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PubMed2000

Agreement among three quality of life measures in patients with ALS.

AIM: To determine the concurrent validity of three self-administered health-related quality of life (HRQOL) questionnaires when administered to patients with amyotrophic lateral sclerosis (ALS). BACKGROUND: ALS is the most common motor neuron disease among adults. As a rapidly progressive and fatal disease, ALS has devastating effects on the patient's relationships, functional capacity and mental health. HRQOL measures include information about patients' physical impairments, functional level, and psychosocial status. This study compares a tool designed for the ALS population, the Sickness Impact Profile ALS-19 (SIP/ALS19), and two tools designed to be used in any population, the Quality of Well-being Scale SA (QWB SA), and the SF-36 Health Survey (SF-36). Correlation of the scores would suggest that each tool is valid as a stand-alone measurement of quality of life for this patient population. METHODS: The SIP/ALS-19, the SF-36, and the QWB SA were self-administered to 19 subjects diagnosed with ALS. The scores for each test were ranked and analyzed for agreement using the Spearman rank correlation coefficient. RESULTS: The SIP/ALS-19 demonstrated moderate to good correlation with the QWB SA and fair correlation with the SF-36. The SF-36 had little to no correlation with the QWB SA. CONCLUSIONS: The study did not demonstrate significant correlation among the three quality of life measures. The SIP/ALS-19, SF-36, and QWB SA each have a different focus in measuring HRQOL. The healthcare practitioner should consider the patient's stage of disease, treatment goals, and type of interventions planned when selecting a HRQOL tool for the ALS patient.

Adult↗
PubMed2002

A comparison of sympathetic outflow to muscles between cervical spondylotic amyotrophy and ALS.

To confirm the diagnostic usefulness of muscle sympathetic nerve activity (MSNA) in differentiation between cervical spondylotic amyotrophy (CSA) and amyotrophic lateral sclerosis (ALS) with cervical spondylosis (CS), MSNA, heart rate (HR) and blood pressure (BP) were recorded in 10 patients with CSA and ALS with CS, and age-matched healthy volunteers at rest and during head-up tilting. There were no differences in age, disability scores, pulmonary function, and HR or BP at rest between ALS and CSA groups. Resting MSNA was significantly greater in patients with ALS with CS than in comparison groups (P<0.001) with virtually no overlap between ALS and the CSA groups. During head-up tilting, changes in BP and MSNA were significantly less in patients with ALS than in patients with other subjects. MSNA at rest clearly differentiated CSA from ALS with CS, suggesting diagnostic utility.

Age Factors↗
PubMed2004

Major stressors facing patients with amyotrophic lateral sclerosis (ALS): a survey to identify their concerns and to compare with those of their caregivers.

OBJECTIVE: To identify and compare the primary existential, physical, and psychosocial stressors affecting patients with ALS and their caregivers. Health care providers, together with patients and their caregivers, are challenged to identify both physical and psychosocial concerns that have the greatest impact on quality of life over the course of a serious illness. It is also helpful to understand the priorities of these concerns from the patients' and caregivers' perspectives so that we can render optimal care and help patients and their families with the myriad problems that accompany a progressive and fatal disease. METHODS: We analyzed responses from the first 66 patients with ALS and 61 ALS caregivers who attended the Baylor College of Medicine, Department of Neurology, Vicki Appel MDA ALS Clinic and who completed our internally generated 19-item survey. Subjects were asked to choose their three most important concerns. For analysis purposes we categorized the data into three domains: existential, physical, and psychosocial. Demographic data were collected. The Appel ALS Rating Scale (AALS) was used to measure disease symptom severity. RESULTS: Sixty-six patients (45 men, 21 women) with a mean age of 57.9 (range 30-82) years and 61 caregivers completed the checklist. At the time the patients completed the survey, their mean AALS total score was 77.0 (range 34-132), indicating mild to moderate disability. The most important stressors identified by patients and caregivers were existential concerns (86.4% of patients and 79.7% of caregivers) and physical stressors (80.3% of patients and 76.3% of caregivers). Less than 50% of both groups endorsed psychosocial stressors (38%). However, when we analyzed the domain specific items, there was a significant difference between patients and caregivers on worries about the patient's dependency (37.9% of patients and 6.8% of caregivers). DISCUSSION: Health care professionals should apply a holistic approach to treatment and care of patients with ALS. Families should be included in the process, and it should not be assumed that patients and caregivers will agree on all issues. Future research should focus on therapeutic interventions to help ALS patients and their families cope with the multiple stressors accompanying a catastrophic illness.

Adaptation, Psychological↗
PubMed2005

Promoting excellence in end-of-life care in ALS.

The type and quality of end-of-life care varies greatly in ALS; the time to initiate end-of-life care is not defined, and decision making is hampered by logistical and financial barriers. There has been no systematic review of these issues in ALS. The goals of this initiative are to: 1) improve end-of-life care for patients with ALS and families based on what limited evidence is available; 2) increase awareness, interest, and debate on the end-of-life care in ALS; and 3) identify areas needed for new prospective clinical research. The ALS Peer Workgroup reviewed the literature and 1) identified the current state of knowledge, 2) analysed the gaps in care, and 3) provided recommendations for standard of care and future research. It was shown that areas of investigation are needed on the incorporation of an interdisciplinary approach to care in ALS that includes: psychosocial evaluation and spiritual care; the use of validated instruments to assess patient and caregiver quality of life; and the establishment of proactive caregiver programs. Several public policy changes that will improve coverage for medical care, hospice, and caregiver costs are also reviewed. More clinical evidence is needed on how to provide optimal end-of-life care specifically in ALS.

Advance Care Planning↗
PubMed1996

Olopatadine (AL-4943A): ligand binding and functional studies on a novel, long acting H1-selective histamine antagonist and anti-allergic agent for use in allergic conjunctivitis.

AL-4943A (Olopatadine) is a new antihistaminic and anti-allergic drug. It was tested for its ability to compete for [3H]pyrilamine, [3H]tiotidine and [3H]N-methyl histamine binding to H1, H2 and H3 histamine receptors, respectively. AL-4943A exhibited the highest affinity (Ki = 41.1 +/- 6.0 nM) for H1-receptors and a significantly lower affinity for H2- (Ki = 43,437 +/- 6,257 nM) and H3-receptors (Ki = 171,666 +/- 6,774 nM), respectively. These data showed AL-4943A to be an H1-selective compound, being 1,059- and 4,177-times more selective for H1- than H2- and H3-receptors. AL-4943A was more H1-selective than levocabastine, ketotifen, antazoline and pheniramine and, also, exhibited a low affinity for 38 nonhistamine receptor binding sites. AL-4943A antagonized histamine-induced phosphoinositide (PI) turnover in cultured human conjunctival epithelial cells (IC50 = 9.5 +/- 1.5 nM, n = 3), human corneal fibroblasts (IC50 = 19 nM) and transformed human trabecular meshwork cells (IC50 = 39.9 nM). These data have shown AL-4943A to be a high affinity, high potency H1-selective histamine antagonist. This information, coupled with a long duration of action in an in vivo model of allergic conjunctivitis, suggests that AL-4943A may be a useful drug to treat various ocular allergic diseases, including allergic conjunctivitis.

Anti-Allergic Agents↗
PubMed2006

Overexpression of an Arabidopsis magnesium transport gene, AtMGT1, in Nicotiana benthamiana confers Al tolerance.

Aluminium (Al) toxicity is the most important limiting factor for crop production in acid soil environments worldwide. In some plant species, application of magnesium (Mg(2+)) can alleviate Al toxicity. However, it remains unknown whether overexpression of magnesium transport proteins can improve Al tolerance. Here, the role of AtMGT1, a member of the Arabidopsis magnesium transport family involved in Mg(2+) transport, played in Al tolerance in higher plants was investigated. Expression of 35S::AtMGT1 led to various phenotypic alterations in Nicotiana benthamiana plants. Transgenic plants harbouring 35S::AtMGT1 exhibited tolerance to Mg(2+) deficiency. Element assay showed that the contents of Mg, Mn, and Fe in 35S::AtMGT1 plants increased compared with wild-type plants. Root growth experiment revealed that 100 microM AlCl(3) caused a reduction in root elongation by 47% in transgenic lines, whereas root growth in wild-type plants was inhibited completely. Upon Al treatment, representative transgenic lines also showed a much lower callose deposition, an indicator of increased Al tolerance, than wild-type plants. Taken together, the results have demonstrated that overexpression of ATMGT1 encoding a magnesium transport protein can improve tolerance to Al in higher plants.

Aluminum↗
PubMed2002

QTL analysis of Al tolerance in recombinant inbred lines of Arabidopsis thaliana.

Quantitative trait loci (QTLs) and epistasis for Arabidopsis thaliana aluminum (Al) tolerance were analyzed using a recombinant inbred (RI) population of 100 lines derived from a cross between Landsberg erecta and Columbia (Col). Root growth of the RI population was determined in hydroponics using solutions containing 0 or 4 micro M of AlCl(3 )and a series of nutrients, except P(i), at pH 5.0. Al tolerance was defined as relative root length [RRL: plus Al/minus Al (%)], and the RI lines ranged from 22.6 to 97.4% with a broad sense heritability of 0.99. Using the composite interval mapping method, two significant single factor QTLs (P<0.05) were detected by RRL on chromosomes 1 and 4, where the Col allele showed positive and negative effects on the Al tolerance. These QTLs could explain about 43% of the total variation of Al tolerance among the RI population. On the other hand, five epistatic loci pairs were identified by the complete pair-wise search method (P<0.0005). No single factor QTL and epistatic loci pairs were shared by the root length in the control and the RRL, suggesting that the loci identified by the RRL would be specific for Al treatment and controlling Al tolerance among the RI population.

Adaptation, Physiological↗
PubMed2004

Effects of aluminum on organic acid metabolism and secretion by red spruce cell suspension cultures and the reversal of Al effects on growth and polyamine metabolism by exogenous organic acids.

In the absence of added Al, the concentration of succinate in cultured red spruce (Picea rubens Sarg.) cells was 15-20 times higher (> 600 nmol g-1FW) than that of citrate or oxalate and 4-6 times higher than that of malate. Addition of AlCl3 (effective monomeric Al concentrations of 0.23 and 0.48 mM) to 3-day-old suspension cultures significantly increased cellular succinate concentrations with a concomitant decrease in cellular oxalate concentrations. However, in the medium of Al-treated cell cultures, both succinate and oxalate concentrations were significantly higher than in the medium of cell cultures without added Al, and oxalate concentrations were several times higher than succinate concentrations. Aluminum did not significantly affect the cellular concentrations of malate, ascorbate and citrate, and none of these organic acids was present in detectable quantities in the medium. Exogenous succinate alone or with Al had no effect on cellular free polyamine concentrations or cell mass. Aluminum caused a significant increase in cellular putrescine concentrations. Addition of malate had a positive effect on growth and completely reversed the effects of Al on cell physiology. In contrast, the addition of oxalate and citrate only partly reversed the effects of Al.

Aluminum↗
PubMed1991

Differential adsorption of Al, Ca, and Mg by roots of red spruce (Picea rubens Sarg.).

The surface adsorption characteristics of red spruce (Picea rubens) roots were examined as a function of changes in external acidity and cation concentrations. Root cation exchange capacity varied significantly with changes in pH, increasing from 110 micromol(c) g(-1) at pH 3.5 to 155 micromol(c) g(-1) at pH 4.5, and reaching 250 micromol(c) g(-1) at pH 7.0. In general, Al adsorption by spruce roots was much greater than either Ca or Mg adsorption under the same initial conditions. However, root affinity for the divalent cations was proportionately much more sensitive to pH changes than was root affinity for Al. The fractions of adsorbed Ca and Mg increased by 50 to 100% as pH increased from 3.5 to 4.5, whereas the fraction of adsorbed Al remained relatively constant at both initial pH conditions. Competition experiments at pH 3.5 and 4.5 indicated that Al adsorption was strongly favored over Ca adsorption, except at low Al concentrations (~10 micromol l(-1)), high solution Ca(2+)/Al(3+) ion activity ratios (> 1.5 to 5.0), and at the higher pH. These results suggest that cell wall exchange sites in red spruce roots will tend to become progressively saturated with Al under the prevailing conditions of many acidic forest soils. To the extent that root adsorbed Al interferes with the active uptake of Ca and Mg, this process of competitive cation adsorption can contribute to impaired mineral nutrition in the spruce forest community.

Journal Article↗
PubMedDate not supplied

Al+++ binding studies and metallic cation effects on bioprosthetic heart valve calcification in the rat subdermal model.

Al+++ preincubation has been shown to inhibit calcification of glutaraldehyde pretreated bovine pericardium calcification in the rat subdermal model. This study was designed to assess in vitro the Al+++ (10(-1) M, 10(-2) M, 10(-3) M preincubations) binding characteristics of glutaraldehyde pretreated bovine pericardium. In vivo studies assessed the ability of AlCl3 (10(-1) M, 10(-2) M, 10(-3) M) preincubations to inhibit calcification after 21 and 60 days in the rat subdermal model. Other in vivo studies investigated the ability of other metallic cations (Fe+++, La+++, and Ga+++) used as a pretreatment to inhibit glutaraldehyde pretreated bovine pericardium calcification after a 21 day rat subdermal implant. Lyophylized glutaraldehyde pretreated bovine pericardium samples were analyzed for Al+++ by neutron activation. In vitro results showed the greatest glutaraldehyde pretreated bovine pericardium Al+++ uptake in specimens incubated in 0.1M AlCl3. Maximal Al+++ uptake occurred by 1 hour. Glutaraldehyde pretreated bovine pericardium Al+++ levels after incubation in 10(-1) M, 10(-2) M, and 10(-3) M AlCl3 for 1 hour were 351.4 +/- 15.8 nM/mg, 96.4 +/- 17.4 nM/mg, and 24.6 +/- 4.9 nM/mg, respectively versus 394.5 +/- 48.0 nM/mg, 105.3 +/- 2.3 nM/mg, 40.0 +/- 8.8 nM/mg, respectively for 3 days. In vivo 21 day rat (50-60 g, male, Sprague-Dawley) subdermal implants of 0.1 M AlCl3, FeCl3, FeCl3 plus citrate, LaCl3, and GaNO3 pretreated glutaraldehyde pretreated bovine pericardium showed calcification inhibition by Al+++, Fe+++, and Fe+++ plus citrate (Ca++ = 5.5 +/- 0.2 micrograms/mg, 13.6 +/- 4.6 micrograms/mg, 5.9 +/- 1.7 micrograms/mg, respectively) compared to control (Ca++ = 63.6 +/- 5.7 micrograms/mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1977

The effect of timing of skin grafts on subsequent survival in ALS-treated, marrow-infused mice.

It has previously been shown that the survival of C3H/He skin grafts can be prolonged on ALS-treated (C57 x A)F1 mice by the injection of C3H/He bone marrow cells 7 days after grafting. Experiments have now been done to study the influence of timing of the skin graft on its subsequent survival. Single grafts were placed either before or after marrow was given. Paired grafts on the same animal were also studied, one placed before and one after marrow was given. Grafts placed before marrow was given, whether single or paired, showed equal and significant prolongation while grafts placed after marrow was given showed only slight prolongation compared with ALS controls. Paired grafts showed distinctly different survival curves depending on their time of placement in relation to injection of marrow. The pattern of graft survival suggests that the graft prolongation achieved is attributable to a mechanism similar to enhancement. Experiments were also done to see whether a state of preexisting immunity to the skin graft donor induced by the injection of marrow could be manipulated to achieve prolonged graft survival. (C57 x A)F1 mice were treated with ALS, given injections of C3H/He marrow, and grafted 56 days later with C3H/He skin either with or without additional ALS at the time of grafting. If no ALS was given grafts were rejected in accelerated fashion, indicating that the previous injection of marrow had sensitized the recipient. With additional ALS, the prolongation of graft survival achieved far exceeded that seen using our standard protocol of skin grafting a week before marrow is given. This represents one of the first demonstrations of positive alteration of a preexisting state of immunity to achieve graft prolongation which exceeds that expected by giving ALS immunosuppression alone to a presensitized animal.

Animals↗
PubMed1980

Effect of splenectomy on specific unresponsiveness to skin allografts induced in ALS-treated, marrow-injected mice.

The role of the spleen in the induction and maintenance of unresponsiveness to skin allografts and in the generation of suppressor cells has been studied in ALS-treated B6AF1 mice grafted with C3H/He skin and injected with C3H/He marrow. B6AF1 mice were splenectomized either before the induction of unresponsiveness or on day +13, +28, or +42 after unresponsiveness was induced. Graft survival in the splenectomized mice was compared to that observed in nonsplenectomized ALS-treated, marrow-injected controls. Graft survival was prolonged equally in all splenectomized groups and the nonsplenectomized controls. To study the effect of the spleen on the generation of suppressor cells, lymph node cells were removed at day +42 from splenectomized ALS-treated, marrow-injected B6AF1 mice bearing C3H/He skin grafts and transferred to ALS-treated B6AF1 recipientso ALS-treated BTAF1 recipients grafted with C3H/He skin. Graft survival in the secondary recipients receiving lymph node cells from splenectomized donors was compared to that observed in ALS-treated B6AF1 mice that received lymph node cells transferred from nonsplenectomized enhanced donors. Suppressor cell activity could be detected in the nodes of splenectomized mice, but a higher dose of lymph node cells was required to transfer unresponsiveness from splenectomized donors compared to nonsplenectomized donors. These results indicate that the spleen is not necessary for the induction or maintenance of unresponsiveness to skin allografts in ALS-treated, marrow-injected mice. In addition, suppressor cells can be generated in the lymph nodes of unresponsive mice in the absence of the spleen, although the production of suppressor cells appears to be less effective in splenectomized mice than in mice with intact spleens.

Animals↗
PubMed1989

Competitive Al Inhibition of Net Mg Uptake by Intact Lolium multiflorum Roots : I. Kinetics.

Aluminum impairs uptake of Mg(2+), but the mechanisms of this inhibition are not understood. The depletion technique was used to monitor net Mg(2+) uptake from nutrient solution by intact, 23-day-old plants of ryegrass (Lolium multiflorum Lam., cv Gulf and Wilo). Activities of Mg(2+) and monomeric Al species in nutrient solution were calculated and used as the basis for expressing the results. The kinetics of net Mg(2+) absorption was resolved into (a) a transpiration-dependent uptake component, (b) a metabolically mediated, discontinuous saturable component that is Al(3+) sensitive and p-chloromercuribenzene sulfonic acid (PCMBS) resistant, and (c) a linear, carbonyl cyanide m-chlorophenylhydrazone resistant, Al(3+) sensitive component that might be a type of facilitated diffusion. Lowering the pH from 6.0 to 4.2 exerted a noncompetitive inhibition of net Mg(2+) uptake, while aluminum at 6.6 micromolar Al(3+) activity exerted competitive inhibition of net Mg(2+) uptake at pH 4.2. The Al(3+)-induced effect was obvious after 30 minutes. Cultivar-specific ability to retain a higher affinity for Mg(2+) by postulated transport proteins in the presence of Al(3+) might be one of the mechanisms of differential Al tolerance among ryegrass cultivars.

Journal Article↗
PubMed1999

Anti-neural antibodies in serum and cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients.

OBJECTIVES: An autoimmune basis has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). This hypothesis is supported by the presence of antibodies that interact with motoneuron antigens in serum of these patients. Against autoimmunity are the discrepances in the frequency of the antibodies appearance and also failure of immunosuppression. The aim of our study was to evaluate the titer of antibodies against GM1-gangliosides, AGM1-gangliosides and anti-sulfatides in paired serum and cerebrospinal fluid samples in the ALS patients. MATERIAL AND METHODS: Serum of 103 and CSF of 79 patients with ALS was examined. The "disease controls" consisted of 22 cases of other motor neuron diseases and 50 healthy, age-matched normals. CSF was drawn at the same time from 79 ALS patients, 6 cases of the "disease controls" and 50 normals. To study the titer of antibodies against GM1-gangliosides, AGM1-gangliosides and sulfatides the ELISA technique has been applied. RESULTS: An increased titer against GM1-gangliosides, AGM1-gangliosides and sulfatides in ALS appeared in serum in 18%, 32%, and 11%, resp., in the "disease controls" the increased antibodies titer appeared in single cases. In CSF the appropriate values in ALS were 20%, 15%, 8%, resp. In the "disease controls" a high antibodies titer was a rare finding. CONCLUSIONS: It is concluded that in some ALS cases and also in some patients with other motor neuron diseases an autoimmune mechanism may contribute to motor neuron injury.

Adult↗
PubMed1988

On the effect of Al(OH)3 as an immunological adjuvant.

Using a mice in a tetanus vaccination system, we have examined the mode of action of the immunological adjuvant, aluminium hydroxide (Al(OH)3), on antibody titers as measured by an ELISA-method. A profound effect of the adjuvant was observed after primary immunizations, increasing titers about 100-fold compared to plain (not adjuvanted) controls. However, no effect on titers could be attributed to a content of Al(OH)3 in the vaccines when used for booster immunizations, as the increase in titers after boosting was either the same for groups given plain or adsorbed toxoids, or even higher in the groups receiving the plain vaccine. Thus, the effect of Al(OH)3 as an adjuvant seems to be exerted mainly on the primary antibody response. Investigating the mode of action by the adjuvant, we adsorbed a certain amount of toxoid onto varying doses of Al(OH)3. An antigen ELISA revealed that all toxoid had been adsorbed to the Al-gel in the preparations. The antibody titers after immunization showed a significantly higher response to toxoid adsorbed to the higher amount of adjuvant, indicating that this effect was most probably due to free, not antigen-bound, Al-particles. Moreover, this effect could be inhibited when BSA was added in excess to the preparation, thereby blocking the free residues on the Al-gel.

Adjuvants, Immunologic↗
PubMed1988

Expression of Nodulation Genes in Rhizobium leguminosarum biovar trifolii Is Affected by Low pH and by Ca and Al Ions.

Early stages in the infection of leguminous plants by Rhizobium spp. are restricted at low pH and are further influenced by the presence of Ca and Al ions. In the experiments reported here, transcriptional and translational fusions of the Escherichia coli lacZ gene to Rhizobium leguminosarum biovar trifolii nodulation (nod) genes were used to investigate the effects of pH and of Ca and Al ions on nod gene expression. The regulatory nodD gene in R. leguminosarum biovar trifolii was constitutively expressed at a range of pH levels between 4.8 and 6.5, and expression was not affected by the addition of 22.5 muM Al or 1,250 muM Ca. Induction of expression of nodA, nodF, and region II nodulation genes in the presence of 5 x 10 M 7,4'-dihydroxyflavone was restricted at a pH of <5.7 and was extremely poor at pH 4.8. Induction of nodA expression was further restricted by 22.5 muM Al over a range of pH levels but was increased in the presence of Ca. The addition of Ca, however, only slightly alleviated the Al-mediated inhibition of nodA induction. Induction of expression of nodA was equally sensitive to low pH in three strains of R. leguminosarum biovar trifolii (ANU845, ANU815, and ANU1184), which exhibited contrasting growth abilities in solution culture at a pH of <5.0. Aluminum, however, differentially affected the induction of nodA in these three strains, with the most Al-tolerant strain for growth being the most Al-sensitive strain for nod gene induction. Poor induction of expression of nodulation genes in R. leguminosarum biovar trifolii was considered to be an important factor contributing to the acid-sensitive step of legume root infection.

Journal Article↗
PubMed1990

Cloning, sequence, and photoregulation of al-1, a carotenoid biosynthetic gene of Neurospora crassa.

Carotenoid biosynthesis is regulated by blue light during growth of Neurospora crassa mycelia. We have cloned the al-1 gene of N. crassa encoding the carotenoid-biosynthetic enzyme phytoene dehydrogenase and present an analysis of its structure and regulation. The gene encodes a 595-residue polypeptide that shows homology to two procaryotic carotenoid dehydrogenases. RNA measurements showed that the level of al-1 mRNA increased over 70-fold in photoinduced mycelia. Transcription run-on studies indicated that the al-1 gene was regulated at the level of initiation of transcription in response to photoinduction. The photoinduced increase of al-1 mRNA levels was not observed in two Neurospora mutants defective in all physiological photoresponses. Analysis of cosmid containing al-1 and of a translocation strain with a breakpoint within al-1 indicated that al-1 transcription proceeds towards the centromere of linkage group I of N. crassa.

Amino Acid Sequence↗
PubMed2004

Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter.

Little is known about global gene expression patterns in the human neurodegenerative disease amyotrophic lateral sclerosis (ALS). To address this, we used high-density oligonucleotide microarray technology to compare expression levels of approximately 6,800 genes in postmortem spinal cord gray matter obtained from individuals with ALS as well as normal individuals. Using Fisher discriminant analysis (FDA) and leave-one-out cross-validation (LOOCV), we discerned an ALS-specific signature. Moreover, it was possible to distinguish familial ALS (FALS) from sporadic ALS (SALS) gene expression profiles. Characterization of the specific genes significantly altered in ALS uncovered a pro-inflammatory terminal state. Moreover, we found alterations in genes involved in mitochondrial function, oxidative stress, excitotoxicity, apoptosis, cytoskeletal architecture, RNA transcription and translation, proteasomal function, and growth and signaling. It is apparent from this study that DNA microarray analysis and appropriate bioinformatics can reveal distinct phenotypic changes that underlie the terminal stages of neurodegeneration in ALS.

Amyotrophic Lateral Sclerosis↗