How often and when Fisher syndrome is overlapped by Guillain-Barré syndrome or Bickerstaff brainstem encephalitis?

BACKGROUND AND PURPOSE: Fisher syndrome (FS) may overlap with Guillain-Barré syndrome (GBS), in particular the pharyngeal-cervical-brachial variant form (PCB-GBS), or Bickerstaff brainstem encephalitis (BBE). Our aim was to elucidate the frequency of this overlap and the patterns of clinical progression in patients with FS. METHODS: Sixty consecutive patients with FS were studied. FS/PCB-GBS was diagnosed when the patients developed pharyngeal, cervical and/or brachial weakness. Patients with flaccid tetraparesis were diagnosed as having FS/conventional GBS. FS/BBE was defined as the development of consciousness disturbances. RESULTS: All 60 patients initially developed the FS clinical triad alone (pure FS). Of these, 30 (50%) patients had pure FS throughout their course, whereas the remaining 50% of patients showed an overlap: PCB-GBS in 14 (23%) patients, conventional GBS in nine (15%) patients and BBE in seven (12%) patients. The median (range) durations from FS onset to progression to FS/PCB-GBS, FS/GBS or FS/BBE were 5 (1-7), 3 (1-4) and 3 (1-5) days, respectively. Patients with overlap syndromes more frequently received immune-modulating treatment, and the outcomes were generally favourable. The frequencies of positivity for anti-GQ1b, GT1a, GD1a, GD1b, GalNAc-GD1a and GM1 antibodies were not significantly different amongst the four groups. CONCLUSIONS: Of the patients with pure FS, 50% later developed an overlap with PCB-GBS, conventional GBS or BBE. The overlap occurred within 7 days of FS onset; thus, physicians should pay attention to the possible development of this overlap during the first week after FS onset.

POEMS syndrome with Guillan-Barre syndrome-like acute onset: a case report and review of neurological progression in 30 cases.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

Neuromuscular transmission is not impaired in axonal Guillain--Barré syndrome.

BACKGROUND: Previous studies have shown that anti-GQ1b antibodies induce massive neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on the neuromuscular junction (NMJ) in human limb muscles, this may explain selective motor involvement in axonal Guillain--Barré syndrome (GBS). METHODS: Axonal-stimulating single-fibre electromyography was performed in the extensor digitorum communis muscle of 23 patients with GBS, including 13 with the axonal form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies. RESULTS: All patients with axonal or demyelinating GBS showed normal or near-normal jitter, and no blocking. CONCLUSION: In both axonal and demyelinating GBS, neuromuscular transmission is not impaired. Our results failed to support the hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse transmission is presumably impaired in the motor nerve terminal axons proximal to the NMJ.

rRNA-based analysis to monitor succession of faecal bacterial communities in Holstein calves.

AIMS: To quantitatively analyse the faecal bacterial communities of Holstein calves and track their succession up to 12 weeks of age. METHODS AND RESULTS: Faecal samples obtained from four female Holstein calves were analysed by the RNA-based, sequence-specific rRNA cleavage method. Twelve scissor probes covering major rumen bacterial groups were used, detecting c. 60-90% of the total 16S rRNAs. At 1 week of age, 16S rRNAs from members of the Bacteroides-Prevotella group (40·0% of the total 16S rRNAs), Faecalibacterium (21·7%), the Clostridium coccoides-Eubacterium rectale group (16·7%) and the Atopobium cluster (10·9%) were detected at high levels. Throughout the 12-week period, rRNAs of the Bacteroides-Prevotella and the Cl. coccoides-Eu. rectale groups constituted the major fraction of microbiota (c. 50-70% of the total). The relative abundances of the Atopobium cluster, Faecalibacterium, and some probiotic bacteria (such as those of the genera Lactobacillus and Bifidobacterium) decreased as the animal aged. Instead, an uncultivated rumen bacterial group, as well as Ruminococcus flavefaciens and Fibrobacter emerged at the detectable levels (1-2%) in the faeces sampled at a postweaning age. In addition, certain bacterial groups that were not covered by the probe suite increased as the animals aged. CONCLUSIONS: Young calves undergo dynamic changes in their intestinal bacterial community during the first 12 weeks of life. As young ruminants undergo metabolic and physiological development in their digestive tracts in the transition from a monogastric to a ruminant animal at an early age, the intestinal bacterial community may reflect such development. SIGNIFICANCE AND IMPACT OF THE STUDY: The succession of the bacterial communities in the faeces of calves was quantitatively monitored in the present study for the first time. The approach used here was demonstrated to be a useful means for determining the populations of predominant faecal bacterial groups in a variety of calf experiments in response to diet, stress and disease.

Effect of educational hospitalization on chronic kidney disease (CKD) patients.

UNLABELLED: Although dietary control is recommended to chronic kidney disease (CKD) patients, improvement of compliance and education of outpatients are very difficult. The purposes of the present study are to estimate the dietary intake of sodium (Na) and protein by measuring urinary Na and urea nitrogen (UN) excretion, and to evaluate the efficacy of educational hospitalization. METHODS: 70 patients (41 men and 29 women) with a mean age of 58.7+/-15.8 years participated in the present study. Most patients had chronic kidney disease (CKD, Stage 3 or 4). Patients were hospitalized to learn about their diseases and dietary restrictions for 1 week. Patients were given low salt (less than 6 g/day) and low protein (0.6-1.0 g/standard body weight kg/day) diet. 24-hour urine samples were collected at the start (Day 2) and on completion (Day 7) of hospitalization. Salt and protein intakes were estimated using patients' 24-hour urine samples. RESULTS: Estimated salt intake was significantly decreased on completion of the hospitalization (Day 7) (p < 0.05). Estimated protein intake was also decreased slightly, but this was not statistically significant. There were significant differences in the changes of body weight, body mass index (BMI), and systolic and diastolic blood pressure between the start (Day 2) and completion (Day 7) of hospitalization. 89% of the patients showed an improved blood pressure without changes of antihypertensive drugs. CONCLUSIONS: It appears that short-term hospitalization is an effective program for achieving dietary and blood pressure control in CKD patients.

Recent advances in methane fermentation technology.

In the past two decades, a number of biotechnologies for anaerobic (methanogenic) wastewater treatment have been created, and practical applications of these processes are now being extended to more recalcitrant wastewaters and to wastewaters at extreme temperatures. Our knowledge of methanogenic organic degradation associated with bioreactors is also accumulating at a rapid rate. The recent advancement of such fundamental understanding is attributed to modern molecular biology techniques applied to the study of microbial communities and to continuous challenges to the cultivation of many important but recalcitrant anaerobes in bioreactors.

Sequence-specific cleavage of 16S rRNA for rapid and quantitative detection of particular groups of anaerobes in bioreactors.

We developed a rapid and simple method for rRNA-based quantitative detection of a specific group of microorganisms in complex ecosystems. The method relies on the sequence-specific scission of 16S rRNA with ribonuclease H (RNase H) and oligonucleotides that specifically hybridize with targeted rRNA molecules. RNAs from a complex community were first mixed with an oligonucleotide and were subsequently digested with RNase H to achieve sequence-dependent rRNA cleavage at the hybridization site. For the quantitative detection of targeted rRNAs, the resulting RNA fragment patterns were analyzed by gel-electrophoresis, which separated and quantified cleaved and intact rRNA fragments. This method enabled the quantitative detection of microbes in a complex microbial community by a relatively simple and fast experimental procedure. We then applied the cleavage method to actual anaerobic microbial communities such as digested sewage sludge and UASB sludges. The results demonstrated that the present method was fully applicable to anaerobic digestor ecosystems containing complex anaerobic microorganisms.

Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study.

OBJECTIVE: POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome. METHOD: This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival. RESULTS: Serum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months. CONCLUSIONS: Serum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.

Yeast tom1 mutant exhibits pleiotropic defects in nuclear division, maintenance of nuclear structure and nucleocytoplasmic transport at high temperatures.

A tom1-1 mutant was isolated from Saccharomyces cerevisiae. At high temperatures, 60% of the cells were arrested as dumbbell forms with a single large nucleus containing duplicated DNA and a short spindle. Electron-microscopy showed electron-dense structures scattered within the nucleus. Indirect immunofluorescent microscopy revealed these structures to be fragmented nucleoli since the dotted structures were stained with anti-Nop1(fibrillarin) antibody in large regions of the nuclei. Fluorescent in situ hybridization analysis using oligo(dT) revealed nuclear accumulation of poly(A)+RNA. We cloned TOM1 which encodes a large protein (380kDa) with a hect (homologous to E6-AP C terminus)-domain at its C terminus. Deletions of either this hect-region or the entire gene made cellular growth temperature-sensitive. Site-directed mutagenesis of the conserved cysteine residue (tom1C3235A) in the hect-domain, supposed to be necessary for thioester-bond formation with ubiquitin, abolished the gene function. When a functional glutathione S-transferase (GST)-tagged hect protein was overproduced, it facilitated the protein conjugation with a myc-tagged ubiquitinRA, while this was not seen when GST-hectC3235A was overproduced. The protein conjugation with a hemagglutinin-tagged Smt3 was not affected by the overproduction of GST-hect. Taken together, we suggest that Tom1 is a ubiquitin ligase. As a multi-copy suppressor of tom1, we isolated STM3/NPI46/FPR3 which encodes a nucleolar nucleolin-like protein. We discuss possible functions of Tom1 with respect to the pleiotropic defects of nuclear division, maintenance of nuclear structure, and nucleocytoplasmic transport.

Establishment of human monoclonal anti-DNA antibody producing cell lines.

We developed a useful method for the establishment of stable cell lines producing human monoclonal anti-DNA antibody by in vitro Epstein-Barr virus infection. The practical limitation for the cloning was overcome by 2 procedures. One was a microculture system using a small number of the culture. Another was enrichment of anti-DNA producing cells at an early stage and prior to the cloning. The combination of these procedures allowed ready derivation of the cell lines secreting monoclonal anti-DNA antibody. Sixteen cell lines were cloned by utilizing colony formation methods in soft agarose. About 14-32 micrograms per ml of IgM with specific antibody activity were obtained in the supernatant of the cells. The antibody reacted with double-stranded and/or single-stranded DNA. These cells have been continuously producing the specific antibody for more than 3 years. We may extend this procedure for obtaining other autoantibodies, such as anti-T cell antibodies.

Design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine sigma ligands as potential antipsychotic drugs.

sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3.

Brain-derived gangliosides suppress the chronic relapsing-remitting experimental autoimmune encephalomyelitis in NOD mice induced with myelin oligodendrocyte glycoprotein peptide.

Chronic relapsing-remitting experimental autoimmune encephalomyelitis (CREAE) induced with myelin oligodendrocyte glycoprotein peptides 35-55 (MOG(35-55)) in NOD mice was successfully treated with brain-derived gangliosides (GA). The GA treatment suppressed the development and severity of CREAE, both clinically and histologically. Spleen cells from the GA-treated mice displayed markedly inhibited levels of MOG(35-55) specific proliferation and interferon-gamma production. Delayed-type hypersensitivity reactions to MOG(35-55) were suppressed by the GA treatment. GA modulate various T cell effector functions in CREAE and may be an effective therapeutic agent for autoimmune demyelinating diseases such as multiple sclerosis.

Anti-IL-12 antibody prevents the development and progression of multiple sclerosis-like relapsing--remitting demyelinating disease in NOD mice induced with myelin oligodendrocyte glycoprotein peptide.

Treatment with monoclonal anti-IL-12 antibody injected on day 0, 7 and 10 after immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in NOD mice resulted in significant suppression of the development and the severity of the chronic relapsing-remitting experimental autoimmune encephalomyelitis (EAE) both clinically and histologically. The spleen cells from anti-IL-12 antibody treated mice displayed markedly inhibited MOG35-55 specific proliferation and IFN-gamma production. MOG35-55 specific antibody production was enhanced by anti-IL-12 antibody treatment. These results suggest that IL-12 is critically involved in the pathogenesis of MOG-induced EAE and that antibody to IL-12 could be an effective therapeutic agent in the clinical treatment of autoimmune demyelinating diseases such as multiple sclerosis (MS).

Quantitative double-tracer autoradiography with tritium and carbon-14 using imaging plates: application to myocardial metabolic studies in rats.

UNLABELLED: A system for 3H- and 14C-labeled macroautoradiography was developed that is able to quantify the tissue radioactivity of two tracers using imaging plates. METHODS: Discrimination between electrons emitted from 3H and 14C is possible on the basis of their different energy distributions. The general use imaging plate with a protective layer detects 14C radioactivity, but it does not detect 3H radioactivity which has a lower energy distribution than 14C. Recently, a 3H-sensitive imaging plate without a protective layer was developed. The 3H distribution image is obtained by subtracting the UR image from the TR image. For quantification of the tissue radioactivity of 3H and 14C, we obtained tissue equivalent values (Bq/mg) of commercially available 3H- and 14C-labeled graded standards using different dilutions of labeled heart paste and liquid scintillation counting. Using the 3H- and 14C-labeled graded standards, we confirmed the validity of the quantification of the 3H-autoradiographic intensity using this subtraction method. We applied this method to a rat model of acute myocardial ischemia to compare regional myocardial free fatty acid uptake determined by beta-methyl[1-14C]heptadecanoic acid to glucose uptake determined by 2-deoxy-D-[1-3H]glucose. RESULTS: Free fatty acid uptake was decreased sharply at the ischemic periphery where glucose uptake was preserved. CONCLUSION: This double-tracer autoradiography with 3H and 14C which has high sensitivity, a high spatial resolution of 50 microns and superior linearity with a wide dynamic range of 10(4) to 10(5) allows accurate quantification of the tissue radioactivity of the two radiopharmaceuticals.

Intrapleural omentum simulating pleural effusion.

We report herein a case of Morgagni hernia of omentum into the pleural space, simulating a pleural effusion on a routine chest radiograph. A 62-year-old man was referred to our clinic for close examination of a pleural effusion-like shadow at the right costophrenic region. He had no history of trauma and no symptoms. Chest computed tomographic scan showed a pleural effusion-like shadow with a fat density. Thoracoscopy revealed a movable omentum-like mass and no significant fluid in the right pleural space. Magnetic resonance imaging and celiac angiography confirmed the herniation of omentum into the right pleural space. This case suggests that a Morgagni hernia must be excluded in a patient with a fat density effusion-like shadow in the pleural space.

Molecular cloning and expression of rat interleukin-1 alpha cDNA.

A cDNA sequence coding for rat interleukin-1 alpha (IL-1 alpha) has been isolated from a cDNA library that was prepared with mRNA derived from LPS-stimulated rat peritoneal macrophages by using human IL-1 alpha cDNA as a probe. The rat cDNA encodes a 270 amino acid residue protein which is homologous (65%) to human IL-1 alpha. The rat cDNA sequence under SV40 early promoter directed the synthesis of biologically active IL-1 in monkey COS-1 cells. Rat IL-1 alpha mRNA is not expressed in spleen, lung, liver or brain, and is also not expressed in these organs of LPS-treated rat except spleen. This suggests that IL-1 alpha is not produced constitutively in various tissues and LPS is not sufficient to induce IL-1 alpha in most tissues. Our data indicate that the IL-1 activities which have been reported to be produced in the brain are not of alpha type. We have constructed a plasmid expressing the carboxy terminal 156 amino acids in Escherichia coli. Recombinant rat IL-1 alpha produced in COS cells or E. coli has cytotoxic activity against the human melanoma cell line A375S1 (GIF activity), which has been reported to be sensitive to human IL-1 alpha and IL-1 beta. This suggests that GIF activity is common to IL-1s derived from various sources.

Immunohistochemical analysis of platelet-derived growth factor-B expression in myocardial tissues in hypertrophic cardiomyopathy.

Intimal and/or medial hyperplasia of intramyocardial small vessels is thought to be one of the causes of myocardial ischemia in hypertrophic cardiomyopathy (HCM). However, the pathogenesis of such vascular lesions in HCM is not yet known. To evaluate the pathogenic role of platelet-derived growth factor (PDGF-B) and basic fibroblast growth factor (b-FGF), which have a potential to induce cellular and molecular changes observed in the vessels in HCM, we examined the expression of these molecules and PDGF receptors in cardiac tissues from six patients with HCM and seven controls using immunohistochemistry. The percentage of PDGF-B positive cells in the myocyte population in HCM was significantly higher than that in controls (52.6 +/- 16.2 (mean +/- SD) vs. 21.6 +/- 9.6, p < 0.01). PDGF-B was also observed in vascular regions in HCM (61.1 +/- 25.5% of arterioles) but not in controls. There were no significant differences in the expression of b-FGF and PDGF receptors in the myocyte and non-myocyte populations and the vascular regions between the HCM and control groups. Our study revealed that the expression of PDGF-B protein was up-regulated in HCM, suggesting the contribution of this molecule to the development of intramyocardial vasculopathy.

Effect of NG-nitro-L-arginine on shock induced by endotoxin and by platelet activating factor in dogs.

When NG-nitro-L-arginine, a nitric oxide synthase inhibitor, administration was started 5 min prior to shock induction in anesthetized dogs, a partial restoration was observed in endotoxin-induced shock and a complete recovery in platelet activating factor (PAF)-induced shock. When NG-nitro-L-arginine infusion was started 5 min after shock induction, no significant recovery was observed in endotoxin-induced shock and a complete recovery in PAF-induced shock. These data indicate that enhanced production of nitric oxide by vascular endothelial cells may contribute to endotoxin- or PAF-induced shock and also that some mediators including inducible nitric oxide synthase and/or cellular damage might be involved in endotoxin-induced shock.

Elevation of plasma endothelin concentrations during endotoxin shock in dogs.

The effect of endotoxin on the release of endothelin, a novel potent vasoconstrictor peptide, was examined in anesthetized dogs and in cultured endothelial cells. Administration of 2.63 mg lipopolysaccharide, E. coli 0111:B4/kg body weight caused shock in the animals and produced a long-lasting increase in the plasma immunoreactive endothelin-1 level that remained higher than the basal level (1.83 pg/ml as mean level) from 30 to 120 min after the injection, with a peak at 90 min (8.15 pg/ml as mean level). In vitro immunoreactive endothelin-1 in a culture medium, in which calf pulmonary artery endothelial cells were incubated in the presence of 10% fetal bovine serum, increased dose dependently with the concentration of added lipopolysaccharide between 0.01 and 10 micrograms/ml. These data indicate that plasma endothelin increases during endotoxin shock and that stimulation by endotoxin, per se, in the presence of serum participates at least partially in the mechanism for its release.