Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema

The expression of two autoimmune thyroid diseases, GD and idiopathic myxoedema, is associated with antibodies to the thyroid-stimulating hormone (TSH) receptor. Thyroid stimulating antibodies (TSAb) in GD are TSH agonists and cause hyperthyroidism as well as goitre, whereas thyroid stimulation blocking antibodies (TSBAb) in idiopathic myxoedema are TSH antagonists and cause hypothyroidism and thyroid atrophy. We investigated the effect of antibodies to TSH receptor on Fas-mediated apoptosis of thyroid epithelial cells (thyrocytes). Human IgG was isolated from healthy donors, patients with GD and idiopathic myxoedema. Human thyrocytes were obtained from surgical specimens. Thyrocytes were cultured in the presence or absence of human IgG with or without interferon-gamma (IFN-γ) or IL-1β for a specified time. After incubation, we examined the level of cAMP in cultured supernatants and both Fas and Bcl-2 expression on thyrocytes. In addition, we examined anti-Fas-mediated apoptosis of thyrocytes. Fas expression on thyrocytes was significantly down-regulated by Graves' IgG and TSH, although idiopathic myxoedema IgG did not affect Fas expression on thyrocytes. Idiopathic myxoedema IgG abrogated the effect of TSH on both cAMP production and inhibition of Fas expression on thyrocytes. Treatment of thyrocytes with IL-1β or IFN-γ caused a marked augmentation of Fas expression on thyrocytes. The increase of Fas expression of thyrocytes induced by IL-1β or IFN-γ was significantly suppressed in the presence of TSH or Graves' IgG. Anti-Fas-induced apoptosis of thyrocytes was observed in thyrocytes treated with IL-1β or IFN-γ, but was markedly inhibited in the presence of TSH or Graves' IgG. Furthermore, idiopathic myxoedema IgG abrogated most of the inhibitory effect of TSH on Fas-mediated apoptosis of thyrocytes treated with IL-1β or IFN-γ. Bcl-2 expression of thyrocytes did not change after stimulation with TSH, Graves' IgG, idiopathic myxoedema IgG, IL-1β or IFN-γ. These results suggest that TSAb found in Graves' patients may be potentially involved in the development of goitre by inhibition of Fas-mediated apoptosis of thyrocytes. In addition, TSBAb inhibit the action of TSH and increase the sensitivity toward Fas-mediated apoptosis of thyrocytes, inducing thyroid atrophy seen in patients with idiopathic myxoedema.     

Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH₂), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH₂ with a K_m value of 3.4 × 10^?5m , at pH 7.3 and 37° being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the V_max value of 4.1 × 10^?9mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu¹⁰-Val¹¹ bond and, surprisingly, His⁹-Leu¹⁰ as well.     

Case of cutaneous Scedosporium apiospermum infection successfully treated with voriconazole

We report a case of cutaneous infection due to Scedosporium apiospermum in a 75-year-old immunocompromised male patient who had received long-term corticosteroid and immunosuppressant therapy for the treatment of nephrotic syndrome. The patient came to our department complaining of erythema with a number of pustules on the dorsal surface of the right hand. S. apiospermum was identified from a culture taken from the pus. After unsuccessful treatment with topical ketoconazole, oral itraconazole and oral terbinafine, the lesion quickly resolved with the daily administration of 400 mg voriconazole. No recurrence was observed despite discontinuation of voriconazole due to drug-induced hepatitis. Voriconazole holds out the promise of an effective treatment for invasive Scedosporium infection.     

A case of Behçet's disease aggravated by gingival infection with methicillin-resistant Staphylococcus aureus

We report a case of Behcet's disease aggravated by gingivitis and carious teeth infected with methicillin-resistant Staphylococcus aureus. Recurrent severe ulcers in the mouth, and on the genitalia and legs were closely linked with the infection, and dramatically improved after extraction of the carious teeth and administration of systemic vancomycin hydrochloride.     

New Electrophysiologic Features and Catheter Ablation of Atrioventricular and Atriofascicular Accessory Pathways:

Catheter Ablation for Mahaim Pathways. Introduction : Several modalities of catheter ablation have been proposed to eliminate Mahaim pathway conduction. However, limited research has been reported on the electrophysiologic nature of this pathway in its entity.
Methods and Results : In seven patients, electrophysiologic study was performed, and radiofrequency energy was applied to investigate the electrophysiologic clues for successful ablation. In all seven patients, the Mahaim pathway was diagnosed as a right-sided atriofascicular or atrioventricular pathway with decremental properties. In two patients, two different kinds of electrograms were recorded through the ablation catheter positioned at the Mahaim pathway location: one was suggestive of conduction over the decremental portion, demonstrating a dulled potential; and the other of nondecremental conduction, demonstrating a spiked potential. All but one of the Mahaim pathways were eliminated successfully at the atrial origin where the spiked Mahaim potential was recorded. Radiofrequency energy application was performed at the slow potential site resulting in failure to eliminate the conduction over the Mahaim pathway. Conduction block at the site between the slow and fast potential recording sites was provoked by intravenous administration of adenosine, concomitant with a decrease in the amplitude of the Mahaim potential. In one patient, the clinical arrhythmia was a sustained monomorphic ventricular tachycardia originating from the ventricular end of the Mahaim fiber.
Conclusion : The identification of Mahaim spiked potentials may be the optimal method to permit their successful ablation. Detailed electrophysiologic assessment is indispensable for successful ablation of tachycardias associated with Mahaim fibers because tachycardias unassociated with Mahaim fibers can occur despite complete elimination of the Mahaim fiber.