Infiltration Of Skeletal Muscle Research Articles

Adipose Tissue Infiltration in Skeletal Muscle of Healthy Elderly Men: Relationships With Body Composition, Insulin Resistance, and Inflammation at the Systemic and Tissue Level

Association between inflammatory markers and intermuscular adipose tissue (IMAT) has been reported. We hypothesized that subclinical inflammation of adipose tissue surrounding and infiltrating muscle could be related to the metabolic and functional abnormalities of the "aging muscle." In 20 healthy elderly men undergoing elective vertebral surgery, IMAT within erector spinae was evaluated by magnetic resonance imaging and body composition by dual-energy x-ray absorptiometry. Fasting glucose, insulin, high-sensitive C-reactive protein (hs-CRP), leptin, adiponectin, and interleukin 6 (IL-6) were measured, and insulin resistance was estimated by homeostasis model assessment (HOMA) index. In subcutaneous adipose tissue (SAT) biopsies near the erector spinae, quantification of gene expression was performed. IMAT showed a significant association with body mass index and total and regional body fat, even after adjustment for age. Insulin, HOMA, and leptin were significantly correlated with IMAT, whereas hs-CRP presented an association of borderline significance. IL-6 expression in SAT was significantly associated with IMAT; IL-6 messenger RNA (mRNA) was negatively associated with adiponectin and peroxisome proliferator-activated receptor gamma expression. In multivariate regression analysis, 68% of IMAT variance was explained by fat mass and age, independent of waist circumference, leptin, HOMA, and IL-6 mRNA. IMAT was primarily related to age and total body adiposity; subclinical inflammation in fat significantly contributes to IMAT.

Greater Adipose Tissue Infiltration in Skeletal Muscle among Older Men of African Ancestry

There is substantial variability across ethnic groups in the predisposition to obesity and associated metabolic abnormalities. Skeletal muscle fat has been identified as an important depot that increases with aging and may contribute to the development of diabetes. We tested whether men of African ancestry have greater calf intermuscular adipose tissue (IMAT), compared to Caucasian men, and whether IMAT is associated with type 2 diabetes (T2D). We measured fasting serum glucose, body mass index, total body fat by dual-energy x-ray absorptiometry, and calf skeletal muscle composition by quantitative computed tomography in 1105 Caucasian and 518 Afro-Caribbean men aged 65+. Compared to Caucasian men, we found greater IMAT and lower sc adipose tissue in Afro-Caribbean men at all levels of total adiposity (P < 0.0001), including the subset of men matched on age and dual-energy x-ray absorptiometry total body fat percentage (P < 0.001). In addition, IMAT was 29 and 23% greater, whereas sc adipose tissue was 6 and 8% lower among Caucasian and Afro-Caribbean men with T2D, respectively, compared to men without T2D (P < 0.01). Observed differences in intermuscular and sc fat, both ethnic and between men with and without T2D, were independent of age, height, calf skeletal muscle and total adipose tissue, and lifestyle factors. Our analyses suggest that despite lower total adiposity, skeletal muscle fat infiltration is greater among African than among Caucasian ancestry men and is associated with T2D in both ethnic groups. Additional studies are needed to determine the mechanisms contributing to ethnic differences in skeletal muscle adiposity and to define the metabolic and health implications of this fat depot.

Validation of an adapted MRI pulse sequence for quantification of fatty infiltration in muscle

The long-term goal of our research is to develop a patient-specific biomechanical model of the supraspinatus muscle and tendon for analyzing the effects of fatty infiltration and pennation angle changes. One input of the model will be the amount and distribution of fat within the muscle. Therefore, the objective of this project was to adapt and validate a novel magnetic resonance imaging pulse sequence for quantifying the extent of fatty infiltration for the supraspinatus muscle. Samples of incremental combinations of muscle and fat from a cow were prepared and scanned with our quantitative MR technique. The MR results were compared to actual fat measurements taken using a Soxtec extraction analyzer. The MR fat quantification results closely match those values determined by Soxtec analysis (R(2)=.98, root mean square deviation=4.9). Our MR fat quantification protocol can be used to accurately quantify fatty infiltration in skeletal muscle. This ability to evaluate skeletal muscle tissue noninvasively will improve the efficacy of evaluation of fatty degeneration in assessing tissue quality preoperatively. This can be important in surgical planning of any musculoskeletal repairs, particularly rotator cuff tears.

Degenerative muscle fiber accelerates adipogenesis of intramuscular cells via RhoA signaling pathway

In some pathological conditions such as Duchenne muscular dystrophy, it has been known that a fatty infiltration in skeletal muscle is often observed and that is also one of primary factors to induce marked decline of muscular strength. However, the mechanism of fatty infiltration, cellular origin of accumulated adipocytes and its significance are not fully understood. The fact that persistent degenerative muscle fibers are present on dystrophic muscle leads us to hypothesize that muscle fiber condition affects fatty infiltration in skeletal muscle. We employed a single fiber culture system to determine whether fiber condition affects an appearance of adipocytes on the fibers. Artificially hyper-contracted muscle fibers (HCF), generated from isolated intact fibers (IF) of rat extensor digitrum longus muscle, were maintained as non-adherent cultures for 5–7 days. Interestingly, there appeared to be considerable numbers of mature adipocytes on HCF, whereas no adipocytes were seen on IF, indicating that cells on HCF spontaneously differentiated into mature adipocytes. Activation of RhoA signaling by the addition of thrombin decreased the number of adipocytes on HCF in a dose-dependent manner, whereas the number of MyoD-positive myoblasts increased. In contrast, Y-27632, a specific inhibitor of Rho kinases (ROCK), induced adipogenic differentiation of cells derived from IF. In addition, administration of Y-27632 into mouse regenerating muscle resulted in fat accumulation in the muscle. Taken together, the present studies clearly demonstrated that muscle fiber condition affects fat accumulation in skeletal muscle and that is possibly mediated by the RhoA signaling pathway.

Adipose Tissue Infiltration of Skeletal Muscle in Children with Cerebral Palsy

To determine whether children with quadriplegic cerebral palsy (QCP) have a greater adipose tissue (AT) infiltration of skeletal muscle than typically developing children (12/group and 5-14 years). Cross-sectional area (CSA) of AT and muscle in the midthigh were assessed with magnetic resonance imaging. Physical activity was assessed with an activity monitor. Children with QCP had 2.3-fold higher intermuscular AT CSA and 51% lower muscle CSA in the midthigh than control subjects. Midthigh intermuscular, subfascial, and subcutaneous AT CSA adjusted for midthigh muscle CSA were higher in children with QCP (all P < .05). Moreover, the proportion of intermuscular AT CSA and subfascial AT CSA relative to subcutaneous AT CSA in the midthigh were 2.5-fold and 1.8-fold higher in children with QCP than control subjects (all P < .05). Children with QCP also had 70% fewer physical activity counts, which was inversely related to intermuscular AT CSA (r = -0.76) and subfascial AT CSA (r = -0.63) adjusted for muscle CSA in the midthigh of children with QCP (both P < 0.05), but not in control subjects. Children with QCP have a greater AT infiltration of skeletal muscle than typically developing children, which is related to their low level of physical activity.

Progesterone and estrogen influence postexercise leukocyte infiltration in overiectomized female rats

Limited research has been conducted on the effects of progesterone alone, or in combination with estrogen, on leukocyte infiltration in skeletal muscle following exercise. To investigate the effects of these female sex hormones, ovariectomized female rats were divided into 4 exercise and 4 control groups: sham, estrogen, progesterone, and a combination of estrogen plus progesterone. Following 8 days of hormone replacement and 24 h postexercise, soleus (red) and superficial (white) vastus muscles were removed and immunostained for His48 (neutrophil)- and ED1 (macrophage)-positive cells. The postexercise increase in leukocyte infiltration was completely (p < 0.05) attenuated with estrogen supplementation alone in both muscle types, relative to sham. Progesterone treatment alone also resulted in a smaller (20%-30%) but significant (p < 0.05) attenuation of postexercise muscle leukocyte infiltration. The combination of estrogen and progesterone treatment did not significantly alter the attenuation seen with estrogen supplementation alone. Hence, progesterone can independently attenuate postexercise muscle leukocyte infiltration, albeit to a lesser degree than estrogen, and it will not negate or accentuate the effect of estrogen.

Excessive Adipose Tissue Infiltration in Skeletal Muscle in Individuals With Obesity, Diabetes Mellitus, and Peripheral Neuropathy: Association With Performance and Function

The primary purpose of this study was to report differences in calf intermuscular adipose tissue (IMAT), muscle strength (peak torque), power, and physical function in individuals with obesity, diabetes mellitus (DM), and peripheral neuropathy (PN) compared with those without these impairments. A secondary purpose was to assess the relationship between IMAT and muscle strength, power, and physical function. Six participants with obesity, DM, and PN (2 women, 4 men; mean age=58 years, SD=10; mean body mass index=36.3, SD=5; mean modified Physical Performance Test [PPT] score=22, SD=3) and 6 age- and sex-matched control subjects without these impairments were assessed and compared in muscle strength, muscle power, physical functioning, and muscle and fat volume, including IMAT in the calf muscles. Muscle, adipose tissue, and IMAT volumes of each calf were quantified by noninvasive magnetic resonance imaging. Muscle strength and power of the plantar-flexor and dorsiflexor muscles were quantified using isokinetic dynamometry. The modified PPT was used to assess physical function. Leg muscle and fat volumes were similar between groups, although IMAT volumes were 2.2-fold higher in the subjects with obesity, DM, and PN (X=120 cm(3), SD=47) than in the control subjects (X=54 cm(3), SD=41). Muscle strength, muscle power, ratio of leg muscle power to leg muscle volume, and modified PPT scores were lower in subjects with obesity, DM, and PN compared with the control subjects. The data indicate that excess fat infiltration in leg skeletal muscles is associated with low calf muscle strength, low calf muscle power, and impaired physical function in individuals who are obese with DM and PN.

Fat Infiltration in Muscle: New Evidence for Familial Clustering and Associations With Diabetes

Increased fat infiltration in skeletal muscle has been associated with diabetes. Quantitative computed tomography (QCT) can be used to measure muscle density, which reflects the lipid content of skeletal muscle such that greater fat infiltration in skeletal muscle is associated with lower muscle density. The relative contribution of genetic and environmental factors to fat infiltration in skeletal muscle has not been assessed. Therefore, our aim is to determine genetic and environmental contributions to measures of skeletal muscle composition, and describe their associations with type 2 diabetes in multigenerational families of African ancestry. Peripheral QCT (pQCT) measures of skeletal muscle density were obtained for the calf in 471 individuals (60% women; mean 43 years) belonging to eight large, multigenerational Afro-Caribbean families (mean family size 51 individuals; 3,535 relative pairs). The proportion of variance in muscle density due to additive genetic effects (residual heritability) was 35.0% (P < 0.001) and significant covariates (age, gender, BMI, and parity) explained 55.0% of the total phenotypic variation in muscle density. Muscle density was lower (P < 0.001) in 62 diabetics (69.5 mg/cm(3)) than in 339 nondiabetics (74.3 mg/cm(3)) and remained significant after adjusting for age, gender, and BMI (P = 0.005) or age, gender, and waist circumference (P = 0.01). Our results provide new evidence that ectopic lipid deposition in skeletal muscle is a heritable trait and is associated with diabetes, independent of overall and central obesity in families of African heritage. Genome-wide screens and candidate gene studies are warranted to identify the genetic factors contributing to ectopic deposition of skeletal muscle fat.

Adipose tissue infiltration in skeletal muscle: age patterns and association with diabetes among men of African ancestry

BackgroundAlthough obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. ObjectiveWe examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged ≥40 y. DesignAnthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). ResultsThe prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/m2) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). ConclusionsThese findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.’

G.P.4.15 CAPN3 mutations in patients with idiopathic eosinophilic myositis: A predystrophic stage of LGMD2A?

Objective and Background: Mutations in the gene encoding calpain-3 (CAPN3) cause autosomal-recessive limb girdle muscular dystrophy type 2A (LGMD2A). In six children, we recently identified CAPN3 mutations as a genetic cause of idiopathic eosinophilic myositis (EM), a rare pathological entity characterised by eosinophilic infiltration of skeletal muscles. Here, we further evaluated the hypothesis of EM being a possible histopathological pre-dystrophic developmental stage of LGMD2A. Methods: We screened CAPN3 for mutations using DHPLC and direct sequencing, in five unrelated patients (four children and one young adult), recruited on the basis of EM diagnosed after histological examination of muscle biopsy samples, without any identified aetiological factor. In addition, information on the presence of eosinophils was retrospectively assessed in 17 genetically confirmed LGMD2A patients and inflammatory changes by analysing haematoxylin-eosin stained cryosections from muscle samples (mean age of biopsy 28 years). Results: Two disease-causing CAPN3 mutations were identified in the five patients affected with idiopathic EM. In one additional patient, only one disease-causing CAPN3 mutation was identified. Additionally, we found a sparse presence of eosinophils in muscle biopsies from 5/17 patients with inflammatory (n = 3 mild focal, n = 2 moderate focal) and myopathic changes (n = 2 mild, n = 2 moderate, n = 1 severe). Conclusion: Our findings confirm mutations in CAPN3 as a genetic cause of eosinophilic myositis. The presence of eosinophils has been discussed before as a component of muscular dystrophy (Cai et al. 2000). The presence of marked eosinophilic infiltrates in EM patients, together with the findings of our retrospective analysis of biopsies from LGMD2A patients might suggest the following possibilities (1) EM associated with CAPN3 mutations could be a distinct phenotype, (2) eosinophilic infiltration might represent an early or transient developmental stage in the inflammation associated with primary calpainopathy.

Statins Inhibit Neutrophil Infiltration in Skeletal Muscle Reperfusion Injury

Neutrophil infiltration is a major determinant of ischemia-reperfusion injury (IRI). Statins improve endothelial function by elevating nitric oxide synthase activity and inhibiting adhesion molecule expression and may, therefore, inhibit IRI-induced neutrophil extravasation. Although statins are protective against myocardial IRI and stroke, a role for statins in ameliorating skeletal muscle IRI has not yet been confirmed. This study, therefore, addressed the hypothesis that simvastatin would attenuate the severity of tissue damage during skeletal muscle IRI. Rats were administered simvastatin for 6 d before 4 h hind limb ischemia and 24 h reperfusion. Neutrophil infiltration was assessed using myeloperoxidase (MPO) assays and tissue damage by quantitative immunohistochemical analysis of collagen IV. The effect of reducing nitric oxide levels on the severity of IRI was assessed by administering the NOS inhibitor, N-Imino-L-ornithine (L-NIO), before ischemia. Simvastatin significantly inhibited IRI-induced MPO activity but not collagen degradation in postischemic skeletal muscle. Inhibition of nitric oxide synthase by L-NIO markedly inhibited neutrophil infiltration and protected against IRI-induced collagen degradation. When both simvastatin and L-NIO were administered before IRI, the IRI-induced elevation in MPO activity was completely inhibited. However, paradoxically, simvastatin counteracted the protective effect of L-NIO against IRI-induced collagen IV degradation. The inhibition by simvastatin of IRI-induced neutrophil infiltration in skeletal muscle suggests that statins may be a useful therapy to attenuate the severity of IRI but their precise mechanisms of action remains to be determined. Nitric oxide also plays a cytotoxic, rather than protective, role in mediating IRI in this model.

P.P.6 05 CAPN3 mutations in patients with idiopathic eosinophilic myositis

Eosinophilic myositis (EM) constitutes a rare pathological entity characterized by eosinophilic infiltration of skeletal muscles, usually associated with parasite infections, systemic disorders, or the intake of drugs or l-tryptophan. The exclusion of such causes defines the spectrum of idiopathic EM. Based on a protein analysis, we identified the gene encoding calpain-3, CAPN3, as a candidate for a subset of idiopathic EM. We screened CAPN3 for mutations using DHPLC and direct sequencing, in six unrelated patients, recruited on the basis of EM diagnosed after histological examination of muscle biopsy samples, without any identified aetiological factor.

CAPN3 mutations in patients with idiopathic eosinophilic myositis

Eosinophilic myositis (EM) constitutes a rare pathological entity characterized by eosinophilic infiltration of skeletal muscles, usually associated with parasite infections, systemic disorders, or the intake of drugs or L-tryptophan. The exclusion of such causes defines the spectrum of idiopathic EM. Based on a protein analysis performed in one affected patient, we identified the gene encoding calpain-3, CAPN3, as a candidate for a subset of idiopathic EM. We screened CAPN3 for mutations using DHPLC and direct sequencing in six unrelated patients, recruited for EM diagnosed after histological examination of muscle biopsy samples, without any identified causative factor. We identified CAPN3 mutations in the six unrelated patients originally diagnosed with idiopathic EM. Mutations in CAPN3 can cause EM. Thus, a subset of idiopathic EM is genetically determined, with an autosomal recessive mode of inheritance. Patients presented with a triad that appears to be indicative of CAPN3 mutations: (1) EM in the first decade, (2) elevated serum creatine phosphokinase levels (isolated or with little corresponding weakness), and (3) inconstant peripheral hypereosinophilia. However, that EM represents a distinct phenotype associated to CAPN3 mutations or, rather, an early histopathological picture of LGMD2A must be further evaluated. Our findings should be of interest toward further investigating the role of calpain-3 in skeletal muscle. Furthermore, patients with idiopathic EM should undergo calpain-3 protein analysis and be considered for subsequent molecular analysis of the CAPN3 gene.

Lymphoma(s) showing epitheliotropism and diffuse skeletal muscle involvement presenting as a polymyopathy in a young dog

A 3-year-old dog presented with a severe polymyopathy and subsequently developed nodular skin lesions. The disease in this dog was caused by lymphoma, showing cutaneous epitheliotropism as well as infiltration of skeletal muscle in conjunction with polymyositis.

Soft Tissue Perineurioma

Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, and intraneural variants. Fewer than 50 soft tissue perineuriomas have been reported to date, and the clinical significance of atypical histologic features is unknown. To characterize these tumors further, 81 soft tissue perineuriomas received between 1994 and 2003 were retrieved from the authors' consult files. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring physicians. Forty-three patients were female and 38 male (mean age, 46 years; range, 10-79 years). Tumor size ranged from 0.3 to 20 cm (mean, 4.1 cm) in greatest dimension. Most patients presented with a painless mass. The tumors arose in a wide anatomic distribution: 36 lower limb, 19 upper limb, 15 trunk, 7 head and neck, 3 retroperitoneum, and 1 paratesticular. Forty-two tumors were situated primarily in subcutis, 25 in deep soft tissue, and 9 were limited to the dermis. Nearly all cases were grossly well circumscribed; 12 showed focal microscopically infiltrative margins. Most tumors had a storiform and focally whorled growth pattern; 17 exhibited fascicular areas. Thirty-eight tumors were hypocellular, 15 were markedly hypercellular, and 7 showed alternating zones of hypocellularity and hypercellularity. Stroma was usually collagenous but in 17 tumors was predominantly myxoid, and in 16 was mixed collagenous and myxoid. Mitoses ranged from 0 to 13 per 30 high power fields (mean, 1); 53 tumors had no mitoses. Based on worrisome cytologic or architectural features, 14 cases were classified as atypical perineuriomas: 12 contained scattered pleomorphic cells, 1 showed an abrupt transition from typical morphology to a markedly hypercellular, fascicular area with cytologic atypia, and 1 exhibited diffuse infiltration of skeletal muscle. All tumors were reactive for epithelial membrane antigen; 50 of 78 (64%) expressed CD34, 22 of 76 (29%) claudin-1, 16 of 77 (21%) smooth muscle actin, and 4 of 81 (5%) S-100 protein. All tumors were negative for glial fibrillary acidic protein, neurofilament protein, and desmin. Clinical follow-up was available for 43 patients (mean, 41 months; range, 6-146 months). Among tumors for which the status of surgical margins was known, 52% were widely excised, 31% were marginally excised, and 18% had positive margins. Only two tumors recurred locally (one of which was atypical): one recurred 10 years following primary excision; and one recurred twice, 5 and 9 years following excision. No tumor metastasized. Soft tissue perineuriomas behave in a benign fashion and rarely recur. Atypical histologic features (including scattered pleomorphic cells and infiltrative margins) seem to have no clinical significance and appear to be akin to those seen in ancient schwannoma and atypical (bizarre) neurofibroma.

Hyaline Body Myopathy: Adulthood Manifestations

Hyaline body myopathy (HBM) is a rare chronic nonprogressive congenital myopathy, with variable patterns of inheritance. We describe a patient with congenital HBM with progression of weakness and increasing muscle pain in adulthood. Three muscle biopsies, done at various times in her life, are reported. Symptoms started during childhood; however, as an adult, following a period of stability with no progression of the disease, the patient became symptomatic with worsening proximal limb weakness, severe aching pain and hypertrophy of calves. Moderate elevations of serum creatine kinase and myopathic features were noted on electrophysiologic testing. Muscle pathology showed significant fatty infiltration of skeletal muscle and increased number of fibers with internal nuclei. Histology demonstrated the presence of subsarcolemmal, well-delineated hyaline areas, which on histochemical studies was shown to be limited to typel fibers. The hyaline bodies were dark with pH 4.2 ATPase and with immunohistochemical studies reacted only with myosin heavy chain slow. Electron microscopy showed the hyaline bodies to be composed of nonmembrane bound, fairly even sized granular material, which merged with the adjacent myofibrils. Earlier muscle biopsies, done during childhood, also revealed presence of similar subsarcolemmal hyaline deposits. There appears to be a pattern of presentation with adulthood progression in HBM, which has not been described before. Further case studies are required to understand the clinical progression in HBM.

Laminin alpha2 is essential for odontoblast differentiation regulating dentin sialoprotein expression.

Laminin alpha2 is subunit of laminin-2 (alpha2beta1gamma1), which is a major component of the muscle basement membrane. Although the laminin alpha2 chain is expressed in the early stage of dental mesenchyme development and localized in the tooth germ basement membrane, its expression pattern in the late stage of tooth germ development and molecular roles are not clearly understood. We analyzed the role of laminin alpha2 in tooth development by using targeted mice with a disrupted lama2 gene. Laminin alpha2 is expressed in dental mesenchymal cells, especially in odontoblasts and during the maturation stage of ameloblasts, but not in the pre-secretory or secretory stages of ameloblasts. Lama2 mutant mice have thin dentin and a widely opened dentinal tube, as compared with wild-type and heterozygote mice, which is similar to the phenotype of dentinogenesis imperfecta. During dentin formation, the expression of dentin sialoprotein, a marker of odontoblast differentiation, was found to be decreased in odontoblasts from mutant mice. Furthermore, in primary cultures of dental mesenchymal cells, dentin matrix protein, and dentin sialophosphoprotein, mRNA expression was increased in laminin-2 coated dishes but not in those coated with other matrices, fibronectin, or type I collagen. Our results suggest that laminin alpha2 is essential for odontoblast differentiation and regulates the expression of dentin matrix proteins.

Pathological and virological assessment of acute HTLV-I-associated myelopathy complicated with encephalopathy and systemic inflammation

HTLV-I-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP), is a chronic inflammatory disease of the spinal cord. Acute cases are uncommon. We report the case of a 41-year-old woman with acute HAM/TSP complicated with encephalitis, an intense inflammatory reaction of the nervous system and lymphocytic infiltration of skeletal muscles, liver, salivary, adrenal and pituitary glands. The immunohistochemical studies of the lymphocytes surrounding blood vessels showed both B- and T-lymphocytes, in similar proportion, with both CD4- and CD8-positive cells. In addition, many perivascular and scattered macrophages were observed. Adult T-cell leukemia/lymphoma (ATL) was ruled out. The marrow aspirate was normal. Serial cerebrospinal fluid (CSF) analysis showed presence of HTLV-I antibodies, but without intrathecal synthesis of specific antibodies. Determination of HTLV-I viral loads demonstrated increased levels in the CSF relative to the peripheral blood and may be associated with widespread inflammation. The pathological and immunological findings may help understand the role of immune-reactive cells in the pathogenesis of HTLV-I-associated myelopathy.

Neutralization of interferon‐γ in neonatal SOCS1−/− mice prevents fatty degeneration of the liver but not subsequent fatal inflammatory disease

Mice lacking the suppressor of cytokine signalling-1 (SOCS1) die within weeks of birth with extensive fatty degeneration of the liver, consistent with acute hepatic toxicity to interferon-gamma (IFN-gamma), and inflammation of multiple organs. We show here that treatment for 1 week from birth with neutralizing antibody to IFN-gamma rescues SOCS1-/- mice from lethal liver disease but the mice subsequently succumb to chronic inflammatory lesions characterized by T-lymphocyte infiltration of skeletal muscle, pancreas, lung, liver and skin. Elevated blood levels of eosinophils, neutrophils and platelets were also observed and the thymic lymphocyte population was depleted of CD4+ CD8+ T cells and showed a reduced CD4 : CD8 ratio. All T-cell populations in thymus, spleen and lymph node exhibited an increased proportion of cells bearing the activation marker CD44. These data suggest an important role for SOCS1 in T-lymphocyte regulation.

Miositis eosinofílica en un niño de 9 años

Eosinophil infiltration of skeletal muscle is rare, but often no etiological factor can be identified and these are isolated eosinophilic myositis. They may be associated with parasite infections or drugs, or be features of rare systemic disorders of hypereosinophilia, such as the myalgia eosinophilia syndrome and the idiopathic hypereosinophilic syndrome. The eosinophilic myopathies should be distinguished from the commoner inflammatory myopathies such as polymyositis and dermatomyositis. A nine year old boy with slight motor clumsiness but normal psychomotor development and neurological findings. Laboratory findings showed slightly raised serum transaminases (SGOT 271, SGPT 157 UI/L), CPK 7517 UI/L and eosinophilia (707/mL). Investigations for myoglobin cysticercosis, trichinosis, hydatidosis and toxicariasis were negative. No parasites were found in the faeces. The gammaglobulins were normal. Anti smooth muscle, antinuclear and anti KLM antibodies were negative. Cardiological studies were normal. His father, mother and two siblings had normal results of laboratory tests. Muscle biopsy showed inflammatory myopathy with abundant eosinophils, no evidence of parasites, no alteration of membrane proteins: dystrophin, sarcoglycan and merosine. Two years later he remains asymptomatic, maintains raised muscle enzyme levels in all tests with figures for CPK between 3,065 and 9,616UI/L, and eosinophilia ranging between 634 and 1,026/mL. Corticosteroid treatment was tried but no response obtained. We consider this to be a case of eosinophilic polymyositis which gives rise to many questions regarding etiopathogenesis, management and prognosis.