ABSTRACT
An 83-year-old man visited an orthopedic hospital for his lower back pain. A compression fracture was noted in his second lumbar vertebra. He had taken pain medication for approximately five weeks, but the pain had worsened and he was unable to walk by himself. He was transferred to our hospital and diagnosed with lumbar spondylodiscitis, an iliopsoas abscess, gas gangrene of his left lower limb, and left massive pleural effusion. He was admitted to the intensive care unit. We drained the abscess and pleural effusion, provided continuous hemodiafiltration under ventilator control, and administered intravenous antibiotics. However, he died from sepsis and multiple organ failure three days following admission. Several days after his death, gram-positive cocci were identified in blood culture, pus from the abscess, and pleural exudate; although the causative organism could not be identified. Two weeks subsequent to his death, 16S ribosomal RNA gene sequencing identified Parvimonas micra in specimens taken from his body.
ABSTRACT
In patients with VATER association, some have vascular anomaly that makes procedure difficult. Pretreatment CT angiography should be necessary for the patients with VATER association's feature.
ABSTRACT
Mutations in the key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosamine kinase, result in distal myopathy with rimmed vacuoles (DMRV)/hereditary inclusion body myopathy (HIBM) in humans. Sialic acid is an acidic monosaccharide that modifies non-reducing terminal carbohydrate chains on glycoproteins and glycolipids, and it plays an important role in cellular adhesions and interactions. In this study, we generated mice with a V572L point mutation in the GNE kinase domain. Unexpectedly, these mutant mice had no apparent myopathies or motor dysfunctions. However, they had a short lifespan and exhibited renal impairment with massive albuminuria. Histological analysis showed enlarged glomeruli with mesangial matrix deposition, leading to glomerulosclerosis and abnormal podocyte foot process morphologies in the kidneys. Glycan analysis using several lectins revealed glomerular epithelial cell hyposialylation, particularly the hyposialylation of podocalyxin, which is one of important molecules for the glomerular filtration barrier. Administering Neu5Ac to the mutant mice from embryonic stages significantly suppressed the albuminuria and renal pathology, and partially recovered the glomerular glycoprotein sialylation. These findings suggest that the nephrotic-like syndrome observed in these mutant mice resulted from impaired glomerular filtration due to the hyposialylation of podocyte glycoproteins, including podocalyxin. Furthermore, it was possible to prevent the nephrotic-like disease in these mice by beginning Neu5Ac treatment during gestation.
Subject(s)
N-Acetylneuraminic Acid/pharmacology , N-Acetylneuraminic Acid/therapeutic use , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/prevention & control , Point Mutation/genetics , Sialoglycoproteins/metabolism , Albuminuria/blood , Albuminuria/complications , Animals , Base Sequence , Biosynthetic Pathways , Blotting, Western , Carbohydrate Epimerases/genetics , Cystatin C/blood , Lectins/metabolism , Mice , Molecular Sequence Data , N-Acetylneuraminic Acid/administration & dosage , Nephrotic Syndrome/enzymology , Nephrotic Syndrome/genetics , Podocytes/drug effects , Podocytes/metabolism , Podocytes/pathology , Podocytes/ultrastructure , Polysaccharides/metabolism , Staining and LabelingABSTRACT
The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p<0.040) and rs3796863 (p<0.005) showed significant associations with a subset of ASD (IQ>70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD.
Subject(s)
ADP-ribosyl Cyclase 1/genetics , Child Development Disorders, Pervasive/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Adolescent , Adult , Aged , Analysis of Variance , Brain/metabolism , Brain/pathology , Child , Child, Preschool , Cohort Studies , Cross-Cultural Comparison , Family Health , Female , Gene Frequency , Genome-Wide Association Study , Genotype , Humans , Immunoenzyme Techniques/methods , Japan , Male , Middle Aged , Oxytocin/blood , Vasopressins/blood , Young AdultABSTRACT
We describe a consanguineous family that had progressive myopathy with rimmed vacuole (RV) formation and amyloid deposition. Patient 1 is a 71-year-old woman with muscle atrophy in the lumbar girdle and lower extremities. Patient 2 is a 40-year-old man (the son of Patient 1) with fatty changes in the biceps femoris muscles. Muscle biopsies revealed myopathic and neurogenic degeneration with RV, necrotic fibers, and interstitial amyloid deposition. Amyloid deposition was detected only in the muscle tissue.
Subject(s)
Amyloid/metabolism , Muscles/metabolism , Muscular Dystrophies/metabolism , Muscular Dystrophies/pathology , Adult , Aged , Family Health , Female , Humans , Male , Muscles/pathology , Muscles/ultrastructure , Muscular Dystrophies/genetics , Vacuoles/metabolism , Vacuoles/pathology , Vacuoles/ultrastructureABSTRACT
Distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive muscular disorder characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood and sparing of the quadricep muscles. The UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene was recently identified as the causative gene for hereditary inclusion body myopathy (HIBM). To investigate whether DMRV and HIBM are allelic diseases, we conducted mutational analysis of the GNE gene of six Japanese DMRV pedigrees and found that all the pedigrees share a homozygous mutation (V572L) associated with a strong linkage disequilibrium, suggesting a strong founder effect in Japanese DMRV pedigrees.