12 to 1.54) and 1.22 (1.06 to 1.40), respectively. For RF+ RA, summary OR for ever, current and past smokers were 1.34 (0.99 to 1.80), 1.29 (0.94 to 1.77) and 1.21 (0.83 to 1.77). Summary OR for 20 or more pack-years of smoking was 1.75 (1.52 to 2.02). CONCLUSION: Smoking is a risk factor for RA, especially RF+ RA men and heavy smokers.

Spinal cord injury is not negligible after TEVAR for lower descending aorta.

OBJECTIVES: To clarify the incidence of spinal cord injury (SCI) after thoracic endovascular aneurysm repair (TEVAR), we investigate the intercostal/lumbar arteries that supply the Adamkiewicz artery (ICA-AKA). PATIENTS: Among 81 patients subjected to TEVAR, we retrospectively reviewed the clinical records of 50 patients (range: 57-86 (median age: 77) years, 41 males) who underwent TEVAR for part of or the whole distal descending aorta (T7 to L2) after identification of ICA-AKA by magnetic resonance angiography (MRA) or computed tomography angiography (CTA). RESULTS: The 50 patients were classified into group A: 17 patients whose patent ICA-AKA was not covered, group B: 24 patients whose ICA-AKA was covered and group C: nine patients in whom no patent ICA-AKA was identified. Only three patients in group B suffered paraplegia and of them two recovered full ambulation. The estimated incidence of permanent and transient paraplegia was 3.7% in all TEVAR patients, 6.0% when part of or the entire distal aorta was covered and 12.5% when the patent ICA-AKA was covered. The length of aortic coverage in patients with paraplegia was >300 mm. CONCLUSIONS: Paraplegia after TEVAR occurred in one of eight patients in whom the stent graft covered ICA-AKA. Long coverage of the aorta including the ICA-AKA was critical. To prevent this serious complication, identification of the ICA-AKA is crucial.

Evaluation of Papillomacular Nerve Fiber Bundle Thickness in Glaucoma Patients with Visual Acuity Disturbance.

PURPOSE: Assessing the papillomacular nerve fiber bundle (PMB) can identify glaucoma patients with decreased visual acuity. In this study, we explore efficient methods for evaluating PMB thickness in glaucoma patients, based on swept source-optical coherence tomography (SS-OCT). METHODS: This study included 347 eyes of 205 open-angle glaucoma (OAG) patients. Patients were excluded if they had best-corrected decimal visual acuity < 0.3, axial length >28 mm, non-glaucoma ocular disease, or systemic disease affecting the visual field. We obtained vertical 12.0 × 9.0 mm 3D volume scans covering both the macular and optic disc regions with SS-OCT (DRI OCT Triton, Topcon), and measured the thickness of the PMB, as well as average macular retinal nerve fiber layer thickness (mRNFLT) and macular ganglion cell complex thickness (mGCCT) in the macular map and temporal-quadrant circumpapillary RNFL thickness (tcpRNFLT). We also measured central-strip RNFLT (csRNFLT) and GCC (csGCCT) in a 1.5 × 6.6 mm area of the scan centered between the fovea and optic nerve head. CsRNFLT and csGCCT were divided lengthwise into three 1.5 × 2.2 mm sections. We then calculated Spearman's rank correlation coefficient between these OCT measurements and visual acuity. Logistic regression analysis was used to find the cutoff value for the OCT measurements to predict logMAR < 0. RESULTS: The correlation coefficients with logMAR were 0.38 for mRNFLT, 0.44 for mGCCT, 0.37 for middle csRNFLT, 0.50 for middle csGCCT, and 0.33 for tcpRNFLT (all P < .0001). For middle csGCCT, the area under the curve indicating decreased visual acuity was 0.80, with a cutoff value of 88.6 µm (P < .001). CONCLUSIONS: We found strong associations between OCT parameters in the PMB, especially middle csGCCT, and visual acuity in patients with OAG. The thickness of the PMB may therefore be valuable information for glaucoma care and may help prevent visual acuity disturbance.

Neuroendocrine ductal carcinoma in situ (NE-DCIS) of the breast--comparative clinicopathological study of 20 NE-DCIS cases and 274 non-NE-DCIS cases.

UNLABELLED: Kawasaki T, Nakamura S, Sakamoto G, Murata S, Tsunoda-shimizu H, Suzuki K, Takahashi O, Nakazawa T, Kondo T & Katoh R (2008) Histopathology53, 288-298Neuroendocrine ductal carcinoma in situ (NE-DCIS) of the breast - comparative clinicopathological study of 20 NE-DCIS cases and 274 non-NE-DCIS cases Aims: To clarify the clinicopathological significance of breast neuroendocrine ductal carcinoma in situ (NE-DCIS), i.e. DCIS in which >50% of cells immunohistochemically express NE markers (chromogranin A and/or synaptophysin), 20 NE-DCIS were studied and the findings compared with those of 274 non-NE-DCIS. METHODS AND RESULTS: NE-DCIS accounted for 6.8% of all DCIS. Mean patient age was 50.4 years for NE-DCIS and 49.6 years for non-NE-DCIS (P = 0.66). The main clinical presentation of NE-DCIS was a bloody nipple discharge, seen in 72%, significantly different from the 5% in non-NE-DCIS cases (P < 0.01). Carcinoma was preoperatively diagnosed in 67% of NE-DCIS and 95% of non-NE-DCIS cases (P < 0.01). NE-DCIS was histologically characterized by a predominantly solid growth of cancer cells with fine-granular cytoplasm and ovoid, or occasionally spindle-shaped nuclei. A well-developed vascular network was also common. Nuclear grades and Van Nuys classification were significantly lower for NE-DCIS than for non-NE-DCIS (P < 0.01). The mean MIB-1 labelling index was 4.3% in NE-DCIS and 8.1% in non-NE-DCIS (P < 0.01). Furthermore, NE-DCIS cases had significantly higher oestrogen and progesterone receptor and lower HER2 scores than non-NE-DCIS cases (P < 0.01). CONCLUSIONS: NE-DCIS has characteristic clinicopathological features and can, therefore, be regarded as a distinct variant of DCIS.

VLA-4 blockade suppresses endotoxin-induced uveitis: in vivo evidence for functional integrin up-regulation.

Leukocyte adhesion to the vascular wall is a critical early step in the pathogenesis of inflammatory diseases and is mediated in part by the leukocyte integrin, VLA-4, which binds to endothelial vascular cell adhesion molecule (VCAM) -1. Here, we investigate VLA-4's role in endotoxin-induced uveitis (EIU). At various time points (6-48 h) after EIU induction, the severity of the inflammation was evaluated by quantifying cell and protein content in the aqueous fluid, firm leukocyte adhesion in the retinal vessels, and the number of extravasated leukocytes into the vitreous. Functional activation of VLA-4 in vivo was investigated in our previously introduced autoperfused micro flow chamber assay. Firm adhesion of EIU leukocytes to immobilized VCAM-1 under physiological blood flow conditions was significantly increased compared with normal controls (P<0.05), suggesting an important role for VLA-4 in EIU. VLA-4 blockade in vivo significantly suppressed all uveitis-related inflammatory parameters studied, decreasing the clinical score by 45% (P<0.01), protein content in the aqueous fluid by 21% (P<0.01), retinal leukostasis by 68% (P<0.01), and leukocyte accumulation in the vitreous by 75% (P<0.01). Our data provide novel evidence for functional up-regulation of VLA-4 during EIU and suggest VLA-4 blockade as a promising therapeutic strategy for treatment of acute inflammatory eye diseases.

Antiapoptotic function of 17AA(+)WT1 (Wilms' tumor gene) isoforms on the intrinsic apoptosis pathway.

The WT1 gene is overexpressed in human primary leukemia and a wide variety of solid cancers. The WT1 gene is alternatively spliced at two sites, yielding four isoforms: 17AA(+)KTS(+), 17AA(+)KTS(-), 17AA(-)KTS(+), and 17AA(-)KTS(-). Here, we showed that 17AA(+)WT1-specific siRNA induced apoptosis in three WT1-expressing leukemia cell lines (K562, HL-60, and Kasumi-1), but not in WT1-non-expressing lymphoma cell line (Daudi). 17AA(+)WT1-specific siRNA activated caspase-3 and -9 in the intrinsic apoptosis pathway but not caspase-8 in the extrinsic one. On the other hand, 17AA(-)WT1-specific siRNA did not induce apoptosis in the three WT1-expressing cell lines. The apoptosis was associated with activation of proapoptotic Bax, which was activated upstream of the mitochondria. Constitutive expression of 17AA(+)WT1 isoforms inhibited apoptosis of K562 leukemia cells induced by apoptosis-inducing agents, etoposide and doxorubicin, through the protection of mitochondrial membrane damages, and DNA-binding zinc-finger region of 17AA(+)WT1 isoform was essential for the antiapoptotic functions. We further studied the gene(s) whose expression was altered by the expression of 17AA(+)WT1 isoforms and showed that the expression of proapoptotic Bak was decreased by the expression of 17AA(+)KTS(-)WT1 isoform. Taken together, these results indicated that 17AA(+)WT1 isoforms played antiapoptotic roles at some points upstream of the mitochondria in the intrinsic apoptosis pathway.

Theophylline accelerates human granulocyte apoptosis not via phosphodiesterase inhibition.

Theophylline, in addition to its bronchodilator effect, is reported to have an antiinflammatory action that may account for its clinical effectiveness in the reduction of inflammatory cells in the airway. In bronchial asthma, such inflammatory cytokines as GM-CSF and IL-5 are upregulated and have been proposed to cause granulocyte infiltration (neutrophils and eosinophils) in the airway by inhibition of granulocyte apoptosis. We examined the abilities of theophylline to counteract the prolongation of human granulocyte survival caused by cytokines. Theophylline was shown to shorten granulocyte survival in a dose-dependent manner. Upon incubation with a therapeutical concentration of theophylline (0.1 mM; 18 microg/ml), percentages of GM-CSF (10 ng/ml)-induced delayed apoptosis increased from 18+/-2% to 38+/-3% (p < 0.02) in neutrophils and from 21+/-2% to 35+/-2% (p < 0.02; 24-h incubation) in eosinophils. The percentage of IL-5 (5 ng/ml)-induced delayed eosinophil apoptosis also increased from 22+/-4% to 33+/-2% (P < 0. 05). In contrast, cyclic AMP (cAMP)-increasing agents (3-isobutylmethylxanthine, dibutyryl cAMP, and rolipram) inhibited granulocyte apoptosis in the control and anti-Fas antibody-treated cells. In eosinophils, the expression of bcl-2 protein decreased after incubation with theophylline. These findings suggest that theophylline accelerates granulocyte apoptosis, which may play an essential role in inflammation, and controls granulocyte longevity regardless of the elevation of intracellular cAMP levels.

Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients.

Cyclic ADP-ribose (cADPR) has been shown to be a mediator for intracellular Ca2+ mobilization for insulin secretion by glucose in pancreatic beta cells, and CD38 shows both ADP-ribosyl cyclase to synthesize cADPR from NAD+ and cADPR hydrolase to hydrolyze cADPR to ADP-ribose. We show here that 13.8% of Japanese non-insulin-dependent diabetes (NIDDM) patients examined have autoantibodies against CD38 and that the sera containing anti-CD38 autoantibodies inhibit the ADP-ribosyl cyclase activity of CD38 (P

Single motor unit F-waves in the thenar muscles studied by the multichannel surface EMG.

The thenar motor units (MUs) were studied by the multichannel surface electromyography (EMG) technique. The median nerve was stimulated at the wrist by repetitive submaximal stimulation. Three hundred consecutive evoked responses were recorded from the thenar muscles of 5 healthy volunteers with a 32 channel matrix-type multielectrode. Seven channel F-wave waveforms in a selected electrode array were classified using a template-matching method. The F-wave parameters, amplitudes, latencies and muscle fiber conduction velocities (MFCVs), were calculated to evaluate the properties of single MU F-wave. Most of the F-waves (93.3%) were composed of a single motor unit action potential (MUAP). The numbers of MU classified from single MU F-waves in 5 subjects were 11, 8, 13, 13 and 13, respectively. Many of them (84.5%) were originated from the abductor pollicis brevis (APB), and there were a few MUs originated from the flexor pollicis brevis (FPB). Significant correlations were found between F-wave amplitudes and latencies in 3 subjects.

Insulin signaling in arteries prevents smooth muscle apoptosis.

OBJECTIVE: Insulin is an antiapoptotic factor of cultured vascular cells, but it is not clear whether it also exerts antiapoptotic effects on vascular cells in vivo. We studied insulin receptor signaling in the arteries of normal and diabetic rats to establish whether insulin exhibits antiapoptotic activity toward vascular smooth muscle cells in vivo as well as in vitro. METHODS AND RESULTS: Western blot analysis and real-time polymerase chain reaction revealed alpha- and beta-subunits of the insulin receptor in association with insulin receptor substrate-1 and phosphatidylinositol 3-kinase in the media of the aorta and carotid artery. The insulin receptor signaling pathway was partially activated under physiological conditions, further activated by intravenous insulin injection, and was attenuated in streptozotocin-induced diabetic rats. Lipopolysaccharide injection induced more apoptosis of vascular smooth muscle cells in diabetic rats than in control rats, whereas insulin prevented apoptosis in the aortic wall. An in vitro study suggested that the antiapoptotic effect of insulin was mediated by phosphatidylinositol 3-kinase. CONCLUSIONS: Insulin is an antiapoptotic factor of vascular smooth muscle cells in vitro and in vivo. Decreased insulin activity on the artery may increase smooth muscle cell death and cause unstable plaque formation associated with diabetes.