ABSTRACT
Diabetes mellitus (DM) is one of the most common chronic disorders of children and adults. Several reports have suggested an increased incidence of maternal transmission in some forms of DM. Therefore, we tested a pedigree with maternally transmitted DM and deafness for mitochondrial DNA mutations and discovered a 10.4 kilobase (kb) mtDNA deletion. This deletion is unique because it is maternally inherited, removes the light strand origin (OL) of mtDNA replication, inhibits mitochondrial protein synthesis, and is not associated with the hallmarks of mtDNA deletion syndromes. This discovery demonstrates that DM can be caused by mtDNA mutations and suggests that some of the heterogeneity of this disease results from the novel features of mtDNA genetics.
Subject(s)
DNA, Mitochondrial/genetics , Deafness/genetics , Diabetes Mellitus, Type 2/genetics , Adult , Base Sequence , DNA Mutational Analysis , Deafness/complications , Deafness/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Female , Humans , Male , Middle Aged , Mitochondria/metabolism , Molecular Sequence Data , Oxidative Phosphorylation , Pedigree , Protein Biosynthesis , Sequence DeletionSubject(s)
Muscles/pathology , Myositis/complications , Radiculopathy/complications , Adult , Electromyography , Humans , Hypertrophy , Leg , Male , Muscle Denervation/adverse effectsABSTRACT
The preparation of immunoreactive derivatives of digoxin for analytical applications is most often carried out by periodate cleavage of the terminal sugar ring (digitoxose) followed by reaction with an enzyme, protein, carrier, or related biological molecules. Here we report an improved and more efficient synthesis which was developed to provide digoxin-phospholipid conjugates useful for liposome immunoassay. The approach used involved the linking of the cleaved digitoxose through a carboxymethyl oxime functionality, which provides much improved yields of readily purified products. The synthetic modification should be applicable to the preparation of analogous phospholipid conjugates involving linkage through a sugar ring (digitoxin, ouabain, and related cardiac glycosides) or to those involving steroids (i.e., 3-digoxigenone) which can be modified to form oxime derivatives remote from key functionalities important for immunorecognition by specific antibody. The characterization of the digoxin-phospholipid conjugates with high-resolution NMR and fast atom bombardment mass spectrophotometry will also be discussed.
Subject(s)
Digoxin/analogs & derivatives , Liposomes , Phosphatidylethanolamines/chemical synthesis , Chemical Phenomena , Chemistry , Digoxin/chemical synthesis , Digoxin/chemistry , Digoxin/isolation & purification , Immunoassay , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Phosphatidylethanolamines/chemistry , Phosphatidylethanolamines/isolation & purification , Spectrometry, Mass, Fast Atom Bombardment , SpectrophotometryABSTRACT
A 9-month-old patient developed a Candida albicans skin abscess at the repair site of a lumbar myelomeningocele. There was no evidence of C. albicans infection elsewhere in the body. The infection may have been acquired at the time of the original myelomeningocele repair at 2 days of age. The abscess was cured by surgical drainage and amphotericin B therapy. This case indicates that laboratories should be aware of C. albicans as an unusual cause of abscess.
