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1.
Neuropediatrics ; 49(2): 150-153, 2018 04.
Article in English | MEDLINE | ID: mdl-29284168

ABSTRACT

Neuronal ceroid lipofuscinoses represent a heterogeneous group of early onset neurodegenerative disorders that are characterized by progressive cognitive and motor function decline, visual loss, and epilepsy. The age of onset has been historically used for the phenotypic classification of this group of disorders, but their molecular genetic delineation has now enabled a better characterization, demonstrating significant genetic heterogeneity even among individuals with a similar phenotype. The rare Congenital Neuronal Ceroid Lipofuscinosis (CLN10) caused by mutations in the CTSD gene encoding for cathepsin D is associated with a dramatic presentation with onset before or around birth. We report on a female born to consanguineous parents who presented at birth with severe neonatal encephalopathy with massive cerebral and cerebellar shrinking on magnetic resonance imaging. Whole exome sequencing with targeted bioinformatic analysis of a panel of genes associated with prenatal/perinatal onset of neurodegenerative disease was performed and revealed the presence of a novel homozygous in-frame deletion in CTSD. Additional functional studies further confirmed the pathogenic character of this variant and established the diagnosis of CLN10 in the patient.


Subject(s)
Cathepsin D/genetics , Mutation/genetics , Neuronal Ceroid-Lipofuscinoses/genetics , Brain Stem/diagnostic imaging , Cerebellum/diagnostic imaging , Female , Humans , Infant , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Neuronal Ceroid-Lipofuscinoses/diagnostic imaging
2.
Brain ; 135(Pt 7): 2022-31, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22586289

ABSTRACT

Cerebral folate transport deficiency is an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 gene coding for folate receptor alpha (FRα). This genetic defect gives rise to a progressive neurological disorder with late infantile onset. We screened 72 children with low 5-methyltetrahydrofolate concentrations in the cerebrospinal fluid and neurological symptoms that developed after infancy. We identified nucleotide alterations in the folate receptor 1 gene in 10 individuals who shared developmental regression, ataxia, profound cerebral hypomyelination and cerebellar atrophy. We found four novel pathogenic alleles, one splice mutation and three missense mutations. Heterologous expression of the missense mutations, including previously described mutants, revealed minor decrease in protein expression but loss of cell surface localization, mistargeting to intracellular compartments and thus absence of cellular binding of folic acid. These results explain the functional loss of folate receptor alpha for all detected folate receptor 1 mutations. Three individuals presenting a milder clinical phenotype revealed very similar biochemical and brain imaging data but partially shared pathogenic alleles with more severely affected patients. Thus, our studies suggest that different clinical severities do not necessarily correlate with residual function of folate receptor alpha mutants and indicate that additional factors contribute to the clinical phenotype in cerebral folate transport deficiency.


Subject(s)
Folate Receptor 1/metabolism , Folic Acid Deficiency/genetics , Folic Acid/metabolism , Mutation/genetics , Adolescent , Alleles , Animals , CHO Cells , Child , Child, Preschool , Cricetinae , Female , Fibroblasts/metabolism , Folate Receptor 1/genetics , Folic Acid Deficiency/diagnosis , Hep G2 Cells , Humans , Magnetic Resonance Imaging/methods , Male , Phenotype , Protein Transport/genetics , Tetrahydrofolates/cerebrospinal fluid
3.
J Inherit Metab Dis ; 35(1): 51-63, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22033733

ABSTRACT

Deficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia. We have studied, at the molecular level, PCC in 54 patients from 48 families comprised of 96 independent alleles. These patients of various ethnic backgrounds came from research centers and hospitals in Germany, Austria and Switzerland. The thorough clinical characterization of these patients was described in the accompanying paper (Grünert et al. 2012). In all 54 patients, many of whom originated from consanguineous families, the entire PCCB gene was examined by genomic DNA sequencing and in 39 individuals the PCCA gene was also studied. In three patients we found mutations in both PCC genes. In addition, in many patients RT-PCR analysis of lymphoblast RNA, lymphoblast enzyme assays, and expression of new mutations in E.coli were carried out. Eight new and eight previously detected mutations were identified in the PCCA gene while 15 new and 13 previously detected mutations were found in the PCCB gene. One missense mutation, p.V288I in the PCCB gene, when expressed in E.coli, yielded 134% of control activity and was consequently classified as a polymorphism in the coding region. Numerous new intronic polymorphisms in both PCC genes were identified. This study adds a considerable amount of new molecular data to the studies of this disease.


Subject(s)
DNA Mutational Analysis , Propionic Acidemia/diagnosis , Propionic Acidemia/genetics , Adolescent , Alleles , Child , Child, Preschool , Escherichia coli/genetics , Female , Humans , Infant , Introns , Lymphocytes/cytology , Male , Mutagenesis , Mutation , Polymorphism, Genetic , Recombinant Proteins/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods
4.
J Inherit Metab Dis ; 35(1): 41-9, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22134541

ABSTRACT

BACKGROUND: Whereas propionic acidemia (PA) is a target disease of newborn screening (NBS) in many countries, it is not in others. Data on the benefit of NBS for PA are sparse. STUDY DESIGN: Twenty PA patients diagnosed through NBS were compared to 35 patients diagnosed by selective metabolic screening (SMS) prompted by clinical findings, family history, or routine laboratory test results. Clinical and biochemical data of patients from 16 metabolic centers in Germany, Austria, and Switzerland were evaluated retrospectively. Additionally, assessment of the intelligent quotient (IQ) was performed. In a second step, the number of PA patients who have died within the past 20 years was estimated based on information provided by the participating metabolic centers. RESULTS: Patients diagnosed through NBS had neither a milder clinical course regarding the number of metabolic crises nor a better neurological outcome. Among NBS patients, 63% were already symptomatic at the time of diagnosis, and <10% of all patients remained asymptomatic. Among all PA patients, 76% were found to be at least mildly mentally retarded, with an IQ <69. IQ was negatively correlated with the number of metabolic decompensations, but not simply with the patients' age. Physical development was also impaired in the majority of patients. Mortality rates tended to be lower in NBS patients compared with patients diagnosed by SMS. CONCLUSION: Early diagnosis of PA through NBS seems to be associated with a lower mortality rate. However, no significant benefit could be shown for surviving patients with regard to their clinical course, including the number of metabolic crises, physical and neurocognitive development, and long-term complications.


Subject(s)
Neonatal Screening/methods , Propionic Acidemia/diagnosis , Adolescent , Austria , Child , Child, Preschool , Female , Germany , Humans , Infant , Infant, Newborn , Intelligence Tests , Male , Outpatients , Retrospective Studies , Surveys and Questionnaires , Switzerland
5.
Ophthalmologe ; 107(7): 616-20, 2010 Jul.
Article in German | MEDLINE | ID: mdl-20454899

ABSTRACT

The neuronal ceroid lipofuscinoses (NCL) are a heterogeneous group of lysosomal diseases with rapidly progressive neurodegeneration and characteristic lipopigmentary lysosomal inclusions. The clinical picture is characterized by motor disturbances, developmental delay, behavioral abnormalities, epilepsy, loss of vision and dementia. Cranial MRI reveals global brain atrophy and in particular early atrophy of the cerebellum. If an NCL disease is suspected initial diagnostic assessment for the CLN1, CLN2, CLN3 and CLN10 subtypes is recommended. The investigations can be done with a dried blood spotted on filter paper. If the results are negative but an NCL disease is still suspected the further approach should be coordinated with an expert in the field. Possible other diagnostic examinations include electron microscopy of the storage material in lymphocytes and skin biopsy specimens or molecular genetic analysis of the suspected NCL gene. At present only symptomatic therapy is available for NCL diseases.


Subject(s)
Genetic Markers/genetics , Genetic Testing/methods , Neuronal Ceroid-Lipofuscinoses/diagnosis , Neuronal Ceroid-Lipofuscinoses/therapy , Vision Disorders/diagnosis , Vision Disorders/therapy , Child , Diagnosis, Differential , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Neuronal Ceroid-Lipofuscinoses/complications , Neuronal Ceroid-Lipofuscinoses/genetics , Tripeptidyl-Peptidase 1 , Vision Disorders/etiology , Vision Disorders/genetics
6.
Clin Genet ; 77(1): 79-85, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19807737

ABSTRACT

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited lysosomal storage diseases and the prototype of childhood onset neurodegenerative disorders. To date, 10 NCL entities (CLN1-CLN10) are known and characterized by accumulation of autofluorescent storage material, age of onset and clinical symptoms. CLN8 was first identified as the causative gene for a late-onset form with progressive epilepsy and mental retardation in Finnish patients. In addition, CLN8 phenotypes were described in Turkish, Israeli and Italian patients with a more rapid progression of visual loss, epilepsy, ataxia and mental decline. Here, we report the first mutations in German (c.611G>T) and Pakistani (c.709G>A) patients. Our findings confirm previous assumptions that the CLN8 variant can occur in many ethnic groups. So far, large CLN gene deletions are only known for the CLN3 gene. Here, we also describe a novel, large CLN8 gene deletion c.544-2566_590del2613 in a Turkish family with a slightly more severe phenotype. Our data indicate that patients with clinical signs of late infantile NCL and characteristic ultrastructural inclusions should also be screened for CLN8 mutations independent of their ethnic origin.


Subject(s)
Membrane Proteins/genetics , Neuronal Ceroid-Lipofuscinoses/genetics , Sequence Deletion , Adolescent , Child , Female , Germany , Humans , Male , Neuronal Ceroid-Lipofuscinoses/ethnology , Neuronal Ceroid-Lipofuscinoses/pathology , Pakistan , Turkey
7.
J Inherit Metab Dis ; 27(4): 449-53, 2004.
Article in English | MEDLINE | ID: mdl-15303001

ABSTRACT

Phenylketonuria, an inborn error of phenylalanine metabolism, occurs with a frequency of about 1 in 10,000 births and is treated with a strict dietary regimen. Recently, some patients with PKU have been found to show increased tolerance towards phenylalanine intake while receiving tetrahydrobiopterin (BH(4)) supplementation. We have treated two infants with BH(4)-responsive PKU with BH(4) for more than 2 years. No additional dietary control was required to maintain blood phenylalanine concentrations in the desired range. Both children have shown normal development. Generally, our results suggest that BH(4) treatment might be an option for some patients with mild PKU, as it frees them from dietary restrictions and thus improves their quality of life.


Subject(s)
Biopterins/analogs & derivatives , Biopterins/therapeutic use , Phenylketonurias/drug therapy , Biopterins/administration & dosage , Circadian Rhythm , Diet , Humans , Infant, Newborn , Phenylalanine/blood , Quality of Life
8.
Neuropediatrics ; 34(5): 261-4, 2003 Jun.
Article in English | MEDLINE | ID: mdl-14598232

ABSTRACT

A remarkable, intermittent sudden-onset vigilance and movement disorder in an exclusively breast-fed infant is reported, which was caused by cobalamin depletion due to maternal vitamin B12 malabsorption. The lack of cobalamin caused a severe encephalopathy in the infant, whose brain displayed a striking loss of volume and a delay of myelination. Proton magnetic resonance spectroscopy revealed an accumulation of lactate in the gray and white matter of the brain and a sustained depletion of choline-containing compounds in the white matter, reflecting a reversible disturbance of oxidative energy metabolism in brain cells and a long-lasting hypomyelination disorder. The clinical picture in conjunction with MRI and spectroscopic data of this case study yields more insight into the functions of cobalamin in the cerebral metabolism.


Subject(s)
Brain Diseases/metabolism , Brain Diseases/pathology , Choline Deficiency/metabolism , Lactic Acid/metabolism , Vitamin B 12 Deficiency/metabolism , Brain Diseases/etiology , Choline Deficiency/complications , Choline Deficiency/diagnosis , Humans , Infant , Magnetic Resonance Spectroscopy , Male , Muscle Hypotonia/diagnosis , Muscle Hypotonia/etiology , Muscle Weakness/diagnosis , Muscle Weakness/etiology , Myelin Sheath/pathology , Vitamin B 12 Deficiency/diagnosis
9.
Amino Acids ; 25(1): 63-8, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12836060

ABSTRACT

We describe six children with tetrahydrobiopterin (BH(4)) responsive phenylalanine hydroxylase (PAH) deficiency. All patients carry two mutant alleles in the PAH gene. Cofactor deficiency was excluded. The effect of BH(4) administration was studied by correlating different oral BH(4) doses with plasma phenylalanine levels under defined protein intake. Our results indicate that oral BH(4) supplementation may be used as long-term treatment for individuals with BH(4)-responsive PAH deficiency, either without or in combination with a less restrictive diet. Previous in vitro studies have demonstrated that BH(4) inhibits PAH tetramers but activates PAH dimers. This may indicate, that BH(4)-responsiveness results from BH(4) induced stabilization of mutant PAH dimers. In addition, interindividual differences in the cellular folding apparatus may determine the tertiary structure and the amount of mutant PAH dimers and hence may account for divergent BH(4)-responsiveness reported for the same PAH genotype.


Subject(s)
Biopterins/analogs & derivatives , Biopterins/metabolism , Phenylalanine Hydroxylase/genetics , Phenylketonurias/metabolism , Biopterins/administration & dosage , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Mutation , Phenylalanine/blood , Phenylalanine Hydroxylase/metabolism , Phenylketonurias/genetics
10.
Hum Mutat ; 21(4): 400, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12655554

ABSTRACT

We report the results of tetrahydrobiopterin (BH4) loading tests in 10 German patients with mild phenylketonuria. A significant decline of phenylalanine values after application of BH4 was observed in all but one patients. Molecular genetic analyses revealed a range of different PAH gene mutations. Re-testing of one patient previously reported as non-responsive to BH4 loading showed a moderate response with a higher dose of BH4. Nevertheless, there appear to be kinetic differences in phenylalanine hydroxylation in patients with the same genotype. Non-responsiveness to 20 mg/kg BH4 was observed only in a single patient who was compound heterozygous for the novel mutation R176P (c.527G>C) and the common null-mutation P281L. In summary, our data are in line with recent reports indicating that BH4 sensitivity is a normal feature of most mild forms of PAH deficiency but may be influenced by other factors.


Subject(s)
Biopterins/analogs & derivatives , Biopterins/metabolism , Phenylalanine Hydroxylase/deficiency , Phenylketonurias/enzymology , Administration, Oral , Amino Acid Substitution/genetics , Amino Acid Substitution/physiology , Biopterins/administration & dosage , Child , Drug Administration Schedule , Humans , Infant , Infant, Newborn , Mutation, Missense/genetics , Neonatal Screening , Phenylalanine/blood , Phenylalanine Hydroxylase/physiology , Phenylketonurias/blood , Phenylketonurias/metabolism
11.
J Arthroplasty ; 16(8): 1078-80, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11740768

ABSTRACT

Soft tissue swelling occasionally can be seen about the incision after a total hip arthroplasty. We report a case of a lateral wall hernia occurring immediately after a total hip arthroplasty that presented as a mass over the proximal aspect of the hip incision.


Subject(s)
Arthroplasty, Replacement, Hip , Hernia, Ventral/diagnosis , Postoperative Complications/diagnosis , Diagnosis, Differential , Female , Hernia, Ventral/surgery , Humans , Middle Aged , Postoperative Complications/surgery , Tomography, X-Ray Computed
12.
Mayo Clin Proc ; 74(8): 785-94, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10473355

ABSTRACT

Shoulder pain is a common entity in a primary care physician's practice. The unique anatomy of the shoulder allows for almost unrestrained motion in all planes. A thorough history and physical examination are important to ensure efficient patient evaluation. Further assessment may include radiographic and diagnostic laboratory tests. This article presents an organized approach to the anatomy, physiology, and pathology of common shoulder disorders for the primary care physician. The distinction between disorders that are intrinsic or extrinsic to the shoulder joint is discussed. Treatment and the need for appropriate referral are described.


Subject(s)
Range of Motion, Articular , Shoulder Joint/pathology , Shoulder Joint/physiopathology , Diagnosis, Differential , Humans , Joint Diseases/diagnosis , Joint Diseases/physiopathology , Radiography , Shoulder Joint/diagnostic imaging
13.
J Inherit Metab Dis ; 22(4): 392-403, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10407776

ABSTRACT

In organotypic corticostriatal and hippocampal slice cultures from rat brain, 3-hydroxyglutaric acid but not glutaric and glutaconic acids induced neurodegeneration by activation of NMDA receptors. Electrophysiological investigations (Xenopus laevis oocytes expressing glutamate receptors; rat mixed cortex culture) revealed no direct interaction of 3-hydroxyglutaric acid with glutamate receptors. We speculate that 3-hydroxyglutaric acid induces a mild energy deprivation that interferes with the voltage-dependent Mg(2+)-block of NMDA receptors.


Subject(s)
Cerebral Cortex/pathology , Glutarates/metabolism , Hippocampus/pathology , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Culture Techniques , Glutarates/pharmacology , Glutarates/urine , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/metabolism
14.
Arthroscopy ; 14(2): 212-4, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9531135

ABSTRACT

Restricted motion of the knee occurs frequently after an intra-articular fracture of the distal femur. Treatment of this complication typically requires open release of the quadriceps muscle. To our knowledge an arthroscopically assisted method of performing a quadricepsplasty has not been previously described. We present such a case and the details of the arthroscopically assisted method that may provide an alternative, minimally invasive means of restoring knee flexion in the setting of a post-traumatic extension contracture.


Subject(s)
Contracture/surgery , Knee Joint , Muscle, Skeletal/surgery , Arthroscopy , Contracture/etiology , Endoscopy/methods , Female , Femoral Fractures/complications , Humans , Knee Joint/diagnostic imaging , Knee Joint/physiopathology , Middle Aged , Radiography , Range of Motion, Articular
15.
Mol Pharmacol ; 52(5): 771-80, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9351967

ABSTRACT

Oligonucleotides that can form a highly stable intramolecular four-stranded DNA structure containing two stacked guanosine-quartets (G-quartets) have been reported to inhibit the replication of the human immunodeficiency virus type 1 (HIV-1) in cell culture. Two possible mechanisms for the observed antiviral activity have been proposed: interference with virus adsorption to the cell and/or inhibition of HIV-1 integrase. We investigated the molecular interaction of G-quartet-containing oligonucleotides with HIV-1 integrase in comparison with random oligonucleotides and dextran sulfate. The prototypical G-quartet-containing oligonucleotide, T30177 (Zintevir), inhibited the overall integration reaction with an IC50 value of 80 nM. A random oligonucleotide was 10-fold less potent, but dextran sulfate was more potent, with an IC50 value of 7 nM. We developed novel kinetic assays to dissect the overall integration reaction in three steps: the formation of the initial stable complex (ISC), the 3'-processing reaction, and the DNA strand-transfer step. We then analyzed the kinetics of the ISC formation and 3'-processing. The rate constant determined for the conversion of ISC into the cleaved product was 0.08 +/- 0.01 min-1. T30177 did not inhibit 3'-processing or DNA strand transfer, whereas dextran sulfate inhibited DNA strand transfer to some extent. Binding studies using surface plasmon resonance technology revealed that both T30177 and dextran sulfate were capable of preventing the binding of integrase to specific DNA. We propose a model in which the interaction of HIV-1 integrase with G-quartets results in the inhibition of the formation of the ISC between integrase and substrate DNA. Finally, we selected for an HIV-1 strain that was resistant to T30177 in cell culture. DNA sequence analysis revealed mutations in the envelope glycoprotein gp120 but not in the integrase gene. Although gp120 seems to be the main target for the antiviral activity in cell culture of G-quartets, the study of their specific inhibition of HIV-1 integrase may lead to the development of effective integrase inhibitors.


Subject(s)
DNA, Viral/drug effects , Guanosine , HIV Integrase Inhibitors/pharmacology , HIV Integrase/drug effects , HIV-1/enzymology , Oligonucleotides/pharmacology , Virus Integration/drug effects , DNA, Viral/analysis , HIV Integrase/genetics , HIV Integrase/metabolism , HIV-1/genetics , Kinetics , Viral Proteins/metabolism
16.
Genomics ; 40(1): 24-30, 1997 Feb 15.
Article in English | MEDLINE | ID: mdl-9070915

ABSTRACT

The four vertebrate glypican-related integral membrane proteoglycans identified so far constitute a discrete family of heparan sulfate proteoglycans that are linked to the cell surface via glycosyl phosphatidylinositol. In addition to the GPI anchor and substitution with heparan sulfate, the members of this family show significant sequence homology and share a unique and characteristic cysteine motif. Starting from an EST entry that showed significant sequence similarity to MXR7 and OCI-5 (coding, respectively, for human and rat glypican-3), we have isolated a human cDNA coding for glypican-5, a novel member of this proteoglycan family. The gene for this novel glypican (GPC5) maps to 13q32. In the adult, it is primarily expressed in brain tissue.


Subject(s)
Chromosomes, Human, Pair 13 , Heparitin Sulfate/genetics , Proteoglycans/genetics , Amino Acid Sequence , Base Sequence , Chromosome Mapping , DNA, Complementary , Extracellular Matrix Proteins , Gene Expression , Glypicans , Heparan Sulfate Proteoglycans , Humans , Molecular Sequence Data , Sequence Homology, Amino Acid
17.
J Cell Biol ; 133(2): 405-16, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8609172

ABSTRACT

The formation of distinctive basic FGF-heparan sulfate complexes is essential for the binding of bFGF to its cognate receptor. In previous experiments, cell-surface heparan sulfate proteoglycans extracted from human lung fibroblasts could not be shown to promote high affinity binding of bFGF when added to heparan sulfate-deficient cells that express FGF receptor-1 (FGFR1) (Aviezer, D., D. Hecht, M. Safran, M. Eisinger, G. David, and A. Yayon. 1994. Cell 79:1005-1013). In alternative tests to establish whether cell-surface proteoglycans can support the formation of the required complexes, K562 cells were first transfected with the IIIc splice variant of FGFR1 and then transfected with constructs coding for either syndecan-1, syndecan-2, syndecan-4 or glypican, or with an antisense syndecan-4 construct. Cells cotransfected with receptor and proteoglycan showed a two- to three- fold increase in neutral salt-resistant specific 125I-bFGF binding in comparison to cells transfected with only receptor or cells cotransfected with receptor and anti-syndecan-4. Exogenous heparin enhanced the specific binding and affinity cross-linking of 125I-bFGF to FGFR1 in receptor transfectants that were not cotransfected with proteoglycan, but had no effect on this binding and decreased the yield of bFGFR cross-links in cells that were cotransfected with proteoglycan. Receptor-transfectant cells showed a decrease in glycophorin A expression when exposed to bFGF. This suppression was dose-dependent and obtained at significantly lower concentrations of bFGF in proteoglycan-cotransfected cells. Finally, complementary cell-free binding assays indicated that the affinity of 125I-bFGF for an immobilized FGFR1 ectodomain was increased threefold when the syndecan-4 ectodomain was coimmobilized with receptor. Equimolar amounts of soluble syndecan-4 ectodomain, in contrast, had no effect on this binding. We conclude that, at least in K562 cells, syndecans and glypican can support bFGF-FGFR1 interactions and signaling, and that cell-surface association may augment their effectiveness.


Subject(s)
Heparitin Sulfate/physiology , Membrane Glycoproteins/physiology , Proteoglycans/physiology , Receptor Protein-Tyrosine Kinases , Receptors, Fibroblast Growth Factor/metabolism , Signal Transduction/physiology , Base Sequence , Cell Differentiation , Cross-Linking Reagents , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/metabolism , Fibroblast Growth Factor 2/pharmacology , Glycophorins/analysis , Glycosaminoglycans/analysis , Hematopoietic Stem Cells/cytology , Heparan Sulfate Proteoglycans , Heparin/pharmacology , Heparitin Sulfate/analysis , Heparitin Sulfate/genetics , Heparitin Sulfate/metabolism , Humans , Lipopolysaccharide Receptors/analysis , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Molecular Sequence Data , Protein Binding , Proteoglycans/genetics , Proteoglycans/metabolism , Receptor, Fibroblast Growth Factor, Type 1 , Receptors, Fibroblast Growth Factor/genetics , Recombinant Fusion Proteins/isolation & purification , Recombinant Fusion Proteins/metabolism , Transfection , Tumor Cells, Cultured
18.
Atherosclerosis ; 118 Suppl: S57-67, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8821466

ABSTRACT

Heparan sulfate (HS), a mixed bag of complex, heterogeneous and highly charged polysaccharides, is an essential co-factor in a large number of receptor-ligand interactions and cellular pathways. These co-factor functions depend on the binding-interactions of the HS chains with the ligand or receptor, or both. These binding interactions and the ensuing functional effects often depend on defined carbohydrate sequences within the HS chains, whereby the required sequences are not always represented within all natural forms of the polysaccharide. The proteins that are substituted with HS resort from a limited number of protein families, with different cellular, subcellular and supramolecular associations, and show differential activities in functional assays. It is likely that the natural co-factor functions of the HS proteoglycans depend on glycan-protein and protein-protein interactions that are subject to modulation, both at the glycan and protein levels.


Subject(s)
Blood Vessels/metabolism , Heparitin Sulfate/physiology , Proteoglycans/physiology , Receptors, Cell Surface/metabolism , Animals , Binding Sites , Blood Vessels/cytology , Cell Division , Humans
19.
Mil Med ; 160(4): 175-7, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7617224

ABSTRACT

U.S. prisoners of war from Operation Desert Storm suffered significant orthopedic injuries. The repatriated prisoners of war (RPOWs) have been medically evaluated over a 3-year period with orthopedic follow-up. A significant proportion of the musculoskeletal injuries were located around the neck and spine, shoulder, and upper extremity. Aircraft ejection was the cause of the majority of these injuries. Lower extremity injuries after ejection, aside from the knee, were not reported. Flail injuries of the lower extremities were absent as well. These results were examined with reference to Vietnam RPOW data.


Subject(s)
Military Personnel , Musculoskeletal System/injuries , Prisoners , Warfare , Adult , Female , Follow-Up Studies , Humans , Male , Middle East , Orthopedics , United States , Wounds and Injuries/therapy
20.
Clin Orthop Relat Res ; (301): 185-90, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8156671

ABSTRACT

Multiple cartilaginous-like bodies (rice bodies) in joints or bursae may be the presenting sign of a more extensive underlying rheumatic condition. Three patients with massive subacromial bursae with rice bodies are described, one of whom had bilateral occurrence. In all patients, excision of the bursa and rice bodies relieved the symptoms. The underlying rheumatic condition continued its course, generally sparing the involved shoulder joint. Review of these cases reinforces the need to provide a thorough examination for systemic rheumatologic disease in patients diagnosed with this lesion.


Subject(s)
Acromioclavicular Joint/surgery , Bursitis/pathology , Joint Loose Bodies/pathology , Adult , Aged , Bursitis/diagnosis , Bursitis/surgery , Diagnostic Imaging , Female , Humans , Joint Loose Bodies/diagnostic imaging , Joint Loose Bodies/surgery , Male , Middle Aged , Radiography
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