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P Wermuth

Publications and source records attributed to P Wermuth.

4 recordsLinked to original sources

Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans.

The tumor suppressor gene FHIT encompasses the common human chromosomal fragile site at 3p14.2 and numerous cancer cell biallelic deletions. To study Fhit function we cloned and characterized FHIT genes from Drosophila melanogaster and Caenorhabditis elegans. Both genes code for fusion proteins in which the Fhit domain is fused with a novel domain showing homology to bacterial and plant nitrilases; the D. melanogaster fusion protein exhibited diadenosine triphosphate (ApppA) hydrolase activity expected of an authentic Fhit homolog. In human and mouse, the nitrilase homologs and Fhit are encoded by two different genes: FHIT and NIT1, localized on chromosomes 3 and 1 in human, and 14 and 1 in mouse, respectively. We cloned and characterized human and murine NIT1 genes and determined their exon-intron structure, patterns of expression, and alternative processing of their mRNAs. The tissue specificity of expression of murine Fhit and Nit1 genes was nearly identical. Because fusion proteins with dual or triple enzymatic activities have been found to carry out specific steps in a given biochemical or biosynthetic pathway, we postulate that Fhit and Nit1 likewise collaborate in a biochemical or cellular pathway in mammalian cells.

Acid Anhydride Hydrolases↗

Quantitative assessment of cardiovascular autonomic function in Guillain-Barre syndrome.

To study the temporal course and the relationship between autonomic failure and motor weakness in Guillain-Barré syndrome (GBS), a total of 164 autonomic function tests were serially applied for up to 1 year in 13 consecutive patients. Results were compared with those obtained in 25 healthy volunteers and 13 patients with other neurological diseases. Parasympathetic function tests comprised heart rate responses to Valsalva maneuver, deep breathing, and active change of posture, whereas sympathetic vasomotor function was assessed by blood pressure responses to handgrip and standing. At the height of the disease, subclinical autonomic involvement of both parasympathetic and sympathetic arms was revealed in the vast majority of patients. Abnormalities of autonomic function tests improved gradually over time, paralleling the recovery of motor function, but were only partially related to clinically significant autonomic dysfunction. Correlation analysis suggested that tachycardia in the context of GBS might be caused by a reduction of sympathetically mediated peripheral vascular tone rather than by vagal failure.

Adult↗

Eyeball pressure testing in the evaluation of serious bradyarrhythmias in Guillain-Barré syndrome.

OBJECTIVE: To investigate the usefulness of eyeball pressure testing (EP) as an indicator for impending serious bradyarrhythmias in patients with Guillain-Barré syndrome (GBS) and its relationship to motor disability. BACKGROUND: Autonomic dysfunction is a common complication in GBS and accounts for a significant number of deaths. Serious bradyarrhythmias are thought to occur only in severe cases but are difficult to predict. METHODS/DESIGN: In 13 consecutive patients with GBS aged 29 to 70 years, 156 EP (6 to 19 per patient) were done serially for up to 1 year. Bilateral moderate pressure was manually applied and sustained for 25 seconds or until abnormal bradycardia developed, defined as heart rate below 40 beats per minute. Disability was graded by a score from 0 to 5 (DS). RESULTS: Four of 13 patients (DS 2/2/3-4/5) showed abnormal sensitivity to EP at least once. In two of them, vagal overreactivity could be demonstrated repeatedly, which gradually resolved within 4 and 10 days. In one patient with a rapid progressive course requiring early cardiopulmonary resuscitation, a highly abnormal EP could be recorded until 1 day after heart arrest. Another patient (DS 3-4) with abnormal EP required cardiac pacing twice because of significant bradycardia. The only other event necessitating pacing occurred in a severely disabled patient (DS 5-4) who never showed abnormal EP. CONCLUSIONS: Vagal overreactivity could be demonstrated in approximately 30% of our patients. It was not restricted to severe motor impairment and was also present in mild-to-moderately disabled patients. In this regard, EP may be a simple and useful bedside test to indicate an increased risk of developing serious bradyarrhythmias in patients with GBS.

Adult↗