A RARE CASE OF GRAVES' THYROTOXICOSIS WITH CONCOMITANT PULMONARY ALVEOLAR PROTEINOSIS.

Background: Graves' disease results in various clinical cardio-pulmonary manifestations such as tachycardia, atrial fibrillation, and pulmonary edema. Clinical Case: A 62-year-old woman presented with palpitations and dyspnea. Laboratory and radiologic examination revealed markedly elevated free T4 (4.79 ng/dL), T3 (4.42 ng/mL), lowered TSH (0.01 uIU/mL), atrial fibrillation and multifocal lung haziness. She was initially diagnosed with atrial fibrillation with pulmonary edema, which subsequently changed to pulmonary alveolar proteinosis by further evaluations such as computed tomography and bronchoscopic biopsy. Conclusion: Pulmonary alveolar proteinosis is a rare lung disease. Clinicians should carefully assess lung lesions in thyrotoxicosis patients as they can be easily mistaken for pulmonary edema in clinical practice.

Probiotics, lactic acid bacteria and bacilli: interesting supplementation for aquaculture.

Probiotics administration in aquafeed is known to increase feed consumption and absorption due to their capacity to release a wide range of digestive enzymes and nutrients which can participate in digestion process and feed utilization, along with the absorption of diet components led to an increase in host's health and well-being. Furthermore, probiotics improve gut maturation, prevention of intestinal disorders, predigestion of antinutrient factors found in the feed ingredients, gut microbiota, disease resistance against pathogens and metabolism. The beneficial immune effects of probiotics are well established in finfish. However, in comparison, similar studies are less abundant in the shellfish. In this review, the discussions will mainly focus on studies reported the last 2 years. In recent studies, native probiotic bacteria were isolated and fed back to their hosts. Although beneficial effects were demonstrated, some studies showed adverse effects when treated with a high concentration. This adverse effect may be due to the imbalance of the gut microbiota caused by the replenished commensal probiotics. Probiotics revealed greatest effect on the shrimp digestive system particularly in the larval and early post-larval stages, and stimulate the production of endogenous enzymes in shrimp and contribute with improved the enzyme activities in the gut, as well as disease resistance.

Delayed axonal degeneration in slow Wallerian degeneration mutant mice detected using diffusion tensor imaging.

Previous studies have shown the feasibility of using diffusion tensor imaging (DTI) as a noninvasive imaging modality to evaluate neurodegeneration in humans and animals. The axial and radial diffusivities derived from DTI were demonstrated to be sensitive markers for axonal and myelin damage, respectively. This study used DTI to evaluate optic nerve degeneration in wild-type and slow Wallerian degeneration (Wld(S)) mutant mice. Longitudinal DTI was performed on optic nerves following high intraocular pressure-induced transient retinal ischemia. The axial diffusivity of wild-type nerves decreased 30% (P<0.05) at 3 days and 40% (P<0.05) at 5-30 days after transient elevation of intraocular pressure. In contrast, the axial diffusivity of Wld(S) nerves did not change at 3 days; decreased by 20% (P<0.05) at 5 days, and continued to decrease by 30% (P<0.05) at 15 days and 40% (P<0.05) at 30 days after transient intraocular pressure elevation, suggesting delayed axonal damage in Wld(S) mice. Radial diffusivity increased 200% (P<0.05) at 15-30 days in the wild-type mice and 100% (P<0.05) at 30 days in the Wld(S) mice after transient intraocular pressure elevation, suggesting delayed myelin damage in Wld(S) mice. DTI detected damage was confirmed with immunohistochemistry using phosphorylated neurofilament and myelin basic protein for assessing axonal and myelin integrity, respectively. These findings support the use of DTI not only to evaluate the progression of neurodegeneration but also to noninvasively demonstrate Wld(S) mutation to delay the Wallerian degeneration.

Neuroanatomic basis of amnestic MCI differs in patients with and without Parkinson disease.

OBJECTIVE: To explore the neuroanatomic basis of amnestic mild cognitive impairment (aMCI) in patients with Parkinson disease (PD; aMCI-PD(+)) and without PD (aMCI-PD(-)). METHODS: A total of 119 patients with aMCI (aMCI-PD(-), n = 78, and aMCI-PD(+), n = 41) underwent T1-weighted MRI, and the image data were analyzed using voxel-based morphometry. RESULTS: No significant differences in demographic characteristics or general cognition were found between patients with aMCI-PD(-) and aMCI-PD(+). Comparisons of neuropsychological tests between groups revealed that patients with aMCI-PD(-) had lower scores in delayed verbal and visual recognition memory, whereas visuospatial dysfunction was more severe in patients with aMCI-PD(+). Gray matter (GM) density in the right temporal and posterior cingular cortices was significantly lower in the aMCI-PD(-) group compared with controls. In contrast, GM density in the aMCI-PD(+) group was significantly lower in the precuneus and left prefrontal and primary motor areas relative to controls. A direct comparison between groups showed that decreased GM density in aMCI-PD(-) relative to aMCI-PD(+) was localized in the right temporal and anterior prefrontal areas, whereas decreased GM density in aMCI-PD(+) relative to aMCI-PD(-) was involved in the bilateral precuneus, left primary motor, and right parietal areas. Memory decline was correlated with temporal area atrophy in aMCI-PD(-) and with posterior cingulate cortex atrophy in aMCI-PD(+). CONCLUSIONS: Our data suggest that different neuroanatomic systems underlie memory dysfunction in patients with aMCI-PD(-) and aMCI-PD(+).

Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial.

OBJECTIVE: B cells and the humoral immune system have been implicated in the pathogenesis of multiple sclerosis (MS). This study sought to evaluate the efficacy, safety, and tolerability of add-on therapy with rituximab, a monoclonal antibody that depletes circulating B cells, in subjects with relapsing MS with breakthrough disease defined by clinical and MRI activity (Class III evidence). METHODS: Thirty subjects with a relapse within the past 18 months despite use of an injectable disease-modifying agent, and with at least 1 gadolinium-enhancing (GdE) lesion on any of 3 pretreatment MRIs, received rituximab administered at 375 mg/m(2) weekly x 4 doses. Three monthly posttreatment brain MRI scans were obtained beginning 12 weeks after the first infusion. Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were obtained at baseline and throughout the posttreatment follow-up. RESULTS: GdE lesions were reduced after treatment with rituximab, with 74% of posttreatment MRI scans being free of GdE activity compared with 26% free of GdE activity at baseline (p < 0.0001). Median GdE lesions were reduced from 1.0 to 0, and mean number was reduced from 2.81 per month to 0.33 after treatment (88% reduction). MSFC improved as well (p = 0.02). EDSS remained stable. CONCLUSION: Rituximab add-on therapy was effective based upon blinded radiologic endpoints in this phase II study. In combination with standard injectable therapies, rituximab was well-tolerated with no serious adverse events. B-cell-modulating therapy remains a potential option for treatment of patients with relapsing MS with an inadequate response to standard injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that add-on rituximab reduces gadolinium-enhancing brain lesions in multiple sclerosis.

Increased diffusivity in acute multiple sclerosis lesions predicts risk of black hole.

OBJECTIVE: Diffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. Inflammation leads to tissue injury, resulting in increased diffusivity and decreased directionality. We hypothesize that DTI can quantify the damage within acute multiple sclerosis (MS) white matter lesions to predict gadolinium (Gd)-enhancing lesions that will persist 12 months later as T1 hypointensities. METHODS: A cohort of 22 individuals underwent 7 brain MRI scans over 15 months. DTI parameters were temporally quantified within regions of Gd enhancement. Comparison to the homologous region in the hemisphere contralateral to the Gd-enhancing lesion was also performed to standardize individual lesion DTI parameters. RESULTS: After classifying each Gd-enhancing region as to black hole outcome, radial diffusivity, mean diffusivity, and fractional anisotropy, along with their standardized values, were significantly altered for persistent black holes (PBHs), and remained elevated throughout the study. A Gd-enhancing region with a 40% elevation in radial diffusivity had a 5.4-fold (95% confidence interval [CI]: 2.1, 13.8) increased risk of becoming a PBH, with 70% (95% CI: 51%, 85%) sensitivity and 69% (95% CI: 57%, 80%) specificity. A model of radial diffusivity, with volume and length of Gd enhancement, was associated with a risk of becoming a PBH of 5.0 (95% CI: 2.6, 9.9). Altered DTI parameters displayed a dose relationship to duration of black hole persistence. CONCLUSIONS: Elevated radial diffusivity during gadolinium enhancement was associated with increased risk for development of a persistent black hole, a surrogate of severe demyelination and axonal injury. An elevated radial diffusivity within active multiple sclerosis lesions may be indicative of more severe tissue injury.

Radial diffusivity in remote optic neuritis discriminates visual outcomes.

OBJECTIVE: Diffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. The goal of this study was to test whether, following a remote episode of optic neuritis (ON), breakdown of myelin and axons within the optic nerve could be detected by alterations in DTI parameters, and whether these alterations would correlate with visual loss. METHODS: Seventy subjects with a history of ON > or =6 months prior underwent DTI of the optic nerves, assessment of visual acuities (VA) and contrast sensitivities (CS), and laboratory measures of visual evoked potentials (VEP) and optical coherence tomography (OCT). RESULTS: Radial diffusivity (RD) correlated with visual acuity (r = -0.61), Pelli-Robson CS (r = -0.60), 5%CS (r = 0.61), OCT (r = -0.78), VEP latency (r = 0.61), and VEP amplitude (r = -0.46). RD differentiated the unaffected fellow nerves from affected nerves in all visual outcome categories. RD also discriminated nerves with recovery to normal from mild visual impairment, and those with mild impairment from profound visual loss. RD differentiated healthy controls from both clinically affected nerves and unaffected fellow nerves after ON. RD differentiated all categories of 5%CS outcomes, and all categories of Pelli-Robson CS with the exception of normal recovery from mildly affected. CONCLUSIONS: Increased optic nerve radial diffusivity (RD) detected by diffusion tensor imaging (DTI) was associated with a proportional decline in vision after optic neuritis. RD can differentiate healthy control nerves from both affected and unaffected fellow nerves. RD can discriminate among categories of visual recovery within affected eyes. Optic nerve injury as assessed by DTI was corroborated by both optical coherence tomography and visual evoked potentials.

Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis.

OBJECTIVES: Determine the utility of optical coherence tomography (OCT) to detect clinical and subclinical remote optic neuritis (ON), its relationship to clinical characteristics of ON and visual function, and whether the retinal nerve fiber layer (RNFL) thickness functions as a surrogate marker of global disease severity. METHODS: Cross-sectional study of 65 subjects with at least 1 clinical ON episode at least 6 months prior. Measures included clinical characteristics, visual acuity (VA), contrast sensitivity (CS), OCT, and visual evoked potentials (VEP). RESULTS: Ninety-six clinically affected optic nerves were studied. The sensitivity of OCT RNFL after ON was 60%, decreasing further with mild onset and good recovery. VEP sensitivity was superior at 81% (p = 0.002). Subclinical ON in the unaffected eye was present in 32%. VEP identified 75% of all subclinically affected eyes, and OCT identified <20%. RNFL thickness demonstrated linear correlations with VA (r = 0.65) and CS (r = 0.72) but was unable to distinguish visual categories <20/50. RNFL was thinner with severe onset and disease recurrence but was unaffected by IV glucocorticoids. OCT measurements were not related to overall disability, ethnicity, sex, or age at onset. The greatest predictor for RNFL in the unaffected eye was the RNFL in the fellow affected eye. CONCLUSIONS: Visual evoked potentials (VEP) remains the preferred test for detecting clinical and subclinical optic neuritis. Optical coherence tomography (OCT) measures were unrelated to disability and demographic features predicting a worse prognosis in multiple sclerosis. OCT may provide complementary information to VEP in select cases, and remains a valuable research tool for studying optic nerve disease in populations.

Optical coherence tomography differs in neuromyelitis optica compared with multiple sclerosis.

BACKGROUND: Neuromyelitis optica (NMO) is associated with destructive inflammatory lesions, resulting in necrosis and axonal injury. Disability from multiple sclerosis (MS) is due to a combination of demyelination and varying axonal involvement. Optical coherence tomography (OCT), by measuring retinal nerve fiber layer (RNFL) as a surrogate of axonal injury, has potential to discriminate between these two conditions. METHODS: Included were 22 subjects with NMO or NMO spectrum disorders and 47 with MS. Seventeen subjects with NMO and all with MS had a remote history of optic neuritis (ON) in at least one eye, at least 6 months before OCT. Linear mixed modeling was used to compare the two diagnoses for a given level of vision loss, while controlling for age, disease duration, and number of episodes of ON. RESULTS: After ON, NMO was associated with a thinner mean RNFL compared to MS. This was found when controlling for visual acuity (56.7 vs 66.6 microm, p = 0.01) or for contrast sensitivity (61.2 vs 70.3 microm, p = 0.02). The superior and inferior quadrants were more severely affected in NMO than MS. CONCLUSIONS: Optic neuritis (ON) within neuromyelitis optica (NMO) is associated with a thinner overall average retinal nerve fiber layer compared to multiple sclerosis, with particular involvement of the superior and inferior quadrants. This suggests that NMO is associated with more widespread axonal injury in the affected optic nerves. Optical coherence tomography can help distinguish the etiology of these two causes of ON, and may be useful as a surrogate marker of axonal involvement in demyelinating disease.

Disability in optic neuritis correlates with diffusion tensor-derived directional diffusivities.

OBJECTIVE: To determine the potential of directional diffusivities from diffusion tensor imaging (DTI) to predict clinical outcome of optic neuritis (ON), and correlate with vision, optical coherence tomography (OCT), and visual evoked potentials (VEP). METHODS: Twelve cases of acute and isolated ON were imaged within 30 days of onset and followed prospectively. Twenty-eight subjects with a remote clinical history of ON were studied cross-sectionally. Twelve healthy controls were imaged for comparison. DTI data were acquired at 3T with a surface coil and 1.3 x 1.3 x 1.3 mm(3) isotropic voxels. RESULTS: Normal DTI parameters (mean +/- SD, microm(2)/ms) were axial diffusivity = 1.66 +/- 0.18, radial diffusivity = 0.81 +/- 0.26, apparent diffusion coefficient (ADC) = 1.09 +/- 0.21, and fractional anisotropy (FA) = 0.43 +/- 0.15. Axial diffusivity decreased up to 2.5 SD in acute ON. The decrease in axial diffusivity at onset correlated with visual contrast sensitivity 1 month (r = 0.59) and 3 months later (r = 0.65). In three subjects followed from the acute through the remote stage, radial diffusivity subsequently increased to > 2.5 SD above normal, as did axial diffusivity and ADC. In remote ON, radial diffusivity correlated with OCT (r = 0.81), contrast sensitivity (r = 0.68), visual acuity (r = 0.56), and VEP (r = 0.54). CONCLUSION: In acute and isolated demyelination, axial diffusivity merits further investigation as a predictor of future clinical outcome. Diffusion parameters are dynamic in acute and isolated optic neuritis, with an initial acute decrease in axial diffusivity. In remote disease, radial diffusivity correlates with functional, structural, and physiologic tests of vision.

Association of extracellular cleavage of E-cadherin mediated by MMP-7 with HGF-induced in vitro invasion in human stomach cancer cells.

BACKGROUND: Proteolytic shedding of the ectodomain of a variety of transmembrane proteins, including cell-to-cell adhesion molecules, has been observed in solid cancers. We have investigated whether extracellular cleavage of E-cadherin mediated by matrix metalloproteinase-7 (MMP-7) is involved in hepatocyte growth factor (HGF) induced in vitro invasion in stomach cancer cells. METHODS: The effects of HGF on the expression of E-cadherin/beta-catenin and MMP-7 at both the protein and mRNA levels were assessed in stomach cancer cells, NUGC-3 and MKN-28, and in cells in which the expression of MMP-7 was downregulated by transfection with a MMP-7 short hairpin RNA plasmid. RESULTS: Treatment with HGF increased the extracellular cleavage of E-cadherin and the release of MMP-7 and reduced the level of E-cadherin in a dose- and time-dependent manner. HGF treatment repressed the phosphorylation of beta-catenin in a Triton-soluble fraction, but enhanced this phosphorylation in a Triton-insoluble fraction. The association of E-cadherin with beta-catenin was decreased by HGF treatment in the Triton-soluble fraction. In addition, treatment of MMP-7 short hairpin RNA transfected NUGC-3 cells with HGF resulted in no extracellular cleavage of E-cadherin and also decreased the in vitro cell invasion. CONCLUSIONS: These results suggest that incubation with HGF mediated the release of MMP-7, resulting in extracellular cleavage of E-cadherin from stomach cancer cells. This might be a key mechanism in HGF-induced in vitro invasion and metastasis.

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury.

Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 h and 24 h post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters--axial diffusivity and relative anisotropy--were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectable on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP stained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose.

Measurement of strain in physical models of brain injury: a method based on HARP analysis of tagged magnetic resonance images (MRI).

Two-dimensional (2-D) strain fields were estimated non-invasively in two simple experimental models of closed-head brain injury. In the first experimental model, shear deformation of a gel was induced by angular acceleration of its spherical container In the second model the brain of a euthanized rat pup was deformed by indentation of its skull. Tagged magnetic resonance images (MRI) were obtained by gated image acquisition during repeated motion. Harmonic phase (HARP) images corresponding to the spectral peaks of the original tagged MRI were obtained, following procedures proposed by Osman, McVeigh and Prince. Two methods of HARP strain analysis were applied, one based on the displacement of tag line intersections, and the other based on the gradient of harmonic phase. Strain analysis procedures were also validated on simulated images of deformed grids. Results show that it is possible to visualize deformation and to quantify strain efficiently in animal models of closed head injury.

Activity of sulphate reducing bacteria according to COD/SO4(2-) ratio of acrylonitrile wastewater containing high sulphate.

This study was performed to evaluate the biodegradability of acrylonitrile wastewater, microbial inhibition effect of acrylonitrile wastewater on removal efficiency and the activity of sulphate reducing bacteria (SRB) according to COD/sulphate ratio. Acrylonitrile wastewater was hardly biodegradable in a biodegradability test, however, SRB activity was 57% for overall consumption of electron donor and it was relatively high value compared to 17% of reference test with glucose. COD removal of acrylonitrile wastewater was improved to 57% and 61% from 20% as the COD/sulphate ratio were 0.5 and 0.3 by sulphate addition to acrylonitrile wastewater. First order reaction rate constants k on organic removal of acrylonitrile wastewater were 0.001, 0.004 and 0.004 at each COD/sulphate ratio of 0.9, 0.5 and 0.3. Thus it was suggested that the activity of SRB was a significant factor for removing organics and sulphate simultaneously in acrylonitrile wastewater.

Influence of nutritional conditions on the mycelial growth and exopolysaccharide production in Paecilomyces sinclairii.

AIMS: The objective of the study was to optimize the submerged culture conditions for the production of exopolysaccharide from Paecilomyces sinclairii. METHODS AND RESULTS: The optimal temperature and initial pH for exopolysaccharide production by Paecilomyces sinclairii in shake flask culture were found to be 30 degrees C and 6.0, respectively. Sucrose (60 g l(-1)) and corn steep powder (10 g l(-1)) were the most suitable carbon and nitrogen source for exopolysaccharide production. CONCLUSIONS: Under optimal culture medium, the maximum exopolysaccharide concentration in a 5-l stirred-tank fermenter indicated 7.4 g l(-1), which was approximately three times higher than that in basal medium. The maximum specific growth rates (micro max) and yield coefficient (Y(P/S)) in the optimal culture medium was 0.16 h(-1) and 0.19, respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The optimal culture conditions reported in this article can be widely applied to the processes for submerged cultures of other mushrooms.

Improving relative anisotropy measurement using directional correlation of diffusion tensors.

A method employing directional correlation of the diffusion tensor, directional-correlation weighted relative anisotropy (DRA), was developed to improve the accuracy of estimated relative anisotropy (RA). The intravoxel directional correlation was established on the same voxel between two identically acquired diffusion tensor images, and the correlation coefficient derived from tensor dot product was employed as the weighting factor applied in the calculation of RA. The effect of noise influence was reduced since the random noise between repeated scans is not directionally correlated. The RA and the inter- and intravoxel DRA estimations were examined on rat brains in vivo. The background noise alters the direction of eigenvectors and the magnitude of eigenvalues. The dispersion angle between repeatedly obtained eigenvectors, representing the extent of directional alteration of eigenvectors, depends on the tissue anisotropy as well as the signal-to-noise ratio (SNR) of the source images. Current results demonstrate that the intravoxel DRA improves the accuracy of RA estimation, increases the relative contrast of gray and white matter, and avoids the partial volume effect commonly seen in the intervoxel operations.

cDNA cloning and sequence analysis of the lectin genes of the Korean mistletoe (Viscum album coloratum).

We previously isolated a lectin of the Korean mistletoe (Viscum album coloratum). The cDNA clones that encode the A- or the B-chain of the Korean mistletoe lectin were cloned by reverse transcriptase polymerase chain reaction (RT-PCR). The mRNAs that were extracted from the Korean mistletoe were amplified, ligated into the pGEM-T easy vector, and screened with a Korean mistletoe lectin-specific probe. The probe was prepared by PCR amplification of the Korean mistletoe DNA using a primer set designed on the basis of amino acid sequences of the Korean mistletoe lectin that we had purified and reported. Unlike a recent report, which states that the European mistletoe lectin gene has no isoforms, several different clones of the A- and B-chains of the Korean mistletoe lectin were cloned from the same primer set. Three clones of each were selected for sequencing. The sizes of the A-chains were 762, 762, and 768 bp, respectively. The B-chain sizes were 798, 789, and 789 bp, respectively. Each of the clones showed significant variation in the amino acids sequence, including the N-linked glycosylation sites of the lectin. The sequence analysis of each of the Korean lectin clones, in comparison with the European mistletoe lectin and the other type II ribosome binding proteins, is discussed in the text. In addition, Southern blot analysis of the Korean mistletoe genomic DNA, restricted by different enzymes and hybridized with the lectin DNA, showed multi-bands, supporting the existence of multicopy genes or a gene family. These data suggest that heterogeneity of the mistletoe lectin is not only introduced by post-translational modifications, but also by expression of isotypes of the lectin genes.