Biomedical subjects

Matthew T Lorincz

Publications and source records attributed to Matthew T Lorincz.

7 recordsLinked to original sources

PubMed2006

Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease.

OBJECTIVE: To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery. DESIGN: A randomized, double-blind, controlled, 2-arm study of 48 patients with the neurologic presentation of Wilson disease. Patients either received 500 mg of trientine hydrochloride 2 times per day or 20 mg of tetrathiomolybdate 3 times per day with meals and 20 mg 3 times per day between meals for 8 weeks. All patients received 50 mg of zinc 2 times per day. Patients were hospitalized for 8 weeks, with neurologic and speech function assessed weekly; discharged taking 50 mg of zinc 3 times per day, and returned annually for follow-up. SETTING: A university hospital referral setting. PATIENTS: Primarily newly diagnosed patients with Wilson disease presenting with neurologic symptoms who had not been treated longer than 4 weeks with an anticopper drug. INTERVENTION: Treatment with either trientine plus zinc or tetrathiomolybdate plus zinc. MAIN OUTCOME MEASURES: Neurologic function was assessed by semiquantitative neurologic and speech examinations. Drug adverse events were evaluated by blood cell counts and biochemical measures. RESULTS: Six of 23 patients in the trientine arm and 1 of 25 patients in the tetrathiomolybdate arm underwent neurologic deterioration (P<.05). Three patients receiving tetrathiomolybdate had adverse effects of anemia and/or leukopenia, and 4 had further transaminase elevations. One patient receiving trientine had an adverse effect of anemia. Four patients receiving trientine died during follow-up, 3 having shown initial neurologic deterioration. Neurologic and speech recovery during a 3-year follow-up period were quite good. CONCLUSION: Tetrathiomolybdate is a better choice than trientine for preserving neurologic function in patients who present with neurologic disease.

Adolescent↗

PubMed2006

Geriatric chorea.

The differential diagnosis, diagnostic evaluation, and treatment of late-onset chorea are reviewed. Late-onset chorea is rare and has a heterogeneous causation. A systematic approach to geriatric chorea greatly enhances a correct diagnosis. An accurate diagnosis is important because many causes of chorea are treatable or or, when heritable, may have significant implications for subsequent generations. Most late-onset chorea is either nonlimiting, requiring no treatment, has a spontaneous remission, or responds to medication. In a minority of patients, chorea is medically refractory or manifestation of an untreatable disorder.

Age Factors↗

PubMed2006

Clinical implications of Parkinson's disease genetics.

Parkinson's disease (PD) is a significant neurodegenerative disease of the elderly, affecting 1 to 2% of those over 60 years of age. The disorder is characterized by resting tremor, bradykinesia, rigidity, postural instability, and pathologically by alpha-synuclein-positive Lewy bodies. For most, the etiology is unknown and it is likely due to a multifactorial interaction of genes and the environment. In a minority, a clear environmental, toxic, or genetic etiology is determined. Six genes have been identified to cause diseases often indistinguishable from sporadic PD. Although accounting for only 1 to 3% of PD, the identification of single genes that cause PD clearly indicate that PD can have solely genetic causes. In addition to single-gene mutations, large familial aggregation and twin studies demonstrate a modest genetic component in idiopathic PD.

Humans↗

PubMed2006

Optimized neuronal differentiation of murine embryonic stem cells: role of cell density.

Neuronally differentiated embryonic stem (ES) cells offer a flexible and extremely potent model to study nervous system development and disease. A variety of protocols have been described to facilitate neuronal differentiation. The density of ES cells used for neuronal differentiation has striking effects on the proportion and purity of the derived neuronal cells. Here, the protocols used to optimize ES cell density in neuronal differentiation with and without an initial aggregation step are described.

Animals↗

PubMed2005

Cerebrotendinous xanthomatosis: possible higher prevalence than previously recognized.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurodegenerative disorder caused by 27-sterol hydroxylase (CYP27) deficiency. OBJECTIVE: To describe clinical features and results of genetic analysis in a family with CTX. DESIGN: Case report. SETTING: University hospital. Subjects A 54-year-old woman with CTX, her family members, and 115 white control subjects. MAIN OUTCOME MEASURES: Results of clinical evaluation and magnetic resonance imaging of the brain in the affected subject; results of mutation analysis of the CYP27 coding sequence in the patient, her parents, and the control subjects. RESULTS: The proband and her affected sibling had classic features of CTX, including presenile cataracts, tendon xanthomas, diarrhea, and a complex neurodegenerative disorder. They were somewhat atypical, however, because their cataracts were congenital, cognitive impairment had been noted in childhood, and the white matter involvement was more severe than usual. The proband was shown to be homozygous for CYP27 mutation R362C. Similar analysis of 115 control subjects identified 1 subject who was a heterozygous carrier for this same CYP27 mutation. CONCLUSIONS: The prevalence of CTX due to CYP27 mutation R362C alone is approximately 1 per 50,000 among white individuals. Although the disorder is rare, this incidence is substantially greater than previously recognized. Greater awareness of CTX is important because specific treatment is available.

Arginine↗

PubMed2005

Embryonic stem cell models of CAG repeat disease.

Nine neurodegenerative disorders are caused by CAG/polyglutamine (polyQ) repeat expansions. The underlying molecular mechanisms responsible for disease specific neurodegeneration remain elusive. In vivo and in vitro models utilizing rodent tissues, immortalized human cell lines, and human post mortem samples have provided insight into disease mechanisms. Concern that cellular and molecular processes observed in these models may not faithfully reproduce human diseases or be useful to identify compounds of therapeutic utility has driven development of new disease models. In addition to their therapeutic potential, stem cells represent a renewable source of tissue that can be directed into neurons and glia and can be used to study neurodegenerative cascades from their inception. Neuronally differentiated human stem cells containing CAG repeat expansions have the potential to accurately replicate human CAG repeat diseases and may be a faithful predictor of which compounds will be of human benefit. As a first step in development of this type of model, we developed murine embryonic stem cell models to study the mechanisms of polyQ tract induced neuronal degeneration.

Animals↗

PubMed2004

Embryonic stem cells expressing expanded CAG repeats undergo aberrant neuronal differentiation and have persistent Oct-4 and REST/NRSF expression.

Nine neurodegenerative disorders are caused by CAG/polyglutamine (polyQ) repeat expansions. The molecular mechanisms responsible for disease-specific neurodegeneration remain elusive. We developed an embryonic stem (ES) cell-based model to probe the role of polyQ tract expansion in neuronal degeneration. ES cells containing expanded CAG repeats in the hypoxanthine phosphoribosyltransferase (Hprt) gene develop features typical of CAG-mediated neuropathology, exhibit length-dependent decrease in survival, undergo aberrant neuronal differentiation as well as persistent Oct-4 and Repressor element-1 transcription factor/neuron restrictive silencer factor (REST/NRSF) expression. This novel model will allow analysis of the molecular pathogenesis of neuronal degeneration and can be used to rapidly screen therapeutic interventions for these fatal diseases.

Cell Differentiation↗