Progressive wild-type transthyretin deposition after liver transplantation preferentially occurs onto myocardium in FAP patients.

To elucidate whether progressive wild-type transthyretin (TTR) deposition can actually occur after liver transplantation (LT), amyloid fibrils were investigated in two familial amyloid polyneuropathy patients with TTR Val30Leu variant, who died 1 year after LT. Amyloid fibrils were extracted from cardiac muscles, sciatic nerves and kidney, which were investigated by the immunoprecipitation-mass spectrometry method and liquid chromatography-ion trap mass spectrometry analysis. The ratio of wild-type to variant TTR in cardiac muscle was approximately 5:5 before LT, but greatly increased to about 9:1 after transplantation. The ratios in sciatic nerves and kidney obtained at autopsy were approximately 5:5. Wild-type TTR was undetectable in kidney amyloid obtained before LT. Our results indicate that paradoxical wild-type TTR deposition after LT can preferentially occur in myocardium, leading to fatal cardiac dysfunction, but it is quite likely that this phenomenon can also occur in other visceral organs.

[Fas antigen gene in thymuses from patients with myasthenia gravis].

The Fas antigen is a cell surface protein that can mediate apoptosis, and plays a major role in functional maturity in clonal deletion of autoreactive T cells in the thymus. Recently a cDNA encoding the human Fas antigen was isolated. It was suggested that a signal-transducing domain, along with inhibitory one, was presented in the cytoplasmic domain of the Fas antigen. We examined whether any abnormality in Fas antigen gene may breakdown the immunotolerance in patients with myasthenia gravis (MG). We used single-strand conformational polymorphism (SSCP) analysis, generally used to screen for unknown mutation, to examine the cytoplasmic cDNA of Fas antigen obtained by reverse transcription (rt)-PCR from mRNA of MG thymuses. Furthermore, we studied in situ expression of Fas antigen mRNA in thymuses from MG patients. Fragments from all the 12 (3 control subjects, and 9 MG patients) thymuses produced by rt-PCR showed equally stained two bands of the two single strands. In the thymuses from both controls and MG patients, the Fas antigen mRNA was mainly expressed in small thymic cells. These cells were located near clustered cells with relatively large cytoplasms in the cortex and sometimes surrounded them, but were also founded in clusters in the follicules. In situ expressions of Fas antigen mRNA were more remarkable in MG thymuses than in control subjects, and in hyperplastic thymuses than in normoplastic ones. These results suggest that mRNA for the cytoplasmic domain of the Fas antigen have no mutation, and its expression is not reduced in thymuses from patients with MG.

[A case of progressive supranuclear palsy showing improvement of rigidity, nuchal dystonia and autonomic failure with trazodone].

A 63-year-old man was admitted to the hospital with a 1,5-year history of progressive dementia, supranuclear ophthalmoplegia, pseudobulbar palsy, rigidity and dystonia in the neck and the upper trunk. Magnetic resonance imagings showed severe atrophy of the frontal lobe and the brainstem. He was diagnosed as having progressive supranuclear palsy (PSP). Rigidity, nuchal dystonia, frequent micturition, and profuse sweating ameliorated after trazodone administration. Furthermore, additional administration of L-dopa and droxidopa improved his pseudobulbar palsy, akinesia, and lack of initiative. Single photon emission tomography using IMP after medication showed increased IMP-uptake in the frontal areas and the basal ganglia compared with that before medication. This patient illustrates a substantial role of impairments in the serotonin system in the production of some PSP symptoms.

Muscle histopathology in myotonic dystrophy in relation to age and muscular weakness.

We studied histopathological changes in the biceps brachii muscle in relation to age and the degree of muscle weakness in 64 patients (aged 11-59 years) with myotonic dystrophy. The proportion of type 1 fibers was unaltered in the adolescent patients compared with control values, but increased with age. The average diameters of all the fiber types were smaller than control values in the adolescents, suggesting immature development; however, there was an increase in diameter with age that was associated with an increase of hypertrophic type 2 fibers. At all ages, type 1 fibers were smaller than type 2 ones. Small angular fibers and small group atrophy consisted mainly of type 1 fibers, their incidences decreasing with age. The severity of muscular weakness was related to the predominance of type 1 fibers, the reduction in the number of hypertrophic type 2 fibers, and the accumulation of adipose cells, but not to the presence of small angular fibers or to small group atrophy.

[In situ expression of IL-1 beta and IL-2 mRNA in thymuses from patients with myasthenia gravis].

The expression of IL-1 beta mRNA and IL-2 mRNA was analyzed in seven thymuses from patients with myasthenia gravis (MG) and in three normal thymuses using in situ hybridization techniques. Cells containing IL-beta mRNA were detected in all seven cases. These IL-1 beta producing cells were mainly located and clustered in the connective structures of thymic septae and peri-lobuler area like anti-keratin AE3 positive cells. The distribution of anti-CD68 positive cells was different from that of IL-1 beta producing cells in thymus of myasthenia gravis patients. IL-2 producing cells were also found in all seven cases, and their frequency (number of cells/mm2) had a tendency to correlate with the severity of the disease. On the other hand, we could not find both IL-1 beta mRNA and IL-2 mRNA in three normal thymuses. These results suggested a possible role of high IL-1 beta and IL-2 production to activate T cells in myasthenia gravis thymus. Furthermore, in situ production of IL-2 might be reflected in the severity of the disease.