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Biomedical subjects

Florian P Thomas

Publications and source records attributed to Florian P Thomas.

11 recordsLinked to original sources
PubMed2006

Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.

Charcot-Marie-Tooth (CMT) neuropathies are common disorders of the peripheral nervous system caused by demyelination or axonal degeneration, or a combination of both features. We previously assigned the locus for autosomal dominant intermediate CMT neuropathy type C (DI-CMTC) to chromosome 1p34-p35. Here we identify two heterozygous missense mutations (G41R and E196K) and one de novo deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated families affected with DI-CMTC. Biochemical experiments and genetic complementation in yeast show partial loss of aminoacylation activity of the mutant proteins, and mutations in YARS, or in its yeast ortholog TYS1, reduce yeast growth. YARS localizes to axonal termini in differentiating primary motor neuron and neuroblastoma cultures. This specific distribution is significantly reduced in cells expressing mutant YARS proteins. YARS is the second aminoacyl-tRNA synthetase found to be involved in CMT, thereby linking protein-synthesizing complexes with neurodegeneration.

Amino Acid Sequence↗
PubMed2006

"A cold wind coming": Heinrich Gross and child euthanasia in Vienna.

Medicine in the German Third Reich became an instrument of Nazi political philosophy that included racial purification using biologic measures. This included an involuntary euthanasia program directed at mentally and physically disabled children. One such effort existed at the Am Spiegelgrund Hospital in Vienna under the direction of Dr Heinrich Gross. This article details the scientific and policy origins of child euthanasia in Vienna, the use of scientific materials obtained for personal and professional gain, and the postwar attempts to reconcile with this abject past.

Austria↗
PubMed2005

Neurological complications of HIV/AIDS.

Neurological complications are common in HIV disease. The spectrum of neurological disorders is broad and involves the central nervous system, or CNS (brain and spinal cord) and the peripheral nervous system, or PNS (nerves outside the brain and spinal cord, and related muscle). Neurological disorders related to HIV often result in reduced quality of life and shortened survival, especially in people with more advanced HIV disease. Nevertheless, some neurological conditions are mild, readily treatable, or reversible. Several have become less common since the introduction of highly active antiretroviral therapy (HAART). And, despite the fact that many anti-HIV drugs are unable to cross the blood-brain barrier and penetrate the brain, recent data published in the Journal of Acquired Immune Deficiency Syndromes support the claim that HAART can improve some neurocognitive functioning.

Antiretroviral Therapy, Highly Active↗
PubMed2004

"Whippets"-induced cobalamin deficiency manifesting as cervical myelopathy.

BACKGROUND: Nitrous oxide (N2O) is inhaled in anesthesia and as a recreational drug from whipped cream dispensers. Its abuse reaches approximately 10% in some age groups. By inactivating cobalamin (Cbl) (vitamin B12), N2O can cause neurologic and hematologic manifestations. We present a case of N2O-induced Cbl deficiency presenting as cervical myelopathy. CASE HISTORY: After regularly inhaling N2O for many months, a 31-year-old man developed limb paresthesiae and ataxia over 3 months. Examination revealed finger pseudoathetosis, hyporeflexia, decreased sensation, and gait ataxia. Brain magnetic resonance imaging (MRI) was normal, but the posterior columns of the cervical and upper thoracic cord revealed patchy nonenhancing hyperintense lesions. Serum Cbl was 98 pg/mL (normal = 170-900 pg/mL). Cbl replacement led to recovery within 3 months. DISCUSSION: This patient presented with the symptoms and signs of Cbl deficiency. The MRI lesions in the posterior columns aided the diagnosis. Physicians need to have a high level of suspicion in cases of unexplained Cbl deficiency and myelopathy.

Adult↗
PubMed2003

Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35.

Dominant intermediate Charcot-Marie-Tooth (DI-CMT) neuropathy is a genetic and phenotypic variant of classical CMT, characterized by intermediate nerve conduction velocities and histological evidence of both axonal and demyelinating features. We report two unrelated families with intermediate CMT linked to a novel locus on chromosome 1p34-p35 (DI-CMTC). The combined haplotype analysis in both families localized the DI-CMTC gene within a 6.3-cM linkage interval flanked by markers D1S2787 and D1S2830. The functional and positional candidate genes, Syndecan 3 (SDC3), and lysosomal-associated multispanning membrane protein 5 (LAPTM5) were excluded for pathogenic mutations.

Charcot-Marie-Tooth Disease↗
PubMed2003

Overwork weakness in Charcot-Marie-Tooth disease.

OBJECTIVE: To determine the incidence of overwork weakness in Charcot-Marie-Tooth disease (CMT). DESIGN: Prospective survey. SETTING: Rehabilitation department for CMT in an Italian tertiary care hospital. PARTICIPANTS: A total of 106 outpatients with CMT, selected for absence of other causes of weakness (age range, 11-69y), and 48 healthy volunteers (controls). INTERVENTIONS: The strength of 2 intrinsic hand muscles (abductor pollicis brevis [APB], first dorsal interosseous) in the dominant and nondominant hands was graded by using manual muscle testing and a modified Medical Research Council (MRC) Scale. MAIN OUTCOME MEASURES: The side of the stronger muscle and the difference in strength between the nondominant and dominant muscles. RESULTS: Muscles were stronger on the nondominant side in 65.57% of patients versus 1.04% of controls, and on the dominant side in .94% of patients versus 84.38% controls. The difference in strength for first dorsal interosseous was .51 in patients and -.32 in controls (P>.01). The difference in strength for APB was .65 in patients and -.35 in controls (P>.01). CONCLUSIONS: CMT muscles in the dominant hand are weaker than in the nondominant hand. This may be the result of overwork weakness.

Adolescent↗