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At least 613 records · Page 34Linked to original sources
PubMed2005

Hypermetabolism in ALS: correlations with clinical and paraclinical parameters.

Despite a reduction in fat-free mass (FFM), a hypermetabolism has been reported with an average of 10% in amyotrophic lateral sclerosis (ALS) patients as compared with a healthy population. The objectives of this study were to confirm the level of hypermetabolism determined by using indirect calorimetry in 168 patients with a probable or a definite ALS and to study correlations with survival. Consecutive evaluations of resting energy expenditure (REE) were performed from diagnosis to the proximity of death in 44 ALS patients. Differences with the calculated value determined a DeltaREE. FFM was given by bioimpedance. At T(1), REE was significantly increased by an average of 14% as compared with the calculated value. 62.3% of ALS patients were considered as hypermetabolic. REE was correlated in univariate analysis with age, sex, clinical form at onset, presence of a denutrition, weight, FFM, phase angle and ALS Functional Rating Scale (ALSFRS). In multivariate analysis, REE was linked to age and FFM. DeltaREE was correlated in univariate analysis with sex, phase angle and manual muscle testing (MMT). In multivariate analysis, age and sex remained significantly correlated. During progression of ALS, REE levels remained higher than calculated values with a trend to decrease at proximity of death, whereas FFM remained stable. From T(1), survival was linked to MMT, ALSFRS, vital capacity, REE and phase angle. We confirmed the existence of a stable hypermetabolic state in ALS which depends mainly on age, sex and FFM. REE is a prognostic factor for survival in univariate analysis.

Age Factors↗
PubMed2006

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1.

LFA-1 (alpha(L)beta(2)) mediates cell-cell and cell-extracellular matrix adhesions essential for immune and inflammatory responses. One critical mechanism regulating LFA-1 activity is the conformational change of the ligand-binding alpha(L) I domain from low-affinity (LA), closed form, to the high-affinity (HA), open form. Most known integrin antagonists bind both forms. Antagonists specific for the HA alpha(L) I domain have not been described. Here, we report the identification and characterization of a human antibody AL-57, which binds to the alpha(L) I domain in a HA but not LA conformation. AL-57 was discovered by selection from a human Fab-displaying library using a locked-open HA I domain as target. AL-57 Fab-phage bound HA I domain-expressing K562 cells (HA cells) in a Mg(2+)-dependent manner. AL-57 IgG also bound HA cells and PBMCs, activated by Mg(2+)/EGTA, PMA, or DTT. The binding profile of AL-57 IgG on PBMCs was the same as that of ICAM-1, the main ligand of LFA-1. In contrast, an anti-alpha(L) murine mAb MHM24 did not distinguish between the HA and LA forms. Moreover, AL-57 IgG blocked ICAM-1 binding to HA cells with a potency greater than MHM24. It also inhibited ICAM-1 binding to PBMCs, blocked adhesion of HA cells to keratinocytes, and inhibited PHA-induced lymphocyte proliferation with potencies comparable with MHM24. These results indicate that specifically targeting the HA I domain is sufficient to inhibit LFA-1-mediated, adhesive functions. AL-57 represents a therapeutic candidate for treatment of inflammatory and autoimmune diseases.

Antibodies, Monoclonal↗
PubMed2000

AL-3138 antagonizes FP prostanoid receptor-mediated inositol phosphates generation: comparison with some purported FP antagonists.

The aim of this study was to pharmacologically characterize the antagonist properties of a novel prostaglandin F2alpha (PGF2alpha) analogue (11-deoxy-16-fluoro PGF2alpha; AL-3138) using a variety of second-messenger assays of prostaglandin receptor subtypes. A detailed comparison was made between AL-3138 and some purported FP receptor antagonists such as PGF2alpha dimethylamine, PGF2alpha dimethylamide, glibenclamide and phloretin using the FP receptor-mediated phosphoinositide turnover assay in A7r5 rat thoracic aorta smooth muscle cells and mouse Swiss 3T3 fibroblasts. The potency and efficacy of AL-3138 as an FP receptor agonist were: EC50 = 72.2 +/- 17.9 nM (Emax = 37%) (n = 3) in A7r5 cells and EC50 = 20.5 +/- 2.8 nM (Emax = 33%) (n = 5) in 3T3 cells. Being a partial agonist, the antagonist potency of AL-3138 against fluprostenol in A7r5 cells was determined to be: Ki = 296 +/- 17 nM (n = 3) and Kb = 182 +/- 44 nM (n = 5) (-log Kb = 6.79 +/- 0.1). AL-3138 exhibited very minimal or no antagonistic effects at EP2, EP4, DP and TP prostaglandin receptors. Both PGF2alpha dimethylamide and PGF2alpha dimethylamine were inactive as FP receptor antagonists, whereas phloretin and glibenclamide were very weak and had -log Kb values of 5.28 +/- 0.09 (n = 3) and 3.58 +/- 0.32 (n = 3), respectively. However, phloretin antagonized functional responses of EP2 and DP prostanoid receptors, and also the V1-vasopressin receptor. AL-3138 competed for [3H]PGF2alpha binding to FP receptors with a relatively high affinity (IC50high = 312 +/- 95 nM) matching its functional antagonist potency. In conclusion, AL-3138 is a more potent and selective FP receptor antagonist than glibenclamide, phloretin, PGF2alpha dimethylamide and PGF2alpha dimethylamine and is therefore a unique and novel pharmacological tool to help characterize FP receptor-mediated functions.

3T3 Cells↗
PubMed2005

The ALSFRSr predicts survival time in an ALS clinic population.

OBJECTIVE: To determine whether the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRSr), a predictor of survival time in ALS clinical trials, predicts survival time in an ALS clinic population. METHODS: The authors prospectively evaluated 267 consecutive patients with ALS at first visit to an ALS clinic using the ALSFRSr and pulmonary function testing. The association of ALSFRSr score at baseline with death or tracheostomy in ALS was examined using Cox proportional hazards models, adjusting for age at baseline, sex, and symptom duration. RESULTS: Of 267 patients with ALS, 103 (39%) reached the endpoint, defined as either death (79 patients) or tracheostomy (24 patients), during a mean follow-up of 1.0 +/- 0.7 years. Among the 103 patients who reached the endpoint during follow-up, 77 (75%) had a baseline ALSFRSr score of less than 38 (the median baseline score of all patients), compared to 53 of 164 (32%) who remained alive without tracheostomy. Patients with a total ALSFRSr score below the median had a 4.4-fold increased risk of death or tracheostomy compared to those who scored above the median (HR: 4.38, 95% CI: 2.79 to 6.86, p < 0.001). Both the total ALSFRSr score at baseline (HR: 0.94, 95% CI: 0.91 to 0.98, p < 0.001) and forced vital capacity at baseline (HR: 0.99, 95% CI: 0.98 to 1.00, p = 0.02) were associated with death or tracheostomy when included in the same Cox model. CONCLUSIONS: In an ALS clinic population, the total Amyotrophic Lateral Sclerosis Functional Rating Scale-revised score at baseline is a strong predictor of death or tracheostomy independently of forced vital capacity and after adjustment for age at baseline, sex, and symptom duration.

Age of Onset↗
PubMed2005

Prevalence and patterns of cognitive impairment in sporadic ALS.

OBJECTIVE: To investigate the prevalence and nature of cognitive changes associated with sporadic amyotrophic lateral sclerosis (ALS) using a large scale study. METHODS: Consecutive patients with sporadic ALS (n = 279) underwent comprehensive neurologic evaluation and neuropsychological testing. Testing data from normal controls (n = 129) were used for classification and comparison purposes. RESULTS: On non-motor, non-speed-dependent tasks, 51% of patients with ALS had evidence of cognitive impairment compared to 5% of controls. Cluster analysis suggested four patient subgroups: 49% intact, 32% with mild impairment, 13% with moderate impairment, and 6% with severe impairment. Forty-one patients (15%) met criteria for frontotemporal dementia (FTD). ALS patient subgroups, excluding the intact group, performed significantly lower on tests of executive function and memory than normal controls. Patients with more severe disease also had deficits in confrontation naming. Although memory function declined with increasing severity of overall cognitive impairment, only two patients had the severe memory loss typical of Alzheimer disease. Cognitive impairment was correlated with clinical measures of word-finding, phrase length, and motor programming. Cognitive impairment was not correlated with depression scores or severity or duration of motor or bulbar symptoms. Patients with bulbar vs limb-onset ALS were not different in either level of impairment or pattern of performance. CONCLUSIONS: These data confirm the presence of cognitive impairment in 50% of patients with ALS and particularly implicate executive dysfunction and mild memory decline in the disease process. More severe impairment occurs in a subset of patients with ALS and has features consistent with FTD.

Adult↗
PubMed1996

ALS.

The cause of ALS is not known but there are four main hypotheses about its etiology. First, an excess of extracellular glutamate in the CNS of patients with ALS resulting from a defect in glutamate reuptake may have excitotoxic effects on motor neurons. Clinical trials suggest the antiglutamate agent riluzole improves survival of patients with the disease. Second, ALS may be an autoimmune disease, but immunologically-based treatments have been unsuccessful. The third hypothesis is that ALS results from a lack of neurotrophic growth factors. Preliminary results from clinical trials indicate recombinant human insulin-like growth factor I offers therapeutic promise. Finally, familial ALS is sometimes linked to a gene encoding a Cu/Zn-binding superoxide dismutase; the mutations in ALS are thought to result in gain of function of dismutase activity. The involvement of superoxide dismutase in sporadic ALS is unclear.

Amyotrophic Lateral Sclerosis↗
PubMed1998

A proton magnetic resonance spectroscopic study in ALS: correlation with clinical findings.

OBJECTIVE: To evaluate neuronal dysfunction in the motor region subcortical white matter in ALS using volumetric localized proton magnetic resonance spectroscopy (1H-MRS). METHODS: Sixteen patients with E1 Escorial definite, probable, or possible ALS and eight healthy age-matched control subjects were studied. The ALS patients were divided into those with limb onset (n = 8) and those with bulbar onset (n = 8). Measurements of the metabolic ratios N-acetylaspartate (NAA)/creatine and phosphocreatine (Cr+PCr), NAA/choline (Cho), and Cho/(Cr+PCr) were correlated with clinical assessments. RESULTS: We found no differences in the metabolic peak area ratios in the motor region when comparing the total ALS group and the control subjects. However, correlations were found between the NAA/(Cr+PCr) ratio and the E1 Escorial category (p = 0.03), the ALS severity scale (p = 0.01), and the Medical Research Council score (p = 0.06). No correlations were found between the NAA/(Cr+PCr) ratio and the Ashworth Spasticity Scale, reflex score, or disease duration (p > 0.16). Bulbar-onset patients had a lower NAA/(Cr+PCr) ratio in the motor region compared with limb-onset patients (p = 0.03). CONCLUSION: In vivo 1H-MRS of the subcortical white matter in the motor region is unlikely to be sensitive enough to detect early disease changes in ALS because there is considerable overlap between the metabolic peak area ratios from patients with ALS and normal control subjects. However, changes in the NAA/(Cr+PCr) metabolic peak area ratios correlate with clinical measures of disease severity, and this measure may be useful in monitoring disease progression.

Adult↗
PubMed2001

Cognitive impairment in sporadic ALS: a pathologic continuum underlying a multisystem disorder.

BACKGROUND: Traditionally considered a motor neuron-selective disorder, the clinical manifestations of ALS can include a frontotemporal dementia. Although the pathologic substrate of cognitive impairment remains to be defined, the presence of ubiquitin-immunoreactive (Ub+) intraneuronal inclusions in cortical regions has been suggested to constitute a pathologic marker of this process. METHODS: The authors compared the neuropathological features of four cognitively impaired patients with ALS, four cognitively intact patients with ALS, and four neurologically normal patients. The extent and load of Ub+ neuronal inclusions, Ub+ dystrophic neurites, and superficial linear spongiosis (SLS) was determined among a number of cortical, hippocampal, and subcortical regions. RESULTS: Although Ub+, alpha-synuclein-negative, and tau-negative neuronal inclusions were observed in both cognitively impaired and cognitively intact patients with ALS, their density and extent was greater among the former, with the difference greatest in the cingulate gyrus. Ub+ neurites were observed in a similar distribution. Only the presence of SLS, affecting the first and second cortical layers, reliably distinguished between the cognitively impaired and cognitively intact ALS subpopulations. In three of four cognitively impaired patients with ALS, SLS was associated with transcortical microglial activation, in the absence of detectable differences in astrocytosis, density of calbindin or parvalbumin neurons, or optical density of synaptophysin and SNAP-25. CONCLUSIONS: Although intraneuronal Ub+ inclusions and dystrophic neurites are observed in both ALS subpopulations, the presence of cognitive impairment was associated with a greater distribution and load of both neuropathologic features, suggesting a disease continuum. Moreover, cognitive impairment was uniformly associated with superficial linear spongiosis, a pathologic feature common to several forms of frontotemporal dementia.

Adult↗
PubMed2002

Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activity.

OBJECTIVE: Transgenic mice that overexpress a human gene encoding mutant cytosolic superoxide dismutase (SOD1) develop a progressive motor neuron loss that resembles human ALS. Why mutant SOD1 initiates motor neuron death is unknown. One hypothesis proposes that the mutant molecule has enhanced peroxidase activity, reducing hydrogen peroxide (H2O2) to form toxic hydroxyl adducts on critical targets. To test this hypothesis, the authors generated transgenic ALS mice with altered levels of glutathione peroxidase (GSHPx), the major soluble enzyme that detoxifies H2O2. METHODS: SOD1(G93A) ALS mice were bred with mice bearing a murine GSHPx transgene that have a four-fold elevation in brain GSHPx levels and with mice having targeted inactivation of the GSHPx gene and reduced brain GSHPx activity. RESULTS: Survival was not prolonged in ALS mice with elevated brain GSHPx activity (p = 0.09). ALS mice with decreased GSHPx brain activity (20% of normal) showed no acceleration of the disease course (p = 0.89). The age at disease onset in the ALS mice was unaffected by brain GSHPx activity. CONCLUSION: The level of GSHPx activity in the CNS of transgenic ALS mice does not play a critical role in the development of motor neuron disease.

Age of Onset↗
PubMed2004

Increased internalisation and degradation of GLT-1 glial glutamate transporter in a cell model for familial amyotrophic lateral sclerosis (ALS).

It has been suggested that glutamate-induced excitotoxicity plays a central role in the development of motor neuron diseases such as amyotrophic lateral sclerosis (ALS). The GLT-1 isoform of the glutamate transporter gene family is the most important transporter involved in keeping extracellular glutamate concentration below neurotoxic levels. Its loss and an increase in extracellular glutamate has been documented in cases of sporadic and familial ALS, as well as in animal models expressing ALS-linked Cu2+-Zn2+ superoxide dismutase (SOD1) mutations, but the underlying molecular mechanisms are still unclear. We developed and characterised a cell model consisting of polarised epithelial Madin-Darby Canine Kidney (MDCK) cell lines stably expressing wild-type SOD1 or the ALS-linked SOD1 G93A mutant, and analysed the expression of glutamate transporters after transient transfection of the corresponding cDNAs. Like ALS patients and animal models of ALS, the G93A-expressing MDCK cell system showed reduced total glial GLT-1 expression, with no change in the expression of the neuronal EAAC1 glutamate transporter isoform. Morphological analysis revealed the intracellular redistribution of GLT-1 to acidic compartments, whereas the surface distribution of other glutamate transporters (neuronal EAAC1 and glial GLAST) was not affected. Moreover, mutant SOD1 affected the cytosolic tail of GLT-1 because reduced protein expression of EAAC-GLT but not GLT-EAAC chimeras was found in G93A-expressing cell lines. GLT-1 downregulation was greatly induced by inhibition of protein synthesis, and prevented by treatment with chloroquine aimed at inhibiting the activity of acidic degradative compartments. Negligible effect on the protein level or distribution of GLT-1 was observed in cells overexpressing wild-type SOD1. The specific decrease in the GLT-1 isoform of glutamate transporters is therefore recapitulated in G93A-expressing MDCK cell lines, thus suggesting an autonomous cell mechanism underlying the loss of GLT-1 in ALS. Our data indicate that the continuous expression of mutant SOD1 causes the downregulation of GLT-1 by increasing the internalisation and degradation of the surface transporter, and suggest that the cytosolic tail of GLT-1 is required to target the transporter to degradation.

Amyotrophic Lateral Sclerosis↗
PubMed1991

[Diabetic peculiarity of the ALS-Ay and ALR-Ay strains].

ALS and ALR mice were developed as mouse models of alloxan-induced diabetes. These strains do not show spontaneous onset of diabetes. When an obesity gene (Ay) was introduced to these two strains, severe diabetic conditions occurred spontaneously in the produced ALS-Ay and ALR-Ay strains. These strains were examined body weight gain, food consumption, water consumption, urinary sugar content, ketone body level and blood sugar level, and subjected to glucose tolerance test. As a result, in comparison with ALS mice, male ALS-Ay mice showed no obesity and very low tolerance to the glucose tolerance test performed 24 weeks after birth. The level of insulin secretion was 5.0 microU/ml or less, showing hardly any secretory reaction. On the other hand, female ALS-Ay mice were obese and showed no marked decrease in glucose tolerance. The level of insulin secretion was high, and the secretory reaction was strong. In ALR-Ay strain, both male and female mice were obese and showed diabetic conditions similar to those of ALS-Ay mice, though the severity tended to be lower. The characteristic features of diabetic conditions in these mice suggest that these strains, particularly ALS-Ay, may serve as useful new-type models of diabetes.

Alloxan↗
PubMedDate not supplied

[Medical science at the time of the Ummayad Califs of Cordoba: Al-Zahrâwî and Ibn Wâfid, knowledgeable Andalusian phamacologists translated for the Christian West].

The Latin translations of major Arabian texts have largely contributed to the rise of medical sciences in christian Western during the middle age. Among the pharmacologist Andalusian erudites who have been translated into Latin language, for example by Gerard de Crémone, Al-Zahrâwî (Albucasis) and Ibn Wâfid are references. Al-Zahrâwî has written about materia medica in several books included in his thirty volume's encyclopaedia: "al-Tasriîf", Ibn Wâfid has given to the medical world two remarkable treatises; a really formulary "kitâb al-wisâd fi l-tibb" though a book of the simple drugs, "al-kitâb fî al-adwiya al-mufrada".

Arab World↗
PubMed2001

Pharmacological treatment of ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from chronic and selective loss of motor neurons in the brain and spinal cord. In 1993, the etiology of ALS has been clarified for a small sub-group of patients with an autosomal-dominant form of this disease. About 10 percent of familial ALS patients have been associated with more than 50 mutations of the gene of the Cu/Zn superoxide dismutase (SOD1). Mutations in the SOD1 gene account for 1 percent of all ALS patients and have therefore limited epidemological and clinical relevance; however, they are of fundamental importance for the understanding of the ALS pathogenesis, and the development of neuroprotective strategies. In two double-blind and placebo-controlled studies the membrane stabilisator riluzole has been shown to be the first neuroprotective compound with a significant effect on survival of ALS patients. The neuroprotective approach reduced therapeutic nihilism in ALS and is a first step in the treatment of this devastating disease.

Amyotrophic Lateral Sclerosis↗
PubMed2001

[The role of mitochondrial respiratory chain in the pathogenesis of ALS].

Mitochondrial dysfunction and abnormal electron chain transport (ECT) may be involved in the pathogenesis of ALS. The aim of this study was to investigate the effect of cerebrospinal fluid (CSF) from ALS patients on the activity of ECT enzymes in mitochondrial cerebral crude preparations in the rats. We found that CSF inhibited the activity of complex I-III in 20%, complex II-III in 12% and complex IV in 33% of the ALS patients. CSF from the controls did not affect the activity of complex I-III and II-III. The effect of the CSF ultrafiltrates with cut off below 5000 daltons on the activity of ECT enzymes was also investigated. The CSF ultrafiltrates inhibited the activity of complex I-III, complex II-III and complex IV in 38%, 44% and 53% of the ALS patients, and in 80%, 53% and 43% of the controls, respectively. The results of this study and our previously reported experiments on the sera of ALS patients may indicate that neurotoxic effects of body fluids from ALS patients could be mediated by inhibition of the respiratory chain enzymes. This confirms an important role of mitochondrial dysfunction in the pathogenesis of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2000

[Coordination and local structure of Si and Al in silicate glasses and melts: X-ray absorption spectroscopic study].

The coordination and local structure of Si and Al in silicate glasses and melts have been studied using Si and Al K-edge X-ray absorption spectroscopy for the first time. It has been verified that in SiO2-P2O5 and Na2O-SiO2-P2O5 join phosphate silicate glasses, Si atoms remains tetrahedrally coordinated with oxygen when the content of P2O5 is below 32 mol%, but partial Si atoms become octahedrally coordinated with oxygen when the content of P2O5 increases above 32 mol%, and the proportion of the octahedrally coordinated Si atoms increases with the increasing content of P2O5. It has also been demonstrated that Al remains four-fold coordinated with oxygen in ambient NaAlSi2O6-NaAlSi3O8 glasses, but in the same composition glasses quenched at 4.4 GPa and 1,575 degrees C, partial Al atoms becomes five- and six-fold coordinated with oxygen, and at the same pressure and temperature, the proportions of five- and six-fold coordinated Al atoms increases with the increasing content of NaAlSi2O6 in the glasses. Thus, the pressure-induced coordination change of Al in aluminosilicate glasses and melts has been observed for the first time by Al K-edge X-ray absorption spectroscopy.

English Abstract↗
PubMed2004

Oxidative damage to proteins in the spinal cord in amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which has been linked to the generation of free radicals and oxidative stress. Oxidative damage to spinal cord proteins is suggested to be a contributory factor to neuronal death in ALS. Since proteins are the major targets for free radicals and the so-called "reactive species", therefore the objective of our study was to identify oxidatively damaged spinal cord proteins. The material consisted of spinal cords of 8 sporadic ALS cases and 5 controls. We estimated the level of protein carbonyl moieties, which react quantitatively with 2,4-dinitrophenylhydrazine (DNPH). Afterwards proteins were separated by SDS-polyacrylamide gel electrophoresis and the protein bound DNPH moieties were detected immunochemically. We also morphologically examined spinal cords after immune staining against DNPH. The protein carbonyl content of the ALS spinal cords significantly increased in all examined cases. In most ALS patients, proteins with 125 kDa, 70 kDa and 36kDa were highly oxidized. The 70-kDa protein was identified immunochemically to be neurofilament 68. The morphological examination of ALS spinal cords indicated a pronounced anti-DNPH immune reaction in neurones of the anterior horns; the reaction in the posterior horns was less intense. Microglia in the white matter was immunoreactive; astroglia was DNPH-negative. Although the exact mechanism by which reactive oxygen species induce motor neurones to die is not known yet, the presented data indicate that they affect spinal cord cellular proteins, including neurofilament 68. In this study, we successfully examined the neurochemical features accompanying motor neuron injury in ALS, and the results may help to develop a rationale anti-oxidative neuroprotective strategy.

Aged↗
PubMed1985

Binding of Al by protein in plasma of patients on maintenance hemodialysis.

Gel filtration of plasma from hemodialysis patients, with use of reagents and apparatus with carefully minimized background Al concentrations, reproducibly showed a single peak for Al, corresponding exactly to the elution position of transferrin. The Al/transferrin molar ratio in adjacent fractions was constant (mean 0.126, SE 0.006) in replicate experiments. In contrast, the association of Al with albumin varied. Using both equilibrium dialysis and gel-filtration techniques, in the presence and absence of calcium or phosphate, we could demonstrate no significant binding of Al by human albumin at Al concentrations of 1 to 12 mumol/L. We saw no Al peak in pooled, concentrated, low-molecular-mass fractions of plasma gel-filtered on Sephadex G-50. Evidently, transferrin is the sole Al-binding protein in plasma of hemodialysis patients.

Aluminum↗
PubMed1984

Hepatic amyloidosis. A histopathologic analysis of primary (AL) and secondary (AA) forms.

The liver is a major site of amyloid deposition. The spectrum of histopathologic changes in the liver was studied in 38 patients with systemic amyloidosis (25 with primary or myeloma-associated amyloidosis [AL] and 13 with secondary, reactive [AA] amyloidosis). Overall architectural distortion, alterations of portal triads, as well as predilection for topographic deposition in the parenchyma and/or blood vessel walls were noted. Significant histopathologic differences in AL or AA amyloid liver involvement included 1) portal fibrosis, seen in 7 of 25 (28%) AL patients and 8 of 13 (62%) AA patients (P = 0.05), 2) parenchymal amyloid deposition in 25 of 25 (100%) AL amyloid and 10 of 13 (77%) AA amyloid patients (P = 0.04), and 3) vascular amyloid deposition found in 17 of 25 (68%) with AL amyloid and 13 of 13 (100%) patients with AA amyloid (P = 0.02). These data vary from the widely held concept that deposition of amyloid is predominantly vascular in the AL form and parenchymal in amyloid AA. Clearly, however, in individual cases significant overlap occurred, and characterization of amyloid types based on morphologic distribution of amyloid deposits may be possible in only a minority of cases. In most cases, differentiation of amyloid AL and amyloid AA forms requires clinical, histochemical, immunochemical, and sometimes more elaborate laboratory amino acid sequence studies for accurate identification.

Amyloid↗