Search PubMed⌕ Search

Biomedical subjects

V Vedanarayanan

Publications and source records attributed to V Vedanarayanan.

7 recordsLinked to original sources
PubMed2004

Tick paralysis.

Tick paralysis results from inoculation of a toxin from tick salivary glands during a blood meal. It is a relatively uncommon neuromuscular disease with a higher prevalence among young girls, although older men who get exposed to ticks may also be affected. It typically presents as an acute ascending paralysis occurring a few days after tick attachment and may result in respiratory failure and death. Patients may report minor sensory symptoms but constitutional signs are usually absent. Deep tendon reflexes are usually hypoactive or absent and ophthalmoplegia and bulbar palsy can occur. Children may be ataxic. Electromyographic studies usually show a variable reduction in the amplitude of compound muscle action potentials but no abnormalities of repetitive nerve stimulation studies. These appear to result from a failure of acetylcholine release at the motor nerve terminal level. There may be subtle abnormalities of motor nerve conduction velocity and sensory action potentials. Removal of the tick results in the very rapid reversal of clinical and physiologic deficits, quicker with North American ticks than with the Ixodes species seen in Australia.

Action Potentials↗
PubMed2002

Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype.

OBJECTIVE: To investigate the molecular basis of autosomal dominant limb-girdle muscular dystrophy (AD-LGMD) in three large new families. METHODS AND RESULTS: Genome-wide linkage was performed to show that the causative gene in all three families localized to chromosome 21q22.3 (Zmax = 10.3; theta = 0). This region contained the collagen VI alpha1 and alpha2 genes, which have been previously shown to harbor mutations causing a relatively mild congenital myopathy with contractures (Bethlem myopathy). Screening of the collagen VI alpha1 and alpha2 genes revealed novel, causative mutations in each family (COL6A1-K121R, G341D; COL6A2-D620N); two of these mutations were in novel regions of the proteins not previously associated with disease. Collagen VI is a ubiquitously expressed component of connective tissue; however, both limb-girdle muscular dystrophy and Bethlem myopathy patients show symptoms restricted to skeletal muscle. To address the muscle-specific symptoms resulting from collagen VI mutations, the authors studied three patient muscle biopsies at the molecular level (protein expression). A marked reduction of laminin beta1 protein in the myofiber basal lamina in all biopsies was found, although this protein was expressed normally in the neighboring capillary basal laminae. CONCLUSIONS: The authors' studies widen the clinical spectrum of Bethlem myopathy and suggest collagen VI etiology should be investigated in dominant limb-girdle muscular dystrophy. The authors hypothesize that collagen VI mutations lead to muscle-specific defects of the basal lamina, and may explain the muscle-specific symptoms of Bethlem and limb-girdle muscular dystrophy patients with collagen VI mutations.

Adolescent↗
PubMed2001

Methylation of the FSHD syndrome-linked subtelomeric repeat in normal and FSHD cell cultures and tissues.

Facioscapulohumeral muscular dystrophy (FSHD) has an unusual molecular etiology. In a putatively heterochromatic subtelomeric region of each chromosome 4 homologue (4q35), unaffected individuals have 11 to about 95 tandem copies of a complex 3.3-kb repeat (D4Z4). Most FSHD patients have less than 10 copies at one allelic 4q35. This has been proposed to lead to the loss of heterochromatinization and, thereby, inappropriate gene expression by position effects, explaining the dominant nature of FSHD and the role of a decreased number of copies of D4Z4 at 4q35 but not at 10q26. Consistent with the proposed heterochromatinization of this repeat, by Southern blot analysis, we found that SmaI, MluI, SacII, and EagI sites in D4Z4 are highly methylated in normal and FSHD cell lines and somatic tissues, including skeletal muscle. Like repeated DNA sequences in the juxtacentromeric heterochromatin of chromosomes 1, 9, and 16, D4Z4 was hypomethylated at numerous CpGs in sperm and in cell lines from patients with an unrelated DNA methyltransferase deficiency syndrome (ICF; immunodeficiency, centromeric region instability, facial anomalies) in contrast to its hypermethylation in non-ICF postnatal somatic tissues. Our data on FSHD samples suggest that the disease-associated 4q35 D4Z4 repeats, which constitute a small percentage of the total D4Z4 repeats, are not generally hypomethylated relative to the other repeats of this sequence. However, in individuals not affected with FSHD, the hypermethylation of tandem, high-copy-number D4Z4 repeats might help stabilize heterochromatinization at allelic 4q35 regions just as hypermethylation elsewhere in the genome has been linked to chromatin compaction.

Bacterial Proteins↗
PubMed2000

A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.

BACKGROUND: Central core disease (CCD) and nemaline rod myopathy are generally considered two genetically and histologically distinct disorders. CCD is defined by the presence of well-demarcated round cores within most myofibers. Nemaline rod myopathy is distinguished by the presence of characteristic nemaline bodies within myofibers. The simultaneous occurrence of both cores and rods in the same muscle biopsy has been described, but no gene mutations have been reported yet for this condition. OBJECTIVE: To describe a family containing 16 affected individuals in six generations with an autosomal dominant congenital myopathy that shows clinical and histologic features of both CCD and nemaline myopathy, and to determine the genetic etiology and protein composition of the cores/rods in this family. METHODS AND RESULTS: The results of linkage analyses excluded involvement of the two autosomal dominant nemaline myopathy loci on chromosome 1, but were consistent with a localization of the disease gene at the CCD locus on chromosome 19q13.1 (ryanodine receptor). SSCP analysis and DNA sequencing identified a novel Thr4637Ala mutation in the transmembrane region of the ryanodine receptor protein. Immunofluorescence studies of patient muscle biopsies showed the central cores to stain for ryanodine receptor. CONCLUSIONS: These data suggest that the occurrence of nemaline bodies can be a secondary feature of CCD, and that genetic studies on previously reported core/rod families should be targeted to the ryanodine receptor locus. The results of the immunofluorescence studies suggest that the cores contain excess abnormal ryanodine receptor protein.

Adolescent↗
PubMed1997

Guillain-Barré syndrome.

GBS is an acquired, monophasic illness of the peripheral nervous system that usually presents with a gait disturbance and clinical features of pain, weakness, and areflexia. The etiology of the disease is immune-mediated and directed against the peripheral nervous system myelin, axon, or both. A careful history, physical examination, and routine laboratory tests are necessary to make a clinical diagnosis and to exclude other disorders that cause acute weakness. Laboratory tests that support the diagnosis, such as an increased CSF protein and abnormal electrodiagnostic studies, may be normal early in the illness. The most serious complications during the acute phase of the disease are respiratory failure and autonomic disturbances. Plasma exchange or IVIG shortens the duration and severity of the disease significantly. The prognosis for children who have GBS generally is excellent for full and functional recovery, using modern intensive care for respiratory support and the management of other complications.

Child↗
PubMed1995

Treatment of childhood dermatomyositis with high dose intravenous immunoglobulin.

Two children with chronic dermatomyositis who were treated with intravenous immunoglobulin (IVIG) for 28 and 12 months, respectively, are reported. Both patients had received prednisone and immunosuppressive agents prior to IVIG treatments and had experienced significant side effects. Strength and functional abilities improved in both patients in a gradual stepwise fashion with IVIG treatment. One patient achieved remission and continues to do well without any immunosuppressive agents; in the other patient, the dose of oral steroids was reduced and other immunosuppressive agents were discontinued. Use of IVIG was associated with headaches, nausea, and vomiting in both patients. IVIG was an useful adjuvant therapy in these 2 children with dermatomyositis without any significant side effects.

Chemotherapy, Adjuvant↗