bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thoracolumbosacral laminectomy in achondroplasia: Long‐term results in 22 patients
Authors: Pyeritz Reed E. , Sack George H. , Udvarhelyi George B. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractNeurologic problems caused by vertebral stenosis in the thoracolumbosacral (TLS) region are common in achondroplasia. Surgical decompression by means of laminectomy is recommended often, but its long‐term results have not been assessed. We reviewed the clinical history of 22 achondroplastic patients who had at least one TLS laminectomy performed before 1981, Symptoms predated the first TLS laminectomy by a mean of 2.3 years (range0.1–17 years). Preoperatively, 91% of patients had motor function impairment, 86% had sensory dysfunction, 86% had neurogenic claudication, 77% had radicular pain, 59% had symptomatic bladder dysfunction, and 32% had fecal incontinence. Only upper motor neurons were affected in 45%, only lower motor neurons in 27%, and both in 27%. Follow‐up after the first TLS laminectomy averaged 8 years. Of the 20 patients who initially improved neurologically, 12 had functional improvement for more than 5 years. However, 11 of these 12 subsequently regressed and 10 had additional laminectomies. Long‐term neurologic and functional improvement was associated with both a short duration of symptoms preopcratively and absence of cervical stenosis. Because of hypertrophic scarring, 9 patients developed compression at the site of the initial TLS laminectomy and required re‐operation 6.4 years (range 1–11 years) later. We conclude that TLS laminectomy is an effective treatment for spinal stenosis if performed early in the course of the neurologic syndrome. However, some patients have, or later develop, compression adjacent to the myelographic site of stenosis, and some develop hypertrophic scarring at the site of initial decompression. We therefore suggest that the first TLS laminectomy extend (1) 3 levels cephalad to the myelographic block, (2) at least to S2, and (3) laterally at least to the facets.
Interspecific genetic complementation analysis with fibroblasts from humans and four species of animals with Chediak‐Higashi syndrome
Authors: Penner Jocelyn D. , Prieur David J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAlthough the autosomal recessive disease Chediak‐Higashi syndrome (CHS) has been described in humans, cats, mink, cattle, mice, killer whales, blue foxes, and silver foxes, and these conditions appear quite similar, no direct evidence of the homology of this disease in the various species has been presented. To determine if CHS in humans, cats, mink, cattle, and mice is due to a mutant gene at the homologous genetic locus in each species, or alternatively, if these are merely similar syndromes, genetic complementa‐tion analysis after interspecific somatic cell (fibroblast) hybridization was performed. “Paracrystal” formation was the criterion used for the determination of complementa‐tion. The initial studies in this report were designed to characterize paracrystal formation in control and CHS fibroblasts of these five species. Most of the control fibroblasts from each species (91–96.6%) formed paracrystals upon incubation with 25 μg/ml of the microtubule depolymerizing agent vinblastine sulfate. A significantly (P < 0.05) smaller percentage of the CHS fibroblasts formed paracrystals after the same incubation (except CHS mice, with 90.2% paracrystals). It was found that 52% of the human CHS fibroblasts, 60% of cat CHS fibroblasts, 47% of mink CHS fibroblasts, and 53.8% of cow CHS fibroblasts formed paracrystals. For genetic complementation analysis, human CHS fibroblasts were fused to cat, mink, cow, or mouse CHS fibroblasts with polyethylene glycol. Control fusions were human CHS fibroblasts fused with human, cat, mink, cow, and mouse normal fibroblasts. The results of complementation analysis after the fusion of human CHS with cow CHS and human CHS with mouse CHS fibroblasts were inconclusive. A lack of complementa‐tion of human CHS with cat CHS and human CHS with mink CHS fibroblasts indicates that the disease is homologous in these species.
Extracellular matrix, cell skeletons, and embryonic development
Authors: Hay Elizabeth D. 
Published: June 2005

AbstractDuring embryonic development, the extracellular matrix (ECM) promotes the production of differentiated products by epithelial cells and the migration of mesenchymal cells, and probably also plays a role in epithelial‐mesenchymal transformation. Here we examine the role of the cell skeleton (actin, microtubules, intermediate filaments) in mediating matrix effects on mesenchymal cell morphology, migration, and formation. The interaction of both epithelial cells and mesenchymal cells with ECM seems to involve the actin cortex, which is best developed in the base of the epithelial cell, where it attaches to underlying matrix via membrane‐intercalated receptors. To interact with the matrix, the fibroblast has appropriate ECM receptors and an actin cortex around the whole cell. The actin cortex is absolutely required for assumption of bipolar shape, elongation, and movement through the matrix. Since the cortex seems to be anchored to the matrix, it is unlikely that it moves during cell migration. A new hypothesis states that the microtubule‐ and intermediate filament‐rich endoplasm, containing the nucleus, moves past the actin cortex‐receptor‐matrix complex into the newly synthesized front end of the mesenchymal cell to effect forward movement. When epithelial cells transform into mesenchyme in the embryo, or when they are induced to do this in vitro, they switch from the keratin intermediate filament profile to one rich in vimentin, and the effect of cell matrix interaction on cell shape is profoundly altered. Vimentin‐actin interactions with ECM may be a major factor in the ability of a cell to become mesenchyma In concluding, we speculate that epithelial‐mesenchymal transformation involves a whole set of tissue specific effector genes whose expression might be mediated by a master gene system.
Ehlers‐Danlos syndrome type IV: A subset of patients distinguished by low serum levels of the amino‐terminal propeptide of type III procollagen
Authors: Steinmann Beat , Superti‐Furga Andrea , Joller‐Jemelka Helen I. , Cetta Giuseppe , Byers Peter H. 
Published: June 2005

AbstractSerum levels of procollagen type III aminopropeptide (P‐III‐NP), a peptide released during conversion of type III procollagen to collagen, were abnormally low in six of 10 patients with Ehlers‐Danlos syndrome (EDS) type IV (arterial‐ecchymotic type) and low‐normal in 4. The serum P‐III‐NP levels correlated with the amount of type III procollagen secreted by the patients' cultured fibroblasts. Serum P‐III‐NP determination is a simple test that identifies a major subgroup of patients with this lifethreatening, dominantly inherited connective tissue disorder and may be especially helpful in making the diagnosis in children.
Skin is a window on heritable disorders of connective tissue
Authors: Holbrook Karen A. , Byers Peter H. 
Published: June 2005

AbstractA skin biopsy contains the macromolecules present in most connective tissues: collagens, elastin, glycoproteins, and proteoglycans. The specific combination and assembly of these matrix components and their interactions with other structures (e.g., epidermal appendages, nerve and vascular networks) and cells are responsible for the distinction among specific regions of the dermis. The matrix components are interactive and interdependent and modification of one of them, by extrinsic (environmental) and/or intrinsic (systemic, genetic, age‐related) factors, may have consequences on the tissue as a whole. The skin, therefore, provides a window through which it is possible to examine how mutations in one connective tissue macromolecule can change the interations among matrix components and affect tissue structure and organization. Light and electron microscopic studies of skin from patients with inherited connective tissue disorders (e.g., Ehlers‐Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, cutis laxa) have led us to the following generalizations about what components change, how individual collagen or elastic fibers are altered and how individual alterations affect overall dermal organization: 1) There is a limited change in the repertoire of collagen fibrils in the skin; 2) there appears to be a greater range of abnormal structure in dermal elastic fibers than in the collagen fibrils; 3) the morphology of the fibroblastic cells may provide clues to the defect in matrix components; 4) similar structural abnormalities result from different molecular defect; 5) a molecular defect in one connective tissue molecule has consequences for the structural properties of other connective tissue components; and 6) although structural alterations in connective tissue fibers are rarely specific for a given disease, there are characteristic patterns of structural change in the matrix that may be used to confirm a diagnosis. These generalizations show that mutations rarely affect only a single aspect of macromolecular function and because of the interactions of matrix components in this complex organ (skin) often disturb the organization of the entire dermis. Genotype‐phenotype relationships are important to understand if effective therapies are to be designed. The structure of skin should provide the next level of integration in our efforts to determine how mutations produce disease.
Congenital myopathy with oculo‐facial abnormalities (Marden‐Walker syndrome)
Authors: Linder Nehama , Mathot Israel , Livoff Alexander , Glass Joseph , Bornstein Ilan , Gross Eva , Yatsiv Shaul , Sommer Annemarie 
Published: June 2005

AbstractMarden‐Walker syndrome present in the neonatal period is characterized by oculo‐facial abnormalities, congenital myopathy, and contractures. A newborn infant with a similar pattern of anomalies is reported, and further evidence for autosomal recessive inheritance as well as new neuropathological findings are included.
Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy
Authors: Rapaport Debora , Passos‐Bueno Maria Rita , Brandão Lydia , Love Donald , Vainzof Mariz , Zatz Mayana 
Published: June 2005

AbstractA total of 162 Duchenne (DMD) patients and two girls with a DMD phenotype were anlysed for deletions in the central region of the dystrophin gene in order to determine if there was a correlation between mental retardation (MR) and the pattern of deletion. Approximately 43% of the patients studied had deletions with two dystrophin cDNAs, cf23a and cf56a, and among 148 patients who were mentally assessed, 50% were mentally retarded. The average IQ in the group of patients with DNA deletions did not differ significantly from those patients with no detectable deletions. However, six unrelated DMD boys with MR showed an identical pattern of deletion. Our observations in the group of patients who had detected DNA deletions suggest that exon 52 of the dystrophin gene may be functionally significant in the manifestation of MR:70% (19/27) of patients with a deletion of this exon were mentally retarded, whereas only 38% (15/39) of MR patients had deletions not involving exon 52. This difference was statistically significant.
Acardiac amorphous twin with prune belly sequence in the co‐twin
Authors: Buntinx Inge M. , Bourgeois Nadia , Buytaert Philippe M. , Dumon Jan E. 
Published: June 2005

AbstractWe describe a twin with acardia acephalus or “Twin Reversed Arterial Perfusion Sequence” and prune belly sequence in the cotwin. In a former quite similar case a prune belly appearance of the co‐twin of an acardiac fetus was found to be secondary to the ascites caused by cardiac failure. In the present case, we are dealing with the prune belly sequence as a separate condition, given the fact there were no signs of ascites or cardiac failure. We also found associated anomalies:agenesis of the left ureter and kidney, dysplastic right kidney and anal atresia. Urinary tract obstruction has never been described in the co‐twin of an acardiac amorphous fetus.
Perspective of biochemical research in the neuronal ceroid‐lipofuscinosis
Authors: Rider J. Alfred , Dawson Glyn , Siakotos Aristotle N. 
Published: June 2005

AbstractThe search for biochemical abnormalities in the neuronal ceroid‐lipofuscinoses (NCL) or Batten disease was initiated with the discovery of normal levels of gangliosides in juvenile amaurotic idiocy. The primary goal of most biochemical studies has been to discover the unique biochemical marker for carriers and at‐risk individuals. Ceroid, the singular pathomorphologic trait of NCL, was isolated and shown to differ from a similar but normal product of aged cells, lipofuscin. In spite of the availability of stored product, the chemical analysis of ceroid has not elucidated the unique biochemical defect in the NCL, as has been the case for other lysosomal storage disorders. The NCL were thought to be a result oflipid peroxidationbecause ceroid is also found in disorders of impaired vitamin E metabolism or results from a diet deficient in the antioxidant, vitamin E. In addition, tissue analysis indicated losses of polyunsaturated fatty acids in affecteds and carriers, as well as the presence of a secondary product of lipid peroxidation, 4‐hydroxynonenal, in affected and carrier NCL dogs. With the exception of a fluorescent compound isolated from retinal ceroid, studies aimed at discovering thedisease‐specific fluorophoresof ceroid have been largely inconclusive. The discovery of elevated dolichols in urine and brain tissue of NCL patients led to another hypothesis, that the basic biochemical defect in NCL involved themetabolism of dolicholsand retinoids. However, the more recent view is that dolichol metabolism is secondary to the unknown NCL lesion. A possible role ofdeficient proteases or protease inhibitorsin NCL was developed after studies showed that inhibition of lysosomal thiol proteases would induce formation of autofluorescent lipopigments in brains of young rats. This initial discovery led to several reports of cathepsin deficiencies which, however, have not been reproducible. The discovery of abnormal storage of normal mitochondrial ATP synthase subunit C protein in NCL has been reported, but the reasons for the storage of this very hydrophobic protein were not apparent. A recent report found a modified amino acid, trimethyllysine in juvenile NCL ceroid. This may provide a reasonable explanation for the storage of the subunit C protein; i.e., the NCL defect may involve abnormal methylation and demethylation of proteins. Finally, localization of genes for 2 types of NCL mapping to 2 different chromosomes is a major advance in resolving the defect in NCL. Localization of genes for other inherited diseases has served as a prelude to the ultimate isolation and characterization of the genetic defect. With further progress in the biochemistry and molecular biology of NCL, the responsible gene product(s) may soon be discovered and characterized.
Evidence for lipase abnormality: High levels of free and triacylglycerol forms of unsaturated fatty acids in neuronal ceroid‐lipofuscinosis tissue
Authors: Banerjee Probal , Dasgupta Amitava , Siakotos Aristotle N. , Dawson Glyn 
Published: June 2005

AbstractTotal lipid obtained from normal and different forms of neuronal ceroid‐lipofuscinoses (NCL) tissues was analyzed by high performance thin layer chromatography (HPTLC). We observed a large (>6‐fold) increase in a lipid band corresponding to triolein for NCL dog pancreas and spleen and juvenile human NCL brain and infantile NCL spleen. The accumulation was less pronounced for the brain samples but apart from increased dolicholmonophosphate levels, other lipids appeared normal. Normal dog, goat, or human spleen contained virtually no triacylglycerol, and of the pathological controls, β‐mannosidosis goat spleen showed no triacylglycerol band at all. A sample of human spleen from a patient with lymphoma‐associated splenomegaly displayed a strong triacylglycerol band, but gas chromatography‐mass spectrometry (GC/MS) of the bands showed an equal increase in both saturated and unsaturated fatty acid containing triacylglycerols in the splenomegaly sample, in keeping with the notion of non‐specific fat deposition in damaged tissue. In contrast, in all the NCL samples (spleen, pancreas, and brain) a prominent increase in the proportion of unsaturated fatty acids was observed in both free fatty acid and/or triacylglycerol bands following GC/MS. The NCL‐English setter dog pancreas showed a major presence of oleic acid (18:1) (twofold increase) as compared to normal, while dog and infantile human NCL spleen samples and juvenile Batten brain (human) displayed a robust increase in linoleic acid (18:2) and sometimes in oleic acid and arachidonic acid (20:4) (for infantile human NCL spleen). For the infantile human NCL spleen sample an increase in linoleic acid in both free fatty acid (3.2‐fold) and triacylglycerol (10‐fold) was observed. This suggests a new mechanism by which polyunsaturated fatty acids can be transported to various parts of an NCL‐affected mammalian body in packages such as triacylglycerol and/or serum albumin:free fatty acid complex. Such polyunsaturated fatty acids could eventually lead to the ceroid‐lipofuscin pigment characteristic of NCl tissues through peroxidation to aldehyde with subsequent Schiff base formation. This could possibly explain the deposition of ceroid‐lipofuscin in widely different and non‐proximal tissues such as the pancreas and the brain.
Mitochondrial ATP synthase subunit c storage in the ceroid‐lipofuscinoses (Batten disease)
Authors: Palmer David N. , Fearnley Ian M. , Walker John E. , Hall Nicholas A. , Lake Brian D. , Wolfe Leonhard S. , Haltia Matti , Martinus Ryan D. , Jolly Robert D. 
Published: June 2005

AbstractThe ceroid‐lipofuscinoses (Batten disease) are neurodegenerative inherited lysosomal storage diseases of children and animals. A common finding is the occurrence of fluorescent storage bodies (lipopigment) in cells. These have been isolated from tissues of affected sheep. Direct protein sequencing established that the major component is identical to the dicyclohexylcarbodiimide (DCCD) reactive proteolipid, subunit c, of mitochondrial ATP synthase and that this protein accounts for at least 50% of the storage body mass. No other mitochondrial components are stored.Direct sequencing of storage bodies isolated from tissues of children with juvenile and late infantile ceroid‐lipofuscinosis established that they also contain large amounts of complete and normal subunit c. It is also stored in the disease in cattle and dogs but is not present in storage bodies from the human infantile form.Subunit c is normally found as part of the mitochondrial ATP synthase complex and accounts for 2–4% of the inner mitochondrial membrane protein. Mitochondria from affected sheep contain normal amounts of this protein. The P1 and P2 genes that code for it are normal as are mRNA levels. Oxidative phosphorylation is also normal.These findings suggest that ovine ceroid‐lipofuscinosis is caused by a specific failure in the degradation of subunit c after its normal inclusion into mitochondria, and its consequent abnormal accumulation in lysosomes. This implies a unique pathway for subunit c degradation. It is probable that the human late infantile and juvenile diseases and the disease in cattle and dogs involve lesions in the same pathway.
Altered protein patterns in brains of children with neuronal ceroid lipofuscinosis
Authors: Wisniewski K. E. , Gordon‐Majszak W. , Maslinski S. , Heaney‐Kieras J. 
Published: June 2005

AbstractThe neuronal ceroid lipofuscinoses (NCL) are a group of inherited neurodegenerative diseases characterized by massive intralysosomal accumulation of storage materials. We have studied the protein patterns in 5 NCL, 5 control, and one Alzheimer disease brains. When protein patterns in NCL and control brain gray matter homogenates were examined by SDS‐PAGE, NCL brains showed an absence or greatly reduced amounts of the Mr 160–180 kDa component and reduced amounts of the Mr 29–36 kDa component. Concomitantly, an increase in several components with Mrs of 45–50 kDa was noted. The 180 kDa polypeptide appears to be a glycoprotein because it was bound to the lectins concanavalin A and Ulex europaeus.Recently, the abnormal processing of amyloid protein precursor (APP) and its potential role in NCL have been suggested. Possible defects in tissue proteases and protease inhibitors may be considered responsible for the presence of these amyloid beta protein precursor fragments.To examine this possibility we are using polyclonal antibodies to the C terminal 672–695 (APP) and monoclonal antibodies to inter‐α‐trypsin inhibitor. Polypeptides with molecular weights of approximately 35–38 kDa were detected in the NCL brain, but not in controls in both cases. These findings suggest abnormal protein processing in NCL brain tissue, disturbances in protein and glycocon‐jugate metabolism, impaired lysosomal function (i.e., metabolic enzyme and/or proteases/ proteinase inhibitor abnormalities), and the involvement of improperly processed APP.
Further delineation of the Simpson‐Golabi‐Behmel (SGB) syndrome
Authors: Gurrieri Fiorella , Cappa Marco , Neri Giovanni 
Published: June 2005

AbstractThe Simpson‐Golabi‐Behmel syndrome is an X‐linked condition characterized by pre‐ and postnatal overgrowth, “coarse” face, postaxial polydactyly, midline defects, and psycho‐motor development ranging from normal to mildly retarded. We report on an additional sporadic patient with novel manifestations, contributing to a more thorough delineation of this syndrome. © 1992 Wiley‐Liss, Inc.
Mucopolysaccharidosis type VII (β‐glucuronidase deficiency): A chronic variant with an oligosymptomatic severe skeletal dysplasia
Authors: de Kremer Raquel D. , Givogri Irene , Argaraña Carlos E. , Hliba Ernesto , Conci Rene , Boldini Catalina D. , Capra Ana P. 
Published: June 2005

AbstractWe report on a 20‐year‐old male with a β‐glucuronidase (GUSB) deficiency mucopoly‐saccharidosis. He had pectus carinatum, gross thoracic kyphoscoliosis, and hip dysplasia, a picture which became conspicuous after age 4 years. Hepatosplenomegaly, herniae, corneal clouding, and neurological abnormalities were absent. Although he had Alder‐type granulations in his polymorpho‐nuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. Electron microscopic examination of skin and gingival biopsies, leukocytes, and cultured skin fibroblasts showed numerous single membrane‐limited vacuoles either empty or filled with fibrillogranular material; this last tissue did not contain metachromatic granules. Radiographs demonstrated a distinct spondyloepiphyseal dysplasia in which the most striking changes were confined to the thoracic spine (flattening and collapse in T7, T8 and T10 vertebral bodies) and to the femoral capital epiphyses (irregularities and fragmentation). The activity of GUSB in the patient's serum, leukocytes, and fibroblasts was severely decreased; the GUSB activity in the serum and leukocytes from the parents and 2 asymptomatic sibs was subnormal. Immunoblot analysis showed very low levels of cross‐reactive material towards anti‐GUSB antiserum in the patient's leukocyte and fibroblast extracts. This patient was more severely affected in his skeleton than other described patients with an oligosymptomatic chronic form. This case broadens the clinical and biochemical picture associated with GUSB deficiency and may represent a new variant of the disease. © 1992 Wiley‐Liss, Inc.