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Objectives The aim of the study was to detect changes in the levels of ferritin heavy chain ( FHC), ferritin light chain ( FLC), and transferrin in the cerebrospinal fluid ( CSF) and serum of amyotrophic lateral sclerosis ( ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Methods Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non- INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised ( ALSFRS-r) scores, and disease progression rates ( DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Results Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. Conclusions This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS. [ABSTRACT FROM AUTHOR]

Objectives Amyotrophic lateral sclerosis ( ALS) is a progressive neurodegenerative disease with complicated pathogenesis. No effective diagnostic test and cure exists for the disease at present. We detected the levels of MIP-1 α in cerebrospinal fluid ( CSF) and serum and then further evaluated whether MIP-1 α levels correlate with the severity and progression of ALS. Methods We used ELISAs to detect MIP-1 α levels from 58 patients with ALS and 45 age- and gender-matched controls. The patients with ALS were also clinically evaluated with the revised ALS functional rating scale ( ALSFRS-r). Moreover, we followed up with 40 cases of ALS by way of call or clinic visit 4 years after enrollment in this study. Finally, we assessed the correlations between MIP-1 α levels and various clinical parameters. Results We found that the levels of MIP-1 α in patients with ALS significantly increased compared to controls and they were positively correlated with duration. MIP-1 α showed negative correlations with disease progression rate and the decrease in ALSFRS-r. Furthermore, the cumulative survival of patients with ALS with high levels of MIP-1 α exceeded patients with low MIP-1 α levels. Conclusions MIP-1 α levels increased in both CSF and serum of patients with ALS, and it may be a potential neuroprotective biomarker in ALS. [ABSTRACT FROM AUTHOR]

Objectives Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by selective motor neuron loss in the brain and spinal cord. The cause of this selective death of motor neurons is still unclear, but among several pathomechanisms that have been discussed, the loss of neurotrophic factors is one hypothesis. Basic fibroblast growth factor 2 (bFGF) may be a potential neurotrophic factor for slowing various neurodegenerative diseases, but its potential role in the prognosis of ALS is not known. Methods To explore the role of bFGF in ALS, we investigated changes in bFGF in the CSF and serum from patients with sALS and from the control group. Furthermore, we analyzed the correlations between bFGF, disease duration, disease progression rate, ALSFRS-r score and survival. Results The level of bFGF increased in both the CSF and serum in sALS patients. It was higher in patients with longer durations. It was negatively correlated with disease progression rates, especially in the later stages of sALS, but showed no linear correlation with ALSFRS-r. In an analysis of the relationship between bFGF and survival, we found that sALS patients with high levels of bFGF had significantly higher cumulative survival rates than patients with low levels of bFGF. Discussion and Conclusion In conclusion, endogenous bFGF increased both in the CSF and serum of sALS patients and it may be a useful biomarker that could predict disease progression and survival. [ABSTRACT FROM AUTHOR]

Following spinal cord injury (SCI), the pathological sequelae which ensue through the secondary mechanisms of degeneration produce myelin deposits which are potent inhibitors of endogenous neuroregeneration. We have enhanced the immune-mediated response following a hemisection lesion by immunizing adult C57Bl/6 female mice against the inhibitor of neurite outgrowth Nogo-A(623–640) peptide. Moderate anti-Nogo-A(623–640) antibody titre levels were obtained by using Montanide as the adjuvant. However, this antibody response was not obtained using incomplete Freund's adjuvant (IFA). Significant benefit in locomotor performance was demonstrated only in animals which were vaccinated with IFA and not with Montanide. No further benefit could be demonstrated with the Nogo-A(623–640) peptide beyond that seen for adjuvant alone. These data imply that generating antibodies against Nogo-A(623–640) in vivo alone is not sufficient to enhance locomotor recovery and that subcutaneous injection of IFA prior to SCI can enhance locomotor performance. [ABSTRACT FROM AUTHOR]

Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin-positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord. [ABSTRACT FROM AUTHOR]

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis. No effective diagnostic test and cure exists for the disease at present. We detected the levels of MIP-1α in cerebrospinal fluid (CSF) and serum and then further evaluated whether MIP-1α levels correlate with the severity and progression of ALS., Methods: We used ELISAs to detect MIP-1α levels from 58 patients with ALS and 45 age- and gender-matched controls. The patients with ALS were also clinically evaluated with the revised ALS functional rating scale (ALSFRS-r). Moreover, we followed up with 40 cases of ALS by way of call or clinic visit 4 years after enrollment in this study. Finally, we assessed the correlations between MIP-1α levels and various clinical parameters., Results: We found that the levels of MIP-1α in patients with ALS significantly increased compared to controls and they were positively correlated with duration. MIP-1α showed negative correlations with disease progression rate and the decrease in ALSFRS-r. Furthermore, the cumulative survival of patients with ALS with high levels of MIP-1α exceeded patients with low MIP-1α levels., Conclusions: MIP-1α levels increased in both CSF and serum of patients with ALS, and it may be a potential neuroprotective biomarker in ALS., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by selective motor neuron loss in the brain and spinal cord. The cause of this selective death of motor neurons is still unclear, but among several pathomechanisms that have been discussed, the loss of neurotrophic factors is one hypothesis. Basic fibroblast growth factor 2 (bFGF) may be a potential neurotrophic factor for slowing various neurodegenerative diseases, but its potential role in the prognosis of ALS is not known., Methods: To explore the role of bFGF in ALS, we investigated changes in bFGF in the CSF and serum from patients with sALS and from the control group. Furthermore, we analyzed the correlations between bFGF, disease duration, disease progression rate, ALSFRS-r score and survival., Results: The level of bFGF increased in both the CSF and serum in sALS patients. It was higher in patients with longer durations. It was negatively correlated with disease progression rates, especially in the later stages of sALS, but showed no linear correlation with ALSFRS-r. In an analysis of the relationship between bFGF and survival, we found that sALS patients with high levels of bFGF had significantly higher cumulative survival rates than patients with low levels of bFGF., Discussion and Conclusion: In conclusion, endogenous bFGF increased both in the CSF and serum of sALS patients and it may be a useful biomarker that could predict disease progression and survival., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) in 21 patients with chronic myelomonocytic leukaemia (CMML) who were treated at the Fred Hutchinson Cancer Research Center between 1990 and 1998. There were 11 male and 10 female patients with a median age of 47.4 years (range 1.0-62.9). Patients were conditioned either with total body irradiation (TBI) and chemotherapy, with or without antithymocyte globulin (n = 19), or with chemotherapy alone (n = 2). The marrow donor was an HLA-identical sibling in 12 patients, an HLA-non-identical related donor in three patients and an unrelated volunteer donor in six patients. All evaluable patients achieved sustained engraftment. Fifteen patients developed grades II-IV acute graft-versus-host disease (GVHD). Nine patients (43.0%) are surviving disease free at 0.7-8.1 years (median 6.9) after transplantation. Five patients relapsed 75-660 d after transplant and all died. Five patients died with organ failure and two died with GVHD and associated infections. The Kaplan-Meier estimates of disease-free survival and relapse at 3 years were 39% and 25% respectively. The probability of survival was improved in patients with shorter disease duration compared with those with a long interval from diagnosis to BMT. Thus, as with other myeloproliferative diseases or myelodysplastic syndromes, BMT offers curative therapy for a proportion of patients with CMML. We suggest that patients with CMML who have a suitable donor should be considered for transplantation, probably early in their disease course. However, it will be important to develop new regimens with enhanced antileukaemic efficacy without further increasing regimen-related toxicity and mortality.