Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population.

The pathogenic mechanisms underlying Schizophrenia (SZ), one of the most frequent mental disorders, are complex and poorly understood. Several evidences suggest that inflammatory processes may underpin some of its neurobiological correlates. The aim of this study was: (i) to analyze the potential association between circulating levels of the C-reactive protein (CRP), a crucial inflammatory marker, and Schizophrenia in Tunisian patients and healthy controls (HC) cohorts; (ii) to investigate the genetic diversity of three CRP variants (rs1417938, rs1130864 and rs1205) and; (iii) to analyze a potential relationship between expression and genetic data and clinical and socio demographical characteristics. CRP polymorphisms were exanimated for 155 patients and 203 HC by taqMan5'-nuclease. High-sensitivity CRP (hs-CRP) serum level was measured in 128 clinically stable out-patient SZ patients and 63 HC subjects via an automated biochemical analyzer. We found that hs-CRP levels were significantly higher in SZ patients as compared to HC. No significant differences were found when the proportions of CRP variants were compared in patients and HC. Further analysis according to clinical and socio demographical characteristics revealed a positive association with age and hypertension. Our data on an original Tunisian sample confirm the previous finding in others population groups.

The potential utility of high-intensity ultrasound to treat osteoarthritis.

Osteoarthritis (OA) is a widespread musculoskeletal disease that reduces quality of life and for which there is no cure. The treatment of OA is challenging since cartilage impedes the local and systemic delivery of therapeutic compounds (TCs). This review identifies high-intensity ultrasound (HIU) as a non-contact technique to modify articular cartilage and subchondral bone. HIU enables new approaches to overcome challenges associated with drug delivery to cartilage and new non-invasive approaches for the treatment of joint disease. Specifically, HIU has the potential to facilitate targeted drug delivery and release deep within cartilage, to repair soft tissue damage, and to physically alter tissue structures including cartilage and bone. The localized, non-invasive ultrasonic delivery of TCs to articular cartilage and subchondral bone appears to be a promising technique in the immediate future.

Improved accuracy and robustness of electron density profiles from JET's X-mode frequency-modulated continuous-wave reflectometers.

JET's frequency-modulated continuous wave (FMCW) reflectometers have been operating well with the current design since 2005, and density profiles have been automatically calculated intershot since then. However, the calculated profiles had long suffered from several shortcomings: poor agreement with other diagnostics, sometimes inappropriately moving radially by several centimeters, elevated levels of radial jitter, and persistent wriggles (strong unphysical oscillations). In this research, several techniques are applied to the reflectometry data analysis, and the shortcomings are significantly improved. Starting with improving the equilibrium reconstruction that estimates the background magnetic field, adding a ripple correction in the reconstructed magnetic field profile, and adding new inner-wall reflection positions estimated through ray-tracing, these changes not only improve the agreement of reconstructed profiles to other diagnostics but also solve density profile wriggles that were present during band transitions. Other smaller but also persistent wriggles were also suppressed by applying a localized correction to the measured beat frequency where persistent oscillations are present. Finally, the burst analysis method, as introduced by Varela et al. [Nucl. Fusion 46 S693 (2006)], has been implemented to extract the beat frequency from stacked spectrograms. Due to the strong suppression of spurious reflections, the radial jitter that sometimes would span several centimeters has been strongly reduced. The stacking of spectrograms has also been shown to be very useful for stacking recurring events, like small gas puff modulations, and extracting transport coefficients that would otherwise be below the noise level.

Two closely spaced nonsense mutations in the DMD gene in a Malaysian family.

In Duchenne muscular dystrophy (DMD), identification of one nonsense mutation in the DMD gene has been considered an endpoint of genetic diagnosis. Here, we identified two closely spaced nonsense mutations in the DMD gene. In a Malaysian DMD patient two nonsense mutations (p.234S>X and p.249Q>X, respectively) were identified within exon 8. The proband's mother carried both mutations on one allele. Multiple mutations may explain the occasional discrepancies between genotype and phenotype in dystrophinopathy.

A key to improved ion core confinement in the JET tokamak: ion stiffness mitigation due to combined plasma rotation and low magnetic shear.

New transport experiments on JET indicate that ion stiffness mitigation in the core of a rotating plasma, as described by Mantica et al. [Phys. Rev. Lett. 102, 175002 (2009)] results from the combined effect of high rotational shear and low magnetic shear. The observations have important implications for the understanding of improved ion core confinement in advanced tokamak scenarios. Simulations using quasilinear fluid and gyrofluid models show features of stiffness mitigation, while nonlinear gyrokinetic simulations do not. The JET experiments indicate that advanced tokamak scenarios in future devices will require sufficient rotational shear and the capability of q profile manipulation.

An adult case of eosinophilic pyloric stenosis maintained on remission with oral budesonide.

We describe an isolated eosinophilic pyloric stenosis in a young female. She was referred for abdominal pain, fever, weight loss and eosinophilia. A sonographic examination revealed a concentric pyloric stenosis, with antral palsy and ascites. The endoscopy confirmed the diagnosis of eosinophilic infiltration of the pylorum. After a short course of systemic steroids, the patient was switched to oral budesonide, which effectively maintained a long-term remission. Eosinophilic gastroenteritis limited to pylorum is exceptional in adults, and in our patient it was not associated with allergic other disorders. This case emphasizes the usefulness of sonografy for diagnosis and monitoring, and the clinical efficacy of oral budesonide.

Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence.

We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV -specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV -specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence.

Influence of magnetic field ripple on the intrinsic rotation of tokamak plasmas.

Using the unique capability of JET to monotonically change the amplitude of the magnetic field ripple, without modifying other relevant equilibrium conditions, the effect of the ripple on the angular rotation frequency of the plasma column was investigated under the conditions of no external momentum input. The ripple amplitude was varied from 0.08% to 1.5% in Ohmic and ion-cyclotron radio-frequency (ICRF) heated plasmas. In both cases the ripple causes counterrotation, indicating a strong torque due to nonambipolar transport of thermal ions and in the case of ICRF also fast ions.

Older Age Group in Pregnancy is Associated with Increased Arterial Stiffness.

Arterial stiffness is an index of vascular health; normal pregnancy is associated with reduced arterial stiffness. This cross sectional study compared arterial stiffness in older (≥35 years) and the younger (≤34 years) age groups of pregnant women. Arterial stiffness was assessed noninvasively in 66 pregnant women between 23 - 32 weeks gestation (41 women ≤ 34 years, 25 women ≥ 35 years) using the parameters pulse wave analysis and pulse wave velocity. Blood pressure (BP), body mass index (BMI), serum total cholesterol (TC) and fasting blood glucose (FBS) were also recorded. Mean ages of the younger and older age groups were 27.6±0.62 and 39.3±0.58 years; no significant difference was seen between the groups in their BMI, TC, FBS, SBP, DBP and gestational age. The older age group of women have increased arterial stiffness (augmentation index 19.4±1.9% vs 13.2±1.6%, p=0.015) and aortic stiffness (pulse wave velocity 8.7±0.3 vs 7.7±0.2 m/s, p=0.004) compared to the younger women. Linear regression analysis showed a positive significant correlation between age and augmentation index (R=0.278, p=0.026), and pulse wave velocity (R=0.350, p=0.004). We conclude that older pregnant women has increased arterial stiffness compared to a younger age group of pregnant women suggesting that vascular changes due to ageing occurs in pregnancy despite cardiovascular adaptations occurring in pregnancy.

MxA protein assay for optimal monitoring of IFN-beta bioactivity in the treatment of MS patients.

OBJECTIVES: Myxovirus resistance protein A (MxA) can be used as a marker of the bioactivity of interferon-beta (IFN-beta) therapy. Two to forty per cent of IFN-beta-treated multiple sclerosis (MS) patients develop IFN-beta-neutralizing antibodies (NAb) with subsequent attenuation of MxA protein induction. The aim of this study was to set up a simple MxA enzyme immunoassay (EIA) for the measurement of MxA protein and to evaluate the EIA test by comparing the results with flow cytometric analysis and the measurement of NAb. METHODS: total of 51 IFN-beta-treated relapsing-remitting MS (RRMS) patients were tested for MxA protein expression by using both MxA EIA assay and flow cytometric analysis. Thirteen patients were confirmed to be NAb-positive. RESULTS: The correlation between EIA and flow cytometric analysis was significant with a wider range of measured levels in the EIA. Patients with NAb had low MxA levels, but in some patients, remaining MxA induction could be detected despite NAb. CONCLUSIONS: The MxA EIA assay seems to be a practical method for large-scale analysis of the bioactivity of IFN-beta treatment.

Screening of dystrophin gene deletions in Malaysian patients with Duchenne muscular dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by rapidly progressive muscle weakness. The disease is caused by deletion, duplication or point mutation of the dystrophin gene, located on the X chromosome (Xp21). Deletion accounts for 60% of the mutations within the 79 exons of the dystrophin gene. Seven exons (43, 44, 45, 46, 49, 50, and 51) were found to be most commonly deleted among the Asian patients. To detect the frequency of deletion of these 7 exons in Malaysian DMD patients, we carried out a molecular genetic analysis in 20 Malaysian DMD patients. The mean age of initial presentation was 60 months (SD 32 months, range 5-120 months). Fourteen patients were found to have deletion of at least one of the seven exons. The remaining six patients did not show any deletion on the tested exons. Deletions of exons 49, 50 and 51 were the most frequent (71.43%) and appear to be the hot spots in our cohort of patients.

Antibody affinity and protection in virus infections.

Affinity of viral antibodies matures slowly after primary virus infections. Recent investigations with human sera and mouse monoclonal antibodies have provided the first evidence for a role of antibody affinity in the pathogenesis of chronic virus infections. More detailed studies are necessary before the rules and exceptions of this phenomenon are revealed.

Survival of patients with early hepatocellular carcinoma treated by percutaneous alcohol injection.

BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma, are detected in cirrhotics, the European Association for the Study of the Liver guidelines recommend to delay histological confirmation and treatment until they increase in size. AIM: To validate this policy by evaluating survival of 450 cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular carcinoma treated by percutaneous alcohol injection. METHODS: Patients were sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to < or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P = 0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months (P = 0.51), respectively. When patients were sorted by Child status, mean survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001). CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated patients with single, early hepatocellular carcinoma sorted by nodular size supports the European Association for the Study of the Liver 'wait-and-see' policy for patients with lesions <10 mm, and suggests that allowing the nodules to grow prior to taking further diagnostic or therapeutic actions would not harm these patients.

Cellular localization of c-jun messenger ribonucleic acid and protein and their relation to the proliferation marker Ki-67 in the human endometrium.

We studied cellular c-jun messenger RNA (mRNA) expression in the human endometrium during the menstrual cycle (n = 47) and in human decidua during pregnancy (n = 8), by using digoxigenin-labeled RNA probes in in situ hybridization. The same tissue samples were also analyzed for c-Jun protein and the proliferation marker Ki-67. In the proliferative endometrium, strong expression of c-jun was detected in luminal and glandular epithelium as well as in fibroblast-like stromal cells. During the early luteal phase, strong hybridization signals were identified in both epithelial and stromal compartments, with the strongest hybridization in the stromal cells beneath the epithelium. c-jun mRNA was markedly diminished in luminal and glandular epithelia of mid- and late secretory phase endometria, but it remained unchanged in the stroma. Regardless of the phase of the menstrual cycle, significant hybridization was identified in endothelial cells in the endometrium and myometrium, and a low signal was detected in myometrial muscle cells as well. During early gestation, weak expression of c-jun mRNA was observed in glandular epithelial cells and in decidualized stromal cells. In term pregnancy decidua, only low-level hybridization was detected in a few decidual cells. Nuclear immunostaining of c-Jun was detected in luminal and glandular epithelia and in stroma throughout the menstrual cycle. The location of Ki-67 antigen was temporally related to the c-jun mRNA expression in cycling endometrium and pregnancy decidua. From our data we conclude that 1) c-jun mRNA is differentially expressed in endometrial epithelial and stromal cells; 2) c-jun mRNA is cyclically regulated in the human endometrial epithelium; 3) c-jun mRNA expression is temporally related to epithelial proliferation in the endometrium; and 4) c-Jun protein is present in the human endometrium throughout the menstrual cycle.

Virus antibody levels in serum and cerebrospinal fluid specimens from patients with optic neuritis.

Virus antibody levels in serum specimens from 77 patients with optic neuritis (ON) were compared with those in healthy controls which had been matched with regard to sex, age and place of residence. A group of 58 patients with various neurological diseases other than multiple sclerosis (MS) or infectious diseases of the central nervous system (CNS) served as a second control group. The ON patients had significantly higher measles antibody titers in serum than the two control groups in both measles HI and HLI tests. Tests of cerebrospinal fluid (CSF) specimens revealed similar differences between ON patients and controls. Tests for antibodies to other viruses showed no statistically significant differences between ON patients and controls. There were several ON patients with normal serum/CSF albumin ratios but low serum/CSF IgG and measles antibody ratios. An increase in measles antibody CSF titers was observed during the study time in two ON patients. The results support the hypothesis that local production of measles antibodies takes place in the CNS of some patients with ON as has been earlier suggested to occur in patients with MS.

Measles and rubella virus antibodies in patients with multiple sclerosis. A longitudinal study of serum and CSF specimens by radioimmunoassay.

A longitudinal study on rubella, measles, and respiratory syncytial virus antibodies in serial serum and CSF specimens from 20 multiple sclerosis (MS) patients was performed, using solid-phase radioimmunoassay. Albumin and immunoglobulin G (IgG) levels were also measured to check the integrity of the blood-brain barrier and the intrathecal IgG production. All the patients had local IgG production in their CNA. A local antibody production against one or more of the viruses studied was evident in 15 patients. Fluctuations in the intrathecal viral antibody synthesis were evident in eight patients. No correlation was found between these changes and the clinical course of the disease. The results suggest that the intrathecal antibody synthesis in MS is only partially against any given virus, and in most patients the bulk of the oligoclonal CSF antibodies is against antigens other than those studied here.

Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis.

We performed a case-control study to assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV), GB virus C/hepatitis G virus (HGV), TT virus, alcohol intake, and tobacco smoking as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis. We prospectively recruited 174 patients with a first diagnosis of HCC admitted to the main hospitals in Brescia, North Italy. On the basis of histological, clinical, and radiological criteria, the presence of cirrhosis was established in 142 cases, excluded in 21 cases, and remained undefined in 11 cases. Among the HCC cases without cirrhosis, a histological picture of normal liver was found in a single patient, chronic viral hepatitis was found in 11 patients, alcoholic hepatitis was found in 5 patients, nonspecific reactive hepatitis was found in 3 patients, and hemochromatosis was found in 1 patient. As controls, we also included 610 subjects unaffected by hepatic diseases and admitted to the same hospitals as cases. The odds ratios for having HCC according to positivity for HCV RNA, HBsAg and/or HBV DNA, and alcohol intake > 80 g/day (95% confidence interval) were as follows, in the presence and absence of cirrhosis, respectively: (a) 33.5 (17.7-63.4) and 19.7 (6-64.8) for HCV RNA; (b) 17.6 (9.0-34.4) and 20.3 (5.7-72.6) for HBsAg; and (c) 5.5 (3.1-9.7) and 4.6 (1.5-13.8) for alcohol intake. No association was found with HGV or TT virus infections or tobacco. This study has shown that most HCC cases arising in the area are due to HBV, HCV, or alcohol intake, in both the presence and absence of cirrhosis.

Antibodies to coronaviruses OC43 and 229E in multiple sclerosis patients.

Multiple sclerosis (MS) and matched control sera had similar antibody titers to coronaviruses OC43 and 229E when tested by a radioimmunoassay method. In contrast, cerebrospinal fluid from MS patients contained coronavirus antibodies more frequently and in higher titers than matched controls. Intrathecal antibody synthesis to OC43 and 229E viruses was detected in 41% (9/22) and 26% (7/27) of MS patients, respectively, but was not found in any of the neurologic control patients. This intrathecal antibody synthesis may mean that coronaviruses play an etiologic or pathogenic role in MS. Alternatively, intrathecal synthesis of coronavirus antibodies may be but part of a generalized and variable intrathecal antibody synthesis that is typical for MS patients.

Neutralizing antibodies reduce MxA protein induction in interferon-beta-1a-treated MS patients.

BACKGROUND: Neutralizing antibodies (NAb) during interferon-beta (IFNbeta) treatment of MS are associated with reduced clinical and MR efficacy. NAb inhibit the IFN- inducible MxA gene expression and neutralize the capability of IFNbeta to inhibit virus growth in vitro. Presently, there is no clear concept of the biologic importance of IFNbeta antibodies; most of the tests applied for the detection of NAb in previous publications are not widely available, and the results are not fully comparable. METHODS: A 1-year prospective study of the development of binding antibodies (BAb) and NAb and their relationship to IFN-inducible MxA protein levels in peripheral blood leukocytes in 20 IFNbeta-1a-treated patients with relapsing-remitting MS was conducted. RESULTS: In seven of nine NAb-positive patients, IFNbeta-1a was unable to induce MxA protein. BAb were detected in 11 patients, and they preceded or paralleled the development of NAb in all the patients. The titer of NAb correlated positively with BAb titer and negatively with MxA expression level. There was also a weaker but clear correlation between BAb titers and MxA levels. CONCLUSIONS: NAb, in most but not all cases, inhibited the in vivo function of IFNbeta. Analysis of MxA protein in lymphocytes together with analysis of NAb is a promising marker for evaluating the biologic effects of IFNbeta treatment in MS patients.

Porcine C1q and the solid-phase immunoassay of human immune complexes.

Experiments were undertaken to determine if porcine C1q could replace human C1q in the solid-phase immunoassay of human immune complexes (ICs). Porcine C1q was obtained by a two-cycle precipitation method involving dialysis against chelating agents in low ionic strength buffer. C1q was adsorbed to polystyrene beads and in vivo- or in vitro-formed ICs binding to the solid-phase C1q were detected with 125I-labeled or horseradish peroxidase-conjugated anti-human gamma antibodies. Unfractionated, heat-aggregated human gamma globulin (delta IgG) could be detected at 20 ng/ml when diluted in buffer only. The detection threshold changed to 40-80 ng delta IgG/ml when the assay was run with buffer containing normal human serum diluted 1: 1000 (the serum dilution used for detecting natural ICs). Analysis of systemic lupus erythematosus sera revealed that 60% contained highly significant levels of ICs (binding greater than or equal to 3 S.D. above the mean of controls). Comparison with platelet aggregation test results revealed a highly significant correlation between the two methods (P less than 0.0001), even though each assay detected ICs in several serum specimens negative in the other test. These results demonstrate that porcine C1q can functionally replace human C1q in the solid-phase immunoassay of human ICs. Since porcine blood is normally a waste product of the meat-processing industry, it is an obvious source of easily isolated C1q for use in such an assay.